Document text
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
1.TITLE PAGE
Vaccine Name and
Compound Number:BNT162 RNA -Based COVID -19 Vaccines, Compound
Number: PF -07302048
Report Title: Interim Report –6 Month Update : A Phase 1/2/3,
Placebo- Controlled, Randomized, Observer -Blind, Dose -
Finding Stud y to Evaluate the Safet y, Tolerability,
Immunogenicit y, and Efficacy of SARS -COV -2 RNA
Vaccine Candidates Against COVI D-19 in Healthy
Individuals
Protocol Number: Protocol C4591001
Sponsor: BioNTech SE
Sponsor Agent: Pfizer I nc
Phase of Development: Phase 1/2/3
First Subject First Visit: 29 April 2020
Primary Completion Date: Not applicable
Data Cutoff Date: 13March 2021
Serology Completion Dat es: 22 March 2021(Phase 1, Visit 8[post- Dose 2 blood draw]
assay completed)
Name and Affiliation of
Coordinating/Leading
Investigator:Stephen Thomas, MD
SUNY Upstate Medical University
725 Irving Ave, Ste. 311
Syracuse, NY 13210
The names of the principal investigators, site addresses,
and number of participants enrolled at each site are
provided in the appendix titled L ist and Description of
Investigators and Service Providers, Appendix 16.1.4 .
Sponsor’s Signatories: John L . Perez, MD, MBA, MA
Vice President, Vaccines Clinical Research and
Development, Pfizer Inc
090177e196e9d406\Approved\Approved On: 29-Apr-2021 16:30 (GMT)
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FDA-CBER-2021-5683-0782605
Interim Clinical Study Report
Protocol C4591001
CONFIDENTIAL
Kenneth Koury , PhD
Clinical Biostatistics Head, Vaccines Clinical Research
and Development, Pfizer Inc
Ugur Sahin, MD
Chief Executive Officer, BioNTech SE
Internal Reports Referenced: Final Anal ysis Interim CSR: C 4591001 dated
03December 2020
Date of Current Version: 29April 2021
Date(s) of Previous
Report(s):Not applicable
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.
090177e196e9d406\Approved\Approved On: 29-Apr-2021 16:30 (GMT)
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Protocol C4591001
CONFIDENTIAL2. SYNOPSI S
3. TABLE OF CONTENTS
1. TI TLE PAGE ................................ ................................ ................................ ..................... 1
2. SYNOPSI S................................ ................................ ................................ ......................... 3
3. TABLE OF CONTENTS ................................ ................................ ................................ ... 3
4. LIST OF ABBREVIATIONS AND DEFINITION OF TERMS ................................ ......
5. ETHI CS................................ ................................ ................................ ..............................
5.1. I ndependent Ethics Committee or I nstitutional Review Board................................ ...
5.2. Ethical Conduct of the Study ................................ ................................ .......................
5.3. Participant Information and Consent................................ ................................ ...........
6. INVESTIGATORS AND STUDY ADMINISTRATIVE STRUCTURE ........................
7. INTRODUCTION ................................ ................................ ................................ .............
8. STUDY OBJECTIVES AND ENDPOINTS ................................ ................................ .....
8.1. Phase 1 ................................ ................................ ................................ .........................
8.2. Phase 2/3................................ ................................ ................................ ......................
9. INVESTIGAT IONAL PL AN................................ ................................ ............................
9.1. Overall St udy Design and Plan ................................ ................................ ....................
9.1.1. Phase 1 ................................ ................................ ................................ ..................
9.1.2. Phase 2/3 ................................ ................................ ................................ ...............
9.2. Discussion of Study Design, Including Choice of Control Groups .............................
9.3. Participant Selection ................................ ................................ ................................ ....
9.4. I nvestigati onal Product ................................ ................................ ................................
9.4.1. Vaccines Administered ................................ ................................ .........................
9.4.2. I dentity of Investigational Product(s) ................................ ................................ ....
9.4.3. Method of Assigning Participants to Treatment Groups................................ .......
9.4.4. Selection of Dose Levels/Regimen ................................ ................................ .......
9.4.4.1. Phase 1 ................................ ................................ ................................ ............
9.4.4.2. Phase 2/3................................ ................................ ................................ .........
9.4.5. Blinding................................ ................................ ................................ .................
9.4.6. Prior and Concomitant Vaccines, Medications, and Procedures ..........................
9.4.7. Vaccine Compliance ................................ ................................ .............................
9.5. Efficacy , Immunogenicity , and Safet y Evaluations ................................ ....................
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CONFIDENTIAL9.5.1. Efficacy and Immunogenicity Evaluations ................................ ...........................
9.5.2. Safet y Evaluations ................................ ................................ ................................ .
9.5.2.1. Clinic al Safety Laboratory Evaluations (Phase 1 Participants Onl y).............
9.5.2.2. Electronic Diary ................................ ................................ ..............................
9.5.2.3. Phase 1 Stopping Rules ................................ ................................ ...................
9.5.2.4. Surveillance of Events That Could Represent Vaccine -Associated
Enhanced COVID -19 and Phase 2/3 Stopping Rule ................................ ............
9.5.2.5. Adverse Events and Serious Adverse Eve nts................................ .................
9.5.2.6. 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. Analysis Sets ................................ ................................ ................................ ...
9.7.2. Determination of Sample Size ................................ ................................ ..............
9.7.3. Efficacy Anal ysis................................ ................................ ................................ ..
9.7.4. I mmunogenicit y Analysis ................................ ................................ .....................
9.7.5. Safet y Anal ysis................................ ................................ ................................ ......
9.7.6. Other Anal yses................................ ................................ ................................ ......
9.7.7. Analy sis Timing ................................ ................................ ................................ ....
9.8. Changes in the Conduct of Study or Planned Analy ses................................ ..............
10. STUDY PARTI CIPANTS ................................ ................................ ...............................
10.1. Disposition of Participants ................................ ................................ .........................
10.1.1. Phase 1 ................................ ................................ ................................ ................
10.1.2. Phase 2/3 Participants ≥16 Years of Age ................................ ..........................
10.1.2.1. Blinded Placebo -Controlled Follow- Up Period ................................ ............
10.1.2.2. Open- Label Follow -Up Period ................................ ................................ .....
10.2. Protocol Deviations ................................ ................................ ................................ ...
10.3. Vaccine Administration and Timing ................................ ................................ .........
10.3.1. Phase 1 ................................ ................................ ................................ ................
10.3.2 . Phase 2/3 Participants ≥16 Years of Age ................................ ..........................
10.4. Data Sets Anal yzed................................ ................................ ................................ ....
10.4.1. Phase 1 ................................ ................................ ................................ ................
10.4.2. Phase 2/3 ................................ ................................ ................................ .............
10.4.2.1. Safet y Population – Phase 2/3 Participants ≥16 Years of Age .................
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CONFIDENTIAL10.4.2.2. Efficacy Populations –Updated Anal ysis................................ ....................
10.5. Demographic and Other Baseline Characteristics ................................ .....................
10.5.1. Phase 1 ................................ ................................ ................................ ................
10.5.2. Phase 2/3 ................................ ................................ ................................ .............
10.5.2.1. Safet y Population – Participants ≥16 Years of Age ................................ ..
10.5.2.1.1. Overall ................................ ................................ ................................ ....
10.5.2.1.1.1. Participants With Confirmed Stable HIV Disease ...........................
10.5.2.1.2. Participants With At L east 6 Months Follow -Up Time – Original
BNT162b2 Participants ................................ ................................ .....................
10.5.2.1.3. Original Placebo Participants Who Then Received BNT162b2 ............
10.5.2.2. All Participants ................................ ................................ .............................
10.5.2.3. Evaluable Efficacy (7 Day s) Population – Blinded Placebo -Controlled
Follow -Up Period ................................ ................................ ................................ .
10.6. Participant Compliance ................................ ................................ ..............................
10.6.1. I mmunogenicit y Blood Samples ................................ ................................ .........
10.6.1.1. Phase 1 ................................ ................................ ................................ ..........
10.6.1.2. Phase 2/3................................ ................................ ................................ .......
10.6.2. E- Diary ................................ ................................ ................................ ................
10.6.2.1. Phase 1 and Phase 2 ................................ ................................ ......................
10.6.2.2. Phase 2/3................................ ................................ ................................ .......
10.7. Prior and Concomitant Vaccines, Medications, and Procedures ...............................
10.7.1. Phase 1 ................................ ................................ ................................ ................
10.7.2. Phase 2/3 Participants ≥16 Years of Age ................................ ..........................
11. EFFI CACY AND IMMUNOGENICITY EVALUATION................................ .............
11.1. Efficacy Results ................................ ................................ ................................ .........
11.1.1. I nterim Anal ysis 1 and Fina l Analy sis of Efficacy ................................ .............
11.1.2. Updated Anal ysis of Efficacy ................................ ................................ .............
11.1.2.1. Updated Anal ysis of Primary Endpoints ................................ ......................
11.1.2.1.1. Vaccine Efficacy Without Prio r Evidence of SARS -CoV -2 Infection –
7 Day s After Dose 2 – Updated Anal ysis................................ .........................
11.1.2.1.2. Vaccine Efficacy With or Without Prior Evidence of SARS -CoV -2
Infection – 7 Day s After Dose 2 –Updated Anal ysis................................ .......
11.1.2.1.3. All Confirmed Cases of COVID -19 After Dose 1 – All- Availa ble
Efficacy Population ................................ ................................ ...........................
11.1.2.1.4. Vaccine Efficacy by Subgroup – Updated Anal ysis..............................
11.1.2.1.4.1. Subgroups of Age, Sex, Race, Ethnicity , and Country ....................
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CONFIDENTIAL11.1.2.1.4.2. Subgroup Analy ses b y Risk Status ................................ ..................
11.1.2.1.4.3. Subgroup Analy ses b y Comorbidit y Status ................................ .....
11.1.2.2. Updated Anal ysis of Secondary Endpoints ................................ ..................
11.1.2.2.1. Efficacy for Severe COVID- 19 Cases –Updated Anal ysis...................
11.1.2.2.1.1. Participants Without Evidence of I nfection Before an d During
Vaccination Regimen ................................ ................................ .....................
11.1.2.2.1.2. Participants With or Without Evidence of Infection Before and
During Vaccination Regimen ................................ ................................ ........
11.1.2.2.1.3. All Confirmed Cases of Severe COVID -19 After Dose 1 – All-
Available Population................................ ................................ ......................
11.1.2.2.1.4. Vaccine Efficacy for Severe COVID- 19 Cases per CDC
Definition – Updated Analy sis................................ ................................ .......
11.1.2.2.1.5. COVID -19 Narratives – Updated Analy sis................................ .....
11.1.2.3. Signs and Sy mptoms of COVI D-19 ................................ .............................
11.1.2.4. Efficacy Conclusions –Updated Anal ysis................................ ....................
11.2. I mmunogenicit y Results ................................ ................................ ............................
11.2.1. Phase 1 ................................ ................................ ................................ ................
11.2.1.1. GMTs and GMCs ................................ ................................ ..........................
11.2.1.2. GMFRs ................................ ................................ ................................ ..........
11.2.1.3. GMRs ................................ ................................ ................................ ............
11.2.1.4. Number (%) of Particip ants Achieving a ≥4-Fold Rise from Baseline ......
11.2.1.5. Phase 1 I mmunogenicity Conclusions ................................ ..........................
11.2.2. Phase 2/3 ................................ ................................ ................................ .............
12. SAFETY EVALUATION ................................ ................................ ...............................
12.1. Phase 1 ................................ ................................ ................................ .......................
12.1.1. L ocal Reacti ons and Sy stemic Events –Phase 1 ................................ ................
12.1.2. Adverse Events – Phase 1 ................................ ................................ ...................
12.1.2.1. Summary of Adverse Events –Phase 1 ................................ ........................
12.1.2.2. Analy sis of Adverse Events –Phase 1 ................................ ..........................
12.1.3. Deaths, Serious Adverse Events, Safet y-Related Participant Withdrawals, and
Other Significant Adverse Events –Phase 1 ................................ ...........................
12.1.3.1. Deaths – Phase 1 ................................ ................................ ...........................
12.1.3.2. Serious Adverse Events –Phase 1 ................................ ................................
12.1.3.3. Safet y-Related Participant Withdrawals –Phase 1 ................................ .......
12.1.3.4. Other Significant Adverse Events –Phase 1 ................................ ................
12.1.3.5. Other Safet y Assessments –Phase 1 ................................ ............................
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CONFIDENTIAL12.1.3.5.1. Pregnancy –Phase 1 ................................ ................................ ...............
12.1.3.6. Analy sis and Discussion of Deaths, Serious Adverse Events, Safety -
Related Participant Withdrawals, and Other Significant Adverse Events –
Phase 1 ................................ ................................ ................................ ..................
12.1.4. Clinical L aboratory Evaluation –Phase 1 ................................ ...........................
12.1.5. Phy sical Examination Findings –Phase 1 ................................ ..........................
12.1.6. Phase 1 Safet y Conclusions ................................ ................................ ................
12.2. Phase 2/3................................ ................................ ................................ ....................
12.2.1. L ocal Reactions –Phas e 2/3 Participants ≥16 Years of Age ..........................
12.2.1.1. Participants with Confirmed Stable HIV Disease ................................ .........
12.2.2. Sy stemic Events –Phase 2/3 Participants ≥16 Years of Age ..........................
12.2.2.1. Participants with Confirmed Stable HIV Disease ................................ .........
12.2.3. Adverse Events – Phase 2/3 Participants ≥16 Years of Age ...........................
12.2.3.1. Blinded Placebo -Controlled Follow- Up Period From Dose 1 to 1 Month
After Dose 2 ................................ ................................ ................................ ..........
12.2.3.1.1. Summary of Adverse Events – Blinded Placebo -Controlled Follow -
Up Period From Dose 1 to 1 Month After Dose 2 ................................ ............
12.2.3.1.1.1. Participants with Confirmed Stable HIV Disease –Blinded
Placebo- Controlled Follow -Up Period From Dose 1 to 1 Month After Dose
2................................ ................................ ................................ ......................
12.2.3.1.2. Analy sis of Adverse Events –Blinded Placebo -Controlled Follow -Up
Period From Dose 1 to 1 Month After Dose 2 ................................ ..................
12.2.3.1.2.1. Adverse Events by System Organ Class and Preferred Term –
Blinded Placebo -Controlled Follow- Up Period From Dose 1 to 1 Month
After Dose 2 ................................ ................................ ................................ ...
12.2.3.1.2.1.1. Participants with Confirmed Stable HIV Disease –Blinded
Placebo- Controlled Follow -Up Period From Dose 1 to 1 Month After
Dose 2 ................................ ................................ ................................ .........
12.2.3.1.2.2. Related Adverse Events b y System Organ Class and Preferred
Term –Blinded Placebo -Controlled Follow- Up Period From Dose 1 to 1
Month After Dose 2 ................................ ................................ .......................
12.2.3.1.2.3. I mmediate Adverse Events – Blinded Placebo -Controlled Follow -
Up Period From Dose 1 to 1 Month After Dose 2 ................................ .........
12.2.3.1.2.4. Severe or Life-Threatening Adverse Events –Blinded Placebo -
Controlled Follow- Up Period From Dose 1 to 1 Month After Dose 2 ..........
12.2.3.2. Blinded Placebo -Controlled Follow- Up Period From Dose 1 to the
Unblinding Date ................................ ................................ ................................ ...
12.2.3.2.1. Summary of Adverse Events – Blinded Placebo -Controlled Follow -
Up Period From Dose 1 to the Unblinding Date ................................ ...............
12.2.3.2.1.1. Participants with Confirmed Stable HIV Disease –Blinded
Placebo- Controlled Follow -Up Period From Dose 1 to the Unblinding
Date ................................ ................................ ................................ ................
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CONFIDENTIAL12.2.3.2.2. Analy sis of Adverse Events –Blinded Placebo -Controlled Follow -Up
Period From Dose 1 to the Unblinding Date................................ .....................
12.2.3.2.2.1. Adverse Events by System Organ Class and Preferred Term –
Blinded Placebo -Controlled Follow- Up Period From Dose 1 to the
Unblinding Date ................................ ................................ .............................
12.2.3.2.2.1.1. Participants with Confirmed Stable HIV Disease –Blinded
Placebo- Controlled Follow -Up Period From Dose 1 to the Unblinding
Date ................................ ................................ ................................ .............
12.2.3.2.2.2. Related Adverse Events b y System Organ Class and Preferred
Term –Blinded Placebo -Controlled Follow- Up Period From Dose 1 to the
Unblinding Date ................................ ................................ .............................
12.2.3.2.2.3. Severe or Life-Threatening Adverse Events –Blinded Placebo -
Controlled Follow- Up Period From Dose 1 to the Unblinding Date .............
12.2.3.3. Open- Label Follow -Up Period – Original BNT162b2 Participants .............
12.2.3.3.1. Summary of Adverse Events – Open -Label Follow -Up Period –
Original BNT162b2 Participants ................................ ................................ .......
12.2.3.3.2. Analy sis of Adverse Events – Open -Label Follow -Up Period –
Original BNT162b2 Participants ................................ ................................ .......
12.2.3.3.2.1. Adverse Events by System Organ Class and Pr eferred Term –
Open -Label Follow -Up Period – Original BNT162b2 Participants ..............
12.2.3.3.2.2. Related Adverse Events b y System Organ Class and Preferred
Term –Original BNT162b2 Participants ................................ .......................
12.2.3.4. Blinded Placebo -Controlled and Open -Label Follow -Up Periods From
Dose 1 t o 6 Months After Dose 2 – Original BNT162b2 Participants .................
12.2.3.4.1. Summary of Adverse Events – Blinded Placebo -Controlled and Open-
Label Follow -Up Periods From Dose 1 to 6 Months After Dose 2 – Original
BNT162b2 Participants ................................ ................................ .....................
12.2.3.4.2. Analy sis of Adverse Events –Blinded Placebo- Controlled and Open-
Label Follow -Up Periods From Dose 1 to 6 Months After Dose 2 – Original
BNT162b2 Participants ................................ ................................ .....................
12.2.3. 4.2.1. 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 Participants ..........
12.2.3.4.2.2. 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 Participants
12.2.3.5. Open- Label Follow -Up Period – Original Placebo Participants Who Then
Received BNT162b2 ................................ ................................ ............................
12.2.3.5.1. Summary of Adverse Events – Open -Label Follow -Up Period –
Original Placebo Participants Who Then Received BNT162b2 .......................
12.2.3.5.2. Analy sis of Adverse Events –Open -Label Follow -Up Period –
Original Placebo Participants Who Then Received BNT162b2 .......................
12.2.3.5.2.1. Adverse Events by System Organ Class and Preferred Term –
Open -Label Follow -Up Period – Original Placebo Participants Who Then
Received BNT162b2 ................................ ................................ ......................
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CONFIDENTIAL12.2.3.5.2.2. Related Adverse Events b y System Organ Class and Preferred
Term –Open -Label Follow -Up Period – Original Placebo Participants
Who Then R eceived BNT162b2 ................................ ................................ ....
12.2.3.5.2.3. I mmediate Adverse Events – Open -Label Follow -Up Period –
Original Placebo Participants Who Then Received BNT162b2 ....................
