A PHASE 3, RANDOMIZED, OBSERVER-BLIND STUDY TO EVALUATE THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF MULTIPLE PRODUCTION LOTS AND DOSE LEVELS OF THE VACCINE CANDIDATE BNT162b2 AGAINST COVID-19 IN HEALTHY PARTICIPANTS 12 THROUGH 50 YEARS OF AGE AND THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF BNT162b2 RNA-BASED COVID-19 VACCINE CANDIDATES AS A BOOSTER DOSE IN HEALTHY PARTICIPANTS 18 THROUGH 50 YEARS OF AGE
Phase: PHASE3
Conditions: SARS-CoV-2 Infection, COVID-19
Sponsor: BioNTech SE

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A PHASE 3, RANDOMIZED, OBSERVER-BLIND STUDY TO EVALUATE THE 
SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF MULTIPLE 
PRODUCTION LOTS AND DOSE LEVELS OF THE VACCINE CANDIDATE 
BNT162b2 AGAINST COVID-19 IN HEALTHY PARTICIPANTS 12 THROUGH 
50 YEARS OF AGE AND THE SAFETY, TOLERABILITY, AND 
IMMUNOGENICITY OF BNT162b2 RNA-BASED COVID-19 VACCINE 
CANDIDATES AS A BOOSTER DOSE IN HEALTHY PARTICIPANTS 18 
THROUGH 50 YEARS OF AGE
Study Sponsor:
BioNTech
Study Conducted By:
Pfizer
Study Intervention Number:
PF-07302048
Study Intervention Name:
BNT162b2 RNA-Based COVID-19 Vaccines
US IND Number:
19736
EudraCT Number:
2020-002641-42
Protocol Number:
C4591017
Phase:
3
Short Title: A Phase 3 Study to Evaluate the Safety, Tolerability, and Immunogenicity of 
Multiple Production Lots and Dose Levels of BNT162b2 RNA-Based COVID-19 Vaccines 
Against COVID-19 in Healthy Participants
This document and accompanying materials contain confidential information belonging to Pfizer.  Except as 
otherwise agreed to in writing, by accepting or reviewing these documents, you agree to hold this information 
in confidence and not copy or disclose it to others (except where required by applicable law) or use it for 
unauthorized purposes.  In the event of any actual or suspected breach of this obligation, Pfizer must be 
promptly notified.

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
Because of the addition of participants 12 through 
17 years of age, multisystem inflammatory syndrome in 
children is added as an AE of special interest.

Added the possibility of assessing S1-binding instead of 
the full-length S-binding IgG levels.

Because of an increased incidence rate of SARS-CoV-2 
in the US, it is expected that more participants will be 
diagnosed with COVID-19 during their time in the 
study; therefore, the nonevaluable rate was increased 
from 15% to 20%.

The criterion to discontinue the study intervention at 
Dose 2 in participants who were diagnosed with 
COVID-19 between Visit 1 and Visit 2 has been 
removed, as the ACIP recommends that vaccination 
should be offered to persons regardless of history of 
prior symptomatic or asymptomatic SARS-CoV-2 
infection.

The exclusion criterion for immunocompromised 
individuals was inadvertently omitted and now appears 
as exclusion criterion 5.

The Benefit/Risk Assessment section has been updated 
to reflect the additional clinical data available for 
BNT162b2.  The Overall Benefit/Risk Conclusions 
section has not changed.

A clarification was made in Section 8.1.1, Biological 
Samples, that no testing of the participant’s DNA will be 
performed.
Original protocol
24 Nov 2020
N/A
This amendment incorporates all revisions to date, including amendments made at the 
request of country health authorities and IRBs/ECs.

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TABLE OF CONTENTS
LIST OF TABLES.....................................................................................................................8
1. PROTOCOL SUMMARY.....................................................................................................9
1.1. Synopsis ....................................................................................................................9
1.2. Schema ....................................................................................................................16
1.2.1. Primary Study.............................................................................................16
1.2.2. Booster Study..............................................................................................17
1.3. Schedule of Activities .............................................................................................18
1.3.1. Primary Study.............................................................................................18
1.3.2. Booster Study..............................................................................................20
2. INTRODUCTION ...............................................................................................................22
2.1. Study Rationale .......................................................................................................22
2.2. Background .............................................................................................................22
2.2.1. Clinical Overview.......................................................................................24
2.3. Benefit/Risk Assessment.........................................................................................24
2.3.1. Risk Assessment.........................................................................................26
2.3.2. Benefit Assessment.....................................................................................28
2.3.3. Overall Benefit/Risk Conclusion................................................................28
3. OBJECTIVES, ESTIMANDS, AND ENDPOINTS ...........................................................28
3.1. Primary Study..........................................................................................................28
3.2. Booster Study..........................................................................................................30
4. STUDY DESIGN.................................................................................................................31
4.1. Overall Design.........................................................................................................31
4.2. Scientific Rationale for Study Design.....................................................................32
4.3. Justification for Dose ..............................................................................................32
4.4. End of Study Definition ..........................................................................................32
5. STUDY POPULATION......................................................................................................33
5.1. Inclusion Criteria.....................................................................................................33
5.2. Exclusion Criteria....................................................................................................34
5.3. Lifestyle Considerations..........................................................................................35
5.3.1. Contraception..............................................................................................35

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5.4. Screen Failures ........................................................................................................36
5.5. Criteria for Temporarily Delaying Enrollment/Randomization/Study 
Intervention Administration (Primary Study) ...........................................................36
6. STUDY INTERVENTION..................................................................................................37
6.1. Study Intervention(s) Administered........................................................................37
6.1.1. Primary Study.............................................................................................37
6.1.2. Booster Study..............................................................................................38
6.1.3. Administration............................................................................................38
6.2. Preparation/Handling/Storage/Accountability ........................................................39
6.2.1. Preparation and Dispensing........................................................................40
6.3. Measures to Minimize Bias: Randomization and Blinding.....................................40
6.3.1. Allocation to Study Intervention ................................................................40
6.3.2. Blinding of Site Personnel..........................................................................40
6.3.3. Blinding of the Sponsor..............................................................................41
6.3.4. Breaking the Blind......................................................................................41
6.4. Study Intervention Compliance...............................................................................42
6.5. Concomitant Therapy..............................................................................................42
6.5.1. Prohibited During the Study.......................................................................42
6.5.2. Permitted During the Study ........................................................................43
6.6. Dose Modification...................................................................................................43
6.7. Intervention After the End of the Study (Primary Study) .......................................43
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL...........................................................................43
7.1. Discontinuation of Study Intervention (Primary Study) .........................................43
7.2. Participant Discontinuation/Withdrawal From the Study.......................................44
7.2.1. Withdrawal of Consent...............................................................................45
7.3. Lost to Follow-up....................................................................................................45
8. STUDY ASSESSMENTS AND PROCEDURES...............................................................46
8.1. Immunogenicity Assessments.................................................................................46
8.1.1. Biological Samples.....................................................................................47
8.2. Safety Assessments .................................................................................................47
8.2.1. Clinical Safety Laboratory Assessments ....................................................48

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8.2.2. Electronic Diary..........................................................................................48
8.2.2.1. Grading Scales...........................................................................48
8.2.2.2. Local Reactions.........................................................................48
8.2.2.3. Systemic Events ........................................................................49
8.2.2.4. Fever..........................................................................................50
8.2.2.5. Antipyretic/Analgesic Medication ............................................51
8.2.3. Pregnancy Testing ......................................................................................51
8.3. Adverse Events and Serious Adverse Events..........................................................51
8.3.1. Time Period and Frequency for Collecting AE and SAE Information.......52
8.3.1.1. Reporting SAEs to Pfizer Safety...............................................53
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF...................53
8.3.2. Method of Detecting AEs and SAEs ..........................................................53
8.3.3. Follow-up of AEs and SAEs.......................................................................53
8.3.4. Regulatory Reporting Requirements for SAEs...........................................53
8.3.5. Exposure During Pregnancy or Breastfeeding, and Occupational 
Exposure ..........................................................................................................54
8.3.5.1. Exposure During Pregnancy......................................................54
8.3.5.2. Exposure During Breastfeeding ................................................55
8.3.5.3. Occupational Exposure .............................................................56
8.3.6. Cardiovascular and Death Events...............................................................56
8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as AEs or SAEs..............................................................................56
8.3.8. Adverse Events of Special Interest.............................................................56
8.3.8.1. Lack of Efficacy........................................................................57
8.3.9. Medical Device Deficiencies......................................................................57
8.3.10. Medication Errors.....................................................................................57
8.4. Treatment of Overdose............................................................................................58
8.5. Pharmacokinetics ....................................................................................................59
8.6. Pharmacodynamics..................................................................................................59
8.7. Genetics...................................................................................................................59
8.8. Biomarkers ..............................................................................................................59
8.9. Immunogenicity Assessments.................................................................................59

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8.10. Health Economics .................................................................................................59
8.11. Study Procedures...................................................................................................59
8.11.1. Visit 1 – Vaccination 1 (Day 1)................................................................59
8.11.2. Visit 2 – Vaccination 2 (19 to 23 Days After Visit 1)..............................62
8.11.3. Visit 3 – 1-Month Follow-up (28 to 35 Days After Visit 2).....................64
Booster Study Procedures ..............................................................................................64
8.11.4. Visit 4 – Vaccination 3 (83 to 97 Days After Visit 2)..............................64
8.11.5. Visit 5 – 1-Week Follow-up (6 to 8 Days After Visit 4)..........................67
8.11.6. Visit 6 – 1-Month Follow-up (28 to 35 Days After Visit 4).....................67
8.12. Unscheduled Visits for a Grade 3 or Suspected Grade 4 Reaction.......................68
9. STATISTICAL CONSIDERATIONS ................................................................................69
9.1. Estimands and Statistical Hypotheses.....................................................................69
9.1.1. Estimands....................................................................................................69
9.1.2. Statistical Hypothesis..................................................................................70
9.2. Sample Size Determination.....................................................................................71
9.3. Analysis Sets ...........................................................................................................73
9.4. Statistical Analyses .................................................................................................74
9.4.1. General Considerations...............................................................................74
9.4.1.1. Analyses for Binary Data ..........................................................75
9.4.1.2. Analyses for Continuous Data...................................................75
9.4.2. Primary Endpoint(s)....................................................................................76
9.4.3. Secondary Endpoints ..................................................................................79
9.5. Interim Analyses .....................................................................................................79
9.6. Data Monitoring Committee or Other Independent Oversight Committee.............80
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS..........................................................................................................81
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations...............81
10.1.1. Regulatory and Ethical Considerations ....................................................81
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the 
Protocol or ICH GCP.........................................................................81
10.1.2. Informed Consent Process ........................................................................82
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10.1.3. Data Protection .........................................................................................83
10.1.4. Dissemination of Clinical Study Data ......................................................83
10.1.5. Data Quality Assurance ............................................................................84
10.1.6. Source Documents....................................................................................86
10.1.7. Study and Site Start and Closure ..............................................................86
10.1.8. Sponsor’s Qualified Medical Personnel ...................................................87
10.2. Appendix 2: Clinical Laboratory Tests .................................................................88
10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ......................................................................89
10.3.1. Definition of AE .......................................................................................89
10.3.2. Definition of SAE.....................................................................................90
10.3.3. Recording/Reporting and Follow-up of AEs and/or SAEs.......................92
10.3.4. Reporting of SAEs....................................................................................95
10.4. Appendix 4: Contraceptive Guidance ...................................................................96
10.4.1. Male Participant Reproductive Inclusion Criteria....................................96
10.4.2. Female Participant Reproductive Inclusion Criteria.................................96
10.4.3. Woman of Childbearing Potential ............................................................97
10.4.4. Contraception Methods.............................................................................98
10.5. Appendix 5: Liver Safety: Suggested Actions and Follow-up Assessments ......100
10.6. Appendix 6: Abbreviations .................................................................................102
11. REFERENCES ................................................................................................................105
LIST OF TABLES
Table 1.
Local Reaction Grading Scale ..................................................................49
Table 2.
Systemic Event Grading Scale..................................................................50
Table 3.
Scale for Fever..........................................................................................51
Table 5.
Probability of Observing an Event Given a Specified Incidence 
Rate With 30 Participants per Group........................................................73
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1. PROTOCOL SUMMARY
1.1. Synopsis
Short Title:  A Phase 3 Study to Evaluate the Safety, Tolerability, and Immunogenicity of 
Multiple Production Lots and Dose Levels of BNT162b2 RNA-Based COVID-19 Vaccines
Against COVID-19 in Healthy Participants
Rationale
A pneumonia of unknown cause detected in Wuhan, China, was first reported in 
December 2019.  In January 2020, the pathogen causing this outbreak was identified as a 
novel coronavirus 2019.  The outbreak was declared a Public Health Emergency of 
International Concern on 30 January 2020.  On 12 February 2020, the virus was officially 
named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the WHO 
officially named the disease caused by SARS-CoV-2 as coronavirus disease 2019 
(COVID-19).  On 11 March 2020, the WHO upgraded the status of the COVID-19 outbreak 
from epidemic to pandemic, which is now spreading globally at high speed.
Based on Phase 2/3 safety, immunogenicity, and efficacy data, BNT162b2 was shown to be 
effective and has been authorized for temporary or emergency use in multiple countries.
BNT162b2 is administered intramuscularly as a 2-dose series spaced 21 days apart at a dose 
of 30 μg each.  Study C4591001 (NCT04368728) is an ongoing Phase 1/2/3 trial designed to 
generate safety, tolerability, immunogenicity, and efficacy data from a novel RNA-based 
vaccine candidate. The trial is being conducted in a heterogeneous study population: eligible 
participants ≥12 years of age, healthy participants, including those participants with stable 
chronic medical conditions, as well as HIV-, HCV-, and HBV-positive participants. 
BNT162b2 was selected from the Phase 1 part of this study based on the overall safety, 
tolerability, and immunogenicity.
To support distribution of this vaccine on a wider scale, the study will evaluate the immune 
response across 4 different BNT162b2 lots manufactured at a commercial scale: 3 lots of 
drug substance manufactured in the United States and 1 lot of drug substance manufactured 
in Europe (Arms 1-4) and describe the safety and tolerability of these different vaccine lots in 
healthy participants.
While the 30-µg dose was selected based on favorable reactogenicity and immunogenicity in 
both younger and older participants, Phase 1 immunogenicity and safety data were also 
robust with the 20-µg dose in the younger population. Investigating the noninferiority of a 
20-µg dose compared with the standard 30-µg dose may support the potential use of a lower 
vaccine dose in the defined population of this study. This will be of value with the demand 
to vaccinate the general population. Therefore, a noninferiority analysis will be performed in 
this study of a 20-µg dose against the standard 30-µg dose.  The 20-µg dose arm (Arm 5) will 
contain the same US-manufactured drug substance as one of the US lots in the study and will 
be compared against that same lot in the noninferiority analysis.

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Note:  In this protocol, the US-manufactured drug substance lots are also referred to as the 
“US lots” and the EU-manufactured drug substance lot is also referred to as the “EU lot.”
In light of the unknowns regarding duration of protection, as well as the emerging variants of 
concern (VOCs), it is important to understand the boostability of BNT162b2, and potential 
heterologous protection against emerging VOC(s).  To this end, a booster study extension has 
been added in protocol amendment 2 in which a small subset of adult participants who 
received Doses 1 and 2 at 30 µg from a designated US lot(s) will receive a single dose of 
either 30 µg BNT162b2 or 30 µg BNT162b2.B.1.351 (BNT162b2s01 vaccine encoding for
the full-length spike protein of South Africa variant B.1.351 [formerly known as 
BNT162b2SA]). This third dose will be administered at approximately 3 months after Dose 2
of BNT162b2.

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Primary Study
Objectives, Estimands, and Endpoints
Objectives
Estimands
Endpoints
Primary Immunogenicity – Lot Comparisons
To demonstrate that the immune 
responses induced by BNT162b2 are 
similar across the 3 US lots (Arms 1,
2, and 3) in participants without 
evidence of SARS-CoV-2 infection 
during the study.
In participants complying with the key 
protocol criteria (evaluable 
participants):
•
GMR from one US lot to another 
lot (Arm 1/Arm 2, Arm 1/Arm 3, 
and Arm 2/Arm 3) 1 month after 
Dose 2
•
Full-length S-binding IgG levels
To demonstrate that the immune 
response induced by the EU lot
(Arm 4) of BNT162b2 is similar to 
the pooled US lots (Arms 1, 2, 
and 3) in participants without 
evidence of SARS-CoV-2 infection 
during the study.
In participants complying with the key 
protocol criteria (evaluable 
participants):
•
GMR from the EU lot (Arm 4) to
the pooled US lots (Arm 4/pooled 
Arms 1, 2, and 3) 1 month after 
Dose 2
•
Full-length S-binding IgG levels
Primary Immunogenicity – Dose Comparison
To demonstrate the noninferiority of
the immune response to prophylactic
BNT162b2 in participants receiving 
20 μg compared to participants
receiving the standard 30-μg dose
(prepared from the same 
manufacturing lot) without evidence 
of SARS-CoV-2 infection during the 
study.
In 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 the 2 dose 
groups 1 month after Dose 2
•
SARS-CoV-2 neutralizing titers
Primary Safety
To evaluate the safety of BNT162b2 
when administered on a 2-dose 
schedule in healthy participants
12 through 50 years of age.
In participants receiving at least 1 dose 
of study intervention from each vaccine 
group (individual and pooled US lots, 
EU lot, 20-μg dose), the percentage of 
participants reporting:
•
Local reactions for up to 7 days
following each dose
•
Systemic events for up to 7 days 
following each dose
•
AEs and SAEs from Dose 1 to 
1 month after Dose 2
•
Local reactions (pain at the 
injection site, redness, and 
swelling)
•
Systemic events (fever, fatigue, 
headache, chills, vomiting, 
diarrhea, new or worsened muscle 
pain, and new or worsened joint 
pain)
•
AEs
•
SAEs
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Secondary Immunogenicity
To describe the immune responses 
induced by different 30-µg dose 
manufacturing lots of BNT162b2.
In evaluable participants from each 
vaccine group (individual and pooled 
US lots, EU lot):

GMCs at baseline (before Dose 1) 
and 1 month after Dose 2

GMFR from baseline (before 
Dose 1) to 1 month after Dose 2

Full-length S-binding IgG levels
To describe the immune responses 
induced by different doses of 
BNT162b2.
In evaluable participants from each 
vaccine group (20 µg and 30 µg from 
the same US lot):

GMCs at baseline (before Dose 1) 
and 1 month after Dose 2

GMFR from baseline (before 
Dose 1) to 1 month after Dose 2

SARS-CoV-2 neutralizing titers
Note:  “US lots” refers to the lots of study vaccine containing drug substance manufactured in the United States.  
“EU lot” refers to the lot of study vaccine containing drug substance manufactured in Europe.

