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Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
Page 1of 1521.TITLE PAGE
Vaccine Name and
Compound Number:BNT162 RNA -Based COVID -19 Vaccines, Compound
Number: PF -07302048
Report Title: Interim Report –Adolescent 6- Month Update : A
Phase 1/2/3, Placebo- Controlled, Randomized,
Observer -Blind, Dose -Finding Study to Evaluate the Safet y,
Tolerability , Immunogenicity , and Efficacy of SARS -CoV-
2 RNA Vaccine Candidates Against COVID -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 (study start); 15 October 2020 (adolescent)
Primary Completion Date: Not applicable
Data Cutoff Date: 02September 2021
Serology Completion Dat es: 29 October 2021
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 Other Service Providers,
Appendix 16.1.4 .
Sponsor’s Signatories: John L . Perez, MD, MBA, MA
Vice President, Vaccines Clinical Research and
Development, Pfizer Inc
090177e198d9edc0\Approved\Approved On: 13-Dec-2021 02:30 (GMT)
Page 1
FDA-CBER-2022-5812-0228424
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
Page 2of 152Kenneth Koury , PhD
Clinical Biostatistics Head, Vaccines Clinical Research
and Development, Pfizer Inc
Eleni Lagkadinou, MD, PhD
Vice President, Clinical Development, BioNTech SE
Internal Reports
Referenced:C4591001 B ooster Interim CSR:
dated 23 August 2021
C4591001 6- Month Update Interim CSR:
dated 29 April 2021
C4591001 Adolescent Interim CSR :
dated 14 April 2021
C4591001 Final Anal ysis Interim CSR:
dated 03 December 2020
Date of Current Version: 12December 2021
Date(s) of Previous
Report(s):03December 2021
GCP STATEMENT
This study was conducted in compliance with Good Clinical Practice (GCP) guidelines 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.
090177e198d9edc0\Approved\Approved On: 13-Dec-2021 02:30 (GMT)
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Protocol C4591001
CONFIDENTIAL2.SYNOPSI S
3.TABLE OF CONTENTS
1. TITLE PAGE................................ ................................ ................................ ..................... 1
2. SYNOPSI S................................ ................................ ................................ ......................... 3
3. TABLE OF CONTENTS ................................ ................................ ................................ ... 3
4. LIST OF ABBREVIATIONS AND DEFINITION OF TERMS ................................ ......
5. ETHICS................................ ................................ ................................ ..............................
5.1. Independent 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 ................................ ................................ ................................ ....
9.3.1. InclusionCriteria................................ ................................ ................................ ...
9.3.2. Exclusion Criteria ................................ ................................ ................................ ..
9.4. Investigational Product ................................ ................................ ................................
9.4.1. Vaccines Administered ................................ ................................ .........................
9.4.2. Identity of Investigational Product(s) ................................ ................................ ....
9.4.3. Method of Assign ing 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 Vacci nes, Medications, and Procedures ..........................
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CONFIDENTIAL9.4.7. Vaccine Compliance ................................ ................................ .............................
9.5. Efficacy , Immunogenicity , and Safet y Evaluations ................................ ....................
9.5.1. Efficacy and Immunogenicity Evaluations ................................ ...........................
9.5.2. Safet y Evaluations ................................ ................................ ................................ .
9.5.2.1. Electronic 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 Analysis................................ ................................ ................................ ..
9.7.4. Immunogenicit y Analysis ................................ ................................ .....................
9.7.5. Safet y Analysis................................ ................................ ................................ ......
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 Participants – Participants 12 Through 15 Years of Age...................
10.1.1. Blinded Placebo -Controlled Follow- Up Period................................ ..................
10.1.2. Open- Label Follow -Up Period ................................ ................................ ............
10.2. Protocol Deviations – Participants 12 Through 15 Years of Age.............................
10.3. Vaccine Administration and Timing –Participants 12 Through 15 Years of Age ...
10.4. Data Sets Anal yzed – Participants 12 Through 15 Years of Age..............................
10.4.1. Safet y Population – Participants 12 Through 15 Years of Age..........................
10.4.2. Efficacy Populations –Updated Anal ysis –Participants 12 Through 15 Years
of Age................................ ................................ ................................ .......................
10.5. Demographic a nd Other Baseline Characteristics –Participants 12 Through 15
Years of Age ................................ ................................ ................................ ................
10.5.1. Safet y Population – Participants 12 Through 15 Year s of Age..........................
10.5.1.1. Overall ................................ ................................ ................................ ..........
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CONFIDENTIAL10.5.1.2. Participants With At L east 6 Months Follow -Up Time – Original
BNT162b2 Recipients 12 Through 15 Years of Age................................ ...........
10.5.1.3. Original Placebo Recipients 12 Through 15 Years of Age Who Then
Received BNT162b2 ................................ ................................ ............................
10.5.2. Evaluable Efficacy (7 Days) Population –Blinded Placebo -Controlled
Follow-up Period – Participants 12 Through 15 Years of Age ...............................
10.6. Participant Compliance –Participants 12 Through 15 Years of Age ........................
10.6.1. Immunogenicit y Blood Samples ................................ ................................ .........
10.6.2. E- Diary................................ ................................ ................................ ................
10.7. Prior and Concomitant Vaccines, Medications, and Procedures – Participants 12
Through 15 Years of Age................................ ................................ ............................
11. EFFICACY EVALUATION ................................ ................................ ...........................
11.1. Updated Efficacy Results –Participants 12 Through 15 Years of Age ....................
11.1.1. Updated Analysis of Efficacy –Blinded Placebo -Controlled Follow -Up
Period................................ ................................ ................................ .......................
11.1.1.1. Vaccine Efficacy From 7 Day s After Dose 2 –Updated Anal ysis...............
11.1.1.1.1. Subgroup Analy ses................................ ................................ .................
11.1.1.2. All Confirmed Cases of COVID -19 After Dose 1 – All- Available Efficacy
Population ................................ ................................ ................................ .............
11.1.1.2.1. Subgroup Ana lyses................................ ................................ .................
11.1.2. Updated Anal ysis of Severe COVID -19 Cases................................ ...................
11.1.2.1. COVID -19 Narratives – Updated Anal ysis................................ ..................
11.1.3. Variants of Concern ................................ ................................ ............................
11.2. Efficacy Conclusions – Updated Anal ysis – Participants 12 Through 15 Years of
Age................................ ................................ ................................ ..............................
12. SAFETY EVALUATION ................................ ................................ ...............................
12.1. Local Reactions and Sy stemic Events –Participant s 12 Through 15 Years of Age .
12.2. Adverse Events – Participants 12 Through 15 Years of Age................................ ....
12.2.1. Blinded Placebo -Controlled Follow-Up Period From Dose 1 to the Unblinding
Date – Participants 12 Through 15 Years of Age................................ ....................
12.2.1.1. Summary of Adverse Events –Blinded Placebo -Controlled Follow -Up
Period From Dose 1 to the Unblinding Date –Participants 12 Through 15
Years of Age ................................ ................................ ................................ .........
12.2.1.1.1. Subgroup Analy ses................................ ................................ .................
12.2.1.2.Adverse Events by System Organ Class and Preferred Term –Blinded
Placebo-Controlled Follow -Up Period From Dose 1 to the Unblinding Date –
Participants 12 Through 15 Years of Age................................ ............................
12.2.1.2.1. Subgroup Analy ses................................ ................................ .................
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CONFIDENTIAL12.2.1.3. Related Adverse Events b y System Organ Class and P referred Term –
Blinded Placebo -Controlled Follow-Up Period From Dose 1 to the Unblinding
Date – Participants 12 Through 15 Years of Age................................ .................
12.2.1.4. I mmediate Adverse Events – Blinded Placebo -Controlled Follow -Up
Period From Dose 1 to the Unblinding Date –Participants 12 Through 15
Years of Age ................................ ................................ ................................ .........
12.2.1.5. Severe or Life-Threatening Adverse Events –Blinded Placebo -Controlled
Follow-Up Period From Dose 1 to the Unblinding Date – Participants 12
Through 15 Years of Age................................ ................................ .....................
12.2.1.6. New Adverse Events After the EUA Snapshot – Blinded Placebo -
Controlled Follow- Up Period From Dose 1 to the Unblinding Date –
Participants 12 Through 15 Years of Age................................ ............................
12.2.1.6.1. Summary of New Adverse Events After the EUA Snapshot – Blinded
Placebo-Controlled Follow -Up Period From Dose 1 to the Unblinding Date –
Participants 12 Through 15 Years of Age................................ .........................
12.2.1.6.2. New Adverse Events After the EUA Snapshot by System Organ Class
and Preferred Term – Blinded Placebo -Controlled Follow -Up Period From
Dose 1 to the Unblinding Date – Participants 12 Through 15 Years of Age....
12.2.1.6.3. New Related Adverse Events After the EUA Snapshot by System
Organ Class and Preferred Term –Blinded Placebo-Controlled Follow- Up
Period From Dose 1 to the Unblinding Date –Participants 12 Through 15
Years of Age ................................ ................................ ................................ ......
12.2.1.6.4. New Severe or L ife-Threatening Adverse Events After the EUA
Snapshot – Blinded Placebo -Controlled Follow- Up Period From Dose 1 to
the Unblinding Date –Participants 12 Through 15 Years of Age....................
12.2.2. Open- Label Follow -Up Period From the Unblinding Date to the Data Cutoff
Date –Original BNT162b2 Recipi ents 12 Through 15 Years of Age.....................
12.2.2.1. Summary of Adverse Events –Open-Label Follow -Up Period – Original
BNT162b2 Recipients 12 Thr ough 15 Years of Age ................................ ...........
12.2.2.2. Adverse Events by System Organ Class and Preferred Term –Open-Label
Follow-Up Period – Original BNT162b2 Recipients 12 Through 15 Years of
Age................................ ................................ ................................ ........................
12.2.2.3. Related Adverse Events b y System Organ Class and Preferred Term –
Open-Label Follow -Up Period – Original BNT162b2 Recipients 12 Through
15 Years of Age ................................ ................................ ................................ ....
12.2.2.4. Severe or Life-Threatening Adverse Events –Open-Label Fol low-Up
Period –Original BNT162b2 Recipients 12 Through 15 Years of Age ..............
12.2.3. Blinded Placebo -Controlled and Open -Label Follow -Up Periods From Dose 1
to 6 Months After Dose 2 – Original BNT162b2 Recipients 12 Through 15 Years
of Age................................ ................................ ................................ .......................
12.2.3.1. Summary of Adverse Events –Blinded Placebo -Controlled and Open -
Label Follow -Up Periods From Dose 1 to 6 Months After Dose 2 – Original
BNT162b2 Recipients 12 Through 15 Years of Age................................ ...........
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CONFIDENTIAL12.2.3.2. Adverse Events by System Organ Class and Preferred Term –Blinded
Placebo-Controlled and Open- Label Follow -Up Periods From Dose 1 to 6
Months After Dose 2 –Original BNT162b2 Recipients 12 Through 15 Years
of Age................................ ................................ ................................ ...................
12.2.3.3. Related Adverse Events b y System Organ Class and Preferred Term –
Blinded Placebo -Controlled and Open -Label Follow -Up Periods From Dose 1
to 6 Months After Dose 2 – Original BNT162b2 Recipients 12 Through 15
Years of Age ................................ ................................ ................................ .........
12.2.3.4. New Adverse Events After the EUA Snapsh ot –Blinded Placebo -
Controlled and Open -Label Follow -Up Periods From Dose 1 to 6 Months After
Dose 2 –Original BNT162b2 Recipients 12 Through 15 Years of Age ..............
12.2.3.4.1. Summary of New Adverse Events After the EUA Snapshot – Blinded
Placebo-Controlled and Open- Label Follow -Up Periods From Dose 1 to 6
Months After Dose 2 –Original BNT162b2 Recipients 12 Through 15 Years
of Age................................ ................................ ................................ ................
12.2.3.4.2. New Adverse Events After the EUA Snapshot by System Organ Class
and Preferred Term –Blinded Placebo -Controlled and Open- Label Follo w-
Up Periods From Dose 1 to 6 Months After Dose 2 –Original BNT162b2
Recipients 12 Through 15 Years of Age................................ ...........................
12.2.3.4.3. New Related Adv erse Events After the EUA Snapshot by System
Organ Class and Preferred Term –Blinded Placebo- Controlled and Open -
Label Follow -Up Periods From Dose 1 to 6 Months After Dose 2 – Original
BNT162b2 Recipients 12 Through 15 Years of Age................................ ........
12.2.4. Open- Label Follow -Up Period From Dose 3 to the Data Cutoff Date –
Original Placebo Recipients 12 Through 15 Years of Age Who Then Received
BNT162b2 Af ter Unblinding ................................ ................................ ...................
12.2.4.1. Summary of Adverse Events –Open-Label Follow -Up Period – Original
Placebo Recipients 12 Through 15 Years of A ge Who Then Received
BNT162b2 After Unblinding ................................ ................................ ................
12.2.4.2. Adverse Events by System Organ Class and Preferred Term –Open-Label
Follow-UpPeriod – Original Placebo Recipients Who Then Received
BNT162b2 After Unblinding – Participants 12 Through 15 Years of Age..........
12.2.4.3. R elated Adverse Events b y System Organ Class and Preferred Term –
Open-Label Follow -Up Period – Original Placebo Recipients Who Then
Received BNT162b2 – Participants 12 Through 15 Years of Age ......................
12.2.4.4. I mmediate Adverse Events – Open-Label Follow -Up Period – Original
Placebo Recipients Who Then Received BNT162b2 –Participants 12 Through
15 Years of Age ................................ ................................ ................................ ....
12.2.4.5. Severe or Life-Threatening Adverse Events –Open-Label Follow -Up
Period –Original Placebo Recipients Who Then Received BNT162b2 –
Participants 12 Through 15 Ye ars of Age ................................ ............................
12.3. Deaths, Serious Adverse Events, Safet y-Related Participant Withdrawals, and
Other Significant Adverse Events –Participants 12 Through 15 Years of Age.........
12.3.1. Deaths ................................ ................................ ................................ ..................
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CONFIDENTIAL12.3.2. Serious Adverse Events – Participants 12 Through 15 Years of Age.................
12.3.2.1. Blinded Placebo -Controlled Follow -Up From Dose 1 to the Unblinding
Date -Participants 12 Through 15 Years of Age................................ .................
12.3.2.1.1. Subgroup Analy ses................................ ................................ .................
12.3.2.1.2. New Serious Adverse Events After the EUA Snapshot.........................
12.3.2.2. Open- Label Follow -Up Period – Original BNT162b2 Recipients 12
Through 15 Years of Age................................ ................................ .....................
12.3.2.3. Blinded Placebo -Controlled and Open -Label Follow -Up Periods From
Dose 1 to 6 Months After Dose 2 – Original BNT162b2 Recipients 12 Through
15 Years of Age ................................ ................................ ................................ ....
12.3.2.3.1. New Serious Adverse Events After the EUA Snapshot.........................
12.3.2.4. Open- Label Follow -Up Period – Original Placebo Recipients Who Then
Received BNT162b2 After Unblinding ................................ ................................
12.3.3. Safet y-Related Participant Withdrawals ................................ .............................
12.3.3.1. Blinded Placebo -Controlled Follow-Up From Dose 1 to the Unblinding
Date -Participants 12 Through 15 Years of Age................................ .................
12.3.3.2. Open- Label Follow -Up Period – Original BNT162b2 Recipients 12
Through 15 Years of Age................................ ................................ .....................
12.3.3.3. Blinded Placebo -Controlled Follow- Up Period From Dose 1 to 6 Months
After Dose 2 – Original BNT162b2 Recipients 12 Through 15 Years of Age ....
12.3.3.4. Open- Label Follow -Up Period – Original Placebo Recipients 12 Through
15 Years of Age Who Then Received BNT162b2 After Unblinding..................
12.3.4. Other Significant Adverse Events................................ ................................ .......
12.3.4.1. FDA -Requested Adverse Events of Clinical Interest ................................ ...
12.3.4.2. Other Adverse Events of Special Interest................................ .....................
12.3.4.2.1. New Adverse Events of Special Interest After the EUA Snapshot ........
12.3.5. Other Safet y Assessments ................................ ................................ ...................
12.3.5.1. Severe COVID -19 Illness................................ ................................ .............
12.3.5.2. Pregnancy......................................................................................................
12.3.6. Analy sis and Discussion of Deaths, Serious Adverse Events, Safet y-Related
Participant Withdrawals, and Other Significant Adverse Events –Phase 2/3 .........
12.4. Safet y Conclusions – Participants 12 Through 15 Years of Age..............................
12.4.1. Blinded Placebo -Controlled Follow-Up Period From Dose 1 to the Unblinding
Date – Participants 12 Through 15 Years of Age................................ ....................
12.4.2. New Adverse Events After the EUA Snapshot – Original BNT162b2
Recipients 12 Through 15 Years of Age................................ ................................ ..