12.2.3.5.2.4. Severe or Life-Threatening Adverse Events –Open -Label Follow -
Up Period – Original Placebo Participants Who The n Received BNT162b2
12.2.3.6. Open- Label Follow -Up Period – Original Placebo Participants, had
COVID -19 Occurrence After Dose 1, and Th en Received BNT162b2 ...............
12.2.3.6.1. Summary of Adverse Events – Original Placebo Participants, had
COVID -19 Occurrence After Dose 1, and T hen Received BNT162b2 ............
12.2.3.6.2. Analy sis of Adverse Events –Original Placebo Participants, had
COVID -19 Occurrence After Dose 1, and Then Received BNT162b2 ............
12.2.4. Deaths, Serious Adverse Events, Safet y-Related Participant Withdrawals, and
Other Significant Adverse E vents – Phase 2/3 Participants ≥16 Years of Age ...
12.2.4.1. Deaths ................................ ................................ ................................ ...........
12.2.4.1.1. Death Narratives ................................ ................................ .....................
12.2.4.2. Serious Adverse Events ................................ ................................ ................
12.2.4.2.1. Blinded Placebo -Controlled Follow- Up From Dose 1 to 1 Month
After Dose 2 ................................ ................................ ................................ ......
12.2.4.2.1.1. Participants with Confirmed Stable HIV Disease ............................
12.2.4.2.2. Blinded Place bo-Controlled Follow- Up Period From Dose 1 to the
Unblinding Date ................................ ................................ ................................
12.2.4.2.2.1. Participants with Confirmed Stable HIV Disease ............................
12.2.4.2.3. Open -Label Follow -Up Period – Original BNT162b2 Participants .......
12.2.4.2.4. Blinded Placebo -Controlled and Open -Label Follow -Up Periods to 6
Months After Dose 2 –Original BNT162b2 Participants ................................ .
12.2.4.2.5. Open -Label Follow -Up Period – Original Placebo Participants Who
Then Received BNT162b2 ................................ ................................ ................
12.2.4.2.6. Open -Label Follow -Up Period – Original Placebo Participants, had
COVID -19 Occurrence After Dose 1, and Then Received BNT162b2............
12.2.4.2.7. Serious Adverse Event Narratives –Phase 2/3 ................................ ......
12.2.4.3. Safet y-Related Participant Withdrawals –Phase 2/3 ................................ ...
12.2.4.3.1. Blinded Placebo -Controlled Follow- Up Period From Dose 1 to 1
Month After Dose 2 ................................ ................................ ...........................
12.2.4.3.2. Blinded Placebo -Controlled Follow- Up Period From Dose 1 to the
Unblinding Date ................................ ................................ ................................
12.2.4.3.3. Open -Label Follow -Up Period – Original BNT162b2 Participants .......
12.2.4.3.4. Blinded Placebo -Cont rolled and Open -Label Follow -Up Periods to 6
Months After Dose 2 –Original BNT162b2 Participants ................................ .
12.2.4.3.5. Open -Label Follow -Up Peri od –Original Placebo Participants Who
Then Received BNT162b2 ................................ ................................ ................
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CONFIDENTIAL12.2.4.3.6. Open -Label Follow -Up Period – Original Placebo Participants, had
COVID -19 Occurrence After Dose 1, and Then Received BNT162b2............
12.2.4.3.7. Narratives of Safety -Related Participant Withdrawals –Phase 2/3 .......
12.2.4.4. Other Significant Adverse Events –Phase 2/3 ................................ .............
12.2.4.4.1. FDA -Requested Adverse Events of Clinical Interest .............................
12.2.4.4.1.1. Hy persensit ivity/Anaphy laxis ................................ ..........................
12.2.4.4.1.2. Bell’s Pals y/Facial Paral ysis................................ ............................
12.2.4.4.1.3. Ly mphadenopathy ................................ ................................ ............
12.2.4.4.1.4. Appendicitis ................................ ................................ .....................
12.2.4.4.2. CDC Adverse Events of Special Interest – Select Standard MedDRA
Queries for COVID -19................................ ................................ ......................
12.2.4.4.3. Other Non- CDC Adverse Events of Special Interest –Select Standard
MedDRA Queries for COVID -19 ................................ ................................ .....
12.2.4.4.4. Narratives of Other Significant Adverse Events –Phase 2/3 .................
12.2.4.5. Other Safet y Assessments –Phase 2/3 ................................ .........................
12.2.4.5.1. Severe COVID -19 Illness – Phase 2/3 ................................ ...................
12.2.4.5.2. Pregnancy –Phase 2/3 (BNT162b2 Recipients) ................................ ....
12.2.4.6. Analy sis and Discussion of Deaths, Serious Adverse Events, Safety -
Related Participant Withdrawals, and Other Significant Adverse Events –
Phase 2/3 ................................ ................................ ................................ ...............
12.2.5. Phase 2/3 Safet y Conclusions ................................ ................................ .............
12.2.5.1. Blinded Placebo -Controlled Follow- Up Period From Dose 1 to 1 Month
After Dose 2 ................................ ................................ ................................ ..........
12.2.5.2. Blinded Placebo -Controlled Follow- Up Period From Dose 1 to the
Unblinding Date ................................ ................................ ................................ ...
12.2.5.3. Open- Label Follow -Up Period – Original BNT162b2 Participants .............
12.2.5.4. B linded Placebo -Controlled and Open -Label Follow -Up Periods to 6
Months After Dose 2 –Original BNT162b2 Participants ................................ ....
12.2.5.5. Open- Label Follow -Up Period – Original Placebo Participants Who Then
Received BNT162b2 ................................ ................................ ............................
12.2.5.6. Open- Label Follow -Up Period – Original Placebo Participants, had
COVID -19 Occurrence After Dose 1, and Then Received BNT162b2 ...............
13. DI SCUSSION AND OVERALL CONCLUSIONS ................................ ........................
13.1. Discussion................................ ................................ ................................ ..................
13.1.1. Phase 1 ................................ ................................ ................................ ................
13.1.2. Phase 2/3 ................................ ................................ ................................ .............
13.2. Overall Conclusions ................................ ................................ ................................ ..
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CONFIDENTIALLIST OF IN -TEXT TABLES
Table 1. Phase 1 Objectives, Estimands, and Endpoints................................ ....................
Table 2. Phase 2/3 Objectives, Estimands, and Endpoints ................................ .................
Table 3. Investigational Product L ot Numbers – Interim – 6 Month Update.....................
Table 4. Anal ysis Populations ................................ ................................ ............................
Table 5. Disposition of All Randomized Subjects –Phase 2/3 Subjects ≥16 Years of
Age................................ ................................ ................................ ..............................
Table 6. Vaccine as Administered by Vaccine Group – Phase 2/3 Subjects ≥16 Years
of Age –All Randomized Subjects ................................ ................................ ...........
Table 7. Vaccine Administration Timing –Phase 2/3 Subjects ≥16 Years of Age –
All Randomized Subjects ................................ ................................ ............................
Table 8. Safet y Population –Phase 2/3 Subjects ≥16 Years of Age ..............................
Table 9. Follow -up Time After Dose 2 – Phase 2/3 Subjects ≥16 Years of Age –
Safety Population ................................ ................................ ................................ ........
Table 10. Efficacy Populations –Blinded Placebo -Controlled Follow- up Period .............
Table 11. Subjects Excluded From Evaluable Efficacy Population Due to Important
Protocol Deviations on or Prior to 7 Day s After Dose 2 –Blinded Placebo -
Control led Follow -up Period ................................ ................................ .......................
Table 12. Demographic Characteristics –Phase 2/3 Subjects ≥16 Years of Age –
Safety Population ................................ ................................ ................................ ........
Table 13. Demographic Characteristics –Subjects With at L east 6 Months of Follow -
up Time After Dose 2 –Phase 2/3 Subjects ≥16 Years of Age (Subjects Who
Originall y Received BNT162b2) – Safet y Population ................................ ..............
Table 14. Demographic Characteristics –Subjects Who Originally Received Placebo
and Then Received BNT162b2 After Unblinding –Phase 2/3 Subjects ≥16 Years
of Age –Safety Population ................................ ................................ .......................
Table 15. Demographic Characteristics – Blinded Placebo -Controlled Follow -up Period
–Subjects Without Evidence of Infection Prior to 7 Day s After Dose 2 – Evaluable
Efficacy (7 Day s) Population ................................ ................................ ......................
Table 16. Vaccine Efficacy – First COVID -19 Occurrence From 7 Day s After Dose 2 –
Blinded Placebo -Controlled Follow-up Per iod –Subjects Without Evidence of
Infection Prior to 7 Day s After Dose 2 –Evaluable Efficacy (7 Day s) Population ....
Table 17. Vaccine Ef ficacy –First COVID -19 Occurrence From 7 Day s After Dose 2 –
Blinded Placebo -Controlled Follow- up Period – Subjects With or Without
Evidence of Infection Prior to 7 Day s After Dose 2 –Evaluable Efficacy (7 Day s)
Population ................................ ................................ ................................ ....................
Table 18. Vaccine Efficacy – First COVID -19 Occurrence After Dose 1 –Blinded
Placebo- Controlled Follow -up Period – Dose 1 All -Available Efficacy Population ..
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CONFIDENTIALTable 19. Vaccine Efficacy – First COVID -19 Occurrence From 7 Day s After Dose 2,
by Subgroup – Blinded Placebo -Controlled Follow -up Period – Subjects Without
Evidence of Infection Prior to 7 Day s After Dose 2 –Evaluable Efficacy (7 Day s)
Population ................................ ................................ ................................ ....................
Table 20. Vaccine Efficacy – First COVID -19 Occurrence From 7 Day s After Dose 2,
by Risk Status –Blinded Placebo -Controlled Follow -up Period – Subjects Without
Evidence of Infection Prior to 7 Day s After Dose 2 –Evaluable Efficacy (7 Day s)
Population ................................ ................................ ................................ ....................
Table 21. Vaccine Efficacy – First COVID -19 Occurrence From 7 Day s After Dose 2,
by Risk Status –Blinded Placebo -Controlled Follow -up Period – Subjects With or
Withou t Evidence of I nfection Prior to 7 Day s After Dose 2 –Evaluable Efficacy
(7 Day s) Population ................................ ................................ ................................ .....
Table 22. Vaccine Efficacy – First COVID -19 Occurrence From 7 Day s After Dose 2,
by Comorbidity Status – Blinded Placebo -Controlled Follow- up Period – Subjects
Without Evidence of I nfection Prior to 7 Day s After Dose 2 –Evaluable Efficacy
(7 Day s) Population ................................ ................................ ................................ .....
Table 23. Vaccine Efficacy – First COVID -19 Occurrence From 7 Day s After Dose 2,
by Comorbidity Status – Blinded Placebo -Controlled Follow- up Period – Subjects
With or With out Evidence of Infection Prior to 7 Day s After Dose 2 – Evaluable
Efficacy (7 Day s) Population ................................ ................................ ......................
Table 24. Vaccine Efficacy – First Seve re COVID -19 Occurrence From 7 Day s After
Dose 2 –Blinded Placebo-Controlled Follow- up Period –Subjects Without
Evidence of Infection Prior to 7 Day s After Dose 2 –Evaluable Efficacy (7 Day s)
Population ................................ ................................ ................................ ....................
Table 25. Vaccine Efficacy – First Severe COVID -19 Occurrence From 7 Day s After
Dose 2 –Blinded Placebo-Controlled Follow- up Period – Subjects With or Without
Evidence of Infection Prio r to 7 Day s After Dose 2 –Evaluable Efficacy (7 Day s)
Population ................................ ................................ ................................ ....................
Table 26. Vaccine Efficacy – First Severe COVID -19 Occurrence After D ose 1 –
Blinded Placebo -Controlled Follow- up Period – Dose 1 All -Available Efficacy
Population ................................ ................................ ................................ ....................
Table 27. Vaccine Efficacy – First Sever e COVID -19 Occurrence Based on CDC -
Definition From 7 Day s After Dose 2 –Blinded Placebo -Controlled Follow -up
Period – Subjects Without Evidence of Infection Prior to 7 Day s After Dose 2 –
Evaluable Efficacy (7 Day s) Population ................................ ................................ .....
Table 28. Vaccine Efficacy – First Severe COVID -19 Occurrence Based on CDC -
Definition From 7 Day s After Dose 2 –Blinded Placebo -Controlled Follow -up
Period – Subjects With or Without Evidence of Infection Prior to 7 Days After
Dose 2 –Evaluable Efficacy (7 Day s) Population ................................ ......................
Table 29. Number (%) o f Subjects Reporting at Least 1 Adverse Event From Dose 1 to
1 Month After Dose 2 – Blinded Placebo -Controlled Follow- up Period – Phase
2/3 Subjects ≥16 Years of Age – Safety Population ................................ ...............
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CONFIDENTIALTable 30. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1 to
1 Month After Dose 2, by S ystem Organ Class and Preferred Term –Blinded
Placebo- Controlled Follow -up Period – Phase 2/3 S ubjects ≥16 Years of Age –
Safety Population ................................ ................................ ................................ ........
Table 31. Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding Date
–Phase 2/3 Subjects ≥16 Years of Age – Safety Population ................................
Table 32. Incidence Rates of at Least 1 Adverse Event From Unblinding Date to Data
Cutoff Date (13MAR2021) –Open -Label Follow -up Period – Subjects Who
Originall y Received BNT162b2 –Phase 2/3 Subjects ≥16 Years of Age –
Safety Population ................................ ................................ ................................ ........
Table 33. 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 ≥16 Years of Age (Subjects Who Originally
Received BNT162b2) –Safety Population ................................ ...............................
Table 34. 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 ≥16 Years of Age (Subjects
Who Originally Receiv ed BNT162b2) –Safet y Population ................................ .......
Table 35. 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 -up Time A fter Dose 2 – Phase 2/3 Subjects ≥
16 Years of Age (Subj ects Who Originally Received BNT162b2) –Safet y
Population ................................ ................................ ................................ ....................
Table 36. Incidence R ates of at Least 1 Adverse Event From Dose 3 to Data Cutoff
Date (13MAR2021) –Open -Label Follow -up Period –Subjects Who Originall y
Received Placebo and Then Received BNT162b2 After Unblinding –Phase 2/3
Subjects ≥16 Years of Age – Safet y Population ................................ ......................
Table 37. Incidence Rates of at Least 1 Adverse Event From Dose 3 to Data Cutoff
Date (13MAR2021), 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 ≥16 Years of Age – Safety
Population ................................ ................................ ................................ ....................
Table 38. Incidence Rates of Deaths From Dose 1 to Unblinding Date –Blinded
Placebo- Controlled Follow -up Period – Phase 2/3 Subjects ≥16 Years of Age –
Safety Population ................................ ................................ ................................ ........
Table 39. Number (%) of Subjects Reporting at Least 1 Serious Adverse Event From
Dose 1 to 1 Month After Dose 2, b y System Organ Class and Preferred Term –
Blinded Placebo -Control led Follow -up Period – Phase 2/3 Subjects ≥16 Years of
Age –Safety Populati on................................ ................................ ............................
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CONFIDENTIALTable 40. Number (%) of Subjects Reporting at Least 1 Se rious 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 ≥16 Years of A ge (Subjects Who Originally Received BNT162b2) –
Safety Population ................................ ................................ ................................ ........
Table 41. Incidence Rates of at Least 1 Serious Adverse Event From Dose 3 to Data
Cutoff Date (13MAR2021), by System Organ Cl ass and Preferred Term – Open -
Label Follow -up Period –Subjects Who Originally Received Placebo and Then
Received BNT162b2 After U nblinding –Phase 2/3 Subjects ≥16 Years of Age
–Safety Population ................................ ................................ ................................ ...
Table 42. Number (%) of Subjects Withdrawn Because of Adverse Events From Dose 1
to 1 Month After Dose 2, by System Organ Class and Preferred Term –Blinded
Placebo- Controlled Follow -up Period – Phase 2/3 Subjects ≥16 Years of Age –
Safety Population ................................ ................................ ................................ ........
Table 43. Number (%) of Subjects Withdrawn Because of Adverse Events From Dos e 1
to 6 Months After Dose 2, by System Organ Class and Preferred Term –Subjects
With at Least 6 Months of Follow -up Time After Dose 2 – Phase 2/3 Subjects ≥
16 Years of Age (Subjects Who Originally Received BNT162b2) –Safet y
Population ................................ ................................ ................................ ....................
Table 44. Incidence Rates of Subjects Withdrawn Because of Adverse Events From
Dose 3 to Data Cutoff Date (13MAR2021), b y System Organ Class and Preferre d
Term –Open -Label Follow -up Period – Subjects Who Originally Received
Placebo and Then Received BNT1 62b2 After Unblinding –Phase 2/3 Subjects ≥
16 Years of Age – Safety Population ................................ ................................ ........
Table 45. Selected Standard MedDRA Queries From Dose 1 to Unblinding Date –
Blinded Placebo -Controlled Follow- up Period – Phase 2/3 Subjects ≥16 Years of
Age –Safet y Population ................................ ................................ ............................
Table 46. Incidence Rates of at Least 1 Adverse Event Category of Special Interest
From Dose 1 to Unblinding Date, b y Adverse Event Category and Preferred Term
–Blinded Placebo -Controlled Follow- up Period –Phase 2/3 Subjects ≥16
Years of Age –Safet y Population ................................ ................................ .............
LIST OF IN -TEXT FIGURES
Figur e 1. Study Schema ................................ ................................ ................................ ......
Figure 2. Cumulative Incidence Curves for the First COVI D-19 Occurrence After Dose
1–Blinded Placebo -Controlled Foll ow-up Period –Dose 1 All -Available Efficacy
Population ................................ ................................ ................................ ....................
Figure 3. Geometric Mean Titers and 95% CIs: SARS- CoV -2 Neutralization Assay –
NT50 –Phase 1, 2 Doses, 21 Day s Apart –BNT162b2 (30 µg)/Placebo –
Evaluable Immunogenicity Population ................................ ................................ .......
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CONFIDENTIALFigure 4. Geometric Mean Conc entrations and 95% CI s: S1 -Binding IgG Level Assay
–Phase 1, 2 Doses, 21 Day s Apart – BNT162b2 (30 μg)/Placebo –Evaluable
Immunogenicit y Population ................................ ................................ ........................
Figure 5. Subjects Reporting Local Reactions, b y Maximum Severity , Within 7 Day s
After Each Dose, b y Age Group (Reactogenicit y Subset) –Phase 2/3 Subjects ≥
16 Years of Age – Safety Population Age Group: 16 Through 55 Years of Age .....
Figure 6. Subjects Reporting Local Reactions, b y Maximum Severity , Within 7 Day s
After Each Dose, b y Age Group (Reactogenicit y Subset) –Phase 2/ 3 Subjects ≥
16 Years of Age – Safety Population Age Group: >55 Years of Age ......................
Figure 7. Subjects Reporting Local Reactions, b y Maximum Se verity , Within 7 Day s
After Each Dose (Reactogenicity Subset) –Blinded Placebo -Controlled Follow -
up Period – Phase 2/3 HIV -Positive Subjects ≥16 Years of Age – Safet y
Population ................................ ................................ ................................ ....................