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Booster Study
Objectives
Estimands
Endpoints
Primary Safety
To evaluate the safety and 
tolerability profile of a third dose of 
study intervention (either BNT162b2 
30 µg or BNT162b2.B.1.351*
30 µg), administered to participants 
(18 through 50 years of age) who 
received two 30-µg doses of 
BNT162b2, approximately 3 months 
after Dose 2.
In participants receiving the third dose 
of study intervention, the percentage of 
participants reporting:

Local reactions for up to 7 days 
following the booster dose

Systemic events for up to 7 days 
following the booster dose

AEs and SAEs from the booster 
dose to 1 month after the booster 
dose

Local reactions (pain at the 
injection site, redness, and 
swelling)

Systemic events (fever, fatigue, 
headache, chills, vomiting, 
diarrhea, new or worsened muscle 
pain, and new or worsened joint 
pain)

AEs

SAEs
Primary Immunogenicity
To describe the immune response 
induced by a third dose of study 
intervention (either BNT162b2
30 µg or BNT162b2.B.1.351*
30 µg).
In evaluable participants from each 
vaccine group (either BNT162b2 30 µg
or BNT162b2.B.1.351 30 µg):

Geometric mean neutralizing titers
at baseline (before Dose 1), 
1 month after Dose 2, before 
Dose 3, and 1 week after and 
1 month after Dose 3

Geometric mean IgG 
concentrations at baseline (before 
Dose 1), 1 month after Dose 2, 
before Dose 3, and 1 week after 
and 1 month after Dose 3

GMFRs from 1 month after Dose 2 
to 1 week after and 1 month after 
Dose 3 and from before Dose 3 to 
1 week after and 1 month after 
Dose 3

The percentages of participants 
with seroresponse§ (based on 
neutralizing titers) to the reference 
strain at 1 month after Dose 2, 
before Dose 3, and 1 week after 
and 1 month after Dose 3

The percentages of participants 
with seroresponse§ (based on 
neutralizing titers) to the B.1.351
variant strain at 1 month after 
Dose 2, before Dose 3, and 1 week 
after and 1 month after Dose 3

SARS-CoV-2 reference-strain 
neutralizing titer†

SARS-CoV-2 B.1.351-strain 
neutralizing titer††

Full-length S-binding IgG levels
* BNT162.B.1.351 = BNT162b2s01 vaccine encoding for the full-length spike protein of South African–origin variant 
B.1.351 (formerly BNT162b2SA).
† SARS-CoV-2 reference-strain neutralizing titers = neutralizing titers against SARS-CoV-2 USA-WA1/2020 virus.
†† SARS-CoV-2 B.1.351-strain neutralizing titers = neutralizing titers against SARS-CoV-2 virus with B.1.351 spike.
§ Seroresponse is defined as ≥4-fold increase from baseline (before Dose 1) to the specified time point. If the baseline 
measurement is below LLOQ, a postvaccination measurement of ≥4 × LLOQ is considered a seroresponse.

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Overall Design
This is a Phase 3, randomized, observer-blind study to evaluate the safety, tolerability, and 
immunogenicity of 4 manufacturing lots of BNT162b2 as a 30-µg dose and an additional
20-µg dose arm using one of the same manufactured 30-µg lots. BNT162b2 is an 
RNA-based COVID-19 vaccine, administered on a 2-dose schedule in healthy participants 
12 through 50 years of age.  Participants will be randomized to 1 of 5 arms in a 2:2:2:1:2 
ratio (Arm 1: Arm 2: Arm 3: Arm 4: Arm 5), where Arms 1, 2, and 3 contain 
US-manufactured drug substance for 30-µg dosing; Arm 4 contains EU-manufactured drug 
substance for 30-µg dosing; and Arm 5 contains US-manufactured drug substance for 20-µg
dosing.  In order to allow for balanced age representation across all arms, the randomization 
will be stratified by age groups: 12 through 17, 18 through 30, and 31 through 50 years.
The duration of the study for each participant will be approximately 2 months. The study
will be conducted in the United States.
Protocol amendment 2 has added a booster study in which a subset of the adult participants 
(18 through 50 years of age) who each received two 30-µg doses of the designated US lot(s) 
will be randomly assigned to 1 of 2 arms in a 1:1 ratio (Booster 1: Booster 2), where 
Booster 1 is BNT162b2 at 30 µg and Booster 2 is BNT162b2.B.1.351 at 30 µg. The third 
dose will be administered approximately 3 months after BNT162b2 Dose 2 of the primary 
study.
The duration of the booster study for each participant will be approximately 1 month.  This 
study is observer-blinded, to minimize changes in study conduct compared with the primary 
study.
Number of Participants
Approximately 340 participants will be randomly assigned to each of the 3 US lots (Arms
1-3) and to the 20-µg arm (Arm 5) and approximately 170 participants will be randomly 
assigned to the EU lot (Arm 4), for a total of approximately 1530 randomized participants.  It 
is expected that approximately 1224 evaluable participants will complete the study, based on 
a 20% nonevaluable rate.
In the booster study, approximately 30 participants will be assigned to each arm for a total of 
60 participants to be enrolled.  It is expected that approximately 48 evaluable participants 
will complete the study, based on a 20% nonevaluable rate.
Data Monitoring Committee or Other Independent Oversight Committee
This study will use a DMC.  The DMC is independent of the study team and includes 
external members.  The DMC charter describes the role of the DMC in more detail.
The DMC will be responsible for ongoing monitoring of the safety of participants in the 
study according to the charter.  This may include, but is not limited to:

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
Contemporaneous review of related AEs up to 1 month after completion of the 
vaccination schedule,

Contemporaneous review of all SAEs up to 1 month after completion of the 
vaccination schedule.
The recommendations made by the DMC to alter the conduct of the study will be forwarded 
to the appropriate Pfizer personnel for final decision.  Pfizer will forward such decisions, 
which may include summaries of aggregate analyses of safety data, to regulatory authorities, 
as appropriate.
Statistical Methods
There are 2 primary immunogenicity objectives on manufacturing lot comparisons. The first 
primary immunogenicity objective will be evaluated by formal hypothesis tests for 
consistency of the immune response induced by BNT162b2 30 µg across the 3 US lots. 
GMRs of the full-length S-binding IgG levels and their 2-sided 95% CIs will be provided for 
each pair of between-lot comparisons (Arm 1 to Arm 2, Arm 1 to Arm 3, and Arm 2 to 
Arm 3) using a 1.5-fold equivalence margin.  Two lots will be considered similar if the 
2-sided 95% CI for the GMR is contained in the interval (0.67, 1.5).  Overall, the lots will be 
considered similar if the 1.5-fold equivalence criterion is met for all 3 between-lot 
comparisons (Arm 1 to Arm 2, Arm 1 to Arm 3, and Arm 2 to Arm 3).
The second primary immunogenicity objective of similarity between the EU lot and the 
3 pooled US lots will be assessed sequentially after the first primary objective is met. Using 
a 1.5-fold equivalence margin, the EU lot and the pooled US lots will be considered similar if 
the 2-sided 95% CI for the GMR of the full-length S-binding IgG levels is contained in the 
interval (0.67, 1.5).
The primary immunogenicity objective of noninferiority of the BNT162b2 20-µg vs 30-µg
dose levels, using a 1.5-fold noninferiority margin, will be achieved if the lower limit of the 
2-sided 95% CI for the GMR of the SARS-CoV-2 neutralizing titers is >0.67.
With 270 evaluable participants per US lot, the study has a power of 91.7% for considering 
the 3 US lots to be similar. The study will also provide 92.8% power for considering the EU 
lot similar to the US lots, with 135 evaluable participants in the EU lot and 810 evaluable 
participants in the pooled US lots. With 270 evaluable participants for the 20-µg and 30-µg 
dose groups (Arm 5 and the corresponding US 30-µg lot [Arm 1, 2, or 3]), the study will 
have a power of 94.7% for declaring noninferiority.  Assuming a nonevaluable rate of 20%, 
the study will randomize approximately 340 participants in each US lot, 170 participants in 
the EU lot, and 340 participants in the 20-µg dose group to achieve the required evaluable 
participants.
The secondary immunogenicity objectives will be evaluated descriptively by GMCs,
GMFRs, and the associated 95% CIs for the full-length S-binding IgG levels for Arms 1

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through 4 and GMTs, GMFRs, and the associated 95% CIs for the SARS-CoV-2 neutralizing 
titers for Arm 5 and the corresponding US 30-µg lot (Arm 1, 2, or 3).
The primary safety objective will be evaluated by descriptive statistics including counts and 
percentages of participants and the associated Clopper-Pearson 95% CIs for local reactions, 
systemic events, and AEs/SAEs, for each vaccine group.
In the booster study, the primary immunogenicity objectives will be evaluated descriptively 
by GMCs, GMFRs, and the associated 95% CIs for the full-length S-binding IgG levels and 
by GMTs, GMFRs, and the associated 95% CIs for the SARS-CoV-2 neutralizing titers for 
both the reference strain and the B.1.351 strain for each vaccine group.  Additionally, the 
percentage of participants with a seroresponse to the reference strain and B.1.351 strain using 
neutralizing titers will be summarized.
The primary safety objective will be evaluated by descriptive statistics including counts and 
percentages of participants and the associated Clopper-Pearson 95% CIs for local reactions, 
systemic events, and AEs/SAEs, for each vaccine group.
1.2. Schema
1.2.1. Primary Study
a.
Arms 1 through 3 are administered a 30-µg dose level of manufacturing lots 1 through 3, respectively, 
containing US-manufactured drug substance.
b.
Arm 4 is administered a 30-µg dose level of manufacturing lot 4, containing EU-manufactured drug substance.
c.
Arm 5 is administered a 20-µg dose level from the corresponding US lot (Arm 1, 2, or 3).

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1.2.2. Booster Study

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2. INTRODUCTION
BNT162b2 is an RNA-based COVID-19 vaccine that is currently being investigated for the 
prevention of COVID-19 in individuals ≥12 years of age.
2.1. Study Rationale
One aim of the study is to demonstrate that a similar immune response is induced by 4 lots of 
BNT162b2 (3 containing drug substance manufactured in the United States, referred to as the 
“US lots,” and 1 containing drug substance manufactured in Europe, referred to as the “EU 
lot”), and describe the safety and tolerability of these different vaccine lots in healthy 
participants, thereby supporting both US and EU manufacturing processes at commercial 
scale. One of the US lots will also be administered at a 20-µg dose and compared with the 
standard 30-µg dose from the same US production lot in a noninferiority analysis. This 
objective will support the potential use of a lower vaccine dose in the defined study 
population, which will be of value, given the demand to vaccinate the general population.
As more data about COVID-19 continue to accrue, the potential duration of protection 
afforded after a wild-type SARS-CoV-2 infection, and by vaccination, remains unknown. If 
a third dose of BNT162b2 becomes necessary, whether it be with the current vaccine or one 
encoding for a VOC, it will be important to understand the safety and immunogenicity when 
the third dose is administered in close proximity to the second dose.
2.2. Background
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 underlying 
cause.  Later in January, the genetic sequence of the 2019-nCoV became available to the 
WHO and the public (MN908947.3), and the virus was categorized in the Betacoronavirus
subfamily.  By sequence analysis, the phylogenetic tree revealed a closer relationship to 
SARS virus isolates than to another coronavirus infecting humans, the MERS virus.1,2
The outbreak was declared a Public Health Emergency of International Concern on 
30 January 2020.3  On 12 February 2020, the virus was officially named as severe acute 
respiratory syndrome coronavirus 2 (SARS-CoV-2), and the WHO officially named the 
disease caused by SARS-CoV-2 as coronavirus disease 2019 (COVID-19).3 SARS-CoV-2 
infections and the resulting disease, COVID-19, have spread globally and on 11 March 2020, 
the WHO characterized the COVID-19 outbreak as a pandemic.4 On 08 January 2021, the 
Center for Systems Science and Engineering at Johns Hopkins University reported more than 
88 million cases globally, with over 1.9 million deaths from 191 countries. The 
United States has reported 21.6 million cases and over 366,000 deaths.5  Since fall of 2020,
the incidence of COVID-19 illnesses is increasing dramatically in many northern hemisphere 
countries, including the United States, France, Germany, Italy, and the United Kingdom,
raising the specter that as temperatures fall and the “respiratory virus season” starts, cases 
may dramatically increase, potentially overwhelming healthcare infrastructures. This 
possibility highlights the importance of developing a COVID-19 vaccine as quickly as 
possible while ensuring that all safety measures are met.

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Based on Phase 2/3 safety, immunogenicity, and efficacy data, BNT162b2 was shown to be 
effective and has been authorized for temporary or emergency use in multiple countries.
As more data about COVID-19 continue to accrue, the potential duration of protection 
afforded after a wild-type SARS-CoV-2 infection, and by vaccination, remains unknown. In 
addition, mutated SARS-CoV-2 VOCs have started to emerge, for example, B.1.1.7
(also known as 20I/501Y.V1, VOC 202012/01 [UK origin]), B.1.351 (also known as 
20H/501Y.V2 [South Africa origin]), and P.1 (also known as 20J/501Y.V3 [Brazil origin]).6
A prophylactic, RNA-based SARS-CoV-2 vaccine provides one of the most flexible and 
fastest approaches available to immunize against the emerging virus.7,8
The development of an RNA-based vaccine encoding a viral antigen, which is then expressed 
by the vaccine recipient as a protein capable of eliciting protective immune responses, 
provides significant advantages over more traditional vaccine approaches.  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 easy and rapid production and the prospect of 
producing high numbers of vaccination doses within a shorter time period than achieved with 
traditional vaccine approaches.  This capability is pivotal to enable the most effective 
response in outbreak scenarios.7,8
In an attempt to prevent the spread of disease and to control the pandemic, numerous 
COVID-19 vaccine candidates are in development.  Two SARS-CoV-2–RNA lipid 
nanoparticle (RNA-LNP) vaccines based on a platform of nucleoside-modified messenger 
RNA (modRNA, BNT162b2) will be evaluated in this study.  Each vaccine candidate 
expresses 1 of 2 antigens:

Primary and booster studies:  BNT162b2 (variant RBP020.2): modRNA encoding the 
Wuhan-Hu-1 reference1 SARS-CoV-2 full-length, P2 mutant, prefusion spike 
glycoprotein (P2 S) (version 9);

Booster study:  BNT162b2s01 (variant RBP020.11): modRNA as above, but encoding 
the P2 S containing B.1.351 variant–specific mutations (South Africa origin), as a 
representative VOC formerly referred to as BNT162b2SA, hereafter referred to as 
BNT162b2.B.1.351.
In light of the unknowns regarding duration of protection, as well as the emerging VOCs, it is 
important to understand the boostability of BNT162, and potential heterologous protection 
against emerging VOC(s).  To this end, a booster study extension has been added in protocol 
amendment 2 in which a small subset of adult participants who received Doses 1 and 2 at 
30 µg from a designated US lot(s) will receive a single dose of either 30 µg BNT162b2 or
30 µg BNT162b2.B.1.351.

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2.2.1. Clinical Overview
Given clinical data from other similarly formulated unmodified messenger RNA liposomal 
vaccines from BioNTech in oncology trials9 and recent published results from clinical trials 
using modRNA influenza vaccines by Moderna,10 the BNT162 vaccines were expected to 
have a favorable safety profile with mild, localized, and transient effects.  BNT162 vaccines 
based on modRNA have now been administered to humans for the first time in Study 
C4591001 (NCT04368728) and the BNT162-01 study conducted in Germany by BioNTech, 
at doses between 1 µg and 100 µg.  The currently available safety and immunogenicity data 
are presented in the BNT162 IB.11
2.3. Benefit/Risk Assessment
There is an ongoing global pandemic of COVID-19 and, based on the data available from the 
C4591001 study, multiple temporary or emergency use authorizations and conditional 
marketing authorizations have been granted for BNT162b2. The available safety and 
immunogenicity data from the ongoing Pfizer/BioNTech clinical trial combined with 
available nonclinical data with BNT162 vaccines, and data from nonclinical studies and 
clinical trials with the same or related RNA components, or antigens, support a favorable 
benefit/risk profile and support continued clinical development of BNT162b2.
In the C4591001 study, BNT162b2 has been shown to elicit increased local and systemic 
adverse reactions as compared to those in the placebo arm, usually lasting a few days. The 
most common solicited adverse reactions were injection site pain (84.1%), fatigue (62.9%), 
headache (55.1%), muscle pain (38.3%), chills (31.9%), joint pain (23.6%), fever (14.2%),
and injection site swelling (10.5%).11  Adverse reactions characterized as reactogenicity were 
generally mild to moderate. The number of participants reporting hypersensitivity-related 
AEs was numerically higher in the vaccine group compared with the placebo group (137 
[0.63%] vs 111 [0.51%]). Severe adverse reactions occurred in 0.0% to 4.6% of participants, 
were more frequent after Dose 2 than after Dose 1, and were generally less frequent in older 
adults (>55 years of age) (<2.8%) as compared to younger participants (≤4.6%). Among 
reported unsolicited AEs, lymphadenopathy occurred much more frequently in the vaccine 
group than the placebo group and is plausibly related to vaccination. SAEs, while 
uncommon (<1.0%), represented medical events that occur in the general population at 
similar frequency as observed in the study.11
No specific safety concerns were identified in subgroup analyses by age, race, ethnicity, 
medical comorbidities, or prior SARS-CoV-2 infection. Although participants 16 through 
17 years of age were enrolled in the Phase 3 trial, safety data for this age group are limited. 
However, available data are consistent with the safety profile in the adult population, and it is 
biologically reasonable to extrapolate the greater safety experience in adults, in particular 
younger adults, to the oldest pediatric age group of 12 through 17 years.  The potential risks 
are based on the observed safety profile to date, which shows mostly mild reactogenicity, low 
incidence of severe or serious events, and no clinically concerning safety observations. The 
preponderance of severe cases of COVID-19 in the placebo group relative to the BNT162b2 

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group (9 of 10) suggests no evidence of VAED.11  Continued clinical investigation is 
justified given:

the urgent need for the development of a more stable prophylactic vaccine for 
COVID-19,

the threat posed by the increasing number of globally distributed outbreaks of
SARS-CoV-2 infection and emerging VOCs,

the potential of the BioNTech platform of RNA-based vaccines to rapidly deliver high 
numbers of vaccine doses in a single production campaign.
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of BNT162b2 may be found in the IB,11 which is the SRSD for this study.

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2.3.1. Risk Assessment
Identified/Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Study Intervention: BNT162b2 RNA-Based COVID-19 Vaccine
Local and systemic reactions to the vaccine may 
occur (injection site redness, injection site swelling, 
and injection site pain; fever, fatigue, headache, 
chills, muscle pain, and joint pain) following 
vaccination.
These are common adverse reactions seen with 
other vaccines12 as well as the COVID-19 vaccine. 
The most common events reported in the C4591001 
study were mild to moderate pain at the injection 
site, fatigue, and headache.

The study employs the use of a reactogenicity 
e-diary to monitor local reactions and systemic 
events in real time.

