019736 S488 M5 c4591007 protocol amend3 track

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PF-07302048 (BNT162 b2 RNA-Based COVID -19 Vaccine)
Protocol C4591007
Final ProtocolAmendment 32, 1006SepAug2021
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 1A PHASE 1 ,OPEN-LABEL DOSE-FINDING STUDY TO EVALUATE S AFETY, 
TOLERABILITY , AND IMMUNOGENICITY ANDPHASE 2/3 
PLACEBO -CONTROLLED, OBSERVER
-BLINDED SAFETY, TOLERABILIT Y,
ANDIMMUNOGENICITY STUDY OF A SARS-COV-2 RNA VACCI NE 
CANDIDATE AGAINST CO VID-19 IN HEALTHY CHILDREN 
AND YOUNG ADULTS
Study Sponsor BioNTech
Study Conducted By Pfizer
Study Intervention Number:PF-07302048
Study Intervention Name: RNA-Based COVID -19 Vaccine
USINDNumber: 19736
EudraCT Number: 2020-005442-42
Protocol Number: C4591007
Phase: 1/2/3
Short Title :A Phase 1 /2/3Study to Evaluate the Safety ,Tolerabilit y, and Immunogenicit y
of an RNA Vaccine Candidate Against COVID -19 in Healthy Children andYoung Adults
This document and accompanying materials contain confidential information belonging to Pfizer.  Except as 
otherwise agreed to in writing, by accepting or reviewing these document s, you agree to hold this information 
in confidence and not copy or disclose it to others (except where required by applicable law) or use it for 
unauthorized purposes.  In the event of any actual or suspected breach of this obligation, Pfizer must be 
promptly notified.
090177e1980860c5\Approved\Approved On: 10-Sep-2021 13:03 (GMT)
FDA-CBER-2021-5683-1078097
PF-07302048 (BNT162 b2 RNA-Based COVID -19 Vaccine)
Protocol C4591007
Final ProtocolAmendment 32, 1006SepAug2021
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 2Protocol Amendment Sum mary of Changes Table
Document History
Document Version Date Summary and Rationale for Changes
Amendment 3 10Sep 2021 Updated to allow  an additional 2250 Phase 2/3 
selected-dose participants <5 years of age ,to enlarge 
the size of the pediatric safety database. This has 
resultedin the total number of participants in this 
portionof the study increasing to approximately 
9000 participants . 
Included blood draw s, procedures, and objectives for 
potential troponinI testing in participants 5 to <12 
and 12 to <16 years.
Added the rationale for collecting serum samples for 
potential troponin I testing . 
Revised an objective and corresponding e ndpointsto 
describe severe COVID -19 cases in participants in 
the selected- dose portion of the study .
Clarifiedthe process for participants who become 
eligible for receipt of BNT162b2 or another 
COVID-19 vaccine prior to Visit 5 (6 -month 
follow-up visit).
Added a second definition of symptoms of severe 
COVID-19 disease per the CDC definition.
Clarified instructions on how to unblind participants 
at the 6-month follow -up visit. 
Updated information on the recording ofnonstudy 
vaccination and concomitant medications . 
Amendment 2 06 Aug2021 Made the following updatesin response to 
commitments made to CBER concerning myocarditis 
and pericarditis :
Insertion of a dditional row  in risk assessment 
table in risk assessment section .
Addition of myocarditis and pericarditis in 
Adverse Events of Special Interest section .
Addition of a procedure to any v isit that occurs 
sooner than 1 month after any vaccination .
Addition of an unplanned visit to capture data 
pertaining to myocarditis and pericarditis .
Revised protocol title to reflect the changes in age 
and dose evaluation. 
Updated to allow anadditional 2250 Phase 2/3 
selected-dose participants to enlarge the size of the 
pediatric safety database.
Added Phase 1/2/3 evaluation of low er dose levels
for children and young adults withcorresponding 
objectives . 
Revisedthe order of Visit 1 activit ies to clarify when 
procedures should be conducted in relation to study 
090177e1980860c5\Approved\Approved On: 10-Sep-2021 13:03 (GMT)
FDA-CBER-2021-5683-1078098
PF-07302048 (BNT162 b2 RNA-Based COVID -19 Vaccine)
Protocol C4591007
Final ProtocolAmendment 32, 1006SepAug2021
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 3Document History
Document Version Date Summary and Rationale for Changes
intervention administration when the visit occurs 
over2 consecutive days .
Added updates and reformatt edactivities in the SoA.
Removed the requirement to conduct a potential 
COVID-19 convalescent visit following each 
potential COVID -19 illness visit . The collection of 
the blood sample w as to support an exploratory 
endpoint,which will be addressed with external data 
and thereby reduce burden to participants and 
caregivers .
Addedacountry-specific appendix that allows
flexibility to conduct scheduled follow-up visits in 
the participant’s home ,ie, site-arranged home health 
visits, as permitted per local guidelines (applicable to 
Poland only ).
Amendment 1 05Mar2021 Added2age groups to the study: participants ≥2 to 
<5 years and ≥6 months to <2 years of age ,to also 
study safety and immunogenicity in these age groups .
Updated e fficacy objectives to apply across ag es 
in which immunobridging has been successful, if 
22 cases are accrued.
Made updates to match Pfizer’s response to 
04February 2021 CBER comments regarding this 
study, ie:
Exclusion criteri on3 applied to all study 
participants rather than just to Phase 1 
participants.
References to “noninferiority ”updated to 
“immunobridging. ”
Made additionsto theexclusion criteria for previous 
or current diagnosis of MIS -C.
Addedto the exclusion criteria receipt of any passive 
antibody therapy specific to COVID -19 within 
90daysprior to enrol lment.
Specified that placebo reci pients who decline 
BNT162b2 will be follow ed for 24 months ( Visits X 
and Y).
Temporary delay of study intervention criteria 
regarding nonstudy vaccination updated to be most 
permissive, ie, to allow easier scheduling around 
childhood routine vaccinations.
Added the following symptoms as prompts to 
complete the COVID -19/MIS-C illness e- diary:
Inability to eat/poor feeding in participants 
<5years of age;
Abdominal pain;
Hospitalization due to confirmed COVID -19 
infection.
090177e1980860c5\Approved\Approved On: 10-Sep-2021 13:03 (GMT)
FDA-CBER-2021-5683-1078099
PF-07302048 (BNT162 b2 RNA-Based COVID -19 Vaccine)
Protocol C4591007
Final ProtocolAmendment 32, 1006SepAug2021
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 4Document History
Document Version Date Summary and Rationale for Changes
Following updates made to the first confirmed 
COVID-19 case definition to accommodate inclusion 
of participants <5 years of age:
Definition of diarrheaadded.
Inability to eat/poor feeding in participants 
<5years of age added as an additional symptom.
Definition of SARS -CoV-2–related hospit alization 
added.
RR and HR required to meet the SARS -CoV-2–
related severe case definition specified by participant 
age.  Table4inserted.
Added that c ell-mediated immune responses will be 
described follow ing isolation of PBMCs in a subset of 
Phase 2/3 par ticipants ≥10years of age.   
Corresponding visit (Visit 3) added approximately 7 
days after Dose 2.
Original p rotocol 05 Feb 2021 N/A
This amendment incorporates all revisions to date, including amendments made at the 
request of country  health authorities and IRBs/ECs.
090177e1980860c5\Approved\Approved On: 10-Sep-2021 13:03 (GMT)
FDA-CBER-2021-5683-1078100
PF-07302048 (BNT162 b2 RNA-Based COVID -19 Vaccine)
Protocol C4591007
Final ProtocolAmendment 32, 1006SepAug2021
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 5TABLE OF CONTENTS
LIST OF TABLES ................................ ................................ ................................ ................... 12
1. PROTOCOL  SUMMARY ................................ ................................ ................................ ...13
1.1. Synopsis................................ ................................ ................................ .................. 13
1.2. Schema ................................ ................................ ................................ .................... 24
1.3. Schedule of Activ ities................................ ................................ ............................. 27
1.3.1. Phase 1 Dose -Finding Portion ................................ ................................ ....27
1.3.2. Phase 1 L ower-Dose Evaluation ................................ ................................ .30
1.3.3. Phase 2/3 Selected -Dose Portion................................ ................................ 32
1.3.3.1. Phase 2/3 Selected -Dose Portion: Participants Who 
Originally Received BNT162b2 or Placebo Recipients Who 
Decline BNT162b2 ................................ ................................ ............36
1.3.3.2. Phase 2/3 Selected -Dose Portion: Participants Who 
Originally Received Placebo ................................ ............................. 37
1.3.4. Phase 2/3 L ower-Dose Evaluation ................................ .............................. 41
2. INTRODUCTION ................................ ................................ ................................ ...............49
2.1. Study  Rationale ................................ ................................ ................................ .......49
2.2. Background ................................ ................................ ................................ .............49
2.2.1. Clinical Overview ................................ ................................ ....................... 52
2.3. Benefit/Risk Assessment................................ ................................ ......................... 52
2.3.1. Risk Assessment................................ ................................ ......................... 54
2.3.2. Ben efit Assessment ................................ ................................ ..................... 57
2.3.3. Overall Benefit/Risk Conclusion ................................ ................................ 57
3. OBJECTI VES, ESTIMANDS, AND ENDPOINTS...........................................................57
3.1. Phase 1 ................................ ................................ ................................ ..................... 58
3.2. Phase 2/3................................ ................................ ................................ ................. 59
4. STUDY DESIGN ................................ ................................ ................................ ................. 65
4.1. Overall Design ................................ ................................ ................................ .........65
4.1.1.Phase 1................................ ................................ ................................ ........66
4.1.2. Phase 2/3................................ ................................ ................................ .....66
4.1.3. Number of Participants................................ ................................ ...............67
4.1.3.1. Phase 1: Open -Label Dose -Finding and Lower -Dose 
Evaluation ................................ ................................ .......................... 67
090177e1980860c5\Approved\Approved On: 10-Sep-2021 13:03 (GMT)
FDA-CBER-2021-5683-1078101
PF-07302048 (BNT162 b2 RNA-Based COVID -19 Vaccine)
Protocol C4591007
Final ProtocolAmendment 32, 1006SepAug2021
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 64.1.3.2. Phase 2/3: Safety, Tolerability , Immunogenicity , and 
Efficacy................................ ................................ .............................. 68
4.1.4. Intervention Groups and Duration ................................ .............................. 70
4.2. Scientific Rationale for Study  Design................................ ................................ .....72
4.3. Justification for Dose ................................ ................................ .............................. 72
4.4. End of Study  Definition ................................ ................................ .......................... 73
5. STUDY POPUL ATION................................ ................................ ................................ ......73
5.1. InclusionCriteria................................ ................................ ................................ .....73
5.2. Exclusion Criteria ................................ ................................ ................................ ....74
5.3. Lifestyle Considerations ................................ ................................ .......................... 76
5.3.1. Contraception ................................ ................................ .............................. 76
5.4. Screen Failures................................ ................................ ................................ ........76
5.5. Criteria for Temporarily  Delaying Enrollment/Randomization/Study  
Intervention Administration ................................ ................................ ...................... 77
6. STUDY INTERVENTIO N................................ ................................ ................................ ..78
6.1. Study  Intervention(s) Administered ................................ ................................ ........78
6.1.1. Administration ................................ ................................ ............................ 79
6.2. Preparation/Handling/Storage/Accountability ................................ ........................ 79
6.2.1. Preparation and Dispensing ................................ ................................ ........80
6.3. Measures to Minimize Bias: Randomization and Blinding.....................................80
6.3.1. Allocation to Study Intervention ................................ ................................ 80
6.3.2. Blinding of Site Personnel (Phase 2/3 Selected -Dose Portion Onl y).........81
6.3.3. Blinding of the Sponsor................................ ................................ ..............81
6.3.4. Breaking the Blind ................................ ................................ ...................... 82
6.4. Study  Intervention Compliance ................................ ................................ ...............83
6.5. Concomitant Therapy ................................ ................................ .............................. 83
6.5.1. Prohibited During the Study ................................ ................................ .......83
6.5.2. Permitted During the Study ................................ ................................ ........85
6.5.3. Recording Nonstudy  Vaccination and Concomitant Medications..............85
6.6. Dose Modification ................................ ................................ ................................ ...85
6.7. Intervention After the End of the Study ................................ ................................ ..86
090177e1980860c5\Approved\Approved On: 10-Sep-2021 13:03 (GMT)
FDA-CBER-2021-5683-1078102
PF-07302048 (BNT162 b2 RNA-Based COVID -19 Vaccine)
Protocol C4591007
Final ProtocolAmendment 32, 1006SepAug2021
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 77. DISCONTINUATION O F STUDY INTERVENTION AND PARTI CIPANT 
DISCONTINUATION/WI THDRAWAL ................................ ................................ ...........86
7.1. Discontinuation of Study  Intervention ................................ ................................ ....86
7.2. Participant Discontinuation/Withdrawal From the Study ................................ .......87
7.2.1. Withdrawal of Consent ................................ ................................ ...............88
7.3. Lost to Follow -up................................ ................................ ................................ ....88
8. STUDY ASSESSMENTS AND PROCEDURES ................................ ............................... 89
8.1. Efficacy  and/or Immunogenicity Assessments ................................ ....................... 90
8.1.1. Immunogenicity................................ ................................ .......................... 94
8.1.2. Biological Samples ................................ ................................ ..................... 94
8.2. Safet y Assessments ................................ ................................ ................................ .94
8.2.1. Phy sical Examinations ................................ ................................ ................ 95
8.2.2. Vital Signs ................................ ................................ ................................ ..95
8.2.3. Clinical Safety  Laboratory  Assessments ................................ .................... 95
8.2.4. Electronic Diary ................................ ................................ .......................... 95
8.2.4.1. Grading Scales ................................ ................................ ...........96
8.2.4.2. L ocal Reactions ................................ ................................ .........96
8.2.4.3. Sy stemic Events ................................ ................................ ........98
8.2.4.4. Fever ................................ ................................ ........................ 100
8.2.4.5. Antipy retic Medication ................................ ........................... 101
8.2.5. Phase 1 Stopping Rules ................................ ................................ ............101
8.2.6. Randomization and Vaccination After a Stopping Rule Is Met in 
Phase 1................................ ................................ ................................ ...........102
8.2.7. Pregnancy  Testing................................ ................................ .................... 102
8.3. Adverse Events and Serious Adverse Events................................ ........................ 102
8.3.1. Time Period and Frequency  for Collecting AE and SAE Information .....103
8.3.1.1. Reporting SAEs to Pfizer Safety ................................ .............105
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF................. 105
8.3.2. Method of Detecting AEs and SAEs ................................ ........................ 105
8.3.3. Follow -up of AEs and SAEs ................................ ................................ .....105
8.3.4. Regulatory Reporting Requirements for SAEs ................................ .........106
090177e1980860c5\Approved\Approved On: 10-Sep-2021 13:03 (GMT)
FDA-CBER-2021-5683-1078103
PF-07302048 (BNT162 b2 RNA-Based COVID -19 Vaccine)
Protocol C4591007
Final ProtocolAmendment 32, 1006SepAug2021
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 88.3.5. Exposure During Pregnancy  or Breastfeeding, and Occupational 
Exposure ................................ ................................ ................................ ........106
8.3.5.1. Exposure During Pregnancy ................................ .................... 106
8.3.5.2. Exposure During Breastfeeding ................................ ..............108
8.3.5.3. Occupational Exposure ................................ ........................... 108
8.3.6. Cardiovascular and Death Events ................................ ............................. 108
8.3.7. Disease -Related Events and/or Disease -Related Outcomes Not 
Qualifying as AEs or SAEs for Dose -Finding/Selected -Dose 
Participants ................................ ................................ ................................ .....109
8.3.8. Adverse Events of Special Interest................................ ........................... 109
8.3.8.1. Lack of Efficacy ................................ ................................ ......110
8.3.9.Medical Device Deficiencies ................................ ................................ ....110
8.3.10. Medication Errors ................................ ................................ ................... 110
8.4. Treatment of Overdose................................ ................................ .......................... 111
8.5. Pharmacokinetics ................................ ................................ ................................ ..111
8.6.Pharmacod ynamics................................ ................................ ................................ 111
8.7.Genetics................................ ................................ ................................ ................. 111
8.8. Biomarkers ................................ ................................ ................................ ............111
8.9. Immunogenicit y Assessments ................................ ................................ ...............111
8.10. Health Economics ................................ ................................ ............................... 111
8.11. Study  Procedures ................................ ................................ ................................ .111
8.11.1. Phase 1 Dose -Finding Portion ................................ ................................ 112
8.11.1.1. Visit 1 – Dose 1 (Day  1)................................ ........................ 112
8.11.1.2. Visit 2 – Dose 2 (19 to 23 Day s After Visit 1) ...................... 115
8.11.1.3. Visit 3 – 7- Day Follow-up Visit (1 Week After Dose 2, 6 
to 8 Days After Visit 2) ................................ ................................ ...117
8.11.1.4. Visi t 4 – 1-Month Follow -up Visit (28 to 35 Day s After 
Visit 2)................................ ................................ ............................. 118
8.11.1.5. Visit 5 – 6- Month Follow -up Visit (175 to 189 Days 
After Visit 2)................................ ................................ .................... 119
8.11.1.6. Visit 6 – 12- Month Follow -up Visit (350 to 378 Day s 
After Visit 2) ................................ ................................ .................... 119
8.11.1.7. Visit 7 – 24- Month Follow -up Visit (714 to 742 Day s 
After Visit 2) ................................ ................................ .................... 120
090177e1980860c5\Approved\Approved On: 10-Sep-2021 13:03 (GMT)
FDA-CBER-2021-5683-1078104
PF-07302048 (BNT162 b2 RNA-Based COVID -19 Vaccine)
Protocol C4591007
Final ProtocolAmendment 32, 1006SepAug2021
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 98.11.2. Phase 1 L ower-Dose Evaluation ................................ ............................. 120
8.11.2.1. Visit 101 – Dose 1 (Day  1)................................ .................... 120
8.11.2.2. Visit 102 – Dose 2 (19 to 23 Day s After Visit 101) ..............123
8.11.2.3. Visit 103 – 7- Day Follow-up Visit (1 Week After Dose 
2, 6 to 8 Day s After Visit 102) ................................ ........................ 125
8.11.2.4. Visit 104 – 1- Month Follow -up Visit (28 to 35 Day s 
After Visit 102) ................................ ................................ ................ 126
8.11.2.5. Visit 105 – 6- Month Follow -up Visit (175 to 189 Day s 
After Visit 102) ................................ ................................ ................ 126
8.11.3. Phase 2/3 Selected- Dose Port ion................................ ............................ 127
8.11.3.1. Visit 1 – Dose 1 (Day  1)................................ ........................ 127
8.11.3.2. Visit 2 – Dose 2 (19 to 23 Day s After Visit 1) ...................... 130
8.11.3.3. Visit 3 – 1- Week Follow -up Visit (After Visit 2) (6 to 8 
Days After Visit 2): Only for Those Participants Having Blood 
Drawn for PBMC Isolation ................................ ............................. 133
8.11.3.4. Visit 4 – 1- Month Follow -up Visit (After Visit 2) (28 to 
35 Days After Visit 2) ................................ ................................ .....133
8.11.3.5. Visit 5 – 6- Month Follow -up Visit (175 to 189 Days 
After Visit 2) ................................ ................................ .................... 134
8.11.4. Phase 2/3 Selected- Dose Portion: Participants Who Originally  
Received BNT162b2 or Placebo Recipients Who Decline BNT162b2 .........135
8.11.4.1. Visit X – 12- Month Follow -up Visit (350 to 378 Day s 
After Visit 2) ................................ ................................ .................... 135
8.11.4.2. Visit Y – 24- Month Follow -up Visit (714 to 742 Day s 
After Visit 2) ................................ ................................ .................... 136
8.11.5. Phase 2/3 Selected -Dose Portion: Participants Who Originally  