Figure 8. Subjects Reporting Sy stemic Events, by Maximum Severity, Within 7 Day s
After Each Dose, b y Age Group (Reactogenicit y Subset) –Phase 2/3 Subjects ≥
16 Years of Age – Safety Population Age Group: 16 Through 55 Years .................
Figure 9. Subjects Reporting Sy stemic Events, by Maximum Severity, Within 7 Day s
After Each Dose, Age Group (Reactogenicity Subset) –Phase 2/3 Subjects ≥16
Years of Age –Safet y Population Age Group: >55 Years ................................ ........
Figure 10. Subjects Reporting S ystemic Events, by Maximum Severity , Within 7 Day s
After Each Dose (Reactogenicity Subset) –Blinded Placebo -Controlled Follow -
up Period – Phase 2/3 HIV -Positive Subjects ≥16 Years of Age – Safet y
Population ................................ ................................ ................................ ....................
Figure 11 Phase 2/3 Safety Anal yses: Time Periods and Anal ysis Groups .......................
Figure 1 2. Forest Plot of Tier 2 Adverse Events Reported From Dose 1 to 1 Month
After Dose 2 – Blinded Placebo -Controlled Follow -up Period – Phase 2/3
Subjects ≥16 Years of Age – Safet y Population ................................ ......................
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CONFIDENTIAL14. TABLES AND FIGURES ............................................................................................... 304
Supplemental Tables ................................ ................................ ................................ ..........
Phase 1 ................................ ................................ ................................ ............................
Conduct of Study ................................ ................................ ................................ .........
14.1. Disposition of All Randomized Subjects –Phase 1, 2 Doses, 21 Days Ap art
–BNT162b2 (30 μg)/Placebo ................................ ................................ ...........
14.2. I mmunogenicit y Populations –Phase 1, 2 Doses, 21 Day s Apart –
BNT162b2 (30 μg)/Placebo ................................ ................................ ..............
14.3. I mmunogenicit y Blood Samples Drawn – Phase 1, 2 Doses, 21 Day s Apart
–BNT162b2 (30 μg)/Placebo –All Randomized Subjects ..............................
Immunogenicit y...........................................................................................................
14.4. Summary ofGeometric Mean Titers/Concentrations –Phase 1, 2 Doses, 21
Days Apart –BNT162b2 (30 μg)/Placebo – Evaluable Immunogenicit y
Population ................................ ................................ ................................ ..........
14.5. Summary of Geometric Mean Titers/Concentrations –Phase 1, 2 Doses, 21
Days Apart –BNT162b2 (30 μg)/Placebo – All-Available Immunogenicit y
Population ................................ ................................ ................................ ..........
14.6. Summary of Geometric Mean Fold Rises From Before Vaccination to Each
Subsequent Time Point – Phase 1, 2 Doses, 21 Days Apart –BNT162b2 (30
μg)/Placebo – Evaluable Immunogenicit y Population ................................ ......
14.7. Summary of Geometric Mean Fold Rises From Before Vaccination to Each
Subsequent Time Point – Phase 1, 2 Doses, 21 Days Apart –BNT162b2 (30
μg)/Placebo – All- Availab le Immunogenicity Population ................................
14.8. Summary of Geometric Mean Ratios –Phase 1, 2 Doses, 21 Day s Apart –
BNT162b2 (30 μg)/Placebo – Evaluable Immunogenicity Population ............
14.9. Summary of Geometric Mean Ratios –Phase 1, 2 Doses, 21 Day s Apart –
BNT162b2 (30 μg)/Placebo – A ll-Available Immunogenicity Population ......
14.10. Number (%) of Subjects Achieving a ≥4-Fold Rise From Before
Vaccination to Each Subsequen t Time Point –Phase 1, 2 Doses, 21 Day s
Apart –BNT162b2 (30 μg)/Placebo –Evaluable I mmunogenicity
Population ................................ ................................ ................................ ..........
14.11. Number (%) of Su bjects Achieving a ≥4- Fold Rise From Before
Vaccination to Each Subsequent Time Point –Phase 1, 2 Doses, 21 Day s
Apart –BNT162b2 (30 μg)/Placebo –All-Available I mmunogenicity
Population ................................ ................................ ................................ ..........
Adverse Events ................................ ................................ ................................ ............
14.12. Number (%) of Subjects Reporting at Least 1 Adverse Event F rom Dose 1
to Unblinding Date –Phase 1 – BNT162b2 (30 μg)/Placebo –Safet y
Population ................................ ................................ ................................ ..........
14.13. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to Unblinding Date, b y System Organ Class and Preferred Term –Phase 1 –
BNT162b2 (30 μg)/Placebo – Safet y Population ................................ ..............
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CONFIDENTIAL14.14. Number (%) of Subjects Reporting at Least 1 Serious Adverse Event From
Dose 1 to Unblinding Date, by System Organ Class and Preferred Term –
Phase 1 – BNT162b2 (30 μg)/Placebo –Safet y Population .............................
Phase 2/3 ................................ ................................ ................................ .........................
Conduct of Study ................................ ................................ ................................ .........
14.15. Dispos ition of All Randomized Subjects, by Age Group –Phase 2/3
Subjects ≥16 Years of Age Age Group: 16- 55 Years ................................ .....
14.16. Disposition of All R andomized Subjects, by Age Group –Phase 2/3
Subjects ≥16 Years of Age Age Group: >55 Years ................................ ........
14.17. Disposition of All Randomized Subjec ts, by Baseline SARS -CoV -2 Status
–Phase 2/3 Subjects ≥16 Years of Age Baseline SARS- CoV -2 Status:
Positive ................................ ................................ ................................ ..............
14.18. Disposition of All Randomized Subjects, by Baseline SARS -CoV -2 Status
–Phase 2/3 Subjects ≥16 Years of Age Baseline SARS- CoV -2 Status:
Negative ................................ ................................ ................................ ............
14.19. Di sposition of All Randomized Subjects, by Ethnicity –Phase 2/3
Subjects ≥16 Years of Age Ethnicity : Hispanic/Latino ................................ ..
14.20. Disposition of All Randomized Subjects, by Ethnicity –Phase 2/3
Subjects ≥16 Years of Age Ethnicity : Non- Hispanic/Non- Latino ..................
14.21. Disposition of All Randomized Subjects, by Ethnicity –Phase 2/3
Subjects ≥16 Years of Age Ethnicity : Not Reported ................................ .......
14.22. Disposition of All Randomiz ed Subjects, by Race –Phase 2/3 Subjects
≥16 Years of Age Race: White ................................ ................................ ........
14.23. Disposition of All Randomized Subjects, by Race –Phase 2/3 Subjects
≥16 Years of Age Race: Black or African American................................ ......
14.24. Disposition of All Randomized Subjects, by Race –Phase 2/3 Subject s
≥16 Years of Age Race: All Others................................ ................................ .
14.25. Disposition of All Randomized Subjects, by Sex –Phase 2/3 Subjects ≥
16 Years of Age Sex: Ma le................................ ................................ ...............
14.26. Disposition of All Randomized Subjects, by Sex –Phase 2/3 Subjects ≥
16 Years of Age Sex: Female................................ ................................ ............
14.27. Follow -up Time After Dose 2, by Age Group – Phase 2/3 Subjects ≥16
Years of Age –Safet y Population Age Group: 16 -55 Years ..........................
14.28. Follow -up Time After Dose 2, by Age Group – Phase 2/3 Subjects ≥16
Years of Age –Safet y Population Age Group: >55 Years .............................
14.29. Follow -up Time After Dose 1 of BNT162b2 – Phase 2/3 Subjects ≥16
Years of Age (Subjects Who Originally Received Placebo) –Safety
Population ................................ ................................ ................................ ..........
14.30. Safet y Population, by Age Group – Phase 2/3 Subjects ≥16 Years of
Age................................ ................................ ................................ ....................
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CONFIDENTIAL14.31. Safet y Population, by Baseline SARS -CoV -2 Status – Phase 2/3 Subjects
≥16 Years of Age ................................ ................................ .............................
14.32 . Safet y Population, by Ethnicit y –Phase 2/3 Subjects ≥16 Years of Age ..
14.33. Safet y Population, by Race –Phase 2/3 Subjects ≥16 Year s of Age ........
14.34. Safet y Population, by Sex – Phase 2/3 Subjects ≥16 Years of Age ..........
14.35. Demographic Characteristics, by Age Group – Phase 2/3 Subjects ≥16
Years of Age –Safet y Population Age Group: 16 -55 Years ..........................
14.36. Demographic Characteristics, by Age Group – Phase 2/3 Subjects ≥16
Years of Age –Safet y Population Age Group: >55 Years .............................
14.37. Demographic Characteristics, by Baseline SARS -CoV -2 Status – Phase
2/3 Subjects ≥16 Years of Age – Safety Population Baseline SARS -CoV -2
Status: Positive ................................ ................................ ................................ ..
14.38. Demographic Characteristics, by Baseline SARS -CoV -2 Status – Phase
2/3 Subjects ≥16 Years of Age – Safety Population Baseline SARS -CoV -2
Status: Negative ................................ ................................ ................................ .
14.39. Demographic Characteristics, by Ethnicit y –Phase 2/3 Subjects ≥16
Years of Age –Safet y Population Ethnicity : Hispanic/Latino .......................
14.40. Demographic Characteristics, by Ethnicit y –Phase 2/3 Subjects ≥16
Years of Age –Safet y Population Ethnicity: Non- Hispanic/Non- Latino .......
14.41. Demographic Characteristics, by Ethnicit y –Phase 2/3 Subjects ≥16
Years of Age –Safet y Population Ethnicity : Not Reported ............................
14.42. Demographic Characteristics, by Race –Phase 2/3 Subjects ≥16 Years
of Age –Safety Population Race: White ................................ ........................
14.43. Demographic Characteristics, by Race –Phase 2/3 Subjects ≥16 Years
of Age –Safety Population Race: Black or African American .......................
14.44. Demographic Characteristics, by Race –Phase 2/3 Subjects ≥16 Years
of Age –Safety Population Race: All Others ................................ .................
14.45. Demographic Characteristics, by Sex –Phase 2/3 Subjects ≥16 Years of
Age –Safet y Population Sex: Male ................................ ................................
14.46. Demographic Characteristics, by Sex –Phase 2/3 Subjects ≥16 Years of
Age –Safet y Population Sex: Female ................................ .............................
14.47. Medical History –Phase 2/3 Subjects ≥16 Years of Age – Safety
Population ................................ ................................ ................................ ..........
14.48. Baseline Charlson Comor bidities –Phase 2/3 Subjects ≥16 Years of
Age –Safet y Population ................................ ................................ ..................
14.49. Baseline Charlson Comorbidities, by Age Group – Phase 2/3 Sub jects ≥
16 Years of Age – Safety Population Age Group: 16- 55 Years .....................
14.50. Baseline Charlson Comorbidities, by Age Group – Phase 2/3 Subj ects ≥
16 Years of Age – Safety Population Age Group: >55 Years ........................
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CONFIDENTIAL14.51. Demographic Characteristics –Blinded Placebo -Controlled Follow -up
Period – Phase 2/3 HIV -Positive Subjects ≥16 Years of Age – Safet y
Population ................................ ................................ ................................ ..........
14.52. Demographic Characteristics –Phase 2/3 Subjects ≥12 Years of Age –
Safety Population ................................ ................................ ..............................
14.53. Demographic Characteristics –Blinded Placebo -Controlled Follow-up
Period – Dose 1 All -Available Efficacy Population ................................ .........
14.54. Demographic Characteristics –Blinded Placebo -Controlled Follow-up
Period – Subjects With or Without Evidence of Infection Prior to 7 Day s
After Dose 2 – Evaluable Efficacy (7 Day s) Population ................................ ..
14.55. E- Diary Transmission (Reactogenicity Subset) –Phase 2/3 Subjects ≥16
Years of Age –Safet y Population ................................ ................................ ...
14.56. Concomitant Vaccines Received After Dose 1 –Phase 2/3 Subjec ts ≥16
Years of Age –Safet y Population ................................ ................................ ...
Efficacy ................................ ................................ ................................ ........................
14.57. Vaccine Efficacy –First COVID -19 Occurrence From 7 Day s After Dose
2 –Blinded Placebo -Controlled Follow- up Period –Subjects Without
Evidence of Infection Prior to 7 Day s After Dose 2 –Dose 2 All -Available
Effic acy Population ................................ ................................ ...........................
14.58. Vaccine Efficacy –First COVID -19 Occurrence From 7 Day s After Dose
2 –Blinded Placebo -Controlled Follow- up Peri od – Subjects With or
Without Evidence of I nfection Prior to 7 Day s After Dose 2 –Dose 2 All -
Available Efficacy Population ................................ ................................ ..........
14.59. Vacc ine Efficacy –First COVID -19 Occurrence From 7 Day s After Dose
2, by Subgroup – Blinded Placebo -Controlled Follow -up Period – Subjects
With or Without Evidence of Infection Prior to 7 Day s After Dose 2 –
Evaluable Efficacy (7 Day s) Population ................................ ...........................
14.60. Vaccine Efficacy –First COVID -19 Occurrence After Dose 1, by
Subgroup –Blinded Placebo -Controlled Follow- up Period –Dose 1 All -
Available Efficacy Population ................................ ................................ ..........
14.61. Vaccine Efficacy –First Severe COVID -19 Occurrence Based on CDC -
Definition After Dose 1 –Blinded Placebo -Controlled Follow -up Period –
Dose 1 All -Available Efficacy Population ................................ ........................
14.62. Summary of Signs and Sy mptoms for First COVID -19 Occurrenc e From 7
Days After Dose 2 – Blinded Placebo -Controlled Follow -up Period –
Subjects Without Evidence of Infection Prior to 7 Day s After Dose 2 –
Evaluable Efficacy (7 Day s) Population ................................ ...........................
14.63. Summary of Signs and Sy mptoms for First COVID -19 Occurrence From 7
Days After Dose 2 – Blinded Placebo -Controlled Follow -up Period –
Subjects With or Without Evidence of Infection Prior to 7 Day s Afte r Dose 2
–Evaluable Efficacy (7 Day s) Population ................................ ........................
14.64. Summary of Signs and Sy mptoms for First COVID -19 Occurrence After
Dose 1 –Blinded Placebo -Controlled Follow- up Period –Dose 1 All -
Available Efficacy Population ................................ ................................ ..........
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CONFIDENTIAL14.65. Summary of Signs and Sy mptoms for First Seve re COVID -19 Occurrence
From 7 Day s After Dose 2 – Blinded Placebo -Controlled Follow- up Period –
Subjects Without Evidence of Infection Prior to 7 Day s After Dose 2 –
Evaluable Efficacy (7 Day s) Population ................................ ...........................
14.66. Summary of Signs and Sy mptoms for First Severe COVID -19 Occurrence
From 7 Day s After Dose 2 – Blinded Placebo -Controlled Follow- up Period –
Subjects With or Without Evidence of In fection Prior to 7 Day s After Dose 2
–Evaluable Efficacy (7 Day s) Population ................................ ........................
14.67. Summary of Signs and Sy mptoms for First Severe COV ID-19 Occurrence
After Dose 1 – Blinded Placebo -Controlled Follow -up Period – Dose 1 All -
Available Efficacy Population ................................ ................................ ..........
Local Reactions................................ ................................ ................................ ............
14.68. L ocal Reactions, by Maximum Severity , Within 7 Day s After Each Dose,
by Age Group (Reactogenicity Subset) –Phase 2/3 Subjects ≥16 Years of
Age –Safet y Population ................................ ................................ ..................
14.69. Onset Day s for Local Reactions, b y Age Group (Reactogenicity Subset)
–Phase 2/3 Subjects ≥16 Years of Age – Safety Population ......................
14.70. Duration (Day s) From First to Last Day of Local Reactions, by Age Group
(Reactogenicity Subset) –Phase 2/3 Subjects ≥16 Years of Age – Safety
Population ................................ ................................ ................................ ..........
14.71. L ocal Reactions, by Maximum Severity , Within 7 Day s After Each Dose,
by Baseline SARS -CoV -2 Status (Reactogenicit y Subset) –Phase 2/3
Subjects ≥16 Years of Age – Safet y Population ................................ ...........
14.72. L ocal Reactions, by Maximum Severity , Within 7 Day s After Each Dose
(Reactogenicity Subset) –Blinded Placebo -Controlled Follow- up Peri od –
Phase 2/3 HIV -Positive Subjects ≥16 Years of Age – Safet y Population .....
14.73. Onset Day s for Local Reactions (Reactogenicity Subset)–Blinded
Placebo- Controlled Follow -up Period – Phase 2/3 HIV -Positive Subjects ≥
16 Years of Age – Safety Population ................................ ..............................
14.74. Duration ( Days) From First to Last Day of Local Reactions
(Reactogenicity Subset) –Blinded Placebo -Controlled Follow- up Period –
Phase 2/3 HIV -Positive Subjects ≥16 Years of Age – Safet y Population .....
Systemic Events ................................ ................................ ................................ ...........
14.75. Sy stemic Events, by Maximum Severity , Within 7 Day s After Each Dose,
by Age Group (Reactogenicity Subset) –Phase 2/3 Subjects ≥16 Years of
Age –Safet y Population ................................ ................................ ..................
14.76. Onset Day s for S ystemi c Events, by Age Group (Reactogenicity Subset)
–Phase 2/3 Subjects ≥16 Years of Age – Safety Population ......................
14.77. Duration (Day s) From Fi rst to Last Day of Sy stemic Events, b y Age
Group (Reactogenicit y Subset) –Phase 2/3 Subjects ≥16 Years of Age –
Safety Population ................................ ................................ ..............................
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CONFIDENTIAL14.78. Sy stemic Events, by Maximum Severity , Within 7 Day s After Each Dose,
by Baseline SARS -CoV -2 Status (Reactogenicit y Subset) –Phase 2/3
Subjects ≥16 Years of Age – Safet y Population ................................ ...........
14.79. Sy stemic Events, by Maximum Severity , Within 7 Day s After Each Dose
(Reactogenicity Subset) –Blinded Placebo -Controlled Follow- up Period –
Phase 2/3 HIV -Positive Subjects ≥16 Years of Age – Safet y Population .....
14.80. Onset Day s for S ystemic Events (Reactogenicity Subset) –Blinded
Placebo- Controlled Follow -up Period – Phase 2/3 HIV -Positive Subjects ≥
16 Years of Age – Safety Population ................................ ..............................
14.81. Duration (Day s) From First to Last Day of Sy stemic Events
(Reactogenicity Subset) –Blinded Placebo -Controlled Follow- up Period –
Phase 2/3 HIV -Positive Subjects ≥16 Years of Age – Safet y Population .....
Adverse Eve nts................................ ................................ ................................ ............
14.82. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 1 Month After Dose 2, by Age Group – Blinded Placeb o-Controlled
Follow -up Period – Phase 2/3 Subjects ≥16 Years of Age – Safet y
Population Age Group: 16 -55 Years ................................ ................................ .
14.83. Number (%) of Sub jects Reporting at Least 1 Adverse Event From Dose 1
to 1 Month After Dose 2, by Age Group – Blinded Placebo -Controlled
Follow -up Period – Phase 2/3 Subjects ≥16 Years of Age – Safet y
Population Age Group: >55 Years ................................ ................................ ....