All study participants will be observed for at 
least 30 minutes after vaccination.
Safety profile of a novel vaccine not yet fully 
characterized.
Adverse reactions (risks) identified from the 
postauthorization safety data include: 
Anaphylaxis, other hypersensitivity reactions 
(eg, rash, pruritus, urticaria, angioedema), pain in 
extremity (injected arm), vomiting, diarrhea.
Data available from the C4591001 study showed 
low incidence of severe or serious events, and no 
clinically concerning safety observations across the
safety population and within demographic 
subgroups based on age, sex, race/ethnicity, 
country, and baseline SARS-CoV-2 status.
Postauthorization safety data surveillance has 
confirmed the safety profile observed in C4591001 
and has resulted in identification of some additional 
adverse reactions (risks) as noted in this table.

Collection of AE and SAE reports from signing 
of the ICD to 1 month after the second dose of 
vaccine.

DMC throughout the study to review all safety 
data.

All participants will be observed for at least 
30 minutes after vaccination.
Theoretical risk for COVID-19 enhancement.
Disease enhancement has been seen following 
vaccination with RSV, feline coronavirus, and 
Dengue virus vaccines. It is a modified and/or 
severe presentation of an infectious disease 
affecting individuals exposed to the wild-type 
pathogen after having received vaccine designed to 
prevent infection. No evidence of disease 
enhancement has been seen in large-scale clinical
study of BNT162b2 in humans or in 
postauthorization surveillance.
Monitoring for cases of COVID-19 developing 
during the study, which will be reported as AESIs.  
Assessments of individual cases for disease 
enhancement is challenging based on current 
understanding of mechanism of pathogenesis, thus 
evaluations of any adverse or unexpected 
imbalances in severe COVID-19 cases may provide 
insight to a potential signal for this theoretical risk.

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Identified/Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Primary study:  Multisystem inflammatory 
syndrome in children (MIS-C)
Febrile hyperinflammatory condition with 
multisystem (≥2 organs) involvement as defined in 
Section 8.3.8.
MIS-C will be collected as an AESI for the duration 
of study participation.
Study Procedures
Participants will be required to attend healthcare 
facilities during the global SARS-CoV-2 pandemic.
Without appropriate social distancing and PPE, 
there is a potential for increased exposure to 
SARS-CoV-2.

Pfizer will work with sites to ensure 
appropriate COVID-19 prevention strategies.

Monitoring for cases of COVID-19 developing 
during the study, which will be reported as 
AESIs.
Venipuncture will be performed during the study.
There is the risk of bleeding, bruising, hematoma 
formation, and infection at the venipuncture site.
Only appropriately qualified personnel will obtain 
the blood draw.

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2.3.2. Benefit Assessment
Benefits to individual participants may include:
•
Receipt of an efficacious or potentially efficacious COVID-19 vaccine during a global 
pandemic
•
Access to COVID-19 diagnostic testing
•
Contributing to research to help others in a time of global pandemic
2.3.3. Overall Benefit/Risk Conclusion
Taking into account the measures taken to minimize risk to participants participating in this 
study, the potential risks identified in association with BNT162b2 are justified by the 
anticipated benefits that may be afforded to healthy participants.
3. OBJECTIVES, ESTIMANDS, AND ENDPOINTS
3.1. Primary Study
Objectives
Estimands
Endpoints
Primary Immunogenicity – Lot Comparisons
To demonstrate that the immune 
responses induced by BNT162b2 are 
similar across the 3 US lots (Arms 1, 
2, and 3) in participants without 
evidence of SARS-CoV-2 infection 
during the study.
In participants complying with the key 
protocol criteria (evaluable 
participants):
•
GMR from one US lot to another 
lot (Arm 1/Arm 2, Arm 1/Arm 3, 
and Arm 2/Arm 3) 1 month after 
Dose 2
•
Full-length S-binding IgG levels
To demonstrate that the immune 
response induced by the EU lot 
(Arm 4) of BNT162b2 is similar to 
the pooled US lots (Arms 1, 2, 
and 3) in participants without 
evidence of SARS-CoV-2 infection 
during the study.
In participants complying with the key 
protocol criteria (evaluable 
participants):
•
GMR from the EU lot (Arm 4) to 
the pooled US lots (Arm 4/pooled 
Arms 1, 2, and 3) 1 month after 
Dose 2
•
Full-length S-binding IgG levels
Primary Immunogenicity – Dose Comparison
To demonstrate the noninferiority of 
the immune response to prophylactic 
BNT162b2 in participants receiving 
20 μg compared to participants 
receiving the standard 30-μg dose 
(prepared from the same 
manufacturing lot) without evidence 
of SARS-CoV-2 infection during the 
study.
In 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 the 2 dose 
groups 1 month after Dose 2
•
SARS-CoV-2 neutralizing titers
CCI

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Objectives
Estimands
Endpoints
Primary Safety
To evaluate the safety of BNT162b2
when administered on a 2-dose 
schedule in healthy participants 
12 through 50 years of age.
In participants receiving at least 1 dose 
of study intervention from each vaccine 
group (individual and pooled US lots, 
EU lot, 20-µg dose), the percentage of 
participants reporting:

Local reactions for up to 7 days 
following each dose

Systemic events for up to 7 days 
following each dose

AEs and SAEs from Dose 1 to 
1 month after Dose 2

Local reactions (pain at the 
injection site, redness, and 
swelling)

Systemic events (fever, fatigue, 
headache, chills, vomiting, 
diarrhea, new or worsened muscle 
pain, and new or worsened joint 
pain)

AEs

SAEs
Secondary Immunogenicity
To describe the immune responses 
induced by different 30-µg dose 
manufacturing lots of BNT162b2.
In evaluable participants from each 
vaccine group (individual and pooled 
US lots, EU lot):

GMCs at baseline (before Dose 1) 
and 1 month after Dose 2

GMFR from baseline (before Dose 
1) to 1 month after Dose 2

Full-length S-binding IgG levels
To describe the immune responses 
induced by different doses of 
BNT162b2.
In evaluable participants from each 
vaccine group (20 µg and 30 µg from 
the same US lot):

GMCs at baseline (before Dose 1) 
and 1 month after Dose 2

GMFR from baseline (before Dose 
1) to 1 month after Dose 2

SARS-CoV-2 neutralizing titers
Note:  “US lots” refers to lots of study vaccine containing drug substance manufactured in the United States.  
“EU lot” refers to the lot of study vaccine containing drug substance manufactured in Europe.

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3.2. Booster Study
Objectives
Estimands
Endpoints
Primary Safety
To evaluate the safety and 
tolerability profile of a third dose of 
study intervention (either BNT162b2 
30 µg or BNT162b2.B.1.351*30 µg) 
administered to participants 
(18 through 50 years of age) who 
received two 30-µg doses of 
BNT162b2, approximately 3 months 
after Dose 2.
In participants receiving the third dose 
of study intervention, the percentage of 
participants reporting:

Local reactions for up to 7 days 
following the booster dose

Systemic events for up to 7 days 
following the booster dose

AEs and SAEs from the booster 
dose to 1 month after the booster 
dose

Local reactions (pain at the 
injection site, redness, and 
swelling)

Systemic events (fever, fatigue, 
headache, chills, vomiting, 
diarrhea, new or worsened muscle 
pain, and new or worsened joint 
pain)

AEs

SAEs
Primary Immunogenicity
To describe the immune response 
induced by a third dose of study 
intervention (either BNT162b2 
30 µg or BNT162b2.B.1.351*
30 µg).
In evaluable participants from each 
vaccine group (either BNT162b2 30 µg
or BNT162b2.B.1.351 30 µg):

Geometric mean neutralizing titers 
at baseline (before Dose 1), 
1 month after Dose 2, before 
Dose 3, and 1 week after and 
1 month after Dose 3

Geometric mean IgG 
concentrations at baseline (before 
Dose 1), 1 month after Dose 2, 
before Dose 3, and 1 week after 
and 1 month after Dose 3

GMFRs from 1 month after Dose 2 
to 1 week after and 1 month after 
Dose 3 and from before Dose 3 to 
1 week after and 1 month after 
Dose 3

The percentages of participants 
with seroresponse§ (based on 
neutralizing titers) to the reference 
strain at 1 month after Dose 2, 
before Dose 3, and 1 week after 
and 1 month after Dose 3

The percentages of participants 
with seroresponse§ (based on 
neutralizing titers) to the B.1.351
variant strain at 1 month after 
Dose 2, before Dose 3, and 1 week 
after and 1 month after Dose 3

SARS-CoV-2 reference-strain 
neutralizing titer†

SARS-CoV-2 B.1.351-strain
neutralizing titer††

Full-length S-binding IgG levels
* BNT162.B.1.351 = BNT162b2s01 vaccine encoding for the full-length spike protein of South African–origin variant 
B.1.351 (formerly BNT162b2SA).
† SARS-CoV-2 reference-strain neutralizing titers = neutralizing titers against SARS-CoV-2 USA-WA1/2020 virus.
†† SARS-CoV-2 B.1.351-strain neutralizing titers = neutralizing titers against SARS-CoV-2 virus with B.1.351 spike.
§ Seroresponse is defined as ≥4-fold increase from baseline (before Dose 1) to the specified time point. If the baseline 
measurement is below LLOQ, a postvaccination measurement of ≥4 × LLOQ is considered a seroresponse.

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4. STUDY DESIGN
4.1. Overall Design
Primary Study
This is a Phase 3, randomized, observer-blind study to evaluate the safety, tolerability, and 
immunogenicity of 4 manufacturing lots of BNT162b2 as a 30-µg dose and an additional 
20-µg dose arm using one of the same manufactured 30-µg lots.  BNT162b2 is an
RNA-based COVID-19 vaccine, administered on a 2-dose schedule in healthy participants 
12 through 50 years of age.  The study will be conducted in the United States.
Participants will be randomized to 1 of 5 arms in a 2:2:2:1:2 ratio (Arm 1: Arm 2: Arm 3: 
Arm 4: Arm 5), where Arms 1, 2, and 3 contain US-manufactured drug substance for 30-µg 
dosing; Arm 4 contains EU-manufactured drug substance for 30-µg dosing; and Arm 5 
contains US-manufactured drug substance for 20-µg dosing.  In order to allow for balanced
age representation across all arms, the randomization will be stratified by age groups: 
12 through 17, 18 through 30, and 31 through 50 years.
The duration of the study for each participant will be approximately 2 months. This study is 
observer-blinded, as the volumes of the 20-µg and the 30-µg doses of investigational vaccine 
are different.
Approximately 340 participants will be randomly assigned to each of the 3 US lots (Arms 
1-3) and to the 20-µg arm (Arm 5) and approximately 170 participants will be randomly 
assigned to the EU lot (Arm 4), for a total of approximately 1530 randomized participants.  It 
is expected that approximately 1224 evaluable participants will complete the study, based on 
a 20% nonevaluable rate.
Booster Study
Protocol amendment 2 has added a booster study in which a subset of the adult participants
(18 through 50 years of age) who each received two 30-µg doses of the designated US lot(s) 
will be randomly assigned to 1 of 2 arms in a 1:1 ratio (Booster 1: Booster 2), where 
Booster 1 is BNT162b2 at 30 µg and Booster 2 is BNT162b2.B.1.351 at 30 µg. The third 
dose will be administered approximately 3 months after BNT162b2 Dose 2 of the primary 
study.
Approximately 30 participants will be assigned to each arm for a total of 60 participants 
enrolled.  It is expected that approximately 48 evaluable participants will complete the study, 
based on a 20% nonevaluable rate.
The duration of the study for each participant will be approximately 1 month.  This study is 
observer-blinded, to minimize changes in study conduct compared with the primary study.  
This facilitates the start of a booster study with the third dose to be given 3 months after the 
receipt of Dose 2.

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4.2. Scientific Rationale for Study Design
This study contains assessments that could be considered standard for a vaccine study.  
Blood samples taken for immunogenicity will establish the level of immune response elicited 
by each arm to provide the necessary data to meet the primary endpoints of the study. 
Immunogenicity will be assessed by the full-length S-binding IgG assay and 2 SARS-CoV-2 
neutralization assays, one with the reference strain and the second with the B.1.351 strain.
To establish if a participant has asymptomatic SARS-CoV-2 infection, nasal swabs for 
SARS-CoV-2 nucleic acid amplification testing (ie, NAAT) and blood samples to measure 
N-binding antibody levels will be taken.  A positive result on either test will result in the 
immunogenicity data from that participant being excluded from the evaluable portion of the 
study population.  All reactogenicity and safety assessments are standard for a study of this 
nature.
This study will not include a placebo, as the aim and design of this study is not to 
demonstrate efficacy.
Human reproductive safety data are not available for BNT162b2, but there is no suspicion of 
human teratogenicity based on the intended mechanism of action of the compound.
Therefore, the use of a highly effective method of contraception is required (see Appendix 4).
4.3. Justification for Dose
Based on data from the Phase 1 component of clinical trial C4591001, after administration of 
Dose 1 and prior to administration of Dose 2, BNT162b2 showed modest increases in 
SARS-CoV-2 neutralizing GMTs over baseline across dose levels (10 µg, 20 µg, and 30 µg)
in both younger and older groups. Overall, BNT162b2 elicited higher antigen-binding and 
neutralizing responses in younger participants than in older participants. The boost effect 
after receiving Dose 2 was most pronounced at the 30-µg dose level for older participants, 
hence its selection as the dose for Phase 2/3 evaluation.11  These data also support 
investigating the lower dose of 20 µg in this younger study population, as the measured 
immune responses in both the 20-µg and 30-µg cohorts were similar with regard to the 
younger age group.
As this 30-µg dose was approved in multiple countries for EUA, the additional booster dose 
will be administered at the same dose.
4.4. End of Study Definition
A participant is considered to have completed the study if he/she has completed all phases 
(as applicable) of the respective study (primary, booster) into which he/she is enrolled,
including the last visit.
The end of the study is defined as the date of the last visit of the last participant in the booster 
study.

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5. STUDY POPULATION
This study can fulfill its objectives only if appropriate participants are enrolled.  The 
following eligibility criteria are designed to select participants for whom participation in the 
study is considered appropriate.  All relevant medical and nonmedical conditions should be 
taken into consideration when deciding whether a particular participant is suitable for this 
protocol.
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted.
5.1. Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria apply:
Age and Sex:
1. Primary study: Male or female participants between the ages of 12 and 50 years, 
inclusive, at Visit 1 (Day 1).
Booster study: Male or female participants between the ages of 18 and 50 years, 
inclusive, at rerandomization.

Refer to Appendix 4 for reproductive criteria for male (Section 10.4.1) and female 
(Section 10.4.2) participants.
Type of Participant and Disease Characteristics:
2. Participants who are willing and able to comply with all scheduled visits, treatment plan, 
laboratory tests, lifestyle considerations, and other study procedures.
3. Healthy participants who are determined by medical history, physical examination 
(if required), and clinical judgment of the investigator to be eligible for inclusion in the 
study.
Note: Healthy participants with preexisting stable disease, defined as disease not 
requiring significant change in therapy or hospitalization for worsening disease during 
the 6 weeks before enrollment, can be included.
Informed Consent:
4. Capable of giving personal signed informed consent/have parent(s)/legal guardian
capable of giving signed informed consent as described in Appendix 1, which includes 
compliance with the requirements and restrictions listed in the ICD and in this protocol.

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5.2. Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions:
1. Other medical or psychiatric 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. Known infection with HIV, HCV, or HBV.
3. History of severe adverse reaction associated with a vaccine and/or severe allergic 
reaction (eg, anaphylaxis) to any component of the study intervention(s).
4. Previous clinical (based on COVID-19 symptoms/signs alone, if a SARS-CoV-2 NAAT 
result was not available) or microbiological (based on COVID-19 symptoms/signs and a 
positive SARS-CoV-2 NAAT result) diagnosis of COVID-19.
5. Immunocompromised individuals with known or suspected immunodeficiency, as 
determined by history and/or laboratory/physical examination.
6. Bleeding diathesis or condition associated with prolonged bleeding that would, in the 
opinion of the investigator, contraindicate intramuscular injection.
7. Women who are pregnant or breastfeeding.
Prior/Concomitant Therapy:
8. Primary study: Previous vaccination with any coronavirus vaccine.
Booster study: Previous vaccination with any coronavirus vaccine outside of this study.
9. Receipt of medications intended to prevent COVID-19.
10. Individuals who receive treatment with radiotherapy or immunosuppressive therapy, 
including cytotoxic agents or systemic corticosteroids (if systemic corticosteroids are 
administered for ≥14 days at a dose of ≥20 mg/day of prednisone or equivalent), eg, for 
cancer or an autoimmune disease, or planned receipt throughout the study.  
Inhaled/nebulized, intra-articular, intrabursal, or topical (skin or eyes) corticosteroids are 
permitted.
11. Receipt of blood/plasma products or immunoglobulin, from 60 days before study 
intervention administration or planned receipt throughout the study.

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Prior/Concurrent Clinical Study Experience:
12. Participation in other studies involving study intervention within 28 days prior to study 
entry and/or during study participation.
13. Previous participation in other studies involving study intervention containing LNPs.
Other Exclusions:
14. Investigator site staff or Pfizer/BioNTech employees directly involved in the conduct of 
the study, site staff otherwise supervised by the investigator, and their respective family 
members.
Additional Exclusion Criteria Specific to the Booster Study:
1. Current febrile illness (body temperature ≥100.4°F [≥38.0°C]) or other acute illness 
within 48 hours before study intervention administration.
2. Receipt of any seasonal or pandemic influenza vaccine within 14 days, or any other 
nonstudy vaccine within 28 days, before study intervention administration.
3. Anticipated receipt of any seasonal or pandemic influenza vaccine within 14 days, or any 
other nonstudy vaccine within 28 days, after study intervention administration.
4. Receipt of short-term (<14 days) systemic corticosteroids.  Inhaled/nebulized, intra-
articular, intrabursal, or topical (skin or eyes) corticosteroids are permitted.
5.3. Lifestyle Considerations
5.3.1. Contraception
The investigator or his or her designee, in consultation with the participant, will confirm that 
the participant has selected an appropriate method of contraception for the individual 
participant and his or her partner(s) from the permitted list of contraception methods 
(see Appendix 4, Section 10.4.4) and will confirm that the participant has been instructed in 
its consistent and correct use.
At time points indicated in the SoA, the investigator or designee will inform the participant
of the need to use highly effective contraception consistently and correctly and document the 
conversation and the participant’s affirmation in the participant’s chart (participants need to 
affirm their consistent and correct use of at least 1 of the selected methods of contraception).  
In addition, the investigator or designee will instruct the participant to call immediately if the 
selected contraception method is discontinued or if pregnancy is known or suspected in the 
participant or partner.

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5.4. Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study but 
are not subsequently randomly assigned to study intervention. 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 SAEs.
Primary study only:  Individuals who do not meet the criteria for participation in this study 
(screen failure) may be rescreened under a different participant number.
5.5. Criteria for Temporarily Delaying Enrollment/Randomization/Study Intervention 
Administration (Primary Study)
The following conditions are temporary or self-limiting and a participant may be vaccinated 
once the condition(s) has/have resolved and no other exclusion criteria are met.  The booster 
study does not include temporary delay criteria.
1. Current febrile illness (body temperature ≥100.4°F [≥38.0°C]) or other acute illness 
within 48 hours before study intervention administration. This includes current 
symptoms that could represent a potential COVID-19 illness (refer to Section 7.1 for 
further guidance):

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 any seasonal or pandemic influenza vaccine within 14 days, or any other 
nonstudy vaccine within 28 days, before study intervention administration.
3. Anticipated receipt of any seasonal or pandemic influenza vaccine within 14 days, or any 
other nonstudy vaccine within 28 days, after study intervention administration.