12.4.3. Open- Label Follow -Up Period – Original BNT162b2 Participants 12 Through
15 Years of Age ................................ ................................ ................................ .......
12.4.4. Blinded Placebo -Controlled and Open -Label Follow -Up Periods to 6 Months
After Dose 2 – Original BNT162b2 Recipients 12 Through 15 Years of Age ........
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CONFIDENTIAL12.4.5. Open- Label Follow -Up Period – Original Placebo Recipients 12 Through 15
Years of Age Who Then Received BNT162b2 ................................ .......................
13. DISCUSSION AND OVERALL CONCLUSIONS ................................ ........................
13.1. Discussion – Participants 12 Through 15 Years of Age............................................
13.2. Overall Conclusions –Participants 12 Through 15 Years of Age ............................
LIST OF IN -TEXT TABLES
Table 1. Phase 2/3 Objectives, Estimands, and Endpoints ................................ ...................
Table 2. Investigational Product L ot Numbers – Interim –Adolescent 6- Month Update ...
Table 3. Anal ysis Populations ................................ ................................ ..............................
Table 4. Disposition of All Randomized Subjects – Phase 2/3 Subjects 12 Through 15
Years of Age ................................ ................................ ................................ ..................
Table 5. Vaccine as Administered –Phase 2/3 Subjects 12 Through 15 Years of Age –
All Randomized Subjects ................................ ................................ ..............................
Table 6. Vaccine Administration Timing – Phase 2/3 Subjects 12 Through 15 Years of
Age – All Randomized Subjects................................ ................................ ...................
Table 7. Safet y Population –Phase 2/3 Subjects 12 Through 15 Years of Age ..................
Table 8. Follow -up Time After Dose 2 – Phase 2/3 Subjects 12 Through 15 Years of
Age –Safety Population ................................ ................................ ................................
Table 9. Follow -up Time Af ter Dose 1 of BNT162b2 –Phase 2/3 Subjects 12 Through
15 Years of Age (Subjects Who Originally Received Placebo) –Safety Population ...
Table 10. Efficacy Populations –Subjects 12 Through 15 Years of Age –Blinded
Placebo-Controlled Follow -up Period ................................ ................................ ...........
Table 11. Demographic Characteristics – Phase 2/3 Subjects 12 Through 15 Years of
Age –Safety Population ................................ ................................ ................................
Table 12. Vaccine Efficacy– First COVID -19 Occurr ence 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 Days) Population ................................ ................................ ........................
Table 13. 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 Days) Population ................................ ................................ .......
Table 14. Vaccine Efficacy– First COVID -19 Occurrence From 7 Day s After Dose 2,
by Subgroup – 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 Days) Population ................................ ........................
Table 15. Vaccine Efficacy– First COVID -19 Occurrence After Dose 1 –Blinded
Placebo-Controlled Follow -up Period – Subjects 12 Through 15 Yea rs of Age –
Dose 1 All -Available Efficacy Population ................................ ................................ ....
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CONFIDENTIALTable 16. Summary of SARS -CoV-2 Variants for the 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 Day s After Dose 2 – Evaluable Efficacy (7 Day s) Population .....................
Table 17. Summary of SARS -CoV-2 Variants of Concern or Variants of Interest for the
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 I nfection Prior to 7 Day s After Dose 2 –Evaluable Efficacy
(7 Days) Population ................................ ................................ ................................ .......
Table 18. Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding Date
–Blinded Placebo -Controlled Follow- up Period – Phase 2/3 Subjects 12 Through
15 Years of Age – Safety Population ................................ ................................ ............
Table 19. Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by System Organ Class and Preferred Term –Blinded Placebo -Controlled
Follow-up Period – Phase 2/3 Subjects 12 Through 15 Years of Age –Safety
Population ................................ ................................ ................................ ......................
Table 20. Number (%) of Subjects Reporting at Least 1 New Adverse E vent After the
EUA Snapshot, From Dose 1 to Unblinding Date –Blinded Placebo -Controlled
Follow-up Period – Phase 2/3 Subjects 12 Through 15 Years of Age –Safety
Population ................................ ................................ ................................ ......................
Table 21. Number (%) of Subjects Reporting at Least 1 New Adverse Event After the
EUA Snapshot, From Dose 1 to Unblinding Date, by System Organ Class and
Preferred Term –Blinded Placebo -Controlled Follow -up Period – Phase 2/3
Subjects 12 Through 15 Years of Age –Safety Population ................................ ..........
Table 22. Number (%) of Subjects Reporting at Least 1 New Related Adv erse Event
After the EUA Snapshot, From Dose 1 to Unblinding Date, b y System Organ Class
and Preferred Term –Blinded Placebo -Controlled Follow -up Period – Phase 2/3
Subjects 12 Through 15 Years of Age –Safety Population ................................ ..........
Table 23. Number (%) of Subjects Reporting at Least 1 New Severe Adverse Event
After the EUA Snapshot, From Dose 1 to Unblinding Date, b y System Organ Class
and Preferre d Term –Blinded Placebo -Controlled Follow -up Period – Phase 2/3
Subjects 12 Through 15 Years of Age –Safety Population ................................ ..........
Table 24. Numb er (%) of Subjects Reporting at Least 1 New Life -Threatening Adverse
Event After the EUA Snapshot, From Dose 1 to Unblinding Date, b y System
Organ Class and Preferred Term –Blinded Placebo-Controlled Follow- up Period –
Phase 2/3 Subjects 12 Through 15 Yea rs of Age –Safety Population .........................
Table 25. Incidence Rates of at Least 1 Adverse Event From Unblinding Date to Data
Cutoff Date (02SEP2021 ) –Open-Label Follow -up Period –Subjects Who
Originally Received BNT162b2 –Phase 2/3 Subjects 12 Through 15 Years of Age
–Safety Population ................................ ................................ ................................ .......
Table 26. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1 to
6 Months After Dose 2 – Subjects With at Least 6 Months of Follow- up Time
After Dose 2 – Phase 2/3 Subjects 12 Through 15 Years of Age (Subjects Who
Originally Received BNT162b2) – Safety Population ................................ ..................
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CONFIDENTIALTable 27. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1 to
6 Months After Dose 2, by Time Period –Subjects With at Least 6 Months of
Follow-up Time After Dose 2 – Phase 2/3 Subjects 12 Through 15 Years of Age
(Subjects Who Originally Received BNT162b2) –Safety Population .........................
Table 28. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1 to
6 Months After Dose 2, by S ystem Organ Class and Preferred Term –Subjects
With at Least 6 Months of Follow -upTime After Dose 2 – Phase 2/3 Subjects 12
Through 15 Years of Age (Subjects Who Originally Received BNT162b2) –Safety
Population ................................ ................................ ................................ ......................
Table 29. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1 to
6 Months After Dose 2, by S ystem Organ Class and Preferred Term and Time
Period –Subjects With at Least 6 Months of Follow -up Time After Dose 2 –Phase
2/3 Subjects 12 Through 15 Years of Age (Subjects Who Originally Received
BNT162b2) –Safety Population ................................ ................................ ...................
Table 30. Number (%) of Subjects Reporting at Least 1 New Adverse Event After the
EUA Snapshot, From Dose 1 to 6 Months After Dose 2 – Subjects With at Least 6
Months of Follow- up Time After Dose 2 – Phase 2/3 Subjects 12 Through 15
Years of Age (Subjects Who Originally Received BNT162b2) –Safety Population ...
Table 31. Number (%) of Subjects Reporting at Least 1 New Adverse Event After the
EUA Snapshot, From Dose 1 to 6 Months After Dose 2, by Time Period –Subjects
With at Least 6 Months of Follow -up Time After Dose 2 – Phase 2/3 Subjects 12
Through 15 Years of Age (Subjects Who Originally Received BNT162b2) –Safety
Population ................................ ................................ ................................ ......................
Table 32. Number (%) of Subjects Reporting at Least 1 New Adverse Event After the
EUA Snapshot, From Dose 1 to 6 Months After Dose 2, by System Organ Class
and Preferred Term –Subjects With at L east 6Months of Follow -up Time After
Dose 2 – Phase 2/3 Subjects 12 Through 15 Years of Age (Subjects Who
Originally Received BNT162b2) – Safety Population ................................ ..................
Table 33. Number (%) of Subjects Reporting at Least 1 New Adverse Event After the
EUA Snapshot, From Dose 1 to 6 Months After Dose 2, by System Organ Class
and Preferred Term and Time Period –Subjects With at Least 6 Months of Follow -
up Time After Dose 2 – Phase 2/3 Subjects 12 Through 15 Years of Age (Subjects
Who Originally Received BNT162b2) –Safety Population ................................ .........
Table 34. Number (%) of Subjects Reporting at Least 1 New Related Adverse Event
After the EUA Snapshot, From Dose 1 to 6 Months After Dose 2, b y System Organ
Class and Preferred Term –Subjects With at Least 6 Months of Follow -up Time
After Dose 2 – Phase 2/3 Subjects 12 Through 15 Years of Age (Subjects Who
Originally Received BNT162b2) – Safety Population ................................ ..................
Table 35. Incidence Rates of at Least 1 Adverse Event From Dose 3 to Data Cutoff
Date (02SEP2021) – Open-Label Follow -up Period –Subjects Who Originally
Received Placebo and Then Received BNT162b2 After Unblinding –Phase 2/3
Subjects 12 Through 15 Years of Age –Safety Population ................................ ..........
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CONFIDENTIALTable 36. Incidence Rates of at Least 1 Adverse Event From Dose 3 to Data Cutoff
Date (02SEP2021), b y System Organ Class and Preferred Term –Open-Label
Follow-up Period – Subjects Who Originall y Received Placebo and Then Received
BNT162b2 After Unblinding –Phase 2/3 Subjects 12 Through 15 Years of Age –
Safety Population ................................ ................................ ................................ ..........
Table 37. Incidence Rates of at Least 1 Serious Adverse Event From Dose 1 to
Unblinding Date, b y System Organ Class and Preferred Term –Blinded Placebo -
Controlled Follow- up Period –Phase 2/3 Subjects 12 Through 15 Years of Age –
Safety Population ................................ ................................ ................................ ..........
Table 38. Number (%) of Subjects Reporting at Least 1 New Serious Adverse Event
After the EUA Snap shot, From Dose 1 to Unblinding Date, by System Organ Class
and Preferred Term –Blinded Placebo -Controlled Follow -up Period – Phase 2/3
Subjects 12 Through 15 Years of Age –Safety Population ................................ ..........
Table 39. Number (%) of Subjects Reporting at Least 1 Serious Adverse Event From
Dose 1 to 6 Months After Dose 2, b y System Organ Class and Preferred Term –
Subjects With at Least 6 Months of Follow- up Time After Dose 2 – Phase 2/3
Subjects 12 Through 15 Years of Age (Subjects Who Originally Received
BNT162b2) –Safety Population ................................ ................................ ...................
Table 40. Number (%) of Subjects Reporting at Least 1 Serious Adverse Event From
Dose 1 to 6 Months After Dose 2, b y System Organ Class and Preferred Term and
Time Period –Subjects With at Least 6 Months of Follow -up Time After Dose 2 –
Phase 2/3 Subjects 12 Through 15 Years of Age (Subjects Who Originally
Received BNT162b2) –Safety Population ................................ ................................ ...
Table 41. Number (%) of Subjects Reporting a t Least 1 New Serious Adverse Event
After the EUA Snapshot, From Dose 1 to 6 Months After Dose 2, b y System Organ
Class and Preferred Term –Subjects With at Least 6 Months of Follow -up Time
After Dose 2 – Phase 2/3 Subjects 12 Through 15 Years of Age (Sub jects Who
Originally Received BNT162b2) – Safety Population ................................ ..................
Table 42. Number (%) of Subjects Reporting at Least 1 New Serious Adverse Event
After the EUA Snapshot, From Dose 1 to 6 Months After Dose 2, b y System Organ
Class and Preferred Term and Time Period – Subjects With at L east 6 Months of
Follow-up Time After Dose 2 – Phase 2/3 Subjects 12 Through 15 Years of Age
(Subjects Who Origi nally Received BNT162b2) –Safety Population .........................
Table 43. Incidence Rates of at Least 1 Serious Adverse Event From Dose 3 to Data
Cutoff Date (02SEP2021), by System Organ Class and Preferred Term –Open-
Label Follow -up Period –Subjects Who Originally Received Placebo and Then
Received BNT162b2 After Unblinding –Phase 2/3 Subjects 12 Through 15 Years
of Age –Safety Population ................................ ................................ ...........................
Table 44. Subjects Reporting an Adverse Event of Ly mphadenopathy –Blinded
Placebo-Controlled Follow -up Period – Phase 2/3 Subjects 12 Through 15 Years of
Age –Safety Population ................................ ................................ ................................
Table 45. Incidence Rates of at Least 1 Adverse Event of Special Interest From Dose 1
to Unblinding Date , by System Organ Class and Preferred Term – Blinded
Placebo-Controlled Follow -up Period – Phase 2/3 Subjects 12 Through 15 Years of
Age –Safety Population ................................ ................................ ................................
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CONFIDENTIALTable 46. Subjects Reporting an Adverse Event of Arthralgia –Blinded Placebo -
Controlled Follow- up Period –Phase 2/3 Subjects 12 Through 15 Years of Age –
Safety Population ................................ ................................ ................................ ..........
Table 47. Number (%) of Subjects Reporting at Least 1 New Adverse Event of Special
Interest After the EUA Snapshot, From Dose 1 to Unblinding Date, b y System
Organ Class and Preferred Term –Blinded Placebo -Controlled Follow- up Period –
Phase 2/3 Subjects 12 Through 15 Years of Age –Safety Population .........................
LIST OF IN -TEXT FIGURES
Figure 1. Cumulative Incidence Curves for the First COVI D-19 Occurrence After Dose
1 –Subjects 12 Through 15 Years of Age –Blinded Placebo -Controlled Follow -up
Period –Dose 1 All -Available Efficacy Population ................................ .....................
Figure 2 Phase 2/3 Safety Analyses of Adolescent Participants: Time Periods and
Analysis Groups ................................ ................................ ................................ ............
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CONFIDENTIAL14. TABLES AND FIGURES ................................ ................................ ...............................
Supplemental Tables ................................ ................................ ................................ ..........
Conduct of Study ................................ ................................ ................................ ...............
14.1. Demographic Characteristics, b y Baseline SARS -CoV-2 Status – Phase 2/3
Subjects 12 Through 15 Years of Age –Safety Population Baseline SARS -
CoV-2 Status: Positive ................................ ................................ ............................
14.2. Demographic Characteristics, b y Baseline SARS -CoV-2 Status – Phase 2/3
Subjects 12 Through 15 Years of Age –Safety Population Baseline SARS -
CoV-2 Status: Negative ................................ ................................ ..........................
14.3. Medical Histo ry–Phase 2/3 Subjects 12 Through 15 Years of Age –Safety
Population ................................ ................................ ................................ ...............
14.4. Baseline Charlson Comorbidities –Phase 2/3 Subjects 12 Th rough 15 Years
of Age –Safety Population ................................ ................................ .....................
14.5. Demographic Characteristics –Subjects With at Least 6 Months of Follow-up
Time After D ose 2 – Phase 2/3 Subjects 12 Through 15 Years of Age (Subjects
Who Originally Received BNT162b2) –Safety Population ................................ ..
14.6. Demographic Characteristics –Subjects Who Originall y Received Placebo
and Then Received BNT162b2 After Unblinding – Phase 2/3 Subjects 12
Through 15 Years of Age –Safety Population ................................ .......................
14.7. Demographic Characteristics –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) Populati on..............
14.8. Demographic Characteristics –Blinded Placebo -Controlled Follow- up Period
–Subjects 12 Through 15 Years of Age –Dose 1 All -Available Efficacy
Population ................................ ................................ ................................ ...............
14.9. Demographic Characteristics –Blinded Placebo -Controlled Follow- up Period
–Subjects 12 Through 15 Y ears of Age and With or Without Evidence of
Infection Prior to 7 Day s After Dose 2 –Evaluable Efficacy (7 Days)
Population ................................ ................................ ................................ ...............
14.10. Conc omitant Vaccines Received After Dose 1 – Phase 2/3 Subjects 12
Through 15 Years of Age –Safety Population ................................ .......................
Efficacy................................ ................................ ................................ .............................
14.11. 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
–Dose 2 All -Available Efficacy Population ................................ ..........................
14.12. Vaccine Efficac y –First COVID -19 Occurrence From 7 Day s After Dose 2,
by Subgroup – 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 Days) Population...............................
14.13. Vaccine Efficacy –First COVID -19 Occurrence After Dose 1, by Subgroup
–Blinded Placebo -Controlled Follow- up Period – S ubjects 12 Through 15
Years of Age –Dose 1 All -Available Efficacy Population ................................ ....
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CONFIDENTIALAdverse Events ................................ ................................ ................................ ..................
14.14. Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by Baseline SARS -CoV-2 Status – Blinded Placebo -Controlled Follow -
up Period – Phase 2/3 Subjects 12 Through 15 Years of Age – Safety
Population Baseline SARS -CoV-2 Status: Positive ................................ ...............
