Document text
Interim Clinical Study Report
Protocol C4591001
CLINICAL STUDY REPORT SYNOPSIS
CONFIDENTIAL
Page 1Vaccine Name and Compound Number: BNT162 RNA -Based COVID -19 Vaccines,
Compound Number: PF-07302048
Report Title: Interim Report – 6 Month Update : A Phase 1/2/3, Placebo -Controlled,
Randomized, Observer -Blind, Dose -Finding Study to Evaluate the Safety , Tolerability ,
Immunogenicit y, and Efficacy of SARS -COV -2 RNA Vaccine Candidates Against
COVID -19 in Healthy Individuals
Protocol Number: C4591001
Sponsor: BioNTech SE
Sponsor Agent : Pfizer Inc
Phase of Development: Phase 1/2/3
First Subject First Visit: 29 April 2020
Last Subject Last Visit: Not applicable
Data Cutoff Date: 13 March 2021
Serology Completion Date s: 22 March 2021 (Phase 1, Visit 8 [post -Dose 2 blood draw]
assay completed)
Coordinating Investigator(s): Stephen Thomas, MD, SUNY Upstate Medical Universit y,
725Irving Ave, Ste. 311, Sy racuse, NY 13210
Refer to Appendix 16.1.4.1 for a list of investigators involved in this study .
Study Center(s): 131 in the United S tates, 9 in Turkey , 6 in Germany , 4 in South Africa,
2 in Brazil, and 1 in Argentina. Refer to Appendix 16.1.4.1 for a list of sites involved in this
study .
Date of Current Version: 29April 2021
Date(s) of Previous Report(s): Not applicable
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Page 2OBJECTIVES
Study Objectives and Endpoints:
Phase 1
The study objective s, estimands, and endpoints presented in Table S 1are from Protocol Amendment 14. Only the primary safety
(Dose 1 to unblinding date [ up to approximately 6 months after Dose 2]) and partial secondary immunogenicity (6 months after
Dose 2) objectives for the BNT162b2 30 µg or corresponding placebo are presented in this interim clinical study report ( CSR).
Exploratory objectives, estimands, and endpoints will be summarized at a lat er time.
Table S 1.Phase 1 Objectives, Estimands, and Endpoints
Objectives Estimands Endpoints Reference
Primary: Primary: Primary:
To describe the safety and
tolerability profiles of
prophylactic BNT162 vaccines
in healthy adults after 1 or
2dosesIn participants receiving at least 1 dose of study
intervention, 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
Adverse events (A Es)from Dose 1 to 1 month after
the last dose
Serious adverse events ( SAEs )from Dose 1 to 6
months after the last doseLocal 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
SAEsInterim data for local reactions and
systemic events reported up to 7 days
after each dose, and AEs and SAEs are
reported from Dose 1 to 1 month after the
last dose for all gro ups evaluated, and to
the cutoff date after Dose 2 for the
BNT162b2 30 µg group only in final
analysis interim CSR dated 03 December
2020.
AEs and SAEs from Dose 1 to the
unblinding date for the BNT162b2 30 µ g
group only are reported in this CSR.
In addition, the percentage of participants with:
Abnormal hematology and chemistry laboratory
values 1 and 7 days after Dose 1; and 7 days after
Dose 2
Grading shifts in hematology and chemistry
laboratory assessments between baseline and 1 and
7days after Dose 1; and before Dose 2 and 7 days
after Dose 2Hematology and chemistry laboratory
parameters.Interim data are reported in final analysis
interim CSR dated 03 December 2020.
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Page 3Table S 1.Phase 1 Objectives, Estimands, and Endpoints
Objectives Estimands Endpoints Reference
Secondary: Secondary: Secondary:
To describe the immune
responses elicited by
prophylactic BNT162 vaccines
in healthy adults after 1 or 2
dosesIn participants complying with the key protocol criteria
(evaluable participants) at the following time points
after receipt of study intervention: 7 and 21 days after
Dose 1; 7 and 14 days and 1, 6, 12, and 24 months after
Dose 2
Geometric mean titers ( GMTs)at each time point
Geometric mean fold rise ( GMFR )from before
vaccination to each subsequent time point after
vaccination
Proportion of participants achieving ≥4-fold rise
from before vaccination to each subsequent time
point after vaccinationSevere acute respiratory syndrome
coronavirus 2 ( SARS -CoV -2)
neutralizing titersInterim data reported up to 1 month after
Dose 2 in final analysis interim CSR
dated 03 December 2 020.
Interim data up to 6 months after Dose 2
for the BNT162b2 30 µg group only are
reported in this CSR.
Geometric mean concentrations ( GMCs )at each time
point
GMFR from prior to first dose of study intervention
to each subsequent time point
Proportion of participants achieving ≥4-fold rise
from before vaccination to each subsequent time
point after vaccinationS1-binding immunoglobulin G (IgG )
levels and receptor -binding domain
(RBD )-binding IgG levelsInterim data reported up to 1 month afte r
Dose 2 in final analysis interim CSR
dated 03 December 2020.
Interim data of S1-binding IgG levels up
to 6 months after Dose 2 for the
BNT162b2 30 µg group only are
reported in this CSR.
Geometric mean ratio ( GMR ), estimated by the ratio
of the geomet ric mean of SARS -CoV -2neutralizing
titers to the geometric mean of binding IgG levels at
each time pointSARS -CoV -2 neutralizing titers
S1-binding IgG levels
RBD -binding IgG levelsInterim data reported up to 1 month after
Dose 2 in final analysis interim CSR
dated 03 December 2020.
Interim data for SARS -CoV -2
neutralizing titers to S1 -binding IgG
levels up to 6 months after Dose 2 for
the BNT162b2 30 µg group only are
reported in this CSR.
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Page 4Table S 1.Phase 1 Objectives, Estimands, and Endpoints
Objectives Estimands Endpoints Reference
Exploratory: Exploratory: Exploratory:
To describe the immune
responses elicited by a third
dose of prophylactic BNT162b2
administered to healthy adults 6
to 12 months after the second
dose of either BNT162b1 or
BNT162b2 GMC/GMT and GMFR at the time of Dose 3 and 7
days and 1 month after Dose 3. SARS -CoV -2 reference -strain
neutralizing titers
SARS -CoV -2 South African ( SA)-
variant neutralizing titers
Full-length S -binding or S1 -binding
IgG levelsData will be reported at a later time.
GMR of SARS -CoV -2 reference -strain
neutralizing titers 1 month after Dose 3 to 1 month
after Dose 2 SARS -CoV -2 reference -strain
neutralizing titersData will be reported at a later time.
GMR of SARS -CoV -2 SA -variant neutralizing
titers 1 month after Dose 3 to SARS -CoV -2
reference -strain neutralizing titers 1 month after
Dose 2 SARS -CoV -2 reference -strain
neutralizing titers
SARS -CoV -2 SA -variant neutralizing
titersData will be reported at a later time.
To describe the safety profile of
a third dose of prophylactic
BNT162b2 administered to
healthy adults 6 to 12 months
after the second dose of either
BNT162b1 or BNT162b2In participants receiving a third dose of BNT162b2, the
percentage of participants reporting:
Local reactions for up to 7 days after Dose 3
Systemic events for up to 7 days after Dose 3
AEs and SAEs from Dose 3 to 1 month after
Dose 3 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
SAEsData will be reported at a later time.
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Page 5Phase 2/3
The study objective s, estimands, and endpoints presented in Table S 2are from Protocol
Amendment 14.
Based on a data cutoff date of 13 March 2021, t his interim C4591001 CSR summarizes
updated efficacy anal yses on an accrued 927 COVID- 19 cases for the first primary endpoint
during blinded follow -up to evaluate duration of protection and the following
immunogenicit y and safety data:
Blinded placebo -controlled follow -up period: from Dose 1 to 1 month after Dose 2 and to
the date of unblinding:
Phase 2/3 safet y ana lysis for participants ≥16 years of age, including participants with
confirmed stable HIV disease, from Dose 1 to 1 month after Dose 2 (no exposure
adjustment because all participants have the same follow-up period) and from Dose 1
to the unblinding date ( exposure adjusted).
Open -label observational follow -up period: from time of unblinding to the data cutoff
date:
Phase 2/3 safet y analysis for original BNT162b2 participants ≥16years of age
Phase 2/3 safet y analysis for original placebo participants ≥16years of age who then
received BNT162b2
Cumulative safety from Dose 1 to at least 6 months after Dose 2: for Phase 2/3 original
BNT162b2 participants ≥16 years of age (inclusive of blinded data and open- label data)
that includes at least 3000 in each age gr oup (16 t hrough 55 years of age, >55 years of
age)
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Page 6Table S 2. Phase 2/3 Objectives, Estimands, and Endpoints
Objectivesa Estimands Endpoints Reference
Primary Efficacy
To evaluate the efficacy of prophylactic
BNT162b2 against confirmed COVID-19
occurring from 7 days after the second
dose in participants without evidence of
infection before vaccinationIn participants complying with the key
protocol criteria (evaluable participants)
at least 7 days after receipt of the second
dose of study intervention: 100 × (1 –
illness rate ratio [IRR] )
[ratio of active vaccine to placebo]COVID -19 incidence per 1000 person -years
of follow -up based on central laboratory or
locally confirmed nucleic acid
amplification test (NAAT )in participants
with no serological or virological evidence
(upto 7 days afte r receipt of the second dose)
of past SARS -CoV -2 infectionPrespecified complete efficacy data
are reported in final analysis interim
CSR dated 03 December 2020.
Updated efficacy data are reported in
this CSR.
To evaluate the efficacy of prophylactic
BNT162b2 against confirmed COVID-19
occurring from 7 days after the second
dose in participants with and without
evidence of infection before vaccinationIn participants complying with the key
protocol criteria (evaluable participants)
at least 7 days afte r receipt of the second
dose of study intervention: 100 × (1 –
IRR)
[ratio of active vaccine to placebo]COVID -19 incidence per 1000 person -years
of follow -up based on central laboratory or
locally confirmed NAATInterim data are reported in final
analys is interim CSR dated
03December 2020.
Updated efficacy data are reported in
this CSR.
Primary Safety
To define the safety profile of
prophylactic BNT162b2 in the first
360participants randomized (Phase 2)In participants receiving at least 1 dose of
study intervention, 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 from Dose 1 to 7 days after the
second dose
SAEs from Dose 1 to 7 days after the
second doseLocal 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
SAEsInterim data are reported in final
analysis interim CSR dated
03December 2020.
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Page 7Table S 2. Phase 2/3 Objectives, Estimands, and Endpoints
Objectivesa Estimands Endpoints Reference
To define the safety profile of
prophylactic BNT162b2 in all
participants randomized in Phase 2/3In participants receiving at least 1 dose of
study intervention, 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 from Dose 1 to 1 month after the
second dose
SAEs from Dose 1 to 6 months after
the second doseAEs
SAEs
In a subset of at least 6000 participants:
o Local reactions (pain at the
injection site, redness, and
swelling)
o Systemic events (fever, fatigue,
headache, chills, vomiting,
diarrhea, new or worsened muscle
pain, and new or worsened joint
pain)Interim data are reported up to
1month after Dose 2 and to the data
cutoff date (14 November 2020) in
final analysis interim CSR dated
03December 2020.
Cumulative interim data up to the
cutoff date are reported in this CSR.
To define the safety profile of
prophylactic BNT162b2 in participants
12 to 15 years of age in Phase 3In participants receiving at least 1 dose of
study intervention, 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 from Dose 1 to 1 month after
the second dose
SAEs from Dose 1 to 6 months after
the second 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
SAEsData will be reported separately .
To describe the safety and tolerability
profile of BNT162b2 SAgiven as 1 or 2
doses to BNT162b2 -experienced
participants, or as 2 doses to BNT162b2 -
naïve participants
To describe the safety and tolerability
profile of BNT162b2 given as a third
dose to BNT162b2 -experienced
participantsIn participants receiving at least 1 dose of
study intervention, 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 from Dose 1 to 1 month after the
last dose
SAEs from Dose 1 to 5 or 6 months
after the last doseLocal 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
SAEsData will be reported at a later time.
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Page 8Table S 2. Phase 2/3 Objectives, Estimands, and Endpoints
Objectivesa Estimands Endpoints Reference
Prim ary Immunogenicity
BNT162b2 -experienced participants
To demonstrate the noninferiority of the
anti–reference strain immune response
after a third dose of BNT162b2 compared
to after 2 doses of BNT162b2, in the
same individualsGMR of reference strain neutralizing titer
(NT)1 month after the third dose of
BNT162b2 to 1 month after the second
dose of BNT 162b2
The difference in percentages of
participants with seroresponse to the
reference strain at 1 month after the third
dose of BNT162b2 and 1 month after the
second dose of BNT162b2SARS -CoV -2 reference strain NTs in
participants with no serological or virological
evidence (up to 1 month after receipt of the
third dose of BNT162b2) of past SARS -CoV -
2 infectionData will be reported at a later time.