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4. Receipt of short-term (<14 days) systemic corticosteroids.  Study intervention 
administration should be delayed until systemic corticosteroid use has been discontinued 
for at least 28 days.  Inhaled/nebulized, intra-articular, intrabursal, or topical (skin or 
eyes) corticosteroids are permitted.
6. STUDY INTERVENTION
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, medical device(s), or study procedure(s) intended to be administered to a study 
participant according to the study protocol.
For the purposes of this protocol, in the primary study, study intervention refers to
BNT162b2, an RNA-based vaccine for immunization against COVID-19.  All 4 production 
lots will be administered at a 30-µg dose and 1 of the lots will also be administered at a 
20-µg dose, with the group names Arms 1, 2, 3, 4, and 5, respectively. The study will 
evaluate a 2-dose (separated by 21 days) schedule in healthy participants 12 through 50 years 
of age.
In the booster study, study intervention refers to BNT162b2 and BNT162b2.B.1.351, 
RNA-based vaccines for immunization against COVID-19.  The study will evaluate a single 
30-µg dose administered 3 months after Dose 2 in the primary study to healthy participants 
18 through 50 years of age.
6.1. Study Intervention(s) Administered
6.1.1. Primary Study
Intervention Name
BNT162b2 
(BNT162 RNA-LNP vaccine utilizing modRNA)
Arm Namea
(group of participants receiving a specific 
vaccine or no vaccine)
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Type
Vaccine
Dose Formulation
modRNA
Unit Dose Strength
250 µg/0.5 mL
Dosage Level
30 µg (Arms 1-4); 20 µg (Arm 5)
Route of Administration
Intramuscular injection
Use
Experimental
IMP or NIMP
IMP
Sourcing
Provided centrally by the sponsor
Packaging and Labeling
Study intervention will be provided in a single-dose glass vial. 
Each vial will be labeled as required per country requirement.
a.
Arms 1, 2, and 3 contain US-manufactured drug substance; Arm 4 contains EU-manufactured drug 
substance; Arm 5 contains US-manufactured drug substance from one of the US lots in the study.

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6.1.2. Booster Study
Intervention Names
BNT162b2a
BNT162.B.1.351 (BNT162b2s01)b
(BNT162 RNA-LNP vaccine utilizing modRNA)
Arm Namea
(group of participants receiving a specific 
vaccine or no vaccine)
Booster 1: BNT162b2
Booster 2: BNT162.B.1.351
Type
Vaccine
Dose Formulation
modRNA
Unit Dose Strength
250 µg/0.5 mL
Dosage Level
30 µg 
Route of Administration
Intramuscular injection
Use
Experimental
IMP or NIMP
IMP
Sourcing
Provided centrally by the sponsor
Packaging and Labeling
Study intervention will be provided in a single-dose glass 
vial.  Each vial will be labeled as required per country 
requirement.
a.
Reference vaccine.
b.
Vaccine with B.1.351 variant–specific mutations. Study intervention label is BNT162b2s01.
6.1.3. Administration
Primary study:  Participants will receive 1 dose of study intervention as randomized at each 
vaccination visit (Visits 1 and 2) separated by 21 days in accordance with the study’s SoA.  
Full details are described in the IP manual.
Booster study: Participants will receive 1 dose of study intervention based on
rerandomization at the vaccination visit (Visit 4).  Participants will be assigned 1 vial of
either BNT162b2 (Booster 1) or BNT162b2.B.1.351 (Booster 2). All participants will 
receive a total dose of 30 µg.
Full details are described in the IP manual.
Study intervention should be administered intramuscularly into the deltoid muscle, preferably 
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 interventions should be performed by an appropriately qualified, 
GCP-trained, and vaccine-experienced member of the study staff (eg, physician, nurse, 

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physician’s assistant, nurse practitioner, pharmacist, or medical assistant) as allowed by 
local, state, and institutional guidance.
Study intervention administration details will be recorded on the CRF.
6.2. Preparation/Handling/Storage/Accountability
1. The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study interventions received and any discrepancies are 
reported and resolved before use of the study intervention.
2. Only participants enrolled in the study may receive study intervention and only 
authorized site staff may supply or administer study intervention. All study interventions
must be stored in a secure, environmentally controlled, and monitored (manual or 
automated recording) area in accordance with the labeled storage conditions with access 
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 days must indicate the minimum and maximum 
temperatures since previously documented for all site storage locations upon return to 
business.
3. Any excursions from the study intervention label storage conditions should be reported to 
Pfizer upon discovery along with any 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 IP 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 study intervention accountability, reconciliation, and record maintenance 
(ie, receipt, reconciliation, and final disposition records), such as the IPAL or 
sponsor-approved equivalent. All study interventions will be accounted for using a study 
intervention accountability form/record.
8. Further guidance and information for the final disposition of unused study interventions 
are provided in the IP manual. All destruction must be adequately documented.  If 
destruction is authorized to take place at the investigator site, the investigator must ensure 
that the materials are destroyed in compliance with applicable environmental regulations, 
institutional policy, and any special instructions provided by Pfizer.

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Upon identification of a product complaint, notify the sponsor within 1 business day of 
discovery as described in the IP manual.
6.2.1. Preparation and Dispensing
See the IP manual for detailed instructions on how to prepare the study intervention for 
administration.  Study intervention should be prepared and dispensed by an appropriately 
qualified and experienced member of the study staff (eg, physician, nurse, physician’s 
assistant, nurse practitioner, pharmacy assistant/technician, or pharmacist) as allowed by 
local, state, and institutional guidance.  A second staff member will verify the preparation 
and dispensing.
Study intervention will be prepared by qualified unblinded site personnel according to the IP 
manual.  The study intervention will be administered in such a way to ensure the participants 
remain blinded.
6.3. Measures to Minimize Bias: Randomization and Blinding
6.3.1. Allocation to Study Intervention
Allocation (randomization) of participants to vaccine groups will proceed through the use of 
an IRT 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 participant number.  The site personnel will then be 
provided with a vaccine assignment and randomization number.  The IRT system will 
provide a confirmation report containing the participant number, randomization number, and 
study intervention allocation assigned.  The confirmation report must be stored in the site’s 
files.
The study-specific IRT reference manual and IP manual will provide the contact information 
and further details on the use of the IRT system.
6.3.2. Blinding of Site Personnel
Primary study:  Because the volumes of the 20-µg and the 30-µg doses of the investigational 
vaccine are different, this study is observer-blinded, which requires the study staff receiving, 
storing, dispensing, preparing, and administering the study interventions to be unblinded.
Booster study:  To align with the primary study, this study is observer-blinded, which 
requires the study staff receiving, storing, dispensing, preparing, and administering the study 
interventions to be unblinded.
All other study and site personnel, including the investigator, investigator staff, and 
participants, will be blinded to study intervention assignments.  In particular, the individuals 
who evaluate participant safety will be blinded.
The responsibility of the unblinded dispenser and administrator must be assigned to an 
individual or individuals who will not participate in the evaluation of any study participants.  

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Contact between the unblinded dispenser and study participants and unblinded administrator 
and study participants should be kept to a minimum.  The remaining site personnel must not 
know study intervention assignments.
In the event of a Quality 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 
accurately.
6.3.3. Blinding of the Sponsor
The majority of sponsor staff will be blinded to study intervention allocation.  The blinded 
study team will become unblinded to the primary study randomization information at the 
time of the database release of the primary study. These same study team members will 
remain blinded to the randomization information for the booster study until completion of 
that phase.
All laboratory testing personnel performing serology assays will remain blinded to study 
intervention assigned/received throughout the testing for the primary study and for the 
booster study, respectively.  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 administration are fulfilled at the 
site will be unblinded for the duration of the study (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 any other study-related activities will review unblinded protocol deviations.
6.3.4. Breaking the Blind
All study participants will receive BNT162b2; blinding refers only to which vaccine lot or 
vaccine dose (primary study) or to which vaccine (booster study) the participant will receive.  
The IRT will be programmed with blind-breaking instructions.  In case of an emergency, the 
investigator has the sole responsibility for determining if unblinding of a participant’s study 
intervention assignment is warranted.  Participant safety must 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 participant’s vaccine assignment unless this could delay further management of 
the participant.  If a participant’s vaccine assignment is unblinded, the sponsor must be 
notified within 24 hours after breaking the blind.  The date and reason that the blind was 
broken must be recorded in the source documentation and CRF.
The study-specific IRT reference manual and IP manual will provide the contact information 
and further details on the use of the IRT system.

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6.4. Study Intervention Compliance
When participants are dosed at the site, they will receive study intervention directly from the 
investigator or designee, under medical supervision.  The date and time of each dose 
administered in the clinic will be recorded in the source documents and recorded in the CRF.  
The dose of study intervention and study participant identification will be confirmed at the 
time of dosing by a member of the study site staff other than the person administering the 
study intervention.
6.5. Concomitant Therapy
The following concomitant medications and vaccinations will be recorded in the CRF:

All vaccinations received from 28 days prior to study enrollment until the 1-month 
follow-up visit (Visit 3, primary study/Visit 6, booster study).

Prohibited vaccines and medications listed in Section 6.5.1 will be recorded, to include 
start and stop dates, name of the medication, dose, unit, route, and frequency.
6.5.1. Prohibited During the Study
Receipt of the following vaccines and medications during the time periods listed below may 
exclude a participant from the per-protocol analysis from that point onwards and, in the 
primary study, may require vaccinations to be discontinued in that participant; however, it is 
anticipated that the participant would not be withdrawn from the study (see Section 7).  
Medications should not be withheld if required for a participant’s medical care.

Unless considered medically necessary, no vaccines other than study intervention should 
be administered within 28 days before and 28 days after each study vaccination.  One 
exception to this is that seasonal and pandemic influenza vaccine can be given at least 
14 days after, or at least 14 days prior to, the administration of study intervention.

Receipt of chronic systemic treatment with known immunosuppressant medications, or 
radiotherapy, within 60 days before enrollment through conclusion of the study.

Receipt of systemic corticosteroids (≥20 mg/day of prednisone or equivalent) for 
≥14 days is prohibited from 28 days prior to enrollment to Visit 3, primary study/Visit 6,
booster study.

Receipt of blood/plasma products or immunoglobulins within 60 days before enrollment 
through conclusion of the study.

Receipt of any other (nonstudy) coronavirus vaccine at any time prior to or during study 
participation is prohibited.

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
Receipt of prophylactic medications intended to prevent symptoms associated with 
COVID-19.  However, if a participant is taking a medication for another condition, even 
if it may have such properties, it should not be withheld prior to study vaccination.

Prophylactic antipyretics and other pain medication to prevent symptoms associated with 
study intervention administration are not permitted.  However, if a participant is taking a 
medication for another condition, even if it may have antipyretic or pain-relieving 
properties, it should not be withheld prior to study vaccination.
6.5.2. Permitted During the Study
The use of antipyretics 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.
6.6. Dose Modification
Not applicable for this study.
6.7. Intervention After the End of the Study (Primary Study)
If the 20-µg dose group (Arm 5) is found to have a suboptimal immune response, as 
determined by the sponsor, this group will be offered a single 30-µg dose outside of the 
study.
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL
7.1. Discontinuation of Study Intervention (Primary Study)
In rare instances, it may be necessary for a participant to permanently discontinue study 
intervention (definitive discontinuation). Reasons for definitive discontinuation of study 
intervention include the following: AEs; participant request; investigator request; pregnancy; 
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 participant does not wish to receive it, it is preferred that the second 
dose be administered.
* A positive SARS-CoV-2 NAAT result without symptoms or a COVID-19 diagnosis 
(signs/symptoms only or signs/symptoms and a positive SARS-CoV-2 NAAT result) should 
not result in discontinuation of study intervention.  If study intervention (Dose 2) has been 
delayed per Section 5.5, because of febrile or other acute illness (Item 1 in the list in 
Section 5.5), and the investigator later diagnoses the signs and symptoms as COVID-19 (with 

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or without a positive SARS-CoV-2 NAAT result), the participant should not be discontinued 
from any further doses of study intervention.
Note that discontinuation of study intervention does not represent withdrawal from the study.
Per the study estimands, if study intervention is definitively discontinued, the participant will 
remain in the study to be evaluated for safety and immunogenicity. See the SoA for data to 
be collected at the time of discontinuation of study intervention and follow-up for any further 
evaluations that need to be completed.
In the event of discontinuation of study intervention, it must be documented on the 
appropriate CRF/in the medical records whether the participant is discontinuing further 
receipt of study intervention or also from study procedures, postvaccination study follow-up, 
and/or future collection of additional information.
7.2. Participant Discontinuation/Withdrawal From the Study
A participant may withdraw from the study at any time at his/her own request.  Reasons for 
discontinuation from the study include the following:

Refused further follow-up;

Lost to follow-up;

Death;

Study terminated by sponsor;

AEs;

Participant request; 

Investigator request;

Protocol deviation.
If a participant 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.  In 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 the CRF 
for all participants.
If a participant withdraws from the study, he/she may request destruction of any remaining 
samples taken and not tested, and the investigator must document any such requests in the 
site study records and notify the sponsor accordingly.

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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 any of the withdrawal/early termination procedures will not be 
viewed as protocol deviations so long as the participant’s safety was preserved.
7.2.1. Withdrawal of Consent
Participants 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 only 
exception to this is when a participant specifically withdraws consent for any further contact 
with him or her or persons previously authorized by the participant to provide this 
information.  Participants should notify the investigator in writing of the decision to 
withdraw consent from future follow-up, whenever possible.  The withdrawal of consent 
should be explained in detail in the medical records by the investigator, as to whether the 
withdrawal is only from further receipt of study intervention or also from study procedures 
and/or postvaccination study follow-up, and entered on the appropriate CRF page.  In 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 appropriately directed 
in accordance with local law.
7.3. Lost to Follow-up
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.
The following actions must be taken if a participant fails to attend a required study visit:

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 participant’s medical record;

Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study.

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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.
The full date of birth will be collected to critically evaluate the immune response and safety 
profile by age.
Study procedures and their timing are summarized in the SoA. Protocol waivers or 
exemptions are not allowed.
Safety issues should be discussed with the sponsor immediately upon occurrence or 
awareness to determine whether the participant should continue or discontinue study 
intervention.
Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct.
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable.
Every effort should be made to ensure that protocol-required tests and procedures are 
completed as described.  However, it is anticipated that from time to time there may be 
circumstances outside the control of the investigator that may make it unfeasible to perform 
the test.  In these cases, the investigator must take all steps necessary to ensure the safety 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 any corrective and preventive 
actions that he or she has taken to ensure that required processes are adhered to as soon as 
possible.  The study team must be informed of these incidents in a timely manner.
For samples being collected and shipped, detailed collection, processing, storage, and 
shipment instructions and contact information will be provided to the investigator site prior 
to initiation of the study.
The total blood sampling volume for individual participants in the primary study is 
approximately 20 mL for participants 12 through 15 years and 40 mL for participants 
≥16 years of age.  The total blood sampling volume for individual participants in the booster 
study is approximately 150 mL for each participant.  Additional blood samples may be taken 
for safety assessments at times specified by Pfizer, provided the total volume taken during 
the study does not exceed 550 mL during any period of 60 consecutive days.
8.1. Immunogenicity Assessments
Serum samples will be obtained for immunogenicity testing at the visits specified in the SoA. 
The tests to be performed will be the full-length S-binding IgG-concentration assay and 

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measurement of SARS-CoV-2 neutralizing titers.  For the primary study, full-length 
S-binding IgG concentrations will be measured for the lot-comparison analyses on all eligible 
samples. Testing for SARS-CoV-2 reference-strain neutralizing titers will be performed on 
all eligible samples for the dose-comparison analysis.  For the booster study, testing for both 
SARS-CoV-2 reference-strain and B.1.351-strain neutralizing titers and full-length S-binding 
IgG concentrations will be performed on all eligible samples.  Note that all immunogenicity 
analyses will be based upon samples analyzed at the central laboratory.
Nasal (midturbinate) swabs at the visits specified in the SoA will be obtained as one of the 
determinations for participants to be included in the evaluable immunogenicity analysis.  
These samples will be tested at the central laboratory using an RT-PCR test (Cepheid, an
NAAT; FDA approved under EUA) to detect SARS-CoV-2.  Another determination for 
participants to be included in the evaluable immunogenicity analysis is the N-binding 
antibody assay.  Blood samples will be taken at visits specified in the SoA and analyzed at 
the central laboratory.  A positive result on either test will result in the immunogenicity data 
from that participant being excluded from the evaluable portion of the study population.  
However, administration of study intervention is not dependent on these test results, which 
will only be available after the study has ended.
8.1.1. 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 assays outlined in the protocol 
may be stored by Pfizer.  Unless a time limitation is required by local regulations or ethical 
requirements, the samples will be stored for up to 15 years after the end of the study and then 
destroyed.  If allowed by the ICD, stored samples may be used for additional testing to better 
understand the immune responses to the vaccine(s) under study in this protocol, to inform the 
development of other products, and/or for vaccine-related assay work supporting vaccine 
programs.  No testing of the participant’s DNA will be performed.
The participant may request that his or her samples, if still identifiable, be destroyed at any 
time; however, any data already collected from those samples will still be used for this 
research.  The biological samples may be shared with other researchers as long as 
confidentiality is maintained and no testing of the participant’s DNA is performed.
8.2. Safety Assessments
Planned time points for all safety assessments are provided in the SoA.  Unscheduled clinical 
laboratory measurements may be obtained at any time during the study to assess any 
perceived safety issues.
A clinical assessment, including medical history, will be performed on all participants at their
first visit to establish a baseline.  Significant medical history and observations from any 
physical examination, if performed, will be documented in the CRF.
AEs and SAEs are collected, recorded, and reported as defined in Section 8.3.

