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PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Protocol Amendment 1 , 05March 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
<12YEARS OF AGE
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 <12 Years of Age
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
inconfidence 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.
090177e19670e6ed\Approved\Approved On: 05-Mar-2021 17:33 (GMT)
FDA-CBER-2021-5683-0779766
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Protocol Amendment 1 , 05March 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 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 r egarding this
study, ie :
Exclusion criteri on3 applied to all study
participants rather than just to Phase 1
participants.
References to “noninferiority ”updated to
“immunobridging. ”
Made a ddition sto the exclusion criteria for previous
or current diagnosi s 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 recipients 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 illnes s 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 hospitalization
added.
RR and HR required to meet the SARS -CoV -2–
related severe cas e definition specified by participant
age. Table 4 inserted.
Added that c ell-mediated immune responses will be
described follow ing isolation of PBMCs in a subset of
090177e19670e6ed\Approved\Approved On: 05-Mar-2021 17:33 (GMT)
FDA-CBER-2021-5683-0779767
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Protocol Amendment 1 , 05March 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
Phase 2/3 participants ≥10years of age.
Corresponding visit (Visit 3) added approximatel y 7
days after Dose 2.
Original p rotocol 05Feb2021 N/A
This amendment incorporates all revisions to date, including amendments made at the
request of country health authorities and IRBs/ECs.
090177e19670e6ed\Approved\Approved On: 05-Mar-2021 17:33 (GMT)
FDA-CBER-2021-5683-0779768
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Protocol Amendment 1 , 05March 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 4TABLE OF CONTENTS
LIST OF TABLES ................................ ................................ ................................ ................... 10
1. PROTOCOL SUMMARY ................................ ................................ ................................ ...11
1.1. Sy nopsis ................................ ................................ ................................ .................. 11
1.2. Schema ................................ ................................ ................................ .................... 20
1.3. Schedule of Activities ................................ ................................ ............................. 21
1.3.1. Phase 1 ................................ ................................ ................................ ........ 21
1.3.2. Phase 2/3................................ ................................ ................................ .....25
1.3.2.1. Phase 2/3 Participants Who Originall y Received
BNT162b2 or Placebo Recipients Who Decline BNT162b2 ............ 28
1.3.2.2. Phase 2/3 Participants Who Originall y Received Placebo ........ 29
2. INTRODUCTION ................................ ................................ ................................ ............... 32
2.1. Study Rationale ................................ ................................ ................................ .......32
2.2. Background ................................ ................................ ................................ ............. 32
2.2.1. Clinical Overview ................................ ................................ ....................... 34
2.3. Benefit/Risk Assessment................................ ................................ ......................... 34
2.3.1. Risk Assessment ................................ ................................ ......................... 36
2.3.2. Ben efit Assessment ................................ ................................ ..................... 38
2.3.3. Overall Benefit/Risk Conclusion ................................ ................................ 38
3. OBJECTI VES, ESTIMANDS, AND ENDPOINTS ...........................................................38
3.1. Phase 1 ................................ ................................ ................................ ..................... 38
3.2. Phase 2/3 ................................ ................................ ................................ ................. 39
4. STUDY DESIGN ................................ ................................ ................................ ................. 43
4.1. Overall Design ................................ ................................ ................................ ......... 43
4.1.1. Phase 1 ................................ ................................ ................................ ........ 43
4.1.2. Phase 2/3................................ ................................ ................................ .....43
4.1.3. Number of Participants................................ ................................ ............... 44
4.1.3.1. Phase 1: Open -Label Dose Finding ................................ ........... 44
4.1.3.2. Phase 2/3: Safety, Tolerability , Immunogenicity , and
Efficacy ................................ ................................ .............................. 44
4.1.4. I ntervention Groups and Duration ................................ .............................. 45
4.2. Scientific Rationale for Study Design ................................ ................................ .....46
090177e19670e6ed\Approved\Approved On: 05-Mar-2021 17:33 (GMT)
FDA-CBER-2021-5683-0779769
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Protocol Amendment 1 , 05March 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 54.3. Justification for Dose ................................ ................................ .............................. 46
4.4. End of Study Definition ................................ ................................ .......................... 46
5. STUDY POPUL ATION ................................ ................................ ................................ ......46
5.1. I nclusion Criteria................................ ................................ ................................ .....47
5.2. Exclusion Criteria ................................ ................................ ................................ ....48
5.3. L ifesty le Considerations ................................ ................................ .......................... 49
5.3.1. Contraception ................................ ................................ .............................. 49
5.4. Screen Failures ................................ ................................ ................................ ........ 50
5.5. Criteria for Temporarily Delay ing Enrollment/Randomization/Study
Intervention Administration ................................ ................................ ...................... 50
6. STUDY INTERVENTIO N................................ ................................ ................................ ..51
6.1. Study Intervention(s) Administered ................................ ................................ ........ 51
6.1.1. Administration ................................ ................................ ............................ 52
6.2. Preparation/Handling/Storage/Accountability ................................ ........................ 52
6.2.1. Preparation and Dispensing ................................ ................................ ........ 53
6.3. Measures to Minimize Bias: Randomization and Blinding.....................................54
6.3.1. Allocation to Study Intervention ................................ ................................ 54
6.3.2. Blinding of Site Personnel (Phase 2/3 Onl y)................................ .............. 54
6.3.3. Blinding of the Sponsor................................ ................................ .............. 54
6.3.4. Breaking the Blind ................................ ................................ ...................... 55
6.4. Study Intervention Compliance ................................ ................................ ............... 55
6.5. Concomitant Therapy ................................ ................................ .............................. 56
6.5.1. Prohibited During the Study ................................ ................................ .......56
6.5.2. Permitted During the Study ................................ ................................ ........ 57
6.5.3. Recording Nonstudy Vaccination and Concomitant Medications..............57
6.6. Dose Modification ................................ ................................ ................................ ...57
6.7. I ntervention After the End of the Study ................................ ................................ ..58
7. DI SCONTINUATION O F STUDY INTERVENTION AND PARTI CIPANT
DISCONTINUATION/WI THDRAWAL ................................ ................................ ........... 58
7.1. Discontinuation of Study Intervention ................................ ................................ ....58
7.2. Participant Discontinuation/Withdrawal From the Study ................................ .......59
7.2.1. Withdrawal of Consent ................................ ................................ ............... 60
090177e19670e6ed\Approved\Approved On: 05-Mar-2021 17:33 (GMT)
FDA-CBER-2021-5683-0779770
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Protocol Amendment 1 , 05March 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 67.3. L ost to Follow -up ................................ ................................ ................................ ....60
8. STUDY ASSESSMENTS AND PROCEDURES ................................ ............................... 61
8.1. Efficacy and/or Immunogenicity Assessments ................................ ....................... 62
8.1.1. I mmunogenicity................................ ................................ .......................... 65
8.1.2. Biological Samples ................................ ................................ ..................... 66
8.2. Safet y Assessments ................................ ................................ ................................ .66
8.2.1. Phy sical Examinations ................................ ................................ ................ 66
8.2.2. Vital Signs ................................ ................................ ................................ ..67
8.2.3. Clinical Safety Laboratory Assessments ................................ .................... 67
8.2.4. Electronic Diary ................................ ................................ .......................... 67
8.2.4.1. Grading Scales ................................ ................................ ........... 67
8.2.4.2. L ocal Reactions ................................ ................................ ......... 68
8.2.4.3. Sy stemic Events ................................ ................................ ........ 69
8.2.4.4. Fever ................................ ................................ .......................... 71
8.2.4.5. Antipy retic Medication ................................ ............................. 72
8.2.5. Phase 1 Stopping Rules ................................ ................................ .............. 72
8.2.6. Randomization and Vaccination After a Stopping Rule Is Met in
Phase 1 ................................ ................................ ................................ ............. 73
8.2.7. Pregnancy Testing ................................ ................................ ...................... 73
8.3. Adverse Events and Serious Adverse Events................................ .......................... 73
8.3.1. Time Period and Frequency for Collecting AE and SAE Information .......74
8.3.1.1. Reporting SAEs to Pfizer Safety ................................ ............... 75
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF ................... 75
8.3.2. Method of Detecting AEs and SAEs ................................ .......................... 75
8.3.3. Follow -up of AEs and SAEs ................................ ................................ .......75
8.3.4. Regulatory Reporting Requirements for SAEs ................................ ........... 76
8.3.5. Exposure During Pregnancy or Breastfeeding, and Occupational
Exposure ................................ ................................ ................................ .......... 76
8.3.5.1. Exposure During Pregnancy ................................ ...................... 76
8.3.5.2. Exposure During Breastfeeding ................................ ................ 78
8.3.5.3. Occupational Exposure ................................ ............................. 78
8.3.6. Cardiovascular and Death Events ................................ ............................... 78
090177e19670e6ed\Approved\Approved On: 05-Mar-2021 17:33 (GMT)
FDA-CBER-2021-5683-0779771
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Protocol Amendment 1 , 05March 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 78.3.7. Disease -Related Events and/or Disease -Related Outcomes Not
Qualifying as AEs or SAEs ................................ ................................ .............. 79
8.3.8. Adverse Events of Special Interest ................................ ............................. 79
8.3.8.1. Lack of Efficacy ................................ ................................ ........ 79
8.3.9. Medical Device Deficiencies ................................ ................................ ......79
8.3.10. Medication Errors ................................ ................................ ..................... 79
8.4. Treatment of Overdose................................ ................................ ............................ 80
8.5.Pharmacokinetics ................................ ................................ ................................ ....81
8.6.Pharmacod ynamics ................................ ................................ ................................ ..81
8.7. Genetics ................................ ................................ ................................ ................... 81
8.8. Biomarkers ................................ ................................ ................................ .............. 81
8.9. I mmunogenicit y Assessments ................................ ................................ ................. 81
8.10. Health Economics ................................ ................................ ................................ .81
8.11. Stud y Procedures ................................ ................................ ................................ ...81
8.11.1. Phase 1 ................................ ................................ ................................ ......81
8.11.1.1. Visit 1 – Dose 1 (Day 1)................................ .......................... 81
8.11.1.2. Visit 2 – Dose 2 (19 to 23 Day s After Visit 1) ........................ 84
8.11.1.3. Visit 3 – 7- Day Follow -up Visit (1 Week After Dose 2, 6
to 8 Day s After Visit 2) ................................ ................................ .....86
8.11.1.4. Visi t 4 – 1-Month Follow -up Visit (28 to 35 Day s After
Visit 2) ................................ ................................ ............................... 87
8.11.1.5. Visit 5 – 6- Month Follow -up Visit (175 to 189 Days
After Vis it 2)................................ ................................ ...................... 88
8.11.1.6. Visit 6 – 12- Month Follow -up Visit (350 to 378 Day s
After Visit 2) ................................ ................................ ...................... 88
8.11.1.7. Visit 7 – 24- Month Follow -up Visit (714 to 742 Day s
After Visit 2) ................................ ................................ ...................... 89
8.11.2. Phase 2/3................................ ................................ ................................ ...89
8.11.2.1. Visit 1 – Dose 1 (Day 1)................................ .......................... 89
8.11.2.2. Visit 2 – Dose 2 (19 to 23 Day s After Visit 1) ........................ 92
8.11.2.3. 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 ................................ ............................... 94
090177e19670e6ed\Approved\Approved On: 05-Mar-2021 17:33 (GMT)
FDA-CBER-2021-5683-0779772
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Protocol Amendment 1 , 05March 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 88.11.2.4. Visit 4 – 1- Month Follow -up Visit (After Visit 2) (28 to
35 Day s After Visit 2) ................................ ................................ .......95
8.11.2.5. Visit 5 – 6- Month Follow -up Visit (175 to 189 Days
After Visit 2) ................................ ................................ ...................... 96
8.11.3. Phase 2/3 Participants Who Originall y Received BNT162b2 or
Placebo Recipients Who Decline BNT162b2 ................................ .................. 97
8.11.3.1. Visit X – 12- Month Follow -up Visit (350 to 378 Day s
