Document text
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
1.TITLE PAGE
Vaccine Name and
Compound Number:BNT162 RNA -Based COVID -19 Vaccines, Compound
Number: PF -07302048
Report Title: Interim Report –Adolescents : A Phase 1/2/3,
Placebo- Controlled, Randomized, Observer -Blind, Dose -
Finding Stud y to Evaluate the Safet y, Tolerability,
Immunogenicit y, and Efficacy of SARS -COV -2 RNA
Vaccine Candidates Against COVI D-19 in Healthy
Individuals
Protocol Number: Protocol C4591001
Sponsor: BioNTech SE
Sponsor Agent: Pfizer I nc
Phase of Development: Phase 1/2/3
First Subject First Visit: 29 April 2020
Primary Completion Date: Not applicable
Data Cutoff Date: 13March 2021
Serology Completion Dat e: 22 March 2021(Phase 2/3, Visit 3[post- Dose 2 blood
draw] assay completed for participants 12 through
25years of age)
Name and Affiliation of
Coordinating/Leading
Investigator:Stephen Thomas, MD
SUNY Upstate Medical University
725 Irving Ave, Ste. 311
Syracuse, NY 13210
The names of the principal investigators, site addresses,
and number of participants enrolled at each site are
provided in the appendix titled L ist and Description of
Investigators and Service Providers, Appendix 16.1.4 .
Sponsor’s Signatories: John L . Perez, MD, MBA, MA
Vice President, Vaccines Clinical Research and
Development, Pfizer Inc
Kenneth Koury , PhD
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 1
FDA-CBER-2022-5812-0234709
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
Clinical Biostatistics Head, Vaccines Clinical Research
and Development, Pfizer Inc
Ugur Sahin, MD
Chief Executive Officer, BioNTech SE
Internal Reports Referenced: Final Anal ysis Interim CSR: C 4591001 dated
03December 2020
Date of Current Version: 14April 2021
Date(s) of Previous
Report(s):Not applicable
GCP STATEMENT
This study was conducted in compliance with Good Clinical Practice (GCP) guidelin es and,
where applicable, local country regulations relevant to the use of new therapeutic agents in
the country /countries of conduct, including the archiving of essential documents.
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 2
FDA-CBER-2022-5812-0234710
16
18
18
18
18
18
19
20
20
20
31
31
33
33
34
35
35
35
35
38
38
38
38
38
40
40
40Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL2. SYNOPSI S
3. TABLE OF CONTENTS
1. TI TLE PAGE ................................ ................................ ................................ ..................... 1
2. SYNOPSI S................................ ................................ ................................ ......................... 3
3. TABLE OF CONTENTS ................................ ................................ ................................ ... 3
4. LIST OF ABBREVIATIONS AND DEFINITION OF TERMS ................................ ......
5. ETHI CS................................ ................................ ................................ ..............................
5.1. I ndependent Ethics Committee or I nstitutional Review Board................................ ...
5.2. Ethical Conduct of the Study ................................ ................................ .......................
5.3. Participant Information and Consent................................ ................................ ...........
6. INVESTIGATORS AND STUDY ADMINISTRATIVE STRUCTURE ........................
7. INTRODUCTION ................................ ................................ ................................ .............
8. STUDY OBJECTIVES AND ENDPOINTS ................................ ................................ .....
8.1. Phase 1 ................................ ................................ ................................ .........................
8.2. Phase 2/3................................ ................................ ................................ ......................
9. INVESTIGAT IONAL PL AN................................ ................................ ............................
9.1. Overall St udy Design and Plan ................................ ................................ ....................
9.1.1. Phase 1 ................................ ................................ ................................ ..................
9.1.2. Phase 2/3 ................................ ................................ ................................ ...............
9.2. Discussion of Study Design, Including Choice of Control Groups .............................
9.3. Participant Selection ................................ ................................ ................................ ....
9.4. I nvestigati onal Product ................................ ................................ ................................
9.4.1. Vaccines Administered ................................ ................................ .........................
9.4.2. I dentity of Investigational Product(s) ................................ ................................ ....
9.4.3. Method of Assigning Participants to Treatment Groups................................ .......
9.4.4. Selection of Dose Levels/Regimen ................................ ................................ .......
9.4.4.1. Phase 1 ................................ ................................ ................................ ............
9.4.4.2. Phase 2/3................................ ................................ ................................ .........
9.4.5. Blinding................................ ................................ ................................ .................
9.4.6. Prior and Concomitant Vaccines, Medications, and Procedures ..........................
9.4.7. Vaccine Compliance ................................ ................................ .............................
9.5. Efficacy , Immunogenicity , and Safet y Evaluations ................................ ....................
Page 3
FDA-CBER-2022-5812-0234711
40
41
41
41
42
42
42
43
43
43
44
44
45
45
46
46
47
48
48
48
50
53
54
54
55
58
58
58
59
59
60
61
62Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL9.5.1. Efficacy and Immunogenicity Evaluations ................................ ...........................
9.5.2. Safet y Evaluations ................................ ................................ ................................ .
9.5.2.1. Electr onic Diary ................................ ................................ ..............................
9.5.2.2. Surveillance of Events That Could Represent Vaccine- Associated
Enhanced COVID -19 and Phase 2/3 Stopping Rule ................................ ............
9.5.2.3. Adverse Events and Serious Adverse Events ................................ .................
9.5.2.4. Events of Special I nterest ................................ ................................ ...............
9.6. Data Qualit y Assurance ................................ ................................ ...............................
9.7. Statistical Methods Planned in the Protocol ................................ ................................
9.7.1 . Statistical and Analy tical Plans................................ ................................ .............
9.7.1.1. Analy sis Sets ................................ ................................ ................................ ...
9.7.2. Determination of Sample Size ................................ ................................ ..............
9.7.3. Efficacy Anal ysis................................ ................................ ................................ ..
9.7.4. I mmunogenicit y Analysis ................................ ................................ .....................
9.7.5. Safet yAnal ysis................................ ................................ ................................ ......
9.7.6. Other Anal yses................................ ................................ ................................ ......
9.7.7. Analy sis Timing ................................ ................................ ................................ ....
9.8. Changes in the Conduct of Study or Planned Analy ses................................ ..............
10. STUDY PARTI CIPANTS ................................ ................................ ...............................
10.1. Disposition of Partici pants ................................ ................................ .........................
10.1.1. Participants 12 Through 15 Years of Age ................................ ...........................
10.1.2. Participants 16 Through 55 Years of Age ................................ ...........................
10.2. Protocol Deviations ................................ ................................ ................................ ...
10.3. Vaccine Administration and Timing ................................ ................................ .........
10.3.1. Participants 12 Through 15 Years of Age ................................ ...........................
10.3.2. Participants 16 Through 55 Years of Age ................................ ...........................
10.4. Data Sets Anal yzed................................ ................................ ................................ ....
10.4.1. Participants 12 Through 15 Years of Age ................................ ...........................
10.4.1.1. Safet y Population ................................ ................................ ..........................
10.4.1.2. Duration of Follow- Up................................ ................................ .................
10.4.1.3. I mmunogenicity Populations ................................ ................................ ........
10.4.1.4. Efficacy Populations ................................ ................................ .....................
10.4.2. Pa rticipants 16 Through 55 Years of Age ................................ ...........................
10.5. Demographic and Other Baseline Characteristics ................................ .....................
Page 4
FDA-CBER-2022-5812-0234712
62
62
64
66
68
68
68
68
69
69
69
69
69
69
69
69
69
69
70
71
72
73
74
74
77
80
82
84
84Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL10.5.1. Participants 12 Through 15 Years of Age ................................ ...........................
10.5.1.1. Safet y Population Participants 12 Through 15 Years of Age....................
10.5.1.2. I mmunogenicity Population Participants 12 Through 15 Years of A ge....
10.5.2. Participants 16 Through 55 Years of Age ................................ ...........................
10.6. Participant Compliance ................................ ................................ ..............................
10.6.1. I mmunogenicit y Blood Samples Participants 12 Through 15 Yea rs of Age ...
10.6.2. E- Diary ................................ ................................ ................................ ................
10.6.2.1. Participants 12 Through 15 Years of Age ................................ ....................
10.6.2.2. Participants 16 Through 55 Years of Age ................................ ....................
10.7. Prior and Concomitant Vaccines, Medications, and Procedures ...............................
10.7.1. Participants 12 Through 15 Years of Age ................................ ...........................
10.7.2. Participants 16 Through 55 Years of Age ................................ ...........................
11. EFFI CACY AND IMMUNOGENICITY EVALUATION................................ .............
11.1. Efficacy Results ................................ ................................ ................................ .........
11.1.1. I nterim Anal ysis 1 and Final Analy sis of Efficacy ................................ .............
11.1.2. Vaccine Efficacy Against COVID -19 Participants 12 Through 15 Years of
Age................................ ................................ ................................ ...........................
11.1.2.1. Confirmed Cases of COVID -19 at Least 7 Day s after Dose 2 Evaluable
Efficacy Population Participants 12 Through 15 Years of Age ........................
11.1.2.1.1. Participants Without Evidence of Infection Before and During
Vaccination Regimen Participants 12 Through 15 Years of Age ..................
11.1.2.1.2. Participants With or Without Evidence of Infection Before and During
Vaccination Regimen Participants 12 Through 15 Years of Age ..................
11.1.2.1.3. All Confirmed Cases of COVID -19 After Dose 1 All-Available
Efficacy Population Participants 12 Through 15 Years of Age.....................
11.1.3. Vaccine Efficacy Against Severe COVID -19 Participants 12 Through 15
Years of Age ................................ ................................ ................................ ............
11.2. Efficacy Conclusions Participants 12 Through 15 Years of Age ...........................
11.3. I mmunogenicit y Results Participants 12 Through 15 Yea rs of Age ......................
11.3.1. Noninferiorit y of Immune Response to Prophylactic BNT162b2 in
Participants 12 Through 15 Years Compared with Particip ants 16 Through 25
Years of Age ................................ ................................ ................................ ............
11.3.2. GMTs Participants 12 Through 15 Years of Age ............................................
11.3.3. GMFRs Participants 12 Through 15 Years of Age................................ ..........
11.3.4 . Seroresponse Rate Participants 12 Through 15 Years of Age .........................
11.3.5. Phase 3 I mmunogenicity Conclusions Participants 12 Through 15 Y ears of
Age................................ ................................ ................................ ...........................
12. SAFETY EVALUATION ................................ ................................ ...............................
Page 5
FDA-CBER-2022-5812-0234713
84
84
87
89
89
91
93
94
94
94
96
97
97
98
99
99
99
99
109
112
112
114
114
114
114
114
115
115Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL12.1. L ocal Reactions ................................ ................................ ................................ .........
12.1.1. Participants 12 Through 15 Years of Age ................................ ...........................
12.1.2. Participants 16 Through 55 Years of Age ................................ ...........................
12.2. Sy stemic Events ................................ ................................ ................................ .........
12.2.1. Participants 12 Through 15 Years of Age ................................ ...........................
12.2.2. Participants 16 Through 55 Years of Age ................................ ...........................
12.3. Adverse Events ................................ ................................ ................................ ..........
12.3.1. Summary of Adverse Events ................................ ................................ ...............
12.3.1.1. Participants 12 Through 15 Years of Age ................................ ....................
12.3.1.1.1. Dose 1 to 1 Month After Dose 2 Participants 12 Through 15 Years
of Age ................................ ................................ ................................ ................
12.3.1.1.2. Dose 1 to Data Cutoff Date Participants 12 Through 15 Years of
Age................................ ................................ ................................ ....................
12.3.1.2. Participants 16 Through 55 Years of Age ................................ ....................
12.3.1.2.1. Dose 1 to 1 Month After Dose 2 Participants 16 Through 55 Years
of Age ................................ ................................ ................................ ................
12.3.1.2.2. Dose 1 to Unblinding Date Participants 16 Through 55 Ye ars of Age
12.3.2. Analy sis of Adverse Events ................................ ................................ ................
12.3.2.1. Adverse Events by System Organ Class and Preferred Term ......................
12.3.2.1.1. Participants 12 Through 1 5 Years of Age ................................ ..............
12.3.2.1.1.1. Dose 1 to 1 Month After Dose 2 Participants 12 Through 15
Years of Age ................................ ................................ ................................ ..
12.3.2.1.1.2. Dose 1 to Data Cutoff Date Participants 12 Through 15 Years of
Age................................ ................................ ................................ .................
12.3.2.1.2. Participants 16 Through 55 Years of Age ................................ ..............
12.3.2.1.2.1. Dose 1 to 1 Month After Dose 2 Participants 16 Through 55
Years of Age ................................ ................................ ................................ ..
12.3.2.1.2.2. Dose 1 to Unblinding Date Participants 16 Through 55 Years of
Age................................ ................................ ................................ .................
12.3.2.2. Related Adverse Events b y System Organ Class and Preferred Term .........
12.3.2.2.1. Dose 1 to 1 Month After Dose 2 Participants 12 Through 15 Years
of Age ................................ ................................ ................................ ................
12.3.2.2.2. Dose 1 to 1 Month After Dose 2 Participants 16 Through 55 Years
of Age ................................ ................................ ................................ ................
12.3.2.3. I mmediate Adverse Events Participants 12 Through 15 Years of Age .....
12.3.2.4. Severe or Life-Threatening Adverse Events ................................ .................
12.3.2.4.1. Dose 1 to 1 Month After Dose 2 Participants 12 Through 15 Years
of Age ................................ ................................ ................................ ................
Page 6
FDA-CBER-2022-5812-0234714
116
116
116
117
117
117
117
121
123
123
123
124
124
124
127
127
127
129
129
129
129
130
130
130
131
132
132
133Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL12.3.2.4.2. Dose 1 to 1 Month After Dose 2 Participants 16 Through 55 Years
of Age ................................ ................................ ................................ ................
12.4. Deaths, Serious Adverse Events, Safet y-Related Participant Withdrawals, and
Other Significant Adverse Events –Phase 2/3 Participants ≥16 Years of Age ......
12.4.1. Deaths ................................ ................................ ................................ ..................
12.4.1.1. Death Narratives ................................ ................................ ...........................
12.4.2. Serious Adverse Events ................................ ................................ .......................
12.4.2.1. Participants 12 Through 15 Years of Age ................................ ....................
12.4.2.1.1. Dose 1 to 1 Month After Dose 2 Participants 12 Through 15 Years
of Age ................................ ................................ ................................ ................
12.4.2.1.2. Dose 1 to Data Cutoff Date Participants 12 Through 15 Years of
Age................................ ................................ ................................ ....................
12.4.2.2. Participants 16 Through 55 Years of Age ................................ ....................
12.4.2.2.1. Dose 1 to 1 Month After Dose 2 Participants 16 Through 55 Years
of Age ................................ ................................ ................................ ................
12.4.2.2.2. Dose 1 to Unblinding Date Participants 16 Through 55 Years of Age
12.4.2.3. Serious Adverse Event Narratives ................................ ................................
12.4.3. Safet y-Related Participant Withdrawals ................................ .............................
12.4.3.1. Participants 12 Through 15 Years of Age ................................ ....................
12.4.3.2. Participants 16 Through 55 Years of Age ................................ ....................
12.4.3.3. Narratives of Safet y-Related Participant Wi thdrawals ................................ .
12.4.4. Other Significant Adverse Events................................ ................................ .......
12.4.4.1. Narratives of Other Significant Adverse Events................................ ...........
12.4.4.2. Other Safet y Assessments ................................ ................................ .............
12.4.4.2.1. Severe COVID -19 Illness ................................ ................................ .......
12.4.4.2.2. Pregnancy ................................ ................................ ...............................
12.4.4.3. Analy sis and Discussion of Deaths, Serious Adverse Events, Safety -
Related Participant W ithdrawals, and Other Significant Adverse Events ............
12.4.5. Safet y Conclusions ................................ ................................ ..............................
12.4.5.1. Participants 12 Through 15 Years of Age ................................ ....................
12.4.5.2. Participants 16 Through 55 Years of Age ................................ ....................
13. DI SCUSSION AND OVERALL CONCLUSIONS ................................ ........................
13.1. Discussion................................ ................................ ................................ ..................
13.2. Overall Conclusions ................................ ................................ ................................ ..
Page 7
FDA-CBER-2022-5812-0234715
22
36
44
48
50
54
55
56
57
58
59
60
61
63
65
66
70
71
72Interim Clinical Study Report
Protocol C4591001
CONFIDENTIALLIST OF IN -TEXT TABLES
Table 1. Phase 2/3 Objectives, Estimands, and Endpoints ................................ .................
Table 2. Investigational Product L ot Numbers Interim Adolescents ...........................
Table 3. Anal ysis Populations ................................ ................................ ............................
Table 4. Disposition of All Randomized Subjects Through 1 Month After Dose 2
Subjects 12 Through 15 and 16 Through 25 Years of Age ................................ .........
Table 5. Disposition of All Randomized Subjects Phase 2/3 Subjects 16 -55 Years of
Age................................ ................................ ................................ ..............................
Table 6. Vaccine as Administered, by Vaccine Group Subjects 12 Through 15 and 16
Through 25 Years of Age (Reactogenicity Subset) ................................ .....................
Table 7. Vaccine Administration Timing Subjects 12 Through 15 and 16 Through 25
Years of Age (Reactogenicity Subset) ................................ ................................ ........
Table 8. Vaccine as Administered by Vaccine Group Phase 2/3 Subjects 16- 55 Years
of Age All Randomized Subjects ................................ ................................ .............
Table 9. Vaccine Administration Timing Phase 2/3 Subjects 16- 55 Years of Age All
Randomized Subjects ................................ ................................ ................................ ..
Table 10. Safet y Population Subjects 12 Through 15 and 16 Through 25 Years of Age
Table 11. Follow -up Time After Dose 2 Subjects 12 Through 15 Years of Age
Safety Population ................................ ................................ ................................ ........
Table 12. Immunogenicity Populations Subjects 12 Through 15 and 16 Through 25
Years of A ge (Immunogenicity Subset) ................................ ................................ ......
Table 13. Follow -up Time After Dose 2 Phase 2/3 Subjects 16- 55 Years of Age
Safety Population ................................ ................................ ................................ ........
Table 14. Demographic Characteristics Subjects 12 Through 15 and 16 Through 25
Years of Age Safet y Population ................................ ................................ ...............
Table 15. Demographic Characteristics Subjects 12 Through 15 and 16 Through 25
Years of Age (Immunogenicity Subset) Dose 2 Evaluable Immunogenicity
Population ................................ ................................ ................................ ....................
Table 16. Demographic Characteristics Phase 2/3 Subjects 16- 55 Years of Age
Safety Population ................................ ................................ ................................ ........
Table 17. Vaccine Efficacy First COVID -19 Occurrence From 7 Day s After Dose 2
Blinded Placebo -Controlled Follow- up Period Subjects 12 Through 15 Years of
Age and Without Evidence of Infection Prior to 7 Day s After Dose 2 Evaluable
Efficacy (7 Day s) Population ................................ ................................ ......................
Table 18. Vaccine Efficacy First COVID -19 Occurrence From 7 Day s After Dose 2
Blinded Placebo -Controlled Follow- up Period Subjects 12 Through 15 Years of
Age and With or Without Evidence of Infection Prior to 7 Day s After Dose 2
Evaluable Efficacy (7 Day s) Population ................................ ................................ .....
Table 19. Vaccine Efficacy First COVID -19 Occurrence After Dose 1 Blinded
Placebo- Controlled Follow -up Period Subjects 12 Through 15 Years of Age
Dose 1 All -Available Efficacy Population ................................ ................................ ..
Page 8
FDA-CBER-2022-5812-0234716
75
76
81
83
95
96
98
99
101
109
119
122Interim Clinical Study Report
Protocol C4591001
CONFIDENTIALTable 20. Summary of Geometric Mean Ratio NT50 Comparison of Subjects 12
Through 15 Years of Age to Subjects 16 Through 25 Years of Age
(Immunogenicity Subset) Subjects Without Evidence of Infection up to 1 Month
After Dose 2 Dose 2 Evaluable Immunogenicity Population ................................ ..
Table 21. Number (%) of Subjects Achieving a ≥ 4-Fold Rise From Before Vaccination
to Each Subsequent Time Point 1 Month After Dose 2 –NT50 –Comparison of
Subjects 12 Through 15 Years of Age to Subjects 16 Through 25 Years of Age
(Immunogenicity Subset) Subjects Without Evidence of Infection up to 1 Month
After Dose 2 Dose 2 Evaluable Immunogenicity Population ................................ ..
Table 22. Summary of Geometric Mean Fold Rise From Befo re Vaccination to Each
Subsequent Time Point, by Baseline SARS -CoV -2 Status NT50 Subjects 12
Through 15 and 16 Through 25 Years of Age (Immunogenicit y Subset) Dose 2
Evaluable Immunogenicity Population ................................ ................................ .......
Table 23. Number (%) of Subjects Achieving a ≥4-Fold Rise From Before Vaccination
to Each Subsequent Time Point, by Baseline SARS -CoV -2 Status – NT50 –
Subjects 12 Through 15 and 16 T hrough 25 Years of Age (I mmunogenicity Subset)
–Dose 2 Evaluable Immuno genicit y Population ................................ ......................
Table 24. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
Through 1 Month After Dose 2 Subjects 12 Through 15 and 16 Through 25
Years of Age (Reactogenicity Subset) Safet y Population ................................ ........
Table 25. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
Through Cutoff Date (13MAR2021), Subjects 12 Through 15 Years of Age
Safety Population ................................ ................................ ................................ ........
Table 26. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1 to
1 Month After Dose 2 Blinded Placebo -Controlled Follow- up Period Phase 2/3
Subjects 16-55 Years of Age Safet y Population ................................ ......................
Table 27. Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding Date
Phase 2/3 Subjects 16 -55 Year s of Age Safet y Population ................................ ...
Table 28. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
Through 1 Month After Dose 2, by System Organ Class and Preferred Term
Subjects 12 Through 15 and 16 Through 25 Years of Age (Reactogenicit y Subset)
Safety Population ................................ ................................ ................................ .....
Table 29. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
Through Cutoff Date (13MAR2021), by System Organ Class and Preferred Term
Subjects 12 Through 15 Years of Age Safet y Population ................................ ........
Table 30. Number (%) of Subjects Reporting at Least 1 Serious Adverse Event From
Dose 1 Through 1 Month After Dose 2, by System Organ Class and Preferred Term
Subjects 12 Through 15 and 16 Through 25 Years of Age (Reactogenicity
Subset) Safet y Population ................................ ................................ ........................
Table 31. Number (%) of Subjects Reporting at Least 1 Serious Adverse Event From
Dose 1 Through Cutoff Date (13MAR2021), b y System Organ Class and Preferred
Term Subjects 12 Through 15 Years of Age Safet y Population ...........................
Page 9
FDA-CBER-2022-5812-0234717
125
31
78
79
86
88
90
92
94Interim Clinical Study Report
Protocol C4591001
CONFIDENTIALTable 32. Number (%) of Subjects Withdrawn Because of Adverse Events From Dose 1
Through 1 Month After Dose 2, b y System Organ Class and Preferred Term
Subjects 12 Through 15 and 16 Through 25 Years of Age (Reactog enicit y Subset)
Safety Population ................................ ................................ ................................ .....
LIST OF IN -TEXT FIGURES
Figure 1. Stud y Schema ................................ ................................ ................................ ......
