019736 S444 M5 c4591007 protocol amend2

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PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Final Protocol Amendment 2 , 06 Aug 2021
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 AND PHASE 2/3 
PLACEBO -CONTROLLED, OBSERVER- BLINDED SAFETY, TOLERABILIT Y,
AND IMMUNOGENICITY 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
USIND Number: 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.
090177e197c0bffd\Approved\Approved On: 06-Aug-2021 19:09 (GMT)
FDA-CBER-2021-5683-1076877
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Final Protocol Amendment 2 , 06 Aug 2021
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 2 06 Aug 2021 Made the following updates in 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 visit that occurs 
sooner than 1 month after any vaccination .
Addition of an unplann ed 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 with corresponding 
objectives . 
Revised the order of Visit 1 activities to clarify when 
procedures should be conducted in relation t o study 
intervention administration when the visit occurs 
over 2 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 .
Added acountry -specific appendix that allow s
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 05Mar 2021 Added 2age 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 u pdates to match Pfizer’s response to 
04February 2021 CBER comments regarding this 
study, ie :
090177e197c0bffd\Approved\Approved On: 06-Aug-2021 19:09 (GMT)
FDA-CBER-2021-5683-1076878
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Final Protocol Amendment 2 , 06 Aug 2021
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
Exclusion criteri on3 applied to all study 
participants rather than just to Phase 1 
participants.
References to “noninferiority ”updated to 
“immunobridging. ”
Made a ddition sto the exclusion criteria for previous 
or current diagnosis of MIS -C.
Addedto the exclusion criteria receipt of any passive 
antibody therapy specific to COVID -19 within 
90days prior 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.
Follow ing updates made to the first confirmed 
COVID -19 case definition to accommodate inclusion 
of participants <5 years of age:
Definition of diarrhea added.
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.  Table 4inserted.
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.
090177e197c0bffd\Approved\Approved On: 06-Aug-2021 19:09 (GMT)
FDA-CBER-2021-5683-1076879
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Final Protocol Amendment 2 , 06 Aug 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 4TABLE OF CONTENTS
LIST OF TABLES ................................ ................................ ................................ ................... 11
1. PROTOCOL  SUMMARY ................................ ................................ ................................ ...12
1.1. Sy nopsis ................................ ................................ ................................ .................. 12
1.2. Schema ................................ ................................ ................................ .................... 21
1.3. Schedule of Activ ities ................................ ................................ ............................. 24
1.3.1. Phase 1 Dose -Finding Portion ................................ ................................ ....24
1.3.2. Phase 1 L ower -Dose Evaluation ................................ ................................ .27
1.3.3. Phase 2/3 Selected -Dose Portion................................ ................................ 29
1.3.3.1. Phase 2/3 Selected -Dose Portion: Participants Who 
Originall y Received BNT162b2 or Placebo Recipients Who 
Decline BNT162b2 ................................ ................................ ............ 33
1.3.3.2. Phase 2/3 Selected -Dose Portion: Participants Who 
Originall y Received Placebo ................................ ............................. 34
1.3.4. Phase 2/3 L ower -Dose Evaluation ................................ .............................. 37
2. INTRODUCTION ................................ ................................ ................................ ............... 39
2.1. Study  Rationale ................................ ................................ ................................ .......39
2.2. Background ................................ ................................ ................................ ............. 39
2.2.1. Clinical Overview ................................ ................................ ....................... 41
2.3. Benefit/Risk Assessment................................ ................................ ......................... 42
2.3.1. Risk Assessment ................................ ................................ ......................... 43
2.3.2. Ben efit Assessment ................................ ................................ ..................... 46
2.3.3. Overall Benefit/Risk Conclusion ................................ ................................ 46
3. OBJECTI VES, ESTIMANDS, AND ENDPOINTS ................................ ........................... 46
3.1. Phase 1 ................................ ................................ ................................ ..................... 46
3.2. Phase 2/3 ................................ ................................ ................................ ................. 47
4. STUDY DESIGN ................................ ................................ ................................ ................. 53
4.1. Overall Design ................................ ................................ ................................ ......... 53
4.1.1. Phase 1 ................................ ................................ ................................ ........ 53
4.1.2. Phase 2/3................................ ................................ ................................ .....54
4.1.3. Number of Participants................................ ................................ ............... 55
4.1.3.1. Phase 1: Open -Label Dose -Finding and Lower -Dose 
Evaluation ................................ ................................ .......................... 55
090177e197c0bffd\Approved\Approved On: 06-Aug-2021 19:09 (GMT)
FDA-CBER-2021-5683-1076880
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Final Protocol Amendment 2 , 06 Aug 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 54.1.3.2. Phase 2/3: Safety, Tolerability , Immunogenicity , and 
Efficacy ................................ ................................ .............................. 56
4.1.4. I ntervention Groups and Duration ................................ .............................. 58
4.2. Scientific Rationale for Study  Design ................................ ................................ .....59
4.3. J ustification for Dose ................................ ................................ .............................. 59
4.4. End of Study  Definition ................................ ................................ .......................... 60
5. STUDY POPUL ATION ................................ ................................ ................................ ......60
5.1. I nclusion Criteria................................ ................................ ................................ .....60
5.2. Exclusion Criteria ................................ ................................ ................................ ....61
5.3. L ifesty le Considerations ................................ ................................ .......................... 63
5.3.1. Contraception ................................ ................................ .............................. 63
5.4. Screen Failures ................................ ................................ ................................ ........ 63
5.5. Criteria for Temporarily  Delay ing Enrollment/Randomization/Study  
Intervention Administration ................................ ................................ ...................... 64
6. STUDY INTERVENTIO N................................ ................................ ................................ ..64
6.1. Study  Intervention(s) Administered ................................ ................................ ........ 65
6.1.1. Administration ................................ ................................ ............................ 65
6.2. Preparation/Handling/Storage/Accountability ................................ ........................ 66
6.2.1. Preparation and Dispensing ................................ ................................ ........ 67
6.3. Measures to Minimize Bias: Randomization and Blinding.....................................67
6.3.1. Allocation to Study Intervention ................................ ................................ 67
6.3.2. Blinding of Site Personnel (Phase 2/3 Selected -Dose Portion Onl y)......... 68
6.3.3. Blinding of the Sponsor................................ ................................ .............. 68
6.3.4. Breaking the Blind ................................ ................................ ...................... 69
6.4. Study  Intervention Compliance ................................ ................................ ............... 69
6.5. Concomitant Therapy ................................ ................................ .............................. 70
6.5.1. Prohibited During the Study ................................ ................................ .......70
6.5.2. Permitted During the Study ................................ ................................ ........ 71
6.5.3. Recording Nonstudy  Vaccination and Concomitant Medications..............71
6.6. Dose Modification ................................ ................................ ................................ ...71
6.7. I ntervention After the End of the Study ................................ ................................ ..72
090177e197c0bffd\Approved\Approved On: 06-Aug-2021 19:09 (GMT)
FDA-CBER-2021-5683-1076881
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Final Protocol Amendment 2 , 06 Aug 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 67. DI SCONTINUATION O F STUDY INTERVENTION AND PARTI CIPANT 
DISCONTINUATION/WI THDRAWAL ................................ ................................ ........... 72
7.1. Discontinuation of Study  Intervention ................................ ................................ ....72
7.2. Participant Discontinuation/Withdrawal From the Study ................................ .......73
7.2.1. Withdrawal of Consent ................................ ................................ ............... 74
7.3. L ost to Follow -up ................................ ................................ ................................ ....74
8. STUDY ASSESSMENTS AND PROCEDURES ................................ ............................... 75
8.1. Efficacy  and/or Immunogenicity Assessments ................................ ....................... 76
8.1.1. I mmunogenicity................................ ................................ .......................... 79
8.1.2. Biological Samples ................................ ................................ ..................... 80
8.2. Safet y Assessments ................................ ................................ ................................ .80
8.2.1. Phy sical Examinations ................................ ................................ ................ 81
8.2.2. Vital Signs ................................ ................................ ................................ ..81
8.2.3. Clinical Safety  Laboratory  Assessments ................................ .................... 81
8.2.4. Electronic Diary ................................ ................................ .......................... 81
8.2.4.1. Grading Scales ................................ ................................ ........... 82
8.2.4.2. L ocal Reactions ................................ ................................ ......... 82
8.2.4.3. Sy stemic Events ................................ ................................ ........ 84
8.2.4.4. Fever ................................ ................................ .......................... 86
8.2.4.5. Antipy retic Medication ................................ ............................. 86
8.2.5. Phase 1 Stopping Rules ................................ ................................ .............. 86
8.2.6. Randomization and Vaccination After a Stopping Rule Is Met in 
Phase 1 ................................ ................................ ................................ ............. 88
8.2.7. Pregnancy  Testing ................................ ................................ ...................... 88
8.3. Adverse Events and Serious Adverse Events................................ .......................... 88
8.3.1. Time Period and Frequency  for Collecting AE and SAE Information .......88
8.3.1.1. Reporting SAEs to Pfizer Safety ................................ ............... 90
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF................... 90
8.3.2. Method of Detecting AEs and SAEs ................................ .......................... 90
8.3.3. Follow -up of AEs and SAEs ................................ ................................ .......91
8.3.4. Regulatory Reporting Requirements for SAEs ................................ ........... 91
090177e197c0bffd\Approved\Approved On: 06-Aug-2021 19:09 (GMT)
FDA-CBER-2021-5683-1076882
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Final Protocol Amendment 2 , 06 Aug 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 78.3.5. Exposure During Pregnancy  or Breastfeeding, and Occupational 
Exposure ................................ ................................ ................................ .......... 91
8.3.5.1. Exposure During Pregnancy ................................ ...................... 91
8.3.5.2. Exposure During Breastfeeding ................................ ................ 93
8.3.5.3. Occupational Exposure ................................ ............................. 93
8.3.6. Cardiovascular and Death Events ................................ ............................... 94
8.3.7. Disease -Related Events and/or Disease -Related Outcomes Not 
Qualify ing as AEs or SAEs for Dose -Finding/Selected -Dose 
Participants ................................ ................................ ................................ .......94
8.3.8. Adverse Events of Special Interest................................ ............................. 94
8.3.8.1. Lack of Efficacy ................................ ................................ ........ 95
8.3.9. M edical Device Deficiencies ................................ ................................ ......95
8.3.10. Medication Errors ................................ ................................ ..................... 95
8.4. Treatment of Overdose................................ ................................ ............................ 96
8.5. Pharmacokinetics ................................ ................................ ................................ ....96
8.6.Pharmacod ynamics ................................ ................................ ................................ ..96