Received Placebo ................................ ................................ ........................... 137
8.11.5.1. Visit A – Dose 3 (175 to 189 Day s After Dose 2 and 
Same Date as Visit 5) ................................ ................................ ......137
8.11.5.2. Visit B – Dose 4 (19 to 23 Days After Visit A) .................... 139
8.11.5.3. Visit C – 1- Month Follow -up Telephone Contact (After 
Dose 4) (28 to 35 Day s After Visit B) ................................ .............140
8.11.5.4. Visit D – 6- Month Follow -up Telephone Contact (After 
Dose 4) (175 to 189 Days After Visit B) ................................ .........141
8.11.5.5. Visit E – 12-Month Follow -up Telephone Contact (After 
Dose 4) (350 to 378 Days After Visit B) ................................ .........142
090177e1980860c5\Approved\Approved On: 10-Sep-2021 13:03 (GMT)
FDA-CBER-2021-5683-1078105
PF-07302048 (BNT162 b2 RNA-Based COVID -19 Vaccine)
Protocol C4591007
Final ProtocolAmendment 32, 1006SepAug2021
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 108.11.5.6. Visit F – 18 -Month Follow -up Telephone Contact (After 
Dose 4) (532 to 560 Days After Visit B) ................................ .........142
8.11.6.Phase 2/3 L ower-Dose Evaluation ................................ .......................... 143
8.11.6.1. Visit 201 – Dose 1 (Day  1)................................ .................... 143
8.11.6.2. Visit 202 – Dose 2 (19 to 23 Day s After Visit 201) ..............145
8.11.6.3. Visit 203 – 1- Month Follow -up Visit (After Visit 2) (28 
to 35 Day s After Visit 202) ................................ ............................. 147
8.11.6.4. Visit 204 – 6- Month Follow -up Visit (175 to 189 Day s 
After Visit 202) ................................ ................................ ................ 148
8.12. Unscheduled Visit for Fever or a Grade 3 or Suspected Grade 4 Reaction ........160
8.13. COVID -19 and M IS-C Surveillance (Dose -Finding/Selected -Dose 
Participants) ................................ ................................ ................................ .............161
8.13.1. Potential COVI D-19/MIS-C Illness Visit (Optimally  Within 3 Days 
After Potential COVID -19 Illness Onset) ................................ ...................... 162
8.13.2. Potential COVI D-19/MIS-C Convalescent Visit (28 to 35 Day s 
After Potential C OVID-19 Illness Visit) ................................ ....................... 164
8.14. Additional Procedures for Monitoring of Potential My ocarditis or 
Pericarditis ................................ ................................ ................................ ...............164
8.15. Communication and Use of Technology ................................ ............................. 165
8.16. SARS -CoV-2 NAAT Nasal (Anterior Nares) Swab Results .............................. 165
9. STATI STICAL CONSI DERATIONS ................................ ................................ ..............166
9.1. Estimands and Statistical Hy potheses................................ ................................ ...166
9.1.1. Estimands ................................ ................................ ................................ ..166
9.1.2. Statistical Hy pothesis................................ ................................ ................ 167
9.1.2.1. Statistical Hy pothesis Evaluation for Immunogenicity ...........167
9.1.2.2. Statistical Hy pothesis Evaluation for Efficacy ........................ 168
9.1.3. Multiplicity  Considerations................................ ................................ ......168
9.2. Sample Size Determination ................................ ................................ ................... 170
9.3. Analy sis Sets................................ ................................ ................................ .........173
9.4. Statistical Analy ses................................ ................................ ............................... 174
9.4.1.General Considerations ................................ ................................ .............174
9.4.1.1. Analy ses for Binary  Data................................ ........................ 175
9.4.1.2. Analy ses for Continuous Data ................................ ................. 175
9.4.2. Primary  Endpoint(s) ................................ ................................ .................. 176
090177e1980860c5\Approved\Approved On: 10-Sep-2021 13:03 (GMT)
FDA-CBER-2021-5683-1078106
PF-07302048 (BNT162 b2 RNA-Based COVID -19 Vaccine)
Protocol C4591007
Final ProtocolAmendment 32, 1006SepAug2021
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 119.4.3. Secondary  Endpoint(s) ................................ ................................ ..............178
9.4.4. Exploratory  Endpoint(s) ................................ ................................ ...........181
9.5. Interim Anal yses................................ ................................ ................................ ...182
9.5.1. Analy sis Timing ................................ ................................ ........................ 182
9.6. Data Monitoring Committee or Other Independent Oversight Committee ...........183
10. SUPPORTING DOCUM ENTATION AND OPERATI ONAL 
CONSIDERATIONS................................ ................................ ................................ ........185
10.1. Appendix 1: Regulatory , Ethical, and Study  Oversight Considerations .............185
10.1.1.Regulatory and Ethical Considerations ................................ .................. 185
10.1.1.1. Reporting of Safety  Issues and Serious Breaches of the 
Protocol or I CH GCP................................ ................................ .......185
10.1.2. Financial Disclosure ................................ ................................ ...............186
10.1.3. Informed Consent Process ................................ ................................ ......186
10.1.4. Data Protection ................................ ................................ ....................... 187
10.1.5. Dissemination of Clinical Study  Data................................ .................... 188
10.1.6. Data Qualit y Assurance ................................ ................................ ..........189
10.1.7. Source Documents ................................ ................................ .................. 190
10.1.8. Study  and Site Start and Closure ................................ ............................ 190
10.1.9. Publication Policy................................ ................................ ................... 191
10.1.10. Sponsor’s Qualified Medical Personnel ................................ ...............192
10.2.Appendix 2: Clinical Laboratory  Tests................................ ............................... 192
10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow -up, and Reporting ................................ ................................ ....193
10.3.1. Definition of AE ................................ ................................ ..................... 193
10.3.2. Definition of SAE ................................ ................................ ................... 194
10.3.3. Recording/Reporting and Follow- up of AEs and/or SAEs ..................... 196
10.3.4. Reporting of SAEs................................ ................................ .................. 199
10.4. Appendix 4: Contraceptive Guidance ................................ ................................ .200
10.4.1. Male Participant Reproductive Inclusion Criteria................................ ..200
10.4.2. Female Participant Reproductive Inclusion Criteria ............................... 200
10.4.3. Woman of Childbearing Potential ................................ .......................... 201
10.4.4. Contraception Methods ................................ ................................ ...........202
090177e1980860c5\Approved\Approved On: 10-Sep-2021 13:03 (GMT)
FDA-CBER-2021-5683-1078107
PF-07302048 (BNT162 b2 RNA-Based COVID -19 Vaccine)
Protocol C4591007
Final ProtocolAmendment 32, 1006SepAug2021
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 1210.5.Appendix 5: Li ver Safety : Suggested Actions and Follow -up Assessments ......203
10.6. Appendix 6: Abbreviations................................ ................................ ................. 205
10.7. Appendix 7: Criteria for Allowing Inclusion of Participants With Chronic 
Stable HIV, HCV, or HBV Infection................................ ................................ ......209
10.8. Appendix 8: Country -Specific Appendix –Applicable to Poland Only............. 209
11. REFERENCES ................................ ................................ ................................ ................ 210
LIST OF TABLES
Table 1. Dose Levels for Each Age Group in the Phase 1 and Phase 2/3 
Dose-Finding/Selected -Dose and Lower -Dose Evaluations .................... 65
Table2. Phase 1 Dose -Finding Participants ................................ ........................... 68
Table 3. Phase 1 L ower-Dose Evaluation Participants ................................ ...........68
Table4. Phase 2/3 Selected -Dose Participants –Blood Draws for 
Immunogenicity/Efficacy Assessments ................................ .................... 69
Table5. Phase 2/3 Selected -Dose Participants –Safety and 
Tolerability /Efficacy Assessments ................................ ........................... 69
Table 6. Phase 2/3 L ower-Dose Evaluation Participants –Blood Draws for 
Immunogenicit y/Efficacy Assessments ................................ .................... 70
Table 7. Phase 2/3 L ower-Dose Evaluation Participants –Safety and 
Tolerability /Efficacy Assessments ................................ ........................... 70
Table8. RR and HR, by  Age, Indicative of Severe S ystemic Illness..................... 91
Table9. Local Reaction Grading Scale................................ ................................ ..97
Table10. Systemic Event Grading Scale for Participants ≥2 Years of Age ............98
Table11. Systemic Event Grading Scale for Participants <2 Years of Age............99
Table12. Scale for Fever ................................ ................................ ........................ 101
Table13. Power Anal ysis for Immunobridging Assessment ................................ .170
Table14. Precision of SARS- CoV-2 Neutralizing Titer GMT .............................. 171
Table15. Power for Vaccine Efficacy  Assessment ................................ ................ 172
Table16. Probability  of Observing at Least 1 AE by  Assumed True Event 
Rates With Different Sample Sizes ................................ ........................ 172
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Page 131.PROTOCOL SUMMARY
1.1.Synopsis
Short Title :A Phase 1/2/3 Study  to Evaluate the Safety ,Tolerabilit y, and Immunogenicit y
of an RNA Vaccine Candidate Against COVID -19 in Healthy  Children and Young Adults .
Rationale
A pneumonia of unknown cause detected in Wuhan, China, was first reported in 
December 2019.  InJanuary2020, the pathogen causing this outbreak was identified as a 
novel coronavirus 2019. On11 March2020, the WHO upgraded the status of the COVID-19 
outbreak from epidemic to pandemic , which is now rapidly spreading worldwide. Children 
have been affected b y both the primary  COVID-19 disease and the less common secondary
inflammatory  complications, including MIS-C.
There are currently  no licensedvaccines to prevent infection with SARS-CoV-2or 
COVID-19 in participants under 16 years of age .  Given the rapid transmission of COVID -19 
and incidence of disease in the United States and elsewhere, the rapid develop ment of an 
effective vaccine is of utmost importance.
A Phase 1/2/3 study  (C4591001 )is currentl ybeing conducted in healthy individual s 12years 
of age and older to investigate the safety , tolerability , immunogenicity ,and efficacy  of the 
prophylactic BNT162 vaccine candidates against COVID -19. The vaccine candidate 
selected for evaluation in the C4591001 P hase 2/3 study  is BNT162b2 at a 30-µg dose level . 
The vaccine is administered as 2 doses approximately  21 days apart.On 18 November 2020, 
the primary  efficacy analysis results were announced, which demonstrate dBNT162b2 to be 
95% effective against COVID -19 beginning 28 day s after the first dose; 170 confirmed cases 
of COVID -19 were evaluated, with 162 observed in t he placebo group versus 8 in the 
vaccine group .Safety data from approximately  38,000 participants randomized 1:1 with a 
median of 2 months of follow -up after the second dose of vaccine showed a favorable safety  
profile at a dose of 30 μg in participants 16 years of age and older. On 11December 2020, 
the US FDA issued an EUA for use in individuals 16 y ears of age and older. Other countries 
have also granted EUA (eg, Canada, Mexico, Bahrain), and Pfizer and BioNTech are 
anticipating further regulatory  decisions in other countries. On 10 May  2021, the US FDA 
issued an EUA for use in individual s 12 to through 15 years of age. Other countries have 
also granted EUA or other authorization/approval for this age group (eg, EMA, UK, 
Switzerland, and the Philippines). BNT162b 2 wasapproved by the FDAon 23 August 2021 
to prevent COVID -19 caused by  SARS-CoV-2 in individuals 16 y ears of age and older .
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Page 14This Phase 1/2/3 study (C4591007) will initiallyevaluate up to 3doselevels of BNT162b2 in 
up to3 age groups (participants ≥5 to <12 y ears, ≥2 to <5 y ears, and ≥ 6monthsto <2 years 
of age) for safety, tolerability , immunogenicit y, and efficacy (depending on successful 
immunobridging and accrual of asufficient number of cases). Phase 1includesthe dose-
findingportion. I nitiation of dose finding in participants ≥5 to <12 y earsof ageis based on 
acceptable blinded safet y datademonstrated in 2260 12-through 15-year-oldsat the 30-µ g 
dose level in the C4591001 study.ThePhase 2/3 BNT162b 2dose level to be used in each 
age group in this study  will be selected based on the Phase 1 safety , tolerability ,and 
immunogenicit y datafrom the same age group. Phase 2/3 
(referred to as the selected-dose
portion of the study )includes animmunobridging analysisof immune responses in 
participants within each age group (participants ≥5 to <12 years, ≥2 to <5 y ears, and ≥ 6
monthsto <2 years of age) to those inparticipants 16 to 25years of ageinthe Phase 3 
C4591001efficacy study.Safety, tolerability ,and efficacy(depending on successful 
immunobridging and accrual of a sufficient number of cases)will also be evaluated in Phase 
2/3 of this study .
Theauthorized dose of BNT162b 2in adolescents and y oung adults 12 years of age and older 
is 30µg,whereas the following doses were selected in the ongoing C4591007 Phase 2/3 
portion: 10 µgin participants 5 to <12 years of ageand 3 µg in participants 6 months to 
<5 yearsof age. With the robust immune responses elicited in adolescents to minimize 
reactogenicity and risk of other AEs and to potentially  unify the dose level sacross children 
and young adults, additional lower dose levels of BNT162b2 (3 µg, 10 µg)will be evaluated 
to determine whether similar immune responses are elicited .For this lower -dose evaluation 
portion, a new cohort of Phase 1 participants will be enrolled in3age groups: >5 to <12, 
12 to <16, and 16 to <30years of age to assess safety , tolerability , and immunogenicity . The 
Phase 2/3 BNT162b2 dose level will be selected based on the Phase 1 assessments . The 
Phase 2/3 part will assess with an immunobridging analysis of immune responses in
participants within each age group to participants in the 30-µgPhase 3 C4591001 effi cacy 
study.
Postmarketing data demonstrate increased risks of my ocarditis and pericarditis, particularly  
within 7 day s following the second dose. The observed risk is higher among males under 40 
years of age than among females and older males. The observed risk is highest in males 12 
through 17 years of age. Although some cases required intensive care support, available data 
from short -term follow -up suggest that most individuals have had resolution of sy mptoms 
with conservative management. Information is n ot yet available about potential long -term 
sequelae. The CDC has published considerations related to my ocarditis and pericarditis after 
vaccination, including for vaccination of individuals with a history  of myocarditis or 
pericarditis ( https://www.cdc.gov /vaccines/covid- 19/clinical -
considerations/my ocarditis.html). Elevated t roponinIlevelmay be an indicator of subclinical 
myocarditis. If testing of troponinI levels in individuals who did not receive BNT162b2 
indicates that troponinI level could be a reliable indicator of potential subclinical 
myocarditis, obtaining serum samples for potential troponinI testing in an additional group 
of participants during the period of increased risk of clinical my ocarditis may  help 
characterize the absenc e/presence and frequency  of subclinical my ocarditis. 
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Page 15OverallDesign
Thisis a Phase 1/2/3 study inhealthy children and young adults.
Dependent upon safet y and/or immunogenicit y data generated during the course of this 
study, and the resulting assessment of benefit -risk, the safet y, tolerability , and 
immunogenicit y of BNT162b2 in participants <6 months of age may  subsequently  be 
evaluated. Participants will range from ≥6 months to <30 y ears of age ,with different dose 
levels assessed in each gr oup.
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Page 16Dose Levels for Each Age Group in the Phase 1 and Phase 2/3 Dose- Finding/Selected -DoseEvaluations ,
Lower-DoseEvaluation s, and Obtaining Serum Samples for Potential Troponin I Testing
Phase 1 Open -Label Dose -Finding Evaluation
≥6 Months to 
<2 Years≥2 to <5 
Years≥5 to <12 
Years12 to <16 
Years16 to <30 
YearsTotal
Dose level 3µg 3/10 µg 10/20/30 µg
Participant s 16a16/32a16/16/16b112
Phase 2/3 Observer- Blinded, Placebo -Controlled Selected -DoseEvaluation
Dose level 3 µg 3 µg 10µg
Participant s22501125
(active 
1500750; 
placebo 3750)22501125
(active1500
750; placebo 
3750)4500
(active 3000; 
placebo 1500)90006750
Phase 1 Open -Label Lower-Dose Evaluation
Planned dose 
level(s) 3 µg 3/10 µgc3/10µgc
Participant s 32 32/32 32/32 160
Phase 2/3 Open -Label Lower- Dose Evaluation
Planned dose 
level TBD TBD TBD
Participant s 300 300 300 900
Phase 2/3 Obtaining Serum Samples for Potential TroponinI Testing
Planned dose
level10µg 30 µg
Participant s 750
(active500;
placebo250)500
(active500; 
placebo0)1250
a.Actual number of participants recruited in the≥6 months to <2 y ears and ≥2 to <5 yearsage groups .
b.Actual number of participants recruited in the≥5 to <12 yearsage group . Dose 1: 16 out of 16 received 
30-µgdose level ; Dose 2: 4out of 16 received 30 -µgdose level and 12 of 16 received 10-µgdose level .
c.Both dose levels will start concurrently .
Phase 1 
Dose-finding:Is the open -label dose -finding portion of the study  that willevaluate safet y, 
tolerability, and immunogenicity  of BNT162b2 administered on a 2 -dose (separated b y 
approximately  21 days) schedule in up to 3 age groups (participants ≥5 to <12 y ears, ≥2 to 
<5 years, and ≥6 months to <2 y ears of age). 
Dosefinding is being initiated in this study  in participants ≥5 to <12 y ears of age based on 
the acceptable blinded safety assessment of the 30- µg dose in 12 -to 15-year-olds in the 
C4591001 study .
The purpose of P hase 1 is to identify preferred dose level(s) of BNT162b 2 from up to 
3different dose levels in each age group.
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Page 17Dependent upon safet y and/or immunogenicit y data generated during the course of this 
study, it is possible that dose levels may not be started, may  be terminated early, and/or may  
be added with dose levels below the lowest stated dose.
Participants will have blood drawn prior to both Dose1and Dose2and 7 day s afterDose2
to assess immunogenicity  to determine the selectedBNT162b 2doselevel for Phase 2/3.
Lower-dose evaluation :Is the open- label lower-doseevaluation portion of the study  that 
willevaluate safet y, tolerability , and immunogenicity  of BNT162b2 on a 2-dose (separated 
by approximately  21 days) schedulein up to 3 age groups ( participants ≥5 to <12 y ears, 12 to 
<16years, and 16to <30years of age) .
The purpose of the Phase 1 lower -dose evaluation is to evaluate safety  and immunogenicit y
of BNT162b2 from up to 2different dose levels in each age group.
Participants will have blood drawn prior to both Dose 1 and Dose 2 and 7 day s afterDose 2 
to assess immunogenicity  to determine the selectedBNT162b2 dose level for the Phase 2/3
lower-dose evaluation portion of the study .
Phase 2/3
Selected-dose:Is the portion of the study  that will evaluate the safet y, tolerability , and 
immunogenicit yin each age group at theselecteddose level from the Phase 1 dose-finding
portion of the study . Efficacy will be evaluated within or acros sage groups in which 
immunobridging is successful, depending on accrual of a sufficient number of casesin those 
age groups .
Participants will have blood drawn at baseline prior to Dose 1and 6 months after Dose 2. 
Immunobridging to participants 16 to 25 years of age in the C4591001 study  will be based on
immunogenicit y data collected at baseline and 1 month after Dose 2.The persistence of the 
immune response will be based on immunogenicity data collected in participants at baseline 
and at 1, 6, 12 ( original BNT162b2 group onl y),and24months after Dose 2 (original 
BNT162b2 group onl y).In addition, efficacy  against confirmed COVID -19 and against 
asymptomatic infection will also be assessed. 
At designated US sites, an additional optional whole blood sample of approximately 10mL 
will be obtained prior to Dose1and at 7 days and 6 months after Dose 2from up to 
approximately  60 participants ≥10yearsof age.  Thesesampleswill be used on an 
exploratory  basis to investigate the postvaccination cell -mediated immune response at these 
timepoints.
At the 6-month follow-up visit,all participants will be unblinded. P articipants who originall y 
received placebo will be offered the opportunit y to receive BNT162b2 as part of the stud y.
Participants ≥12 years of age who originall y received placebo and become eligible for receipt 
of BNT162b2 or another COVID -19 vaccine according to local or national recommendations 
prior to 6months after Dose2Visit 5according to recommendations (detailed separatel y and 
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Page 18available in the electronic study  reference portal) will have the opportunity to receive 
BNT162b2(10µg or 3 µg) based on age at the time of approval .If a participant turns 12 
years of age during the study , he or she has the following 2 options: receive 10 µg within the 
study (following provision of informed consent) or receive a BNT162b2 30 -µg dose outside 
of the study . 
Lower-doseevaluation : Is the portion of the study  thatwill evaluate the safety , tolerability , 
and immunogenicit yin each age group at the selected dose level from the Phase 1 lower-dose 
evaluation .
In this open -label stud y, all participants will have blood drawn at baseline prior to Dose 1 
and at 1 and6 months after Dose 2. Immunobridging to comparator participants inthe 
C4591001 study  will be based on immunogenicity data collected at baseline and 1 month 
after Dose 2. The persistence of the immune response will be based on immunogenicit y data 
collected in participants at baseline and1and 6 months after Dose 2.
Obtaining serum samples for potentialtroponinI testing: If testing of troponinI levels in 
individuals who did not receive BNT162b2 indicates that troponinI level could be a reliable 
indicator of potential subclinical myocarditis, obtaining serum samples for potential 
troponinI testing during the period of increased risk of clinical my ocarditis may  help 
characterize the absence/presence and frequency of subclinical myocarditis. To assess, a n 
additional group of participants will be included: 5 to <12 y ears: 750 participants randomized 
2:1 to receive BNT162b2 10 µg or placebo ,and500 participants 12to<16years of age: 
open-label receipt of BNT162b2 30 µg.
