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PF-07302048 (BNT162 RNA- Based COVID- 19 Vaccines)
Protocol C4591015
Protocol Amendment 2, 02March 2021
PFIZER CONFIDENTIAL
CT02- GSOP Maternal Immunization Protocol Template (Phase 1 2 3 4) (15 May 2020)
TMF Doc ID: 164.01
Page 1A PHASE 2/3,PLACEBO -CONTROLLED, RANDOMIZED, OBSERVE R-BLIND
STUDY TO EVALUATE TH E SAFETY, TOLERABILI TY,AND
IMMUNOGEN ICITY OF A SARS -COV -2 RNA VACCI NE CANDIDATE
(BNT162b 2) AGAINST COVID -19 IN HEALTHY PREGNANT WOMEN 18 YE ARS
OF AGE AND OLDER
Study Sponsor:
Study Conducted By:
Study Intervention Number :BioNTech
Pfizer
PF-07302048
Study Intervention Name: RNA -Based COVID -19 Vaccine s
USIND Number: 19736
EudraCT Number: 2020
-005444- 35
Protocol Number: C4591015
Phase: Phase 2/3
Short Title : A Phase 2/3 Study to Evaluate the Safety , Tolerabilit y,and Immunogen icity
of SARS -CoV -2 RNA Vaccine Candidate (BNT162b2) A gainst COVID -19 in Healthy
Pregnant Women 18 Years of Age and Older
This document and accompanying materials contain confidential information belonging to Pfizer. Except as
otherwise agreed to in writing, by accepting or reviewing these document s, you agree to hold this
information in confidence and not copy or di sclose 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.
090177e19668bad9\Approved\Approved On: 02-Mar-2021 22:33 (GMT)
FDA-CBER-2021-5683-0779916
PF-07302048 (BNT162 RNA- Based COVID- 19 Vaccines)
Protocol C4591015
Protocol Amendment 2, 02March 2021
PFIZER CONFIDENTIAL
CT02- GSOP Maternal Immunization Protocol Template (Phase 1 2 3 4) (15 May 2020)
TMF Doc ID: 164.01
Page 2Protocol Amendment Summary of Changes Table
Document History
Document Version Date Summary and Rationale for Changes
Protocol amendment
202March 2021 Section 1.3.1 and Section 1.3.2 :
expanded the 1- month postdelivery visit
window b y 1week to allow for potential
earlier vaccination of BNT162b2 to
participants originally randomized to
receive placebo.
Section 1.3.3 : removed “equivalent visit
number for maternal participants” from
the Infant SoA since this will differ for
maternal participants originall y
randomized to placebo who will go on
to receive BNT162b2 at 1 month after
delivery and follow a different SoA.
Section 2.3: added a sentence to clarify
that the protocol is a PASS.
Section 5.1.1 : corrected the calculation
of GA in the third trimester, replacing
“second trimester” with “third
trimester,” and updated the discrepancy
of day s between the LMP -determined
GA from >10 to >21 days.
Removed references to
thumbprinting the I CD, since
illiterate participants will not be
enrolled from certain regions .
Clarified in Section 8.2.2 that field
workers would be used in the case of
poor network connection for e -diary
completion .
Section 5.1.1, Section 8.16.3 ,and
Section 10.4: added criteria for inclusion
of maternal participants with stable
HIV, hepatitis B, or hepatitis C in Phase
3.
090177e19668bad9\Approved\Approved On: 02-Mar-2021 22:33 (GMT)
FDA-CBER-2021-5683-0779917
PF-07302048 (BNT162 RNA- Based COVID- 19 Vaccines)
Protocol C4591015
Protocol Amendment 2, 02March 2021
PFIZER CONFIDENTIAL
CT02- GSOP Maternal Immunization Protocol Template (Phase 1 2 3 4) (15 May 2020)
TMF Doc ID: 164.01
Page 3Document History
Document Version Date Summary and Rationale for Changes
Updated the Objectives, Estimands, and
Endpoints to add a safet y objective f or
the first 600 randomized maternal
participants to support interim
analysis/submission report.
Per CBER feedback, updated the
term “NI” to “immunobridging”
todescribe the immunogenicity
comparison between
nonrandomized populations in
the protocol.
Added a footnote to clarify that
HIV-infected participants will
not be included in anal yses of
the objectives. Anal yses among
HIV-infected women and their
infants will be summarized
separately .
Section 8.1.1 and Section 8.13.1 : added
a second definition of symptoms of
severe COVID -19 disease per the CDC
definition.
Section 8.2.3 : clarified that stopping
rules are in place during Phase 2 only ,
with no overlap into Phase 3.
Clarified that a stud y pause may not
prevent administration of Dose 2 for
enrolled participants .
Modified stopping rule 7 to include
a trigger of preterm premature
rupture of membranes .
Stopping rule 4: removed
assessment of laboratory
abnormalities, as these data are not
collected in this study .
090177e19668bad9\Approved\Approved On: 02-Mar-2021 22:33 (GMT)
FDA-CBER-2021-5683-0779918
PF-07302048 (BNT162 RNA- Based COVID- 19 Vaccines)
Protocol C4591015
Protocol Amendment 2, 02March 2021
PFIZER CONFIDENTIAL
CT02- GSOP Maternal Immunization Protocol Template (Phase 1 2 3 4) (15 May 2020)
TMF Doc ID: 164.01
Page 4Document History
Document Version Date Summary and Rationale for Changes
Section 8.11.1 , Visit 1: removed the
requirement of a repeat fetal scan to
clarify that an earlier scan done at ≥18
weeks ’GA can be used to confirm
singleton pregnancy and rule out fetal
anomalies.
Section 8.15: clarified that exclusion
criterion 2 is not met if the participant
meets the criteria for confirmed
COVID -19 with or without symptoms
and can receive Vaccination 2.
Section 8.16: to align with current
recommendations, investigators may
exercise judgment on review of
inclusion and exclusion criteria ahead of
vaccination with BNT162b2 for
participants who originally received
placebo.
Section 8.3.1 and Section 8.3.7 : inserted
language to clarify that p otential
COVID -19/MIS- C illnesses and their
sequelae that are consistent with the
clinical endpoint definition should not
be recorded as AEs .
Appendix 3 : removed an erroneous
partially completed sentence from the
second paragraph.
Protocol amendment
128 January 2021 Based on availability of BNT162b2 in
high-risk pregnant women and evidence
of safet y in the real -world setting, the
sentinel cohort of N=50 in Phase 2 was
removed.
Based on feedback from an external
advisory board, inclusion criterion 10
was u pdated to allow enrollment of
participants with a p repregnancy BMI of
≤40 kg/m2.
090177e19668bad9\Approved\Approved On: 02-Mar-2021 22:33 (GMT)
FDA-CBER-2021-5683-0779919
PF-07302048 (BNT162 RNA- Based COVID- 19 Vaccines)
Protocol C4591015
Protocol Amendment 2, 02March 2021
PFIZER CONFIDENTIAL
CT02- GSOP Maternal Immunization Protocol Template (Phase 1 2 3 4) (15 May 2020)
TMF Doc ID: 164.01
Page 5Document History
Document Version Date Summary and Rationale for Changes
Clarified language in inclusion
criterion 1 that GA dating for maternal
participants who underwent assisted
reproduction technology can be
referenced in the SRM.
Corrected the list of prohibited
medications under Section 6.5.1 .
Clarified language in the Objectives,
Estimands, and Endpoints table for
consistency .
Added exploratory objectives to
evaluate incidence rates of COVID -19
and as ymptomatic SARS -CoV -2
infect ion through the entire follow -up
among the maternal participants
receiving BNT162b2.
Updated the VE assessment to reflect
the reduced accrual of time following
the unblinding of participants at 1 month
after delivery .
Clarified the unblinding at 1 month af ter
delivery for participants originall y
randomized to placebo who go on to
receive BNT162b2.
Updated Section 2.3, Benefit -Risk
Assessment, to include data from the
DART studies.
In line with current recommendations,
removed the requirement to discontinue
study intervention because of a
diagnosis of COVID -19 during the
study .
Added the requirement to record
antipy retic medication in the e -diary
during the 7 -day vaccination period ,as
this was omitted in error.
090177e19668bad9\Approved\Approved On: 02-Mar-2021 22:33 (GMT)
FDA-CBER-2021-5683-0779920
PF-07302048 (BNT162 RNA- Based COVID- 19 Vaccines)
Protocol C4591015
Protocol Amendment 2, 02March 2021
PFIZER CONFIDENTIAL
CT02- GSOP Maternal Immunization Protocol Template (Phase 1 2 3 4) (15 May 2020)
TMF Doc ID: 164.01
Page 6Document History
Document Version Date Summary and Rationale for Changes
Added editorial changes in the
document to clar ify where field
workers/site staff may be required to
call/visit maternal participants at home
(applicable to regions where illiterate
participants may be enrolled).
Clarified that participants originall y
randomized to placebo who go on to
receive BNT162b 2 at 1 month after
delivery will not participate in
surveillance for as ymptomatic
SARS -CoV -2 infection.
Clarified that AEs will be collected from
the signing of the ICD to 1 month after
Vaccination 4 (Visit 103) for those
maternal participants who originall y
received placebo and who go on to
receive BNT162b2 at 1 month after
delivery .
Original protocol 21 December 2020 N/A
This amendment incorporates all revisions to date, including amendments made at the
request of country health authorities and IRBs/ECs.
090177e19668bad9\Approved\Approved On: 02-Mar-2021 22:33 (GMT)
FDA-CBER-2021-5683-0779921
PF-07302048 (BNT162 RNA- Based COVID- 19 Vaccines)
Protocol C4591015
Protocol Amendment 2, 02March 2021
PFIZER CONFIDENTIAL
CT02- GSOP Maternal Immunization Protocol Template (Phase 1 2 3 4) (15 May 2020)
TMF Doc ID: 164.01
Page 7TABLE OF CONTENTS
LIST OF TABLES ................................ ................................ ................................ ................... 13
1. PROTOCOL SUMMARY ................................ ................................ ................................ ...14
1.1. Sy nopsis ................................ ................................ ................................ .................. 14
1.2. Schema ................................ ................................ ................................ .................... 21
1.3. Schedule of Activities ................................ ................................ ............................. 22
1.3.1. Schedule of Activities for Maternal Participants ................................ ........ 22
1.3.2. Schedule of Activities for Maternal Participants Who Were
Originall y Assigned to Placebo ................................ ................................ .......27
1.3.3. Schedule of Activities for Infant Participants ................................ ............. 28
2. INTRODUCTION ................................ ................................ ................................ ............... 29
2.1. Study Rationale ................................ ................................ ................................ .......29
2.2. Background ................................ ................................ ................................ ............. 29
2.2.1. Clinical Overview ................................ ................................ ....................... 30
2.3. Ben efit/Risk Assessment ................................ ................................ ......................... 32
2.3.1. Risk Assessment ................................ ................................ ......................... 33
2.3.2. Benefit Assessment ................................ ................................ ..................... 35
2.3.3. Overall Benefit/Risk Conclusion ................................ ................................ 35
3. OBJECTI VES, ESTIMANDS, AND ENDPOINTS ...........................................................35
4. STUDY DESIGN ................................ ................................ ................................ ................. 39
4.1. Overall Design ................................ ................................ ................................ ......... 39
4.2. Scientific Rationale for Study Design ................................ ................................ .....40
4.3. Justification for Dose ................................ ................................ .............................. 40
4.4. End of Study Definition ................................ ................................ .......................... 40
5. STUDY POPUL ATION ................................ ................................ ................................ ......41
5.1. I nclusion Criteria ................................ ................................ ................................ .....41
5.1.1. Mat ernal Participants................................ ................................ .................. 41
5.1.2. I nfant Participants ................................ ................................ ....................... 43
5.2. Exclusion Criteria ................................ ................................ ................................ ....43
5.2.1. Maternal Participants................................ ................................ .................. 43
090177e19668bad9\Approved\Approved On: 02-Mar-2021 22:33 (GMT)
FDA-CBER-2021-5683-0779922
PF-07302048 (BNT162 RNA- Based COVID- 19 Vaccines)
Protocol C4591015
Protocol Amendment 2, 02March 2021
PFIZER CONFIDENTIAL
CT02- GSOP Maternal Immunization Protocol Template (Phase 1 2 3 4) (15 May 2020)
TMF Doc ID: 164.01
Page 85.2.2. I nfant Participants ................................ ................................ ....................... 45
5.3. L ifesty le Considerations ................................ ................................ .......................... 46
5.4. Screen Failures ................................ ................................ ................................ ........ 46
5.5. Criteria for Temporarily Delay ing Randomization/Study Intervention
Administration ................................ ................................ ................................ ........... 46
6. STUDY INTERVENTIO N................................ ................................ ................................ ..47
6.1. Study Intervention(s) Administered ................................ ................................ ........ 47
6.1.1. Administration ................................ ................................ ............................ 48
6.2. Preparation/Handling/Storage/Accountability ................................ ........................ 48
6.2.1. Preparation and Dispensing ................................ ................................ ........ 49
6.3. Measures to Minimize Bias: Randomization and Blinding ................................ .....50
6.3.1. Allocation to Study Intervention ................................ ................................ 50
6.3.2. Blinding of Site Personnel Until the 1- Month Postdelivery Visit .............. 50
6.3.3. Blinding of Site Personnel Prior to the 1- Month Postdelivery Visit .......... 51
6.3.4. Blinding of the Sponsor................................ ................................ .............. 52
6.3.5. Breaking the Blind ................................ ................................ ...................... 52
6.4. Study Intervention Compliance ................................ ................................ ............... 53
6.5. Concomitant Therapy ................................ ................................ .............................. 53
6.5.1. Prohibited During the Study –Maternal Participants ................................ .53
6.5.2. Permitted During the Study –Maternal Participants ................................ ..54
6.5.3. Recording Nonstudy Vaccinations and Con comitant Medications –
Maternal Participants ................................ ................................ ....................... 54
6.5.4. Prohibited During the Study –Infant Participants ................................ ......54
6.5.5. Permitted During the Study – Infant Participants................................ .......54
6.5.6. Recording Concomitant Medications – Infant Participants ........................ 55
6.6. Dose Modification ................................ ................................ ................................ ...55
6.7. I ntervention After the End of the Study ................................ ................................ ..55
7. DI SCONTINUATION O F STUDY INTERVENTION AND PARTI CIPANT
DISCONTINUATION/WI THDRAWAL ................................ ................................ ........... 55
7.1. Discontinuation of Study Intervention ................................ ................................ ....55
7.2. Participant Discontinuation/Withdrawal From the Study ................................ .......56
7.2.1. Withdrawal of Consent ................................ ................................ ............... 57
090177e19668bad9\Approved\Approved On: 02-Mar-2021 22:33 (GMT)
FDA-CBER-2021-5683-0779923
PF-07302048 (BNT162 RNA- Based COVID- 19 Vaccines)
Protocol C4591015
Protocol Amendment 2, 02March 2021
PFIZER CONFIDENTIAL
CT02- GSOP Maternal Immunization Protocol Template (Phase 1 2 3 4) (15 May 2020)
TMF Doc ID: 164.01
Page 97.3. L ost to Follow -up ................................ ................................ ................................ ....57
8. STUDY ASSESSMENTS AND PROCEDURES ................................ ............................... 57
8.1. Efficacy and/or Immunogenicity Assessments ................................ ....................... 59
8.1.1. Maternal Participants................................ ................................ .................. 59
8.1.2. I nfant Participants ................................ ................................ ....................... 61
8.1.3. I mmunogenicity................................ ................................ .......................... 63
8.1.4. Total Volume of Blood Collected – Maternal Participants ........................ 64
8.1.5. Total Volume of Blood Collected – Infant Participants ............................. 64
8.1.6. Biological Samples ................................ ................................ ..................... 64
8.2. Safet y Assessments ................................ ................................ ................................ .65
8.2.1. Cli nical Safety Laboratory Assessments ................................ .................... 65
8.2.2. Electronic Diary ................................ ................................ .......................... 65
8.2.2.1. Grading Scales ................................ ................................ ........... 66
8.2.2.2. L ocal Reactions ................................ ................................ ......... 66
8.2.2.3. Sy stemic Events ................................ ................................ ........ 67
8.2.2.4. Fever ................................ ................................ .......................... 69
8.2.2.5. Antipy retic Medication ................................ ............................. 70
8.2.3. Stopping Rules................................ ................................ ............................ 70
8.2.4. Surveillance of Events That Could Represent Enhanced COVID -19 ........ 71
8.2.5. Clinical Safety Laboratory Assessments ................................ .................... 71
8.3. Adverse Events and Serious Adverse Events................................ .......................... 71
8.3.1. Time Period and Frequency for Collecting AE and SAE Information .......72
8.3.1.1. Reporting SAEs to Pfizer Safety ................................ ............... 73
8.3.1.2. Recording Nonserious AEs and SAEs in the CRF.................... 74
8.3.2. Method of Detecting AEs and SAEs ................................ .......................... 74
8.3.3. Follow -up of AEs and SAEs ................................ ................................ .......74
8.3.4. Regulatory Reporting Requirements for SAEs ................................ ........... 75
8.3.5. Additional Exposure Scenarios That May Resu lt From the Exposure
to the Study Intervention ................................ ................................ .................. 75
8.3.5.1. Environmental Exposure During Pregnancy............................. 75
8.3.5.2. Exposure During Breastfeeding ................................ ................ 77
8.3.5.3. Occupational Exposure ................................ ............................. 77
090177e19668bad9\Approved\Approved On: 02-Mar-2021 22:33 (GMT)
FDA-CBER-2021-5683-0779924
PF-07302048 (BNT162 RNA- Based COVID- 19 Vaccines)
Protocol C4591015
Protocol Amendment 2, 02March 2021
PFIZER CONFIDENTIAL
CT02- GSOP Maternal Immunization Protocol Template (Phase 1 2 3 4) (15 May 2020)
TMF Doc ID: 164.01
Page 108.3.6. Cardiovascular and Death Events ................................ ............................... 77
8.3.7. Disease -Related Events and/or Disease -Related Outcomes Not
Qualifying as AEs or SAEs ................................ ................................ .............. 78
8.3.8. Adverse Events of Special Interest................................ ............................. 78
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. P harmacokinetics ................................ ................................ ................................ ....80
8.6. Pharmacod ynamics ................................ ................................ ................................ ..80
8.7.Genetics ................................ ................................ ................................ ................... 80
8.8. Biomarkers ................................ ................................ ................................ .............. 80
8.9. I mmunogenicit y Assessments ................................ ................................ ................. 80
8.10. Health Economics ................................ ................................ ................................ .80