To demonstrate the noninferiority of the
anti-SA immune response after 1 dose of
BNT162b2 SAcompared to the anti–
reference strain immune response after 2
doses of BNT162b2, in the same
individualsGMR of SA NT 1 month after 1 dose of
BNT162b2 SAto the reference strain NT 1
month after the second dose of
BNT162b2
The difference in percentages of
participants with seroresponse to the SA
strain at 1 month after 1 dose of
BNT162b2 SAand seroresponse to the
reference strain at 1 month after the
second dose of BNT162b2SARS -CoV -2 SA and reference strain NTs in
participants with no serological or virological
evidence (up to 1 month after receipt of 1
dose of BNT162b2 SA) of past SARS -CoV -2
infectionData will be reported at a later time.
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Page 9Table S 2. Phase 2/3 Objectives, Estimands, and Endpoints
Objectivesa Estimands Endpoints Reference
BNT162b2 -naïve participants
To demonstrate the noninferiority of the
anti-SA immune response after 2 doses of
BNT162b2 SAcompared to the anti–
reference strain immune response after 2
doses of BNT162b2 GMR of SA NT 1 month after the second
dose of BNT162b2 SAto the reference
strain NT 1 month after the second dose
of BNT162b2
The difference in percentages of
participants with seroresponse to the SA
strain at 1 month after the second dose of
BNT162b2 SAand seroresponse to the
reference strain at 1 month after the
second dose of BNT162b2SARS -CoV -2 SA and reference strain NTs in
participants with no serological or virological
evidence (up to 1 month after receipt of the
second dose of BNT162b2 SAor BNT162b2 as
appropriate) of past SARS-CoV -2 infectionData will be reported at a later time.
Secondary Efficacy
To evaluate the efficacy of prophylactic
BNT162b2 against confirmed COVID-19
occurring from 14 days after the second
dose in participants without evidence of
infection before vaccinationIn participants complying with the key
protocol criteria (evaluable participants)
at least 14 days after recei pt of the second
dose of study intervention:
100 × (1 –IRR) [ratio of active vaccine
to placebo]COVID -19 incidence per 1000 person -years
of follow -up based on central laboratory or
locally confirmed NAAT in participants with
no serological or virological evidence (up to
14 days after receipt of the second dose) of
past SARS -CoV -2 infectionPrespecified complete efficacy data
are reported in final analysis interim
CSR dated 03 December 2020.
To evaluate the efficacy of prophylactic
BNT162b2 against confirmed COVID -19
occurring from 14 days after the second
dose in participants with and without
evidence of infection before vaccinationIn participants complying with the key
protocol criteria (evaluable participants)
at least 14 days after receipt of th e second
dose of study intervention:
100 × (1 –IRR) [ratio of active vaccine
to placebo]COVID -19 incidence per 1000 person -years
of follow -up based on central laboratory or
locally confirmed NAATPrespecified complete efficacy data
are reported in final analysis interim
CSR dated 03 December 2020.
To evaluate the efficacy of prophylactic
BNT162b2 against confirmed severe
COVID -19 occurring from 7 days and
from 14 days after the second dose in
participants without evidence of infection
before vaccinationIn participants complying with the key
protocol criteria (evaluable participants)
at least 7 days
and
at least 14 days
after receipt of the second dose of study
intervention: 100 × (1 –IRR)
[ratio of active vaccine to placebo]Confirmed severe COVID -19 incidence per
1000 person -years of follow -up in
participants with no serological or virological
evidence (up to 7 days and up to 14 days after
receipt of the second dose) of past
SARS -CoV -2 infectionPrespecified complete efficacy data
are reporte d in final analysis interim
CSR dated 03 December 2020.
Updated efficacy data occurring from
at least 7 days after the second dose
only are reported in this CSR.
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Page 10Table S 2. Phase 2/3 Objectives, Estimands, and Endpoints
Objectivesa Estimands Endpoints Reference
To evaluate the efficacy of prophylactic
BNT162b2 against confirmed severe
COVID -19 occurrin g from 7 days and
from 14 days after the second dose in
participants with and without evidence of
infection before vaccinationIn participants complying with the key
protocol criteria (evaluable participants)
at least 7 days
and
at least 14 days
after receipt of the second dose of study
intervention: 100 × (1 –IRR)
[ratio of active vaccine to placebo]Confirmed severe COVID -19 incidence per
1000 person -years of follow -upPrespecified complete efficacy data
are reported in final analysis interim
CSR dated 03 December 2020.
Updated efficacy data occurring from
at least 7 days after the second dose
only are reported in this CSR.
To describe the efficacy of prophylactic
BNT162b2 against confirmed COVID-19
(according to the CDC-defined
symptoms) occurring from 7 days and
from 14 days after the second dose in
participants without evidence of infection
before vaccinationIn participants complying with the key
protocol criteria (evaluable participants)
at least 7 days
and
at least 14 days
after rec eipt of the second dose of study
intervention: 100 × (1 –IRR)
[ratio of active vaccine to placebo]COVID -19 incidence per 1000 person -years
of follow -up based on central laboratory or
locally confirmed NAAT in participants with
no serological or virolog ical evidence (up to 7
days and up to 14 days after receipt of the
second dose) of past SARS-CoV -2 infectionPrespecified complete efficacy data
are reported in final analysis interim
CSR dated 03 December 2020.
To describe the efficacy of prophylactic
BNT162b2 against confirmed COVID-19
(according to the Centers for Disease
Control and Prevention (United States)
(CDC )-defined symptoms) occurring
from 7 days and from 14 days after the
second dose in participants with and
without evidence of infection bef ore
vaccinationIn participants complying with the key
protocol criteria (evaluable participants)
at least 7 days
and
at least 14 days
after receipt of the second dose of study
intervention: 100 × (1 –IRR)
[ratio of active vaccine to placebo]COVID -19incidence per 1000 person -years
of follow -up based on central laboratory or
locally confirmed NAATPrespecified complete efficacy data
are reported in final analysis interim
CSR dated 03 December 2020.
To evaluate the efficacy of prophylactic
BNT162b2 against non -S seroconversion
to SARS-CoV -2 in participants without
evidence of infection or confirmed
COVID -19In participants complying with the key
protocol criteria (evaluable participants):
100 × (1 –IRR) [ratio of active vaccine
to placebo]Incidence of asymptomatic SARS -CoV -2
infection per 1000 person -years of follow -up
based on SARS -CoV -2 nucleoprotein
(N)-binding antibody seroconversion in
participants with no serological or virological
evidence of past SARS -CoV -2 infection or
confirmed COVID -19Data will be reported at a later time.
To evaluate the efficacy of prophylactic
BNT162b2 against asymptomatic SARS -
CoV -2 infection in participants without
evidence of infection up to the start of the
asymptomatic surveillance periodIn participants complyin g with the key
protocol criteria (evaluable participants):
100 × (1 –IRR) [ratio of active vaccine
to placebo]Incidence of asymptomatic SARS -CoV -2
infection per 1000 person -years of follow -up
based on central laboratory –confirmed
NAAT in participants with no serological or
virological evidence (up to the start of the Data will be reported at a later time.
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Page 11Table S 2. Phase 2/3 Objectives, Estimands, and Endpoints
Objectivesa Estimands Endpoints Reference
asymptomatic surveillance period) of past
SARS -CoV -2 infection
Secondary Immunogenicity
To demonstrate the noninferiority of the
immune response to prophylactic
BNT162b2 in participants 12 to 15 years
of age compared to participants 16 to 25
years of ageGMR, estimated by the ratio of the
geometric mean of SARS -CoV -2
neutralizing titers in the 2 age groups
(12-15 years of age to 16 -25 years of age)
1month after completion of vaccinationSARS -CoV -2 neutralizing titers in
participants with no serological or virological
evidence (up to 1 month after receipt of the
second dose) of past SARS -CoV -2 infectionData will be reported separate ly.
BNT162b2 -expe rienced participants
To demonstrate the noninferiority of the
anti-SA immune response after a third
dose of BNT162b2 compared to the anti –
reference strain immune response after 2
doses of BNT162b2, in the same
individuals GMR of SA NT 1 month after the third
dose of BNT162b2 to the reference strain
NT 1 month after the second dose of
BNT162b2
The difference in percentages of
participants with seroresponse to the SA
strain at 1 month after the third dose of
BNT162b2 and seroresponse to the
reference stra in at 1 month after the
second dose of BNT162b2SARS -CoV -2 SA and reference strain NTs in
participants with no serological or virological
evidence (up to 1 month after receipt of the
third dose of BNT162b2) of past SARS -CoV -
2 infectionData will be reporte d at a later time.
To demonstrate the noninferiority of the
anti–reference strain immune response
after 1 dose of BNT162b2 SAcompared to
after 2 doses of BNT162b2, in the same
individuals GMR of reference strain NT 1 month
after 1 dose of BNT162b2 SAto 1month
after the second dose of BNT162b2
The difference in percentages of
participants with seroresponse to the
reference strain at 1 month after 1 dose of
BNT162b2 SAand 1 month after the
second dose of BNT162b2SARS -CoV -2 reference strain NTs in
participants with no serological or virological
evidence (up to 1 month after receipt of 1
dose of BNT162b2 SA) of past SARS -CoV -2
infectionData will be reported at a later time.
To descriptively compare the anti-SA
immune response after 1 dose of
BNT162b2 SAand a third dose of
BNT162b2 GMR of SA NT 1 month after 1 dose of
BNT162b2 SAto 1month after the third
dose of BNT162b2
The difference in percentages of
participants with seroresponse to the SA
strain at 1 month after 1 dose of SARS -CoV -2 SA NT in participants with no
serological or virological evidence (up to 1
month after receipt of 1 dose of BNT162b2 SA
or the third dose of BNT162b2) of past
SARS -CoV -2 infectionData will be reported at a later time.
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Page 12Table S 2. Phase 2/3 Objectives, Estimands, and Endpoints
Objectivesa Estimands Endpoints Reference
BNT162b2 SAand 1 month after the third
dose of BNT162b2
To descriptively compare the anti-SA
immune response after 2 doses of
BNT162b2 SAand the anti –reference
strain immune response after 2 doses of
BNT162b2, in the same individuals GMR of SA NT 1 month after the second
dose of BNT162b2 SAto the refere nce
strain NT 1 month after the second dose
of BNT162b2
The difference in percentages of
participants with seroresponse to the SA
strain at 1 month after the second dose of
BNT162b2 SAand seroresponse to the
reference strain at 1 month after the
second do se of BNT162b2SARS -CoV -2 SA and reference strain NTs in
participants with no serological or virological
evidence (up to 1 month after receipt of the
second dose of BNT162b2 SA) of past
SARS -CoV -2 infectionData will be reported at a later time.
BNT162b2 -naïve participants
To demonstrate a statistically greater
anti-SA immune response after 2 doses of
BNT162b2 SAcompared to after 2 doses
of BNT162b2 GMR of SA NT 1 month after the second
dose of BNT162b2 SAto 1month after the
second dose of BNT162b2
The difference in percentages of
participants with seroresponse to the SA
strain at 1 month after the second dose of
BNT162b2 SAand 1 month after the
second dose of BNT162b2SARS -CoV -2 SA NTs in participants with no
serological or virological evidence (up to 1
month after receipt of the second dose of
BNT162b2 SAor BNT162b2 as appropriate)
of past SARS -CoV -2 infectionData will be reported at a later time.
To descriptively compare the anti–
reference strain immune response after 2
doses of BNT162b2 SAand after 2 doses
of BNT162b2 GMR of reference strain NT 1 month
after the second dose of BNT162b2 SAto
1month after the second dose of
BNT162b2
The difference in percentages of
participants with seroresponse to
reference strain at 1 month after the
second dose of BNT162b2 SAand 1 month
after the second dose of BNT162b2SARS -CoV -2 reference strain NTs in
participants with no serological or virological
evidence (up to 1 month after receipt of the
second dose of BNT162b2 SAor BNT162b2 as
appropriate) of past SARS-CoV -2 infectionData will be reported at a later time.
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Page 13Table S 2. Phase 2/3 Objectives, Estimands, and Endpoints
Objectivesa Estimands Endpoints Reference
Exploratory
To describe the efficacy of prophylactic
BNT162b2 against confirmed COVID-19
occurring from 7 days after the second
dose through the blinded follow -up
period in participants without, and with
and without, evidence of infection before
vaccinationIn participants complying with the key
protocol criteria (evaluable participants)
after receipt of the second dose of study
intervention:
100 × (1 –IRR) [ratio of active vaccine
to placebo]COVID -19 incidence per 1000 person -years
of blinded follow -up based on central
laboratory or locally confirmed NAATInterim d ata arereported in this CSR.