14.15. Incidence Rates of at Least 1 Adverse Eve nt From Dose 1 to Unblinding
Date, by Baseline SARS -CoV-2 Status – Blinded Placebo -Controlled Follow -
up Period – Phase 2/3 Subjects 12 Through 15 Years of Age –Safety
Population Baseline SARS -CoV-2 Status: Negative ................................ ..............
14.16. Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by Ethnicity –Blinded Placebo -Controlled Follow -up Period – Phase 2/3
Subjects 12 Through 1 5 Years of Age – Safety Population Ethnicity :
Hispanic/Latino ................................ ................................ ................................ ......
14.17. Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblind ing
Date, by Ethnicity –Blinded Placebo -Controlled Follow -up Period – Phase 2/3
Subjects 12 Through 15 Years of Age –Safety Population Ethnicity: Non-
Hispanic/Non- Latino................................ ................................ ..............................
14.18. Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by Race –Blinded Placebo -Controlled Follow -up Period – Phase 2/3
Subjects 12 Through 15 Years of Age –Safety Population Race: White ..............
14.19. Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by Race –Blinded Placebo -Controlled Follow -up Period – Phase 2/3
Subjects 12 Through 15 Years of Age –Safety Population Race: Black or
African American ................................ ................................ ................................ ...
14.20. Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by Race –Blinded Placebo -Controlled Follow -up Period – Phase 2/3
Subjects 12 Through 15 Years of Age –Safety Population Race: All Others .......
14.21. Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by Sex –Blinded Placebo -Controlled Follow -up Period – Phase 2/3
Subjects 12 Through 15 Years of Age –Safety Population Sex: Male ..................
14.22. Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by Sex –Blinded Placebo -Controlled Follow -up Period – Phase 2/3
Subjects 12 Through 15 Years of Age –Safety Population Sex: Female ..............
14.23. Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by System Organ Class and Preferred Term, by Baseline SARS -CoV-2
Status –Blinded Placebo -Controlled Follow- up Period – Phase 2/3 Subjects 12
Through 15 Years of Age –Safety Population Baseline SARS -CoV-2 Status:
Positive................................ ................................ ................................ ...................
14.24. Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by System Organ Class and Preferred Term, by Baseline SARS -CoV-2
Status –Blinded Placebo -Controlled Follow- up Period – Phase 2/3 Subjects 12
Through 15 Years of Age –Safety Population Baseline SARS -CoV-2 Status:
Negative................................ ................................ ................................ ..................
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CONFIDENTIAL14.25. Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by System Organ Class and Preferred Term, by Ethnicity –Blinded
Placebo-Controlled Follow -up Period – Phase 2/3 Subjects 12 Throug h 15
Years of Age –Safety Population Ethnicity : Hispanic/L atino...............................
14.26. Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unbl inding
Date, by System Organ Class and Preferred Term, by Ethnicity –Blinded
Placebo-Controlled Follow -up Period – Phase 2/3 Subjects 12 Through 15
Years of Age –Safety Population Ethnicity: Non- Hispanic/Non- Latino..............
14.27. Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by System Organ Class and Preferred Term, by Race –Blinded Placebo -
Controlled Follow- up Period –Phase 2/3 Subjects 12 Through 15 Years of
Age –Safety Population Race: White ................................ ................................ ....
14.28. Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by System Organ Class and Preferred Term, by Race –Blinded Placebo -
Controlled Follow- up Period –Phase 2/3 Subjects 12 Through 15 Years of
Age –Safety Population Race: Black or African American ................................ ..
14.29. Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by System Organ Class and Preferred Term, by Race –Blinded Placebo -
Controlled Follow-up Period –Phase 2/3 Subjects 12 Through 15 Years of
Age –Safety Population Race: All Others ................................ .............................
14.30. Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by System Organ Class and Preferred Term, by Sex –Blinded Placebo -
Controlled Follow- up Period –Phase 2/3 Subjects 12 Through 15 Years of
Age –Safety Population Sex: Male ................................ ................................ ........
14.31. Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by System Organ Class and Preferred Term, by Sex –Blinded Placebo -
Controlled Follow- up Period –Phase 2/3 Subjects 12 Through 15 Years of
Age –Safety Population Sex: Female ................................ ................................ ....
14.32. Incidence Rates of at Least 1 Related Adverse Event From Dose 1 to
Unblinding Date, b y System Organ Class and Preferred Term –Blinded
Placebo-Controlled Follow -up Period – Phase 2/3 Subjects 12 Through 15
Years of Age –Safety Population ................................ ................................ ..........
14.33. Incidence Rates of at Least 1 Severe Adverse Event From Dose 1 to
Unblinding Date, b y System Organ Class and Preferred Term –Blinded
Placebo-Controlled Follow -up Period – Phase 2/3 S ubjects 12 Through 15
Years of Age –Safety Population ................................ ................................ ..........
14.34. Incidence Rates of at Least 1 Life -Threatening Adverse Event From Dose 1
to Unblinding Date, b y System Organ Class and Preferred Term –Blinded
Placebo-Controlled Follow -up Period – Phase 2/3 Subjects 12 Through 15
Years of Age –Safety Population ................................ ................................ ..........
14.35. Incidence Rates of at Least 1 Adverse Event From Unblinding Date to Data
Cutoff Date (02SEP2021), by System Organ Class and Preferred Term –
Open-Label Follow -up Period –Subjects Who Originall y Received BNT16 2b2
–Phase 2/3 Subjects 12 Through 15 Years of Age –Safety Population ................
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CONFIDENTIAL14.36. Incidence Rates of at Least 1 Related Adverse Event From Unblinding Date
to Data Cutoff Date (02SEP2021), by System Organ Class and Preferred Term
–Open-Label Follow -up Period –Subjects Who Originall y Received
BNT162b2 –Phase 2/3 Subjects 12 Through 15 Years of Age –Safety
Population ................................ ................................ ................................ ...............
14.37. Incidence Rates of at Least 1 Severe Adverse Event From Unblinding Date
to Data Cutoff Date (02SEP2021), by System Organ Class and Preferred Term
–Open-Label Follow -up Period –Subjects Who Originall y Received
BNT162b2 –Phase 2/3 Subjects 12 Through 15 Years of Age –Safety
Population ................................ ................................ ................................ ...............
14.38. Number (%) of Subjects Reporting at Least 1 Related Adverse Event From
Dose 1 to 6 Months After Dose 2, b y System Organ Class and Preferred Term
– Subjects With at Least 6 Months of Follow- up Time After Dose 2 – Phase
2/3 Subjects 12 Through 15 Ye ars of Age (Subjects Who Originally Received
BNT162b2) –Safety Population ................................ ................................ ............
14.39. Number (%) of Subjects Reporting at Least 1 Adverse E vent From Dose 3 to
7 Days After Dose 3, b y System Organ Class and Preferred Term –Open-
Label Follow -up Period –Subjects Who Originally Received Placebo and
Then Received BNT162b2 After Unblinding – Phase 2/3 Subjects 12 Through
15 Years of Age – Safety Population ................................ ................................ .....
14.40. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 4 to
7 Days After Dose 4, b y System Organ Class and Preferred Term – Open-
Label Follow -up Period –Subjects Who Originally Received Placebo and
Then Received BNT162b2 After Unblinding – Phase 2/3 Subjects 12 Through
15 Years of Age – Safety Population ................................ ................................ .....
14.41. Incidence Rates of at Least 1 Related Adverse Event From Dose 3 to Data
Cutoff Date (02SEP2021), by System Organ Class and Preferred Term –
Open-Label Follow -up Period –Subjects Who Originall y Received Placebo
and Then Received BNT162b2 After Unblinding – Phase 2/3 Subjects 12
Through 15 Years of Age –Safety Population ................................ .......................
14.42. Number (%) of Subjects Reporting at Least 1 I mmediate Adverse Event
After Vaccination (Dose 3/4), by System Organ Class and Preferred Term –
Open-Label Follow -up Period –Subjects Who Originall y Received Placebo
and Then Received BNT162b2 After Unblinding – Phase 2/3 Subjects 12
Through 15 Years of Age –Safety Population ................................ .......................
14.43. Incidence Rates of at Least 1 Severe Adverse E vent From Dose 3 to Data
Cutoff Date (02SEP2021), by System Organ Class and Preferred Term –
Open-Label Follow -up Period –Subjects Who Originall y Received Placebo
and Then Received BNT162b2 After Unblinding – Phase 2/3 Subjects 12
Through 15 Years of Age –Safety Population ................................ .......................
14.44. Incidence Rates of at Least 1 Serious Adverse Event From Dose 1 to
Unblinding Date, b y System Organ Class an d Preferred Term, by Baseline
SARS-CoV-2 Status – Blinded Placebo -Controlled Follow -up Period – Phase
2/3 Subjects 12 Through 15 Years of Age –Safety Population Baseline SARS -
CoV-2 Status: Negative ................................ ................................ ..........................
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CONFIDENTIAL14.45. Incidence Rates of at Least 1 Serious Adverse Event From Dose 1 to
Unblinding Date, b y System Organ Class and Preferred Term, by Ethnicity –
Blinded Placebo -Controlled Follow- up Period – Phase 2/3 Subjects 12
Through 15 Years of Age –Safety Population Ethnicity: Hispanic/Latino ...........
14.46. Incidence Rates of at Least 1 Ser ious Adverse Event From Dose 1 to
Unblinding Date, b y System Organ Class and Preferred Term, by Ethnicity –
Blinded Placebo -Controlled Follow- up Period – Phase 2/3 Subjects 12
Through 15 Years of Age –Safety Population Ethnicity: Non -Hispanic/Non -
Latino................................ ................................ ................................ ......................
14.47. Incidence Rates of at Least 1 Serious Adverse Event From Dose 1 to
Unblinding Date, b y System Organ Class and Preferred Term, by Race –
Blinded Placebo -Controlled Follow- up Period – Phase 2/3 Subjects 12
Through 15 Years of Age –Safety Population Race: White ................................ ..
14.48. Incidence Rates of at Least 1 Serious Adverse Event From Dose 1 to
Unblinding Date, b y System Organ Class and Preferred Term, by Race –
Blinded Placebo -Controlled Follow- up Period – Phase 2/3 Subjects 12
Through 15 Years of Age –Safety Population Race: Black or African
American ................................ ................................ ................................ ................
14.49. Incidence Rates of at Least 1 Serious Adverse Event From Dose 1 to
Unblinding Date, b y System Organ C lass and Preferred Term, by Race –
Blinded Placebo -Controlled Follow- up Period – Phase 2/3 Subjects 12
Through 15 Years of Age –Safety Population Race: All Others ...........................
14.50. Incidence Rates of at Least 1 Serious Adverse Event From Dose 1 to
Unblinding Date, b y System Organ Class and Preferred Term, by Sex –
Blinded Placebo -Controlled Follow- up Period – Phase 2/3 Subjects 12
Through 15 Years of Age – Safety Population Sex: Male ................................ .....
14.51. Incidence Rates of at Least 1 Serious Adverse Event From Dose 1 to
Unblinding Date, b y System Organ Class and Preferred Term, b y Sex –
Blinded Placebo -Controlled Follow- up Period – Phase 2/3 Subjects 12
Through 15 Years of Age –Safety Population Sex: Female ................................ ..
14.52. Incidence Rates of at Least 1 Serious Adverse Event From Unblinding Date
to Data Cutoff Date (02SEP2021), by System Organ Class and Preferred Term
–Open-Label Follow -up Period –Subjects Who Originall y Received
BNT162b2 –Phase 2/3 Subjects 12 Through 15 Years of Age –Safety
Population ................................ ................................ ................................ ...............
14.53. Incidence Rates of Subjects Withdrawn Because of Adverse Events From
Dose 1 to Unblinding Date, by System Organ Class and Preferred Term –
Blinded Placebo -Controlled Follow- up Period – Phase 2/3 Subjects 12
Through 15 Years of Age –Safety Population ................................ .......................
Supplemental Figures ................................ ................................ ................................ .........
Subject Narratives...............................................................................................................
15. REFERENCES ................................ ................................ ................................ ................
ERRATA
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Page 16of 15216. 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 Sheet and Informed
Consent Document (ICD)
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
Authority '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 (Subject 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
immunoassay 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 (Not applicable)
16.2.7. Adverse Events by Subject
16.2.8. Individual Laboratory Measurements by Subject
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Page 17of 15216.3. 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
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Page 18of 1524.LIST OF ABBR EVIATIONS AND DEFINI TION OF TERMS
Abbreviation Definition
AE adverse event
ACIP Advisory Committee on Immunization Practices
AESI adverse event of special interest
BDR blinded data review
BMI body mass index
CDC Centers for Disease Control and Prevention (United States)
CI confidence interval
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
EKG electrocardiogram
GCP Good Clinical Practice
GMC geometric mean concentration
GMFR geometric mean fold rise
GMR geometric mean ratio
GMT geometric mean titer
HBc Ab hepatitis B core antibod y
HBsAg hepatitis B surface antigen
HBV hepatitis B virus
HCV hepatitis C virus
HCV Ab hepatitis C virus antibody
HIV human immunodeficiency virus
ICD informed consent document
ICH International Council for Harmonisation
IEC independent ethics committee
IgG immunoglobulin G
IgM immunoglobulin M
IRB institutional review board
IRC internal review committee
IRR illness rate ratio
IRT interactive response technology
IWR interactive Web -based response
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
P2 S SARS -CoV -2 full -length, P2 mutant, prefusion spike gl ycoprotein
PCR polymerase chain reaction
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Page 19of 152Abbreviation Definition
PD protocol deviation
PT preferred term
QA quality assurance
QTL quality tolerance limit
RCDC reverse cumulative distribution curve
RDC remote data capture
RNA ribonucleic acid
SA South Africa
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
VOC variant of concern
VOI variant of interest
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Page 20of 1525.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
partic ipating 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 safet y of trial participants.
5.3.Participant Information and Consent
In this clinical stud y report, the terms “participa nt” 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 by the investig ator, obtained a signed and dated ICD from each participant’s
parent(s)/guardian(s) before an y stud y-specific activity was performed. Informed 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
This study was undertaken by Pfizer and BioNTech SE and conducted at 29sites in the
United States for adolescent participants 12 through 15 years of age as of the dat a cutoff date
(02 September 2021 ) (Appendix 16.1.4.1 ).Due to live database and on going nature of the
study , there is a discrepancy in the number of participants screened/randomized in
Appendix 16.1.4.1 compared with the results tables.
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 testi ng
laboratories involved in this study , with the tests that they performed.
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 .
No sites were terminated from the study to date.
7.INTRODUCTION
In December 2019, a pneumonia outbreak of unknown cause occurred in Wuhan, China .
InJanuary 2020, it became clear that a novel coronavirus was the underl ying cause. On
11March 2020 , the WHO characterized the COVID -19outbreak as apandemic1, which has 090177e198d9edc0\Approved\Approved On: 13-Dec-2021 02:30 (GMT)
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Page 21of 152spread rapidly globall y. A proph ylactic, RNA -based SARS -CoV -2 vaccine provides one of
the most flexible and fastest approaches available to immunize against COVID -19.2,3
This ongoing Phase 1/2/3 study is the registrational and pivotal study of the prophy lactic
BNT162b2 vaccine candidate against COVID -19in healthy individuals ≥12 y ears of age that
was initiated in April 2020 .
This ongoing study has demonstrated the safet y, tolerability , immunogenicity , and efficacy of
BNT162b2 when administered as 2 doses of 30 µg given approximately 21 day s apart , which
was the basis of the current authorizations and approvals. Study C4591001 data supporting
authorization or licensure for the 2-dose series in participants ≥ 12 years of age are
summarized below:
Phase 1 evaluated safet y and immunogenicit y results in healthy adult participants across
dose levels of 2 vaccine candidates, BNT162b1 a nd BNT162b2 . The Phase 1
reactogenicity and immunogenicity profiles, combined with available nonclinical animal
study data, led to the selection of BNT162b2 at the 30- µg dose level to advance to
Phase 2/3 evaluation.
Phase 2/3 evaluate defficacy of BNT162b 2 30 µg , and provide d additional safety,
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 a
data cutoff date of 14 November 2020 were previously reported in the C4591001 Fi nal
Analysis Interim CSR ,dated 03 December 2020. On 11 December 2020, the US FDA
issued an EUA for use of BNT162b2 at 30 µg in individuals ≥16 y ears of age.
For adolescents (12 through 15 years of age), i mmunobridgin g and safet y (median
≥2months follow -up) were compared with young adults 16 through 25 years of age were
reported in the adolescent interim CSR, dated 14 April 2021. Immunogenicity data from
adolescent (and young adult) participants showed robust neutralizing GMTs after
vaccination with 2 doses of BNT162b2 at 30 µg . In addition, descriptive efficacy
analyses during blinded placebo -controlled follow -up period conducted on all confirmed
COVID -19 cases accrued up to the data cutoff date of 13 March 2021 for adolescents
(12through 15 years of age) showed estimated VE was 100.0% for cases reported from at
least 7 days after Dose 2 in individuals without and with or without evidence of prior
SARS -CoV -2 infection before and during vaccination regimen . On 10 May 2021, the US
FDA issued an EUA for use in individuals 12 to 15 y ears of age. At present, t here are
currentl y no licensed vaccines to immunize against COVI D-19 for individuals 12 to 15
years of age in the US .