Figure 2. Geometric Mean Titers: SARS -CoV -2 Neutralization Assay NT50
Subjects 12- 15 and 16- 25 Years of Age (Immunogenicity Subset) Dose 2
Evaluable Immunogenicity Populati on
................................ ................................ .......
Figure 3. Reverse Cumulative Distribution Curves, SARS -CoV -2 Neutralization Assay
NT50 Subjects 12 Through 15 and 16 Through 25 Years of Age
(Immunogenicity Subset) Dose 2 Evaluable Immunogenicity Population ..............
Figure 4. Participants Reporting Local Reactions, by Maximum Severity , Within 7
Days After Each Dose Reactogenicity Subset for Phase 2/3 Anal ysis Safety
Population by Age Group: 12 -15 Years and 16- 25 Years ................................ ...........
Figure 5. Participants Reporting Local Reactions, by Maximum Severity , Within 7
Days After Each Dose – Reactogenicit y Subset for Phase 2/3 Subjects ≥16 Years
of Age –Safety Population by Age Group: 16- 55 Years ................................ ..........
Figure 6. Participants Reporting S ystemic Events, by Maximum Severity , Within 7
Days After Each Dose Reactogenicity Subset for Phase 2/3 Anal ysis Safety
Population by Age Group: 12 -15 Y ears and 16- 25 Years ................................ ...........
Figure 7. Participants Reporting S ystemic Events, by Maximum Severity , Within 7
Days After Each Dose – Reactogenic ity Subset for Phase 2/3 Subjects ≥16 Years
of Age –Safety Population by Age Group: 16- 55 Years ................................ ..........
Figure 8. Phase 2/3 Safety Analy ses: T ime Periods and Anal ysis Groups ........................
Page 10
FDA-CBER-2022-5812-0234718
135
135
135
137
162
164
244
245
247
248
249
251
251
252
253
254
254
258
260Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL14. TABLES AND FIGURES ............................................................................................... 134
Supplemental Tables ................................ ................................ ................................ ..........
Conduct of Study ................................ ................................ ................................ .............
14.1. Demographic Characteristics Subjects 12 Through 15 and 16 Through 25
Years of Age (Reactogenicity Subset) Safet y Population ................................ .
14.2. Medical History Subjects 12 Through 15 and 16 Through 25 Years of Age
(Reactogenicity Subset) Safety Population ................................ .......................
14.3. Demographic Characteristics Subjects 12 Through 15 and 16 Through 25
Years of Age (Immunogenicity Subset) Dose 2 All -Available
Immunogenicit y Population ................................ ................................ .................
14.4. Medical History Phase 2/3 Subjects 16- 55 Years of Age Safet y Population
14.5. I mmunogenicit y Blood Samples Drawn Subjects 12 Through 15 and 16
Through 25 Years of Age (Immunogenicit y Subset) ................................ ...........
14.6. E- Diary Transmission Subjects 12 Through 15 and 16 Through 25 Years of
Age (Reactogenicit y Subset) Safet y Population ................................ ................
14.7. E-D iary Transmission (Reactogenicity Subset) Phase 2/3 Subjects 16 -55
Years of Age Safet y Population ................................ ................................ ........
14.8. Concomitant Vaccines Receiv ed From After Dose 1 Through 1 Month After
Dose 2 Subjects 12 Through 15 and 16 Through 25 Years of Age
(Reactogenicity Subset) Safety Population ................................ .......................
14.9. Concomitant Vaccines Received After Dose 1 Phase 2/3 Subjects 16-55
Years of Age Safet y Population ................................ ................................ ........
Immunogenic ity................................ ................................ ................................ ..............
14.10. Summary of Geometric Mean Titers, b y Baseline SARS -CoV -2 Status
NT50 Subjects 12 Through 15 and 16 Through 25 Years of A ge
(Immunogenicity Subset) Dose 2 Evaluable Immunogenicity Population .......
14.11. Summary of Geometric Mean Titers, b y Baseline SARS -CoV -2Status
NT50 Subjects 12 Through 15 and 16 Through 25 Years of Age
(Immunogenicity Subset) Dose 2 All -Available Immunogenicit y Population .
14.12. Summary of Geometric Mean Fold Rise From Before Vaccination to Each
Subsequent Time Point, by Baseline SARS -CoV -2 Status NT50 Subjects
12 Through 15 and 16 Through 25 Years of Age (I mmunogenicity Subset)
Dose 2 All -Available Immunogen icity Population ................................ ..............
Local Reactions................................ ................................ ................................ ...............
14.13. L ocal Reactions, by Maximum Severity , Within 7 Day s After Each Dose
Subjects 12 Through 15 and 16 Through 25 Years of Age (Reactogenicit y
Subset) Safet y Population ................................ ................................ ..................
14.14. Onset Day s for Local Reactions Subjects 12 Through 15 and 16 Through
25 Years of Age (Reactogenicity Subset) Safet y Population ............................
14.15. Duration (Day s) From First to Last Day of Local Reactions Subjects 12
Through 15 and 16 Through 25 Years of Age (Reactogenicit y Subset) Safety
Population ................................ ................................ ................................ .............
Page 11
FDA-CBER-2022-5812-0234719
262
264
266
268
268
277
281
285
290
293
297
297
320
330
340
366Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL14.16. L ocal Reactions, by Maximum Severity , Within 7 Day s After Each Dose
(Reactogenicity Subset) Phase 2/3 Subjects 16 -55 Years of Age Safet y
Population ................................ ................................ ................................ .............
14.17. Onset Day s for Local Reactions (Reactogenicity Subset) Phase 2/3
Subjects 16-
55 Years of Age Safet y Population ................................ ...............
14.18. Duration (Day s) From First to Last Day of Local Reactions (Reactogenicity
Subset) Phase 2/3 Subjects 16 -55 Years of Age Safety Population ...............
Systemic Events ................................ ................................ ................................ ..............
14.19. Sy stemic Events, by Maximum Severity , Within 7 Day s After Each Dose
Subjects 12 Through 15 and 16 Through 25 Years of Age (Reactogenicit y
Subset) Safet y Population ................................ ................................ ..................
14.20. Onset Day s for Systemic Events Subjects 12 Through 15 and 16 Through
25 Years of Age (Reactogenicity Subset) Safet y Population ............................
14.21. Duration (Day s) From First to Last Day of Sy stemic Events Subjects 12
Through 15 and 16 Through 25 Years of Age (Reactogenicit y Subset) Safety
Population ................................ ................................ ................................ .............
14.22. Sy stemic Events, by Maximum Severity , Within 7 Day s After Each Dose
(Reactogenicity Subset) Phase 2/3 Subjects 16 -55 Years of Age Safet y
Population ................................ ................................ ................................ .............
14.23. Onset Day s for S ystemic Events (Reactogenicity Subset) Phase 2/3
Subjects 16-
55 Years of Age Safet y Population ................................ ...............
14.24. Duration (Day s) From First to Last Day of Sy stemic Events (Reactogenicity
Subset) Phase 2/3 Subjects 16 -55 Years of Age Safety Population ...............
Adverse Events ................................ ................................ ................................ ................
14.25. Number (%) of Sub jects Reporting at Least 1 Adverse Event From Dose 1 to
1 Month After Dose 2, by S ystem Organ Class and Preferred Term Blinded
Placebo- Controlled Follow -up Period Phase 2/3 Subjects 16-55 Years of Age
Safety Population ................................ ................................ ...............................
14.26. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1 to
7 Day s After Dose 1, b y System Organ Class and Preferred Term Blinded
Placebo- Contro lled Follow -up Period Phase 2/3 Subjects 16-55 Years of Age
Safety Population ................................ ................................ ...............................
14.27. Number (%) of Subjects Reporting at Least 1 Ad verse Event From Dose 2 to
7 Day s After Dose 2, b y System Organ Class and Preferred Term Blinded
Placebo- Controlled Follow -up Period Phase 2/3 Subjects 16-55 Years of Age
Safety Population ................................ ................................ ...............................
14.28. I ncidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, b y System Organ Class and Preferred Term Phase 2/3 Subjects 16 -55
Years of Age Safet y Population ................................ ................................ ........
14.29. Number (%) of Subjects Reporting at Least 1 Related Adverse Event From
Dose 1 Through 1 Month After Dose 2, by System Organ Class and Prefer red
Term Subjects 12 Through 15 and 16 Through 25 Years of Age
(Reactogenicity Subset) Safety Population ................................ .......................
Page 12
FDA-CBER-2022-5812-0234720
368
376
377
378
380
381
386
388
392
398
400
401Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL14.30. Number (%) of Subje cts Reporting at Least 1 Related Adverse Event From
Dose 1 to 1 Month After Dose 2, b y System Organ Class and Preferred Term
Blinded Placebo -Controlled Follow- up Period Phase 2/3 Subjects 16-55
Years of Age Safet y Population ................................ ................................ ........
14.31. Number (%) of Subjects Reporting at Least 1 I mmediate Adverse Event
After Dose 1, b y System Organ Class and Preferred Term Subjects 12
Through 15 and 16 Through 25 Years of Age (Reactogenicit y Subset) Safety
Population ................................ ................................ ................................ .............
14.32. Number (%) of Subjects Reporting at Least 1 I mmediate Adve rse Event
After Dose 2, b y System Organ Class and Preferred Term Subjects 12
Through 15 and 16 Through 25 Years of Age (Reactogenicit y Subset) Safety
Population ................................ ................................ ................................ .............
14.33. Number (%) of Subjects Reporting at Least 1 Severe Adverse Event From
Dose 1 Through 1 Month After Dose 2, by System Organ Class and Preferred
Term Subjects 12 Through 15 and 16 Through 25 Years of Age
(Reactogenicity Subset) Safety Population ................................ .......................
14.34. Number (%) of Subjects Reporting at Least 1 L ife-Threatening Adverse
Event From Dose 1 Through 1 Month After Dose 2, by System Organ Class
and Preferred Term Subjects 12 Through 15 and 16 Through 25 Years of
Age (Reactogenicit y Subset) Safet y Population ................................ ................
14.35. Number (%) of Subjects Reporting at Least 1 Severe Adverse Event From
Dose 1 to 1 Month After Dose 2, b y System Organ Class and Preferred Term
Blinded Placebo -Controlled Follow- up Period Phase 2/3 Subjects 16-55
Years of Age Safet y Population ................................ ................................ ........
14.36. Number (%) of Subjects Reporting at Least 1 L ife-Threatening Adverse
Event From Dose 1 to 1 Month After Dose 2, b y System Organ Class and
Preferred Term Blinded Placebo -Controlled Follow -up Period Phase 2/3
Subjects 16-55 Years of Age Safet y Population ................................ ...............
14.37. Number (%) of Subjects Reporting at Least 1 Serious Adverse Event From
Dose 1 to 1 Month After Dose 2, b y System Organ Class and Preferred Term
Blinded Placebo -Controlled Follow- up Period Phase 2/3 Subjects 16-55
Years of Age Safet y Population ................................ ................................ ........
14.38. I ncidence Rates of at Least 1 Serious Adverse Event From Dose 1 to
Unblinding Date, b y System Organ Class and Preferred Term Phase 2/3
Subjects 16-55 Years of Age Safet y Population ................................ ...............
14.39. Number (%) of Subjects Withdrawn Because of Advers e Events From Dose
1 to 1 Month After Dose 2, by System Organ Class and Preferred Term
Blinded Placebo -Controlled Follow- up Period Phase 2/3 Subjects 16-55
Years of Age Safet y Population ................................ ................................ ........
Supplemental Figures ................................ ................................ ................................ .........
Subject Narratives (12 Through 15 Years of Age)................................ .............................
15.REFERENCES ................................................................................................................ 402
ERRATA
Page 13
FDA-CBER-2022-5812-0234721
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
16. APPENDI CES
16.1. Study Information
16.1.1. Final Protocol and Protocol Amendments
16.1.2. Sample Case Report Form(s) (CRF)/Data Collection Tool(s) (DCT)
16.1.3. Independent Ethics Committees (I ECs) or Institutional Review
Boards (IRBs) and Sample Standard Subject Information She et and
Informed Consent Document (I CD)
16.1.4. List and Description of Investigators and Service Providers
16.1.5. Signatures of Principal or Coordinating/Leading Investigator(s) or
Sponsor's Responsible Medical Officer, Depending on the Regulatory
Authori ty's Requirement
16.1.5.1. Sponsor and Sponsor Agent
16.1.5.2. CSR I nvestigator Declaration
16.1.6. Listing of Subjects Receiving Investigational Product From
Specific Batches, Where More Than One Batch Was Used
16.1.7. Randomization Scheme and Codes (Subj ect Identification and
Vaccine Assigned)
16.1.8 . Audit Certificates
16.1.9. Documentation of Statistical Methods
16.1.10. Documentation of Interlaboratory Standardization Methods (and
Quality Assurance Procedures if Used) (Refer to Module 5.3.1.4 for
immun oassay and RT -PCR methods)
16.1.11. Publications Based on the Study
16.1.12. Important Publications Referenced in the Report (Available on
Request)
16.1.13. I ndependent Oversight Committees
16.2. Subject Data Listings
16.2.1. Discontinued Subjects
16.2.2. Protocol Deviations
16.2.3. Subjects Excluded From the Analy sis
16.2.4. Demographic Data
16.2.5. Subject Compliance Data
16.2.6. Assay Data
16.2.7. Adverse Events by Subject
16.2.8. Individual Laboratory Measurements by Subject
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 14
FDA-CBER-2022-5812-0234722
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
16.3. Case Report Form(s) (CRF) or Data Collection Tool(s) (DCT)
16.3.1. CRFs (or DCTs) For Deaths, Other Serious Adverse Events, and
Subject Withdrawals due to Adverse Events
16.3.2. Other CRFs (or DCTs)
16.4. Individual Subject Data Listings
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 15
FDA-CBER-2022-5812-0234723
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
4. LIST OF ABBREVIATION S AND D EFINITION OF TERMS
Abbreviation Definition
AE adverse event
AESI adverse event of special interest
BDR blinded data review
BLQ below the level of quantitation
BMI body mass index
CDC Centers for Disease Control and Prevention (United States)
COVID -19 coronavirus disease 2019
CRF case report form
CRO contract research organization
CSR clinical study report
CV curriculum vitae
DCT data collection tool
DMC data monitoring committee
e-diary electronic diary
EU European Union
FSFV first subject first visit
GCP Good Clinical Practice
GMC geometric mean concentration
GMFR geometric mean fold rise
GMR geometric mean ratio
GMT geometric mean titer
HIV human immunodeficiency virus
IA interim analy sis
ICD informed consent document
ICH International Council for Harmonisation
IEC independent ethics committee
IgG immunoglobulin G
IND Investigational New Drug
IRB institutional review board
IRC internal review committee
IRR illness rate ratio
IRT interactive response technology
LLOQ lower limit of quantitation
LNP lipid nanoparticle
MedDRA Medical Dictionary for Regulatory Activities
modRNA nucleoside -modified messenger ribonucleic acid
NAAT nucleic acid amplification test
N-binding SARS -CoV -2 nucleoprotein binding
NT50 neutralizing titer 50
P2 S SARS -CoV -2 full -length, P2 mutant, prefusion spike gl ycoprotein
PD protocol deviation
PT preferred term
QA quality assurance
QTL quality tolerance limit
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 16
FDA-CBER-2022-5812-0234724
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
Abbreviation Definition
RBD receptor -binding domain
RCDC reverse cumulative distribution curve
RDC remote data capture
RNA ribonucleic acid
SAE serious adverse event
SAP statistical analy sis plan
SARS severe acute respiratory syndrome
SARS -CoV -2 severe acute respiratory syndrome coronavirus 2
SMQ standardized MedDRA queries
SOC system organ class
TME targeted medical event
US United States
VE vaccine efficacy
VOC variant of concern
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 17
FDA-CBER-2022-5812-0234725
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
5.ETHICS
5.1. Independent Ethics Committee or Institutional Review Board
The final protocol, an y amendments ( Appendix 16.1.1), and ICD ( Appendix 16.1.3.2) were
reviewed and approved by the IRBs and/or
IECs for each of the investigational centers
participating in the stud y. The I RBs and IECs are listed in Appendix 16.1.3. 1.
5.2.Ethical Conduct of the Study
This study was conducted in compliance with the ethical principles originating in or derived
from the Declaration of Helsinki and in compliance with all ICH GCP guidelines . In
addition, all local regulatory requirements were followed, in particular, those affording
greater protection to the sa fety of trial participants.
5.3.Participant Information and Consent
In this clinical stud y report, the terms “participant” and “subject” are used interchangeabl y.
A signed and dated informed consent was required before an y stud y-specific activity was
performed . If the participant was not able to legally sign consent, the investigator, or a person
designated b y the investigator, obtained a signed and dated ICD from each participant’s
parent(s)/guardian(s) before an y stud y-specific activity was performed. Informe d consent
was collected as detailed in the protocol. Refer to Appendix 16.1.1, Protocol Section 10.1.2
for further information regarding informed consent.
6. INVESTIGATORS AND ST UDY ADMINISTRATIVE S TRUCTURE
The study was conducted by investigators contracted by and under the direction of Pfizer .
The investigators were responsible for adhering to the study procedures described in the
protocol, for keeping records of the study intervention, and for ensuring accurate completion
of the CRFs and DCTs supplied by Pfizer.
This study was undertaken by Pfizer and BioNTech S E and conducted at 153sites: 131 in the
United States, 9 in Turkey , 6in Germany , 4in South Africa, 2 in Brazil, and 1in Argentina
(Appendix 16.1.4.1 ).
Phase 3 participants ≥16 y ears of age were enrolled at sites in the US, Brazil, Argentina,
Turkey , South Africa, and German y. Participants 12- 15 years of age were enrolled at sites in
the US.
Refer to Appendix 16.1.4 for a list of investigators and sites (including participants by
country ) and a list of service providers and external clinical testing laboratories involved in
this study . Refer to Appendix 16.1.10 for a list of internal and external clinical testing
laboratories involved in this study , with the tests that they performed.
No sites were terminated from the study to date.
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 18
FDA-CBER-2022-5812-0234726
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
7.INTRODUCTION
This study is ongoing, and participants are continuing to be evaluated . The final analysis
interim C4591001 CSR dated 0 3December 2
020, reported ongoing Phase 1andPhase 2
safet y and immunogenicity data , combined Phase 2/3 safet y data, andcomplete dprespecified
hypothesis testing of efficacy .Efficacy analy ses were event -driven, based on accrued events
for all Phase 2/3 participants ≥12 y ears of age. The prespe cified interim analy sis was
conducted on an accrued 94 evaluable COVID -19 cases (data cutoff date:
04November 2020), and the final anal ysis was conducted on an accrued 170 evaluable
COVID 19 cases (data cutoff date: 14 November 2020).
Phase 1 evaluation o f safety and immunogenicity dose-level finding results in participants
18through 55 and 65 through 85 years of age led to the selection of 1 of 2 vaccine
candidate s, BNT162b1 and BNT162b2. Both constructs were safe and well tolerated ( except
for BNT162b1 at 100 μg). Given that the reactogenicity profile for BNT162b2 wa s more
favorable than BNT162b1 in both y ounger and older adults with similar immunogenicit y
results, and with non -human primate challenge studies showing that BNT162b2 led to earlier
virus clearance and no evidence of virus in the lung, BNT162b2 at the 30 µg dose level was
selected and advanced into the Phase 2/3 expanded cohort and efficacy evaluation.
Phase 2 of the stud y (for which enrollment has completed) comprised the evaluation of sa fety
and immunogenicit y data for the first 360 participants 18through 85 years of age (180 from
active vaccine group and 180 from placebo group) that enter edthe study after completion of
Phase 1 to evaluate BNT162b2 30 µg in a larger cohort. Overall, Pha se 2 safet y and
immunogenicit y results were consistent with those observed in Phase 1.
Phase 2/3 evaluate dthe efficacy of BNT162b2 30 µg , and provide dadditional safet y,
efficacy ,and immunogenicity data in a larger population . Prespecified efficacy
(event-driven) in participants ≥12 y ears of age and ongoing safet y data in participants
≥16years of age with a median of at least 2 months of follow -up after Dose 2 and up to the
data cutoff date of 14 November 2020 were previously reported in the final analy sis interim
CSR dated 03 December 2020.
At the time of th e final analy sis interim CSR dated 03 December 2020, participants
16 through 91years of age were anal yzed for the first 37,706 participants for safet y.
Individuals 12 t hrough 15years of age we re later permitted to enroll in the study .
On 14 December 2020, the process of disclosing vaccine assignments for all trial participants
≥16years of age began. Hence, for each trial participant, there are 2 periods in the study :
enrollment into the obser ver-blind phase until the date of vaccine disclosure and the time in
the study after disclosure. Participants who were originall y randomized to BNT162b2, are
continuing to be followed for safety as specified in the protocol. The safety data for
participant s originally randomized to placebo prior to disclosure of vaccine assignment are
standard blinded data that contribute to controlled assessment of safet y compared to
individuals randomly assigned to BNT162b2. After vaccine treatment disclosure and the
admi nistration of BNT162b2, the placebo participants can no longer be used for direct
comparison with those originall y randomized to BNT162b2. Given that individuals were
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 19
FDA-CBER-2022-5812-0234727
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
unblinded on different day s after 14 December 2020, the anal ysis of the observer-blinded,
placebo- controlled portion of the study display s rates of AEs adjusted for exposure time.
In this report, interim data are presented up to 1 month after Dose 2 and up to the data cutoff
date for blinded follow -uponly (13 March 2021) andsummariz esthe following participant
age groups :
Adolescents (12
-15 years of age): immunobridging and safet y (median ≥2 months
follow -up); descriptive efficacy anal yses during blinded placebo -controlled follow -up
period conducted on allconfirmed COVID -19 cases ac crued up to the data cutoff date of
13March 2021
Young adults (16- 25 years of age): reference group for 12 -15 years immunogenicity
and descriptive safet y analysis comparisons
Adults (16 -55 years of age): prot ocol specified ‘y ounger adult’ age stratum, to provide
reference safet y data from analyses of participants with longer -term follow -up. Note, these
data are for comparative purposes and do not include a full independent safety evaluation.
A full independent safet y evaluation for Phase 2/3 participants ≥16years of age will be
reported separatel yat a later time .
8. STUDY OBJECTIVES AND ENDPOINTS
8.1.Phase 1
Phase 1 results are not presented in this report. Refer to Appendix 16.1.1, Protocol
Section 3.1 for thestudy objectives, estimands, and endpoints.
8.2.Phase 2/3
The study objective , estimands, and endpoints presented in Table 1are from
Appendix 16.1.1, Protocol Amendment 14. Those previously reported in the final anal ysis
interim C4591001 CSR dated 0 3December 2020, Section 8 , are based on Appendix 16.1.1,
Protocol Amendment 9.
Final efficacy anal yses were completed and reported in the final anal ysis interim CSR dated
03December 2020 along with safet y and immunogenicity data available at that time (data
cutoff date 14 November 2020). This CSR reported prespecified efficacy (event -driven) in
participants ≥12 y ears of age and ongoing safet y data in participants ≥16 years of age with a
median of at least 2 months of follow -up after Dose 2 and up to the data cutoff date.
This CSR presents safety , efficacy ,and immunogenicity data for adolescents 12 through
15years of age up to the data cutoff date (13 March 2021). Data are included from y oung
adults 16 through 25 years of age for immunobridging analy ses and descriptive safet y
analysis comparisons. Longer -term reference safety data are also presented from the adult 16
through 55 years of age stratum up to the date of participant unblinding. Note, these data are
for comparative purposes and do not include a full independent safet y evaluation.