8.11. Study Procedures – Maternal Participants ................................ ............................ 81
8.11.1. Visit 1: Screening (- 28 Day s to Vaccination 1) ................................ ........ 81
8.11.1.1. Visit 2 – Vaccination 2 (Clinic: 19- 23 Day s After
Vaccination 1) ................................ ................................ ................... 84
8.11.1.2. Visit 3 – 2- Week Postvaccination Follow -up (Clinic) ............ 86
8.11.1.3. Visit 4 – 1-Month Postvaccination Follow- up Visit
(Clinic: 28 -35 Day s After Visit 2) ................................ ..................... 87
8.11.1.4. Visit 5 – Delivery ................................ ................................ ....88
8.11.1.5. Visit 6 – 1- Week Postdelivery Follow -up (Telephone
Call: 7 -10 Day s After Delivery ) ................................ ........................ 89
8.11.1.6. Visit 7 – 1- Month Postdelivery Follow -up (Clinic: 21 to
35 Day s After Delivery ) ................................ ................................ ....89
8.11.1.7. Visit 8 – 6- Month Postdelivery Follow -up(Clinic: 160 -
200 Day s After Delivery) ................................ ................................ ..90
8.12. Unscheduled Visit for Reactogenicity Events ................................ ....................... 90
8.13. COVID -19 Surveillance (All Maternal Participants) ................................ ............ 91
8.13.1. Potential Maternal COVI D-19 Illness Visit (Optimally Within 3
Days After Potential COVID- 19 Illness Onset) ................................ ............... 92
8.13.2. Potential Maternal COVI D-19 Convalescent Visit (28 to 35 Day s
After Potential COVID -19 Illness Visit) ................................ ........................ 94
090177e19668bad9\Approved\Approved On: 02-Mar-2021 22:33 (GMT)
FDA-CBER-2021-5683-0779925
PF-07302048 (BNT162 RNA- Based COVID- 19 Vaccines)
Protocol C4591015
Protocol Amendment 2, 02March 2021
PFIZER CONFIDENTIAL
CT02- GSOP Maternal Immunization Protocol Template (Phase 1 2 3 4) (15 May 2020)
TMF Doc ID: 164.01
Page 118.14. Communication and Use of Technology ................................ ............................... 94
8.15. SARS -CoV -2 NAAT Results From Visits 1 and 2 and Potential COVID -19
Illness Visits ................................ ................................ ................................ .............. 95
8.16. Procedures for Administration of BNT162b2 to Those Originally Assigned
to Placebo ................................ ................................ ................................ .................. 96
8.16.1. Visit 101 – Vaccination 3 – 1-Month Postdelivery Follow -up
(Clinic: 21 to 35 Day s After Delivery ) ................................ ............................ 96
8.16.2. Visit 102 – Vaccination 4 (19 to 23 Day s After Visit 101) ...................... 97
8.16.3. Visit 103 – 1- Month Follow -up Telephone Contact (After
Vaccination 4) (28 to 35 Day s After Visit 102) ................................ ............... 98
8.17. Study Procedures – Infant Participants ................................ ................................ .98
8.17.1. Infant Participants: Visit 1 –Delivery ................................ ...................... 98
8.17.2. Visit 2 – 1- Week Postdelivery Follow -up (Telephone Call: 7 -10
Days After Visit 1)................................ ................................ ........................... 99
8.17.3. Visit 3 – 6- Months-of- Age Follow -up (Clinic: 160 -200 Day s After
Visit 1) ................................ ................................ ................................ ........... 100
8.18. COVID -19 Surveillance (All Infant Participants) ................................ ............... 100
8.18.1. Potential I nfant COVID -19/MIS- C Illness Visit (Optimally Within
3 Day s After Potential COVID- 19 Illness Onset) ................................ .......... 101
8.18.2. Potential I nfant COVID -19 Convalescent Visit (28 to 35 Day s
After Potential COVID -19 Illness Visit) ................................ ....................... 103
9. STATI STICAL CONSI DER ATIONS ................................ ................................ .............. 103
9.1. Estimands and Statistical Hy potheses ................................ ................................ ...104
9.1.1. Estimands ................................ ................................ ................................ ..104
9.1.2. Statistical Hypotheses ................................ ................................ ............... 104
9.1.2.1. Statistical Hy pothesis Evaluation for Immunogenicity ........... 104
9.1.2.2. Statistical Hy pothesis Evaluation for Vaccine Efficacy .......... 105
9.1.3. Multiplicity Consideration................................ ................................ ........ 105
9.2. Sample Size Determination ................................ ................................ ................... 105
9.3. Analy sis Sets ................................ ................................ ................................ ......... 107
9.4. Statistical Analy ses................................ ................................ ............................... 108
9.4.1. General Considerations ................................ ................................ ............. 108
9.4.1.1. Analy ses for Binary Data ................................ ........................ 108
9.4.1.2. Analy ses for Continuous Data ................................ ................. 109
090177e19668bad9\Approved\Approved On: 02-Mar-2021 22:33 (GMT)
FDA-CBER-2021-5683-0779926
PF-07302048 (BNT162 RNA- Based COVID- 19 Vaccines)
Protocol C4591015
Protocol Amendment 2, 02March 2021
PFIZER CONFIDENTIAL
CT02- GSOP Maternal Immunization Protocol Template (Phase 1 2 3 4) (15 May 2020)
TMF Doc ID: 164.01
Page 129.4.2. Primary Endpoint(s) ................................ ................................ .................. 110
9.4.3. Secondary Endpoint(s) ................................ ................................ .............. 111
9.4.4. Exploratory Endpoint(s) ................................ ................................ ........... 112
9.5.Interim Anal yses................................ ................................ ................................ ...113
9.5.1. Analy sis Timing ................................ ................................ ........................ 113
9.6. Data Monitoring Committee or Other Independent Oversight Committee ........... 113
10. SUPPORTING DOCUM ENTATION AND OPERATI ONAL
CONSI DERATIONS ................................ ................................ ................................ ........ 114
10.1. Appendix 1: Regulatory , Ethical, and Study Oversight Considerations ............. 114
10.1.1. Regulatory and Ethical Considerations ................................ .................. 114
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the
Protocol or I CH GCP ................................ ................................ .......114
10.1.2. Financial Disclosure ................................ ................................ ............... 115
10.1.3. I nformed Consent Process ................................ ................................ ......115
10.1.4. Data Protection ................................ ................................ ....................... 116
10.1.5. Dissemination of Clinical Study Data ................................ .................... 116
10.1.6. Data Qualit y Assurance ................................ ................................ .......... 118
10.1.7. Source Documents ................................ ................................ .................. 119
10.1.8. Study and Site Start and Closure ................................ ............................ 119
10.1.9. Publication Policy................................ ................................ ................... 120
10.1.1 0. Sponsor’s Qualified Medical Personnel ................................ ............... 121
10.2. Appendix 2: Adverse Events: Definitions and Procedures for Recording,
Evaluating, Follow -up, and Reporting ................................ ................................ ....122
10.2.1. Definition of AE ................................ ................................ ..................... 122
10.2.2. Definition of SAE................................ ................................ ................... 123
10.2.3. Recording/Reporting and Follow- up of AEs and/or SAEs ..................... 124
10.2.4. Reporting of SAEs................................ ................................ .................. 127
10.3. Appendix 3: L iver Safety : Suggested Actions and Follow -up Assessment s ...... 129
10.4. Appendix 4: Criteria for Allowing Inclusion of Participants With Chronic
Stable HIV, HCV, or HBV Infection ................................ ................................ ......131
10.5. Appendix 5: Abbreviations ................................ ................................ ................. 132
11.REFERENCES ................................ ................................ ................................ ................ 136
090177e19668bad9\Approved\Approved On: 02-Mar-2021 22:33 (GMT)
FDA-CBER-2021-5683-0779927
PF-07302048 (BNT162 RNA- Based COVID- 19 Vaccines)
Protocol C4591015
Protocol Amendment 2, 02March 2021
PFIZER CONFIDENTIAL
CT02- GSOP Maternal Immunization Protocol Template (Phase 1 2 3 4) (15 May 2020)
TMF Doc ID: 164.01
Page 13LIST OF TABLES
Table 1. Guideline for Infant Blood Draw, if Cord Blood Sample Was Not
Obtained ................................ ................................ ................................ ....64
Table 2. Local Reaction Grading Scale ................................ ................................ ..67
Table 3. Systemic Event Grading Scale ................................ ................................ ..68
Table 4. Scale for Fever ................................ ................................ .......................... 69
Table 5. Power Anal ysis for Immunobridging Assessment ................................ .106
Table 6. Power for Vaccine Efficacy Assessment ................................ ................ 106
Table 7. Probability of Observing at Least 1 AE by Assumed T rue Event
Rates With Different Sample Sizes ................................ ........................ 107
090177e19668bad9\Approved\Approved On: 02-Mar-2021 22:33 (GMT)
FDA-CBER-2021-5683-0779928
PF-07302048 (BNT162 RNA- Based COVID- 19 Vaccines)
Protocol C4591015
Protocol Amendment 2, 02March 2021
PFIZER CONFIDENTIAL
CT02- GSOP Maternal Immunization Protocol Template (Phase 1 2 3 4) (15 May 2020)
TMF Doc ID: 164.01
Page 141.PROTOCOL SUMMARY
1.1.Synopsis
Short Title: A Phase 2/3 Study to Evaluate the Safety , Tolerabilit y,and Immunogen icity of a
SARS -CoV -2 RNA Vaccine Candidate (BNT162b2) Against COVID -19 in Healthy
Pregnant Women 18 Y ears of Age and Older
Rationale
In December 2019, a pneumonia outbreak of unknown cause occurred in Wuhan, China. In
January 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, th e phylogenetic tree revealed a closer relationship to
SARS virus isolates than to another coronavirus infecting humans, the MERS virus.
SARS -CoV -2 infections and the resulting disease, COVID -19, have spread globall y,
affecting a growing number of countries.
On 11 March 2020, the WHO characterized the COVID -19 outbreak as a pandemic. Global
case rates and deaths have continued to increase , with the United States reporting the most
cases and deaths of any other country . At the time of this communic ation, the number of
confirmed cases continues to rise globall y. There are currentl y no vaccines or effective
antiviral drugs to prevent SARS -CoV -2 infections or the disease it causes, COVID -19.
Pregnant women are at risk for acquiring SARS -CoV -2 infecti on and COVID -19. Pregnancy
may confer increased risk of severe COVID- 19 because of phy siological changes during
pregnancy that can increase susceptibility to respiratory infections and subsequent rapid
progression to respiratory failure. Additionall y, pregnant women with COVID- 19 have been
reported to have higher rates of preterm birth, cesarean delivery , fetal distress, and infants
requiring neonatal intensive care. Prevention of SARS -CoV -2 infection and COVID -19 is
critically important in pregnant wome n.
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.
BNT162b2 is a SARS -CoV -2–RNA -LNP vaccine based on a platform of modRNA with
blunted innate immune sensor –activating capacit y and augmented expression encoding the
P2S.
This study will describe the safet y of BNT162b2 in pregnant women and their infants. It will
also assess the immunogenicity of BNT162b2 in pregnant women, the tran sfer of antibody to
their infant s, and the kinetics of antibody transfer in the infant.
090177e19668bad9\Approved\Approved On: 02-Mar-2021 22:33 (GMT)
FDA-CBER-2021-5683-0779929
PF-07302048 (BNT162 RNA- Based COVID- 19 Vaccines)
Protocol C4591015
Protocol Amendment 2, 02March 2021
PFIZER CONFIDENTIAL
CT02- GSOP Maternal Immunization Protocol Template (Phase 1 2 3 4) (15 May 2020)
TMF Doc ID: 164.01
Page 15Objectives , Estimands, and Endpoints
ObjectivesaEstimands Endpoints
Prim ary Safety Prim ary Safety Prim ary Safety
To describe the safety and
tolerability of prophylactic
BNT162b2 when
administered to maternal
participants 18 years of age
or older vaccinated at 2 4to
34 w eeks’ gestation in the
first approximately 600
randomized maternal
participants .In maternal participants receiving
at least 1 dose of study
intervention from each vaccine
group, the percentage of maternal
participants reporting:
Local reactions for up to
7days following each dose
Systemic events for up to
7days following each dose
AEs from Dose 1 through
1month after Dose 2
SAEs from Dose 1 through
1month after deliveryProm pted local reactions (redness,
swelling, and pain at the injection
site)
Prom pted systemic even ts (fever,
fatigue, headache, chills, vomiting,
diarrhea, new or w orsened muscle
pain, and new or w orsened joint
pain)
AEs
SAEs
To describe the safety and
tolerability of prophylactic
BNT162b2 when
administered to maternal
participants 18 years of age
or older vaccinated at 24 to
34 w eeks’ gestation .In maternal participants receiving
at least 1 dose of study
intervention from each vaccine
group, the percentage of maternal
participants reporting:
Local reactions for up to 7
days followi ng each dose
Systemic events for up to 7
days following each dose
AEs from Dose 1 through
1month after Dose 2
SAEs from Dose 1 through 1
month after deliveryProm pted local reactions (redness,
swelling, and pain at the injection
site)
Prom pted systemic events (fever,
fatigue, headache, chills, vomiting,
diarrhea, new or w orsened muscle
pain, and new or w orsened joint
pain)
AEs
SAEs
Prim ary Immunogenicity Prim ary Immunogenicity Prim ary Immunogenicity
To demonstrate the
immunobridging ofthe
immune response to
prophylactic BNT162b2 in
maternal participants
18years of age or older
vaccinated at 24 to 34 w eeks’
gestation to the immune
response in nonpregnant
women 18 years of age or
older from the C4591001
study without evidence of
pastSARS -CoV -2 infection .In maternal participants
complying with the key protocol
criteria (evaluable maternal
participants) and no serological
or virological evidence (up to 1
month after receipt of the second
dose) of pastSARS -CoV- 2
infection:
GMR, estima ted by the ratio
of the geometric mean of
SARS -CoV- 2 neutralizing
titers in pregnant w omen to
those in nonpregnant women
1month after Dose 2SARS -CoV- 2 neutralizing titers
To demonstrate the
immunobridging of the
immune response to
prophylactic BNT162b2 in
maternal participants
18years of age or older
vaccinated at 24 to 34 w eeks’ In maternal participants
complying with the key protocol
criteria (evaluable participants):
GMR, estimated by the ratio
of the geometric mean of
SARS -CoV- 2 neutralizing
titers in pregnant w omen to SARS -CoV- 2 neutralizing titers
090177e19668bad9\Approved\Approved On: 02-Mar-2021 22:33 (GMT)
FDA-CBER-2021-5683-0779930
PF-07302048 (BNT162 RNA- Based COVID- 19 Vaccines)
Protocol C4591015
Protocol Amendment 2, 02March 2021
PFIZER CONFIDENTIAL
CT02- GSOP Maternal Immunization Protocol Template (Phase 1 2 3 4) (15 May 2020)
TMF Doc ID: 164.01
Page 16ObjectivesaEstimands Endpoints
gestation to the immune
response in nonpregnant
women 18 years of age or
older from the C4591001
study with and without
evidence of prior
SARS -CoV -2 infection .those in nonpregnant female
participants 1 month after
Dose 2
Secondary Secondary Secondary
If at least 12cases are
observed:
To evaluate the efficacy of
prophylactic BNT162b2
against confirmed
COVID -19 occurring from 7
days after Dose 2 through 1
month after delivery in
mater nalparticipants 18
years of age or older
vaccinated at 24 to 34 w eeks’
gestation without evidence of
prior SARS -CoV -2 infection .In maternal participants
complying with the key protocol
criteria (evaluable participants)
and no serological or virologic al
evide nce (prior to 7 days after
receipt of Dose 2) of pastSARS -
CoV- 2 infection :
100 × (1 –IRR) [ratio of
active vaccine to placebo]COVID -19 incidence per 1000
person -years of blinded follow -up
based on central laboratory or locally
confirmed NAAT
If at least 12cases are
observed:
To evaluate the efficacy of
prophylactic BNT162b2
against confirmed
COVID -19 occurring from 7
days after Dose 2 through 1
month af ter delivery in
maternal participants 18
years of age or older
vaccinated at 24 to 34 w eeks’
gestation with and without
evidence of prior SARS -
CoV -2 infection .In maternal participants
complying with the key protocol
criteria (evaluable participants):
100 × (1 –IRR) [ratio of
active vaccine to placebo]COVID -19 incidence per 1000
person -years o f blinded follow -up
based on central laboratory or locally
confirmed NAAT
To describe the efficacy of
prophylactic BNT162b2
against asymptomatic
SARS -CoV- 2 infection
through 1 month after
delivery in maternal
participants 18 years of age
or older vaccinated at 24 to
34 w eeks’ gestation without
evidence of prior SARS -
CoV -2 infection .In evaluable maternal participants
without serological or virologic al
evidence of prior SARS -CoV- 2
infection :
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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FDA-CBER-2021-5683-0779931
PF-07302048 (BNT162 RNA- Based COVID- 19 Vaccines)
Protocol C4591015
Protocol Amendment 2, 02March 2021
PFIZER CONFIDENTIAL
CT02- GSOP Maternal Immunization Protocol Template (Phase 1 2 3 4) (15 May 2020)
TMF Doc ID: 164.01
Page 17ObjectivesaEstimands Endpoints
To describe the immune
response over time and
persistence of prophylactic
BNT162b2 when
administered to maternal
participants 18 years of age
or older vaccinated at 24 to
34 w eeks’ gestation . In maternal participants
complying with the key protocol
criteria (evaluable maternal
participants ) from each vaccine
group:
GMC s/GMT s, at baseline
(before Dose 1) , 2 w eeks
after Dose 2, 1month after
Dose 2 ,at delivery ,and
6months after delivery
GMFR sfrom baseline
through 2 weeks after
Dose 2, 1 month after
Dose 2,at delivery, and
6months after deliveryFull-length S -binding IgG levels
SARS -CoV- 2 neutralizing titers
To assess the safety of
maternal immunization in
infants born to maternal
participants 18 years of age
or older w ho were vaccinated
with BNT162b2 during
pregnancy .In infants born to maternal
participants receiving at least 1
dose of study intervention from
each vaccine group, the
percentage of infants with:
Specific birth outcomes
AEs from birth through 1
month of age
SAEs andAESIs (major
congenital anomalies,
developmental delay)
through 6months of ageSpecific birth outcomes
AEs from birth through 1 month of
age
SAEs and AESIs (major congenital
anomalies, developmental delay)
through 6 months of age
To describe the immune
response in infants born to
maternal participants
vaccinated w ith prophylactic
BNT162b2 during
pregnancy.In infants born to evaluable
maternal participants from each
vaccine group:
GMC sand GMFR s, at birth
and 6months after deliveryFull-length S -binding IgG levels
Exploratory Exploratory Exploratory
To describe the incidence of
confirmed COVID -19 among
maternal participants who
were vaccinated with
BNT162b2 .In maternal participants who
received BNT162b2 ( at initial
randomization and at 1 month
after delivery ):
Incidence per 1000
person -years of follow -upCOVID -19 incidence per 1000
person -years of follow -up based on
central laboratory or locally
confirmed NAAT
To describe the incidence of
asymptomatic SARS -CoV -2
infection through 6 months
after delivery in maternal
participants 18 years of age
or older vaccina ted at 24 to
34 w eeks’ gestation with
BNT162b2 at initial
randomization and withoutIn maternal participants who
received BNT162b2 at initial
randomization and without
evidence of prior SARS -CoV- 2
infection :
Incidence per 1000 person -
years of follow -upIncidence of asymptomatic SARS -
CoV- 2 infection per 1000 person -
years of follow -up based on N-
binding antibody seroconversion
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FDA-CBER-2021-5683-0779932
PF-07302048 (BNT162 RNA- Based COVID- 19 Vaccines)
Protocol C4591015
Protocol Amendment 2, 02March 2021
PFIZER CONFIDENTIAL
CT02- GSOP Maternal Immunization Protocol Template (Phase 1 2 3 4) (15 May 2020)
TMF Doc ID: 164.01
Page 18ObjectivesaEstimands Endpoints
evidence of prior
SARS -CoV -2 infection .