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Acute reactions within the first 30 minutes will be assessed and documented in the AE CRF.
The safety parameters also include reactogenicity e-diary reports of local reactions, systemic 
events (including fever), and use of antipyretic medication that occur in the 7 days after 
administration of the study intervention.  These prospectively self-collected occurrences of 
local reactions and systemic events are graded as described in Section 8.2.2.
8.2.1. Clinical Safety Laboratory Assessments
Clinical safety laboratory assessments will not be collected in this study.
See Section 10.5, Appendix 5, for suggested actions and follow-up assessments in the event 
of potential DILI.
8.2.2. Electronic Diary
Participants will be required to complete a reactogenicity e-diary through an application 
installed on a provisioned device or on the participant’s own personal device.  All 
participants will be asked to monitor and record local reactions, systemic events, and 
antipyretic medication usage for 7 days from the day of administration of the study 
intervention.  The reactogenicity e-diary allows recording of these assessments only within a 
fixed time window, thus providing the accurate representation of the participant’s experience 
at that time.  Data on local reactions and systemic events reported in the reactogenicity 
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.
At intervals agreed to by the vendor and Pfizer, these data will be transferred electronically 
into Pfizer's database for analysis and reporting.  Generally, 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 safety review.
The investigator or designee must obtain stop dates from the participant for any ongoing 
local reactions, systemic events, or use of antipyretic medication on the last day that the 
reactogenicity e-diary was completed.  The stop dates should be documented in the source 
documents and the information entered in the CRF.
8.2.2.1. 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 grading scales for 
healthy adult volunteers enrolled in preventive vaccine clinical trials.12
8.2.2.2. Local Reactions
During the reactogenicity e-diary reporting period, participants will be asked to assess 
redness, swelling, and pain at the injection site and to record the symptoms in the 

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reactogenicity e-diary.  If a local reaction persists beyond the end of the reactogenicity 
e-diary period following vaccination, the participant will be requested to report that 
information.  The investigator will enter this additional information in the CRF.
Redness and swelling will be measured and recorded in measuring device units 
(range: 1 to 21) and then categorized during analysis as absent, mild, moderate, or severe 
based on the grading scale in Table 1.  Measuring device units can be converted to 
centimeters according to the following formula: 1 measuring device unit = 0.5 cm.  Pain at 
the injection site will be assessed by the participant as absent, mild, moderate, or severe 
according the grading scale in Table 1.
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 clinically 
indicated.  Only an investigator or medically 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.
Table 1.
Local Reaction Grading Scale
Mild
(Grade 1)
Moderate
(Grade 2)
Severe
(Grade 3)
Potentially Life 
Threatening
(Grade 4)
Pain at the 
injection site
Does not interfere 
with activity
Interferes with activity
Prevents daily 
activity
Emergency room visit 
or hospitalization for 
severe pain
Redness
>2.0 cm to 5.0 cm 
(5 to 10 measuring 
device units)
>5.0 cm to 10.0 cm 
(11 to 20 measuring 
device units)
>10 cm 
(≥21 measuring 
device units)
Necrosis or exfoliative 
dermatitis
Swelling
>2.0 cm to 5.0 cm 
(5 to 10 measuring 
device units)
>5.0 cm to 10.0 cm 
(11 to 20 measuring 
device units)
>10 cm 
(≥21 measuring 
device units)
Necrosis
8.2.2.3. Systemic Events
During the reactogenicity e-diary reporting period, participants will be asked to assess 
vomiting, diarrhea, headache, fatigue, chills, new or worsened muscle pain, and new or 
worsened joint pain and to record the symptoms in the reactogenicity e-diary.  The symptoms 
will be assessed by the participant as absent, mild, moderate, or severe according to the 
grading scale in Table 2.
If a Grade 3 systemic event is reported in the reactogenicity e-diary, a telephone contact 
should occur to ascertain further details and determine whether a site visit is clinically 
indicated.  Only an investigator or medically qualified person is able to classify a 
participant’s systemic event as Grade 4.  If a participant experiences a confirmed Grade 4 
systemic event, the investigator must immediately notify the sponsor and, if it is determined 

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to be related to the administration of the study intervention, further vaccinations will be 
discontinued in that participant.
Table 2.
Systemic Event Grading Scale
Mild 
(Grade 1)
Moderate 
(Grade 2)
Severe 
(Grade 3)
Potentially Life 
Threatening 
(Grade 4)
Vomiting
1-2 times in 
24 hours
>2 times in 
24 hours
Requires IV 
hydration
Emergency room visit 
or hospitalization for 
hypotensive shock
Diarrhea
2 to 3 loose stools 
in 24 hours
4 to 5 loose stools 
in 24 hours
6 or more loose stools 
in 24 hours
Emergency room visit 
or hospitalization for 
severe diarrhea
Headache
Does not interfere 
with activity
Some interference 
with activity
Prevents daily routine 
activity
Emergency room visit 
or hospitalization for 
severe headache
Fatigue/tiredness
Does not interfere 
with activity
Some interference 
with activity
Prevents daily routine 
activity
Emergency room visit 
or hospitalization for 
severe fatigue
Chills
Does not interfere 
with activity
Some interference 
with activity
Prevents daily routine 
activity
Emergency room visit 
or hospitalization for 
severe chills
New or worsened 
muscle pain
Does not interfere 
with activity
Some interference 
with activity
Prevents daily routine 
activity
Emergency room visit 
or hospitalization for 
severe new or worsened 
muscle pain
New or worsened 
joint pain
Does not interfere 
with activity
Some interference 
with activity
Prevents daily routine 
activity
Emergency room visit 
or hospitalization for 
severe new or worsened 
joint pain
Abbreviation: IV = intravenous.
During the 7 days following each vaccination, potential COVID-19 symptoms that overlap 
with solicited systemic events (ie, fever, chills, new or increased muscle pain, diarrhea, 
vomiting) should be assessed by the investigator.
If, in the investigator’s opinion, the symptoms are considered more likely to be vaccine 
reactogenicity, but a participant is required to demonstrate that they are SARS-CoV-2–
negative, a local SARS-CoV-2 test may be performed: if positive, the symptoms should be 
recorded as an AE rather than as systemic events in the reactogenicity e-diary.
8.2.2.4. Fever
In order to record information on fever, a thermometer will be given to participants with 
instructions on how to measure oral temperature at home.  Temperature will be collected in 
the reactogenicity e-diary in the evening daily during the reactogenicity e-diary reporting 
period.  It will also be collected at any time during the reactogenicity e-diary data collection 

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periods when fever is suspected.  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 programmatically converted to degrees Celsius and 
then categorized according to the scale shown in Table 3 during analysis.
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.  Only an investigator or medically qualified person is able to confirm a 
participant’s fever as >40.0°C (>104.0°F).  If a participant experiences a confirmed fever 
>40.0°C (>104.0°F), the investigator must immediately notify the sponsor and, if it is 
determined to be related to the administration of the study intervention, further vaccinations 
will be discontinued in that participant.
Table 3.
Scale for 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)
8.2.2.5. Antipyretic/Analgesic Medication
The use of antipyretic/analgesic medication to treat symptoms 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. Pregnancy Testing
Pregnancy tests may be urine or serum tests, but must have a sensitivity of at least 
25 mIU/mL.  Pregnancy tests will be performed in WOCBP at the times listed in the SoA, 
immediately before the administration of each vaccine dose.  A negative pregnancy test result 
will be required prior to the participant’s receiving the study intervention.  Pregnancy tests 
may also be repeated if requested by IRBs/ECs or if required by local regulations.  In the 
case of a positive confirmed pregnancy, the participant will be withdrawn from 
administration of study intervention but may remain in the study.
8.3. Adverse Events and Serious Adverse Events
The definitions of an AE and an SAE can be found in Appendix 3.
AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, or 
the participant's parent(s)/legal guardian).

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The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible to pursue 
and obtain adequate information both to determine the outcome and to assess whether the 
event meets the criteria for classification as an SAE or caused the participant to discontinue 
the study intervention (see Section 7.1).
Each participant/parent(s)/legal guardian will be questioned about the occurrence of AEs in a 
nonleading manner.
In addition, the investigator may be requested by Pfizer Safety to obtain specific follow-up 
information in an expedited fashion.
8.3.1. Time Period and Frequency for Collecting AE and SAE Information
During the primary study, the time period for actively eliciting and collecting AEs and SAEs 
(“active collection period”) for each participant begins from the time the 
participant/parent(s)/legal guardian provides informed consent, which is obtained before the 
participant’s participation in the study (ie, before undergoing any study-related procedure 
and/or receiving study intervention), through and including Visit 3 (1-month follow-up).  In 
addition, any AEs occurring up to 48 hours after the blood draw and nasal swab collection at 
Visit 3 must be recorded in the CRF.
During the booster study, the time period for actively eliciting and collecting AEs and SAEs 
(“active collection period”) for each participant begins from the time the participant provides 
informed consent, which is obtained before the participant’s enrollment into the booster 
study at Visit 4 (ie, before undergoing any study-related procedure and/or receiving study 
intervention), through and including Visit 6 (1-month follow-up).  In addition, any AEs 
occurring up to 48 hours after the blood draw and nasal swab collection at Visit 6 must be 
recorded in the CRF.
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 assessment.
For participants who are screen failures, the active collection period ends when screen failure 
status is determined.
If the participant withdraws from the study and also withdraws consent for the collection of 
future information, the active 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 Reporting Form.
Investigators are not obligated to actively seek AEs or SAEs after the participant has 
concluded study participation.  However, if the investigator learns of any SAE, including a 
death, at any time after a participant has completed the study, and he/she considers the event 

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to be reasonably related to the study intervention, the investigator must promptly report the 
SAE to Pfizer using the Vaccine SAE Reporting Form.
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 Reporting Form immediately 
upon awareness and under no circumstance should this exceed 24 hours, as indicated in 
Appendix 3. The investigator will submit any updated SAE data to the sponsor within 
24 hours of it being available.
8.3.1.2. Recording Nonserious AEs and SAEs on 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.
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 3.
Care will be taken not to introduce bias when detecting AEs and/or SAEs.  Open-ended and 
nonleading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences.
8.3.3. Follow-up of AEs and SAEs
After the initial AE/SAE report, the investigator is required to proactively 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.  Any 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 3.
8.3.4. 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 safety of participants and the safety of a 
study intervention under clinical investigation are met.

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The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation.  The 
sponsor will comply with country-specific regulatory requirements relating to safety 
reporting to the regulatory authority, IRBs/ECs, and investigators.
Investigator safety reports must be prepared 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 review 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. Exposure During Pregnancy or Breastfeeding, and Occupational Exposure
Exposure to the study intervention under study during pregnancy or breastfeeding and 
occupational exposure are reportable to Pfizer Safety within 24 hours of investigator 
awareness.
8.3.5.1. Exposure During Pregnancy
An EDP occurs if: 

A female participant is found to be pregnant while receiving or after discontinuing study 
intervention.

A male participant who is receiving or has discontinued study intervention exposes a 
female partner prior to or around the time of conception.

A female is found to be pregnant while being exposed or having been exposed to study 
intervention due to environmental exposure. Below are examples of environmental 
exposure during pregnancy:

A female family member or healthcare provider reports that she is pregnant after 
having been exposed to the study intervention by inhalation or skin contact.

A male family member or healthcare provider who has been exposed to the study 
intervention by inhalation, or skin contact then exposes his female partner prior to or 
around the time of conception.
The investigator must report EDP to Pfizer Safety within 24 hours of the investigator’s 
awareness, irrespective of whether an SAE has occurred. The initial information submitted 
should include the anticipated date of delivery (see below for information related to 
termination of pregnancy).

If EDP occurs in a participant or a participant’s partner, the investigator must report 
this information to Pfizer Safety on the Vaccine SAE Reporting Form and an EDP 
Supplemental Form, regardless of whether an SAE has occurred. Details of the 

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pregnancy will be collected after the start of study intervention and until 1 month
after the last dose of study intervention.

If EDP occurs in the setting of environmental exposure, the investigator must report 
information to Pfizer Safety using the Vaccine SAE Reporting Form and EDP 
Supplemental Form. Since the exposure information does not pertain to the 
participant enrolled in the study, the information is not recorded on a CRF; however, 
a copy of the completed Vaccine SAE Reporting Form is maintained in the ISF.
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 Safety 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 
integrity of the terminated fetus should be assessed by gross visual inspection (unless 
preprocedure test findings are conclusive for a congenital anomaly 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 anomaly), the investigator should follow the procedures 
for reporting SAEs. Additional information about pregnancy outcomes that are reported to 
Pfizer Safety 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 delays). In the case of paternal exposure, the 
investigator will provide the participant with the Pregnant Partner Release of Information 
Form to deliver to his partner.  The investigator must document in the source documents that 
the participant was given the Pregnant Partner Release of Information Form to provide to his 
partner.
8.3.5.2. Exposure During Breastfeeding
An exposure during breastfeeding occurs if: 

A female participant is found to be breastfeeding while receiving or after 
discontinuing study intervention.

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
A female is found to be breastfeeding while being exposed or having been exposed to 
study intervention (ie, environmental exposure). An example of environmental 
exposure during breastfeeding is a female family member or healthcare provider who 
reports that she is breastfeeding after having been exposed to the study intervention 
by inhalation or skin contact.
The investigator must report exposure during breastfeeding to Pfizer Safety 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 ISF.
An exposure during breastfeeding report is not created when a Pfizer drug specifically 
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, family members, and other roles that are involved in the 
trial participant’s care.
The investigator must report occupational exposure to Pfizer Safety within 24 hours of the 
investigator’s awareness, regardless of whether there is an associated SAE.  The information 
must be reported using the Vaccine SAE Reporting Form.  Since the information does not 
pertain to a participant enrolled in the study, the information is not recorded on a CRF; 
however, a copy of the completed Vaccine SAE Reporting Form is maintained in the ISF.
8.3.6. Cardiovascular and Death Events
Not applicable.
8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as AEs 
or SAEs
Not applicable.
8.3.8. Adverse Events of Special Interest
This section provides information on AESIs that may be detected during the study:

Confirmed COVID-19 diagnosis (clinical signs/symptoms and positive SARS-CoV-2 
NAAT test)

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
Clinically confirmed cases of MIS-C13 defined as follows:

An individual <21 years of age presenting with fever (≥38.0°C for ≥24 hours or 
report of subjective fever lasting ≥24 hours), AND

Laboratory evidence of inflammation (based on local laboratory ranges) including, 
but not limited to, one or more of the following: an elevated CRP, ESR, fibrinogen, 
procalcitonin, D-dimer, ferritin, LDH, or IL-6, elevated neutrophils, reduced 
lymphocytes, and low albumin; AND

Evidence of clinically severe illness requiring hospitalization, with multisystem (>2) 
organ involvement (cardiac, renal, respiratory, hematologic, gastrointestinal,
dermatologic, or neurological); AND

No alternative plausible diagnoses; AND

Positive for current or recent SARS-CoV-2 infection by NAAT (RT-PCR), serology, 
or antigen test; or COVID-19 exposure within the 4 weeks prior to the onset of 
symptoms
All AESIs must be reported as an AE or SAE following the procedures described in
Section 8.3.1 through Section 8.3.4. An AESI is to be recorded as an AE or SAE on the 
CRF. In addition, an AESI that is also an SAE must be reported using the Vaccine SAE 
Reporting Form.
8.3.8.1. Lack of Efficacy
Lack of efficacy is reportable to Pfizer Safety only if associated with an SAE.
8.3.9. Medical Device Deficiencies
Not applicable.
8.3.10. Medication Errors
Medication errors may result from the administration or consumption of the study 
intervention by the wrong participant, or at the wrong time, or at the wrong dosage strength.
Exposures to the study intervention under study may occur in clinical trial settings, such as 
medication errors.
Safety Event
Recorded on the CRF
Reported on the Vaccine SAE 
Reporting Form to Pfizer Safety 
Within 24 Hours of Awareness
Medication errors 
All (regardless of whether 
associated with an AE)
Only if associated with an SAE

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Medication errors include:

Medication errors involving participant exposure to the study intervention;

Potential medication errors or uses outside of what is foreseen in the protocol that do or 
do not involve the study participant;

The administration of expired study intervention;

The administration of an incorrect study intervention;

The administration of an incorrect dosage;

The administration of study intervention that has undergone temperature excursion from 
the specified storage range, unless it is determined by the sponsor that the study 
intervention under question is acceptable for use.
Such medication errors occurring to a study participant are to be captured on the medication 
error page of the CRF, which is a specific version of the AE page.
In the event of a medication dosing error, the sponsor should be notified within 24 hours.
Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error is recorded on the medication error page of the CRF and, if 
applicable, any associated AE(s), serious and nonserious, are recorded on the AE page of the 
CRF.
Medication errors should be reported to Pfizer Safety within 24 hours on a Vaccine SAE 
Reporting Form only when associated with an SAE.
8.4. Treatment of Overdose
For this study, any dose of study intervention greater than 1 dose of study intervention within 
a 24-hour time period will be considered an overdose.
Pfizer does not recommend specific treatment for an overdose.
In the event of an overdose, the investigator should:
1. Contact the medical monitor within 24 hours.
2. Closely monitor the participant for any AEs/SAEs.
3. Document the quantity of the excess dose as well as the duration of the overdose in 
the CRF.
4. Overdose is reportable to Safety only when associated with an SAE.

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Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the medical monitor based on the clinical evaluation of the participant.
8.5. Pharmacokinetics
Pharmacokinetic parameters are not evaluated in this study.
8.6. Pharmacodynamics
Pharmacodynamic parameters are not evaluated in this study.
8.7. Genetics
Genetics (specified analyses) are not evaluated in this study.
8.8. Biomarkers
Biomarkers are not evaluated in this study.
8.9. Immunogenicity Assessments
Immunogenicity assessments are described in Section 8.1.
8.10. Health Economics
Health economics/medical resource utilization and health economics parameters are not 
evaluated in this study.
8.11. Study Procedures
8.11.1. Visit 1 – Vaccination 1 (Day 1)
Before enrollment and before any study-related procedures are performed, voluntary, written, 
study-specific informed consent will be obtained from the participant or his/her 
parent(s)/legal guardian, as appropriate.  Each signature on the ICD must be personally dated 
by the signatory.  The investigator or his or her designee will also sign the ICD.  A copy of 
the signed and dated ICD must be given to the participant/parent(s)/legal guardian.  The 
source data must reflect that the informed consent was obtained before participation in the 
study.
It is anticipated that the procedures below will be conducted in a stepwise manner. The visit 
may be conducted across 2 consecutive days; if so, all steps from assessing the inclusion and 
exclusion criteria onwards must be conducted on the same day.

Assign a single participant number using the IRT system.

Obtain the participant’s demography (including date of birth, sex, race, and ethnicity).  
The full date of birth will be collected to critically evaluate the immune response and 
safety profile by age.

Obtain any medical history of clinical significance.

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
Perform a clinical assessment. If the clinical assessment indicates that a physical 
examination is necessary to comprehensively evaluate the participant, perform a physical 
examination and record any findings in the source documents and, if clinically 
significant, record on the medical history CRF.

Measure the participant’s height and weight.

Measure the participant’s body temperature.

Perform urine pregnancy test on WOCBP as described in Section 8.2.3.

Discuss contraceptive use as described in Section 10.4.

Record nonstudy vaccinations as described in Section 6.5.

Ensure and document that all of the inclusion criteria and none of the exclusion criteria 
are met.

Ensure that the participant meets none of the temporary delay criteria as described in
Section 5.5.

Collect a blood sample (approximately 20 mL for participants ≥16 years of age and 
approximately 10 mL for participants 12 through 15 years of age) for immunogenicity 
testing and to test for prior COVID-19.  Please refer to the ISF for further instructions.

Obtain a nasal (midturbinate) swab (collected by site staff) for determination of current 
SARS-CoV-2 status. Please refer to the ISF for further instructions.

A blinded site staff member selects the age stratum and obtains the randomization 
number using the IRT system.  An unblinded site staff member then enters the participant 
number (SSID) and randomization number to assign the study intervention allocation 
number.

