A Phase II Trial to Evaluate the Safety and Immunogenicity of SARS-CoV-2 Monovalent and Multivalent RNA-based Vaccines in Healthy Subjects
Phase: PHASE2
Conditions: SARS-CoV-2 Infection, COVID-19, SARS-CoV-2 Acute Respiratory Disease, SARS (Disease)
Sponsor: BioNTech SE



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1 
PROTOCOL SUMMARY 
1.1 
Trial synopsis 
Trial number: BNT162-17 
Trial title 
A Phase II trial to evaluate the safety and immunogenicity of SARS-CoV-2 monovalent and 
multivalent RNA-based vaccines in healthy subjects 
Trial rationale 
BioNTech has developed ribonucleic acid (RNA)-based vaccine candidates using a platform 
approach that enables the rapid development of vaccines against emerging viral diseases, 
including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The BNT162b 
platform uses modified RNA (modRNA). The BNT162b platform member BNT162b2 (Comirnaty, 
Pfizer-BioNTech COVID-19 vaccine) has received emergency use authorization or conditional/full 
marketing authorization in numerous countries worldwide for the prevention of Coronavirus 
Disease 2019 (COVID-19). As demonstrated by BNT162b2, lipid nanoparticle (LNP)-formulated 
RNA-based vaccines provide one of the most flexible, scalable and fastest approaches to provide 
protection against the emerging viruses like SARS-CoV-2 (Mulligan et al. 2020; Rauch et al. 2018; 
Sahin et al. 2014; Walsh et al. 2020). 
As more data about COVID-19 continue to accrue, the potential duration of protection, after SARS-
CoV-2 natural infection and by vaccination, remains unknown. Further, although SARS-CoV-2 
presents a mutation rate lower than that of other RNA viruses, it continues to evolve, generating 
new variants that arouse concern due to increased transmissibility or anticipated reduction in 
neutralization by antibodies generated during previous infection or vaccination. These variants 
include a variant with high prevalence globally, B.1.1.7 (known as Alpha) and further variants 
including B.1.351 (known as Beta), P.1 (known as Gamma), B.1.617.1 and B.1.617.2 (the latter 
known as Delta), and B.1.1.529 (Omicron) and its subvariants B.1.1.529.1 (BA.1) and B.1.1.529.5 
(BA.5). BNT162b2 induces a robust immune response against SARS-CoV-2, including both 
humoral and multifunctional T-cell responses, and emerging vaccine effectiveness data confirm its 
effectiveness against COVID-19 in populations with high prevalence of those variants. If evidence 
emerges that particular variants do appear to influence vaccine effectiveness and prevail in 
different countries, it will be beneficial to be prepared to implement BNT162b2-based vaccines 
against variant strains able to boost memory responses against conserved SARS-CoV-2 epitopes 
while concurrently targeting novel neutralizing epitopes of escaping circulating strains. 
On 26 November 2021, the World Health Organization (WHO) designated the SARS-CoV-2 virus 
variant B.1.1.529, named Omicron, a variant of concern (VOC; WHO webpage “Update on 
Omicron”). Initially detected in South Africa, this variant rapidly distributed across the world. The 
SARS-CoV-2 Omicron variant is known to have a concerning number of mutations (more than 30) 
in the spike protein that are associated with reduced neutralization by convalescent and vaccinee 
sera (Schmidt et al. 2021). The original Omicron strain has since been renamed B.1.1.529.1 
(known as Omicron BA.1), with the Omicron lineage having expanded into multiple sublineages. 
Reflective of the SARS-CoV-2 Omicron (BA.1) variant’s decreased sensitivity to neutralizing 
antibodies elicited by previous viral variants or vaccines based on those, incidence of SARS-CoV-2 
infection peaked in January 2022 (WHO webpage “COVID-19 Weekly Epidemiological Update”). In 

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the US, prevalence of the SARS-CoV-2 Omicron (BA.1) variant reached 89.2 to 98.8% during that 
time frame (US Centers for Disease Control and Prevention [CDC] webpage “COVID Data Tracker 
– Variant Proportions”, accessed 09 February 2022). Meanwhile it was confirmed that two-dose
vaccination schedules with the available vaccines based on the SARS-CoV-2 wild-type strain
provide lower protection against infection with the SARS-CoV-2 Omicron variant(s) compared to
the previous variants or the wild-type strain. A third dose of an RNA-based vaccine appears to
temporarily increase protection (UK Health Security Agency 2022), but reinfection rates with the
SARS-CoV-2 Omicron variant(s) are likely higher than with the SARS-CoV-2 Delta variant
(Ferguson et al. 2021).
As of 04 August 2022, no Omicron-specific variant vaccines were authorized, and there were no 
vaccination recommendations for subjects who experienced a breakthrough infection with the 
SARS-CoV-2 Omicron variant. On 31 August 2022, the US Food and Drug Administration (FDA) 
authorized the bivalent vaccine, BNT162b2 and BNT162b2 Omicron (B.1.1.529 sub-lineage 
BA.4/5), for a booster vaccination in individuals 12 years of age and older. 
On 18 April 2023, the US FDA amended the BNT162b2 emergency use authorization to simplify 
the vaccination schedule for most individuals, including that most unvaccinated individuals may 
receive a single dose of a variant-modified vaccine (rather than two doses). The effectiveness of a 
single dose was supported by observational data from England on the effectiveness of one dose of 
monovalent BNT162b2, and that, among individuals 12 to 17 years of age who had received only 
one dose of BNT162b2, those who had evidence of previous infection with Alpha, Delta, or 
Omicron variants had increased protection against symptomatic Omicron infection compared with 
those with no evidence of previous infection. 
To combat these evolving SARS-CoV-2 strains, the sponsor has initiated clinical investigation of 
BNT162b2-based vaccines against variant strains as monovalent vaccines and as a multivalent 
vaccine (i.e., a combination of two monovalent vaccines). These BNT162b2-based vaccines are 
named “BNT162b2” plus the variant strain targeted by the RNA-encoded open reading frame 
(ORF), e.g., BNT162b2 (B.1.1.7) has an RNA that encodes the SARS-CoV-2 strain B.1.1.7 spike 
(S) protein. The BNT162b2-based vaccines against variant strains have the same LNP formulation
and RNA components as BNT162b2 except that the RNAs differ slightly in their encoded ORF.
Each RNA component leads to expression of S proteins with the amino acid changes seen in the
SARS-CoV-2 strains B.1.1.7, B.1.351, B.1.617.2, and B.1.1.529.1, respectively. For further details,
see Table 8.
This trial (BNT162-17) aims to investigate the safety and immunogenicity of the BNT162b2-based 
vaccines against variant strains, i.e., BNT162b2 (B.1.1.7 + B.1.617.2), BNT162b2 (B.1.1.7), 
BNT162b2 (B.1.617.2), and BNT162b2 (B.1.1.529) *: 
•
BNT162b2 (B.1.1.7 + B.1.617.2), a multivalent vaccine comprising a 1:1 mixture of
BNT162b2 (B.1.1.7) and BNT162b2 (B.1.617.2).
•
BNT162b2 (B.1.1.7), a monovalent vaccine that expresses the full length SARS-CoV-2
Alpha S protein bearing mutations preserving neutralization-sensitive sites.
•
BNT162b2 (B.1.617.2), a monovalent vaccine that expresses the full length SARS-CoV-2
Delta S protein bearing mutations preserving neutralization-sensitive sites.
•
BNT162b2 (B.1.1.529), a monovalent vaccine that expresses the full length SARS-CoV-2
Omicron S protein bearing mutations preserving neutralization-sensitive sites.
* Note: In this protocol, “B.1.1.529” refers to variant B.1.1.529.1 (known as Omicron BA.1)
unless stated otherwise.

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The two viral strains included in the multivalent vaccine BNT162b2 (B.1.1.7 + B.1.617.2) are 
selected to favor cross-reactive antibody responses and to also include dominant strains in terms 
of global prevalence at the time of this trial. The thorough clinical investigation of 
BNT162b2 (B.1.1.7 + B.1.617.2) in Parts A and B will support preparedness for the case that a 
multivalent BNT162b2-based vaccine against COVID-19 is needed to allow broad coverage 
against circulating strains at global level and to avoid the complexity of handling multiple 
monovalent vaccines in parallel. 
To support the clinical evaluation of the multivalent vaccine BNT162b2 (B.1.1.7 + B.1.617.2), the 
monovalent BNT162b2 vaccines BNT162b2 (B.1.1.7) and BNT162b2 (B.1.617.2) will also be 
individually investigated clinically in Parts A and B. Data from Part B of the trial will be used to 
evaluate the immunogenicity of one dose of variant-modified BNT162b2 (multivalent B.1.1.7 + 
B.1.617.2) in vaccine-naïve seropositive individuals. To supplement real world evidence that a
single dose is effective, immunogenicity results from this analysis will fill the evidence gap for use
of the single dose of BNT162b2 in individuals 12 years of age and older who have not been
previously vaccinated with a COVID-19 vaccine. The Alpha (B.1.1.7) and Delta (B.1.617.2)
BNT162b2 variants are no longer epidemiologically relevant. Experience with other variant-
modified versions of BNT162b2 is relevant because all have the same LNP formulation and RNA
components except that the RNAs differ slightly in their encoded ORF and the available data has
demonstrated that immune response(s) to vaccine-encoded strain(s) are similar. To provide a
robust comparison, as well as assessing neutralizing titers (NTs) against Alpha and Delta, NTs
against the more contemporaneous B.1.1.529.5 (Omicron BA.5) will also be assessed. Finally, to
bridge to the efficacy demonstrated with the original BNT162b2 vaccine, although not encoded by
the investigational vaccine in this trial, NTs against the reference strain will be compared between
vaccine-naïve seropositive individuals after one dose of BNT162b2 (B.1.1.7 + B.1.617.2) and
vaccine-naïve seronegative individuals after two doses of original BNT162b2 (from trial
BNT162-02 / C4591001; NCT04368728).
Part C will investigate if administration of one dose of either BNT162b2 (B.1.1.529) or BNT162b2 
after previous infection with the SARS-CoV-2 Omicron variant will elicit an immune response 
against the SARS-CoV-2 Omicron variant in subjects who have been vaccinated with any 
authorized COVID-19 RNA-based vaccine and were subsequently diagnosed with a SARS-CoV-2 
infection from January 2022 onwards (and limited to a period when there was a high prevalence of 
SARS-CoV-2 Omicron infections). In addition, Part C (Cohort 9) will evaluate the immune response 
reached after infection with the SARS-CoV-2 Omicron variant. 

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two doses of BNT162b2 against the reference strain observed in subjects from the Phase III 
BNT162-02 / C4591001 trial. Part B will further include the same assessments of the B cell and 
T cell compartments as described in Part A in a pre-defined sample size of the cohort population. 
Based on data from Part A, the dosage, sample size and trial groups planned in Part B may be 
adjusted via a protocol amendment. 
Part C will include healthy subjects who were previously vaccinated with two or three doses of any 
authorized COVID-19 RNA-based vaccine and were subsequently diagnosed with a SARS-CoV-2 
infection from January 2022 onwards (and limited to a period when there was a high prevalence of 
SARS-CoV-2 Omicron infections). Part C will compare immune responses against the 
SARS-CoV-2 Omicron variant after one dose of 30 µg monovalent BNT162b2 (B.1.1.529) vaccine 
vs the immune response after one dose of 30 µg BNT162b2. In addition, Part C (Cohort 9) will 
evaluate the immune response reached after infection with the SARS-CoV-2 Omicron variant. 
Part A 
Part A consists of six parallel cohorts of approximately n = 20 subjects each, which will enroll 
subjects 18 to 55 years of age (Cohorts 1 to 6). 
Cohorts 1 to 5 will enroll subjects who received two injections of 30 µg BNT162b2, at least 
6 months after the second BNT162b2 dose in the following five cohorts: 
•
Cohort 1: Subjects will receive one dose of 30 µg multivalent vaccine BNT162b2 (B.1.1.7
+ B.1.617.2) on Day 1 (baseline in this trial), consisting of a 1:1 mixture of two BNT162b2
monovalent vaccines: 15 µg BNT162b2 (B.1.1.7) and 15 µg BNT162b2 (B.1.617.2).
•
Cohort 2: Subjects will receive two doses of 30 µg multivalent vaccine BNT162b2 (B.1.1.7
+ B.1.617.2), one each on Day 1 and on Day 56 (8 weeks apart).
•
Cohort 3: Subjects will receive one dose of 30 µg monovalent vaccine BNT162b2 (B.1.1.7)
on Day 1.
•
Cohort 4: Subjects will receive one dose of 30 µg monovalent vaccine
BNT162b2 (B.1.617.2) on Day 1.
•
Cohort 5: Subjects will receive one dose of 30 µg BNT162b2 on Day 1.
Cohort 6 will enroll subjects who have not received any prior prophylactic vaccine against 
COVID-19. 
•
Cohort 6: Subjects will receive three doses of 30 µg multivalent vaccine
BNT162b2 (B.1.1.7 + B.1.617.2), one each on Day 1 and Day 21 and the third dose
~6 months after the second dose.
Part B 
Part B will be initiated after review of reactogenicity and available immunogenicity data of Part A 
(Cohorts 1, 4, 6) by the SRC. 
Part B consists of three cohorts of n = 300 subjects each (~375 subjects will be enrolled in each 
cohort to ensure there are 300 evaluable subjects), which will enroll subjects 18 to 85 years old; 
~60% of these subjects should be 18 to 55 years old and ~40% should be 56 to 85 years old: 
•
Cohort 1 will enroll subjects from the trial BNT162-02 / C4591001 who received two
injections of 30 µg BNT162b2, at least 6 months after the second BNT162b2 dose.
Subjects will receive on Day 1 one dose of 30 µg multivalent vaccine BNT162b2 (B.1.1.7 +
B.1.617.2).

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• 
Cohort 4 will enroll subjects from the trial BNT162-02 / C4591001 who received two 
injections of 30 µg BNT162b2, at least 6 months after the second BNT162b2 dose. 
Subjects will receive on Day 1 one dose of 30 µg monovalent vaccine 
BNT162b2 (B.1.617.2). 
• 
Cohort 6 will enroll subjects who have not received any prior prophylactic vaccine against 
COVID-19. Subjects will receive 30 µg multivalent vaccine BNT162b2 (B.1.1.7 + 
B.1.617.2), one each on Day 1 and Day 21 and the third dose ~6 months after the second 
dose. Approximately 15 subjects at preselected sites in Part B will be evaluated in terms of 
cell-mediated immunity. 
Part C 
Part C consists of n = ~225 subjects who previously received two or three injections of any 
authorized COVID-19 RNA-based vaccine and were subsequently diagnosed with SARS-CoV-2 
infection from January 2022 onwards (limited to a period when there was a high prevalence of 
SARS-CoV-2 Omicron infections). 
Subjects in Part C will be randomized in a 2:2:1 ratio into three cohorts; ~90 subjects each in 
Cohorts 7 and 8 (to ensure ~80 evaluable subjects in each cohort after 11% dropout) and 
45 subjects in Cohort 9. Randomization will be stratified by age group (18 to 55 years of age or 56 
to 85 years of age) and by number of prior doses of COVID-19 RNA-based vaccine (two or three 
doses). 
The sponsor may terminate the enrollment into Cohort 9 at any time in case the evolving 
COVID-19 epidemiology and/or the recommendations issued in the context of national vaccination 
campaigns no longer support enrollment of the trial population in a realistically feasible time. 
Cohorts 7 to 9 will enroll subjects 18 to 85 years old; ~60% of these subjects should be 18 to 
55 years old and ~40% should be 56 to 85 years old: 
• 
Cohort 7: Subjects will receive one dose of 30 µg monovalent vaccine 
BNT162b2 (B.1.1.529) on Day 1. 
• 
Cohort 8: Subjects will receive one dose of 30 µg BNT162b2 on Day 1. 
• 
Cohort 9: No vaccination will be given to Cohort 9 subjects within 3 months after Visit 1. 
After the 3-month follow-up period, subjects in Cohort 9 will be offered a BNT162b2 
vaccination, depending on the epidemiological situation, local regulatory authority 
recommendations, and/or variant vaccine authorization status. 
Approximately 25 subjects at preselected sites in each cohort of Part C will be evaluated in terms 
of cell-mediated immunity. 
For further trial design background, see Section 4.1. 
For a summary of the trial as a flow diagram, see the Schema in Section 1.2. For the planned 
assessments and visits, see the Schedule of Activities (SoA) in Section 1.3. 
Duration of all trial periods 
Depending on the cohort, the planned trial duration for a subject in this trial is up to ~61 weeks (for 
the cohort with the longest duration: ≤1 week of screening, 8 weeks between IMP doses, and 
~52 weeks-follow-up after the last IMP dose). 
The estimated planned trial start (first subject first visit) and trial end (last subject last visit) are 
Q3-2021 and Q3-2023. 

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Trial population 
This trial will enroll healthy volunteers: 
i. 
Part A: Who are 18 to 55 years old. 
ii. 
Part B: Who are 18 to 85 years old (~60% should be 18 to 55 years old and ~40% 56 to 
85 years old). 
iii. 
Part C: Who are 18 to 85 years old (~60% should be 18 to 55 years old and ~40% 56 to 
85 years old). 
iv. 
For Cohorts 1 to 5: In Part A, who have received the BNT162b2 vaccine (30 µg, two-dose 
regimen) in either a clinical trial or as part of the governmental vaccination programs at 
least 6 months before Visit 0. Subjects who are currently enrolled in the Phase III trial 
BNT162-02 / C4591001, have already been unblinded, and have previously received two 
doses of BNT162b2 with Dose 2 at least 6 months earlier can be included (for Cohorts 1 
and 4 in Part B, prior enrollment and dosing in the trial BNT162-02 / C4591001 is 
mandatory). At enrollment into Part B of this trial, their participation in the trial BNT162-02 / 
C4591001 will be terminated. Subjects should have not experienced COVID-19 based on 
medical history. 
v. 
For Cohort 6: Who are COVID-19 vaccine-naïve and have not experienced COVID-19 
based on their medical history. 
vi. 
For Part C, Cohorts 7, 8, and 9: Who have received two or three documented doses of any 
authorized COVID-19 RNA-based vaccine (e.g., BNT162b2 [Comirnaty] or the Moderna 
vaccine [Spikevax]) prior to being diagnosed with SARS-CoV-2 infection from January 2022 
onwards (and limited to a period when there was a high prevalence of SARS-CoV-2 
Omicron infections) that is documented with a result from a nucleic acid amplification-based 
test (NAAT) for SARS-CoV-2. 
Planned enrollment is ~1,470 subjects; ~120 in Part A (~20 in each of the six cohorts), ~1,125 in 
Part B (~375 in each of the three cohorts), and ~225 in Part C (~80 in each of Cohort 7 and 
Cohort 8 and ~45 in Cohort 9). 