To describe the serological
responses among maternal
participants to the
BNT162b2 vaccine candidate
in cases of:
Confirmed COVID -19
Confirmed severe
COVID -19
SARS -CoV- 2 infection
without confirmed
COVID -19In each subset of evaluable
maternal participants from each
vaccine group with:
Confirmed COVID -19
Confirmed severe
COVID -19
SARS -CoV- 2 infection but
no confirmed COVID -19
GMCs/GMTs and GMFRs at
baseline , 1month after
Dose 2,at delivery ,and
6months after deliveryFull-length S -binding IgG levels
SARS -CoV- 2 neutralizing titers
To describe the immune
response toprophylactic
BNT162b2 betw een Dose 1
and Dose 2 when
administered to maternal
participants 18 years of age
or older vaccinated at 2 7to
34 w eeks’ gestation in the
Phase 2 portion of the study .In evaluable maternal
participants:
GMCs/GMTs at baseline and
before Dose 2
GMFRs from baseline to
before Dose 2Full-length S -binding IgG levels
SARS -CoV- 2 neutralizing titers
To describe the immune
response in infants born to
breastfeeding maternal
participants vaccinated with
prophylactic BNT162b2
during pregn ancy .In infants born to maternal
participants from each vaccine
group , based on t he breastfeeding
status :
GMCs and GMFRs, at birth
and 6 months after delivery Full-length S -binding IgG levels
To describe the safety of
maternal immunization in
infants born to breastfeeding
maternal participants
vaccinated w ith prophylactic
BNT162b2 during
pregnancy .In infants born to maternal
participants receiving at least 1
dose of study intervention from
each vaccine group, based on the
breas tfeeding status, the
percentage of infants with:
AEs from birth through 1
month of age
SAEs andAESIs (major
congenital anomalies,
developmental delay)
through 6 months of ageAEs from birth through 1 month of
age
SAEs and AESIs(major congenital
anomalies, developmental delay)
through 6months of age
To describe the incidence of
confirmed COVID -19 in
infants born to maternal
participants who were
vaccinated w ith BNT162b2
during pregnancy .In infants born to maternal
participan ts from each vaccine
group:
Incidence rate of infant
participants with confirmed
COVID -19 COVID -19 incidence per 1000
person -years of follow -up based on
central laboratory or locally
confirmed NAAT
090177e19668bad9\Approved\Approved On: 02-Mar-2021 22:33 (GMT)
FDA-CBER-2021-5683-0779933
PF-07302048 (BNT162 RNA- Based COVID- 19 Vaccines)
Protocol C4591015
Protocol Amendment 2, 02March 2021
PFIZER CONFIDENTIAL
CT02- GSOP Maternal Immunization Protocol Template (Phase 1 2 3 4) (15 May 2020)
TMF Doc ID: 164.01
Page 19ObjectivesaEstimands Endpoints
To describe MIS -C cases in
infants born to maternal
participants who were
vaccinated w ith BNT162b2
during pregnancy .In infants born to maternal
participants from each vaccine
group:
Incidence rate of MIS -C MIS-C incidence per 1000
person -years of follow -up
a.HIV-infected participants will not be included in analyses of the objectives, but in separate exploratory
analyses . Analyses among HIV -infected w omen and their infants will be summarized se parately.
Overall Design
This will be a global Phase 2/3, randomized, placebo- controlled, observer -blind study
evaluating the safet y, tolerability, and immunogenicity of 30µg of BNT162b2 or placebo
administered in 2 doses, 21 day s apart, in approximately 4000 healthy pregnant women
18years of age or older vaccinated at24 to 34 weeks’ gestation. Participants will be
randomized 1:1 to receive BNT162b2 or placebo (saline).
The Phase 2 portion of the study will include approximately 350 pregna nt women
randomized 1:1 to receive BNT162b2 or placebo (saline) at27to 34 weeks’ gestation .The
IRC willreview safet y data through 7 day s after the second dose for all Phase 2 participants
and if BNT162b2 is deemed safe and tolerable , enrollment in Phase 3 will commence.
The Phase 3 portion of this study will assess the safety , tolerability , and immunogenicit y of
BNT162b2 among pregnant women enrolled at24 to34 weeks’ gestation .
Maternal participants who originall y received placebo will receive BNT 162b2 at defined
time points as part of the study .
Number of Participants
Approximately 350healthy pregnant women will be enrolled in the Phase 2 portion of the
study .Approximately 3650 healthy pregnant women will be enrolled in the Phase 3 portion .
Intervention Groups and Duration
Thisstudy will evaluate a 2- dose (separated b y 21 days) schedule of 30 µg of the
investigational BNT162b2 RNA vaccine candidate (BNT162 RNA -LNP vaccine utilizing
modRNA and encoding the P2 S) for active immunization agains t COVID -19.
Health y pregnant women will be randomized in a 1:1 ratio to receive a 2-dose schedule of
either:
BNT162b2 (BNT162 RNA -LNP vaccine utilizing modRNA and encoding the P2 S) at a
dose of 30 µg OR
Normal saline solution for injection (0.9% NaCl inje ction).
090177e19668bad9\Approved\Approved On: 02-Mar-2021 22:33 (GMT)
FDA-CBER-2021-5683-0779934
PF-07302048 (BNT162 RNA- Based COVID- 19 Vaccines)
Protocol C4591015
Protocol Amendment 2, 02March 2021
PFIZER CONFIDENTIAL
CT02- GSOP Maternal Immunization Protocol Template (Phase 1 2 3 4) (15 May 2020)
TMF Doc ID: 164.01
Page 20Each maternal participant will participate in the study for approximately up to 10 months
depending on the vaccine group to which she was randomized. H er infant will participate in
the study for approximately 6 months. The stud y duration will be approximately 14 months.
Data Monitoring Committee or Other Independent Oversight Committee
The study will utilize an IRC, an internal Pfizer committee that will be used during the
Phase 2 portion of the study to closel y monitor safety.
The study will include stopping rules, which may result in a pause to study vaccination
follow ed bya review and recommendation b y the IRC.
The study will use an external DMC to monitor vaccine safet ythroughout the study .
Statistical Methods
The primary safet y objective will be evaluated b y descriptive summary statistics for local
reactions, s ystemic events, AEs, and SAEs, for each vaccine group. Descriptive summary
statistics will include counts and percentages of participants with the indicated endpoint and
the associated Clopper -Pearson 95% CIs. A 3-tier approach will be used to summarize AEs.
The AEs ,including SAEs, reported in the open -label follow -up period will be summarized
separately from those reported during the blinded follow -up period for maternal participants.
The safet y objective related to infants born to maternal participants , including birth
outcomes, AEs, SAEs, andAESIs,will be eval uated in a similar way .
There are 2primary immunogenicity objectives; each will be evaluated b y a formal
hypothesis test for immunobridging of SARS -CoV -2 neutralizing titers 1 month after Dose 2
in a subset of maternal participan tscompared to a group of randoml y selected nonpregnant
women within t he same age group from the C4591001 study .Both model -based and
unadjusted GMRs will be provided along with associated 2- sided 95% CIs. The fixed
sequential test ingprocedure will be used for ty pe I error control . Thecompari son for
participants without evidence of prior SARS -CoV -2 infection will be conducted first ,and
immunobridging success will be declared if the lower bound of the 2 -sided 95% CI for the
GMR of the pregnant women relative to the nonpregnant women is greater than 0. 67. The
immunobridging for participants with and without evidence of prior SARS -CoV -2 infection
will be assessed only if the immunobridging success for participants without evidence of
prior SARS -CoV -2 infection is declared.
Other immunogenicity objectives will be evaluated d escriptivel yby GMTs/GMCs and
GMFRs of full-length S- binding IgG levels and/or SARS -CoV -2 neutralizing titers and
associated 2- sided 95% CI s.
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FDA-CBER-2021-5683-0779935
PF-07302048 (BNT162 RNA- Based COVID- 19 Vaccines)
Protocol C4591015
Protocol Amendment 2, 02March 2021
PFIZER CONFIDENTIAL
CT02- GSOP Maternal Immunization Protocol Template (Phase 1 2 3 4) (15 May 2020)
TMF Doc ID: 164.01
Page 21The secondary efficacy objectives are to evaluate VE against the confirmed COVID -19
illness during the blinded follow- up period, which is defined as VE = 100 × (1–IRR).IRR
is calculated as the ratio of first confirmed COVID -19 illness rate in the vaccine group to the
corresponding illness rate in the placebo group. Hypothesis testin g will be conducted onl y if
at least 12 cases are accrued.
VEagainst as ymptomatic infection will be evaluated descriptivel y.
Theincidence rates of confirmed COVID -19and asy mptomatic infection per 1000
person -years of follow -up in maternal participants after their receipt of BNT162b2
throughout the stud y will be provided with the associated 2 -sided 95% CIs.
The incidence rateof confirmed COVID -19 and incidence rateof confirmed MIS-Cin infant
participants ,andassociated 2 -sided 95% CIs, will also be provided according to the vaccine
group towhich the maternal participants were randomized .
1.2.Schema
Not applicable .
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FDA-CBER-2021-5683-0779936
PF-07302048 (BNT162 RNA- Based COVID- 19 Vaccines)
Protocol C4591015
Protocol Amendment 2, 02March 2021
PFIZER CONFIDENTIAL
CT02- GSOP Maternal Immunization Protocol Template (Phase 1 2 3 4) (15 May 2020)
TMF Doc ID: 164.01
Page 221.3. S chedule of Activ ities
The SoA table provides an overview of the protocol visits and procedures. Refer to theSTUDY ASSESSMENTS AND
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 pr otect the well -being of the participant .
An unplanned potential COVID-19 illness visit and unplanned potential COVID- 19 convalescent visit are required at any time
between Visit 1 (Vaccination 1) and Visit 8 (6-month postdelivery visit,the final study visit) or Visit 103 (1- month follow -up phone
contact) that potential COVID -19symptoms are reported, including MIS- C.
1.3.1. Schedule of Activities for Maternal Participants
Visit Number (Maternal
Participants)1 2 3 4 5 6 7 8 Unplanned Unplanned
Visit Description Screening :
-28 Days to
Vaccination
1Vaccination
22-Week
Post–
Vaccination
2 Follow -
upa1-Month
Post–
Vaccination
2
Follow -upaDelivery 1-Week
Postdelivery
Follow -up Call1-Month
Postdelivery
Follow -upb6-Month
Postdelivery
Follow -up
For
Participants
Originally
Randomi zed
to Receive
BNT162b2Potential
COVID -19
Illness VisitcPotential
COVID -19
Convalescent
Visit
Visit Window (Days) Day 1
Visit 119 to 23
Days After
Visit 111 to 17
Days After
Visit 228 to 35
Days After
Visit 2Varies 7 to 10 Days
After Delivery21to 35
Days After
Delivery160 to
200Days
After
DeliveryOptimally
Within 3
Days After
Potential
COVID -19
Illness
Onset28 to 35
Days After
Potential
COVID -19
Illness Visit
Type of Visit Clinic Clinic Clinic Clinic Hospital Phone Call Clinic Clinic
Obtain informed consent X
Assign single participant identifier X
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FDA-CBER-2021-5683-0779937
PF-07302048 (BNT162 RNA- Based COVID- 19 Vaccines)
Protocol C4591015
Protocol Amendment 2, 02March 2021
PFIZER CONFIDENTIAL
CT02- GSOP Maternal Immunization Protocol Template (Phase 1 2 3 4) (15 May 2020)
TMF Doc ID: 164.01
Page 23Visit Number (Maternal
Participants)1 2 3 4 5 6 7 8 Unplanned Unplanned
Visit Description Screening :
-28 Days to
Vaccination
1Vaccination
22-Week
Post–
Vaccination
2 Follow -
upa1-Month
Post–
Vaccination
2
Follow -upaDelivery 1-Week
Postdelivery
Follow -up Call1-Month
Postdelivery
Follow -upb6-Month
Postdelivery
Follow -up
For
Participants
Originally
Randomi zed
to Receive
BNT162b2Potential
COVID -19
Illness VisitcPotential
COVID -19
Convalescent
Visit
Visit Window (Days) Day 1
Visit 119 to 23
Days After
Visit 111 to 17
Days After
Visit 228 to 35
Days After
Visit 2Varies 7 to 10 Days
After Delivery21to 35
Days After
Delivery160 to
200Days
After
DeliveryOptimally
Within 3
Days After
Potential
COVID -19
Illness
Onset28 to 35
Days After
Potential
COVID -19
Illness Visit
Type of Visit Clinic Clinic Clinic Clinic Hospital Phone Call Clinic Clinic
Obtain demography X
Record current alcohol and tobacco
usageX
Obtain medical history ,including
obstetric and gestational historyX
Phase 3 only: For participants who
are HIV -positive, record latest
CD4 count and HIV viral loadX X X X X X
Record LMP and EDD X
Measure vital signs X X X
Perform physical examination X
Perform targeted physical
examinationX X
Perform obstetric examination X X X
Perform obstetric ultrasound X
Record nonstudy vaccine information X X X X X X X X
Record concomitant medication
associated with an adverse event or
serious adverse eventX X X X X X X Xd
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FDA-CBER-2021-5683-0779938
PF-07302048 (BNT162 RNA- Based COVID- 19 Vaccines)
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PFIZER CONFIDENTIAL
CT02- GSOP Maternal Immunization Protocol Template (Phase 1 2 3 4) (15 May 2020)
TMF Doc ID: 164.01
Page 24Visit Number (Maternal
Participants)1 2 3 4 5 6 7 8 Unplanned Unplanned
Visit Description Screening :
-28 Days to
Vaccination
1Vaccination
22-Week
Post–
Vaccination
2 Follow -
upa1-Month
Post–
Vaccination
2
Follow -upaDelivery 1-Week
Postdelivery
Follow -up Call1-Month
Postdelivery
Follow -upb6-Month
Postdelivery
Follow -up
For
Participants
Originally
Randomi zed
to Receive
BNT162b2Potential
COVID -19
Illness VisitcPotential
COVID -19
Convalescent
Visit
Visit Window (Days) Day 1
Visit 119 to 23
Days After
Visit 111 to 17
Days After
Visit 228 to 35
Days After
Visit 2Varies 7 to 10 Days
After Delivery21to 35
Days After
Delivery160 to
200Days
After
DeliveryOptimally
Within 3
Days After
Potential
COVID -19
Illness
Onset28 to 35
Days After
Potential
COVID -19
Illness Visit
Type of Visit Clinic Clinic Clinic Clinic Hospital Phone Call Clinic Clinic
Record prohibited medications X X
Review eligibility criteria X X
Review temporary delay criteria X X
Review continued eligibility X X X X X X
Explain/review participant
communication methods (including
for e-diary completion), assist the
participant with downloading the
app, or issue provisioned device, if
requiredX
Record systemic events at baseline in
the e -diaryX
Assign participant randomization and
container numberX
Collect blood sample for
immunogenicity assessment (~20 mL
per blood sample) X XeX X X X X
Obtain nasal (midturbinate swab) X X Xd
Administer study intervention X X
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Page 25Visit Number (Maternal
Participants)1 2 3 4 5 6 7 8 Unplanned Unplanned
Visit Description Screening :
-28 Days to
Vaccination
1Vaccination
22-Week
Post–
Vaccination
2 Follow -
upa1-Month
Post–
Vaccination
2
Follow -upaDelivery 1-Week
Postdelivery
Follow -up Call1-Month
Postdelivery
Follow -upb6-Month
Postdelivery
Follow -up
For
Participants
Originally
Randomi zed
to Receive
BNT162b2Potential
COVID -19
Illness VisitcPotential
COVID -19
Convalescent
Visit
Visit Window (Days) Day 1
Visit 119 to 23
Days After
Visit 111 to 17
Days After
Visit 228 to 35
Days After
Visit 2Varies 7 to 10 Days
After Delivery21to 35
Days After
Delivery160 to
200Days
After
DeliveryOptimally
Within 3
Days After
Potential
COVID -19
Illness
Onset28 to 35
Days After
Potential
COVID -19
Illness Visit
Type of Visit Clinic Clinic Clinic Clinic Hospital Phone Call Clinic Clinic
Assess acute reactions for at least 30
minutes after study intervention
administrationX X
Provide/ensure participant has a
thermometer and measuring deviceX X
Review reactogenicity e -diary data
(daily review is optimal during the
active diary period of 7 days
following study intervention
administration)
Review ongoing reactogenicity e -
diary symptoms with participant and
obtain stop datesX X
Record pregnancy outcome
informationX X
Record AEs and SAEs as
appropriatefX X X X XdXdX XdXdXd
Collect e -diary or assist the
participant to delete applicationX
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Page 26Visit Number (Maternal
Participants)1 2 3 4 5 6 7 8 Unplanned Unplanned
Visit Description Screening :
-28 Days to
Vaccination
1Vaccination
22-Week
Post–
Vaccination
2 Follow -
upa1-Month
Post–
Vaccination
2
Follow -upaDelivery 1-Week
Postdelivery
Follow -up Call1-Month
Postdelivery
Follow -upb6-Month
Postdelivery
Follow -up
For
Participants
Originally
Randomi zed
to Receive
BNT162b2Potential
COVID -19
Illness VisitcPotential
COVID -19
Convalescent
Visit
Visit Window (Days) Day 1
Visit 119 to 23
Days After
Visit 111 to 17
Days After
Visit 228 to 35
Days After
Visit 2Varies 7 to 10 Days
After Delivery21to 35
Days After
Delivery160 to
200Days
After
DeliveryOptimally
Within 3
Days After
Potential
COVID -19
Illness
Onset28 to 35
Days After
Potential
COVID -19
Illness Visit
Type of Visit Clinic Clinic Clinic Clinic Hospital Phone Call Clinic Clinic
Collection of COVID -19–related
clinical and laboratory information
(including local diagnosis)X X
Abbreviations: EDD = estimated delivery date; HIV = human immunodeficiency virus; LMP = last menstrual period.
a.The 2 -week postvaccination follow -up and 1 -month postvaccination follow -up visits will not be performed if delivery occurs before the visits. If delivery
occurs before Vaccinati on2, the second dose should be given as soon as possible after delivery. Once delivery occurs, the visit windows are calculated
based on the delivery date.
b.All maternal participants will be unblinded. Placebo recipients will be given BNT162b2 and move to follow the procedures in Section 1.3.2 .
c.The COVID- 19 illness visit may be conducted as an in -person or telehealth visit.
d.Only AEs occurring up to 48 hours after each blood draw and nasal midturbinate swab collection must be recorded.
e.Prevaccination blood samples for immunogenicity will be drawn from maternal participants in Phase 2 only.
f.The investigator and site staff will ensure the active elicitation and collection of AEs and SA Es through 1 month after Vaccination 2. From 1 month after
Vaccination 2 until the 6-month postdelivery follow -up, SAEs will be collected.