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 20
FDA-CBER-2022-5812-0234728
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
This study is ongoing; results for objectives outside of the scope of this CSR, including full
independent safet y evaluation for participants ≥16 y ears of age, will be reported separatel y at
a later time (Table 1).
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 21
FDA-CBER-2022-5812-0234729
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
Table 1. Phase 2/3 Objectives, Estimands, and Endpoints
Objectivesa Estimands Endpoints Reference
Primary Efficacy
To evaluate the efficacy of prophylactic
BNT162b2 against confirmed
COVID -19 occurring from 7 days after
the second dose in participants without
evidence of infection before vaccinationIn participants complying with the key
protocol criteria (evaluable participants) at
least 7 days after receipt of the second dose
of study intervention: 100 × (1 – IRR)
[ratio of active vaccine to placebo]COVID -19 incidence per 1000 person -years
of follow -up based on central laboratory or
locally confirmed NAAT in participants with
no serological or virological evidence (up to 7
days after receipt of the second dose) of past
SARS -CoV -2 infectionPrespecified complete efficacy data
are reported in final analysis interim
CSR dated 03 December 2020.
Updated efficacy data for participants
12 through 15 years of age only are
reported in this CSR.
To evaluate the efficacy of prophylactic
BNT162b2 against confirmed
COVID -19 occurring from 7 days after
the second dose in participants with and
without evid ence of infection before
vaccinationIn participants complying with the key
protocol criteria (evaluable participants) at
least 7 days after receipt of the second dose
of study intervention: 100 × (1 – IRR)
[ratio of active vaccine to placebo]COVID -19 incidence per 1000 person -years
of follow -up based on central laboratory or
locally confirmed NAATInterim data are reported in final
analysis interim CSR dated
03December 2020.
Updated efficacy data for participants
12 through 15 years of age only are
reported in this CSR.
Primary Safety
To define the safety profile of
prophylactic BNT162b2 in the first
360participants randomized (Phase 2)In participants receiving at least 1 dose of
study intervention, the percentage of
participants reporting:
Local reactions for up to 7 days
following each dose
Systemic events for up to 7 days
following each dose
AEs from Dose 1 to 7 days after the
second dose
SAEs from Dose 1 to 7 days after the
second doseLocal reactions (pain at the injection site,
redness, and s welling)
Systemic events (fever, fatigue, headache,
chills, vomiting, diarrhea, new or worsened
muscle pain, and new or worsened joint
pain)
AEs
SAEsInterim data are reported in final
analysis interim CSR dated
03December 2020.
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 22
FDA-CBER-2022-5812-0234730
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
Table 1. Phase 2/3 Objectives, Estimands, and Endpoints
Objectivesa Estimands Endpoints Reference
To define the safety profile of
prophylactic BNT162b2 in all
participants randomized in Phase 2/3In participants receiving at least 1 dose of
study intervention, the percentage of
participants reporting:
Local reactions for up to 7 days
following each dos e
Systemic events for up to 7 days
following each dose
AEs from Dose 1 to 1 month after the
second dose
SAEs from Dose 1 to 6 months after the
second doseAEs
SAEs
In a subset of at least 6000 participants:
o Local reactions (pain at the
injection site, redness, and
swelling)
o Systemic events (fever, fatigue,
headache, chills, vomiting,
diarrhea, new or worsened muscle
pain, and new or worsened joint
pain)Interim data are reported up to
1month after Dose 2 and to the data
cutoff date (14 November 2020) in
final analysis interim CSR dated
03December 2020.
Interim data for local reactions and
systemic events reported up to 7 days
after each dose , and AEs and SAEs
are reported from Dose 1 to 1 month
after Dose 2 and to the unblinding
date are reported in this CSR.
To define the safety profile of
prophylactic BNT162b2 in participants
12 to 15 years of age in Phase 3In participants receiving at least 1 dose of
study intervention, the percentage of
participants reporting:
Local reactions for up to 7 days
following each dose
Systemic events for up to 7 days
following each dose
AEs from Dose 1 to 1 month after the
second dose
SAEs from Dose 1 to 6 months after
the second dose Local reactions (pain at the injection
site, redness, and swelling )
Systemic events (fever, fatigue,
headache, chills, vomiting, diarrhea, new
or worsened muscle pain, and new or
worsened joint pain)
AEs
SAEsData from Dose 1 to 1 month after
Dose 2 are reported in this CSR.
Interim data for local reactions and
systemic events reported up to 7 days
after each dose, and AEs and SAEs are
reported from Dose 1 to 1 month after
Dose 2 and to the cutoff date are
reported in this CSR .
To describe the safety and tolerability
profile of BNT162b2 SAgiven as 1 or 2
doses to BNT162b2 -experienced
participants, or as 2 doses to
BNT162b2 -naïve participants
To describe the safety and tolerability
profile of BNT162b2 given as a third
dose to BNT162b2 -experienced
participantsIn participants receiving at least 1 dose of
study intervention, the percentage of
participants reporting:
Local reactions for up to 7 days
following each dose
Systemic events for up to 7 days
following each dose
AEs from Dose 1 to 1 month after the
last dose
SAEs from Dose 1 to 5 or 6 months
after the last doseLocal reactions (pain at the injection site,
redness, and swelling)
Systemic events (fever, fatigue, headache,
chills, vomiting, diarrhea, new or
worsened muscle pain, and new or
worsened joint pain)
AEs
SAEsData will be repor ted at a later time.
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 23
FDA-CBER-2022-5812-0234731
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
Table 1. Phase 2/3 Objectives, Estimands, and Endpoints
Objectivesa Estimands Endpoints Reference
Prim ary Immunogenicity
BNT162b2 -experienced participants
To demonstrate the noninferiority of the
anti–reference strain immune response
after a third dose of BNT162b2
compared to after 2 doses of
BNT162b2, in the same individualsGMR of reference strain NT 1 month after
the third dose of BNT162b2 to 1 month
after the second dose of BNT162b2
The difference in percentages of
participants with seroresponse to the
reference strain at 1 month after the third
dose of BNT162b2 and 1 mont h after the
second dose of BNT162b2SARS -CoV -2 reference strain NTs in
participants with no serological or virological
evidence (up to 1 month after receipt of the
third dose of BNT162b2) of past SARS -CoV -
2 infectionData will be reported at a later time.
To demonstrate the noninferiority of the
anti-SA immune response after 1 dose
of BNT162b2 SAcompared to the anti–
reference strain immune response after
2 doses of BNT162b2, in the same
individualsGMR of SA NT 1 month after 1 dose of
BNT162b2 SAto the ref erence strain NT 1
month after the second dose of BNT162b2
The difference in percentages of
participants with seroresponse to the SA
strain at 1 month after 1 dose of
BNT162b2 SAand seroresponse to the
reference strain at 1 month after the second
dose of BNT162b2SARS -CoV -2 SA and reference strain NTs in
participants with no serological or virological
evidence (up to 1 month after receipt of 1
dose of BNT162b2 SA) of past SARS -CoV -2
infectionData will be reported at a later time.
BNT162b2 -naïve participan ts
To demonstrate the noninferiority of the
anti-SA immune response after 2 doses
of BNT162b2 SAcompared to the anti–
reference strain immune response after
2 doses of BNT162b2 GMR of SA NT 1 month after the second
dose of BNT162b2 SAto the reference strain
NT 1 month after the second dose of
BNT162b2
The difference in percentages of
participants with seroresponse to the SA
strain at 1 month after the second dose of
BNT162b2 SAand seroresponse to the
reference strain at 1 month after the second
dose of BNT162b2SARS -CoV -2 SA and reference strain NTs in
participants with no serological or virological
evidence (up to 1 month after receipt of the
second dose of BNT162b2 SAor BNT162b2 as
appropriate) of past SARS-CoV -2 infectionData will be reported at a later time.
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 24
FDA-CBER-2022-5812-0234732
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
Table 1. Phase 2/3 Objectives, Estimands, and Endpoints
Objectivesa Estimands Endpoints Reference
Secondary Efficacy
To evaluate the efficacy of prophylactic
BNT162b2 against confirmed
COVID -19 occurring from 14 days
after the second dose in participants
without evidence of infection before
vaccinationIn participants complying with the key
protocol criteria (evaluable participants) at
least 14 days after receipt of the second
dose of study intervention:
100 × (1 –IRR) [ratio of active vaccine to
placebo]COVID -19 incidence per 1000 person -years
of follow -up based on central laboratory or
locally confirmed NAAT in participants with
no serological or virological evidence (up to
14 days after receipt of the second dose) of
past SARS -CoV -2 infectionPrespecified complete efficacy data
are reported in final ana lysis interim
CSR dated 03 December 2020.
To evaluate the efficacy of prophylactic
BNT162b2 against confirmed
COVID -19 occurring from 14 days
after the second dose in participants
with and without evidence of infection
before vaccinationIn participants complying with the key
protocol criteria (evaluable participants) at
least 14 days after receipt of the second
dose of study intervention:
100 × (1 –IRR) [ratio of active vaccine to
placebo]COVID -19 incidence per 1000 person -years
of follow -up based on c entral laboratory or
locally confirmed NAATPrespecified complete efficacy data
are reported in final analysis interim
CSR dated 03 December 2020.
To evaluate the efficacy of prophylactic
BNT162b2 against confirmed severe
COVID -19 occurring from 7 days and
from 14 days after the second dose in
participants without evidence of
infection before vaccinationIn participants complying with the key
protocol criteria (evaluable participants)
at least 7 days
and
at least 14 days
after receipt of the second dose of study
intervention: 100 × (1 –IRR)
[ratio of active vaccine to placebo]Confirmed severe COVID -19 incidence per
1000 person -years of follow -up in
participants with no serological or virological
evidence (up to 7 days and up to 14 days after
receipt of the second dose) of past
SARS -CoV -2 infectionPrespecified complete efficacy data
are reported in final analysis interim
CSR dated 03 December 2020.
Updated efficacy data occurring from
at leas t7 days after the second d ose
for participants 12 through 15 years
of age only are reported in this CSR.
To evaluate the efficacy of prophylactic
BNT162b2 against confirmed severe
COVID -19 occurring from 7 days and
from 14 days after the second dose in
participants with and without evidence
of infection before vaccinationIn participants complying with the key
protocol criteria (evaluable participants)
at least 7 days
and
at least 14 days
after receipt of the second dose of study
intervention: 100 × (1 –IRR)
[ratio of ac tive vaccine to placebo]Confirmed severe COVID -19 incidence per
1000 person -years of follow -upPrespecified complete efficacy data
are reported in final analysis interim
CSR dated 03 December 2020.
Updated efficacy data occurring from
at leas t7 days aft er the second dose
for participants 12 through 15 years
of age only are reported in this CSR.
To describe the efficacy of prophylactic
BNT162b2 against confirmed
COVID -19 (according to the
CDC -defined symptoms) occurring
from 7 days and from 14 days after the
second dose in participants without
evidence of infection before vaccinationIn participants complying with the key
protocol criteria (evaluable participants)
at least 7 days
and
at least 14 days
after receipt of the second dose of study
interventio n: 100 × (1 –IRR)
[ratio of active vaccine to placebo]COVID -19 incidence per 1000 person -years
of follow -up based on central laboratory or
locally confirmed NAAT in participants with
no serological or virological evidence (up to 7
days and up to 14 days after receipt of the
second dose) of past SARS-CoV -2 infectionPrespecified complete efficacy data
are reported in final analysis interim
CSR dated 03 December 2020.
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 25
FDA-CBER-2022-5812-0234733
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
Table 1. Phase 2/3 Objectives, Estimands, and Endpoints
Objectivesa Estimands Endpoints Reference
To describe the efficacy of prophylactic
BNT162b2 against confirmed
COVID -19 (according to the
CDC -defined symptoms) occurring
from 7 days and from 14 days after the
second dose in participants with and
without evidence of infection before
vaccinationIn participants complying with the key
protocol criteria (evaluable participants)
at least 7 days
and
at least 14 days
after receipt of the second dose of study
intervention: 100 × (1 –IRR)
[ratio of active vaccine to placebo]COVID -19 incidence per 1000 person -years
of follow -up based on central laboratory or
locally confirmed NAATPrespecified complete efficacy data
are reported in final analysis interim
CSR dated 03 December 2020.
To evaluate the efficacy of prophylactic
BNT162b2 against non -S
seroconversion to SARS -CoV -2 in
participants without evidence of
infection or confirme d COVID -19In participants complying with the key
protocol criteria (evaluable participants):
100 × (1 –IRR) [ratio of active vaccine to
placebo]Incidence of asymptomatic SARS -CoV -2
infection per 1000 person -years of follow -up
based on N -binding antibody seroconversion
in participants with no serological or
virological evidence of past SARS -CoV -2
infection or confirmed COVID -19Data will be reported at a later time.
To evaluate the efficacy of prophylactic
BNT162b2 against asymptomatic
SARS -CoV -2 infection in participants
without evidence of infection up to the
start of the asymptomatic surveillance
periodIn participants complying with the key
protocol criteria (evaluable participants):
100 × (1 –IRR) [ratio of active vaccine to
placebo]Incidenc e of asymptomatic SARS -CoV -2
infection per 1000 person -years of follow -up
based on central laboratory –confirmed
NAAT in participants with no serological or
virological evidence (up to the start of the
asymptomatic surveillance period) of past
SARS -CoV -2 infectionData will be reported at a later time.
Secondary Immunogenicity
To demonstrate the noninferiority of the
immune response to prophylactic
BNT162b2 in participants 12 to 15
years of age compared to participants
16 to 25 years of ageGMR, estimated by the ratio of the
geometric mean of SARS -CoV -2
neutralizing titers in the 2 age groups (12 -
15 years of age to 16 -25 years of age) 1
month after completion of vaccinationSARS -CoV -2 neutralizing titers in
participants with no serological or virological
evidence (up to 1 month after receipt of the
second dose) of past SARS -CoV -2 infectionData are reported in this CSR .
BNT162b2 -experienced participants
To demonstrate the noninferiority of the
anti-SA immune response after a third
dose of BNT162b2 compared to the
anti–reference strain immune response
after 2 doses of BNT162b2, in the same
individuals GMR of SA NT 1 month after the third
dose of BNT162b2 to the reference strain
NT 1 month after the second dose of
BNT162b2
The difference in percentages of
participants with seroresponse to the SA
strain at 1 month after the third dose of
BNT162b2 and seroresponse to the SARS -CoV -2 SA and reference strain NTs in
participants with no serological or v irological
evidence (up to 1 month after receipt of the
third dose of BNT162b2) of past SARS -CoV -
2 infectionData will be reported at a later time.
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 26
FDA-CBER-2022-5812-0234734
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
Table 1. Phase 2/3 Objectives, Estimands, and Endpoints
Objectivesa Estimands Endpoints Reference
reference strain at 1 month after the second
dose of BNT162b2
To demonstrate the noninferiority of the
anti–reference strain immune response
after 1 dose of BNT162b2 SAcompared
to after 2 doses of BNT162b2, in the
same individuals GMR of reference strain NT 1 month after
1 dose of BNT162b2 SAto 1month after the
second dose of BNT162b2
The difference in percentages of
participants with seroresponse to the
reference st rain at 1 month after 1 dose of
BNT162b2 SAand 1 month after the second
dose of BNT162b2SARS -CoV -2 reference strain NTs in
participants with no serological or virological
evidence (up to 1 month after receipt of 1
dose of BNT162b2 SA) of past SARS -CoV -2
infectionData will be reported at a later time.
To descriptively compare the anti-SA
immune response after 1 dose of
BNT162b2 SAand a third dose of
BNT162b2 GMR of SA NT 1 month after 1 dose of
BNT162b2 SAto 1month after the third
dose of BNT162b2
The d ifference in percentages of
participants with seroresponse to the SA
strain at 1 month after 1 dose of
BNT162b2 SAand 1 month after the third
dose of BNT162b2SARS -CoV -2 SA NT in participants with no
serological or virological evidence (up to 1
month after receipt of 1 dose of BNT162b2 SA
or the third dose of BNT162b2) of past
SARS -CoV -2 infectionData will be reported at a later time.
To descriptively compare the anti-SA
immune response after 2 doses of
BNT162b2 SAand the anti –reference
strain immune respo nse after 2 doses of
BNT162b2, in the same individuals GMR of SA NT 1 month after the second
dose of BNT162b2 SAto the reference strain
NT 1 month after the second dose of
BNT162b2
The difference in percentages of
participants with seroresponse to the SA
strain at 1 month after the second dose of
BNT162b2 SAand seroresponse to the
reference strain at 1 month after the second
dose of BNT162b2SARS -CoV -2 SA and reference strain NTs in
participants with no serological or virological
evidence (up to 1 month a fter receipt of the
second dose of BNT162b2 SA) of past
SARS -CoV -2 infectionData will be reported at a later time.
BNT162b2 -naïve participants
To demonstrate a statistically greater
anti-SA immune response after 2 doses
of BNT162b2 SAcompared to after 2
doses of BNT162b2 GMR of SA NT 1 month after the second
dose of BNT162b2 SAto 1month after the
second dose of BNT162b2
The difference in percentages of
participants with seroresponse to the SA
strain at 1 month after the second dose of SARS -CoV -2 SA NTs in participants with no
serological or virological evidence (up to 1
month after receipt of the second dose of
BNT162b2 SAor BNT162b2 as appropriate)
of past SARS -CoV -2 infectio nData will be reported at a later time.
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 27
FDA-CBER-2022-5812-0234735
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
Table 1. Phase 2/3 Objectives, Estimands, and Endpoints
Objectivesa Estimands Endpoints Reference
BNT162b2 SAand 1 month after the second
dose of BNT162b2
To descriptively compare the anti–
reference strain immune response after
2 doses of BNT162b2 SAand after 2
doses of BNT162b2 GMR of reference strain NT 1 month after
the second dose of BNT162b2 SAto
1month after the second dose of
BNT162b2
The difference in percentages of
participants with seroresponse to reference
strain at 1 month after the second dose of
BNT162b2 SAand 1 month after the second
dose of BNT162b2SARS -CoV -2 reference strain NTs in
participants with no serological or virological
evidence (up to 1 month after receipt of the
second dose of BNT162b2 SAor BNT162b2 as
appropriate) of past SARS-CoV -2 infectionData will be reported at a later time.
Exploratory
To describe the efficacy of prophylactic
BNT162b2 against confirmed
COVID -19 occurring from 7 days after
the second dose through the blinded
follow -up period in participants
without, and with and without, evidence
of infection before vaccinationIn participants complying with the key
protocol criteria (evaluable participants)
after receipt of the second dose of study
intervention:
100 × (1 –IRR) [ratio of active vaccine to
placebo]COVID -19 incidence per 1000 person -years
of blinded follow -up based on central
laboratory or locall y confirmed NAATData will be reported at a later time.
To describe the incidence of confirmed
COVID -19 through the entire study
follow -up period in participants who
received BNT162b2 at initial
randomization or subsequentlyIn participants who received BNT162b2 (at
initial randomization or subsequently):
Incidence per 1000 person-ye ars of follow-
upCOVID -19 incidence per 1000 person -years
of follow -up based on central laboratory or
locally confirmed NAATData will be reported at a later time.
To evaluate the immune response over
time to prophylactic BNT162b2 and
persistence of immune response in
participants with and without
serological or virological evidence of
SARS -CoV -2 infection before
vaccinationGMC/GMT and GMFR at baseline and 1,
6, 12, an d 24 months after completion of
vaccinationFull-length S -binding or S1 -binding IgG
levels
SARS -CoV -2 neutralizing titersGMTs and GMFRs of SARS -CoV -2
neutralizing titers up to 1 month after
Dose 2 in participants 12 through 15
and 16 through 25 arereported in this
CSR .
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 28
FDA-CBER-2022-5812-0234736
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
Table 1. Phase 2/3 Objectives, Estimands, and Endpoints
Objectivesa Estimands Endpoints Reference
To describe the incidence of non -S
seroconversion to SARS -CoV -2
through the entire study follow-up
period in participants who received
BNT162b2 at initial randomization In participants who received BNT162b2 at
initial randomization :
Incidence per 1000 person-ye ars of follow-
upIncidence of asymptomatic SARS -CoV -2
infection per 1000 person -years of follow -up
based on N -binding antibody seroconversion
in participants with no serological or
virological evidence of past SARS -CoV -2
infec tion or confirmed COVID -19Data will be reported at a later time.
To describe the efficacy of prophylactic
BNT162b2 against asymptomatic
SARS -CoV -2 infection in participants
with evidence of infection up to the
start of the asymptomatic surveillance
periodIn participants complying with the key
protocol criteria (evaluable participants):
100 × (1 –IRR) [ratio of active vaccine to
placebo]Incidence of asymptomatic SARS -CoV -2
infection per 1000 person -years of follow -up
based on central laboratory –confirmed
NAAT in participants with serological or
virological evidence (up to the start of the
asymptomatic surveillance period) of past
SARS -CoV -2 infectionData will be reported at a later time.
To describe the serological responses to
the BNT vaccine can didate and
characterize the SARS -CoV -2 isolate in
cases of:
Confirmed COVID-19
Confirmed severe COVID -19
SARS -CoV -2 infection without
confirmed COVID -19Full S -binding or S1 -binding IgG levels
SARS -CoV -2 neutralizing titers
Identification of SARS -CoV -2 variants(s)Data will be reported at a later time.
To describe the safety, immunogenicity,
and efficacy of prophylactic BNT162b2
in individuals with confirmed stable
HIV diseaseAll safety, immunogenicity, and efficacy
endpoints described aboveData will be reported at a later time.
To describe the safety and
immunogenicity of prophylactic
BNT162b2 in individuals 16 to 55 years
of age vaccinated with study
intervention produced by
manufacturing “Process 1” or “Process
2”b AEs
SAEs
SARS -CoV -2 neutralizing titersData will be reported at a later time.
To describe the immune response to
any VOCs not already specifiedGeometric mean NT for any VOCs not
already specified, after any dose of
BNT162b2 SAor BNT162b2 SARS -CoV -2 NTs for any VOCs not
already specifiedData will be reported at a later time.
To describe the cell -mediated immune
response, and additional humoral
immune response parameters, to the Data will be reported at a later time.
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 29
FDA-CBER-2022-5812-0234737
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
Table 1. Phase 2/3 Objectives, Estimands, and Endpoints
Objectivesa Estimands Endpoints Reference
reference strain and SA in a subset of
participants:
7 Days and 1 and 6 months after
BNT162b2 SAgiven as 1 or 2 doses
to BNT162b2 -experienced
participa nts
7 Days and 1 and 6 months after
BNT162b2 SAgiven as 2 doses to
BNT162b2 -naïve participants
7 Days and 1 and 6 months after
BNT162b2 given as a third dose to
BNT162b2 -experienced
participants
a.HIV-positive participants in Phase 3 were not included in analyses of the objectives, w ith the exception of the specific explorat ory objective.
b.See Appendix 16.1.1 Protocol S ection 6.1.1 for a description of the manufacturing process.
Source: Appendix 16.1.1, Protocol Section 3.2.
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 30
FDA-CBER-2022-5812-0234738
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
9.INVESTIGATIONAL PLAN
9.1.Overall Study Design and Plan
This is a Phase 1/2/3, randomized, multinational, placebo -controlled, observer -blind, dose
finding , vaccine candidate –selection, and efficacy study in health y individuals.