8.7. Genetic s................................ ................................ ................................ ................... 96
8.8. Biomarkers ................................ ................................ ................................ .............. 96
8.9. I mmunogenicit y Assessments ................................ ................................ ................. 96
8.10. Health Economics ................................ ................................ ................................ .97
8.11. Study  Procedures ................................ ................................ ................................ ...97
8.11.1. Phase 1 Dose -Finding Portion ................................ ................................ ..97
8.11.1.1. Visit 1 – Dose 1 (Day  1)................................ .......................... 97
8.11.1.2. Visit 2 – Dose 2 (19 to 23 Day s After Visit 1) ...................... 100
8.11.1.3. Visit 3 – 7- Day Follow -up Visit (1 Week After Dose 2, 6 
to 8 Day s After Visit 2) ................................ ................................ ...102
8.11.1.4. Visi t 4 – 1-Month Follow -up Visit (28 to 35 Day s After 
Visit 2) ................................ ................................ ............................. 103
8.11.1.5. Visit 5 – 6- Month Follow -up Visit (175 to 189 Days 
After V isit 2) ................................ ................................ .................... 104
8.11.1.6. Visit 6 – 12- Month Follow -up Visit (350 to 378 Day s 
After Visit 2) ................................ ................................ .................... 104
8.11.1.7. Visit 7 – 24- Month Follow -up Visit (714 to 742 Day s 
After Visit 2) ................................ ................................ .................... 105
090177e197c0bffd\Approved\Approved On: 06-Aug-2021 19:09 (GMT)
FDA-CBER-2021-5683-1076883
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Final Protocol Amendment 2 , 06 Aug 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 88.11.2. Phase 1 L ower -Dose Evaluation ................................ ............................. 105
8.11.2.1. Visit 101 – Dose 1 (Day  1)................................ .................... 105
8.11.2.2. Visit 102 – Dose 2 (19 to 23 Day s After Visit 101) .............. 108
8.11.2.3. Visit 103 – 7- Day Follow -up Visit (1 Week After Dose 
2, 6 to 8 Day s After Visit 102) ................................ ........................ 110
8.11.2.4. Visit 104 – 1- Month Follow -up Visit (28 to 35 Day s 
After Visit 102) ................................ ................................ ................ 111
8.11.2.5. Visit 105 – 6- Month Follow -up Visit (175 to 189 Day s 
After Visit 102) ................................ ................................ ................ 111
8.11.3. Phase 2/3 Selected- Dose Port ion................................ ............................ 112
8.11.3.1. Visit 1 – Dose 1 (Day  1)................................ ........................ 112
8.11.3.2. Visit 2 – Dose 2 (19 to 23 Day s After Visit 1) ...................... 115
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 ................................ ............................. 118
8.11.3.4. Visit 4 – 1- Month Follow -up Visit (After Visit 2) (28 to 
35 Day s After Visit 2) ................................ ................................ .....118
8.11.3.5. Visit 5 – 6- Month Follow -up Visit (175 to 189 Days 
After Visit 2) ................................ ................................ .................... 119
8.11.4. Phase 2/3 Selected- Dose Portion: Participants Who Originally  
Received BNT162b2 or Placebo Recipients Who Decline BNT162b2 ......... 120
8.11.4.1. Visit X – 12- Month Follow -up Visit (350 to 378 Day s 
After Visit 2) ................................ ................................ .................... 120
8.11.4.2. Visit Y – 24- Month Follow -up Visit (714 to 742 Day s 
After Visit 2) ................................ ................................ .................... 121
8.11.5 . Phase 2/3 Selected -Dose Portion: Participants Who Originally  
Received Placebo ................................ ................................ ........................... 122
8.11.5.1. Visit A – Dose 3 (175 to 189 Day s After Dose 2 and 
Same Date as Visit 5) ................................ ................................ ......122
8.11.5.2. Visit B – Dose 4 (19 to 23 Days After Visit A) .................... 124
8.11.5.3. Visit C – 1- Month Follow -up Telephone Contact (After 
Dose 4) (28 to 35 Day s After Visit B) ................................ ............. 125
8.11.5.4. Visit D – 6- Month Follow -up Telephone Contact (After 
Dose 4) (175 to 189 Days After Visit B) ................................ ......... 126
8.11.5.5. Visit E – 12-Month Follow -up Telephone Contact (After 
Dose 4) (350 to 378 Days After Visit B) ................................ ......... 127
090177e197c0bffd\Approved\Approved On: 06-Aug-2021 19:09 (GMT)
FDA-CBER-2021-5683-1076884
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Final Protocol Amendment 2 , 06 Aug 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 98.11.5.6. Visit F – 18 -Month Follow -up Telephone Contact (After 
Dose 4) (532 to 560 Days After Visit B) ................................ ......... 127
8.11.6. Phase 2/3 L ower -Dose Evaluation ................................ .......................... 128
8.11.6.1. Visit 201 – Dose 1 (Day  1)................................ .................... 128
8.11.6.2. Visit 202 – Dose 2 (19 to 23 Day s After Visit 201) .............. 130
8.11.6.3. Visit 203 – 1- Month Follow -up Visit (After Visit 2) (28 
to 35 Day s After Visit 202) ................................ ............................. 132
8.11.6.4. Visit 204 – 6- Month Follow -up Visit (175 to 189 Day s 
After Visit 202) ................................ ................................ ................ 133
8.12. Unscheduled Visit for Fever or a Grade 3 or Suspected Grade 4 Reaction ........ 134
8.13. COVID -19 and M IS-C Surveillance (Dose -Finding/Selected -Dose 
Participants) ................................ ................................ ................................ ............. 135
8.13.1. Potential COVI D-19/MI S-C Illness Visit (Optimally  Within 3 Days 
After Potential COVID -19 Illness Onset) ................................ ...................... 137
8.13.2. Potential COVI D-19/MI S-C Convalescent Visit (28 to 35 Day s 
After Potential C OVID -19 Illness Visit) ................................ ....................... 139
8.14. Additional Procedures for Monitoring of Potential My ocarditis or 
Pericarditis ................................ ................................ ................................ ............... 139
8.15. Communication and Use of Technology ................................ ............................. 139
8.16. SARS -CoV -2 NAAT Nasal (Anterior Nares) Swab Results .............................. 140
9. STATI STICAL CONSI DERATIONS ................................ ................................ .............. 141
9.1. Estimands and Statistical Hy potheses ................................ ................................ ...141
9.1.1. Estimands ................................ ................................ ................................ ..141
9.1.2. Statistical Hy pothesis ................................ ................................ ................ 141
9.1.2.1. Statistical Hy pothesis Evaluation for Immunogenicity ........... 141
9.1.2.2. Statistical Hy pothesis Evaluation for Efficacy ........................ 142
9.1.3. Multiplicity  Considerations ................................ ................................ ......143
9.2. Sample Size Determination ................................ ................................ ................... 144
9.3. Analy sis Sets ................................ ................................ ................................ ......... 147
9.4. Statistical Analy ses................................ ................................ ............................... 148
9.4.1. General Considerations ................................ ................................ ............. 148
9.4.1.1. Analy ses for Binary  Data ................................ ........................ 148
9.4.1.2. Analy ses for Continuous Data ................................ ................. 149
9.4.2. Primary  Endpoint(s) ................................ ................................ .................. 150
090177e197c0bffd\Approved\Approved On: 06-Aug-2021 19:09 (GMT)
FDA-CBER-2021-5683-1076885
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Final Protocol Amendment 2 , 06 Aug 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 109.4.3. Secondary  Endpoint(s) ................................ ................................ .............. 151
9.4.4. Exploratory  Endpoint(s) ................................ ................................ ........... 154
9.5. I nterim Anal yses................................ ................................ ................................ ...155
9.5.1. Analy sis Timing ................................ ................................ ........................ 155
9.6. Data Monitoring Committee or Other Independent Oversight Committee ........... 156
10. SUPPORTING DOCUM ENTATION AND OPERATI ONAL 
CONSI DERATIONS ................................ ................................ ................................ ........ 158
10.1. Appendix 1: Regulatory , Ethical, and Study  Oversight Considerations ............. 158
10.1.1. Regulatory and Ethical Considerations ................................ .................. 158
10.1.1.1. Reporting of Safety  Issues and Serious Breaches of the 
Protocol or I CH GCP ................................ ................................ .......158
10.1.2. Financial Disclosure ................................ ................................ ............... 159
10.1.3. I nformed Consent Process ................................ ................................ ......159
10.1.4. Data Protection ................................ ................................ ....................... 160
10.1.5. Dissemination of Clinical Study  Data ................................ .................... 161
10.1.6. Data Qualit y Assurance ................................ ................................ .......... 162
10.1.7. Source Documents ................................ ................................ .................. 163
10.1.8. Study  and Site Start and Closure ................................ ............................ 163
10.1.9. Publication Policy................................ ................................ ................... 164
10.1.1 0. Sponsor’s Qualified Medical Personnel ................................ ............... 165
10.2. Appendix 2: Clinical Laboratory  Tests ................................ ............................... 165
10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow -up, and Reporting ................................ ................................ ....166
10.3.1. Definition of AE ................................ ................................ ..................... 166
10.3.2. Definition of SAE ................................ ................................ ................... 167
10.3.3. Recording/Reporting and Follow- up of AEs and/or SAEs ..................... 169
10.3.4. Reporting of SAEs................................ ................................ .................. 172
10.4. Appendix 4: Contraceptive Guidance ................................ ................................ .173
10.4.1. Male Participant Reproductive Inclusion Criteria ................................ ..173
10.4.2. Female Participant Reproductive Inclusion Criteria ............................... 173
10.4.3. Woman of Childbearing Potential ................................ .......................... 174
10.4.4. Contraception Methods ................................ ................................ ........... 175
090177e197c0bffd\Approved\Approved On: 06-Aug-2021 19:09 (GMT)
FDA-CBER-2021-5683-1076886
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Final Protocol Amendment 2 , 06 Aug 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 1110.5. Appendix 5: Li ver Safety : Suggested Actions and Follow -up Assessments ......176
10.6. Appendix 6: Abbreviations ................................ ................................ ................. 178
10.7. Appendix 7: Criteria for Allowing Inclusion of Participants With Chronic 
Stable HIV, HCV, or HBV Infection ................................ ................................ ......182
10.8. Appendix 8: Country -Specific Appendix –Applicable to Poland Only............. 182
11. REFERENCES ................................ ................................ ................................ ................ 183
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 .................... 53
Table 2. Phase 1 Dose -Finding Participants ................................ ........................... 55
Table 3. Phase 1 L ower -Dose Evaluation Participants ................................ ........... 55
Table 4. Phase 2/3 Selected -Dose Participants –Blood Draws for 
Immu nogenicit y/Efficacy  Assessments ................................ .................... 56
Table 5. Phase 2/3 Selected -Dose Participants –Safet y and 
Tolerability /Efficacy  Assessments ................................ ........................... 57
Table 6. Phase 2/3 L ower -Dose Evaluation Participants –Blood Draws for 
Immunogenicit y/Efficacy  Assessments ................................ .................... 57
Table 7. Phase 2/3 L ower -Dose Evaluation Participants –Safety  and 
Tolerability /Efficacy  Assessments ................................ ........................... 57
Table 8. RR and HR, by  Age, Indicative of Severe S ystemic I llness ..................... 77
Table 9. Local Reaction Grading Scale ................................ ................................ ..83
Table 10. Systemic Event Grading Scale for Participants ≥2 Years of Age ............ 84
Table 11. Systemic Event Grading Scale for Participants <2 Years of Age ............ 85
Table 12. Scale for Fever ................................ ................................ .......................... 86
Table 13. Power Anal ysis for Immunobridging Assessment ................................ .144
Table 14. Precision of SARS- CoV -2 Neutralizing Titer GMT .............................. 145
Table 15. Power for Vaccine Efficacy  Assessment ................................ ................ 146
Table 16. Probability  of Observing at Least 1 AE by  Assumed True Event 
Rates With Different Sample Sizes ................................ ........................ 146
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FDA-CBER-2021-5683-1076887
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Final Protocol Amendment 2 , 06 Aug 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 121.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.  InJanuary 2020, the pathogen causing this outbreak was identified as a 
novel coronavirus 2019. On11 March 2020 , 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 licensed vaccines to prevent infection with SARS -CoV -2or 
COVID -19.  Given the rapid transmission of COVID -19 and incidence of disease in the 
United States and elsewhere, the rapid development of an effective vaccine is of utm ost 
importance .