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Page 271.3.2. Schedule of Activities for Maternal Participants Who Were Originally Assigned to Placebo
Visit Number (Maternal Participants) 101 102 103
Visit Description 1-Month Postdelivery Follow -up
Vaccination 3Vaccination 4 1-Month
Telephone Contact
Follow -up
Visit Window (Days) 21to 35 Days After Delivery 19 to 23 Days After Visit
10128 to 35 Days After Visit
102
Type of Visit Clinic Clinic Phone Call
Confirm the participant originally received only placebo at Vaccination
1/2. Secondary confirmation by another site staff member is requiredX
Collect prohibited medication use X X X
For participants who are HIV-positive, record latest
CD4 count and HIV viral loadX X
Revie w and consider eligibility X X
Revie w temporary delay criteria X X
Collect blood sample for immunogenicity assessment ~20mL
Obtain nasal (midturbinate) swab X X
Obtain vaccine vial allocation via IRT X X
Administer BNT162b2 X X
Assess acute reactions for at least 30 minutes after study intervention
administrationX X
Collect AEs and SAEs as appropriate X X X
Contact the participant by telephone X
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Page 281.3.3. Schedule of Activities for Infant Participants
Visit Number (Infant Participants) 1 2 3
Unplanned Unplanned
Visit Description Delivery 1-Week
Postdelivery
Follow -up6-Month s-of-Age
Follow -upPotential
COVID -19
Illness VisitPotential
COVID -19
Convalescent
Visit
Visit Window (Days) Varies 7to 10Days After
Delivery160to 200Days
After DeliveryOptim ally
Within 3 Days
After Potential
COVID -19
Illness Onset28 to 35 Days
After Potential
COVID -19
Illness Visit
Type of Visit Hospital Phone Call Clinic
Assign single participant identifier X
Record demography and available birth information X
Measure v ital signs X
Perform p hysical examination X
Record concomitant medication associated with an adverse event /serious
adverse eventX X X
Review eligibility X
Review continued eligibility X X
Record breastfeeding information X X
Collect blood sample for immunogenicity assessment (up to ~5mL per
blood sample depending on weight )X X
Cord blood sample (~10 mL) for immunogenicity assessment Xa
Record adverse events X XbXb X X
Record serious adverse events and adverse events of special interest X X X X X
Collect prohibited medication use X X
Obtain nasal swab X
Collection of COVID -19–related clinical and laboratory information
(including local diagnosis)X X
Abbreviations: HIV = human immunodeficiency virus; IRT = interactive response technology.
a.If cord blood is unavailable, a blood sample may be collected from the infant participant up to 72 hours after birth but preferably within 24 hours after birth.
b.Active AE collection through 1 month of age.
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Page 292.INTRODUCTION
The BNT162b2 RNA -based COVID -19 vaccine is currentl y being investigated for
prevention of COVID -19 in healthy pregnant women.
2.1.Study Rationale
The purpose of the study is to describe the safet y, tolerability, and immunogenicity of
BNT162 b2RNA -based COVID -19 vaccine against COVI D-19 in health y pregnant women.
There are currently no licensed vaccines to prevent infection with SARS -CoV -2 or
COVID -19. Pregnant women are at risk of acquiring SARS -CoV -2infection , developing
COVID -19and COVID -19–associated complications. Given the global crisis of COVID -19
and fast expansion of the disease globall y, the rapid development of an effective vaccine for
use in this population 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 Janua ry, the genetic sequence of the 2019 -nCoV became available to the
WHO and public (MN908947.3), and the virus was categorized in the Betacoronavirus
subfamily . By sequence anal ysis, the phy logenetic tree revealed a closer relationship to
SARS virus isolate s 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 countries ,andon 11 March 2020, the WHO characterized the
COVID -19 outbreak as a pandemic.3 On 16 December 2020, The Center for Sy stems
Science and Engineering at Johns Hopkins University reported more than 73million cases
globall y, with over 1. 6million deaths from 191countries. Global case rates and deaths have
continued to increase ,with the United States reporting the most cases and deaths of any other
country . There are currently no vaccines broadly available to prevent SARS -CoV -2
infections or the disease it causes, COVID -19.4
Pregnant women are at risk for acquiring SAR S-CoV -2 infection and COVID -19.5,6,7
Pregnancy may confer increased risk of severe COVID -19because of physiological changes
during pregnancy that can increase susceptibility to respiratory infections and subsequent
rapid progression to respiratory failure .8Additionally , pregnant women with COVID -19
have been reported to have higher rates of preterm birth, cesarean delivery , fetal distress, and
infants requiring neonatal intensive care .8,9,10,11While COVID -19 in children is reported less
commonly than in adults, infants <1 y ear of age , if infected with SARS -CoV -2,may be at
increased risk of severe disease ,and younger age groups have increasing rates of
COVID -19–associated hospitalization .12,13Prevention of SARS -CoV -2 infection and
COVID -19 is critically important in pregnant women ,and maternal immunization may
confer some protection to the ir infants .
Given the rapid transmissio n of COVID -19 and incidence of disease in the United States and
elsewhere, the rapid development of an effective vaccine is of utmost importance.
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Page 30A proph ylactic, RNA -based SARS -CoV -2 vaccine provides one of the most flexible and
fastest approaches availabl e to immunize against the emerging virus.14,15The development
of an RNA -based vaccine encoding a viral antigen, which is then expressed by the vaccine
recipient as a protein capable of eliciting protective immune responses, provides significant
advantages over more traditional vaccine approaches. 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 e nable the most effective response in outbreak
scenarios .14,15
There are no ongoing COVID -19 vaccine studies including pregnant women. Vaccination of
pregnant women has been used globally to protect both women and their infants against
influenza and as a mechanism to protect infants against pertussis. Several studies have
demonstrated that maternal immunization is safe for both mother and infant and an important
strategy to protect pregnant women and their infants against infectious diseases. Currentl y
maternal immunization studies are being conducted as part of the develop ment of novel RSV
and GBS vaccines .16,17
BNT162b2 is a SARS -CoV -2–RNA -LNP vaccine based on a platform of modRNA with
blunted innate immune sensor –activating capacity and augmented expression encoding the
P2 S.
This study will describe the safet y of BNT162b2 in pregnant women and their infants. Itwill
also assess the immunogenicity of BNT162b2 in pregnant women, the transfer of antibody to
their infant s, and the kinetics of antibody transfer in the infant.
2.2.1. Clinical Overvie w
Prior to this study , clinical data from BNT162b2 established a favorable safet y profile
characterized b ymild, localized, and transient effects. BNT162 vaccines based on modRNA
have now been administered to >19,000 people18at the 30 -µgdose level using a 2 -dose
schedule since the C4591001 Ph ase 1/2/3 study started in the United States and other
countries . BNT162b2 was also evaluated in the BNT162- 01 study conducted in Germany by
BioNTech, at dose levels between 1 µg and 100 µg.19
Study C4591001 is a Phase 1/2/3, multicenter, multinational, randomized, placebo-
controlled, observer -blind, dose -finding, vaccine candidate– selection, and efficacy study in
healthy individuals. The study consists of 2 parts: Phase 1: to identify the preferred vaccine
candidate (BNT162b1 or BNT162b2) and dose level (10 µg, 20 µg, 30 µg, or 100 µg [for
BNT162b1]); Phase 2/3: an expanded -cohort and efficacy study for the selected vaccine
candidate (BNT162b2).
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Page 31The Phase 1 study population included health y participants 18 to 55 years and 65 to 85 years
of age. Enrollment in C4591001 Phase 1 is complete and, although follow -up continues, the
available safet y data from Phase 1 participants in Study C4591001 show that BNT162b2
reactogenicity , AEs, and laboratory results were consistent with those commonly associated
with vaccination. The observed reactogenicity was generall y mild or moderate (primarily
pain at the injection site) and short-lived. The local reactions tended to be more frequent
after the second dose. There w as no redness or swelling reported b y participants in the 65 -to
85-year age group who received BNT162b2 .20
Regarding s ystemic events, 17% of the 18- to 55-year-oldparticipants and 8% of those in the
65-to 85-year age group reported fever (≥38.0 °Cto 38.9° C) after the second dose of 30 µg
of BNT162b2. Severe s ystemic events (fatigue, headache, chills, muscle pain ,and joint pa in)
were reported in small numbers of younger recipients of this vaccine candidate, but no severe
systemic events were reported in older recipients, and no Grade 4 s ystemic events were
reported .20
No unexpected AEs or SAEs were reported. Through 1 month after receipt of the second
vaccine, A Es that were considered by investigators to be related to the study intervention
were reported in 25% of participants 18 to 55 years of age who received 30 µg of
BNT162b2; no AEs were reported b y the older population who received the same dose .20
The available immunogenicity data from Phase 1 participants show that BNT162b2 induced
a robust IgG -binding response to S1 and SARS -CoV -2 neutralizing response.
Immunogenicit y also substantially increased following the second dose of vaccine.
BNT162b2 induces a strong antigen -specific T H1-skewed CD4+ response and a strong
antigen -specific CD8+ response.
Based on the safety , tolerability ,and immunogenicity data generated from Phase 1, the
vaccine candidate selected for the Phase 2/3 part of the study was BNT162b2 at a dose of
30µg. This phase of the study is currently ongoing and is evaluating the efficacy of the
study intervention .
The Phase 2/3 portion of C4591001 is ongoing in participants ≥12years of age.
There are 2 primary efficacy endpoints in the Phase 2/3 part of the C4591001 study . The
first is to evaluate the efficacy of prophy lactic BNT162b2 against confirmed COVID -19 in
participants without evidence of prior SARS -CoV -2 infection, and the second is to evaluate
the efficacy of prophy lactic BNT162b2 against confirmed COVID- 19 in participants
regardless of evidence of prior SARS -CoV -2 infection . Cases of COVID -19 are defined by
the presence of specified symptoms plus a NAAT for SARS -CoV -2 at least 7 day s following
the second dose of vaccine.
The primary safet y objective include sdefinition of the safet y profile of prophylactic
BNT162b2 as measured by solicited local reactions and sy stemic events within 7 day s after
vaccination, AE s,and SAE s.
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Page 32The currently available safet y and immunogenicity data are presented in the BNT162 IB.
2.3.Benefit/Risk Assessment
There is an ongoing global pandemic of COVID -19 with no preventive vaccines broadl y
available for pregnant women . While there were no data available from clinical trials on the
use of BNT162 vaccines in pregnant women, preliminary data are available from theongoing
Phase 1/2/3 clinical trial evaluating the use of BNT162 b2 30 -µg doses administered 21 day s
apart in nonpregnant adults .
The Phase 2/3 portion of the C4591001 study has reached the final efficacy analysisand
demonstrates that BNT162b2 iseffective ,with 95% observed VE ,against COVID -19 among
individuals 16 y ears of age and older. Safet y evaluation is ongoing ;however ,~19,000
participants have safet y data available for at least 2 months of follow- up after the second
dose. In general, BNT162b2 had a favorable safety profile. BNT162b2 recipients reported
more reactogenicit y events compared to placebo recipients. In general, local reactions were
mostly mild tomoderate in severity and resolved within 1 to 2 day s after onset. Severe
fatigue was reported in 3.8% of BNT162b2 recipients; however, these events were transient.
Few participants in either group had severe AEs, SAEs, or AEs leading to withdrawal from
the study .18
These data s uggest a favorable risk/benefit profile in pregnant women. Anticipated AEs after
vaccination in maternal participants are expected to be manageable using routine
symptom -driven standard of care as determined by the investigators . As a result, the profil e
of these vaccine candidates supported initiation of this PASS clinical study .This
interventional study is designated as a PASS, identified as Category 3 in the EU RMP, and is
conducted as a conditional marketing approval commitment to the EMA and Swiss medic and
an emergency use authorization commitment to the US FDA and numerous other health
authorities under respective national emergency use legislation.
DART studies have been completed. In summary , administration of BNT162b2 to female
rats twice befo re the start of mating and twice during gestation at the human clinical dose
was associated with nonadverse effects (bod y weight, food consumption ,and effects
localized to the injection site) after each dose administration. However, there were no effects
of BNT162b2 administration on mating performance, fertility , or an y ovarian or uterine
parameters in the female rats or on embry o-fetal or postnatal survival, growth, or
development in the offspring. An immune response was confirmed in female rats following
administration of each vaccine candidate and these responses were also detectable in the
offspring (fetuses and pups). Additional details are included in the IB .
More detailed information about the known and expected benefits and risks and reasonabl y
expected AEs of BNT162b2 may be found in the IB, which is the SRSD for this study .
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Page 332.3.1. Risk Assessment
Potential Risk of Clinical Significance Summary of Data/Rationale for Risk Mitigation Strategy
Study Int ervention :BNT162 RNA -Based COVID- 19 Vaccine
Potential for 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.These are common adverse reactions seen with
other vaccines, as noted in the FDA CBER
guidelines on toxicity grading scales for healthy
adult volunteers enrolled in preventive vaccine
clinical trials .21Phase 1 data from the C4591001 study
demonstrated that the 30 -µg dose had a
tolerable reactogenicity profile .18
Thisstudy employs the use of a reactogenicity
e-diary to monitor local reactions and systemic
events in real time.
All participants will be observed for at least
30 minutes after vaccination.
In addition, t he study will enroll a small er
subset of pregnant women in Phase 2 (N=350)
and have a review of 7-day safety data by an
IRC before expansion of the study into Phase
3.
Unknown AEs with a novel vaccine.There arelimited data available because of the
ongoing C4591001 study (Phase 1 completed ,
Phase 2/3 ongoing). To date , the safety and
tolerability profile of BNT162b2 is consistent
with what hasbeen expected from nonclinical
studies and clinical studies in other RNA- based
compounds .22,23An IRC (in Phase 2) will review safety.
Stopping rules will be in place for Phase 2 ,
which may result in a pause to study
vaccination followed by a review and
recommendation by the IRC.
A DMC will be used throughout the study to
review all safety data.
All participants will be observed for at least
30 minutes after vaccination .
AE and SAE reports will be collected from the
signing of the ICD through 1month after the
second dose of vaccine.
In maternal partici pants who receive
BNT162 b21 mo nth after delivery ,AEs will be
collected from the signing of the ICD to
1month after Vaccination 4 (Visit 103)for
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Page 34Potential Risk of Clinical Significance Summary of Data/Rationale for Risk Mitigation Strategy
those maternal participants who originally
received placebo and go on to receive
BNT162b2 .
Potential for COVID -19 enhancement. Disease enhancement has been seen following
vaccination with RSV, feline coronavirus, and
Dengue virus vaccines.Eligibility criteria will exclude any pregnant
participants who have had a previous clinical
(signs/symptoms only) or microbiological
(signs/symptoms and positive SARS -CoV- 2
NAAT result) diagnosis of COVID -19.
Monitoring for cases of COVID -19 developing
during the study will be reported.
Potential for adverse obstetric and/or neonatal
outcomes following vaccination .There are no ongoing COVID -19 vaccine studies
including pregnant women and ,therefore ,the
potential for adverse obstetric an d/or neonatal
outcomes following vaccination while pregnant is
unknown.Stopping rules for obstetric and neonatal AEs
occurring after study vaccination and/or
possibly deemed related to study vaccination in
the Phase 2 portion of the trial . If a stopping
rule is triggered , apause of study vaccination
willbe put in place until there is a review of all
relevant safety events and evaluation by the
IRC.
Study Procedures
Participants will be required to attend healthcare
facilities during the global SARS -CoV -2pandemic.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 illness visits can be
conducted via telehealth, without the need for
an in -person visit, if required, with the
maternal participant performing a self -swab or
obtaining a swab from her infant .
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 ill
obtain the blood draw .
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Page 352.3.2. Benefit Assessment
Benefits to individual maternal participants may include:
Receipt of a potentiall y efficacious COVID -19 vaccine during a global pandemic .
Access to COVID -19 diagnostic and antibody testing .
Contributing to research to help others in a time of global pandemic .
Potential antibody protection for infants born to mothers who were vaccinated with
COVID -19 vaccine.
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 associa tion with BNT162 RNA -based COVID -19
vaccine are justified b y the anticipated benefits that may be afforded to healthy participants.