To describe the incidence of confirmed
COVID -19 through the entire study
follow -up period in participants who
received BNT162b2 at initial
randomization or subsequentlyIn participants who received BNT162b2
(at initial randomization or
subsequently):
Incidence per 1000 person-ye ars of
follow -upCOVID -19 incidence per 1000 person -years
of follow -up based on cen tral laboratory or
locally confirmed NAATData will be reported at a later time.
To evaluate the immune response over
time to prophylactic BNT162b2 and
persistence of immune response in
participants with and without serological
or virological evidence of SARS -CoV -2
infection before vaccinationGMC/GMT and GMFR at baseline and 1,
6, 12, and 24 months after completion of
vaccinationFull-length S -binding or S1 -binding IgG
levels
SARS -CoV -2 neutralizing titersInterim data for Phase 2 (first
360participants) only up to 1 month
after Dose 2 are reported for
S1-binding IgG levels and
SARS -CoV -2 neutr alizing titers in
final analysis interim CSR dated
03December 2020.
Phase 2/3 d ata will be reported at a
later time
To describe the incidence of non -S
seroconversion to SARS -CoV -2 through
the entire study follow -up period in
participants who received BNT162b2 at
initial randomization In participants who received BNT162b2
at initial randomization:
Incidence per 1000 person-ye ars of
follow -upIncidence of asymptomatic SARS -CoV -2
infection per 1000 person -years of follow -up
based on N -binding antibody seroconversion
in participants with no serological or
virological evidence of past SARS -CoV -2
infection or confirmed COVID -19Data will be reported at a later time.
To describe the efficacy of prophylactic
BNT162b2 against asymptomatic SARS -
CoV -2 infection in participants with
evidence of infection up to the start of the
asymptomatic surveillance periodIn participants complying with the key
protocol criteria (evaluable participants):
100 × (1 –IRR) [ratio of active vaccine
to placebo]Incidence of asymptomatic SARS -CoV -2
infection per 1000 person -years of follow -up
based on central laboratory –confirmed
NAAT in participants with sero logical or
virological evidence (up to the start of the Data will be reported at a later time.
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Page 14Table S 2. Phase 2/3 Objectives, Estimands, and Endpoints
Objectivesa Estimands Endpoints Reference
asymptomatic surveillance period) of past
SARS -CoV -2 infection
To describe the serological responses to
the BNT vaccine candidate and
characterize the SARS -CoV -2 isolate in
cases of:
Confirmed COVID-19
Confirmed severe COVID -19
SARS -CoV -2 infection without
confirmed COVID -19Full S -binding or S1 -binding IgG levels
SARS -CoV -2 neutralizing titers
Identification of SARS -CoV -2 variants(s)Data will be reported at a later time.
To describe the safety, immunogenicity,
and efficacy of prophylactic BNT162b2
in individuals with confirmed stable HIV
diseaseAll safety, immunogenicity, and efficacy
endpoints described aboveSafety data only in participants with
confirmed stable HIV disease are
reported in this CSR.
To describe the safety and
immunogenicity of prophylactic
BNT162b2 in individuals 16 to 55 years
of age vaccinated with study intervention
produced by manufacturing “Process 1”
or “Process 2” AEs
SAEs
SARS -CoV -2 neutralizing titersData will be reported at a later time.
To describe the immune response to any
variants of concern ( VOCs )not already
specifiedGeometric mean NT for any VOCs not
already specified, after any dose of
BNT162b2 SAor BNT162b2 SARS -CoV -2 NTs for any VOCs not
already specifiedData will be reported at a later time.
To describe the cell -mediated immune
response, and additional humoral
immune response parameters, to the
reference strain and SA in a subset of
participants:
7 Days and 1 and 6 months after
BNT162b2 SAgiven as 1 or 2 doses to
BNT162b2 -experienced participants
7 Days and 1 and 6 months after
BNT162b2 SAgiven as 2 doses to
BNT162b2 -naïve participantsData will be reported at a later time.
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Page 15Table S 2. Phase 2/3 Objectives, Estimands, and Endpoints
Objectivesa Estimands Endpoints Reference
7 Days and 1 and 6 months after
BNT162b2 given as a third dose to
BNT1 62b2 -experienced participants
a.HIV-positive participants in Phase 3 were not included in analyses of the objectives, w ith the exception of the specifi c exploratory objective.
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Page 16METHODS
Study Design: This is a Phase 1/2/3, randomized, multinational, placebo -controlled,
observer -blind, dose -finding, vaccine candidate– selection, and efficacy study in healthy
individuals.
The study consists of 2 parts: Phase 1 to identify preferred vaccine candidate(s) and dose
level(s); and Phase 2/3 as an expanded cohort and efficacy part. These parts, and the
progression between them, are detailed in Figure S 1.
Figure S 1.Study Schema
Phase 1 For each vaccine candidate (4:1 randomization active:placebo)
Age: 18-55 y Age: 65-85 y
Low-dose -level 2 -dose group (n=15)
IRC (safety) IRC (safetyLow-dose -level 2 -dose group (n=15)after Dose 1)
Mid-dose -level 2 -dose group (n=15)
IRC (safety)IRC (safetyMid-dose -level 2 -dose group (n=15)after Dose 1)
High -dose -level 2 -dose group (n=15)
IRC (safetyHigh -dose -level 2 -dose group (n=15)after Dose 1)
IRC choice of group(s) for Phase 2/3
(safety & immunogenicity after Doses 1 and 2)
Phase 2/3 Single vaccine candidate (1:1 randomization active:placebo)
Safety and immunogenicity analysis of
Phase 2 data (first 360 participants)
by unblinded team (these participants
will also be included in Phase 3
analyses)Age: ≥12
(Stratified 12 -15, 16-55, or >55)
BNT162b2 30 µg or placebo 2 doses
(n~21,999 per group, total n~ 43,998)
Abbreviation: IRC = internal review committee
Note: Participants ≥16 years of age who originally received placebo were offered the opportunity to receive BNT162b2 at
defined points as part of the study
The study evaluated the safet y, tolerability , and immunogenicit y of 3 different SARS -CoV -2
RNA vaccine candidates against COVID- 19 and the Phase 2/3 efficacy of 1 selected
candidate based on Phase 1 results:
As a 2 -dose (separated by 21 day s) schedule;
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Page 17At various dose levels in Phase 1;
As a booster; (data will be reported at a later time)
In various age groups:
Phase 1: 18 to 55 and 65 to 85 y ears of age;
Phase 2: ≥18 years of age (stratified as 18 to 55 years and >55 to 85 years);
Phase 3: ≥12 years of age (stratified as 12 to 15, 16 to 55, or >55 years of age).
To facilitate rapid review of data in real time, Pfizer and BioNTech staff were unblinded to
vaccine allocation for the participants in Phase 1, and remain blinded for the Phase 2/3
portion of study except those who were design ated for unblinded activities following the
protocol and the data blinding plan .
Planned Booster and Variant Strain Evaluation
Planned booster and VOC evaluation are not included in this report and will be reported at a
later time.
Unblinding Consideration s
The study was unblinded in stages once all ongoing participants either had been individually
unblinded or had concluded their 6 -month post –Dose 2 study visit, as follows:
Phase 1 (after Visit 8).
Phase 2/3, ≥16 y ears of age (after Visit 4).
Phase 3, 12 through 15 years of age (after Visit 4).
Original Phase 3 participants rerandomized to assess boostability and protection against
emerging VOCs (after Visit 306) (data will be reported at a later time).
Participants ≥16 y ears of age who originall y received placebo and became eligible for receipt
of BNT162b2 according to recommendations detailed separately , and available in the
electronic stud y reference portal, had the opportunity to receive BNT162b2 in a phased
manner as part of the study . The investigator ensured the participant met at least 1 of the
recommendation criteria.
Any Phase 1 placebo recipient who had not already been offered the opportunity to receive
BNT162b2 was given this opportunity no later than at the approximate time participants in
Phase2/3 reached Visit 4. Any Phase 2/3 placebo recipient ≥16 y ears of age who had not
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Page 18alread y been offered the opportunity to receive BNT162b2 was given this opportunity no
later than 6 months after Vaccination 2 (at the time of the originall y planned Visit 4).
Any participant who originally received placebo but then went on to receive BNT162b2 was
moved to a new visit schedule to receive both doses of BNT162b2 at each of 2 additional
vaccination visits (Visits 101 and 102).
Phase 1
Each group (vaccine candi date/dose level/age group) was comprised of 15 participants
randomized 4:1 to receive active vaccine or placebo (12 participants randomized to active
vaccine and 3 to placebo, such that the placebo participants across the groups would produce
a roughly comparabl y-sized cohort).
For each vaccine candidate/dose level/age group, safet y precautions included: additional
safet y assessments, controlled enrollment, application of stopping rules, and I RC review of
safet y data to determine if dose escalation could p roceed.
Groups of participants 65 to 85 y ears of age were not started until safet y data for the RNA
platform were deemed acceptable at the same, or a higher, dose level in the 18 to 55 years of
age group b y the IRC.
In this phase, 13 groups were studied, c orresponding to a total of 195 participants.
Following review of all available safety and immunogenicity data through 14 day s after
Dose 2 for BNT162b1 and BNT162b2, both vaccine constructs were considered strong
candidates to proceed to Phase 2/3.
Planned Evaluations
A third dose of BNT162b2 30 µg will be given to Phase 1 participants approximately 6 to
12 months after their second dose of BNT162b1 or BNT162b2 to evaluate safet y and
immunogenicit y for boostability and potential heterologous protection against emerging
VOCs.
Participants were expected to participate for up to a maximum of approximately 26 months.
Phase 2/3
Safety and immunogenicity data generated during the Phase 1 portion of this study and the
BioNTech study conducted in Germany (BNT162 -01) supported BNT162b2 at a dose of
30µg as the vaccine candidate to proceed into Phase 2/3.
The Phase 2 part of the stu dy was comprised of the first 360 participants enrolled
(1:1randomization between BNT162b2 and placebo, stratified by age groups [18 through
55years and >55 through 85 y ears] with approximately 50% in each age stratum) to assess
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Page 19safet y data through 7 days after Dose 2 and immunogenicity data through 1 month after
Dose 2 from these Phase 2 360 participants. Enrollment continued during Phase 2 and these
participants are included in the efficacy evaluation in the Phase 3 part of the study .
Participants in th e ongoing Phase 3 part of the study are ≥12 years of age (stratified as
12through 15, 16 through 55, or >55 years of age). The 12- through 15 -year stratum
comprised up to approximately 2000 participants enrolled at selected investigational sites. It
was planned to enroll a minimum of 40% of participants in the >55 y ears of age stratum.
Participants in Phase 3 were randomized 1:1 to receive either active vaccine or placebo.
Efficacy anal yses for Phase 2/3 part of the stud y were event -driven. The prespecif ied interim
analysis was conducted on an accrued 94 evaluable COVID -19 cases for the first primary
efficacy endpoint (data cutoff date: 04 November 2020), and the final analy sis was conducted
on an accrued 170 evaluable COVID -19 cases for the first primary efficacy endpoint (data
cutoff date: 14 November 2020). These data are reported in the final analy sis interim CSR
dated 03 December 2020 and included all study participants in the efficacy populations
≥12years of age.
At the time of the final analy sis of efficacy , relatively few participants 12 through 15 years of
age had enrolled in the study , and no COVID -19 cases in this age group accrued at that time.
Updated efficacy analy ses during blinded placebo- controlled follow -up period were
conducted on cases accrued up to the data cutoff date of 13 March 2021 to evaluate duration
of protection. This report presents these anal yses of all confirmed COVID- 19 cases and any
cases meeting protocol -and CDC -defined criteria for severe cases.
It is planned that partic ipants would participate for approximately 26months.
Planned Evaluations
Phase 2/3 (which is ongoing) includes additional planned anal yses which are not included in
this report and will be reported separatel y.
In Phase 3, noninferiority of immune respon se to prophy lactic BNT162b2 in participants
12through 15 years of age to response in participants 16 through 25 years of age will be
assessed based on the GMR of SARS -CoV -2 neutralizing titers using a 1.5 -fold margin.
The safet y and immunogenicity of prophy lactic BNT162b2 in individuals 16 through
55years of age vaccinated with BNT162b2 manufactured with “Process 1” and each lot
of BNT162b2 manufactured with “Process 2”, which was developed to support an
increased scale of manufacture.
Boostability and homologous/heterologous protection against emerging VOCs will allow
the evaluation of safet y and immunogenicity of BNT162b2 SA.