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Trial treatments 
IMP name: 
• BNT162b2 
• BNT162b2 (B.1.1.7 + B.1.617.2) 
• BNT162b2 (B.1.1.7) 
• BNT162b2 (B.1.617.2) 
• BNT162b2 (B.1.1.529) 
Type: 
Vaccine (BNT162 RNA-LNP vaccine utilizing modRNA). 
Use: 
Experimental 
Administration 
route: 
Intramuscular (IM); upper arm, musculus deltoideus. The same arm may be used 
for both immunizations. The non-dominant arm is preferred. 
Dosing regimen: 
Part A: 
• Cohort 1: One dose of 30 µg BNT162b2 (B.1.1.7 + B.1.617.2), consisting of a 1:1 
mixture of 15 µg BNT162b2 (B.1.1.7) and 15 µg BNT162b2 (B.1.617.2), given on 
Day 1. 
• Cohort 2: Two doses of 30 µg BNT162b2 (B.1.1.7 + B.1.617.2), one each on 
Day 1 and Day 56. 
• Cohort 3: One dose of 30 µg BNT162b2 (B.1.1.7) on Day 1. 
• Cohort 4: One dose of 30 µg BNT162b2 (B.1.617.2) on Day 1. 
• Cohort 5: One dose of 30 µg BNT162b2 on Day 1. 
• Cohort 6: Three doses (on Day 1, Day 21, and the third dose ~6 months after the 
second dose) of 30 µg BNT162b2 (B.1.1.7 + B.1.617.2). 
 
Part B: 
• Cohort 1: One (on Day 1) dose of 30 µg BNT162b2 (B.1.1.7 + B.1.617.2). 
• Cohort 4: One (on Day 1) dose of 30 µg BNT162b2 (B.1.617.2). 
• Cohort 6: Three doses (on Day 1, Day 21, and the third dose ~6 months after the 
second dose) of 30 µg BNT162b2 (B.1.1.7 + B.1.617.2). 
 
Part C: 
• Cohort 7: One dose of 30 µg BNT162b2 (B.1.1.529) on Day 1. 
• Cohort 8: One dose of 30 µg BNT162b2 on Day 1. 
• Cohort 9: No IMP injection within 3 months of Visit 1. 
Note: BNT162b2 (B.1.1.529) refers to the monovalent vaccine specific for SARS-CoV-2 Omicron subvariant BA.1, i.e., 
B.1.1.529.1. 
 

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1.2
Schema (graphical representation of the trial)
Figure 1:
Schema - Safety and immunogenicity of SARS-CoV-2 monovalent and multivalent RNA-based vaccines in healthy subjects
“A” = assignment to cohort; “R” = randomization.
* An optional additional lower dose level may be tested in each of the cohorts in up to 20 additional subjects per cohort.
** No history of COVID-19 and/or clinical or evidence of prior infection with SARS-CoV-2 at screening (Visit 0).

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i 
If an ad hoc visit occurs in combination with a planned visit, blood sampling will only be ≤120 mL for T-cell and B-cell response assessments and one 20 mL sample for serological testing for 
SARS-CoV-2 N-binding antibodies and humoral immunogenicity assessments. 
j 
Subjects who receive non-trial SARS-CoV-2 vaccinations will be discontinued, resulting in an early termination visit. For subjects who receive non-trial SARS-CoV-2 vaccinations, there will be no 
blood sampling for humoral immunogenicity or T-cell and B-cell response assessments at the early termination visit. 
k 
For consenting subjects. 
l 
For any visits >1 month after IMP injection, only prohibited medications should be recorded. 
 
Abbreviations: AE = adverse event; AESI = AE of special interest; ECG = electrocardiogram; e-diary = electronic diary or an equivalent application; EOT = end of trial; FU = follow-up; h = hour(s); IMP = 
investigational medicinal product; mon = month(s); N-binding = nucleocapsid-binding; NAAT = nucleic acid amplification-based test; SAE = serious AE; SARS-CoV-2 = the virus leading to COVID-19; 
SoA = schedule of activities; Vax = vaccination (i.e., IMP injection); wk = week(s); WOCBP = women of childbearing potential; yr = year(s). 

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b 
If the result from an oral swab for NAAT-based SARS-CoV-2 is not older than 24 h at the planned time of IMP injection, availability of the test result from the Visit 1 on Day 1 
is optional. 
c 
Issue thermometer or other measuring device for subjects to measure their oral body temperature each day and if they experience flu-like symptoms. 
d 
All swabs will be analyzed, even if no COVID-19 symptoms are shown. 
e 
5 mL blood will be taken from this sample for genetics (human leukocyte antigen typing). 
f 
For any visits >1 month after each IMP injection, only IMP-related AEs, trial procedure-related AEs, AESIs, any SAEs. In addition, all AEs linked to confirmed COVID-19 
cases will be recorded. 
g 
The 12-lead ECG at Visit 1 can be skipped if the 12-lead ECG from Visit 0 was performed within 24 h prior to the planned IMP dose. 
h 
For subjects rolling over from the trial BNT162-02 / C4591001 (NCT04368728), the recording will start from IMP allocation during Visit 1 (after eligibility is confirmed and the 
subject is withdrawn from the trial BNT162-02 / C4591001). 
i 
If an ad hoc visit occurs in combination with a planned visit, blood sampling will only be ≤120 mL for T-cell and B-cell response assessments and one 20 mL sample for 
serological testing for SARS-CoV-2 N-binding antibodies and humoral immunogenicity assessments. 
j 
Subjects who receive non-trial SARS-CoV-2 vaccinations will be discontinued, resulting in an early termination visit. For subjects who receive non-trial SARS-CoV-2 
vaccinations, there will be no blood sampling for humoral immunogenicity or T-cell and B-cell response assessments at the early termination visit. 
k 
For consenting subjects. 
l 
For any visits >1 month after each IMP injection, only prohibited medications should be recorded. 
 
Abbreviations: AE = adverse event; AESI = AE of special interest; ECG = electrocardiogram; e-diary = electronic diary or an equivalent application; EOT = end of trial; FU = follow-
up; h = hour(s); IMP = investigational medicinal product; mon = month(s); N-binding = nucleocapsid-binding; NAAT = nucleic acid amplification-based test; SAE = serious AE; 
SARS-CoV-2 = the virus leading to COVID-19; SoA = schedule of activities; Vax = vaccination (i.e., IMP injection); wk = week(s); WOCBP = women of childbearing potential; yr = 
year(s). 
 

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Note: The SoA allows for ad hoc visits for SARS-CoV-2 testing for symptomatic or asymptomatic subjects. 
a 
At Visit 0: complete physical examination including body weight, vital signs (oral body temperature, heart rate, blood pressure [systolic and diastolic]), blood and urine clinical 
laboratory tests; at Visit 1, Visit 3, and Visit 6: symptom-orientated physical examination. 
b 
If the result from an oral swab for NAAT-based SARS-CoV-2 is not older than 24 h at the planned time of IMP injection, availability of the test result from Visit 1 on Day 1 is 
optional. 
c 
Issue thermometer or other measuring device for subjects to measure their oral body temperature each day and if they experience flu-like symptoms. 
d 
All swabs will be analyzed, even if no COVID-19 symptoms are shown. 
e 
5 mL blood will be taken from this sample for genetics (human leukocyte antigen typing). 
f 
For any visits >1 month after each IMP injection, only IMP-related AEs, trial procedure-related AEs, AESIs, any SAEs. In addition, all AEs linked to confirmed COVID-19 
cases will be recorded. 
g 
The 12-lead ECG at Visit 1 can be skipped if the 12-lead ECG from Visit 0 was performed within 24 h prior to the planned IMP dose. 
h 
If an ad hoc visit occurs in combination with a planned visit, blood sampling will only be ≤120 mL for T-cell and B-cell response assessments and one 20 mL sample for 
serological testing for SARS-CoV-2 N-binding antibodies and humoral immunogenicity assessments. 
i 
Except IMP injection, i.e., all procedures should be performed before IMP administration. The third injection can be administered earlier than 6 months post-Dose 2 if 
supported by local legislation. For subjects who are not administered Dose 3, only the following activities will be done: record concomitant medications, AEs, and 
pregnancies, and take oral swabs and blood draws. 
j 
Visit 7 and Visit 8 are planned visits only for subjects who receive the third vaccination. 
k 
Subjects who receive non-trial SARS-CoV-2 vaccinations will be discontinued, resulting in an early termination visit. For subjects who receive non-trial SARS-CoV-2 
vaccinations, there will be no blood sampling for humoral immunogenicity or T-cell and B-cell response assessments at the early termination visit. 
l 
For any visits >1 month after each IMP injection, only prohibited medications should be recorded. 
 
Abbreviations: AE = adverse event; AESI = AE of special interest; ECG = electrocardiogram; e-diary = electronic diary or an equivalent application; EOT = end of trial; FU = follow-
up; h = hour(s); IMP = investigational medicinal product; mon = month(s); N-binding = nucleocapsid-binding; NAAT = nucleic acid amplification-based test; SAE = serious AE; 
SARS-CoV-2 = the virus leading to COVID-19; SoA = schedule of activities; Vax = vaccination (i.e., IMP injection); wk = week(s); WOCBP = women of childbearing potential; yr = 
year(s). 

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n 
~15 subjects at preselected sites in Part B will be evaluated in terms of cell-mediated immunity. 
o 
For any visits >1 month after each IMP injection, only prohibited medications should be recorded. 
 
Abbreviations: AE = adverse event; AESI = AE of special interest; ECG = electrocardiogram; e-diary = electronic diary or an equivalent application; EOT = end of trial; FU = follow-
up; h = hour(s); IMP = investigational medicinal product; mon = month(s); N-binding = nucleocapsid-binding; NAAT = nucleic acid amplification-based test; SAE = serious AE; 
SARS-CoV-2 = the virus leading to COVID-19; SoA = schedule of activities; Vax = vaccination (i.e., IMP injection); wk = week(s); WOCBP = women of childbearing potential; yr = 
year(s). 
 

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b 
If the result from an oral swab for NAAT-based SARS-CoV-2 is not older than 24 h at the planned time of IMP injection, availability of the test result from Visit 1 on Day 1 is 
optional. 
c 
Issue thermometer or other measuring device for subjects to measure their oral body temperature each day and if they experience flu-like symptoms. 
d 
All swabs will be analyzed, even if no COVID-19 symptoms are shown. 
e 
For any visits >1 month after each IMP injection, only IMP-related AEs, trial procedure-related AEs, AESIs, any SAEs. In addition, all AEs linked to confirmed COVID-19 
cases will be recorded. 
f 
Blood samples will be stored and may be analyzed retrospectively for additional clinical parameters (troponin, cytokine). 
g 
The 12-lead ECG at Visit 1 can be skipped if the 12-lead ECG from Visit 0 was performed within 24 h prior to the planned IMP dose. 
h 
The recording will start from IMP allocation during Visit 1 (after eligibility is confirmed). 
i 
Biomarker/PBMC subgroup (~25 subjects in each cohort). 
j 
If an ad hoc visit occurs in combination with a planned visit, blood sampling will only be ≤135 mL for T-cell and B-cell response assessments and one 30 mL sample for 
serological testing for SARS-CoV-2 N-binding antibodies and humoral immunogenicity assessments. 
k 
A 5 mL blood sample will be taken for genetics (HLA typing) within the biomarker/PBMC subgroup (~25 subjects in each cohort). 
l 
Subjects who receive non-trial SARS-CoV-2 vaccinations will be discontinued, resulting in an early termination visit. For subjects who receive non-trial SARS-CoV-2 
vaccinations, there will be no blood sampling for humoral immunogenicity or T-cell and B-cell response assessments at the early termination visit. 
m 
For any visits >1 month after each IMP injection, only prohibited medications should be recorded. 
n 
SARS-CoV-2 N-binding antibodies assessment only to be done by local lab when no historic NAAT result is available to prove prior SARS-CoV-2 infection. 
 
Abbreviations: AE = adverse event; AESI = AE of special interest; ECG = electrocardiogram; e-diary = electronic diary or an equivalent application; EOT = end of trial; FU = follow-
up; h = hour(s); HLA = human leukocyte antigen; IMP = investigational medicinal product; mon = month(s); N-binding = nucleocapsid-binding; NAAT = nucleic acid amplification-
based test; PBMC = peripheral blood mononuclear cell; SAE = serious AE; SARS-CoV-2 = the virus leading to COVID-19; SoA = schedule of activities; Vax = vaccination (i.e., IMP 
injection); wk = week(s); WOCBP = women of childbearing potential; yr = year(s). 
 

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Note: The SoA allows for ad hoc visits for SARS-CoV-2 testing for symptomatic or asymptomatic subjects. 
a 
At Visit 0: complete physical examination including body weight and vital signs (oral body temperature, heart rate, blood pressure [systolic and diastolic]); at Visit 1: symptom-
orientated physical examination. 
b 
SARS-CoV-2 N-binding antibodies assessment only to be done by local lab when no historic NAAT result is available to prove prior SARS-CoV-2 infection.  
c 
Issue thermometer or other measuring device for subjects to measure their oral body temperature each day and if they experience flu-like symptoms. 
d 
All swabs will be analyzed, even if no COVID-19 symptoms are shown. 
e 
Subjects who receive non-trial SARS-CoV-2 vaccinations will be discontinued, resulting in an early termination visit. For subjects who receive non-trial SARS-CoV-2 
vaccinations, there will be no blood sampling for humoral immunogenicity or T-cell and B-cell response assessments at the early termination visit. 
f 
Blood samples will be stored and may be analyzed retrospectively for additional clinical parameters (troponin, cytokine). 
g 
The 12-lead ECG at Visit 1 can be skipped if the 12-lead ECG from Visit 0 was performed within 24 h of Visit 1. 
h 
The recording will start during Visit 1 (after eligibility is confirmed). 
i 
Biomarker/PBMC subgroup (~25 subjects). 
j 
If an ad hoc visit occurs in combination with a planned visit, blood sampling will only be ≤135 mL for T-cell and B-cell response assessments. 
k 
A 5 mL blood sample will be taken for genetics (HLA typing) within the biomarker/PBMC subgroup (~25 subjects). 
l 
For any visits >1 month after Visit 1, only trial procedure-related AEs, AESIs, any SAEs. In addition, all AEs linked to confirmed COVID-19 cases will be recorded. 
m 
For any visits >1 month after Visit 1, only prohibited medications should be recorded. 
 
Abbreviations: AE = adverse event; AESI = AE of special interest; ECG = electrocardiogram; EOT = end of trial; h = hour(s); mon = month(s); HLA = human leukocyte antigen; 
N-binding = nucleocapsid-binding; NAAT = nucleic acid amplification-based test; PBMC = peripheral blood mononuclear cell; SAE = serious AE; SARS-CoV-2 = the virus leading to 
COVID-19; SoA = schedule of activities; wk = week(s); WOCBP = women of childbearing potential. 