3.OBJECTIVES , ESTIMANDS ,AND ENDPOINTS
ObjectivesaEstimands Endpoints
Prim ary Safety Prim ary Safety Prim ary Safety
To describe the safety and
tolerability of prophylactic
BNT162b2 when administered to
maternal participants 18 years of
age or older vaccinated at 2 4to 34
weeks’ gestation in the first
approximately 600 randomized
maternal participants .In maternal participants
receiving at least 1 dose of
study intervention from each
vaccine group, the percentage of
maternal participants reporting:
Local reactions for up to
7days following each dose
Systemic events for up to
7days following each dose
AEs from Dose 1 through
1month after Dose 2
SAEs from Dose 1 through
1 month after deliveryProm pted local reactions
(redness, swelling, and pain at
the injection site)
Prom pted systemic events (fever,
fatigue, headache, chills,
vomiting, diarrhea, new or
worsened muscle pain, and new
or worsened joint pain)
AEs
SAEs
To describe the safety and
tolerability of prophylactic
BNT162b2 when administered to
maternal participants 18 years of
age or older vaccinated at 24 to 34
weeks’ gestation .In maternal participants
receiving at least 1 dose of
study intervention from each
vaccine group, the percentage of
maternal participants reporting:
Local reactions for up to
7days following each dose
Systemic events for up to
7days following each dose
AEs from Dose 1 through 1
month after Dose 2
SAEs from Dose 1 through
1month after deliveryProm pted local reactions
(redness, swelling, and pain at
the injection site)
Prom pted systemic events (fever,
fatigue, headache, chills,
vomiting, diarrhea, new or
worsened muscle pain, and new
or worsened joint pain)
AEs
SAEs
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Page 36ObjectivesaEstimands Endpoints
Prim ary Immunogeni city Prim ary Immunogenicity Prim ary Immunogenicity
To demonstrate the
immunobridging of the immune
response to prophylactic
BNT162b2 inmaternal
participants 18 years of age or
older vaccinated at 24 to 34
weeks’ gestation to the immune
response in nonpregnant women
18 years of age or older from the
C4591001 study without evidence
of pastSARS -CoV -2 infection .In maternal participants
complying with the key
protocol criteria (evaluable
maternal participants) and no
serological or virologic al
evidence (up to 1 month after
receipt of the second dose) of
pastSARS -CoV -2 infection:
GMR, estimated by the
ratio of the geometric mean
of SARS -CoV -2
neutralizing titers in
pregnant w omen to th ose in
nonpregnant women
1month after Dose 2 SARS -CoV -2 neutralizing titers
To demonstrate the
immunobridging of the immune
response to prophylactic
BNT162b2 inmaternal
participa nts18 years of age or
older vaccinated at 24 to 34
weeks’ gestation to the immune
response in nonpregnant women
18 years of age or older from the
C4591001 study with and without
evidence of prior SARS -CoV- 2
infection .In maternal participants
complying with the key
protocol criteria (evaluable
participants):
GMR, estimated by the
ratio of the geometric mean
of SARS -CoV -2
neutralizing titers in
pregnant w omen to th ose in
nonpregnant female
participants 1 month after
Dose 2 SARS -CoV -2 neutralizing titers
Secondary Secondary Secondary
If at least 12 cases are observed:
To evaluate the efficacy of
prophylactic BNT162b2 against
confirmed COVID -19 occurring
from 7 days after Dose 2 through
1month after delivery in maternal
participants 18 years of age or
older vaccinated at 24 to 34
weeks’ gestation without evidence
of prior SARS -CoV -2 infection .In maternal participants
complying with the key
protocol criteria (evaluable
participants) and no serological
or virological evidence (prior to
7 days after receipt of Dose 2)
of pastSARS -CoV -2 infection :
100 × (1 –IRR) [ratio of
active vaccine to placeb o]COVID -19 incidence per 1000
person -years of blinded follow -
up based on central laboratory or
locally confirmed NAAT
If at least 12 cases are observed:
To evaluate the efficacy of
prophylactic BNT162b2 against
confirmed COVID -19 occurring
from 7 days after Dose 2 through
1month after delivery in maternal
participants 18 years of age or
older vaccinated at 24 to 34
weeks’ gestation with and without
evidence of prior SARS -CoV- 2
infection .In maternal participants
complying with the key
protocol criteria (evaluable
participants):
100 × (1 –IRR) [ratio of
active vaccine to placebo]COVID -19 incidence per 1000
person -years of blinded follow -
up based on central laboratory or
locally confirmed NAAT
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Page 37ObjectivesaEstimands Endpoints
To describe the efficacy of
prophylactic BNT162b2 against
asymptomatic SARS -CoV -2
infection through 1 month after
delivery in maternal participants
18 years of age or older vaccinated
at 24 to 34 weeks’ gestation
without evidence of prior
SARS -CoV -2 infection .In evaluable maternal
participants without serological
or virological evidence of prior
SARS -CoV- 2 infection :
100 × (1 –IRR) [ratio of
active vaccine to placebo]Incidence of asymptomatic
infection of SARS -CoV -2 based
on N- binding antibody
seroconversion
To describe the immune response
over time and persistence of
prophylactic BNT162b2 when
administered to maternal
participants 18 years of age or
older vaccinated at 24 to 34
weeks’ gestation . In maternal participants
complying with the key
protocol crit eria (evaluable
maternal participants) from
each vaccine group:
GMCs/GMTs, at baseline
(before Dose 1) ,2 weeks
after Dose 2, 1 month after
Dose 2 ,at delivery ,and
6months after delivery
GMFRs from baseline
through 2 weeks after
Dose 2, 1 month after
Dose 2, at delivery ,and
6months after deliveryFull-length S -binding IgG levels
SARS -CoV- 2 neutralizing titers
To assess the safety of maternal
immunization in infants born to
maternal participants 18 years of
age or older who w erevaccinated
with BNT162b2 during pregnancy .In infants born to maternal
participants receiving at least 1
dose of study intervention from
each vaccine group, the
percentage of infants with:
Specific birth outcomes
AEs from birth through 1
month of age
SAEs andAESIs(major
congenital anomalies,
developmental delay)
through 6months of ageSpecific birth outcomes
AEs from birth through 1 month
of age
SAEs andAESIs (major
congenital anomalies,
developmental delay) through 6
months of age
To describe the immune response
in infants born to maternal
participants vaccinated with
prophylactic BNT162b2 during
pregnancy .In infants born to evaluable
maternal participants from each
vaccine group:
GMC sand GMFR s, at birth
and 6months after deliveryFull-length S -binding IgG levels
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Exploratory Exploratory Exploratory
To describe the incidence of
confirmed COVID -19 among
maternal participants who were
vaccinated with BNT162b2 .In maternal participants who
received BNT162b2 ( at initial
randomization and at 1 month
after delivery ):
Incidence per 1000
person -years of follow -upCOVID -19 incidence per 1000
person -years of follow -up based
on central laboratory or locally
confirmed NAAT
To describe the incidence of
asymptomatic SARS -CoV -2
infection through 6 months after
delivery in maternal participants
18 years of age or older vaccinated
at 24 to 34 weeks’ gestation with
BNT162b2 at initial randomization
and without evidence of prior
SARS -CoV -2 infection .In maternal participants who
receive d BNT162b2 at initial
randomization and without
evidence of prior SARS -CoV- 2
infection :
Incidence per 1000
person -years of follow -upIncidence of asymptomatic
SARS -CoV- 2 infection per 1000
person -years of follow -up based
on N- binding antibody
seroconversion
To describe the serological
responses among maternal
participants to the BNT162b2
vaccine candidate in cases of:
Confirmed COVID -19
Confirmed severe COVID- 19
SARS -CoV- 2 infection
without confirmed COVID -19In each subset of evaluable
maternal participants from each
vaccine group with:
Confirmed COVID -19
Confirmed severe
COVID -19
SARS -CoV- 2 infection but
no confirmed COVID -19
GMCs/GMTs and GMFRs
at baseline ,1 month after
Dose 2 ,at delivery ,and
6months after deliveryFull-length S -binding IgG levels
SARS -CoV- 2 neutralizing titers
To describe the immune response
toprophylactic BNT162b2
betw een Dose 1 and Dose 2 when
administered to maternal
participants 18years of age or
older vaccinated at 2 7to 34
weeks’ gestation in the Phase 2
portion of the study .In evaluable maternal
participants:
GMCs/GMTs at baseline
and before Dose 2
GMFRs from baseline to
before Dose 2Full-length S -binding IgG levels
SARS -CoV- 2 neutralizing titers
To describe the immune response
in infants born to breastfeeding
maternal participants vaccinated
with prophylactic BNT162b2
during pregnancy .In infants born to maternal
participants from each vaccine
group , based on the
breastfeeding status :
GMCs and GMFRs, at birth
and 6 months after deliveryFull-length S -binding IgG levels
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Protocol Amendment 2, 02March 2021
PFIZER CONFIDENTIAL
CT02- GSOP Maternal Immunization Protocol Template (Phase 1 2 3 4) (15 May 2020)
TMF Doc ID: 164.01
Page 39ObjectivesaEstimands Endpoints
To describe the safety of maternal
immunization in infants born to
breastfeeding maternal participants
vaccinated w ith prophylactic
BNT162b2 during pregnancy .In infants born to maternal
participants receiving at least 1
dose of study intervention from
each vaccine group, based on
the breastfeeding status, the
percentage of infants with:
AEs from birth through
1month of age
SAEs and AESIs(major
congenital anomalies,
developmental delay)
through 6months of ageAEs from birth through 1 month
of age
SAEs andAESIs (major
congenital anomalies,
developmental delay) through 6
months of age
To describe the incid ence of
confir med COVID -19 in infants
born to maternal participants who
were vaccinated with BNT162b2
during pregnancy .In infants born to maternal
participants from each vaccine
group :
Incidence rate of infant
participants with confirmed
COVID -19COVID -19 incidence per 1000
person -years of follow -up based
on central laboratory or locally
confirmed NAAT
To describe MIS -C cases in infants
born to maternal participants who
were vaccinated with BNT162b2
during pregnancy .In infants born to maternal
participants from each vaccine
group:
Incidence rate of MIS -CMIS-C incidence per 1000
person -years of follow -up
a.HIV-infected participants will not be included in analyses of the objectives, but in separate exploratory
analyses .Analyses among HIV -infected w omen and their infants will be summarized separately .
4.STUDY DESIGN
4.1.Overall Design
This will be a global Phase 2/3, randomized, placebo- controlled, observer -blind study in
approximately 4000 healthy pregnant women 18 years of age or older vaccinated during their
24to 34 weeks’ gestation. This study will evaluate the safety , tolerability , and
immunogenicit y of 2 doses of BNT162b2 or placebo administered 21 days apart. The
Phase 2 portion ofthe study will include approximately 350 pregnant women randomized 1:1
to receive BNT162b2 or placebo (saline) during their 27 to 34 weeks’ gestation . Safety data
through 7 day s after the second dose (where Day 1 is the day of vaccination) for all Pha se 2
participants will be reviewed b y the Pfizer IRC and if BNT162b2 is deemed safe and
tolerable, enrollment in the Phase 3portion of the study will commence . The Phase 3 portion
of this study will assess the safet y, tolerability , and immunogenicit y ofBNT162b2 in 3650
pregnant women enrolled during their24 to34 weeks’ gestation who will be randomized in a
1:1ratio to receive BNT162b2 or placebo (saline). Maternal participants who originally
received placebo will receive BNT162b2 at defined time points as part of the study .
The study is observer -blinded, as the ph ysical appearance of the investigational vaccine and
the placebo may differ. The participant, investigator, study coordinator, and other site staff
will be blinded through the 1-month postdelivery visit for each maternal participant . At the
study site, only the dispenser(s)/administrator(s) are unblinded.
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Page 40Each maternal participant will participate in the study for approximately up to 10months
depending on the vaccine gr oup to which she was randomized . Her infant will participate in
the study for approximately 6 months. The stud y duration will be approximately 14 months.
For each placebo recipient who will go on to receive BNT162b2 and follow a new visit
schedule ( Section 1.3.2 ), she will participate in the study for up to 7 month s, and her infant
will participate in the study for approximately 6months.
The study will use an external DMC throughout study conduct. A Pfizer IRC will be used
during the Phase 2 portion of the study to closel y monitor safety .
The study will include stopping rules, which may result in a pause to study vaccination
follow ed bya review and recommendation b y the IRC.
4.2.Scientific Rationale for Study Design
There are currently no licensed vaccines to prevent infection with SARS -CoV -2 or
COVID -19. Pregnant women are at risk of acquiring SARS -CoV -2infection , developing
COVID -19 and COVID -19–associated complications. Given the global crisis of COVID -19
and fast expansion of the disease globall y, the rapid development of an effective vaccine for
use in this population is of utmost importance.
This study is being conducted as astandard maternal immunization safety and
immunogeni cityclinical trial; however , additional surveillance for COVID -19 has been
included as part of the study to assess efficacy (based on a minimal number of cases) as well
asto monitor the potential risk of disease enhancement and severe disease in pregnant
women and their infants with COVI D-19 . If a participant experiences s ymptoms, as detailed
in Section 8.13, a COVID -19 illness and subsequent convalescent visit will occur. As part of
these visits, samples (nasal swab and blood) will be taken for antigen and antibody
assessment as well as recording of COVID -19–related clinical and laboratory information
(including local diagnosis).
4.3.Justification for Dose
Based on data from the Phase 1 component of clinical trial C4591001, the BNT162b2
vaccine candidate was selected at a dose of 30 µg for Phase 2/3 evaluation in C45 91001 .
4.4.End of Study Definition
A participant and her infant are considered to have completed the study if they have
completed all phases of the study ,including the last visit.
The end of the stud y is defined as the date of the last visit of the last participant in the study .
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Page 415.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 approp riate. All relevant medical and nonmedical conditions should be
taken into consideration when deciding whether a particular participant is suitable for this
protocol .
Prospective approval of protocol deviations to recruitment and enrollment criteria ,also
known as protocol waivers or exemptions, is not permitted .
5.1. Inclusion Criteria
Participants are eligible to be included in the study onl y if all of the following criteria appl y.
NOTE: In countries/locales where certain prenatal assessments are not routine ly performed,
prerandomization assessments and test results to confirm maternal participant eligibility for
this clinical trial can be obtained and reviewed b y the investigator or qualified designee up to
28 day s prior to vaccination.
Maternal participants must provide informed consen t prior to performing any procedures,
including those that are being done exclusively to meet study eligibility criteria.
5.1.1. Maternal Participants
Age and Sex:
1.Health y women ≥18 y ears of age who are between 24 0/7 and 34 0/7 weeks ’ gestation on
the day of planned first vaccination, with an uncomplicated, singleton pregnancy , who
are at no known increased risk for complications.
a.Phase 2 participan ts will include healthy women ≥18 y ears of age who are between
27 0/7 and 34 0/7 weeks ’gestation on the day of planned vaccination, with an
uncomplicated, singleton pregnancy , who are at no known increased risk for
complications.
GA will be documented based on one of the following co mposite criteria based on timing
and availability of data on the L MP, ultrasound examination , and phy sical examination ,for
natural pregnancies. Please refer to the SRM for GA dating among women who underwent
assisted reproduction technology .The earliest ultrasound data available during the current
pregnancy should be used to establish GA:
a.First -Trimester Data Available (data obtained at ≤13 6/7 weeks):
The date of the first day of the reported LMP may be used to establish the GA if
corrobora ted b y a first -trimester ultrasound.
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Page 42If there is a discrepancy of >7 day s between the LMP -determined GA and a
first-trimester ultrasound OR the L MP is uncertain/unknown, then the GA should be
determined using the first- trimester ultrasound.
b.Second- Trimeste r Data Available (data obtained at 14 0/7 to 27 6/7 weeks):
The date of the first day of the reported LMP may be used to establish the GA if
corroborated b y a second -trimester ultrasound or a phy sical examination including
fundal height.
If there is a disc repancy of >10 day s between the LMP -determined GA and the
second -trimester ultrasound OR if the L MP is uncertain/unknown, then the GA
should be determined using the second -trimester ultrasound.
c.Third -Trimester Data Available (data obtained at ≥ 28 weeks):
The date of the first day of the reported LMP may be used to establish the GA if
corroborated b y a third- trimester ultrasound or a phy sical examination including
fundal height.
If there is a discrepancy of > 21days between the LMP -determined GA and the
third-trimester ultrasound OR if the L MP is uncertain/unknown, then the GA should
be determined using the third -trimester ultrasound.
Type of Participant and Disease Characteristics:
2.Participants who are w illing and able to compl y with scheduled visits, treat ment plan,
laboratory tests, and other study procedures.
3.Receiving prenatal standard of care based on country requirements.
4. Had an ultrasound examination performed at ≥ 18 weeks of pregnancy with no significant
fetal abnormalities observed, based on the inv estigator ’s judgment.
5.Health y participants who are d etermined by medical history , phy sical examination, and
clinical judgment to be appropriate for inclusion in the study .Note: Participants with
preexisting stable disease, defined as disease not requirin g significant change in therap y
or hospitalization for worsening disease during the 6 weeks before enrollment, can be
included. Specific criteria for Phase 3 participants with known stable infection with HI V,
HCV, or HBV can be found in Section 10.4.
6.Documented negative HIV antibody test (Phase 2 only ), syphilis test, and HBV surface
antigen test during this pregnancy and prior to randomization (Visit 1).
7.Intention to deliver at a hospital or birthing facility where stud y procedures can be
conducted .
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Page 438.Expected to be available for the duration of the study and can be contacted by telephone
during stud y participation.
9.Participant is willing to give informed consent for her infant to participate in the study .
Weight:
10.Prepregnancy BMI of ≤ 40 kg/m2. If prepregnancy BMI is not available, the BMI at the
time of the first obstetric visit during the current pregnancy may be used.
Informed Consent:
11.Capable of giving signed informed consent as described in Appendix 1,which includes
compliance with the requirements and restrictions listed in the I CDand in this protocol .
5.1.2. Infant Participants
1.Evidence of a signed and dated ICD signed b y the parent(s) .
The maternal participant must sign an ICD for herself and her fetus/infant before
taking part in the study . The father of the fetus/infant must sign an ICD if required by
local requirements.
2.Parent(s) willing and able to comply with scheduled visits, treatment plan, laboratory
tests,and other study procedures.
5.2. Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply :
5.2.1. Maternal Participants
Medical Conditions:
1.Other medical or psy chiatric condition including recent (within the past year) or active
suicidal ideation /behavior or laboratory abnormality that may increase the risk of study
participation or , in the investigator’s judgment, make the participant inappropriate for the
study .
2.Previous clinical (based on COVID -19 s ymptoms/signs alone, if a SARS -CoV -2 NAAT
result was not available) or microbiological (based on COVID -19 s ymptoms/signs and a
positive SARS -CoV -2 NAAT result) diagnosis of COVID -19.
3.History of severe adverse reaction associated with a vaccine and/or severe allergic
reaction (eg, anaph ylaxis) to any component of the study intervention or any related
vaccine.
4.Participant s with known or suspected immunodeficiency .
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Page 445.Bleedi ng diathesis or condition associated with prolonged bleeding that would in the
opinion of the investigator contraindicate intramuscular injection.
6.Phase 2 only: A prior or current major illness of the mother or conditions of the fetus
that, in the investigator’s judgment, will substantially increase the risk associated with the
participant ’s participation in, and completion of, the study or could preclude the
evaluation of the participant ’s response ,including but not limited to the following:
Gestational hy pertension or preeclampsia -eclampsia
Placental abnormalit y
Polyhydramnios or oligohy dramnios
Significant bleeding or blood clotting disorder
Gestational diabetes
Any signs of pr emature labor with the current pregnancy or having ongoing
intervention (medical/surgical) in the current pregnancy to prevent preterm birth
Prior stillbirth or neonatal death, prior low birth weight or preterm delivery , prior
history of at least 3 miscarr iages, prior pregnancies numbering greater than 5, or
previous infant with a known genetic disorder or major congenital anomaly
7.For Phase 2 only :Maternal participants with a history of stable chronic diseases that are
known to be associated with increased risk of obstetrical or neonatal complications (as
defined above in exclusion criter ion6) should not be included.