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Page 20An intensive period of surveillance to evaluate the efficacy of BNT162b2 against
asymptomatic SARS CoV -2 infection is being conducted at selected sites among
Phase 2/3 participants.
Inclusion/Exclusion Criteria: Inclusion and exclusion criteria presented are reflected
through Protocol Amendment 13 for this ongoing study . Updated inclusion and exclusion
criteria of the subset of par ticipants receiving the booster dose against emerging VOCs based
on Protocol Amendment 14 are not analy zedin this report, and therefore ,are not presented in
this sy nopsis.
Participants were eligible to be included in the study only if all of the followin g criteria
apply :
Inclusion Criteria:
Age and Sex:
1.Male or female participants between the ages of 18 and 55 y ears, inclusive, 65 and
85years, inclusive (Phase 1), or ≥12 y ears (Phase 2/3), at randomization. Note that
participants <18 years of age cannot be enrolled in the EU.
Type of Participant and Disease Characteristics:
2.Participants who were willing and able to comply with all scheduled visits, vaccination
plan, laboratory tests, lifesty le considerations, and other study procedures.
3.Health y participan ts who were determined by medical history , phy sical examination
(ifrequired), 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, could be included.
4.Phase 2/3 only: Participants who, in the judgment of the investigator, were at higher risk
for acquiring COVID -19 (including, b ut not limited to, use of mass transportation,
relevant demographics, and frontline essential workers).
Informed Consent:
5. Capable of giving personal signed informed consent/have parent(s)/legal guardian
capable of giving signed informed consent which included compliance with the
requirements and restrictions listed in the informed consent document (ICD) and in the
protocol.
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Page 21Exclusion Criteria:
Participants were excluded from the stud y if an y of the following criteria applied:
Medical Conditions:
1.Other medical or psy chiatric condition including recent (within the past year) or active
suicidal ideation/behavior or laboratory abnormality that increased the risk of study
participation or, in the investigator’s judgment, made the participant inappropriate fo r the
study .
2.Phases 1 and 2 only: Known infection with human immunodeficiency virus (HIV),
hepatitis C virus (HCV), or hepatitis B virus (HBV).
3.History of severe adverse reaction associated with a vaccine and/or severe allergic
reaction (eg, anaph ylaxis) t o any component of the study intervention(s).
4.Receipt of medications intended to prevent COVID -19.
5.Previous clinical (based on COVID -19 s ymptoms/signs alone, if a SARS -CoV -2 NAAT
result was not available) or microbiological (based on COVID -19 s ymptoms/sign s and a
positive SARS -CoV -2 NAAT result) diagnosis of COVID -19.
6.Phase 1 only: Individuals at high risk for severe COVID -19, including those with any of
the following risk factors:
Hypertension
Diabetes mellitus
Chronic pulmonary disease
Asthma
Current vapi ng or smoking
History of chronic smoking within the prior y ear
Chronic liver disease
Stage 3 or worse chronic kidney disease (glomerular filtration rate <60 mL/min/1.73 m2)
Resident in a long- term facility
Body mass index (BMI) >30 kg/m2
Anticipating the n eed for immunosuppressive treatment within the next 6 months
7.Phase 1 only: Individuals currentl y working in occupations with high risk of exposure to
SARS -CoV -2 (eg, healthcare worker, emergency response personnel).
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Page 228.Immunocompromised individuals with known or suspected immunodeficiency , as
determined b y history and/or laboratory /physical examination.
9.Phase 1 only: Individuals with a history of autoimmune disease or an active autoimmune
disease requiring therapeutic intervention, including but not limited to : systemic or
cutaneous lupus ery thematosus, autoimmune arthritis/rheumatoid arthritis, Guillain -Barré
syndrome, multiple sclerosis, Sjögren’s s yndrome, idiopathic thrombocytopenia purpura,
glomerulonephritis, autoimmune thy roiditis, giant cell arteritis ( temporal arteritis),
psoriasis, and insulin -dependent diabetes mellitus (type 1).
10. Bleeding diathesis or condition associated with prolonged bleeding that would, in the
opinion of the investigator, contraindicate intramuscular injection.
11.Women who are pregn ant or breastfeeding.
Prior/Concomitant Therapy:
12.Previous vaccination with any coronavirus vaccine.
13.Individuals who received treatment with immunosuppressive therapy , including cy totoxic
agents or s ystemic corticosteroids, eg, for cancer or an autoimmune disease, or planned
receipt throughout the study . If systemic corticosteroids were administered short term
(<14 days) for treatment of an acute illness, participants should not have been enrolled
into the study until corticosteroid therapy had been discont inued for at least 28 day s
before stud y intervention administration. I nhaled/nebulized (except for participants in
Phase 1 – see exclusion criterion 14), intra- articular, intrabursal, or topical (skin or ey es)
corticosteroids were permitted.
14.Phase 1 only: Regular receipt of inhaled/nebulized corticosteroids.
15.Receipt of blood/plasma products or immunoglobulin, from 60 day s before study
intervention administration or planned receipt throughout the stud y.
Prior/Concurrent Clinical Study Experience:
16.Participati on in other studies involving study intervention within 28 day s prior to study
entry and/or during study participation.
17.Previous participation in other studies involving study intervention containing lipid
nanoparticles.
Diagnostic Assessments:
18.Phase 1 only: Positive serological test for SARS- CoV -2 immunoglobulin M (IgM)
and/or IgG antibodies at the screening visit.
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Page 2319.Phase 1 only: Any screening hematology and/or blood chemistry laboratory value that
meets the definition of a ≥Grade 1 abnormality .
Note: With the exception of bilirubin, participants with any stable Grade 1 abnormalities
(according to the toxicity grading scale) may be considered eligible at the discretion of
the investigator. (Note: A “stable” Grade 1 laboratory abnormalit y is defined as a report
of Grade 1 on an initial blood sample that remains ≤ Grade 1 upon repeat testing on a
second sample from the same participant.)
20.Phase 1 only: Positive test for HIV, hepatitis B surface antigen (HBsAg), hepatitis B
core antibodies (HBc Abs), or hepat itis C virus antibodies (HCV Abs) at the screening
visit.
21.Phase 1 only: SARS -CoV -2 NAAT -positive nasal swab within 24 hours before receipt of
study intervention.
Other Exclusions:
22.Investigator site staff or Pfizer/BioNTech employees directly involved in th e conduct of
the study , site staff otherwise supervised by the investigator, and their respective famil y
members.
Vaccines Administered: The vaccine candidate selected for Phase 2/3 evaluation was
BNT162b2 at a dose of 30 µg. This report evaluated a 2 -dose (separated b y 21 days)
schedule of the following for active immunization against COVID -19 or saline placebo:
BNT162b2 (BNT162 RNA -LNP vaccine containing modRNA that encodes P2 S): 30 µg
Normal saline (0.9% sodium chloride solution for injection)
The fi nal analy sis interim C4591001 CSR dated 03 December 2020 for BNT162b1 and
BNT162b2 presented other candidate dose levels previously evaluated.
A list of the study interventions administered in this study and their representative lot
numbers is provided in Table S3 .
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Page 24Table S3. Investigational Product Lot Numbers – Interim – 6 Month Update
Investigational
Product Phase ManufacturerVendor Lot
Number
(Manufacturer) Lot Numbera(Pfizer)
BNT162b1 (10 µg,
20µg, 30 µg, and
100µg)1 BioNTech BCV10320 -A E220395 -0001L
BNT162b2 (10 µg,
20µg, and 30 µg)1 BioNTech BCV40420 -A E220395 -0004L
Normal saline (0.9%
sodium chloride
solution for injection)1 Pfizer DK1589 20-001592
BNT162b2 (30 µg) 2/3 BioNTech BCV40420 -A
BCV40420 -A
BCV40420 -A
BCV40420 -A
BCV40420 -A
BCV40620 -A
BCV40620 -A
BCV40620 -B
BCV40620 -B
BCV40620 -C
BCV40620 -C
BCV40620 -D
BCV40620 -D
BCV40720 -A
BCV40720 -A
BCV40720 -B
BCV40720 -CE220395 -
0006L003/P220395 -
0012L
E220395 -
0035L002/P220395 -
0048L
E220395 -
0035L003/P220395 -
0048L
EU2065896/E220395 -
0004L
PA2070104/P220395 -
0008L
PA2071394/P220395 -
0029L
PA2072393/P220395 -
0019L
PA2071395/P220395 -
0016L
PA2072396/P220395 -
0016L
PA2071396/P220395 -
0047L
PA2072439/P220395 -
0047L
PA2072442/P220395 -
0042L
PA2072765/P220395 -
0042L
PA2074172/P220395 -
0053L
PA2074998/P220395 -
0060L
PA2074173/P220395 -
0051L
PA2074071/P220395 -
0052L
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Page 25Table S3. Investigational Product Lot Numbers – Interim – 6 Month Update
ED3938 PA2074300/P220395 -
0021L
ED3938
ED3938
ED3938
EE3813
EE3813
EE8493Z
EE3813
EE3813
EE3813
EJ0553ZEU2074330/E220395 -
0036L
PA2074300/P220395 -
0022L
PA2074300/P220395 -
0023L
PA2074838/P220395 -
0024L
PA2074838/P220395 -
0020L
PA2077905/P220395 -
0026L
NC2075485/P220395 -
0068L
NC2075485/P220395 -
0074L
NC2075485/P220395 -
0077L
PA2085061/P220395 -
0070L
Normal saline (0.9%
sodium chloride
solution for injection)2/3 Pfizer DK1589;20 -001592
DK1589;20 -001776
DK2074;20 -002029
DK2074;20 -002108
DK2074;20 -002221
DK2074;20 -002221
DK2074;20 -002221
DK2074;20 -002221
DK2074;20 -002221
DK2074;20 -002221
DK2074;20 -002221
DK2074;20 -002221
DK2074;20 -002221
DK2074;20 -002221PA2064251/P220395 -
0005L
PA2065311/P220395 -
0007L
PA2067775/P220395 -
0030L
PA2067774/P220395 -
0013L
PA2069407/P220395 -
0031L
PA2069407/P220395 -
0032L
PA2069407/P220395 -
0033L
PA2069407/P220395 -
0034L
PA2069407/P220395 -
0044L
PA2069407/P220395 -
0045L
PA206940 7/P220395 -
0046L
PA2069407/P220395 -
0054L
PA2069407/P220395 -
0055L
PA2069407/P220395 -
0056L
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Page 26Table S3. Investigational Product Lot Numbers – Interim – 6 Month Update
DK2074;20 -002221
DK2074;20 -002221
DK2074;20 -002221PA2069407/P220395 -
0062L
PA2069407/P220395 -
0065L
PA2069407OTH/E220395 -
0049L
Note: C4591001 End of Study Information and Quality Control (QC) Record for Study Drug Appendix (Section D)
dated 17Mar2021 w as used to create this table.
a. Lot number assigned to the investigational product by Pfizer Global Clinical Supply.
Protocol C4591001 Investigational Product Lot Numbers Table – Interim –6 Month Update, Final, Version 1.0,
18Mar2021.
Efficacy and Immunogenicity Evaluations: Efficacy was assessed for potential cases of
COVID -19and described in the final anal ysis interim C4591001 CSR dated
03December 2020 .The prespecified interim analy sis was conducted on an accrued
94evaluable COVID -19 cases (data cutoff date: 04 November 2020), and the final anal ysis
was conducted on an accrued 170 evaluable COVID -19 cases for the first primary efficacy
endpoint (data cutoff date: 14 November 2020). These anal yses included data from all
participants in Phase 3 age groups (12 -15, 16- 55, and >55 y ears of age) at the time of the
analyses.Prespecified primary and secondary efficacy endpoint analy ses were completed per
protocol as of 14 November 2020, and no additional formal h ypothesis testing of clinicall y
confirmed COVID -19 cases is planned. At the time of the final anal ysis, there were relativel y
few participants 12 -15 years of age enrolled in the study and no COVID -19 cases in this age
group accrued at that time (14 Novembe r 2020). In this report, efficacy was assessed based
on all cases in participants ≥12 years of age accrued in blinded follow -up to a data cutoff date
of 13 March 2021.
Confirmed COVID -19: presence of at least 1 of the following s ymptoms and SARS -CoV -2
NAAT -positive during, or within 4 day s before or after, the s ymptomatic period, either at the
central laboratory or at a local testing facility (using an acceptable test):
Fever;
New or increased cough;
New or increased shortness of breath;
Chills;
New or increased muscle pain;
New loss of taste or smell;
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Page 27Sore throat;
Diarrhea;
Vomiting.