14.84. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 1 Month After Dose 2 –Blinded Placebo -Controlled Follow- up Period
–Phase 2/3 HIV -Positive Sub jects ≥16 Years of Age –Safety Population
14.85. Tier 2 Adverse Events Reported From Dose 1 to 1 Month After Dose 2, by
System Organ C lass and Preferred Term – Blinded Placebo -Controlled
Follow -up Period – Phase 2/3 Subjects ≥16 Years of Age – Safet y
Population ................................ ................................ ................................ ..........
14.86. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 1 Month After Dose 2, by System Organ Class and Preferred Term, b y
Age Group –Blinded Placebo -Controlled Follow -up Period – Phase 2/3
Subjects ≥16 Years of Age – Safet y Popul ation Age Group: 16- 55 Years ...
14.87. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 1 Month After Dose 2, by System Organ Class and Preferred Term, b y
Age Group –Blinded Placebo -Controlled Follow -up Period – Phase 2/3
Subjects ≥16 Years of Age – Safet y Popul ation Age Group: >55 Years ......
14.88. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 7 Day s After Dose 1, by System Organ Class and Preferred Term –
Blinded Placebo -Controlled Follow- up Period – Phase 2/3 Subjects ≥16
Years of Age –Safet y Population ................................ ................................ ...
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CONFIDENTIAL14.89. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 2
to 7 Day s After Dose 2, by System Organ Class and Preferred Term –
Blinded Pl acebo -Controlled Follow- up Period – Phase 2/3 Subjects ≥16
Years of Age –Safet y Population ................................ ................................ ...
14.90. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 7 Day s After Dose 1, by System Organ Class and Preferred Term, by Age
Group –Blinded Placebo-Controlled Follow- up Period –Phase 2/3
Subjects ≥16 Years of Age – Safet y Popula tion Age Group: 16- 55 Years ...
14.91. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 7 Day s After Dose 1, by System Organ Class and Preferred Term, by Age
Group –Blinded Placebo-Controlled Follow- up Period –Phase 2/3
Subjects ≥16 Years of Age – Safet y Popula tion Age Group: >55 Years......
14.92 . Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 2
to 7 Day s After Dose 2, by System Organ Class and Preferred Term, by Age
Group –Blinded Placebo-Controlled Follow- up Period –Phase 2/3
Subjects ≥16 Years of Age – Safet y Popula tion A ge Group: 16- 55 Years ...
14.93. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 2
to 7 Day s After Dose 2, by System Or gan Class and Preferred Term, by Age
Group –Blinded Placebo-Controlled Follow- up Period –Phase 2/3
Subjects ≥16 Years of Age – Safet y Popula tion Age Group: >55 Years......
14.94. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 1 Month After Dose 2, by System Organ Class and Preferred Term –
Blinded Placebo -Controlled Follow- up Period – Phase 2/3 HIV -Positive
Subjects ≥ 16 Years of Age – Safet y Popul ation ................................ ..........
14.95. Number (%) of Subjects Reporting at Least 1 Related Adverse Event From
Dose 1 to 1 Month A fter Dose 2, b y System Organ Class and Preferred Term
–Blinded Placebo -Controlled Follow- up Period –Phase 2/3 Subjects ≥16
Years of Age –Safet y Population ................................ ................................ ...
14.96. Number (%) of Subjects Reporting at Least 1 Related Adverse Event From
Dose 1 to 1 Month After Dose 2, b y System Organ Class and Preferred
Term, b y Age Group –Blinded Placebo -Controlled Follow- up Period –
Phase 2/3 Subjects ≥16 Years of Age – Safety Population Age Group: 16 -
55 Years ................................ ................................ ................................ .............
14.97. Number (%) of Subjects Reporting at Least 1 Related Adverse Event Fro m
Dose 1 to 1 Month After Dose 2, b y System Organ Class and Preferred
Term, b y Age Group –Blinded Placebo -Controlled Follow- up Period –
Phase 2/3 Subjects ≥16 Years of Age – Safety Population Age Group: >55
Years ................................ ................................ ................................ ..................
14.98. Number (%) of Subjects Reporting at Least 1 I mmediate Adverse Event
After Dose 1, b y System Organ Class and Preferred Term –Blinded
Placebo- Controlled Follow -up Period – Phase 2/3 Subjects ≥16 Years of
Age –Safet y Population ................................ ................................ ..................
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CONFIDENTIAL14.99. Number (%) of Subjects Reporting at Least 1 I mmediate Adverse Event
After Dose 2, b y System Organ Class and Preferred Term –Blinded
Placebo- Controlled Follow -up Period – Phase 2/3 Subjects ≥16 Years of
Age –Safet y Population ................................ ................................ ..................
14.100. Number (%) of Subjects Reporting at Least 1 Severe Adverse Event
From Dose 1 to 1 Month After Dose 2, b y System Organ Class and Preferred
Term –Blinded Placebo-Controlled Follow- up Period –Phase 2/3
Subjects ≥16 Years of Age – Safet y Population ................................ ...........
14.101. Number (%) of Subjects Reporting at Least 1 L ife-Threatening Adverse
Event From Dose 1 to 1 Month After Dos e 2, b y System Organ Class and
Preferred Term –Blinded Placebo -Controlled Follow -up Period – Phase
2/3 Subjects ≥16 Years of Age – Safety Population ................................ .....
14.102. Number (%) of Subjects Reporting at Least 1 Severe Adverse Event
From Dose 1 to 1 Month After Dose 2, b y System Organ Class and Preferred
Term, b y Age Group –Blinded Placebo -Controlled Follow- up Period –
Phase 2/3 Subjects ≥16 Years of Age – Safety Population Age Group: 16 -
55 Years ................................ ................................ ................................ .............
14.103. Number (%) of Subjects Reporting at Least 1 Severe Adverse Event
From Dose 1 to 1 Month After Dose 2, by System Organ Class and Preferred
Term, b y Age Group –Blinded Placebo -Controlled Follow- up Period –
Phase 2/3 Subjects ≥16 Years of Age – Safety Population Age Group: >55
Years ................................ ................................ ................................ ..................
14.104. Number (%) of Subjects Reporting at Least 1 L ife-Threatening Adverse
Event From Dose 1 to 1 Month After Dose 2, b y System Organ Class and
Preferred Term, b y Age Group –Blinded Placebo -Controlled Follow-up
Period – Phase 2/3 Subjects ≥16 Years of Age –Safety Population Age
Group: 16- 55 Years ................................ ................................ ...........................
14.105. Number (%) of Subjects Reporting at Least 1 L ife-Threatening Adverse
Event From Dose 1 to 1 Month After Dose 2, b y System Organ Class and
Preferred Term, b y Age Group –Blinded Placebo-Controlled Follow-up
Period – Phase 2/3 Subjects ≥16 Years of Age –Safety Popula tion Age
Group: >55 Years ................................ ................................ ..............................
14.106. I ncidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, b y Age Group –Phase 2/3 Subjects ≥16 Years of Age –Safety
Population Age Group: 16 -55 Years ................................ ................................ .
14.107. I ncidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, b y Age Group –Phase 2/3 Subjects ≥16 Years of Age –Safety
Population Age Group: >55 Years ................................ ................................ ....
14.108. I ncidence Rates o f at Least 1 Adverse Event From Dose 1 to Unblinding
Date, b y Baseline SARS -CoV -2 Status – Phase 2/3 Subjects ≥16 Years of
Age –Safet y Population Baseline SARS -CoV -2 Status: Positive ..................
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CONFIDENTIAL14.109. I ncidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, b y Baseline SARS -CoV -2 Status – Phase 2/3 Subjects ≥16 Years of
Age –Safet y Population Baseline SARS -CoV -2 Status: Negative ................
14.110. I ncidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, b y Ethnicity –Phase 2/3 Subjects ≥16 Years of Ag e –Safet y
Population Ethnicity : Hispanic/Latino ................................ ..............................
14.111. I ncidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, b yEthnicity –Phase 2/3 Subjects ≥16 Years of Age –Safet y
Population Ethnicity : Non -Hispanic/Non- Latino ................................ ..............
14.112. I ncidence Rates of at L east 1 Adverse Event From Dose 1 to Unblinding
Date, b y Ethnicity –Phase 2/3 Subjects ≥16 Years of Age –Safet y
Population Ethnicity : Not Reported ................................ ................................ ..
14.113. I ncidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, b y Race –Phase 2/3 Subjects ≥16 Years of Age – Safety
Population Race: White ................................ ................................ .....................
14.114. I ncidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, b y Race –Phase 2/3 Subjects ≥16 Years of Age – Safety
Population Race: Black or African American ................................ ...................
14.115. I ncidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, b y Race –Phase 2/3 Subjects ≥16 Years of Age – Safety
Population Race: All Others ................................ ................................ ..............
14.116. I ncidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, b y Sex –Phase 2/3 Subjects ≥16 Years of Age – Safet yPopulation
Sex: Male ................................ ................................ ................................ ...........
14.117. I ncidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, b y Sex –Phase 2/3 Subjects ≥16 Years of Age – Safet y Population
Sex: Female ................................ ................................ ................................ .......
14.118. I ncidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date –Blinded Placebo -Controlled Follow- up Period – Phase 2/3 HIV -
Positive Subjects ≥16 Years of Age – Safety Population ..............................
14.119. I ncidence Rate s of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, b y System Organ Class and Preferred Term –Phase 2/3 Subjects ≥
16 Years of Age – Safety Population ................................ ..............................
14.120. I ncidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, b y System Organ Class and Preferred Term, by Age Group – Phase
2/3 Subjects ≥16 Years of Age – Safety Population Age Group: 16 -55
Years ................................ ................................ ................................ ..................
14.121. I ncidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, b y System Organ Class and Preferred Term, by Age Group – Phas e
2/3 Subjects ≥16 Years of Age – Safety Population Age Group: >55 Years
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CONFIDENTIAL14.122. I ncidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, b y System Organ Class and Preferred Term, by Baseline SARS -CoV -2
Status –Phase 2/3 Subjects ≥16 Years of Age –Safety Population
Baseline SARS -CoV -2 Status: Positive ................................ ............................
14.123. I ncidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, b y System Organ Class and Preferred Term, by Baseline SARS -CoV -2
Status –Phase 2/3 Subjects ≥16 Years of Age –Safety Population
Baseline SARS -CoV -2 Status: Negative ................................ ...........................
14.124. I ncidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, b ySystem Organ Class and Preferred Term, by Ethnicity –Phase 2/3
Subjects ≥16 Years of Age – Safet y Population Ethnicity : Hispanic/Latino
14.125. I ncidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, b y System Organ Class and Preferred Term, by Ethnicity –Phase 2/3
Subjects ≥16 Years of Age – Safet y Population Ethnicity : Non -
Hispanic/Non- Latino ................................ ................................ .........................
14.126. I ncidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, b y System Organ Class and Preferred Term, by Ethnicity –Phase 2/3
Subje cts ≥16 Years of Age – Safet y Population Ethnicity : Not Reported ....
14.127. I ncidence Rates of at Least 1 Adverse Event From Dose 1 to Unb linding
Date, b y System Organ Class and Preferred Term, by Race –Phase 2/3
Subjects ≥16 Years of Age – Safet y Population Race: White .......................
14.128. I ncidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, b y System Organ Class and Preferred Term, by Race –Phase 2/3
Subjects ≥16 Years of Age – Safet y Population Race: Black or African
American ................................ ................................ ................................ ...........
14.129. I ncidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, b y System Organ Class and Preferred Term, by Race –Phase 2/3
Subjects ≥16 Years of Age –Safet y Population Race: All Others ................
14.130. I ncidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, b y System Organ Class and Preferred Term, by Sex –Phase 2/3
Subjects ≥16 Years of Age – Safet y Population Sex: Male ..........................
14.131. I ncidence Rates of a t Least 1 Adverse Event From Dose 1 to Unblinding
Date, b y System Organ Class and Preferred Term, by Sex –Phase 2/3
Subjects ≥16 Years of Age – Safet y Population Sex: Female .......................
14.132. I ncidence Rates of at Least 1 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 HIV -Positive Subjects ≥16 Years
of Age –Safety Population ................................ ................................ .............
14.133. I ncidence Rates of at Least 1 Related Adverse Event From Dose 1 to
Unblinding Date, b y System Organ C lass and Preferred Term –Phase 2/3
Subjects ≥16 Years of Age – Safet y Population ................................ ...........
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CONFIDENTIAL14.134. I ncidence Rates of at Least 1 Related Adverse Event From Dose 1 to
Unblinding Date, b y System Organ Class and Preferred Term, by Age Group
–Phase 2/3 Subjects ≥16 Years of Age – Safety Population Age Group:
16-55 Years ................................ ................................ ................................ .......
14.135. I ncidence Rates of at Least 1 Related Adverse Event From Dose 1 to
Unblinding Date, b y System Organ Class and Preferred Term, by Age Group
–Phase 2/3 Subjects ≥16 Years of Age – Safety Population Age
Group: >55 Years ................................ ................................ ..............................
14.136. I ncidence Rates of at Least 1 Severe Adverse Event From Dose 1 to
Unblinding Date, b y System Organ Class and Preferre d Term –Phase 2/3
Subjects ≥16 Years of Age – Safet y Population ................................ ...........
14.137. I ncidence Rates of at Least 1 Life -Threatening Adverse Event F rom Dose
1 to Unblinding Date, b y System Organ Class and Preferred Term –Phase
2/3 Subjects ≥16 Years of Age – Safety Population ................................ .....
14.13 8. Incidence Rates of at Least 1 Severe Adverse Event From Dose 1 to
Unblinding Date, b y System Organ Class and Preferred Term, by Age Group
–Phase 2/3 Subjects ≥16 Years of Age – Safety Population Age Group:
16-55 Years ................................ ................................ ................................ .......
14.139. I ncidence Rates of at Least 1 Severe Adverse Event From Dose 1 to
Unblinding Date, b y System Organ Class and Preferred Term, by Age Group
–Phase 2/3 Subjects ≥16 Years of Age – Safety Population Age
Group: >55 Years ................................ ................................ ..............................
14.140. I ncidence Rates of at Least 1 Life -Threatening Adverse Event From Dose
1 to Unblinding Date, b y System Organ Class and Preferred Term, by Age
Group –Phase 2/3 Subjects ≥16 Years of Age –Safety Population Age
Group: 16- 55 Years ................................ ................................ ...........................
14.141. I ncidence Rates of at Least 1 Life -Threatening Adverse Event From Dose
1 to Unblinding Date, b y System Organ Class and Preferred Term, by Age
Group –Phase 2/3 Subjects ≥16 Years of Age –Safety Population Age
Group: >55 Year s................................ ................................ ..............................
14.142. I ncidence Rates of at Least 1 Adverse Event From Unblinding Date to
Data Cutoff Date (13MAR2021), by System Organ Class and P referred
Term –Open -Label Follow -up Period – Subjects Who Originally
Received BNT162b2 – Phase 2/3 Subjects ≥16 Years of Age –Safet y
Population ................................ ................................ ................................ ..........
14.143. I ncidence Rates of at Least 1 Related Adverse Event From Unblinding
Date to Data Cutoff Date (13MAR2021), by System Organ Class and
Preferred Term –Open -Label Follow -up Period –Subjects Who
Originall y Received BNT162b2 –Phase 2/3 Subj ects ≥16 Y ears of Age –
Safety Population ................................ ................................ ..............................
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CONFIDENTIAL14.144. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose
1 to 6 Months Aft er Dose 2, by Age Group – Subjects With at L east 6
Months of Follow- up Time After Dose 2 – Phase 2/3 Subjects ≥16 Years
of Age (Subjects Who Originall y Received B NT162b2) – Safet y Population
Age Group: 16 -55 Years ................................ ................................ ...................
14.145. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose
1 to 6 Months After Dose 2, by Age Group – Subjects With at L east 6
Months of Follow- up Time After Dose 2 –Phase 2/3 Subjects ≥16 Years
of Age (Subjects Who Originall y Received B NT162b2) – Safet y Population
Age Group: >55 Years ................................ ................................ ......................
14.146. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose
1 to 6 Months After Dose 2, by System Organ Class and Preferred Term, by
Age Group –Subjects With at Least 6 Months of Follow-up Time After
Dose 2 –Phase 2/3 Subjects ≥16 Years of Age ( Subjects Who Originally
Received BNT162b2) –Safety Population Age Group: 16- 55 Years ..............
14.147. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose
1 to 6 Months After Dose 2, by System Organ Class and Preferred Term, by
Age Group –Subjects With at Least 6 Months of Follow-up Time After
Dose 2 –Phase 2/3 Subjects ≥16 Years of Age (Subjects Who Originally
Received BNT162b2) –Safety Population Age Group: >55 Years ..................
14.148. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose
1 to 6 Months Aft er 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 ≥16 Year s of Age (Subjects Who Originally
Received BNT162b2) –Safety Population ................................ .......................
14.149. 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 ≥16 Years of Age (Subjects Who Originally
Received BNT162b2) –Safety Population ................................ .......................
14.150. 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, b y Age Group –Subjects With at Least 6 Months of
Follow -up Time After Dose 2 –Phase 2/3 Subjects ≥16 Years of Age
(Subjects Who Originally Received BNT162b2) –Safety Population Age
Group: 16- 55 Years ................................ ................................ ...........................
14.15 1. 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, b y Age Group –Subjects With at Least 6 Months of
Follow -up Time After Dose 2 – Phase 2/3 Subjects ≥16 Year s of Age
(Subjects Who Originally Received BNT162b2) –Safety Population Age
Group: >55 Years ................................ ................................ ..............................
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CONFIDENTIAL14.152. I ncidence Rates of at Least 1 Adverse Event From Dose 3 to Data Cutoff
Date (13MAR2021), b y Baseline SARS -CoV -2 Status –Open -Label Follow -
up Period – Subjects Who Originall y Received Placebo and Then Received
BNT162b2 After Unblinding –Phase 2/3 Subjects ≥16 Years of Age –
Safety Popula tion Baseline SARS -CoV -2 Status: Positive ...............................
14.153. I ncidence Rates of at Least 1 Adverse Event From Dose 3 to Data Cutoff
Date (13MAR2021), b y Baseline SARS -CoV -2 Status –Open -Label Follow -
up Period – Subjects Who Originall y Received Placebo and Then Received
BNT162b2 After Unblinding –Phase 2/3 Subjects ≥16 Years of Age –
Safety Population Baseline SARS -CoV -2 Status: Negative .............................
14.154. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose
3 to 7 Day s After Dose 3, by System Organ Class and Preferred Term –
Open -Label Follow -up Period –Subjects Who Originall y Received Placebo
and Then Received BNT162b2 After Unblin ding –Phase 2/3 Subjects ≥16
Years of Age –Safet y Population ................................ ................................ ...
14.155. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose
4 to 7 Day s After Dose 4, by System Organ Class and Preferred Term –
Open -Label Follow -up Period –Subjects Who Originall y Received Placebo
and Then Received BNT162b2 After Unblin ding –Phase 2/3 Subjects ≥16
Years of Age –Safet y Population ................................ ................................ ...