Number of Participants
Phase 1: Open -Label Dose -Finding and Lower-Dose Evaluation
Phase 1isanopen-label study thatwill consist of up to 3 different dose levels in each age 
group,with a minimum of 16 participants per dose level (total of 144 participants) forthe
dose-findingevaluation and a minimum of 32 participants per dose level (total of 160
participants) for the lower-doseevaluation .
Phase 1 Dose-Finding Participants
Age Group Total Up to 3 Dose Levels of BNT162b2aActive Placebo
≥5 to <12 Years 48 16/16/16 16 N/A
≥2 to <5Years 48 16/16/16 16 N/A
≥6Monthsto <2years 48 16/16/16 16 N/A
a.A dose level may be expanded to enroll more than 16 participants subjectsper dose level. 
Phase 1 Lower-Dose Evaluation Participants
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Page 19Age Group Total Up to 2Dose Levels of BNT162b 2aActive Placebo
≥5 to <12 Years 32 32 32 N/A
12 to <16 Years 64 32/32 32 N/A
16 to <30Years 64 32/32 32 N/A
a.A dose level may be expanded to enroll more than 32participants subjectsper dose level. 
Phase 2/3: Safety, Tolerability, Immunogenicity, and Efficacy
Selected-dose: Is theportion of the study that will evaluate thesafety, tolerability ,and 
immunogenicit yof the selected dose levelin each age group from the Phase 1 dose-finding
portion of the study ,witha total of approximately  90006750participants, as an additional 
2250 participants will be included to further enlarge the size of the pediatric safety database .  
Participants will be randomized in a 2:1ratio toreceive active vaccine or placebo .
Approximately  450 participants (300intheactive vaccine group and 150 in the placebo 
group) randomized in each age group in this phase will contribute to theimmunobridging 
analysis at 1month after Dose 2 and will contribute to the overall anal ysis of the persistence 
of immune response at 6 months after Dose 2 .  These participants will be enrolled from both 
US and EU sites to ensure this subset is representative of the whole stud y.
For the persistence time points of 12 and 24 months afterDose 2,approximately
70participants from each age group in the original BNT162b2 vaccine groupwill have an 
immunogenicit yblood draw in order to contribute to the anal ysis.All approximately  
90006750participants will contribute to the VE analysis for conditional VE and 
asymptomatic infection . Approximately  4500 participants who had post –Dose 1 blood 
sample collection will contribute to the asy mptomatic infection analy sis.Efficacy will be 
evaluated with in or across age groups in which immunobridging is successful, depending on 
accrual of a sufficient number of cases in those age groups.
Phase 2/3 Selected-DoseParticipants –Blood Draws for Immunogenicity/Efficacy Assessments 
All Age Groups ≥5 to <12 Years of Age ≥2 to <5 Years and ≥6 
Months to <2 Years of Agea
Total Active Placebo TotalActivePlacebo Total Active Placebo
Baseline blood 
draw 90006750600045003000 4500 3000 1500 2250 11251500750 750375
1 Month after Dose 
21350 900 450 450 300 150 450 300 150
6 Months after 
Dose 24500 3000 1500 2250 1500 750 1125 750 375
12 Months after 
Dose 2 210 210 N/A 70 70 N/A 70 70 N/A
24 Months after 
Dose 2210 210 N/A 70 70 N/A 70 70 N/A
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Page 20Phase 2/3 Selected-DoseParticipants –Blood Draws for Immunogenicity/Efficacy Assessments 
a.Number of participants shown is for each of these 2younger age groups .
All participants will contribute to the safet y,tolerability , and efficacyassessments.
Phase 2/3 Selected-DoseParticipants –Safety and Tolerability /Efficacy Assessment s
Age Total Active Placebo
≥5 to <12 Years 4500 3000 1500
≥2 to <5 Years 22501125 1500750 750375
≥6 Months to <2 Years 22501125 1500750 750375
All age groups 90006750 60004500 30002250
Lower-dose evaluation : Is the open-label portion of the study  thatwill evaluate the safet y, 
tolerability ,and immunogenicity of the selected dose level in each age group from the Phase 
1lower-dose evaluation, with a total of approximately  900active participants.  
Approximately  300active participants in each age group in this phase will contribute to the 
immunobridging anal ysis at 1month after Dose 2 and the overall anal ysis of the persistence 
of immune response at 6 months after Dose 2.  These participants will be enrolled from both 
US and EU sites to ensure this subset is representative of the whole stud y.
Phase 2/3 Lower-Dose Evaluation Participants –Blood Draws for Immunogenicity /Efficacy
Assessments 
All Age Groups ≥5 to <12, 12 to 16 Years , and 16 to 
<30Years of Agea
Total Active Active Placebo
Baseline blood draw  900 900 300 N/A
1 Month after Dose 2 900 900 300 N/A
6 Months after Dose 2 900 900 300 N/A
a.Number of participants shown is for each of these 2 older age group s.
All participants will contribute to the safet y,tolerability , and efficacy assessments.
Phase 2/3 Lower-Dose Evaluation Participants –Safety and Tolerability /Efficacy Assessments
Total Active Placebo
900 900 N/A
Obtaining serum samples for potential troponinI testing: 750 participants 5 to <12 y ears 
of age (randomized 2:1 to receive BNT162b2 10 µg or placebo) and 500 participants 12 to 
<16years of age (open -label receipt of BNT162b2 30 µg).
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Page 21        
      
Sum ofAge Groups
Currently Included in 
Potential Troponin I 
TestingWithin Protocol5 to <12Years of Age
Placebo-Controlled 
(2:1 Randomization)12 to <16Years of Age
Open-Label
Total Active Placebo Total Active Placebo Total Active Placebo
Baseline blood 
draw 1250 1000 250 750 500 250 500 500 N/A
4 Days after 
Dose 21250 1000 250 750 500 250 500 500 N/A
Intervention Groups and Duration
Phase 1
Dose-finding: Dosingwill begin at the low-doselevelin participants ≥5 to <12 y ears of age .
Controlled enrollment will be required for the first dose level studied in each age group.  
Only a limited number of participants (~4) are dosed before allowing dosing in the remaining 
participants (~12) in the sam e age and dose -level group. The IRC will review safety  data 
(e-diary and AE) acquired up to 7 days after Dose 1 for the low-doselevelgroup; upon 
confirmation of an acceptable safet y assessment by the IRC:
Dosing maycommence at the mid -doselevel in th e same age group, and   
Dosing maycommence at the low -dose level in participants ≥2 to <5 y ears of age.  
The same process will be followed when moving updoselevels in each age group, and when 
progressing between age groups at the low-dose level as shown in Section 1.2.  Dosing may  
commence at the low -dose level in participants ≥ 6 months to <2 y ears of age after IRC 
review of safet y data (e-diary and AE) acquired up to 7 days after Dose 1 at the low -dose 
level from participants ≥2 to <5 y ears of age.
In each age group, i f the low-doselevel is considered notacceptable based on safet y 
assessment after Dose 1 , the mid-doselevelor high-doselevelwill not commence .In this 
case, an optional lower dose level may commence.   Dependent on the results obtained, dose
level(s)may be omitted. In each age group, i fthe mid-dose level is considered not 
acceptable based on sa fety assessment after Dose 1, the high-dose level will not commence. 
Based on safety assessments, t he second dose may  be given at a lower dose level.
Duration of the dose-findingportion of the study: Participants are expected to participate 
for up to a maximum of approximately  26months.
Lower-dose evaluation :As higher doses have been assessed in each age group, all age/dose 
levels will proceed concurrentl y.
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Page 22Duration of the lower-doseevaluation portion of the study :Participants are expected to 
participate for up to a maximum of approximately  6months.
Phase 2/3
Selected-dose: Progression of each age group into Phase 2/3 will occur independentl y; it is 
therefore possible that each age group may not start Phase 2/3 concurrentl y and the dose 
level selected for Phase 2/3 may  differ by age group.  For each age group t o proceed to 
Phase2/3, safety, tolerability ,and immunogenicity data from 7 days after Dose2 for the 
selected vaccine dose levelin that age group from Phase 1 will be confirmed to be 
acceptable .
Duration of the selected-doseportion of the study :Participants are expected to participate 
for upto a maximum of approximately  26months.
Lower-dose evaluation : Progression of each age group into Phase 2/3 will occur 
independentl y; it is therefore possible that each age group may  not start Phase 2/3 
concurrently ,and the dose level selected for Phase 2/3 may  differ by age group.  For each 
age group t o proceed to Phase 2/3, safety, tolerability, and immunogenicity data from 7 day s 
after Dose 2 for the selected vaccine dose level in that age group from Phase 1 will be 
confirmed to be acceptable .
Duration of the lower-dose evaluation portion of the study : Participants are expected to 
participate for up to a maximum of approximately  6months.
Obtaining serum samples for potential troponinI testing:Progression of each age group 
will occur concurrentl y.
Duration of obtaining serum samples for potential troponinI testing: Participants are 
expected to participate for up to a maximum of approximately  6months.
Data Monitoring Committee or Other Independent Oversight Committee
The study  will utilize an IRC, an internal Pfizer committee that will review data to allow 
dosefindin gin Phase 1.
An external DMC will review cumulative unblinded data and monitor vaccine safet y 
throughout the stud y.
Statistical Methods
Immunobridging of the immune response to prophy lactic BNT162b2 in participants within 
each age group totheresponse in participants in the comparator group from Phase 2/3 of the 
C4591001 study will be assessed separately for each age group and based on the GMR of 
SARS-CoV-2 neutralizing titers using a 1.5 -fold margin and the difference in percentages of 
participants with seroresponse using a 10% margin . 
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Page 23Within each age group , immunobridging based on GMR and seroresponse difference will be 
assessed sequentially  in the order specified .Immunobridging success based on GMR will be 
declaredif the lower limit of the 95% CI for the GMR (eachage groupto the comparator age 
group from the C4591001 study)is >0.67and the point estimate of the GMR is ≥0.8. 
Immunobridging success based on the seroresponse difference will be declared if the lower
limit of the 95% CI  for the difference in percentages of participants with seroresponse is 
>-10%. Since seroresponse is not directly  linked to an antibody  level associated with 
protection against COVID- 19, if the seroresponse endpoint nearl y misses the noninferiorit y 
criteria, the totalit y of evidence willbe evaluated, including RCDCsand the proporti on of 
participants with neutralizing titer s ≥LLOQ.
A sample size of 225evaluable participants in each age group evaluated in this study  andthe 
corresponding comparator group from the C4591001 study will provide a power of 90. 4% 
and 92.6% to declare immu nobridging successbased on GMR and seroresponse difference, 
respectivel y. The immunogenicity  data from the 300 active vaccine recipients in
approximately 450participant s randomized in each age group in the Phase 2 /3selected-dose
portion of the study , and approximately  300 participants enrolled in each age group in the 
Phase 2/3 lower-dose evaluation portion of the study , will be used for the immunobridging
assessment.
The other immunogenicity objectives will be evaluated descriptively  by GMT, GMFR,and 
the associated 95% CIs for SARS-CoV-2 neutralizing titers at the various time points.
The secondary  efficacy objectives are to evaluate VE, defined as 100 ×(1–IRR),against the 
confirmed COVID -19 illness , in each of the 2 age groups ( ≥5 to <12 years,≥6 months to 
<2yearsand ≥2to <5yearscombined )or acrossallage group swhere immunobridging 
success is declared in thePhase 2/3 selected- dose portion of the study  (if the required number 
ofcases are not accrued in eitherofthe 2individual age groups).IRR is calculated as the 
ratio of the first confirmed COVID -19 illness rate in the vaccine group to the corresponding 
illness rate in the placebo group. With the assumption of a true VE of 75%, 22 cases will 
provide 70% power to conclude true VE >20%.Hypothesis testing for the specific age 
groups (≥5 to <12 years, ≥6 months to <2 years and ≥2 to <5years combined )will be 
conducted onl y ifat least 22 cases are accrued in thoseage group s. However, i f 22 cases are 
not accrued in either of the 2 age groups ( ≥5 to <12 y ears, ≥6 months to <2 years and ≥2 to 
<5years combined) where immunobridging success is declared, but 22 cases are accrued
across all the age groups where immunobridging success is dec lared, then hypothesis testing 
will be conduct ed acrossthe age groups with imm unobridging success. 
VEagainst as ymptomatic infection will be evaluated descriptively. VE estimate and 2 -sided 
95% CI for VE will be provided using the Clopper -Pearson method.
The primary  safety objective will be evaluated b y descriptive summary  statistics for local 
reactions, s ystemic events ,andAEs/SAEs for each vaccine and age group.  A 3- tier approach 
will be used to summarize AEs in the Phase 2/3 selected-dose portion of the study .
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CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 241.2.Schema
≥5 to <12 Years ≥2 to <5 Years ≥6 Months to <2 Years
Phase 1
All participants receive BNT162b2Phase 1
All participants receive BNT162b2Phase 1
All participants receive BNT162b2
Low-dose level(n=16)aLow-doselevel (n=16)aLow-doselevel (n=16)a
IRC IRCbIRC IRCbIRC
Mid-dose level (n=16) Mid-doselevel (n=16) Mid-doselevel (n=16)
IRC IRC IRC
High-dose level (n=16) High-doselevel (n=16) High-doselevel (n=16)
IRC cIRC cIRC c
Phase 2/3
Participants randomized to receive 2:1 
BNT162b2 : placeboPhase 2/3
Participants randomized to receive 
2:1 BNT162b2 : placeboPhase 2/3
Participants randomized to receive 2:1 
BNT162b2 : placebo
a.In each age group, if the low -dose level is considered not acceptable based on safety assessment after Dose 1, the mid-dose level or high -dose level will not commence.  In 
this case, an optional lower dose level may commence.   
b.The IRC will review safety data (e -diary and AE) acquired up to 7 days after Dose 1 in the low -dose-level group, and d osing may commence at the low -dose level in the 
next age group based upon confirmation of an acceptable safety assessment at this review.
c. IRC choice of dose level for each age group.  Dependent on safety, tolerability, and immunogenicity data from 7 days after Do se 2 in each age group.
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CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 25Phase 1/2/3 Lower-Dose Evaluation
≥5 to <12 Years 12 to <16 Years 16 to <30Years
Phase 1
All participants receive BNT162b2
Low-dose level(n=32)Phase 1
All participants receive BNT162b2
Low-doselevel (n=32)and
Mid-doselevel (n=32)aPhase 1
All participants receive BNT162b2
Low-doselevel (n=32)and
Mid-doselevel (n=32)a
IRCbIRCbIRCb
Phase 2/3
All participants to receiveBNT162b2Phase 2/3
All participants to receive BNT162b2Phase 2/3
All participants to receive BNT162b2
a.Low-and mid-dose levels will start concurrently.
b.IRC choice of dose level for each age group.  Dependent on safety, tolerability, and immunogenicity data from 7 days after Do se 2 in each age group.
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CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 26Dose Levels for Each Age Group in the Phase 1 and Phase 2/3 Dose- Finding/Selected -DoseEvaluations ,and Lower-Dose Evaluations ,andObtaining 
Serum Samples for Potential Troponin I Testing
Phase 1 Open-Label Dose-Finding Evaluation
≥6 Months to 
<2Years≥2 to <5 Years ≥5 to <12 Years 12 to <16 Years 16 to <30 Years Total
Dose level 3µg 3/10 µg 10/20/30 µg
Participant s 16a16/32a16/16/16b112
Phase 2/3 Observer- Blinded, Placebo -Controlled Selected-DoseEvaluation
Dose level 3 µg 3 µg 10 µg
Participant s 22501125
(active 1500750; 
placebo 3750)22501125
(active 1500750; 
placebo 750375)4500
(active 3000; 
placebo 1500)90006750
Phase 1Open-LabelLower-Dose Evaluation
Planned dose 
level(s) 3 µg 3/10µgc3/10µgc
Participant s 32 32/32 32/32 160
Phase 2/3 Open-Label Lower-Dose Evaluation
Planned dose level TBD TBD TBD
Participant s 300 300 300 900
Phase 2/3 Obtaining Serum Samples for Potential Troponin I Testing
Planned dose level 10 µg 30 µg
Participant s 750
(active 500; placebo
250)500
(active 500;  
placebo 0)1250
a.Actual number of participants recruited inthe ≥6 months to <2 years and ≥2 to <5 yearsage groups .
b.Actual number of participants recruited in the ≥5 to <12 years age group. Dose 1: 16 out of 16 received 30 -µg dose level; Dose 2: 4 out of 16 received 30-µg dose level 
and 12 of 16 received 10-µg dose level.
c.Both dose levels will start concurrently .
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CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 271.3. Schedule of Activ ities
The SoAtable provides an overview of the protocol visits and procedures.  Refer to the Study  Assessments a nd Procedures section of 
the protocol for detailed information on each procedure and assessment required for compliance with the pr otocol.
The investigator may  schedule visits (unplanned visits) in addition to those listed i n the SoA table, in order to conduct evaluations or 
assessments required to protect the well -being of the participant .
1.3.1.Phase 1Dose-FindingPortion
An unplanned potential COVID -19/MIS-Cillness visit isrequired at an y time for the duration of the study that COVID -19/MIS-C
symptoms are reported .  During the 7 day s following each dose, potential COVID -19/MIS-Csymptoms that overlap with specific 
systemicevents (ie, fever, chills, new or increased muscle pain, diarrhea, vomiting) should not trigger a potential COVID -19/MIS-C
illness visit unless, in the investigator’s opinion ,the clinical picture is more indicative of a possible COVID -19/MIS-Cillness rather 
than vaccine reactogenicity .For details, see Section 8.13.
Visit Number 1 2 3 4 5 6 7 Unplanned
Visit Description Dose 1aDose 2 7 Day 
Follow-up 
Visit 
(1 Week 
After Dose 
2)1-Month
Follow-up 
Visit6-Month
Follow-up 
Visit12-Month 
Follow-up 
Visit24-Month 
Follow-up 
VisitPotential COVID -19/ MIS -C 
Illness 
Visitb
Visit Window (Days) Day 1 19 to 23 
Days After 
Visit 16 to 8 Days 
After Visit 
228 to 35 
Days After 
Visit 2175 to 189 
Days After 
Visit 2350 to 378 
Days After 
Visit 2714 to 742 
Days After 
Visit 2Optimally Within 3 Days 
After Potential 
COVID-19/MIS-C Illness 
Onset
Type of Visit Clinic Clinic Clinic Clinic or 
TelephonecTelephone Telephone Clinic or 
TelephoneClinic or 
Telehealth
Obtain informed consent and assent (if appropriate) X
Assign participant number X
Obtain demography and significant medical history 
dataX
Confirm use of contraceptives (if appropriate) X X X X
Collect nonstudy vaccine information X X X X X
Collect prohibited medication use X X X X X X X
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Page 28Visit Number 1 2 3 4 5 6 7 Unplanned
Visit Description Dose 1aDose 2 7 Day 
Follow-up 
Visit 
(1 Week 
After Dose 
2)1-Month
Follow-up 
Visit6-Month
Follow-up 
Visit12-Month 
Follow-up 
Visit24-Month 
Follow-up 
VisitPotential COVID -19/ MIS -C 
Illness 
Visitb
Visit Window (Days) Day 1 19 to 23 
Days After 
Visit 16 to 8 Days 
After Visit 
228 to 35 
Days After 
Visit 2175 to 189 
Days After 
Visit 2350 to 378 
Days After 
Visit 2714 to 742 
Days After 
Visit 2Optimally Within 3 Days 
After Potential 
COVID-19/MIS-C Illness 
Onset
Type of Visit Clinic Clinic Clinic Clinic or 
TelephonecTelephone Telephone Clinic or 
TelephoneClinic or 
Telehealth
Confirm eligibility X X
Review temporary delay criteria X X
Measure vital signs (including body temperature) X X
Perform physical examination (including height and 
weight)dX X
Perform urine pregnancy test (only for female 
participants biologically capable of having children)X X
Obtain randomization number and study intervention 
allocationX
Obtain anterior nasal swab X X X
Collect blood sample for immunogenicity ~5 mL ~5 mL ~5 mL
Administer study intervention X X
Assess acute reactions for at least 30 minutes after 
study intervention administrationX X
Explain communication methods (including for e -
diary completion), assist with downloading the app, or 
issue provisioned device, if requiredX
Providea thermometer and caliper (measuring) deviceX
Reactivate reactogenicity e -diary X
Ensure the participant’s parent(s)/legal guardian/has a 
caliper device and thermometerX
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Page 29Visit Number 1 2 3 4 5 6 7 Unplanned
Visit Description Dose 1aDose 2 7 Day 
Follow-up 
Visit 
(1 Week 
After Dose 
2)1-Month
Follow-up 
Visit6-Month
Follow-up 
Visit12-Month 
Follow-up 
Visit24-Month 
Follow-up 
VisitPotential COVID -19/ MIS -C 
Illness 
Visitb
Visit Window (Days) Day 1 19 to 23 
Days After 
Visit 16 to 8 Days 
After Visit 
228 to 35 
Days After 
Visit 2175 to 189 
Days After 
Visit 2350 to 378 
Days After 
Visit 2714 to 742 
Days After 
Visit 2Optimally Within 3 Days 
After Potential 
COVID-19/MIS-C Illness 
Onset
Type of Visit Clinic Clinic Clinic Clinic or 
TelephonecTelephone Telephone Clinic or 
TelephoneClinic or 
Telehealth
Ask the participant’s parent(s)/legal guardian to 
complete e -diary and ensure the participant’s 
parent(s)/legal guardian remains comfortable with 
chosen e-diary platformX X
Review reactogenicity e-diary data (daily review is 
optimal during the active diary period)
Review ongoing reactogenicity e-diary symptoms and 
obtain stop dates X X
Collect AE se X X X X X
Collect SAEsf X X X X X X
Collect e-diary or assist the participant’s 
parent(s)/legal guardian to delete applicationX
Collection of COVID -19/MIS-C–related clinical and 
laboratory information (including local diagnosis)X
Abbreviations: AESI = adverse event of special interest; CRF = case report form; MIS -C = multisystem inflammatory syndrome in children ; SMS = short message service .
a. The visit may be conducted across 2 consecutive days; if so, please refer to Section 8.11.1.1.
b.Potential MIS -C visit: Hospitalization for a severe illness with no other alternative etiology.
c.Contact can be made via email or SMS. If no response is obtained or responses do not satisfy visit requirements, a telephone call should be made.
d. A physical examination will include, at a minimum, assessments of general appearance, lungs, cardiovascular system, and lymph nodesurvey. Height and weight will be 
collected only at Visit 1.
e.Refer to Section 8.3.1 for the time period for collecting AEs/AESIs. Any AEs occurring up to 48 hours after blood draw and anterior nasal swab collection must be recorded 
(see Section 8.3.1).Note: Potential COVID-19/MIS -C illnesses and their sequelae that are consistent with the clinical endpoint definition (Section 8.1) should not be recorded 
as AEs. These data will be captured to describe disease endpoints for lack -of-efficacy assessment data only on the relevant pages of th e CRF, as these are expected endpoints.
f.Refer to Section 8.3.1for the time period for collecting SAEs.