The study consists of 2 parts: Phase 1 to identify preferred vaccine candidate(s) an d dose
level(s); and Phase 2/3 as an expanded cohort and efficacy part. These parts, and the progression
between them, are detailed in Figure 1.
Figure 1.Study Schema
Phase 1 For each vaccine candidate (4:1 randomization active:placebo)
Age: 18-55 y Age: 65-85 y
Low-dose -level 2 -dose group (n=15)
IRC (safety) IRC (safetyLow-dose -level 2 -dose group (n=15)after Dose 1)
Mid-dose -level 2 -dose group (n=15)
IRC (safety)IRC (safetyMid-dose -level 2 -dose group (n=15)after Dose 1)
High -dose -level 2 -dose group (n=15)
IRC (safetyHigh -dose -level 2 -dose group (n=15)after Dose 1)
IRC choice of group(s) for Phase 2/3
(safety & immunogenicity after Doses 1 and 2)
Phase 2/3 Single vaccine candidate (1:1 randomization active:placebo)
Safety and immunogenicity analysis of
Phase 2 data (first 360 participants)
by unblinded team (these participants
will also be included in Phase 3
analyses)Age: ≥12
(Stratified 12 -15, 16-55, or >55)
BNT162b2 30 µg or placebo 2 doses
(n~21,999 per group, total n~43,998)
Source: Appendix 16.1.1, Protocol Section 1.2
Note: Participants ≥16 years of age who originally received placebo w ereoffered the opportunity to receive BNT162b2 at
defined points as part of the study.
The study evaluated the safet y, tolerability , and immunogenicit y of 3different SARS -CoV -2
RNA vaccine candidates against COVID- 19 and the Phase 2/3 efficacy of 1 selected candidate
based on Phase 1 results:
As a 2 -dose (separated by 21 day s) schedule;
At various dose levels in Phase 1;
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 31
FDA-CBER-2022-5812-0234739
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
As a booster; (data will be reported at a later time)
In various age groups:
Phase 1: 18 to 55 and 65 to 85 y ears of age;
Phase 2: ≥18 years of age (stratified as 18 to 55 years and >55 to 85 years);
Phase 3: ≥12 years of age (stratified as 12 to 15, 16 to 55, or >55 y ears of age).
To facilitate rapid review of data in real time, Pfizer and BioNTech staff were unblinded to
vaccine allocation for the participants in Phase 1 , and remain blinded for the Phase 2/3 portion of
study except those who were designated for unblinded activities following the protocol and the
data blinding plan .
Refer to Appendix 16.1.1, Protocol Section 4.1 for further detail on the overall study design.
Planned Booster and Variant Strain Evaluation
Planned booster and VOC evaluation are not included in this report and will be reported at a later
time.
Refer to Appendix 16.1.1, Protocol Section 4.1.2for further details on the booster dose and new
cohort for Phase 2/3 to evaluate potential homologous and heterologous protection against
emerging SARS -CoV -2 VOCs .
Unblinding Considerations
The study was unblinded in stages once all ongoing participants either had been individually
unblinded or had concluded their 6 -month post –Dose 2 study visit, as follows:
Phase 1 (after Visit 8).
Phase 2/3, ≥16 y ears of age (after Visit 4).
Phase 3, 12 through 15 years of age (after Visit 4).
Original Phase 3 participants rerandomized to assess boostability and protection against
emerging VOCs (after Visit 306) (data will be reported at a later time).
Participants ≥16 y ears of age who originall y received placebo and became eligible for receipt of
BNT162b2 according to recommendations detailed separately, and available in the electronic
study reference portal, had the opportunity to receive BNT162b2 in a phased manner as part of
the study . The investigator ensured the participant met at least 1 of the recommendation criteria.
Adolescents 12 through 15 y ears of age remain blinded in this study , as BNT162b2 vaccination
eligibility in all markets/regions is currentl y for 16 years of a ge and older. Note that a few
participants in the 12 through 15 years of age group turned 16 years of age after stud y enrollment
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 32
FDA-CBER-2022-5812-0234740
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
and thus became eligible for unblinding to treatment assignment and vaccination under the
emergency use or conditional authoriz ation in their country /region.
9.1.1. Phase 1
Phase 1 safet y follow -up isongoing, and p articipants were expected to participate for up to a
maximum of approximately 26 months . This interim report only describes Phase 2/3 adolescents
12 through 15 years of age , with reference comparison to y oung adults 16 through 25 y ears of
age and adults 16 through 55 y ears of age . Refer to Appendix 16.1.1, Protocol Section 4.1.1 for
further details on the Phase 1 study design.
9.1.2. Phase 2/3
Safety and immunogenicity data generat ed during the Phase 1 portion of this study and the
BioNTech study conducted in Germany (BNT162 -01) supported BNT162b2 at a dose of 30 µg
as the vaccine candidate to proceed into Phase 2/3 (see Section 9.4.4 ).
The Phase 2 part of the study was comprised of the first 360 participants enrolled
(1:1randomization between BNT162b2 and placebo, stratifie d by age groups [18 t hrough
55years and >55 t hrough 85 years] with approximately 50% in each age stratum) to assess safety
data through 7 days after Dose 2 and immunogenicity data through 1 month after Dose 2 from
these Phase 2 360 participants . Enrollmen t continued during Phase 2 and these participants are
included in the efficacy evaluation in the Phase 3 part of the study .
Participants in the ongoing Phase 3 part of the study are ≥12 years of age (stratified as
12through 15, 16 through 55, or >55 years of age) . The 12- through 15-year stratum comprise d
up to approximately 2200 participants enrolled at selected investigational sites . It was planned to
enroll a minimum of 40% of participants in the > 55yearsof age stratum . Participants in Phase 3
were randomized 1:1 to receive either active vaccine or placebo .
Efficacy anal yses for Phase 2/3 part of the study were event -driven. The prespecified interim
analysis was conducted on an accrued 94 evaluable COVID -19 cases (data cutoff date:
04November 2020) , and the final anal ysis was conducted on an accrued 170 evaluable
COVID -19 cases (data cutoff date : 14November 2020 ). These data are reported in the final
analysis interim CSR dated 03 December 2020 and included all study participants in the efficacy
populations ≥ 12 years of age .
At the time of the final analy sis of efficacy , few participants 12 through 15 y ears of age had
enrolled in the study , and no COVID -19 cases reported in this age group accrued at that time .
Updated efficacy analy sesduring blinded placebo -controlled follow -upperiod were conducted
on cases accrued in the 12 through 15 y ears of age group up to the data cutoff date of 13 March
2021 to evaluate duration of protection. This report presents these anal yses of all confirm ed
COVID -19 cases and any cases meeting protocol -and CDC -defined criteria for severe cases for
participants 12 through 15 y ears of age.
Noninferiorit y of immune response to proph ylactic BNT162b2 in participants 12 through
15years of age to response in pa rticipants 16 through 25 years of age w ereassessed based on the
GMR of SARS -CoV -2 neutralizing titers 1 month after Dose 2 using a 1.5- fold margin.
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 33
FDA-CBER-2022-5812-0234741
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
Safety data are included for adolescents 12 through 15 y ears of age through 1 month after Dose 2
and to the data cutoff date (13 March 2021) and include descriptive comparisons to participants
(reactogenicit y subset) in the group 16 through 25 y ears of age . Safet y data from participants
16through 55 years of age are included for comparative purposes
,and afull independent safet y
evaluation of this age group along with participants >55 y ears of age will be reported separatel y
at a later time .
Itis planned that participants would participate for approximately 26months .
Planned Eval uation s
Phase 2/ 3 (which is ongoing) includ es additional planned anal yses which are not included in this
report and will be reported at a later time .
The safet y and immunogenicity of prophy lactic BNT162b2 in individuals 16 through
55years of age vaccinated with BNT162b2 manufactured with “Process 1” and each lot of
BNT162b2 manufactured with “Process 2” , which was developed to support an increased
scale of manufacture (Appendix 16.1.1, Protocol Section 6.1.1).
Boostability and homologous/heterologous protection against emerging VOCs will allow the
evaluation of safet y and immunogenicity of BNT162b2 SA(Appendix 16.1.1, Protocol
Section s 4.1 .1and 4.1.2 ).
An intensive period of surveillance to evaluate the efficacy of BNT162b2 against
asymptomatic SARS CoV -2 infection is being conducted at selected sites among Phase 2/3
participants (Appendix 16.1.1, Protocol Section 8.1.5).
Refer to Appendix 16.1.1, Protocol Section 4.1.2 for further detail on the Phase 2/3 study design,
including the planned analy ses.
9.2. Discussion of Study Design, Including Choice of Control Groups
The purpose of the study is to describe the safet y, tolerability, and immunogenicity of 2 BNT162
RNA -based COVID -19 vaccine candidates against COVID -19, and the efficacy of one (selected)
candidate, in healthy individuals . To assess boostability in a subset of Phase 3 participants, a
third candidate, will also be assessed against emerging SARS- CoV -2 VOCs.
The study is observer -blinded, as the ph ysical appearance of the investigational vaccine
candidates and the placebo may differ . The participant, investigator, study coordinator, and other
site staff are blinded . At the study site, onl y the dispenser( s)/administrator(s) are unblinded.
The study consists of 3 placebo -controlled phases. Placebo is used as the control, as there is no
licensed comparator vaccine available.
Phase 1 was designed to identify preferred vaccine candidate(s) and dose level(s) f or further
development based on safety , tolerability , and immunogenicit y.
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 34
FDA-CBER-2022-5812-0234742
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
Phase 2 was designed to expand knowledge of the safet y and immunogenicity of the vaccine
candidate selected from Phase 1.
Phase 2/3 was designed to evaluate the efficacy of the vac cine candidate selected for
development, and to provide additional safet y and immunogenicit y data in a larger population,
including adolescents (adolescents were later permitted to enroll as part of Phase 3).Boostability
will also be assessed (reported at a later time) .
Refer to Appendix 16.1.1, Protocol Section 4.2for further detail of the rationale of the stud y
design.
9.3.Participant Selection
Refer to the final analysis interim C4591001 CSR dated 0 3December 2020 , Sections 9.3.1 ,
9.3.2 , 9.3.3, and 9.3.4 for inclusion criteria, exclusion criteria, criteria for temporarily delay ing
vaccine administration, and details for withdrawal of participants from the study , respectivel y,
based on Appendix 16.1.1, Protocol Amendment 9. There were no changes to inclusi on and
exclusion criteria from Protocol Amendments 10 through 13. Refer to Appendix 16.1.1, Protocol
Amendment 14, for updated inclusion and exclusion criteria of the subset of participants
receiving the booster dose against emerging VOCs.
9.4.Investigational Product
9.4.1. Vaccines Administered
The vaccine candidate selected for Phase 2/3 evaluation was BNT162b2 at a dose of 30 µg.The
study evaluated a 2 -dose (separated b y 21 days) schedule of the following for active
immunization against COVID -19 or saline placebo in participants 12 through 15 years of age and
reference groups (16 through 25 and 16 through 55 years of age) :
BNT162b2 (BNT162 RNA -LNP vaccine containing modRNA that encodes P2 S): 30 µg
Normal saline (0.9% sodium chloride solution for injection)
Refer to Appendix 16.1.1, Protocol Sections 6.1and 6.1.2for details of the study intervention(s)
and study intervention administration.
9.4.2. Identity of Investigational Product(s)
Refer to Appendix 16.1.1, Protocol Section 6.2 for details on preparation, stor age, and
dispensing.
A list of the study interventions administered in this study and their respective lot numbers is
provided in Table 2 below.
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 35
FDA-CBER-2022-5812-0234743
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
Table 2. Investigational Product Lot Numbers – Interim –Adolescents
Investigational
Product Phase ManufacturerVendor Lot Number
(Manufacturer)
Lot Numbera(Pfizer)
BNT162b2 (30 µg) 2/3 BioNTech BCV40420 -A
BCV40420 -A
BCV40420 -A
BCV40420 -A
BCV40420 -A
BCV40620 -A
BCV40620 -A
BCV40620 -B
BCV40620 -B
BCV40620 -C
BCV40620 -C
BCV40620 -D
BCV40620 -D
BCV40720 -A
BCV40720 -A
BCV40720 -B
BCV40720 -C
ED3938E220395 -
0006L003/P220395 -
0012L
E220395 -
0035L002/P220395 -
0048L
E220395 -
0035L003/P220395 -
0048L
EU2065896/E220395 -
0004L
PA2070104/P220395 -
0008L
PA2071394/P220395 -
0029L
PA2072393/P220395 -
0019L
PA2071395/P220395 -
0016L
PA2072396/P220395 -
0016L
PA2071396/P220395 -
0047L
PA2072439/P220395 -
0047L
PA2072442/P220395 -
0042L
PA207276 5/P220395 -
0042L
PA2074172/P220395 -
0053L
PA2074998/P220395 -
0060L
PA2074173/P220395 -
0051L
PA2074071/P220395 -
0052L
PA2074300/P220395 -
0021L
ED3938
ED3938
ED3938
EE3813
EE3813
EE8493ZEU2074330/E220395 -
0036L
PA2074300/P220395 -
0022L
PA2074300/P220395 -
0023L
PA2074838/P220395 -
0024L
PA2074838/P220395 -
0020L
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 36
FDA-CBER-2022-5812-0234744
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
Table 2. Investigational Product Lot Numbers – Interim –Adolescents
EE3813
EE3813
EE3813
EJ0553ZPA2077905/P220395 -
0026L
NC2075485/P220395 -
0068L
NC2075485/P220395 -
0074L
NC2075485/P220395 -
0077L
PA2085061/P220395 -
0070L
Normal saline (0.9%
sodium chloride solution
for injection)2/3 Pfizer DK1589;20 -001592
DK1589;20 -001776
DK2074;20 -002029
DK2074;20 -002108
DK2074;20 -002221
DK2074;20 -002221
DK2074;20 -002221
DK2074;20 -002221
DK2074;20 -002221
DK2074;20 -002221
DK2074;20 -002221
DK2074;20 -002221
DK2074;20 -002221
DK2074;20 -002221
DK2074;20 -002221
DK2074;20 -002221
DK2074;20 -002221PA2064251/P220395 -
0005L
PA2065311/P220395 -
0007L
PA2067775/P220395 -
0030L
PA2067774/P220395 -
0013L
PA2069407/P220395 -
0031L
PA2069407/P220395 -
0032L
PA2069407/P220395 -
0033L
PA2069407/P220395 -
0034L
PA2069407/P220395 -
0044L
PA2069407/P220395 -
0045L
PA2069407/P220395 -
0046L
PA2069407/P220395 -
0054L
PA2069407/P220395 -
0055L
PA2069407/P220395 -
0056L
PA2069407/P220395 -
0062L
PA2069407/P220395 -
0065L
PA2069407OTH/E220395 -
0049L
Note: C4591001 End of Study Information and Quality Control (QC) Record for Study Drug Appendix (Section D)
dated 07Apr 2021 was used to create this table.
a. Lot number assigned to the investigational product by Pfizer Global Clinical Supply.
Protocol C4591001 Investigational Product Lot Numbers Table –Interim –Adolescents, Final , Version 2.0, 09Apr 2021.
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 37
FDA-CBER-2022-5812-0234745
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
9.4.3. Method of Assigning Participants to Treatment Groups
Allocation (randomization) of participants to vaccine groups proceeded through the use of an
IRT s ystem (I WR).
Refer to Appendix 16.1.1, Protocol Section 6.3.1 for details on investigational product
assignment.
9.4.4. Selection of
Dose Levels /Regimen
9.4.4.1. Phase 1
Section 9.4.1 provides details on the doses administered in Phase 1.
Refer to Appendix 16.1.1, Protocol Section 6 for details of the dose and regimen.
9.4.4.2. Phase 2/3
The totality of data from Phase 1 as reported in the final anal ysis interim C4591001 CSR dated
03December 2020 identified BNT162b2 at 30 µgas the candidate for Phase 2/3 evaluation.
Refer to Appendix 16.1.1, Protocol Section 6 for deta ils of the dose and regimen.
9.4.5. Blinding
The study staff receiving, storing, dispensing, preparing, and administering the study
interventions were unblinded . All other study and site personnel, including the investigator,
investigator staff, and participants, were blinded to study intervention assignments.
To facilitate rapid review of data in real time, Pfizer and BioNTech staff were unblinded to stud y
intervention allocation for the participants in the Phase 1 portion of the study . The majority of
sponsor staff and all personnel directl y involved in study conduct were and remain blinded to
study intervention allocation in Phase 2/3 . All laboratory testing personnel performing serology
assay s remain blinded to study intervention assigned/received throughout a ll phases of the study .
The following sponsor staff were unblinded in Phase 2/3(further details are provided in a data
blinding plan) :
Those study team members who were involved in ensuring that protocol requirements for
study intervention preparation, handling, allocation, and administration are fulfilled at the site
were unblinded at the site level for the duration of the study (eg, unblinde d study manager,
unblinded clinical research associate).
Unblinded clinician(s), who were not direct members of the stud y team and did not
participate in an y other study -related activities, reviewed unblinded protocol deviations.
An unblinded statistical team supporting interactions with, and interim analy ses for, the
DMC (see Appendix 16.1.1, Protocol Section 9.6 )and the final analy sisinterim CSR
(03December 2020) . This is comprised of a statistician, programmer(s), a clinical scientist,
and a medical monitor who review edcases of severe COVID- 19 as they were received, and
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 38
FDA-CBER-2022-5812-0234746
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
review edAEs at least weekly for additional potential cases of severe COVID -19 (see
Appendix 16.1.1, Protocol Section 8.2.3).
An unblinded submissions team was responsible for preparing documents to support
regulatory activities that may have been required while the study is ongoing . This team was
only unblinded at the group level and did not have access to individual participant
assignments . The programs that produced the summa ry tables were developed and validated
by the blinded study team, and these programs were run b y the same unblinded statistical
team supporting DMC reviews . The submissions team did not have access to unblinded
COVID -19 cases unless efficacy was achieved at either an interim analy sis or the final
analysis, as determined by the DMC.
After the formal data release of the final efficacy analy sis of at least 164 cases, which was
considered the primary completion of the study efficacy objectives, additional limited
statisticians and programmers were unblinded at the participant level to prepare unblinded
analyses and other regulatory activities. A group of statisticians and programmers remained
blinded as part of the blinded study team and continue supporting the blinded conduct of the
study .
After the stud y data used for submission became public, the blinded study team also had
access to those data, and was unblinded at a group level.
When a participant who originall y received placebo received BNT162b2 per
Appendix 16.1.1, Protocol Section 1.3.3 , the study team w asunblinded to the participant’s
original study intervention allocation.
The study wasunblinded in stages once all ongoing p articipants either ha dbeen individually
unblinded or ha dconcluded their 6 -month post –Dose 2 study visit, as follows:
Phase 1 (after Visit 8).
Phase 2/3, ≥16 y ears (after Visit 4).
Phase 3, 12 through 15 years (after Visit 4).
Participants ≥16 y ears of age who originall y received placebo and became eligible for receipt of
BNT162b2 according to recommendations detailed separately, and available in the electronic
study reference portal, had the opportunity to receive BNT162b2 in a phased manner as part of
the study . The investigator ensured the participant met at least 1 of the recommendation criteria.
Adolescents 12 through 15 y ears of age remain blinded in this study , as BNT162b2 vaccination
eligibility in all markets/regions is currentl y for 16 years of age and older. Note that a few
participants in the 12 through 15 years of age group turned 16 years of age after stud y enrollment
and thus became eligible for unblinding to treatment assignment and vaccination under the
emergency use or conditional authorization in their country /region.
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 39
FDA-CBER-2022-5812-0234747
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
Refer to Appendix 16.1.1, Protocol Section 6.3.2 for details on blinding of the site personnel,
Protocol Section 6.3.3 for details on blinding of Pfizer and BioNTech, and Protocol Section 6.3.4
forcircumstances when the blind could be broken.
9.4.6. Prior and Concomitant Vaccines, Medications, and Procedures
Prohibited During the Study
Participants may have been excluded from the per -protocol anal ysis and may not have received
further required stud y vacci nations upon receipt of the vaccines and medications prohibited
during the time periods specified in Appendix 16.1.1, Protocol Section 6.5.1; however,
participants were not withdrawn from the study . Medications were not withheld if required for a
participa nt’s medical care.
Prophy lactic antipy retics and other pain medication to prevent symptoms associated with study
intervention administration were not permitted. However, if a participant was taking a
medication for another condition, even if it had antipy retic or pain -relieving properties, it was not
withheld prior to study vaccination.
Permitted During the Study
Refer to Appendix 16.1.1, Protocol Section 6.5 for details on prior and concomitant vaccines,
medications and procedures that were allowed or prohibited.
9.4.7. Vaccine Compliance
Participants dosed at the site received study intervention directly from the investigator or
designee, under medical supervision.
Refer to Appendix 16.1.1, Protocol Section 6.4 for details of compliance with study interventi on.
9.5.Efficacy, Immunogenicity, and Safety Evaluations
9.5.1. Efficacy and Immunogenicity Evaluations
Efficacy (prespecified) was assessed for potential cases of COVID -19and described in the final
analysis interim C4591001 CSR dated 03 December 2020 . The prespecif ied interim analy sis was
conducted on an accrued 94 evaluable COVID -19 cases (data cutoff date: 04November 2020),
and the final analy sis was conducted on an accrued 170 evaluable COVID -19 cases (data cutoff
date: 14November 2020 ).These anal yses included data from all participants in Phase 3 age
groups (12-15, 16- 55, and >55 y ears of age) at the time of the anal yses.Prespecified primary and
secondary efficacy endpoint analy ses were completed per protocol as of 14 November 2020, an d
no additional formal h ypothesis testing of clinically confirmed COVID -19 cases is planned. At
the time of the final analysis, there were few participants 12- 15 years of age enrolled in the stud y
and no COVID -19 cases reported in this age group accrued at that time (14 November 2020). In
this report, e fficacy wasassessed based on all cases in participants 12 through 1 5 years of age
accrued in blinded follow -up to a data cutoff date of 13 March 2021 .
For immunogenicity testing, the following assays were pe rformed in participants 12 through
15yearsof age:
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 40
FDA-CBER-2022-5812-0234748
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
SARS -CoV -2 neutralization assay (reference strain)
Refer to
Appendix 16.1.1, Protocol Section 8.1for details on efficacy and immunogenicit y
evaluations.
9.5.2. Safety Evaluations
Safety evaluations are as described in Appendix 16.1.1, Protocol Section 8.2.
9.5.2.1. Electronic Diary
All participants 12 through 15 years of age and asubset of participants 16 through 55 years of
age (including the young adults 16 through 25 years of age) were asked to monitor and record
local reactions, sy stemic events, and antipy retic/pain medication usage for 7 days, following
administration of study intervention using an e -diary . All other participants did not complete a n
e-diary but hadtheir local reactions and s ystemic events reported as AEs in accordance with
Appendix 16.1.1, Protocol Section 8.3.2 (see also Section 9.5.2.3).
Use of an e -diary allowed recording of these assessments within a fixed time window and
provided an accurate representation of the participant’s experience at that time . For participants
who were not in the reactogenicity subset, local reactio ns and s ystemic events consistent with
reactogenicity were reported as AEs (Section 9.5.2.3 ).
Refer to Appendix 16.1.1, Protocol Section 8.2.2 for additional details on use of the e -diary .