Unblinded site staff member(s) will dispense/administer 1 dose of study intervention into 
the deltoid muscle of the preferably nondominant arm.  Please refer to the IP manual for 
further instruction on this process.

Blinded site staff must observe the participant for at least 30 minutes after study 
intervention administration for any acute reactions.  Record any acute reactions 
(including time of onset) in the participant’s source documents and on the AE page of the 
CRF, and on an SAE form as applicable.

Explain the e-diary technologies available for this study (Section 8.2.2), and assist the 
participant in downloading the study application onto the participant’s own device or 
issue a provisioned device if required.

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
Provide instructions on reactogenicity e-diary completion and ask the participant to 
complete the reactogenicity e-diary from Day 1 through Day 7, with Day 1 being the day 
of vaccination.

Ask the participant to contact the site staff or investigator immediately if the participant 
experiences any of the following from Day 1 through Day 7 after vaccination (where Day 
1 is the day of vaccination) to determine if an unscheduled reactogenicity visit is 
required: 

Fever ≥39.0°C (≥102.1°F).

Redness or swelling at the injection site measuring greater than 10 cm 
(>20 measuring device units).

Severe pain at the injection site.

Any severe systemic event.

Issue a measuring device to measure local reactions at the injection site and a 
thermometer for recording daily temperatures and provide instructions on their use.

Record AEs/SAEs as described in Section 8.3.

Ask the participant to contact the site staff or investigator if a medically attended event 
(eg, doctor’s visit, emergency room visit) or hospitalization occurs.

Ask the participant to contact the site staff or investigator if he/she develops symptoms of 
a COVID-19 infection, as defined by the CDC,14 including:

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.

Schedule an appointment for the participant to return for the next study visit.

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
Remind the participant to bring the reactogenicity e-diary to the next visit.

Complete the source documents.

The investigator or an authorized designee completes the CRFs and an unblinded 
dispenser/administrator updates the study intervention accountability records.
The investigator or appropriately qualified designee reviews the reactogenicity e-diary data 
online following vaccination to evaluate participant compliance and as part of the ongoing 
safety review.  Daily review is optimal during the active diary period.
8.11.2. Visit 2 – Vaccination 2 (19 to 23 Days After Visit 1)

Record AEs/SAEs as described in Section 8.3.

Review the participant’s reactogenicity e-diary data.  Collect stop dates of any 
reactogenicity e-diary events ongoing on the last day that the reactogenicity e-diary was 
completed and record stop dates in the CRF if required.

Perform urine pregnancy test on WOCBP as described in Section 8.2.3.

Discuss contraceptive use as described in Section 10.4.

Record nonstudy vaccinations as described in Section 6.5.

Record details of any of the prohibited medications specified in Section 6.5.1 received by 
the participant if required for his or her clinical care.

Ensure and document that all of the inclusion criteria and none of the exclusion criteria 
are met. If not, the participant may not receive further study intervention but will remain 
in the study to be evaluated for safety, immunogenicity, and efficacy (see Section 7.1).

Measure the participant’s body temperature.

Ensure that the participant meets none of the temporary delay criteria as described in
Section 5.5.

Unblinded site staff member(s) will dispense/administer 1 dose of study intervention into 
the deltoid muscle of the preferably nondominant arm.  Please refer to the IP manual for 
further instruction on this process.

Blinded site staff must observe the participant for at least 30 minutes after study 
intervention administration for any acute reactions.  Record any acute reactions 
(including time of onset) in the participant’s source documents and on the AE page of the 
CRF, and on an SAE form as applicable.

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
Ensure the participant has a measuring device to measure local reactions at the injection 
site and a thermometer for recording daily temperatures.

Ensure the participant remains comfortable with the chosen e-diary platform, confirm 
instructions on e-diary completion, and ask the participant to complete the reactogenicity 
e-diary from Day 1 through Day 7, with Day 1 being the day of vaccination.

Ask the participant to contact the site staff or investigator immediately if the participant 
experiences any of the following from Day 1 through Day 7 after vaccination (where Day 
1 is the day of vaccination) to determine if an unscheduled reactogenicity visit is 
required: 

Fever ≥39.0°C (≥102.1°F).

Redness or swelling at the injection site measuring greater than 10 cm 
(>20 measuring device units).

Severe pain at the injection site.

Any severe systemic event.

Ask the participant to contact the site staff or investigator if a medically attended event 
(eg, doctor’s visit, emergency room visit) or hospitalization occurs.

Ask the participant to contact the site staff or investigator if he/she develops symptoms of 
a COVID-19 infection, as defined by the CDC,14 including:

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.

Schedule an appointment for the participant to return for the next study visit.

Remind the participant to bring the reactogenicity e-diary to the next visit.

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
Complete the source documents.

The investigator or an authorized designee completes the CRFs and an unblinded 
dispenser/administrator updates the study intervention accountability records.

The investigator or appropriately qualified designee reviews the reactogenicity e-diary 
data online following vaccination to evaluate participant compliance and as part of the 
ongoing safety review.  Daily review is optimal during the active diary period.
8.11.3. Visit 3 – 1-Month Follow-up (28 to 35 Days After Visit 2)

Record AEs/SAEs as described in Section 8.3.

Review the participant’s reactogenicity e-diary data.  Collect stop dates of any 
reactogenicity e-diary events ongoing on the last day that the reactogenicity e-diary was 
completed and record stop dates in the CRF if required.

Record nonstudy vaccinations as described in Section 6.5.

Record details of any of the prohibited medications specified in Section 6.5.1 received by 
the participant if required for his or her clinical care.

Discuss contraceptive use as described in in Section 10.4.

Collect a blood sample (approximately 20 mL for participants ≥16 years of age and 
approximately 10 mL for participants 12 through 15 years of age) for immunogenicity 
testing and to test for prior COVID-19.

Obtain a nasal (midturbinate) swab (collected by site staff) for determination of current 
SARS-CoV-2 status.

Collect the participant’s reactogenicity e-diary or assist the participant to remove the 
study application from his or her own personal device.

Complete the source documents.

The investigator or an authorized designee completes the CRFs.
Booster Study Procedures
8.11.4. Visit 4 – Vaccination 3 (83 to 97 Days After Visit 2)
Before vaccination and before any study-related procedures are performed, voluntary, 
written, study-specific informed consent (via an ICD addendum) will be obtained from the 
participant.  Each signature on the ICD addendum must be personally dated by the signatory.  
The investigator or his or her designee will also sign the ICD addendum.  A copy of the 

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signed and dated ICD addendum must be given to the participant.  The source data must 
reflect that the informed consent was obtained before participation in the booster study.
It is anticipated that the procedures below will be conducted in a stepwise manner.

Perform urine pregnancy test on WOCBP as described in Section 8.2.3.

Discuss contraceptive use as described in Section 10.4.

Record nonstudy vaccinations as described in Section 6.5.

Record details of any of the prohibited medications specified in Section 6.5.1 received by 
the participant if required for his or her clinical care.

Measure body temperature.

Ensure and document that all of the inclusion criteria and none of the exclusion criteria 
are met.

Collect a blood sample (approximately 50 mL) for immunogenicity testing and to test for 
prior COVID-19.  Please refer to the ISF for further instructions.

Obtain a nasal (midturbinate) swab (collected by site staff) for determination of current 
SARS-CoV-2 status.  Please refer to the ISF for further instructions.

A blinded site staff member obtains the single subject ID (SSID) number and the 
participant’s randomization number from the IRT system. The SSID number will not be 
used as the primary identifier for the participant (outside of Impala), but must be included 
in the participant’s source documents and transcribed into the CRF.  An unblinded site 
staff member then enters the SSID and randomization number to assign the study 
intervention allocation number.

Unblinded site staff member(s) will dispense/administer 1 dose of study intervention into 
the deltoid muscle of the preferably nondominant arm.  Please refer to the IP manual for 
further instruction on this process.

Blinded site staff must observe the participant for at least 30 minutes after study 
intervention administration for any acute reactions.  Record any acute reactions 
(including time of onset) in the participant’s source documents and on the AE page of the 
CRF, and on an SAE form as applicable.

Ensure the participant remains comfortable with the chosen e-diary platform and assist 
the participant in downloading the study application onto the participant’s own device or 
issue a provisioned device if required.

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
Review instructions on e-diary completion, and ask the participant to complete the 
reactogenicity e-diary from Day 1 through Day 7, with Day 1 being the day of 
vaccination.

Ask the participant to contact the site staff or investigator immediately if the participant 
experiences any of the following from Day 1 through Day 7 after vaccination (where 
Day 1 is the day of vaccination) to determine if an unscheduled reactogenicity visit is 
required: 

Fever ≥39.0°C (≥102.1°F).

Redness or swelling at the injection site measuring greater than 10 cm 
(>20 measuring device units).

Severe pain at the injection site.

Any severe systemic event.

Issue a measuring device to measure local reactions at the injection site and a 
thermometer for recording daily temperatures and provide instructions on their use.

Record AEs/SAEs as described in Section 8.3.

Ask the participant to contact the site staff or investigator if a medically attended event 
(eg, doctor’s visit, emergency room visit) or hospitalization occurs.

Ask the participant to contact the site staff or investigator if he/she develops symptoms of 
a COVID-19 infection, as defined by the CDC,14 including:

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.

Schedule an appointment for the participant to return for the next study visit.

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
Remind the participant to bring the reactogenicity e-diary to the next visit.

Complete the source documents.

The investigator or an authorized designee completes the CRFs and an unblinded 
dispenser/administrator updates the study intervention accountability records.
The investigator or appropriately qualified designee reviews the reactogenicity e-diary data 
online following vaccination to evaluate participant compliance and as part of the ongoing 
safety review.  Daily review is optimal during the active diary period.
8.11.5. Visit 5 – 1-Week Follow-up (6 to 8 Days After Visit 4)

Discuss contraceptive use as described in Section 10.4.

Record nonstudy vaccinations as described in Section 6.5.

Record details of any of the prohibited medications specified in Section 6.5.1 received by 
the participant if required for his or her clinical care.

Collect a blood sample of approximately 50 mL for immunogenicity testing.

Record AEs as described in Section 8.3.

Ask the participant to contact the site staff or investigator if a medically attended event 
(eg, doctor’s visit, emergency room visit) or hospitalization occurs.

If the participant has completed e-diary reporting by Visit 5, the e-diary may be collected 
or app deleted.

Schedule an appointment for the participant to return for the next study visit.

Complete the source documents.

The investigator or an authorized designee completes the CRFs.
8.11.6. Visit 6 – 1-Month Follow-up (28 to 35 Days After Visit 4)

Discuss contraceptive use as described in in Section 10.4.

Record nonstudy vaccinations as described in Section 6.5.

Record details of any of the prohibited medications specified in Section 6.5.1 received by 
the participant if required for his or her clinical care.

Collect a blood sample (approximately 50 mL) for immunogenicity testing and to test for 
prior COVID-19.

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
Obtain a nasal (midturbinate) swab (collected by site staff) for determination of current 
SARS-CoV-2 status.

Review the participant’s reactogenicity e-diary data.  Collect stop dates of any 
reactogenicity e-diary events ongoing on the last day that the reactogenicity e-diary was 
completed and record stop dates in the CRF if required.

Record AEs/SAEs as described in Section 8.3.

Collect the participant’s reactogenicity e-diary or assist the participant to remove the 
study application from his or her own personal device.

Complete the source documents.

The investigator or an authorized designee completes the CRFs.
8.12. Unscheduled Visits for a Grade 3 or Suspected Grade 4 Reaction
If a Grade 3 local reaction (Section 8.2.2.2), systemic event (Section 8.2.2.3), or fever 
(Section 8.2.2.4) is reported in the reactogenicity e-diary, a telephone contact should occur to 
ascertain further details and determine whether a site visit is clinically indicated. If a 
suspected Grade 4 local reaction (Section 8.2.2.2), systemic event (Section 8.2.2.3), or fever 
(Section 8.2.2.4) is reported in the reactogenicity e-diary, a telephone contact or site visit 
should occur to confirm whether the event meets the criteria for Grade 4.

A site visit must be scheduled as soon as possible to assess the participant unless any of 
the following is true:

The participant is unable to attend the unscheduled visit.

The local reaction/systemic event is no longer present at the time of the telephone 
contact.

The participant recorded an incorrect value in the reactogenicity e-diary (confirmation of 
a reactogenicity e-diary data entry error).

The PI or authorized designee determined it was not needed.

This telephone contact will be recorded in the participant’s source documentation and the 
CRF.

If the participant is unable to attend the unscheduled visit, or the PI or authorized 
designee determined it was not needed, any ongoing local reactions/systemic events must 
be assessed at the next study visit.

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
During the unscheduled visit, the reactions should be assessed by the investigator or a 
medically qualified member of the study staff such as a study physician or a study nurse, 
as applicable to the investigator’s local practice, who will:

Measure body temperature (°F/°C).

Measure minimum and maximum diameters of redness (if present).

Measure minimum and maximum diameters of swelling (if present).

Assess injection site pain (if present) in accordance with the grades provided in 
Section 8.2.2.2.

Assess systemic events (if present) in accordance with the grades provided in 
Section 8.2.2.3.

Assess for other findings associated with the reaction and record on the AE page of the 
CRF, if appropriate.
The investigator or an authorized designee will complete the unscheduled visit assessment 
page of the CRF.
9. STATISTICAL CONSIDERATIONS
Methodology for summary and statistical analyses of the data collected in this study is 
described here and further detailed in a SAP, which will be maintained by the sponsor.  The 
SAP may modify what is outlined in the protocol where appropriate; however, any major 
modifications of the primary endpoint definitions or their analyses will also be reflected in a 
protocol amendment.
9.1. Estimands and Statistical Hypotheses
9.1.1. Estimands
The estimands corresponding to each primary and secondary objective are described in the 
tables in Section 3.
The estimands to evaluate the immunogenicity objectives are based on the evaluable 
immunogenicity population (Section 9.3). These estimands estimate the vaccine effect in the 
hypothetical settings where participants follow the study schedules and protocol requirements 
as directed. The estimands address the objective of estimating the maximum potential 
difference between 2 groups, since the impact of noncompliance is likely to diminish the 
observed difference between the 2 groups. Missing antibody results will not be imputed. 
Immunogenicity results that are below the LLOQ will be set to 0.5 × LLOQ in the analysis; 
this may be adjusted once additional data on the assay characteristics become available.

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In the primary safety objective evaluations, missing reactogenicity e-diary data will not be 
imputed. Missing AE start dates will be imputed according to Pfizer safety rules. No other 
missing information will be imputed in the safety analysis.
9.1.2. Statistical Hypothesis
Primary Study
There are 2 primary immunogenicity objectives on manufacturing lot comparisons. The first
primary immunogenicity objective is to assess the similarity of the immune response induced 
by BNT162b2 30 µg across the 3 US lots. The null hypothesis (H01) is
H01: |ln(µ1)-ln(µ2)| ≥ln(1.5) or |ln(µ1)-ln(µ3)| ≥ln(1.5) or |ln(µ2)-ln(µ3)| ≥ln(1.5)
where ln (1.5) corresponds to a 1.5-fold equivalence margin, and ln(µ1), ln(µ2), and ln(µ3) are 
the natural log of the geometric mean of full-length S-binding IgG levels measured 1 month 
after Dose 2 from participants receiving BNT162b2 30 µg from the US lots in Arm 1, Arm 2,
and Arm 3, respectively.
Two lots will be considered similar if the 2-sided 95% CI for the GMR is contained in the 
interval (0.67, 1.5).  The 3 lots will be considered similar if the 1.5-fold equivalence criterion 
is met for all 3 between-lot comparisons (Arm 1 to Arm 2, Arm 1 to Arm 3, and Arm 2 to 
Arm 3).
The second primary immunogenicity objective is to assess the similarity of the immune 
response induced by BNT162b2 30 µg in the EU lot to the US lots. The null hypothesis 
(H02) is
H02: |ln(µ4)-ln(µp)| ≥ln(1.5) 
where ln (1.5) corresponds to a 1.5-fold equivalence margin, and ln(µ4) and ln(µp) are the 
natural log of the geometric mean of full-length S-binding IgG levels measured 1 month after 
Dose 2 from participants receiving the BNT162b2 30 µg from the EU lot and the 3 pooled 
US lots, respectively.
The EU lot and the US lots will be considered similar if the 2-sided 95% CI for the GMR is 
contained in the interval (0.67, 1.5).
The primary immunogenicity objective on dose comparison is to assess the noninferiority of 
immune response of 20 µg to the standard 30-µg dose (prepared from the same lot).  The null 
hypothesis is
H03: ln(µ20)-ln(µ30) ≤ln(0.67) 
where ln (0.67) corresponds to a 1.5-fold noninferiority margin and ln(µ20) and ln(µ30) are the 
natural log of the geometric mean of the SARS-CoV-2 neutralizing titers measured 1 month

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Booster Study
The study size in each vaccine group is not based on any formal hypothesis test for any 
endpoint. All statistical analyses will be descriptive.
The primary safety objectives include the endpoints for AEs reported within 1 month after 
vaccination. With 30 participants in each vaccine group, if the true AE rate is 1%, the 
probability of observing at least 1 AE is 26% (Table 5).
Table 5.
Probability of Observing an Event Given a Specified Incidence 
Rate With 30 Participants per Group
True Rate of an AE
Probability of Observing at Least 1 AE
0.5%
14.0%
1%
26.0%
2%
45.5%
4%
70.6%
5%
78.5%
10%
95.8%
9.3. Analysis Sets
Primary Study
For purposes of analysis, the following analysis sets are defined:
Participant
Analysis Set
Description
Enrolled
All participants who have a signed ICD.
Randomized
All participants who are assigned a randomization number in the IRT
system.
Evaluable 
immunogenicity
All eligible randomized participants who receive 2 doses of the vaccine 
to which they are randomized with Dose 2 received within the 
predefined window, have at least 1 valid and determinate 
immunogenicity result from the blood sample collected within an 
appropriate window at 1 month after the Dose 2 visit, are negative for 
SARS-CoV-2 infection during the study, and have no other important 
protocol deviations as determined by the clinician.
All-available 
immunogenicity
All participants who receive at least 1 dose of the study intervention 
with at least 1 valid and determinate immunogenicity result after 
vaccination.
Safety
All randomized participants who receive at least 1 dose of the study 
intervention.