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Page 301.3.2.Phase 1 Lower-Dose Evaluation
Visit Number 101 102 103 104 105
Visit Description Dose 1aDose 2 7-Day Follow -up Visit 
(1 Week After Dose 2)1-Month
Follow-up Visit6-Month
Follow-up Visit
Visit Window (Days) Day 1 19 to 23 Days 
After Visit 1016 to 8 Days 
After Visit 10228 to 35 Days 
After Visit 102175 to 189 Days 
After Visit 102
Type of Visit Clinic Clinic Clinic Clinic or TelephonebTelephone
Obtain informed consent and assent (if appropriate) X
Assign participant number X
Obtain demography and significant medical history data X
Confirm use of contraceptives (ifappropriate) X X X X
Collect nonstudy vaccine information X X X X X
Collect prohibited medication use X X X X
Confirm eligibility X X
Review temporary delay criteria X X
Measure vital signs (including body temperature) X X
Perform clinical assessmen tc X X
Perform urine pregnancy test (only for female participants 
biologically capable of having children)X X
Obtain randomization number and study intervention 
allocationX
Obtain anterior nasal swab X X
Collect blood sample for immunogenicityd~20 mL/~10 mL/
~5mL~20 mL/~10 mL/
~5mL~20 mL/~10 mL/
~5mL
Administer study intervention X X
Assess acute reactions for at least 30 minutes after study 
intervention administrationX X
Explain communication methods (including for e -diary 
completion), assist with downloading the app, or issue 
provisioned device, if requiredX
Providea thermometer and caliper (measuring) device X
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Page 31Visit Number 101 102 103 104 105
Visit Description Dose 1aDose 2 7-Day Follow -up Visit 
(1 Week After Dose 2)1-Month
Follow-up Visit6-Month
Follow-up Visit
Visit Window (Days) Day 1 19 to 23 Days 
After Visit 1016 to 8 Days 
After Visit 10228 to 35 Days 
After Visit 102175 to 189 Days 
After Visit 102
Type of Visit Clinic Clinic Clinic Clinic or TelephonebTelephone
Reactivate reactogenicity e -diary X
Ensure the participant or participant’s parent(s)/legal 
guardian has a caliper device and thermometerX
Ask the participant or participant’s parent(s)/legal 
guardian to complete e-diary and ensure the participant’s 
parent(s)/legal guardian remains comfortable with chosen 
e-diary platformX X
Review reactogenicity e-diary data (daily review is 
optimal during the active diary period)
Review ongoing reactogenicity e-diary symptoms and 
obtain stop dates X X
Collect AEse X X X X X
Collect SAEsf X X X X X
Collect e-diary or assist the participantor participant’s 
parent(s)/legal guardian to delete applicationX
Abbreviations: AESI = adverse event of special interest; CRF = case report form ;SMS = short message service .
a.The visit may be conducted across 2 consecutive days; if so, please refer to Section 8.11.2.1.
b.Contact can be made via email or SMS. If no response is obtained or responses do not satisfy visit requirements, a telephone call should be made.
c.Including, if indicated, a physical examination.
d.20 mL is to be collected from participants ≥16 years of age; 10 mL is to be collected from participants 12 to <16years of age ;5 mL is to be collected from participants 5 to 
<12years of age.
e.Refer to Section 8.3.1 for the time period for collecting AEs/AESIs. Any AEs occurring up to 48 hours after blood draw and anterior nasal swab collection must be recorded 
(see Section 8.3.1). 
f.Refer to Section 8.3.1for the time period for collecting SAEs.
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Page 321.3.3.Phase 2/3 Selected-DosePortion
An unplanned potential COVID-19 /MIS-C illness visit isrequired at an y time for the duration of the study that potential 
COVID-19/MIS-Csymptoms are reported .During the 7 day s following each dose, potential COVID -19/MIS-Csymptoms that 
overlap with specific s ystemicevents (ie, fever, chills, new or increased muscle pain, diarrhea, vomiting) should not trigger a potential 
COVID-19/MIS-Cillness visit unless, in the investigator’s o pinion, the clinical picture is more indicative of a possible 
COVID-19/MIS-Cillness rather than vaccine reactogenicit y.For details, see Section 8.13.
Administration of BNT162b2 to those originally assigned to placebo: At the 6-month follow -up visit, all participants will be 
unblinded. Participants who originall y received placebo will be offered the opportunity  to receive BNT162b2 as part of the study . 
Participants who originally  received placebo and become eligible for receipt of BNT162b2 or another COVID -19 vaccine according to 
local or national recommendations prior to 6 months after Dose2 (detailed separately  and available in the electronic stud y reference 
portal) will be advised to contact the site to determine whether theycan receive BNT162b2 (10 µg or 3 µg) based on age at the time of 
approval. If aparticipant turns 12 y ears of age during the study , he or she has thefollowing 2 options: receive 10 µg within the study  
(following provision of informed consent) or receive a BNT162b2 30 -µg doseoutside of the study . At the 6month (Visit 5) followup 
visit, all participants will be unblinded . Participants who originall y received placebo will be offered the opportunity to receive 
BNT162b2 as part of the study .Participants who become eligible for receipt of BNT162b2 or another COVID 19 vaccine according 
to local or national recommendations prior to Visit 5 (detailed separatel y, and available in the electronic study  reference portal )will
have the opportunit y to receive the EUA approved dose level of BNT162b2 .When contacted, the site will conduct a telephone visit to 
confirmeligibility  and, if the participant is eligible and wants to receive BNT162b2 in the event that he or she originall y received
placebo, the site will unblind the participant’s study intervention allocation to determine whether the participant received BNT162b2 
or placebo. I f he or she originall y received placebo and wants to receive BNT162b2 (10 µg or 3 µg) , the participant will move to the 
SoA in Section 1.3.3.2 for his or her remaining visits. Participants who originally  received BNT162b2 or placebo recipients who 
decline BNT162b2 will move to the S oA in Section 1.3.3.1.
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Page 33Visit Number 1 2 3 4 5 Unplanned
Visit Description Dose 1a Dose 2 1-Week
Follow-up Visitb1-Month
Follow-up Visit6-Month
Follow-up VisitcPotential COVID -19 
Illness/MIS-C Visitd
Visit Window (Days) Day 1 19 to 23 Days After 
Visit 16 to 8 Days After 
Visit 228 to 35 Days After 
Visit 2175 to 189 Days 
After Visit 2Optimally Within 3 Days 
After Potential 
COVID-19/MIS-C Illness 
Onset
Type of Visit Clinic Clinic Clinic Clinic or 
TelephoneeClinic Clinic or 
Telehealth
Obtain informed consent and assent (if 
appropriate)X
Assign participant number X
Obtain demography and significant 
medical history dataX
For participants who are HIV positive, 
record latest CD4 count and HIV viral 
loadX X X
Confirm use of contraceptives 
(ifappropriate)X X X X
Collect nonstudy vaccine information X X X X X
Collect prohibited medication use X X X X X
Confirm eligibility X X
Review temporary delay criteria X X
Measure vital signs (including body 
temperature) X X
Perform physical examination 
(including height and weight )fX X
Perform urine pregnancy test (only for 
female participants biologically capable 
of having children)X X
Obtain randomization number and study 
intervention allocationX
Obtain anterior nasal swab X X X
Collect blood sample for 
immunogenicity~5mL ~5mLg ~5mLh
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Page 34Visit Number 1 2 3 4 5 Unplanned
Visit Description Dose 1a Dose 2 1-Week
Follow-up Visitb1-Month
Follow-up Visit6-Month
Follow-up VisitcPotential COVID -19 
Illness/MIS-C Visitd
Visit Window (Days) Day 1 19 to 23 Days After 
Visit 16 to 8 Days After 
Visit 228 to 35 Days After 
Visit 2175 to 189 Days 
After Visit 2Optimally Within 3 Days 
After Potential 
COVID-19/MIS-C Illness 
Onset
Type of Visit Clinic Clinic Clinic Clinic or 
TelephoneeClinic Clinic or 
Telehealth
Collect blood sample for PBMC 
isolationb~10mL ~10mL ~10mL
Administer study intervention X X
Assess acute reactions for at least 30 
minutes after study intervention
administrationX X
Explain communication methods 
(including for e -diary completion), 
assist with downloading the app, or 
issue provisioned device, if requiredX
Providethermometer and caliper 
(measuring) deviceX
Reactivate reactogenicity e -diary X
Ensure the participant’s parent(s)/legal 
guardian has a caliper device and 
thermometerX
Ask the participant’s parent(s)/legal 
guardian to complete e-diary and ensure 
the participant’s parent(s)/legal guardian 
remains comfortable with chosen e -
diary platform X X
Review reactogenicity e -diary data 
(daily review is optimal during the 
active diary period)
Review ongoing reactogenicity e -diary 
symptoms and obtain stop datesX X
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Page 35Visit Number 1 2 3 4 5 Unplanned
Visit Description Dose 1a Dose 2 1-Week
Follow-up Visitb1-Month
Follow-up Visit6-Month
Follow-up VisitcPotential COVID -19 
Illness/MIS-C Visitd
Visit Window (Days) Day 1 19 to 23 Days After 
Visit 16 to 8 Days After 
Visit 228 to 35 Days After 
Visit 2175 to 189 Days 
After Visit 2Optimally Within 3 Days 
After Potential 
COVID-19/MIS-C Illness 
Onset
Type of Visit Clinic Clinic Clinic Clinic or 
TelephoneeClinic Clinic or 
Telehealth
Collect AEs as appropriateiX X X X X X
Collect SAEs as appropriatejX X X X X X
Unblind the participant and move to 
either Section 1.3.3.1or Section 1.3.3.2X
Collection of COVID -19/MIS-C–
related clinical and laboratory 
information (including local diagnosis)X
Abbreviation s: AESI = adverse event of special interest; CRF = case report form; HIV = human immunodeficiency virus; MIS-C = multisystem inflammatory syndrome in 
children; PBMC = peripheral blood mononuclear cell; SMS = short message service.
a.This visit may be conducted across 2 consecutive dates; if so, please refer to Section 8.11.3.1.
b.Applicable at designated sites only for participants ≥10yearsof age whose parent(s)/legal guardian have given consent for this additional blood draw.
c. For Phase 2/3 participants who originally received placebo, it is preferable that Visit 5 and Visit A ( Section 1.3.3.2) occur on the same day.
d.Potential MIS -C visit: Hospitalization for a severe illness with no other alternative etiology.
e.Contact can be made via email or SMS. If no response is obtained or responses do not satisfy visit requirements, a telephone call should be made.
f. A physical examination will include, at a minimum, assessments of general appearance, lungs, cardiovascular system, and lymph node survey. Height and weight will be 
collected only at Visit 1.
g. Approximately 450 randomized participants i n each age group will have blood drawn at 1 month after Dose 2.
h.Not required for the additional 45002250participants included to enlarge the size of the pediatric safety database.
i.Refer to Section 8.3.1 for the time period for collecting AEs/AESIs. Any AEs occurring up to 48 hours after blood draw and anterior nasal swab collection must be recorded 
(see Section 8.3.1). Note: Potential COVID -19/MIS-C illnesses and their sequelae that are consistent with the clinical endpoint definition ( Section 8.1) should n ot be 
recorded as AEs. These data will be captured to describe disease endpoints for lack -of-efficacy assessment data only on the relevant pages of the CRF, as these are expected 
endpoints.
j.Refer to Section 8.3.1for the time period for collecting SAEs.
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CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 361.3.3.1.Phase 2/3 Selected -DosePortion: Participants Who Originally Received BNT162b2 or Placebo Recipients Who Decline 
BNT162b2
After unblinding at the 6-month follow -up visitVisit 5, or before if eligible per local or national recommendations, participants who 
originally received BNT162b2 or placebo recipients who decline BNT162b2 will follow this SoA for their remaining visits.
An unplanned potential COVID-19 /MIS-C illness visit isrequired at an y time for the duration of the study that potential 
COVID-19/MIS-Csymptoms are reported.
Visit Number Visit X Visit Y Unplanned
Visit Description 12-Month Follow -up Visit 24-Month Follow-up Visit Potential COVID -19 
Illness/MIS-C Visita
Visit Window (Days) 350 to 378 Days After Visit 2 714 to 742 Days After Visit 2 Optimally Within 3 Days 
After Potential COVID -
19/MIS-C Illness Onset
Type of Visit Clinic or TelephonebClinic or Telephone Clinic or Telehealth
For participants who are HIV positive, record latest CD4 count and HIV viral load X X
Collect prohibited medication use X X X
Obtain anterior nasal swab X
Collect blood sample for immunogenicityc~5mL ~5mL
Collect A Es as appropriatedX X X
Collect e-diary or assist the participant’s parent(s)/legal guardian to delete 
applicationX
Collection of COVID-19/MIS-C–related clinical and laboratory information 
(including local diagnosis)X
Abbreviation s: CRF = case report form; HIV = human immunodeficiency virus ; MIS-C = multisystem inflammatory syndrome in children ; SMS = short message service.
a.Potential MIS -C visit: Hospitalization for a severe illness with no other alternative etiology .
b.Contact can be made via email or SMS. If no response is obtained or responses do not satisfy visit requirements, a telephone call should be made. 
c.The participants who are part of the evaluation of persistence of immune response will have blood drawn either at Visit X or Visit Y. 
d.Any AEs occurring up to 48 hours after blood draw and anterior nasal swab collection must be recorded (see Section 8.3.1).  Note: Potential COVID-19/MIS -C illnesses 
and their sequelae that are consistent with the clinical endpoint definition ( Section 8.1) should not be recorded as AEs.  These data will be captured to describe disease 
endpoints for lack -of-efficacy assessment data only on the relevant pages of the CRF, as t hese are expected endpoints.
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CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 371.3.3.2.Phase 2/3 Selected -DosePortion: Participants Who Originally Received Placebo
At the 6-month (Visit 5) follow -up visit, all participants will be unblinded.  Participants who originally  received placebo will be 
offered the opportunit y to receive BNT162b2 as part of the stud y.  Participants who become eligible for receipt of BNT162b2 or 
another COVID 19 vaccine according to local or national recommendations prior to Visit 5 (detailed separately , and available in the 
electronic stud y reference portal) will have the opportunity  to receive the EUA approved dose level of BNT162b2 .  Participants who 
originally received placebo and become eligible for receipt of BNT162b2 or another COVID -19 vaccine according to local or national 
recommendations pr ior to 6 months after Dose 2 (detailed separatel y and available in the electronic study reference portal) will be 
advised to contact the site to determine whether theycan receive BNT162b2 (10 µg or 3 µg) based on age at the time of approval. If a 
participant turns 12 years of age during the stud y, he or she has the following 2 options: receive 10 µg within the study  (following 
provision of informed consent) or receive a BNT162b2 30- µg dose outside of the study .When contacted, the site will conduct a 
telephone visit to confirm eligibility  and, if the participant is eligible and wants to receive BNT162b2 in the event that he or she 
originally received placebo, the site will unblind the participant’s stud y intervention allocation to determine whether the participant 
received BNT162b2 or placebo . If he or she originally  received placebo and wants to receive BNT162b2 (10µg or 3 µg) , the 
participant will move to theSoA inthis for his or her remaining visits. Participants who originally  received BNT162b2 or placebo 
recipients who decline BNT162b2 will move to the S oA in Section 1.3.3.1.
An unplanned potential COVID-19/MIS- C illness visit isrequired at an y time for the duration of the study  that potential 
COVID-19/MIS-Csymptoms are reported. During the 7 day s following each dose, potential COVID -19/MIS-Csymptoms that 
overlap with specific s ystemic events (ie, fever, chills, new or increased muscle pain, diarr hea, vomiting) should not trigger a potential 
COVID-19/MIS-Cillness visit unless, in the investigator’s opinion ,the clinical picture is more indicative of a possible COVID -19 
illness rather than vaccine reactogenicit y.For details, see Section 8.13.
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CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 38Visit Number A B C D E F Unplanned
Visit Description Dose 3 Dose 4 1-Month
Follow-up Visit6-Month
Follow-up Visit12-Month 
Follow-up Visit18-Month 
Follow-up VisitPotential 
COVID-19 
Illness/MIS-C 
Visita
Visit Window (Days) From 
Recommendation
bor 
175 to 189 Days 
After Dose 219 to 23 Days 
After Visit A28 to 35 Days 
After Visit B175 to 189 Days 
After Visit B350 to 378 Days 
AfterVisit B532to 560Days 
After Visit BOptimally Within 
3 Days After 
Potential 
COVID-19 
Illness Onset
Type of Visit Clinic Clinic TelephonecbTelephone Telephone Clinic or 
TelephoneClinic or 
Telehealth
Confirm participant meets 
local/national recommending criteria
or is at least 175 days after Dose2 
(Visit 2)X
Confirm participant originally 
received placeboX
For participants who are HIV- positive, 
record latest CD4 count and HIV viral 
loadX X X X X
Confirm use of contraceptives 
(ifappropriate)X X X
Collect prohibited medication use X X X X X X X
Review and consider eligibility X X
Review temporary delay criteria X X
Measure vital signs (including body 
temperature)X X
Perform physical examinationdcX X
Perform urine pregnancy test (only for 
female participants biologically 
capable of having children)X X
Obtain anterior nasal swab X X X
Collect blood sample for 
immunogenicityXed
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CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 39Visit Number A B C D E F Unplanned
Visit Description Dose 3 Dose 4 1-Month
Follow-up Visit6-Month
Follow-up Visit12-Month 
Follow-up Visit18-Month 
Follow-up VisitPotential 
COVID-19 
Illness/MIS-C 
Visita
Visit Window (Days) From 
Recommendation
bor 
175 to 189 Days 
After Dose 219 to 23 Days 
After Visit A28 to 35 Days 
After Visit B175 to 189 Days 
After Visit B350 to 378 Days 
AfterVisit B532to 560Days 
After Visit BOptimally Within 
3 Days After 
Potential 
COVID-19 
Illness Onset
Type of Visit Clinic Clinic TelephonecbTelephone Telephone Clinic or 
TelephoneClinic or 
Telehealth
Obtain vaccine vial allocation via IRT X
Administer BNT162b2 X X
Assess acute reactions for at least 30 
minutes after study intervention 
administrationX X
Collect A Es as appropriatefeX X X X
Collect SAEs as appropriategfX X X X X
Collect e-diary or assist the 
participant’s parent(s)/legal guardian 
to delete applicationX
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CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 40Visit Number A B C D E F Unplanned
Visit Description Dose 3 Dose 4 1-Month
Follow-up Visit6-Month
Follow-up Visit12-Month 
Follow-up Visit18-Month 
Follow-up VisitPotential 
COVID-19 
Illness/MIS-C 
Visita
Visit Window (Days) From 
Recommendation
bor 
175 to 189 Days 
After Dose 219 to 23 Days 
After Visit A28 to 35 Days 
After Visit B175 to 189 Days 
After Visit B350 to 378 Days 
AfterVisit B532to 560Days 
After Visit BOptimally Within 
3 Days After 
Potential 
COVID-19 
Illness Onset
Type of Visit Clinic Clinic TelephonecbTelephone Telephone Clinic or 
TelephoneClinic or 
Telehealth
Collection of COVID -19/MIS-C–
related clinical and laboratory 
information (including local 
diagnosis)X
Abbreviation s: AESI = adverse event of special interest; CRF = case report form; HIV = human immunodeficiency virus ; IRT = interactive response technology; MIS -C = 
multisystem inflammatory syndrome in children ; SMS = short message service.
a.a.Potential MIS -C visit: Hospitalization for a severe illness with no other alternative etiology.
b. b. For participants who become eligible according to recommendations detailed separately and available in the electronic study r eference portal.
c.Contact can be made via email or SMS.  If no response is obtained or responses do no t satisfy visit requirements, a telephone call should be made.
d.c.A physical examination will include, at a minimum, assessments of general appearance, lungs, cardiovascular system, and lymph node survey.
e.d.Blood draw is only for participants who become e ligible for receipt of BNT162b2 or another COVID -19 vaccine according to local or national recommendations prior 
to Visit 5.
f.e.Refer to Section 8.3.1 for the time period for collecting AEs/AESIs. Any AEs occurring up to 48 hours after blood draw and anterior nasal swab collection must be 
recorded (see Section 8.3.1).Note: Potential COVID -19/MIS-C illnesses and their sequelae that are consistent with the clinical endpoint definition ( Section 8.1) should 
not be recorded as AEs.  These data will be captured to describe disease endpoints for lack -of-efficacy assessment data only on the relevant pages of the CRF, as these are 
expected endpoints.
g.f.Refer to Section 8.3.1for the time period for collecting SAEs.