Refer to Appendix 16.1.1, Protocol Section 8.2.2.2 , Protocol Section 8.2.2.3 , Protocol
Section 8.2.2.4 , Protocol Section 8.2.2.5 for details on grading of prompted local reactions,
systemic events, fever, and use of antipy retic/pain medications, respectively.
9.5.2.2. Surveillance of Events That Could Represent Vaccine -Associated Enhanced
COVID -19 and Phase 2/3 Stopping Rule
Participants in all phases of the study were surveilled for potential COVID -19 illness from
Visit 1 onwards . If a participant experienced an y potential sy mptoms for COVID -19 illness, a
COVID -19 illness and subsequent convalescent visit (i n-person or telehealth) occurred . As part
of these visits, samples (nasal [midturbinate] swab and blood) were taken for antigen and
antibody assessment as well as recording of COVID-19–related clinical and laboratory
information (including local diagnosis).
In Phase 2/3, the unblinded team supporting the DMC, including an unblinded medical monitor,
reviewed cases of severe COVID -19 as they were received and reviewed AEs at least weekl y for
additional potential cases of severe COVID -19. At any point, the unblinded team may have
discussed with the DMC chair whether the DMC should review cases for an adverse imbalance
of cases of COVID -19 and/or severe COVID -19 between the vaccine and placebo groups.
The stopping rule w astriggered when the 1- sided probability of observing the same or a more
extreme case split was 5% or less when the true incidence of severe disease was the same for
vaccine and placebo participants, and alert criteria were triggered when this probability was less
than 11% . In addition, when the total number of severe cases waslow (15 or less), the unblinded
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 41
FDA-CBER-2022-5812-0234749
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
team supporting the DMC implemented the alert rule when a reverse case split of 2:1 or worse
was observed
.
When the total number of severe cases was 2 0 or less, the stopping rule and alert rules in
Appendix 16.1.1, Protocol Table 10 and Table 11 , respectivel y, applied.
Refer to Appendix 16.1.1, Protocol Section 8.13 for details on COVID -19 surveillance, and
Protocol Section 8.2.4 for details on Phase 2/3 stopping rules.
9.5.2.3. Adverse Events and Serious Adverse Events
AEs were collected during the stud y from the signing of the ICD through and including 1 month
after Dose 2 ( Visit 3 for Phase 2/3 participants).
Acute reactions (immediate AEs) were collected within the first 30 minutes after administration
of the study intervention .
SAEs were collected from the signing of the ICD to approximately 6 months after the last dose
of study intervention ( Visit 4 for Phase 2/3 participants).
Refer to Appendix 16.1.1, Protocol Section 8.3for additional details for collecting AEs and
SAEs.
9.5.2.4. Events of Special Interest
While AESI s were not prespecified in the protocol, Pfizer utilizes a safet y review as part of the
signal detection processes that highlights specified T MEs of clinical interest. TMEs are specific
AE terms reviewed on an ongoing basis b y routine safet y data review procedures throughout the
clinical study .Although not prespecified in the protocol, TMEs are maintained in a separate list
as part of the Safet y Surveillance Review Plan for the vaccine program. By definition, TMEs are
considered to be AESIs specific for a product or program's protocol(s). They are based on review
of known pharmacology , toxicology findings, possible class effects, published literatur e, and
potential signals arising from safet y data assessments.
The list of TMEs is customized for each development program and is d ynamic. For this study,
the list of TMEs includes events of interest because of their association with COVID -19 and
terms of interest for vaccines in general. Terms are chosen from the MedDRA dictionary and
may include PTs, high level term, high level group terms, or standardized MedDRA queries
(SMQs; all evaluated as broad and narrow) .
Other events of clinical interest identi fied b y the sponsor were also review ed and summarized
(Section 12.4.4 ).
9.6. Data Quality Assurance
A number of steps were taken in the planning and implementation of this study to ensure that the
data collected were accurate, consistent, complete, and reliable . This study used an RDC sy stem
and handheld diary device or application . The CRFs were designed to be used with ease.
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 42
FDA-CBER-2022-5812-0234750
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
Investigators were required to review the diary data online at frequent intervals to evaluate
participant compliance and as part of the ongoing safet y review. Furthermore, diary data were
made available to Pfizer and Pfizer’s representative online to ena ble ongoing review.
Representatives of Pfizer conducted routine reviews, using both on -site and remote access
options with the investigational sites while the study was in progress to check the accuracy and
completeness of the data being entered into the R DC sy stem . During these visits, critical data
were verified against participant source documents, and queries regarding missing or
contradictory data were resolved
. In addition, study procedures were reviewed, and protocol
deviations were discussed with th e investigator . Telephone and email contact was maintained
with the investigators between site visits. In addition, the overall study conduct was subject to
internal quality review by Pfizer.
The quality risk management plan used in this study documents risks and controls that are in
place throughout the life of the study . In this study, QTL s were defined during the quality risk
management planning.
The accuracy of the clinical database was verified through a series of processes. Potential errors
were id entified through the generation of automatic queries during data entry and manual queries
during data review . Clinical data were reviewed on an ongoing basis, and a BDR was conducted
to identify any undetected data issues or concerns requiring correction . Once all participant data
had been entered and all data queries closed, a final data management review was performed,
and the database was declared read y for statistical anal ysis.
This CSR has been subject to quality control review by Pfizer or Pfizer’s d esignee.
Quality assurance audits were performed at selected sites by Pfizer’s own independent qualit y
assurance group or b y a CRO and/or individual contract personnel under the group’s direction .
These audits were conducted according to Pfizer’s procedure s and GCP guidelines.
Refer to the final anal ysis interim C4591001 CSR dated 03 December 2020 for previousl y
reported data qualit y issues.
9.7.Statistical Methods Planned in the Protocol
9.7.1. Statistical and Analytical Plans
Detailed methodology for summarization and statistical anal yses of the data collected in this
study is documented in the SAP ( Appendix 16.1.9). An y major modifications of the primary
endpoint definition and/or its analy sis subsequent to the protocol finalization were reflected in a
protocol ame ndment.
9.7.1.1. Analysis Sets
The anal ysis populations presented in this report are defined in Table 3.
Refer to Appendix 16.1.9, SAP Section 4for details of all other planned analy sis sets.
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 43
FDA-CBER-2022-5812-0234751
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
Table 3. Analysis Populations
Population Description
Enrolled All participants who had a signed ICD.
Randomized All participants who were assigned a randomization number in the IWR system.
Dose 2 evaluable
immunogenicityAll eligible randomized participants who received 2 doses of the vaccine to which they
were randoml y assigned, with Dose 2 received w ithin the predefined window (19-42 days
after Dose 1), had at least 1 valid and determinate immunogenicity result from the blood
collection within an appropriate w indow after Dose 2 (28 -42 days after Dose 2 for
Phase 2/3), and had no other important protocol deviations as determined by the clinician.
Dose 2 all -available
immunogenicityAll randomized participants who received at least 1 dose of the study intervention with at
least 1 valid and determinate immunogenicity res ult after Dose 2.
Evaluable efficacy
(7 days)All eligible randomized participants who received all vaccination(s) as randomized ,with
Dose 2 received w ithin the predefined window (19-42 days after Dose 1) and had no other
important protocol deviations as determined by the clinician on or before 7 days after Dose
2.
Dose 1 all -available
efficacyAll randomized participants who rec eived at least 1 vaccination.
Dose 2 all -available
efficacyAll randomized participants who completed 2 vaccination doses.
Safety All randomized participants who received at least 1 dose of the study intervention.
9.7.2. Determination of Sample Size
Refer to Appendix 16.1.1, Protocol Section 9.2, and Appendix 16.1.9, SAP Section 5.1.3for
details of the sample size determination.
9.7.3. Efficacy Analysis
The efficacy assessment in Phase 2/3 portion of the study was event -driven. VE with respect to
the first primary efficacy endpoint was assessed at the first interim anal ysis (at least 62 cases) at
94 cases (data cutoff date: 04 November 2020) . At the final anal ysis (at least 164 cases) vaccine
efficacy with respect to all efficacy endpoints was assessed on an accrued 170 evaluable
COVID -19 cases (data cutoff date: 14 November 2020) for both primary and all secondary
efficacy endpoints. No additional formal hy pothesis testing of clinicall y confirmed COVID -19
cases is planned.
Assessment of VE of BNT162b2 was pe rformed for confirmed COVID-19 cases observed at
least 7 day s after the receipt of Dose 2 onwards among participants either without or with or
without serological or virological evidence (up to 7 days after receipt of the second dose) of past
SARS -CoV -2 infection. VE was estimated b y 100% × (1 –IRR), where IRR was the ratio of
COVID -19 illness rate in the BNT162b2 group to the corresponding illness rate in the placebo
group (Appendix 16.1.9, SAP Appendix 3with details on the calculation of I RR and VE) .
Updated efficacy analy ses during blinded placebo- controlled follow -up were conducted for
participants 12 through 15 y ears of age based on the data cutoff date of 13 March 2021. The
point estimate of VE in the blinded follow- up period and associated 2 -sided 95% CI was derived
using the Clopper Pearson method adjusted for surveillance time. In addition to the protocol
definition of severe COVID -19, supportive anal yses using the CDC definition of severe COVID -
19 was also performed .
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 44
FDA-CBER-2022-5812-0234752
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
The efficacy anal ysis for Ph ase 2/3 is also described in Appendix 16.1.1, Protocol Section 9.4.2
and Appendix 16.1.9, SAP Section 6.1.3(primary ),SAP Section 6.2.2 (secondary ), and
SAP Section 6 .3.2 (exploratory ).
9.7.4. Immunogenicity Analysis
For participants randomized to the BNT162b2 groups with no serological or virological evidence
(up to 1 month after receipt of the second dose) of past SARS- CoV -2 infection, the GMR of
SARS -CoV -2 50% neutralizing titers in participants 12 to 15 y ears of age to those in par ticipants
16 to 25 y ears of age and 2 -sided 95% CIs w ere provided at 1 month after Dose 2 for
noninferiority assessment. The GMR and its 2 -sided 95% CI w erederived by calculating
differences in means and CI s on the natural log scale of the titers based o n the Student’s
t-distribution and then exponentiating the results. The difference in means on the natural log
scale w ere12 to 15 y ears minus 16 to 25 years. Noninferiority w asdeclared if the lower bound
of the 2- sided 95% CI for the GMR was greater than 0.67, using 1.5- fold noninferiority margin .
In addition, the difference in percentages of participants (12 to 15 y ears –16 to 25 y ears)
achieving a ≥4 -fold rise in SARS -CoV -2 neutralizing titers from before vaccination to 1 month
after Dose 2 were provided. The associated 2 -sided 95% CI for the difference in percentage was
calculated using the Miettinen and Nurminen method .
For immunogenicity results of SARS -CoV -2 neutralizing titers concentrations, the GMT w as
computed along with associated 95% CIs . The GMT w ascalculated as the mean sof assay results
after making the logarithm transformation and then exponentiating the mean sto express results
on the original scale. Two -sided 95% CIs were obtained by taking log transforms of assay
result s, calculating th e 95% CIswith reference to Student’s t -distribution, and then
exponentiating the confidence limits.
The GMFR was calculated by exponentiating the mean of the difference of logarithmicall y
transformed assay results (later time point – earlier time point). Two-sided CI s were obtained by
calculating CIs using Student’s t -distribution for the mean difference of the logarithmicall y
transformed assay results and exponentiating the confidence limits .
The exact 95% CIs for binary endpoints were computed using th e Fdistribution
(Clopper -Pearson method).
Titers below the LLOQ or denoted as BLQ were set to 0.5 × LLOQ for analysis.
The immunogenicit y analy sis is further described in Appendix 16.1.1, Protocol Section 9.4.1 and
Appendix 16.1.9, SAP Section 6.2.1.4 and SAP Section 6.3.2 .
9.7.5. Safety Analysis
The primary safet y objective was evaluated b y descriptive summary statistics for local reactions,
systemic events, and AEs/SAEs for each vaccine group . A 3-tier approach was used to
summarize AEs in Phase 2/3. Under this approach , AEs were classified into 1 of 3 tiers:
Tier 1 events are prespecified events of clinical importance and are identified in a list in the
product’s S afety Review Plan; there are no Tier 1 AEs identified for this program.
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 45
FDA-CBER-2022-5812-0234753
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
Tier 2 events were t hose that were not Tier 1 but were considered “relatively common”;
a MedDRA preferred term is defined as a Tier 2 event if there are at least 1% of participants
with the AE term in at least 1 vaccine group .
Tier 3 events were those that were neither Tier 1 nor Tier 2.
The safet y analysis is described in Appendix 16.1.1, Protocol Section 9.4.3 and Appendix 16.1.9,
SAP Section 6.1.1 .
9.7.6. Other Analyses
Other anal yses are described in Appendix 16.1.1, Protocol Section 9.4.4 , and Appendix 16.1.9,
SAP Section 6.3. 4.
9.7.7. Analysis Timing
During Phase 2/3, IAs were planned to be performed by an unblinded statistical team after
accrual of at least 62, 92, and 120 cases . For operational reasons, the first interim anal ysis was
conducted after accrual of greater than 62 cases (94 cases), and the final analy sis of efficacy was
conducted after accrual of at least 164 cases (170 cases) .
Statistical analy ses were described for the following data in the final analysis interim C4591001
CSR dated 0 3December 2020:
Comple te safet y and immunogenicit y anal ysis approximately 1month after Dose 2 for
Phase 1. Results for participants randomized to BNT162b1 100 µg summarized up to
3weeks after Dose 1 for safet y, and approximately 7 weeks after Dose 1 for
immunogenicit y.
Safet y data through 7 days after Dose 2 and immunogenicity data through 1 month after
Dose 2 (immunogenicity not available at this time) from the first 360 participants enrolled
(180 to active vaccine and 180 to placebo, stratified equally between 18 to 55 years and >55
to 85 y ears) in Phase 2/3.
Safety data through 1 month after Dose 2 from at least 6000 participants ≥16years of age
enrolled (3000 to active vaccine and 3000 to placebo) in Phase 2/3. Additional anal yses of
safet y data (with longer follow -up and/or additional participants) may have been conducted if
required for regulatory purposes.
One IA for efficacy after accrual of atleast 62 cases (performed at 94 cases).
Statistical analy ses were carried out as the following data bec ame available and are reported in
this CSR :
Safety data through 1 month after Dose 2 and noninferiorit y comparison of SARS -CoV -2
neutralizing titers in participants 12 t hrough 15 years of age compared to those in participants
16 through 25 years of age, 1 month after Dose 2. Safety data for participants 16 through
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 46
FDA-CBER-2022-5812-0234754
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
55years of age are included for comparative purposes and do not include a full independe nt
safet y evaluation ( these will be reported separately ).
Updated efficacy analy sis for participants 12 through 15 years of age based on the data cutoff
date of 13 March 2021
Statistical analy ses will be carried out as the following data become available and reported at a
later time :
Complete safet y anal ysis up to approximately 6 months after Dose 2 for all participants
≥16years of age in Phase 2/3, and safety and immunogenicit y anal ysis for Phase 1
participants in the BNT162b 2
30µgdose group.
Descriptive anal ysis of immunogenicit y and safety of “Process 1” and “Process 2” material,
1month after Dose 2 .
Complete safet y and immunogenicit y anal ysis approximately 1 month after Dose 3 for
Phase 3 participants included in the booster evaluation and approximately 1 month after Dose
2 for newl y enrolled Phase 3 participants included in the BNT162b2 SAevaluation.
Analysis of efficacy against asy mptomatic SARS -CoV -2 (determined b y asymptomatic
seroconversion of N -binding antibody and/or as ymptomatic SARS -CoV -2 infection based on
central laboratory –confirmed NAAT) when a sufficient number of cases have accrued to
evaluate th eobjective (s).
Complete immunogenicity anal ysis approximately 6 months after Dose 2 for all participants
in Phase 2/3.
Complete e fficacy and persistence -of-immunogenicity analy sis after complete data are
available or at the end of the study .
All analy ses conducted on Phase 2/3 data while the study is ongoing w asperformed b y an
unblinded statistical team.
The anal ysis timing is describ ed in Appendix 16.1.1, Protocol Section 9.5, and Appendix 16.1.9,
SAP Section 7.
9.8.Changes in the Conduct of Study or Planned Analyses
Changes in stud y conduct are described in Appendix 16.1.1, Protocol Amendment Summary of
Changes Table . Changes to the orig inal planned analy sis are described in SAP v 5.0
(Appendix 16.1.9, SAP Section 1).
Additional changes in study conduct or planned analy sis not noted in the protocol or SAP were
previously reported in Section 9.8 of the final analy sis interim C4591001 CSR dated
03December 2020. Changes in study conduct or planned anal ysis not noted in the protocol or
SAP in this interim CSR were as follows:
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 47
FDA-CBER-2022-5812-0234755
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
Ad hoc summary tables of AEs within 7 day s after each dose were generated in order to
evaluate whether AEs repor ted may have been attributed to reactogenicity events in
participants who did not have an e -diary to report reactogenicity .
10.STUDY PARTICIPANTS
10.1. Disposition of Participants
10.1.1. P articipants 1 2Through 15 Years of Age
The disposition of adolescents (12 -15 yearsof age) and y oung adults (16 -25 years of age) was
similar in BNT162b2 and placebo groups through 1 month after Dose 2 (Table 4). Most
participants randomized in both age groups ( ≥97.4%) received Dose 1 and Dose 2. Among
adolescents, 7 participants (0.6%) in the BNT162b2 group and 17 participants (1.5%) in the
placebo group discontinued from the vaccination period and are continuing in the study for
safet y follow
-up. Most participants across age groups completed the visit at 1 month after Dose 2
(≥94.5%).
Among adolescents who discontinued from vaccination period but c ontinue din the study up to
the 1 month post Dose 2 visit , 2 participants discontinued due to AEs, both in the BNT162b2
group (p yrexia considered by the investigator as related to study intervention, and unrelated
anxiety /depression; refer to Section 12.4.3.1 ) and none in the placebo group.
No adolescents in the BNT162b2 and 2 participants in the placebo group withdrew from the
study before the 1 month post Dose 2 visit.
A total of 49 adolescent participants withdrew from the vaccination period when they turned
16years of age after entering the stud y and became eligible to be unblinded to receive
BNT162b2 vaccination; of these, 19/49 re ceived Dose 3 and Dose 4 (BNT162b2)
(Appendix 16.1.7.2.1 ). Participants originally randomized to placebo who received Dose 3 of
BNT162b2 (per protocol; refer to Section 9.1) continued in open -label follow -up in the study ,
but their data were censored at the time of unblinding with regard to analy ses in this report .
Information for these participants are provided for SAEs (refer to Section 12.4.2.1 ) or other
significant AEs (refer toSection 12.4.4 ).
Table 4.Disposition of All Randomized Subjects Through 1 Month After Dose 2 –
Subjects 12 Through 15 and 16 Through 25 Years of Age
Vaccine Group (as Randomized)
BNT162b2 (30 μg) Placebo
12-15 Years
(Na=1134)
nb(%)16-25 Years
(Na=1875)
nb(%)12-15 Years
(Na=1130)
nb(%)16-25 Years
(Na=1913)
nb(%)
Randomized 1134 (100.0) 1875 (100.0) 1130 (100.0) 1913 (100.0)
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 48
FDA-CBER-2022-5812-0234756
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
Table 4.Disposition of All Randomized Subjects Through 1 Month After Dose 2 –
Subjects 12 Through 15 and 16 Through 25 Years of Age
Vaccine Group (as Randomized)
BNT162b2 (30 μg) Placebo
12-15 Years
(Na=1134)
nb(%)16-25 Years
(Na=1875)
nb(%)12-15 Years
(Na=1130)
nb(%)16-25 Years
(Na=1913)
nb(%)
Not vaccinated 3 (0.3) 6 (0.3) 1 (0.1) 7 (0.4)
Vaccinated
Dose 1 1131 (99.7) 1869 (99.7) 1129 (99.9) 1906 (99.6)
Dose 2 1124 (99.1) 1826 (97.4) 1117 (98.8) 1836 (96.0)
Completed 1 -month post –Dose 2 visit (vaccination period) 1118 (98.6) 1803 (96.2) 1102 (97.5) 1807 (94.5)
Discontinued from vaccination period but continue in the study
up to 1 -month post –Dose 2 visit7 (0.6) 13 (0.7) 17 (1.5) 42 (2.2)
Discontinued after Dose 1 and before Dose 2 7 (0.6) 12 (0.6) 10 (0.9) 36 (1.9)
Discontinued after Dose 2 and before 1 -month post –Dose 2
visit0 1 (0.1) 7 (0.6) 6 (0.3)
Reason for discontinuation from vaccination period
No longer meets eligibility criteria 3 (0.3) 4 (0.2) 10 (0.9) 26 (1.4)
Withdrawal by subject 0 6 (0.3) 1 (0.1) 1 (0.1)
Pregnancy 0 1 (0.1) 0 3 (0.2)
Adverse event 2 (0.2) 1 (0.1) 0 0
Physician decision 1 (0.1) 0 0 2 (0.1)
Protocol deviation 0 0 1 (0.1) 2 (0.1)
Lost to follow -up 0 0 0 1 (0.1)
Other 1 (0.1) 1 (0.1) 5 (0.4) 7 (0.4)
Withdrawn from the study before 1 -month post –Dose 2 visit 0 45 (2.4) 2 (0.2) 56 (2.9)
Withdrawn after Dose 1 and before Dose 2 0 25 (1.3) 1 (0.1) 34 (1.8)
Withdrawn after Dose 2 and before 1-month post –Dose 2 visit 0 20 (1.1) 1 (0.1) 22 (1.2)
Reason for withdrawal from the study
Lost to follow -up 0 29 (1.5) 0 32 (1.7)
Withdrawal by subject 0 14 (0.7) 0 19 (1.0)
Protocol deviation 0 0 1 (0.1) 1 (0.1)
Withdrawal by parent/guardian 0 1 (0.1) 1 (0.1) 0
Adverse event 0 0 0 1 (0.1)
Physician decision 0 0 0 1 (0.1)
Other 0 1 (0.1) 0 2 (0.1)
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 49
FDA-CBER-2022-5812-0234757
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
Table 4.Disposition of All Randomized Subjects Through 1 Month After Dose 2 –
Subjects 12 Through 15 and 16 Through 25 Years of Age
Vaccine Group (as Randomized)
BNT162b2 (30 μg) Placebo
12-15 Years
(Na=1134)
nb(%)16-25 Years
(Na=1875)
nb(%)12-15 Years
(Na=1130)
nb(%)16-25 Years
(Na=1913)
nb(%)
Note: Human immunodeficiency virus (HIV) -positive subjects are included in this summary but not included in the analyses of
the overall study objectives.
Note: Subjects randomized but did not sign informed consent or had a significant quality event due to lack of PI oversight are
not included in any analysis population.
a. N = number of randomized subjects in the specified group. This value is the denominator for the percentage calculations.
b. n = Number of subjects with the specified characteri stic.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (19:20) Source Data: adds Table Generation: 27MAR2021 (06:06)
(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:
./nda2_unblinded/C4591001_BLA/adds_s002_ped_rand
10.1.2. Participant s 16 Through 55 Years of Age
The d isposition of randomized adult participants (16-55 years of age) was similar in the
BNT162b2 and placebo groups during the blinded follow -up period (Table 5). Most participants
randomized ( 97.7%) received Dose 1 and Dose 2. There were 278 (2.1%) participants in the
BNT162b2 group and 388(3.0%)participants in the placebo group who discontinued fr om the
vaccination period. Most participants (95.8%) completed the 1 month post Dose 2 visit and
25.5% of the BNT162b2 group participants completed the 6 months post Dose 2 (25.5%) visit as
of the data cutoff date. There were 608 participants in the BNT162b2 and placebo groups who
were withdrawn from the study (2.0% and 2.7%, respectivel y), most ly due to lost to
follow -up(1.2%) or withdrawn b y subject (0.9%).