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TABLE OF CONTENTS 
1 
PROTOCOL SUMMARY 
2 
1.1 
Trial synopsis 
2 
1.2 
Schema (graphical representation of the trial) 
19 
1.3 
Schedule of activities 
20 
TABLE OF CONTENTS 
40 
LIST OF TABLES 
43 
LIST OF FIGURES 
44 
ABBREVIATIONS/TERMS 
45 
2 
INTRODUCTION 
47 
2.1 
Background 
47 
2.1.1 
Overview of the disease 
47 
2.1.2 
Introduction to the trial treatment 
48 
2.2 
Trial rationale 
49 
2.3 
Benefit/risk assessment 
52 
2.3.1 
Risk assessment 
52 
2.3.2 
Benefit assessment 
56 
2.3.3 
Overall benefit/risk conclusion 
56 
3 
OBJECTIVES AND ENDPOINTS 
57 
4 
TRIAL DESIGN 
66 
4.1 
Overall design 
66 
4.2 
Scientific rationale for the trial design 
70 
4.3 
Justification for dose 
71 
4.4 
Trial completed and end of trial definitions 
71 
4.5 
Duration of all trial periods 
72 
5 
TRIAL POPULATION 
72 
5.1 
Inclusion criteria 
72 
5.2 
Exclusion criteria 
74 
5.3 
Lifestyle considerations 
75 
5.4 
Screen failures 
76 
6 
TRIAL TREATMENTS 
76 
6.1 
IMPs administered 
77 
6.2 
Preparation/handling/storage/accountability 
77 
6.3 
Measures to minimize bias: randomization and blinding 
78 
6.4 
Trial treatment compliance 
78 

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6.5 
Concomitant therapy 
78 
6.5.1 
Permitted concomitant therapies 
78 
6.5.2 
Prohibited concomitant therapies 
79 
6.5.3 
Recording of concomitant therapy 
79 
6.6 
Dose modifications 
80 
6.7 
Access to trial treatment after the end of the trial 
80 
7 
DISCONTINUATION OF TRIAL TREATMENT AND TRIAL SUBJECT 
DISCONTINUATION/WITHDRAWAL 
80 
7.1 
Discontinuation of trial treatment 
80 
7.1.1 
Criteria to permanently discontinue IMP administration 
80 
7.1.2 
Criteria for temporarily delaying enrollment or administration of IMP 
80 
7.2 
Trial subject discontinuation or withdrawal from the trial 
81 
7.3 
Lost to follow-up 
81 
7.4 
Replacement of permanently discontinued trial subjects 
82 
8 
TRIAL ASSESSMENTS AND PROCEDURES 
82 
8.1 
Efficacy assessments 
82 
8.2 
Safety assessments 
82 
8.2.1 
Clinical assessment 
82 
8.2.2 
Oral body temperature (in °C or °F) 
83 
8.2.3 
Subject e-diaries for assessment of reactogenicity (local and systemic reactions) 
84 
8.2.4 
Oral swabs for NAAT-based SARS-CoV-2 testing for screening and surveillance 
86 
8.2.5 
Serological testing for SARS-CoV-2 N-binding antibodies 
87 
8.2.6 
SARS-CoV-2 sequencing 
87 
8.3 
Adverse events and SAEs 
87 
8.3.1 
Time period and frequency for collection of AE, AESI, and SAE information 
87 
8.3.2 
Method of detecting AEs and SAEs 
88 
8.3.3 
Follow-up of AEs and SAEs 
88 
8.3.4 
Regulatory reporting requirements for SAEs 
88 
8.3.5 
Pregnancy testing and handling of pregnancies 
89 
8.3.6 
Death events 
89 
8.3.7 
Disease-related events/outcomes not qualifying as AEs or SAEs 
90 
8.3.8 
Adverse events of special interest 
90 
8.4 
Treatment of overdose 
90 
8.5 
Treatment for specific adverse reactions 
90 
8.6 
Safety stopping criteria 
91 
8.7 
Pharmacokinetics 
92 
8.8 
Pharmacodynamics 
92 
8.9 
Genetics 
92 

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8.10 
Immune responses 
92 
8.10.1 
Humoral immunogenicity assessments 
93 
8.10.2 
T and B cell-mediated immune responses 
93 
8.10.3 
Explorative research 
93 
8.11 
Baseline data 
94 
8.11.1 
Demographic data 
94 
8.11.2 
Medical history 
94 
8.12 
Blood collection 
94 
9 
STATISTICAL CONSIDERATIONS 
95 
9.1 
Statistical hypotheses 
95 
9.1.1 
GMT non-inferiority 
95 
9.1.2 
SR non-inferiority 
96 
9.1.3 
Multiplicity considerations 
96 
9.2 
Sample size determination 
96 
9.2.1 
Part A 
97 
9.2.2 
Part B 
97 
9.2.3 
Part C 
98 
9.3 
Analysis sets 
99 
9.4 
Statistical analyses 
99 
9.4.1 
General considerations 
99 
9.4.2 
Safety endpoints 
99 
9.4.3 
Immunogenicity endpoints 
100 
9.4.4 
Exploratory endpoints 
101 
9.4.5 
Other safety analyses 
101 
9.4.6 
Other analyses 
102 
9.5 
Interim analyses 
102 
9.6 
Data monitoring committee 
102 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
102 
10.1 
Regulatory, ethical, and trial oversight considerations 
102 
10.1.1 
Regulatory and ethical considerations 
102 
10.1.2 
Financial disclosure 
103 
10.1.3 
Informed consent process 
103 
10.1.4 
Data protection 
104 
10.1.5 
Committees - SRC 
104 
10.1.6 
Dissemination of clinical trial data 
104 
10.1.7 
Data quality assurance 
105 
10.1.8 
Source documents 
106 
10.1.9 
Trial and site start and closure 
106 
10.1.10 
Publication policy 
107 

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10.1.11 
Protocol preparation and approval 
107 
10.2 
Clinical laboratory tests 
107 
10.3 
Adverse events: Definitions and procedures for recording, evaluating, follow-up, and 
reporting 
108 
10.3.1 
Definition of AE, TEAE, and AESIs 
108 
10.4 
Contraceptive guidance and collection of pregnancy information 
115 
10.4.1 
Definitions 
116 
10.4.2 
Contraception guidance 
117 
10.4.3 
Collection of pregnancy information 
118 
10.4.4 
Sperm donation 
118 
10.5 
Genetics 
118 
10.6 
Liver safety: Suggested actions and follow-up assessments 
118 
10.7 
Investigators and trial administrative structure 
118 
10.7.1 
Investigators and trial site personnel 
118 
10.7.2 
Trial site personnel assigned trial-related duties 
119 
10.7.3 
Contract research organizations 
119 
10.7.4 
The sponsor and sponsor’s personnel 
119 
10.8 
Country-specific requirements 
119 
10.9 
Protocol amendments and updates 
120 
10.9.1 
Amendment 1.0 (update from protocol version 1.0 to 2.0) 
120 
10.9.2 
Amendment 2.0 (update from protocol version 2.0 to 3.0) 
120 
10.9.3 
Amendment 3.0 (update from protocol version 3.0 to 4.0) 
120 
10.9.4 
Amendment 4.0 (update from protocol version 4.0 to 5.0) 
120 
10.9.5 
Amendment 5.0 (update from protocol version 5.0 to 6.0) 
121 
10.9.6 
Amendment 6.0 (update from protocol version 6.0 to 7.0) 
121 
10.10 
Data collection and management 
122 
10.10.1 
Case report forms 
122 
10.10.2 
Trial subject reported outcomes 
122 
10.10.3 
Data management 
123 
10.10.4 
Investigator’s Site File and the TMF 
123 
11 
REFERENCES 
123 
 
LIST OF TABLES 
Table 1: 
Schedule of events for Part A, Cohorts 1, 3, 4, and 5; one dose of either 
BNT162b2 (B.1.1.7 + B.1.617.2), or BNT162b2 (B.1.1.7), or BNT162b2 (B.1.617.2), or 
BNT162b2 in BNT162b2-experienced subjects 
20 
Table 2: 
Schedule of events for Part A, Cohort 2; two doses of BNT162b2 (B.1.1.7 + B.1.617.2) 
in BNT162b2-experienced subjects 
23 

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Table 3: 
Schedule of events for Part A, Cohort 6; three doses of BNT162b2 (B.1.1.7 + 
B.1.617.2) in COVID-19 vaccine-naïve subjects 
26 
Table 4: 
Schedule of events for Part B, Cohort 1 with one dose of BNT162b2 (B.1.1.7 + 
B.1.617.2) in BNT162b2-experienced subjects and Cohort 4 with one dose of 
BNT162b2 (B.1.617.2) in BNT162b2-experienced subjects 
29 
Table 5: 
Schedule of events for Part B, Cohort 6; three doses of BNT162b2 (B.1.1.7 + 
B.1.617.2) in COVID-19 vaccine-naïve subjects 
31 
Table 6: 
Schedule of events for Part C, Cohorts 7 and 8; one dose of BNT162b2 (B.1.1.529) or 
BNT162b2 in subjects who received two or three doses of any COVID-19 RNA-based 
vaccine prior to a SARS-CoV-2 infection from January 2022 onwards 
35 
Table 7: 
Schedule of events for Part C, Cohort 9; no vaccination (within 3-month period) in 
subjects who received two or three doses of any COVID-19 RNA-based vaccine prior 
to a SARS-CoV-2 infection from January 2022 onwards 
38 
Table 8: 
SARS-CoV-2 variant strains tracked by the WHO 
47 
Table 9: 
Local reaction grading scale 
84 
Table 10: Systemic reaction grading scale 
85 
Table 11: Power analysis for immunogenicity GMT hypotheses 
97 
Table 12: Power analysis for immunogenicity SR hypotheses 
98 
Table 13: Power analysis for immunogenicity GMT comparison 
98 
 
LIST OF FIGURES 
Figure 1: 
Schema - Safety and immunogenicity of SARS-CoV-2 monovalent and multivalent 
RNA-based vaccines in healthy subjects 
19 

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In addition to mutations, additions or deletions near the receptor binding domain (RBD) of 
the S protein, which is responsible for attaching to the human angiotensin cell receptor 2 
and resulting in host infection, and/or other key changes (e.g., deletions) circumventing 
antibody detection (e.g., around Y144 in the N terminal domain) are increasingly 
recognized. More specifically, newer mutations of the S protein not only provide the virus 
with greater transmissibility and affinity/avidity for cellular attachment but may also render 
the variant strains less susceptible to virus neutralization, thus allowing increases in overall 
infection rates. 
Because successful prophylactic COVID-19 vaccines are designed to primarily work by 
inducing neutralizing antibodies, an increased sense of urgency has again risen to 
anticipate and combat SARS-CoV-2 evolution through numerous tactics. These tactics 
include characterization of evolving variant sequences of SARS-CoV-2 with respect to 
vaccine-induced immune response breadth and other key functional immune response 
parameters. 
2.1.2 
Introduction to the trial treatment 
The development of an RNA-based vaccine encoding a viral antigen that is translated to 
protein by the vaccinated organism to induce a protective immune response provides 
significant advantages over more conventional vaccine approaches. RNA-based vaccines 
have some advantages over DNA, protein subunit, inactivated or live attenuated virus 
vaccines. First, safety: The RNA is degraded by normal cellular processes, is non-
infectious, non-integrating, and poses no risk of insertional mutagenesis. Second, 
efficiency: Delivery of RNA results in transient translation that can be controlled by 
modifications in the untranslated regions, cap, poly(A) tail, and coding sequences. These 
modifications can make the RNA more stable and highly translatable. Efficient in vivo 
delivery can be achieved by formulating RNA into carrier LNPs that promote rapid uptake 
and enable RNA expression in the cytoplasm. Third, production: Manufacturing of 
conventional protein subunits, inactivated virus or replication-defective virus vaccines is 
time consuming and involves multiple pieces of manufacturing equipment. Protein vaccine 
production and purification require optimization for each mammalian or insect cell culture 
system. In addition, each production system introduces the potential for improper folding 
and altered glycosylation patterns of the protein, particularly when produced in insect cells. 
In contrast, RNA-based vaccine production does not require individualized cell culture 
systems and unique purification systems for each vaccine antigen. Uniformly optimized 
transcription and purification techniques can be used to produce any RNA sequence. 
Furthermore, because RNA sequences are processed in vivo as would occur during viral 
infection, glycosylation patterns of the antigens are similar to those seen after natural 
infection. 
As demonstrated by the SARS-CoV-2 RNA-LNP-based vaccine BNT162b2, LNP-
formulated RNA-based vaccines provide one of the most flexible, scalable and fastest 
approaches to provide protection against the emerging viruses like SARS-CoV-2 
(Mulligan et al. 2020; Rauch et al. 2018; Sahin et al. 2014; Walsh et al. 2020). BNT162b2 
(Comirnaty, Pfizer-BioNTech COVID-19 vaccine) received emergency use authorization or 
conditional/full marketing authorization in numerous countries worldwide for the prevention 

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of COVID-19. Administration of BNT162b2 to millions of individuals in the post-
authorization setting has confirmed the benefit-risk profile seen in clinical trials. 
The BNT162b2-based vaccines against variant strains, BNT162b2 (B.1.1.7), 
BNT162b2 (B.1.351), BNT162b2 (B.1.617.2), BNT162b2 (B.1.1.7 + B.1.617.2), and 
BNT162b2 (B.1.1.529), have the same LNP formulation and RNA components as 
BNT162b2 except that the RNAs differ slightly in their encoded ORF. Each RNA 
component leads to expression of S proteins with the amino acid changes seen in the 
respective SARS-CoV-2 strains B.1.1.7, B.1.351, B.1.617.2, and B.1.1.529. For further 
details, see Table 8. 
The BNT162b2-based vaccines against variant strains are named by combining the parent 
vaccine name “BNT162b2” with the name of the SARS-CoV-2 strain from which the 
S protein encoded by the RNA originates, e.g., BNT162b2 (B.1.1.7) has an RNA that 
encodes the SARS-CoV-2 strain B.1.1.7 S protein. 
For further details on the BNT162 family of RNA-based vaccines, see the current 
BNT162 investigator’s brochure (IB). 
2.2 
Trial rationale 
Efficacy and immunogenicity data from clinical studies have demonstrated that the 
BNT162b2 (30 µg) two-dose regimen induces a strong immune response and high vaccine 
efficacy and protection against COVID-19 across a spectrum of individuals ≥12 years of 
age: those with or without prior exposure to SARS-CoV-2 and those in higher risk 
categories based on age, race, ethnicity, and/or comorbidity. The sponsor has 
accumulated significant experience on the safety of BNT162b2 in the BNT162-02 / 
C4591001 trial (NCT04368728), which was the basis of the BNT162b2 authorization for 
emergency use and the conditional/full marketing authorizations given in numerous 
countries worldwide for the prevention of COVID-19 (Feldman et al. 2019; Polack et al. 
2020). Administration of BNT162b2 to millions of individuals in the post-authorization 
setting has confirmed its favorable benefit-risk profile. For details, see the current 
BNT162 IB. 
As more data about COVID-19 continue to accrue, the potential duration of protection, 
after SARS-CoV-2 natural infection and by vaccination, remains unknown. Further, 
although SARS-CoV-2 presents a mutation rate lower than that of other RNA viruses, it 
continues to evolve, generating new variants that arouse concern due to increased 
transmissibility or anticipated reduction in neutralization by antibodies generated during 
previous infection or vaccination (Dan et al. 2021, Abdool Karim and de Oliveira 2021). 
These variants include a variant with high prevalence globally, B.1.1.7 (known as Alpha) 
and further variants including B.1.351 (known as Beta), P.1 (known as Gamma), B.1.617.1 
and B.1.617.2 (the latter known as Delta), and B.1.1.529 (Omicron) and its subvariants 
B.1.1.529.1 (BA.1) and B.1.1.529.5 (BA.5). BNT162b2 induces a robust immune response 
against SARS-CoV-2, including both humoral and multifunctional T-cell responses, and 
emerging in vitro cross-neutralization data and vaccine effectiveness data confirm its 
effectiveness against COVID-19 in populations with high prevalence of those variants (Liu 
et al. 2021, Abu-Raddad et al. 2021). If evidence emerges that particular variants do 
appear to influence vaccine effectiveness and prevail in different countries, it will be 

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beneficial to be prepared to implement BNT162b2-based vaccines against variant strains 
able to boost memory responses against conserved SARS-CoV-2 epitopes while 
concurrently targeting novel neutralizing epitopes of escaping circulating strains. 
On 26 November 2021, the WHO designated the SARS-CoV-2 virus variant B.1.1.529, 
named Omicron, a VOC (WHO webpage “Update on Omicron”). Initially detected in South 
Africa, this variant rapidly distributed across the world. The SARS-CoV-2 Omicron variant 
is known to have a concerning number of mutations (more than 30) in the spike protein 
that are associated with reduced neutralization by convalescent and vaccinee sera 
(Schmidt et al. 2021). The original Omicron strain has since been renamed B.1.1.529.1 
(known as Omicron BA.1), with the Omicron lineage having expanded into multiple 
sublineages. 
Reflective of the SARS-CoV-2 Omicron (BA.1) variant’s decreased sensitivity to 
neutralizing antibodies elicited by previous viral variants or vaccines based on those, 
incidence of SARS-CoV-2 infection peaked in January 2022 (WHO webpage “COVID-19 
Weekly Epidemiological Update”). In the US, prevalence of the SARS-CoV-2 Omicron 
variant reached 89.2 to 98.8% during that time frame (CDC webpage “COVID Data 
Tracker – Variant Proportions”, accessed 09 February 2022). Meanwhile it was confirmed 
that two-dose vaccination schedules with the available vaccines based on the SARS-CoV-
2 wild-type strain provide lower protection against infection with the SARS-CoV-2 Omicron 
variant(s) compared to the previous variants or the wild-type strain. A third dose of an 
RNA-based vaccine appears to temporarily increase protection (UK Health Security 
Agency 2022), but reinfection rates with the SARS-CoV-2 Omicron variant(s) are likely 
higher than with the SARS-CoV-2 Delta variant (Ferguson et al. 2021). 
As of 04 August 2022, no Omicron-specific variant vaccines were authorized, and there 
were no vaccination recommendations for subjects who experienced a breakthrough 
infection with the SARS-CoV-2 Omicron variant. On 31 August 2022, the US FDA 
authorized the bivalent vaccine, BNT162b2 and BNT162b2 Omicron (B.1.1.529 sub-
lineage BA.4/5), for a booster vaccination in individuals 12 years of age and older. 
On 18 April 2023, the US FDA amended the BNT162b2 emergency use authorization to 
simplify the vaccination schedule for most individuals, including that most unvaccinated 
individuals may receive a single dose of a variant-modified vaccine (rather than two 
doses). The effectiveness of a single dose was supported by observational data from 
England on the effectiveness of one dose of monovalent BNT162b2, and that, among 
individuals 12 to 17 years of age who had received only one dose of BNT162b2, those 
who had evidence of previous infection with Alpha, Delta, or Omicron variants had 
increased protection against symptomatic Omicron infection compared with those with no 
evidence of previous infection. 
To combat these evolving SARS-CoV-2 strains, the sponsor has initiated clinical 
investigation of BNT162b2-based vaccines against variant strains as monovalent vaccines 
and as a multivalent vaccine (i.e., a combination of two monovalent vaccines). These 
BNT162b2-based vaccines are named “BNT162b2” plus the variant strain targeted by the 
RNA-encoded ORF, e.g., BNT162b2 (B.1.1.7) has an RNA that encodes the SARS-CoV-2 
strain B.1.1.7 spike (S) protein. The BNT162b2-based vaccines against variant strains 
have the same LNP formulation and RNA components as BNT162b2 except that the 