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CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 411.3.4.Phase 2/3 Lower -Dose Evaluation
Visit Number 201 202 203 204
Visit Description Dose 1a Dose 2 1-Month
Follow-up Visit6-Month
Follow-up Visit
Visit Window (Days) Day 1 19 to 23 Days After 
Visit 20128 to 35 Days After 
Visit 202175 to 189 Days After 
Visit 202
Type of Visit Clinic Clinic Clinic Clinic 
Obtain informed consent and assent (if appropriate) X
Assign participant number X
Obtain demography and significant medical history data X
For participants who are HIV-positive, record latest CD4 
count and HIV viral loadX X X
Confirm use of contraceptives (if appropriate) X X X
Collect nonstudy vaccine information X X X X
Collect prohibited medication use X X X
Confirm eligibility X X
Review temporary delay criteria X X
Measure vital signs (including body temperature) X X
Perform clinical assessmentb X X
Perform urine pregnancy test (only for female participants 
biologically capable of having children)X X
Obtain randomization number and study intervention 
allocationX
Obtain anterior nasal swab X X
Collect blood sample for immunogenicityc ~20 mL/~10 mL /~5 mL ~20 mL/~10 mL/~5 mL ~20 mL/~10 mL/~5 mL
Administer study intervention X X
Assess acute reactions for at least 30 minutes after study 
intervention administrationX X
Explain communication methods (including for e -diary 
completion), assist with downloading the app, or issue 
provisioned device, if requiredX
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CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 42Visit Number 201 202 203 204
Visit Description Dose 1a Dose 2 1-Month
Follow-up Visit6-Month
Follow-up Visit
Visit Window (Days) Day 1 19 to 23 Days After 
Visit 20128 to 35 Days After 
Visit 202175 to 189 Days After 
Visit 202
Type of Visit Clinic Clinic Clinic Clinic 
Providethermometer and caliper (measuring) device X
Reactivate reactogenicity e-diary X
Ensure the participant or participant’s parent(s)/legal 
guardian has a caliper device and thermometerX
Ask the participant or participant’s parent(s)/legal guardian 
to complete e -diary and ensure the participant or 
participant’s parent(s)/legal guardian remains comfortable 
with chosen e -diary platform X X
Review reactogenicity e -diary data (daily review is optimal 
during the active diary period)
Review ongoing reactogenicity e -diary symptoms and 
obtain stop datesX X
Collect AEs as appropriated X X X X
Collect SAEs as appropriatee X X X X
Collection of COVID 19/MISCrelated clinical and 
laboratory information (including local diagnosis)
Abbreviation s: AESI = adverse event of special interest; CRF = case report form; HIV = human immunodeficiency virus .
a. This visit may be conducted across 2 consecutive dates; if so, please refer to Section 8.11.6.1.
b.Including, if indicated, a physical examination.
c.20 mL is to be collected from participants ≥16 years of age; 10 mL is to be collected from participants 12 to <16 years of age; 5 mL is to be collected from 
participants 5 to <12 years of ag e.
d.Refer to Section 8.3.1 for the time period for collecting AEs/AESIs. Any AEs occurring up to 48 hours after blood draw  and anterior nasal swab collection 
must be recorded (see Section 8.3.1).
e.Refer to Section 8.3.1for the time period for collecting AESIs/SAEs.
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CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 431.3.5.Phase 2/3 Assessment of Obtaining Serum Samples for Potential Troponin I Testing (5 to <12 Years of Age, 
Placebo-Controlled , and12 to <16 Years of A ge, Open-Label)
Administration of BNT162b2 to those originally assigned to placebo: At the 6-month follow -up visit, all participants will be 
unblinded. Participants who originall y received placebo will be offered the opportunity  to receive BNT162b2 as part of the study . 
Participants who originally  received placebo and become eligible for receipt of BNT162b2 or another COVID -19 vaccine according to 
local or national recommendations prior to 6 months after Dose2 (detailed separately  and available in the electronic stud y reference 
portal) will be advised to contact the site to determine whether theycan receive BNT162b2 (10 µg or 3 µg) based on age at the time of 
approval. If a participant turns 12 y ears of age during the study , he or she has the following 2 options: receive 10 µg within the study  
(following provision of informed consent) or receive a BNT162b2 30 -µg dose outside of the study . When contacted, the site will 
conduct a telephone visit to confirm elig ibility and, if the participant is eligible and wants to receive BNT162b2 in the event that he or 
she originally  received placebo, the site will unblind the participant’s study intervention allocation to determine whether t he 
participant received BNT162b2 or placebo. I f he or she originally  received placebo and wants to receive BNT162b2 (10 µg or 3 µg) , 
the participant will move to the SoA in Section 1.3.5.1for his or her remaining visits. Participants who received BNT162b2 will 
continue in the study  as originall y planned .
Visit Number 301 302 303 304 305
Visit Description Dose 1aDose 2 4-Day
Follow-up Visit1-Month
Follow-up Visit6-Month
Follow-up Visitb
Visit Window (Days) Day 1 19 to 23 Days After 
Visit 3012to 5Days After 
Visit 30228 to 35 Days After 
Visit302175 to 189 Days After 
Visit 302
Type of Visit Clinic Clinic Clinic TelephonebTelephone
Obtain informed consent and assent X
Assign participant number X
Obtain demography and significant medical history 
dataX
For participants who are HIV positive, record latest 
CD4 count and HIV viral loadX X X
Confirm use of contraceptives (if appropriate) X X X X
Collect nonstudy vaccine information X X X X X
Collect prohibited medication use X X X X
Confirm eligibility X X
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Protocol C4591007
Final ProtocolAmendment 32, 1006SepAug2021
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 44Visit Number 301 302 303 304 305
Visit Description Dose 1aDose 2 4-Day
Follow-up Visit1-Month
Follow-up Visit6-Month
Follow-up Visitb
Visit Window (Days) Day 1 19 to 23 Days After 
Visit 3012to 5Days After 
Visit 30228 to 35 Days After 
Visit302175 to 189 Days After 
Visit 302
Type of Visit Clinic Clinic Clinic TelephonebTelephone
Review temporary delay criteria X X
Measure vital signs (including body temperature) X X
Perform clinical assessmen tcX X
Perform urine pregnancy test (only for female 
participants biologically capable of having 
children)X X
Obtain randomization number and study 
intervention allocationX
Obtain anterior nasal swab X X
Collect blood sample forpotentialtroponin level 
testing~5mL ~5 mL
Administer study intervention X X
Assess acute reactions for at least 30 minutes after 
study intervention administrationX X
Explain communication methods (including for e --
diary completion), assist with downloading the app, 
or issue provisioned device, if requiredX
Providethermometer and caliper (measuring) 
deviceX
Reactivate reactogenicity e -diary X
Ensure the participant’s parent(s)/legal guardian 
has a caliper device and thermometerX
Ask the participant’s parent(s)/legal guardian to 
complete e -diary and ensure the participant’s 
parent(s)/legal guardian remains comfortable with 
chosen e-diary platform X X
Review reactogenicity e -diary data (daily review is 
optimal during the active diary period)
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CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 45Visit Number 301 302 303 304 305
Visit Description Dose 1aDose 2 4-Day
Follow-up Visit1-Month
Follow-up Visit6-Month
Follow-up Visitb
Visit Window (Days) Day 1 19 to 23 Days After 
Visit 3012to 5Days After 
Visit 30228 to 35 Days After 
Visit302175 to 189 Days After 
Visit 302
Type of Visit Clinic Clinic Clinic TelephonebTelephone
Review ongoing reactogenicity e -diary symptoms 
and obtain stop datesX X
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Final ProtocolAmendment 32, 1006SepAug2021
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CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 46Visit Number 301 302 303 304 305
Visit Description Dose 1aDose 2 4-Day
Follow-up Visit1-Month
Follow-up Visit6-Month
Follow-up Visitb
Visit Window (Days) Day 1 19 to 23 Days After 
Visit 3012to 5Days After 
Visit 30228 to 35 Days After 
Visit302175 to 189 Days After 
Visit 302
Type of Visit Clinic Clinic Clinic TelephonebTelephone
Collect AEs as appropriatedX X X X
Collect SAEs as appropriateeX X X X X
Unblind the participant and move to either 
Section 1.3.5.1orcontinue on this So A as 
appropriatefX
Collect e-diary or assist the participant’s 
parent(s)/legal guardian to delete applicationX
Abbreviations: AESI = adverse event of special interest; HIV = human immunodeficiency virus; SMS = short message service ;SoA = schedule of activities .
a.This visit may be conducted across 2 consecutive dates; if so, please refer to Section8.11.7.1.
b.Contact can be made via email or SMS.  If no response is obtained or responses do not satisfy visit requirements, a telephone call should be made.
c.Including, if indicated, a physical examination .
d.Refer to Section 8.3.1 for the time period for collecting AEs/AESIs. Any AEs occurring up to 48 hours after blood draw  and anterior nasal swab collection 
must be recorded (see Section 8.3.1).  
e.Refer to Section 8.3.1for the time period for collecting SAEs.
f.This is applicable to the 5-to <12-year-oldage group (placebo -controlled). 
1.3.5.1. Phase 2/3 Assessment of Obtaining Serum Samples for Potential Troponin I Testing:Participants Who Originally 
Received Placebo (5 to <12 Years of Age)
Visit Number A1 B1 C1 D1
Visit Description Dose 3 Dose 4 1-Month
Follow-up Visit6-Month
Follow-up Visit
Visit Window (Days) From Recommendationaor 
175 to 189 Days After Dose 219 to 23 Days After Visit A1 28 to 35 Days After Visit B1 175 to 189 Days After 
VisitB1
Type of Visit Clinic Clinic TelephonebTelephone
Confirm participant meets local/national 
recommending criteria or is at least 175 days after 
Dose 2 (Visit 302)X
Confirm participant originally received placebo X
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CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 47Visit Number A1 B1 C1 D1
Visit Description Dose 3 Dose 4 1-Month
Follow-up Visit6-Month
Follow-up Visit
Visit Window (Days) From Recommendationaor 
175 to 189 Days After Dose 219 to 23 Days After Visit A1 28 to 35 Days After Visit B1 175 to 189 Days After 
VisitB1
Type of Visit Clinic Clinic TelephonebTelephone
For participants who are HIV-positive, record latest 
CD4 count and HIV viral loadX X X
Confirm use of contraceptives (if appropriate) X X X
Collect prohibited medication use X X X X
Review and consider eligibility X X
Review temporary delay criteria X X
Measure vital signs (including body temperature) X X
Perform clinical assessmentcX X
Perform urine pregnancy test (only for female 
participants biologically capable of having children)X X
Obtain anterior nasal swab X X
Collect blood sample for potential troponin level
testingXd
Obtain vaccine vial allocation via IRT X
Administer BNT162b2 X X
Assess acute reactions for at least 30 minutes after 
study intervention administrationX X
Collect A Es as appropriateeX X X
Collect SAEs as appropriatefX X X X
Abbreviation s: AESI = adverse event of special interest; HIV = human immunodeficiency virus; IRT = interactive response technology; SMS = short message service.
a.For participants who become eligible according to recommendations detailed separately and available in the electronic study reference portal.
b.Contact can be made via email or SMS.  If no response is obtained or responses do not satisfy visit requirements, a telephone call should be made.
c.Including, if indicated, a physical examination .
d.Blood draw  is only for pa rticipants who become eligible for receipt of BNT162b2 or another COVID -19 vaccine according to local or national
recommendations prior to Visit 303.
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Page 48Visit Number A1 B1 C1 D1
Visit Description Dose 3 Dose 4 1-Month
Follow-up Visit6-Month
Follow-up Visit
Visit Window (Days) From Recommendationaor 
175 to 189 Days After Dose 219 to 23 Days After Visit A1 28 to 35 Days After Visit B1 175 to 189 Days After 
VisitB1
Type of Visit Clinic Clinic TelephonebTelephone
e.Refer to Section 8.3.1 for the time period for collecting AEs/AESIs. Any AEs occurring up to 48 hours after blood draw  and anterior nasal swab collection 
must be recorded (see Section 8.3.1).  
f.Refer to Section 8.3.1for the time period for collecting SAEs.
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Page 492.INTRODUCTION
The BNT162b2 RNA -based COVID -19 vaccine is being investigated for prevention of 
COVID-19 in healthy  children.
2.1.Study Rationale
The purpose of the dose-finding/selected -dosestudy is torapidly describe the safet y, 
tolerability ,immunogenicity , and efficacy(depending on accrual of sufficient cases) of the 
BNT162b2 RNA -based COVID -19 vaccine candidate against COVID- 19 in healthy  children. 
There are currently  no licensed vaccines to prevent infection with SARS-CoV-2or 
development of COVID-19in participants under 16 y ears of age .  Given the global crisis of 
COVID-19 and fast expansion of the disease in the United States and elsewhere, the rapid 
development of an effective vaccine is of utmost importance.
With the robust immune responses elicited in adolescents with BNT162b2, t he purpose of the 
lower-dose evaluation is to determine whether additional lower dose levels of BNT162b2 
(3µg, 10 µg) will not only to minimize reactogenicity  and risk of other AEs but as well to 
potentially  unify the dose levels across children and y oung adults.
Postmarketing data demonstrate increased risks of my ocarditis and pericarditis, particularly  
within 7 day s following the second dose. The observed risk is higher among males under 
40years of age than among females and older males. The observed risk is highest in males 
12 through 17 years of age. Although some cases required intensive care support, available 
data from short -term follow -up suggest that most individuals have had resolution of 
symptoms with conserv ative management. Information is not y et available about potential 
long-term sequelae. The CDC has published considerations related to my ocarditis and 
pericarditis after vaccination, including for vaccination of individuals with a history  of 
myocarditis or pericarditis ( https://www.cdc.gov/vaccines/covid -19/clinical -
considerations/my ocarditis.html).1Elevated t roponinI level may be an indicator of 
subclinical my ocarditis. If testing of t roponinI levels in individuals who did not receive 
BNT162b2 indicates that troponinI level could be a reliable indicator of potential subclinical 
myocarditis, obtaining serum samples for potential troponinI testing in an additional group 
ofparticipants during the period of increased risk of clinical my ocarditismay help 
characterize the absence/presence and frequency  of subclinical my ocarditis.
2.2.Background
In December 2019, a pneumonia outbreak of unknown cause occurred in Wuhan, China.  
InJanuary 2020, it became clear that a novel coronavirus (2019 -nCoV) was the underl ying 
cause.  Later in January , the genetic sequence of the 2019 -nCoV became available to the 
WHO and public (MN908947.3), and the virus was categorized in the Betacoronavirus
subfamily .  By sequence anal ysis, the phy logenetic tree revealed a closer relationship to 
SARS virus isolates than to another coronavirus infecting humans, the MERS virus.2,3
SARS-CoV-2 infections and the resulting disease, COVID -19, have spread globall y,
affecting a growing number of infections in countries worldwide .Children have been 
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Page 50affected b y both the primary  COVID-19 disease and the less common secondary
inflammatory  complications, including MIS-C.4,5
On 11 March 2020, the WHO characterized the CO VID-19 outbreak as a pandemic.6  
TheWHO Weekly  Epidemiology  Update Report dated 27September 2020 noted more than 
32.7 million COVID -19 cases and 991,000 deaths globally, including 16,233,110 confirmed 
cases with 546,864 deaths in the Americas
.7  COVID-19 is generally  milder in children than 
adults, possibly  because common risk factors for severe COVID -19 in adults are generall y 
less prevalent in pediatric age groups. Children present with fever and dry cough over half 
the time and symptoms can include GIsymptoms, including diarrhea and vomiting, and in 
some cases canbe the only  presenting features. Pulmonary involvement in sy mptomatic 
children is generally  mild.8,9,10Nevertheless, severe cases, including those requiring 
intensive care support, have been reported.4Of US children diagnosed with COVID -19,
5.7% to 20% were hospitalized, including 0.58% to 2.0% admitted to an I CU.11
MIS-C, an emerging condition that appears to be temporally  related to recent exposure to 
SARS-CoV-2, has been described and frequently requires ICUadmission, and may  have a 
fatal outcome.5,12MIS-C is a febrile hy perinflammatory  condition with frequent evidence of 
cardiac damage and dermatologic, mucocutaneous, and GI features.12The syndrome appears 
to have some overlap with Kawasaki disease shock sy ndrome.13,14Compared with Kawasaki 
disease, patients with MIS- C are older, have more card iac injury , and are more likely  to be 
black, Hispanic, or of South Asian descent.15As of 29June 2020, approximately 1000 cases 
have been reported.15As of 29 July  2020, a total of 570 cases were reported in the US to the 
CDC.  Of these, 86.0% involved 4 or more organ sy stems, 63.9% of patients required ICU 
admission, and severe complications included cardiac d ysfunction (40.6%), shock (35.4%), 
myocarditis (22.8%), coronary  artery dilation or aneury sm (18.6%), and acute kidney  injury 
(18.4%).16Death rate s of 2% to 4% have been reported.15MIS-C has been reported in many  
countries throughout North America, Europe, Asia, and Latin America ,17including the 
US,5,12Italy,18and France.19The United States currently has the most reported cases 
globally,with thenumber of confirmed cases continu ingto rise globall y. BNT162b2 was 
approved b y the FDA on 23 August 2021 to prevent COVID-19 caused b y SARS-CoV-2 in 
individuals 16 y ears of age and older. There are currently no licensed vaccines or effective 
antiviral drugs to prevent SARS CoV 2 infections or the disease it causes, COVID 19.20
A prophylactic, RNA -based SARS -CoV-2 vaccine provides one of the most flexible and 
fastest approaches available to immunize against the emerging virus.21,22
The development of an RNA -based vaccine encoding a viral antigen, which is then expressed 
by the vaccine recipient as a protein capable of eliciting protective immune responses, 
provides significant advantages over more tradi tional vaccine approaches.  Unlike live 
attenuated vaccines, RNA vaccines do not carry the risks associated with infection and may  
be given to people who cannot be administered live virus (eg, pregnant women and 
immunocompromised persons).  RNA -based vacci nes are manufactured via a cell- free in 
vitro transcription process, which allows an eas y and rapid production and the prospect of 
producing high numbers of vaccination doses within a shorter time period than achieved with 
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Page 51traditional vaccine approaches.  This capability  is pivotal to enable the most effective 
response in outbreak scenarios.21,22
A Phase 1/2/3 study  (C4591001 )is being conducted in healthy  individuals 1 2years of age 
and older to investigate the safet y, tolerability , immunogenicit y,and efficacy  of the 
prophylactic BNT162 vaccine candidates against COVID -19.The vaccine candidate 
selected for evaluation in the C4591001 Phase 2/3 study  is BNT162b2 at a dose level of 
30µg and as 2doses given approximately  21 days apart. On 18 November 2020, the primary  
efficacy analysis results were announced, which demonstrate dBNT162b2 to be 95% 
effective against COVID -19 beginning 7 day s after the seconddose;170 confirmed cases of 
COVID-19 were evaluated, with 162 observed in the placebo group versus 8 in the vaccine 
group.Safety data from approximately  38,000 participant s randomized 1:1 with a median of 
2 months of follow -up after the second dose of vaccine showed a favorable safet y profile at a 
dose of 30 μg in participants 16 y ears of age and older .23On 11 December 2020, the US 
FDA issued an EUA for use in individuals 16 years of age and older. Other countries have 
also granted EUA (eg, Canada, Mexico, Bahrain), and Pfizer and BioNTech are anticipating 
further regulatory  decisions in other countries.24On 10 May 2021, the US FDA issued an 
EUA for use in individuals 12 to through 15 years of age. Other countries have also granted 
EUAor other authorization/approval for this age group (eg, EMA, UK, Switzerland, andthe 
Philippines).