The second definition, which may be updated as more is learned about COVID -19, includes
the following additional sy mptoms defined b y the CDC (listed at
https://www.cdc.gov/coronavirus/2019 -ncov/s ymptoms- testing/sy mptoms.html):
Fatigue;
Headache;
Nasal congestion or runny nose;
Nausea.
Confirmed severe COVID- 19: confirmed COVID -19 and presence of at least 1 of the
following:
Clinical signs at rest indicative of severe s ystemic illness (RR ≥30 breaths per minute,
HR ≥ 125 beats per minute, SpO 2≤93% on room air at sea level, or PaO 2/FiO 2
<300 mm Hg);
Respiratory failure (defined as needing high -flow oxy gen, noninvasive ventilati on,
mechanical ventilation, or ECMO);
Evidence of shock (SBP <90 mm Hg, DBP <60 mm Hg, or requiring vasopressors);
Significant acute renal, hepatic, or neurologic d ysfunction;
Admission to an intensive care unit (ICU);
Death.
In addition to the above speci fied definition of severe COVID -19, an efficacy anal ysis for
any severe COVID -19 cases was conducted using the CDC definition of severe COVID-19
(hospitalization, admission to the I CU, intubation or mechanical ventilation, or death).
For i mmunogenicity testing, the following assay s were performed inPhase 1 and Phase 2 and
will be performed in Phase 2 /3, with the exception of the RBD -binding IgG assay :
SARS -CoV -2 neutralization assay (reference strain and SA variant [data from SA variant
will be reported at a later time])
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Page 28Full length S -binding or S1 -binding IgG levels (most relevant to BNT162b2 which
encodes P2 S)
RBD- binding IgG level assay (most relevant to BNT162b1, which encodes the RBD,
Phase 1 only , and previously reported in the final anal ysis inte rim C4591001 CSR dated
03December 2020) )
Safety Evaluations:
Local Reactions and Sy stemic Events: All participants in Phase 1 and a subset of at least the
first 6000 participants randomized in Phase 2/3 were asked to monitor and record local
reactions, sy stemic events, and antipy retic/pain medication usage for 7 days following
administration of the study intervention using an e -diary . Anyparticipants in Phase 3 who are
HIV-positive or 12 t hrough 15 years of age may also have been included in this subset (will
be reported at a later time). In addition, participants 16 through 17 years of age enrolled
under Protocol Amendment 9 (finalized 29 October 2020) and onwards were included in the
reactogenicity subset. All other participants, including those who or iginally received placebo
and then received BNT162b2 under Protocol Amendment 10 and onwards, did not complete
an e-diary but had their local reactions and s ystemic events reported as AEs.
For local reactogenicit y, during the reactogenicit y e-diary reporti ng period, participants were
asked to assess redness, swelling, and pain at the injection site and to record the sy mptoms in
the reactogenicit y e-diary. If a local reaction persisted bey ond the end of the reactogenicity e-
diary period following vaccination, the participant was requested to report that information.
Redness and swelling were measured and recorded in measuring device units (range: 1to21)
and then categorized during anal ysis as absent, mild, moderate, or sev ere based on the
grading scale. Pain at the injection site was assessed by the participant as absent, mild,
moderate, or severe according the grading scale.
For s ystemic reactogenicity , during the reactogenicity e-diary reporting period, participants
were asked to assess vomiting, diarrhea, headache, fatigue, chills, new or worsened muscle
pain, and new or worsened joint pain and to record the sy mptoms in the reactogenicit y e-
diary . The sy mptoms were assessed by the participant as absent, mild, moderate, o r severe
according to the grading scale.
Temperature was collected in the reactogenicit y e-diary in the evening daily during the
reactogenicity e-diary reporting period and at an y time during the reactogenicity e-diary data
collection periods when fever w as suspected. Fever is defined as an oral temperature of
≥38.0 °C (100.4 °F). The highest temperature for each day was recorded in the reactogenicit y
e-diary .
The investigator or designee obtained stop dates from the participant for any ongoing local
reactio ns, systemic events, or use of antipy retic medication on the last day that the
reactogenicity e-diary was completed.
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Page 29AEs and SAEs : AEs were reported b y the participant (or, when appropriate, by a caregiver,
surrogate, or the participant's legally authorize d representative). The time period for activel y
eliciting and collecting AEs and SAEs (“active collection period”) for each participant began
from the time the participant provided informed consent, which was 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 7(1 month after Dose 2) for
Phase 1 participants, and Visit 3 (1 month after Dose 2) for Phase 2/3 participants. In
addition , any AEs occurring up to 48 hours after each subsequent blood draw were recorded
on the CRF. SAEs were collected from the time the participant provides informed consent to
approximately 6 months after the last dose of study intervention (Visit 8 for Phase 1
participants and Visit 4 for Phase 2/3 participants).
Additionally , for those participants who originally received placebo but went on to receive
BNT162b2 at Vaccinations 3 and 4, AEs were collected from the time the participant
provided informed consent (for receipt of Vaccinations 3 and 4) through and including
Visit 103. SAEs were collected from the time the participant provides informed consent (for
receipt of Vaccinations 3 and 4) to approximately 6 months after the second dose of
BNT162b2 (Visit 10 4).
Acute reactions (immediate AEs) were collected within the first 4 hours after administration
of the study intervention (for the first 5 participants vaccinated in each Phase 1 group), and
within the first 30 minutes (for the remainder of participants).
Statistical Methods:
Efficacy Analysis: The efficacy assessment in Phase 2/3 portion of the study was event
driven. Vaccine efficacy (VE)with respect to the first primary efficacy endpoint was
assessed at the first interim analy sis (at least 62 cases) at 94 cases (data cutoff date:
04November 2020). At the final anal ysis, VE with respect to the first primary efficacy
endpoint (at least 16 4cases) was assessed on an accrued 170 evaluable COVID -19 cases
(data cutoff date: 14 November 2020) and also included VE for the second primary and all
secondary efficacy endpoints. No additional formal hypothesis testing of clinically confirmed
COVID -19cases is planned.
Assessment of VE of BNT162b2 was performed for confirmed COVID -19 cases observed at
least 7 day s after the receipt of Dose 2 onwards among participants without or with or
without serological or virological evidence (up to 7 days after re ceipt of the second dose) of
past SARS -CoV -2 infection. VE was estimated b y 100% × (1 –IRR), where I RR was the
ratio of COVID -19 illness rate in the BNT162b2 group to the corresponding illness rate in
the placebo group.
Updated descriptive efficacy analy ses during blinded placebo -controlled follow -up were
conducted based on the data cutoff date of 13 March 2021 for the primary efficacy endpoints
and for the secondary efficacy endpoint of severe disease, including subgroup anal yses.
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Page 30The point estimate of VE in the blinded follow -up period and associated 2 -sided 95% CI was
derived using the Clopper Pearson method adjusted for surveillance time, and the posterior
probability (ie, P[VE >30%| data]) was provided for the primary endpoints and secondary
endpoints of severe disease. In addition to the protocol definition of severe COVID -19,
supportive anal yses using the CDC definition of severe COVID -19 was also performed.
COVID -19 cases and severe COVID -19 cases occurring after Dose 1 were also summarized
descript ively and previously reported in the final analysis interim C4591001 CSR dated
03December 2020. Updated COVID -19 and severe COVID -19 cases after Dose 1 were
summarized descriptively based on the data cutoff date of 13 March 2021.
Immunogenicity Analysis: For immunogenicity results of SARS -CoV -2 neutralizing titers
and S1 -or RBD -binding IgG concentrations, the GMT or GMCs were computed along with
associated 95% confidence intervals (CIs). The GMT and GMC were calculated as the mean s
of assay results after making the logarithm transformation and then exponentiating the means
to express results on the original scale. Two -sided 95% CI s were obtained by taking log
transforms of assay results, calculating the 95% CIswith reference to Student’s t -distribution,
and then exponentiating the confidence limits.
The GMFR was calculated by exponentiating the mean of the difference of logarithmicall y
transformed assay results (later time point – earlier time point). Two -sided CI s were obtained
by calculating CIs using Student’s t -distribution for the mean difference of the
logarithmicall y transformed assay results and exponentiating the confidence limits.
The GMR was calculated as the mean of the difference of logarithmically transformed assay
results (eg, SARS -CoV -2 neutralizing titers minus S1- binding IgG levels for each
participant) and exponentiating the mean. Two -sided CI s were obtained by calculating CIs
using Student’s t -distribution for the mean difference of the logarithmically transformed
assay results and exp onentiating the confidence limits.
The exact 95% CIs for binary endpoints were computed using the F distribution
(Clopper -Pearson method).
Titers/concentrations below the lower limit of quantitation (LLOQ) or denoted as below the
level of quantitation (BLQ ) were set to 0.5 × LLOQ for analy sis.
Safety Analysis: The primary safet y objective was evaluated b y descriptive summary
statistics for local reactions, sy stemic events, AEs/SAEs, and abnormal hematology and
chemistry laboratory parameters (Phase 1 only ;reported in the final analy sis interim
C4591001 CSR dated 03 December 2020 ), for each vaccine group. A 3 -tier approach was
used to summarize AEs in Phase 2/3. Under this approach ,AEs were classified into 1 of
3tiers:
Tier 1 events are prespecified event s of clinical importance and are identified in a list in
the product’s Safety Review Plan; there are no Tier 1 AEs identified for this program.
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Page 31Tier 2 events were those that were not Tier 1 but were considered “relatively common”;
aMedDRA preferred term is defined as a Tier 2 event if there are at least 1% of
participants with the AE term in at least 1 vaccine group .
Tier 3 events were those that were neither Tier 1 nor Tier 2.
Other Analysis : The safety results for individuals with confirmed stable HI V disease w ere
summarized descriptively. Furthermore, VE may be assessed if there is a sufficient number
of COVID -19 cases in this group of participants.
AEs and SAEs reported during the open- label follow -up period were summarized separately
for participants who were unblinded at the time of being eligible for receipt of BNT162b2
according to recommendations detailed separatel y, and available in the electronic study
reference portal, or no later than at approximately Visit 4. To account for differ ent durations
of follow -up time due to unblinding in the study , AEs and SAEs during the blinded follow -up
period and open label follow -up period were summarized as incidence rates adjusted by
exposure time.
RESULTS –PHASE 1
Participant Disposition and Dem ography: All participants in each age group (18 through
55 and 65 through 85 years) randomized to the BNT162b2 group completed the visit at
6months after Dose 2, with most of these visits occurring during the open -label follow -up
period. All participants in each age group randomized to the placebo group received both
doses of BNT162b2 (Dose 3 and Dose 4 in the study ) during the open -label period and
completed the visit at 1 month after Dose 4, as of the data cutoff date of 13 March 2021. No
participants w ere withdrawn from the study up to the data cutoff date.
Demographics for Phase 1 healthy participants were previousl y reported in the final anal ysis
interim C4591001 CSR dated 03 December 2020.
Immunogenicity Results:
Geometric Mean Titers (GMTs) and Ge ometric Mean Concentrations (GMCs)
Among participants who received the 30 µg dose level of BNT162b2, in both age groups, the
observed SARS -CoV -2 serum 50% neutralizing GMTs declined from 1 month after Dose 2
(Day 52) to 6 months after Dose 2 (Day 202). In the y ounger age group, GMTs were 179.2 at
1 month after Dose 2 and 54.7 at 6 months after Dose 2; in the older age group GMTs
declined from 151.6 to 29.0. Observed S1-binding IgG GMCs demonstrated similar declines.
Geometric Mean Fold Rises (GMFRs)
In the younger and older age groups, respectivel y, GMFRs of SARS -CoV -2 serum 50%
neutralizing titers from before vaccination with BNT162b2 30 µg to each subsequent time
point were 2.9 and 1.7 at Day 21(before Dose 2); 17.9 and 15.2 at 1 month after Dose 2; 5.5
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Page 32and 2.9 at 6 months after Dose 2. Results for GMFRs of S1- binding IgG concentrations
reflected similar trends.
Geometric Mean Ratios (GMRs)
At 6 months after Dose 2 of BNT162b2 30 µg, GMRs of SARS -CoV -2 50% neutralizing
titers to S1- binding IgG levels were 0.057 in the younger age group and 0.052 in the older
age group. These values are similar to those observed at Day 21 .
Number (%) of Participants Achieving a ≥4-Fold Rise from Baseline
In the younger age group, the proportions of participants achieving a ≥4 -fold rise in
SARS -CoV -2 50% neutralizing titers from before vaccination to each time point were:
50.0% (6/12) at Day 21; 100.0% (11/11) at 1 month after Dose 2; and 60.0% (6/10) at
6months after Dose 2 of BNT162b2 30 µg. In the older age group, these proportions were
9.1% (1/11) at Day 21; 81.8% (9/11) at 1month after Dose 2; and 27.3% (3/11) at 6 months
after Dose 2 of BNT162b2 30µg.