Follow -up to 6 months after Dose 2 was provided in t he C4591001 6- Month Update
Interim CSR ,dated 29 April 2021 , and provide dup to 6 months of additional safet y,
efficacy , and immunogenicity follow -up data . The report included anal ysis of safet y
during the blinded and post -unblin ding (open -label) periods through 6 months post -Dose
2for partic ipants ≥16years of age , and updated efficacy analysisbased on all confirmed
COVID -19 cases inparticipants ≥12 years of age that accrued in blinded follow -up to a 090177e198d9edc0\Approved\Approved On: 13-Dec-2021 02:30 (GMT)
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Page 22of 152data cutoff date of 13 March 2021 .On 23 August 2021, the US FDA granted licensure of
COMI RNATY (BNT162b2) for individuals ≥16 years of age.
Based on a data cutoff date of 02 September 2021 , this interim report foradolescent
participants 12 to 15 y ears of age summarizes updated descriptive efficacy anal yses from
7days after Dose 2 during blinded placebo -controlled follow -up(Section 11.1) and the
following safet y data, as ordered:
Blinded placebo -controlled follow -up period f rom Dose 1 to the date of unblinding for
BNT1 62b2 and placebo participants , including new AEs that were reported after the
EUA snapshot date (based on events on or after the data cutoff date of 13March 2021)
(Sectio n 12.2.1 )
Open -label observational follow -up period of original BNT162b2 recipients from the date
of unbli nding to the data cutoff date (Section 12.2.2 )
Cumulative safety from Dose 1 to at least 6 months after Dose 2, inclusive of blinded
data and open -label data for orig inal BNT162b2 recipients, including new AEs that were
reported after the EUA snapshot date ( Section 12.2.3 )
Open -label observational follow -up period f or original placebo recipients who then
received BNT162b2 from the first dose of BNT162b2 to the data cutoff date
(Section 12.2.4 )
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 the study objectives, estimands, and endpoints.
8.2.Phase 2/3
The study objective s, estimands, and endpoi ntspresented in Table 1are from Appendix 16.1.1,
Protocol Amendment 18. This report summarizes safet y and immunogenicity for adolescent
participants only,as described in Section 7.
Study objectives and endpoint analy ses that were either previousl y reported, or will be
reported at a later time, are indicated with gray shading and per the ‘reference’ column in
Table 1.
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Page 23of 152Table 1. Phase 2/3 Objectives, Estimands, and Endpoints
ObjectivesaEstimands Endpoints Reference
Prim ary 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
(upto 7 days after receipt of the second
dose) of past SARS-CoV -2 infectionPrespecified complete efficacy data are
reported in fin al analysis interim CSR dated
03December 2020.
Updated efficacy data arereported in the
6-month update interim CSR dated
29April 2021.
Efficacy data from 7 days after Dose 2to the
data cutoff date (13 March 2021) for
participants 12 through 15 years of age only
are reported in the adolescent interim CSR
dated 14 April 2021 .
To evaluate the efficacy of prophylactic
BNT162b2 against confirmed
COVID -19 occurring from 7 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 after receipt of the second
dose of study intervention:
100 × (1 – IRR)
[ratio of active vaccine to placebo]COVI D-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 03 December 2020.
Updated efficacy data arereported in the
6-month update interim CSR dated
29April 2021.
Efficacy data from 7 days after Dose 2 to the
data cutoff date (13 March 2021) for
participants 12 through 15 years of age only
are reported in the adolescent interim CSR
dated 14 April 2021 .
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Page 24of 152Table 1. Phase 2/3 Objectives, Estimands, and Endpoints
ObjectivesaEstimands Endpoints Reference
Prim ary 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 e ach 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 doseLocal reactions (pain at the injection
site, redness, and swelling)
Systemic events (fever, fatig ue,
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 03 December 2020.
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 dose
Systemic events for up to 7 days
following each dose
AEs fr om Dose 1 to 1 month after the
second dose
SAEs from Dose 1 to 6 months after
the second doseAEs
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 1 month after
Dose 2 and to the data cutoff date
(14November 2020) in final analysis interim
CSR dated 03 December 2020.
Cumulative interim data up to cutoff date
(13March 2021) are reported in the 6 -month
update interim CSR dated 29 April 2021.
Interim adolescent data for local reactions
and systemic events reported up to 7 days
after each dose , and AEs and SAEs are
reported from Do se1 to 1 month after Dose
2 and to the data cutoff date (13 March 2021)
are reported in th e adolescent interim CSR
dated 14 April 2021 .
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Page 25of 152Table 1. Phase 2/3 Objectives, Estimands, and Endpoints
ObjectivesaEstimands Endpoints Reference
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
SAEsInterim d ata are reported up to 1month after
Dose 2 and to the data cutoff date
(13Marc h 2021) in the adolescent interim
CSR dated 14 April 2021 .
Interim data for AEs and SAEs reported up
to 6 months after Dose 2 and to the data
cutoff date (02 Septembe r 2021) are reported
in this CSR.
To describe the safety and tolerability
profile of BNT162b2 SAgiven as 1 or
2doses 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
participants in the subset for evaluation
of boostability and protection against
emerging VOCsIn 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 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
SAEsInterim d ata for BNT162b2 given as a third
dose to BNT162b2 -experienced participants
only are reported up to 1 month after Dose 3
and to the data cutoff date (17June 2021) in
the booster interim CSR dated
23August 2021 .
To describe the safety and tolerability
profil e of BNT162b2 given as a third
dose at least 6 months after the second
dose of BNT162b2 (or BNT162b2 SA)
for participants who received a third
dose as part of protocol amendment 18In participants receiving at least 1 dose
of study intervention, the percent age of
participants reporting:
AEs from Dose 3 to 1 month after
Dose 3
SAEs from Dose 3 to 6 months after
Dose 3AEs
SAEsInterim data for BNT162b2 given as a third
dose to BNT162b2 -experienced participants
only are reported up to 1 month after Dose 3
and to the data cutoff date (17 June 2021) in
the booster interim CSR dated
23August 2021 .
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Page 26of 152Table 1. Phase 2/3 Objectives, Estimands, and Endpoints
ObjectivesaEstimands 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 at
30µgcompared to after 2 doses of
BNT162b2, in the same individualsGMR of reference strain NT 1 month
after the third dose of BNT162b2 at
30µgto 1month 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 at 30 µgand 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 third dose of
BNT162b2 at 30 µg) of past
SARS -CoV -2 infectionInterim data for BNT162b2 given as a third
dose to BNT162b2 -experienced participants
are reported up to 1 month after Dose 3 and to
the data cutoff date (17 June 2021) in the
booster int erim CSR dated 2 3August 2021 .
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 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 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 t ime.
BNT162b2 -naïve participants
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 m onth 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.
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ObjectivesaEstimands 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
03December 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 c omplying 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 ce ntral laboratory or locally
confirmed NAATPrespecified complete efficacy data are
reported in final analysis interim CSR dated
03December 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
protoco l 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 -upin
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
03December 2020.
Updated efficacy data occurring from at least
7 days after the second dose only are
reported in the 6 -month update interim CSR
dated 29 April 2021 .
Updated efficacy data occurring from at least
7 days after the second dose for participants
12throu gh 15 years of age only are reported
in theadolescent interim CSR dated
14April 2021 .
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 a nd 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 -upPrespecified complete efficacy data are
reported in final analysis interim CSR dated
03December 2020.
Updated efficacy data occurring from at leas t
7days after the second dose only are
reported in the 6 -month update interim CSR
dated 29 April 2021 .
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ObjectivesaEstimands Endpoints Reference
Updated efficacy data occurring from at least
7 days after the second dose for participants
12through 15 years of age only are reported
in theadolescent interim CSR dated
14April 2021 .
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
intervention: 100 × (1 –IRR)
[ratio of active va ccine 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 p ast
SARS -CoV -2 infectionPrespecified complete efficacy data are
reported in final analysis interim CSR dated
03December 2020.
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
03December 2020.
To evaluate the efficacy of prophylactic
BNT162b2 against non -S
seroconversion to SARS -CoV -2 in
participants without evidence of
infection or confirmed 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]Incidence 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 eviden ce (up to the start of Data will be reported at a later time.
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ObjectivesaEstimands Endpoints Reference
the asymptomatic surveillance period)
of past SARS -CoV -2 infection
Secondary Immunogenicity
To demonstrate the noninferiority of the
immune response to prophylactic
BNT162b2 in participants 12 to
15years 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 infectionInterim data are reported in the adolescent
interim CSR dated 14 April 2021.
BNT162b2 -experienced participants
To demonstrate the noninferiority of the
anti-SA immune response after a third
dose of BNT162b2 at 30 µgcompared
to the anti –reference strain immune
response after 2 doses of BNT162b2,
inthe same individuals GMR of SA NT 1 month after the third
dose of BNT162b2 at 30 µgto 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
BNT162b 2at 30 µgand 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 third dose of
BNT162b2 at 30µg) of past
SARS -CoV -2 infectionData will be reported at a later time .
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 strain 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.
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Page 30of 152Table 1. Phase 2/3 Objectives, Estimands, and Endpoints
ObjectivesaEstimands Endpoints Reference
To descriptively compare the anti-SA
immune response after 1 dose of
BNT162b2 SAand a third dose of
BNT162b2 at 30 µgGMR of SA NT 1 month after 1 dose of
BNT162b2 SAto 1month after the third
dose of BNT162b2 at 30 µg
The difference in percentages of
participants with serorespo nse to the SA
strain at 1 month after 1 dose of
BNT162b2 SAand 1 month after the third
dose of BNT162b2 at 30 µgSARS -CoV -2 SA NT in participants
with no serological or virological
evidence (up to 1 month after receipt of
1 dose of BNT162b2 SAor the third dose
of BNT162b2 at 30 µg) 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 response 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 virologi cal evidence (up to 1 month
after 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 BNT162b2 SAand 1 month after the
second dose of BNT162b2SARS -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 infectionData will be reported at a later time.
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Page 31of 152Table 1. Phase 2/3 Objectives, Estimands, and Endpoints
ObjectivesaEstimands Endpoints Reference
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
1month 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 vaccinati onIn 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 locally
confirmed NAATInterim data arereported in the 6 -month
update interim CSR dated 29 April 2021.
Updated efficacy data from 7 days after
Dose 2through the blinded follow -up period
for participants 12 through 15 years of age
are provided in this CSR.
To describe the incidence of confirmed
COVID -19 through the entire study
follow -up period prior to receiving the
third dose of BNT162b2 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
confi rmed NAATData will be reported at a later time.
To describe the incidence of confirmed
COVID -19 after receiving the third
dose of BNT162b2In participants who received the third
dose of BNT162b2:
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.
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Page 32of 152Table 1. Phase 2/3 Objectives, Estimands, and Endpoints
ObjectivesaEstimands Endpoints Reference
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, and 24 months after completion
of vaccinationFull-length S -binding or S1 -binding
IgG levels
SARS -CoV -2 neutralizing titersInterim data for Phase 2 (first
360participants) only up to 1 month after
Dose 2 are reported for S1 -binding IgG
levels and SARS-CoV -2 neutra lizing titers in
final analysis interim CSR dated
03December 2020.
GMTs and GMFRs of SARS -CoV -2
neutralizing titers up to 1 month after Dose 2
in participants 12 through 15 and 16 through
25 years of age arereported in the adole scent
interim CSR dated 14 April 2021 .
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 infection 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 infe ction 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 candidate and
characterize the SARS -CoV -2 isolate in
cases of:
Confirmed COVID-19
Confirmed severe COVID -19
SARS -CoV -2 infection without
confirmed COVID -19Full 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.
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Page 33of 152Table 1. Phase 2/3 Objectives, Estimands, and Endpoints
ObjectivesaEstimands Endpoints Reference
To describe the safety,
immunogenicity, and efficacy of
prophylactic BNT162b2 in individuals
with confirmed stable HIV diseaseAll safety, immunogenicity, and
efficacy endpoints described aboveSafety data only in participants with
confirmed stable HIV disease are reported in
the 6 -month update interim CSR dated
29April 2021.
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 immune response to a
third dose of BNT162b2 (at 30 µg or a
lower dose of 5 µg or 10 µg) or a third
or fourth dose of BNT162b2 SA GMTs at Dose 3 and subsequent
time points
 GMFRs from Dose 3 to subsequent
time points SARS -CoV -2 reference strain NTs Interim data for BNT162b2 30 µg given as a
third dose to BNT162b2 -experienced
participants are reported in the booster
interim CSR dated 2 3August 2021 .
To describe the cell -mediated immune
response, and additional humoral
immune response parameters, to the
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
participants
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
participantsData will be reported at a later time.
a.HIV-positive participants in Phase 3 were not included in analyses of the objectives, w ith the exception of the specific exploratory objective.
b. See Appendix 16.1.1, Protocol Section 6.1.1 for a description of the manufacturing process.
Source: Appendix 16.1.1, Protocol Section 3.2.
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Page 34of 1529.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) and dose
level(s); and Phase 2/3 as an expanded cohort and efficacy part. The stud y evaluated the
safet y, tolerabilit y, 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;
As a booster (Dose 3) ; (see Boos tability and Variant Strain Evaluation)
In various age groups:
Phase 1: 18 to 55 and65 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.
Boostability and Variant Strain Evaluation s
Immunogenicit y and safety evaluations of boostability were conducted in a subset of Phase 3
participants at selected sites in the US who receive da third dose of BNT162b2 at 30 µg at
least 6 months after their second dose , and results are reported in the booster interim CSR
dated 23 A ugust 2021. Evaluations of boostability in Phase 1 participants and a further subset
of Phase 3 participants receiv inga third, lower, dose of BNT162b2 at 5 or 10 µg will be
reported at a later time .
Evaluations of VOC strains of SARS -CoV -2 (in participants who receive a SARS -CoV -2
variant encoding vaccine that encodes the Beta variant originally identified in South Afric a
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Page 35of 152[BNT162b2 SA] as a third dose) are not included in this report and will be reported at a later
time.
Refer to Appendix 16.1.1, Protocol Section 4.1.1 for further details on the booster (Dose 3)
for Phase 1, and Appendix 16.1.1, Protocol Section 4.1.2 for further details on the booster
(Dose3) 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 to be unblinded in stages once all ongoing participants either had been
individually unblinded or had concluded their 6 -month post–Dose 2 or post -Dose 3 study
visit, in the following sequence :
Phase 1 (after Visit 8 [6-month post-Dose 2 visit] ).
Phase 2/3, ≥16 y ears of age (after Visit 4 [6-month post-Dose 2 visit] ).
Phase 3, 12 through 15 years of age (after Visit 4 [6-month post-Dose 2 visit] ).
Original Phase 3 participants rerandomized to assess boostability and protection against
emerging VOCs (after Visit 30 6) (data not included in this report ).
Participants who originally received placebo and became eligible for receipt of BNT162b2
according to recommendations detailed separatel y, and available in the electronic study
reference portal, had the opportunity toreceive BNT162b2 in a phased manner as part of the
study . The investigator ensured the participant met at least 1 of the recommendation criteria
based upon US recommendation .
Any Phase 1 placebo recipient who had not already been offered the opportunity to receive
BNT162b2 was given this opportunity no later than at the approximate time participants in
Phase 2/3 reached Visit 4. Any Phase 2/3 placebo recipient who had not already been offered
the opportunity to receive BNT162b2 was given this opportunity no later than 6 months after
Vaccination 2 (at the time of the originall y planned Visit 4).
Any participant who originally received placebo but then went on to receive BNT162b2 was
moved to a new visit schedule to receive both doses of BNT162b2 at each of 2additional
vaccination visits (Visits 101 and 102) (Appendix 16.1.1, Protocol Section 1.3.3 ).
9.1.1. Phase 1
Phase 1 safet y follow -up is ongoing, and participants areexpected to participate for up to a
maximum of approximately 26 months.
Refer to Appendix 16.1.1, Protocol Section 4.1.1 for further details on the Phase 1 study
design.
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Page 36of 1529.1.2. Phase 2/3
The Phase 2 part of the study was comprised of the first 360 participants enrolled
(1:1randomization between BNT162b2 and placebo, stratified 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 360 Phase 2 participants. Enrollment continued during Phase 2 and these
participants were 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 to15 years of age stratum
comprise dup to approximately 2000 participants enrolled at selected investigational sites .
Itwas planned to enroll a minimum of 40% of participants in the >55 yearsof 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 for the first prima ry
efficacy endpoint (data cutoff date : 04November 2020 ), and the final analy sis was conducted
on an accrued 170 evaluable COVID -19 cases for the first primary efficacy endpoint (data
cutoff date : 14November 2020 ). These data are reported in the final analy sis interim CSR
dated 03 December 2020 and included all study participants in the efficacy populations
≥12years of age.