After Visit 2) ................................ ................................ ...................... 97
8.11.3.2. Visit Y – 24- Month Follow -up Visit (714 to 742 Day s
After Visit 2) ................................ ................................ ...................... 98
8.11.4. Phase 2/3 Participants Who Originall y Received Placebo ....................... 98
8.11.4.1. Visit A – Dose 3 (175 to 189 Day s After Dose 2 and
Same Date as Visit 5) ................................ ................................ ........ 98
8.11.4.2. Visit B – Dose 4 (19 to 23 Days After Visit A) .................... 100
8.11.4.3. Visit C – 1- Month Follow -up Telephone Contact (After
Dose 4) (28 to 35 Day s After Visit B) ................................ ............. 102
8.11.4.4. Visit D – 6- Month Follow -up Telephone Contact (After
Dose 4) (175 to 189 Days After Visit B) ................................ ......... 102
8.11.4.5. Visit E – 12-Month Follow -up Telephone Contact (After
Dose 4) (350 to 378 Days After Visit B) ................................ ......... 103
8.11.4.6. Visit F – 18 -Month Follow -up Telephone Contact (After
Dose 4) (532 to 560 Days After Visit B) ................................ ......... 103
8.12. Unscheduled Visit for Fever or a Grade 3 or Suspected Grade 4 Reaction ........ 104
8.13. COVID -19 and M IS-C Surveillance (All Participants) ................................ ......105
8.13.1. Potential COVI D-19/MI S-C Illness Visit (Optimally Within 3 Day s
After Potential COVID -19 Illness Onset) ................................ ...................... 106
8.13.2. Potential COVI D-19/MI S-C Convalescent Visit (28 to 35 Day s
After Potential COVID -19 Illness Visit) ................................ ....................... 108
8.14. Communication and Use of Technology ................................ ............................. 109
8.15. SARS -CoV -2 NAAT Nasal (Anterior Nares) Swab Results .............................. 109
9. STATI STICAL CONSI DERATIONS ................................ ................................ .............. 110
9.1. Estimands and Statistical Hy potheses ................................ ................................ ...110
9.1.1. Estimands ................................ ................................ ................................ ..110
9.1.2. Statistical Hy pothesis ................................ ................................ ................ 111
9.1.2.1. Statistical Hy pothesis Evaluation for Immunogenicity ........... 111
090177e19670e6ed\Approved\Approved On: 05-Mar-2021 17:33 (GMT)
FDA-CBER-2021-5683-0779773
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Protocol Amendment 1 , 05March 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 99.1.2.2. Statistical Hy pothesis Evaluation for Efficacy ........................ 111
9.1.3. Multiplicity Considerations ................................ ................................ ......112
9.2. Sample Size Determination ................................ ................................ ................... 112
9.3. Analy sis Sets ................................ ................................ ................................ ......... 115
9.4. Statistic al Analy ses................................ ................................ ............................... 116
9.4.1. General Considerations ................................ ................................ ............. 116
9.4.1.1. Analy ses for Binary Data ................................ ........................ 116
9.4.1.2. Analy ses for Continuous Data ................................ ................. 117
9.4.2. Primary Endpoint(s) ................................ ................................ .................. 117
9.4.3. Secondary Endpoint(s) ................................ ................................ .............. 119
9.4.4. Exploratory Endpoint(s) ................................ ................................ ........... 120
9.5. I nterim Anal yses................................ ................................ ................................ ...121
9.5.1. Ana lysis Timing ................................ ................................ ........................ 121
9.6. Data Monitoring Committee or Other Independent Oversight Committee ........... 122
10. SUPPORTING DOCUM ENTATION AND OPERATI ONAL
CONSI DERATIONS ................................ ................................ ................................ ........ 123
10.1. Appendix 1: Regulatory , Ethical, and Study Oversight Considerations ............. 123
10.1.1. Regulatory and Ethical Considerations ................................ .................. 123
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the
Protocol or I CH GCP ................................ ................................ .......123
10.1.2. Financial Disclosure ................................ ................................ ............... 124
10.1.3. I nformed Consent Process ................................ ................................ ......124
10.1.4. Data Protection ................................ ................................ ....................... 125
10.1.5. Dissemination of Clinical Study Data ................................ .................... 126
10.1.6. Data Qualit y Assurance ................................ ................................ .......... 127
10.1.7. Source Documents ................................ ................................ .................. 128
10.1.8. Study and Site Start and Closure ................................ ............................ 128
10.1.9. Publication Policy................................ ................................ ................... 129
10.1.10. Sponsor’s Qualified Medical Personnel ................................ ............... 130
10.2. Appendix 2: Clinical Laboratory Tests ................................ ............................... 130
10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording,
Evaluating, Follow -up,and Reporting ................................ ................................ ....131
090177e19670e6ed\Approved\Approved On: 05-Mar-2021 17:33 (GMT)
FDA-CBER-2021-5683-0779774
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Protocol Amendment 1 , 05March 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 1010.3.1. Definition of AE ................................ ................................ ..................... 131
10.3.2. Definition of SAE................................ ................................ ................... 132
10.3.3. Recording/Reporting and Follow- up of AEs and/or SAEs ..................... 134
10.3.4. Reporting of SAEs................................ ................................ .................. 137
10.4. Appendix 4: Contraceptive Guidance ................................ ................................ .138
10.4.1. Male Participant Reproductive Inclusion Criteria ................................ ..138
10.4.2. Female Participant Reproductive Inclusion Criteria ............................... 138
10.4.3. Woman of Childbearing Potential ................................ .......................... 139
10.4.4. Contraception Methods ................................ ................................ ........... 140
10.5. Appendix 5: Li ver Safety : Suggested Actions and Foll ow-up Assessments ......141
10.6. Appendix 6: Abbreviations ................................ ................................ ................. 143
10.7. Appendix 7: Criteria for Allowing Inclusion of Participants With Chronic
Stable HIV, HCV, or HBV Infection ................................ ................................ ......146
11. REFERENCES ................................ ................................ ................................ ................ 147
LIST OF TABLES
Table 1. Phase 1 Participants ................................ ................................ .................. 44
Table 2. Phase 2/3 Participants –Blood Draws for Immunogenicity /Effic acy
Assessments ................................ ................................ .............................. 45
Table 3. Phase 2/3 Participants –Safety and Tolerability /Efficacy
Assessments ................................ ................................ .............................. 45
Table 4. RR and HR, by Age, Indicative of Severe S ystemic I llness ..................... 63
Table 5. Local Reaction Grading Scale ................................ ................................ ..68
Table 6. Systemic Event Grading Scale for Participants ≥2 to <12 Years of
Age................................ ................................ ................................ ............ 69
Table 7. Systemic Event Grading Scale for Participants ≥6 Months to <2
Years of Age ................................ ................................ ............................. 70
Table 8. Scale for Fever ................................ ................................ .......................... 71
Table 9. Power Anal ysis for Immunobridging Assessment ................................ .113
Table 10. Precision of SARS- CoV -2 Neutralizing Titer GMT .............................. 113
Table 11. Power for Vaccine Efficacy Assessment ................................ ................ 114
Table 12. Probability of Observing at Least 1 AE by Assumed True Event
Rates With Different Sample Sizes ................................ ........................ 114
090177e19670e6ed\Approved\Approved On: 05-Mar-2021 17:33 (GMT)
FDA-CBER-2021-5683-0779775
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Protocol Amendment 1 , 05March 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 111.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 < 12Years of Age .
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 vacci nes 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 utmost
importance .
A Phase 1/2/3 study (C45910 01)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 38,0 00 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 11 December 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.
This Phase 1/2/3 study (C4591007) will evaluat e 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 safety , tolerability , immunogenicit y, and efficacy (depending on successful
immunobridging and accrual of asuffici ent 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 2259 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 includes animmunobridging
analysisof immune responses in participants within each age group (participants ≥5 to
<12years, ≥2 to <5 y ears, and ≥ 6months to <2 years of age) to those in participants 16 to
090177e19670e6ed\Approved\Approved On: 05-Mar-2021 17:33 (GMT)
FDA-CBER-2021-5683-0779776
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Protocol Amendment 1 , 05March 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 1225years of age inthe Phase 3 C45 91001 efficacy study .Safet y, 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 .
Objectives , Estimands, and Endpoints
The age groups referred to in the objectives and estimands below are partic ipants ≥5 to
<12years, ≥2 to <5 y ears, and ≥ 6months to <2 years of age .
Phase 1
Objectives Estimands Endpoints
Primary: Primary: Primary:
To describe the safety and tolerability
profiles of prophylactic BNT162 b2at
each dose level in each age groupIn 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 ≥5 to <12 years 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
irritab ility)
 AEs
 SAEs
Secondary: Secondary: Secondary:
To describe the immune responses
elicited by prophylactic BNT162 b2at
each dose level in each age groupIn participants complying with the key
protocol criteria (evaluable
participants) in each age group :
At baseline , before Dose 2 ,and7 days
after Dose 2 ,
 GMTs at each time point
 GMFR from before Dose 1
(baseline) to each subsequent time
point after vaccination SARS -CoV -2 neutralizing titers
Exploratory : Exploratory : Exploratory :
To describe COVID -19and 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
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CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 13Phase 1
Objectives Estimands Endpoints
To describe MIS -C cases with and
without evidence of past SARS-CoV -2
infection Confirmed cases as per CDC
criteria
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 inthe participants included
in the Phase 2/3 immunobridging
analysis 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 t o 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 1 month
after Dose 2Participants ≥5 to <12 years 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
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 6months
after Dose 2Participants ≥5 to <12 years 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, decre ased
appetite, drowsiness, and
irritability )
 AEs
 SAEs
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CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 14Phase 2/3
Objectives Estimands Endpoints
Primary Immunogenicity : Primary Immunogenicity : Primary Immunogenicity :
To demonstrate immunobridging of the
immune response elicited by
prophylactic BNT162b2 at the dose
level selected per age group
inPhase 2/3 participants without
serological or virological evidence (up
to 1 month after receipt of Dose 2) of
past SARS -CoV -2 infection:In participants complying with the key
protocol criteria (evaluable
participants) and no serological or
virological evidence (up to 1 month
after receipt of Dose 2) of past
SARS -CoV -2 infection:  SARS -CoV -2 neutralizing titers
 In participants ≥5 to <12 y ears of
age compared to participants 16 to
25years of age from Phase 2/3 of
theC4591001 study GMR, estimated by the ratio of the
geometric mean of SARS -CoV -2
neutralizing titers in participants
≥5 to <12 years of age to those in
participants 16 to 25 yea rs of age 1
month after Dose 2
 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 2
 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
Secondary Immunogenicity /Efficacy : Secondary Immunogenicity /Efficacy :Secondary Immunogenicity/Efficacy :
To describe the immune responses
elicited by prophylactic BNT162b2 at
the dose level selected per age group
and persistence of immune response in
Phase 2/3 participants without
serological or virologic alevidence of
pastSARS -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
In all age groups where
immunobridging is successful, i f at
least 22 cases are accrued across those
age groups :
To evaluate the efficacy of prophylactic
BNT162b2 against confirmed
COVID -19 occurring from 7 days after
Dose 2 in participants without evidence
of past SARS -CoV -2 infection In participants complying with the key
protocol criter ia (evaluable
participants) and with no serological or
virological evidence (prior to 7 days
after receipt of Dose 2) of past
SARS -CoV -2 infection:
100 × (1 –IRR) [ratio of active vaccine
to placebo] Confirmed COVID-19 incidence
from 7 days after Dose 2 per 1000
person -years of follow -up
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Page 15Phase 2/3
Objectives Estimands Endpoints
In all age groups where
immunobridging is successful, i f at
least 22 cases are accrued across those
age groups :
To evaluate the efficacy of prophylactic
BNT162b2 against confirmed
COVID -19 occurring from 7 days after
Dose 2 in participants with or without
evidence of past SARS -CoV -2
infection In participants complying with the key
protocol criteria (evaluable
participants) and with o r without
serological or virological evidence
(prior to 7 days after receipt of Dose 2 )
of past SARS -CoV -2 infection:
100 × (1 –IRR) [ratio of active vaccine
to placebo] Confirmed COVID-19 incidence
from 7 days after Dose 2 per 1000
person -years of follow -up
To describe the efficacy of prophylactic
BNT162b2 against asymptomatic
infection in participants 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 vacc ine
to placebo] Incidence of asymptomatic
infection of SARS -CoV -2 based
on N -binding antibody
seroconversion
Exploratory: Exploratory: Exploratory:
To evaluate the immune response over
time to prophylactic BNT162b2 at the
dose level selected per 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,
 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 immune response
(non-S) to SARS -CoV -2 in Phase 2/3
participants with and without
confirmed COVID -19 during the study N-binding antibody
To describe COVID -19 and severe
COVID -19 cases in all participants
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 an d
without evidence of past SARS-CoV -2
infection Confirmed cases as per CDC
criteria
To describe the serological responses in
Phase 2/3 participants to BNT162b 2at
thedose level selected per 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
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PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Protocol Amendment 1 , 05March 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 16Phase 2/3
Objectives Estimands Endpoints
To describe the safety and
immunogenicity of prophylactic
BNT162b2 at the dose level selected
per 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:
 7 days and1 and 6 months after
Dose 2
Overall Design
This is a Phase 1/2/3 study inhealthy children <1 2years of age.