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RNAs differ slightly in their encoded ORF. Each RNA component leads to expression of 
S proteins with the amino acid changes seen in the SARS-CoV-2 strains B.1.1.7, B.1.351, 
B.1.617.2, and B.1.1.529.1, respectively. For further details, see Table 8. 
The safety and immunogenicity of a monovalent BNT162b2-based vaccine, 
BNT162b2 (B.1.351), is under evaluation in the BNT162-02 / C4591001 trial. This 
approach will allow an evaluation of immunogenicity of the monovalent vaccine 
BNT162b2 (B.1.351) against the reference ancestral SARS-CoV-2 strain (Wuhan-
Hu-1/USA-WA1) and the selected B.1.351 variant strain, using immunobridging to the 
immune response after two doses of BNT162b2 as a primary vaccination series. 
This trial (BNT162-17) aims to investigate the safety and immunogenicity of the 
BNT162b2-based vaccines against variant strains BNT162b2 (B.1.1.7 + B.1.617.2), 
BNT162b2 (B.1.1.7), BNT162b2 (B.1.617.2), and BNT162b2 (B.1.1.529) *: 
• BNT162b2 (B.1.1.7 + B.1.617.2), a multivalent vaccine comprising a 1:1 mixture of 
BNT162b2 (B.1.1.7) and BNT162b2 (B.1.617.2). 
• BNT162b2 (B.1.1.7), a monovalent vaccine that expresses the full length 
SARS-CoV-2 Alpha S protein bearing mutations preserving neutralization-sensitive 
sites. 
• BNT162b2 (B.1.617.2), a monovalent vaccine that expresses the full length 
SARS-CoV-2 Delta S protein bearing mutations preserving neutralization-sensitive 
sites. 
• BNT162b2 (B.1.1.529), a monovalent vaccine that expresses the full length 
SARS-CoV-2 Omicron S protein bearing mutations preserving neutralization-
sensitive sites. 
* Note: In this protocol, “B.1.1.529” refers to variant B.1.1.529.1 (known as Omicron 
BA.1) unless stated otherwise. 
The two viral strains included in the multivalent vaccine BNT162b2 (B.1.1.7 + B.1.617.2) 
are selected to favor cross-reactive antibody responses and to also include dominant 
strains in terms of global prevalence at the time of this trial. The thorough clinical 
investigation of BNT162b2 (B.1.1.7 + B.1.617.2) in Parts A and B will support 
preparedness for the case that a multivalent BNT162b2-based vaccine against COVID-19 
is needed to allow broad coverage against circulating strains at global level and to avoid 
the complexity of handling multiple monovalent vaccines in parallel. 
To support the clinical evaluation of the multivalent vaccine BNT162b2 (B.1.1.7 + 
B.1.617.2), the monovalent BNT162b2 vaccines BNT162b2 (B.1.1.7) and 
BNT162b2 (B.1.617.2) will also be individually investigated clinically in Parts A and B. Data 
from Part B of the trial will be used to evaluate the immunogenicity of one dose of variant-
modified BNT162b2 (multivalent B.1.1.7 + B.1.617.2) in vaccine-naïve seropositive 
individuals. To supplement real world evidence that a single dose is effective, 
immunogenicity results from this analysis will fill the evidence gap for use of the single 
dose of BNT162b2 in individuals 12 years of age and older who have not been previously 
vaccinated with a COVID-19 vaccine. The Alpha (B.1.1.7) and Delta (B.1.617.2) 
BNT162b2 variants are no longer epidemiologically relevant. Experience with other 

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BNT162b2 variants is relevant because all BNT162b2 variants have the same LNP 
formulation and RNA components except that the RNAs differ slightly in their encoded 
ORF and the available data has demonstrated that immune response(s) to vaccine-
encoded strain(s) are similar. To provide a robust comparison, as well as assessing NTs 
against Alpha and Delta, NTs against the more contemporaneous B.1.1.529.5 (Omicron 
BA.5) will also be assessed. Finally, to bridge to the efficacy demonstrated with the original 
BNT162b2 vaccine, although not encoded by the investigational vaccine in this trial, NTs 
against the reference strain will be compared between vaccine-naïve seropositive 
individuals after one dose of BNT162b2 (B.1.1.7 + B.1.617.2) and vaccine-naïve 
seronegative individuals after two doses of original BNT162b2 (from trial 
BNT16202 / C4591001; NCT04368728). 
Part C will investigate if administration of one dose of either BNT162b2 (B.1.1.529) or 
BNT162b2 after previous infection with the SARS-CoV-2 Omicron variant will elicit an 
immune response against the SARS-CoV-2 Omicron variant in subjects who have been 
vaccinated with any authorized COVID-19 RNA-based vaccine and were subsequently 
diagnosed with a SARS-CoV-2 infection from January 2022 onwards (and limited to a 
period when there was a high prevalence of SARS-CoV-2 Omicron infections). In addition, 
Part C (Cohort 9) will evaluate the immune response reached after infection with the 
SARS-CoV-2 Omicron variant. 
2.3 
Benefit/risk assessment 
Typically, healthy trial volunteers participating in clinical trials can expect no direct health 
benefits; however, subjects in this trial may be offered doses of BNT162b2, for which 
extensive clinical and post-authorization data have been collected. Trial subjects may also 
receive BNT162b2-based monovalent or multivalent vaccines, or different schedules of 
BNT162b2, for which efficacy and safety may have not been demonstrated yet (see 
Section 2.3.2). This trial is also designed to minimize the risks to trial subjects while 
maximizing the potential value of knowledge it is designed to provide. 
For further information on the expected benefits and risks for injection with BNT162b2, 
including the reference safety information, see the current BNT162 IB. 
2.3.1 
Risk assessment 
General risks of vaccines: 
• The vaccines used in this trial may have side effects, some of which are listed 
below. Note that these lists do not include all individual side effects ever seen with 
these vaccines. The more serious or common side effects with a known or possible 
relationship to the vaccine are listed. 
• Rarely, a vaccine may cause allergic reactions such as rash or difficulty breathing. 
Allergic reactions may be life-threatening. All trial subjects will be queried for a 
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• Side effects seen from giving a vaccine by injection into the muscle include local 
reactions at the injection site such as redness, itchiness, tenderness, pain, and 
swelling. 
• All vaccines can cause fever, chills, rash, aches and pains in the muscles or joints, 
nausea and loss of appetite, headache, dizziness, and feeling tired. Most people 
are still able to do their planned activities after getting a vaccine. Rarely, people 
experience side effects that limit their normal activities or make them go to their 
doctor. 
• Very rarely, a vaccine may cause an autoimmune disease in a person or may make 
an autoimmune disease worse. 
Risks related to BNT162b2, BNT162b2 (B.1.1.7 + B.1.617.2), BNT162b2 (B.1.1.7), 
BNT162b2 (B.1.617.2), and BNT162b2 (B.1.1.529): 
• BNT162b2 has received temporary authorization for emergency use, conditional 
marketing authorization approval, and/or full authorization in more than 
100 countries globally. Full approval of a two-dose regimen of BNT162b2 30 μg in 
individuals ≥16 years of age was granted by the US FDA on 23 AUG 2021. The 
safety profile of BNT162b2 based on available data in the ongoing Phase II/III trial 
BNT162-02 / C4591001 is favorable. The US FDA has also authorized emergency 
use of BNT162b2 as first booster dose and second booster dose in various 
populations. Since its first marketing authorization in December 2020, BNT162b2 
has been administered to hundreds of millions of individuals worldwide. 
• The safety of BNT162b2 after two doses was evaluated in subjects 5 years of age 
and older. The trial BNT162-02 / C4591001 enrolled ~46,000 subjects 12 years of 
age or older. The trial BNT162-07 / C4591007 (NCT048166443) enrolled 
~4,500 (data cutoff date of 29 OCT 2021) subjects 5 through less than 12 years of 
age. Additionally, 306 existing Phase III subjects at least 18 through 55 years of 
age in the trial BNT162-02 / C4591001 received a booster dose (third dose) of 
BNT162b2 ~6 months after the second dose (data cutoff date of 17 JUN 2021). The 
overall safety profile for the booster dose (third dose) was similar to that seen after 
two doses. 

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• The safety of BNT162b2 was evaluated in subjects 16 years of age and older after 
two doses. In the trial BNT162-02 / C4591001, a total of 22,026 subjects 16 years 
of age or older received at least one dose of BNT162b2 and a total of 
22,021 subjects 16 years of age or older received placebo (as of the data cutoff 
date of 13 MAR 2021). The most frequent adverse reactions in subjects 16 years of 
age and older that received two doses were injection site pain (>80%), fatigue 
(>60%), headache (>50%), myalgia (>40%), chills (>30%), arthralgia (>20%), 
pyrexia and injection site swelling (>10%) and were usually mild or moderate in 
intensity and resolved within a few days after vaccination. A lower frequency of 
reactogenicity events was associated with greater age. The safety profile in 
545 subjects receiving BNT162b2, that were seropositive for SARS-CoV-2 at 
baseline, was similar to that seen in the general population. The trial BNT162-02 / 
C4591001 also included 200 subjects with confirmed stable human 
immunodeficiency virus (HIV) infection. The safety profile of the subjects receiving 
BNT162b2 (n = 100) in the individuals with stable HIV infection was similar to that 
seen in the general population. 
• The safety of BNT162b2 was evaluated in subjects 18 years of age and older after 
booster dose (third dose). A subset from trial BNT162-02 / C4591001 Phase II/III 
subjects of 306 adults at least 18 through 55 years of age who completed the 
primary BNT162b2 two-dose course, received a booster dose (third dose) of 
BNT162b2 ~6 months (range of 4.8 to 8.0 months) after receiving Dose 2. The 
most frequent adverse reactions in subjects 18 through 55 years of age were 
injection site pain (>80%), fatigue (>60%), headache (>40%), myalgia (>30%), 
chills and arthralgia (>20%). 
• The most common adverse reactions (seen ≥1/10) were headache, diarrhea, 
arthralgia, myalgia, injection site pain, fatigue, chills, pyrexia, and injection site 
swelling, and (seen ≥1/100 to <1/10) were vomiting, nausea, and injection site 
redness. 
• Special warnings and precautions for use have been defined for anaphylaxis, 
myocarditis and pericarditis, acute severe febrile illness, coagulation disorders, for 
immunocompromised individuals, and for stress-related responses associated with 
the process of vaccination itself. For details see the current BNT162 IB. 
• Hypersensitivity to the BNT162b2 active substance and/or to any of the excipients 
is a contraindication. 
• Although not seen to date, it cannot yet be ruled out that the trial IMPs could make 
a later COVID-19 illness more severe. 
• Since BNT162b2 and the vaccines BNT162b2 (B.1.1.7 + B.1.617.2), 
BNT162b2 (B.1.1.7), BNT162b2 (B.1.617.2), and BNT162b2 (B.1.1.529) use the 
same RNA platform and LNP formulation, they are expected to share the same 
formulation-based risks. 

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• BNT162b2 and the vaccines BNT162b2 (B.1.1.7 + B.1.617.2), BNT162b2 (B.1.1.7), 
BNT162b2 (B.1.617.2), and BNT162b2 (B.1.1.529) differ slightly in the RNA-
encoded ORF. Despite this difference, the safety and immunogenicity of the 
vaccine variants is not anticipated to be any different than for the parent vaccine 
BNT162b2. 
Risks associated with trial-specific procedures: 
• There is the risk of bleeding, bruising, hematoma formation, and infection at the 
venipuncture site. To minimize this risk, only appropriately qualified personnel will 
draw blood. 
• The volume of blood drawn at any visit is kept to the amounts required to support 
the objectives of this trial. 
Mitigations for vaccine-related and trial risks: 
• In general, the listed risks of IM injection can be managed using routine symptom-
driven standard of care. Treatment of these events is dependent on the discretion 
of the investigators. As the parent vaccine BNT162b2 has been authorized for 
emergency use or been given conditional/full marketing authorization in numerous 
countries worldwide, and use since then has confirmed the favorable benefit-risk 
profile, procedures routine for monitoring Phase I trials are not planned. 
• All trial-specific procedures will be performed by qualified trial site personnel. 
• Trial subjects will be observed at the site for at least 30 minutes after each IMP 
injection. 
• Equipment to treat anaphylaxis will be readily available. 
• 12-lead electrocardiogram (ECG) will be recorded before and at 7 days after each 
IMP injection and at any time point if clinically indicated. 
• Volunteers with any current or history of cardiovascular diseases, e.g., myocarditis, 
pericarditis, myocardial infarction, congestive heart failure, cardiomyopathy or 
clinically significant arrhythmias, are specifically excluded from this trial. 
• To minimize the risk to trial subjects, the Medical Monitor and the SRC will regularly 
review and evaluate the safety data including any emerging SAEs or AESIs. For 
details, see Section 10.1.5. 
• Human reproductive safety data are limited for BNT162b2. Therefore, although 
human teratogenicity is not suspected based on the intended pharmacology of the 
compound, the use of contraception is required in this trial (see Section 10.4). For 
further details, see in the current BNT162 IB. 

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The risks and mitigations linked to the COVID-19 pandemic while participating in the trial 
include the following: 
• The risk of becoming SARS-CoV-2 infected or unknowingly spreading the virus 
during participation in the trial; therefore, trial subjects will continue to be required 
to practice social distancing and infection prevention practices, i.e., to follow any 
local laws or guidance. 
• Provision of site contact numbers for subjects to contact the trial site during their 
participation should they require guidance or experience symptoms suggestive of 
SARS-CoV-2 infection. 
• If the subject reports symptoms of illness, e.g., enhanced respiratory disease or flu-
like symptoms, the subject will be asked to return to the site for diagnostic 
measures. More specifically, respiratory disease or progression of flu-like 
symptomatology, such as non-resolution of the symptoms after 3 days, i.e., 
symptom kinetics that are inconsistent with SARS-CoV-2 RNA immunization, will 
trigger diagnostic measures, i.e., antigen and diagnostic nucleic acid SARS-CoV-2 
testing. 
2.3.2 
Benefit assessment 
The parent vaccine BNT162b2 has been authorized for emergency use or been given 
conditional/full marketing authorization in numerous countries worldwide. Since then, 
pharmacovigilance data after BNT162b2 administration to hundreds of millions of 
individuals worldwide has confirmed the favorable benefit-risk profile. Thus, subjects in this 
trial administered BNT162b2 will have access to vaccination with a vaccine proven to be 
safe and effective protection against COVID-19. 
Although not yet proven in clinical trials, the BNT162b2 vaccine variants are also expected 
to provide a safe and effective protection against COVID-19, therefore subjects in this trial 
administered the BNT162b2-based vaccine variants are expected to have access to a safe 
and effective protection against COVID-19 caused by new variants of the SARS-CoV-2 
variants. 
Participation in this trial could also help the trial subject indirectly. The clinical laboratory 
tests, physical examinations, and other safety assessments performed while participating 
in this trial could uncover previously undiagnosed health problems. The trial subject will 
have access to real-time SARS-CoV-2 diagnostic testing. Also, by participating in this trial, 
trial subjects may better understand how vaccines can help protect against COVID-19. 
2.3.3 
Overall benefit/risk conclusion 
Overall, based on all available data, the sponsor considers the benefit/risk ratio for this trial 
to be acceptable. 

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SAE = serious adverse event; SARS-CoV-2 = Severe Acute Respiratory Syndrome Coronavirus 2; SR = seroresponse; 
VNT = virus neutralization test; VOC = variant(s) of concern. 
4 
TRIAL DESIGN 
4.1 
Overall design 
This is a Phase II open-label trial. 
This trial consists of three parts, Part A, Part B, and Part C, and will evaluate the safety 
and immunogenicity of a third booster injection of the multivalent vaccine 
BNT162b2 (B.1.1.7 + B.1.617.2), and the safety and immunogenicity of a third booster 
injection of the monovalent vaccine BNT162b2 (B.1.617.2) or BNT162b2 (B.1.1.7), in 
subjects who have received two doses of the parent vaccine BNT162b2 at 30 µg, at least 
6 months after the second dose of BNT162b2. It will also evaluate the safety and 
immunogenicity of a three-dose regimen of BNT162b2 (B.1.1.7 + B.1.617.2) in subjects 
who have not received prior COVID-19 vaccination. In addition, the safety and 
immunogenicity of BNT162b2 (B.1.1.529) or BNT162b2 given as a third or fourth vaccine 
dose to RNA COVID-19 vaccine-experienced subjects with history of SARS-CoV-2 
infection will be evaluated and contrasted with the natural immune response reached after 
infection with the SARS-CoV-2 Omicron variant. 
Part A will describe, in parallel subject cohorts, the safety and the immunogenicity of 
BNT162b2 (B.1.1.7 + B.1.617.2) in relation to the corresponding monovalent vaccines 
BNT162b2 (B.1.1.7) and BNT162b2 (B.1.617.2), and the parent vaccine BNT162b2. 
Comprehensive assessments of the humoral and cell-mediated immune responses in 
those groups will evaluate if the immunological responses to each antigen is undeterred by 
the addition of additional antigens in BNT162b2 (B.1.1.7 + B.1.617.2). Further, analyses of 
the B cell compartment, including memory B cells, will assess if BNT162b2 (B.1.1.7 + 
B.1.617.2) as a booster in prior vaccinated subjects elicits a qualitatively improved 
anamnestic response, with expansion of a diversified memory B cell population able to 
cross-neutralize conserved and unique strain epitopes. Part A will provide rapid 
information about the safety and the immunogenicity of the multivalent BNT162b2 (B.1.1.7 
+ B.1.617.2) vaccine in a previously vaccinated group and in a vaccine-naïve population, 
and will inform Part B in terms of dosage and sample size. 
Part B will be initiated after review of reactogenicity and available immunogenicity data of 
Part A (Cohorts 1, 4, 6) by the SRC. Part B will compare the immune response after one 
dose or after two doses of the multivalent BNT162b2 (B.1.1.7 + B.1.617.2) vaccine against 
the variant strains or after one dose of multivalent BNT162b2 (B.1.1.7 + B.1.617.2) 
vaccine against the reference strain vs the immune response after two doses of 
BNT162b2 against the reference strain observed in subjects from the Phase III BNT162-02 
/ C4591001 (NCT04368728) trial. Part B will also compare the immune response after one 
dose of the monovalent vaccine BNT162b2 (B.1.617.2) against the variant strain vs the 
immune response after two doses of BNT162b2 against the reference strain observed in 
subjects from the Phase III BNT162-02 / C4591001 trial. Part B will further include the 
same assessments of the B cell and T cell compartments as described in Part A in a pre-
defined sample size of the cohort population. 