At the time of the final analy sis of efficacy (CSR dated 03 December 2020) , relativel y few
participants 12 to15 years of age had enrolled in the study , and no COVID -19 cases in this
age group accrued at that time . In the adolescent interim CSR dated 14 April 2021 ,
noninferiority of immune response to prophy lactic BNT162b2 in participants 12 to15 years
of age to response in particip ants 16 to 25 years of age wasassessed based on the GMR of
SARS -CoV -2 neutralizing titers using a 1.5 -fold margin and reported in the adolescent
interim CSR dated 14 April 2021 and in an EUA amendment, which supported issuance of
the EUA for use in indivi duals 12 to 15 y ears of age .Additionally , the adole scent interim
CSR also presented updated descriptive efficacy analy ses for participants 12 to 15 y ears of
age, based on confirmed cases COVID -19 reported from at least 7 days after Dose 2 through
the data cutoff date (13 March 2021), with an observed VE of 100% irrespective of evidence
of prior infection with SARS -CoV -2. No severe COVID- 19 cases were reported in this age
group, based on either protocol definition (ie, per FDA criteria) or per CDC criteria for
severit y.
Updated efficacy analy sesduring theblinded placebo -controlled follow -upperiod were
conducted on cases accrued up to the data cutoff date of 13 March 2021 to evaluate duration
of protection and reported in the 6- month update interim CSR dated 29 April 2021, which
presented these anal yses of all confirmed COVID -19 cases and an y cases meeting protocol -
and CDC -defined criteria for severe cases.
Itis planned that participants would participate in the study for approximately 26months
from t he time of enrollment.
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Page 37of 152This interim report for participants 12 to 15 y ears of age includes updated efficacy anal yses
from 7days after Dose 2 and safet y analyses up to 6 months after Dose 2 and tothe data
cutoff date (02 September 2021).
Refer to Append ix 16.1.1, Protocol Section 4.1.2for further detail on the Phase 2/3 study
design , including the planned anal yses.
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
2BNT162 RNA -based COVID -19 vaccine candidates against COVID- 19, and the efficacy
of 1(selected) candidate, in healthy individuals. B oostability is being assessed in asubset of
Phase 3 participants, including with a protot ype vaccine that targets a SARS- CoV -2 VOC.
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 av ailable.
Phase 1 was designed to identify preferred vaccine candidate(s) and dose level(s) for further
development based on safety , tolerability , and immunogenicit y.
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 vaccine candidate selected for
development, and to provide additional safet y and immunogenicit y data in a larger
population, including adolescents (adolescents were l ater permitted to enroll as part of
Phase 3).Boostabilit y wasalso assessed.
Refer to Appendix 16.1.1, Protocol Section 4.2for further detail of the rationale of the stud y
design.
9.3.Participant Selection
9.3.1. Inclusion Criteria
Participants were eligible to be included in the study only if all of the following criteria
applied:
Age and Sex:
1.Male or female participants between the ages of 18 and 55years, inclusive, and 65 and
85years, inclusive (Phase 1), or ≥12 years(Phase 2/3), at randomization.
For the boostability and protection -against -VOCs subset:
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Page 38of 152Existing participants enrolled to receive a third dose of BNT162b2 at 30 µg or
BNT162b2 SA; male or female participants between the ages of 18 and 55 years,
inclusive, at rerandomization.
Newl y enrolled parti cipants enrolled to receive 2 doses of BNT162b2 SA; male or
female participants between the ages of 18 and 55 y ears, inclusive, at enrollment.
Existing participants enrolled to receive a third dose of BNT162b2 at 5 or 10 µg;
male or female participants ≥18 years at rerandomization.
Note that participants <18 y ears of age c ould not be enrolled in the EU.
Refer to Appendix 4 for reproductive criteria for male ( Appendix 16.1.1, Protocol
Section 10.4.1 ) and female ( Appendix 16.1.1, Protocol Section 10.4.2 ) participants.
Type of Participant and Disease Characteristics:
2.Participants who were willing and able to comply with all scheduled visits, vaccination
plan, laboratory tests, lifesty le considerations, and other study procedures.
3.Health y participants who were determined b y medical history, ph ysical examination
(ifrequired) , and clinical judgment of the investigator to be eligible for inclusion in the
study .
Note : Healthy participants with preexisting stable disease, defined as disease not requiring
signific ant change in therapy or hospitalization for worsening disease during the 6 weeks
before enrollment, could be included. Specific criteria for Phase 3 participants with k nown
stable infection with HIV, HCV, or HBV can be found in Appendix 16.1.1, Protocol Section
10.8.
4.Phase 2/3 only: Participant swho, in the judgment of the investigator, wereat higher risk
for acquiring COVID -19 (including, but not limited to , use of mass transportation,
relevant demographics, and frontline essential workers) .
5.Boostabilit y and protection -against -VOCs existing participant subset only:
Participants who provided a serum sample at Visit 3, with Visit 3 occurring within the
protocol -specified window.
Informed Consent:
6.Capable of giving personal signed informed consent/have pare nt(s)/legal guardian
capable of giving signed informed consent as described in Appendix 16.1.1,
Protocol Appendix 1, which include dcompliance with the requirements and restrictions
listed in the I CD and in th e protocol.
9.3.2. Exclusion Criteria
Participants were excluded from the study if an y of the following criteria appl ied:
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Page 39of 152Medical Conditions:
1.Other medical or psy chiatric condition including recent (within the past year) or active
suicidal ideation/behavior or laboratory abnormality that increased the risk of study
participation or, in the investigator’s judgment, made the participant inappropriate for the
study .
2.Phases 1 and 2 only: Known infection with HIV, HCV, or HBV.
3.History of severe adverse reaction assoc iated with a vaccine and/or severe allergic
reaction (eg, anaph ylaxis) to any component of the study intervention(s).
4.Receipt of medications intended to prevent COVID -19.
5.Previous clinical (based on COVID -19 s ymptoms/signs alone, if a SARS -CoV -2 NAAT
resul t was not available) or microbiological (based on COVID -19 s ymptoms/signs and a
positive SARS -CoV -2 NAAT result) diagnosis of COVID -19.
6.Phase 1 only: Individuals at high risk for severe COVID -19, including those with any of
the following risk factors:
Hypertension
Diabetes mellitus
Chronic pulmonary disease
Asthma
Current vaping or smoking
History of chronic smoking within the prior y ear
Chronic liver disease
Stage 3 or worse chronic kidney disease (glomerular filtration rate <60 mL/min/1.73 m2)
Resident in a long -term facility
BMI >30 kg/m2
Anticipating the need for immunosuppressive treatment within the next 6 months
7.Phase 1 only: Individuals currentl y working in occupations with high risk of exposure to
SARS -CoV -2 (eg, healthcare worker, emergency response personnel).
8. Immunocompromised individuals with known or suspected immunodeficiency , as
determined b y history and/or laboratory /physical examination.
9.Phase 1 only: Individuals with a history of autoimmune disease or an active autoimmune
disease requiring therapeutic intervention, including but not limited to: sy stemic or
cutaneous lupus ery thematosus, autoimmune arthritis/rheumatoid arthritis, Guillain -Barré
syndrome, multiple sclerosis, Sjögren’s s yndrome, idiopathic thrombocytopenia purpura,
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Page 40of 152glomerulonephritis, autoimmune thy roiditis, giant cell arteritis (temporal arteritis),
psoriasis, and insulin -dependent diabetes mellitus (type 1).
10. Bleeding diathesis or condition associated with prolonged bleeding that would, in the
opinion of the investigator, contr aindicate intramuscular injection.
11.Women who are pregnant or breastfeeding.
Prior/Concomitant Therapy:
12.Previous vaccination with any coronavirus vaccine.
13.Individuals who received treatment with immunosuppressive therapy , including cy totoxic
agents or s ystemic corticosteroids, eg, for cancer or an autoimmune disease, or planned
receipt throughout the study . If systemic corticosteroids were administered short term
(<14 days) for treatment of an acute illness, participants should not have been enrolled
into th e study until corticosteroid therapy had been discontinued for at least 28 day s
before stud y intervention administration. I nhaled/nebulized (except for participants in
Phase 1 – see exclusion criterion 14), intra- articular, intrabursal, or topical (skin or eyes)
corticosteroids were permitted.
14.Phase 1 only: Regular receipt of inhaled/nebulized corticosteroids.
15.Receipt of blood/plasma products or immunoglobulin, from 60 day s before study
intervention administration or planned receipt throughout the stud y.
Prior/Concurrent Clinical Study Experience:
16.Participation in other studies involving study intervention within 28 day s prior to study
entry through and including 28 day safter the last dose of study intervention, with the
exception of non-Pfizer intervention al studies for prevention of COVID 19, which are
prohibited throughout study participation.
17.Previous participation in other studies involving study intervention containing lipid
nanoparticles.
Diagnostic Assessments:
18.Phase 1 only: Positive serological test for SARS- CoV -2 IgM and/or IgG antibodies at
the screening visit.
19.Phase 1 only: Any screening hematology and/or blood chemistry laboratory value that
meets the definition of a ≥Grade 1 abnormality .
Note: With the exception of bil irubin, participants with any stable Grade 1 abnormalities
(according to the toxicity grading scale) may be considered eligible at the discretion of the
investigator. (Note: A “stable” Grade 1 laboratory abnormality is defined as a report of Grade
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Page 41of 1521 on an initial blood sample that remains ≤ Grade 1 upon repeat testing on a second sample
from the same participant.)
20.Phase 1 only: Positive test for HIV, HBsAg, HBc Abs, or HCV Abs at the screening
visit.
21.Phase 1 only: SARS -CoV -2 NAAT -positive nasal swab within 24 hours before receipt of
study intervention.
Other Exclusions:
Investigator site staff or Pfizer/BioNTech employees directly involved in the conduct of the
study , site staff otherwise supervised by the investigator, and their respective family
members.
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:
BNT162b2 (BNT162 RNA -LNP vaccine containing modRNA that encodes theP2 S):
30µg
Normal saline (0.9% sodium chloride solution for injection)
Refer to Appendix 16.1.1, Protocol Sections 6.1and 6.1.2for details of other planned or
ongoing study intervention(s) and study intervention administration that will be reported at a
later time.
9.4.2. Identity of Investigational Product(s)
Refer to Appendix 16.1.1, Protocol Section 6.2 for details on preparation, storage, and
dispensing.
A list of the study interventions administered in this study and their respective lot numbers is
provided in Table 2.
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Page 42of 152Table 2. Investigational Product Lot Numbers – Interim – Adolescent 6- Month
Update
Investigational Product ManufacturerVendor Lot
Number
(Manufacturer) Lot Numbera(Pfizer)
BNT162b2 (30 µg) BioNTech BCV40720 -A
BCV40720 -A
BCV40720 -B
BCV40720 -C
ED3938
ED3938
ED3938
EE3813
EE3813
EE3813
EE3813
EE3813
ER9449Z
ER9449Z
EE8493Y
EJ0553ZPA2074172/P220395 -0053L
PA2074998/P220395 -0060L
PA2074173/P220395 -0051L
PA2074071/P220395 -0052L
PA2074300/P220395 -0021L
PA2074300/P220395 -0022L
PA2074300/P220395 -0023L
NC2075485/P220395 -0068L
NC2075485/P220395 -0074L
NC2075485/P220395 -0077L
PA2074838/P220395 -0020L
PA2074838/P220395 -0024L
PA2096794/P220395 -0079L
PA2096794/P220395 -0082L
PA2087473/P220395 -0073L
PA2085061/P220395 -0070L
Placebo (n ormal saline 0.9%
sodium chloride solution)Pfizer 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 -002221PA2069407/P220395 -0032L
PA2069407/P220395 -0033L
PA2069407/P220395 -0034L
PA2069407/P220395 -0044L
PA2069407/P220395 -0045L
PA2069407/P220395 -0046L
PA2069407/P220395 -0055L
PA2069407/P220395 -0062L
PA2069407/P220395 -0065L
Diluent (n ormal saline 0.9%
sodium chloride solution)Pfizer DK2074
DK1589
DK158920-002221
20-001776
20-001592
Note: C4591001 End of Study Information and Quality Control (QC) Record for Study Drug Appendix
(Section D) dated 08Oct2021 was used to create this table.
a. Lot number assigned to the investigational product or diluent by Pfizer Global Clinical Supply.
Protocol C4591001 Investigational Product Lot Numbers Table – Interim –Adolescent 6 -Month Update,
Final, Version 1.0, 15Oct2021.
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.
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Page 43of 1529.4.4. 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 fo r 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 03 December 2020 identified BNT162b2 at 30 µgas the candidate for Phase 2/3
evaluation.
Refer to Appendix 16.1.1, Protocol Section 6 for details 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,
investigat or 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
study intervention allocation for the participants in the Phase 1 portion of the study . Sponsor
staff and all personnel directly involved in study conduct were 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 study wasto be unblinded in stages once all ongoing participants either ha dbeen
individually unblinded or ha dconcluded their 6 -month post–Dose 2 or post -Dose 3 study
visit, as follows:
Phase 1 (after Visit 8).
Phase 2/3, ≥16 y ears (after Visit 4).
Phase 3, 12 to 15 years (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 who originall y received placebo and became eligible for receipt of BNT162b2
according to recommendations detailed separatel y, 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.
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 personn el, and
Protocol Section 6.3.4 for circumstances when the blind could be broken.
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Page 44of 1529.4.6. 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 study vaccinations 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 participant’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 anoth er condition, even if it had antipy retic or pain -relieving properties, it was
not withheld prior to study vaccination.
Permitted During the Study
The use of antip yretics and other pain medication to treat sy mptoms associated with study
intervention administration or ongoing conditions was permitted.
Medication other than that described as prohibited in Appendix 16.1.1, Protocol Section 6.5.1
required for treatment of preexisting stable conditions was permitted.
Inhaled, topical, or localized injectio ns of corticosteroids (eg, intra -articular or intrabursal
administration) were permitted.
Refer to Appendix 16.1.1, Protocol Section 6.5.2for details on prior and concomitant
vaccines, medications and procedures that were allowed.
9.4.7. Vaccine Compliance
Parti cipants 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
intervention.
9.5.Efficacy, Immunogenicity, and Sa fety Evaluations
9.5.1. Efficacy and Immunogenicity Evaluations
Efficacy was assessed based on all cases in participants 12 through 15 y ears of age accrued in
blinded follow -up to a data cutoff date of 13 March 2021 in the adolescent interm CSR, dated
14 April 2021 .
In this report, updated descriptive efficacy anal yses forparticipants 12 through 15 years of
age accrued during blinded placebo -controlled follow -upare summarized up to a data cutoff
date of 02 September 2021 .
Immunogenicit y evaluations in pa rticipants 12 through 15 years of age are not included in
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Page 45of 152this interim report. The i mmune response to BNT162b2 30µgin adolescents 12 through
15years of age was previously reported to be noninferior (an d in fact exceeded) the immune
response in young adu lts 16 through 25 years of age (ie, successful immunobridging) , as
detailed in the adolescent interim report dated 14 April 2021.
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
There are no new e -diary data presented in this report (previousl y reported in the adolescent
interim CSR, dated 14 April 2021).
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 event s, fever, and use of antip yretic/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 , prior to protocol amendment 16 (28 May 2021), subsequent
convalescent visit (in -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.
When the total number of severe cases was 20 or less, stopping rule sand 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 Eve nts 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.
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Page 46of 152SAEs were collected from the signing of the ICD to approximately 6 months after the last
dose of study intervention (Visit 4 for Pha se 2/3 participants).
For those participants who originall y received placebo but went on to receive BNT162b2 at
Vaccinations 3 and 4, AEs were collected from the time the participant provide dinformed
consent (for receipt of Vaccinations 3 and 4) through and including Visit 103(1-month
follow -up after Vaccination 4) . SAEs were collected from the time the participant provide d
informed consent (for receipt of Vaccinations 3 and 4) to approximately 6 months after the
second dose of BNT162b2 (Visit 1 04).
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
Myocarditis and pericarditis were included as AESI s inProtocol A mendment 18
(07September 2021).
Pfizer alsoutilizes a safety 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 by routine safet y data review procedures throughout the clinical study. Althoug h 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
AESI s specific for a product or program's protocol(s). They are base d on review of known
pharmacology , toxicology findings, possible class effects, published literature, and potential
signals arising from safety 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 M edDRA queries (SMQs; all evaluated as broad and narrow) .
Other events of clinical interest identified b y the sponsor in the reported safety dataset were
also review ed and summarized (Section 12.3.4 ).
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
system and handheld diary device or application . The CRFs were designed to be used with
ease.
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 enable 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
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Page 47of 152and completeness of the data being entered into the RDC sy stem . During these visits, critical
data were verified against participant source documents, and queries regarding missing or
contrad ictory data were resolved. In addition, study procedures were reviewed, and protocol
deviations were discussed with the investigator . Telephone and email contact was maintained
with the investigators between site visits. In addition, the overall study cond uct 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 p lanning .