14.156. I ncidence Rates of at Least 1 Adverse Event From Dose 3 to Data Cutoff
Date (13MAR2021), b y System Organ Class and Preferred Term, by
Baseline SARS -CoV -2 Status –Open -Label Follow -up Period – Subjects
Who Originally Received Placebo and Then Rece ived BNT162b2 After
Unblinding –Phase 2/3 Subjects ≥16 Years of Age – Safet y Population
Baseline SARS -CoV -2 Status: Positive ................................ ............................
14.157. I ncidence Rates of at Least 1 Adverse Event From Dose 3 to Data Cutoff
Date (13MAR2021), b y System Organ Class and Preferred Term, by
Baseline SARS -CoV -2 Status –Open -Label Follow -up Period – Subjects
Who Originally Received Placebo and Then Rece ived BNT162b2 After
Unblinding –Phase 2/3 Subjects ≥16 Years of Age – Safet y Population
Baseline SARS -CoV -2 Status: Negative ................................ ...........................
14.158. I ncidence Rates of at Least 1 Related Adverse E vent From Dose 3 to
Data Cutoff Date (13MAR2021), by System Organ Class and Preferred
Term –Open -Label Follow -up Period – Subjects Who Originally Received
Placebo and Then Received BNT162b2 After Unb linding – Phase 2/3
Subjects ≥16 Years of Age – Safet y Population ................................ ...........
14.159. Number (%) of Subjects Reporting at Least 1 I mmediate Adverse Event
After Vaccination (Dose 3/4), by System Organ Cla ss and Preferred Term –
Open -Label Follow -up Period –Subjects Who Originall y Received Placebo
and Then Received BNT162b2 After Un blinding –Phase 2/3 Subjects ≥16
Years of Age –Safet y Population ................................ ................................ ...
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Cutoff Date (13MAR2021), by System Organ Class and Preferred Term –
Open -Label Follow -up Period –Subjects Who Orig inally Received Placebo
and Then Received BNT162b2 After Unbl inding –Phase 2/3 Subjects ≥16
Years of Age –Safet y Population ................................ ................................ ...
14.161. I ncidence Rates of at Least 1 Life -Threatening Adverse Event From Dose
3 to Data Cutoff Date (13MAR2021), by System Organ Class and Preferred
Term –Open -Label Follow -up Period – Subjects Who Originally Received
Placebo and Then Received BNT162b2 After Unbl inding – Phase 2/3
Subjects ≥16 Years of Age – Safet y Population ................................ ...........
14.162. I ncidence Rates of at Least 1 Adverse Event From Dose 3 to Dat a Cutoff
Date (13MAR2021) –Open -Label Follow -up Period –Subjects Who
Originall y Received Placebo, had COVID -19 Occurrence After Dose 1 and
Then Received BNT162b2 After Unblinding – Phase 2/3 Subjects ≥16
Years of Age –Safet y Population ................................ ................................ ...
14.163. I ncidence Rates of at Least 1 Adverse Event From Dose 3 to Data Cutoff
Date (13MAR2021), b y System Organ Class and Preferred Term –Open -
Label F ollow -up Period –Subjects Who Originally Received Placebo, had
COVID -19 Occurrence After Dose 1 and Th en Received BNT162b2 After
Unblinding –Phase 2/3 Subjects ≥16 Years of Age – Safet y Population ...
14.164. Number (%) of Subjects Reporting at Least 1 Serious Adverse Event
From Dose 1 to 1 Month After Dose 2, b y System Organ Class and Preferred
Term, b y Age Group –Blinded Placebo -Controll ed Follow -up Period –
Phase 2/3 Subjects ≥16 Years of Age – Safety Population Age Group: 16 -
55 Years ................................ ................................ ................................ .............
14.165. Number (%) of Subjects Rep orting at Least 1 Serious Adverse Event
From Dose 1 to 1 Month After Dose 2, b y System Organ Class and Preferred
Term, b y Age Group –Blinded Placebo -Controlled Follow- up Period –
Phase 2/3 Subjects ≥16 Years of Age – Safety Population Age Group: >55
Years ................................ ................................ ................................ ..................
14.166. I ncidence Rates of at Least 1 Serious Adverse Event From Dose 1 to
Unblinding Date, b y System Organ Class and Preferred Term –Phase 2/3
Subjects ≥16 Years of Age – Safet y Population ................................ ...........
14.167. I ncidence Rates of at Least 1 Serious Adverse Event From Dose 1 to
Unblinding Date, b y System Organ Class and Preferred Term, by Age Group
–Phase 2/3 Subjects ≥16 Years of Age – Safety Population Age Group:
16-55 Years ................................ ................................ ................................ .......
14.168. I ncidence Rates of at Least 1 Serious Adverse Event From Dose 1 to
Unblinding Date, b y System Organ Class and Preferred Term, by Age Group
–Phase 2/3 Subjects ≥16 Years of Age – Safety Population Age
Group: >55 Years ................................ ................................ ..............................
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Unblinding Date, b y System Organ Class and Preferred Term, by Baseline
SARS -CoV -2 Status – Phase 2/3 Subjects ≥16 Years of Age – Safet y
Population Baseline SARS -CoV -2 Status: Positive ................................ ..........
14.170. I ncidence Rates of at Least 1 Serious Adverse Event From Dose 1 to
Unblinding Date, b y System Organ Class and Preferred Term, by Baseline
SARS -CoV -2 Status – Phase 2/3 Subjects ≥16 Years of Age – Safet y
Population Baseline SARS -CoV -2 Status: Negat ive................................ ........
14.171. I ncidence Rates of at Least 1 Serious Adverse Event From Dose 1 to
Unblinding Date, b y System Organ Class and Preferred Term, by Ethnicit y
–Phase 2/3 Subjects ≥16 Years of Age – Safety Population Ethnicity :
Hispanic/Latino ................................ ................................ ................................ .
14.172. I ncidence Rates of at Least 1 Serious Adverse Event F rom Dose 1 to
Unblinding Date, b y System Organ Class and Preferred Term, by Ethnicit y
–Phase 2/3 Subjects ≥16 Years of Age – Safety Population Ethnicity :
Non-Hispanic/Non- Latino ................................ ................................ .................
14.173. I ncidence Rates of at Least 1 Serious Adverse Event From Dose 1 to
Unblinding Date, b y System Organ Class and Preferred Term, by Ethnicit y
–Phase 2/3 Subjects ≥16 Years of Age – Safety Population Ethnici ty:
Not Reported ................................ ................................ ................................ .....
14.174. I ncidence Rates of at Least 1 Serious Adverse Event From Dose 1 to
Unblinding Date, b y System Organ Class and Preferred Term, by Race –
Phase 2/3 Subjects ≥16 Years of Age – Safet y Population Race: White ......
14.175. I ncidence Rates of at Least 1 Ser ious Adverse Event From Dose 1 to
Unblinding Date, b y System Organ Class and Preferred Term, by Race –
Phase 2/3 Subjects ≥16 Years of Age – Safet y Population Race: Black or
African American ................................ ................................ ..............................
14.176. I ncidence Rates of at Least 1 Serious Adverse Event From Dose 1 to
Unblinding Date, b y System Organ Class and Preferred Term, by Race –
Phase 2/3 Subjects ≥16 Years of Age – Safet y Population Race: All Others
14.177. I ncidence Rates of at Least 1 Serious Adverse Event From Dose 1 to
Unblinding Date, b y System Organ Class and Preferred Term, by Sex –
Phase 2/3 Subjects ≥16 Years of Age – Safet y Population Sex: Male ..........
14.178. I ncidence Rates of at Least 1 Seriou s Adverse Event From Dose 1 to
Unblinding Date, b y System Organ Class and Preferred Term, by Sex –
Phase 2/3 Subjects ≥16 Years of Age – Safet y Population Sex: Female ......
14.179. I ncidence 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 HIV -Positive Subjects ≥
16 Years o f Age –Safety Population ................................ ..............................
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Date to Data Cutoff Date (13MAR20 21), by System Organ Class and
Preferred Term –Open -Label Follow -up Period –Subjects Who
Originall y Received BNT162b2 –Phase 2/3 Subjects ≥16 Y ears of Age –
Safety Population ................................ ................................ ..............................
14.181. 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, b y Age Group –Subjects With at Least 6 Months of
Follow -upTime After Dose 2 –Phase 2/3 Subjects ≥16 Years of Age
(Subjects Who Originally Received BNT162b2) –Safety Population Age
Group: 16- 55 Years ................................ ................................ ...........................
14.182. 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, b y Age Group –Subjects With at Least 6 Months of
Follow -up Time After Dose 2 – Phase 2/3 Sub jects ≥16 Years of Age
(Subjects Who Originally Received BNT162b2) –Safety Population Age
Group: >55 Years ................................ ................................ ..............................
14.183. Number (%) of Subje cts 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 L east 6 Months of
Follow -up Time After Dose 2 – Phase 2/3 Subjects ≥16 Years of Age
(Subjects W ho Originally Received BNT162b2) –Safety Population ...........
14.184. I ncidence Rates of at Least 1 Serious Adverse Event From Dose 3 to
Data Cutoff Date (13MAR2021), by System Organ Class and Preferred
Term, b y Baseline SARS -CoV -2 Status – Open -Label Follow -up Period –
Subjects Who Originally Received Placebo and T hen Received BNT162b2
After Unblinding – Phase 2/3 Subjects ≥16 Years of Age – Safety
Population Baseline SARS -CoV -2 Status: Positive ................................ ..........
14.185. I ncidence Rates of at Least 1 Serious Adverse Event From Dose 3 to
Data Cuto ff Date (13MAR2021), by System Organ Class and Preferred
Term, b y Baseline SARS -CoV -2 Status – Open -Label Follow -up Period –
Subjects Who Originally Received Placebo and T hen Received BNT162b2
After Unblinding – Phase 2/3 Subjects ≥16 Years of Age – Safet y
Population Baseline SARS -CoV -2 Status: Negative ................................ ........
14.186. I ncidence Rates of at Least 1 Serious Adverse Event From Dose 3 to
Data Cutoff Date (13MAR2021), by System Organ Class and Preferred
Term –Open -Label Follow -up Period – Subjects Who Originally Received
Placebo, had COVID -19 Occurrence After Dose 1 and Then Received
BNT162b2 After Unblinding –Phase 2/3 Subjects ≥16 Years of Age –
Safety Population ................................ ................................ ..............................
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CONFIDENTIAL14.187. Number (%) of Subjects Withdrawn Because of Adverse Events From
Dose 1 to 1 Month After Dose 2, b y System Orga n Class and Preferred
Term, b y Age Group –Blinded Placebo -Controlled Follow- up Period –
Phase 2/3 Subjects ≥16 Years of Age – Safet y Pop ulation Age Group: 16 -
55 Years ................................ ................................ ................................ .............
14.188. Number (%) of Subjects Withdrawn Because of Adverse Events From
Dose 1 to 1 Month After Dose 2, b y System Organ Class and Preferred
Term, b y Age Group –Blinded Placebo -Controlled Follow- up Period –
Phase 2/3 Subjec ts ≥16 Years of Age – Safet y Pop ulation Age Group: >55
Years ................................ ................................ ................................ ..................
14.189. I ncidence Rates of Subjects Withdrawn Because of Adverse Events From
Dose 1 to Unblinding Date, by System Organ Class and Preferred Term –
Phase 2/3 Subjects ≥16 Years of Age – Safet y Population ...........................
14.190 . Incidence Rates of Subjects Withdrawn Because of Adverse Events From
Dose 1 to Unblinding Date, by System Organ Class and Preferred Term, b y
Age Group –Phase 2/3 Subjects ≥16 Years of Age – Safet y Population
Age Group: 16 -55 Years ................................ ................................ ...................
14.191. I ncidence Rates of Subjects Withdrawn Because of Adverse Events From
Dose 1 to Unblinding Date, by System Organ Class and Preferred Term, b y
Age Grou p –Phase 2/3 Subjects ≥16 Years of Age – Safet y Population
Age Group: >55 Years ................................ ................................ ......................
14.192. I ncidence Rates of Subjects Withdrawn Because of Adverse Events From
Unblinding Date to Data Cutoff Date (13MAR2021), by System Organ Class
and Preferred Term –Open -Label Follow -up Period –Subjects Who
Originall y Received BNT162b2 –Phase 2/3 Subjects ≥16 Years of Age –
Safety Population ................................ ................................ ..............................
14.193. Number (%) of Subjects Withdrawn Because of Adverse Events From
Dose 1 to 6 Months After Dose 2, b y System Organ Class and Preferred
Term, by Age Group – Subjects With at Least 6 Months of Follow- up Time
After Dose 2 – Phase 2/3 Subjects ≥16 Years of Age (Subjects Who
Originall y Received BNT162b2) – Safet y Population Age Group: 16-55
Years ................................ ................................ ................................ ..................
14.194. Number (%) of Subjects Withdrawn Because of Adverse Events From
Dose 1 to 6 Months After Dose 2, b y System Organ Class and Preferred
Term, b y Age Group –Subjects With at Least 6 Months of Follow- up Time
After Dose 2 – Phase 2/3 Subjects ≥16 Years of Age (Subjects Who
Originall y Received BNT162b2) – Safet y Population Age Group: >55 Years
14.195. Subjects Reporting Lymphadenopath y –Blinded Placebo -Controlled
Follow -up Period – Phase 2/3 Subjects ≥16 Years of Age – Safet y
Population ................................ ................................ ................................ ..........
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Dose 1 to Unblinding Date, by System Organ Class and Preferred Term –
Blinded Placebo -Controlled Follow- up Period – Phase 2/3 Subjects ≥16
Years of Age – Safet y Population ................................ ................................ ...
14.197. I ncidence Rates of Arthralgia Reported ≥8 Day s After Either Dose 1 or
Dose 2 –Blinded Placebo-C ontrolled Follow -up Period –Phase 2/3
Subjects ≥16 Years of Age – Safet y Population ................................ ...........
Additional ....................................................................................................................
14.198. Demographic Characteristics, b y Age Groups –Phase 2/3 Subjects ≥16
Years of Age –Safet y Population ................................ ................................ ...
Supplemental Figures ................................ ................................ ................................ .........
14.1. Reverse Cumulative Distribution Curves, SARS- CoV -2 Neutralization Assay –
NT50 –Phase 1, 2 Doses, 21 Day s Apart – 18-55 Years of Age – BNT162b2 (30
μg)/Placebo – Evaluable Immunogenicit y Population ................................ .............
14.2. Reverse Cumulative Distribution Curves, SARS- CoV -2 Neutralization Assay –
NT50 –Phase 1, 2 Doses, 21 Day s Apart – 65-85 Years of Age – BNT162b2 (30
μg)/Placebo – Evaluable Immunogenicit y Population ................................ .............
14.3. Reverse Cumulative Distribution Curves, S1-Binding IgG Level Assay – Phase
1, 2 Doses, 21 Day s Apart – 18-55 Years of Age – BNT162b2 (30 μg)/Placebo –
Evaluable Immunog enicity Population ................................ ................................ ....
14.4. Reverse Cumulative Distribution Curves, S1-Binding IgG Level Assay – Phase
1, 2 Doses, 21 Day s Apart – 65-85 Y ears of Age –BNT162b2 (30 μg)/Placebo –
Evaluable Immunogenicity Population ................................ ................................ ....
Subject Narratives...............................................................................................................
15.REFERENCES ................................................................................................................ 1584
ERRATA
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16. APPENDI CES
16.1. Study Information
16.1.1. Final Protocol and Protocol Amendments
16.1.2. Sample Case Report Form(s) (CRF)/Data Collection Tool(s) (DCT)
16.1.3. Independent Ethics Committees (I ECs) or Institutional Review
Boards (IRBs) and Sample Standard Subject Information Sheet and
Informed Consent Document (I CD)
16.1.4. List and Description of Investigators and Service Providers
16.1.5. Signatures of Principal or Coordinating/Leading Investigator(s) or
Sponsor's Responsible Medical Officer, Depending on the Regulatory
Authority 's Requirement
16.1.5.1. Sponsor and Sponsor Agent
16.1.5.2. CSR Investigator 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 I dentification 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
16.2.7. Adverse Events by Subject
16.2.8. Individual Laboratory Measurements by Subject
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16.3. Case Report Form(s) (CRF) or Data Collection Tool(s) (DCT)
16.3.1. CRFs (or DCTs) For Deaths, Other Serious Adverse Events, and
Subject Withdrawals due to Adverse Events
16.3.2. Other CRFs (or DCTs)
16.4. Individual Subject Data Listings
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4. LIST OF ABBREVIATION S AND DEFINITION OF TERMS
Abbreviation Definition
AE adverse event
AESI adverse event of special interest
BDR blinded data review
BLQ below the level of quantitation
BMI body mass index
CDC Centers for Disease Control and Prevention (United States)
COVID -19 coronavirus disease 2019
CRF case report form
CRO contract research organization
CSR clinical study report
CV curriculum vitae
DCT data collection tool
DMC data monitoring committee
e-diary electronic diary
ECMO extracorporeal membrane ox ygenation
EU European Union
FiO 2 fraction of inspired ox ygen
FSFV first subject first visit
GCP Good Clinical Practice
GMC geometric mean concentration
GMFR geometric mean fold rise
GMR geometric mean ratio
GMT geometric mean titer
HBV hepatitis B virus
HCV hepatitis C virus
HCV Ab hepatitis C virus antibody
HIV human immunodeficiency virus
HR heart rate
IA interim analy sis
ICD informed consent document
ICH International Council for Harmonisation
ICU intensive care unit
IEC independent ethics committee
IgG immunoglobulin G
IND Investigational New Drug
IRB institutional review board
IRC internal review committee
IRR illness rate ratio
IRT interactive response technology
LLOQ lower limit of quantitation
LNP lipid nanoparticle
MedDRA Medical Dictionary for Regulatory Activities
modRNA nucleoside -modified messenger ribonucleic acid
NAAT nucleic acid amplification test
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Abbreviation Definition
N-binding SARS -CoV -2 nucleoprotein binding
NT50 neutralizing titer 50
P2 S SARS -CoV -2 full -length, P2 mutant, prefusion spike gl ycoprotein
PaO 2 partial pressure of oxygen, arterial
PD protocol deviation
PT preferred term
PY person -years
QA quality assurance
QTL quality tolerance limit
RBD receptor -binding domain
RCDC reverse cumulative distribution curve
RDC remote data capture
RNA ribonucleic acid
RR respiratory rate
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
SpO 2 oxygen saturation as measured by pulse oximetry
TME targeted medical event
US United States
VE vaccine efficacy
VOC variant of concern
WBC white blood cell
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5.ETHICS
5.1. Independent Ethics Committee or Institutional Review Board
The final protocol, an y amendments (Appendix 16.1.1), and ICD ( Appendix 16.1.3.2 ) were
reviewed and approved by the IRBs and/or IECs for each of the investigational centers
participating in the stud y. The I RBs and IECs are listed in Appendix 16.1.3. 1.
5.2.Ethical Conduct of the Study
This stud y 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 “participant” and “subject” are used interchangeabl y.
A signed and dated informed consent was required before an y stud y-specific activity was
performed . If the participant was not able to legally sign consent, the investigator, or a person
designated b y the investigator, obtained a signed and dated ICD from each participant’s
parent(s)/guardian(s) before an y stud y-specific ac tivity 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
The study was conducted by investigators contracted by and under the direction of Pfizer .