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.
Phase 1 is the open -label dose-finding portion of the study to evaluate safety , tolerability ,
and immunogenicit y of BNT162b2 ona 2-dose ( separated b y approximately 21 day s)
schedule in up to 3 age groups ( participants ≥5 to <12 years, ≥2 to <5 y ears, and ≥ 6months
to <2 years of age) . Dosefinding is being initiated in this study in participants ≥5 to
<12years of age based on the acceptable blinded safet y assessment of the 30-µ g dose in
12-to 15-year-oldsin 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 final BNT162b 2dose level for Phase 2/3.
Phase 2 /3will evaluate the safet y, tolerability , and immunogenicit yin each age group at the
selected dose level from Phase 1. E fficacy will be evaluated across all age groups in which
immunobridging is successful, depending on accrual of a sufficient number of cases across
those age groups .
All 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
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Protocol Amendment 1 , 05March 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 17immunogenicit 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 confi rmed COVID -19 and against
asymptomatic infection will also be assessed.
At designated 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 cell -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.
Number of Participants
Phase 1 isanopen -label dose-finding study thatwill consist of up to 3 different dose level s
in each age group, with 1 6 participants per dose level (total of 144 participants).
Phase 1 Participants
Age Group Total Up to 3 Dose Levels of BNT162b2 Active 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
Phase 2 /3will evaluate the safet y, tolerability ,and immunogenicit yof the selected dose level
in each age group from Phase 1, with a total of approximately 4500 participants. Participants
will be randomized in a 2:1ratio to receive active vaccine or placebo .
Approximately 450 participants ( 300intheactive vaccine group and 150 in the placebo
group ) randomized in each age group in this phase will contribute to 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 4500
participants will contribute to the VEanalysis for conditional VEand asymptomatic
infection . Efficacy will be evaluated across all age groups in which immunobridging is
successful, depending on accrual of a sufficient number of cases across those age gr oups.
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Protocol Amendment 1 , 05March 2021
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CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 18Phase 2/3 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 4500 3000 1500 2250 1500 750 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 Participants –Safety and Tolerability /Efficacy Assessment s
Total Active Placebo
4500 3000 1500
Intervention Groups and Duration
Phase 1 :Dose finding will begin at the low-dose level in participants ≥5 to <12 y ears of age .
The I RC 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 commence 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 .
Phase 2/3: Progression of each age group into Phase 2/3 will occur independently ; 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 group t o proceed to
Phase 2/3, safet y, tolerability ,and immunogenicity data from 7 day s after Dose2 for the
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CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 19selected vaccine dose level in that age group from Phase 1 will b e confirmed to be
acceptable .
Duration: Participants are expected to participate for up to a maximum of approximately
26months.
Data Monitoring Committee or Other Independent Oversight Committee
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 pa rticipants within
each age group totheresponse in participants 1 6to 25 y ears of age 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. Immunobridging success will be
declared if the lower limit of the 95% CI for the GMR (each agegroup to the 16-to 25-year
age group from C4591001) is >0.67. A sample size of 225evaluable participants in each age
group will provide a power of 90. 4% to de clare immunobridging success. T he
immunogenicit y data from the active vaccine recipients inapproximately 450participant s
randomized in each age group in Phase 2/3 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 allage group s where immunobri dging success is declared .
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. Hypothesis testing will be
conducted onl y ifat least 22 cases are accrued in those age group s. With the assumption of a
true VE of 75%, 22 cases will provide 70% power to conclude true VE >20%.
VEagainst as ymptomatic infection will be evaluated descrip tively. VE estimate and 2 -sided
95% CI for VE will be provided using the Clopper -Pearson method.
The primary 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 Phase 2/3.
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CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 201.2.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 IRCb IRC
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)
IRCcIRCcIRCc
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 1in the low-dose -level group , and
dosing 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 le vel for each age group. Dependent on safety, tolerability, and immunogenicity data from 7 days
after Dose 2 in each age group.
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PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
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Protocol Amendment 1 , 05March 2021
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CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 211.3. 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
An unplanned potential COVID-19 /MIS-Cillness visit and unplanned potential COVI D-19 /MIS-C convalescent visit are required at
any time for the duration of the study that COVID -19/MIS-Csymptoms are reported . During the 7 day s following each dose,
potential COVID -19/MIS -Csymptoms that overlap with specific s ystemic events (ie, fever, chills, new or increased muscle pain,
diarrhea, vomiting) should not trigger a potential COVID-19 /MIS-C illness visit unless, in the investigator’s opinion ,the clinical
picture is more indicative of a possible COVID -19/MIS-Cillness rat her than vaccine reactogenicit y.For details, see Section 8.13 .
Visit Number 1 2 3 4 5 6 7 Unplanned Unplanned
Visit Description Dose 1aDose 2 7 Day Follow -
up Visit
(1 W eek 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
VisitbPotential COVID -19/
MIS -C Convalescent
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 2350 to 378
Days After
Visit 2714 to 742
Days After
Visit 2Optimally Within 3
Days After Potential
COVID -19/MIS -C
Illness Onset28 to 35 Days After
Potential COVID -
19/MIS-C
Illness Visit
Type of Visit Clinic Clinic Clinic Clinic or
TelephoneTelephone Telephone Clinic or
TelephoneClinic or
Telehea lthClinic
Obtain informed consent and
assent (if appropriate)X
Assign participant number X
Obtain demography and
significant medical history dataX
Measure vital signs (including
body temperature)X X
Perform targeted physical
examination including height and
weightcX X
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Protocol Amendment 1 , 05March 2021
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CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 22Visit Number 1 2 3 4 5 6 7 Unplanned Unplanned
Visit Description Dose 1aDose 2 7 Day Follow -
up Visit
(1 W eek 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
VisitbPotential COVID -19/
MIS -C Convalescent
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 2350 to 378
Days After
Visit 2714 to 742
Days After
Visit 2Optimally Within 3
Days After Potential
COVID -19/MIS -C
Illness Onset28 to 35 Days After
Potential COVID -
19/MIS-C
Illness Visit
Type of Visit Clinic Clinic Clinic Clinic or
TelephoneTelephone Telephone Clinic or
TelephoneClinic or
Telehea lthClinic
Perform u rine p regnancy test
(only for female participants
biologically capable of having
children)X X
Confirm use of contraceptives
(ifappropriate)X X X X
Collect nonstudy vaccine
information X X X X X
Collect prohibited medication use X X X X X X X X
Review temporary delay criteria X X
Confirm eligibility X X
Obtain randomization number and
study intervention allocationX
Obtain anterior nasal swab X X X
Collect blood sample for
immunogenicity~5 mL ~5mL ~5 mL ~5 mL
Administer study intervention X X
Assess acute reactions for at least
30minutes 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
Protocol Amendment 1 , 05March 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 23Visit Number 1 2 3 4 5 6 7 Unplanned Unplanned
Visit Description Dose 1aDose 2 7 Day Follow -
up Visit
(1 W eek 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
VisitbPotential COVID -19/
MIS -C Convalescent
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 2350 to 378
Days After
Visit 2714 to 742
Days After
Visit 2Optimally Within 3
Days After Potential
COVID -19/MIS -C
Illness Onset28 to 35 Days After
Potential COVID -
19/MIS-C
Illness Visit
Type of Visit Clinic Clinic Clinic Clinic or
TelephoneTelephone Telephone Clinic or
TelephoneClinic or
Telehea lthClinic
Provide a thermometer and
caliper (measuring) deviceX
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
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 AEsd X X X X X X
Collect SAEse X 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 X
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PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Protocol Amendment 1 , 05March 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 24Visit Number 1 2 3 4 5 6 7 Unplanned Unplanned
Visit Description Dose 1aDose 2 7 Day Follow -
up Visit
(1 W eek 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
VisitbPotential COVID -19/
MIS -C Convalescent
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 2350 to 378
Days After
Visit 2714 to 742
Days After
Visit 2Optimally Within 3
Days After Potential
COVID -19/MIS -C
Illness Onset28 to 35 Days After
Potential COVID -
19/MIS-C
Illness Visit
Type of Visit Clinic Clinic Clinic Clinic or
TelephoneTelephone Telephone Clinic or
TelephoneClinic or
Telehea lthClinic
Abbreviations: CRF = case report form; MIS -C = multisystem inflammatory syndrome in children.
a.The visit may be conducted across 2 consecutive days; if so, all steps from assessing the inclusion and exclusion criteria onwards must be conducted on the
day of vaccination.
b.Potential MIS -C visit: hospitalization for a seve re illness with no other alternative etiology.
c.Height and weight will be collected only at Visit 1.
d.Any AEs occurring up t o 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. T hese data w ill 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.
e.Refer to Section 8.3.1 forthetime period for collecting SAEs .
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PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
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Protocol Amendment 1 , 05March 2021
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CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 251.3.2. Phase 2/3
An unplanned potential COVID-19 /MIS- C illness visit and unplanned potential COVID -19/MIS-C convalescent visit are required at
any 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 even ts (ie, fever, chills, new or increased muscle
pain, diarrhea, vomiting) should not trigger a potential COVI D-19 /MIS-Cillness visit unless, in the investigator’s opinion ,the clinical
picture is more indicative of a possible COVID -19/MIS-Cillness rather than vaccine reactogenicit 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.
Visit Number 1 2 3 4 5 Unplanned Unplanned
Visit Description Dose 1aDose 2 1-Week
Follow -up
Visitb1-Month
Follow -up
Visit6-Month
Follow -up
VisitcPotential COVID -19
Illness/MIS-C VisitdPotential COVID -19/
MIS -C Convalescent
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 2Optimally Within 3
Days After Potential
COVID -19/MIS -C
Illness Onset28 to 35 Days After
Potential COVID -
19/MIS -C Illness
Visit
Type of Visit Clinic Clinic Clinic Clinic or
TelephoneClinic Clinic or
TelehealthClinic
Obtain informed consent and assent (if appropriate) X
Assign participant number X
Obtain demography and significant medical history
dataX
Measure vital signs (including body temperature) X X
Perform targeted physical examination including
height and weighte X X
For participants who are HIV positive, record latest
CD4 count and HIV viral loadX X X
Perform urine pregnancy test (only for female
participants biologically capable of having children)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 X
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Page 26Visit Number 1 2 3 4 5 Unplanned Unplanned
Visit Description Dose 1aDose 2 1-Week
Follow -up
Visitb1-Month
Follow -up
Visit6-Month
Follow -up
VisitcPotential COVID -19
Illness/MIS-C VisitdPotential COVID -19/
MIS -C Convalescent
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 2Optimally Within 3
Days After Potential
COVID -19/MIS -C
Illness Onset28 to 35 Days After
Potential COVID -
19/MIS -C Illness
Visit
Type of Visit Clinic Clinic Clinic Clinic or
TelephoneClinic Clinic or
TelehealthClinic
Review temporary delay criteria X X
Confirm eligibility X X
Obtain randomization number and study
intervention allocationX
Obtain anterior nasal swab X X X
Collect blood sample for immunogenicity ~5mL ~5mLf~5mL ~5mL
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) device X
Ensure the participant’s parent(s)/legal guardian has
a caliper device and thermometerX
Ask the participant’s parent(s)/legal guardian to
complete e -diary and ensure the participant’s
parent(s)/legal guardian remains comfortable with
chosen e -diary platform X X
Review reactogenicity e -diary data (daily review is
optimal during the active diary period)
Review ongoing reactogenicity e -diary symptoms
and obtain stop datesX X
Collect AEs as appropriategX X X X X X X
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PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
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Protocol Amendment 1 , 05March 2021
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CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 27Visit Number 1 2 3 4 5 Unplanned Unplanned
Visit Description Dose 1aDose 2 1-Week
Follow -up
Visitb1-Month
Follow -up
Visit6-Month
Follow -up
VisitcPotential COVID -19
Illness/MIS-C VisitdPotential COVID -19/
MIS -C Convalescent
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 2Optimally Within 3
Days After Potential
COVID -19/MIS -C
Illness Onset28 to 35 Days After
Potential COVID -
19/MIS -C Illness
Visit
Type of Visit Clinic Clinic Clinic Clinic or
TelephoneClinic Clinic or
TelehealthClinic
Collect SAEs as appropriatehX X X X X X X
Unblind the participant and move to either
Section 1.3.2.1 or Section 1.3.2.2X
Collection of COVID -19/MIS -C–related clinical
and laboratory information (including local
diagnosis)X X
Abbreviation s: CRF = case report form; HIV = human immunodeficiency virus ; MIS -C = multisystem inflammatory syndrome in children; PBMC = peripheral blood
mononuclear cell .
a.This visit may be conducted across 2 consecutive dates; if so, all steps from assessing the inclusion and exclusion criteria onwards must be conducted on the
day of vaccination .
b.Applicable at designated sites only for participants ≥10years of age who separent(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 5and Visit A (Section 1.3.2.2 ) occur on the same day.
d.Potential MIS -C visit: hospitalization for a severe illness with no other alternative etiology.
e.Height and weight will be collected only at Visit 1.
f.Only approximately 450 randomized participants in each age group willhave blood drawn at 1 month after Dose 2.
g.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 w ill be captured to describe disease endpoints for lack -of-efficacy assessment data only on the relevant pages of the CRF, as these are expected
endp oints.
h.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)
Protocol C4591007
Protocol Amendment 1 , 05March 2021
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CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 281.3.2.1. Phase 2/3 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 and unplanned potential COVID-19 /MIS-C convalescent visit are required at
any time for the duration of the study that potential COVID -19/MIS-C symptoms are reported.