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Based on data from Part A, the dosage, sample size and trial groups planned in Part B 
may be adjusted via a protocol amendment. 
Part C will include healthy subjects who were previously vaccinated with two or three 
doses of any authorized COVID-19 RNA-based vaccine and were subsequently diagnosed 
with a SARS-CoV-2 infection from January 2022 onwards (and limited to a period when 
there was a high prevalence of SARS-CoV-2 Omicron infections). Part C will compare 
immune responses against the SARS-CoV-2 Omicron variant after one dose of 30 µg 
monovalent BNT162b2 (B.1.1.529) vaccine vs the immune response after one dose of 
30 µg BNT162b2. In addition, Part C (Cohort 9) will evaluate the immune response 
reached after infection with the SARS-CoV-2 Omicron variant. 
Part A 
Part A consists of six parallel cohorts of approximately n = 20 subjects each, which will 
enroll subjects 18 to 55 years of age (Cohorts 1 to 6). 
Cohorts 1 to 5 will enroll subjects who received two injections of 30 µg BNT162b2, at least 
6 months after the second BNT162b2 dose in the following five cohorts: 
• Cohort 1: Subjects will receive one dose of 30 µg multivalent vaccine 
BNT162b2 (B.1.1.7 + B.1.617.2) on Day 1 (baseline in this trial), consisting of a 1:1 
mixture of two BNT162b2 monovalent vaccines: 15 µg BNT162b2 (B.1.1.7), and 
15 µg BNT162b2 (B.1.617.2). 
• Cohort 2: Subjects will receive two doses of 30 µg multivalent vaccine 
BNT162b2 (B.1.1.7 + B.1.617.2), one each on Day 1 and on Day 56 (8 weeks 
apart). 
• Cohort 3: Subjects will receive one dose of 30 µg monovalent vaccine 
BNT162b2 (B.1.1.7) on Day 1. 
• Cohort 4: Subjects will receive one dose of 30 µg monovalent vaccine 
BNT162b2 (B.1.617.2) on Day 1. 
• Cohort 5: Subjects will receive one dose of 30 µg BNT162b2 on Day 1. 
Cohort 6 will enroll subjects who have not received any prior prophylactic vaccine against 
COVID-19. 
• Cohort 6: Subjects will receive three doses of 30 µg multivalent vaccine 
BNT162b2 (B.1.1.7 + B.1.617.2), one each on Day 1 and Day 21 and the third dose 
~6 months after the second dose. 
Part A will comprehensively describe, through the parallel Cohorts 1 to 5, the safety and 
the immunogenicity of one or two doses of the multivalent vaccine BNT162b2 (B.1.1.7 + 
B.1.617.2), in relation to the corresponding monovalent vaccine BNT162b2 (B.1.1.7) and 
BNT162b2 (B.1.617.2) vaccines, and the parent vaccine BNT162b2. A total dose of 30 µg 
is selected for the BNT162b2-based vaccines against variant strains to be tested in this 
trial, based on preliminary safety results of the monovalent vaccine BNT162b2 (B.1.351) 
vaccine against the SARS-CoV-2 B.1.351 variant strain, currently being tested as a third 
booster dose in the BNT162-02 / C4591001 trial. For Cohorts 1 to 4, an optional additional 

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lower dose level may be tested in up to 20 additional subjects per cohort, based on safety 
and immunogenicity data obtained with the 30 µg dosage level. 
Comprehensive assessments of the humoral and cell-mediated immune responses in 
Cohorts 1 to 5 will evaluate if the immunological responses to each VOC is unaffected by 
the addition of additional antigens in the multivalent vaccine BNT162b2 (B.1.1.7 + 
B.1.617.2). Further, analyses of the B cell compartment, including memory B cells, will 
assess if the multivalent vaccine BNT162b2 (B.1.1.7 + B.1.617.2) as a booster in prior 
vaccinated subjects elicits a qualitatively improved anamnestic response, with expansion 
of a diversified memory B cell population able to cross-neutralize conserved and unique 
strain epitopes. 
Twenty (20) subjects who are COVID-19 vaccine-naïve and have not experienced 
COVID-19, will be enrolled in Cohort 6 to receive BNT162b2 (B.1.1.7 + B.1.617.2) given 
as a three-dose regimen – the first and second doses administered on Day 1 and Day 21 
and the third dose ~6 months after the second dose. 
Part B 
Part B will be initiated after review of reactogenicity and available immunogenicity data of 
Part A (Cohorts 1, 4, 6) by the SRC. 
Part B consists of three cohorts of n = 300 subjects each (~375 subjects will be enrolled in 
each cohort to ensure there are 300 evaluable subjects), which will enroll subjects 18 to 
85 years old; ~60% of these subjects should be 18 to 55 years old and ~40% should be 56 
to 85 years old: 
• Cohort 1 will enroll subjects from the trial BNT162-02 / C4591001 who received 
two injections of 30 µg BNT162b2, at least 6 months after the second BNT162b2 
dose. Subjects will receive on Day 1 one dose of 30 µg multivalent vaccine 
BNT162b2 (B.1.1.7 + B.1.617.2). 
• Cohort 4 will enroll subjects from the trial BNT162-02 / C4591001 who received 
two injections of 30 µg BNT162b2, at least 6 months after the second BNT162b2 
dose. Subjects will receive on Day 1 one dose of 30 µg monovalent vaccine 
BNT162b2 (B.1.617.2). 
• Cohort 6 will enroll subjects who have not received any prior prophylactic vaccine 
against COVID-19. Subjects will receive 30 µg multivalent vaccine 
BNT162b2 (B.1.1.7 + B.1.617.2), one each on Day 1 and Day 21 and the third dose 
~6 months after the second dose. Approximately 15 subjects at preselected sites in 
Part B will be evaluated in terms of cell-mediated immunity. 
Part B will expand the safety information of the multivalent vaccine BNT162b2 (B.1.1.7 + 
B.1.617.2) as one booster dose in BNT162b2-experienced subjects, and as two-dose, 
primary vaccination regimen in subjects who are COVID-19 vaccine-naïve and have not 
experienced COVID-19. 
Part B will also determine based on geometric mean ratios (GMR) of neutralizing titers and 
seroresponse rate, if the immune response of the multivalent vaccine BNT162b2 (B.1.1.7 
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dose of multivalent BNT162b2 (B.1.1.7 + B.1.617.2) vaccine against the reference strain, 
and the immune response of the monovalent vaccine BNT162b2 (B.1.617.2) against the 
B.1.617.2 strain, is immunobridged to the immune response observed against the 
reference strain in selected existing subjects from the Phase III trial BNT162-02 / 
C4591001, who received two doses of BNT162b2. The selection will ensure comparable 
distribution of age and sex in the control group and the BNT162b2 (B.1.1.7 + B.1.617.2) 
and BNT162b2 (B.1.617.2) groups. To achieve 300 evaluable subjects for each of the 
immunobridging comparisons, 20% non-evaluable rate is estimated, which results in the 
enrollment of 375 subjects in each of Part B cohorts. 
In addition, Part B will compare the immune response against the reference and the 
variant strains after one or two doses of multivalent vaccine BNT162b2 (B.1.1.7 + 
B.1.617.2), compared to after two doses of BNT162b2 in subjects from the Phase III 
BNT162-02 / C4591001 trial. 
Part C 
Part C consists of n = ~225 subjects who previously received two or three injections of any 
authorized COVID-19 RNA-based vaccine and were subsequently diagnosed with 
SARS-CoV-2 infection from January 2022 onwards (limited to a period when there was a 
high prevalence of SARS-CoV-2 Omicron infections). 
Subjects in Part C will be randomized in a 2:2:1 ratio into three cohorts; ~90 subjects each 
in Cohorts 7 and 8 (to ensure ~80 evaluable subjects in each cohort after 11% dropout) 
and 45 subjects in Cohort 9. Randomization will be stratified by age group (18 to 55 years 
of age or 56 to 85 years of age) and by number of prior doses of COVID-19 RNA-based 
vaccine (two or three doses). 
The sponsor may terminate the enrollment into Cohort 9 at any time in case the evolving 
COVID-19 epidemiology and/or the recommendations issued in the context of national 
vaccination campaigns no longer support enrollment of the trial population in a realistically 
feasible time. 
Cohorts 7 to 9 will enroll subjects 18 to 85 years old; ~60% of these subjects should be 18 
to 55 years old and ~40% should be 56 to 85 years old: 
• Cohort 7: Subjects will receive one dose of 30 µg monovalent vaccine 
BNT162b2 (B.1.1.529) on Day 1. 
• Cohort 8: Subjects will receive one dose of 30 µg BNT162b2 on Day 1. 
• Cohort 9: No vaccination will be given to Cohort 9 subjects within 3 months after 
Visit 1. After the 3-month follow-up period, subjects in Cohort 9 will be offered a 
BNT162b2 vaccination, depending on the epidemiological situation, local regulatory 
authority recommendations, and/or variant vaccine authorization status. 
Approximately 25 subjects at preselected sites in each cohort of Part C will be evaluated in 
terms of cell-mediated immunity. 
For a summary of the trial as a flow diagram, see the Schema in Section 1.2. For the 
planned assessments and visits, see the SoA in Section 1.3. 

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4.2 
Scientific rationale for the trial design 
The scientific rationale for this trial design is the following: 
• The trial will comprehensively characterize the safety of the multivalent BNT162b2-
based vaccine BNT162b2 (B.1.1.7 + B.1.617.2), both in subjects who are 
BNT162b2-experienced, and in subjects who are COVID-19 vaccine-naïve and 
have not experienced COVID-19. 
• To enhance the generalizability of trial results, Part B will include subjects 18 to 
85 years old, including younger and older adults, and Parts A and B will include 
subjects with pre-existing stable disease. 
• The trial design allows assessment if the immune responses to each antigen (i.e., 
the S protein of the SARS-CoV-2 strain B.1.1.7 or B.1.617.2) is unaffected by the 
addition of additional antigens in the multivalent vaccine BNT162b2 (B.1.1.7 + 
B.1.617.2). It also allows assessment if the multivalent vaccine BNT162b2 (B.1.1.7 
+ B.1.617.2) as one booster dose in BNT162b2-experienced subjects: 
o Elicits a qualitatively improved anamnestic response able to cross-neutralize 
conserved and unique strain epitopes. 
o Is quantitatively non-inferior to the immune response after two doses of the 
parent vaccine BNT162b2. 
• In subjects who have previously received a two-dose regimen of BNT162b2 as a 
primary vaccination series and who will receive BNT162b2 (B.1.1.7 + B.1.617.2), it 
is anticipated that one dose of BNT162b2 (B.1.1.7 + B.1.617.2) will sufficiently 
boost the immune response against each of the B.1.1.7, B.1.617.2, and the 
reference strains. To investigate if a two-dose regimen of BNT162b2 (B.1.1.7 + 
B.1.617.2) given in a longer time interval in vaccine-experienced subjects, will 
result in optimized safety and immune response (Goel et al. 2021, Payne et al. 
2021, Tauzin et al. 2022), subjects in Cohort 2 (Part A) will also receive a second 
dose of BNT162b2 (B.1.1.7 + B.1.617.2) administered after a longer time interval of 
8 weeks post-Dose 1. 
• The thorough clinical investigation of the multivalent vaccine BNT162b2 (B.1.1.7 + 
B.1.617.2) will support preparedness for the case that a multivalent BNT162b2-
based vaccine against COVID-19 is needed to allow broad coverage against 
circulating strains at global level and to avoid the complexity of handling multiple 
monovalent vaccines in parallel. 
• The trial design will also provide safety and immunobridging data for the 
monovalent vaccine BNT162b2 (B.1.617.2) as a booster dose in subjects who are 
BNT162b2-experienced. 
• Part C of the trial will characterize the safety of BNT162b2 and 
BNT162b2 (B.1.1.529) in subjects who are COVID-19 RNA-based vaccine-
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• Part C further allows assessment of the immune responses to each antigen (i.e., 
the S protein of the reference ancestral SARS-CoV-2 strain [Wuhan-Hu-1/ 
USA-WA1] or B.1.529). Part C also allows assessment of whether vaccination with 
the Omicron-specific vaccine BNT162b2 (B.1.1.529) in COVID-19 RNA-based 
vaccine-experienced individuals who experienced a SARS-CoV-2 Omicron 
breakthrough infection: 
o Is quantitatively superior to the immune response after one dose of the 
parental vaccine BNT162b2. 
o Elicits a qualitatively improved anamnestic response able to cross-neutralize 
conserved and unique strain epitopes. 
• The thorough clinical comparison of the variant-specific vaccine 
BNT162b2 (B.1.529) with the parental vaccine BNT162b2 in COVID-19 RNA-based 
vaccine-experienced individuals that had a breakthrough infection in Part C will 
generate information on the comparative breadth and magnitude of immune 
responses in this situation, potentially supporting the choice of booster vaccine in 
this population. 
• The subjects who will not receive a BNT162b2-based vaccine in Cohort 9 in Part C 
will bring valuable information about the magnitude, quality, and duration of 
immune responses post breakthrough infection in COVID-19 RNA-based vaccine-
experienced individuals that will serve to contrast responses after an additional 
vaccination with the variant-specific vaccine BNT162b2 (B.1.529) or with the 
parental vaccine BNT162b2. 
4.3 
Justification for dose 
The vaccine BNT162b2 (30 µg BNT162b2 given as a course of two doses at least 21 days 
apart) has been authorized for emergency use or been given conditional/full marketing 
authorization in numerous countries worldwide. Since then, pharmacovigilance data after 
administration in millions of individuals worldwide has confirmed this regimen to be safe 
and effective for protection against COVID-19. This trial will therefore use the authorized 
dose regimen for BNT162b2 administration. 
Although not yet proven in clinical trials, the safety and immunogenicity of the BNT162b2 
vaccine variants – BNT162b2 (B.1.1.7 + B.1.617.2), BNT162b2 (B.1.1.7), 
BNT162b2 (B.1.617.2), and BNT162b2 (B.1.1.529) – is not expected to differ from that for 
the parent vaccine BNT162b2, and therefore the authorized dose regimen for BNT162b2 
will be used for the vaccines against variant strains. 
Where a 1:1 mixture of two vaccines against different viral strains is administered 
(Cohorts 1, 2, and 6), 15 µg of each vaccine will be administered, such that the total dose 
does not exceed 30 µg. 
4.4 
Trial completed and end of trial definitions 
A trial subject is considered to have completed the trial if they have completed all planned 
visits as listed in the SoA (see Section 1.3). 

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The end of the trial is defined as the date of the last visit of the last subject in the trial. 
4.5 
Duration of all trial periods 
Depending on the cohort, the planned trial duration for a subject in this trial is up to 
~61 weeks (for the cohort with the longest duration: ≤1 week of screening, 8 weeks 
between IMP doses, and ~52 weeks-follow-up after the last IMP dose). 
The estimated planned trial start (first subject first visit) and trial end (last subject last visit) 
are Q3-2021 and Q3-2023. 
5 
TRIAL POPULATION 
Investigators should always use good clinical judgment in considering a volunteer’s overall 
fitness for trial participation. 
5.1 
Inclusion criteria 
Volunteers are eligible for enrollment into this trial if all of the following criteria apply: 
1 
Have given informed consent by signing the informed consent form (ICF) before 
initiation of any trial-specific procedures. 
2 
Volunteers who at the time of consent are: 
• 
Part A: 18 to 55 years old. 
• 
Part B: 18 to 85 years old (~60% should be 18 to 55 years old and ~40% 56 to 85 years 
old). 
• 
Part C: 18 to 85 years old (~60% should be 18 to 55 years old and ~40% 56 to 85 years 
old). 
3 
For Cohorts 1 to 5: in Part A, have received BNT162b2 vaccine (30 µg, two-
dose regimen) in either a clinical trial or as part of the governmental vaccination 
programs at least 6 months before Visit 0. Subjects who are currently enrolled in 
the Phase III BNT162-02 / C4591001 trial, have already been unblinded, and 
have previously received two doses of BNT162b2 with Dose 2 at least 6 months 
earlier can be included (for Cohorts 1 and 4 in Part B, prior enrollment and 
dosing in the BNT162-02 / C4591001 trial is mandatory). At enrollment into 
Part B of this trial, their participation in the BNT162-02 / C4591001 trial will be 
terminated. Subjects should have not experienced COVID-19 based on medical 
history. 
4 
For Cohort 6: Are COVID-19 vaccine-naïve and have not experienced 
COVID-19 based on their medical history. 
5 
Are willing and able to comply with all scheduled visits, vaccination plan, 
laboratory tests, lifestyle considerations, and other trial procedures. 

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6 
Are overall healthy at Visit 0 in the clinical judgment of the investigator based on 
the medical history, clinical assessment (including physical examination, vital 
signs, blood and urine clinical laboratory tests, 12-lead ECG, and oral swab for 
NAAT-based SARS-CoV-2 testing).  
Note: Healthy volunteers with pre-existing stable disease, defined as disease not 
requiring significant change in therapy or hospitalization for worsening disease 
during the 12 weeks before Visit 0, can be included. 
 