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Booster Study
For purposes of analysis, the following analysis sets are defined:
Participant 
Analysis Set
Description
Enrolled
All participants who have a signed ICD at Visit 4.
Randomized
All participants who are assigned a randomization number at Visit 4 in 
the IRT system.
Booster evaluable 
immunogenicity
All eligible randomized participants who receive 2 doses of the vaccine 
to which they are randomized in the primary study with Dose 2 
received within the predefined window, receive Dose 3 to which they 
are randomized in the booster study with Dose 3 received within the 
predefined window, have at least 1 valid and determinate 
immunogenicity result from the blood sample collected within an 
appropriate window at 1 month after the Dose 3 visit, are negative for 
SARS-CoV-2 infection during the primary and booster studies, and 
have no other important protocol deviations as determined by the 
clinician.
Booster 
all-available 
immunogenicity
All participants who receive Dose 3 with at least 1 valid and 
determinate immunogenicity result after Dose 3.
Safety
All randomized participants who receive Dose 3.
9.4. Statistical Analyses
The SAP will be developed and finalized before any analyses are performed and will 
describe the analyses and procedures for accounting for missing, unused, and spurious data.  
This section is a summary of the planned statistical analyses of the primary and secondary 
endpoints.
9.4.1. General Considerations
Unless stated otherwise, “vaccine group” in this section refers to participants receiving any 
1 of the three 30-µg US lots, the (30-µg) EU lot, or the 20-µg dose group for the primary 
study and to participants receiving BNT162b2 at 30 µg or BNT162b2.B.1.351 at 30 µg (refer 
to Section 4.1). CIs for all endpoints in the statistical analysis will be presented as 2-sided at 
the 95% level unless specified otherwise.
For all the immunogenicity endpoints, the analysis will be based on the evaluable 
immunogenicity population. An additional analysis will be performed based on the 
all-available immunogenicity population if there is a large enough difference in sample size 
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population.  Participants will be summarized according to the vaccine group to which they 
were randomized.
The safety analyses will be based on the safety population.  Participants will be summarized 
by vaccine group according to the investigational products they actually received.
9.4.1.1. Analyses for Binary Data
Descriptive statistics for categorical variables (eg, proportions) are the percentage (%), the 
numerator (n) and the denominator (N) used in the percentage calculation, and the 95% CIs 
where applicable.
The exact 95% CI for binary endpoints for each group will be computed using the 
F distribution (Clopper-Pearson).
9.4.1.2. Analyses for Continuous Data
Unless otherwise stated, descriptive statistics for continuous variables are n, mean, median, 
standard deviation, minimum, and maximum.
9.4.1.2.1. Geometric Mean Ratios
Model-Based
As the primary approach, the GMR and associated 95% CI will be calculated by 
exponentiating the difference in LS means and the corresponding CIs based on analysis of 
logarithmically transformed assay results using a linear regression model.
Unadjusted
The GMRs will be calculated as the mean of the difference of logarithmically transformed 
assay results between 2 vaccine groups and exponentiating the mean.  Two-sided CIs will be 
obtained by calculating CIs using Student’s t-distribution for the mean difference of the 
logarithmically transformed assay results and exponentiating the confidence limits.
9.4.1.2.2. Geometric Means
The geometric means will be calculated as the mean of the assay results after making the 
logarithm transformation and then exponentiating the mean to express results on the original 
scale.  Two-sided 95% CIs will be obtained by taking log transforms of assay results, 
calculating the 95% CI with reference to Student’s t-distribution, and then exponentiating the 
confidence limits.
9.4.1.2.3. Geometric Mean Fold Rises
GMFRs are defined as ratios of the results at a later time point to the results at an earlier time 
point.  GMFRs are limited to participants with nonmissing values at both time points.

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GMFRs will be calculated as the mean of the difference of logarithmically transformed assay 
results (later time point minus earlier time point) and exponentiating the mean.  The 
associated 2-sided 95% CIs will be obtained by constructing CIs using Student’s 
t-distribution for the mean difference on the logarithm scale and exponentiating the 
confidence limits.
9.4.1.2.4. Reverse Cumulative Distribution Curves
Empirical RCDCs will plot proportions of participants with values equal to or exceeding a 
specified assay value versus the indicated assay value, for all observed assay values.  Data 
points will be joined by a step function with data points on the left side of the step.
9.4.2. Primary Endpoint(s)
Primary Study
Endpoint
Statistical Analysis Methods
Immunogenicity
GMRs of full-length S-binding IgG levels between the US lots
For full-length S-binding levels, the GMRs for each between-lot 
comparison (Arm 1/Arm 2, Arm 1/Arm 3, and Arm 2/Arm 3) at 
1 month after Dose 2 will be provided along with associated 2-sided 
95% CIs (see Section 9.4.1.2.1).
Using a 1.5-fold equivalence margin, 2 lots will be considered similar if 
the 2-sided 95% CI for each GMR is contained in the interval 
(0.67, 1.5).
GMR of full-length S-binding IgG levels between the EU lot and 
the 3 US lots
The GMR of the EU lot (Arm 4) to the pooled US lots (Arm 4/pooled 
Arms 1, 2, and 3) at 1 month after Dose 2 will be provided along with 
associated 2-sided 95% CIs (see Section 9.4.1.2.1).
Using a 1.5-fold equivalence margin, the EU lot Arm 4) and the pooled 
US lots (Arms 1-3) will be considered similar if the 2-sided 95% CI for 
the GMR is contained in the interval (0.67, 1.5).

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Endpoint
Statistical Analysis Methods
GMR of SARS-CoV-2 neutralizing titers between the 20-µg dose
and the corresponding 30-µg dose
The GMR of the 20-µg dose (Arm 5) to the corresponding 30-µg dose 
(Arm 1, 2, or 3) (20 µg/30 µg) at 1 month after Dose 2 will be provided 
along with associated 2-sided 95% CIs (see Section 9.4.1.2.1).
Using a 1.5-fold noninferiority margin, noninferiority of the 20-µg dose
(Arm 5) to the corresponding 30-µg dose (Arm 1, 2, or 3) will be 
declared if the lower limit of the 2-sided 95% CI for the GMR is >0.67.
As the primary approach for these similarity and noninferiority
assessments, a linear regression model that includes a term for age and 
vaccine group will be used to calculate the adjusted GMR and 2-sided 
95% CI.  The unadjusted GMR and CI will also be calculated.
Safety
Descriptive statistics will be provided for each reactogenicity endpoint 
for each dose and vaccine group.  Local reactions and systemic events 
from Day 1 through Day 7 after each vaccination will be presented by 
severity and cumulatively across severity levels.  Descriptive summary 
statistics will include counts and percentages of participants with the 
indicated endpoint and the associated Clopper-Pearson 95% CIs (see 
Section 9.4.1.1).
AEs and SAEs will be categorized according to MedDRA terms.  
Counts, percentages, and the associated Clopper-Pearson 95% CIs of 
AEs and SAEs from Dose 1 to 1 month after Dose 2 will be provided 
for each vaccine group.
Booster Study
Endpoint
Statistical Analysis Methods
Immunogenicity
GMCs of full-length S-binding IgG levels
For full-length S-binding IgG levels, GMCs and 2-sided 95% CIs will 
be provided for each vaccine group at baseline (before Dose 1),
1 month after Dose 2, before Dose 3, and 1 week after and 1 month 
after Dose 3.
Statistical methods are described in Section 9.4.1.2.2.

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Endpoint
Statistical Analysis Methods
GMFRs of full-length S-binding IgG levels
For full-length S-binding IgG levels, the GMFRs and 2-sided 95% CIs 
will be provided for each vaccine group from 1 month after Dose 2 to 
1 week after and 1 month after Dose 3 and from before Dose 3 to 
1 week after and 1 month after Dose 3.
GMFRs will be limited to participants with nonmissing values at both 
time points being considered.  The statistical methods are described in 
Section 9.4.1.2.3.
GMTs of SARS-CoV-2 reference-strain neutralizing titers and 
SARS-CoV-2 B.1.351-strain neutralizing titers
For SARS-CoV-2 neutralizing titers, GMTs and 2-sided 95% CIs will 
be provided for each vaccine group at baseline (before Dose 1),
1 month after Dose 2, before Dose 3, and 1 week after and 1 month 
after Dose 3.
Statistical methods are described in Section 9.4.1.2.2.
GMFRs of SARS-CoV-2 reference-strain neutralizing titers and 
SARS-CoV-2 B.1.351-strain neutralizing titers
For SARS-CoV-2 neutralizing titers, the GMFRs and 2-sided 95% CIs 
will be provided for each vaccine group from 1 month after Dose 2 to 
1 week after and 1 month after Dose 3 and from before Dose 3 to 
1 week after and 1 month after Dose 3.
GMFRs will be limited to participants with nonmissing values at both 
time points being considered.  The statistical methods are described in 
Section 9.4.1.2.3.
Percentage of participants with seroresponse* to the SARS-CoV-2
reference strain and SARS-CoV-2 B.1.351 strain in neutralizing 
titers
The percentage of participants with a seroresponse to the reference 
strain and to the B.1.351 strain (and corresponding 2-sided Clopper-
Pearson 95% CI) will be provided by vaccine group at 1 month after 
Dose 2, before Dose 3, and 1 week after and 1 month after Dose 3 (see 
Section 9.4.1.1).
* Seroresponse is defined as ≥4-fold increase from baseline (before Dose 1) to the specified time point. If the 
baseline measurement is below LLOQ, a postvaccination measurement of ≥4 × LLOQ is considered a 
seroresponse.

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9.6. Data Monitoring Committee or Other Independent Oversight Committee
This study will use a DMC. The DMC is independent of the study team and includes 
external members.  The DMC charter describes the role of the DMC in more detail.
The DMC will be responsible for ongoing monitoring of the safety of participants in the 
study according to the charter. This may include, but is not limited to:

Contemporaneous review of related AEs up to 1 month after completion of the 
vaccination schedule,

Contemporaneous review of all SAEs up to 1 month after completion of the 
vaccination schedule.
The recommendations made by the DMC to alter the conduct of the study will be forwarded 
to the appropriate Pfizer personnel for final decision.  Pfizer will forward such decisions, 
which may include summaries of aggregate analyses of safety data, to regulatory authorities, 
as appropriate.

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10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations
10.1.1. Regulatory and Ethical Considerations
This study will be conducted in accordance with the protocol and with the following:

Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and CIOMS International Ethical Guidelines;

Applicable ICH GCP guidelines;

Applicable laws and regulations, including applicable privacy laws.
The protocol, protocol amendments, ICD, SRSD(s), and other relevant documents 
(eg, advertisements) must be reviewed and approved by the sponsor and submitted to an 
IRB/EC by the investigator and reviewed and approved by the IRB/EC before the study is 
initiated.
Any amendments to the protocol will require IRB/EC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants.
The investigator will be responsible for the following:

Providing written summaries of the status of the study to the IRB/EC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/EC;

Notifying the IRB/EC of SAEs or other significant safety findings as required by 
IRB/EC procedures;

Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/EC, European regulation 536/2014 
for clinical studies (if applicable), and all other applicable local regulations.
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
regulatory authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the study 
intervention, Pfizer should be informed immediately.
In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study participants against any immediate hazard, and 
of any serious breaches of this protocol or of ICH GCP that the investigator becomes aware 
of.

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10.1.2. Informed Consent Process
The investigator or his/her representative will explain the nature of the study to the 
participant or his or her parent(s)/legal guardian and answer all questions regarding the study.  
The participant or his or her parent(s)/legal guardian should be given sufficient time and 
opportunity to ask questions and to decide whether or not to participate in the trial. When
consent is obtained from a participant’s parent(s)/legal guardian, the participant’s assent 
(affirmative agreement) must be subsequently obtained when the participant has the capacity 
to provide assent, as determined by the IRB/EC.  If study participants are minors who reach 
the age of majority during the study, as recognized under local law, they must be reconsented 
as adults to remain in the study.
Participants must be informed that their participation is voluntary. Participants or their
parent(s)/legal guardian will be required to sign a statement of informed consent that meets 
the requirements of 21 CFR 50, local regulations, ICH guidelines, HIPAA requirements, 
where applicable, and the IRB/EC or study center.
The investigator must ensure that each study participant or his or her parent(s)/legal guardian
is fully informed about the nature and objectives of the study, the sharing of data related to 
the study, and possible risks associated with participation, including the risks associated with 
the processing of the participant’s personal data.
The participant must be informed that his/her personal study-related data will be used by the 
sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant or his or her parent(s)/legal guardian.
The participant must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB/EC members, and by inspectors from regulatory authorities.
The investigator further must ensure that each study participant or his or her parent(s)/legal 
guardian is fully informed about his or her right to access and correct his or her personal data 
and to withdraw consent for the processing of his or her personal data.
The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date the written consent was obtained.
The authorized person obtaining the informed consent must also sign the ICD.
Participants must be reconsented to the most current version of the ICD(s) during their 
participation in the study.
A copy of the ICD(s) must be provided to the participant or his or her parent(s)/legal 
guardian.  Participants who are rescreened are required to sign a new ICD.
Unless prohibited by local requirements or IRB/EC decision, the ICD will contain a separate 
section that addresses the use of samples for optional additional research. The optional 
additional research does not require the collection of any further samples.  The investigator 

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or authorized designee will explain to each participant the objectives of the additional
research. Participants will be told that they are free to refuse to participate and may 
withdraw their consent at any time and for any reason during the storage period.
10.1.3. Data Protection
All parties will comply with all applicable laws, including laws regarding the implementation 
of organizational and technical measures to ensure protection of participant data.
Participants’ personal data will be stored at the study site in encrypted electronic and/or paper 
form and will be password protected or secured in a locked room to ensure that only 
authorized study staff have access.  The study site will implement appropriate technical and 
organizational measures to ensure that the personal data can be recovered in the event of 
disaster.  In the event of a potential personal data breach, the study site will be responsible 
for determining whether a personal data breach has in fact occurred and, if so, providing 
breach notifications as required by law.
To protect the rights and freedoms of participants with regard to the processing of personal 
data, participants will be assigned a single, participant-specific numerical code. Any 
participant records or data sets that are transferred to the sponsor will contain the numerical 
code; participant names will not be transferred. All other identifiable data transferred to the 
sponsor will be identified by this single, participant-specific code. The study site will 
maintain a confidential list of participants who participated in the study, linking each 
participant’s numerical code to his or her actual identity and medical record identification. In 
case of data transfer, the sponsor will protect the confidentiality of participants’ personal data 
consistent with the clinical study agreement and applicable privacy laws.
10.1.4. Dissemination of Clinical Study Data
Pfizer fulfills its commitment to publicly disclose clinical study results through posting the 
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov), the EudraCT, and/or 
www.pfizer.com, and other public registries in accordance with applicable local 
laws/regulations.  In addition, Pfizer reports study results outside of the requirements of local 
laws/regulations pursuant to its SOPs.
In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country in 
which the study was conducted.
www.clinicaltrials.gov
Pfizer posts clinical trial results on www.clinicaltrials.gov for Pfizer-sponsored interventional 
studies (conducted in patients) that evaluate the safety and/or efficacy of a product, 
regardless of the geographical location in which the study is conducted.  These results are 
submitted for posting in accordance with the format and timelines set forth by US law.

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EudraCT
Pfizer posts clinical trial results on EudraCT for Pfizer-sponsored interventional studies in 
accordance with the format and timelines set forth by EU requirements.
www.pfizer.com
Pfizer posts public disclosure synopses (CSR synopses in which any data that could be used 
to identify individual participants have been removed) on www.pfizer.com for 
Pfizer-sponsored interventional studies at the same time the corresponding study results are
posted to www.clinicaltrials.gov.
Documents within marketing authorization packages/submissions
Pfizer complies with the European Union Policy 0070, the proactive publication of clinical 
data to the EMA website.  Clinical data, under Phase 1 of this policy, includes clinical 
overviews, clinical summaries, CSRs, and appendices containing the protocol and protocol 
amendments, sample CRFs, and statistical methods.  Clinical data, under Phase 2 of this 
policy, includes the publishing of individual participant data.  Policy 0070 applies to new 
marketing authorization applications submitted via the centralized procedure since 
01 January 2015 and applications for line extensions and for new indications submitted via 
the centralized procedure since 01 July 2015.
Data Sharing
Pfizer provides researchers secure access to patient-level data or full CSRs for the purposes 
of “bona-fide scientific research” that contributes to the scientific understanding of the 
disease, target, or compound class. Pfizer will make available data from these trials 
24 months after study completion.  Patient-level data will be anonymized in accordance with 
applicable privacy laws and regulations.  CSRs will have personally identifiable information 
redacted.
Data requests are considered from qualified researchers with the appropriate competencies to 
perform the proposed analyses. Research teams must include a biostatistician. Data will not 
be provided to applicants with significant conflicts of interest, including individuals 
requesting access for commercial/competitive or legal purposes.
10.1.5. Data Quality Assurance
All participant data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (eg, laboratory data). The investigator is 
responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the CRF.
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF.

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The investigator must ensure that the CRFs are securely stored at the study site in encrypted 
electronic and/or paper form and are password protected or secured in a locked room to 
prevent access by unauthorized third parties.
The investigator must permit study-related monitoring, audits, IRB/EC review, and 
regulatory agency inspections and provide direct access to source data documents.  This
verification may also occur after study completion.  It is important that the investigator(s) 
and their relevant personnel are available during the monitoring visits and possible audits or 
inspections and that sufficient time is devoted to the process.
Monitoring details describing strategy (eg, risk-based initiatives in operations and quality 
such as risk management and mitigation strategies and analytical risk-based monitoring), 
methods, responsibilities, and requirements, including handling of noncompliance issues and 
monitoring techniques (central, remote, or on-site monitoring), are provided in the 
monitoring plan.
The sponsor or designee is responsible for the data management of this study, including 
quality checking of the data.
Study monitors will perform ongoing source data verification to confirm that data entered 
into the CRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements.
Records and documents, including signed ICDs, pertaining to the conduct of this study must 
be retained by the investigator for 15 years after study completion unless local regulations or 
institutional policies require a longer retention period. No records may be destroyed during 
the retention period without the written approval of the sponsor. No records may be 
transferred to another location or party without written notification to the sponsor. The 
investigator must ensure that the records continue to be stored securely for as long as they are 
maintained.
When participant data are to be deleted, the investigator will ensure that all copies of such 
data are promptly and irrevocably deleted from all systems.
The investigator(s) will notify the sponsor or its agents immediately of any regulatory 
inspection notification in relation to the study.  Furthermore, the investigator will cooperate 
with the sponsor or its agents to prepare the investigator site for the inspection and will allow 
the sponsor or its agent, whenever feasible, to be present during the inspection.  The 
investigator site and investigator will promptly resolve any discrepancies that are identified 
between the study data and the participant's medical records.  The investigator will promptly 
provide copies of the inspection findings to the sponsor or its agent.  Before response 
submission to the regulatory authorities, the investigator will provide the sponsor or its 
agents with an opportunity to review and comment on responses to any such findings.

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10.1.6. Source Documents
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the investigator site.
Data reported on the CRF or entered in the eCRF that are from source documents must be 
consistent with the source documents or the discrepancies must be explained. The 
investigator may need to request previous medical records or transfer records, depending on 
the study. Also, current medical records must be available.
Definition of what constitutes source data can be found in the study monitoring plan.
Description of the use of computerized system is documented in the Data Management Plan.
10.1.7. Study and Site Start and Closure
The study start date is the date on which the clinical study will be open for recruitment of 
participants.
The first act of recruitment is the date of the first participant’s first visit and will be the study 
start date.
The sponsor designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor. Study sites will be closed upon 
study completion. A study site is considered closed when all required documents and study 
supplies have been collected and a study-site closure visit has been performed.
The investigator may initiate study-site closure at any time upon notification to the sponsor 
or designee if requested to do so by the responsible IRB/EC or if such termination is required 
to protect the health of study participants.
Reasons for the early closure of a study site by the sponsor may include but are not limited 
to:

Failure of the investigator to comply with the protocol, the requirements of the 
IRB/EC or local health authorities, the sponsor's procedures, or GCP guidelines;

Inadequate recruitment of participants by the investigator;

Discontinuation of further study intervention development.
If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the ECs/IRBs, the regulatory authorities, and any CRO(s) used in the study of 
the reason for termination or suspension, as specified by the applicable regulatory 
requirements. The investigator shall promptly inform the participant and should assure 
appropriate participant therapy and/or follow-up.