The accuracy of the clinical database was verified through a series of processes. Potential
errors were identified 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 d eclared read y for statistical
analysis.
This CSR has been subject to quality control review by Pfizer or Pfizer’s designee.
Quality assurance audits were performed at selected sites by Pfizer’s own independent
quality assurance group or by a CRO and/or individual contract personnel under the group’s
direction . These audits were conducted according to Pfizer’s procedures and GCP guidelines.
For the time period applicable tothis interim report, there were 2 audits conducted f or sites
that enrolled adolescen t participants (Appendix 16.1.8 ).
Refer to the final anal ysis interim CSR dated 03 December 2020 for previously reported data
quality issues. There were none reported in the adolescent CSR dated 14 April 2021, or in the
6-month update interim CSR dated 29 April 2021.
9.7.Statistical Methods Planned in the Protocol
9.7.1. Statistical and Analytical Plans
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 other planned analysis sets to be
reported at a later time .
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Page 48of 152Table 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.
Evaluable efficacy
(7 days)All eligible randomized participants who received all vaccination(s) as randomized,
with Dose 2 received within the predefined window (19-42 days after Dose 1) and had
no other important protocol deviations as determined by the clinician on or before
7days after Dose 2.
Dose 1 all -available
efficacyAll randomized participants who received 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
In Phase 3, a pproximately 2,000 participants enrolled were anticipated to be 12 to 15 y ears of
agebased on regulatory requirements for the safety database .
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
62cases) at 94 cases (data cutoff date: 04 November 2020). At the final analy sis (at least
164cases) VEwith respect to all efficacy endpoints was assessed on an accrued
170evaluable COVID -19 cases (data cutoff date: 14 November 2020) for both primary and
all secondary efficacy endpoints. No additional formal hypothesis testing of clinically
confirmed COVID- 19 cases is planned.
Assessment of VE of BNT162b2 was performed 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 da ys after receipt of the second dose) of
past SARS -CoV -2 infection. VE was estimated b y 100% × (1 –IRR), where I RR 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 IRR
and VE).
Efficacy anal yses 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
(adolescent interim CSR, dated 14April 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 analy ses using the CDC definition of severe COVID -19 were also
performed.
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Page 49of 152In this report, updated efficacy anal yses during blinded placebo -controlled follow -up were
conducted for participants 12 through 15 years of age based on the data cutoff date of
02 Septemb er 2021 . In addition to the protocol definition of severe COVID- 19, supportive
analyses using the CDC definition of severe COVID -19 were also performed.
The efficacy anal ysis for Phase 2/3 is also described in Appendix 16.1.1, Protocol
Section 9.4.2 and Ap pendix 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
Immunogenicit y evaluations in participants 12 -15 years of age are not included in this
interim report.
In the adolesce nt interim report dated 14 April 2021 ,the GMR of SARS -CoV -2 50%
neutralizing titers in adolescents 12 -15 years of age to those in young adults 16-25 years of
age and 2 -sided 95% CIs were provided at 1 month after Dose 2 for noninferiority
assessment. The immune response to BNT162b2 30 µg in SARS- CoV -2 50% neutralizing
titers in adolescents 12 -15 years of age was noninferior (and in fact exceeded) the immune
response in young aduts 16 -25 years of age (ie, successful immunobridging).
The immunogenicit y analy sis is further described in Appendix 16.1.1, Protocol Section 9.4.1 ,
and Appendix 16.1.9, SAP Sections 6.2.1.1 through 6.2.1.3 for Phase 1, and
Appendix 16.1.9, SAP Section 6.2.1.4 and SAP Section 6.3.3for Phase 2/3.
9.7.5. Safety Analysi s
The primary safet y objective was evaluated b y descriptive summary statistics for local
reactions, sy stemic events, and AEs/SAEs for each vaccine group . There are no new
reactogenicity data in this report (previously reported in the adolescent interim CSR , dated
14April 2021).
Descriptive summary statistics included counts and percentages of participants with the
indicated endpoint and the associated Clopper- Pearson 2- sided 95% CIs. Incidence rates
accountedfor differential follow -up time and the associated 2 -sided 95% CI were also
provided.
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(primary ).
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
Statistical a nalysesfor participants 12 through 15 years of age were described for the
following data in the adolescent interim CSR dated 14 April 2021 :
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Page 50of 152Safety data through 1 month af ter Dose 2 and noninferiorit y comparison of SARS -CoV -2
neutralizing titers in participants 12 through 15 years of age compared to those in
participants 16 through 25 y ears of age, 1 month after Dose 2. Safet y data for participants
16through 55years of age were included for comparative purposes and d idnot include a
full independent safety evaluation (these will be reported separatel y).
Descriptive efficacy analy sis for participants 12 through 15 y ears of age based on the data
cutoff date of 13 March 2021 .
Statistical analy ses for participants 12 through 15 years of age are reported for the following
data in this CSR :
Complete safet y anal ysis at6 months after Dose 2 for adolescent participants in Phase 3;
andanalysis of available safety resultsup to the data cutoff date for this report.
Updated descriptive efficacy analy sis for participants 12 through 15 years of age during
the blinded placebo -controlled follow -up period based on the data cutoff date of
02September 2021.
The anal ysis timing is described 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 original planned anal ysis are described in SAP v 7.0
(Appendix 16.1.9, SAP Section 1).
Additional changes in study conduct or planned analy sis not noted in the protocol or SAP
were previousl y reported in Section 9.8 of the fin al analy sis interim CSR dated 03 December
2020 and Section 9.8 of the adolescent interim CSR dated 14 April 2021 . Changes in study
conduct or planned anal ysis not noted in the protocol or SAP in this interim CSR were as
follows:
In Phase 2/3, for original adolescent placebo participants in the open -label follow -up
period who then received BNT162b2 after unblinding, summary tables of AEs within
7days after each dose were generated in order to evaluate whether AEs reported may
have been attributed to reactog enicit y events in participants who did not have an e diary
to report reactogenicit y. Although this was not specified in the SAP, this was prespecified
in analy sis and reporting plan before database release.
Per regulatory request, ad hoc safet y tables wer e generated which summarized new AEs
reported after the EUA snapshot date (based on events on or after a data cutoff date of
13March 2021) for the blinded placebo- controlled and open -label follow -up periods .
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Page 51of 15210.STUDY PARTICIPANTS
10.1. Disposition of Participants –Participants 12Through 15 Years of Age
10.1.1. Blinded Placebo -Controlled Follow -Up Period
During the blinded placebo -controlled follow -up period, t here were 3 (0.3%) participants in
the BNT162b2 group and 14 (1.2%) participants in the placebo group who discontinued from
the vaccination period (Dose 1 to 1 month after Dose 2) ( Table 4). Most participants
completed the visit at 1 month after Dose 2 ( ≥97.0%). Few participants i n the BNT162b2 and
placebo groups were withdrawn from the study (0.4% and 1.2%, respectively ), and all were
because of withdrawal by the participant, withdrawal by parent/guardian, or they were lost to
follow -up.
10.1.2. Open -Label Follow -Up Period
Individuals have been unblinded asthey became locally eligible and wish edto know their
vaccine assignment to confirm prior vaccination with BNT162b2 (if randomized to this
group), or to receive BNT162b2 (if randomized to placebo). Participants who origin ally
received BNT162b2 continue dto be followed in an open -label manner. Participant swho
originall y received placebo were offered BNT162b2 vaccination (Doses 3 and 4 [first and
second dose of BNT162b2 30 µg, respectivel y]) and thereafter followed in an op en-label
manner.
Most participants in the BNT162b2 ( 98.1%) and placebo ( 97.0%) groups completed the
1month post -Dose 2 visit before unblinding ( Table 4).
A total of 4 (0.4%) original BNT162b2 adolescent participants received Dose 1 of
BNT162b2 during the blinded placebo -controlled follow -up period and then received Dose 2
of BNT162b2 30 µg during the open- label follow -up period (when they were unblinded)
(Table 4). There were 45 (4.0%) participants withdrawn from the study (Table 4), and most
were because o f other reasons (21 of 23 participants were enrolled into Study C4591031 to
evaluate a booster dose of BNT162b2) (Appendix 16.2.1 ).
During the open- label follow -up period, most participants originally randomized tothe
placebo group received Doses 3 and 4 ( 89.4% and 87.8%, first and second dose of
BNT162b2 30 µg, respectively ). There were 47 (4.2%) participants who were withdrawn
from the study after unblinding and before Dose 3. There were few participants in this group
(who received at least the first dose of BNT162b2 30 µg)who were withdrawn from the
study (0.5%) , and most were because of withdrawals by the participant, or they were lost to
follow -up ( Table 4).
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Page 52of 152Table 4. Disposition of All Randomized Subjects – Phase 2/3 Subjects 12 Through
15 Years of Age
Vaccine Group (as Randomized)
BNT162b2 (30 μg)
(Na=1134)
nb(%)Placebo
(Na=1130)
nb(%)Total
(Na=2264)
nb(%)
Randomized 1134 (100.0) 1130 (100.0) 2264 (100.0)
Not vaccinated 3 (0.3) 1 (0.1) 4 (0.2)
Original blinded placebo -controlled follow -up period
Vaccinated 1131 (99.7) 1129 (99.9) 2260 (99.8)
Dose 1 1131 (99.7) 1129 (99.9) 2260 (99.8)
Dose 2 1124 (99.1) 1117 (98.8) 2241 (99.0)
Discontinued from original blinded placebo-controlled
vaccination periodc3 (0.3) 14 (1.2) 17 (0.8)
Reason for discontinuation
No longer meets eligibility criteria 0 7 (0.6) 7 (0.3)
Protocol deviation 0 2 (0.2) 2 (0.1)
Adverse event 1 (0.1) 0 1 (0.0)
Physician decision 1 (0.1) 0 1 (0.0)
Withdrawal by subject 0 1 (0.1) 1 (0.0)
Withdrawal by parent/guardian 0 1 (0.1) 1 (0.0)
Other 1 (0.1) 3 (0.3) 4 (0.2)
Unblinded before 1 -month post –Dose 2 visit 12 (1.1) 21 (1.9) 33 (1.5)
Completed 1 -month post –Dose 2 visit 1113 (98.1) 1096 (97.0) 2209 (97.6)
Withdrawn from the study 5 (0.4) 14 (1.2) 19(0.8)
Withdrawn after Dose 1 and before Dose 2 0 0 0
Withdrawn after Dose 2 and before 1 -month post –Dose 2 visit 0 3 (0.3) 3 (0.1)
Withdrawn after 1 -month post –Dose 2 visit 5 (0.4) 11 (1.0) 16 (0.7)
Reason for withdrawal from the study
Withdrawal by subject 1 (0.1) 7 (0.6) 8 (0.4)
Withdrawal by parent/guardian 1 (0.1) 5 (0.4) 6 (0.3)
Lost to follow -up 3 (0.3) 2 (0.2) 5 (0.2)
Open -label follow -up period
Originally randomized to BNT162b2 1107 (97.6)
Received Dose 2/unplanned dose 4 (0.4)
Completed 1 -month post –Dose 2 visit 15 (1.3)
Completed 6 -month post –Dose 2 visit 1065 (93.9)
Withdrawn from the study 45 (4.0)
Withdrawn before 6-month post –Dose 2 visit 25 (2.2)
Withdrawn after 6 -month post –Dose 2 visit 20 (1.8)
Reason for withdrawal from the study
Withdrawal by subject 7 (0.6)
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Page 53of 152Table 4. Disposition of All Randomized Subjects – Phase 2/3 Subjects 12 Through
15 Years of Age
Vaccine Group (as Randomized)
BNT162b2 (30 μg)
(Na=1134)
nb(%)Placebo
(Na=1130)
nb(%)Total
(Na=2264)
nb(%)
Withdrawal by parent/guardian 7 (0.6)
Lost to follow -up 6 (0.5)
Protocol deviation 1 (0.1)
No longer meets eligibility criteria 1 (0.1)
Other 23 (2.0)
Originally randomized to placebo 1108 (98.1)
Withdrawn from the study after unblinding and before Dose 3 47 (4.2)
Received Dose 3 (first dose of BNT162b2 [30 μg]) 1010 (89.4)
Received Dose 4 (second dose of BNT162b2 [30 μg]) 992 (87.8)
Discontinued from open -label vaccination periodd5 (0.4)
Reason for discontinuation from open -label vaccination period
Protocol deviation 4 (0.4)
Withdrawal by subject 1 (0.1)
Completed 1 -month post –Dose 4 visit 933 (82.6)
Withdrawn from the study 6 (0.5)
Withdrawn after Dose 3 and before Dose 4 5 (0.4)
Withdrawn after Dose 4 and before 1 -month post –Dose 4 visit 0
Withdrawn after 1 -month post –Dose 4 visit 1 (0.1)
Reason for withdrawal from the study
Withdrawal by subject 3 (0.3)
Lost to follow -up 2 (0.2)
Protocol deviation 1 (0.1)
a. N = number 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 -controll ed vaccination period is defined as the time period from Dose 1 to 1 -month post –
Dose 2 visit.
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]) visit.
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Page 54of 15210.2. Protocol Deviations – P articipants 12 Through 15 Years of Age
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 by remote monitoring of electronic CRFs, and review of the project databases
(interactive response technology¸ clinical and safety databases, vendor database for e -diary
data, and programmatic output from the clinical datab ase). All PDs were documented in a
designated clinical trial management s ystem.
Appendix 16.2.2 lists important PDs in all Phase 3 participants 12 through 15 y ears of age
that may have significantly impacted the completeness, accuracy , and/or reliability of the
study data or that may have significantly 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.
10.3. Vaccine Administration and Timing – Participants 12 Through 15 Years of Age
All adolescent participants who received Doses 1 and 2 were administered study intervention
as randomized . Three (0.3%) participants in the BNT162b2 group and 1 (0.1%) participant in
the placebo group were not vacc inated with an y study intervention (Table 5).
After unblinding, 89.4% of original adolescent placebo participants received Dose 3 (first
dose of BNT162b2 30 µg) and 87.7% received Dose 4 (second dose of BNT162b2 30 µg) at
the time of the data cutoff date.
The majority of participants received Dose 2 between 21 to 27 d ays after Dose 1 in the
BNT162b2 ( 65.0%) and placebo ( 64.5%) groups ( Table 6). After unblinding, most original
placebo participants received Dose 4 (second dose of BNT162b2 30 µg) between 14 to
20 (23.4%) daysand 21 to 27 ( 61.2% ) day s after Dose 3.
Table 5.Vaccine as Administered – Phase 2/3 Subjects 12 Through 15 Years of Age
–All Randomized Subjects
Vaccine Group (as Randomized)
Vaccine (as Adm inistered) BNT162b2 (30 μg)
(Na=1134)
nb(%)Placebo
(Na=1130)
nb(%)
Vaccinated 1131 (99.7) 1129 (99.9)
Not vaccinated 3 (0.3) 1 (0.1)
Dose 1
BNT162b2 (30 μg) 1131 (99.7) 0
Placebo 0 1129 (99.9)
Dose 2
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Page 55of 152Table 5.Vaccine as Administered – Phase 2/3 Subjects 12 Through 15 Years of Age
–All Randomized Subjects
Vaccine Group (as Randomized)
Vaccine (as Adm inistered) BNT162b2 (30 μg)
(Na=1134)
nb(%)Placebo
(Na=1130)
nb(%)
BNT162b2 (30 μg) 1128 (99.5) 0
Placebo 0 1119 (99.0)
Dose 3
First dose BNT162b2 (30 μg) 1010 (89.4)
Dose 4
Second dose BNT162b2 (30 μg) 992 (87.8)
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.
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Table 6.Vaccine Administration Timing –Phase 2/3 Subjects 12 Through 15 Years
of Age – All Randomized Subjects
Vaccine Group (as Randomized)
BNT162b2 (30 μg)
(Na=1134)
nb(%)Placebo
(Na=1130)
nb(%)
Randomized 1134 (100.0) 1130 (100.0)
Not vaccinated 3 (0.3) 1 (0.1)
Dose 1 1131 (99.7) 1129 (99.9)
Dose 2c1128 (99.5) 1119 (99.0)
Protocol defined window
<19 Days 2 (0.2) 1 (0.1)
19-23 Daysd1073 (94.6) 1065 (94.2)
>23 Days 53 (4.7) 53 (4.7)
Weekly Intervals
<14 Days 0 0
14-20 Days 358 (31.6) 364 (32.2)
21-27 Days 737 (65.0) 729 (64.5)
28-34 Days 23 (2.0) 15 (1.3)
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Page 56of 152Table 6.Vaccine Administration Timing –Phase 2/3 Subjects 12 Through 15 Years
of Age – All Randomized Subjects
Vaccine Group (as Randomized)
BNT162b2 (30 μg)
(Na=1134)
nb(%)Placebo
(Na=1130)
nb(%)
35-41 Days 4 (0.4) 4 (0.4)
42-48 Days 1 (0.1) 1 (0.1)
49-55 Days 1 (0.1) 3 (0.3)
>55 Days 4 (0.4) 3 (0.3)
Dose 3 (first dose of BNT162b2 [30 μg]) 1010 (89.4)
Dose 4 (second dose of BNT162b2 [30 μg])e992 (87.8)
Protocol defined window
<19 Days 6 (0.5)
19-23 Daysd905 (80.1)
>23 Days 81 (7.2)
Weekly Intervals
<14Days 0
14-20 Days 264 (23.4)
21-27 Days 691 (61.2)
28-34 Days 26 (2.3)
35-41 Days 5 (0.4)
42-48 Days 3 (0.3)
49-55 Days 2 (0.2)
>55 Days 1 (0.1)
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. Protocol -specified time fra me.
e. Days calculated since Dose 3.