The investigators were responsible for adhering to the study procedures described in the
protocol, for keeping records of the study intervention, and for ensuring accurate completion
of the CRFs and DCTs supplied by Pfizer .
This study was undertaken by Pfizer and BioNTech and conducted at 153sites: 131 in the
United States, 9 in Turkey , 6in Germany , 4in South Africa, 2 in Brazil, and 1in Argentina
(Appendix 16.1.4.1 ).
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 test ing
laboratories involved in this study , with the tests that they performed.
No sites were terminated from the study to date.
7.INTRODUCTION
This study is ongoing, and participants are continuing to be evaluated . The final analysis
interim C4591001 CSR dated 03December 2020, reported ongoing Phase 1andPhase 2
safet y and immunogenicity data , combined Phase 2/3 safet y data, andcomplete dprespecified
hypothesis testing of efficacy .Efficacy analy ses were event -driven, based on accrued events
for all Phase 2/3 participants ≥12 y ears of age. The prespecified interim analy sis was
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conducted on an accrued 94 evaluable COVID -19 cases for the first primary efficacy
endpoint (data cutoff dat e: 04 November 2020), and the final anal ysis was conducted on an
accrued 170 evaluable COVID -19 cases for the first primary efficacy endpoint (data cutoff
date: 14 November 2020).
Phase 1 evaluation of safety and immunogenicity dose-level finding results in participants
18through 55 and 65 through 85 years of age led to the selection of 1 of 2 vaccine
candidate s, BNT162b1 and BNT162b2. Both constructs were safe and well tolerated ( except
for BNT162b1 at 100 μg). Given that the reactogenicity profile for BN T162b2 wa s more
favorable than BNT162b1 in both y ounger and older adults with similar immunogenicit y
results, and with non -human primate challenge studies showing that BNT162b2 led to earlier
virus clearance and no evidence of virus in the lung1,BNT162b2 at the 30 µg dose level was
selected and advanced into the Phase 2/3 expanded cohort and efficacy evaluation.
Phase 2 of the stud y (for which enrollment has completed) comprised the evaluation of safet y
and immunogenicit y data for the first 360 participan ts 18through 85 years of age (180 from
active vaccine group and 180 from placebo group) that enter edthe study after completion of
Phase 1 to evaluate BNT162b2 30 µg in a larger cohort. Overall, Phase 2 safet y and
immunogenicit y results were consistent wi th those observed in Phase 1.
Phase 2/3 evaluate dthe efficacy of BNT162b2 30 µg , and provide dadditional safet y,
efficacy ,and immunogenicity data in a larger population . Prespecified efficacy
(event -driven) in participants ≥12 y ears of age ( relatively few participants 12 through
15years of age had enrolled in the study , and no COVID -19 cases in this age group accrued
at that time )and ongoing safet y data in participants ≥16years of age with a median of at least
2months of follow -up after Dose 2 and u p to the data cutoff date of 14 November 2020 were
previously reported in the final anal ysis interim CSR dated 03 December 2020.
At the time of th e final analy sis interim CSR dated 03 December 2020, the first
37,706 participants 16 through 91years of age were anal yzed for safety . Individuals
12 through 15years of age were later permitted to enroll in the study , and results for these
participants will be reported separatel y.
On 14 December 2020, the process of disclosing vaccine assignments for all trial participants
≥16 y ears of age began. Hence, for each trial participant, there are 2periods in the study :
enrollment into the observer- blind phase until the date of vaccine disclosure and the time in
the study after disclosure. Participants who originally were randomized to BNT162b2, are
continuing to be followed for safety as specified in the protocol. The safety data for
participants who originally were randomized to and received placebo prior to disclosure of
vaccine assignment are standard blinded data that contribute to controlled assessment of
safet y compared to individuals who were randomly assigned to BNT162b2. After vaccine
treatment disclosure and the administration of BNT162b2, the placebo participants can no
longer be used for direct comparison with those who originall y were randomized to
BNT162b2. Given that individuals were unblinded on different day s after
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Based on a data cutoff date of 13 March 2021, t his interim C4591001 CSR summarizes
updated efficacy anal yses on an accrued 927 COVID -19 cases for the f irst primary endpoint
during blinded follow -up to evaluate duration of protection and the following
immunogenicit y and safety data :
Blinded placebo -controlled follow -up period: from Dose 1 to 1 month after Dose 2 and to
the date of unblinding:
Phase 1 follow -up of safety from Dose 1 to the unblinding date (up to approximately
6 months after Dose 2 ) and immunogenicit y 6 months after Dose 2 for the BNT162b2
30-µggroup on lyin participants ≥18through 55 and 65 through 85 years of age .
Phase 2/3 safet y analysis for participants ≥16years of ag e, including participants with
confirmed stable HI V disease, from Dose 1 to 1 month after Dose 2 (no exposure
adjustment because all participants have the same follow-up period) and from Dose 1
to the unblinding date (exposure adjusted).
Open -label observ ational follow -up period: from time of unblinding to the data cutoff
date:
Phase 2/3 safet y analysis for original BNT162b2 participants ≥16years of age
Phase 2/3 safet y analysis for original placebo participant s ≥16years of age who then
received BNT162b2
Cumulative safety from Dose 1 to at least 6 months after Dose 2: for Phase 2/3 original
BNT162b2 participants ≥16 years of age (inclusive of blinded data and open- label data)
that includes at least 3000 in each age group (16 t hrough 55 years of age, >55 years of
age)
8. STUDY OBJECTIVES AND ENDPOINTS
8.1.Phase 1
Refer to the final analysis interim C4591001 CSR dated 0 3December 2020 , Section 8 for the
study objectives, estimands, and endpoints reported based on Appendix 16.1.1, Protocol
Amendment 9.
The study objective s, estimands, and endpoints presented in Table 1 are from
Appendix 16.1.1, Protocol Amendment 14. Only the primary safet y (Dose 1 to unblinding
date [up to approximately 6 months after Dose 2 ]) and partial secondary immunogenicit y
(6months after Dose 2) objectives for the BNT162b2 30 µg or corresponding placebo are
presented in this interim CSR . Exploratory objectives, estimands, and endpoints will be
summarized at a later time .
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Table 1.Phase 1 Objectives, Estimands, and Endpoints
Objectives Estimands Endpoints Reference
Primary: Primary: Primary:
To describe the safety and tolerability
profiles of prophylactic BNT162
vaccines in healthy adults after 1 or 2
dosesIn 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 6 months a fter the last
doseLocal reactions (pain at the injection site
redness, and swelling)
Systemic events (fever, fatigue,
headache, chills, vomiting, diarrhea, new
or worsened muscle pain, and new or
worsened joint pain)
AEs
SAEsInterim data for local reactions and
systemic events reported up to 7 days
after each dose, and AEs and SAEs are
reported from Dose 1 to 1 month after the
last dose for all groups evaluated , and to
the cutoff date after Dose 2 for the
BNT162b2 30 µg group only in final
analysis interim CSR dated 03 December
2020 .
AEs and SAEs from Dose 1 to the
unblinding date for the BNT162b2 30 µg
group only are reported in this CSR .
In addition, the percentage of participants with:
Abnormal hematology and chemistry laboratory
values 1 and 7 days after Dose 1; and 7 days
after Dose 2
Grading shifts in hematology and chemistry
laboratory assessments between baseline and
1and 7 days after Dose 1; and before Dose 2
and 7 days after Dose 2Hematology and chemistry laboratory
param eters detailed in Appendix 16.1.1,
Protocol Section 10.2Interim data are reported in final analysis
interim CSR dated 03 December 2020.
Secondary: Secondary: Secondary:
To describe the immune responses
elicited by prophylactic BNT162
vaccines in healthy adults after 1 or
2 dosesIn participants complying with the key protocol
criteria (evaluable participants) at the following
time points after receipt of study intervention: 7 and
21days after Dose 1; 7 and 14 days and 1, 6, 12,
and 24 months afte r Dose 2
GMTs at each time point
GMFR from before vaccination to each
subsequent time point after vaccination
Proportion of participants achieving ≥4-fold rise
from before vaccination to each subsequent time
point after vaccinationSARS -CoV -2 neutralizing titers Interim data reported up to 1month af ter
Dose 2 in final analysis interim CSR
dated 03 December 2020.
Interim data up to 6 months after Dose 2
for the BNT162b2 30 µg group only are
reported in this CSR.
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Table 1.Phase 1 Objectives, Estimands, and Endpoints
Objectives Estimands Endpoints Reference
GMCs at each time point
GMFR from prior to first dose of study
intervention to each subsequent time point
Proportion of participants achieving ≥4-fold rise
from before vaccination to each subsequent time
point after vaccinationS1-binding IgG levels and RBD- binding
IgG levelsInterim data reported up to 1 month after
Dose 2 in final analysis interim CSR
dated 03 December 2020.
Interim data of S1 -binding IgG levels up
to 6 months after Dose 2 for the
BNT162b2 30 µg group only are
reported in this CSR.
GMR, estimated by the ratio of the geometric
mean of SARS -CoV -2 neutralizing titers to the
geometric mean of binding IgG levels at each
time pointSARS -CoV -2 neutralizing titers
S1-binding IgG levels
RBD -binding IgG levelsInterim data reported up to 1 month after
Dose 2 in final analys is interim CSR
dated 03 December 2020.
Interim data for SARS -CoV -2
neutralizing titers to S1 -binding IgG
levels up to 6 months after Dose 2 for
the BNT162b2 30 µg group only are
reported in this CSR.
Exploratory: Exploratory: Exploratory:
To describe the immune responses
elicited by a third dose of
prophylactic BNT162b2
administered to healthy adults 6 to
12 months after the second dose of
either BNT162b1 or BNT162b2 GMC/GMT and GMFR at the time of Dose 3
and 7 days and 1 month after Dose 3. SARS -CoV -2 reference -strain
neutralizing titers
SARS -CoV -2 SA -variant neutralizing
titers
Full-length S -binding or S1 -binding
IgG levelsData will be reported at a later time.
GMR of SARS -CoV -2 reference -strain
neutralizing titers 1 month after Dose 3 to 1
month after Dose 2 SARS -CoV -2 reference -strain
neutralizing titersData will be reported at a later time.
GMR of SARS -CoV -2 SA -variant neutralizing
titers 1 month after Dose 3 to SARS -CoV -2
reference -strain neutralizing titers 1 month
after Dose 2 SARS -CoV -2 reference -strain
neutralizing titers
SARS -CoV -2 SA -variant neutralizing
titersData will be reported at a later time.
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Table 1.Phase 1 Objectives, Estimands, and Endpoints
Objectives Estimands Endpoints Reference
To describe the safety profile of a
third dose of prophylactic
BNT162b2 administered to healthy
adults 6 to 12 months after the
second dose of either BNT162b1 or
BNT162b2In participants receiving a third dose of BNT162b2,
the percentage of participants reporting:
Local reactions for up to 7 days after Dose 3
Systemic events for up to 7 days after Dose 3
AEs and SAEs from Dose 3 to 1 month after
Dose 3 Local reactions (pain at the injection
site, redness, and swelling)
Systemic events (fever, fatigue,
headache, chills, vomiting, diarrhea,
new or worsened muscle pain, and
new or worsened joint pain)
AEs
SAEsData will be reported at a later time.
Source: Appendix 16.1.1, Protocol Section 3.1 .
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8.2.Phase 2/3
Refer to the final anal ysis interim C4591001 CSR dated 03 December 2020, Section 8 for the
study objectives, estimands, and endpoints reported based on Appendix 16.1.1, Protocol
Amendment 9.
The study objective s, estimands, and endpoints presented in Table 2 are from
Appendix 16.1.1, Protocol Amendment 14. This report summarizes results as described in
Section 7.
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Table 2. Phase 2/3 Objectives, Estimands, and Endpoints
Objectivesa Estimands Endpoints Reference
Primary Efficacy
To evaluate the efficacy of prophylactic
BNT162b2 against confirmed
COVID -19 occurring from 7 days after
the second dose in participants without
evidence of infection before vaccinationIn participants complying with the key
protocol criteria (evaluable participants) at
least 7 days after receipt of the second dose
of study intervention: 100 × (1 – IRR)
[ratio of active vaccine to placebo]COVID -19 incidence per 1000 person -years
of follow -up based on central laboratory or
locally confirmed NAAT in participants with
no serological or virological evidence (up to 7
days after receipt of the second dose) of past
SARS -CoV -2 infectionPrespecified complete efficacy data
are reported in final analysis interim
CSR dated 03 December 2020.
Updated efficacy data are reported in
this CSR.
To evaluate the efficacy of prophylactic
BNT162b2 against confirmed
COVID -19 occurring from 7 days after
the second dose in participants with and
without 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 NAATInterim data are reported in final
analysis interim CSR dated
03December 2020.
Updated effi cacy data are reported in
this CSR.
Primary Safety
To define the safety profile of
prophylactic BNT162b2 in the first
360participants randomized (Phase 2)In participants receiving at least 1 dose of
study intervention, the percentage of
participants reporting:
Local reactions for up to 7 days
following each dose
Systemic events for up to 7 days
following each dose
AEs from Dose 1 to 7 days after the
second dose
SAEs from Dose 1 to 7 days after the
second doseLocal reactions (pain at the injection site,
redness, and swelling)
Systemic events (fever, fatigue, headache,
chills, vomiting, diarrhea, new or worsened
muscle pain, and new or worsened joint
pain)
AEs
SAEsInterim data are reported in final
analysis interim CSR dated
03December 2020.
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Table 2. Phase 2/3 Objectives, Estimands, and Endpoints
Objectivesa Estimands Endpoints Reference
To define the safety profile of
prophylactic BNT162b2 in all
participants randomized in Phase 2/3In participants receiving at least 1 dose of
study intervention, the percentage of
participants reporting:
Local reactions for up to 7 days
following each dos e
Systemic events for up to 7 days
following each dose
AEs from Dose 1 to 1 month after the
second dose
SAEs from Dose 1 to 6 months after the
second doseAEs
SAEs
In a subset of at least 6000 participants:
o Local reactions (pain at the
injection site, redness, and
swelling)
o Systemic events (fever, fatigue,
headache, chills, vomiting,
diarrhea, new or worsened muscle
pain, and new or worsened joint
pain)Interim data are reported up to
1month after Dose 2 and to the data
cutoff date (14 November 2020) in
final analysis interim CSR dated
03December 2020.
Cumulative i nterim data up to cutoff
date are reported in this CSR.
To define the safety profile of
prophylactic BNT162b2 in participants
12 to 15 years of age in Phase 3In participants receiving at least 1 dose of
study intervention, the percentage of
participants reporting:
Local reactions for up to 7 days
following each dose
Systemic events for up to 7 days
following each dose
AEs from Dose 1 to 1 month after the
second dose
SAEs from Dose 1 to 6 months after
the second dose Local reactions (pain at the injection
site, redness, and swelling)
Systemic events (fever, fatigue,
headache, chills, vomiting, diarrhea, new
or worsened muscle pain, and new or
worsened joint pain)
AEs
SAEsData will be repor ted separately .
To describe the safety and tolerability
profile of BNT162b2 SAgiven as 1 or 2
doses to BNT162b2 -experienced
participants, or as 2 doses to
BNT162b2 -naïve participants
To describe the safety and tolerability
profile of BNT162b2 given as a third
dose to BNT162b2 -experienced
participantsIn participants receiving at least 1 dose of
study intervention, the percentage of
participants reporting:
Local reactions for up to 7 days
following each dose
Systemic events for up to 7 days
following each dose
AEs from Dose 1 to 1 month after the
last dose
SAEs from Dose 1 to 5 or 6 months
after the last doseLocal reactions (pain at the injection site,
redness, and swelling)
Systemic events (fever, fatigue, headache,
chills, vomiting, diarrhea, new or
worsened muscle pain, and new or
worsened joint pain)
AEs
SAEsData will be reported at a later time.
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Table 2. Phase 2/3 Objectives, Estimands, and Endpoints
Objectivesa Estimands Endpoints Reference
Primary Immunogenicity
BNT162b2 -experienced participants
To demonstrate the noninferiority of the
anti–reference strain immune response
after a third dose of BNT162b2
compared to after 2 doses of
BNT162b2, in the same individualsGMR of reference strain NT 1 month after
the third dose of BNT162b2 to 1 month
after the second dose of BNT162b2
The difference in percentages of
participants with seroresponse to the
reference strain at 1 month after the third
dose of BNT162b2 and 1 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 BN T162b2) of past SARS -CoV -
2 infectionData will be reported at a later time.
To demonstrate the noninferiority of the
anti-SA immune response after 1 dose
of BNT162b2 SAcompared to the anti–
reference strain immune response after
2 doses of BNT162b2, in the same
individualsGMR of SA NT 1 month after 1 dose of
BNT162b2 SAto the 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 time.
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 month after the second
dose of BNT162b2SARS -CoV -2 SA and reference strain NTs in
participants with no serological or virological
evidence (up to 1 month after receipt of the
second dose of BNT162b2 SAor BNT162b 2 as
appropriate) of past SARS-CoV -2 infectionData will be reported at a later time.
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Table 2. Phase 2/3 Objectives, Estimands, and Endpoints
Objectivesa Estimands Endpoints Reference
Secondary Efficacy
To evaluate the efficacy of prophylactic
BNT162b2 against confirmed
COVID -19 occurring from 14 days
after the second dose in participants
without evidence of infection before
vaccinationIn participants complying with the key
protocol criteria (evaluable participants) at
least 14 days after receipt of the second
dose of study intervention:
100 × (1 –IRR) [ratio of active vaccine to
placebo]COVID -19 incidence per 1000 person -years
of follow -up based on central laboratory or
locally confirmed NAAT in participants with
no serological or virological evidence (up to
14 days after receipt of the second dose) of
past SARS -CoV -2 infectionPrespecif ied complete efficacy data
are reported in final analysis interim
CSR dated 03 December 2020.
To evaluate the efficacy of prophylactic
BNT162b2 against confirmed
COVID -19 occurring from 14 days
after the second dose in participants
with and without eviden ce 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 inci dence per 1000 person -years
of follow -up based on central laboratory or
locally confirmed NAATPrespecified complete efficacy data
are reported in final analysis interim
CSR dated 03 December 2020.
To evaluate the efficacy of prophylactic
BNT162b2 against confirmed severe
COVID -19 occurring from 7 days and
from 14 days after the second dose in
participants without evidence of
infection before vaccinationIn participants complying with the key
protocol criteria (evaluable participants)
at least 7 days
and
at least 14 days
after receipt of the second dose of study
intervention: 100 × (1 –IRR)
[ratio of active vaccine to placebo]Confirmed severe COVID -19 incidence per
1000 person -years of follow -up in
participants with no serological or virological
evidence (up to 7 days and up to 14 days after
receipt of the second dose) of past
SARS -CoV -2 infectionPrespecified complete efficacy data
are reported in final analysis interim
CSR dated 03 December 2020.
Updated efficacy data occurring from
at leas t7 days after the second dose
only are reported in this CSR.