Note: Volunteers who had hepatitis C (HCV) infection, but have completed 
curative treatment based on the medical history can be included. Volunteers 
who had or have hepatitis B (HBV) or HIV based on the medical history cannot 
be included. 
7 
Agree not to enroll in another trial of an IMP, starting after Visit 0 and 
continuously until the last planned visit in this trial. 
8 
Women of childbearing potential (WOCBP) must test negative in a urine beta-
human chorionic gonadotropin (β-HCG) test at Visits 0 and 1. For a definition of 
“WOCBP”, see Section 10.4.1. 
9 
WOCBP must agree to practice a highly effective form of contraception starting 
at Visit 0 and continuously until 28 days after their last IMP administration in this 
trial. For a definition of “highly effective form of contraception”, see 
Section 10.4.2. 
10 
WOCBP must confirm that they practiced an acceptable form of contraception 
for the 14 days prior to Visit 0. For a definition of “acceptable form of 
contraception”, see Section 10.4.2. 
11 
WOCBP must agree not to donate eggs (ova, oocytes) for the purposes of 
assisted reproduction starting after Visit 0 and continuously until 28 days after 
their last IMP injection in this trial. 
12 
Men who are sexually active with a WOCBP and have not had a vasectomy 
must agree to use a highly effective form of contraception with their female 
partner of childbearing potential starting after Visit 0 and continuously until 
28 days after their last IMP injection in this trial. 
13 
Men must be willing to refrain from sperm donation, starting after Visit 0 and 
continuously until 28 days after their last vaccination. 
14 
For Part C, Cohorts 7, 8, and 9: have received two or three documented doses 
of any authorized COVID-19 RNA-based vaccine (e.g., BNT162b2 [Comirnaty] 
or the Moderna vaccine [Spikevax]) prior to being diagnosed with SARS-CoV-2 
infection from January 2022 onwards (and limited to a period when there was a 
high prevalence of SARS-CoV-2 Omicron infections). 
 
Note: The interval between the last COVID-19 RNA-based vaccine administered 
and randomization should be >4 months. 

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The latest prior diagnosed SARS-CoV-2 infection should be at least 2 months 
before randomization. The latest SARS-CoV-2 infection should be documented 
with a result from a NAAT (as a preferable option). In case no historic NAAT 
result is available proving prior SARS-CoV-2 infection, the local positive result of 
SARS-CoV-2 N-binding antibodies done at screening will be sufficient. 
5.2 
Exclusion criteria 
Volunteers are not eligible for enrollment if any of the following criteria apply: 
1 
Any existing condition which may affect vaccine injection and/or assessment of 
local reactions assessment, e.g., tattoos, severe scars, etc. 
2 
Any bleeding diathesis or condition associated with prolonged bleeding that 
would, in the opinion of the investigator, contraindicate intramuscular injection. 
3 
Any medical or psychiatric condition including recent (within the past year) or 
active suicidal ideation/behavior or laboratory abnormality that, in the 
investigator’s judgment, make the subject inappropriate for the trial. 
4 
Any current febrile illness (body temperature ≥38.0°C/≥100.4°F) or other acute 
illness within 48 h prior to Day 1/IMP injection in this trial. 
5 
Any current or history of cardiovascular diseases, e.g., myocarditis, pericarditis, 
myocardial infarction, congestive heart failure, cardiomyopathy or clinically 
significant arrhythmias, unless such disease is not considered relevant for 
participation in this trial in the investigator’s judgment. 
6 
History of COVID-19 and/or clinical (based on clinically confirmed COVID-19 
symptoms/signs alone if a SARS-CoV-2 NAAT result was not available) or 
microbiological (based on COVID-19 symptoms/signs and a positive SARS-
CoV-2 NAAT result) evidence of prior infection with SARS-CoV-2 at screening 
(Visit 0). 
 
Note: not applicable for Part C. 
7 
History of Guillain-Barré syndrome. 
8 
Known or suspected immunodeficiency. 
9 
History of severe adverse reaction associated with a vaccine and/or severe 
allergic reaction (e.g., anaphylaxis) to any component of the trial IMPs. 
10 
History or known allergy, hypersensitivity, or intolerance to the trial IMP including 
any excipients of the IMPs in this trial. 
11 
Have received any SARS-CoV-2 vaccination other than BNT162b2 (30 µg 
BNT162b2 given as a course of two doses ~21 days apart). 
 
Note: not applicable for Part C. 
12 
Have received a live or live attenuated vaccine within 28 days prior to Day 1/IMP 
injection. 

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13 
Have received any other vaccines within 14 days before or after any IMP 
injection, e.g., influenza, tetanus, pneumococcal, hepatitis A or B. When 
possible standard or care vaccinations should be planned with the trial IMP 
administrations in mind. 
14 
Individuals who receive treatment with radiotherapy or immunosuppressive 
therapy, including cytotoxic agents or systemic corticosteroids (if systemic 
corticosteroids are administered for ≥14 days at a dose of ≥20 mg/day of 
prednisone or equivalent), e.g., for cancer or an autoimmune disease, or 
planned receipt throughout this trial. Inhaled/nebulized, intraarticular, intrabursal, 
or topical (skin or eyes) corticosteroids are permitted. 
15 
Receipt of blood/plasma products or immunoglobulin, from 60 days before IMP 
administration or planned receipt throughout this trial. 
16 
Participation in other trials involving IMP within 28 days or 5 half-lives (whichever 
is longer) prior to Visit 1 and/or during trial participation, besides participation in 
trials with BNT162b2. 
17 
Are pregnant or breastfeeding or are planning pregnancy within 28 days after 
last IMP treatment. 
18 
Are vulnerable individuals as per ICH E6 definition, i.e., are individuals whose 
willingness to volunteer in a clinical trial may be unduly influenced by the 
expectation, whether justified or not, of benefits associated with participation, or 
of a retaliatory response from senior members of a hierarchy in case of refusal 
to participate. 
19 
For Part C, Cohorts 7, 8, and 9: Vaccination with other non-RNA or unauthorized 
COVID-19 vaccines.  
20 
For Part C, Cohorts 7, 8, and 9: Vaccination with any COVID-19 vaccine after 
SARS-CoV-2 infection from January 2022 onwards (and limited to a period when 
there was a high prevalence of SARS-CoV-2 Omicron infections). 
5.3 
Lifestyle considerations 
When at the trial site, trial subjects will not be allowed to smoke or to drink alcohol. 
The trial subjects will be required to remain at the site for at least 30 minutes after each 
IMP injection. 
Subjects will be asked to avoid strenuous exercise beyond their usual exercise routine for 
7 days after each IMP administration. 
The trial subjects will be required to practice prescribed forms of contraception and not to 
donate sperm or eggs (ova, oocytes) for the purposes of assisted reproduction, starting at 
Visit 0 and continuously until 28 days after their last IMP administration in this trial. See 
inclusion criteria 9 to 13. For subjects randomized to Cohort 9 these criteria only apply until 
randomization (Visit 1) and no further restrictions are required. In addition, the investigator 
or designee will instruct the trial subjects to call immediately if the selected contraception 

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method is discontinued or if pregnancy is known or suspected in the trial subject or 
partner. 
Trial subjects will be required to continue following guidance from their health authorities 
on recommended social behaviors (e.g., mask wearing, social distancing) based on their 
vaccination status before trial participation. 
5.4 
Screen failures 
Screen failures are defined as individuals who consent to participate in the trial but who 
are not subsequently allocated to IMP. 
A minimal set of screen failure information is required to ensure transparent reporting of 
screening failures to meet the Consolidated Standards of Reporting Trials (CONSORT) 
publishing requirements and to respond to queries from regulatory authorities. Minimal 
information includes demography, date the ICF was signed, the reasons for screen 
failures, and any SAEs, if applicable. 
If agreed with the Medical Monitor rescreening is allowed at the discretion of the 
investigators. Rescreened subjects will need to re-consent and will be assigned a new trial 
subject number. 
6 
TRIAL TREATMENTS 
Trial treatment is defined as any investigational treatment(s), marketed product(s), 
intended to be administered to a trial subject according to the trial protocol. 

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6.1 
IMPs administered 
IMP name: 
• BNT162b2 
• BNT162b2 (B.1.1.7 + B.1.617.2) 
• BNT162b2 (B.1.1.7) 
• BNT162b2 (B.1.617.2) 
• BNT162b2 (B.1.1.529) 
Type: 
Vaccine (BNT162 RNA-LNP vaccine utilizing modRNA). 
Use: 
Experimental 
Administration 
route: 
Intramuscular (IM); upper arm, musculus deltoideus. The same arm may be used 
for both immunizations. The non-dominant arm is preferred. 
Dosing regimen: 
Part A: 
• Cohort 1: One dose of 30 µg BNT162b2 (B.1.1.7 + B.1.617.2), consisting of a 1:1 
mixture of 15 µg BNT162b2 (B.1.1.7) and 15 µg BNT162b2 (B.1.617.2), given on 
Day 1. 
• Cohort 2: Two doses of 30 µg BNT162b2 (B.1.1.7 + B.1.617.2), one each on 
Day 1 and Day 56. 
• Cohort 3: One dose of 30 µg BNT162b2 (B.1.1.7) on Day 1. 
• Cohort 4: One dose of 30 µg BNT162b2 (B.1.617.2) on Day 1. 
• Cohort 5: One dose of 30 µg BNT162b2 on Day 1. 
• Cohort 6: Three doses (on Day 1, Day 21, and the third dose ~6 months after the 
second dose) of 30 µg BNT162b2 (B.1.1.7 + B.1.617.2). 
 
Part B: 
• Cohort 1: One (on Day 1) dose of 30 µg BNT162b2 (B.1.1.7 + B.1.617.2). 
• Cohort 4: One (on Day 1) dose of 30 µg BNT162b2 (B.1.617.2). 
• Cohort 6: Three doses (on Day 1, Day 21, and the third dose ~6 months after the 
second dose) of 30 µg BNT162b2 (B.1.1.7 + B.1.617.2). 
 
Part C: 
• Cohort 7: One dose of 30 µg BNT162b2 (B.1.1.529) on Day 1. 
• Cohort 8: One dose of 30 µg BNT162b2 on Day 1. 
• Cohort 9: No IMP injection within 3 months of Visit 1. 
Sourcing: 
Provided centrally by the sponsor. 
Packaging and 
labeling: 
IMP will be provided in glass vials as open-label supply. Each vial will be labeled as 
required per country requirements. For details, see the Pharmacy Manual. 
Note: BNT162b2 (B.1.1.529) refers to the monovalent vaccine specific for SARS-CoV-2 Omicron subvariant BA.1, i.e., 
B.1.1.529.1. 
6.2 
Preparation/handling/storage/accountability 
The principal investigator is responsible for IMP (and any components thereof) 
accountability, reconciliation, and record maintenance (i.e., receipt, reconciliation, and final 
disposition records). 
For instructions on IMP preparation, handling, and storage, see the Pharmacy Manual. 

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All IMPs (and any components thereof) must be stored in a secure, environmentally 
controlled, and monitored (manual or automated) area in accordance with the labeled 
storage conditions with access limited to the investigator and authorized trial site 
personnel. 
The preparation of solution for injection will be performed by aseptic handling procedures 
by pharmaceutical personnel or other trained personnel at the trial site. Further guidance 
and information for the final disposition of unused IMP (and any components thereof) is 
provided in the Pharmacy Manual. 
6.3 
Measures to minimize bias: randomization and blinding 
Laboratory personnel who will analyze the samples to generate immunogenicity data for 
the primary and secondary immunogenicity endpoints in Part B will be blinded to the 
source of samples (BNT162-17 vs BNT162-02 / C4591001) or the actual treatment. 
Randomization will be applied to Part C of the trial only. At randomization, subjects will be 
stratified by the following factors: age group (18 to 55 years of age or 56 to 85 years of 
age); number of prior doses of RNA-based vaccines (two or three doses). 
6.4 
Trial treatment compliance 
All IMP injections will be administered by a physician or by qualified medical personnel. 
The date and time of each IMP injection must be recorded in the source documents and 
recorded in the case report form (CRF). The IMP dose and trial subject identification will 
be confirmed at the time of administration by a member of the trial site personnel other 
than the person administering the IMP. 
6.5 
Concomitant therapy 
6.5.1 
Permitted concomitant therapies 
For healthy volunteers with pre-existing stable disease, defined as disease not requiring 
significant change in therapy or hospitalization for worsening disease during the 12 weeks 
before Visit 0, the continued use of the ongoing stable therapy is allowed. 
The use of antipyretics and other pain medication to treat symptoms after IMP 
administration or for ongoing conditions is permitted, but not for prophylaxis. See the 
guidance on antipyretics and other pain medication in Section 6.5.2. 
Inhaled, topical, or localized injections of corticosteroids (e.g., intraarticular or intrabursal 
administration) are permitted. 
Administration of nonsteroidal anti-inflammatory drugs (NSAIDs), e.g., 
paracetamol/acetaminophen at doses of up to 4 g/day, is permitted to treat symptoms after 
IMP administration or for ongoing conditions (but not for prophylaxis). Other concomitant 
medication may be considered on a case by case basis by the investigator, if required 
after consultation with the sponsor’s Medical Monitor. 

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6.5.2 
Prohibited concomitant therapies 
Trial subjects should not receive any live or live attenuated vaccination within 28 days 
before or after any IMP injection, e.g., measles, mumps, and rubella (MMR); oral polio 
vaccine (OPV); varicella; yellow fever unless medically indicated. See exclusion criteria 11. 
Trial subjects should not receive any other vaccines within 14 days before or after any IMP 
injection, e.g., influenza, tetanus, pneumococcal, hepatitis A or B. When possible, 
standard or care vaccinations should be planned with the trial IMP administrations in mind. 
See exclusion criteria 12. 
Trial subjects should not receive treatment with radiotherapy or immunosuppressive 
therapy, including cytotoxic agents or systemic corticosteroids (if systemic corticosteroids 
are administered for ≥14 days at a dose of ≥20 mg/day of prednisone or equivalent), e.g., 
for cancer or an autoimmune disease, or planned receipt throughout this trial. 
Inhaled/nebulized, intraarticular, intrabursal, or topical (skin or eyes) corticosteroids are 
permitted. See exclusion criteria 13. 
Receipt of blood/plasma products or immunoglobulins from Visit 0 or planned receipt 
throughout this trial. See exclusion criteria 14. 
Trial subjects should not receive any non-trial SARS-CoV-2 vaccine during the BNT162-17 
trial. 
Trial subjects should not receive prophylactic antipyretics and other pain medication to 
prevent symptoms associated with IMP administration. However, if a trial subject is taking 
a medication for another condition, even if it may have antipyretic or pain-relieving 
properties, it should not be withheld prior to IMP administration in this trial. 
Trial subjects should not receive prophylactic medications intended to prevent symptoms 
associated with COVID-19. However, if a trial subject is taking a medication for another 
condition, even if it may have such properties, this does not exclude the volunteer from 
enrollment into this trial. 
6.5.3 
Recording of concomitant therapy 
Any medication or vaccine (including over-the-counter or prescription medicines, vitamins, 
and/or herbal supplements, or other specific categories of interest) that the trial subject 
receives from Visit 0 until Visit 1, and for 1 month after each IMP dose (at the times listed 
in the SoA, Section 1.3), and any medications due to medical history started before Visit 0 
(i.e., prior medication) must be recorded in the CRF along with the: 
• Reason for use 
• Dates of administration including start and end dates 
• Dosage information including dose and frequency 
Prohibited medications should be recorded in the CRF for the whole duration of trial 
subject participation in the trial. 

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6.6 
Dose modifications 
In Part A, for Cohorts 1 to 4, an optional additional lower dose level may be tested in up to 
20 additional subjects per cohort. 
6.7 
Access to trial treatment after the end of the trial 
Not applicable. 
7 
DISCONTINUATION OF TRIAL TREATMENT AND TRIAL SUBJECT 
DISCONTINUATION/WITHDRAWAL 
7.1 
Discontinuation of trial treatment 
7.1.1 
Criteria to permanently discontinue IMP administration 
Note that discontinuation from IMP does not represent withdrawal/discontinuation from the 
trial. Trial subjects permanently discontinued from IMP administration should still complete 
all assessments planned in the SoA (Section 1.3). 
Reasons for definitive discontinuation from IMP include the following: 
• SAEs warranting discontinuation; 
• other trial-related safety concerns; 
• subject or investigator request; 
• pregnancy; 
• deterioration in trial subject health at the time of IMP injection (at the discretion of 
the investigator). 
In the event of trial subject permanent discontinuation from IMP, it must be documented on 
the appropriate CRF/in the medical records if the trial subject is discontinuing further 
receipt of trial treatment, or also from trial procedures, post-treatment follow-up, future 
collection of additional information and/or consent. 
7.1.2 
Criteria for temporarily delaying enrollment or administration of IMP 
The are no criteria defined which trigger temporarily delaying trial subject enrollment. 
There are medical conditions or situations which may delay administration of IMP as 
follows: 
• Current febrile illness (body temperature ≥38.0°C/≥100.4°F) or other acute illness 
within 48 h before any IMP administration. This includes current symptoms that 
could represent a potential COVID-19 illness. 
• The second IMP injection may also be delayed for medical reasons (e.g., influenza 
vaccination) and such delays should be as short as possible, e.g., ≤3 weeks for 
non-live or attenuated vaccines, ≤5 weeks for live attenuated vaccines, ≤12 weeks 
if SARS-CoV-2 infection is confirmed, etc. 

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The circumstances leading to any delayed administration of IMP and the resulting delay 
should be discussed with the sponsor’s Medical Monitor. 
7.2 
Trial subject discontinuation or withdrawal from the trial 
A trial subject may withdraw from the trial at any time at his/her own request or may be 
discontinued from the trial at any time at the discretion of the investigator for safety, 
behavioral, compliance, or administrative reasons. Withdrawals are expected to be 
uncommon. 
Reasons for discontinuation from the trial include the following: 
• Refused further trial procedures 
• Lost to follow-up 
• Death 
• Trial terminated by sponsor 
• Trial subject request 
• Investigator request 
• Important protocol deviation per the investigator after consultation with the 
Medical Monitor 
• Receipt of non-trial SARS-CoV-2 vaccination during the trial 
If the trial subject withdraws consent for data processing, the sponsor may retain and 
continue to use any data collected before such a withdrawal of consent. 
For trial subjects who withdraw consent, the investigator must clarify whether consent for 
research sample storage/processing (if given) is also withdrawn. If yes, then they must be 
informed that any research samples collected will be destroyed. The investigator must 
document research sample destruction in the Investigator’s Site File (ISF) and inform the 
sponsor about the withdrawal of consent immediately. 
If possible, permanently discontinued trial subjects will complete all assessments planned 
for the Early Termination Visit. 
7.3 
Lost to follow-up 
A trial subject will be considered lost to follow-up if they repeatedly fail to return for 
scheduled visits and is unable to be contacted by the trial site. 
The following actions must be taken if a trial subject fails to return to the trial site for a 
required trial visit: 
• The trial site must attempt to contact the trial subject and reschedule the missed 
visit as soon as possible and counsel the trial subject on the importance of 
maintaining the assigned visit schedule and ascertain whether or not the trial 
subject wishes to continue in the trial. 