Open -label data for participants who were unblinded, including original placebo participant who
received open -label BNT162b2 30 µg as Dose 3/Dose 4, are shown in Table 5for reference but
not discussed further for safet y analyses.
Table 5. Disposition of All Randomized Subjects –Phase 2/3 Subjects 16- 55 Years of
Age
Vaccine Group (as Randomized)
BNT162b2 (30μg)
(Na=13104)
nb(%)Placebo
(Na=13132)
nb(%)Total
(Na=26236)
nb(%)
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 50
FDA-CBER-2022-5812-0234758
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
Table 5. Disposition of All Randomized Subjects –Phase 2/3 Subjects 16- 55 Years of
Age
Vaccine Group (as Randomized)
BNT162b2 (30μg)
(Na=13104)
nb(%)Placebo
(Na=13132)
nb(%)Total
(Na=26236)
nb(%)
Randomized 13104 (100.0) 13132 (100.0) 26236 (100.0)
Not vaccinated 31 (0.2) 32 (0.2) 63 (0.2)
Original blinded placebo -controlled follow -up period
Vaccinated 13073 (99.8) 13100 (99.8) 26173 (99.8)
Dose 1 13073 (99.8) 13100 (99.8) 26173 (99.8)
Dose 2 12802 (97.7) 12825 (97.7) 25627 (97.7)
Discontinued from original blinded placebo-controlled
vaccination periodc278 (2.1) 388 (3.0) 666(2.5)
Reason for discontinuation
Lost to follow -up 132 (1.0) 128 (1.0) 260 (1.0)
Withdrawal by subject 81 (0.6) 117 (0.9) 198 (0.8)
No longer meets eligibility criteria 23 (0.2) 94 (0.7) 117 (0.4)
Adverse event 15 (0.1) 12 (0.1) 27 (0.1)
Pregnancy 6 (0.0) 6 (0.0) 12 (0.0)
Protocol deviation 2 (0.0) 6 (0.0) 8 (0.0)
Physician decision 3 (0.0) 4 (0.0) 7 (0.0)
Medication error without associated adverse event 2 (0.0) 1 (0.0) 3 (0.0)
Death 0 2 (0.0) 2 (0.0)
Withdrawal by parent/guardian 1 (0.0) 0 1 (0.0)
Other 13 (0.1) 18 (0.1) 31 (0.1)
Unblinded before 1 -month post –Dose 2 visit 175 (1.3) 182(1.4) 357 (1.4)
Completed 1 -month post –Dose 2 visit 12586 (96.0) 12555 (95.6) 25141 (95.8)
Withdrawn from the study 259 (2.0) 349 (2.7) 608 (2.3)
Withdrawn after Dose 1 and before Dose 2 138 (1.1) 155 (1.2) 293 (1.1)
Withdrawn after Dose 2 and before 1 -month post –Dose 2
visit85 (0.6) 104 (0.8) 189 (0.7)
Withdrawn after 1 -month post –Dose 2 visit 36 (0.3) 90 (0.7) 126 (0.5)
Reason for withdrawal from the study
Lost to follow -up 150 (1.1) 160 (1.2) 310 (1.2)
Withdrawal by subject 88 (0.7) 147 (1.1) 235 (0.9)
Protocol deviation 3 (0.0) 20 (0.2) 23 (0.1)
Adverse event 6 (0.0) 3 (0.0) 9 (0.0)
Death 3 (0.0) 5 (0.0) 8 (0.0)
Physician decision 2 (0.0) 3(0.0) 5 (0.0)
No longer meets eligibility criteria 1 (0.0) 2 (0.0) 3 (0.0)
Pregnancy 0 1 (0.0) 1 (0.0)
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 51
FDA-CBER-2022-5812-0234759
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
Table 5. Disposition of All Randomized Subjects –Phase 2/3 Subjects 16- 55 Years of
Age
Vaccine Group (as Randomized)
BNT162b2 (30μg)
(Na=13104)
nb(%)Placebo
(Na=13132)
nb(%)Total
(Na=26236)
nb(%)
Medication error without associated adverse event 1 (0.0) 0 1 (0.0)
Withdrawal by parent/guardian 1 (0.0) 0 1 (0.0)
Other 4 (0.0) 8 (0.1) 12 (0.0)
Open -label follow -up period
Originally randomized to BNT162b2 11858 (90.5)
Received Dose 2/unplanned dose 61 (0.5)
Completed 1 -month post –Dose 2 visit 141 (1.1)
Completed 6 -month post –Dose 2 visit 3341 (25.5)
Withdrawn from the study 58 (0.4)
Withdrawn before 6 -month post –Dose 2 visit 56 (0.4)
Withdrawn after 6 -month post –Dose 2 visit 2 (0.0)
Reason for withdrawal from the study
Withdrawal by subject 32 (0.2)
Protocol deviation 17 (0.1)
Lost to follow -up 3 (0.0)
Physician decision 2 (0.0)
Adverse event 1 (0.0)
No longer meets eligibility criteria 1 (0.0)
Other 2 (0.0)
Originally randomized to placebo 12299 (93.7)
Withdrawn from the study after unblinding and before
Dose 3284 (2.2)
Received Dose 3 (first dose of BNT162b2 [30 μg]) 11405 (86.8)
Received Dose 4 (second dose of BNT162b2 [30 μg]) 8586 (65.4)
Discontinued from open -label vaccination periodd16 (0.1)
Reason for discontinuation from open -label vaccination
period
Withdrawal by subject 5 (0.0)
Pregnancy 4 (0.0)
Adverse event 3 (0.0)
Protocol deviation 3 (0.0)
Lost to follow -up 1 (0.0)
Completed 1 -month post –Dose 4 visit 3424 (26.1)
Withdrawn from the study 8 (0.1)
Withdrawn after Dose 3 and before Dose 4 6 (0.0)
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 52
FDA-CBER-2022-5812-0234760
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
Table 5. Disposition of All Randomized Subjects –Phase 2/3 Subjects 16- 55 Years of
Age
Vaccine Group (as Randomized)
BNT162b2 (30μg)
(Na=13104)
nb(%)Placebo
(Na=13132)
nb(%)Total
(Na=26236)
nb(%)
Withdrawn after Dose 4 and before 1 -month post –Dose 4
visit2 (0.0)
Withdrawn after 1 -month post –Dose 4 visit 0
Reason for withdrawal from the study
Withdrawal by subject 7 (0.1)
Protocol deviation 1 (0.0)
Note: Human immunodeficiency virus (HIV) -positive subjects are included in this summary but analyzed and reported
separately.
Note: Subjects randomized but did not sign informed consent or had a significant quality event due to lack of PI oversight ar e
not included in any analysis population.
Note: Because of a dosing error, Subject C4591001 1088 10881077 received an additional dose of BNT162b2 (30 µg) at an
unscheduled visit after receiving 1 dose of BNT162b2 (30 µg) and 1 dose of placebo.
a. N = nu mber of randomized subjects in the specified group, or the total sample. This value is the denominator for the
percentage calculations.
b. n = Number of subjects with the specified characteristic.
c. Original blinded placebo -controlled vaccinatio n period is defined as the time period from Dose 1 to 1 month post –Dose 2.
d. Open -label vaccination period is defined as the time period from Dose 3 (first dose of BNT162b2 [30 µg]) to 1 month
post–Dose 4 (second dose of BNT162b2 [30 µg]).
PFIZER CO NFIDENTIAL SDTM Creation: 25MAR2021 (19:20) Source Data: adds Table Generation: 31MAR2021 (18:10)
(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:
./nda2_unblinded/C4591001_EUA_1655/adds_s002_all_1655_rand
10.2. Protocol Deviations
PDs were identified throughout the stud y by monitoring of informed consent documentation,
source documents, and other clinical trial –related documents. In addition, PDs were identified b y
remote monitoring of electronic CRFs, and review of the project database s (interactive response
technology¸ clinical and safet y databases, vendor database for e -diary data, and programmatic
output from the clinical database). All PDs were documented in a designated clinical trial
management s ystem.
Appendix 16.2.2.1and Appendix 16.2.2.2 list important PDs in participants 12 through 25 years
of age and participants 16 through 55 years of age , respectivel y,that may have significantl y
impacted the completeness, accuracy , and/or reliability of the study data or that may have
significantl y affected a participant’s rights, safety, or well -being .
A formal acknowledgment by the study team was made that deviations were reviewed and GCP
compliance was maintained.
Details of important PDs with the potential to impact the statistic al anal ysis populations or to
impact the assessment of safet y of the participants are discussed below:
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 53
FDA-CBER-2022-5812-0234761
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
10.3. Vaccine Administration and Timing
10.3.1. Participants 12 Through 15 Years of Age
For the adolescent and young adult groups, almost all participants were adminis tered study
intervention as randomized (Table 6). 100% received Dose 1. In the adolescent group , 99.4% and
98.9% received Dose 2 of BNT162b2 and placebo, respectivel y. In the young adult group ,
97.6% and 95.2% received Dose 2 of BNT162b2 and placebo, respectivel y.
The majority of participants received Dose 2 between 21 to 27days after Dose 1 in the
BNT162b2 ( 65.2% for the adolescent group and 60.3% for the young adult group ) and placebo
(64.6% for the adolescent group and 58.2% for the y oung adult group ), followed by 14 to
20days after Dose 1 in the BNT162b2 ( 31.7%for adolescent group and 34.1% fo r the young
adult group ) and placebo ( 32.2%for theadolescent group and 34.0% for the y oung adult group)
(Table 7).
Table 6.Vaccine as Administered, by Vaccine Group –Subjects 12 Through 15 and 16
Through 25 Years of Age (Reactogenicity Subset)
Vaccine Group (as Randomized)
BNT162b2 (30 μg) Placebo
Vaccine (as Adm inistered) 12-15 Years
(Na=1131)
nb(%)16-25 Years
(Na=539)
nb(%)12-15 Years
(Na=1129)
nb(%)16-25 Years
(Na=564)
nb(%)
Vaccinated 1131 (100.0) 539 (100.0) 1129 (100.0) 564 (100.0)
Not vaccinated 0 0 0 0
Dose 1
BNT162b2 (30 μg) 1131 (100.0) 539 (100.0) 0 0
Placebo 0 0 1129 (100.0) 564 (100.0)
Dose 2
BNT162b2 (30 μg) 1124 (99.4) 526 (97.6) 0 0
Placebo 0 0 1117 (98.9) 537 (95.2)
Note: Human immunodeficiency virus (HIV) -positive subjects are included in this summary but not included in the analyses of
the overall study objectives.
a. N = number of subjects in the specified group. This value is the denominator for the percentag e calculations.
b. n = Number of subjects with the specified characteristic.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (23:24) Source Data: adsl Table Generation: 27MAR2021 (02:54)
(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:
./nda2_unblinded/C4591001_BLA/advx_s002_adm_ped_rand
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 54
FDA-CBER-2022-5812-0234762
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
Table 7.Vaccine Administration Timing –Subjects 12 Through 15 and 16 Through 25
Years of Age (Reactogenicity Subset)
Vaccine Group (as Randomized)
BNT162b2 (30 μg) Placebo
12-15Years
(Na=1131)
nb(%)16-25 Years
(Na=539)
nb(%)12-15 Years
(Na=1129)
nb(%)16-25 Years
(Na=564)
nb(%)
Randomized 1131 (100.0) 539 (100.0) 1129 (100.0) 564 (100.0)
Not vaccinated 0 0 0 0
Dose 1 1131 (100.0) 539 (100.0) 1129 (100.0) 564 (100.0)
Dose 2c1124 (99.4) 526 (97.6) 1117 (98.9) 537 (95.2)
<14 Days 0 0 0 0
14 to 20 Days 358 (31.7) 184 (34.1) 364 (32.2) 192 (34.0)
21 to 27 Days 737 (65.2) 325 (60.3) 729 (64.6) 328 (58.2)
28 to 34 Days 23 (2.0) 7 (1.3) 15 (1.3) 6 (1.1)
35 to 41 Days 4 (0.4) 5 (0.9) 4 (0.4) 4 (0.7)
42 to 48 Days 1 (0.1) 1 (0.2) 1 (0.1) 1 (0.2)
49 to 55 Days 1 (0.1) 0 3 (0.3) 2 (0.4)
>55 Days 0 4 (0.7) 1 (0.1) 4 (0.7)
Note: Human immunodeficiency virus (HIV) -positive subjects are included in this summary but not included in the analyses of
the overall study objectives.
a. N = number of subjects in the specified group. This value is the denominator for the percentag e calculations.
b. n = Number of subjects with the specified characteristic.
c. Days calculated since Dose 1.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (23:24) Source Data: adsl Table Generation: 27MAR2021 (02:11)
(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:
./nda2_unblinded/C4591001_BLA/advx_s002_time_ped_rand
10.3.2. Participants 16 Through 55 Years of Age
For the adult group , almost all participants were administered study intervention as randomized
(Table 8). 99.7% received Dose 1 and 98.1% received Dose 2 of BNT162b2 in the BNT162b2
group. In participants originall y randomized to placebo, 99.7% received Dose 1 and 97.7%
received Dose 2 of placeb o, and 86.8% received Dose 3 and 65.4% received Dose 4 of
BNT162b2 after unblinding.
For Dose 1, 2 participants randomized to the placebo group received BNT162b2, 1 participant
randomized to the BNT162b2 group received placebo, and vaccination for 1 partic ipant
randomized to the BNT162b2 group could not be determined. For Dose 2, 1 participant
randomized to the placebo group received BNT162b2, and 2 participants randomized to the
BNT162b2 group received placebo.
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 55
FDA-CBER-2022-5812-0234763
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
The majority of participants received Dose 2 between 21 to 27days after Dose 1 in the
BNT162b2 ( 62.7%) and placebo ( 62.7%), followed by 14 to 20 day s after Dose 1 in the
BNT162b2 ( 32.7%) and placebo ( 32.3%)(Table 9).In participants originally randomized to
placebo, 86.8% received BNT162b2 after unblinding (Dose 3) and t he majority of participants
received Dose 4 between 21 to 27 day s after Dose 3 (44.1%), followed b y 14 to 20 day s after
Dose 3 (19.5% ).
Table 8.Vaccine as Administered by Vaccine Group – Phase 2/3 Subjects 16- 55 Years
of Age – All Randomized Subjects
Vaccine Group (as Randomized)
Vaccine (as Adm inistered) BNT162b2 (30 μg)
(Na=13104)
nb(%)Placebo
(Na=13132)
nb(%)
Vaccinated 13073 (99.8) 13100 (99.8)
Not vaccinated 31 (0.2) 32 (0.2)
Dose 1
BNT162b2 (30 μg) 13071 (99.7) 2 (0.0)
Placebo 1 (0.0) 13098 (99.7)
Indeterminate vaccinec1 (0.0) 0
Dose 2
BNT162b2 (30 μg) 12860 (98.1) 1 (0.0)
Placebo 2 (0.0) 12824 (97.7)
Indeterminate vaccinec0 0
Dose 3
First dose BNT162b2 (30 μg) 11405 (86.8)
Indeterminate vaccinec0
Dose 4
Second dose BNT162b2 (30 μg) 8586 (65.4)
Indeterminate vaccinec0
Note: Human immunodeficiency virus (HIV) -positive subjects are included in this summary but analyzed and reported
separately.
a. N = number of subjects in the specified group. This value is the denominator for the percentage calculations.
b. n = Number of subjects with the specified characteristic.
c. "Indeterminate vaccine" refers to subjects whose vaccine (as administered) could not be determined.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (23:24) Source Data: adsl Table Generation: 28MA R2021 (12:39)
(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:
./nda2 unblinded/C4591001 EUA 1655/advx s002 adm 1655 rand
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 56
FDA-CBER-2022-5812-0234764
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
Table 9.Vaccine Administration Timing –Phase 2/3 Subjects 16- 55 Years of Age – All
Randomized Subjects
Vaccine Group (as Randomized)
BNT162b2 (30 μg)
(Na=13104)
nb(%)Placebo
(Na=13132)
nb(%)
Randomized 13104 (100.0) 13132 (100.0)
Notvaccinated 31 (0.2) 32 (0.2)
Dose 1 13073 (99.8) 13100 (99.8)
Dose 2c12862 (98.2) 12825 (97.7)
<14 Days 0 1 (0.0)
14 to 20 Days 4280 (32.7) 4245 (32.3)
21 to 27 Days 8221 (62.7) 8239 (62.7)
28 to 34 Days 158 (1.2) 200 (1.5)
35 to 41 Days 62 (0.5) 61 (0.5)
42 to 48 Days 43 (0.3) 34 (0.3)
49 to 55 Days 23 (0.2) 20 (0.2)
>55 Days 75 (0.6) 25 (0.2)
Dose 3 (first dose of BNT162b2 [30 μg]) 11405 (86.8)
Dose 4 (second dose of BNT162b2 [30 μg])d8586 (65.4)
<14 Days 1 (0.0)
14 to 20 Days 2564 (19.5)
21 to 27 Days 5788 (44.1)
28 to 34 Days 152 (1.2)
35 to 41 Days 56 (0.4)
42 to 48 Days 18 (0.1)
49 to 55 Days 6 (0.0)
>55 Days 1 (0.0)
Note: Human immunodeficiency virus (HIV) -positive subjects are included in this summary but analyzed and reported
separately.
a. N = number of subjects in the specified group. This value is the denominator for the percentage calculations.
b. n = Number of subjects with the specified characteristic.
c. Days calculated since Dose 1.
d. Days calculated since Dose 3.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (23:24) Source Data: adsl Table Generation: 28MAR2021 (14:23)
(Cutoff Date: 13M AR2021, Snapshot Date: 25MAR2021) Output File:
./nda2_unblinded/C4591001_EUA_1655/advx_s002_time_1655_rand
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 57
FDA-CBER-2022-5812-0234765
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
10.4. Data Sets Analyzed
10.4.1. Participants 12 Through 15 Years of Age
10.4.1.1. Safety Population
The safet y populations, including subsets and exclusions, the adolescent and y oung adult groups
were similar in the corresponding BNT162b2 and placebo groups (Table 10
). Safet y analysis
results hereafter are presented for adol escent and young adult safet y population (including the
reactogenicity subset) up to 1 month after Dose 2 and for all available data up to the data cutoff
date (13 March 2021).
Table 10.Safety Population – Subjects 12 Through 15 and 16 Through 25 Years of Age
Vaccine Group (as Administered)
12-15 Years 16-25 Years
BNT162b2 (30
μg)
naPlacebo
naTotal
naBNT162b2 (30
μg)
naPlacebo
naTotal
na
Randomizedb2264 3788
Vaccinated 1131 1129 2260 (99.8) 1869 1906 3775 (99.7)
Safety population 1131 1129 2260 (99.8) 1867 1903 3770 (99.5)
Reactogenicity subset 1131 1129 2260 (99.8) 537 561 1098 (29.0)
HIV-positive 0 0 0 1 0 1 (0.0)
Excluded from safety population 4 (0.2) 18 (0.5)
Reason for exclusion
Subject did not receive study
vaccine4 (0.2) 13 (0.3)
Unreliable data due to lack of PI
oversight0 5 (0.1)
Note: Human immunodeficiency virus (HIV) -positive subjects are included in this summary but not included in the analyses of
the overall study objectives.
a. n = Number of subjects with the specified characteristic, or the total sample.
b. This va lue is the denominator for the percentage calculations.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (23:24) Source Data: adsl Table Generation: 27MAR2021 (04:09)
(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:
./nda2 unblinded/C4591001 B LA/adsl s003 saf pop ped
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 58
FDA-CBER-2022-5812-0234766
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
10.4.1.2. Duration of Follow- Up
The median duration of follow -up for adolescents was >2 months after Dose 2. Almost all
(98.3%) of adolescent participants had at least 1 month of follow -up after Dose 2, and 1308 out
of 2260 enrolled adolescents (57.9%) had at least 2 months of follow -up after Dose 2 (Table 11).
Table 11.Follow -up Time After Dose 2 – Subjects 12 Through 15 Years of Age – Safet y
Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)
(Na=1131)
nb(%)Placebo
(Na=1129)
nb(%)Total
(Na=2260)
nb(%)
Subjects (%) with length of follow -up of:
Total exposure from Dose 2 to cutoff date
<1 Month 13(1.1) 25 (2.2) 38 (1.7)
≥1 Month to <2 months 458 (40.5) 456 (40.4) 914 (40.4)
≥2 Months to <3 months 612 (54.1) 599 (53.1) 1211 (53.6)
≥3 Months 48 (4.2) 49 (4.3) 97 (4.3)
Note: Follow -up time was calculated to the cutoff date or the date of unblinding, whichever date was earlier.
a. N = number of subjects in the specified group, or the total sample. This value is the denominator for the percentage
calculations.
b. n = Number of subjects with the specified characteristic.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (23:24) Source Data: adsl Table Generation: 27MAR2021 (00:54)
(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File: ./nda2_unblinded/C459100 1_BLA/adsl_fu_d2_ped_saf
10.4.1.3. Immunogenicity Populations
For immunogenicity analy ses, it was planned to select a random sample of 280 participants in the
BNT162b2 group for each of the two age groups as an immunogenicit y subset for the NI
assessment. The immunogenicity subset was chosen to reflect the population tested which
received BNT162b2 or placebo.
The Dose 2 evaluable immunogenicit y population for adolescents 12 -15 years of age included
209 participants in the BNT162b2 group and 36 participants in the placebo group), and for young
adults 16- 25 years of age included 186 participants in the BNT162b2 group and 32 participants
in the placebo group. Reasons for participant exclusion from the evaluable immunogenicit y
populations are shown in Table 12. The majorit y of exclusions were due to participants not
having at least 1 valid and determinate immunogenicity result after Dose 2, mostly as the result
of testing lab oratory supply limitation of the qualified viral lot and were generall y balanced
across age and vaccine groups.