To evaluate the efficacy of prophylactic
BNT162b2 against confirmed severe
COVID -19 occurring from 7 days and
from 14 days after the second dose in
participants with and without evidence
of infection before vaccinationIn participants complying with the key
protocol criteria (evaluable participants)
at least 7 days
and
at least 14 days
after receipt of the second dose of study
intervention: 100 × (1 –IRR)
[ratio of active vaccine to plac ebo]Confirmed severe COVID -19 incidence per
1000 person -years of follow -upPrespecified complete efficacy data
are reported in final analysis interim
CSR dated 03 December 2020.
Updated efficacy data occurring from
at leas t7 days after the second dose
only are reported in this CSR.
To describe the efficacy of prophylactic
BNT162b2 against confirmed
COVID -19 (according to the
CDC -defined symptoms) occurring
from 7 days and from 14 days after the
second dose in participants without
evidence of infection before vaccinationIn participants complying with the key
protocol criteria (evaluable participants)
at least 7 days
and
at least 14 days
after receipt of the second dose of study
intervention: 100 × (1 –IRR)
[ratio of active vaccine to placebo]COVID -19 incidence per 1000 person -years
of follow -up based on central laboratory or
locally confirmed NAAT in participants with
no serological or virological evidence (up to 7
days and up to 14 days after receipt of the
second d ose) of past SARS -CoV -2 infectionPrespecified complete efficacy data
are reported in final analysis interim
CSR dated 03 December 2020.
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Table 2. Phase 2/3 Objectives, Estimands, and Endpoints
Objectivesa Estimands Endpoints Reference
To describe the efficacy of prophylactic
BNT162b2 against confirmed
COVID -19 (according to the
CDC -defined symptoms) o ccurring
from 7 days and from 14 days after the
second dose in participants with and
without evidence of infection before
vaccinationIn participants complying with the key
protocol criteria (evaluable participants)
at least 7 days
and
at least 14 days
after receipt of the second dose of study
intervention: 100 × (1 –IRR)
[ratio of active vaccine to placebo]COVID -19 incidence per 1000 person -years
of follow -up based on central laboratory or
locally confirmed NAATPrespecified complete efficacy data
are reported in final analysis interim
CSR dated 03 December 2020.
To evaluate the efficacy of prophylactic
BNT162b2 against non -S
seroconversion to SARS -CoV -2 in
participants without evidence of
infection or 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 o f 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 1 000 person -years of follow -up
based on central laboratory –confirmed
NAAT in participants with no serological or
virological evidence (up to the start of the
asymptomatic surveillance period) of past
SARS -CoV -2 infectionData will be reported at a later tim e.
Secondary Immunogenicity
To demonstrate the noninferiority of the
immune response to prophylactic
BNT162b2 in participants 12 to 15
years of age compared to participants
16 to 25 years of ageGMR, estimated by the ratio of the
geometric mean of SARS -CoV -2
neutralizing titers in the 2 age groups (12 -
15 years of age to 16 -25 years of age) 1
month after completion of vaccinationSARS -CoV -2 neutralizing titers in
participants with no serological or virological
evidence (up to 1 month after receipt of the
second dose) of past SARS -CoV -2 infectionData will be reported separately .
BNT162b2 -experienced participants
To demonstrate the noninferiority of the
anti-SA immune response after a third
dose of BNT162b2 compared to the
anti–reference strain immune response
after 2 doses of BNT162b2, in the same
individuals GMR of SA NT 1 month after the third
dose of BNT162b2 to the reference strain
NT 1 month after the second dose of
BNT162b2
The difference in percentages of
participants w ith seroresponse to the SA
strain at 1 month after the third dose of
BNT162b2 and seroresponse to the SARS -CoV -2 SA and reference strain NTs in
participants with no serological or virological
evidence (up to 1 month after receipt of the
third dose of BNT162b2) of past SARS -CoV -
2 infectionData will be reported at a later time.
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Table 2. Phase 2/3 Objectives, Estimands, and Endpoints
Objectivesa Estimands Endpoints Reference
reference strain at 1 month after the second
dose of BNT162b2
To demonstrate the noninferiority of the
anti–reference strain immune response
after 1 dose of BNT162b2 SAcompared
to after 2 doses of BNT162b2, in the
same individuals GMR of reference strain NT 1 month after
1 dose of BNT162b2 SAto 1month after the
second dose of BNT162b2
The difference in percentages of
participants with seroresponse to the
reference st rain at 1 month after 1 dose of
BNT162b2 SAand 1 month after the second
dose of BNT162b2SARS -CoV -2 reference strain NTs in
participants with no serological or virological
evidence (up to 1 month after receipt of 1
dose of BNT162b2 SA) of past SARS -CoV -2
infectionData will be reported at a later time.
To descriptively compare the anti-SA
immune response after 1 dose of
BNT162b2 SAand a third dose of
BNT162b2 GMR of SA NT 1 month after 1 dose of
BNT162b2 SAto 1month after the third
dose of BNT162b2
The d ifference in percentages of
participants with seroresponse to the SA
strain at 1 month after 1 dose of
BNT162b2 SAand 1 month after the third
dose of BNT162b2SARS -CoV -2 SA NT in participants with no
serological or virological evidence (up to 1
month after receipt of 1 dose of BNT162b2 SA
or the third dose of BNT162b2) of past
SARS -CoV -2 infectionData will be reported at a later time.
To descriptively compare the anti-SA
immune response after 2 doses of
BNT162b2 SAand the anti –reference
strain immune 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 virological
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 af ter the second dose of SARS -CoV -2 SA NTs in participants with no
serological or virological evidence (up to 1
month after receipt of the second dose of
BNT162b2 SAor BNT162b2 as appropriate)
of past SARS -CoV -2 infectionData will be reported at a later time.
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Table 2. Phase 2/3 Objectives, Estimands, and Endpoints
Objectivesa Estimands Endpoints Reference
BNT162b2 SAand 1 month after the second
dose of BNT162b2
To descriptively compare the anti–
reference strain immune response after
2 doses of BNT162b2 SAand after 2
doses of BNT162b2 GMR of reference strain NT 1 month after
the second dose of BNT162b2 SAto
1month after the second dose of
BNT162b2
The difference in percentages of
participants with seroresponse to reference
strain at 1 month after the second dose of
BNT162b2 SAand 1 month after the second
dose of BNT162b2SARS -CoV -2 reference strain NT s in
participants with no serological or virological
evidence (up to 1 month after receipt of the
second dose of BNT162b2 SAor BNT162b2 as
appropriate) of past SARS-CoV -2 infectionData will be reported at a later time.
Exploratory
To describe the efficacy of prophylactic
BNT162b2 against confirmed
COVID -19 occurring from 7 days after
the second dose through the blinded
follow -up period in participants
without, and with and without, evidence
of infection before vaccinationIn participants complying with the key
protocol criteria (evaluable participants)
after receipt of the second dose of study
intervention:
100 × (1 –IRR) [ratio of active vaccine to
placebo]COVID -19 incidence per 1000 person -years
of blinded follow -up based on central
laboratory o r locally confirmed NAATInterim d ata are reported in this CSR.
To describe the incidence of confirmed
COVID -19 through the entire study
follow -up period in participants who
received BNT162b2 at initial
randomization or subsequentlyIn participants who received BNT162b2 (at
initial randomization or subsequently):
Incidence per 1000 person-ye ars of follow-
upCOVID -19 incidence per 1000 person -years
of follow -up based on central laboratory or
locally confirmed NAATData will be reported at a later time.
To evaluate the immune response over
time to prophylactic BNT162b2 and
persistence of immune response in
participants with and without
serological or virological evidence of
SARS -CoV -2 infection before
vaccinationGMC/GMT and GMFR at baseline and 1,
6, 12, and 24 months after completion of
vaccinationFull-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 neutr alizing titers in
final analysis interim CSR dated
03December 2020.
Phase 2/3 d ata will be reported at a
later time.
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Table 2. Phase 2/3 Objectives, Estimands, and Endpoints
Objectivesa Estimands Endpoints Reference
To describe the incidence of non -S
seroconversion to SARS -CoV -2
through the entire study follow-up
period in participants who received
BNT162b2 at initial randomization In participants who received BNT162b2 at
initial randomization:
Incidence per 1000 person-ye ars of follow-
upIncidence of asymptomatic SARS -CoV -2
infection per 1000 person -years of follow -up
based on N -binding a ntibody 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 o f asymptomatic SARS -CoV -2
infection per 1000 person -years of follow -up
based on central laboratory –confirmed
NAAT in participants with serological or
virological evidence (up to the start of the
asymptomatic surveillance period) of past
SARS -CoV -2 infectio nData 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 -19Full S -binding or S1 -binding IgG levels
SARS -CoV -2 neutralizing titers
Identification of SARS -CoV -2 variants(s)Data will be reported at a later time.
To describe the safety, immunogenicity,
and efficacy of prophylactic BNT162b2
in individuals with confirmed stable
HIV diseaseAll safety, immunogenicity, and efficacy
endpoints described aboveSafety data only in participants with
confirmed stable HIV disease are
reported in this CSR.
To describe the safety and
immunogenicity of prophylactic
BNT162b2 in individuals 16 to 55 years
of age vaccinated with study
intervention produced by
manufacturing “Process 1” or “Process
2”b AEs
SAEs
SARS -CoV -2 neutralizing titersData will be reported at a later time.
To describe the immune response to
any VOCs not already specifiedGeometric mean NT for any VOCs not
already specified, after any dose of
BNT162b2 SAor BNT162b2 SARS -CoV -2 NTs for any VOCs not
already specifiedData will be reported at a later time.
To describe the cell -mediated immune
response, and additional humoral
immune response parameters, to the Data will be reported at a later time.
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Table 2. Phase 2/3 Objectives, Estimands, and Endpoints
Objectivesa Estimands Endpoints Reference
reference strain and SA in a subset of
participants:
7 Days and 1 and 6 months after
BNT162b2 SAgiven as 1 or 2 doses
to BNT162b2 -experienced
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
BNT1 62b2-experienced
participants
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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9.INVESTIGATIONAL PLAN
9.1.Overall Study Design and Plan
This is a Phase 1/2/3, randomized, multinational, placebo -controlled, observer -blind, dose
finding , vaccine candidate –selection, and efficacy study in health y individuals.
The study consists of 2 parts: Phase 1 to identify preferred vaccine candidate(s) and dose
level(s); and Phase 2/3 as an expanded cohort and efficacy part. These parts, and the
progression between them, are detailed in Figure 1.
Figure1.Study Schema
Phase 1 For each vaccine candidate (4:1 randomization active:placebo)
Age: 18-55 y Age: 65-85 y
Low-dose -level 2 -dose group (n=15)
IRC(safety) IRC (safetyLow-dose -level 2 -dose group (n=15)after Dose 1)
Mid-dose -level 2 -dose group (n=15)
IRC (safety)IRC (safetyMid-dose -level 2 -dose group (n=15)after Dose 1)
High -dose -level 2 -dose group (n=15)
IRC (safetyHigh -dose -level 2 -dose group (n=15)after Dose 1)
IRC choice of group(s) for Phase 2/3
(safety & immunogenicity after Doses 1 and 2)
Phase 2/3 Single vaccine candidate (1:1 randomization active:placebo)
Safety and immunogenicity analysis of
Phase 2 data (first 360 participants)
by unblinded team (these participants
will also be included in Phase 3
analyses)Age: ≥12
(Stratified 12 -15, 16-55, or >55)
BNT162b2 30 µg or placebo 2 doses
(n~21,999 per group, total n~43,998)
Source: Appendix 16.1.1, Protocol Section 1.2
Note: Participants ≥16 years of age who originally received placebo w ereoffered the opportunity to receive BNT162b2 at
defined points as part of the study.
The study evaluated the safet y, tolerability , and immunogenicit y of 3different SARS -CoV -2
RNA vaccine candidates against COVID- 19 and the Phase 2/3 efficacy of 1 selected
candidate based on Phase 1 results:
As a 2 -dose (separated by 21 day s) schedule;
At various dose levels in Phase 1;
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As a booster; (data will be reported at a later time)
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 st udyexcept those who were designated for unblinded activities following the
protocol and the data blinding plan .
Refer to Appendix 16.1.1, Protocol Section 4.1 for further detail on the overall study design.
Planned Booster and Variant Strain Evaluation
Planned booster and VOC evaluation are not included in this report and will be reported at a
later time.
Refer to Appendix 16.1.1, Protocol Section 4.1.1 for further details on the booster dose for
Phase 1, and Appendix 16.1.1, Protocol Section 4.1.2for further details on the booster dose
and new cohort for Phase 2/3 to evaluate potential homologous and heterologous protection
against emerging SARS -CoV -2 VOCs .
Unblinding Considerations
The study was unblinded in stages once all ongoing participants either had been individually
unblinded or had concluded their 6 -month post –Dose 2 study visit, as follows:
Phase 1 (after Visit 8).
Phase 2/3, ≥16 y ears of age (after Visit 4).
Phase 3, 12 through 15 years of age (after Visit 4).
Original Phase 3 participants rer andomized to assess boostability and protection against
emerging VOCs (after Visit 306) (data will be reported at a later time).
Participants ≥16 y ears of age who originall y received placebo and became eligible for receipt
of BNT162b2 according to recommen dations detailed separately , and available in the
electronic stud y 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.
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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 ≥16 y ears of age w ho had not
alread y 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 r eceive 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
Each group (vaccine candidate/dose level/age group) was c omprised of 15 participants
randomized 4:1 to receive active vaccine or placebo (12 participants randomized to active
vaccine and 3 to placebo, such that the placebo participants across the groups would produce
a roughly comparabl y-sized cohort).
For each vaccine candidate/dose level/age group, safet y precautions included :additional
safet y assessments ( Section 9.5.2 and Appendix 16.1.1, Protocol Section 8.2 ), controlled
enrollment, application of stopping rules, and IRC review of safet y data to determine if dose
escalation could proceed.
Groups of participants 65 to 85 y ears of age were not started until safet y data for the RNA
platform were deemed acceptable at the same, or a higher, dose level in the 18 to 55 years of
age group b y the IRC.
In this phase, 13 groups were studied, corresponding to a total of 195 participants.
Following review of all available safety and immunogenicity data through 14 day s after
Dose 2 for BNT162b1 and BNT162b2, both vaccine constructs were considered strong
candidates to proceed to Phase 2/3. See Section 9.4.4 for details on selection of final
candidate and dose for Phase 2/3.
Planned Eval uations
A third dose of BNT162b2 30µg will be given to Phase 1 participants approximately 6 to
12 months after their second dose of BNT162b1 or BNT162b2 to evaluate safet y and
immunogenicit y for b oostability and potential heterologous protection against emerging
VOCs ( Appendix 16.1.1, Protocol Section 4.1.1 ).
Participants were expected 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.
9.1.2.Phase 2/3
Safety and immunogenicity data generated during the Phase 1 portion of this study and the
BioNTech study conducted in Germany (BNT162 -01) supported BNT162b2 at a dose of
30µg as the vaccine candidate to proceed into Phase 2/3 (see Section 9.4.4 ).
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The Phase 2 part of the study was comprised of the first 360 participants enrolled (1:1
randomization 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 Phase 2 360 participants. Enrollment continued during Phase 2 and these
participants are included in the efficacy evaluation in the Phase 3 part of the study .
Participants in the ongoing Phase 3 part of the study are ≥12 years of age (stratified as
12through 15, 16 through 55, or >55 years of age) . The 12- through 15-year stratum
comprise dup to approximately 2000 participants enrolled at selected investigational sites . It
was planned to enroll a minimum of 40% of participants in the >55 years of 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 primary
efficacy endpoint (data cutoff date : 04November 2020 ), and the fin al 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 parti cipants in the efficacy populations ≥12
years of age.
At the time of the final analy sis of efficacy , relatively few participants 12 through 15 years of
age had enrolled in the study , and no COVID -19 cases in this age group accrued at that time .
Updated efficacy analy sesduring blinded placebo -controlled follow -upperiod were
conducted on cases accrued up to the data cutoff date of 13 March 2021 to evaluate duration
of protection. This report presents 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 for approximately 26months .
Planned Eval uations
Phase 2/ 3 (which is ongoing) includ es additional planned anal yses which are not include d in
this report and will be reported separatel y.
In Phase 3, noninferiority of immune response to prophylactic BNT162b2 in participants
12through 15 years of age to response in participants 16 through 25 years of age w ill be
assessed based on the GMR of SARS -CoV -2 neutralizing titers using a 1.5 -fold margin.
The safet y and immunogenicity of prophy lactic BNT162b2 in individuals 16 through
55years of age vaccinated with BNT162b2 manufactured with “Process 1” and each lot
of BNT162b2 manufactured with “Process 2” , which was developed to support an
increased scale of manufacture (Appendix 16.1.1, Protocol Section 6.1.1).
Boostability and homologous/heterologous protection against emerging VOCs will allow
the evaluation of safet y and immunogenicity of BNT162b2 SA(Appendix 16.1.1, Protocol
Section s 4.1 .1and 4.1.2 ).
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An intensive period of surveillance to evaluate the efficacy of BNT162b2 against
asymptomatic SARS CoV -2 infection is being conducted at selected sites among
Phase 2/3participants (Appendix 16.1.1, Protocol Section 8.1.5).
Refer to Appendix 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 one (selected) candidate, in healthy individuals. To assess boostability in a subset of
Phase 3 participants, a third candidate, will also be assessed against emerging SARS -CoV -2
VOCs.
The study is observer -blinded, as the ph ysical appearance of the investigational vaccine
candidates and the placebo may differ . The participant, investigator, study coordinator, and
other site staff are blinded. At the study site, onl y the dispenser(s)/administrator(s) are
unblinded.
The study consists of 3 placebo -controlled phases. Placebo is used as the control, as there is
no licensed comparator vaccine available.
Phase 1 was designed to identify preferred vaccine candidate(s) and dose level(s) 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 la ter permitted to enroll as part of
Phase 3; data will be reported separatel y).Boostability will also be 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
Refer to the final analysis interim C4591001 CSR dated 0 3December 2020 , Section s 9.3.1 ,
9.3.2 , 9.3.3, and 9.3.4 for inclusion criteria, exclusion criteria, criteria for temporarily
delay ing vaccine administration, and details for withdrawal of participants from the st udy,
respectivel y,based on Appendix 16.1.1, Protocol Amendment 9. There were no changes to
inclusion and exclusion criteria from Protocol Amendments 10 through 13. Refer to
Appendix 16.1.1, Protocol Amendment 1 4, for updated inclusion and exclusion criteria of the
subset of participants re ceiving the booster dose against emerging VOCs.
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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.
This reportevaluated a 2 -dose (separated b y 21 day s) schedule of the following for active
immunization against COVID -19 or saline placebo :
BNT162b2 (BNT162 RNA -LNP vaccine containing modRNA that encodes P2 S): 30 µg
Normal saline (0.9% sodium chloride solution for injection)
Refer the final anal ysis interim C4591001 CSR dated 03 December 2020 for BNT162b1 and
BNT162b2 other candidate dose levels previousl y evaluated.
Refer to Appendix 16.1.1, Protocol Sections 6.1and 6.1.2for details of the study
intervention( s) and study intervention administration , including the planned BNT162b2 SA
variant .
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 3below.