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• Before a trial subject is deemed lost to follow-up, the investigator or designee must 
make every effort to regain contact with the trial subject (where possible, three 
telephone calls and, if necessary, a certified letter to the trial subject’s last known 
mailing address or local equivalent methods). These contact attempts should be 
documented in the trial subject’s medical record. 
• If the trial subject continues to be unreachable, they will be considered to have 
withdrawn from the trial. 
7.4 
Replacement of permanently discontinued trial subjects 
Permanently discontinued trial subjects will not be replaced. 
8 
TRIAL ASSESSMENTS AND PROCEDURES 
Trial subjects must have given informed consent (i.e., have signed the ICF) before 
initiation of any trial-specific procedures are performed. 
Protocol waivers or exemptions are not allowed. 
Immediate safety concerns should be discussed with the sponsor immediately upon 
occurrence or awareness to determine if the trial subject should continue or discontinue 
IMP administration. 
Adherence to the trial protocol requirements, including those specified in the SoA, is 
essential and required for trial conduct. 
All screening evaluations must be completed and reviewed to confirm that potential trial 
subjects meet all eligibility criteria. The investigator will maintain a screening log to record 
details of all trial subjects screened and to confirm eligibility or record reasons for 
screening failure, as applicable. 
See the SoA (Section 1.3) for all planned time points for assessments. 
8.1 
Efficacy assessments 
Not applicable. 
8.2 
Safety assessments 
Planned time points for all safety assessments are provided in the SoA (Section 1.3). 
8.2.1 
Clinical assessment 
8.2.1.1 
Physical examinations including body weight 
Body weight (in kg or pounds) will be measured and recorded at screening. 
Subject height (in cm or inches) will be measured and recorded. 
Complete and symptom-orientated physical examinations will be performed at the time 
points listed in the SoA in Section 1.3. 

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• A (complete) physical examination will include, at a minimum, assessments of the 
cardiovascular, respiratory, gastrointestinal, and neurological systems. 
• A symptom-orientated physical examination includes an overall health judgment. 
8.2.1.2 
Vital signs 
Vital signs comprising oral body temperature, heart rate, and blood pressure (systolic and 
diastolic) will be assessed at the times given in the SoA (Section 1.3). 
Blood pressure and heart rate measurements will be assessed with a completely 
automated device. Manual techniques will be used only if an automated device is not 
available. 
Vitals signs measurements should be preceded by at least 5 minutes of rest for the trial 
subject in a quiet setting without distractions (e.g., television, cell phones). 
Vital signs will be measured with trial subjects in seated position. 
8.2.1.3 
Clinical laboratory tests 
See Section 10.2 for the list of clinical laboratory tests to be performed at baseline and the 
limited times given in the SoA (Section 1.3). 
All protocol-required clinical laboratory tests (see Section 10.2) must be conducted in 
accordance with the local laboratory standard. The investigator must review the laboratory 
report, document this review with signature and date. 
If laboratory values from non-protocol-specified laboratory assessments performed at the 
laboratory require a change in trial subject management or are considered clinically 
significant by the investigator (e.g., SAE, AE), then the results must be recorded in the 
CRF. 
8.2.1.4 
Electrocardiograms 
Standard 12-lead ECGs will be recorded at the times given in the SoA (Section 1.3) using 
an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, 
and corrected QT (QTc; according to Bazett) intervals. 
All ECGs will be judged by the investigator as clinically significant (yes/no); only the 
investigator assessment, description of abnormalities, and heart rate will be recorded in 
the CRF. 
For reporting and surveillance purposes, all ECGs may be forwarded to a central vendor 
for assessment. 
8.2.2 
Oral body temperature (in °C or °F) 
Oral body temperature (in °C or °F) will be assessed at the times given in the SoA 
(Section 1.3). Body temperature will be measured and recorded to one decimal place. 
Body temperature will be converted to °C for reporting. 

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8.2.4 
Oral swabs for NAAT-based SARS-CoV-2 testing for screening and 
surveillance 
Oral swabs for (NAAT-based) SARS-CoV-2 testing will be collected by trial site personnel 
at the time points provided in the SoA (Section 1.3). 
The NAAT-based analysis of oral swabs for SARS-CoV-2 will be performed by a local 
laboratory. The most commonly used devices eventually come with pre-defined test panels 
that test for a range of pathogens and not just for SARS-CoV-2. Thus, inevitably and 
automatically, incidental data for the pathogens other than SARS-CoV-2 will be generated 
when using such devices. Since this incidental data is not required by this trial, only the 
results for SARS-CoV-2 will be recorded in the CRF, analyzed, and reported as described 
in this protocol. If a test result for SARS-CoV-2 or another pathogen must be reported to 
relevant authorities, this notification will be done by the trial site. 
Additionally, any potentially SARS-CoV-2 – infected and/or symptomatic trial subjects will 
be asked to return ad hoc to the site for SARS-CoV-2 diagnostics as soon as possible. 
Oral swabs for SARS-CoV-2 genomic sequencing will also be collected and analyzed at a 
later time point at a central laboratory. 
Instructions on the sample handling and shipping to the analysis site will be provided in a 
Laboratory Manual. The methodology used includes NAAT-based analysis and  
SARS-CoV-2 digital drop polymerase chain reaction (ddPCR). 
The below definition of “confirmed COVID-19” cases for the purpose of surveillance during 
the trial is based on the US FDA guidance for Industry “Development and Licensure of 
Vaccines to Prevent COVID-19”. 
Confirmed COVID-19: presence of one or more of the below symptoms and SARS-CoV-2 
NAAT positive test either at the central laboratory or at a local testing facility (using a 
certified test): 
• 
Fever or chills 
• 
New or increased cough 
• 
New or increased shortness of breath or difficulty breathing 
• 
Fatigue 
• 
Headache 
• 
New or increased muscle or body aches (pain) 
• 
New loss of taste or smell 
• 
Sore throat 
• 
Congestion or runny nose 
• 
Nausea or vomiting 
• 
Diarrhea 

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8.2.5 
Serological testing for SARS-CoV-2 N-binding antibodies 
Blood will be drawn by trial site personnel for serological testing for SARS-CoV-2 
N-binding antibodies by serum SARS-CoV-2 nucleocapsid protein enzyme-linked 
immunosorbent assay (ELISA) testing at the time points provided in the SoA (Section 1.3). 
SARS-CoV-2 nucleocapsid protein ELISA testing will be performed at a central laboratory 
(not applicable for Part C screening). 
8.2.6 
SARS-CoV-2 sequencing 
Swabs for SARS-CoV-2 genomic sequencing storage will be collected by trial site 
personnel at the time points provided in SoA (Section 1.3). 
The swabs will be inserted into collection tubes pre-filled with stabilizer solution. The 
swabs must be stored in the central laboratory at a minimum -70°C/-94°F until the end of 
the trial. 
SARS-CoV-2 genomic sequencing including SARS-CoV-2-ddPCR will be performed, even 
if no COVID-19 symptoms are shown. 
Instructions on the sample handling and shipping to the analysis site will be provided in a 
Laboratory Manual. 
The outcome of SARS-CoV-2 genomic sequencing would be SARS-CoV-2 S antigen 
sequences and/or whole genome sequences and assigned (where possible) to known viral 
variants. 
8.3 
Adverse events and SAEs 
The investigator and any qualified designees are responsible for detecting, documenting, 
and recording events that meet the definition of an AE or SAE or AESI and are responsible 
for following up all AEs and SAEs. 
Solicited events that are derived from the subject e-diaries should not be additionally 
reported as AEs unless the event meets criteria for an SAE or starts after Day 7 or starts 
on Days 1 to 7 and continues past Day 7. 
In addition, all solicited Grade 4 events need to be medically confirmed. 
8.3.1 
Time period and frequency for collection of AE, AESI, and SAE 
information 
All AEs, AESI, and SAEs (including a death) will be recorded at the time points listed in the 
SoA in Section 1.3. 
For subjects who receive a non-trial SARS-CoV-2 vaccination, AEs/SAEs will be collected 
as specified above until the date when the subject was vaccinated with the non-trial 
SARS-CoV-2 vaccine. The AEs/SAEs expected to be captured after non-trial SARS-CoV-2 
vaccination are within the frame of post-marketing safety data reporting. 
Cohort 9 subjects will be offered a booster vaccination with the locally marketed Pfizer-
BioNTech RNA-based COVID-19 vaccine after the EOT has been completed. If subjects 
choose to receive this vaccination, the recording and follow-up of any safety events will 

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follow post-marketing rules and such events will not be recorded within the trial 
documentation. 
Investigators are not obligated to actively seek AEs or SAEs at any time after a trial 
subject has been discharged from the trial, however, if the investigator learns of any SAE 
(including a death), that they consider to be reasonably related to the IMP administration 
or trial participation, the investigator must promptly notify the sponsor. 
8.3.2 
Method of detecting AEs and SAEs 
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Section 10.3. 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended 
and non-leading verbal questioning of the trial subject is the preferred method to inquire 
about AE occurrences. 
8.3.3 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the investigator is required to proactively follow each trial 
subject at subsequent visits/contacts. All AEs/SAEs will be followed until resolution, 
stabilization, the event is otherwise explained, or the trial subject is lost to follow-up (as 
defined in Section 7.3). Further information on follow-up procedures is provided in 
Section 10.3.1.7. 
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by the sponsor 
to elucidate the nature and/or causality of the AE or SAE as fully as possible. This may 
include additional laboratory tests or investigations, histopathological examinations, or 
consultation with other healthcare professionals. 
New or updated information will be recorded in the originally completed CRF. 
The investigator must submit any updated SAE data to the sponsor within 24 h of receipt 
of the information as indicated in Section 10.3.1.10. 
All ongoing AEs/SAEs will be followed until resolution, considered by the investigator to be 
stable or chronic (resolved with sequelae), the trial subject is lost to follow-up or the trial 
subject withdraws consent. If no final status is reached by the time the trial subject is 
discharged from the trial, the investigator must confirm the unavailability of a final status. 
8.3.4 
Regulatory reporting requirements for SAEs 
Prompt notification of an SAE/AESI via the provided SAE/AESI form by the investigator to 
the sponsor within 24 h of the site’s awareness is essential so that legal obligations and 
ethical responsibilities for the safety of trial subjects, and the safety of a trial treatment 
under clinical investigation and regulatory reporting obligations are met. 
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies involved in the conduct of trials with the same IMP about the safety of 
a trial treatment under clinical investigation. The sponsor will comply with country-specific 
regulatory requirements relating to safety reporting to the regulatory authorities, 
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investigators. The execution of expedited reporting to the different entities may be 
delegated as detailed in the trial Safety Management Plan. 
All serious adverse reactions, the nature, severity or outcome of which is not consistent 
with the reference safety information are “unexpected serious adverse reactions”. The 
expectedness assessment for all related SAEs is based on the reference safety 
information included in Section 7.8.2 of the current BNT162 IB. 
Safety reports will be prepared for suspected unexpected serious adverse reactions 
(SUSARs) according to local regulatory requirements and sponsor policy and forwarded to 
investigators as necessary. 
For the IMP, it is the sponsor’s or delegate’s responsibility to perform SUSAR reporting to 
the applicable regulatory authorities, IECs/IRBs, within the timelines stipulated in the 
respective country regulations. Reporting to the investigators will follow country-specific 
regulatory requirements and applicable guidelines. 
An investigator who receives an investigator safety report describing an SAE or other 
specific safety information (e.g., summary or listing of SAEs) from the sponsor should 
review it and then file it together with the IB. If required by local requirements, the 
investigator will notify the relevant IECs/IRBs. 
8.3.5 
Pregnancy testing and handling of pregnancies 
For WOCBP, pregnancy tests will be performed using commercial kits at the times given in 
the SoA (see Section 1.3). 
Pregnancy information (information on trials subjects who become pregnant or information 
for female partners of male trial subjects who become pregnant) will be collected for 
pregnancies that occurred after the date of the first injection of IMP until the subject 
terminates or completes the trial. 
Pregnancy information will only be collected after obtaining written informed consent from 
the pregnant female subject (or if a male subject’s partner becomes pregnant, written 
informed consent from both). 
As described in Section 7.1.1, subject pregnancy will trigger permanent discontinuation of 
IMP administration. 
If a pregnancy is reported, the investigator should inform the sponsor within 24 h of 
learning of the pregnancy and should follow the procedures outlined in Section 10.4. 
Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAEs. 
8.3.6 
Death events 
Any death that occurs within the observation period will be reported as an SAE. 
In case of a fatal event, the event term should not be “death” but the underlying event 
which led to death (death = outcome). If there is more than one AE in a fatal case, only for 
the AE leading to death the outcome “fatal” should be selected. If the cause of death is 

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unknown and cannot be ascertained at the time of reporting, “unexplained death” should 
be documented as event term. 
8.3.7 
Disease-related events/outcomes not qualifying as AEs or SAEs 
Not applicable. 
8.3.8 
Adverse events of special interest 
The following will be reported as AESIs: 
• Myocarditis (all Levels of Certainty including “Possible cases” (1 to 3) as per 
Brighton Collaboration Case Definition) 1 to 3 (Possible Case), 
Myocarditis_Version_1.0_15 July 2021_FINAL_for Posting) 
• Pericarditis (all Levels of Certainty including “Possible cases” (1 to 3) as per 
Brighton Collaboration Case Definition) 1 to 3 (Possible case), 
Pericarditis_Version_1.0_15 July 2021_FINAL_for Posting) 
• Anaphylaxis 
• Thromboembolic events (e.g., deep vein thrombosis, stroke, myocardial infarction) 
• Immune thrombocytopenia 
• Immune based neurologic events (e.g., optic neuropathy, Guillain-Barré syndrome) 
If an AESI is reported, the investigator should inform the sponsor as outlined in 
Section 10.3.1.10. For the treatment of myocarditis and pericarditis, see Section 8.5. 
8.4 
Treatment of overdose 
Any dose of trial treatment above the planned doses specified in this protocol will be 
considered an overdose. In the event of overdose: 
• Closely monitor the trial subject for any AE/SAE and laboratory abnormalities (at 
least for 7 days). 
• (At the discretion of the investigator) Give symptomatic treatment. 
• Inform the sponsor’s Medical Monitor as soon as possible; the sponsor’s Medical 
Monitor should agree with the investigator regarding any action triggered, e.g., trial 
subject withdrawal from the trial or (if applicable) trial treatment. 
• Document the quantity of the excess dose overdose in the CRF. 
8.5 
Treatment for specific adverse reactions 
The adverse reactions determined for BNT162b2 from the available unblinded clinical trial 
data (from BNT162-02 / C4591001) are mostly reflective of mild to moderate local and 
systemic reactogenicity events. The most frequent adverse reactions in trial subjects 
16 years of age and older were injection site pain, fatigue, headache, myalgia and chills, 
arthralgia, pyrexia and injection site swelling, and were usually mild or moderate in 
intensity and resolved within a few days after vaccination. Additional adverse reactions 

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determined from the clinical trial data are lymphadenopathy, nausea and malaise. Since 
authorization of BNT162b2, anaphylaxis has been reported and determined to be an 
adverse reaction. For details see the current BNT162 IB. 
Treatment of these adverse reactions is at the discretion of the investigators; however, the 
following suggestions are provided: 
• After the first occurrence of flu-like symptomatology including fever, subjects can be 
treated with standard therapeutic dose of acetaminophen (preferable), or a 
nonsteroidal anti-inflammatory drug if acetaminophen is contraindicated. 
• Ensure adequate hydration of trial subjects on the day of immunization, e.g., by 
asking trial subjects to drink water (0.5 to 1.0 L) before each site visit and during 
the ~2 h after each immunization per trial site standard. 
If subjects experience enhanced respiratory disease or progression of flu-like 
symptomatology, such as non-resolution of the symptoms after 3 days, symptom kinetics 
that are inconsistent with a relationship to RNA immunization, additional diagnostic 
measures should be considered, and the Medical Monitor should be informed. 
If any trial subjects report symptoms that could represent myocarditis or pericarditis, 
please follow the CDC Clinical Considerations for myocarditis and pericarditis following 
COVID-19 vaccination published on 28 MAY 2021 (https://www.cdc.gov/vaccines/covid-
19/clinical-considerations/myocarditis.html): 
• For initial evaluation, consider an ECG, troponin level, and inflammatory markers 
such as C-reactive protein and erythrocyte sedimentation rate. In the setting of 
normal ECG, troponin, and inflammatory markers, myocarditis or pericarditis is 
unlikely. 
• Consider consultation with: 
• Cardiology for assistance with cardiac evaluation and management. 
• Infectious disease and/or rheumatology to assist in this evaluation. 
Where available, evaluate for potential etiologies of myocarditis and pericarditis, 
particularly acute COVID-19 infection (e.g., polymerase chain reaction [PCR] testing), prior 
SARS-CoV-2 infection (e.g., detection of SARS-CoV-2 nucleocapsid-binding antibodies), 
and other viral etiologies (e.g., enterovirus PCR and comprehensive respiratory viral 
pathogen testing. 
8.6 
Safety stopping criteria 
The SRC will review and evaluate the collected safety data for Part A, Part B, and Part C 
independently. The SRC will review and evaluate all reported SAEs and AESIs from the 
trial approximately every 4 weeks during the trial until all subjects have completed 28 days 
follow-up and as described in the SRC charter. 
A decision to stop treatment for an individual subject or to terminate the trial may be taken 
by the sponsor and investigator if safety concerns are identified by the SRC. 