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 59
FDA-CBER-2022-5812-0234767
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
Table 12.Immunogenicity Populations – Subjects 12 Through 15 and 16 Through 25
Years of Age (Immunogenicity Subset)
Vaccine Group (as Randomized)
BNT162b2 (30 μg) Placebo
12-15 Years 16-25 Years 12-15 Years 16-25 Years
na(%) na(%) na(%) na(%)
Randomizedb280 (100.0) 280 (100.0) 50 (100.0) 50 (100.0)
Dose 2 all -available immunogenicity population 210 (75.0) 191(68.2) 36 (72.0) 34 (68.0)
Subjects excluded from Dose 2 all-available immunogenicity
population70 (25.0) 89 (31.8) 14 (28.0) 16 (32.0)
Reason for exclusion
Did not receive Dose 2 1 (0.4) 0 0 0
Did not have at least 1 valid and determinate
immunogenicity result after Dose 269 (24.6) 89 (31.8) 14 (28.0) 16 (32.0)
Dose 2 evaluable immunogenicity population 209 (74.6) 186 (66.4) 36 (72.0) 32 (64.0)
Subjects excluded from Dose 2 evaluable immunogenicity
population71 (25.4) 94 (33.6) 14 (28.0) 18 (36.0)
Reason for exclusionc
Did not receive 2 doses of the vaccine to which they were
randomly assigned1 (0.4) 0 0 0
Did not receive Dose 2 within 19 -42 days after Dose 1 1 (0.4) 2 (0.7) 0 2 (4.0)
Did not have at least 1 valid and determinate
immunogenicity result after Dose 269 (24.6) 89 (31.8) 14 (28.0) 16 (32.0)
Did not have blood collection within 28- 42 days after Dose
23 (1.1) 16 (5.7) 0 3 (6.0)
Had important protocol deviation(s) as determined by the
clinician0 0 0 1 (2.0)
a. n = Number of subjects with the specified characteristic.
b. These values are the denominators for the percentage calculations.
c. Subjects may have been excluded for more than 1 reason.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (23:24) Source Data: adsl Table Generation: 27MAR2021 (00:54)
(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:
./nda2_unblinded/C45 91001_BLA/adva_s008_imm_pop_ped
10.4.1.4. Efficacy Populations
The protocol prespecified final anal ysis of efficacy was completed with a data cutoff date of
14 November 2020. At that time, few adolescents (12- 15 years of age) had enrolled in the study ,
precluding a meaningful efficacy evaluation. An analy sis was perfo rmed with all accrued cases
during blinded follow -up to a data cutoff date of 13 March 2021, for efficacy in adolescents.
In the efficacy anal yses, adolescents in the efficacy populations included:
Evaluable efficacy population without evidence of SARS -CoV -2 infection prior to 7 days
after Dose 2: N=1005 in the BNT162b2 group and N=978 in the placebo group (Table 17).
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 60
FDA-CBER-2022-5812-0234768
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
Evaluable eff icacy population with or without evidence of SARS -CoV -2 infection prior to
7days after Dose 2: N=1119 in the BNT162b2 group and N=1110 in the placebo group
(Table 18).
Dose 1 all -available efficacy popula tion: N=1131 in the BNT162b2 group and N=1129 in the
placebo group (Table 19).
Since the efficacy populations include nearl y the same number of participants in each grou p as in
the safet y population (Table 10), the demographics of the efficacy populations are essentially the
same as the safety population.
10.4.2. Participants 16 Through 55 Yea rs of Age
The safet y population age group of adults (16 -55 years of age) included 13,069 participants in
the BNT162b2 group and 13,095 participants in the placebo group (Table 13).
Duration of follow -up was ≥4 months after Dose 2 for 57.8% of adult participants (16-55years
of age) during the blinded placebo -controlled follow -up period ( Table 13). As of the data cutoff
date, the proportion of participants in the age group with blinded follow -up to at least 6months
after Dose 2 included 10.4% in the BNT162b2 group and 8.2% in the plac ebo group. When the
total exposure time from Dose 2 to the data cutoff date is considered, 6666 participants
16-55years of age (51.0%) had ≥6 months of follow -up time.
Table 13.Follow -up Time After Dose 2 – Phase 2/3 Subjects 16- 55 Years of Age –Safety
Population
Vaccine Group (as Administered)
BNT162b2 (30μg)
(Na=13069)
nb(%)Placebo
(Na=13095)
nb(%)Total
(Na=26164)
nb(%)
Subjects (%) with length of follow -up of:
Original blinded placebo -controlled follow -up period
<2 Months 917 (7.0) 962 (7.3) 1879 (7.2)
≥2 Months to <4 months 4448 (34.0) 4726 (36.1) 9174 (35.1)
≥4 Months to <6 months 6343 (48.5) 6327 (48.3) 12670 (48.4)
≥6 Months 1361 (10.4) 1080 (8.2) 2441 (9.3)
Total exposure from Dose 2 to cutoff date
<2 Months 305 (2.3)
≥2 Months to <4 months 552 (4.2)
≥4 Months to <6 months 5546 (42.4)
≥6 Months 6666 (51.0)
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 61
FDA-CBER-2022-5812-0234769
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
Table 13.Follow -up Time After Dose 2 – Phase 2/3 Subjects 16- 55 Years of Age –Safety
Population
Vaccine Group (as Administered)
BNT162b2 (30μg)
(Na=13069)
nb(%)Placebo
(Na=13095)
nb(%)Total
(Na=26164)
nb(%)
Note: Human immunodeficiency virus (HIV) -positive subjects are included in this summary but analyzed and reported
separately.
a. N = number of subjects in the specified group, or the total sample. This value is the denominator for the percentage
calcu lations.
b. n = Number of subjects with the specified characteristic.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (23:24) Source Data: adsl Table Generation: 31MAR2021 (17:26)
(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:
./nda2_u nblinded/C4591001_EUA_1655/adsl_fu_d2_1655_saf
10.5. Demographic and Other Baseline Characteristics
10.5.1. Participants 12 Through 15 Years of Age
10.5.1.1. Safety Population –Participants 12 Through 15 Years of Age
Demographic characteristics for adolescents (12 -15 years of age) and young adults (16 -25 years
of age) were similar in the corresponding BNT162b2 and placebo groups in the safet y population
(Table 14). Overall, most adolescent participants in the BNT162b2 group were White ( 85.9%),
with 4.6% Black participants and 6.4% Asian participants, and other racial groups were < 3.0%.
There were 11.7% Hispanic/L atino participants. The m edian age of adolescents in the
BNT162b2 gro up was 14.0 years and 50.1% were male. Obese adolescents (based on age -and
sex-specific bod y mass index) made up 11.3% (placebo group) to 12.6% (BNT162b2 group) of
this age group in the safety population.
Note that for safet y endpoint analyses of adolesce nts that included comparative data from y oung
adults, the y oung adult group anal yzed was the reactogenicity subset (ie, those participants in the
young adult group who completed an e -diary for reactogenicity in addition to AE reporting).
Demographic chara cteristics for the adolescents and y oung adults in the reactogenicit y subset
were similar to those in the safet y population ( Supplemental Table 14.1 ).
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 62
FDA-CBER-2022-5812-0234770
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
Table 14.Demographic Characteristics – Subjects 12 Through 15 and 16 Through 25
Years of Age –Safety P opulation
Vaccine Group (as Administered)
BNT162b2 (30 μg) Placebo
12-15 Years
(Na=1131)
nb(%)16-25 Years
(Na=1867)
nb(%)12-15 Years
(Na=1129)
nb(%)16-25 Years
(Na=1903)
nb(%)
Sex
Male 567 (50.1) 921 (49.3) 585 (51.8) 882 (46.3)
Female 564 (49.9) 946 (50.7) 544 (48.2) 1021 (53.7)
Race
White 971 (85.9) 1443 (77.3) 962 (85.2) 1510 (79.3)
Black or African American 52 (4.6) 189 (10.1) 57 (5.0) 179 (9.4)
American Indian or Alaska Native 4 (0.4) 32 (1.7) 3 (0.3) 18 (0.9)
Asian 72 (6.4) 108 (5.8) 71 (6.3) 108 (5.7)
Native Hawaiian or other Pacific Islander 3 (0.3) 10 (0.5) 0 3 (0.2)
Multiracial 23 (2.0) 76 (4.1) 29 (2.6) 74 (3.9)
Not reported 6 (0.5) 9 (0.5) 7 (0.6) 11 (0.6)
Racial designation
Japanese 5 (0.4) 3 (0.2) 2 (0.2) 6 (0.3)
Ethnicity
Hispanic/Latino 132 (11.7) 604 (32.4) 130 (11.5) 575 (30.2)
Non-Hispanic/non -Latino 997 (88.2) 1259 (67.4) 996 (88.2) 1322 (69.5)
Not reported 2 (0.2) 4 (0.2) 3 (0.3) 6 (0.3)
Country
Argentina 0 282 (15.1) 0 287 (15.1)
Brazil 0 160 (8.6) 0 142 (7.5)
Germany 0 11 (0.6) 0 20 (1.1)
South Africa 0 69 (3.7) 0 75 (3.9)
Turkey 0 12 (0.6) 0 15 (0.8)
USA 1131 (100.0) 1333 (71.4) 1129 (100.0) 1364 (71.7)
Age at vaccination (years)
Mean (SD) 13.6 (1.11) 21.0 (2.99) 13.6 (1.11) 21.0 (2.98)
Median 14.0 22.0 14.0 21.0
Min, max (12, 15) (16, 25) (12, 15) (16, 25)
Baseline SARS -CoV -2 status
Positivec46 (4.1) 100 (5.4) 47 (4.2) 104 (5.5)
Negatived1028 (90.9) 1754 (93.9) 1023 (90.6) 1789 (94.0)
Missing 57 (5.0) 13 (0.7) 59 (5.2) 10 (0.5)
Body mass index (BMI) Obesee
Yes 143 (12.6) 353 (18.9) 128 (11.3) 385 (20.2)
No 988 (87.4) 1514 (81.1) 1001 (88.7) 1518 (79.8)
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 63
FDA-CBER-2022-5812-0234771
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
Table 14.Demographic Characteristics – Subjects 12 Through 15 and 16 Through 25
Years of Age –Safety P opulation
Vaccine Group (as Administered)
BNT162b2 (30 μg) Placebo
12-15 Years
(Na=1131)
nb(%)16-25 Years
(Na=1867)
nb(%)12-15 Years
(Na=1129)
nb(%)16-25 Years
(Na=1903)
nb(%)
Abbreviation: SARS -CoV -2 = severe acute respiratory syndrome coronavirus 2.
Note: Human immunodeficiency virus (HIV) -positive subjects are included in this summary but analyzed and reported
separately.
a. N = number of subjects in the specified group, or the total sample. This value is the denominator for the percentage
calcu lations.
b. n = Number of subjects with the specified characteristic.
c. Positive N -binding antibody result at Visit 1, positive NAAT result at Visit 1, or medical history of COVID -19.
d. Negative N -binding antibody result at Visit 1, negati ve NAAT result at Visit 1, and no medical history of COVID-19.
e. For 12 through 15 years age group, obesity is defined as a BMI at or above the 95th percentile. Refer to the CDC growth
charts at https://www.cdc.gov/growthcharts/html_charts/bmiagerev. htm. For 16 through 25 years age group, obesity is defined
as BMI ≥30.0 kg/m2.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (23:24) Source Data: adsl Table Generation: 01A PR2021 (22:23)
(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:
./nda 2 unblinded/C4591001 BLA1/adsl s005 demo ped saf
Participants in the reactogenicity subset had a diverse medical history profile consistent with that
of individuals in the general population in the same age group ( Supplemental Table 14.2). For
adolescents i n the BNT162b2 group, immune s ystem disorders ( 398 [35.2 %]), respiratory
disorders (178 [15.7%]), skin and subcutaneous tissue disorders (169 [14.9%]), surgical and
medical procedures ( 110 [9.7% ]), and social circumstances (104 [9.2%]), and nervous s ystem
disorders ( 94 [8.3%]) SOCs were most frequently reported.
10.5.1.2. Immunogenicity Population –Participants 12 Through 15 Years of Age
In the Dose 2 evaluable immunogenicit y population adolescent (12 -15 years of age) BNT162b2
group, 50.7% of participants were male; 88.0% were White, 7.7% were Black or African
American, and 2.4% were Asian; 10.5% were Hispanic/Latino; and the median age was 14 y ears
(Table 15). Baseline SARS -CoV -2 status was positive for 4.8% of adolescent participants in the
BNT162b2 group. Obese adolescents (based on age -and sex -specific body mass index) made up
8.3% (placebo group) to 11.5% (BNT162b2 group) of this age group in the evalua ble
immunogenicit ypopulation.
Demographics were generally similar for BNT162b2 and placebo, and inadolescents and young
adults 16- 25 years of age.
Demographics of the evaluable immunogenicit y population were similar to those in the
all-available immunog enicity population (Supplemental Table 14. 3). Likewise, the
immunogenicit y population demographics were generally similar to those in the safet y
population (Table 14).
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 64
FDA-CBER-2022-5812-0234772
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
Table 15.Demographic Characteristics – Subjects 12 Through 15 and 16 Through 25
Years of Age (Immunogenicity Subset) – Dose 2 Evaluable Immunogenicity
Population
Vaccine Group (as Randomized)
BNT162b2 (30 μg) Placebo
12-15 Years
(Na=209)
nb(%)16-25 Years
(Na=186)
nb(%)12-15 Years
(Na=36)
nb(%)16-25 Years
(Na=32)
nb(%)
Sex
Male 106 (50.7) 92 (49.5) 21 (58.3) 14 (43.8)
Female 103 (49.3) 94 (50.5) 15 (41.7) 18 (56.3)
Race
White 184 (88.0) 147 (79.0) 31 (86.1) 28 (87.5)
Black or African American 16 (7.7) 15 (8.1) 3 (8.3) 2 (6.3)
American Indian or Alaska Native 1 (0.5) 3 (1.6) 0 1 (3.1)
Asian 5 (2.4) 10 (5.4) 1 (2.8) 1 (3.1)
Native Hawaiian or other Pacific Islander 0 3 (1.6) 0 0
Multiracial 3 (1.4) 6 (3.2) 1 (2.8) 0
Not reported 0 2 (1.1) 0 0
Racial designation
Japanese 1 (0.5) 0 0 0
Ethnicity
Hispanic/Latino 22 (10.5) 31 (16.7) 2 (5.6) 7 (21.9)
Non-Hispanic/non -Latino 187 (89.5) 154 (82.8) 34 (94.4) 25 (78.1)
Not reported 0 1 (0.5) 0 0
Country
USA 209 (100.0) 186 (100.0) 36 (100.0) 32 (100.0)
Age at vaccination (years)
Mean (SD) 13.5 (1.12) 20.6 (3.09) 13.4 (1.17) 20.3 (3.05)
Median 14.0 21.0 13.0 19.5
Min, max (12, 15) (16, 25) (12, 15) (16, 25)
Baseline SARS -CoV -2 status
Positivec10 (4.8) 8 (4.3) 2 (5.6) 1 (3.1)
Negatived194 (92.8) 178 (95.7) 33 (91.7) 31 (96.9)
Missing 5 (2.4) 0 1 (2.8) 0
Body mass index (BMI) Obesee
Yes 24 (11.5) 43 (23.1) 3 (8.3) 4 (12.5)
No 185 (88.5) 143 (76.9) 33 (91.7) 28 (87.5)
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 65
FDA-CBER-2022-5812-0234773
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
Table 15.Demographic Characteristics – Subjects 12 Through 15 and 16 Through 25
Years of Age (Immunogenicity Subset) – Dose 2 Evaluable Immunogenicity
Population
Vaccine Group (as Randomized)
BNT162b2 (30 μg) Placebo
12-15 Years
(Na=209)
nb(%)16-25 Years
(Na=186)
nb(%)12-15 Years
(Na=36)
nb(%)16-25 Years
(Na=32)
nb(%)
Abbreviation: SARS -CoV -2 = severe acute respiratory syndrome coronavirus 2.
Note: Human immunodeficiency virus (HIV) -positive subjects are included in this summary but analyzed and reported
separately.
a. N = number of subjects in the specified group, or the total sample. This value is the denominator for the percentage
calcu lations.
b. n = Number of subjects with the specified characteristic.
c. Positive N -binding antibody result at Visit 1, positive NAAT result at Visit 1, or medical history of COVID -19.
d. Negative N -binding antibody result at Visit 1, negati ve NAAT result at Visit 1, and no medical history of COVID-19.
e. For 12 through 15 years age group, obesity is defined as a BMI at or above the 95th percentile. Refer to the CDC growth
charts at https://www.cdc.gov/growthcharts/html_charts/bmiagerev. htm. For 16 through 25 years age group, obesity is defined
as BMI ≥30.0 kg/m2.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (23:24) Source Data: adsl Table Generation: 02A PR2021 (00:07)
(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:
./nda 2_unblinded/C4591001_BLA1/adsl_s005_demo_ped_d2_ei
10.5.2. Participants 16 Through 55 Years of Age
Demographic characteristics for Phase 2/3 adults in the 16 -55 years of age group were similar in
the BNT162b2 and placebo groups (Table 16).Overall, most adult participants were White
(78.2 %), with 11.0% Black participants and 5.4% Asian participants, and other racial groups
were < 6.0%. There were 30.8% Hispanic/Lati no participants. The m edian age was 40.0 years
and 49.9% of participants were male. Obese adults made up 33.7% of this safet y population.
Table 16.Demographic Characteristics – Phase 2/3 Subjects 16- 55 Years of Age –Safety
Population
Vaccine Gr oup (as Administered)
BNT162b2 (30 μg)
(Na=13069)
nb(%)Placebo
(Na=13095)
nb(%)Total
(Na=26164)
nb(%)
Sex
Male 6640 (50.8) 6412 (49.0) 13052 (49.9)
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 66
FDA-CBER-2022-5812-0234774
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
Table 16.Demographic Characteristics – Phase 2/3 Subjects 16- 55 Years of Age –Safety
Population
Vaccine Gr oup (as Administered)
BNT162b2 (30 μg)
(Na=13069)
nb(%)Placebo
(Na=13095)
nb(%)Total
(Na=26164)
nb(%)
Female 6429 (49.2) 6683 (51.0) 13112 (50.1)
Race
White 10221 (78.2) 10251 (78.3) 20472 (78.2)
Black or African American 1429 (10.9) 1436 (11.0) 2865 (11.0)
American Indian or Alaska Native 165 (1.3) 153 (1.2) 318 (1.2)
Asian 703 (5.4) 712 (5.4) 1415 (5.4)
Native Hawaiian or other Pacific Islander 43 (0.3) 21 (0.2) 64 (0.2)
Multiracial 437 (3.3) 438 (3.3) 875 (3.3)
Not reported 71 (0.5) 84 (0.6) 155 (0.6)
Racial designation
Japanese 39 (0.3) 41 (0.3) 80 (0.3)
Ethnicity
Hispanic/Latino 4047 (31.0) 4023 (30.7) 8070 (30.8)
Non-Hispanic/non -Latino 8967 (68.6) 9011 (68.8) 17978 (68.7)
Not reported 55 (0.4) 61 (0.5) 116 (0.4)
Country
Argentina 1975 (15.1) 1973 (15.1) 3948 (15.1)
Brazil 1191 (9.1) 1189 (9.1) 2380 (9.1)
Germany 134 (1.0) 139 (1.1) 273 (1.0)
South Africa 328 (2.5) 330 (2.5) 658 (2.5)
Turkey 190 (1.5) 197 (1.5) 387 (1.5)
USA 9251 (70.8) 9267 (70.8) 18518 (70.8)
Age at vaccination (years)
Mean (SD) 39.0 (10.76) 38.7 (10.75) 38.9 (10.76)
Median 40.0 40.0 40.0
Min, max (16, 55) (16, 55) (16, 55)
Baseline SARS -CoV -2 status
Positivec517 (4.0) 541 (4.1) 1058 (4.0)
Negatived12466 (95.4) 12485 (95.3) 24951 (95.4)
Missing 86 (0.7) 69 (0.5) 155 (0.6)
Body mass index (BMI)
Underweight (<18.5 kg/m2) 199 (1.5) 224 (1.7) 423 (1.6)
Normal weight ( ≥18.5 kg/m2-24.9 kg/m2) 4208 (32.2) 4268 (32.6) 8476 (32.4)
Overweight ( ≥25.0 kg/m2-29.9 kg/m2) 4258 (32.6) 4178 (31.9) 8436 (32.2)
Obese ( ≥30.0 kg/m2) 4401 (33.7) 4421 (33.8) 8822 (33.7)
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 67
FDA-CBER-2022-5812-0234775
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
Table 16.Demographic Characteristics – Phase 2/3 Subjects 16- 55 Years of Age –Safety
Population
Vaccine Gr oup (as Administered)
BNT162b2 (30 μg)
(Na=13069)
nb(%)Placebo
(Na=13095)
nb(%)Total
(Na=26164)
nb(%)
Missing 3 (0.0) 4 (0.0) 7 (0.0)
Abbreviation: SARS -CoV -2 = severe acute respiratory syndrome coronavirus 2.
Note: Human immunodeficiency virus (HIV) -positive subjects are included in this summary but analyzed and reported
separately.
a. N = number of subjects in the specified group, or the total sample. This value is the denominator for the percentage
calcu lations.
b. n = Number of subjects with the specified characteristic.
c. Positive N -binding antibody result at Visit 1, positive NAAT result at Visit 1, or medical history of COVID -19.
d. Negative N -binding antibody result at Visit 1, negati ve NAAT result at Visit 1, and no medical history of COVID-19.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (23:24) Source Data: adsl Table Generation: 31MAR2021 (17:35)
(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:
./nda2_unblinded/C45 91001_EUA_1655/adsl_s005_demo_all_1655_saf
Adult participants had a diverse medical history profile consistent with that of individuals in the
general population in the same age group ( Supplemental Table 14.4).In the BNT162b2 group,
conditions in the surgical and medical procedures ( 3976 [30.4%] ), metabolism and nutrition
disorders ( 2414 [18.5 %]), psy chiatric disorders ( 2695 [20.6%]), and immune system disorders
(3238 [24.8 %])SOCs were most frequently reported.
10.6. Participant Compliance
10.6.1. Immunogenicity Blood Samples –Participants 12 Through 15 Years of Age
Most participants in the adolescent and young adult group s (≥90.0% ) had immunogenicit y blood
samples taken within the protocol specified time frames from 28 to 35 day s after Dose 2
(Supplemental Table 14.5).
10.6.2. E- Diary
10.6.2.1. Participants 12 Through 15 Years of Age
Overall, transmission of e -diary data for each day during the 7 days after Dose 1 of BNT162b2
was ≥87.6 % (range: 87.6 % to 96.3%) and ≥87.9 % (range: 87.9 % to 94.8%) for the adolescent
and young adult groups , respectivel y (Supplemental Table 14. 6). After Dose 2 of BNT162b2 for
the adolescent group , transmission of e -diary data was 75 .8%on Day 1 and ranged from 81.2%
to 87.5%for each day during Day 2 through Day 7. After Dose 2 of BNT162b2 for the young
adult group , transmission of e -diary data was 7 1.8%on Day 1 and ranged from 78.5% to 83.2%
for each day during Day 2 through Day 7.Transmission rates were similar in the BNT162b2
group sand the placebo group s.
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 68
FDA-CBER-2022-5812-0234776
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
10.6.2.2. Participants 16 Through 55 Years of Age
Overall, transmission of e -diary data for adults 16 -55 years of age was ≥89.1% (range: 89.1% to
94.3%) for each day during the 7 days after Dose 1 of BNT162b2 (Supplemental Table 14.7).
After Dose 2 of BNT162b2, transmission of e- diary data was 76.8 % on Day 1 and ranged from
82.6% to 85.9% for each day during Day 2 through Day 7. Transmission rates were similar in
the BNT162b2 group and the placebo group.
10.7. Prior and Concomitant Vaccines, Medications, and Procedures
10.7.1. Participants 12 Through 15 Years of Age
A small percentage of participants 12 through 15 and 16 through 25 years of age in either group
(≤3.2 %) received an y concomitant vaccine from after Dose 1 through 1 month after Dose 2 , and
most concomitant vaccines received were the influe nzavaccine ( Supplemental Table 14.8).