A Phase 1/2/3 study  (C4591001 )is currentl y being conducted in healthy  individual s 12years 
of age and older to investigate the safety , tolerability , immunogenicity ,and efficacy  of the 
prophy lactic 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 v accine is administered as 2 doses approximately  21 day s apart. On 18 November 2020, 
the primary  efficacy  analy sis 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 the placebo group versus 8 in the
vaccine group .Safet y 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 y ears of age and older. On 1 1December 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 1 0 May  2021, the US FDA 
issued an EUA for use in individual s12 to 15 y ears of age. Other countries have also 
granted EUA or other authorization/approval for this age group (eg, EMA, UK, Switzerland,
and t he Philippines).
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FDA-CBER-2021-5683-1076888
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Final Protocol Amendment 2 , 06 Aug 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 13This Phase 1/2/3 study (C4591007) will initially evaluate up to 3dose levels of BNT162b2 in 
up to 3 age groups (participants ≥5 to <12 y ears, ≥2 to <5 y ears, and ≥ 6months to <2 years 
of age) for safet y, tolerability , immunogenicit y, and efficacy (depending on successful 
immunobridging an d accrual of asufficient number of cases). Phase 1 include sthe dose -
finding portion. I nitiation of dose finding in participants ≥5 to <12 y ears of age is based on 
acceptable blinded safet y data demonstrated 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 data from the same age group. Phase 2/3 (referred to as the selected -dose
portion of the study )includes animmunobridging anal ysisof immune responses in 
participants within each age group (participants ≥5 to <12 years, ≥2 to <5 y ears, and ≥ 6
months to <2 years of age) to those in participants 16 to 25years of age inthe Phase 3 
C4591001 efficacy  study .Safety , tolerability ,and e fficacy (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 30 µg,whereas the following doses were selected in the ongoing C4591007 Phase 2/3 
portion: 10 µgin participants 5 to <12 years of age and 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 y oung 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 with an 
immunobridging analysis of immune responses in participants within each age group to 
participants in the 30-µgPhase 3 C4 591001 efficacy  study .
Overall Design
This is a Phase 1/2/3 study inhealthy  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, the safet y, tolerability , and 
immunogenicit y of BNT162b2 in participants <6 months of age may  subsequently  be 
evaluate d. Participants will range from ≥6 months to <30 y ears of age ,with different dose 
levels assessed in each group .
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PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Final Protocol Amendment 2 , 06 Aug 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 14Dose Levels for Each Age Group in the Phase 1 and Phase 2/3 Dose- Finding/Selected -Dose and 
Lower -Dose Evaluation s
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 -Dose Evaluation
Dose level 3 µg 3 µg 10µg
Participant s 1125
(active 750; 
placebo 375)1125
(active 750; 
placebo 375)4500
(active 3000; 
placebo 1500)6750
Phase 1 Open -Label Lower- Dose Evaluation
Planned dose 
level (s) 3 µg 3/10 µgc3/10 µgc
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
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 years age 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 will evaluate safet y, 
tolerability, and immunogenicity  of BNT162b2 administered on a 2 -dose (separated b y 
approximately  21 day s) 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). 
Dose finding 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 BNT162b2 from up to 
3different 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/or may  
be added with dose levels below the lowest stated dose.
Participants will have blood drawn prior to both Dose 1and Dose 2and 7 day s after Dose 2
to assess immunogenicity  to determine the selected BNT162b 2dose level for Phase 2/3.
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FDA-CBER-2021-5683-1076890
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Final Protocol Amendment 2 , 06 Aug 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 15Lower -dose evaluation :Is the open- label lower -dose evaluation portion of the study  that 
willevaluate safet y, tolerability , and immunogenicity  of BNT162b2 on a 2-dose (separated 
by approximately  21 days) schedule in up to 3 age groups ( participants ≥5 to <12 y ears, 12 to 
<16years, 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 prior to both Dose 1 and Dose 2 and 7 day s after Dose 2 
to assess immunogenicity  to determine the selected BNT162b2 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 theselected dose 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 cases in 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 y ears 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 Dose 1and at 7 day s and 6 months after Dose 2 from up to 
approximately  60 participants ≥10yearsof age.  Thesesample swill be used on an 
exploratory  basis to investigate the postvaccination c ell-mediated immune response at these 
time points.
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 according to recommendations (detailed separatel y and available in the 
electronic stud y reference portal) will have the opportunity  to receive BNT16 2b2.
Lower -doseevaluation : Is the portion of the study  that will evaluate the safety , tolerability , 
and immunogenicit yin each age group at the selected dose level from the Phase 1 lower -dose 
evaluation .
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FDA-CBER-2021-5683-1076891
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Final Protocol Amendment 2 , 06 Aug 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 16In this open -label stud y, all participants will have blood drawn at baseline prior to Dose 1 
and at 1 and 6 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.
Number of Participants
Phase 1: Open -Label Dose -Finding and Lower -Dose Evaluation
Phase 1 isanopen -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-finding evaluation and a minimum of 32 participants per dose level (total of 160
participants) for the lower -dose evaluation .
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
≥6Months to <2years 48 16/16/16 16 N/A
a.A dose level may be expanded to enroll more than 16 subjects per dose level. 
Phase 1 Lower -Dose Evaluation 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 32subjects per dose level. 
Phase 2 /3: Safety, Tolerability, Immunogenicity, and Efficacy
Selected -dose: Is the portion of the study that will evaluate thesafet y, tolerability ,and 
immunogenicit yof the selected dose level in each age group from the Phase 1 dose-finding
portion of the study ,with a total of approximately  6750 participants as an additional 2250 
participants will be included to enlarge the size of the pediatric safet y database .  Participants 
will be randomized in a 2:1ratio to receive active vaccine or placebo .
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FDA-CBER-2021-5683-1076892
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Final Protocol Amendment 2 , 06 Aug 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 17Approximately  450 participants (300 intheactive vaccine group and 150 in the placebo 
group ) randomized in each age group in this phase will contribute to the immunobridging 
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 after Dose 2 ,approximately
70participants from each age group in the original BNT162b2 vaccine group will have an 
immunogenicit yblood draw in order to contribute to the anal ysis.All approximately  6750 
participants will contribute to the VEanalysis for conditional VEand asymptomatic 
infection . Efficacy  will be evaluated within 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 -Dose Participants –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 Total Active Placebo Total Active Placebo
Baseline blood draw  6750 4500 3000 4500 3000 1500 1125 750 375
1 Month after Dose 2 1350 900 450 450 300 150 450 300 150
6 Months after Dose 2 4500 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 2 210 210 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 efficacy assessments.
Phase 2/3 Selected -Dose Participants –Safety and Tolerability /Efficacy Assessment s
Age Total Active Placebo
≥5 to <12 Years 4500 3000 1500
≥2 to <5 Years 1125 750 375
≥6 Months to <2 Years 1125 750 375
All age groups 6750 4500 2250
Lower -dose evaluation : Is the open -label portion of the study  that will 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 1 month after Dose 2 and the overall anal ysis of the persistence 
of immune response at 6 months after Dose 2.  Th ese participants will be enrolled from both 
US and EU sites to ensure this subset is representative of the whole stud y.
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FDA-CBER-2021-5683-1076893
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Final Protocol Amendment 2 , 06 Aug 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 18Phase 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 groups.
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
Intervention Groups and Duration
Phase 1
Dose -finding : Dosing will begin at the low-dose level in 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 same age and dose -level group. The IRC will 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 may commence at the mid -dose level in the same age group, and   
Dosing may commenc e at the low -dose level in participants ≥2 to <5 y ears of age.  
The same process will be followed when moving updose level s 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 , the mid-dose level or high -dose level will 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 safety  assessment after Dose 1, the high-dose level will not commence. 