This Phase 1/2/3 study (C4591007) will initiallyevaluate up to 3 different dose levels of 
BNT162b2 in up to 3 age groups ( participants ≥5 to <12 years, ≥2 to <5 y ears, and 
≥6monthsto <2 years of age).  Safet y, tolerability, immunogenicit y,and efficacy (depending 
on successful immunobridging and accrual of a sufficient number of cases) will be evaluated .
Phase 1 includes the dose -findingportion.  Initiation of dose finding in participants ≥5 to 
<12years of age will be based on the acceptable blinded safet y datademonstrated in 2260
12-through15-year-oldsat the 30-µ g dose level in the C4591001 study .25The Phase 2/3 
BNT162b 2dose level to be used in each age group in this study  will be selected based on the 
Phase 1 safet y, tolerability, and immunogenicit y datafrom the same age group. Phase 2/3
(referred to as the selected -doseportion of the study )includes an immunobridging analy sisof
immune responses in participants ≥6 months to <12years of age to th ose in participants 16to 
25 years of agein the Phase 3 C45 91001 efficacy  study. Safety,tolerability ,and efficacy  
(depending on successful immunobridging and accrual of a sufficient number of cases) will 
also be evaluated in Phase 2/3 of this study .
The authorized dose of BNT162b2 in adolescents and y oung adults 12 y ears and older is 
30µg,whereas in the Phase 2/3 portion of the ongoing C4591007 study the following doses 
were selected: 10 µgin participants 5 to <12 years of ageand 3 µg in participants 6 months 
to <5 yearsof age. With the robust immune responses elicited in adolescents to minimize 
reactogenicity  and the risk of other AEs and to potentially  unify the dose levels across 
children and young adults, additional lower dose levels of BNT162b2 (3 µg, 10 µg) will be 
evaluated to determine whether similar immune responses are elicited. For this lower -dose 
evaluation portion, a new cohort of Phase 1 participants will be enrolled in 3age groups: 
>5 to <12, 12 to <16, 16 to <30 years of age to assess safet y, tolerability , and 
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Page 52immunogenicit y.The Phase 2/3 BNT162b2 dose level will be selected based on the Phase 1 
assessments . The Phase 2/3 part will assess with an immunobridging analysis of immune 
responses in participants within each age group to participants in the 30 -µgPhase3 
C4591001 efficacy  study. 
Postmarketing data demonstrate increased risks of my ocarditis and pericarditis, particularly  
within 7 day s following the second dose. The observed risk is higher among males under 
40years of age than among females and older males. The observed risk is highest in males 
12 through 17 years of age. Although some cases required intensive care support, available 
data from short -term follow -up suggest that most individuals have had resolution of 
symptoms with conservative managemen t. Information is not y et available about potential 
long-term sequelae. The CDC has published considerations related to my ocarditis and 
pericarditis after vaccination, including for vaccination of individuals with a history  of 
myocarditis or pericarditis ( https://www.cdc.gov/vaccines/covid -19/clinical -
considerations/my ocarditis.html ).1Elevated t roponinI level may be an indicator of 
subclinical my ocarditis. If testing of troponinI levels in individuals who did not receive 
BNT162b2 indicates that troponinI level could be a reliable indicator of potential subclinical 
myocarditis, obtaining serum samples for potential troponinI testingin an additional group 
of participants during the period of increased risk of clinical my ocarditis may  help 
characterize the absence/presence and frequency  of subclinical my ocarditis.
2.2.1. Clinical Overview
The BNT162 vaccine candidates use an RNA to deliver genetic information to cells , where it 
is used to express proteins for the therapeutic effect. This vaccine is for the prevention of 
COVID-19.Prior to this study , clinical data from the BNT162b2 vaccine established a 
favorable safety  profile,with mild, localized, and transient ef fects. The C4591001 study26is 
currently in Phase 3,which includes >40,000 individuals in the US and other countries ,of 
whom>21,000 participants have now been administered BNT162b2 at the 30-µg dose level 
ona 2-dose schedule.27Vaccine-related enhanced disease for vaccines against related 
coronaviruses (SARS -CoV-1 and MERS) has been reported onl y in animal models.28,29To 
date, no enhanced disease has been observed in SARS -CoV-2 animal models with any  
SARS-CoV-2 vaccine platform, including RNA -based vacc ines. Such effects have not been 
documented so far for SARS -CoV-2.The currently  available safet y and immunogenicit y 
data are presented in the BNT162 IB.
2.3.Benefit/Risk Assessment
There is an ongoing global pandemic of COVID -19 with no approved or licensed preventive 
options available.  However, based on the data available from the C4591001 study , multiple 
temporary  or emergency  use authorizations have been granted. The available safet y and 
immunogenicit y data from the ongoing Pfizer/BioNTech clinical tria l combined with 
available nonclinical data with BNT162 vaccines, and data from nonclinical studies and 
clinical trials with the same or related RNA components, or antigens, support a favorable 
benefit/risk profile and support continued clinical development of BNT162b2.
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Page 53In the C4591001 stud y, BNT162b2 has been shown to elicit increased local and systemic 
adverse reactions as compared to those in the placebo arm, usuall y lasting a few days. The 
most common solicited adverse reactions were injection site rea ctions (84.1%), fatigue 
(62.9%), headache (55.1%), muscle pain (38.3%), chills (31.9%), joint pain (23.6%), and 
fever (14.2%). Adverse reactions characterized as reactogenicity  were generally  mild to 
moderate. The number of participants reporting hy persensitivity-related AE s was 
numericall y higher in the active vaccine group compared with the placebo group 
(137[0.63%] vs 111 [0.51%]). Severe adverse reactions occurred in 0.0% to 4.6% of 
participants, were more frequent after Dose 2 than after Dose 1, an d were generall y less 
frequent in older adults (>55 years of age) (<2.8%) as compared to y ounger participants 
(≤4.6%). Among reported unsolicited A Es, lymphadenopathy  occurred much more 
frequently in the active vaccine group than the placebo group and is plausibly related to 
vaccination. SAEs, while uncommon (<1.0%), represented medical events that occur in the 
general population at similar frequency  as observed in the study.23
No specific safet y concerns were identified in subgroup anal yses by age, race, ethnicit y, 
medical comorbidities, or prior SARS -CoV-2 infection. The risks are based on the observed 
safety profile to date, which shows mostly  mild reactogenicit y, low incidence of severe or 
serious events, and no clinically  concerning safet y observations. The preponderance of 
severe cases of COVID -19 in the placebo group relative to the BNT162b2 group (9 of 10) 
suggests no evidence of VAED. Continued clinical investigation is justified given the:
Urgent need for the development of a more stable prophy lactic vaccine for COVID -19;
Threat posed b y the increasing number of globall y distributed outbreaks of SARS -CoV-2 
infection;
Potential of the BioNTech platform of RNA -based vaccines to rapidly  deliver high 
numbers of vaccine doses in a single production campaign. 
More detailed information about the known and expected benefits and risks and reasonabl y 
expected AEs of BNT162b2 may  be found in the IB, which is the SRSD for this study .
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Page 542.3.1.Risk Assessment
Potential Risk of Clinical Significance Summary of Data/Rationale for Risk Mitigation Strategy
Study Interven tion(s) [BNT162b2 RNA- Based COVID-19 Vaccine] 
Local and systemic reactions to the vaccine may 
occur (injection site redness, injection site swelling, 
and injection site pain, fever, fatigue, headache, 
chills, muscle pain, and joint pain) following 
vaccination.These are common adverse reactions seen with 
other vaccines as well as the COVID -19 vaccine. 
The most common events reported in the C4591001 
study were mild to moderate pain at the injection 
site, fatigue ,and headache.The study employs the use of a reactogenicity 
e-diary to monitor local reactions and systemic 
events in real time.
All study participants will be observed for at 
least 30 minutes after vaccination.
The safety profile of a novel vaccine is not yet fully 
characterized.
Adverse reactions (risks) identified from the 
postauthorization safety data include: Anaphylaxis, 
other hypersensitivity reactions (eg ,rash, pruritus, 
urticaria, angioedema), and pain in extremity 
(injected arm) .Data available from the C4591001 study showed 
low incidence of severe or serious events, and no 
clinically concerning safety observations across the 
safety population and within demographic 
subgroups based on age, sex, race/ethnicity, 
country, and baseline SARS -CoV-2 status. 
Postauthorization safety data surveillance has 
confirmed the safety profile observed in the 
C4591001 study and has resulted in identification of 
some additional adverse reactions (risks) as noted in 
this table.AE and SAE reports will be collected from the 
signing of the ICD to 1 month after the second 
dose of vaccine.
DMC willreview all safety data throughout the 
study.
All participants will be observed for at least 30 
minutes after vaccination.
Unknown A Es with a novel vaccine in children <12
years of age .Data available from the C4591001 study showed 
low incidence of severe or serious events, and no 
clinically concerning safety observations. The 
vaccine appears to be safe and w ell-tolerated across 
the safety population and within demographic 
subgroups based on age, sex, race/ethnicity, 
country, and baseline SARS -CoV-2 status.The current Phase 3 C4591001 study includes
participants 12years of age and older.
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Page 55Potential Risk of Clinical Significance Summary of Data/Rationale for Risk Mitigation Strategy
Potential for COVID -19 enhancement. Disease enhancement has been seen following RSV, 
feline coronavirus, and dengue virus vaccin ations. 
No evidence of disease enhancement has been seen 
in a large-scale clinical study of BNT162b2 in 
humans or in postauthorization surveillance.No evidence of disease enhancement has been 
reported in the C4591001 study to date.27
Temporary delay criteria defer vaccination of 
participants with symptoms of potential 
COVID-19. All participants , with the exception 
of Phase 2/3 lower-dose evaluation
participants, are followed for any potential
COVID-19 illness, including markers of 
severity, and have blood samples taken for 
potential measurement of SARS -CoV-2 
neutralizing titers.
For Phase 1/2/3 lower-dose evaluation 
participants ,cases of COVID -19 developing 
during the study are monitored and will be 
reported as AESIs.
MIS-C. Febrile hyperinflammatory condition with 
multisystem (≥2)organinvolvement as defined in 
Section 8.1.MIS-C will be prospectively collected as a potential 
for COVID-19/MIS-Cillness visit sfor the duration 
of study participation. 
Very rare cases of anaphylaxis, myocarditis ,and 
pericarditis have been reported after authorization in 
recipients of BNT162b2 .Anaphylaxis: The estimated rate is 5.0 per million 
doses administered.
Myocarditis and pericarditis: Very rare cases of 
myocarditis and pericarditis have been reported 
following vaccination with mRNA COVID -19 
vaccines. Typically, the cases have occurred more 
often in younger men and after the second dose of 
the vaccine and w ithin 14 days after vaccination . 
These are generally mild cases ,and individuals tend 
to recover within a short time following standard 
treatment and rest. Healthcare professionals should 
be alert to the signs and symptoms of myocarditis 
and pericarditis in vaccine recipients.Specific reference to these risks is made within the 
ICD, with instruction to contact a healthcare 
professional if a case is suspected.
For anaphylaxis, there is an on -site 30-minute 
observation period after vaccination.
Instructions for handling suspected cases of
myocarditis and pericarditis are found in 
Section 8.14.
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Study Procedures 
Participants will be required to attend healthcare 
facilities during the global SARS -CoV-2 pandemic.Without appropriate social distancing and PPE, 
there is a potential for increased exposure to 
SARS-CoV-2.Pfizer will work with sites to ensure an appropriate 
COVID-19 prevention strategy. Potential 
COVID-19/MIS-C illness visits can be conducted 
via telehealth, without the need for an in -person 
visit, if required, with the participant ’s
parent(s)/legal guardian performing a n anterior
nasal swab for the participant.
Venipuncture will be performed during the study. There is the risk of bleeding, bruising, hematoma 
formation, and infection at the venipuncture site.Only appropriately qualified personnel will obtain 
the blood draw . To minimize the total amount of 
blood drawn, all participants in Phase 1 and 
participants contributing to the immunogenicity 
analysis in Phase 2/3 will have at most 3 planned 
blood draws, with all remaining participants having 
2 planned blood draws.
Very rare cases of anaphylaxis, myocarditis ,and 
pericarditis have been reported after authorization in 
recipients of BNT162b2 .Anaphylaxis: The estimated rate is 5.0 per million 
doses administered.
Myocarditis and pericarditis: Very rare cases of 
myocarditis and pericarditis have been reported 
following vaccination with mRNA COVID 19 
vaccines. Typically, the cases have occurred more 
often in younger men and after the second dose of 
the vaccine and w ithin 14 days after vaccination. 
These are generally mild cases and individuals tend 
to recover within a short time following standard 
treatment and rest. Healthcare professionals should 
be alert to the signs and symptoms of myocarditis 
and pericarditis in vaccine recipients.Specific reference to these risks is made within the 
ICD, with instruction to contact a healthcare 
professional if a c ase is suspected.
For anaphylaxis, there is an on site for a 30 minute 
observation period after vaccination.
Instructions for handling suspected cases of 
myocarditis and pericarditis are found in 
Section 8.14
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Page 572.3.2.Benefit Assessment
Benefits to individual participants may  include:
Receipt of a n efficacious COVID-19 vaccine during a global pandemic
Access to COVID -19 diagnostic testing
Contributing to research to help others in a time of global pandemic
2.3.3.Overall Benefit /Risk Conclusion
Taking into account the measures taken to minimize risk to participants participating in this 
study, the potential risks identified in a ssociation with BNT162b2 RNA -based COVID -19
vaccine are justified b y the anticipated benefits that may  be afforded to healthy  participants.
3.OBJECTIVES, ESTIMAND S, AND ENDPOINTS
The dose-finding/selected -dose age groups referred to in the objectives and est imands below 
are participants ≥5 to <12 years, ≥2 to <5 years, and ≥6 monthsto <2 years of age .
The lower -dose age groups referred to in the objectives and estimands below are a separate 
cohort of participants ≥5to <12years, 12 to <16 years, and 16 to < 30 years of age. 
The obtaining- serum-samples-for-potential-troponinI-testingage groups referred to in the 
objectives and estimands below are a separate cohort of p articipants ≥5to <12years and 12 
to <16 years.
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Page 583.1.Phase 1
Phase 1
Objectives Estimands Endpoints
Primary: Primary: Primary: 
To describe the safety and tolerability 
profiles of prophylactic BNT162b2 at 
each dose level in each age group.In participants receiving at least 1 dose 
of study intervention, the percentage of 
participants in each age group 
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 
Dose 2
SAEs from Dose 1 to 6 months 
after Dose 2Participants 16 to <30, 12 to <16, ≥5 to 
<12,and ≥2 to <5 years of age:
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
SAEs 
Participants ≥6monthsto <2 yearsof 
age:
Local reactions ( tenderness at the 
injection site, redness, and 
swelling)
Systemic events (fever, decreased 
appetite, drowsiness, and 
irritability )
AEs
SAEs 
Secondary: Secondary: Secondary: 
To describe the immune responses 
elicited by prophylactic BNT162b2 at 
each dose level in each age groupIn participants complying with the key 
protocol criteria (evaluable 
participants) in each age group : 
GMTs at 7 days after Dose 2SARS-CoV-2 neutralizing titers
Exploratory: Exploratory: Exploratory:
To describe COVID -19 and severe 
COVID-19 cases with and without 
serological or virological evidence of 
past SARS -CoV-2 infectionConfirmed COVID-19 cases 
Confirmed severe COVID -19 
cases
To describe MIS -C cases with and 
withoutevidence of past SARS -CoV-2 
infectionConfirmed cases as per CDC 
criteria 
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Page 593.2.Phase 2/3
Phase 2/3
Objectives Estimands Endpoints
Primary Safety: Primary Safety: Primary Safety: 
To define the safety profile of 
prophylactic BNT162b2 at the selected 
dose level in all participants (selected-
dose,lower-dose, and obtaining-serum-
samples-for-potential -troponin I-
testingportions of the study ) 
randomized in Phase 2/3 in each age 
groupIn participants receiving at least 1 dose 
of study intervention from each vaccine 
group, the percentage of participants in 
each age group 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 
Dose 2
SAEs from Dose 1 to 6 months 
after Dose 2Participants 16 to <30, 12 to <16, ≥5 to 
<12,and ≥2 to <5 years of age:
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
SAEs
Participants ≥6 months to <2 years of 
age:
Local reactions (tenderness at the 
injection site, redness, and 
swelling)
Systemic events (fever, decreased 
appetite, drowsiness, and 
irritability)
AEs
SAEs 
Primary Immunogenicity
(Selected -Dose): Primary Immunogenicity
(Selected -Dose):Primary Immunogenicity
(Selected -Dose):
To immunobridge the immune 
response elicited by prophylactic 
BNT162b2 between Phase 2/3 
participants at the dose selected in each 
age group and participants 16 to 25 
years of age from the C4591001 study 
without serological or virological 
evidence (up to 1 month after receipt of 
Dose 2) of past SARS -CoV-2 infection :In participants complying with the key 
protocol criteria (evaluable 
participants) and no serological or 
virological evidence (up to 1 month 
after receipt of Dose 2) of past 
SARS-CoV-2 infection: SARS-CoV-2 neutralizing titers 
In participants ≥5 to <12 years of 
age compared to participants 16 to 
25years of age from Phase 2/3 of 
theC4591001 studyGMR, estimated by the ratio of the 
geometric mean of SARS -CoV-2 
neutralizing titers in participants 
≥5 to <12 years of age to those in
participants 16 -25 years of age 1 
month after Dose 2 from Phase 2/3 
of the C4591001 study
The difference in percentages of 
participants with seroresponseain 
participants ≥5 to <12 years of age 
and participants 16 to 25 years of 
age from Phase 2/3 of the 
C4591001 study
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Page 60Phase 2/3
Objectives Estimands Endpoints
In participants ≥2 to <5 years of 
age compared to participants 16 to 
25years of age from Phase 2/3 of 
theC4591001 studyGMR, estimated by the ratio of the 
geometric mean of SARS -CoV-2 
neutralizing titers in participants 
≥2 to <5 years of age to those in 
participants 16 to 25 years of age 1 
month after Dose 2from Phase 2/3 
of the C4591001 study
The difference in percentages of 
participants with seroresponse in 
participants ≥2 to <5 years of age 
and participants 16 to 25years of 
age from Phase 2/3 of the 
C4591001 study
In participants ≥6 months to 
<2years of age compared to 
participants 16 to 25 years of 
agefrom Phase 2/3 of 
theC4591001 studyGMR, estimated by the ratio of the 
geometric mean of SARS -CoV-2 
neutralizing titers in participants 
≥6 months to <2 years of age to 
those in participants 16 to 25 years 
of age 1 month after Dose 2 from 
Phase 2/3 of the C4591001 study
The difference in percentages of 
participants with seroresponse in 
participants ≥6 months to <2 years 
of age and participants 16 to 25 
years of age from Phase 2/3 of the 
C4591001
Secondary Immunogenicity 
(Lower-Dose Evaluation):Secondary Immunogenicity 
(Lower-Dose Evaluation):Secondary Immunogenicity 
(Lower-Dose Evaluation):
To immunobridge the immune 
response elicited by prophylactic 
BNT162b2 between Phase 2/3 
participants at the lower dose level 
selected in each age group and 
participants 16 to 25 years of age from 
the C4591001 study without 
serological or virological eviden ce (up 
to 1 month after receipt of Dose 2) of 
past SARS -CoV-2 infection: In participants complying with the key 
protocol criteria (evaluable 
participants) and no serological or 
virological evidence (up to 1 month 
after receipt of Dose 2) of past 
SARS-CoV-2 infection:SARS-CoV-2 neutralizing titers
In participants ≥5 to <12 years of 
age compared to participants 16 to 
25years of age from Phase 2/3 of 
theC4591001 studyGMR, estimated by the ratio of the 
geometric mean of SARS -CoV-2 