With respect to S1 -binding IgG concentrations, 100% of participants in both age groups had
a ≥4-fold increase from baseline at each of these time points .
Immunogenicity Conclusions:
For Phase 1 participants who received BNT162b2 30 µg, a t 6 months after Dose 2, SARS -
CoV -2 serum neutralizing titers and serum S1 -binding IgG concentrations had decreased
relative to those observed at 1 month after Dose 2, but remained higher than values observed
at prevaccination and compared with the placebo group .
Safety Results:
Local Reactions and Systemic Events
The majority of reactogenicity events were mild or moderate in severit y. Local and s ystemic
reactogenicity events after each dose for both BNT162b1 and BNT162b2 in older adults
were milder and less frequent than those observed in y ounger adults. Reactogenicity was
generall y higher after Dose 2 than Dose 1.
Adverse Events
From Dose 1 of BNT162b2 30 µg to the unblinding date, 6 (50.0%) participants in the
younger age group and 3 (25.0%) participants in the older age group reported at least 1 AE.
Two (16.7%) participants in the BNT162b2 30 µg younger age group and 1 (8.3%)
participant in the BNT162b2 30 µg older age group reported at least 1 severe AE. In the
BNT162b2 30 µg younger age group, 3 (25.0%) partic ipants reported at least 1 related AE
and 1 (8.3%) participant reported 1 severe SAE.
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Page 33No AEs were reported in either the younger or older participants in the placebo group. No
SAEs or related AEs were reported in the BNT162b2 30 µg older age group. No AEs leading
to withdrawal, life -threatening AEs, or deaths were reported in either the younger or older
participants in the BNT162b2 30 µg group.
From Dose 1 of BNT162b2 30 µg to the unblinding date, AEs were most commonly reported
in the system organ class ( SOC )of nervous s ystem disorders (3 [25. 0%] participants in the
younger age group and 1 [8.3%] participant in the older age group), followed by
musculoskeletal and connective tissue disorders (1 [8.3%] participant in each age group). All
AEs by preferred term ( PT)were reported b y no more than 1 participant.
There were no Phase 1 participants randomized to BNT162b2 30 µg or corresponding
placebo who died through the data cutoff date of 13 March 2021. From Dose 1 to the
unblinding date, 1 participant in the BNT162b2 30 µg younger age group reported a severe
SAE (neuritis) that was assessed by the investigator as not related to study intervention . No
Phase 1 participants randomized to BNT162b2 30 µg or corresponding placebo reported an y
AEs leading to withdra wal from the study from Dose 1 to the unblinding date. AEs of special
interest were not defined for Phase 1 of this study. Pregnancy was not reported in any Phase
1 participants through the data cutoff date of 13 March 2021.
Clinical Laboratory Evaluation
Clinical laboratory evaluations, presented in final anal ysis interim C4591001 CSR dated
03December 2020 ,showed a transient decrease in ly mphocy tes that was observed in all age
and dose groups after Dose 1, which resolved within a few days, were not assoc iated with
any other clinical sequelae, and were not considered clinically relevant.
Physical Examination Findings
Overall, there were fewer abnormalities noted during phy sical examinations after BNT162b2
than after BNT162b1 in both age groups. Full detail s of phy sical examinations are presented
in the final anal ysis interim C4591001 CSR dated 03 December 2020.
Safety Conclusions:
BNT162b2 30 µg was safe and well tolerated at up to 6 months after Dose 2.
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Page 34RESULTS –PHASE 2/3
AE safet y data are from either the blinded placebo -controlled follow -up period, the open-
label observational follow- up period, or both. The time periods and safet y anal ysis groups are
presented below in Figure S 2.
Blinded placebo -controlled follow -up period from Dose 1 to 1 month after Dose 2
(frequencies)
Blinded placebo- controlled follow -up p eriod from Dose 1 to the unblinding date(IRs)
Open -label follow -up period –original BNT162b2 participants (IRs)
Blinded placebo -controlled and open -label follow -up periods from Dose 1 to
6months after Dose 2 – original BNT162b2 participants (frequencies)
Open -label follow -up period –original place bo participants who then received
BNT162b2 (I Rs)
For AE anal yses bey ond 1 month after Dose 2, and for AEs after unblinding, IRs per
100Person- Years are reported (as opposed to frequencies) to account for the variable
exposure since unblinding began for in dividual participants.
In this ongoing study , tables summarizing participant withdrawals may include some
participants who were reported as withdrawn but remain in the study and are continuing to be
evaluated. These participants are documented in the Errat a.
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Page 35Figure S 2. Phase 2/3 Safety Analyses: Time Periods and Analysis Groups
Participant Disposition and Demography:
During the blinded placebo -controlled follow -up period, 11253 (51.1%) participants in the
BNT162b2 group and 11316 (51.4%) participants in the placebo group had follow- up time
between ≥4 months to <6 months after Dose 2. From Dose 2 to the cutoff date (blinded
placebo- controlled and open- label follow -up periods, inclusive) , 12006 (54.5%) participants
in the BNT162b2 g roup had a total follow -up time of ≥6months.
Disposition – Blinded Placebo- Controlled Follow -UpPeriod
During the blinded placebo -controlled follow -up period, most participants randomized
received Dose 1 (99.8%) and Dose 2 (98.1%). There were 352 (1.6%) participants in the
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Page 36BNT162b2 group and 528 (2.4%) participants in the placebo group who discontinued from
the vaccination period. Most participants completed the visit at 1 month post- Dose 2
(≥96.4%). Few participants in the BNT162b2 and placebo groups wer e withdrawn from the
study (1.6% and 2.2%, respectively ), and most were due to withdrawals by the participant, or
they were lost to follow -up.
There were 7 participants with special data issues: 8 participant identification numbers from
4participants who enrolled into the study more than once and 3 participants whose vaccine
assignment was not confirmed in the interactive response technology (IRT)at the time of
data cutoff.
Three participants who were randomized and vaccinated, but actual vaccine assignment
was not confirmed in the IRT at the time of data cutoff. Participants were vaccinated as
per the case report form ( CRF ), but due to the inability to confirm consistency between
the data in the CRF and IRT ,these participants were not assigned to an y actual dosing
group.
During the conduct of this study , 4 participants were each randomized twice with
different participant identification numbers at 2different sites. Because the significant
misconduct of these participant scompromised the integrit y of the stud y data, results from
these participant s were excluded from all efficacy and safet y analyses, including
disposition and demographic tabulations.
Disposition – Open -Label Follow -Up Period
Individuals ≥16 y ears of age have been unblinded as they became locall y eligible and wished
to know their vaccine assignment to confirm prior vaccination with BNT162b2 (if
randomized to this group), or to receive BNT162b2 (if randomized to placebo). Unblinded
recipients originall y rando mized to BNT162b2 continue to be followed in an open -label
manner. Unblinded recipients originall y randomized to placebo are offered BNT162b2
vaccination (Doses 3 and 4 [first and second dose of BNT162b2 30 µg, respectivel y]) and
thereafter followed in an open -label manner.
Most participants in the BNT162b2 (96.8%) and placebo (96.4%) groups completed the
1month post -Dose 2 visit before unblinding.
A total of 87 (0.4%) Phase 2/3 original BNT162b2 participants received Dose 1 of
BNT162b2 during the blinded placebo -controlled follow -up period and then received Dose 2
of BNT162b2 30 µg during the open- label follow -up period (when they were unblinded) .
There were 105 (0.5%) participants withdrawn from the study , and most were due to
withdrawals b y the participa nt or because of a protocol deviation .
During the open- label follow -up period, most participants originally randomized in the
placebo group received Doses 3 and 4 (88.8% and 72.4%, respectively )of BNT162b2. There
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Page 37were few participants in this group (0.1%) who were withdrawn from the study , and most
were due to withdrawals by the participant.
The dispos ition of HIV-positive participants is included in this summary but summarized
separately in safet y analyses.
Disposition of all participants ≥16 y ears of age randomized was similar by age group.
Demographics – Safety Population
Overall
Demographic characteristics for all Phase 2/3 participants ≥16 y ears of age were similar in
the BNT162b2 and placebo groups. Overall, most participants were White (82.0%), wi th
9.6% Black or African American participants and 4.3% Asian participants, and all other
racial groups were ≤2.5%. There were 25.9% Hispanic/Latino participants. Median age was
51.0 years and 50.9% of participants were male. Obesity was reported in 34.4% of
participants in this safety population.
Baseline SARS -CoV -2 status was positive (defined as positive N -binding antibody result at
Visit 1, positive NAAT result at Visit 1, or medical history of COVID -19) in 3.1% of
participants in the BNT162b2 group an d 3.3% of participants in the placebo group.
Demographic characteristics for participants with confirmed stable HIV disease were similar
in the BNT162b2 and the placebo groups. Overall, 54.5% of participants were Black or
African American, 40.5% of partici pants were White, and all other racial groups were ≤1.5%.
There were 16.0% Hispanic/L atino participants. Median age was 49.5 years and 67.5% of
participants were male. Obese participants made up 39.0% of this population.
Participants With At Least 6 Months Follow -Up Time –Original BNT162b2 Participants
Overall, most Phase 2/3 participants ≥16 y ears of age who originall y received BNT162b2
and had at least 6 months of follow- up time after Dose 2 were White (86.4%), with 7.1%
Black or African American participants and 3.8% Asian participants, and other racial groups
were ≤1.6%. There were 27.8% Hispanic/Latino participants. Median age was 53.0 years and
50.3% of participants were male. Obese participants made up 34.2% of this safet y
population.
Original Placebo Participants W ho Then Received BNT162b2
Overall, most participants who originall y received placebo and received BNT162b2 later
during the open -label follow -up period were White (83.1%), with 8.3% Black or African
American participants and 4.3% Asian participants, and all other racial groups were ≤2.6%.
There were 25.5% Hispanic/L atino participants. Median age was 51.0 years and 50.2% of
participants were male. Obese participants made up 34.4% of this safet y population.
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Page 38All Participants
Demo graphic characteristics for all participants (including adolescents) were similar in the
BNT162b2 group and the placebo group.
Evaluable Efficacy (7 Days )Population –Blinded Placeb o-Controlled Follow -Up Period
Demographics of participants in the updated evaluable efficacy population for participants
without evidence of infection prior to 7 day s after Dose 2 were similar between BNT162b2
and placebo groups. This anal ysis population had generall y similar demographics compared
to the safet y population .
Effic acy Results:
Updated Analysis – Efficacy Against Confirmed COVID -19
In the updated descriptive efficacy anal ysis (cutoff date 13 March 2021), among
participants in the evaluable efficacy population without evidence of SARS -CoV -2
infection before and during the vaccination regimen, the estimated VE against confirmed
COVID -19 occurring at least 7 days after Dose 2 was 91.3% ( 2-sided 95% CI : 89.0%,
93.2%), with 77 cases in the BNT162b2 group and 850 cases in the placebo group.
Among participants with or without evidence of SARS -CoV -2 infection before and
during the vaccination regimen, the estimated VE against confirmed COVID -19
occurring at least 7 day s after Dose 2 was 91.1% ( 2-sided 95% CI: 88.8%, 93.0%), with
81 and 873 cases in the BNT162b2 and place bo groups, respectivel y.
All cases of confirmed COVID -19 are accounted for in the anal yses of VE in the
all-available (modified intention -to-treat) population (regardless of evidence of infection
before or during the vaccination regimen). In this anal ysis,the estimated VE against all
cases occur ring at any time after Dose 1 was 87.8% (2 -sided 95% CI: 85.3%, 89.9%),
with 131 cases in the BNT162b2 group and 1034 cases in the placebo group.
In this same all -available (modified intention -to-treat) population, the estimated VE
against all cases occurring ≥7days after Dose 2 was 9 1.2%. The estimated VE was
91.7% from ≥11 day s after Dose 1 to before Dose 2, 96.2% for cases occurring from
≥7days after Dose 2 to <2 months after Dose 2, 90.1%for the period from ≥2months to
<4months after Dose 2, and 83.7% for the period ≥4months after Dose 2.
Efficacy in Demographic and Risk Subgroups
Among participants without evidence of SARS -CoV -2 infection before and during the
vaccination regimen (eff icacy evaluable popul ation), estimated VE against COVID-19
occurring at least 7 days after Dose 2 was evaluated for demographic and risk subgroups,
with results as follows:
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Page 39Estimated VE was ≥90% in most demographic subgroups, similar to the estimated 91.3%
overall VE.
High VE was observed across age subgroups, with an estimated VE of 100.0% in 12 to
15year olds, 90.6% in 16 to 64 y ear olds, 94.5% in those ≥65 y ears, and 96.2% in those
≥75years of age.