Based on safet y assessments, t he second dose may  be given at a lower dose level .
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FDA-CBER-2021-5683-1076894
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Final Protocol Amendment 2 , 06 Aug 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 19Duration of the dose-f inding portion of the study: Participants are expected to participate 
for up to a maximum of approximately  26months.
Lower -dose e valuation :As higher doses have been assessed in each age group, all age/dose 
levels will proceed concurrentl y.
Duration 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 b y age group.  For each age gr oup t o proceed to 
Phase 2/3, safet y, tolerability ,and immunogenicity data from 7 day s after Dose2 for the 
selected vaccine dose level in 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 up to a maximum of approximately  26months.
Lower -dose e valuation : 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 b y 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 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.
Data Monitoring Committee or Other Independent Oversight Committ ee
The study  will utilize an IRC, an internal Pfizer committee that will review data to allow 
dose finding in 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 separatel y 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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FDA-CBER-2021-5683-1076895
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Final Protocol Amendment 2 , 06 Aug 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 20Within 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 
declared if the lower limit of the 95% CI for the GMR (each age group to the comparator age 
group from the C4591001 study )is >0.67 and 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 RCDCs and the proportion of 
participants with neutralizing titer s ≥LLOQ .
A sample size of 225evaluable participants in each age group evaluated in this study  and the 
corresponding comparator group from the C4591001 study  will provide a power of 90. 4% 
and 92.6% to declare immunobridging success based 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 across allage group swhere immunobridging 
success is declared in the Phase 2/3 selected- dose portion of the study  (if the required number 
ofcases are not accrued in either ofthe 2 individual 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 
group s (≥5 to <12 years, ≥6 months to <2 years and ≥2 to <5 years combined ) will be 
conducted onl y ifat least 22 cases are accrued in those age 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 conducted across the 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 prim ary safet y 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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FDA-CBER-2021-5683-1076896
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Final Protocol Amendment 2 , 06 Aug 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 211.2.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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FDA-CBER-2021-5683-1076897
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Final Protocol Amendment 2 , 06 Aug 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 22Phase 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 receive BNT162b2Phase 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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PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
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PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 23Dose Levels for Each Age Group in the Phase 1 and Phase 2/3 Dose- Finding/Selected -Dose and Lower -Dose Evaluations
Phase 1 Open -Label Dose -Finding Evalu ation
≥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 16a16/32a16/16/16b112
Phase 2/3 Observer- Blinded, Placebo -Controlled Selected -Dose Evaluation
Dose level 3 µg 3 µg 10 µg
Participant 1125
(active 750; placebo 
375)1125
(active 750; placebo 
375)4500
(active 3000; 
placebo 1500)6750
Phase 1 Open -Label Lower -Dose Evaluation
Planned dose 
level(s) 3 µg 3/10 µgc3/10 µgc
Participant 32 32/32 32/32 160
Phase 2/3 Open -Label Lower -Dose Evaluation
Planned dose level TBD TBD TBD
Participant 300 300 300 900
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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PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Final Protocol Amendment 2 , 06 Aug 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 241.3. S chedule of Activ ities
The SoA table 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 protocol.
The investigator may  sche dule 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 1 Dose -Finding Portion
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-C symptoms that overlap with specific 
systemic events (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 clinic al picture is more indicative of a possible COVID-19 /MIS-C illness 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
Confirm eligibility X X
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FDA-CBER-2021-5683-1076900
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Final Protocol Amendment 2 , 06 Aug 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 25Visit 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
Review temporary delay criteria X X
Measure vital signs (including body temperature) X X
Perform physical examination (including height and 
weig ht)dX X
Perform u rine p regnancy 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
Provide a thermometer and caliper (measuring) device X
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 platformX X
090177e197c0bffd\Approved\Approved On: 06-Aug-2021 19:09 (GMT)
FDA-CBER-2021-5683-1076901
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Final Protocol Amendment 2 , 06 Aug 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 26Visit 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
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: 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 respon se 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 node survey . Height and weight will be 
collected only at Visit 1.
e. 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 e ndpoints.
f. Refer to Section 8.3.1 for the time period for collecting SAEs.
090177e197c0bffd\Approved\Approved On: 06-Aug-2021 19:09 (GMT)
FDA-CBER-2021-5683-1076902
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Final Protocol Amendment 2 , 06 Aug 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 271.3.2. 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 16 to 8 Days 
After Visit 228 to 35 Days 
After Visit 2175 to 189 Days 
After Visit 2
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 (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
Review temporary delay criteria X X
Measure vital signs (including body temperature) X X
Perform clinical assessmen tc X X
Perform u rine p regnancy 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
Provide a thermometer and caliper (measuring) device X
090177e197c0bffd\Approved\Approved On: 06-Aug-2021 19:09 (GMT)
FDA-CBER-2021-5683-1076903
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Final Protocol Amendment 2 , 06 Aug 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 28Visit 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 16 to 8 Days 
After Visit 228 to 35 Days 
After Visit 2175 to 189 Days 
After Visit 2
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 participant or participant’s 
parent(s)/legal guardian to delete application
Abbreviations: 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 physic al 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. 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 8.3.1 for the time period for collecting SAEs.
090177e197c0bffd\Approved\Approved On: 06-Aug-2021 19:09 (GMT)
FDA-CBER-2021-5683-1076904
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Final Protocol Amendment 2 , 06 Aug 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 291.3.3. Phase 2/3 Selected -Dose Portion
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-C symptoms 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, 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-C illness rather than vaccine r eactogenicit y.For details, see Section 8.13.
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.Parti cipants 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 )willhave the opportunity  to receive the EUA -approved dose level of BNT162b2 .  
Visit 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 (if appropriate) 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
090177e197c0bffd\Approved\Approved On: 06-Aug-2021 19:09 (GMT)
FDA-CBER-2021-5683-1076905
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Final Protocol Amendment 2 , 06 Aug 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 30Visit 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
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
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
Provide thermometer and c aliper (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 X X
090177e197c0bffd\Approved\Approved On: 06-Aug-2021 19:09 (GMT)
FDA-CBER-2021-5683-1076906
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Final Protocol Amendment 2 , 06 Aug 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 31Visit 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
participant’s parent(s)/legal guardian remains 
comfortable with chosen e -diary platform 
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
090177e197c0bffd\Approved\Approved On: 06-Aug-2021 19:09 (GMT)
FDA-CBER-2021-5683-1076907
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Final Protocol Amendment 2 , 06 Aug 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 32Visit 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 1.3.3.1 or Section 1.3.3.2X
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; 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 ≥10years of 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, cardiovascula r 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 2250 participants includ ed to enlarge the size of the pediatric safety database.
i. 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.
j. Refer to Section 8.3.1 for the time period for collecting SAEs.
090177e197c0bffd\Approved\Approved On: 06-Aug-2021 19:09 (GMT)
FDA-CBER-2021-5683-1076908
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Final Protocol Amendment 2 , 06 Aug 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 331.3.3.1. Phase 2/3 Selected -Dose Portion : Participants Who Originally Received BNT162b2 or Placebo Recipients Who Decline 
BNT162b2
After unblinding at Visit 5, 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-C symptoms 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) 350to 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.
090177e197c0bffd\Approved\Approved On: 06-Aug-2021 19:09 (GMT)
FDA-CBER-2021-5683-1076909
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Final Protocol Amendment 2 , 06 Aug 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 341.3.3.2. Phase 2/3 Selected -Dose Portion : 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 .  
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-C symptoms 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, 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 
illness r ather than vaccine reactogenicit y.For details, see Section 8.13.
Visit 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) 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 
After Visit B532to 560Days 
After Visit BOptimally Within 3 Days 
After Potential COVID -19 
Illness Onset
Type of Visit Clinic Clinic TelephonebTelephone Telephone Clinic or 
TelephoneClinic or Telehealth
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 examinationcX X
090177e197c0bffd\Approved\Approved On: 06-Aug-2021 19:09 (GMT)
FDA-CBER-2021-5683-1076910
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Final Protocol Amendment 2 , 06 Aug 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 35Visit 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) 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 
After Visit B532to 560Days 
After Visit BOptimally Within 3 Days 
After Potential COVID -19 
Illness Onset
Type of Visit Clinic Clinic TelephonebTelephone Telephone Clinic or 
TelephoneClinic or Telehealth
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 immunogenicity Xd
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 X
Collect SAEs as appropriatefX X X X X
Collect e -diary or assist the participant’s 
parent(s)/legal guardian to delete 
applicationX
090177e197c0bffd\Approved\Approved On: 06-Aug-2021 19:09 (GMT)
FDA-CBER-2021-5683-1076911
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Final Protocol Amendment 2 , 06 Aug 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 36Visit 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) 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 
After Visit B532to 560Days 
After Visit BOptimally Within 3 Days 
After Potential COVID -19 
Illness Onset
Type of Visit Clinic Clinic TelephonebTelephone Telephone Clinic or 
TelephoneClinic or Telehealth
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; IRT = interactive response technology; 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. A physical examination will include, at a minimum, assessments of general appearance, lungs, cardiovascular system, and lymph node survey.
d. Blood draw is only for participants who become eligible for receipt of BNT162b2 or another COVI D-19 vaccine according to local or national recommendations prior to 
Visit 5.
e. 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 expecte d endpoints.
f.Refer to Section 8.3.1 for the time period for collecting SAEs.
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PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
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Final Protocol Amendment 2 , 06 Aug 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 371.3.4. 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 1 28 to 35 Days After Visit 2 175 to 189 Days After Visit 
2
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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PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Final Protocol Amendment 2 , 06 Aug 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 38Visit 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 1 28 to 35 Days After Visit 2 175 to 189 Days After Visit 
2
Type of Visit Clinic Clinic Clinic Clinic 
Provide thermometer and c aliper (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/MIS -C–related clinical and 
laboratory information (including local diagnosis)
Abbreviation s: CRF = case report form; HIV = human immunodeficiency virus .
a. T his 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 age .
d.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 8.3.1 for the time period for collecting SAEs.
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FDA-CBER-2021-5683-1076914
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Final Protocol Amendment 2 , 06 Aug 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 392.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 -dose study  is to rapidly 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 -19.  Given the glob al 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.