Visit Number Visit X Visit Y Unplanned Unplanned
Visit Description 12-Month
Follow -up Visit24-Month
Follow -up VisitPotential COVID -19 Illness/MIS -C
VisitaPotential COVID -19/MIS -C
Convalescent Visit
Visit Window (Days) 350 to 378 Days
After Visit 2714 to 742 Days
After Visit 2Optimally Within 3 Days After
Potential COVID -19/MIS -CIllness
Onset28 to 35 Days After Potential
COVID -19/MIS -CIllness
Visit
Type of Visit Clinic or
TelephoneClinic or
TelephoneClinic or Telehealth Clinic
For participants who are HIV positive, record latest CD4 count and
HIV viral loadX X
Collect prohibited medication use X X X X
Obtain anterior nasal swab X
Collect blood sample for immunogenicityb~5mLc~5mLc ~5mL
Collect A Es as appropriated 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 X
Abbreviation s: CRF = case report form; HIV = human immunodeficiency virus ; MIS -C = multisystem inflammatory syndrome in children .
a. Potential MIS -C visit: hospitalization for a severe illness with no other alternative etiology .
b. T he participants who are part of the evaluation of persistence of immune response will have blood drawn either at Visit X or Visit Y.
c. If the participants had an unplanned potential COVID -19/MIS -C convalescent visit within ≤42days before the scheduled visit ( Visit X or Visit Y ) and if a blood sample
was collected as part of the convalescent visit, or if the participant originally received placebo and declines the offer of BNT162b2, blood sample collection at the scheduled
visit isnot required.
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 sequ elae that are consistent with the clinical endpoint definition ( Section 8.1) should not be recorded as AE s. 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.
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PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Protocol Amendment 1 , 05March 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 291.3.2.2. Phase 2/3 Participants Who Originally Received Placebo
Participants who originally received placebo and accept the offer for receiving BNT162b2 will follow t his SoA after unblinding at
Visit 5 (in Section 1.3.2).
An unplanned potential COVID-19/MIS- C illness visit and unplanned potential C OVID -19/MIS- C convalescent visit are required at
any 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 COVI D-19 /MIS-Cillness visit unless, in the investigator’s opinion ,the clinical
picture is more indic ative of a possible COVID -19 illness rather than vaccine reactogenicit y.For details, see Section 8.13.
Visit Number A B C D E F Unplanned 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
VisitaPotential
COVID -19/M
IS-C
Convalescent
Visit
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 560
Days After
Visit BOptimally
Within 3 Days
After
Potential
COVID -19
Illness Onset28 to 35 Days
After
Potential
COVID -19
Illness Visit
Type of Visit Clinic Clinic Telephone Telephone Telephone Clinic or
TelephoneClinic or
TelehealthClinic
Confirm participant originally received placebo X
Measure vital signs (including body temperature) X X
Perform targeted physical examination X X
For participants who are HIV positive, record latest
CD4 count and HIV viral loadX X X X X
Perform urine pregnancy test (only for female
participants biologically capable of having children)X X
Confirm use of contraceptives (if appropriate) X X X
Collect prohibited medication use X X X X X X X X
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PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
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CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 30Visit Number A B C D E F Unplanned 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
VisitaPotential
COVID -19/M
IS-C
Convalescent
Visit
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 560
Days After
Visit BOptimally
Within 3 Days
After
Potential
COVID -19
Illness Onset28 to 35 Days
After
Potential
COVID -19
Illness Visit
Type of Visit Clinic Clinic Telephone Telephone Telephone Clinic or
TelephoneClinic or
TelehealthClinic
Obtain anterior nasal swab X X X
Collect blood sample for immunogenicity ~5 mL
Review temporary delay criteria X X
Review and consider eligibility X X
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 appropriateb X X X X X
Collect SAEs as appropriatecX X X X X X
Collect e -diary or assist the participant’s
parent(s)/legal guardian to delete applicationX
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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 31Visit Number A B C D E F Unplanned 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
VisitaPotential
COVID -19/M
IS-C
Convalescent
Visit
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 560
Days After
Visit BOptimally
Within 3 Days
After
Potential
COVID -19
Illness Onset28 to 35 Days
After
Potential
COVID -19
Illness Visit
Type of Visit Clinic Clinic Telephone Telephone Telephone Clinic or
TelephoneClinic or
TelehealthClinic
Collection of COVID -19/MIS -C–related clinical
and laboratory information (including local
diagnosis)X X
Abbreviation s: CRF = case report form; HIV = human immunodeficiency virus; IRT = interactive response technology; MIS-C = multisystem inflammatory syndrome in children .
a. Potential MIS -C visit: hospitalization for a severe illness with no other alternative etiology .
b. 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 sequ elae that are consistent with the clinical endpoint definition ( Section 8.1) should not be recorded as AE s. 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 .
c. Refer to Section 8.3.1 forthetime period for collecting SAEs .
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Page 322.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 study is to rapidly describe the safet y, tolerabilit y,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
global crisis of COVID -19 and fast expansio
n of the disease in the United States and
elsewhere, the rapid development of an effective vaccine is of utmost importance.
2.2.Background
In December 2019, a pneumonia outbreak of unknown cause occurred in Wuhan, China.
InJanuary 2020, it became clear that a novel coronavirus (2019- nCoV) was the underl ying
cause. Later in January , the genetic sequence of the 2019 -nCoV became available to the
WHO and public (MN908947.3), and the virus was categorized in the Betacoronavirus
subfamily . By sequence anal ysis, the ph ylogenetic 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 secondary
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 generally 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
MIS-C, an emerging condition that appears to be temporally related to recent 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 perinflamm atory 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, Hispanic, or of South Asian descent.14As of 29June 2020, approximately 1000 cases
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Page 33have 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 complications included cardiac d ysfunction (40.6%), shock (35.4%),
myocarditis (22.8%), coronary artery dilation or aneury sm (18.6%), and acute kidney injury
(18.4%).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 vaccines 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 vir us.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 approache s. Unlike live
attenuated vaccines, RNA vaccines do not carry the risks associated with infection and may
be given to people who cannot be administered live virus (eg, pregnant women and
immunocompromised persons). RNA -based 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 enable 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 Phase 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 demonstra tedBNT162b2 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 participan ts randomized 1:1 with a median of
2 months of follow -up after the second dose of vaccine showed a favorable safet y profile at a
dose of 30 μg in participants 16 y ears of age and older .22On 11 December 2020, the US
FDA issued an EUA for use in individual s 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.
This Phase 1/2/3 study (C4591007) will evaluate up to 3 different dose levels of BNT162b2
in children in up to 3 age groups ( participants ≥5 to <12 years, ≥2 to <5 y ears, and ≥ 6months
to <2 years of age). S afety , tolerabilit y, immunogenicity ,and efficacy (depending on
successful immunob ridging 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
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Page 34<12years of age will be based on the acceptable blinded safet y data demonstrated in 2259
12-through 15-year-oldsat the 30-µ g dose level in the C4591001 study .23The 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
includes an immunobridging analy sisofimmune responses in participants ≥6 months to
<12years of age to th ose in participants 16to 25 years of age in the Phase 3 C45 91001
efficacy study . Safety,tolerability ,and eff icacy (depending on successful immunobridging
andaccrual of a sufficient number of cases) will also be evaluated in Phase 2/3 of this study .
2.2.1. Clinical Overview
The BNT162 vaccine candidates use an RNA to deliver genetic information to cells, where it
is used to express proteins for the therapeutic effect. This vaccine is for the prevention of
COVID -19. Prior to this study , clinical data from the BNT162b2 vaccine established a
favorable safety profile ,with mild, localized, and transient effects. The C4591001 study24is
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 .25Vaccine -related enhanced disease for vaccines against related
coronaviruses (SARS -CoV -1 and MERS) has been reported onl y in animal models.26,27To
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
documented so far for SARS -CoV -2.The currently available safet y and immunogenicit y
data are presented in the BNT162 IB.
2.3.Benefit/Risk Assessment
There is an ongoing global pandemic of COVID -19 with no approved or licensed preventive
options available. However, based on the data available from the C4591001 study , multiple
temporary or emergency use authorizations have been granted. The available safet y and
immunogenicit y data from the ongoing Pfizer/BioNTech clinical trial combined w ith
available nonclinical data with BNT162 vaccines, and data from nonclinical studies and
clinical trials with the same or related RNA components, or antigens, support a favorable
benefit/risk profile and support continued clinical development of BNT162b2 .
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 reactions 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 hy persensitivity -related A Es 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 gener ally 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
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Page 35vaccination. 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. Although participants 16 through
17years of ag e were enrolled in the Phase 3 trial, safet y data for this age group are limited.
However, available data are consistent with the safety profile in the adult population, and it is
biologicall y reasonable to extrapolate the greater safet y experience in adu lts, in particular
younger adults, to the oldest pediatric age group of 16 through 17 years. The potential risks
are based on the observed safet y profile to date, which shows mostly mild reactogenicity , low
incidence of severe or serious events, and no cl inically 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.22
In order for the stud y population to be as representative and diverse as possible, the inclusion
of participants with known chronic stable HIV, HCV, or HBV is permitted in Phase 2/3.
Individuals with chronic viral diseases are at increas ed risk for COVID -19 complications and
severe disease. In addition, with the currently available therapies for their treatment, man y
individuals with chronic stable HIV, HCV, orHBV infections are less likely to be at
increased safety risk as a participant in this vaccine study than individuals with other chronic
stable medical conditions.
More detailed information about the known and expected benefits and risks and reasonabl y
expected AEs of BNT162 b2RNA -based COVID -19 vaccine may be found in the IB, which
is the SRSD for this study.
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Page 362.3.1. Risk Assessment
Potential Risk of Clinical Significance Summary of Data/Rationale for Risk Mitigation Strategy
Study Intervention(s) [ BNT162b2 RNA- Based COVID-19 Vaccine]
Potential for greater local reactions (injection site
redness, injection site swelling, and injection site
pain) and systemic events (fever, fatigue, headache,
chills, vomiting, diarrhea, muscle pain, and joint
pain) following vaccination as compared to
adults /adolescents in the C4591001 study .These are common adverse reactions seen with
other vaccines, as noted in the FDA CBER
guidelines on toxicity grading scales for healthy
adult and adolescent volunteers in preventive
vaccine clinical trials .28The most common events
report ed in C4591001 w ere mild to moderate pain
at the injection site, fatigue, and headache.22To address reactogenicity concerns, dose finding
has been included as outlined. In addition, the study
employs the use of a reactogenicity e- diary to
monitor local reactions and systemic event s in real
time. All study participants will be observed for at
least 30 minutes after vaccination.
Unknown A Es with a novel vaccine in children
≥6months to <1 2years 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, co untry, and baseline SARS -CoV -2
status.The current Phase 3 C4591001 study include s
participants 12years of age and older .
Potential for COVID -19 enhancement. Disease enhancement has been seen following
vaccination with RSV, feline coronavirus, and
Dengue virus vaccines.No evidence of disease enhancement has been
reported in the C4591001 study to date.25
Temporary delay criteria defer vaccination of
participants w ith symptoms of potential COVID -19.
All 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.
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.
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Page 37Potential Risk of Clinical Significance Summary of Data/Rationale for Risk Mitigation Strategy
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. Potential
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 .
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 Phase 1 and
participants contributing to the immunogenicity
analysis in Phase 2/3 will have at most 3 planned
blood draws ,with all remaining participants having
2planned blood draw s.