neutralizing titers in participants 
≥5 to <12 years of age to those in 
participants 16 to 25 years of age 1 
month after Dose 2 from Phase 2/3 
of the C4591001 study
The difference in percentages of 
participants with seroresponse in 
participants ≥5 to <12 years of age 
and participants 16 to 25 years of 
age from Phase 2/3 of the 
C4591001 study
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Page 61Phase 2/3
Objectives Estimands Endpoints
In participants 12 to <16 years of 
age compared to participants 16 to 
25years of age from Phase 2/3 of 
theC4591001 studyGMR, estimated by the ratio of the 
geometric mean of SARS -CoV-2 
neutralizing titers in participants 
12 to <16 years of age to those in 
participants 16 to 25 years of age 1 
month after Dose 2 from Phase 2/3 
of the C4591001 study
The difference in percentages of 
participants with seroresponse in 
participants 12 to <16 years of age 
and participants 16 to 25 years of 
age from Phase 2/3 of the 
C4591001 study
In participants 1 6 to <30years of 
age compared to participants 16 to 
55years of age from Phase 2/3 of 
theC4591001 studyGMR, estimated by the ratio of the 
geometric mean of SARS -CoV-2 
neutralizing titers in participants 
16 to <30 years of age to those in 
participants 16 to 55 years of age 1 
month after Dose 2 from Phase 2/3 
of the C4591001 study
The difference in percentages of 
participan ts with seroresponse in 
participants 16 to <30 years of age 
and 16 to 55 years of age from 
Phase 2/3 of the C4591001 study
Secondary Immunogenicity/Efficacy: Secondary Immunogenicity/Efficacy: Secondary Immunogenicity/Efficacy: 
To describe the immune responses 
elicited by prophylactic BNT162b2 at 
the dose level selected in each age 
group and persistence of immune 
response in Phase 2/3 participants 
without serological or virological 
evidence of past SARS -CoV-2 
infectionIn evaluab le participants with no 
serological or virological evidence of 
past SARS -CoV-2 infection from each 
vaccine and age group:
At baseline (before Dose 1) and 1, 6, 12 
(for the original BNT162b2 group 
only), and 24 (for the original 
BNT162b2 group only) months after 
Dose 2,
GMTs at each time point
GMFRs from before Dose 1 to 
each subsequent time point after 
Dose 2SARS-CoV-2 neutralizing titers
To evaluate the efficacy of prophylactic 
BNT162b2 against confirmed 
COVID-19 occurring from 7 days after 
Dose 2 during the blinded follow -up 
period in participants in the selected -
dose portionof the study without 
evidence of past SARS -CoV-2 
infection In participants complying with the key 
protocol criteria (evaluable 
participants) and with no serological or 
virological evidence (prior to 7 days 
after receipt of Dose 2) of past 
SARS-CoV-2 infection:Confirmed COVID-19 incidence 
from 7 days after Dose 2 per 1000 
person-years of blinded follow -up
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Page 62Phase 2/3
Objectives Estimands Endpoints
In the ≥5 to <12 years age group 
in the selected -dose portionof the 
study, if immunobridging is 
successful and if at least 22 cases 
are accrued100 × (1 –IRR) [ratio of active 
vaccine to placebo]
In the ≥6 months to <2years and 
≥2 to <5years age groups in the 
selected-dose portionof the study 
where immunobridging is 
successful, if at least 22 cases are 
accrued across those age groups100 × (1 –IRR) [ratio of active 
vaccine to placebo]
In all age groups in the selected-
dose portionof the study where 
immunobridging is successful, if 
at least 22 cases are accrued 
across those age groups and if the 
above 2individual age groups ( ≥5 
to <12 years, ≥6 months to 
<2years and ≥2 to <5years 
combined) did not accrue 22 cases100 × (1 –IRR)[ratio of active 
vaccine to placebo]
To evaluate the efficacy of prophylactic 
BNT162b2 against confirmed 
COVID-19 occurring from 7 days after 
Dose 2 during the blinded follow -up 
period in participants in the selected -
dose portionof the study with or 
without evidence of past SARS -CoV-2 
infection In participants complying with the key 
protocol criteria (evaluable 
participants) and with or without 
serological or virological evidence 
(prior to 7 days after receipt of Dose 2) 
of past SARS -CoV-2 infection:Confirmed COVID-19 incidence 
from 7 days after Dose 2 per 1000 
person-years of blinded follow -up 
In ≥5 to <12 years age group in 
the selected -dose portionof the 
study, if immunobridging is 
successful and if at least 22 cases 
are accrued100 × (1 – IRR)[ratio of active 
vaccine to placebo]
In ≥6 months to <2 years and ≥2 
to <5years age groups in the 
selected-dose portionof the study 
where immunobridging is 
successful, if at least 22 cases are 
accrued across those age groups100 × (1 –IRR) [ratio of active 
vaccine to placebo]
In all age groups in the selected-
dose portionof the study where 
immunobridging is successful, if 
at least 22 cases are accrued 
across those age groups and if the 
above two individual age groups 
(≥5 to <12 years of age, ≥6 
months to <2 years and ≥2 to 
<5years combined) did not accrue 
22 cases 100 × (1 –IRR) [ratio of active 
vaccine to placebo]
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Page 63Phase 2/3
Objectives Estimands Endpoints
To describe the efficacy of prophylactic 
BNT162b2 against asymptomatic 
infection in participants in the selected -
dose portionof the study without 
evidence of past SARS -CoV-2 
infectionIn evaluable participants without 
serological or virological evidence of 
past SARS -CoV-2 infection from each 
vaccine group:
100 × (1 –IRR) [ratio of active vaccine 
to placebo]Incidence of asymptomatic infection of 
SARS-CoV-2 based on N -binding 
antibody seroconversion 
Exploratory: Exploratory: Exploratory:
To describe the efficacy of prophylactic 
BNT162b2 against confirmed 
COVID-19 occurring from 7 days after 
Dose 2 through the blinded follow-up 
period in participants in the selected -
dose portionof the study without, and 
with and without, evidence of past 
SARS CoV -2 infection in each age 
group and in all age groups combinedIn 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 o n central 
laboratory or locally confirmed 
NAAT
To evaluate the immune response over 
time to prophylactic BNT162b2 at the  
dose level selected in each age group 
and persistence of immune response in 
Phase 2/3 participants with and without 
serological or virological evidence of 
past SARS -CoV-2 infectionIn evaluable participants with or 
without serological or virological 
evidence of past SARS -CoV-2 
infection from each vaccine group:
At baseline and at 1, 6, 12 (for the 
original BNT162b2 group only), and 24
(for the original BNT162b2 group 
only) months after Dose 2,
GMCs and/or GMTs at each time 
point
GMFRs from before Dose 1 to 
each subsequent time point after 
Dose 2Full-length S-binding IgG levels 
and/or SARS -CoV-2 neutralizing 
titers
To describe COVID19 andsevere 
COVID-19 cases in participants in the 
selected-dose portionof the study with 
and without serological or virological 
evidence of past SARS -CoV-2 
infectionConfirmed COVID-19 cases
Confirmed COVID-19 cases 
resulting in hospitalization
Confirmed severe COVID -19 
cases
To describe MIS -C cases with and 
without evidence of past SARS-CoV -2 
infection in participants in the selected -
dose portionof the studyConfirmed cases as per CDC 
criteria 
To describe the serological responses in 
Phase 2/3 participants in participants in 
the selected -dose portionof the study
to BNT162b2 at the dose level selected 
in each age group in cases of:
Confirmed COVID-19
Confirmed severe COVID -19
SARS-CoV-2 infection without 
confirmed COVID -19SARS-CoV-2 neutralizing titers
To describe the safety and 
immunogenicity of prophylactic 
BNT162b2 at the dose level selected in 
each age group in children with stable 
HIV diseaseAll safety and immunogenicity 
endpoints described above will be 
analyzed descriptively
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Page 64Phase 2/3
Objectives Estimands Endpoints
To describe the cell -mediated immune 
response, and additional humoral 
immune response parameters, to the 
reference strain in a subset of 
participants:
At baseline and at 7 days and 6 
months after Dose 2
To describe the frequency of elevated 
troponinI levels at baseline and after
Vaccination 2 if testing is indicated 
based upon data accrued outside of this 
study
a.Seroresponse is defined as achieving a ≥4-fold rise from baseline (before Dose 1).  If the baseline measurement is 
below the LLOQ, the postvaccination measure of ≥4 × LLOQ is considered seroresponse. 
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Page 654.STUDY DESIGN
4.1.Overall Design
This is a Phase 1/2/3 study  in healthy  children and y oung adults.
Dependent upon safet y and/or immunogenicit y data generated during the course of this 
study, and the resulting assessment of benefit -risk, thesafety, tolerability , and 
immunogenicit y of BNT162b2 in participants <6 months of age may  subsequently  be 
evaluated.Participants will r ange from ≥6 m onthsto <30 years of agewithdifferent dose 
levels assessed in each group .
Table 1.Dose Levels for Each Age Group in the Phase 1 and Phase 2/3 
Dose-Finding/Selected -DoseEvaluations, and Lower-Dose Evaluations ,
and Obtaining Serum Samples for Potential Troponin I Testing
Phase 1 Open -Label Dose -Finding Evaluation
≥6 Months to 
<2 Years≥2 to <5 
Years≥5 to <12 
Years12 to <16 
Years16 to <30 
YearsTotal
Dose level 3µg 3/10 µg 10/20/30 µg
Participant s 16a16/32a16/16/16b 112
Phase2/3 Observer- Blinded, Placebo -Controlled Selected -DoseEvaluation
Dose level 3 µg 3 µg 10 µg
Participant s22501125
(active 
1500750; 
placebo 
750375)22501125
(active 
1500750; 
placebo 
750375)4500
(active 3000; 
placebo 1500)90006750
Phase 1Open-Label Lower-Dose Evaluation
Planned dose 
level(s) 3 µg 3/10µgc3/10µgc
Participant s 32 32/32 32/32 160
Phase 2/3 Open -Label Lower-Dose Evaluation
Planned dose 
level TBD TBD TBD
Participant s 300 300 300 900
Phase 2/3 Obtaining Serum Samples for Potential Troponin I Testing
Planned dose 
level10 µg 30 µg
Participants 750
(active 500; 
placebo250)500
(active 500; 
placebo0)1250
a.Actual number of participants recruited in the≥6 months to <2 y ears and ≥2 to <5 yearsage groups .
b.Actual number of participants recruited inthe≥5 to <12 yearsage group . Dose 1: 16 out of 16 received 
30-µg dose level; Dose 2: 4 out of 16 received 30 -µg dose level and 12 of 16 received 10-µg dose level.
c.Both dose levels will start concurrently.
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Page 664.1.1.Phase 1
Dose-finding:Is the open -label dose -findingportion of the study that willevaluate safet y, 
tolerability, and immunogenicity  of BNT162b2 administered on a 2-dose (separated b y 
approximately  21days) schedule in up to 3 age groups ( participants ≥5 to <12 y ears, 
≥2 to <5 y ears, and ≥ 6monthsto <2 years of age).
Dosefinding is being initiated in this study  in particip ants ≥5 to <12 y ears of age based on 
the acceptable blinded safety assessment of the 30-µ g dose in 12-to 15-year-olds in the 
C4591001 study .
The purpose of P hase 1 is to identify preferred dose level(s) of BNT162b2 from up to 3 
different dose levels in each age group.
Dependent upon safet y and/or immunogenicit y data generated during the course of this 
study, it is possible that dose levels may not be started, may  be terminated early , and/ormay 
beadded with dose levels below the lowest stated dose.
Participants will have blood drawn prior to both Dose 1 and Dose 2 and 7 day s after Dose 2 
to assess for immunogenicity  to determine the final BNT162b2 dose level for the Phase 2/3.
Lower-doseevaluation :Is the open- labellower-dose evaluation portion of the study  that 
willevaluate safet y, tolerability , and immunogenicity  of BNT162b2 on a 2-dose (separated 
by approximately  21 days) schedulein up to 3 age groups ( participants ≥5 to <12 y ears, 12 to 
<16 years, and 16 to <30years of age) .
The purpose of the Phase 1 lower -dose evaluation is to evaluate safety  and immunogenicit y 
of BNT162b2 from up to 2different dose levels in each age group.
Participants will have blood drawn p rior to both Dose 1 and Dose 2 and 7 day s after Dose 2 
to assess immunogenicity  to determine the selectedBNT162b2 dose level for the Phase 2/3
lower-dose evaluation portion of the study .
4.1.2.Phase 2/3
Selected-dose:Is the portion of the study  thatwill evaluate safet y, tolerability , and 
immunogenicit y in each age group at the selected dose level from the Phase 1 dose-finding
portion of the study . Efficacy will be evaluated within or across age groups in which 
immunobridging is successful, dependin g on accrual of a sufficient number of cases in those 
age groups.
Participants will have blood drawn at baseline prior to Dose 1 and 6 months after Dose 2. 
Immunobridging to participants 1 6to 25years of age in the C4591001 study will be based on 
immunog enicity data collected at baseline and 1 month after Dose 2. The persistence of the 
immune response will be based on immunogenicity  data collected in participants at baseline 
and at 1, 6, 12 (original BNT162b2 group onl y),and24 monthsafter Dose 2 (original 
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Page 67BNT162b2 group onl y). In addition, efficacy  against confirmed COVID -19 and against 
asymptomatic infection will also be assessed.
At designated US sites, an additional optional whole blood sample of approximately  10 mL 
will be obtained prior to Dose 1 and at 7 day s and 6 months after Dose 2 from up to 
approximately  60 participants ≥ 10 years of age.  These samples will be used on an 
exploratory  basis to investigate the postvaccination cell -mediated immune response at these 
time points.
At thea6-month follow -up visit,all participants will be unblinded. Participants who 
originally received placebo will be offered the opportunity to receive BNT162b2 as part of 
the study.Participants ≥12years of age who originally  received placebo and become eligible 
for receipt of BNT162b2 or another COVID -19 vaccine according tolocal or national
recommendations prior to 6 months after Dose 2(detailed separatel y,and available in the 
electronic stud y reference portal )will have the opportunity  to receive BN T162b2(10 µg or 3 
µg)based on age at the time at the approval .If a participant turns 12 years of age during the 
study, he or she has the following 2 options: receive 10 µg within the study (following 
provision of informed consent) or receive a BNT162b2 30-µg dose outside of the study . 
Lower-dose evaluation :Is the portion of the study  thatwill evaluate the safety , tolerability , 
and immunogenicit y in each age group at the selected dose level from the Phase 1 lower-dose 
evaluation . 
In this open -label stud y, all participants will have blood drawn at baseline prior to Dose 1 
and at 1 and6 months after Dose 2.  Immunobridging to comparator participants in the 
C4591001 study  will be based on immunogenicity  data collected at baseline and 1 month 
after Dose 2.  The persistence of the immune response will be based on immunogenicit y data 
collected in participants at baseline and1 and 6 months after Dose 2. 
Obtaining serum samples for potential troponinI testing: If testing of troponinI levels in 
individuals who did not receive BNT162b2indicates that troponinIlevelcould be a reliable 
indicator of potential subclinical myocarditis, obtaining serum samples for potential 
troponinI testing during the period of increased risk of clinica l myocarditis may  help 
characterize the absence/presence and frequency  of subclinical my ocarditis. To assess, an 
additional group of participants will be included: 5 to <12 y ears: randomized 2:1 to receive 
BNT162b2 10 µg or placebo, and 12to <16years of age:  open-label receipt of BNT162b2 
30 µg.
4.1.3.Number of Part icipants
4.1.3.1.Phase 1: Open-Label Dose-Findingand Lower -Dose Evaluation
Phase 1 is an open- label study  that will consist of up to 3 different dose levels in each age 
group, with a minimum of 16 participants per dose level (total of 1 44participants) for the 
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Page 68dose-finding evaluation and a minimum of 32 participants per dose level (total of 160 
participants) for the lower-doseevaluation ; seeTable2and Table 3.
Table2.Phase 1 Dose-Finding Participants
Age Group Total Up to 3 D ose Levelsof BNT162b2aActive Placebo
≥5 to <12 Years 48 16/16/16 16 N/A
≥2 to <5Years 48 16/16/16 16 N/A
≥6 Monthsto <2years 48 16/16/16 16 N/A
a.A dose level may be expanded to enroll more than 16 participants subjectsper dose level.
Table 3.Phase 1 Lower-DoseEvaluation Participants
Age Group Total Up to 2Dose Levels of BNT162b 2aActive Placebo
≥5 to <12 Years 32 32 32 N/A
12 to <16 Years 64 32/32 32 N/A
16 to <30Years 64 32/32 32 N/A
a.A dose level may be expanded to enroll more than 32 participants subjectsper dose level. 
4.1.3.2.Phase 2/3: Safety, Tolerability ,Immunogenicity, and Efficacy
Selected-dose:Is the portion of the study  that will evaluate the safet y, tolerability ,and 
immunogenicit yof the selected dose level in each age group at the selected dose level from 
Phase 1dosefinding,with a total of approximately  6750 9000 participants as an additional 
2250 participants will be included to further enlarge the size of the pediatric safet y database .  
Participants will be randomized in a 2:1ratio toreceive active vaccine or placebo (Table4).
Approximately  450 participants (300 in the activevaccine groupand 150 i n the placebo 
group) randomized in each age group in this phase will contribute to the immunobridging 
analysisat 1month after Dose 2and will contribute to the overall anal ysis of the persistence 
of immune response at 6 months after Dose 2. These participants will be enrolled from both 
US and EU sites to ensure this subset is representative of the whole stud y.
For the persistence time points of 12 and 24 months after Dose 2, a pproximately 70 
participants from each age group in the original BNT162b2 group will have an 
immunogenicit y blood draw in order to contribute to the anal ysis. All approximately  6750 
9000 participants will contribute to the VE analysis for conditional VEand asymptomatic 
infection.Approximately 4500 partic ipants who had post –Dose 1 blood sample collection 
will contribute to the a symptomatic infection analy sis.Efficacy will be evaluated within or 
acrossage groups in which immunobridging is successful, depending on accrual of a 
sufficient number of cases in those age groups.
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Page 69At designated US sites, an additional optional whole blood sample of approximately 10mL 
will be obtained prior to Dose1and at 7 day s and 6 months after Dose 2 from up to 
approximately  60 participants ≥10years of age .  Thesesampleswill be used on an 
exploratory  basis to investigate the postvaccination cell -mediated immune response at these 
timepoints.
Table4.Phase 2/3 Selected -DoseParticipants –Blood Draws for 
Immunogenicity/Efficacy A ssessments
All Age Groups ≥5 to <12 Years of Age ≥2 to <5 Years and 
≥6Months to <2 Yearsof 
Agea
Total Active Placebo TotalActivePlacebo Total Active Placebo
Baseline blood 
draw67509000450060003000 4500 3000 1500 1125 22507501500375750
1 Month after 
Dose 21350 900 450 450 300 150 450 300 150
6 Months after 
Dose 24500 3000 1500 2250 1500 750 1125 750 375
12 Months after 
Dose 2210 210 N/A 70 70 N/A 70 70 N/A
24 Months after 
Dose 2210 210 N/A 70 70 N/A 70 70 N/A
a.Number of participants shown is for each of these 2younger age groups .
All participants will contribute to the safet y,tolerability , and efficacyassessments ( Table5).
Table5.Phase 2/3 Selected -Dose Participants –Safety and Tolerability/Efficacy 
Assessments
Age Total Active Placebo
≥5 to <12 Years 4500 3000 1500
≥2 to <5 Years 11252250 7501500 375750
≥6 Months to <2 Years 11252250 7501500 375750
All age groups 67509000 45006000 22503000
Lower-dose evaluation :Is the open-label portionof the study  thatwill evaluate the safety , 
tolerability ,and immunogenicity of the selected dose level in each age group from the 
Phase1lower-dose evaluation ,with a total of approximately  900active participants
(Table 6).  
Approximately  300active participants in each age group in this phase will contribute to the 
immunobridging anal ysis at 1month after Dose 2 and the overall analysis of the persistence 
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Page 70of immune response at 6 months after Dose 2.  These participants will be enrolled from both 
US and EU sites to ensure this subset is representative of the whole stud y.
Table 6.Phase 2/3 Lower -Dose Evaluation Participants – Blood Draws for 
Immunogenicity/Efficacy Assessments
All Age Groups ≥5 to <12, 12 to <16 Years, and 16 to 
<30Years of Ag ea
Total Active Active Placebo
Baseline blood draw  900 900 300 N/A
1 Month after Dose 2 900 900 300 N/A
6 Months after Dose 2 900 900 300 N/A
a.Number of participants shown is for each of these 2 older age group s.
All participants will contribute to the safet y,tolerability , and efficacy assessments (Table 7).
Table 7.Phase 2/3 Lower -Dose Evaluation Participants – Safety and 
Tolerability/Efficacy Assessments
Total Active Placebo
900 900 N/A
Obtaining serum samples for potential troponinI testing: 750 participants 5 to <12 y ears 
of age (randomized 2:1 to receive BNT162b2 10 µg or placebo) and 500 participants 12 to 
<16years of age (open -label receipt of BNT162b2 30 µg).