10.7.2. Participants 16 Through 55 Years of Age
A small percentage of participants 16 through 55 years of age in either group ( ≤9.9%) received
any concomitant vaccine after Dose 1, and most concomitant vaccines received were the
influenza vaccine ( Supplemental Table 14.9).
11.EFFICACY AND IMMUNOG ENICITY EVALUATION
11.1. Efficacy Results
11.1.1. Interim Analysis 1 and Final Ana lysisof Efficacy
VEwas demonstrated that BNT162b2 at 30 µg provided protection against COVID- 19 in
participants who had no evidence of prior infection with SARS -CoV -2, including across
demographic subgroups, with severe cases observed predominantl y in the placebo group .
Efficacy results of the first successful interim analy sis (first primary efficacy objective only )
based on an accru ed94 cases (data cutoff date: 04 November 2020), and the final anal ysis of
efficacy based on an acc rued 170cases (data cutoff date: 14 November 2020) are presented in
Section 11.1 of the C4591001 final anal ysis interim CSR dated 03 Decem ber2020 .
11.1.2. Vaccine Efficacy Against COVID -19 –Participants 12Through 15 Years of Age
11.1.2.1. Confirmed Cases of COVID -19 at Least 7 Days after Dose 2 –Evaluable Efficacy
Population –Participants 12 Through 15 Years of Age
11.1.2.1.1. Participants Without Evidence of Infec tion Before and During Vaccination
Regimen –Participants 12 Through 15 Years of Age
As of the data cutoff date (13 March 2021), confirmed COVID- 19 cases in the evaluable efficacy
population adolescent group (12 -15years of age) without evidence of prior SARS -CoV -2
infection at least 7 days after Dose 2 included 0 cases in the BNT162b2 group and 16 cases in
the placebo group. The observed VE was 100% (2 -sided 95% CI: 75.3%, 100.0%) ( Table 17).
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 69
FDA-CBER-2022-5812-0234777
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
Table 17.Vaccine Efficacy – First COVID -19 Occurrence From 7 Days After Dose 2 –
Blinded Placebo -Controlled Follow -up Period –Subjects 12 Through 15 Years
of Age and Without Evidence of Infection Prior to 7 Days After Dose 2 –
Evaluable Effica cy (7 Days) Population
Vaccine Group (as Randomized)
BNT162b2 (30 μg)
(Na=1005)Placebo
(Na=978)
Efficacy Endpoint n1bSurveillance
Timec(n2d)n1bSurveillance
Timec(n2d)VE (%) (95% CIe)
First COVID -19 occurrence from 7 days
after Dose 20 0.154 (1001) 16 0.147 (972) 100.0 (75.3, 100.0)
Abbreviations: N -binding = SARS -CoV -2 nucleoprotein– binding; NAAT = nucleic acid amplification test;
SARS -CoV -2 = severe acute respiratory syndrome coronavirus 2; VE = vaccine efficacy.
Note: Subjects who had no serological or virological evidence (prior to 7 days after receipt of the last dose) of past SARS -CoV -
2 infection (ie, N -binding antibody [serum] negative at Visit 1 and SARS -CoV -2 not detected by NAAT [nasal swab] at Visits 1
and 2), and had n egative NAAT (nasal swab) at any unscheduled visit prior to 7 days after Dose 2 were included in the analysis.
a. N = number of subjects in the specified group.
b. n1 = Number of subjects meeting the endpoint definition.
c. Total surveillance time in 1000 person -years for the given endpoint across all subjects within each group at risk for the
endpoint. Time period for COVID-19 case accrual is from 7 days after Dose 2 to the end of the surveillance period.
d. n2 = Number of subjects at risk for the endpoint.
e. Confidence interval (CI) for VE is derived based on the Clopper and Pearson method adjusted for surveillance time.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (19:19) Source Data: adc19ef Table Generation: 30MAR2021
(22:23)
(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:
./nda2 unblinded/C4591001 BLA/adc19ef ve cov 7pd2 peds wo eval
11.1.2.1.2. Participants With or Without Evidence of Infection Before and During
Vaccination Regimen – Participants 12 Through 15 Years of Age
Confirmed COVID -19 cases in the evaluable efficacy population adolescent group (12 -15years
of age) with or without evidence of prior SARS -CoV -2 infection at least 7 days after Dose 2
included 0 cases in the BNT162b2 group and 18 cases in the placeb o group. The observed VE
was 100.0% (2 -sided 95% CI : 78.1%, 100.0%) (Table 18).
Relative to the anal ysis of cases in participants without prior evidence of SARS -CoV -2 infection
(Table 17), 2 additional cases reported in the placebo group of the evaluable efficacy population
with or without evidence of prior SARS -CoV -2 infection befor e and during vaccine regimen
occurred in participants who were baseline negative serostatus for SARS -CoV -2, and had a
negative NAAT at Visit 1 followed b y a positive NAAT (confirmed b y the central laboratory) at
Visit 2 (Appendix 16.2.8.1.2 ).
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 70
FDA-CBER-2022-5812-0234778
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
Table 18.Vaccine Efficacy – First COVID -19 Occurrence From 7 Days After Dose 2 –
Blinded Placebo -Controlled Follow -up Period –Subjects 12 Through 15 Years
of Age and With or Without Evidence of Infection Prior to 7 Days After Dose 2
–Evaluable Efficacy (7 Da ys) Population
Vaccine Group (as Randomized)
BNT162b2 (30 μg)
(Na=1119)Placebo
(Na=1110)
Efficacy Endpoint n1bSurveillance
Timec(n2d)n1bSurveillance
Timec(n2d)VE (%) (95% CIe)
First COVID -19 occurrence from 7 days after
Dose 20 0.170 (1109) 18 0.163 (1094) 100.0 (78.1, 100.0)
Abbreviation: VE = vaccine efficacy.
a. N = number of subjects in the specified group.
b. n1 = Number of subjects meeting the endpoint definition.
c. Total surveillance time in 1000 person -years for the given endpoint across all subjects within each group at risk for the
endpoint. Time period for COVID-19 case accrual is from 7 days after Dose 2 to the end of the surveillance period.
d. n2 = Number of subjects at risk for the endp oint.
e. Confidence interval (CI) for VE is derived based on the Clopper and Pearson method adjusted for surveillance time.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (19:19) Source Data: adc19ef Table Generation: 30MAR2021
(22:24)
(Cutoff Date: 13M AR2021, Snapshot Date: 25MAR2021) Output File:
./nda2 unblinded/C4591001 BLA/adc19ef ve cov 7pd2 peds eval
11.1.2.1.3. All Confirmed Cases of COVID -19 After Dose 1 – All- Available Efficacy
Population – Participants 12 Through 15 Years of Age
As of the data cutoff date (13 March 2021), confirmed COVID- 19 cases in the Dose 1 all -
available efficacy (modified intention -to-treat) population adolescent group (12-15 years of age)
included 3 cases in the BNT162b2 group and 35 cases in the placebo grou p, with an observed
VE of 91.6% (2 -sided 95% CI:73.5%, 98.4%) (Table 19).
The time interval from after Dose 1 to prior to receiving Dose 2 included 3 cases in the
BNT162b2 group and 12 cases in the placebo group; these 3 cases in the BNT162 group, which
comprised all COVID -19 cases reported in the BNT162b2 group in this population at any time,
all occurred within the period from after Dose 1 to <11 days after Dose 1. All 3 of these cases in
the BNT162b2 group occurred in participants who had baseline SARS -CoV -2 negative status.
The observed VE for BNT162b2 in adolescents in the Dose 1 all -available population was 100.0%
(ie, all cases were confined to the placebo gro up) for all time intervals starting from ≥11days after
Dose 1 to before Dose 2, through ≥2 months after Dose 2 and <4 months after Dose 2.
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 71
FDA-CBER-2022-5812-0234779
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
Table 19.Vaccine Efficacy – First COVID -19 Occurrence After Dose 1 –Blinded
Placebo- Controlled Follow -up Pe riod – Subjects 12 Through 15 Years of Age –
Dose 1 All -Available Efficacy Population
Vaccine Group (as Randomized)
BNT162b2 (30 μg)
(Na=1131)Placebo
(Na=1129)
Efficacy Endpoint
Subgroupn1bSurveillance
Timec(n2d)n1bSurveillance
Timec(n2d)VE (%) (95% CIe)
First COVID -19 occurrence after Dose 1 3 0.257 (1120) 35 0.250 (1119) 91.6 (73.5, 98.4)
After Dose 1 to before Dose 2 3 12 75.0 (7.4, 95.5)
After Dose 1 to <11 days after Dose 1 3 4 25.0 (-343.3, 89.0)
≥11 Days after Dose 1 to before Dose 2 0 8 100.0 (41.4, 100.0)
Dose 2 to 7 days after Dose 2 0 5 100.0 (-9.1, 100.0)
≥7 Days after Dose 2 0 18 100.0 (77.3, 100.0)
≥7 days after Dose 2 to <2 Months after
Dose 20 16 100.0 (74.1, 100.0)
≥2 Months after Dose 2 to <4 Months
after Dose 20 2 100.0 (-432.5, 100.0)
Abbreviation: VE = vaccine efficacy.
a. N = number of subjects in the specified group.
b. n1 = Number of subjects meeting the endpoint definition.
c. Total surveillance time in 1000 person -years for the given endpoint across all subjects within each group at risk for the
endpoint. Time period for COVID-19 case accrual is from Dose 1 to the end of the surveillance period.
d. n2 = N umber of subjects at risk for the endpoint.
e. Confidence interval (CI) for VE is derived based on the Clopper and Pearson method (adjusted for surveillance time for
overall row).
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (19:19) Source Data: adc19e f Table Generation: 30MAR2021
(22:24)
(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:
./nda2 unblinded/C4591001 BLA/adc19ef ve cov pd1 peds aai
11.1.3. Vaccine Efficacy Against Severe COVID -19 –Participants 12Through 15 Years of
Age
No severe COVID -19 cases (per protocol definition or CDC criteria) were reported in
adolescents (12 -15years of age) as of the data cutoff date (13 March 2021)
(Appendix 16.2.8.1.1 ).
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 72
FDA-CBER-2022-5812-0234780
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
11.2. Efficacy Conclusions –Participants 12Through 15 Years of Age
Descriptive efficacy analy ses were conducted for the adolescent group on cases accrued during
blinded follow -up period through the data cutoff date of 13 March 2021.
In the adolescent group, in theefficacy anal yses in the evaluable efficacy population based on
cases reported from at least 7 days after Dose 2 through the data cutoff date, the observed VE
was 100% ( 0 and 16 cases in the BNT162b2 and placebo group, respectively , with 2 -sided 95%
CI: 75.3%, 100%) for individuals without evidence of prior SARS -CoV -2 infec tion before and
during vaccination regimen, and 100% ( 0 and 18 cases in the BNT162b2 and placebo group,
respectivel y, with 2-sided 95% CI : 78.1%, 100%) for those with or without evidence of prior
SARS -CoV -2 infection before and during vaccination regimen.
The efficacy anal ysis for the Dose 1 all -available (modified intention -to-treat) population
included 3 cases in the BNT162b2 group and 35 cases in the placebo group, with an observed
VE of 91.6% (2 -sided 95% CI : 73.5%, 98.4%), with no cases reported in th e BNT162b2 group
starting from ≥11 day s after Dose 1.
No severe cases were reported in the 12- 15 years of age group as of the date cutoff date.
Overall, these efficacy data strongl y support BNT162b2 use in adolescents 12 -15years of age.
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 73
FDA-CBER-2022-5812-0234781
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
11.3. Immunogenicity Re sults –Part icipants 12 Through 15 Years of Age
11.3.1. Noninferiority of Immune Response to Prophylactic BNT162b2 in Participants
12Through 15 Years Compared with Participants 16 Through 25 Years of Age
Geometric Mean Ratio ( GMR )in Neutralization Titers
The immune response to BNT162b2 in adolescents 12- 15 years of age was noninferior to that
observed in young adults 16- 25 years of age, based on SARS -CoV -2 50% neutralizing titers at
1month after Dose 2, in participants without prior evidence of SARS -COV -2infection, and in
fact greatl y exceeded the response observed in young adults. The GMT ratio of adolescents to
young adults was 1.76 (2-sided 95% CI: 1.47, 2.10), meeting the 1.5- fold NI criterion (ie, lower
bound of the 2- sided 95% CI for GMR >0.67) (Table 20). Of note, the lower bound of the
2-sided 95% CI for the GMR is >1 which indicates a statistically greater response in the
adolescents than that of young adults.
Seroresponse
Among participants without prior e vidence of SARS- CoV -2 infection up to 1 month afterDose2
of BNT162b2, high proportions (97.9% of adolescents and 100.0% of young adults) had a
≥4-fold rise (seroresponse) in SARS- CoV -2 50% neutralizing titer s from before vaccination to
1month after Dose 2. The difference in proportions of participants who had a ≥4-fold rise
between the two age groups (adolescents –young adults) was -2.1% (2- sided 95% CI: - 6.0%,
0.9%) (Table 21).
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 74
FDA-CBER-2022-5812-0234782
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
Table 20.Summary of Geometric Mean Ratio –NT50 – Comparison of Subjects 12 Through 15 Years of Age to Subjects 16
Through 25 Years of Age (Immunogenicity Subset) –Subjects Without Evidence of Infection up to 1 Month After
Dose 2 –Dose 2 Evaluable I mmunogenicity Population
Vaccine Group (as Randomized)
BNT162b2 (30 μg)
12-15 Years 16-25 Years 12-15 Years/16 -25 Years
Assay Dose/
Sampling
Time PointanbGMTc
(95% CIc)nbGMTc
(95% CIc)GMRd
(95% CId)Met Noninferiority Objectivee
(Y/N)
SARS -CoV -2 neutralization assay -NT50
(titer)2/1 Month 190 1239.5
(1095.5, 1402.5)170 705.1
(621.4, 800.2)1.76
(1.47, 2.10)Y
Abbreviations: GMR = geometric mean ratio; GMT = geometric mean titer; LLOQ = lower limit of quantitation;
NT50 = 50% neutralizing titer; SARS -CoV -2 = severe acute respiratory syndrome coronavirus 2.
Note: Subjects who had no serological or virological evidence (up to 1 month after receipt of the last dose) of past SARS -CoV -2 infection (ie, N -binding antibody [ serum]
negative at Visit 1 and SARS -CoV -2 not detected by NAAT [nasal swab] at Visits 1 and 2), and had negative NAAT (nasal swab) at any unscheduled visit up to 1 m onth after
Dose 2 were included in the analysis.
a. Protocol -specified timing for blood sample collection.
b. n = Number of subjects with valid and determinate assay results for the specified assay at the given dose/sampling time point .
c. GMTs and 2 -sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on the Student t distribution). Assay results
below the LLOQ were set to 0.5 × LLOQ.
d. GMRs and 2 -sided 95% CIs were calculated by exponentiating the mean difference of the logarithms of the titers (Group 1 [12 -15 years] – Group 2 [16 -25 years]) and the
corresponding CI (based on the Student t distribution).
e. Noninferiority is declared if the lower bound of the 2-sided 95% CI for the GMR is greater than 0.67.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (23:25) Sourc e Data: adva Table Generation: 27MAR2021 (04:54)
(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File: ./nda2 unblinded/C4591001 BLA/adva s001 gmr ped ev eval
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 75
FDA-CBER-2022-5812-0234783
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
Table 21.Number (%) of Subjects Achieving a ≥4-Fold Rise From Before Vaccination to Each Subsequent Time Point 1
Month After Dose 2 –NT50 –Comparison of Subjects 12 Through 15 Years of Age to Subjects 16 Through 25
Years of Age (Immunogenicity Subset) – Subjects Without Evidence of Infection up to 1 Month After Dose 2 –
Dose 2 Evaluable Immunogenicity Population
Vaccine Group (as Randomized)
BNT162b2 (30 μg)
12-15 Years 16-25 Years Difference
Assay Dose/
Sampling
Time PointaNbnc(%)
(95% CId)Nbnc(%)
(95% CId)%e(95% CIf)
SARS -CoV -2 neutralization assay -NT50 (titer) 2/1 Month 143 140(97.9)
(94.0, 99.6)124 124(100.0)
(97.1, 100.0)-2.1 (-6.0, 0.9)
Abbreviations: LLOQ = lower limit of quantitation; NT50 = 50% neutralizing titer; SARS -CoV -2 = severe acute respiratory syndrome coronavirus 2.
Note: Subjects who had no serological or virological evidence (up to 1 month after receipt of the last dose) of past SARS -CoV -2 infection (ie, N -binding antibody [serum]
negative at Visit 1 and SARS -CoV -2 not detected by NAAT [nasal swab] at Visits 1 and 2), and had negative NAAT (nasal swab) at any unscheduled visit up to 1 m onth after
Dose 2 w ere included in the analysis.
Note: Baseline assay results below the LLOQ were set to LLOQ in the analysis.
a. Protocol -specified timing for blood sample collection.
b. N = number of subjects with valid and determinate assay results for the specifi ed assay both before vaccination and at the given dose/sampling time point. These values are
the denominators for the percentage calculations.
c. n = Number of subjects with ≥4-fold rise from before vaccination for the given assay at the given dose/sam pling time point.
d. Exact 2 -sided CI based on the Clopper and Pearson method.
e. Difference in proportions, expressed as a percentage (12 -15 years –16-25 years).
f.2-Sided CI, based on the Miettinen and Nurminen method for the difference in proportions, expressed as a percentage.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (23:25) Source Data: adva Table Generation: 27MAR2021 (05:56)
(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File: ./nda2 unblinded/C4591001 BLA/adva s003 4fol d ped eval
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 76
FDA-CBER-2022-5812-0234784
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
11.3.2. GMTs –Participants 12 Through 15 Years of Age
At 1 month after Dose 2 (Day 52) of BNT162b2, substantial increases above baseline in
SARS -CoV -2 50% neutralizing GMTs were observed in both age groups, with a greater
magnitude of increase in the adolescent group compared with the young adult group
(Figure 2, Figure 3, and Supplemental Table 14.10). The neutralizing GMT in adolescents at
1month after Dose 2 was approximately 1.76 -fold that of the y oung adult group. As
expected, the neutralizing GMTs were low in both placebo groups.
Geometric Mean Titers (GMTs) by Baseline SARS- CoV-2 Status
Vaccination with BNT162b2 induced an increased immune response (GMTs) at 1 month after
Dose 2 for all participants, regardless of baseline SARS -CoV -2 positive or negative status.
Adolescents who were baseline SA RS-CoV -2 positive had SARS -CoV -2 50% neutralizing
GMTs approximately 1.89 -fold that of adolescents who were baseline negative ( Supplemental
Table 14.10). Asimilar pattern was observed for baseline SARS -CoV -2 positive versus
negative young adults.
SARS -CoV -2 50% neutralizing titers for the Dose 2 all- available immunogenicity population
were similar to those observed for the evaluable immunogenicit y population ( Supplemental
Table 14.11).
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 77
FDA-CBER-2022-5812-0234785
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
Figure 2. Geometric Mean Titers: SARS- CoV -2 Neutralization Assay –NT50 –Subjects 12- 15 and 16- 25 Years of Age
(Immunogenicity Subset) –Dose 2 Evaluable Immunogenicity Population
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 78
FDA-CBER-2022-5812-0234786
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
Figure 3. Reverse Cumulative Distribution Curves, SARS -CoV -2 Neutralization Assay –NT50 – Subjects 12 Through 15 and
16 Through 25 Years of Age (Immunogenicity Subset) – Dose 2 Evaluable Immunogenicity Population
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 79
FDA-CBER-2022-5812-0234787
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
11.3.3. GMFRs –Participants 12 Through 15 Years of Age
The GMFRs of SARS -CoV -2 50% serum neutralizing titers from before vaccination to
1 month after Dose 2 of BNT162b2 were robust, with a greater magnitude of rise in the
adolescent group (118.3) compared with the young adult group (71.2) (Table 22).
GMFR in Titers by Baseline SARS -CoV-2 Status
The GMFRs were higher in the adolescent compared to y oung adu lt group 1 month after the
second dose. Given the limited sample size for those positive at baseline, the GMFRs were
numericall y higher in those who were negative at baseline (Table 22).
GMFRs of SARS -CoV -2 50% neutralizing titers for the Dose 2 all-available immunogenicit y
population were similar to those observed for the evaluable immunogenicity population
(Supplemental Table 14. 12).
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 80
FDA-CBER-2022-5812-0234788
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
Table 22.Summary of Geometric Mean Fold Rise From Before Vaccination to Each Subsequent Time Point, by Baseline
SARS -CoV -2 Status –NT50 – Subjects 12 Through 15 and 16 Through 25 Years of Age (Immunogenicity Subset)
–Dose 2 Evaluable Immunogenicity Population
Vaccine Group (as Randomized)
BNT162b2 (30 μg) Placebo
12-15 Years 16-25 Years 12-15 Years 16-25 Years
Assay Dose/
Sampling
Time PointaBaseline
SARS -CoV -2
StatusbncGMFRd
(95% CId)ncGMFRd
(95% CId)ncGMFRd
(95% CId)ncGMFRd
(95% CId)
SARS -CoV -2 neutralization assay -NT50
(titer)2/1 Month ALL 154 118.3
(101.4, 137.9)135 71.2
(61.3, 82.7)29 1.4
(1.0, 1.9)24 1.1
(0.9, 1.3)
POS 8 47.6
(26.4, 86.0)5 47.1
(3.1, 721.4)1 1.1
(NE, NE)0 NE
(NE, NE)
NEG 145 125.0
(106.9, 146.2)130 72.3
(62.9, 83.2)27 1.4
(1.0, 2.0)24 1.1
(0.9, 1.3)
Abbreviations: COVID -19 = coronavirus disease 2019; GMFR = geometric mean fold rise; LLOQ = lower limit of quantitation;
NAAT = nucleic acid amplification test; N -binding = SARS -CoV -2 nucleoprotein –binding; NE = not estimable; NEG = negative;
NT50 = 50% neutralizing titer; POS = positive; SARS -CoV -2 = severe acute respiratory syndrome coronavirus 2.
a. Protocol -specified timing for blood sample collection.
b. POS = po sitive N -binding antibody result at Visit 1, positive NAAT result at Visit 1, or medical history of COVID -19. NEG = negative N -binding antibody result at Visit 1,
negative NAAT result at Visit 1, and no medical history of COVID -19. ALL = irrespective of ba seline SARS -CoV -2 status, including missing baseline status.
c. n = Number of subjects with valid and determinate assay results for the specified assay both prevaccination time points and a t the given dose/sampling time point.
d. GMFRs and 2 -sided 95% CIs were calculated by exponentiating the mean logarithm of fold rises and the corresponding CIs (based on the Student t distribution). Assay
results below the LLOQ were set to 0.5 × LLOQ in the analysis.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (2 3:25) Source Data: adva Table Generation: 27MAR2021 (04:54)
(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File: ./nda2 unblinded/C4591001 BLA/adva s002 gmfr ped eval
090177e196c6dcb4\Approved\Approved On: 14-Apr-2021 04:53 (GMT)
Page 81
FDA-CBER-2022-5812-0234789
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
11.3.4. Seroresponse Rate –Participants 12 Through 15 Years of Age
Proportions of participants with a ≥4-fold rise in SARS -CoV -2 50% neutralizing titers from
before vaccination to 1 month after Dose 2 of BNT162b2 (seroresponse rate) were 98.1% in
adolescents and 99.3% in y oung adults (Table 23). As expected, very few
…[truncated]