8.Phase 3: Current major illness of the mother or conditions of the fetus that, in the
investigator’s judgment, will substantially increase the risk associated with the
participant ’s participation in, and completion of, the study or could preclude the
evaluation of the participant ’s response ,including but not limited to the following:
Uncontrolled gestational hypertension
Preeclampsia -eclampsia
Placental abnormalit y
Polyhydramnios or oligohy dramnios
Significant bleeding or blood clotting disorder
Uncontrolled gestational d iabetes
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Page 45Any signs of premature labor with the current pregnancy or having ongoing
intervention (medical/surgical) in the current pregnancy to prevent preterm birth
Prior stillbirth or neonatal death, preterm delivery (≤34weeks), or previous infant
with a known genetic disorder or major congenital anomaly .
Prior/Concomitant Therapy:
9.Previous vaccination with any coronavirus vaccine.
10.Receipt of medications intended to prevent COVID -19.
11.Receipt of blood/plasma products or immunoglobulin, from 60 day s before
administration of study intervention, or planned receipt through delivery , with 1
exception, anti- D immunoglobulin (eg, RhoGAM), which can be given at any time.
12.Current alcohol abuse or illicit drug use.
13.Participants who receive treatment with immunosuppressive therapy ,including cy totoxic
agents or sy stemic corticosteroids, eg, for cancer or an autoimmune disease, or planned
receipt through the postvaccination blood draw.
Prior/Concurrent Clinical Study Experience:
14. Participation in other studies involving study intervention within 28 day s prior to study
entry and/or during study participation.
15.Previous participation in other studies involving study intervention containing LNP s.
Diagnostic Assessments:
16. Not applicable .
Other Exclusions:
17. Investigat orsite staff or Pfizer employ ees directl y involved in the conduct of the study ,
site staff otherwise supervised by the investigator, and their respective family members .
18.Participant swhose unborn baby has been fathe red by investigational site staff members
directly involved in the conduct of the study ortheir famil y members, site staff members
otherwise supervised by the investigator, or Pfizer employees directly involved in the
conduct of the stud y.
5.2.2. Infant Particip ants
1.Infant who is a direct descendant (eg, child or grandchild) of the study personnel.
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TMF Doc ID: 164.01
Page 465.3.Lifestyle Considerations
No restrictions required.
5.4.Screen Failures
Screen failures are defined as maternal participants who consent to participate in the clinical
study but are not subsequently randomly assigned to study intervention . 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 demography , screen failure details,
eligibility criteria, and any SAE.
Maternal participants who do not meet the criteria for participa tion in this study (screen
failure) may be rescreened.
5.5. Criteria for Temporarily Delaying Randomization/Study Intervention
Administration
The following conditions are temporary or self -limiting and a maternal participant may be
vaccinated once the condit ion(s) has/have resolved and no other exclusion criteria are met.
1.Current febrile illn ess (temperature 38.0° C [100.4 °F]) or other acute illness within
48hours before study intervention administration. This includes current s ymptoms that
could represent a potential COVID -19 illness:
New or increased cough;
New or increased shortness of breath;
Chills;
New or increased muscle pain;
New loss of taste/smell;
Sore throat;
Diarrhea;
Vomiting.
2.Receipt of an yseasonal or pandemic influenza vaccine in the previous 14 day s.
3. Anticipated receipt of any seasonal or pandemic influenza vaccine in the 7 day safter
study intervention administration.
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Page 474.Receipt of a tetanus -, diphtheria -,and/or pertussis -containing vaccine in the previous
14days.
5.Anticipated r eceipt of a tetanus -, diphtheria- , and/or pertussis- containing vaccine in the
7daysafter stud y intervention administration.
6.Receipt of short -term (<14 day s) systemic corticosteroids. Study interve ntion
administration should be delay ed until sy stemic corticosteroid use has been discontinued
for at least 28 day s. Inhaled/nebulized, intra -articular, intrabursal, or topical (skin or
eyes) corticosteroids are permitted.
6. STUDY INTERVENTION
Study interve ntion is defined as any investigational intervention(s), marketed product(s),
placebo, medical device(s) , or study procedure(s) intended to be administered to a study
participant according to the study protocol.
The study will evaluate 2 doses of BNT162b2 or placebo administered 21 day s apart for
active immunization against COVI D-19 in health y pregnant women 18 years of age or older
vaccinated during their 24 to 34 weeks’ gestation. The Phase 2 portion of the study will
include a subset (N= 350) of pregnant women during their 27 to 34 weeks’ gestation.
The investigational RNA vaccine candidate or saline placebo are the 2 potential study
interventions that may be administered to pregnant maternal participant s(randomized 1:1) :
BNT162b2 (BNT162 RNA -LNP vaccine utilizing modRNA and encoding the P2 S):
30 µg
Normal saline (0.9% NaCl solution for injection)
6.1.Study Intervention(s) Administered
Intervention Name BNT162b2
(BNT162 RNA -LNP V accine
Utilizing m odRNA)Saline Placebo
Type Vaccine Placebo
Dose Form ulation modRNA Normal saline (0.9% NaCl solution
for injection)
Unit Dose Strength(s) 250 µg/0.5 mL N/A
Dosage Level(s) 30-µg N/A
Route of Adm inistration Intramuscular injection Intramuscular injection
Use Experimental Placebo
IMP or NIMP IMP IMP
Sourcing Provided centrally by the sponsor Provided centrally by the sponsor
Packaging and Labeling Study intervention will be provided in
a glass vial as open -label supply. Each
vial will be labeled as required per
country requirement .Study interventi on will be provided in
a glass or plastic vial as open -label
supply. Each vial will be labeled as
required per country requirement .
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Page 486.1.1. Administration
Maternal participants will receive 1 dose of study intervention as randomized at each
vaccination visit (Visits 1 and 2) in accordance with the study ’s SoA (Section 1.3.1 ). Full
details are described in the I P manual.
At 1 month after delivery, m aternal participant swho originall y received placebo will receive
1 dose of BNT162b2 at each additional vaccination visit (Visits 101 and 102) in accordance
with the SoA in Section 1.3.2 .
Study intervention should be administered intramuscularl y into the deltoid muscle, preferabl y
of the nondominant arm, by 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 intervention s should be performed b y an appr opriately qualified,
GCP -trained, and vaccine- experienced member of the study staff (eg, physician, nurse,
physician’s assistant, nurse practitioner, pharmacist, or medical assistant) as allowed by
local, state, and institutional guidance.
Study intervent ionadministration details will be recorded on the CRF.
6.2.Preparation/Handling/Storage/Accountability
1.The investigator or designee must confirm that appropriate temperature conditions have
been maintained during transit for all study intervention sreceived a nd an y discrepancies
are reported and resolved before use of the stud y intervention.
2.Only maternal participants enrolled in the study may receive study intervention and only
authorized site staff may supply or administer study intervention. All study int erventions
must be stored in a secure, environmentall y controlled, and monitored (manual or
automated recording ) area in accordance with the labeled storage conditions with access
limited to the investigator and authorized site staff. At a minimum, daily minimum and
maximum temperatures for all site storage locations must be documented and available
upon request. Data for nonworking day s must indicate the minimum and maximum
temperature ssince previously documented for all site storage locations upon retu rn to
business.
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Page 493.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 maintenance
(ie, receipt, reconciliation, and final disposition records) , such as the IPAL or
sponsor -approved equivalent . All study intervention swill be accounted for using a study
intervention accountability form/record.
8.Further gu idance and information for the final disposition of unused study interventions
are provided in the I P manual. All destruction must be adequatel y documented. If
destruction is authorized to take place at the investigator site, the investigator must ensure
that the materials are destroy ed in compliance with applicable environmental regulations,
institutional policy , and any special instructions provided by Pfizer.
Upon identification of a product complaint, notify the sponsor w ithin 1 business day of
discover y as described in the I P manual.
6.2.1. Preparation and Dispensing
See the IP manual for instructions on how to prepare the study intervention for
administration. Study intervention should be prepared and dispensed b y an appropriatel y
qualified and experienced member of the stud y staff (eg, ph ysician, nurse, phy sician’s
assistant, nurse practitioner, pharmacy assistant/technician, or pharmacist) as allowed by
local, state, and institutional guidance. A second staff member will verify the dispensing.
Study intervention and placebo will be prepared by qualified unblinded site personnel
according to the IP manual. The study intervention will be administered in such a way asto
ensure that the maternal participants remain blinded.
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Page 506.3.Measures to Minimize Bias: Randomization and Blinding
6.3.1. Allocation to Study I ntervention
Maternal participant s will be allocated (randomiz ed)to a vaccine group as described below.
The infants of the maternal participant s will be assigned a participant number at birth.
Allocation of maternal participants to vaccine groups will proceed through the use of an IRT
system (IWR). The site personnel (study coordinator or specified designee) will be required
to enter or select information including but not limited to the user’s ID and password, the
protocol number, and the maternal participant number. The site personnel will then be
provided with a vaccine assignment, randomization number, and DU or container number
when study intervention is being supplied via the IRT sy stem. The IRT s ystem will provide
a confirmation report containing the maternal participant number, randomization number,
and DU or container number assigned. The confirmation report must be stored in the site’s
files.
Study intervention will be dispensed at the study visits summarized in the SoA.
The study -specific I RT reference manual and I P manual will provide the contact information
and further details on the use of the IRT s ystem.
Maternal participants will be assigned to receive study intervention according to
randomization scheme. Investigators will remain blinded to each maternal participant’s
assigned study intervention until 1 month after delivery .
6.3.2. Blinding of Site Personnel Until the 1 -Month Postdel ivery Visit
In this observ er-blinded study , the study staff receiving, storing, dispensing, preparing, and
administering the stud y interventions will be unblinded. All other study and site personnel,
including the investigator, investigator staff, and maternal participants, will b e blinded to
study intervention assignments. I n particular, the individuals who evaluate maternal
participant safety will be blinded. Because the BNT162 RNA -based COVID -19 vaccine
candidate and placebo are different in phy sical appearance, the study intervention sy ringes
will be administered in a manner that prevents the maternal 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 maternal stud y
participants. Contact between the unblinded dispenser and maternal stud y participants and
unblinded administrator and maternal study participants should be kept to a minimum. The
remaining site personnel must not know study intervention assignments.
In the event of a Qualit y Assurance audit, the auditor(s) will be allowed access to unblinded
study intervention records at the site(s) to verify that randomization/dispen sing has been done
accuratel y.
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Page 51To allow administration of BNT162b2 to maternal participants who originally received
placebo, site staff will be unblinded to individual participants’ original study intervention
allocation at the 1 -month postdelivery visit.
6.3.3. Blinding of Site Personnel Prior to the 1-Month Postd elivery Visit
To allow administration of BNT162b2 to maternal participants who originally received
placebo, site staff will be unblinded to individual participants’ original study intervention
allocation at the 1 -month postdelivery visit . Prior to unblinding maternal partic ipants at the
1-month postdelivery visit , this is an observer -blinded study . 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 maternal
participants, will be blinded to study intervention assignments until the 1- month postdelivery
visit for each participant. I n particular, the individuals who evaluate maternal participant
safet y prior to unblinding maternal partic ipants at the 1 -month postdelivery visit will be
blinded.
Because the BNT162 RNA -based COVID -19 vaccine candidate and placebo are different in
physical appearance, the study intervention s yringes will be administered in a manner that
prevents the maternal studyparticipants from identify ing the study intervention ty pe based on
its appearance during the blinded portion of the study .
The responsibil ity of the unblinded dispenser and administrator must be assigned to an
individual or individuals who will not participate in the evaluation of an y maternal study
participants prior to the maternal participant being unblinded . Contact between the
unblinde d dispenser and blinded maternal study participants and unblinded administrator and
blinded maternal study participants should be kept to a minimum. The remaining site
personnel must not know study intervention assignments until the maternal participant i s
unblinded at the 1 -month post delivery visit.
In the event of a Qualit y Assurance audit, the auditor(s) will be allowed access to unblinded
study intervention records at the site(s) to verify that randomization/dispensing has been done
accuratel y.
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Page 526.3.4. Blind ing of the Sponsor
The study team will be unblinded to the participant’s study intervention allocation when
maternal participants complete the 1- month postdelivery visit. Prior to unblinding the
maternal partici pants at the 1-month postdelivery visit the m ajority of sponsor staff will be
blinded to study intervention allocation. All laboratory testing personnel performing
serology assay s will remain blinded to study intervention assigned/received. The following
sponsor staff, who will have no part in the blinded conduct of the study , will be unblinded
(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 admin istration are fulfilled at the
site will be unblinded for the duration of the stud y (eg, unblinded study manager,
unblinded clinical research associate).
Unblinded clinician(s) who are not direct members of the study team and will not
participate in an y other study -related activities will review unblinded protocol deviations.
An unblinded team supporting interactions with, and anal yses for, the DMC
(seeSection 9.6). This will comprise a statistician, programmer(s), and a medical
monitor and/or a clinical scientist who will review cases of severe COVID -19 as they are
received, and will review AEs at least weekly for additional potential cases of severe
COVID -19 (see Section 8.2.4 ).
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.
6.3.5. Breaking the Blind
The I RT will be programmed with blind -breaking instructions. In case of an emergency , the
investigator has the sole responsibility for determining if unblinding of a maternal
participant’s vaccine assignment is warranted. Participant safet y must always 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 maternal participant’s vaccine assignment unless this could delay further
management of the participant.
If a maternal 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 referen ce manual and IP manual will provide the contact information
and further details on the use of the IRT s ystem.
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Page 53Instructions on how to unblind participants ahead of administration of BNT162b2 to placebo
recipients will be provided separately : this unblinding will NOT be performed in the I RT.
6.4. Study Intervention Compliance
When maternal participants are dosed at the site, they will receive study intervention directly
from the investigator or designee, under medical supervision. The date and time of each dose
administered in the clinic will be recorded in the source documents and recorded in the CRF.
The dose of stud y intervention and maternal study participant identification will be
confirmed at the time of dosing b y a member of the study site staff other than the person
administering the stud y intervention.
6.5. Concomitant Therapy
6.5.1. Prohibi ted During the Study – Maternal Participants
Receipt of the following vaccines and medications during the time periods listed below may
exclude a maternal participant from the per -protocol analy sis from that point onwards, and
may require vaccinations to be discontinued in that participant; however, it is anticipated that
the maternal participant would not be withdrawn from the study (see Section 7). Medications
should not be withheld if required for a maternal participant’s medical care.
Unless considered medically necessary , no vaccines other than study intervention should
be administered within 14days before and 7 days after each study vaccination , including
seasonal and pandemic influenza vaccine s.
Receipt of chronic s ystemic treatment with known immunosuppressant medications
within 60 day s before enrollment through conclusion of the study .
Receipt of s ystemic cor ticosteroids ( ≥20 mg/day of prednisone or equivalent) for
≥14days is prohibited from 28 day s prior to enrollment through Visit 3
Receipt of blood/plasma products or immunoglobulins within 60 day s before enrollment
through conclusion of the study .
Receipt of an y other (nonstudy ) coronavirus vaccine 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. How ever, if a maternal participant is
taking a medication for another condition, even if it may have antipy retic or
pain- relieving properties, it should not be withheld prior to study vaccination.
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Page 546.5.2. Permitted During the Study – Maternal Participants
The use of antipy retics 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 Vaccinations and Concomitant Medications – Maternal
Participants
The following concomitant medications and vaccinations will be recorded in the CRF:
All vaccinations received from 14 day s prior to study enrollment until the 6 -month
follow -up visit for participants originall y randomized to receive BNT162b2 .
Any medication taken to treat AEs from the signing of the ICD through the final study
visit be recorded in the CRF .
Prohibited medications listed in Section 6.5.1 will be recorded in the CRF, to include
start and stop dates, name of the medication, dose, unit, route, and frequency from the
signing of the ICD through the final study visit.
6.5.4. Prohibited During the Study – Infant Participants
Investigational vaccines, drugs, or medical devices are prohibited during the course of the
study .
6.5.5. Permitted During the Study – Infant Participants
ONLY routine treatments, routine vaccinations, and routine procedures
(eg,circumcision) are permitted at any time during the study , in accordance with national
recommendations, medical stand ard of care, or accepted practice.
Prescription and nonprescript ion medications, vitamins, minerals, and herbal remedies
are permitted during infant participant participation in the study .
Local anesthetic may be applied to the site of the blood draw, as appropriate.
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Page 556.5.6. Recording Concomitant Medications – Infant Participa nts
The following concomitant medications will be recorded in the CRF:
Any medication staken to treat AEs and/orSAEs from Visit 1through the final study
visit.
6.6. Dose Modification
Dose modification is not applicable in this study .
6.7.Intervention A fter the End of the Study
No intervention will be provided to maternal or infant 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 include the following : AEs; participant request; investigator request; protocol
deviation (including no longer meeting all the inclusion criteria, or meeting 1 or more
exclusion criteria). In general, unless the investigator considers it unsafe to administer the
second dose, or the maternal participant does not wish to receive it, it is preferred that the
second dose be administered. Note: following Vaccination 1, a positive SARS -CoV -2
NAAT result without symptoms or a COVID- 19 diagnosis (signs/sy mptoms only or
signs/sy mptoms and a positive SARS -CoV -2 NAAT result) should not result in
discontinuation from the study intervention.
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 ,and immunogenicity . See the SoA
for data to be collected at the time of discontinuation of study intervention and follow -up for
any further eval uations that need to be completed.
In the event of discontinuation of study intervention, it must be documented on the
appropriate CRF/in the medical records whether the participant is discontinuing further
receipt of stud y intervention or also from study procedures, post vaccination study follow -up,
and/or future collection of additional information.
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Page 567.2.Participant Discontinuation/ Withdrawal F rom the Study
A maternal participant may withdraw from the study at any time at her own request or the
infant participant may be withdrawn at an y time at the request of his/her parent(s) . Reasons
for discontinuation from the study include the following:
Refused further follow -up;
Lost to follow -up;
Death ;
Study terminated by sponsor ;
AEs;
Maternal participant request;
Investigator request;
Protocol deviation.
If aparticipant does not return for a scheduled visit, every effort should be made to contact
the participant. All attempts to contact the participant and information received during
contact attempts must be documented in the participant’s source document. I n any
circumstance, every effort should be made to document participant outcome, if possible.
The investigator or his or her designee should capture the reason for withdrawal in t he CRF
for all participants.