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Page 382.3.2. Benefit Assessment
Benefits to individual participants may include:
Receipt of a n efficacious COVID-19 vaccine during a global pand emic
Access to COVID -19 diagnostic testing
Contributing to research to help others in a time of global pandemic
2.3.3. Overall Benefit /Risk Conclusion
Taking into account the measures taken to minimize risk to participants participating in this
study , the potential risks identified in 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 age groups referred to in the objectives and estimands below are participants ≥5 to
<12years, ≥2 to <5 y ears, and ≥ 6months to <2 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 ≥5 to <12 years 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, drowsiness, and
irritability )
 AEs
 SAEs
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Page 39Phase 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 :
At baseline , before Dose 2, and 7 days
after Dose 2,
 GMTs at each time point
 GMFR from before Dose 1
(baseline) to each subsequent time
point after vaccination 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 participants included in
the Phase 2/3 immunobridging analysis
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 1 month
after Dose 2Participants ≥5 to <12 years 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 wo rsened 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
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Page 40Phase 2/3
Objectives Estimands Endpoints
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 partic ipants 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 ≥5 to <12 years 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 mo nths to <2 years of
age:
 Local reactions ( tenderness at the
injection site, redness, and
swelling)
 Systemic events (fever, decreased
appetite, drowsiness, and
irritability )
 AEs
 SAEs
Primary Immunogenicity: Primary Immunogenicity: Primary Immunogenicity:
To demonstrate immunobridging of the
immune response elicited by
prophylactic BNT162b2 at the dose
level selected per age group
inPhase 2/3 participants without
serological or virological evidence (up
to 1 month after receipt of Dose 2) of
past SARS -CoV -2 infection:In participants complying with the key
protocol criteria (evaluable
participants) and no serological or
virological evidence (up to 1 month
after receipt of Dose 2) of past
SARS-CoV -2 infection:  SARS -CoV -2 neutralizing titers
 In participants ≥5 to <12 years of
age compared to participants 1 6to
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
 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 2
 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
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Page 41Phase 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 per 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
In all age groups where
immunobridging is successful, i f at
least 22 cases are accrued across those
age groups :
To evaluate the efficacy of prophylactic
BNT162b2 against confirmed
COVID -19 occurring from 7 days after
Dose 2 in participants without evidence
of past SARS -CoV -2 infectionIn 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:
100 × (1 –IRR) [ratio of active vaccine
to placebo] Confirmed COVID-19 incidence
from 7 days after Dose 2 per 1000
person -years of follow -up
In all age groups where
immunobridging is successful, i f at
least 22 cases are accrued across those
age groups :
To evaluate the efficacy of prophylactic
BNT162b2 against confirmed
COVID -19 occurring from 7 days after
Dose 2 in participants with or without
evidence of past SARS -CoV -2
infection In participants complying with the key
protocol criteria (ev aluable
participants) and with o r without
serological or virological evidence
(prior to 7 days after receipt of Dose 2)
of past SARS -CoV -2 infection:
100 × (1 –IRR) [ratio of active vaccine
to placebo] Confirmed COVID-19 incidence
from 7 days after Dose 2 per 1000
person -years of follow -up
To describe the efficacy of prophylactic
BNT162b2 against asymptomatic
infection in participants 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
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Page 42Phase 2/3
Objectives Estimands Endpoints
Exploratory: Exploratory: Exploratory:
To evaluate the immune response over
time to prophylactic BNT162b2 at the
dose level selected per 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,
 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 immune response
(non-S) to SARS -CoV -2 in Phase 2/3
participants with and without
confirmed COVID -19 during the study N-binding antibody
To describe COVID -19 and severe
COVID -19 cases in all participants
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 Confirmed cases as per CDC
criteria
To describe the serological responses in
Phase 2/3 participants to BNT162b2 at
the dose level selected per 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
per 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:
 7 days and 1 and 6 months after
Dose 2
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Page 434.STUDY DESIGN
4.1.Overall Design
This is a Phase 1/2/3 study in healthy children <1 2years of age.
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.
4.1.1. Phase 1
Phase 1 is the open -label dose -finding portion of the study to evaluate safety , tolerability , and
immunogenicit y 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). D ose finding is being initiated in this study in particip ants ≥5
to <12 y ears of age based on the acceptable blinded safet y assessment of the 30 -µg dose in
12-to 15-year-oldsin the C4591001 study .
The purpose of P hase 1 is to identify preferred dose level(s) of BNT162b2 from up to 3
different dose levels in each age group.
Dependent upon safet y and/or immunogenicit y data generated during the course of this
study , it is possible that dose levels may not be started, may be terminated early , and/or may
beadded with dose levels below the lowest stated dose.
Participants will have blood drawn prior to both Dose 1 and Dose 2 and 7 day s after Dose 2
to assess for immunogenicity to determine the final BNT162b2 dose level for the Phase 2/3.
4.1.2. Phase 2/3
Phase 2/3 will evaluate safet y, tolerability , and immunogenicit y in each age group atthe
selected dose level from Phase 1. Efficacy will be evaluated across all age groups in which
immunobridging is successful, depending on accrual of a sufficient number of cases across
those age groups.
All participants will have blood drawn at baseli ne 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
immunogenicit y data collected at baseline and 1 month after Dose 2. The persistence of the
immune response will be b ased 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 against confirmed COVID -19 and against
asymptomatic infectio n will also be assessed.
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 part of the stud y.
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Page 444.1.3. Number of Participants
4.1.3.1. Phase 1 : Open-L abel Dose Finding
This open -label dose -finding phase will consist of up to 3 different dose levels in each age
group ,with 16participants per dose level ,and a total of 144participants; seeTable 1.
Table 1.Phase 1 Participants
Age Group Total Up to 3 D ose Levelsof BNT162b2 Active Placebo
≥5 to <12 Years 48 16/16/16 16 N/A
≥2 to <5Years 48 16/16/16 16 N/A
≥6 M onths to <2 years 48 16/16/16 16 N/A
4.1.3.2. Phase 2 /3: Safety, Tolerability ,Immunogenicity, and Efficacy
Phase 2/3 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, with a total of approximately 4500
participants. Participants will be randomized in a 2:1ratio to receive active vaccine or
placebo (Table 2).
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 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, 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 4500
participants will contribute to the VEanalysis for conditional VEand as ymptomatic
infection . Efficacy will be evaluated across all age groups in which immunobridging is
successful, depending on accrual of a sufficient number of cases across those age groups.
At de signated 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 ≥10years of age . Thesesample swill be used on an
exploratory basis to investigate the postvaccination cell -mediated immune response at these
time points.
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Page 45Table 2. Phase 2/3 Participants – Blood Draws for Immunogenicity/Efficacy
Assessments
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 4500 3000 1500 2250 1500 750 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 3).
Table 3. Phase 2/3 Participants –Safety and Tolerability/Efficacy Assessments
Total Active Placebo
4500 3000 1500
4.1.4. Intervention Groups and Duration
Phase 1 : Dose finding will begin at the low- dose level in participants ≥5 to <12 y ears of age .
The I RC will review safety data (e -diary and AE) acquired up to 7 day s after Dose 1 forthe
low-dose group ; upon confirmation of an acceptable safet y assessment by the I RC:
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 years of age.
In each age group, i f the low -dose level is considered not acceptable 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 safet y assessment after Dose 1, the high -dose level will not commence.
Based on safet y assessment, the second dose may be given at a lower dose level.
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Page 46Phase 2/3: Progression of each age group into Phase 2/3 will occur independently ; 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 in each age group. For each age group t o proceed to
Phase 2/3, safet y, tolerability , and immunogenicity data from 7 day s after Dose 2 for the
selected vaccine dose level in the age group from Phase 1 will be confirmed to be acceptable.
Duration: Participants are expected to participate for up to a maximum of approximately
26months.
4.2.Scientific Rationale for Study Design
Additional surveillance for COVID -19 will be conducted as part of the study , given the
potential risk of disease enhancement . If a participant experiences s ymptoms, as detailed in
Section 8.13, a COVID -19/MIS-Cillness visit and subsequent convalescent visit will occur.
As part of these visits, samples ( anterior nasal swab and blood [convalescent visit] ) will be
taken for antigen and antibody assessment as well as recording of COVID-19 /MIS-C– related
clinical and laboratory information (including local diagnosis).
Human reproductive safety data are not available for BNT162b2 RNA -based COVID -19
vaccine, but there is no suspicion of human teratogenicity based on the intended mechanism
of action of the compound. Therefore, the us e of a highl y effective method of contraception
is required (see Appendix 4 ) for WOCBP.
4.3.Justification for Dose
Based on acceptable blinded safet y data in 2259 12-through 1 5-year-olds at the 30- µg dose
level in the C4591001 study , dosefinding is considered in this study using the same vaccine
candidate .23 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 t o another dose level in this age group or initiating the younger age groups .
4.4.End of Study Definition
A participant is considered to have completed the study if he/she has completed all phases of
the study ,including the last visit.
The end of the study is defined as the date of the last visit of the last participant in the study .
5. STUDY POPULATION
This study can fulfill its objectives only if appropriate participant s are enrolled. The
following eligibility criteria are designed to select participant s for whom participation in the
study is considered appropriate. All relevant medical and nonmedical conditions should be
taken into consideration when deciding whether a particular participant is suitable for this
protocol .
Prospective approval of protoc ol deviations to recruitment and enrollment criteria ,also
known as protocol waivers or exemptions, is not permitted .
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Page 475.1. 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 participants ≥6 months to <12years of age ,at the time of randomization ,
at Visit 1.
Refer to Appendix 4 for reproductive criteria for male ( Section 10.4.1 ) and female
(Section 10.4.2 ) participants.
Type of 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 inve stigator to be eligible for inclusion in the study.
Note: Healthy participants with preexisting stable disease, defined as disease not
requiring significant change in the therap y or hospitalization for worsening disease
during the 6 weeks before enrollment , can be included.
Phase 2/3: Specific criteria for such p articipants with known stable infection 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 whose
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 day s 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 p articipant’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 IC D and in this protocol. Depending on the age of the participant
and accor ding to local requirements, participants will also be asked to provide assent as
appropriate (verbal or written).
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Page 48The investigator, or a person designated b y the investigator, will obtain written or
electronically signed informed consent ( and assent )from each study participant’s legal
guardian (as defined in Appendix 1 )and the participant’s assent, when applicable, before any
study -specific activity is performed . All legal guardians should be fully informed, and
participan ts should be informed to the fullest extent possible, about the study in language and
terms they are able to understand. The investigator will retain the original copy 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.
5.Other medical or psy chiatric condition includin g recent (within the past year) or active
suicidal ideation /behavior or laboratory abnormality that may increase the risk of study
participation or , in the investig ator’s judgment, make the participant inappropriate for the
study .
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.Immunocompromised 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.
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.
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Page 4912. Individuals who receive treatment with immunosuppressive therapy , including cy totoxic
agents or s ystemic corticosteroids, eg, for cancer or an autoimmune disease, or planned
receipt throughout the study . If 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 therapy has been discontinued for at least 28 day s before
study intervention administration. Inhaled/ nebulized, intra -articular, intrabursal, or
topical (skin or ey es) corticosteroids are permitted.
13. Receipt of blood/plasma products, immunoglobulin, or monoclonal antibodies, from 60
days before study intervention administration , or receipt of an y passive antibody therapy
specific to COVID -19 from 90 day s before study intervention administration, or planned
receipt throughout the study .
Prior/Concurrent Clinical Study Experience:
14.Participation in other studies involving study intervention within 28 day s prior to study
entry and/or during st udy participation.
15.Previous participation in other studies involving study intervention containing LNPs .
Diagnostic Assessments:
Not applicable .
Other Exclusions:
16. Participants who are direct descendants (child or grandchild) of investigational site staff
members or Pfizer/BioNT ech 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 vaccinat ion.
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 co ntraception 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 d ocument 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
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Page 50instruct the participant ’s parent(s)/legal guardi anto 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 c onsent 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 respond 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.
5.5. Criteria for Temporarily Delaying Enrollment/Randomization/Study Intervention
Administration
The following conditions are temporary or self -limiting and a participant ma y 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
infection is an exclusion criteri on):
New or increased cough;
New or increased shortness of breath;
Diarrhea;
Vomiting ;
Chills;
New or incre ased muscle pain;
New l oss of taste/smell;
Sore throat;
Nausea ;
Abdominal pain ;
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Page 51Inability to eat/poor feeding in participants <5 y ears of age .
2.Receipt of an y nonlive vaccine within 14 day s, or any livevaccine within 28 days,
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 pe rmitted.
6.STUDY INTERVENTION
Study intervention is defined as a ny investigational intervention(s), marketed product(s),
placebo, medical device(s) , or study procedure(s) intended to be administered to a study
participant according to the study protocol.
Phase 1 will evaluate a 2 -dose (separated b yapproximately 21 day s) schedule of up to
3different dose levels of RNA vaccine candidate BNT162b2 for active immunization against
COVID -19,to determine the final dose level of BNT162b 2in Phase 2/3 for each age group .