Table3.Investigati onal Product Lot Numbers – Interim – 6 Month Update
Investigational
Product PhaseManufacturerVendorLot
Number
(Manufacturer) Lot Numbera(Pfizer)
BNT162b1 (10 µg,
20µg, 30 µg, and
100µg)1 BioNTech BCV10320 -A E220395 -0001L
BNT162b2 (10 µg,
20µg, and 30 µg)1 BioNTech BCV40420 -A E220395 -0004L
Normal saline (0.9%
sodium chloride
solution for injection)1 Pfizer DK1589 20-001592
BNT162b2 (30 µg) 2/3 BioNTech BCV40420 -A
BCV40420 -A
BCV40420 -A
BCV40420 -AE220395 -
0006L003/P220395 -
0012L
E220395 -
0035L002/P220395 -
0048L
E220395 -
0035L003/P220395 -
0048L
EU2065896/E220395 -
0004L
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Table3.Investigati onal Product Lot Numbers – Interim – 6 Month Update
BCV40420 -A
BCV40620 -A
BCV40620 -A
BCV40620 -B
BCV40620 -B
BCV40620 -C
BCV40620 -C
BCV40620 -D
BCV40620 -D
BCV40720 -A
BCV40720 -A
BCV40720 -B
BCV40720 -C
ED3938PA2070104/P220395 -
0008L
PA2071394/P220395 -
0029L
PA2072393/P220395 -
0019L
PA2071395/P220395 -
0016L
PA2072396/P220395 -
0016L
PA2071396/P220395 -
0047L
PA2072439/P220395 -
0047L
PA2072442/P220395 -
0042L
PA2072765/P220395 -
0042L
PA2074172/P220395 -
0053L
PA2074998/P220395 -
0060L
PA2074173/P220395 -
0051L
PA2074071/P220395 -
0052L
PA2074300/P220395 -
0021L
ED3938
ED3938
ED3938
EE3813
EE3813
EE8493Z
EE3813
EE3813
EE3813
EJ0553ZEU2074330/E220395 -
0036L
PA2074300/P220395 -
0022L
PA2074300/P220395 -
0023L
PA2074838/P220395 -
0024L
PA2074838/P220395 -
0020L
PA2077905/P220395 -
0026L
NC2075485/P220395 -
0068L
NC2075485/P220395 -
0074L
NC2075485/P220395 -
0077L
PA2085061/P220395 -
0070L
Normal saline (0.9%
sodium chloride
solution for injection)2/3 Pfizer DK1589;20 -001592
DK1589;20 -001776
DK2074;20 -002029PA2064251/P220395 -
0005L
PA2065311/P220395 -
0007L
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Table3.Investigati onal Product Lot Numbers – Interim – 6 Month Update
DK2074;20 -002108
DK2074;20 -002221
DK2074;20 -002221
DK2074;20 -002221
DK2074;20 -002221
DK2074;20 -002221
DK2074;20 -002221
DK2074;20 -002221
DK2074;20 -002221
DK2074;20 -002221
DK2074;20 -002221
DK2074;20 -002221
DK2074;20 -002221
DK2074;20 -002221PA2067775/P220395 -
0030L
PA2067774/P220395 -
0013L
PA2069407/P220395 -
0031L
PA2069407/P220395 -
0032L
PA2069407/P220395 -
0033L
PA2069407/P220395 -
0034L
PA2069407/P220395 -
0044L
PA2069407/P220395 -
0045L
PA2069407/P220395 -
0046L
PA2069407/P220395 -
0054L
PA2069407/P220395 -
0055L
PA2069407/P220395 -
0056L
PA2069407/P220395 -
0062L
PA2069407/P220395 -
0065L
PA2069407OTH/E220395 -
0049L
Note: C4591001 End of Study Information and Quality Control (QC) Record for Study Drug Appendix (Section D)
dated 17Mar2021 was used to create this table.
a. Lot number assigned to the investigational product by Pfizer Global Clinical Supply.
Protocol C4591001 Investigational Product Lot Numbers Table – Interim –6 Month Update ,Final, Version 1.0,
18Mar2021.
9.4.3. Method of Assigning Participants to Treatment Groups
Allocation (randomization) of participants to vaccine gro ups proceeded through the use of an
IRT s ystem (I WR).
Refer to Appendix 16.1.1, Protocol Section 6.3.1 for details on investigational product
assignment.
9.4.4.Selection of Dose Levels/Regimen
9.4.4.1.Phase 1
Section 9.4.1 provides details on the doses administered in Phase 1.
Refer to Appendix 16.1.1, Protocol Section 6 for details of the dose and regimen.
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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,
investigator staff, and participants, were blinded to study intervention assignments.
To facilitate rapid review of data in real time, Pfizer and BioNTech staff were unblinded to
study intervention allocation for the participants in the Phase 1 portion of the study . The
majority of sponsor staff and all personnel directl y involved in study conduct were a nd
remain blinded to study intervention allocation in Phase 2/3 . All laboratory testing personnel
performing serology assay s remain blinded to study intervention assigned/received
throughout all phases of the study . The following sponsor staff were unblind ed in Phase 2/3
(further details are provided in a data blinding plan) :
Those study team members who were involved in ensuring that protocol requirements for
study intervention preparation, handling, allocation, and administration are fulfilled at the
site were unblinded at the site level for the duration of the study (eg, unblinde d study
manager, unblinded clinical research associate).
Unblinded clinician(s), who were not direct members of the stud y team and did not
participate in an y other study -related activities, reviewed unblinded protocol deviations.
An unblinded statistical team supporting interactions with, and interim analy ses for, the
DMC (see Appendix 16.1.1, Protocol Section 9.6 )and the final analy sisinterim CSR
(03December 2020) . This is comprised of a statistician, programmer(s), a clinical
scientist, and a medical monitor who review edcases of severe COVID -19 as they were
received, and review edAEs at least weekl y for additional potential cases of severe
COVID -19 (see Section 9.5.2.3 ).
An unblinded submissions team was responsible for preparing documents to support
regulatory activities that may have been required while the study is ongoing . This team
was only unblinded at the gr oup level and did not have access to individual participant
assignments . The programs that produced the summary tables were developed and
validated b y the blinded study team, and these programs were run b y the same unblinded
statistical team supporting DMC reviews . The submissions team did not have access to
unblinded COVID -19 cases unless efficacy was achieved at either an interim analy sis or
the final anal ysis, as determined by the DMC.
After the formal data release of the final efficacy analysis of at least 164 first
primary -endpoint cases, which was considered the primary completion of the study
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efficacy objectives, additional limited statisticians and programmers were unblinded at
the participant level to prepare unblinded anal yses and ot her regulatory activities. A
group of statisticians and programmers remained blinded as part of the blinded study
team and continue supporting the blinded conduct of the study .
After the stud y data used for submission became public, the blinded study team also had
access to those data, and was unblinded at thegroup level.
When a participant who originall y received placebo received BNT162b2 per
Appendix 16.1.1, Protocol Section 1.3.3 , the study team w asunblinded to the
participant’s original study interven tion allocation.
The study wasunblinded in stages once all ongoing participants either ha dbeen individually
unblinded or ha dconcluded their 6 -month post –Dose 2 study visit, as follows:
Phase 1 (after Visit 8).
Phase 2/3, ≥16 y ears (after Visit 4).
Phas e 3, 12 through 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 ≥16 y ears of age who originall y received placebo and became eligible for receipt
of BNT162b2 according to recommendations detailed separately , and available in the
electronic stud y 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, and Protocol
Section 6.3.4 for circumstances when the blind could be broken.
9.4.6.Prior and Concomitant Vaccines, Medications, and Procedures
Prohibited During the Study
Participants may have been excluded from the per -protocol anal ysis and may not have
received further required 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 t he 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 wa s taking a
medication for another condition, even if it had antipy retic or pain -relieving properties, it was
not withheld prior to study vaccination.
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Permitted During the Study
Refer to Appendix 16.1.1, Protocol Section 6.5 for details on prior and concomitant vaccines,
medications and procedures that were allowed or prohibited.
9.4.7.Vaccine Compliance
Participants dosed at the site received study intervention directly from the investigator or
designee, under medical supervision.
Refer to Appendix 16.1.1, Protocol Section 6.4 for details of compliance with study
intervention.
9.5.Efficacy, Immunogenicity, and Safety Evaluations
9.5.1.Efficacy and Immunogenicity Evaluations
Efficacy (prespecified) was assessed for potential cases of COVID -19and described in the
final anal ysis interim C4591001 CSR dated 03 December 2020 . The prespecified interim
analysis was conducted on an accrued 94 evaluable COVID -19 cases (data cutoff date:
04November 2020) , and the final anal ysis was conducted on an accr ued 170evaluable
COVID -19 cases for the first primary efficacy endpoint (data cutoff date :
14November 2020 ). These anal yses included data from all participants in Phase 3 age
groups (12-15, 16- 55, and >55 y ears of age) at the time of the anal yses.Prespe cified primary
and secondary efficacy endpoint analy ses were completed per protocol as of 14 November
2020, and no additional formal hypothesis testing of clinically confirmed COVID -19 cases is
planned. At the time of the final anal ysis, there were relativel y few participants 12- 15 years
of age enrolled in the study and no COVID -19 cases in this age group accrued at that time
(14November 2020). In this report, efficacy was assessed based on all cases in all
participants ≥12years of age accrued in b linded follow -up to a data cutoff date of
13March 2021 .
For immunogenicity testing, the following assay s were performed in Phase 1 and Phase 2 and
will be performed in Phase 2 /3with exception of the RBD -binding IgG assay :
SARS -CoV -2 neutralization assay (reference strain and SA variant [data from SA variant
will be reported at a later time])
Full length S -binding or S1-binding IgG levels (most relevant to BNT162b2 which
encodes P2 S)
RBD- binding IgG level assay (most relevant to BNT162b1, which encodes th e RBD,
Phase 1 only , and previously reported in the final anal ysis interim C4591001 CSR dated
03December 2020)
Refer to Appendix 16.1.1, Protocol Section 8.1for details on efficacy and immunogenicit y
evaluations.
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9.5.2.Safety Evaluations
Safety evaluations are as described in Appendix 16.1.1, Protocol Section 8.2.
9.5.2.1. Clinical Safety Laboratory Evaluations (Phase 1 Participants Only)
Clinical safety laboratory evaluations were onl y conducted for Phase 1 participants and
described in Appendix 16.1.1, Protocol Section 8.2.1 , and reported in the final anal ysis
interim CSR dated 03 December 2020 . The laboratory tests performed are described in
Appendix 16.1.1, Protocol Appendix 2 .
9.5.2.2.Electronic Diary
All participants in Phase 1 and a subset of at leas t the first 6000 participants randomized in
Phase 2/3 recorded local reactions, s ystemic events, and antipy retic/pain medication usage
for 7 day s, following administration of study intervention using an e -diary . Anyparticipants
in Phase 3 who are HIV -positive or 12 t hrough 15 years of age may also have been included
in this subset . In addition, participants 16 through 17 years of age enrolled under P rotocol
Amendment 9 (finalized 29October 2020) and onwards w ereincluded in the reactogenicit y
subset . All other participants, including those who originall y received placebo and then
received BNT162b2 under Protocol A mendment 10 and onwards, didnot complete a n
e-diary but hadtheir local reactions and s ystemic events reported as AEs in accordance with
Appendix 16.1.1, Protocol Section 8.3.2 (see also Section 9.5.2.5).
Use of an e -diary allowed recording of these assessments within a f ixed time window and
provided an accurate representation of the participant’s experience at that time . For
participants who were not in the reactogenicity subset, local reactions and sy stemic events
consistent with reactogenicity were reported as AEs (Section 9.5.2.5 ).
Refer to Appendix 16.1.1, Protocol Section 8.2.2 for additional details on use of the e -diary ,
includi ng details for participants receiving the booster dose against emerging VOCs . 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 reaction s, systemic events,
fever, and use of antipy retic/pain medications, respectivel y.
9.5.2.3.Phase 1 Stopping Rules
Stopping rules were in place for all Phase 1 participants, based on review of AE data and
e-diary reactogenicit y data, until the start of Phase 2/3 or 30 day s after the administration of
the second dose of study intervention in Phase 1, whichever was later. These data were
monitored on an ongoing basis by the investigator (or medicall y qualified designee), Pfizer,
and BioNTech in order to promptly identify and flag an y event that potentially contributes to
a stopping rule.
Refer to Appendix 16.1.1, Protocol Section 8.2.3 for details on Phase 1 stopping rules.
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9.5.2.4.Surveillance of Events That Could Rep resent 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,
aCOVID -19 illness and 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).
During Phase 1, Pfizer and BioNTech conducted unblinded reviews of the data, including for
the purpose of safet y assessment. All NAAT -confirmed cases in Phase 1 were reviewed
contemporaneousl y by the IRC and the DMC.
In Phase 2/3, the unblinded team supporting the DMC, including an unblinded medical
monitor, reviewed cases of severe COVID -19 as they were received and reviewed AEs at
least weekl y for additional potential cases of severe COVID -19. At an y point, the unblinded
team may have discussed with the DMC chair whether the DMC should review cases for an
adverse imbalance of cases of COVID -19 and/or severe COVID -19 between the vaccine and
placebo groups.
The stopping rule w astriggered when the 1- sided probability of observing the same or a
more extreme case split was 5% or less when the true incidence of severe disease wasthe
same for vaccine and placebo participants, and alert criteria were triggered when this
probability was less than 11% . In add ition, when the total number of severe cases waslow
(15 or less), the unblinded team supporting the DMC implement edthe alert rule when a
reverse case split of 2:1 or worse was observed.
When the total number of severe cases was 20 or less, the stopping rule and alert rules in
Appendix 16.1.1, Protocol Table 10 and Table 11 , respectivel y, applied.
Refer to Appendix 16.1.1, Protocol Section 8.13 for details on COVID -19 surveillance, and
Protocol Section 8.2.4 for details on Phase 2/3 stopping rules.
9.5.2.5. Adverse Events and Serious Adverse Events
AEs were collected during the stud y from the signing of the ICD through and including
1month after Dose 2 (Visit 7 for Phase 1 participants and Visit 3 for Phase 2/3 participants).
Acute reactions (immediate AEs) were collected within the first 4 hours after administration
of the study intervention (for the first 5 participants vaccinated in each Phase 1 group), and
within the first 30 minutes (for the remainder of participants).
SAEs were collecte d from the signing of the ICD to approximately 6 months after the last
dose of study intervention (Visit 8 for Phase 1 participants and Visit 4 for Phase 2/3
participants).
Additionally , for those participants who originally received placebo but went on to receive
BNT162b2 at Vaccinations 3 and 4, AEs w erecollected from the time the participant
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provide dinformed consent (for receipt of Vaccinations 3 and 4) through and including
Visit 103. SAEs were collected from the time the participant provides informed consent (for
receipt of Vaccinations 3 and 4) to approximately 6 months after the second dose of
BNT162b2 (Visit 104).
Refer to Appendix 16.1.1, Protocol Section 8.3for additional details for collecting AEs and
SAEs , including details for participants r eceiving the booster dose against emerging VOCs .
9.5.2.6.Events of Special Interest
While AESI s were not prespecified in the protocol, Pfizer utilizes a safet y review as part of
the signal detection processes that highlights specified TMEs of clinical interest. TM Es
arespecific AE terms reviewed on an ongoing basis by routine safet y data review procedures
throughout the clinical study .Although not prespecified in the protocol, TMEs are
maintained in a separate list as part of the Safet y Surveillance Review Plan f or the vaccine
program. By definition, TMEs are considered to be AESIs specific for a product or program's
protocol(s). They are based on review of known pharmacology , toxicology findings, possible
class effects, published 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 i n general. Terms are chosen from the
MedDRA dictionary and may include PTs, high level term, high level group terms, or
standardized MedDRA queries (SMQs; all evaluated as broad and narrow) .
Other events of clinical interest identified b y the sponsor were also reviewe d and
summarized ( Section 12.2.4.4 ).
9.6. Data Quality Assurance
A number of steps were taken in the planning and implementati on 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 revie w 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
and completeness of the data being entered into the RDC sy stem . During these visits, critic al
data were verified against participant source documents, and queries regarding missing or
contradictory data were resolved. In addition, study procedures were reviewed, and protocol
deviations were discussed with the investigator . Telephone and email co ntact was maintained
with the investigators between site visits. In addition, the overall study conduct was subject
to internal quality review by Pfizer.
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The quality risk management plan used in this study documents risks and controls that are in
place thr oughout the life of the study . In this study, QTL s were defined during the quality
risk management planning.
The accuracy of the clinical database was verified through a series of processes. Potential
errors were 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 enter ed and all data queries closed, a final data
management review was performed, and the database was declared ready for statistical
analysis.
This CSR has been subject to quality control review by Pfizer or Pfizer’s designee.
Quality assurance audits were p erformed 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.
Refer to the final anal ysis interim C4591001 CSR dated 03 December 2020 for previousl y
reported data qualit y issues.
9.7.Statistical Methods Planned in the Protocol
9.7.1. Statistical and Analytical Plans
Detailed methodology for summarization and statistical anal yses of the data collected in this
study is documented in the SAP ( Appendix 16.1.9). An y major modifications of the primary
endpoint definition and/or its analy sis subsequent to the protocol finalization were reflected
in a protocol amendment.
9.7.1.1.Analysis Sets
The anal ysis populations presented in this report are defined in Table 4.
Refer to Appendix 16.1.9, SAP Section 4for details of all other planned analy sis sets ,
including planned immunogenicity populations for the booster dose and efficacy populations
for seroconversion and asy mptomatic surveillance .
Table4.Analysis Populations
Population Description
Enrolled All participants who had a signed ICD.
Randomized All participants who were assigned a randomization number in the IWR system.
Dose 1 evaluable
immunogenicityFor Phase 1 only, all eligible randomized participants who received the vaccine to
which they were randomly assigned at the first dose, had at least 1 valid and
determinate immunogenicity result from the blood collection w ithin an appropriate
window after Dose 1 (same as visit window, ie, within 19 -23 day s after Dose 1) and
had no other important protocol deviations as determined by the clinician.
Dose 2 evaluable
immunogenicityAll eligible randomized participants who received 2 doses of the vaccine to wh ich they
were randomly assigned, with Dose 2 received w ithin the predefined window (19-42
days after Dose 1), had at least 1 valid and determinate immunogenicity result from the
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Table4.Analysis Populations
Population Description
blood collection w ithin an appropriate w indow after Dose 2 (6 -8 days after Dos e 2 for
Phase 1 and 28 -42 days after Dose 2 for Phase 2/3), and had no other important
protocol deviations as determined by the clinician.
Dose 1 all -available
immunogenicityFor Phase 1 only: a ll randomized participants who received at least 1 dose of th e study
intervention with at least 1 valid and determinate immunogenicity result after Dose 1
but before Dose 2.
Dose 2 all -available
immunogenicityAll randomized participants who received at least 1 dose of the study intervention with
at least 1 valid a nd determinate immunogenicity result after Dose 2.
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
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 VEwith
respect to the first primary efficacy endpoint (atleast 164 cases) was assessed on an accrued
170evaluable COVID -19 cases(data cutoff date: 14 November 2020) and also included VE
for the second primary and all secondary efficacy endpoints. No additional formal hy pothesis
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 days 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 correspon
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