If a participant withdraws from the study , she may request destruction of any remaining
samples taken and not tested, and t he investigator must document any such requests in the
site study records and notify the sponsor accordi ngly.
If the participant withdraws from the study and also withdraws consent (see Section 7.2.1)
for disclosure of future information, no further evaluations should be performed and no
additional data should be collected. The sponsor may retain and continue to use any data
collected before such withdrawal of consent.
Lack of completion of all or an y of the withdrawal/earl y termination procedures will not be
viewed as protocol deviations so long as the participant ’s safet y was preserved.
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Page 577.2.1. Withdrawal of Consent
Participant s who request to discontinue receipt of study intervention will remain in the study
and must continue to be followed for protocol -specified follow -up procedures. The onl y
exception to this is when a participant specificall y withdraws consent for any further contact
with her. Participant s 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 the withdrawal is
only from further receipt of study intervention or also from study procedur es and/or
postvaccination study follow -up, and entered on the appropriate CRF page. I n the event that
vital status (whether the participant is alive or dead) is being measured, publicly available
information should be used to determine vital status only as appropriatel y directed in
accordance with local law.
7.3.Lost to Fol low-up
A maternal participant will be considered lost to follow -up if she repeatedly fails to return for
scheduled visits and is unable to be contacted b y the study site.
The following actions must be taken if a participant fails to return for scheduled visits and is
unable to be contacted b y the study site:
The site must attempt to contact the participant and reschedule the missed visit as
soon as possible and counsel the participant on the importance of maintaining the
assigned visit schedule and ascertain whether or not the participant wishes 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 (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 par ticipant’s medical record.
Should the participant continue to be unreachable, she will be considered to have
withdrawn from the study.
8.STUDY ASSESSMENTS AND PROCEDURES
The investigator (or an appropriate delegate at the investigator site) must obtain a signed and
dated ICD before performing any study -specific procedures.
Study procedures and their timing are summarized in the SoA. Protocol waivers or
exemptions are not allowed.
The full date of birth will be collected to critically evaluate the immune response and safet y
profile b y age.
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Page 58Safety 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 st udy 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 maternal
participants meet all eligibility criteria. The investigator will maintain a screening log to
record details of all maternal participants screened and to confirm eligibility or record
reasons for screening failure, as applicable.
Procedures conducted as part of the maternal participant ’sroutine clinical management and
obtained before signing of the I CD may be utilized for baseline and/or screening purposes
provided the procedures met the protocol -specified criteria and were performed within the
time frame defined in the SoA .
Every effort should be made to ensure that protocol -required tests and procedures are
completed as described. However, it is anticipated that from time to time there may be
circumstances outside the control of the investigator that may make it unfeasible to perform
the test. I n these cases, the investigator must take all steps necessary to ensure the safet y and
well-being of the participant. When a 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 has taken to ensure that required processes are adhered to as soon as
possible. The study team must be informed of these incidents in a timely manner.
For samples being collected and shipped, detailed colle ction, 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 in this study is depen dent on when a maternal participant is
enrolled and which vaccine she is given while pregnant. It is expected that most maternal
participant swill have to give up to 6blood samples (20mL each) .
Additionally , 20 mL of blood for maternal participants will be taken at an unplanned
convalescent visit at any time a maternal participant develops respiratory symptoms
indicating a potential COVI D-19 infection. Maternal participants would therefore have a
total blood sampling volume of approximately up to 140mLduring the study period.
Additional blood sam ples may be taken for safety assessments at times specified b y Pfizer,
provided the total volume taken during the stud y does not exceed 550 mL during an y period
of 60 consecutive day s. Approximately 10 mL of cord blood will be taken from each infant
participant ; if cord blood is unavailable, a blood sample of up to 5 mL (based on weight) will
be collected. A 5-mL blood sample will be collected from each infant at the 6- month
postdelivery visit ;in addition ,a blood sample of up to 5 m L will be collected at each
convale scent illness visit.
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Page 598.1.Effica cy and/or Immunogenicity Assessments
Surveillance for potential cases of COVID -19 will occur throughout a maternal and infant
participant’s involvement in the study . If, at any time, a materna l or infant participant
develops acute respiratory illness (see Section 8.13), for the purposes of the study he or she
will be considered to potentially have a COVID -19 illness. I n this circumstance, the
maternal participant 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
collection of a nasal swab, 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, clinical information and results from
local standard- of-care tests (as detailed in Section 8.13) will be assessed. T he 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 if it was obtained
using 1 of the following assay s:
Cepheid Xpert Xpress SARS -CoV-2
Roche cobas SARS -CoV -2 real -time RT -PCR test (EUA200009/A001)
Abbott Molecular/RealTime SARS -CoV -2 assay (EUA200023/A001)
8.1.1. M aternal Participant s
Two definitions of SARS- CoV -2–related cases, and SARS -CoV -2–related severe cases, will
be considered (for both, the onset date of the case will be the date that s ymptoms were first
experienced b y the maternal participant ; ifnew sy mptoms are reported within 4 day s after
resolution of all previous sy mptoms, they will be considered as part of a single illness):
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 at the central laboratory or at a local testing facility (using an acceptable test):
Fever;
New or increased cough;
New or increased shortness of breath;
New or increased muscle pain;
New loss of taste or smell;
Sore throat;
Diarrhea;
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Page 60Vomiting .
The second definition , which may be updated as more is learned about COVID- 19, will
include the following additional sy mptoms defined by the CDC (listed at
https://www.cdc.gov/coronavirus/2019 -ncov/s ymptoms- testing/sy mptoms.html):
Fatigue;
Headache;
Nasal congestion or runny nose;
Nausea.
Confirmed Severe COVID -19: confirmed COV ID-19 and presence of at least 1 of the
following:
Clinical signs at rest indicative of severe s ystemic illness (RR ≥30 breaths /min,
HR ≥ 125 beats /min, SpO 2≤93% on room air at sea level, or PaO 2/FiO 2<300 mm Hg);
Respiratory failure (defined as needing high-flow oxy gen, noninvasive ventilation,
mechanical ventilation, or ECMO);
Evidence of shock (SBP <90 mm Hg, DBP <60 mm Hg, or requiring vasopressors);
Significant acute renal, hepatic, or neurologic d ysfunction *;
Admission to an I CU;
Death.
The second d efinition , which may be updated as more is learned about COVID- 19, will
include the following additional outcomes defined by the CDC (listed at
https://www.cdc.gov/coronavirus/2019 -ncov/need -extra -precautions/people- with-medical -
conditions.html ):
Hospital ization ;
Admission to the I CU;
Intubation or mechanical ventilation;
Death.
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Page 618.1.2. Infant Participants
Two definitions of SARS -CoV -2–related cases, and SARS -CoV -2–related severe cases, will
be considered (for both, the onset date of the case will be the date that s ymptoms were first
experienced by theinfant participant ;if new s ymptoms are reported within 4 days after
resolution of all previous sy mptoms, they will be considered as part of a single illness).
Signs and s ymptoms of an acute respiratory illness will not beconsidered a potential
COVID -19–related illness if they occur within the first 72 hours after birth.
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 at the central l aboratory or at a local testing facility (using an acceptable test):
Fever;
New or increased cough;
New or increased shortness of breath;
Diarrhea;
Vomiting.
The second definition , which may be updated as more is learned about COVID- 19, will
include the following 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 PI ,it is deemed necessary :
Nasal conge stion or runny nose;
Poor appetite or poor feeding;
Abdominal pain (colic) .
Confirmed Severe Infant COVID -19:confirmed COVID -19 and presence of at least 1 of
the following:
Clinical signs at rest indicative of severe s ystemic illness:
RR(breaths /min): >50from birth to 1 week of age , ≥40 from 1 week to 1 month of
age, ≥34 from 1month to 6 months of age ;
HR(beats /min): >180;
SpO 2≤92% on room air or >50% F iO2to maintain ≥92% ,or PaO 2/FiO 2
<300 mmHg24;
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Page 62Respiratory failure (defined as needing high -flow oxy gen including nasal CPaP/BiPaP,
noninvasive ventilation, mechanical ventilation, or ECMO);
Evidence of shock or cardiac failure:
SBP ( mmHg)(<5thpercentile for age):
<65 from birth to 1 week of age, <75 from 1 week to 1 month of age, <100 from
1 month to 6 months of age;
OR
Requiring vasoactive drugs to maintain BP in the normal range;
Significant acute renal failure: serum creatinine >2 times ULNfor 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 d ysfunction: Glasgow Coma Scale s core < 11or acute change in
mental status with a decrease in Glasgow Coma Scale score ≥3 points from abnormal
baseline;
Admission to an I CU;
Death.
Confirmed Multisystem Inflammatory Syndrome in Children (MIS -C) definition25:
as per the CDC MIS -C case definition:
An infant 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
lympho cytes,and low albumin ;AND
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 echocardiogra m,
arrhythmia);
oRenal (eg, acute kidney injury or renal failure);
oRespiratory (eg,pneumonia, ARDS, pulmonary embolism);
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Page 63oHematologic (eg ,elevated D -dimers, thrombophilia, or thrombocy topenia);
oGI/hepatic (eg ,elevated bilirubin, elevated liver enzy mes, 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.
The following are applicable for both maternal and infant participants:
The DMC may recommend modification of the definition of severe dis ease according to
emerging information.
* A small group of blinded case reviewers (medically qualified Pfizer staff members) will
review all potential COVID -19 illness events. If a NAAT- confirmed case in Phase 2/3 may
be considered severe, or not, solely on the basis of these criteri a,the blinded data will be
reviewed b y the case reviewers to assess whether the criterion is met; the majority opinion
will prevail.
In addition, a serological definition will be used for participants without clinical presentation
of COVID -19:
Confirmed seroconversion to SARS -CoV -2 without confirmed COVID -19: a positive
N-binding antibody result in a participant with a prior negative N- binding antibody result .
8.1.3. 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
Full-length S-binding IgG levels
N-binding antibody assay
Note that all immunogenicity analy ses will be based upon samples anal yzed at the central
laboratory.
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Page 648.1.4. Total Volume of Blood Collected –Maternal Participants
The total volume of blood collected for antibod y assessment over the course of the stud y will
be up to approximately 120mL (~20 mL/visit) and an additional 20 mL during each
unplanned convalescent visit at any time a participant develops respiratory sy mptoms
indicating a potential COVID -19 infection .
8.1.5. Total Volume of Blood Collected –Infant Participants
Blood samples will be collected according to the directive 2001/20/EC: Ethical
consideration sfor clinical trials on medicinal products conducted with mi nors.26
All infants will have a cord blood sample collected at birth. The total volume of cord blood
to be collected for antibody assessment in this study will be approximately 10 mL .
If cord blood is unavailable, a blood sample may be collected from the infant participant up
to 72 hours after birth but preferabl y within 24 hours after birth. The infant’s weight must be
used to determine the volume of blood that can be collected (see Table 1).
The maximum volume of blood collected from the infant in the absence of cord blood will be
no more than 5 mL at planned study visits (based on weight) .An additional sample of up to
5mL may be collected during each unplanned con valescent visit at an y time a n infant
participant develops respiratory symptoms indicating a potential COVID -19 infection .
Table 1.Guideline for Infant Blood Draw, if Cord Blood Sample Was Not Obtained
Body Weight (in kg) Approxim ate Volume of Blood (in mL) to Be
Collected
<1.3 No blood draw
1.3 -≤2.4 1.0
>2.4 -≤3.7 2.0
>3.7 -≤4.9 3.0
>4.9 -≤6.2 4.0
>6.2 5.0
8.1.6. 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 re quired b y local regulations or ethical
requirements, the samples will be stored for up to 15 y ears 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 material will be performed.
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Page 65The maternal participant may request that her orherinfant’s samples, if still identifiable, be
destroy ed 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 lon g
as confidentiality is maintained and no testing of the participant’s DNA material is
performed.
8.2.Safety Assessments
Planned time points for all safety assessments are provided in the SoA. Unscheduled clinical
laboratory measurement s 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 maternal
participants at thefirst visit to establish a baseline. Significant medical history and
observations from an y physical examination 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 after vaccination will be assessed and documented
in the AE CRF.
The safet y parameters also include reactogenicit y e-diary reports of local reac tions and
systemic events (including fever) and use of antipy retic medication that occur in the 7 day s
after administration of the study intervention , where Day 1 is the day of vaccination .
Reactogenicit y will not be collected in the e -diary for placebo recipients who subsequently
receive BNT162b2 1 month following delivery . These prospectivel y self -report ed
occurrences of loca lreactions and sy stemic events are graded as described in Section 8.2.2 .
8.2.1. Clinical Safety Laboratory Assessments
Clinical safety laboratory a ssessments will n ot be collected in this study .
8.2.2. Electronic Diary
Maternal participants 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 maternal
participant’s own personal device. Maternal p articipants will be asked to monitor and record
local reactions, sy stemic events, and antipy retic medication usage for 7 days following
administration of the study intervention , where Day 1 is the day ofvaccination . 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 ,systemic events, and antipy retic medication usage reported in
the reactogenicit y e-diary will be transferred electronically 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.
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Page 66Maternal partic ipants originall y randomized to placebo who subsequentl yreceive BNT162b2
1 month following delivery , will not complete a reactogenicit y e-diary but will have their
local reactions and s ystemic events detected and reported as AEs in accordance with
Section 8.3.2 .
If the maternal participant lives in an area with poor network connection (certain countries
only),a study staff/ field worker may visit the maternal participant in herhome or contact her
via phone dail yafter vaccination to assess and record local reactions, s ystemic events, and
temperature each day (beginning in the morning) for 6 days following vaccination (Day 2
through Day 7)where this sy stem of follow- up is well established. Maternal participants
may call the site and report additional local reactions and sy stemic events at an y time during
the Day 1 through Day 7 reporting period. The study staff/ field worker will be required to
record these data on a provisioned device or an application on a personal device, thus
providing the accurate representation of the maternal participant’s experience at that time.
For events persisting on Day 7 and use of antipy retic medication continuing onDay 7, the
field worker will continue to visit the participant and record information until resolution.
At intervals agreed to b y the vendor and Pfizer, these data will be transferred electronicall y
into Pfizer 's database for anal ysis and reporting. These data do not need to be reported by the
investigator in the CRF as AEs.
Investigators (or designee) will be required to review 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, sy stemic events, or use of antipyretic medication on the last day that the
reactogenicity e-diary was completed. The stop dates shoul d be documented in the source
documents and the information entered in the CRF.
8.2.2.1. 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 gradi ng scales for
healthy adult volunteers enrolled in preventive vaccine clinical trials .21
8.2.2.2. Local Reactions
During the reactogenicit y e-diary reporting period, maternal participants/study staff
member/field worker will be asked to assess redness, swelling, and pain at the injection site
and to record the s ymptoms in the reactogenicity e-diary . If a local reaction persists bey ond
the end of the reactogenicity e-diary period following vaccination, the maternal parti cipant
will be requested to report that information. The investigator /field staff will enter this
additional information in the CRF.
Redness and swelling will be measured and recorded by the maternal participants/study staff
member/field worker in measur ing device units (range: 1 to 21) and then categorized during
analysis as absent, mild, moderate, or severe based on the grading scale in Table 2.
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Page 67Measuring device uni ts 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 by the
participant as absent, mild, moderate, or severe according tothe grading scale in Table 2.
If a Grade 3 local reaction is reported in the reactogenicity e-diary , a telephone contact
should occur to ascertain further details and determine whether a site visit is clin ically
indicated. Onl y 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
reaction, 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.
Where appropriate , the site staff/field worker will educate the maternal participant regarding
signs and s ymptoms that would prompt site contact.
Table 2.Local Reaction Grading Scale
Mild
(Grade 1)Moderate
(Grade 2)Severe
(Grade 3)Potentially Life
Threatening
(Grade 4)
Pain at the
injection siteDoes not interfere
with activityInterferes with
activityPrevents daily
activity Emergency room
visit or
hospitalization for
severe pain
Redness >2.0cm to 5.0 cm
(5 to 10 measuring
device units)>5.0 cm to 10.0 cm
(11 to 20 measuring
device units)>10cm
(≥21measuring
device units)Necrosis or
exfoliative
dermatitis
Swelling >2.0cm to 5.0 cm
(5 to 10 measuring
device units)>5.0 cm to 10.0 cm
(11 to 20 measuring
device units)>10cm
(≥21measuring
device units)Necrosis
8.2.2.3. Systemic Events
Prior to vaccination on Day 1 , a baseline assessment of fatigue, headache, vomiting,
nausea, diarrhea, muscle pain, and joint pain will be recorded in the e -diary .
During the reactogenicit y e-diary reporting period, maternal participants will be asked to
assess vomiting, diarrhea, headach e, fatigue, chills, new or worsened muscle pain, and new
or worsened joint pain and to record the s ymptoms in the reactogenicity e-diary . Based on
local practice in certain countries/locales, a stud y staff member/field worker will call or visit
maternal p articipants daily after vaccination to assess the presence of sy stemic events during
the reactogenicit y reporting period. The s ymptoms will be assessed b y the maternal
participant as absent, mild, moderate, or severe according to the grading scale in Table 3.
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Page 68Maternal participants will also be instructed to contact site staff if they visit the emergency
room or are hospitalized for severe fatigue, headache, vomiting, na usea, diarrhea, muscle
pain, or joint pain within 7 day s after vaccination. Based on local practice in certain
countries/locales, maternal participants will be referred to the appropriate healthcare facility
at the discretion of the study staff/field work er if there are an y concerns, as appropriate. In
the event that the maternal participant does not call, the investigator or qualified designee
will contact the maternal participant. The study staff/field worker may also contact the
maternal participant to obtain additional information on events entered into the e- diary .
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
indica ted. Onl y an investigator or medicall y qualified person is able to classify a maternal
participant’s s ystemic event as Grade 4. If a maternal participant experiences a confirmed
Grade 4 s ystemic event, the investigator must immediatel y 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 maternal participant.
Table 3.Systemic Event Grading Scale
Mild
(Grade 1)Moderate
(Grade 2)Severe
(Grade 3)Potentially Life
Threatening
(Grade 4)
Vom iting 1-2 times in 24 hours >2 times in 24 hours Requires IV
hydrationEmergency room
visit or
hospitalization for
hypotensive shock
Diarrhea 2 to 3 loose stools in
24 hours4 to 5 loose stools in
24hours6 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
hospitaliza tion for
severe headache
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 interference
with activityPrevents daily
routine activityEmergency roo m
visit or
hospitalization for
severe ne w or
worsen edmuscle
pain
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Page 69Table 3.Systemic Event Grading Scale
Mild
(Grade 1)Moderate
(Grade 2)Severe
(Grade 3)Potentially Life
Threatening
(Grade 4)
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 edjoint pain
Abbreviation: IV = intravenous.