The investigation alRNA vaccine candidate andsaline placebo ,in Phase 2/3 , 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.
Normal salin e (0.9% sodium chloride solution for injection).
6.1.Study Intervention(s) Administered
Intervention Name BNT162b2
(BNT162 RNA -LNP V accine Utilizing
modRNA)Saline Placebo
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
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Page 52Intervention Name BNT162b2
(BNT162 RNA -LNP V accine Utilizing
modRNA)Saline Placebo
Packaging and
LabelingStudy intervention will be provided in a
glass vial as open -label supply. Each vial
will be labeled as required per country
requirement .Study intervention will be provided in a glass
or plastic vial as open -label supply. Each vial
will be labeled as required per country
requirem ent.
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 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 IP manual.
For participants ≥2to <12 y ears 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.
For participants 6months to <2 years of age, s tudy intervention should be administered
intramuscularl y into the anterior thigh muscle, preferabl y 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 qualif ied,
GCP -trained, and vaccine- experienced member of the study staff (eg, ph ysician, nurse,
physician’s assistant, nurse practitioner, pharmacist, or medical assistant) as allowed by
local, state, and institutional guidance.
Study intervention administrati on details will be recorded on the CRF.
6.2.Preparation/Handling/Storage/Accountability
1.The investigator or designee must confirm appropriate temperature conditions have been
maintained during transit for all study intervention sreceived and an y discrepancies are
reported and resolved before use of the stud y intervention.
2.Only participants enrolled in the study may receive study intervention and only
authorized site staff may supply or administer study intervention. All study interventions
must be stored in a secure, environmentally controlled, and monitored (manual or
automated recording ) area in accordance with the labeled storage conditions with access
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Page 53limited to the investigator and authorized site staff. At a minimum, daily minimum and
maximum temperature s 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 site 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 by the storage conditions
stated on the label.
5.Study interventions should be stored in their original containers.
6.See the IP manual for storage conditions of the study intervention .
7. The investigator, institution, or the head of the medical institution (where applicable) is
responsible for stud y intervention accountability , reconciliation, and record mainte nance
(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 des troyed in compliance with applicable environmental regulations,
institutional policy , and any special instructions provided by Pfizer.
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. Study intervention should be prepared and dispensed by an appropriatel y
qualified and experienced member of the stud y staff (eg, phy sician, 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 Phase 2/3) will be prepared b y qualified
unblinded site personnel accordi ng to the I P manual. The study intervention will be
administered in such a way as to ensure the participants remain blinded.
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Page 546.3.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 sele ct 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 infor mation
and further details on the use of the IRT s ystem.
6.3.2. Blinding of Site Personnel (Phase 2/3 O nly)
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, will 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 manner 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 the 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 assignments.
At Visit 5 (6 months after Dose 2), to allow administration of BNT162b2 to participants who
originall y received placebo, site staff will be unblinded to an individual participant’s original
vaccine allocation .
6.3.3. Blinding of the Sponsor
For the Phase 1 in which only active vacc ine is being administered, blinding is not applicable
tothe participants in Phase 1 . The majorit y of sponsor staff will be blinded to s tudy
intervention allocation for Dose s1 and 2 in Phase 2/3. All laboratory personnel performing
serology assay s will remain blinded to study intervention assigned/received throughout the
study in Phase 2/3. The following sponsor staff, who will have no part in the blinded
conduct of the stud y, will be unblinded in Phase 2/3 (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
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Page 55site 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) .
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. This team will only be unblinded at the group level and not have access to
individual participant assignments. The programs that produce the summary tables will
be developed and validated by the blinded study team, and these programs will be run by
the unblinded DMC team.
At Visit 5 , when a participant who originally received placebo receives BNT162b2 per
the SoA in Section 1.3.2.2, 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 Phase 2/3 up to Visit 5 , the IRT will be programmed with blind -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 safety
must alway s be the first consideration in making 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 recorded 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 th e CRF. The dose of study intervention and study participant
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Page 56identification will be confirmed at the time of dosing by a member of the study site staff
other than the person administering the study intervention.
6.5. Concomitant Therapy
6.5.1. Prohibited During the St udy
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 onwards, 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 within 14 days, or any live vaccine 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 systemic corticosteroids ( >2mg/kg/dose of prednisone or equivalent) for ≥14
days is prohibited from 28 day s prior to enrollment through Visit 4 .
Receipt of blood/plasma products, immunoglobulins, or monoclonal antibodies is
prohibited within 60 days before enrollment through conclusion of the study.
Receipt of an y passive antibody therap y specific to COVID -19 is prohibited within 90
days before enroll ment through conclusion of the study .
Receipt of an y other (nonstudy ) coronavirus vac cine at an y time prior to or during stud y
participation is prohibited.
Prophy lactic antipy retics and other pain medication to prevent s ymptoms associated with
study intervention administration are not permitted. However, if a participant is taking a
medic ation 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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Page 576.5.2. Permitted During the Study
The use of antip yretics and other pain medication to treat symptoms associated with study
intervention administration or ongoing conditions is permitted.
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 intrabursal
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 participants and Visit 5 for
Phase 2/3 participants) .
Details of an y blood/plasma products, immunoglobulins (eg, IVIG ), or
immunomodulators ( eg, anakinra, tocilizumab) during stud y participa tion.
Antiplatelet s (eg, aspirin, clopidogrel) or anticoagulants (eg, heparin, exoparin, warfarin) .
Any prescribed medication to treat potential COVID -19 or MIS -C illness cases .
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 pa rticipant receives 1 dose 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 f or administration of the additional dose.
Measure the participant’s body temperature.
Perform urine pregnancy test on WOCBP as described in Section 8.2.7.
Discuss contraceptive use as described in Section 5.3.1 .
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Page 58Ensure that the participant meets none of the temporary delay criteria as described in
Section 5.5.
Unblinded site staff member(s) will dispense/administer 1 dose of study inter vention into
the deltoid muscle of the (preferabl y)nondominant arm. Please refer to the I P manual for
further instruction on th is process.
Blinded site staff must observe the participant for at least 30 minutes after study
intervention administration for any 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 ’s parent(s)/legal gu ardian should continue to adhere to the participant’s
current visit schedule ,but the participant must be followed for nonserious AEs for 1
month and SAEs 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 vis it(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 discontinuation) . 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 8.15).
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 .
See 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.
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Page 59In the event of discontinuation of study intervention, it must be documented on the
appropriate CRF/in the m edical 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 guardian . 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
the participant ’s parent(s)/legal guardian . All attempts to contact the 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 docu ment participant outcome, if possible.
The 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 study , the 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 recor ds and notify the sponsor accordingl y.
If the participant’s parent(s)/legal guardian or a child who has provided assent during any
phase of the stud y 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 collected before such withdrawal of consent.
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Page 60Lack 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 who has provided assent during an y phase of the stud y,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 protocol -specified
follow -up procedures. The only exception to this is when a participant ’s parent(s)/legal
guardian specificall y withdraws consent for an y further contact with persons previously
authorized to provide this information. The p articipant ’s paren t(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 b y the investigator, as to whether t he withdrawal is onl y 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 participant is
alive or dead) is be ing 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 the participant’s parent(s)/legal guardian is unable to be contacted by the
study 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 ’s parent(s)/legal guardian and reschedule
the missed visit as soon as possible and counsel the participant ’s parent(s)/legal guardian
on the importance of maintaining the assigned visit schedule and ascertain whethe r or not
the 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’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;
Should the participant’s parent(s)/legal guardian continue to be unreachable, the
participant will be considered to have withdrawn from the study .
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Page 618.STUDY ASSESSMENTS A ND PROCEDURES
The investigator (or an appropriate delegate at the investigator sit e) 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 stud y 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 elig ibility criteria. The investigator will maintain a screening log to
record details of all participants screened and to confirm eligibility or record reasons for
screening failure, as applicable.
Every effort should be made to ensure that protocol -requir ed 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 mus t take all steps necessary to ensure the safet y and
well-being of the participant. When a protocol -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 ha s 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 in this study is approximately
15 mL for Phase 1 and Phase 2/3 participants who will contribute to immunogenicity
assessment s. The remaining Phase 2/3participants will have a 10-mL 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 a pproximately 45mL. Additionally , 5mL of
blood will be taken at an unplanned convalescent visit at any time a participant develops
symptoms indicating a potential COVID -19/MIS-C infection. Note : If the participants had
an unplanned potential COVID -19/MI S-C convalescent visit within ≤42 days before the
scheduled visit ( Visit Xor Y) and if a blood sample was collected as part of the convalescent
visit, blood sample collection at the scheduled visit is not required.
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Page 628.1.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 develops anacute illness (described in Section 8.13), for the
purposes of the stud y he or she will be considered to potentially have COVID -19 illness.29 In
this circumstance, the participant’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 personne l (clinical vis it) or b y a participant ’sparent/legal guardian , which
will be tested at a central laboratory using a nRT-PCR test (Cepheid; FDA approved under
EUA) or other equivalent nucleic acid amplification –based test (ie, NAAT), to detect
SARS -CoV -2. In addition, c linical 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 1of the following assay s:
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 definit ions) of SARS -CoV -2–related cases, SARS -CoV -2–
related severe cases , and MIS-Cwill be considered in assessing COVID -19/MIS-C cases. In
all cases, the onset date of the case will be the date that sy mptoms were first experienced by
the participant ; if new symptoms are reported within 4 day s after resolution of all previous
symptoms, they will be considered as part of a single illness:
SARS -CoV -2–Related Cases
Confirmed COVID -19, first definition :presence of at least 1 of the following s ymptoms
and SARS -CoV -2 NAAT positive during, or within 4 day s before or after, the sy mptomatic
period, either atthecentral laboratory or at a local testing facility (using an acceptable test),
which trigger sa potential COVID -19 illness visit ( see Section 8.13.1 ):
Fever;
New or increased cough;
New or increased shortness of breath;
Chills;
New or increased muscle pain;
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Page 63New l oss of taste or smell;
Sore throat;
Diarrhea ,as defined b y ≥3 loose stools/day ;
Vomiting ;
Inability to eat/poor feeding in participants <5 y ears of age
The second definition , which may be updated as more is learned about COVID- 19, will
include the followi ng additional sy mptoms defined by the CDC (listed at
https://www.cdc.gov/coronavirus/2019 -ncov/s ymptoms- testing/sy mptoms.html ),but does not
trigger a potential COVID -19 illness visit unless in the opinion of the PI deemed necessary :
Fatigue;
Headache;
Nasal congestion or runny nose;
Nausea or abdominal pain10
SARS -CoV -2–related hospitalization definition :confirmed COVID -19 and
hospitalization .
SARS -CoV -2–related severe case definition :confirmed COVID -19 and presence of at least
1 of the following triggers a potential COVID -19 illness visit :
Clinical signs at rest indicative of severe s ystemic illness :
RR(breaths /min)and HR(beats /min)as shown in Table 4;30
SpO 2≤92% on room air or >50% FiO 2to maintain ≥92%, or PaO 2/FiO 2
<300 mmHg;
Table 4.RR and HR , by Age ,Indicative of Severe Systemic Illness
Participant Age RR HR
6to <9 Months >61 >168
9 Months to <12 m onths >58 >161
12to <18 Months >53 >156
18to <24 Months >46 >149
2to <3 Years >38 >142
3to <4 Years >33 >136
4to <6 Years >29 >131
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Page 64Table 4.RR and HR , by Age ,Indicative of Severe Systemic Illness
Participant Age RR HR
6to <8 Years >27 >123
8to <12 Years >25 >115
Abbreviations: HR = heat rate; RR = respiratory rate.
Note: This table is based on data obtained from : Fleming S, Thompson M, Stevens R, et al. Normal ranges of
heart rate and respiratory rate in children from birth to 18 years of age: a systematic review of observational
studies. Lancet. 2011;377 (9770) :1011 -8.
Respiratory failure (defined as needing high -flow oxy gen,including CPaP , BiPaP ,
noninvasive ventilation, mechanical ventilation, or ECMO);
Evidence of shock or cardiac failure :
SBP ( mmHg):
<70 + (age in years × 2) for age up to 10 years,<90 + (age in years ×2) for
age ≥10years ; orrequiring vasoactive drugs to maintain BP in the normal
range ;
Significant acute renal failure : serum creatinine ≥2 times UL Nfor age or 2 -fold increase
in baseline creatinine ;
Significant GI /hepatic failure: total bilirubin ≥4 mg/dL or ALT 2 times ULN for age;
Significant neurologic aldysfunction : Glasgow Coma Scale score ≤11 or acute change in
mental status with a decrease in Glasgow Coma Scale score ≥3 points from abnormal
baseline32;
Admission to an I CU;
Death.