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10.4. Data Sets Analyzed –Participants 12 Through 15 Years of Age
10.4.1. Safety Population –Participants 12 Through 15 Years of Age
The safet y population of adolescent participants included 1131 participants in the BNT162b2
group and 1129 participants in the placebo group (Table 7). Four participants were excluded
from the safety population because they did not receive an y stud y intervention .
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Page 57of 152Table 7.Safety Population – Phase 2/3 Subjects 12 Through 15 Years of Age
Vaccine Group (as Administered)
BNT162b2 (30 μg)
naPlacebo
naTotal
na(%)
Randomizedb2264
Vaccinated 1131 1129 2260 (99.8)
Safety population 1131 1129 2260 (99.8)
Excluded from safety population 4 (0.2)
Reason for exclusion
Subject did not receive study vaccine 4 (0.2)
a. n = Number of subjects with the specified characteristic, or the total sample.
b. This value is the denominator for the percentage calculations.
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During the blinded placebo -controlled follow -up period, median follow -up time for
adolescent participants was 4.4 months. There were 634 (56.1 %)and 629 ( 55.7%)of
participants in the BNT162b2 andplacebo groups, respectivel y,who had f ollow -up time
between ≥4 months to <6 months after Dose 2 ( Table 8). From Dose 2 to the cutoff date,
740 (65.4 %) of participants in the BNT162b2 group had a total f ollow -up time between ≥8 to
<10months, which was composed of blinded and unblinded exposure. There were few
participants (18 total) with follow -up time of <6 months, as most adolescent participants
12-15 years of age should have had ≥6 months of follow -up by the data cutoff date
(02September 2021) , and also corresponding with the number of participants who withdrew
from the study (Table 4).
For original adolescent placebo recipients who received at least the first dose of BNT162b2,
median follow -up time was 3.8 months, and 65.0% of these participants had f ollow -up time
between ≥2months to < 4months after Dose 1of BNT 162b2 ( Table 9).
Table 8.Follow -up Time After Dose 2 – Phase 2/3 Subjects 12 Through 15 Years of
Age –Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)
(Na=1131)
nb(%)Placebo
(Na=1129)
nb(%)Total
(Na=2260)
nb(%)
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Page 58of 152Table 8.Follow -up Time After Dose 2 – Phase 2/3 Subjects 12 Through 15 Years of
Age –Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)
(Na=1131)
nb(%)Placebo
(Na=1129)
nb(%)Total
(Na=2260)
nb(%)
Original blinded placebo -controlled follow -up period
<2 Months 45 (4.0) 62 (5.5) 107 (4.7)
≥2-<4 Months 300 (26.5) 294 (26.0) 594 (26.3)
≥4-<6 Months 634 (56.1) 629 (55.7) 1263 (55.9)
≥6 Months 152 (13.4) 144 (12.8) 296 (13.1)
Mean (SD) 4.5 (1.24) 4.4 (1.27) 4.4 (1.26)
Median 4.4 4.4 4.4
Min, max (0.0, 10.8) (0.0, 9.1) (0.0, 10.8)
Total follow -up period from Dose 2 to cutoff date
<2 Months 8 (0.7)
≥2-<4 Months 0
≥4-<6 Months 10 (0.9)
≥6-<8 Months 326 (28.8)
≥8-<10 Months 740 (65.4)
≥10 Months 47 (4.2)
Mean (SD) 8.3 (1.03)
Median 8.4
Min, max (0.0, 10.9)
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.
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Page 59of 152Table 9.Follow -up Time After Dose 1 of BNT162b2 –Phase 2/3 Subjects 12
Through 15 Years of Age (Subjects Who Originally Received Placebo) –
Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)
(Na=1010)
nb(%)
Open -label follow -up period
<2 Months 66 (6.5)
≥2-<4 Months 656 (65.0)
≥4-<6 Months 228 (22.6)
≥6 Months 60 (5.9)
Mean (SD) 3.8 (1.09)
Median 3.8
Min, max (0.1, 8.6)
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.
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10.4.2. Efficacy Populations – Updated Analysis –Participants 12 Through 15 Years of
Age
The proportions of participants included in the updated efficacy populations w eresimilar in
the BNT162b2 and placebo groups (Table 10).Most participants excluded from the
evaluable efficacy population were because they did not receive all vaccinations as
randomized or did not receive Dose 2 within the predefined window (19 -42 day s after
Dose 1).
Table 10.Efficacy Populations – Subjects 12 Through 15 Years of Age –Blinded
Placebo- Controlled Follow -up Period
Vaccine Group (as Randomized)
BNT162b2 (30 μg)
na(%)Placebo
na(%)Total
na(%)
Randomizedb1134 (100.0) 1130 (100.0) 2264 (100.0)
Dose 1 all -available efficacy population 1131 (99.7) 1129 (99.9) 2260 (99.8)
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Page 60of 152Table 10.Efficacy Populations – Subjects 12 Through 15 Years of Age –Blinded
Placebo- Controlled Follow -up Period
Vaccine Group (as Randomized)
BNT162b2 (30 μg)
na(%)Placebo
na(%)Total
na(%)
Subjects without evidence of infection before Dose 1 1083 (95.5) 1078 (95.4) 2161 (95.5)
Subjects excluded from Dose 1 all -available efficacy population 3 (0.3) 1 (0.1) 4 (0.2)
Reason for exclusionc
Did not receive at least 1 vaccination 3 (0.3) 1 (0.1) 4 (0.2)
Dose 2 all -available efficacy population 1123 (99.0) 1117 (98.8) 2240 (98.9)
Subjects without evidence of infection prior to 7 days after Dose
21061 (93.6) 1037 (91.8) 2098 (92.7)
Subjects excluded from Dose 2 all -available efficacy population 11 (1.0) 13 (1.2) 24 (1.1)
Reason for exclusionc
Did not receive 2 vaccinations 10 (0.9) 13 (1.2) 23 (1.0)
Unblinded prior to 7 days after Dose 2 1 (0.1) 0 1 (0.0)
Evaluable efficacy (7 days) population 1119 (98.7) 1109 (98.1) 2228 (98.4)
Subjects without evidence of infection prior to 7 days after Dose
21057 (93.2) 1030 (91.2) 2087 (92.2)
Subjects excluded from evaluable efficacy (7 days) population 15 (1.3) 21 (1.9) 36 (1.6)
Reason for exclusionc
Randomized but did not meet all eligibility criteria 1 (0.1) 1 (0.1) 2 (0.1)
Did not receive all vaccinations as randomized or did not receive
Dose 2
within the predefined window (19 -42 days after Dose 1)14 (1.2) 19 (1.7) 33 (1.5)
Unblinded prior to 7 days after Dose 2 1 (0.1) 0 1 (0.0)
Had other important protocol deviations on or prior to 7 days
after Dose 20 3 (0.3) 3 (0.1)
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.
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10.5. Demographic and Other Baseline Characteristics –Participants 12 Through 15
Years of Age
10.5.1. Safety Population – Participants 12 Through 15 Years of Age
10.5.1.1. Overall
Demographic characteristics for adolescents (12-15 years of age) were similar in the
BNT162b2 and placebo groups in the safet y population, and all adolescents were enrolled at
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Page 61of 152sites in the United States ( Table 11). Most adolescent participants in the BNT162b2 group
were White ( 85.8%), with 4.6% Black or African American participants and 6.4% Asian
participants, and other racial groups were ≤2.1%. There were 11.7% Hispanic/L atino
participants. The m edian age of adol escents in the BNT162b2 group was 14.0 years and
50.1% were male. Obese adolescents of this age group (based on age -and sex -specific BM I)
made up 11.3% (placebo group) to 12.6% (BNT162b2 group) .
Table 11.Demographic Characteristics – Phase 2/3 Subjects 12 Through 15 Years of
Age –Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)
(Na=1131)
nb(%)Placebo
(Na=1129)
nb(%)Total
(Na=2260)
nb(%)
Sex
Male 567 (50.1) 585 (51.8) 1152 (51.0)
Female 564 (49.9) 544 (48.2) 1108 (49.0)
Race
White 970 (85.8) 962 (85.2) 1932 (85.5)
Black or African American 52 (4.6) 57 (5.0) 109 (4.8)
All others 109 (9.6) 110 (9.7) 219 (9.7)
American Indian or Alaska Native 4 (0.4) 3 (0.3) 7 (0.3)
Asian 72 (6.4) 71 (6.3) 143 (6.3)
Native Hawaiian or other Pacific Islander 3 (0.3) 0 3 (0.1)
Multiracial 24 (2.1) 29 (2.6) 53 (2.3)
Not reported 6 (0.5) 7 (0.6) 13(0.6)
Racial designation
Japanese 5 (0.4) 2 (0.2) 7 (0.3)
Ethnicity
Hispanic/Latino 132 (11.7) 130 (11.5) 262 (11.6)
Non-Hispanic/non -Latino 997 (88.2) 996 (88.2) 1993 (88.2)
Not reported 2 (0.2) 3 (0.3) 5 (0.2)
Country
USA 1131 (100.0) 1129 (100.0) 2260 (100.0)
Baseline SARS -CoV -2 status
Positivec46 (4.1) 50 (4.4) 96 (4.2)
Negatived1083 (95.8) 1078 (95.5) 2161 (95.6)
Missing 2 (0.2) 1 (0.1) 3 (0.1)
Comorbiditiese
Yes 249 (22.0) 242 (21.4) 491 (21.7)
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Page 62of 152Table 11.Demographic Characteristics – Phase 2/3 Subjects 12 Through 15 Years of
Age –Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)
(Na=1131)
nb(%)Placebo
(Na=1129)
nb(%)Total
(Na=2260)
nb(%)
No 882 (78.0) 887 (78.6) 1769 (78.3)
Obesef
Yes 143 (12.6) 128 (11.3) 271 (12.0)
No 988 (87.4) 1001 (88.7) 1989 (88.0)
Age at vaccination (years)
Mean (SD) 13.6 (1.11) 13.6 (1.11) 13.6 (1.11)
Median 14.0 14.0 14.0
Min, max (12, 15) (12, 15) (12, 15)
Abbreviation: SARS -CoV -2 = severe acute respiratory syndrome coronavirus 2.
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.
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, negative NAAT result at Visit 1, and no medical history of COVID -
19.
e. Number of subjects who have 1 or more comorbidities that increase the risk of severe COVID -19 disease: defined as
subjects who had at least one of the Charlson comorbidity index category or BMI ≥95thpercentile.
f.Obese is defined as BMI ≥95thpercentile from the growth chart. Refer to the CDC growth char ts at
https://www.cdc.gov/growthcharts/html charts/bmiagerev htm.
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Overall, t here were 96 (4.2%) and 2161 (95.6%) participants who were baseline SARs -CoV -
2 positive and negative, respectivel y (Table 11,andSupplemental Tables 14.1 and 14.2).
Considering the baseline positive subgroup had fewer participants than the negative subgroup
overall, t here were no clinically meaningful differences in demographics in the 2 vaccine
groups bySARS -CoV -2 status.
Adolescent participants had a diverse medical history profile consistent with that of
individuals in the general population in the same age group ( Supplemental Table 14.3). For
adolescents i n the BNT162b2 group, conditions in the immune sy stem disorders
(399 [35. 3%]; of which 241 [21.3%] were seasonal allergy );psychiatric disorders
(293 [25.9%] , with frequently reported PTs of a ttention deficit hy peractivity disorder
(182 [16.1%]), anxiety (107 [9.5%]), and depression (51 [4.5%]); respiratory, thoracic, and
mediastinal disorders (179[15.8%]); and skin and subcutaneous tissue disorders (170
[15.0%]) SOCs were most frequentl y reported .
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Page 63of 152There were 123 (10.9%) and 136 (12.0%) participants in the BNT162 b2 and placebo groups,
respectivel y, who had any comorbidit y (per the Charlson comorbidity index) (Supplemental
Table 14.4), which was mostly chronic pulmonary disease (119 [10.5%] and 127 [11.2%]
participants, respectivel y).
10.5.1.2. Participants With At Least 6 Months Follow -Up Time –Original BNT162b2
Recipients 12 Through 15 Years of Age
Demographic characteristics for all original BNT162b2 adolescent recipients who had at
least 6 months of follow- up time after Dose 2 are presented in Supplemental Table 14.5 and
were similar to demographic characteristics i n the BNT162b2 group overall ( Table 11).
10.5.1.3. Original Placebo Recipients 12 Through 15 Years of Age Who Then Rece ived
BNT162b2
Demographic characteristics for all original placebo adolescent recipients who then received
BNT162b2 later during the open -label follow -up period are presented in Supplemental
Table 14.6 and were similar to demographic characteristics in the placebo group overall
(Table 11).
10.5.2. Evaluable Efficacy (7 Days) Po pulation –Blinded Placebo -Controlled Follow -up
Period –Participants 12 Through 15 Years of Age
Demographics of participants in the evaluable efficacy (7 day s) population for adolescent
participants without evidence of infection prior to 7 days after Dose 2 were similar in the
BNT162b2 and placebo groups ( Supplemental Table 14.7 ). This anal ysis population had
generall y similar demographics compared with the safet y population (refer to Section
10.5.1.1 ).
Demographic characteristics for the Dose 1all-available efficacy population and for
participants with or without evidence of infection prior to 7 days after Dose 2 (evaluable
efficacy [7 day s] population) were similar to those in the evaluable efficacy (7 day s)
population (Supplemental Tables 14.8and 14.9, respectively ).
10.6. Participant Compliance – P articipants 12 Through 15 Years of Age
10.6.1. Immunogenicity Blood Samples
Refer to the adolescent interim C4591001 CSR dated 14 April 2021, Section 10.6.1 for
details about immunogenicity blood samples taken in adolescent participants.
10.6.2. E- Diary
Refer to the adolescent interim C4591001 CSR dated 14 April 2021, Section 10.6.2 for
details oftransmission about e-diary data in adolescent participan ts.
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Page 64of 15210.7. Prior and Concomitant Vaccines, Medications, and Procedures –Participants 12
Through 15 Years of Age
A small percentage of adolescent participants in either group ( ≤2.8% ) received a concomitant
vaccine after Dose 1, and the most concomitant vaccine re ceived w astheinfluenza vaccine
(Supplemental Table 14.10 ).
11.EFFICACY EVALUATION
11.1. Updated Efficacy Results – Participants 12 Through 15 Years of Age
In this CSR, u pdated descriptive efficacy anal yses in adolescent participants 12 through
15years of age were performed with all cases accrued during blinded placebo -controlled
follow -up (through the cut -off date of 02 September 2021 ), including subgroup anal yses, and
for protocol -defined severe cases and CDC -defined severe cases .
11.1.1. Updated Analysis of Efficacy –Blinded Placebo -Controlled Follow -Up Period
11.1.1.1. Vaccine Efficacy From 7Days After Dose 2 – Updated Analysis
Among adolescent participants without evidence of SARS -CoV -2 infection before and
during the vaccination regimen, the estimated VE against confirmed COVID -19 occurring at
least 7 days after Dose 2 was 100.0% (2 -sided 95% CI : 86.8%, 100.0% ), with 0 and 28 cases
in the BNT162 b2 and placebo group s, respectivel y (Table 12).
The VEof BNT162b2 for the same efficacy endpoint based on the Dose 2 all- available
efficacy population was 100.0% (2 -sided 95% CI: 87.2%, 100.0% ), with 0and 29cases in
the BNT162b2 and placebo group , respectively (Supplemental Table 14.11).