8.2.2.4. Fever
In order to record information on fever, a thermometer will be given to maternal participants
with instructions on how to measure oral temperature at home. Temperature will be
collected in the reactogenicity e-diary in the evening dail y during the reactogenicity e -diary
reporting period. It will also be collected at an y time during the reactogenicity e-diary data
collection periods when fever is suspected. Similarly , based on local practice in certain
countries/locales, the study staff/field worker will call or visit maternal participants daily
during the reactogen icity reporting period to collect the temperature.
Fever is defined as an oral temperature of ≥38.0 °C (100.4 °F). The highest temperature for
each day will be recorded in the reactogenicity e-diary . Temperature will be measured and
recorded to 1 decimal place . Temperatures recorded in degrees Fahrenheit will be
programmaticall y converted to degrees Celsius and then categorized during anal ysis
according to the scale shown in Table 4.
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 maternal
participant’s fever as >40.0 °C (>104.0°F). If a maternal participant ex periences 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 maternal particip ant.
Table 4.Scale f or Fever
≥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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Page 708.2.2.5. 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).
8.2.3. Stopping Rules
The following stopping rules are in place for all Phase 2 maternal participants, based on
review of AE data and e- diary reactogenicit y data, until the start of Phase 3 .Stopping rules
do not apply to maternal participants who initially received placebo and subsequently receive
BNT162b2 .These data will be monitored on an ongoing basis b y the investigator (or
medically qualified designee) and sponsor in order to promptly identify and flag an y event
that potentially contributes to a stopping rule.
In the event that sponsor personnel confirm that a stopping rule is met, the following actions
will commence:
The IRC will review all appropriate data.
The stopping rule will PAUSE randomization and study intervention administration for
participants receiving the first dose. Maternal participants scheduled to receive Dose 2 at
the time of a study pause may proceed with vaccination.
The DMC will review all appropriate data.
For all participants vaccinated, all other routine study conduct activities, including
ongoing data ent ry, reporting of AEs, participant reactogenicity e-diary completion,
blood sample collection, and participant follow -up, will continue during the pause.
A stopping rule is met if any of the following rules occur after administration of
investigational BNT1 62b2; data from placebo recipients will not contribute to the stopping
rules. Reactogenicity e-diary data confirmed by the investigator as being entered by the
participant in error will not contribute toward a stopping rule.
Stopping Rule Criteria:
1.If any participant vaccinated with BNT162b2 develops an SAE that is assessed by the
investigator as possibly related, or for which there is no alternative, plausible, attributable
cause.
2.If any participant vaccinated with BNT162b2 develops a Grade 4 local reaction or
systemic event after vaccination that is assessed as possibly related by the investigator, or
for which there is no alternative, plausible, attributable cause.
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FDA-CBER-2021-5683-0779985
PF-07302048 (BNT162 RNA- Based COVID- 19 Vaccines)
Protocol C4591015
Protocol Amendment 2, 02March 2021
PFIZER CONFIDENTIAL
CT02- GSOP Maternal Immunization Protocol Template (Phase 1 2 3 4) (15 May 2020)
TMF Doc ID: 164.01
Page 713.If any participant vaccinated with BNT162b2 develops a fever >40.0°C (>104.0°F) for at
least 1 daily measurement after vaccination 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 BNT162b2 report the same or similar severe
(Grade 3) AE after vaccination, assessed as possibly related by the investigator, or for
which there is no alternative, plausible, attributable cause.
5.If any participant dies or requires ICU admission due to SARS -CoV -2 infection; if this
stopping rule is me t, all available clinical and preclinical safet y and immunogenicity data
should be reviewed to evaluate for enhanced COVID -19.
6.If any participant vaccinated with BNT162b2 experiences an y of the following within
7days after vaccination, where Day 1 is the day of vaccination: severe vaginal bleeding
(eg, partial abruption); severe preeclampsia; eclampsia; HELLP s yndrome;
life-threatening sequelae of preeclampsia (eg, pulmonary edema) ;stillbirth ;or fetal loss.
7.If ≥2 maternal participants vaccinated with BNT162b2 experience premature delivery or
preterm premature rupture of membranes within 14 day s after vaccination.
8.2.4. Surveillance of Events That Could Represent Enhanced COVID -19
The unblinded team supporting the DMC, including an unblinded medical monitor, will
review cases of severe COVID- 19 as they are received and will review AEs at least weekl y
for additional potential cases of severe COVID -19. At any point, the unblinded team may
discuss with the DMC chair whether the DMC should review cases.
The purpose of these reviews will be to identify whether any features of each case appear
unusual, in particular ,greater in severit y, compared to available information at the time of
review. Indicators of severity may include accelerated deterioration, need for hospitalization,
need for ventilation, or death.
Observed rates of these indicators will be compared with what could be expected in a
population similar to the study participants based upon available information at the time of
review.
8.2.5. Clinical Safety Laboratory Assessments
Clinical safety laboratory assessments will not be collected in this study .
8.3. Adverse Events and Serious Adverse Events
The definitions of an AE and an SAE can be found in Appendix 2.
AEs will be reported b y the maternal participant (or the parent [s]for the infant participant ).
090177e19668bad9\Approved\Approved On: 02-Mar-2021 22:33 (GMT)
FDA-CBER-2021-5683-0779986
PF-07302048 (BNT162 RNA- Based COVID- 19 Vaccines)
Protocol C4591015
Protocol Amendment 2, 02March 2021
PFIZER CONFIDENTIAL
CT02- GSOP Maternal Immunization Protocol Template (Phase 1 2 3 4) (15 May 2020)
TMF Doc ID: 164.01
Page 72The investigator and an y qualified designees are responsible for detecting, documenting, and
recording events that meet the definition of an AE or SAE and remai n responsible to pursue
and obtain adequate information both to determine the outcome and to assess whether the
event meets the criteria for classification as an SAE or caused the participant to discontinue
thestudy intervention (see Section 7.1).
Each maternal participant and parent of the infant participant will be questioned about the
occurrence of AEs in a nonleading manner.
In addition, the investigator may be requested by Pfizer Safet y to obtain specific follow -up
information in an expedited fashion.
The procedures described in this section pertain to bo th the infant participant and maternal
participant, unless otherwise indicated.
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 materna l participant including her fetus begins from the time the maternal
participant provides informed consent, which is obtained before participation in the study
(ie,before undergoing any study -related procedure and/or receiving study intervention ),
through and including a minimum of 28 calendar days after the last administration of the
study intervention .
In this stud y, the investigator and site staff will ensure the active elicitation and collection of
AEs and SAEs through Visit 4.
From Visit 4 through Visit 8, SAEs will be collected for maternal participants originall y
randomized to BNT162b2 .In addition , AEs occurring up to 48 hours after blood draws and
collection of nasal swab sthat are related to stud y procedures must be reported i n the CRF.
Additionally , for those maternal participants who originall y received placebo but go on to
receive BNT162b2 at Visit 101 and Visit 10 2, AEs and SAEs will be collected through and
1 month after the second dose of BNT162b2 (Visit 103).
For the infant participant, the time period for actively eliciting and collecting nonserious AEs
(“active collection period”) begins at birth and continues through and including 1 month after
birth. SAEs and AESI s will be collected from birth through and including 6 months of age.
Follow -up by the investigator continues throughout and after the active collection period and
until the AE or SAE or its sequelae resolve or stabilize at a level acceptable to the
investigator and Pfizer concurs with that as sessment.
For maternal participants who are screen failures, the active collection period ends when
screen failure status is determined.
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FDA-CBER-2021-5683-0779987
PF-07302048 (BNT162 RNA- Based COVID- 19 Vaccines)
Protocol C4591015
Protocol Amendment 2, 02March 2021
PFIZER CONFIDENTIAL
CT02- GSOP Maternal Immunization Protocol Template (Phase 1 2 3 4) (15 May 2020)
TMF Doc ID: 164.01
Page 73If the participant withdraws from the study and also withdraws consent for the collection of
future information, the ac tive collection period ends when consent 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 R eport ingForm.
Investigators are not obligated to actively seek AEs or SAEs after the participant has
concluded stud y 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.
Note : Potential COVID -19/MI S-C illnesses and their seque lae that are consiste nt 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 collection period as described in
Section 8.3.1 are reported to Pfizer Safety on the Vaccine SAE Report ingForm ,if
applicable ,immediatel y upon awareness and under no circumstance should thisexceed
24hours .
If the outcome of the pregnancy meets the criteria for an SAE (ie, ectopic pregnancy ,
spontaneous abortion, including miscarriage and missed abortion, intrauterine fetal demise,
neonatal death defined as those that occur within 1 month of birth, or congenital anomaly [in
a live -born bab y, a terminated fetus, an intrauterine fetal demise, or a neonatal death]), the
investigator should follow the procedures for reporting SAEs. In addition, infant deaths after
1 month of age should be reported as SAEs.
Further follow -upmay be requested by the sponsor and will be handled on a case- by-case
basis (eg, follow -upon preterm infants to identify developmental delay s).
SAEs occurring in the mother after the active collection period has ended are reported to
Pfizer Safety if the investigator becomes aware of them; at a minimum, all SAEs that the
investigator believes have at least a reasonable possibility of being related to study
intervention must be reported to Pfizer Safet y.
For those SAEs or deaths that occur to the infant after the active collection period should be
reported when the investigator believes the SAE or death has at least a reasonable possibility
of being related to study intervention .
090177e19668bad9\Approved\Approved On: 02-Mar-2021 22:33 (GMT)
FDA-CBER-2021-5683-0779988
PF-07302048 (BNT162 RNA- Based COVID- 19 Vaccines)
Protocol C4591015
Protocol Amendment 2, 02March 2021
PFIZER CONFIDENTIAL
CT02- GSOP Maternal Immunization Protocol Template (Phase 1 2 3 4) (15 May 2020)
TMF Doc ID: 164.01
Page 748.3.1.2. Recording Nonserious AEs and SAEs in the CRF
All nonserious AEs and SAEs occurring in a participant during the active collection period,
which begins after obtaining informed consent as described in Section 8.3.1 , will be recorded
on the AE section of the CRF.
The investigator is to record on the CRF all directly observed and all spontaneously reported
AEs and SAEs reported by the participant.
The investigator obtains general information on the pregnancy and its outcome for all study
participants. The investigator will follow the pregnancy until comp letion (or until pregnancy
termination). In the case of a live birth, the structural integrity of the neonate can be assessed
at the time of birth. In the event of a termination, the reason(s) for termination should be
specified and, if clinically possib le, the structural integrit y of the terminated fetus should be
assessed b y gross visual inspection (unless preprocedure test findings are conclusive for a
congenital anomal y and the findings are reported).
If the outcome of the pregnancy meets the criteria for an SAE (ie, ectopic pregnancy ,
spontaneous abortion, including miscarriage and missed abortion, intrauterine fetal demise,
neonatal death defined as those deaths that occur within 1 month of birth, or congenital
anomaly (in a live -born baby , a termina ted fetus, an intrauterine fetal demise, or a neonatal
death), the investigator should record this information in the CRF. I n addition, infant deaths
after 1 month of age should be recorded in the CRF as SAEs.
8.3.2. Method of Detecting AEs and SAEs
The method of recording, evaluating, and assessing causality of AEs and SAEs and the
procedures for completing and transmitting SAE reports are provided in Appendix 2.
Care will be taken not to introduce bias when detecting AEs and/or SA Es. Open- ended and
nonleading verbal questioning of the participant is the preferred method to inquire about
AEoccurrences.
8.3.3. Follow -up of AEs and SAEs
After the initial AE/SAE report, the investigator is required to proactivel y follow each
participant at subsequent visits/contacts. For each event, the investigator must pursue and
obtain adequate information until resolution, stabilization, the event is otherwise explained,
or the participant is lost to follow- up (as defined in Section 7.3).
In general, follow -up information will include a description of the event in sufficient detail to
allow for a complete medical assessment of the case and independent determination of
possible causality . An y information relevant to the event, such as concomitant medications
and illnesses, must be provided. In the case of a participant death, a summary of available
autopsy findings must be submitted as soon as possible to Pfizer Safety .
Further information on follow -up procedures is given in Appendix 2.
090177e19668bad9\Approved\Approved On: 02-Mar-2021 22:33 (GMT)
FDA-CBER-2021-5683-0779989
PF-07302048 (BNT162 RNA- Based COVID- 19 Vaccines)
Protocol C4591015
Protocol Amendment 2, 02March 2021
PFIZER CONFIDENTIAL
CT02- GSOP Maternal Immunization Protocol Template (Phase 1 2 3 4) (15 May 2020)
TMF Doc ID: 164.01
Page 758.3.4. Regulatory Reporting Requirements for SAEs
Prompt notification by the investigator to the sponsor of an SAE is essential so that legal
obligations and ethical responsibilities towards the safet y of participants and the safet y of a
study intervention under clinical investigation are met.
The sponsor has a legal responsibility to notify both the local regulatory authority and other
regulatory agencies about the sa fety of a stud y intervention under clinical investigation. The
sponsor will comply with country -specific regulatory requirements relating to safet y
reporting to the regulatory authorit y, IRBs/ECs , and investigators.
Investigator safety reports must be pre pared for SUSARs according to local regulatory
requirements and sponsor policy and forwarded to investigators as necessary .
An investigator who receives SUSARs or other specific safety information (eg, summary or
listing of SAEs) from the sponsor will revi ew and then file it along with the SRSD(s) for the
study and will notify the IRB/EC, if appropriate according to local requirements.
8.3.5. Additional Exposure Scenarios That May Result From the Exposure to the Study
Intervention
8.3.5.1. Environmental Exposure During Pregnancy
Environmental exposure occurs when, during the performance of job duties, a person
(whether a healthcare professional or otherwise) gets in unplanned direct contact with the
study intervention , which may or may not lead to the occurrence of an AE . Such persons
may include HCPs, family members, and other roles that are involved in the trial
participant’s care.
Note: This does NOT apply to maternal participants enrolled in this trial.
The scenarios below describe environmental exposures that could lead to an EDP:
A female is found to be pregnant while being exposed or having been exposed to
study intervention byenvironmental exposure. Below are some examples:
A female family member or healthcare provider reports that she is pregnant after
having been exposed to the study intervention by inadvertent product
administration via needlestick .
A male famil y member or healthcare provider who has been exposed to the study
intervention then exposes his female partner prior to or around the time of
concepti on.
090177e19668bad9\Approved\Approved On: 02-Mar-2021 22:33 (GMT)
FDA-CBER-2021-5683-0779990
PF-07302048 (BNT162 RNA- Based COVID- 19 Vaccines)
Protocol C4591015
Protocol Amendment 2, 02March 2021
PFIZER CONFIDENTIAL
CT02- GSOP Maternal Immunization Protocol Template (Phase 1 2 3 4) (15 May 2020)
TMF Doc ID: 164.01
Page 76The investigator must report EDP to Pfizer Safety within 24 hours of the investigator’s
awareness, irrespective of whether an SAE has occurred. The investigator must report
information to Pfizer Safety using the Vaccine SAE Report ingForm and EDP Sup plemental
Form. The initial information submitted should include the anticipated date of delivery
(see below for information related to termination of pregna ncy). Since the exposure
information does not pertain to the participant enrolled in the study , the information is not
recorded on a CRF; however, a cop y of the completed Vaccine SAE Report ingForm is
maintained in the investigator site file.
Follow -up is conducted to obtain general information on the pregnancy and its outcome for
all EDP reports with an unknown outcome. The investigator will follow the pregnancy until
completion (or until pregnancy termination) and notify Pfizer Safet y of the outcome as a
follow -up to the initial EDP Supplemental Form.
In the case of a live birth, the structural integrity of the neonate can be assessed at the time of
birth. In the event of a termination, the reason(s) for termination should be specified and, if
clinically possible, the structural integrit y of the terminated fetus should be assessed b y gross
visual inspection (unless preprocedure test findings are conclusive for a congenital anomal y
and the findings are reported).
Abnormal pregnancy outcomes are considered SAEs. If the outcome of the pregnancy meets
the criteria for an SAE (ie, ectopic pregnancy , spontaneous abortion, intrauterine fetal
demise, neonatal death, or congenital anomal y [in a live -born bab y, a terminated fetus, an
intrauterine fetal demise, or a neonatal death]), the investigator should follow the procedures
for reporting SAE s.
Additional information about pregnancy outcomes that are reported to Pfizer Safet y as SAEs
follows:
Spontaneous abortion including miscarriage and missed abortion;
Neonatal deaths that occur within 1 month of birth should be reported, without regard
to causality , as SAEs. In addition, infant deaths after 1 month should be reported as
SAEs when the investigator assesses the infant death as related or possibly related to
exposure to the study intervention.
Additional information regarding the EDP may be requested by the sponsor. Further
follow -up of birth outcomes will be handled on a case- by-case basis (eg, follow -up on
preterm infants to identify developmental dela ys).
090177e19668bad9\Approved\Approved On: 02-Mar-2021 22:33 (GMT)
FDA-CBER-2021-5683-0779991
PF-07302048 (BNT162 RNA- Based COVID- 19 Vaccines)
Protocol C4591015
Protocol Amendment 2, 02March 2021
PFIZER CONFIDENTIAL
CT02- GSOP Maternal Immunization Protocol Template (Phase 1 2 3 4) (15 May 2020)
TMF Doc ID: 164.01
Page 778.3.5.2. Exposure During Breastfeeding
Exposure -during -breastfeeding reports are not expected for maternal participants who
breastfeed a child delivered during the study .
Environmental exposure during breastfeeding occurs when a female family member or
healt hcare provider who reports that she is breastfeeding after having been exposed to the
study intervention (eg, by inhalation or skin contact ). The investigator must report exposure
during breastfeeding to Pfizer Safet y within 24 hours of the investigator’s awareness,
irrespective of whether an SAE has occurred. The information must be reported using the
Vaccine SAE Reporting Form . When exposure during breastfeeding occurs in the setting of
environmental exposure, the exposure information does not pertain to the participant enrolled
in the study , so the information is not recorded on a CRF. However, a copy of the completed
Vaccine SAE Reporting Form is maintained in the investigator site file.
An exposure -during -breastfeeding report is not created when a Pfizer drug specificall y
approved for use in breastfeeding women (eg, vitamins) is administered in accord with
authorized use. However, if the infant experiences an SAE associated with such a drug, the
SAE is reported together with the exposure during breastfeeding.
8.3.5.3. Occupational Exposure
An occupational exposure occurs when a person receives unplanned direct contact with the
study intervention, which may or may not lead to the occurrence of an AE. Such persons
may include healthcare providers , famil y members, and other roles that are involved in the
trial participant’s care.
The investigator must report occupational exposure to Pfizer Safet y within 24
…[truncated]

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