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 av ailable 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.1,2
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 
affected b y both the primary  COVID -19 disease and the less common secondar y
inflammatory  complications, including MIS-C.3,4
On 11 March 2020, the WHO characterized the COVID -19 outbreak as a pandemic.5  
TheWHO Weekly  Epidemiology  Update Report dated 27September 2020 noted more than 
32.7 million COVID -19 cases and 991,000 deaths globall y, including 16,233,110 confirmed 
cases with 546,864 deaths in the Americas.6  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 genera lly mild.7,8,9Nevertheless, severe cases, including those requiring intensive 
care support, have been reported.3Of US children diagnosed with COVID -19,5.7% to 20% 
were hospitalized , including 0.58% to 2.0% admitted to an I CU.10
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PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Final Protocol Amendment 2 , 06 Aug 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 40MIS-C, an emerging condition that appears to be temporally  related to recen t exposure to 
SARS -CoV -2, has been described and frequentl y requires ICU admission, and may  have a 
fatal outcome.4,11MIS-C is a febrile hy perinflammatory  condition with frequent evidence of 
cardiac damage and dermatologic, mucocutaneous, and GI features .11The sy ndrome appears 
to have some overlap with Kawasaki disease shock sy ndrome.12,13Compared with Kawasaki 
disease, patients with MIS- C are older, have more cardiac injury , and are more likely  to be 
black, Hispani c, or of South Asian descent.14As of 29June 2020, approximately 1000 cases 
have been reported.14As 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 complicati ons 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%).15Death rates of 2% to 4% have been reported.14MIS-C has been reported in many  
countries throughout North America, Europe, Asia, and Latin America ,16including the 
US,4,11Italy,17and France.18The United States currently  has the most reported cases 
globall y,with the number of confirmed cases continu ingto rise globall y. There are currently  
no licensed vaccine s or effective antiviral drugs to prevent SARS -CoV -2 infections or the 
disease it causes, COVID -19.19
A proph ylactic, RNA -based SARS -CoV -2 vaccine provides one of the most flexible and 
fastest approaches available to immunize against the emerging virus.20,21
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 traditional vaccine approaches.  Unl ike 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 vaccines 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 
traditional vaccine approaches.  This capability  is pivotal to e nable the most effective 
response in outbreak scenarios.20,21
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 
prophy lactic BNT162 vaccine candidates against COVID -19. The vaccine candidate 
selected for evaluation in the C4591001 P hase 2/3 study  is BNT162b2 at a dose level of 
30µg and as 2 doses given approximately  21 days apart. On 18 November 2020, the primary  
efficacy  anal ysis results were announced, which demonstrate d BNT162b2 to be 95% 
effective against COVID -19 beginning 7 day s after the second dose; 170 confirmed cases of 
COVID -19 were evaluated, with 162 observed in the placebo group versus 8 in the vaccine 
group .Safet y data from approximately  38,000 participants randomiz ed 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 .22On 11 December 2020, the US 
FDA issued an EUA for use in individuals 16 y ears o f age and older. Other countries have 
also granted EUA (eg, Canada, Mexico, Bahrain), and Pfizer and BioNTech are anticipating 
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PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Final Protocol Amendment 2 , 06 Aug 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 41further regulatory  decisions in other countries.23On 10 May  2021, the US FDA issued an 
EUA for use in individuals 12 to 15 y ears of age. Other countries have also granted EUA or 
other authorization/approval for this age group (eg, EMA, UK, Switzerland, andthe 
Philippines).
This Phase 1/2/3 study  (C4591007) will initially evaluate 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 
≥6months to <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 -finding portion .  Initiation of dose finding in participants ≥5 to 
<12years of age will be based on the acceptable blinded safet y data demonstrated in 2260
12-through 15-year-oldsat the 30-µ g dose level in the C4591001 study .24The 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 data from the same age group. Phase 2/3
(referred to as the selected -dose portion of the study )includes an immunobridging analy sisof
immune responses in participants ≥6 months to <12 years of age to th ose in participants 16to 
25 years of age in 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 C459 1007 study the following doses 
were selected: 10 µgin participants 5 to <12 years of age and 3 µg in participants 6 months 
to <5 y earsof 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 
immunogenicit y. The Phase 2/3 BNT162b2 dose level will be selected based on t he Phase 1 
assessments with an immunobridging analy sis of immune responses in participants within 
each age group to participants in the 30- µgPhase 3 C4591001 efficacy  study . 
2.2.1. Clinical Overview
The BNT162 vaccine candidates use an RNA to deliver genetic in formation 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 effects. The C4591001 study25is 
currentl y 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 .26Vaccine -related enhanced disease for vaccines against related 
coronaviruses (SARS -CoV -1 and MERS) has been reported onl y in animal models.27,28To 
date, no enhanced disease has been observed in SARS -CoV -2 animal models with any  
SARS -CoV -2 vaccine platform, including RNA -based vaccines. Such effects have not been 
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PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
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PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 42documented 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 trial 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 c ontinued clinical development of BNT162b2.
In 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 reac tions were injection site reactions (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 hypersensitivity -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, and 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 
frequentl y 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 .22
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 
safet y profile to date, which sho ws 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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PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Final Protocol Amendment 2 , 06 Aug 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 432.3.1. Risk Assessment
Potential Risk of Clinical Significance Summary of Data/Rationale for Risk Mitigation Strategy
Study Intervention(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 comm on 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 react ogenicity 
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 s afety profile of a novel vaccine is not yet fully 
characterized.
Adverse reactions (risk s) 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 include s
participants 12years of age and older .
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Page 44Potential 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.26
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 low er-dose evaluation 
participants ,cases of COVID -19 developing 
during the study are m onitored and will be 
reported as AESIs.
MIS-C. Febrile hyperinflammatory condition with 
multisystem (≥2)organ involvement 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. 
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 w ill work with sites to ensure an appropriate 
COVID -19 prevention strategy. Poten tial 
COVID -19/MIS -Cillness 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 .
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Page 45Potential Risk of Clinical Significance Summary of Data/Rationale for Risk Mitigation Strategy
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 w illobtain 
the blood draw .To m inimize the total amount of 
blood drawn, all participants in Phas e 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 
2planned blood draw s.
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 ismade within the 
ICD, with instruction to contact a healthcare 
professio nal if a case issuspected .
For anaphylaxis, there is an on-sitefor a 30-minute 
observation period after vaccination .
Instruction s forhandling suspected cases of 
myocarditis and pericarditis are found in 
Section 8.14
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PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 462.3.2. 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 r isks identified in association 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 estimands below 
are participants ≥5 to <12 years, ≥2 to <5 years, and ≥6 months to <2 years of age .
The lower -dose age groups referred to in the objectives and estimands below are a separate 
cohort of participan ts ≥5to <12 years, 12 to <16 years, and 16 to < 30 years of age. 
3.1.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 ≥6months to <2 years of 
age:
 Local reactions ( tenderness at the 
injection site, redness, and 
swelling)
 Systemic events (fever, decreased 
appetite, dro wsiness, and 
irritability )
 AEs
 SAEs 
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FDA-CBER-2021-5683-1076922
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Final Protocol Amendment 2 , 06 Aug 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 47Phase 1
Objectives Estimands Endpoints
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 
without evidence of past SARS-CoV -2 
infection Confirmed cases as per CDC 
criteria 
3.2.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
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 
090177e197c0bffd\Approved\Approved On: 06-Aug-2021 19:09 (GMT)
FDA-CBER-2021-5683-1076923
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Final Protocol Amendment 2 , 06 Aug 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 48Phase 2/3
Objectives Estimands Endpoints
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 rec eipt 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 ne utralizing 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
 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 P hase 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
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FDA-CBER-2021-5683-1076924
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Final Protocol Amendment 2 , 06 Aug 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 49Phase 2/3
Objectives Estimands Endpoints
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 evidence (up 
to 1 month after receipt of Dose 2) of 
past SARS -CoV -2 infecti on: 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 2 5 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
 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 i n 
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 <30 years 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 
participants with seroresponse in 
participants 16 to <30 years of a ge 
and 16 to 55 years of age from 
Phase 2/3 of the C4591001 study
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FDA-CBER-2021-5683-1076925
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Final Protocol Amendment 2 , 06 Aug 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 50Phase 2/3
Objectives Estimands Endpoints
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 evaluable 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 participan ts in the selected -
dose portion of 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
In the ≥5 to <12 years age group 
in the selected -dose portion of 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 <2 years and 
≥2 to <5 years age groups in the 
selected -dose portion of 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 portion of 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 <5 years 
combined) did not accrue 22 cases100 × (1 –IRR) [ratio of active 
vaccine to placebo]
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FDA-CBER-2021-5683-1076926
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Final Protocol Amendment 2 , 06 Aug 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 51Phase 2/3
Objectives Estimands Endpoints
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 portion of 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 portion of 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 <5 years age groups in the 
selected -dose portion of 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 portion of 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]
To describe the efficacy of prophylactic 
BNT162b2 against asymptomatic 
infection in participants in the selected -
dose portion of 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 portion of the study without, and 
with and without, evidence of past 
SARS CoV -2 infection in each age 
group and in all age groups combinedIn pa rticipants 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
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FDA-CBER-2021-5683-1076927
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Final Protocol Amendment 2 , 06 Aug 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 52Phase 2/3
Objectives Estimands Endpoints
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 COVID -19 and severe 
COVID -19 cases in participants in the 
selected -dose portion of 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 portion of the study Confirmed cases as per CDC 
criteria 
To describe the serological responses in 
Phase 2/3 participants in participants in 
the selected -dose portion of 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
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
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 sero response. 
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PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Final Protocol Amendment 2 , 06 Aug 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 534.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, the safet y, tolerability , and 
immunogenicit y of BNT162b2 in participants <6 months of age may  subsequently  be 
evaluated. Participants will r ange from ≥6 months to <30 y ears of a gewith different 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 -Dose and Lower -Dose Evaluations
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
Phase 2/3 Observer- Blinded, Placebo -Controlled Selected -Dose Evaluation
Dose level 3 µg 3 µg 10 µg
Participant s 1125
(active 750; 
placebo 375)1125
(active 750; 
placebo 375)4500
(active 3000; 
placebo 1500)6750
Phase 1 Open -Label Lower -Dose Evaluation
Planned dose 
level (s) 3 µg 3/10 µgc3/10 µgc
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
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 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.