Table 12.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 Effic acy (7 Days) Population
Vaccine Group (as Randomized)
BNT162b2 (30 μg)
(Na=1057)Placebo
(Na=1030)
Efficacy Endpoint
Subgroupn1bSurveillance
Timec(n2d)n1bSurveillance
Timec(n2d)VE (%) (95% CIe)
First COVID -19 occurrence from 7
days after Dose 20 0.343 (1043) 28 0.322 (1019) 100.0 (86.8, 100.0)
≥7 days after Dose 2 to <2 Months
after Dose 20 0.138 (1043) 15 0.133 (1019) 100.0 (73.2, 100.0)
≥2 Months after Dose 2 to <4
Months after Dose 20 0.148 (1008) 10 0.139 (957) 100.0 (58.0, 100.0)
≥4 Months after Dose 2 0 0.057 (723) 3 0.050 (682) 100.0 (-112.1, 100.0)
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Page 65of 152Table 12.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 Effic acy (7 Days) Population
Vaccine Group (as Randomized)
BNT162b2 (30 μg)
(Na=1057)Placebo
(Na=1030)
Efficacy Endpoint
Subgroupn1bSurveillance
Timec(n2d)n1bSurveillance
Timec(n2d)VE (%) (95% CIe)
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 detecte d by NAAT [nasal
swab] at Visits 1 and 2, and had negative 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 surveil lance period for
the overall row and from start to the end of the range stated for each time interval.
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 adjust ed for surveillance time.
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Among participants with or without evidence of SARS -CoV -2 infection before and during
the vaccination regimen, estimated VE against confirmed COVID -19 occurring at least
7days after Dose 2 was 100.0% (2 -sided 95% CI: 87.5%, 100.0% ), with 0and 30cases in
the BNT162b2 and placebo groups, respectively (Table 13).For the 2 additional cases in
adolescent participants with evidence of SARS -CoV -2 infection (ascompared with those
without evidence of infection from Table 12), both participants were SARS -CoV -2 negative
at baseline .
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Page 66of 152Table 13.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 Days) Population
Vaccine Group (as Randomized)
BNT162b2 (30 μg)
(Na=1119)Placebo
(Na=1109)
Efficacy Endpoint
Subgroupn1bSurveillance
Timec(n2d)n1bSurveillance
Timec(n2d)VE (%) (95% CIe)
First COVID -19 occurrence from 7
days after Dose 20 0.362 (1098) 30 0.345 (1088) 100.0 (87.5, 100.0)
≥7 days after Dose 2 to <2 Months
after Dose 20 0.146 (1098) 17 0.142 (1088) 100.0 (76.4, 100.0)
≥2 Months after Dose 2 to <4
Months after Dose 20 0.155 (1061) 10 0.148 (1022) 100.0 (57.4, 100.0)
≥4 Months after Dose 2 0 0.061 (767) 3 0.055 (726) 100.0 (-117.8, 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 for
the overa ll row and from start to the end of the range stated for each time interval.
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.
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11.1.1.1.1. Subgroup Analyses
In the evaluable efficacy (7 day s) population , among participants without and with or without
evidence of SARS -CoV -2 infection before and during the vaccination regimen, the estimated
VE was 100.0% for all subgroups (Table 14and Supplemental Table 14.1 2, respectivel y).
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Page 67of 152Table 14.Vaccine Efficacy – First COVID -19 Occurrence From 7 Days After Dose 2,
by Subgroup –Blinded Placebo -Controlled Follow -up Per iod –Subjects 12
Through 15 Years of Age and Without Evidence of Infection Prior to 7
Days After Dose 2 – Evaluable Efficacy (7 Days) Population
Vaccine Group (as Randomized)
BNT162b2 (30 μg)
(Na=1057)Placebo
(Na=1030)
Efficacy Endpoint
Subgroupn1bSurveillance
Timec(n2d)n1bSurveillance
Timec(n2d)VE (%) (95% CIe)
First COVID -19 occurrence from 7 days
after Dose 2
Overall 0 0.343 (1043) 28 0.322 (1019) 100.0 (86.8, 100.0)
Sex
Male 0 0.175 (524) 16 0.165 (526) 100.0 (75.5, 100.0)
Female 0 0.169 (519) 12 0.157 (493) 100.0 (66.5, 100.0)
Race
White 0 0.293 (898) 26 0.272 (867) 100.0 (85.8, 100.0)
Black or African American 0 0.017 (41) 2 0.018 (49) 100.0 (-470.9, 100.0)
Ethnicity
Hispanic/Latino 0 0.042 (119) 7 0.036 (113) 100.0 (41.2, 100.0)
Non-Hispanic/non -Latino 0 0.300 (922) 21 0.285 (903) 100.0 (81.7, 100.0)
Country
USA 0 0.343 (1043) 28 0.322 (1019) 100.0 (86.8, 100.0)
Comorbiditiesf
Yes 0 0.078 (230) 9 0.068 (213) 100.0 (55.5, 100.0)
No 0 0.266 (813) 19 0.254 (806) 100.0 (79.5, 100.0)
Obeseg
Yes 0 0.046 (134) 6 0.036 (110) 100.0 (33.9, 100.0)
No 0 0.298 (909) 22 0.287 (909) 100.0 (82.4, 100.0)
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Page 68of 152Table 14.Vaccine Efficacy – First COVID -19 Occurrence From 7 Days After Dose 2,
by Subgroup –Blinded Placebo -Controlled Follow -up Per iod –Subjects 12
Through 15 Years of Age and Without Evidence of Infection Prior to 7
Days After Dose 2 – Evaluable Efficacy (7 Days) Population
Vaccine Group (as Randomized)
BNT162b2 (30 μg)
(Na=1057)Placebo
(Na=1030)
Efficacy Endpoint
Subgroupn1bSurveillance
Timec(n2d)n1bSurveillance
Timec(n2d)VE (%) (95% CIe)
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 negative 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.
f.Comorbidities are defined as having at least one of the Charlson comorbidity index category or obesity (BMI ≥95th
percentile).
g. Obese is defined as BMI ≥95thpercentile from the growth chart. Refer to the CDC growth charts at
https://www.cdc.gov/growthcharts/html charts/bmiagerev htm.
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11.1.1.2. All Confirmed Cases of COVID -19 After Dose 1 – All- Available Efficacy
Population
All reports of COVID -19 with onset at any time after Dose 1 are accounted for in Table 15,
which provides a summary of VEfor all adolescent participants in the Dose 1 all -available
efficacy (modified intention -to-treat) population adjusted for exposure , regardless of
evidence of i nfection before or during the vaccination regimen. Among these participants, the
estimated VE against confirmed COVID -19 occurring after Dose 1 was 94.0% (2 -sided 95%
CI: 81.3%, 98.8%), with 3and 48 cases of COVID -19 in the BNT162b2 and placebo group s,
respectivel y. All3 cases in the BNT162b2 group occurred <11days after Dose 1and in
participants who had baseline SARS -CoV -2 negative status , and represented all cases
reported in this group at any time.
The observed VE for BNT162b2 in adolescents in the Dose 1 all -available efficacy population
was 100.0% (ie, all cases were confined to the placebo group) for all time intervals starting
from ≥11days after Dose 1 to before Dose 2 through ≥4months after Dose 2.
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Page 69of 152Table 15.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
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
13 0.450 (1109) 48 0.434 (1114) 94.0 (81.3, 98.8)
After Dose 1 to before Dose 2 3 0.065 (1109) 12 0.065 (1114) 75.1 (7.6, 95.5)
After Dose 1 to <11 days after Dose
13 0.033 (1109) 4 0.033 (1114) 24.7 (-345.0, 89.0)
≥11 Days after Dose 1 to before
Dose 20 0.032 (1106) 8 0.031 (1110) 100.0 (42.0, 100.0)
Dose 2 to 7 days after Dose 2 0 0.021 (1103) 5 0.021 (1100) 100.0 (-8.7, 100.0)
≥7 Days after Dose 2 0 0.364 (1102) 31 0.348 (1095) 100.0 (87.9, 100.0)
≥7 days after Dose 2 to <2 Months
after Dose 20 0.146 (1102) 17 0.143 (1095) 100.0 (76.3, 100.0)
≥2 Months after Dose 2 to <4
Months after Dose 20 0.156 (1065) 10 0.149 (1029) 100.0 (57.3, 100.0)
≥4 Months after Dose 2 0 0.062 (770) 4 0.056 (732) 100.0 (-37.7, 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 perio d for COVID -19 case accrual is from Dose 1 to the end of the surveillance period for the overall
row and from start to the end of the range stated for each time interval.
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.
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The early onset of protection is readily apparent in Figure 1, which display s cumulative
incidence for the first COVID -19 occurrence after Dose 1 among all vaccinated participants
based on Dose 1 all -available efficacy (modified intention -to-treat) popul ation. Disease onset
appears to track together for BNT162b2 and placebo until approximately 11days after
Dose 1(consistent with the data shown in Table 15), at which point the curves diverge, with
cases steadil y accumulating in the placebo group, while remaining flat with no more cases in
the BNT162b2 group.
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Page 70of 152Figure 1. Cumulative Incidence Curves for the First COVID- 19 Occurrence After Dose 1 –Subjects 12 Through 15 Years of
Age –Blinded Placebo -Controlled Follow -up Period – Dose 1 All -Available Efficacy Population
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Page 71of 15211.1.1.2.1. Subgroup Analyses
Additionally , in subgroup anal ysesforVE based on the Dose 1 all -available efficacy
(modified intention -to-treat) population (Supplemental Table 14.13 ), the observed subgroup
VEs based on the Dose 1 all- available population were generally similar to those based on
the evaluable efficacy population except for a few subgroups that the number of participants
and cases were too small to provide robust estimates . The observed VEs for all subgroup s
were ≥88.7% ex cept for one subgroup ( race, all others) with 1 case in each group :American
Indian or Alaska native in placebo and Asian in BNT162b2. Due to the small number of
partic ipants, the data must be interpreted with caution .
11.1.2. Updated Analysis of Severe COVID -19 Cases
No severe COVID -19 cases (per protocol definition or CDC criteria) were reported in
participants 12 -15years of age as of the data cutoff date ( 02 September 2021)
(Appendix 16.2.8.1.1 ).
11.1.2.1. COVID -19 Narratives – Updated Analysis
One participant in the pl acebo group had multiple positive COVI D-19 NAAT results
(Appendix 16.2.8.4.1 ). The n arrative for this participant is provided in Section 14 COVI D-19
Case (Severe and/or Multiple) .
11.1.3. Variants of Concern
Among the 30 placebo participants with or without evidence of SARS -CoV -2 infection
before and during the vaccination regimen and had COVID -19 cases , most variants
sequenced were neither VOI nor VOC except for the B.1.1.7 (Alpha) (Table 17), which was
found in 23.3% of placebo participants ( Table 16). There were no cases belonging to the
Beta, Gamma, Delta, Lambda, or Mu variants ( Table 17). Importantl y, all of the cases in the
efficacy anal yses occurred between 02November 2020 to 19 May 2021 , which is before the
Delta surge in the US. ( Appendix 16.2.8. 1.2).
Table 16.Summary of SARS -CoV -2 Variants for the 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
Infecti on Prior to 7 Days After Dose 2 – Evaluable Efficacy (7 Days)
Population
Vaccine Group (as Randomized)
BNT162b2 (30 μg)
(Na=0)Placebo
(Na=30)Total
(Na=30)
SARS -CoV -2 Lineageb
(WHO Classification)nc(%) nc(%) nc(%)
B.1 0 1 (3.3) 1 (3.3)
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Page 72of 152Table 16.Summary of SARS -CoV -2 Variants for the 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
Infecti on Prior to 7 Days After Dose 2 – Evaluable Efficacy (7 Days)
Population
Vaccine Group (as Randomized)
BNT162b2 (30 μg)
(Na=0)Placebo
(Na=30)Total
(Na=30)
SARS -CoV -2 Lineageb
(WHO Classification)nc(%) nc(%) nc(%)
B.1.1.222 0 1 (3.3) 1 (3.3)
B.1.1.29 0 1 (3.3) 1 (3.3)
B.1.1.519 0 1 (3.3) 1 (3.3)
B.1.1.7 (Alpha) 0 7 (23.3) 7 (23.3)
B.1.142 0 1 (3.3) 1 (3.3)
B.1.2 0 10 (33.3) 10 (33.3)
B.1.243 0 1 (3.3) 1 (3.3)
B.1.361 0 1 (3.3) 1 (3.3)
B.1.369 0 1 (3.3) 1 (3.3)
B.1.400 0 1 (3.3) 1 (3.3)
B.1.427 0 2 (6.7) 2 (6.7)
B.1.526 0 1 (3.3) 1 (3.3)
Unknownd0 1 (3.3) 1 (3.3)
Abbreviation: SARS -CoV -2 = severe acute respiratory syndrome coronavirus 2.
a. N = number of subjects with first COVID -19 occurrence. This value is the denominator for the percentage
calculations.
b. Based on PANGO lineages (cov -lineages.org).
c. n = Number of subjects with the specified characteristic.
d. Include indeterminate result and not quantifiable (QNS) samples.
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Page 73of 152Table 17.Summary of SARS -CoV -2 Variants of Concern or Variants of Interest for
the 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 o f Infection Prior to 7 Days After Dose
2 –Evaluable Efficacy (7 Days) Population
Vaccine Group (as Randomized)
BNT162b2 (30 μg)
(Na=0)Placebo
(Na=30)Total
(Na=30)
SARS -CoV -2 Lineageb
(WHO Classification)nc(%) nc(%) nc(%)
B.1.1.7 (Alpha) 0 7 (23.3) 7 (23.3)
B.1.351 (Beta) 0 0 0
P.1 (Gamma) 0 0 0
B.1.617.2 (Delta) 0 0 0
C.37 (Lambda) 0 0 0
B.1.621 (Mu) 0 0 0
Other 0 22 (73.3) 22 (73.3)
Unknownd0 1 (3.3) 1 (3.3)
Abbreviation: SARS -CoV -2 = severe acute respiratory syndrome coronavirus 2.
a. N = number of subjects with first COVID -19 occurrence. This value is the denominator for the percentage
calculations.
b. Based on PANGO lineages (cov -lineages.org).
c. n = Number of subjects with the specified characteristic.
d. Include indeterminate result and not quantifiable (QNS) samples.
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11.2. Efficacy Conclusions –Updated Analysis –Participants 12 Through 15 Years of
Age
In the updated descriptive efficacy anal ysis (data cutoff date 02 September 2021),
among participants in the evaluable efficacy population without evidence of SARS -
CoV -2 infection before and during the vaccination regimen, the estimated VE against
confirmed COVID -19 occurring at least 7 day s after Dose 2 was 100% (2 -sided 95%
CI: 86.8%, 100%), with 0 cases in the BNT162b2 group and 28 cases in the placebo
group. Among participants with or without evidence of SARS -CoV -2 infection before
and during the vaccination regimen, the estimated VE against confirmed COVID -19
occurr ing at least 7 day s after Dose 2 was 100% (2-sided 95% CI: 87.5%, 100%),
with 0and 30cases in the BNT162b2 and placebo groups, respectively .For the
2 additional cases in adolescent participants with evidence of SARS- CoV -2 infection
as compared with those without evidence of infection, both participants were SARS-
CoV -2 negative at baseline.
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Page 74of 152Among participants without and with or without evidence of SARS -CoV -2 infection
before and during the vaccination regimen (evaluable efficacy population), VE
against C OVID -19 occurring at least 7 day s after Dose 2 was evaluated for
demographic and risk subgroups, and the estimated VE was 100.0% for all
subgroups .
From the analy sis of a ll cases of confirmed COVID -19 based onthe all- available
(modified intention -to-treat) population (regardless of evidence of infection before or
during the vaccination regimen) ,the estimated VE against all cases occurring at any
time after Dose 1 was 94.0% (2 -sided 95% CI: 81.3%, 98.8%), with 3cases in the
BNT162b2 group (all occurring within <11 day s after Dose 1 and in participants who
had baseline SARS -CoV -2 negative status) and 48cases in the placebo group.
No severe COVID -19 cases (per protocol definition or CDC criteria) were reported in
participants 12 -15 years of age as of the data cutoff date (02 September 2021) .
Most variants sequenced were neither VOI nor VOC except for the B.1.1.7 (Alpha)
found in 23.3% of placebo participants. A ll of the cases in the efficacy analy ses
occurred be tween 02 November 2020 to 19 May 2021, which is before the Delta
surge in the US.
12.SAFETY EVALUATION
Refer to the C4591001 6- Month Update I nterim CSR ,dated 29 April 2021, Sections 12.1 and
12.2,for details of safet y evaluations previousl y conducted in Phase 1and Phase 2/3 of the
study (aspreviousl y submitted ).
12.1. Local Reactions and Systemic Events – P articipants 12 Through 15 Years of Age
There are no new reactogenicity data presented in this report since the adolescent interim
CSR, dated 14 April 2021.
The majority of reactogenicity events previously reported in adolescent participants were
mild or moderate in severity and short -lived after dosing ( ie, median onset mostly between
1-3days after dosing and resolution within 1 -3days after onset ) (full details in
Section s 12.1.1 and 12.1.2 of the adolescent interim C4591001 CSR dated 14April 2021).
12.2. Adverse Events –Participants 12 Through 15 Years of Age
AE safet y data are from either the blinded placebo -controlled follow -up period, the
open -label observational follow -up period, or both. The time periods and safety anal ysis
groups are presented below and in Figure 2. AEs reported from Dose 1 to 1 month after
Dose 2 during the blinded placebo- controlled foll
…[truncated]

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