Confirmed MIS -Cdefinition :31asper the CDC MI S-C case definition :
An individual <21 y ears of age presenting with fever (≥38.0 °C for ≥ 24 hours or report of
subjective fever lasting ≥24 hours );AND
Laboratory evidence of inflammation (based on local laboratory ranges) i ncluding, but
not limited to, 1or more of the following: an elevated CRP, ESR, fibrinogen,
procalcitonin, D-dimer, fer ritin, LDH, or IL-6, elevated neutrophils, reduced
lymphocy tes,and low albumin ;AND
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Page 65Evidence of clinically severe illness requiring hospitalization (definition as noted above
for severe disease) , with multisy stem ( ≥2) organ involvement :
oCardiac (eg,shock, elevated troponin, elevated BNP, abnormal echocardiogram,
arrhythmia) ;
oRenal (eg,acute kidney injury );
oRespiratory (eg,pneumonia, ARDS, pulmonary embolism) ;
oHematologic (eg,elevated D -dimers, thrombophilia, or thrombocy topenia) ;
oGI/hepatic (eg,elevated bilirubin, elevated liver enzymes, or diarrhea) ;
oDermatologic (eg,rash, mucocutaneous lesions) ;
oNeurological (eg,CVA, aseptic meningitis, encephalopathy ); AND
No alternative plausible diagnoses; AND
Positive for current or recent SARS- CoV -2 infection by RT-PCR, serology, or antigen
test; OR
COVID -19 exposure within the 4 weeks prior to the onset of s ymptoms.
Serological definition will be used for participants without clinical presentation of
COVID -19:
Confirmed seroconversion to SARS -CoV -2 without confirmed COVID -19: positive N -
binding antibod y result in a participant with a prior negative N -binding antibody result ;
Current or recent exposure is established b y SARS -CoV -2 infection b y RT -PCR,
serology , or antigen test; or COVID -19 exposure within the 4 weeks prior to the onset of
symptoms ;
Past serological and virological status is established by SAR S-CoV -2 PCR or history of
reported COVID -19.
8.1.1. Immunogenicity
Serum samples will be obtained for immunogenicity testing at the visits specified in the SoA.
The following assay s will be performed:
SARS -CoV -2 neutralization assay to establish immune responses to prefusion spike
glycoprotein
N-binding antibody assay to establish prior serological exposure to SARS -CoV -2
Note that all immunogenicity analy ses will be based upon samples anal yzed at the central
laboratory .
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Page 66At designated sites, an ad ditional optional whole blood sample of approximately 10mL will
be obtained prior to Dose 1, and at 7 day s and 6 months after Dose 2 ,from up to
approximately 60 participants ≥10years of age for isolation of PBMCs . Thesesample swill
be used on an exploratory basis to investigate the postvaccination cell- mediated immune
response at these time points.
8.1.2. Biological Samples
Blood and nasal swab samples will be used only for scientific research. Each sample will be
labeled with a code so that the laboratory personnel testing the samples will not know the
participant’s identity . Samples that remain after performing assay s outlined in the protocol
may be stored by Pfizer. Unless a time limitation is required by local regulations or ethical
requirements, t he samples will be stored for up to 15 years after the end of the study and then
destroy ed. If allowed by the I CD, stored samples may be used for additional testing to better
understand the immune responses to the vaccine(s) under stud y in this protocol, to inform the
development of other products, and/or for vaccine- related assay work supporting vaccine
programs. No testing of the participant’s DNA will be performed.
The participant’s parent(s)/legal guardian may request that the participant’s samples, i f still
identifiable, be destro yed at any time; however, any data already collected from those
samples will still be used for this research. The biological samples may be shared with other
researchers as long as confidentiality is maintained ,and no testi ng of the participant’s DNA
is performed.
8.2.Safety Assessments
Planned time points for all safety assessments are provided in the SoA . Unscheduled clinical
laboratory measurements may be obtained at any time during the stud y to assess any
perceived safety issues.
A clinical assessment, including medical history , will be performed on all participants at their
first visit to establish a baseline. Signi ficant medical history and observations from any
physical examination, if performed, will be documented in the CRF.
AEs and SAEs are collected, recorded, and reported as defined in Section 8.3.
Acute reactions within the first 30 minutes will be assessed and documented in the AE CRF.
The safet y parameters also include reactogenicit y e-diary reports of local reactions and
systemic events (including fever) and use of antipy retic med ication that occur in the 7 day s
after administration of the study intervention. These prospectively self-collected occurrences
of loca lreactions and s ystemic events are graded as described in Section 8.2.4
8.2.1. Physical Examinations
A brief targeted physical examination will include, at a minimum, measurement of height
and weight, assessments of general appearance, lungs, cardiovascular s ystem, and lymph
node survey .
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Page 67Investigators should pay special attention to clinical signs related to previous serious
illnesses.
8.2.2. Vital Signs
Temperature, pulse rate, and RRwill be assessed in all participants . BP will be assessed in
participants ≥5 years of age.
8.2.3. Clinical Safety Laboratory Assessments
Clinical safety laboratory assessments will not be collected in this study .
8.2.4. Electronic Diary
The participant ’s parent(s)/legal guardian will be required to complete a reactogenicit y e-
diary through an application (see Section 8.14) installed on a provisioned device or on the
person aldevice of theparticipant’s parent(s)/legal guardian . At the time of randomiz ation,
all participants’ parents/legal guardian swill be asked to monitor and record local reactions,
systemic events, and antipy retic medication use for 7 days following administration of the
study intervention (Dose 1 and Dose 2) . The reactogenicity e-diary allows recording of these
assessments only within a fixed time window, thus providing the accurate representation of
the participant’s experience at that time. Data on local reactions and s ystemic events
reported in the reactogenicity e-diary will be transferred electronicall y to a third- party
vendor, where they will be available for review by investigators and the Pfizer clinicians at
all times via an internet-based portal. At intervals agreed to b y the vendor and Pfizer, these
data will be transferred electronicall y into Pfizer's database for an alysis and reporting. These
data do not need to be reported by the investigator in the CRF as AEs.
Those participants who originally received placebo and then received BNT162b2 will
not complete a reactogenicity e-diary but will have their local reactions and systemic
events detected and reported as AEs in accordance with Section 8.3.1 .
Investigators (or designee) will be required to re view the reactogenicity e-diary data online at
frequent intervals as part of the ongoing safet y review.
The investigator or designee must obtain stop dates from the participant for any ongoing
local reactions, systemic events ,or use of antipy retic medication on the last day that the
reactogenicity e-diary was completed. The stop dates should be documented in the source
documents and the information entered in the CRF.
8.2.4.1. Grading Scales
The grading scales used in this study to assess local reactions and systemic events as
described below are derived from the FDA CBER guidelines on toxicity grading scales for
healthy adult and adolescent volunteers enrolled in preventive vaccine clinical t rials.28
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CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 688.2.4.2. Local Reactions
During the reactogenicit y e-diary reporting period, participant s’parents/legal guardi answill
be asked to assess redness, swelling, and pain/tenderness at the injection site and to record
the sy mptoms in the reactogenicit y e-diary daily for 7 day s (Day s 1 through 7) after each
vaccination . If a local reaction persists bey ond the end of the reactogenicity e-diary period
following vaccination, the participant ’sparents/legal guardians will be requested to report
that information. The investigator will enter this additional information in the CRF.
Redness and swelling will be measured and recorded in caliper units ( measuring device units;
range: 1to14for pediatric caliper device ) for the first 7 days following vaccination (Day s 1
through 7), and then categorized as mild, moderate, or severe using the scale shown in
Table 5. Measuring device units can be converted to centimeters according to the following
formula: 1 measuring device unit = 0.5 cm. Pain at the injection site will be assessed for
participant s ≥2to <12 yearsof age as absent, mild, moderate, or severe according tothe
grading scale in Table 5. Tenderness at the injection site will be assessed forparticipants
≥6months to <2 y earsof age as absent, mild, moderate, or severe according tothe grading
scale in Table 5.
If redness or swelling >14 caliper units is reported in the reactogenicity e-diary ,a telephone
contact should occur to ascertain further details and determine whether a site visit is
clinically indicated. If Grade 3 pain or tenderness at the injection site is reported in the
reactogenicity e-diary ,a telephone contact should occur to ascertain further details and
determine whether a site visit is clinically indicated. Only an investigator or medicall y
qualified person is able to classify a participant ’s local reaction as Grade 4. If a participant
experiences a confirmed Grade 4 local re action, the investigator must immediately notify the
sponsor and, if it is determined to be related to the administration of the study intervention ,
further vaccinations will b e discontinued in that participant.
Table 5.Local Reaction Grading Scale
Participant
AgeMild
(Grade 1)Moderate
(Grade 2)Severea
(Grade 3)aPotentially Life
Threatening
(Grade 4)b
Pain at the
injection site≥2 to <12
YearsDoes not
interfere with
activityInterferes
with activityPrevents daily
activityEmergency room visit or
hospitalization for severe
pain (tenderness) at the
injection site
Tenderness at
injection site≥6Months
to
<2 yearsHurts if gently
touched
(eg,whimpers,
winces, protests ,
or withdraws) Hurts if
gently
touched with
crying Causes limitation
of limb
movement Emergency room visit or
hospitalization for severe
pain (tenderness) at the
injection site
Redness ≥6 Months
to
<12 years1 to 4 caliper
units (or
measuring
device units)
=
0.5 to 2.0 cm5 to 14 caliper
units (or
measuring
device unit)
=
>2.0 to 7.0 cm>14 caliper units
(ormeasuring
device unit)
=
>7 cmNecrosis or exfoliative
dermatitis
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Protocol C4591007
Protocol Amendment 1 , 05March 2021
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CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 69Table 5.Local Reaction Grading Scale
Participant
AgeMild
(Grade 1)Moderate
(Grade 2)Severea
(Grade 3)aPotentially Life
Threatening
(Grade 4)b
Swelling ≥6 Months
to
<12 years1 to 4 caliper
units (or
measuring
device units)
=
0.5 to 2.0 cm5 to 14 caliper
units (or
measuring
device units)
=
>2.0 to 7.0 cm>14 caliper units
(or measuring
device units)
=
>7 cmNecrosis
a.Parent(s)/legal guardians of the p articipants experiencing local reactions >14caliper units ( >7cm) are to
be contact edby the study site . An unscheduled visit may be required.
b.Only an investigator or qualified designee is able to classify a participant’s local reaction as Grade 4,
after clinical evaluation of the participant or documentation from another medically qualified source
(eg,emergency room or hospital record). Grade 4 local reactions will be collected on the AE case report
form and assessed by the investigator using the AE intensity grad ing scale as detailed in Section 10.3.3 .
8.2.4.3. Systemic Events
If a Grade 3 s ystemic event is reported in the reactogenicity e-diary ,a telephone contact
should occur to ascertain further details and determine whether a site visit is clinically
indicated. Only an investigator or medicall y qualified person is able to cla ssify a
participant’s s ystemic event as Grade 4. If a participant experiences a confirmed Grade 4
systemic event , the investigator must immediately notify the sponsor and, if it is determined
to be related to the administration of the study intervention , further vaccinations will be
discontinued in that participant.
8.2.4.3.1. Participants ≥2 to <12 Y ears of Age
During the reactogenicit y e-diary reporting period, the participant’s parent(s)/legal guardian
will be asked to assess vomiting, diarrhea, headache, fatigue, chills, new or worsened muscle
pain, and new or worsen ed joint pain and to record the sy mptoms in the reactogenicit y
e-diary . The s ymptoms will be assessed by the participant ’s parent (s)/legal guardian as
absent, mild, moderate, or severe according to the grading scale in Table 6.