4.1.1. Phase 1
Dose -finding: Is the open -label dose -finding portion of the study  that will evaluate 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 ≥ 6months to <2 years of age).
Dosefinding is b eing 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 .
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FDA-CBER-2021-5683-1076929
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Final Protocol Amendment 2 , 06 Aug 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 54The 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/or may 
beadded with dose le vels 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) schedule in up to 3 age groups ( participants ≥5 to <12 y ears, 12 to 
<16 y ears, 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 prior to both Dose 1 and Dose 2 and 7 day s after Dose 2 
to assess immunogenicity  to determine the selected BNT162b2 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  that will 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, depending 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 25 years of age in the C4591001 study will be based on 
immunogenicity data collected at baseline and 1 month after Dos e 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 month safter Dose 2 (original 
BNT162b2 group onl y). In addition, efficacy  agains t 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 a 6-month follow -up visit, all participants will be unblinded. Participants who originall y 
received placebo will be offered the opportunit y to receive BNT162b2 as pa rt of the stud y.
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PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Final Protocol Amendment 2 , 06 Aug 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 55Participants ≥12years of age who originall y received placebo and become eligible for receipt 
of BNT162b2 according to recommendations (detailed separatel y, and available in the 
electronic stud y reference portal )will have the opportunit y to receive BNT162b2.
Lower -dose evaluation :Is the portion of the study  that will 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 pa rticipants will have blood drawn at baseline prior to Dose 1 
and at 1 and 6 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. 
4.1.3. Number of Part icipants
4.1.3.1. Phase 1 : Open-L abel Dose-Finding and 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 144participants) for the 
dose-finding evaluation and a minimum of 32 participants per dose level (total of 160 
participants) for the lower -dose evaluation ; seeTable 2and Table 3.
Table 2.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 <5 Y ears 48 16/16/ 16 16 N/A
≥6 M onths to <2 years 48 16/16/16 16 N/A
a.A dose level may be expanded to enroll more than 16 subjects per dose level.
Table 3.Phase 1 Lower -Dose Evaluation 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 subjects per dose level. 
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FDA-CBER-2021-5683-1076931
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Final Protocol Amendment 2 , 06 Aug 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 564.1.3.2. 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 1 dose finding ,with a total of approximately  6750 participants as an additional 2250 
participants will be included to enlarge the size of the pediatric safet y database .  Participants 
will be randomized in a 2:1ratio to receive active vaccine or placebo (Table 4).
Approximately  450 participants (300 in the active vaccine group and 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 
participants will contribute to the VEanalysis for conditional VEand as ymptomatic 
infection . Efficacy  will be evaluated within or across age groups in which immunobridging 
is successful, depending on accrual of a sufficient number of cases in those age groups.
At designated US sites, an a dditional optional whole blood sample of approximately 10mL 
will be obtained prior to Dose 1and at 7 day s and 6 months after Dose 2 from up to 
approximately  60 participants ≥10years of age .  Thesesample swill be used on an 
exploratory  basis to investig ate the postvaccination cell-mediated immune response at these 
time points.
Table 4.Phase 2/3 Selected -Dose Participants –Blood Draws for 
Immunogenicity/Efficacy A ssessments
All Age Groups ≥5 to <12 Years of Age ≥2 to <5 Years and
≥6Months to <2 Years of 
Agea
Total Active Placebo Total Active Placebo Total Active Placebo
Baseline blood draw 6750 4500 3000 4500 3000 1500 1125 750 375
1 Month after Dose 2 1350 900 450 450 300 150 450 300 150
6 Months after Dose 2 4500 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 2 210 210 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 efficacy assessments ( Table 5).
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FDA-CBER-2021-5683-1076932
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Final Protocol Amendment 2 , 06 Aug 2021
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CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 57Table 5.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 1125 750 375
≥6 Months to <2 Years 1125 750 375
All age groups 6750 4500 2250
Lower -dose evaluation :Is the open -label portion of the study  that will evaluate the safety , 
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
(Table 6 ).  
Approximately  300active participants in each age group in this phase will contribute to the 
immunobridging anal ysis at 1 month 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.
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 groups.
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
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Page 584.1.4. Intervention Groups and Duration
Phase 1 open-l abel dose-finding : Dosing will begin at the low -dose level in 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 
will r eview 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 may commence at the mid -dose level 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 dose level s 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-dose level or high- dose level will 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 f the mid -dose level is considered not 
acceptable based on safety assessment after Dose 1, the high-dose level will not comm ence. 
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 t o 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 will be 
confirmed to be acceptable .  
Duration: Participants are expected to participate for up to a maxim um of approximately  
26months.
Phase 1 lower -dose evaluation : As safet y 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
TheIRC will review safety  data (e -diary  and AE s) acquired up to 7 day s after Dose 2.
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Page 59Phase 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.  
Duration: 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-C in Phase 1 dose -finding and Phase 2/3 
selected- dose participants will be conducted as part 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-C illness visit 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 teratogenici ty based on the intended mechanism 
of action of the compound. Therefore, the use of a highl y effective method of contraception 
is required (see Appendix 4 ) for WOCBP.
4.3.Justification for Dose
Dose -finding andselected -doseevaluation :Based on acceptable blinded safet y data in 
2260 12 -through 1 5-year-olds at the 30- µg dose level in the C4591001 study , dose-finding is 
considered in this study using the same vaccine candidate .24  Therefore, this study  will start 
with a 10-µgdose level 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 another dose level in 
this age group or initiating the younger age groups (20 µg, 30 µgwith an option of 3 µg).
Lower -dose e valuation (participants 5 to <12, 12 to <16, 16 to <30 years of age ):The 
authorized dose of BNT162b2 in adolesc ents and y oung adults 12 y earsof age and 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 age and 3 µg in participants 6 months 
to <5 y earsof 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 y oung adults, additional lower dose levels of BNT162b2 (3 µg, 10 µg) will be evaluated 
todetermine 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 immu nogenicity . The 
Phase 2/3 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 604.4.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 collect ion 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 par ticipation 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 onl y if all of the following criteria appl y:
Age and Sex :
1. Male or female partic ipants ≥6 months to <12years of age ,at the time of randomization , 
at Visit 1forthedose-finding /selected- dose evaluation and for participants ≥5 to <30
yearsof age , at the time of randomization, at Visit 1 for the lower -dose evaluation .
Refer to Appendix 4 for reproductive criteria for male ( Section 10.4.1 ) and female 
(Section 10.4.2 ) participants.
Type o f Participant and Disease Characteristics:
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,
lifesty le considerations, and other study  procedures.
3.Health y 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.
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Page 61Phase 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.
4.Participants are ex pected to be available for the duration of the study  and wh ose 
parent(s)/legal guardian can be contacted b y telephone during study participation.
5. Negative urine pregnancy  test for female participants who are biologically capable of 
having children.
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:
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 :
Medical Conditions:
1.Phase 1 only: Past clinical (based on COVID -19 sy mptoms/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. P revious or current diagnosis of MIS-C.
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Page 625.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 investig ator’s judgment, make the participant inappropriate for the 
study .Note: T his includes both conditions that may increase the risk associated with 
study intervention 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: S table t ype 1 diabetes and hypothy roidism are permitted .
9. Bleeding diathesis or condition associated with prolonged bleeding that would, in the 
opinion of the investigator, contraindicate intramuscular injection.
10.Female who ispregnant or breastfeeding.
Prior/Concomitant Therapy:
11.Previous vaccination with any  coronavirus vaccine.
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 s ystemic 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.
13. Receipt of blood/plasma products, immun oglobulin, 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 .
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Page 63Diagnostic 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 directl y 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 method 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 /enrolled in the study . A 
minimal set of screen failure information is required to ensure transparent reporting of screen 
failure 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  SAE s.
Individuals who do not meet the criteria for participation in this study  (screen failure) may be 
rescreened under a different participant number.
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Page 645.5. 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 resolved 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 COVID -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 l oss 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.
6.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 according to t he study  protocol. In Phase 2/3, the selected -dose portion is 
placebo- controlled and the lower -dose evaluation portion is open- label .
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Page 65Phase 1 will evaluate a 2 -dose (separated b yapproximately 21 day s) schedule of up to
3different dose levels ofRNA vacci ne candidate BNT162b2 for active immunization against 
COVID -19,to determine the final dose level of BNT162b 2in Phase 2/3 for each age group .  
The investigation alRNA vaccine candidate andsaline placebo ,in Phase 2/3 of the selected-
dose portion, are the 2potential study  interventions that may  be administered to a study  
participant:
BNT162b2 (BNT162 RNA -LNP vaccine utilizing modRNA and encoding the P2 S):
10µg, 20 µg, and 30µg,with an option for 3 µg, another dose level .
Normal saline (0.9% sodium chl oride solution for injection) .
6.1.Study Intervention(s) Administered
Intervention Name BNT162b2 
(BNT162 RNA -LNP V accine 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 µgN/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 interventio n 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 w ith dose 
levels below the low est stated dose .
6.1.1. 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 selected- dose participants 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, s tudy intervention should be administered 
intramuscularl y into the deltoid muscle, preferably of the nondominant arm . Study 
intervention will be administered by an unblinded administrator.
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Page 66For 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, p harmacist, or medical assistant) as allowed by  
local, state, and institutional guidance. 
Study  intervention administration details will be recorded on the CRF.
6.2.Preparation/Handling/Storage/Accountability
1.The investigator or designee must confirm appropria te 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 interventions
must be stored in a secure, environmentall y controlled, and monitored (manual or 
automated recording ) area in accordance with the labeled storage condition s with access 
limited to the investigator and authorized site staff.  At a minimum, daily  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 return 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 sit e should actively  pursue 
options for returning the study  intervention to the storage conditions described in the 
labeling, as soon as possible.  Once an excursion is identified, the study  intervention must 
be 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 b y 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 .
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Page 677. The investigator, institution, or the head of the medi cal institution (where applicable) is 
responsible for stud y intervention accountability , reconciliation, and record maintenance 
(ie, receipt, reconciliation, and final disposition records) , such as the IPAL or sponsor -
approved equivalent . All study  intervention swill be accounted for using a study  
intervention accountability  form/record .