        
      
Sum ofAge Groups
Currently Included in 
Potential Troponin I 
TestingWithin Protocol5 to <12Years of Age
Placebo-Controlled
(2:1 Randomization)12 to <16Years of Age
Open-Label
Total Active Placebo Total Active Placebo Total Active Placebo
Baseline blood 
draw 1250 1000 250 750 500 250 500 500 N/A
4 Days after 
Dose 21250 1000 250 750 500 250 500 500 N/A
4.1.4. Intervention Groups and Duration
Phase 1open-label dose-finding: Dosing will begin at the low -doselevelin participants 
≥5 to <12 y ears of age . Controlled enrollment will be required for the first dose level studied 
in each age group.  Onl y a limited number of participants (~4) are dosed before allowing 
dosing in the remaining participants (~12) in the same age and dose -level group. The IRC 
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Page 71will review safety  data (e-diary and AE) acquired up to 7 day s after Dose 1 for the low-dose 
level group ; upon confirmation of an acceptable safet y assessment by the IRC:
Dosing maycommence at the mid -doselevel in the same age group, and  
Dosing may  commence at the low -dose level in participants ≥2 to <5 y ears of age.  
The same process will be followed when moving up doselevels in each age group, and when 
progressing between age groups at the low -dose level as shown in Section 1.2.  Dosing may  
commence at the low -dose level in participants ≥ 6 months to <2 y ears of age after IRC 
review of safet y data (e-diary and AE) acquired up to 7 day s after Dose 1 at the low -dose 
level from participants ≥2 to <5 y ears of age.
In each age group, i f the low-dose level is considered notacceptable based on safet y 
assessment after Dose 1, themid-doselevel or high- doselevel will not commence . In this 
case, an optional lower dose leve l may commence.  Dependent on the results obtained, dose
level(s)may be omitted. In each age group, i f the mid-dose level is considered not 
acceptable based on safety assessment after Dose 1, the high-dose level will not commence. 
Based on safet y assessment, the second dose may be given at a lower dose level.
Phase 2/3 selected-dose: Progression of each age group into Phase 2/3 will occur 
independentl y; it is therefore possible that each age group may  not start Phase 2/3 
concurrently  and the dose level selected for Phase 2/3 may  differ in each age group.  For each 
age group t o proceed to Phase 2/3, safet y, tolerability , and immunogenicity data from 7 day s 
after Dose 2 for the selected vaccine dose level in the age group from Phase 1 wi ll be 
confirmed to be acceptable .  
Duration: Participants are expected to participate for up to a maximum of approximately  
26months.
Phase 1 lower-dose evaluation : As safety has been assessed at higher dose levels in all 3 
age groups, each dose and age level will occur concurrentl y:
≥5 to <12 Years : 3µg
12 to <16 Years, 16 to <30 Years: 3µgand 10µg
The IRC will review safety  data (e-diary and AEs) acquired up to 7 day s after Dose 2.
Phase 2/3 l ower-dose evaluation: Progression of each age group into Phase 2/3 will occur 
independentl y; it is therefore possible that each age group may  not start Phase 2/3 
concurrently ,and the dose level selected for Phase 2/3 may  differ in each age group.  For 
each age group t o proceed to Phase 2/3, safet y, tolerability, and immunogenicity data from 7 
days after Dose 2 for the selected vaccine dose level in the age group from Phase 1 will be 
confirmed to be acceptable.  
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Page 72Duration: Participants are expected to participate for up to a maximum of approximately  
6months.
Obtaining serum samples for potential troponinI testing: Progression of each age group 
will occur concurrentl y.
Duration of obtaining s erum samples for potential troponinI testing: Participants are 
expected to participate for up to a maximum of approximately  6months.
4.2.Scientific Rationale for Study Design
Additional surveillance for COVID -19/MIS-Cin Phase 1 dose -findingand Phase 2/3 
selected-doseparticipants will be conducted as pa rt of the study , given the potential risk of 
disease enhancement . If a participant experiences sy mptoms, as detailed in Section 8.13, a 
COVID-19/MIS-Cillnessvisit will occur and an anterior nasal swab) will be taken for 
antigen assessment as well as recording of COVID -19/MIS-C–related clinical and laboratory  
information (including local diagnosis). For participants in the lower-dose evaluation, 
COVID-19/MIS-C will be reported as AESIs.
Human reproductive safety  data are not available for BNT162b2 RNA -based COVID -19 
vaccine, but there is no suspicion of human teratogeni city based on the intended mechanism 
of action of the compound. Therefore, the use of a highly effective method of contraception 
is required (see Appendix 4 ) for WOCBP.
4.3.Justification for Dose
Dose-findingandselected-doseevaluation :Based on acceptable blinded safet y datain 
2260 12-through 1 5-year-olds at the 30- µg dose level in the C4591001 study, dose-findingis 
considered in this study using the same vaccine candidate .25  Therefore, this study  will start 
with a 10-µgdoselevel for Phase 1 participants ≥5 to <12 y ears of age , which was well 
tolerated in adults 18 to 55years of age in C4591001, before moving to anotherdoselevelin 
this age group or initiating the younger age groups (20 µg, 30 µgwith an option of 3 µg).
Lower-dose evaluation (participants 5 to <12, 12 to <16, 16 to <30 years of age ):The 
authorized dose of BNT162b2 in adolescents and young adults 12 yearsof ageand older is 
30µg,whereas in the ongoing C4591007 Phase 2/3 portion of the study  the following doses 
were selected: 10 µgin participants 5 to <12 years of ageand 3 µg in participants 6 months 
to <5 yearsof age. With the robust immune responses elicited in adolescents to minimize 
reactogenicity and risk of other AEs and to potentially  unify thedose levels across children 
and young adults, additional lower dose levels of BNT162b2 (3 µg, 10 µg) will be evalua ted 
to determine whether similar immune responses are elicited. For this lower -dose evaluation 
portion, a new cohort of Phase 1 participants will be enrolled in 3age groups: >5 to <12, 
12 to <16, 16 to <30 years of age to assess safet y, tolerability , and immunogenicity . The 
Phase2/3 BNT162b2 dose level will be selected based on the Phase 1 assessments with an 
immunobridging anal ysis of immune responses in participants within each age group to 
participants in the 30 -µgPhase 3 C4591001 efficacy  study. 
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Page 73Obtaining serum samples for potential troponinI testing (5 to <12 years of age, 
placebo-controlled ,and12 to <16 years of age, open -label): The authorized dose of 
BNT162b2 in adolescents and y oung adults 12 y ears of age and older is 30 µg, whereas in 
the ongoing C4591007 Phase 2/3 portion of the study , 10 µgin participants 5 to <12 y ears 
was selected.
4.4.End of Study Definition
A participant is considered to have completed the study  if he/she has completed all phases of 
the study,including the last visit.
The end of the study  is defined as the date of the last visit of the last participant in the study .
5. STUDY POPULATION
This study  can fulfill its objectives only  if appropriate participant s are enrolled , including 
participants across diverse and representative racial and ethnic backgrounds. Use of a 
prescreener for stud y recruitment purposes will include collection of information, that 
reflects the enrollment of a diverse participant population including, where permitted under 
local regulations, age, sex, and race, and ethnicity.   The following eligibility criteria are 
designed to select participant s for whom participation in the study  is considered appropriate.  
All relevant medical and nonmedical conditions should be taken into consideration when 
deciding whether a particular participant is suitable for this protocol.
Prospective approval of protocol deviations to recruitment and enrollment criteria ,also 
known as protocol waivers or exemptions, is not permitted .
5.1. Inclusion Criteria
Participants are eligible to be included in the study  only if all of the following criteria appl y:
Ageand Sex:
1.Male or female participants between≥6 months andto<12years of age ,at the time of 
randomization, at Visit 1forthedose-finding/selected-doseevaluation and for 
participants between ≥5 andto<30yearsof age, at the time of randomization, at Visit 1
for the lower-doseevaluation .
For theobtaining -serum-samples- for-potential- troponin I-testingportion of the 
study:
Male or female participants between ≥5 and<16years of age .
Refer to Appendix 4 for reproductive criteria for male ( Section 10.4.1) and female 
(Section 10.4.2) participants.
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Page 74Type of Participant and Disease Characteristics:
1.2.Participants’ parent(s)/legal guardian(s ) and participants, as age appropriate, who are 
willing and able to comply  with all scheduled visits, treatment plan, laboratory  tests,
lifestyle considerations, and other study  procedures.
2.3.Healthy participants who are determined b y medical history, ph ysical examination ,and 
clinical judgment of the investigator to be eligible for inclusion in the study.
Note:Healthy participants with preexisting stable disease, defined as disease not 
requiring significant change in the therap y or hospitalization for worsening disease 
during the 6 weeks before enrollment , can be included.
Phase 2/3: Specific criteria for such p articipants with known stable infecti on with HIV, 
HCV, or HBV can be found in Section 10.7.
3.4.Participants are ex pected to be available for the duration of the study  and whose 
parent(s)/legal guardian can be contacted b y telephone during study participation.
4.5. Negative urine pregnancy  test for female participants who are biologically capable of 
having children.
5.6.Female participant of childbearing potential or male participant able to father children 
who is willing to use a highl y effective method of c ontraception as outlined in this 
protocol for at least 28 days after the last dose of study intervention if at risk of 
pregnancy  with her/his partner ; or female participant not of childbearing potential or male 
participant not able to father children.
Informed Consent:
6.7.The participant or participant’s parent(s)/legal guardian is c apable of giving signed 
informed consent as described in Appendix 1 ,which includes compliance with the 
requirements and restrictions listed in the I CDand in this protocol.  Depending on the age 
of the participant and according to local requirements, participants will also be asked to 
provide assent as appropriate (verbal or written).
The investigator, or a person designated b y the investigator, will obtain written or 
electronically  signed informed consent ( and assent)from each stud y participant or
participant’s legal guardian (as defined in Appendix 1 )and the participant’s assent, when 
applicable, before an y study-specific activity  is performed . All legal guardians should be 
fully informed, and participants should be informed to the fullest extent possible, about the 
study in language and t erms they  are able to understand. The investigator will retain the 
original cop y of each participant's signed consent/assent document.
5.2. Exclusion Criteria
Participants are excluded from the study  if any of the following criteria apply :
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Page 75Medical Conditions:
1.Phase 1 only: Pastclinical (based on COVID -19 symptoms/signs alone, if a 
SARS-CoV-2 NAAT result was notavailable) or microbiological (based on COVID -19 
symptoms/signs and a positive SARS -CoV-2 NAAT result) diagnosis of COVID -19.
2.Phase 1 only: Known infection with HIV, HCV, or HBV.
3.Receipt of medications intended to prevent COVID -19.
4. Previous or current diagnosis of MIS-C.
5.Other medical or psy chiatric condition including recent (within the past year) or active 
suicidal ideation /behavior or labo ratory abnormality  that may increase the risk of study 
participation or , in the investigator’s judgment, make the participant inappropriate for the 
study.Note: This includes both conditions that may increase the risk associated with 
studyintervention administration or a condition that may interfere with the interpretation 
of study results
6.History of severe adverse reaction associated with a vaccine and/or severe allergic 
reaction (eg, anaph ylaxis) to any  component of the study  intervention(s).
7.Immunoc ompromised individuals with known or suspected immunodeficiency , as 
determined b y history and/or laboratory /physical examination.
8.Individuals with a history of autoimmune disease or an active autoimmune disease 
requiring therapeutic intervention, including but not limited to sy stemic lupus 
erythematosus. Note: Stable type 1 diabetes and hypothyroidismare permitted .
9. Bleeding diathesis or condition associated with prolonged bleeding that would, in the 
opinion of the investigator, contraindicate intramuscular injection.
10.Femalewho ispregnant or breastfeeding.
Prior/Concomitant Therapy:
11.Previous vaccination with any  coronavirusvaccine.
12.Individuals who receive treatment with immunosuppressive therapy , including cy totoxic 
agents or s ystemic cortico steroids, eg, for cancer or an autoimmune disease, or planned 
receipt throughout the study .  If systemic corticosteroids have been administered short 
term (<14 day s) for treatment of an acute illness, participants should not be enrolled into 
the study until corticosteroid therap y has been discontinued for at least 28 days before 
study intervention administration.  Inhaled/ nebulized,intra -articular, intrabursal, or 
topical (skin or ey es) corticosteroids are permitted.
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Page 7613. Receipt of blood/plasma products, immunoglobulin, or monoclonal antibodies, from 60 
days before study  intervention administration , or receipt of an y passive antibody  therapy 
specific to COVID -19 from 90 day s before study  intervention administration, or planned 
receipt throughout the study .
Prior/Concurrent Clinical Study Experience:
14.Participation in other studies involving study  intervention within 28 day s prior to study  
entry and/or during study participation.
15.Previous participation in other studies involving study  intervention containing LNPs.
Diagnostic Assessments:
Not applicable .
Other Exclusions:
16. Participants who are direct descendants (child or grandchild) of investigational site staff 
members or Pfizer/Bio NTech emplo yees directly involved in the conduct of the study , 
site staff otherwise supervised by  the investigator, and their respective family  members.
5.3.Lifestyle Considerations
5.3.1.Contraception
All male and female participants who, in the opinion of the investigator, are biologically  
capable of having children must agree to use a highly  effective method of contraception 
consistently  and correctly  for at least 28 day s after the last study  vaccination.
The investigator or his or her designee, in consultation with the participant , will confirm that 
the participant has selected an appropriate me thod of contraception for the individual 
participant and his or her partner(s) from the permitted list of contraception methods 
(seeAppendix 4 ,Section 10.4.4)and will confirm that the participant has been instructed in 
its consistent and correct use.  At time points indicated in the SoA , the investigator or 
designee will inform the participant of the need to use highl y effective contraception 
consistently  and correctly  and document the conversation and the participant’s affirmation in 
the participant ’s chart (participant s need to affirm their consistent and correct use of at least 1 
of the selected methods of contraception).  In addition, the investigator or designee will 
instruct the participant or participant ’s parent(s)/legal guardi anas applicable to call 
immediately  if the selected contraception method is discontinued or if pregnancy  is known or 
suspected in the participant or partner.
5.4.Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study  but 
are not subsequently  randomly  assigned to study intervention /enrolledin the study . A 
minimal set of screen failure information is required to ensure transparent reporting of screen 
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Page 77failure participants to meet the CONSORT publishing requirements and to r espond to queries 
from regulatory  authorities. Minimal information includes demograph y, screen failure 
details, eligibility  criteria, and any  SAEs.
Individuals who do not meet the criteria for participation in this study  (screen failure) may be 
rescreened under a different participant number.
5.5. Criteria for Temporarily Delaying Enrollment/Randomization/Study Intervention 
Administration
The following conditions are temporary  or self-limiting and a participant may  be vaccinated 
once the condition(s) has/have r esolved and no other exclusion criteria are met.
1.Current febrile illness (body  temperature ≥100.4°F [ ≥38°C]) or other acute illness within 
48 hours before study intervention administration. This includes current s ymptoms that 
could represent a potential C OVID-19 illness (forPhase 1,confirmed COVID -19 
diagnosis is an exclusion criterion):
New or increased cough; 
New or increased shortness of breath;
Diarrhea;
Vomiting ;
Chills; 
New or increased muscle pain;
New loss of taste/smell;
Sore throat;
Nausea;
Inability to eat/poor feeding in participants <5 y ears of age .
2.Receipt of a ny nonlive vaccine, any  seasonal or pandemic influenza vaccine, or any  
rotavirus vaccine within 14 day s before study  intervention administration, or any other 
live vaccine (ie ,excluding live influenza and rotavirus vaccines) within 28 day s before 
study intervention administration.
3.Anticipated receipt of any vaccine between Dose s 1 and 2, or between Doses 3 and 4, of 
study intervention, or within 7 day s after Dose 2 or 4.
4.Receipt of short -term (<14 day s) systemic corticosteroids.  Study  intervention 
administration should be delay ed until sy stemic corticosteroid use has been discontinued 
for at least 28 days.  Inhaled/nebulized, intra -articular, intrabursal, or topical (skin or 
eyes) corticosteroids are permitted.
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Page 786.STUDY INTERVENTION
Study intervention is defined as any  investigational intervention(s), marketed product(s), 
placebo, medical device(s) , or study procedure(s) intended to be administered to a study  
participant acco rding to the study  protocol. In Phase 2/3, the selected-dose portion and 
obtaining -serum-samples-for-potential-troponinI-testing(5 to <12 yearsold)portionsis are
placebo-controlled and the lower -dose evaluation portionand obtaining -serum-samples-for-
potential-troponinI-testing(12 to <16 y earsold)portionsis areopen-label.
Phase 1will evaluate a 2 -dose (separated b yapproximately 21 days) schedule of up to
3different dose levels of RNA vaccine candidate BNT162b2 for active immunization against 
COVID-19,to determine the final dose level of BNT162b 2in Phase 2/3for each age group .  
The investigation alRNA vaccine candidate andsaline placebo ,in Phase 2/3 of the selected-
doseportionand obtaining -serum-samples-for-potential- troponinI-testing(5 to <12 y ears 
old)portions, are the 2 potential study interventions that may  be administered to a study  
participant:
BNT162b2 (BNT162 RNA -LNP vaccine utilizing modRNA and encoding the P2 S):
10µg, 20µg, and 30µg,with an option for 3 µgor,another dose level .
Normal saline (0.9% sodium chloride solution for injection).
6.1.Study Intervention(s) Administered
Intervention Name BNT162b2 
(BNT162 RNA -LNP Vaccine Utilizing 
modRNA)Saline Placebo(Selected-Dose)
Type Vaccine Placebo
Dose Form ulation modRNA Normal saline (0.9% sodium chloride 
solution for injection)
Unit Dose 
Strength(s)250 µg/0.5 mL N/A
Dosage Level(s)a10µg, 20µg,or30µg,with an option for 
3 µgor another dose levelN/A
Route of 
AdministrationIntramuscular injection Intramuscular injection
Use Experimental Placebo
IMP or NIMP IMP IMP
Sourcing Provided centrally by the sponsor Provided centrally by the sponsor
Packaging and 
LabelingStudy intervention will be provided in a 
glass vial as open -label supply. Each vial 
will be labeled as required per country 
requirement .Study intervention will be provided in a 
glass or plastic vial as open -label supply.
Each vial will be labeled as required per 
country requirement .
a.Dependent upon safety and/or immunogenicity data generated during the course of this study ,it is 
possible that dose levels may not be started, may be terminated early, and/or may be added with dose 
levels below the low est stated dose .
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Page 796.1.1.Administration
Participants will receive 1 dose of study  intervention as randomized at each vaccination visit 
(Visits 1 and 2 , and Visit A and Visit B for Phase 2/3 selecteddoseparticipants who go on to 
receive BNT162b2) in accordance with the study ’s SoA.  The volume to be administered 
may vary by dose level; full details are described in the I P manual.
For participants ≥2to years of age, study  intervention shouldbe administered 
intramuscularl y into the deltoid muscle, preferably of the nondomi nant arm. Study 
intervention will be administered by an unblinded administrator.
For participants <2 years of age, study  intervention should be administered intramuscularl y 
into the anterior thigh muscle, preferably  of the left leg .  Study intervention will be 
administered b y an unblinded administrator.
Standard vaccination practices must be observed and vaccine must not be injected into blood 
vessels.  Appropriate medication and other supportive measures for management of an acute 
hypersensitivity  reaction should be available in accordance with local guidelines for standard 
immunization practices.
Administration of study interventions should be performed b y an appropriately  qualified, 
GCP-trained, and vaccine- experienced member of the study staff (eg, ph ysician, nurse, 
physician’s assistant, nurse practitioner, pharmacist, or medical assistant) as allowed by  
local, state, and institutional guidance. 
Study intervention administration details will be recorded on the CRF.
6.2.Preparation/Hand ling/Storage/Accountability
1.The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study  intervention sreceived and an y discrepancies are 
reported and resolved before use of the stud y intervention.
2.Only participants enrolled in the study  may receive study  intervention and only  
authorized site staff may  supply or administer study  intervention. All study intervention s
must be stored in a secure, environmentall y controlled, and monitored (manual or 
automated recording ) area in accordance with the labeled storage conditions with access 
limited to the investigator and authorized site staff.  At a minimum, dai ly minimum and 
maximum temperatures for all site storage locations must be documented and available 
upon request.  Data for nonworking day s must indicate the minimum and maximum 
temperature ssince previously  documented for all site storage locations upon r eturn to 
business.
3.Any excursions from the study  intervention label storage conditions should be reported to 
Pfizer upon discovery  along with an y actions taken.  The site should actively  pursue 
options for returning the study  intervention to the storage co nditions described in the 
labeling, as soon as possible.  Once an excursion is identified, the study  intervention must 
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Page 80be quarantined and not used until Pfizer provides permission to use the study  
intervention.  Specific details regarding the definition of an excursion and information the 
site should report for each excursion will be provided to the site in the I P manual.
4.Any storage conditions stated in the SRSD will be superseded by  the storage conditions 
stated on the label.
5.Study interventions should be stored in their original containers.
6.See the IP manual for storage conditions of the study  intervention .
7. The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for stud y intervention accountability , reconciliation, and record maintenance 
(ie, receipt, reconciliation, and final disposition records) , such as t
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