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Study termination is also provided for in the clinical study agreement.  If there is any conflict 
between the contract and this protocol, the contract will control as to termination rights.
10.1.8. Sponsor’s Qualified Medical Personnel
The contact information for the sponsor's appropriately qualified medical personnel for the 
study is documented in the study contact list located in the supporting study documentation
electronic system.
To facilitate access to appropriately qualified medical personnel on study-related medical 
questions or problems, participants are provided with a contact card at the time of informed 
consent.  The contact card contains, at a minimum, protocol and study intervention
identifiers, participant numbers, contact information for the investigator site, and contact 
details for a contact center in the event that the investigator site staff cannot be reached to 
provide advice on a medical question or problem originating from another healthcare 
professional not involved in the participant’s participation in the study.  The contact number 
can also be used by investigator staff if they are seeking advice on medical questions or 
problems; however, it should be used only in the event that the established communication 
pathways between the investigator site and the study team are not available.  It is therefore 
intended to augment, but not replace, the established communication pathways between the 
investigator site and the study team for advice on medical questions or problems that may 
arise during the study.  The contact number is not intended for use by the participant directly, 
and if a participant calls that number, he or she will be directed back to the investigator site.

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10.2. Appendix 2: Clinical Laboratory Tests
A pregnancy test will be performed at times defined in the SoA section of this protocol:  
Visit 1 (Vaccination 1/Day 1) and Visit 2 (Vaccination 2/19-23 days after Visit 1).

Pregnancy test (β-hCG):  Local urine testing will be standard for the protocol unless 
serum testing is required by local regulation or IRB/EC for female participants of 
childbearing potential.
Unscheduled clinical laboratory measurements may be obtained at any time during the study 
to assess any perceived safety issues.  Investigators must document their review of each 
laboratory safety report.

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Hospitalization for elective treatment of a preexisting condition that did not worsen from 
baseline is not considered an AE.
d. Results in persistent disability/incapacity

The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions.

This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, 
and accidental trauma (eg, sprained ankle) which may interfere with or prevent 
everyday life functions but do not constitute a substantial disruption.
e.
Is a congenital anomaly/birth defect
f.
Other situations:

Medical or scientific judgment should be exercised in deciding whether SAE 
reporting is appropriate in other situations such as important medical events that 
may not be immediately life-threatening or result in death or hospitalization but may 
jeopardize the participant or may require medical or surgical intervention to prevent 
one of the other outcomes listed in the above definition. These events should 
usually be considered serious.

Examples of such events include invasive or malignant cancers, intensive treatment 
in an emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization, or development of drug dependency 
or drug abuse.

Suspected transmission via a Pfizer product of an infectious agent, pathogenic or 
non-pathogenic, is considered serious. The event may be suspected from clinical 
symptoms or laboratory findings indicating an infection in a patient exposed to a 
Pfizer product.  The terms “suspected transmission” and “transmission” are 
considered synonymous.  These cases are considered unexpected and handled as 
serious expedited cases by pharmacovigilance personnel.  Such cases are also 
considered for reporting as product defects, if appropriate.

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10.4. Appendix 4: Contraceptive Guidance
10.4.1. Male Participant Reproductive Inclusion Criteria
Male participants are eligible to participate if they agree to the following requirements during 
the intervention period and for at least 28 days after the last dose of study intervention, which 
corresponds to the time needed to eliminate reproductive safety risk of the study 
intervention(s):

Refrain from donating sperm.
PLUS either:

Be abstinent from heterosexual intercourse with a female of childbearing potential as 
their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and 
agree to remain abstinent.
OR

Must agree to use a male condom when engaging in any activity that allows for 
passage of ejaculate to another person.

In addition to male condom use, a highly effective method of contraception may be 
considered in WOCBP partners of male participants (refer to the list of highly 
effective methods below in Section 10.4.4).
10.4.2. Female Participant Reproductive Inclusion Criteria
A female participant is eligible to participate if she is not pregnant or breastfeeding, and at 
least 1 of the following conditions applies:

Is not a WOCBP (see definitions below in Section 10.4.3).
OR

Is a WOCBP and using an acceptable contraceptive method as described below 
during the intervention period (for a minimum of 28 days after the last dose of study 
intervention).  The investigator should evaluate the effectiveness of the contraceptive 
method in relationship to the first dose of study intervention.
The investigator is responsible for review of medical history, menstrual history, and recent 
sexual activity to decrease the risk for inclusion of a woman with an early undetected 
pregnancy.

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10.4.3. Woman of Childbearing Potential
A woman is considered fertile following menarche and until becoming postmenopausal 
unless permanently sterile (see below).
If fertility is unclear (eg, amenorrhea in adolescents or athletes) and a menstrual cycle cannot 
be confirmed before the first dose of study intervention, additional evaluation should be 
considered.
Women in the following categories are not considered WOCBP:
1. Premenopausal female with 1 of the following:

Documented hysterectomy;

Documented bilateral salpingectomy;

Documented bilateral oophorectomy.
For individuals with permanent infertility due to an alternate medical cause other than the 
above, (eg, mullerian agenesis, androgen insensitivity), investigator discretion should be 
applied to determining study entry.
Note: Documentation for any of the above categories can come from the site personnel’s 
review of the participant’s medical records, medical examination, or medical history 
interview.  The method of documentation should be recorded in the participant’s medical 
record for the study.
2. Postmenopausal female:

A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause.  In addition, a

high FSH level in the postmenopausal range must be used to confirm a 
postmenopausal state in women under 60 years of age and not using hormonal 
contraception or HRT.

Female on HRT and whose menopausal status is in doubt will be required to use 
one of the nonestrogen hormonal highly effective contraception methods if they 
wish to continue their HRT during the study.  Otherwise, they must discontinue 
HRT to allow confirmation of postmenopausal status before study enrollment.

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10.4.4. Contraception Methods
Contraceptive use by men or women should be consistent with local availability/regulations 
regarding the use of contraceptive methods for those participating in clinical trials.
1. Implantable progestogen-only hormone contraception associated with inhibition of 
ovulation.
2. Intrauterine device.
3. Intrauterine hormone-releasing system.
4. Bilateral tubal occlusion.
5. Vasectomized partner:

Vasectomized partner is a highly effective contraceptive method provided that the 
partner is the sole sexual partner of the WOCBP and the absence of sperm has been 
confirmed. If not, an additional highly effective method of contraception should be 
used. The spermatogenesis cycle is approximately 90 days.
6. Combined (estrogen- and progestogen-containing) hormonal contraception associated 
with inhibition of ovulation:

Oral;

Intravaginal;

Transdermal;

Injectable.
7. Progestogen-only hormone contraception associated with inhibition of ovulation:

Oral;

Injectable.
8. Sexual abstinence:

Sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated 
with the study intervention.  The reliability of sexual abstinence needs to be evaluated 
in relation to the duration of the study and the preferred and usual lifestyle of the 
participant.

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9. Progestogen-only oral hormonal contraception where inhibition of ovulation is not the 
primary mode of action.
10. Male or female condom with or without spermicide.
11. Cervical cap, diaphragm, or sponge with spermicide.
12. A combination of male condom with either cervical cap, diaphragm, or sponge with 
spermicide (double-barrier methods).

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10.5. Appendix 5: Liver Safety: Suggested Actions and Follow-up Assessments 
Potential Cases of Drug-Induced Liver Injury
Humans exposed to a drug who show no sign of liver injury (as determined by elevations in 
transaminases) are termed “tolerators,” while those who show transient liver injury, but adapt 
are termed “adaptors.”  In some participants, transaminase elevations are a harbinger of a 
more serious potential outcome.  These participants fail to adapt and therefore are 
"susceptible" to progressive and serious liver injury, commonly referred to as DILI.  
Participants who experience a transaminase elevation above 3 × ULN should be monitored 
more frequently to determine if they are an “adaptor” or are “susceptible.”
LFTs are not required as a routine safety monitoring procedure in this study.  However, 
should an investigator deem it necessary to assess LFTs because a participant presents with 
clinical signs/symptoms, such LFT results should be managed and followed as described 
below.
In the majority of DILI cases, elevations in AST and/or ALT precede TBili elevations 
(>2 × ULN) by several days or weeks.  The increase in TBili typically occurs while 
AST/ALT is/are still elevated above 3 × ULN (ie, AST/ALT and TBili values will be 
elevated within the same laboratory sample).  In rare instances, by the time TBili elevations 
are detected, AST/ALT values might have decreased.  This occurrence is still regarded as a 
potential DILI.  Therefore, abnormal elevations in either AST OR ALT in addition to TBili 
that meet the criteria outlined below are considered potential DILI (assessed per Hy’s law 
criteria) cases and should always be considered important medical events, even before all 
other possible causes of liver injury have been excluded.
The threshold of laboratory abnormalities for a potential DILI case depends on the 
participant’s individual baseline values and underlying conditions.  Participants who present 
with the following laboratory abnormalities should be evaluated further as potential DILI 
(Hy’s law) cases to definitively determine the etiology of the abnormal laboratory values:

Participants with AST/ALT and TBili baseline values within the normal range who 
subsequently present with AST OR ALT values >3 × ULN AND a TBili value 
>2 × ULN with no evidence of hemolysis and an alkaline phosphatase value 
<2 × ULN or not available.

For participants with baseline AST OR ALT OR TBili values above the ULN, the 
following threshold values are used in the definition mentioned above, as needed, 
depending on which values are above the ULN at baseline:

Preexisting AST or ALT baseline values above the normal range: AST or ALT 
values >2 times the baseline values AND >3 × ULN; or >8 × ULN (whichever is 
smaller).

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
Preexisting values of TBili above the normal range: TBili level increased from 
baseline value by an amount of at least 1 × ULN or if the value reaches 
>3 × ULN (whichever is smaller).
Rises in AST/ALT and TBili separated by more than a few weeks should be assessed 
individually based on clinical judgment; any case where uncertainty remains as to whether it 
represents a potential Hy’s law case should be reviewed with the sponsor.
The participant should return to the investigator site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the abnormal results.  This evaluation should 
include laboratory tests, detailed history, and physical assessment.
In addition to repeating measurements of AST and ALT and TBili for suspected cases of 
Hy’s law, additional laboratory tests should include albumin, CK, direct and indirect 
bilirubin, GGT, PT/INR, total bile acids, and alkaline phosphatase.  Consideration should 
also be given to drawing a separate tube of clotted blood and an anticoagulated tube of blood 
for further testing, as needed, for further contemporaneous analyses at the time of the 
recognized initial abnormalities to determine etiology.  A detailed history, including relevant 
information, such as review of ethanol, acetaminophen/paracetamol (either by itself or as a 
coformulated product in prescription or over-the-counter medications), recreational drug, 
supplement (herbal) use and consumption, family history, sexual history, travel history, 
history of contact with a jaundiced person, surgery, blood transfusion, history of liver or 
allergic disease, and potential occupational exposure to chemicals, should be collected.  
Further testing for acute hepatitis A, B, C, D, and E infection and liver imaging (eg, biliary 
tract) and collection of serum samples for acetaminophen/paracetamol drug and/or protein 
adduct levels may be warranted.
All cases demonstrated on repeat testing as meeting the laboratory criteria of AST/ALT and 
TBili elevation defined above should be considered potential DILI (Hy’s law) cases if no 
other reason for the LFT abnormalities has yet been found.  Such potential DILI (Hy’s law) 
cases are to be reported as SAEs, irrespective of availability of all the results of the 
investigations performed to determine etiology of the LFT abnormalities.
A potential DILI (Hy’s law) case becomes a confirmed case only after all results of 
reasonable investigations have been received and have excluded an alternative etiology.

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10.6. Appendix 6: Abbreviations
The following is a list of abbreviations that may be used in the protocol.
Abbreviation
Term
2019-nCoV
novel coronavirus 2019
ACIP
Advisory Committee on Immunization Practices
AE
adverse event
AESI
adverse event of special interest
ALT
alanine aminotransferase
AST
aspartate aminotransferase
-hCG
beta-human chorionic gonadotropin
CBER
Center for Biologics Evaluation and Research
CDC
Centers for Disease Control and Prevention (United States)
CFR
Code of Federal Regulations
CI
confidence interval
CIOMS
Council for International Organizations of Medical Sciences
CK
creatine kinase
CONSORT
Consolidated Standards of Reporting Trials
COVID-19
coronavirus disease 2019
CRF
case report form
CRO
contract research organization
CRP
C-reactive protein
CSR
clinical study report
DILI
drug-induced liver injury
DMC
data monitoring committee
DNA
deoxyribonucleic acid
EC
ethics committee
ECG
electrocardiogram
eCRF
electronic case report form
e-diary
electronic diary
EDP
exposure during pregnancy
EMA
European Medicines Agency
ESR
erythrocyte sedimentation rate
EU
European Union
EUA
emergency use authorization
EudraCT
European Clinical Trials Database
FDA
Food and Drug Administration
FSH
follicle-stimulating hormone
GCP
Good Clinical Practice
GGT
gamma-glutamyl transferase
GMC
geometric mean concentration

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Abbreviation
Term
GMFR
geometric mean fold rise
GMR
geometric mean ratio
HBV
hepatitis B virus
HCV
hepatitis C virus
HIPAA
Health Insurance Portability and Accountability Act
HIV
human immunodeficiency virus
HRT
hormone replacement therapy
IB
investigator’s brochure
ICD
informed consent document
ICH
International Council for Harmonisation
ID
identification
IgG
immunoglobulin G
IL-6
interleukin-6
IMP
investigational medicinal product
IND
investigational new drug
INR
international normalized ratio
IP manual
investigational product manual
IPAL
Investigational Product Accountability Log
IRB
institutional review board
IRT
interactive response technology
ISF
investigator site file
IV
intravenous(ly)
IWR
interactive Web-based response
LDH
lactate dehydrogenase
LFT
liver function test
LLOQ
lower limit of quantitation
LNP
lipid nanoparticle
LS
least squares
MedDRA
Medical Dictionary for Regulatory Activities
MERS
Middle East respiratory syndrome
MIS-C
multisystem inflammatory syndrome in children
modRNA
nucleoside-modified messenger ribonucleic acid
N
SARS-CoV-2 nucleoprotein
N/A
not applicable
NAAT
nucleic acid amplification test 
NIMP
noninvestigational medicinal product
P2 S
SARS-CoV-2 full-length, P2 mutant, prefusion spike glycoprotein
PCR
polymerase chain reaction
PI
principal investigator
PPE
personal protective equipment
PT
prothrombin time

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Abbreviation
Term
RCDC
reverse cumulative distribution curve
RNA
ribonucleic acid
RSV
respiratory syncytial virus
RT-PCR
reverse transcription–polymerase chain reaction
S
spike protein
S1
spike protein S1 subunit
SAE
serious adverse event
SAP
statistical analysis plan
SARS
severe acute respiratory syndrome
SARS-CoV-2
severe acute respiratory syndrome coronavirus 2
SoA
schedule of activities
SOP
standard operating procedure
SRSD
single reference safety document
SSID
single subject identification
SUSAR
suspected unexpected serious adverse reaction
TBili
total bilirubin
Th 1
T-helper type 1
UK
United Kingdom
ULN
upper limit of normal
US
United States
VOC
variant of concern
WHO
World Health Organization
WOCBP
woman/women of childbearing potential

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11. REFERENCES
1
Virus Pathogen Resource (ViPR). Strain details for severe acute respiratory syndrome-
related coronavirus strain Wuhan-Hu-1. Available from: 
https://www.viprbrc.org/brc/viprStrainDetails.spg?ncbiAccession=MN908947&decorat
or=corona.  Accessed: 11 Aug 2020.
2
Zhu N, Zhang D, Wang W, et al. A novel coronavirus from patients with pneumonia in 
China, 2019. N Engl J Med. 2020;382(8):727-33.
3
World Health Organization. Timeline: WHO's COVID-19 response. Available from: 
https://www.who.int/emergencies/diseases/novel-coronavirus-2019/interactive-
timeline#!. Accessed: 08 Jan 2021.
4
World Health Organization. WHO Director-General's opening remarks at the media 
briefing on COVID-19. Available from: https://www.who.int/dg/speeches/detail/
who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19---11-march-
2020. Published: 11 Mar 2020. Accessed: 01 Apr 2020.
5
COVID-19 dashboard by the Center for Systems Science and Engineering (CSSE) at 
Johns Hopkins University.  Available from: 
https://gisanddata.maps.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299
423467b48e9ecf6. Accessed: 08 Jan 2021.
6
Centers for Disease Control and Prevention. Emerging SARS-CoV-2 variants. Available 
from: https://www.cdc.gov/coronavirus/2019-ncov/more/science-and-
research/scientific-brief-emerging-variants.html. Updated: 28 Jan 2021. Accessed: 
10 Feb 2021.
7
Rauch S, Jasny E, Schmidt KE, et al. New vaccine technologies to combat outbreak 
situations. Front Immunol. 2018;9:1963.
8
Sahin U, Karikó K, Türeci Ö. mRNA-based therapeutics—developing a new class of 
drugs. Nat Rev Drug Discov. 2014;13(10):759-80.
9
BioNTech RNA Pharmaceuticals GmbH. CorVAC/BNT162 Investigator’s Brochure. 
Mainz, Germany: BioNTech RNA Pharmaceuticals GmbH; 25 Mar 2020.
10
Feldman RA, Fuhr R, Smolenov I, et al. mRNA vaccines against H10N8 and H7N9 
influenza viruses of pandemic potential are immunogenic and well tolerated in healthy 
adults in phase 1 randomized clinical trials. Vaccine. 2019;37(25):3326-34.
11
BioNTech RNA Pharmaceuticals GmbH. BNT162/PF-07302048 Investigator’s 
Brochure. Mainz, Germany: BioNTech RNA Pharmaceuticals GmbH; 29 Jan 2021.

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12
US Food and Drug Administration. Guidance for industry: toxicity grading scale for 
healthy adult and adolescent volunteers enrolled in preventive vaccine clinical trials. 
Rockville, MD: Center for Biologics Evaluation and Research; September 2007.
13
Centers for Disease Control and Prevention. Multisystem inflammatory syndrome in 
children (MIS-C) associated with coronavirus disease 2019 (COVID-19).  Available 
from:  https://emergency.cdc.gov/han/2020/han00432.asp.  Updated:  14 May 2020.  
Accessed:  15 Jan 2021.
14
Centers for Disease Control and Prevention.  Symptoms of COVID-19.  Available from: 
https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html.  
Updated: 22 Feb 2021. Accessed: 29 Apr 2021.

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