8.Further guidance and information for the final disposition of unused study  interventions 
are provided in the I P manual. All destruction must be adequatel y documented.  If
destruction is authorized to take place at the investigator site, the investigator must ensure 
that the materials are destroy ed in compliance with applicable environmental regulations, 
institutional policy , and any  special instructions provided by  Pfizer.
9.Upon identification of a product complaint, notify the sponsor w ithin 1 business day  of 
discovery  as described in the I P manual.
6.2.1. Preparation and Dispensing
See the IP manual for instructions on how to prepare the stud y intervention for 
administration.  St udy intervention should be prepared and dispensed by  an appropriatel y
qualified and experienced member of the stud y staff (eg, ph ysician, nurse, phy sician’s 
assistant, nurse practitioner, pharmacy  assistant/technician, or pharmacist) as allowed b y 
local, state, and institutional guidance.   A second staff member will verify  the dispensing.
Study  intervention and placebo (for Dose s1 and 2 in the Phase 2/3 selected- dose portion of 
the study ) will be prepared by  qualified unblinded site personnel accordi ng to the IP manual.  
The study  intervention will be administered in such a way  as to ensure the participants 
remain blinded.
6.3.Measures to Minimize Bias: Randomization and Blinding
6.3.1. Allocation to Study Intervention
Allocation (randomization) of participants to vaccine groups will proceed through the use of 
an IRT s ystem (I WR).  The site personnel (study  coordinator or specified designee) will be 
required to enter or select information including but not limited to the user’s I D and 
password, the protocol number, and the participant number.  The site personnel will then be 
provided with a vaccine assignment and randomization number.  The IRT sy stem will 
provide a confirmation report containing the participant number, randomization number, and 
study  intervention allocation assigned.  The confirmation report must be stored in the site’s 
files.
The study -specific I RT reference manual and I P manual will provide the contact information 
and further details on the use of the IRT s ystem.
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Page 686.3.2. Blinding of Site Personnel (Phase 2/ 3 Selected -Dose Portion Only)
The study  staff receiving, storing, dispensing, preparing, and administering the study  
interventions will be unblinded.  All other study  and site personnel, including the 
investigator, investigator staff, and participants, wil l be blinded to study  intervention 
assignments.  In particular, the individuals who evaluate participant safet y will be blinded.  
Because BNT162b2 and placebo are different in phy sical appearance, the study  intervention 
syringes will be administered in a m anner that prevents the study  participants from 
identify ing the study  intervention ty pe based on its appearance.
The responsibility  of the unblinded dispenser and administrator must be assigned to an 
individual or individuals who will not participate in th e evaluation of an y study  participants.  
Contact between the unblinded dispenser and study participants and unblinded administrator 
and study  participants should be kept to a minimum.  The remaining site personnel must not 
know study  intervention assignmen ts.
6.3.3. Blinding of the Sponsor
At the 6- month (Visit 5/Phase 2/3) selected -dose 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 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 study  reference portal) 
will h ave the opportunity to receive the EUA -approved dose level of BNT162b2.  
For the participants in Phase 1 and in the Phase 2/3 lower -dose evaluation, in which only  
active vacc ine is being administered, blinding is not applicable. T he majority  of sponsor 
staff will be blinded to study  intervention allocation for Dose s1 and 2 in the Phase 2/3
selected- dose portion of the study .  All laboratory  personnel performing serology  assay s will 
remain blinded to study  intervention assigned/received throughout the stu dyin the Phase 2/3
selected- dose portion of the study . The following sponsor staff, who will have no part in the 
blinded conduct of the study , will be unblinded in the Phase 2/3 selected -dose portion of the 
study  (further details will be provided in a data blinding plan):
Those study  team members who are involved in ensuring that protocol requirements for 
study  intervention preparation, handling, allocation, and administration are fulfilled at the 
site will be unblinded for the duration of the stud y (eg , unblinded study manager, 
unblinded clinical research associate).
Unblinded clinician(s) who are not direct members of the study  team and will not 
participate in an y other study -related activities will review unblinded protocol deviations.
An unblinded team supporting interactions with, and anal yses for, the DMC 
(seeSection 9.6).  This will comprise a statistician and programmer(s) .
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Page 69An unblinded submissions team will be responsible for preparing unblinded anal yses and 
documents to support regulatory  activities that may  be required while the study  is 
ongoing. With the exception of a small group of statisticians and programmers, who will 
become unblinded at the participant level at the time of the first planned reporting event 
for the Phase 2/3 selected- dose portion of the study  for a given age group to perform the 
analyses,other members of this team will only  be unblinded at the group level and not 
have access to individual participant assignments. A separate group of statisticians and 
programmers will remain blinded and continue supporting the blinded conduct of the 
study . 
At Visit 5 orother time during the Phase 2/3 selected- dose portion of the study , when a 
participant who originally  received placebo receives BNT162b2 per the SoA in 
Section 1.3.3.2 or become eligible for receipt of BNT162b2 according to 
recommendations, the study  team will become unblinded to the participant’s original 
study  intervention allocation.
After the stud y data used for submission become public, the blinded study  team will also 
have access to those data and become unblinded at a group level.
6.3.4. Breaking the Blind
For the Phase 2/3 selected -dose portion of the study  up to Visit 5 , the IRT will be 
programmed with b lind-breaking instructions. In case of an emergency , the investigator has 
the sole responsibility  for determining if unblinding of a participant’s study  intervention
assignment is warranted. Participant safet y must always be the first consideration in ma king 
such a determination. If the investigator decides that unblinding is warranted, the 
investigator should make every  effort to contact the sponsor prior to unblinding a 
participant’s vaccine assignment unless this could delay  further management of the 
participant. If a participant’s vaccine assignment is unblinded, the sponsor must be notified 
within 24 hours after breaking the blind. The date and reason that the blind was broken must 
be re corded in the source documentation and CRF.
The study -specific I RT reference manual and I P manual will provide the contact information 
and f urther details on the use of the IRT s ystem.
Instructions on how to unblind participants at Visit 5 will be provided separately .
6.4. Study Intervention Compliance
When participants are dosed at the site, they  will receive study  intervention directly  from the 
investigator or designee, under medical supervision.  The date and time , as well as the 
anatomical location, of each dose administered in the clinic will be recorded in the source 
documents and recorded in the CRF.  The dose of study  intervention and study  participant 
identification will be confirmed at the time of dosing by  a member of the study  site staff 
other than th e person administering the study  intervention.
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Page 706.5. Concomitant Therapy
6.5.1. Prohibited During the Study
Receipt of the following vaccines and medications during the time periods listed below may  
exclude a participant from the per -protocol anal ysisfrom that point o nwards , and may  
require vaccinations to be discontinued in that participant; however, it is anticipated that the 
participant would not be withdrawn from the study  (see Section 7).
Medications or vaccinations should not be withheld if required for a participant’s medical 
care.
Receipt of an y nonlive vaccine , any  seasonal or pandemic influenza vaccine, or any  
rotavir us vaccine within 14 day s, or any  live vaccine (ie, excluding live influenza and 
rotavirus vaccines) within 28 days, before study  intervention administration.
Receipt of an y 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.
Receipt of chronic s ystemic treatment with known immunosuppressant medications, or 
radiotherap y, is prohibited within 60 day s before enrollment through conclusion of the 
study .
Receipt of s ystemic corticosteroids (>2 mg/kg/dose of prednisone or equivalent) for 
≥14 day s is prohibited from 28 day s prior to enrollment through Visit 4 (1-month follow -
up after Dose 2) . 
Receipt of blood/plasma products, immunoglobulins, or monoclonal antibodies is 
prohibited within 60 days befo re enrollment through conclusion of the study . 
Receipt of an y passive antibody  therap y,including monoclonal antibodies ,specific to 
COVID -19 is prohibited within 90 days before enrol lment through conclusion of the 
study .
Receipt of an y other (nonstudy ) coronavirus vaccine at any  time prior to or during study  
participation is prohibited.
Prophy lactic antipy retics and other pain medication to prevent symptoms associated with 
study  intervention administration are not permitted.  However, if a participant istaking a 
medication for another condition, even if it may  have antipy retic or pain -relieving 
properties, it should not be withheld prior to study vaccination.
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CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 716.5.2. Permitted During the Study
The use of antip yretics and other pain medication to treat symptoms a ssociated with study  
intervention administration or ongoing conditions is permitted.
The use of topical anesthetics for blood draws ispermitted.
Medication other than that described as prohibited in Section 6.5.1 required for treatment of 
preexisting stable conditions is permitted.
Inhaled, topical, or localized injections of corticosteroids (eg, intra -articular or in trabursal 
administration) are permitted .
6.5.3. Recording Nonstudy Vaccination and Concomitant Medications
Thefollowing nonstudy  vaccinations (to include start date) and concomitant medications (to 
include start and stop dates andname of the medication )will be recorded in the CRF if 
administration occurred during stud y participation ,unless otherwise noted :
Details of an y nonstudy  vaccinations received from 28 day s prior to study  enrollment 
until the 6 -month follow -up visit (Visit 5 for Phase 1 participa nts and Visit 5 for 
Phase 2/3selected- dose participants) .
Prohibited medications (not intended to treat COVID-19/MIS- C illness) listed in 
Section 6.5.1 of the protocol will be recorded in the prohibited medication CRF.
Any prescribed medication to treat or intended to treat COVID -19/MI S-C illness,
including receipt of antiplatelets (eg, aspirin, clopidogrel) or anticoagulants (eg, heparin, 
enoxaparin, warfarin) ,will be recorded in the concomitant medication CRF within the 
COVID -19 illness visit.
6.6. Dose Modification
This protocol allows some alteration of vaccine dose for individual participants and/or dose 
level from the currentl y outlined dosing schedule.  For reasons of reactogenicity , tolerability , 
or safet y, the IRC may  recommend to reduce the second dose of study  intervention and/or 
increase the interval between doses.
If, because of a medication error, a participant receives 1 d ose of BNT162b2 at Visit 1 and 
1dose of placebo at Visit 2 (or vice versa), the participant should be offered the possibility  to 
receive a second dose of BNT162b2 at an unscheduled visit. In this situation:
Obtain informed consent for administration of the additional dose.
Measure the participant’s body  temperature.
Perform urine pregnancy test on WOCBP as described in Section 8.2.7.