Table 6.Systemic Event Grading Scale for Participants ≥2 to <12 Y ears of Age
Mild
(Grade 1)Moderate
(Grade 2)Severe
(Grade 3)Potentially Life
Threatening
(Grade 4)a
Vom iting 1-2 times in
24hours>2 times in
24hoursRequires IV
hydrationEmergency room visit
or hospitalization for
hypotensive shock
Diarrhea 2 to 3 loose stools in
24 hours4 to 5 loose stools
in 24 hours6 or more loose
stools in 24 hoursEmergency room visit
or hospitalization for
severe diarrhea
Headache Does not interfere
with activitySome interference
with activityPrevents daily
routine activityEmergency room visit
or hospitalization for
severe headache
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Page 70Table 6.Systemic Event Grading Scale for Participants ≥2 to <12 Y ears of Age
Mild
(Grade 1)Moderate
(Grade 2)Severe
(Grade 3)Potentially Life
Threatening
(Grade 4)a
Fatigue/ tiredness Does not interfere
with activitySome interference
with activityPrevents daily
routine activityEmergency room visit
or hospitalization for
severe fatigue
Chills Does not interfere
with activitySome interference
with activityPrevents daily
routine activityEmergency room visit
or hospitalization for
severe chills
New or worsen ed
muscle painDoes not interfere
with activitySome interf erence
with activityPrevents daily
routine activityEmergency room visit
or hospitalization for
severe ne w or worsen ed
muscle pain
New or worsen ed
joint painDoes not interfere
with activitySome interference
with activityPrevents daily
routine activityEmergency room visit
or hospitalization for
severe ne w or worsen ed
joint pain
Abbreviation: IV = intravenous.
a.Only an investigator or qualified designee is able to classify a participant’ s systemic event as Grade 4,
after clinical evaluation of the participant or documentation from another medically qualified source
(eg,emergency room or hospital record). Grade 4 local reactions will be collected on the AE case report
form and assessed by the investigator using the AE intensity grading scale as detailed in Section 10.3.3 .
8.2.4.3.2. Participants ≥6 Months to <2 Years of Age
During the reactogenicit y e-diary reporting period, the participant’s parent(s)/legal guardian
will be asked to assess decreased appetite, drowsiness, and irritability and to record the
symptoms in the reactogenicity e-diary . The s ymptoms will be assessed by the participant’s
parent(s)/legal guardian as absent, mild, moderate, or severe according to the grading scale in
Table 7.
Table 7.Systemic Event Grading Scale for Participants ≥6 Months to <2 Years of
Age
Mild
(Grade 1)Moderate
(Grade 2)Severe
(Grade 3)Potentially Life
Threatening
(Grade 4)a
Decreased
appetite (loss of
appetite)Decreased
interest in
eating Decreased oral
intake Refusal to feed Emergency room visit or
hospitalization for severe
decreased appetite (loss of
appetite)
Drowsiness
(increased sleep) Increased or
prolonged
sleeping bouts Slightly subdued
interfering with
daily activity Disabling ;not
interested in usual
daily activityEmergency room v isitor
hospitalization for severe
drowsiness (increased
sleep)
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PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Protocol Amendment 1 , 05March 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 71Table 7.Systemic Event Grading Scale for Participants ≥6 Months to <2 Years of
Age
Mild
(Grade 1)Moderate
(Grade 2)Severe
(Grade 3)Potentially Life
Threatening
(Grade 4)a
Irritability
(fussiness)
(synonym ous
with restless
sleep; decreased
sleep) Easily
consolable Requiring
increased
attention Inconsolable;
crying cannot be
comforted Emergency room visit or
hospitalization for severe
irritability (fussiness)
Abbreviation: IV = intravenous.
a.Only an investigator or qualified designee is able to classify a participant’s systemic event as Grade 4, after
clinical evaluation of the participant or documentation from another medically qualified source
(eg,emergency room or hospital record). Grade 4 local reactions will be collected on the AE case report
form and assessed by the investigator us ing the AE intensity grading scale as detailed in Section 10.3.3 .
8.2.4.4. Fever
In order to record information on fever, a thermometer will be given to participants with
instructions on how to measure temperature at home. Temperatures will be taken orally for
participants ≥2 to <12 yearsof age, and axillary for participants <2 yearsof age.
Temperature will be collected in the reactogenicity e-diary in the evening daily during the
reactogenicity e-diary reporting period. I t will also be collected at any time during the
reactogenicity e-diary data collection periods when fever is su spected. Fever is defined as a
temperature of ≥38.0 °C (100.4 °F). The highest temperature for each day will be recorded in
the reactogenicit y e-diary. Temperature will be measured and recorded to 1 decimal place .
Temperatures recorded in degrees Fahrenh eit will be programmatically converted to degrees
Celsius and then categorized according to the scale shown in Table 8during anal ysis.
If a fever of ≥39.0°C (102.1 °F) is reported in the reactogenicity e-diary , a telephone contact
should occur to ascertain further details and determine whether a site visit is clinically
indicated. Onl y an investigator or medicall y qualified person is able to confirm a
participant’s fe ver as >40.0°C (>104.0°F). If a participant experiences a confirmed fever
>40.0 °C (>104.0°F), the investigator must immediately notify the sponsor and, if it is
determined to be related to the administration of the study intervention, further vaccinations
will be discontinued in that participant.
Table 8.Scale for Fever
Range
≥38.0-38.4°C (100.4 -101.1 °F)
>38.4-38.9°C (101.2 -102.0 °F)
>38.9-40.0°C (102.1 -104.0 °F)
>40.0 °C (>104.0 °F)
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FDA-CBER-2021-5683-0779836
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Protocol Amendment 1 , 05March 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 728.2.4.5. Antipyretic Medication
The use of antip yretic medication to treat s ymptoms associated with study intervention
administration will be recorded in the reactogenicity e-diary daily during the reporting period
(Day 1 through Day 7).
8.2.5. Phase 1 Stopping Rules
The following stopping rule s apply by age group and are in place for all Phase 1 participants,
based on review of AE data and e -diary reactogenicity data , until the start of Phase 2/3 or 30
days after the last dose of study intervention in Phase 1 in each age group , whichever is lat er.
These data will be monitored on an ongoing basis by the investigator (or medicall y qualified
designee) and sponsor in order to promptly identify and flag any event that potentially
contributes to a stopping rule.
The sponsor study team will be unblind ed during Phase 1, so will be able to assess whether
or not a stopping rule has been met on the basis of a participant’s individual study
intervention allocation.
In the event that sponsor personnel confirm that a stopping rule is met, the following action s
will commence:
The I RC will review all appropriate data.
The stopping rule will PAUSE randomization and study intervention administration for
all dose levels in the impacted age group.
The DMC will review all appropriate data.
For all participants vaccinated, all other routine study conduct activit ies, including
ongoing data entry , reporting of AEs, participant reactogenicity e-diary completion,
blood sample collection, and participant follow -up, will continue during the pause.
A stopping rule is me t if any of the following rules occur after administration of
investigational BNT162 b2.Reactogenicit y e-diary data confirmed by the investigator as
being entered b y the participant in error will not contribute toward a stopping rule.
The BNT162b 2dose le vels within an age group will contribute to stopping rules together .
Stopping Rule C riteria for Each BNT162b2 Dose Level :
1.If any participant vaccinated with the BNT162b2 candidate at an y dose level develops an
SAE that is assessed by the investigator as po ssibly related, or for which there is no
alternative, plausible, attributable cause.
2.If any participant vaccinated with the BNT162b2 candidate at an y dose level develops a
Grade 4 local reaction or sy stemic event after vaccination (see Section 8.2.4 ) that is
090177e19670e6ed\Approved\Approved On: 05-Mar-2021 17:33 (GMT)
FDA-CBER-2021-5683-0779837
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Protocol Amendment 1 , 05March 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 73assessed as possibl y related by the investigator, or for which there is no alternative,
plausible, attributable cause.
3.If any participant vaccinated with the BNT162 b2candidate at an y dose level develops a
fever >40.0°C (>104.0° F) for at least 1 daily measurement after vaccination
(seeSection 8.2.4 )that is assessed as possibl y related by the investigator, or for which
there is no alternative, plausible, attributable cause.
4.If any 2 participants vaccinated with the BNT162 b2candidate at an y dose level within
the same age group report the same or similar severe (Grade 3) AE after vaccination,
assessed as possibl y related by the investigator, or for which there is no alternative,
plausible, attributable cause.
5.If any participa ntdies or requires ICU admission due to SARS -CoV -2 infection; if this
stopping rule is met, all available clinical and preclinical safet y and immunogenicity data
should be reviewed to evaluate for enhanced COVID -19.
8.2.6. Randomization and Vaccination After a S topping Rule Is Met in Phase 1
Once the IRC and DMC have reviewed the safet y data and provided guidance, a notification
will be sent from the sponsor to the sites with guidance on how to proceed.
8.2.7. Pregnancy Testing
Pregnancy tests may be urine or serum tests, but must have a sensitivity of at least
25mIU/mL. Pregnancy tests will be performed in WOCBP atthe times listed in the SoA,
immediately before the administration of each vaccine dose. A negative pregnancy test result
will be required prior to the participant’s receiving the study intervention . Pregnancy tests
may also be repeated if requested by IRBs/ECs or if required b y local regulations. I n the
case of a positive confirmed pregnancy , the participant will be withdrawn from
administration of study intervention but may remain in the study .In the case of a positive
pregnancy test for a female participant, it is a responsibility of investigator to share the
information with the participant’s parent(s)/l egal guardian.
8.3. Adverse Events and Serious Adverse Events
The definitions of an AE and an SAE can be found in Appendix 3 .
AEswill be reported b y the participant's parent(s)/legal guardian .
The investigator and an y qualified designees are responsible for detecting, documenting, and
recording events that meet the definition of an AE or SAE and remain responsible to pursue
and obtain adequate information both to determine the outcome and to ass ess whether the
event meets the criteria for classification as an SAE or caused the participant to discontinue
the study intervention (see Section 7.1).
Each participant s’ parent/legal guardian will be questioned about the occurrence of AEs in a
nonleading manner.
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FDA-CBER-2021-5683-0779838
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
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Protocol Amendment 1 , 05March 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 74In addition, the investigator may be requested by Pfizer Safet y to obtain specific follow -up
information in an expedited fashion.
8.3.1. Time Period and Frequency for C ollecting AE and SAE Information
The time period for actively eliciting and collecting AEs and SAEs (“active collection
period”) for each participant begins from the time the participant ’s parent(s)/legal guardian
provides informed consent, which is obtained before the participant’s participation in the
study (ie, before undergoing an y stud y-related procedure and/or receiving study
intervention), through and including 1 month after Dose 2
(Phase 1 – Visit 4; Phase 2/ 3 –Visit 4 ). In addition, any AEs occurring up to 48hours after
each subsequent blood draw and nasal swab collection must be recorded on the CRF.
SAEs will be collected from the time the participant provides informed consent through
6months after Dose 2 (Phase 1 –Visit 5 ; Phase 2/3 – Visit 5 ).
Phase 2/3 Participants Who Originally Received Placebo:
At Visit 5 ,all participants will be unblinded and if they originall y received placebo will be
offered BNT162b2. For p articipants who originally received placebo and go on to receive
BNT162b2 as Dose 3 and Dose 4, the time period for activel y eliciting and collecting AEs
and SAEs will continue from the receipt of BNT162b2 (Dose 3 and Dose 4), through and
including 1 month after Dose 4 (Visit C). SAEs will be collected from the time ofreceipt of
BNT162b2 (Dose 3 and Dose 4) through approximately 6 months after Dose 4 of BNT162b2
(Visit D).
Follow -up by the investigator continues throughout and after the active collection p eriod and
until the AE or SAE or its sequelae resolve or stabilize at a level acceptable to the
investigator and Pfizer concurs with that assessment.
For participants who are screen failures, the active collection period ends when screen failure
status is determined.
If the participant who provided assent in any phase of the study or the participant’s
parent(s)/legal guardian withdraws from the study and also withdraws consent /assent for the
collection of future information, the active collection period end s when consent /assent is
withdrawn.
If a participant definitively discontinues or temporarily discontinues study intervention
because of an AE or SAE, the AE or SAE must be recorded on the CRF and the SAE
reported using the Vaccine SAE Report ingForm.
Investigators are not obligated to activel y seek AE sor SAE safter the participant has
concluded study participation . However, if the investigator learns of an y SAE, including a
death, at an y time after a participant has completed the study , and he/she considers the event
to be reasonably related to the study intervention, the investigator must promptly report the
SAE to Pfizer using the Vaccine SAE Report ingForm .
090177e19670e6ed\Approved\Approved On: 05-Mar-2021 17:33 (GMT)
FDA-CBER-2021-5683-0779839
PF-07302048 (BNT162 b2 RNA- Based COVID -19 Vaccine)
Protocol C4591007
Protocol Amendment 1 , 05March 2021
PFIZER CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (15 May 2020)
Page 75Note : Potential COVID -19/MI S-C illnesses and their seque lae 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.
8.3.1.1. Reporting SAEs to Pfizer Safety
All SAEs occurring in a participant during the active co llection period as described in
Section 8.3.1 are reported to Pfizer Safety on the Vaccine SAE Reporting Form i mmediatel y
upon awareness and under no circumstance should this exceed 24 hours, as indicated in
Appendix 3.The investigator will submit any updated SAE data to the sponsor within
24 hours of it being available.
8.3.1.2. Recording Non serious AEs and SAEs on the CRF
All nons
…[truncated]

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