The estimated VE was 86.5% in Argentina, 86.2% in Brazil, 92.6% in the United States,
and 100.0% in South Africa, German y, and Turkey.
The estimated VE was similar for participants at risk (91.6%) and participants not at risk
(91.0%). The estimated VE for participants ≥65 years of age and at risk was 91.8%, as
compared with 9 8.1% for those ≥65 y ears of age and not at risk. The estimated VE was
similar in obese (91.6%) and non -obese (91.1%) participants. When evaluated by type of
comorbidity , the estimated VE was >85% for participants with each comorbidity
evaluated, including any malignancy , cardiovascular disease, chronic pulmonary disease,
diabetes, obesit y, and h ypertension.
Efficacy Against Severe Cases of COVID -19
Among participants without evidence of SARS -CoV -2 infection before and during the
vaccination regimen (evaluable efficacy population), the estimated VE against FDA -
defined severe COVID -19 (protocol definition) occurring at least 7 days after Dose 2 was
95.3% (2 -sided 95% CI: 71.0%, 99.9%), with 1 and 21 cases in the BNT162b2 and
placebo groups, respectively . Similarly , the estimated VE was also 95.3% (2-sided
95% CI: 70.9%, 99.9%) among participants with or without evidence of SARS -CoV -2
infection, also with 1 and 21 cases in the BNT162b2 and placebo groups, respectivel y.
Among participants without evidence of SARS -CoV -2 infection before and during the
vaccination regimen (evaluable efficacy population), the estimated VE against CDC -
defined severe COVID -19 occurring at least 7 days a fter Dose 2 was 100.0% (2- sided
95% CI : 88.1%, 100.0%), with 0 and 32 cases in the BNT162b2 and placebo groups,
respectivel y. Similarly, the estimated VE was also 100.0% (2-sided 95% CI: 88.0%,
100.0%) among participants with or without evidence of SARS -CoV-2 infection, also
with 0 and 32 cases in the BNT162b2 and placebo groups, respectively .
Among participants in the Dose 1 all -available (modified intention -to-treat) population
(regardless of evidence of infection before or during the vaccination regimen) , the
estimated VE against FDA -defined severe cases of COVID -19 occurring at any time after
Dose 1 was 96.7% (2- sided 95% CI: 80.3%, 99.9%), with 1 case of severe COVID -19 in
the BNT162b2 group compared to 30 cases in the placebo group.
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Page 40Safety Results:
Blinded Placebo -Controlled Follow -Up Period From Dose 1 to 1 Month After Dose 2
Local Reactions and Systemic Events
Local reactions were generall y similar in frequency after each dose, and s ystemic events
generall y increased in frequency and severit y after Dose 2 compared to Dose 1. Local and
systemic reactogenicity events were well -tolerated and short -lived (median durations of
1.0to 2.0 day s).
Reactogenicit y events after each dose of BNT162b2 in older adults were generall y milder
and less frequent than those observed in younger adults. The majority of reactogenicit y
events were mild or moderate in severit y. No Grade 4 events were reported other than fever
in 1 participant.
There were 177 BNT162b2 and 187 placebo participants with baseline positive
SARS -CoV -2 status, and 4701 BNT162b2 and 4690 placebo participants with baseline
negative SARS -CoV -2 status. Differences observed in local reactions and sy stemic events by
baseline SARS -CoV -2 status were not clinically meaningful. Note that the baseline
SARS -CoV-2 positive subgroup included far fewer participants the negative subgroup, so
their results should be interpreted with caution .
Adverse Events
Most AEs from Dose 1 to 1 month after Dose 2 were mild or moderate in severit y. The
percentages of overall part icipants who reported at least 1 AE and at least 1 related AE were
higher in the BNT162b2 group (30.2% and 23.9%, respectivel y) as compared with the
placebo group (13.9% and 6.0%, respectively), which upon anal ysis, was attributed to
reactogenicity events r eported as AEs within 7 days after each dose. Severe AEs were
reported b y 1.2% and 0.7% in in the BNT162b2 and placebo groups respectively , and life -
threatening AEs were similar (0.1% in both groups).
Most Tier 2 AEs were reactogenicit y events and all wer e reported in 4 SOCs: general
disorders and administration site conditions, musculoskeletal and connective tissue disorders,
nervous s ystem disorders, and gastrointestinal disorders. The proportions of participants
reporting Tier 2 AEs were generally highe r in the BNT162b2 group (N=21,926; ranging from
1.1% to 13.3%) than in the placebo group (N=21,921; ranging from 0.3% to 1.9%).
Most reported AEs were in SOCs with reactogenicity events. The most frequently reported
AEs in the BNT162b2 group by PT overall were injection site pain, py rexia, fatigue ,chills,
headache, and m yalgia. During this time period from Dose 1 to 1 month after Dose 2, most of
these AEs were reported during the e -diary 7-day reporting period. The frequency of AEs in
the SOC of investigat ions was higher in the BNT162b2 group as compared with the placebo
group (mainly due to the higher frequency of the PT Body temperature increased. A number
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Page 41of events were identified as occurring at a higher frequency than placebo within the 7 -day
period af ter either dose of BNT162b2 when reactogenicity is expected to be reported such as
pain in extremity , decreased appetite, lethargy , asthenia, malaise, night sweats, and
hyperhidrosis. These events are interpreted as attributable to the experience of local reactions
and sy stemic events after vaccination with BNT162b2.
Nineteen stud y participants reported events in the Hepatobiliary Disorders SOC
(14BNT162b2 recipients and 5 placebo recipients). Of the 19 total participants,
3participants had hepatic events: 1 in the BNT162b2 group (alcoholic cirrhosis) and 2 in the
placebo group ( hepatic cirrhosis and nonalcoholic fatty liver disease). The remaining
16participants reported biliary events: 13 participants in the BNT162b2 group and
3 participants in th e placebo group :
In the BNT162b2 group, 8 participants reported cholelithiasis (1 reported an event each
of cholelithiasis and cholecy stitis), 1 participant reported cholecy stitis acute,
2participants reported biliary colic, and 1 participant each reported bile duct stone /biliary
dyskinesia.
In the placebo group, there were 3 participants who reported the following: 1 participant
reported an event each of cholecy stitis acute and cholelithiasis, 1 participant reported
cholecy stitis acute, and 1 participant reported choleli thiasis.
Most related AEs were reactogenicit y events and in the SOC of general disorders and
administration site conditions, reported b y 4650 (21.2%) BNT162b2 recipients and
883 (4.0%) placebo recipients. Among the BNT162b2 participants who had AEs of
lymphadenopathy , 62 of 83 participants had events assessed b y the investigator as related to
study intervention; the majority of lymphadenopathy events occurred in the arm and neck
region and were reported within 1to 4days after vaccination.
SAEs were simila r in the BNT162b2 (0.6%) and placebo (0.5%) groups. There were 3 SAEs
reported in the BNT162b2 group that were assessed by the investigator as related to study
intervention (ly mphadenopathy ; shoulder injury related to vaccine administration [SI RVA],
errone ously administered into or near the shoulder joint capsule; and ventricular arrh ythmia ).
Few participants in the BNT162b2 group (0.1%) and placebo group (0.2%) were withdrawn
because of AEs. There were 3 deaths in the BNT162b2 group (cardiac arrest ,Shige lla sepsis,
and atherosclerosis) and 5 deaths in the placebo group ( death [undetermined], my ocardial
infarction [2 participants], haemorrhagic stroke, and overdose) ; none were assessed as related
to study intervention.
For the subset of HIV -positive participants, local reactions, s ystemic events, and AEs showed
generall y similar trends as the overall population.
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Page 42Blinded Placebo -Controlled Follow -Up Period From Dose 1 to the Unblinding Date
Adverse Events
Most AEs from D ose 1 to the unblinding date were mild or moderate in severity . The IR of at
least 1 AE in the BNT162b2 group (83.2 per 100 person -years[PY]) was greater as
compared with the placebo group (43.4 per 100 PY), which upon anal ysis, was attributed to
reactoge nicity events reported as AEs within 7 day s after each dose. IRs of severe AEs,
SAEs, and AEs leading to withdrawal were ≤4.3, ≤3.3, and ≤0.6 per 100 PY, respectively , in
both groups. IRs for discontinuations because of related AEs were 0.2 per 100 PY in t he
BNT162b2 group and 0.1 per 100 PY in the placebo group. AEs with the highest IRs in the
BNT162b2 group b y PT overall were injection site pain, p yrexia, fatigue, chills, headache,
and my algia . The IR of AEs in the SOC of investigations was higher in the BNT162b2 group
than in the placebo group mainly due to the higher I R of body temperature increased in the
BNT162b2 group.
In the nervous s ystems disorder SOC, there were 4 participants who reported facial paral ysis
in the BNT162b2 group (compared to 1 in the placebo group). There is an additional case of
facial paresis in the placebo group. Hence there are 4 cases of facial paral ysis/paresis in the
in the BNT162b2 group and 2 in the placebo group.
The I Rs for hepatobiliary disorders was 0.3 per 100 PY and 0.2 per 100 PY in the
BNT162b2 and placebo group, respectively. There were 24 participants in the BNT162b2
group who had AEs in the SOC of hepatobiliary disorders compared to 16 participants in the
placebo group.
A total of 11 cases ofreported PTs associated with deafness included: Deafness, Deafness
unilateral , Deafness neurosensory , Hypoacusis, and Sudden hearing loss. Six participants
were randomized to the BNT162b2 group (age range 43to 65 years of age) ,and
5participantswere randomized t o placebo (age range 36 to 74 years of age). The toxicity
grades were mostl y mild or moderate, with one being severe (BNT162b2 group). In the
BNT162b2 group, 2 events were deemed related to study vaccine b y the investigator. None
of the reported events wer e SAEs.
In addition to the 3 related SAEs reported from Dose 1 to 1 month after Dose 2, there were
2additional related SAEs reported after 1 month post Dose 2 up to the unblinding date in the
BNT162b2 group that were assessed b y the investigator as relate d to study intervention:
paraesthesia (BNT162b2 group) and psoriatic arthropathy (placebo).
IRs of participants withdrawn because of AEs were 0.5 per 100 PY in the BNT162b2 group
and 0.6 per 100 PY in the placebo group. From Dose 1 to the unblinding date, there were a
total of 15 deaths in the BNT162b2 group and 14 in the placebo group ( which included 12 in
the BNT162b2 group and 9 in the placebo group from 1 month post Dose 2 to the unblinding
date) ; none of these deaths were assessed b y the investigator as related to study intervention.
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Page 43For the subset of HIV -positive participants, I Rs of AEs showed generall y similar trends as
the overall population.
Subgroup Analyses
For the subset of participants who were SARS- CoV -2 positive at baseline, IR of AEs
followed similar trends found in the overall AE analy sis. Given the differences in exposure
(2.5 vs 80.4) b y baseline SARS -CoV -2 positive and negative status, respectively , direct
comparisons should be interpreted with caution. The overall rate of AEs is 70.7 p er 100 PY
(95% CI : 60.7, 81.9) (baseline positive) compared with 83.6 per 100 PY (95% CI : 81.7, 85.7)
(baseline negative). For other SOCs, the IR were either numericall y lower or similar for the
baseline positive group compared to the baseline negative gro up. Overall, there is no
evidence that individuals who are positive at baseline report AEs at a higher frequency than
those who are negative at baseline.
In the BNT162b2 group, overall IRs for participants reporting at least 1 AE were highest for
participa nts of all other races (120.1 per 100 PY) compared to White participants (83.1 per
100 PY), with Black or African American participants having the lowest IR (53.5 per
100 PY). The IR for nausea in the BNT162b2 group was higher in participants of all other
races (4.7 per 100 PY BNT162b2 vs 1.6 per 100 PY placebo) and White participants (3.4 per
100 PY BNT162b2 vs 1.0 per 100 PY placebo) than in Black or African American
participants where the IR was similar in both vaccine groups (1.3 per 100 PY BNT162b2 vs
1.2 per 100 PY placebo).
In the BNT162b2 group, the I R for participants reporting at least 1 AE was higher in non-
Hispanic/non -Latino participants (85.4 per 100 PY BNT162b2 and 41.6 per 100 PY placebo )
and Hispanic/Latino participants (78.4 per 100 PY BNT1 62b2 and 47.9 per 100 PY placebo)
and lowest in the group where ethnicity was not reported (49.4 per 100 PY BNT162b2 and
43.3 per 100 PY placebo ). IRs were higher for mainly reactogenicit y events (chills, fatigue,
myalgia, diarrhea, injection site reaction s [pain , erythema, and swelling], pain, py rexia, and
headache) as well as l ymphadenopath y, nausea, influenza like illness, malaise, increased
body temperature, and pain in extremity .