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PFIZER CONFIDENTIAL
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Page 72Discuss contraceptive use as described in Section 5.3.1 .
Ensure that the participant meets none of the temporary  delay  criteria as de scribed in
Section 5.5.
Unblinded site staff member(s) will dispense/administer 1 dose of study  intervention into 
the deltoid muscle of the (preferabl y)nondominant arm.  Please refer to the I P manual for 
further instruction on this process.
Blinded site staff must observe the pa rticipant for at least 30 minutes after study  
intervention administration for an y acute reactions.  Record an y acute reactions 
(including time of onset) in the participant’s source documents and on the AE page of the 
CRF, and on an SAE form as applicable.
The participant or participant’s parent(s)/legal gu ardian as applicable should continue to 
adhere to the participant’s current visit schedule ,but the participant must be followed for 
nonserious AEs for 1 month and S AEs for 6 months after the second dose of BNT162b2. 
This will require AEs to be elicited b y unscheduled telephone contact(s) and/or in -person 
visit(s).
6.7.Intervention A fter the End of the Study
No intervention will be provided to study  participants at the end of the study .
7.DISCONTINUATION OF S TUDY INTERVENTION AN D PARTICIPANT 
DISCONTINUATION/WITH DRAWAL
7.1.Discontinuation of Study Intervention
In rare instances, it may  be necessary  for a participant to permanentl y discontinue study  
intervention (definitive disconti nuation). Reasons for definitive discontinuation of study  
intervention may include the following : AEs, participant or participant’s parent(s)/legal 
guardian’s request; investigator request; pregnancy ; protocol deviation (including no longer 
meeting all t he inclusion criter ia or meeting 1 or more exclusion criteria). In general, unless 
the investigator considers it unsafe to administer the second dose, or the participant does not 
wish to receive it, it is preferred that the second dose be administered.
Note:Phase 1 participants with a positive SARS -CoV -2 NAAT result without symptoms do 
not meet exclusion criterion 1 and this should not result in discontinuation of study  
intervention . However, a confirmed COVID -19 diagnosis with the presence of at least 1of 
the sy mptoms meets ex clusion criterion 1and the participant should be discontinued from
study  intervention (see Section 8.16).
Note that discontinuation of study  intervention does not represent withdrawal from the stud y.
Per the study  estimands, i f study  intervention is definitively  discontinued, the participant will 
remain in the study  to be evaluated for safet y, tolerability , immunogenicit y, and efficacy .
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Page 73See the SoA for data to be collected at the time of discontinuation of study  intervention and 
follow -up for an y further evaluations that need to be completed.
In the event of discontinuation of study  intervention, it must be documented on the 
appropriate CRF/in the medical records whether the participant is discontinuing further 
receipt of stud y intervention or also from study  procedures, post vaccination study  follow -up, 
and/or future collection of additional information.
7.2.Participant Discontinuation/ Withdrawal F rom the Study
A participant may  withdraw from the study  at an y time at therequest of the participant or his 
or her parent(s) and/or legal guardia n.  Reasons for discontinuation from the study  include 
the following:
Refused further follow -up;
Lost to follow -up;
Death ;
Study  terminated by  sponsor ;
AEs;
Participant/ participant’s parent(s)/legal guardian request;
Investigator request;
Protocol deviation.
If a participant does not return for a scheduled visit, every  effort should be made to contact
him or her or the participant ’s parent(s)/legal guardian as applicable . All attempts to contact 
the participant or participant’s parent(s)/legal guardian and information received during 
contact attempts must be documented in the participant’s source document. In an y 
circumstance, every  effort should be made to document participant outcome, if possible.
The participant or participant’s parent(s)/legal guardian should be questioned regarding the 
reason for the participant’s withdrawal. The investigator or his or her designee should 
capture the reason for withdrawal in the CRF for all participants.
If a participant withdraws from the stud y, the participant or participant ’sparent(s)/legal 
guardian may  request destruction of any  remaining samples taken and not tested, and the 
investigator must document an y such requests in the site study records and notify the sponsor 
accordingl y.
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Page 74If the participant or participant’s parent(s)/legal guardian or a child who has provided assent 
during an y phase of the study  withdraws from the study  and also withdraws consent /assent
(Section 7.2.1 ) for disclosure of further information, no further evaluations should be 
performed and no additional data should be collected. The sponsor may retain and continue 
to use an y data c ollected before such withdrawal of consent.
Lack of completion of all or an y of the withdrawal/earl y termination procedures will not be 
viewed as protocol deviations so long as the participant ’s safet y was preserved.
7.2.1. Withdrawal of Consent
A participant, a participant who has provided assent during an y phase of the study, or a 
participant ’s parent(s)/legal guardian who request sto discontinue receipt of study  
intervention ,will remain in the study ,and the participant must continue to be followed for 
protoc ol-specified follow -up procedures.  The only exception to this is when a participant or
participant ’s parent(s)/legal guardian specificall y withdraws consent for any further contact 
with persons previousl y authorized to provide this information.  Theparticipant or
participant ’s parent(s)/legal guardian should notify  the investigator in writing of the decision 
to withdraw consent from future follow- up, whenever possible.  The withdrawal of consent 
should be explained in detail in the medical records by  the investigator, as to whether the 
withdrawal is only  from further receipt of study  intervention or also from study  procedures 
and/or post vaccination study  follow -up, and entered on the appropriate CRF page.  In the 
event that vital status (whether the partic ipant is alive or dead) is being measured, publicl y 
available information should be used to determine vital status only  as appropriately  directed 
in accordance with local law.
7.3.Lost to Fol low-up
A participant will be considered lost to follow- up if he or she repeatedl y fails to return for 
scheduled visits and theparticipant or participant’s parent(s)/legal guardian is unable to be 
contacted b y the stud y site.
The following actions must be taken if a participant or participant ’s parent(s)/legal guardian
fails to attend a required study visit:
The site must attempt to contact the participant or participant ’s parent(s)/legal guardian and 
reschedule the missed visit as soon as possible and counsel the participant or participant ’s 
parent(s)/legal guardian on th e importance of maintaining the assigned visit schedule and 
ascertain whether or not the participant or participant’s parent(s)/legal guardian wishes for 
the participant to and/or should continue in the study ;
Before a participant is deemed lost to follow- up, the investigator or designee must make 
every  effort to regain contact with the participant or participant’s parent(s)/legal guardian 
(where possible, 3 telephone calls and, if necessary , a certified letter to the participant’s last 
known mailing address or local equivalent methods). These contact attempts should be 
documented in the participant’s medical record ;
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Page 75Should the participant or participant’s parent(s)/legal guardian continue to be unreachable, 
the participant will be considered to have withdr awn from the study .
8.STUDY ASSESSMENTS A ND PROCEDURES
The investigator (or an appropriate delegate at the investigator site) must obtain a signed and 
dated ICD before performing any  study -specific procedures.
The fulldate of birth will be collected to criticall y evaluate the immune response and safet y 
profile b y age.
Study  procedures and their timing are summarized in the SoA. Protocol waivers or 
exemptions are not allowed.
Safety  issues should be discussed with the sponsor immediately  upon occurrence or 
awareness to determine whether the participant should continue or discontinue study  
intervention.
Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for stud y conduct.
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility  criteria. The investigator will maintain a screening log to 
record details of all pa rticipants screened and to confirm eligibility  or record reasons for 
screening failure, as applicable.
Every  effort should be made to ensure that protocol -required tests and procedures are 
completed as described.  However, it is anticipated that from time to time there may  be 
circumstances outside the control of the investigator that may  make it unfeasible to perform 
the test.  I n these cases, the investigator must take all steps necessary  to ensure the safet y and 
well-being of the participant.  When a prot ocol-required test cannot be performed, the 
investigator will document the reason for the missed test and an y corrective and preventive 
actions that he or she has taken to ensure that required processes are adhered to as soon as 
possible.  The study  team must be informed of these incidents in a timely manner.
For samples being collected and shipped, detailed collection, processing, storage, and 
shipment instructions and contact information will be provided to the investigator site prior 
to initiation of the study .
The total blood sampling volume for individual participant s <12 years of age in this study  is 
approximately  15 mL for Phase 1 and Phase 2/3 participants who will contribute to 
immunogenicit y assessment s. The remaining Phase 2/3participants will h ave a 10mL blood 
draw. Those participants in the subset who consent to additional blood collection for 
isolation of PBMCs may  have a total blood sampling volume up to approximately  45mL. 
Phase 1 and Phase 2/3 lower -dose evaluation participants 12 to <16 years of age willhave a n 
individual total blood sampling volume of approximately  30 mL , and those > 16 years of age 
will have an individual total blood sampling volume of approximately  60 mL .
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Page 768.1.Efficacy and/or Immunogenicity Assessments
Surveillance for potential cases of COVID -19and MIS-C will occur throughout a 
participant ’s involvement in the study to describe both COVI D-19 and MIS-C.
If, at an y time, a participant in the Phase 1 dose -finding /Phase 2/3 selected- dose portions of 
the study  develops an acute illness (described in Section 8.13), for the purposes of the study  
he or she will be considered to potentially  have COVID -19 illness.29  In this circumstance, 
theparticipant ’s parent(s) /legal guardian should contact the site .  An in-person or telehealth 
visit should occur, and assessments should be conducted as specified in the SoA.  The 
assessments will include a nasal (anterior nares ) swab sample collection either b y site staff 
perso nnel (clinical visit) or by  a participant ’sparent/legal guardian , which will be tested at a 
central laboratory  using a nRT-PCR test (Cepheid; US FDA -approved under EUA) or o ther 
equivalent nucleic acid amplification– based test (ie, NAAT), to detect SARS- CoV -2.  In 
addition, clinical information and results from local standard-of-care tests (as detailed in 
Section 8.13) will be assessed. The central laboratory  NAAT result will be used for the case 
definition, unless no result is available from the central laboratory , in which case a local 
NAAT result may be used ifit was obtained using 1 of the following assays:
Cepheid Xpert Xpress SARS -CoV -2
Roche C obas SARS -CoV -2 Real -Time RT -PCR test (EUA200009/A001)
Abbott Molecular/RealTime SARS -CoV -2 assay  (EUA200023/A001)
Two definitions (first and second definition s) of SARS -CoV -2–related cases, SARS -CoV -2–
related
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