Overall, females reported a higher IR of AEs (91.0 per 100 PY BNT162b2, 46.8 per 100 PY
placebo) than males (76.0 per 100 PY BNT162b2, 40.1 per 100 PY placebo), with a greater
difference in the BNT162b2 groups than in the placebo groups. The higher I Rs in females
were due to reactogenicity AEs (vomiting, chills, fatigue, py rexia, my algia, and headache) as
well as other AEs (ly mphadenopathy , nausea, pain, increased body temperature, and pain in
extremity ). There were sex appropriate differences as well, such as higher IRs in the SOC of
cardi acdisorders in males (1.2 per 100 PY) versus females (0.9 per 100 PY) and lower IRs in
the SOC of reproductive sy stem and breast disorders in males (0.3 per 100 PY) versus
females (0.9 per 100 PY).
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Page 44Overall, no clinicall y meaningful differences in IRs of SAEs were observed by baseline
SARS -CoV-2 status, ethnicity , race, or sex subgroups . IRs were similar in the BNT162b2
and place bo groups for each of the subgroups.
Other Significant Adverse Events
Safety evaluations were conducted for AEs of clinical interest: anaphy laxis, Bell’s Pals y,
lymphadenopathy , and appendicitis based on feedback from the FDA. CDC -defined AESIs
associated with COVID -19 vaccination were evaluated in the blinded placebo- controlled
period of the stud y. Additional terms bey ond those designated by the CDC as AESIs were
evaluated in a medical review to assess potential imbalances between the BNT162b2 and
placebo groups, and further characterized in the case of such an imbalance.
Lym phadenopathy was reported in 87 (1.0 per 100 PY) participants in the BNT162b2 group
compared to 8 (0.1 per 100 PY) participants in the placebo group. The majority of events
were mild to moderate; only 3 severe events of l ymphadenopath y were reported (all in the
BNT162b2 group). The median onset of l ymphadenopathy after Dose 1 and before Dose 2
was 5 .5 day s in the BNT162b2 group and 5.0 days in the placebo group; median onset after
Dose 2 was shorter in the BNT162b2 group versus the placebo group (2.0 day s vs 7.0 day s).
The median duration of lymphadenopath y was 5.5 days in the BNT162b2 group and 4.0 days
in the placebo group. As previously reported in the final anal ysis interim C4591001 CSR
dated 03 December 2020, 1 was a related SAE.
There were 14 cases of appendicitis and 1 case of appendicitis perforated in the BNT162b2
group, and 9 cases of append icitis, 2 cases of complicated appendicitis, and 1 appendicitis
perforated in the placebo group. Appendicitis cases were all reported as SAEs, and none of
the cases were considered related to study intervention.
Most AESI s are reported in higher numbers in the placebo group or were equal in the
BNT162b2 and placebo groups . The allergic reaction evaluation did not identify anaphy laxis
reactions associat edwith the vaccine. Note, there was an anaphy lactoid reaction reported
2days after receiving open -label BNT162b2 (Dose 3) in an originall y placebo -randomized
participant who was unblinded to receive BNT162b2, and who had a significant ongoing
medical history of drug hy persensitivity and other allergies. For angioedema the freq uencies
were low and very similar in the BNT162b2 (0.14%) and placebo (0.13%) groups . For
hypersensitivity reactions most of the reactions were due to rash, rash maculo -papular, and
rash papular and were not reported within 7 day s after either dose. Overa ll, the evaluation of
cases report ing allergic reactions supports standard precautions for allergic reactions should
be taken in the clinic when vaccinating.
There were 2 cases of optic neuritis reported in the BNT162b2 group that occurred 79 and
81days after vaccination with BNT162b2. Both were considered not related to vaccine.
Given the few number of events, non -proximity to vaccination and investigators judgement,
there is not enough information to assess causality at this time.
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Page 45AESI evaluations were performed for blinded placebo- controlled follow -up. There were
4cases of Bell’s palsy reported in the BNT162b2 group (previousl y reported in the final
analysis interim C4591001 CSR dated 03 December 2020). Since then there have been
2additional cases in the placebo group during blinded placebo -controlled follow -up, and
there have been 4 additional cases of Bells’ palsy identified during the open -label follow -up
period thatare included for completeness : 3cases in placebo participants who became
unblinded and were then vaccinated with BNT162b2, and 1 participant who was originally
randomized to BNT162b2, was unblinded, and developed Bell’s pals y 154 day safter the
second dose of BNT162b2.
There were 2 cases of encephalopath y in the vaccine group and none in the placebo. Both
cases had clear etiologic causes (uremia and toxic encephalopath y after a fall with
hypotension, diverticulum, and a urinary tract infection) and hence are not associated with
the vaccine.
Open -Label Follow -Up Period – Original BNT162b2 Participants
During open- label follow -up for the original BNT162b2 group from unblinding date through
the data cutoff date, most AEs were mild or moderate in severit y. The IRs for any AE, at
least 1 related AE, and severe AE were 8.8 per 100 PY, 0.7 per 100 PY, and 1.6 per 100 PY,
respectivel y, which is markedly reduced relative to those from Dose 1 to the unblinding date
(83.2, 62.9, 4.3 respectively. The IR of life -threatening AEs is 0.4 per 100 PY (95% CI : 0.2,
0.8), which is similar to the I R from Dose 1 to the unblinding date, 0.6 per 100 PY (95% CI :
0.4, 0.8). Overall, the rates in all SOCs after the unblinding date decreased or remained
similar to those in the blinded placebo -controlled period. The IR for the SOC of injury ,
poisoning and proc edural complications was 1.4 per 100 PY, with the PT fall having the
highest IR (0.4 per 100 PY). The IR for the SOC of vascular disorders was 0.8 per 100 PY,
with the PT hy pertension having the highest I R (0.6 per 100 PY).
The I Rs of related AEs were highest for reactogenicity events and in the SOC of general
disorders and administration site conditions reflecting AEs from their initial vaccinations.
One participant in the younger age group had 1 SAE of my ocardial infarction assessed by the
investigator as related to study intervention.
The I R of participants withdrawn because of AEs was 0.1 per 100 PY . There were
3additional deaths (road traffic accident, lung metastases, and m yocardial infarction) ; none
of these deaths were assessed by the investigator a s related to study intervention.
Blinded Placebo -Controlled and Open -Label Follow -Up Periods to 6 Months After Dose 2
–Original BNT162b2 Participants
For the 12,006 participants with at least 6 months of follow -up time , mostAEs were mild or
moderate in s everity from Dose 1 to 6 months after Dose 2 .There were 28.8% of participants
who reported at least 1 AE, and 18.7% of participants reported at least 1 related AE. The
most frequently reported AEs in the BNT162b2 group were reactogenicit y events. Severe
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Page 46AEs and SAEs were reported by 2.1% and 1.6%, respectivel y. One participant discontinued
because of an AE (not related).
Most related AEs were reactogenicit y events and in the SOC of general disorders and
administration site conditions. The AE of l ymphadeno pathy in 29 (0. 2%) participants was
assessed b y the investigator as related to stud y interv ention
The number of participants with SAEs increase dfrom 0.5% (Dose 1 to 1 month after the
Dose 2) to 1.1% (1 month after Dose 2 to 6 months after Dose 2). However , the number of
related SAEs remain edlow. There were 2 participants with related SAEs reported: SI RVA,
erroneousl y administered into or near the shoulder joint capsule reported from Dose 1 to 1
month after Dose 2; and paraesthesia, reported from 1 month a fter Dose 2 to 6 months after
Dose 2.
There were no deaths.
AE frequencies decreased over time from 1 month after the second dose to 6 months after the
second dose without an increase b y SOC.
Overall, BNT162b2 at 30 µg was well tolerated with at least 6 months of follow -up after
Dose 2.
Open -Label Follow -Up Period – Original Placebo Participants Who Then Received
BNT162b2
For the 19,525 original placebo participants who then received BNT162b2 after unblinding ,
most AEs were mild or moderate in severity from Dose 3 through the data cutoff date .The
IR of at least 1 AE was 205.4 per 100 PY, which was greater than the IR in original
BNT162b2 participants (83.2 per 100 PY ), due to the shorter exposure time in original
placebo participants compared with original BNT162b2 participants (23.8 per 100 PY vs
83.4 per 100 PY ). However, the IRs for life -threatening AE, SAE, AEs leading to withdrawal
and deaths were similar (0.5 per 100 PY, 2.7 per 100 PY, 0.8 per 100 PY, 0.1 per 100 PY vs
0.6 per 100 PY, 3.2 per 100 PY, 0.5 per 100 PY, 0.2 per 100 PY, respectively ).The IR of
related AEs was 189.5 per 100 PY and IRs of related AEs were highest for reactogenicity
events and in the SOC of general disorders and administration site conditions. Immediate
AEs were low in frequ ency (0.6%) and most were in the SOC of general disorders and
administration site conditions, primarily injection site reactions, with injection site pain
(0.4%) most frequently reported. From Dose 3 (first Dose of BNT162b2) to the data cutoff
date, the se vere AE IR was 6.0 per 100 PY in original placebo participants .
One participant had 1 SAE of anaph ylactoid r eaction 2days after receiving BNT162b2 that
was assessed as related to study intervention.
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Page 47The I R of participants withdrawn because of AEs was 0.8 per 100 PY . There were 2 deaths
(cardiorespiratory arrest and completed suicide) ; none of these deaths were assessed b y the
investigator as related to study intervention.
Overall, AEs after receipt of BNT162b2 in placebo participants showed a similar safe ty
profile as that observed in the participants originally randomized to BNT162b2.
Open -Label Follow -Up Period – Original Placebo Participants, had COVID-19
Occurrence After Dose 1, and Then Received BNT162b2
For original placebo participants who had COVID -19 occurrence after Dose 1 and then
received BNT162b2, IRs for an y AE and at least 1 related AE were 256.8 per 100 PY and
240.9 per 100 PY, respectively . Most AEs reported from Dose 3 (the first dose of
BNT16 2b2) to the data cutoff date were in SOCs with reactogenicity events. IRs of severe
AEs, SAEs, and AEs leading to withdrawal were 4.6 per 100 PY, 3.4 per 100 PY, and 3.4 per
100 PY. The I R for discontinuations because of related AEs was 3.4 per 100 PY, and no
participants died.
SAE rates were similar in these participants (3.4per 100 PY ; 95% CI : 0.7, 10.0) compared to
those originall y randomized to BNT162b2 (3.2per 100 PY ; 95% CI : 2.8, 3.6) . None of the
SAEs in the original placebo participants who developed COVID -19 and subsequently were
vaccinated with BNT162b2 were related to BNT162b2. There were 3 participants with AEs
leading to withdrawal that were assessed as related to BNT162b2: 1 participant with an AE
of allergy to vaccine, 1 participant wi th an AE of pain, and 1 participant with 5 AEs (chills,
injection site pain, my algia, headache, and diarrhea) . No deaths were reported in placebo
participants who developed COVID -19 and subsequently were vaccinated with BNT162b2.
Overall, a similar safet y profile wa s observed for this population compared to those
originall y randomized to BNT162b2.
Pregnancy
At the time of the data cutoff date (13 March 2021), a total of 50 participants who had
received BNT162b2 had reported pregnancies, including 42 parti cipants originall y
randomized to the BNT162b2 group and 8 participants originall y randomized to the placebo
group who then received BNT162b2. In total, 12 participants (n=6 each in the randomized
BNT162b2 and placebo groups) withdrew from the blinded place bo-controlled vaccination
period of the study due to pregnancy, and 4 participants originall y randomized to placebo
who then received BNT162b2 withdrew from the open -label vaccination period due to
pregnancy . These participants continue to be followed for pregnancy outcomes.
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Interim Clinical Study Report
Protocol C4591001
CLINICAL STUDY REPORT SYNOPSIS
CONFIDENTIAL
Page 48Overall Conclusion(s):
In Phase 1, BNT162b2 at 30 µg induced a robust immune response 1 month after Dose 2
which decreased relative to those observed at 1 month after Dose 2, but remained higher
than values observed at prevaccination and compared with the placebo group . The safet y
profile was satisfactory in both y ounger and older adults up to the unblinding date
(approximately 6months after Dose 2).
In Phase 2/3, updated efficacy anal ysis continued to show that BNT162b2 at 30 µg
provided a high level of protection against COVID-19 . This was shown in participants
irrespective of evidence of prior infection with SARS -CoV -2and across various
demographic subgroups. Severe cases were observed predominantl y in the placebo group.
The tole rability and safety profile of BNT162b2 30 µg in participants ≥16years of age at
up to 6 months after Dose 2 was acceptable throughout the follow-up period (to the data
cutoff date) and consistent with results previously reported.
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