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All SAEs and SUSARs will be reviewed by the SRC as soon as possible. Any trial SAE or 
SUSAR in Part A may trigger a temporary stop of IMP administration to new subjects in 
Part A until the SRC has reviewed and discussed the relevant data and agree on a 
recommendation to allow or permanently stop further IMP administration for Part A. 
8.7 
Pharmacokinetics 
Not applicable. 
8.8 
Pharmacodynamics 
Not applicable. 
8.9 
Genetics 
Blood and/or isolated peripheral blood mononuclear cells (PBMCs) of subjects in the 
biomarker/PBMC subgroup may be used for human leukocyte antigen (HLA) typing to 
allow additional analysis, e.g., characterization of T-cell receptor or B-cell receptor 
repertoire and/or phenotypic characterization of antigen-specific T cells. Data generated 
with these additional analyses may provide information about the HLA dependency of 
immune response (e.g., if distinct HLA types have stronger/better immune response 
towards SARS-CoV-2). 
Blood samples will only be used for genetic analysis if the trial subjects have provided 
separate informed consent for this genetic analysis. 
8.10 
Immune responses 
Immune responses will be assessed at the times listed in the SoA (Section 1.3). 
Instructions on the sample collection, handling, and shipping will be provided in a 
Laboratory Manual. 
If recommended by the SRC, e.g., for subjects who present AEs which are potentially 
immune mediated, stored samples may be tested retrospectively for relevant clinical 
parameters (e.g., troponin, cytokine). 
Leftover biosamples (blood, the derived PBMCs, or serum), after completion of the 
serology assessments will be used for the analyses as described in Section 8.10.3 (i.e., for 
explorative biomarker/immunogenicity research purposes). 
Trial subjects will be asked if leftover biosamples may also be used for explorative 
research purposes, e.g., to develop methods, assays, etc., related to BNT162 vaccine 
candidates. The use of leftover samples for these purposes will require a separate 
informed consent (see Section 10.1.3). 

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8.10.1 
Humoral immunogenicity assessments 
Humoral immunogenicity assessments comprise: 
• Humoral immunogenicity assessments: A functional antibody titer, e.g., virus 
neutralization test (VNT) or an equivalent assay (e.g., pseudo-virus neutralization 
test [pVNT]), or serum immunoglobulin (Ig) ELISA. 
• Seronegative is defined as titers below the starting dilution (i.e., below the limit of 
detection for the assay). 
• SR after immunization is defined as follows: 
• for seronegative pre-immunization sera: a titer which is 4-fold the limit of detection. 
• for seropositive pre-immunization sera: a titer which is 4-fold the measured pre-
immunization titer. 
8.10.2 
T and B cell-mediated immune responses 
For a subset of subjects in Parts A, B, or C, samples will be collected for assessment of 
T cell- and B cell-mediated immune responses to VOCs and reference strains: 
• T-cell responses include responses mediated by immune cells such as CD4 and 
CD8 T cells and their functional phenotypic subset by, e.g., enzyme-linked 
immunospot (ELISpot), intracellular cytokine staining (ICS), multimer analyses, 
cytokine secretion assays, flow cytometry, and other tests. 
• These analyses may further include CD4 and CD8 T cells, Th1-specific cytokines 
(e.g., IFN-gamma, TNF-alpha, IL-2, or IL-12) and Th2-specific cytokines (e.g., IL-4, 
IL-5, IL-10, IL-13) to analyze the induction of either balanced Th1/Th2 responses, 
or of unbalanced Th1-dominant or Th2-dominant immune responses, respectively. 
• B cell analyses will include characterization of SARS-CoV-2 S protein-specific 
B cells to identify B cells recognizing conserved and strain-specific epitopes, further 
single cell variability diversity joining analysis and somatic hyper-mutation analysis 
may also be performed. 
• Some of the sample may be used for sequencing of trial subjects’ antibody and/or 
B cell receptor heavy- and light-chain genes, T-cell receptor genes, and/or mRNAs, 
for further understanding the B cell, T cell, and antibody repertoires. 
8.10.3 
Explorative research 
For consenting subjects in all cohorts, after completion of the planned investigations of the 
immune response, any residual biosamples may be used for explorative 
biomarker/immunogenicity research. In addition, in Cohorts 1 to 5 (inclusive), additional 
blood will be drawn for explorative biomarker/immunogenicity research at the times given 
in the SoA (Section 1.3). 
This research may include investigation of vaccine-induced immune responses, including 
against SARS-CoV-2 variants by use of, but not limited to, phenotypic or functional 
characterization of antigen-specific B cells and T cells (e.g., by flow cytometry-based 
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repertoire (e.g., by next generation sequencing, in subjects that consent to genetic testing 
[see Section 10.1.3]) and multiplex-cytokine analysis. This explorative research may also 
be used to develop methods, assays, etc. 
In addition, residual biosamples may be stored and analysis may be performed on 
exploratory biomarkers thought to play a role in the mechanism of action of BNT162 and 
other BioNTech vaccine candidates to evaluate their association with observed clinical 
responses to BNT162 or other vaccine candidates. 
Biosamples for explorative research purposes will be retained for use for up to 5 years 
after the end of the trial. Subjects will be informed about biosample storage and consent 
will be obtained. The tube with the biosample will be labeled with a number (optionally also 
with a bar code) to keep the subject’s identity confidential; the tube label will not include 
information that could be used to identify the subject. Results of the analyses will be linked 
to the clinical information collected during the trial using this specific number. The analysis 
will only be carried out on the basis of the label data and biosamples. Research 
biosamples and all data generated using the biosamples, will be handled in accordance 
with applicable laws and regulations; this includes requirements applicable for data 
protection, for biosample shipment outside Germany, and a potential withdrawal of 
consent. The results of the sample analysis for explorative research will not be shared with 
the subject. 
8.11 
Baseline data 
8.11.1 
Demographic data 
At screening, the following demographic data will be recorded for all trial subjects: 
• Age (in years/months) 
• Sex (male/female) 
• Ethnic group 
8.11.2 
Medical history 
Medical history information will be recorded at the times given in the SoA (Section 1.3). 
8.12 
Blood collection 
The total blood volume drawn over any 46-day period in any cohort is always less than 
550 mL. Additional blood samples may be taken, e.g., for safety assessments after AEs or 
SAEs or ad hoc COVID-19 visits. Assuming there are no COVID-19 visits, the total volume 
of blood drawn for subjects in each cohort is summarized below. 
 

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9.1.2 
SR non-inferiority 
The primary statistical hypothesis for SR non-inferiority for each variant and reference 
strain is: 
H0: π variant – π reference ≤ -10% vs H1: π variant – π reference > -10% 
where π variant is the SR against the VOC at 1 month after booster dose or 1 month after 
the second dose of BNT162b2 (B.1.1.7 + B.1.617.2) or SR against the reference strain at 
3 weeks after one dose of BNT162b2 (B.1.1.7 + B.1.617.2) and π reference is the SR against 
the reference strain at 1 month after second dose of BNT162b2. 
The SR VOC non-inferiority success for Cohorts 1 and 6 will be declared if the lower 
bounds of the 2-sided 95% CIs for the difference of (1) SR of B.1.1.7 – SR of reference 
and (2) SR of B.1.617.2 – SR of reference are both greater than -10%. The SR reference 
strain non-inferiority success for Cohort 6 will be declared if the lower bounds of the 
2-sided 95% CIs for the difference in SRs of reference is greater than -10%. The SR VOC 
non-inferiority success for Cohort 4 will be declared if the lower bound of the 2-sided 95% 
CI for the difference of SR of B.1.617.2 – SR of reference is greater than -10%. 
SR is defined as a ≥4-fold rise in neutralizing titer from baseline. For subjects with a 
baseline titer less than the lower limit of quantitation (<LLOQ), seroresponse is defined as 
a post-vaccination titer of ≥4× LLOQ. 
9.1.3 
Multiplicity considerations 
Multiplicity considerations are only relevant for Part B. The fixed sequential testing 
procedure will be used for multiplicity control for each cohort separately, all at 1-sided 
2.5% level of significance. 
For Cohort 1 and Cohort 4, the hypotheses will be tested in the following sequence: 
• Non-inferiority in terms of GMTs 
• Non-inferiority in terms of SRs 
For Cohort 6, the hypotheses will be tested in the following sequence: 
• Non-inferiority of immune response against reference strain in terms of GMT 
• Non-inferiority of immune response against reference strain in terms of SR 
• Non-inferiority of immune response against VOCs vs reference strain in terms of 
GMTs 
• Non-inferiority of immune response against VOCs vs reference strain in terms of 
SRs 
 
9.2 
Sample size determination 
Planned enrollment is ~1,470 subjects; ~120 in Part A (~20 in each of the six cohorts), 
~1,125 in Part B (~375 in each of the three cohorts), and ~225 in Part C (~80 in each of 
Cohort 7 and Cohort 8 and ~45 in Cohort 9). 

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For each injection, the number and percentage of subjects reporting at least one local 
reaction or systemic reaction (i.e., solicited data collected using subject e-diaries) will be 
summarized for each of the following types using the Safety Set: 
• Any local reactions or systemic reactions 
• Grade ≥3 local reactions or systemic reactions 
Moreover, the number and percentage of subjects reporting at least one local reaction will 
be summarized by worst grade using the Safety Set. 
Unsolicited TEAEs 
The number and percentage of subjects reporting at least one treatment-emergent 
adverse event (TEAE; defined in Section 10.3.1) will be summarized by PT nested within 
system organ class for each of the following AE types using the Safety Set: 
• Any AE 
• Related AE 
• Grade of AE 
• Related Grade ≥3 AE 
• AESI 
• Any solicited AE that starts on Days 1 to 7 and continues longer than 7 d post-
vaccination or starts after Day 7 or is an SAE 
• Any SAE 
• Related SAE 
Moreover, the number and percentage of subjects with any AE will be summarized by 
worst grade by PT nested within system organ class. 
Additional AE analyses may be described in the SAP. 
9.4.3 
Immunogenicity endpoints 
The immunogenicity endpoints are defined in Section 3. The scheduled time points for 
assessment are given in the SoA (see Section 1.3). 
9.4.3.1 
Geometric mean ratios 
The GMT non-inferiority for each Part B cohort will be tested using GMR for the 
Immunogenicity Analysis Set, estimated by the ratio of GMT of VOC specific NT 1 month 
after the final trial dose to the GMT of reference specific NT 1 month after the second dose 
of BNT162b2 or ratio of GMT of reference strain NT at 3 weeks after one dose of 
BNT162b2 (B.1.1.7 + B.1.617.2) to 1 month after the second dose of BNT162b2. A linear 
regression model with age, sex and group (each Part B cohort vs reference) as 
explanatory variables and natural log transformed antibody titers as dependent variable 
will be used to calculate the adjusted GMR and 2-sided 95% CI. 

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The GMR of Part C Cohorts 7 over Cohort 8 will be reported for the Immunogenicity 
Analysis Set, estimated by the ratio of GMT of VOC specific NT 1 month after one dose of 
IMP in Cohort 8 to that of Cohort 7. 
As exploratory analysis, unadjusted GMR for the Immunogenicity Analysis Set, 95% CIs 
will also be reported for the above comparisons. 
The detailed statistical methodology will be specified in the SAP. 
9.4.3.2 
Seroresponse 
The SR non-inferiority for Part B will be tested using difference (SR variant – SR 
reference) for the Immunogenicity Analysis Set, estimated by the difference of VOC 
specific SR 1 month after the final trial dose to reference specific SR 1 month after Dose 2 
of BNT162b2 or difference of reference strain SR at 3 weeks after one dose of 
BNT162b2 (B.1.1.7 + B.1.617.2) to reference strain SR at 1 month after the second dose 
of BNT162b2. The difference will be estimated using minimum risk weights and stratified 
by sex and age group (18 to 55 years, 56 to 85 years). The associated 95% CI will be 
calculated using stratified Newcombe confidence interval weighted with minimum risk to 
combine the stratum components and continuity correction. 
The SR difference of Part C Cohort 7 vs Cohort 8 will be reported for the Immunogenicity 
Analysis Set, estimated by the difference of VOC specific SR 1 month after one dose of 
IMP in Cohort 8 to that of Cohort 7. The difference will be estimated using minimum risk 
weights and stratified by randomization stratification factors; associated 95% CI will be 
calculated using stratified Newcombe confidence interval weighted with minimum risk to 
combine the stratum components and continuity correction. 
As exploratory analysis, unadjusted difference of SR for the Immunogenicity Analysis Set 
will be calculated as the difference in SRs between VOC and reference. The 95% CI will 
be obtained using Newcombe Score Confidence Limits. 
9.4.3.3 
Geometric means 
The geometric means on NT for each cohort will be calculated separately for Part A, 
Part B, and Part C as the mean of the assay results after making the logarithm 
transformation and then exponentiating the mean to express results on the original scale. 
Two-sided 95% CIs will be obtained by taking log transforms of assay results, calculating 
the 95% CI with reference to Student’s t-distribution, and then exponentiating the 
confidence limits. 
9.4.4 
Exploratory endpoints 
The exploratory endpoints are defined in Section 3. Exploratory analyses will be described 
in the SAP. 
9.4.5 
Other safety analyses 
All other safety analyses will be based on the Safety Set and will be summarized 
descriptively by group unless otherwise stated. 
Details of the other safety analyses will be described in the SAP. 

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9.4.6 
Other analyses 
Other analyses will be described in the SAP. 
9.5 
Interim analyses 
No formal interim statistical analysis is planned. Primary immunogenicity analysis for all 
Part B cohorts and for Part C Cohorts 7 and 8 will be performed after completion of 
1-month post-dose visit. 
9.6 
Data monitoring committee 
No Data Monitoring Committee is planned. An SRC is planned, for details see 
Section 10.1.5. 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1 
Regulatory, ethical, and trial oversight considerations 
This trial will be conducted in according to this protocol, the ethical principles that have 
their origin in the Declaration of Helsinki, Good Clinical Practice (GCP), and applicable 
regulatory requirements. 
10.1.1 
Regulatory and ethical considerations 
This trial will be conducted in accordance with the protocol and with the following: 
• Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and the Council for International Organizations of Medical 
Sciences (CIOMS) International Ethical Guidelines 
• Applicable GCP Guidelines 
• Applicable laws and regulations 
The protocol, protocol amendments, ICF, IB, and other relevant documents (e.g., 
advertisements) must be submitted to the relevant IEC/IRB for review and (if required) 
approval by the IEC/IRB before the trial is initiated. 
Any amendments to the protocol will require IEC/IRB approval before implementation of 
changes made to the trial design, except for changes necessary to eliminate an immediate 
hazard to trial subjects. 
The coordinating investigator or delegate will be responsible for the following: 
• Providing written summaries of the status of the trial to the relevant IEC/IRB 
annually or more frequently in accordance with the requirements, policies, and 
procedures established by the IECs/IRBs. 
• Notifying the IECs/IRBs of SAEs or other significant safety findings as required by 
IEC/IRB procedures. 

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• Providing oversight of the conduct of the trial at the site and adherence to 
requirements of ICH guidelines, the IECs/IRBs, EU 536/2014 (if applicable), and all 
other applicable local regulations. 
The principal investigator, any investigator(s), the sponsor, or personnel at other 
establishments must cooperate with any inspection of the documents, facilities, records, 
and other resources deemed appropriate by the inspecting authorities to be related to the 
trial and that may be located at the trial site, at the sponsor, or at other establishments. 
The sponsor must be notified as soon as possible about any upcoming regulatory authority 
inspection. 
10.1.2 
Financial disclosure 
All investigators will provide the sponsor with sufficient, accurate financial information as 
requested to allow the sponsor to submit complete and accurate financial certification or 
disclosure statements to the appropriate regulatory authorities. Investigators are 
responsible for providing information on financial interests during the course of the trial and 
for 1 year after completion of the trial. 
10.1.3 
Informed consent process 
Informed consent must be obtained before any trial-specific screening procedure is 
performed. 
Trial subjects must be informed that their participation is voluntary. 
The investigator or his/her representative will explain the nature of the trial to the trial 
subject and answer all questions regarding the trial. 
Trial subjects will be required to sign a statement of informed consent that meets the 
requirements of local regulations (e.g., 21 CFR 50), ICH GCP guidelines, Health Insurance 
Portability and Accountability Act (HIPAA) requirements, where applicable, and the 
IECs/IRBs or trial site. 
The medical record must include a statement that written informed consent was obtained 
before the trial subject was enrolled in the trial and the date the written consent was 
obtained. The authorized person obtaining the informed consent must also sign the ICF. 
Trial subjects must be informed in a timely manner if new information becomes available 
that may impact their willingness to participate in the trial. If required, trial subjects will be 
re-consented to updated written information and consent forms. 
Trial subjects who are rescreened must re-consent. 
A copy of the ICF(s) must be provided to the trial subject. 
Trial subjects must be re-consented to the most current version of the ICF during their 
participation in the trial. 
Separate informed consent will be obtained for the use of leftover blood for genetics (see 
Section 8.9) and for research purposes (see Section 8.10.3). 

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10.1.4 
Data protection 
Trial subjects will be assigned a unique identifier by the investigator according to the 
sponsor specifications on unique identifier assignment. Any trial subject records or 
datasets that are transferred to the sponsor will contain the identifier only; trial subject 
names or any information which would make the trial subject identifiable will not be 
transferred. 
Trial subjects must be informed that his/her personal trial-related data will be used by the 
sponsor in accordance with local data protection laws. The level of disclosure must also be 
explained to the trial subject who will be required to give consent for their data to be used 
as described in the informed consent. 
Trial subjects who withdraw consent must be informed that the data collected up until 
consent was withdrawn will still be used by the sponsor as described in the ICF. 
Trial subjects must be informed that their medical records may be examined by sponsor 
quality assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IEC/IRB members, and by inspectors from regulatory authorities. 
10.1.5 
Committees - SRC 
Safety reviews of the unblinded data will be conducted by the SRC approximately every 
4 weeks and on an ad hoc basis. The SRC will review all safety data, including AESIs, and 
SAEs, as well as laboratory data and other relevant safety data. 
After all subjects enrolled into Part A, Part B, and Part C have completed their 1-month 
follow-up visit, the SRC members will continue to receive safety data (related AEs, AESIs, 
SAEs) on a monthly basis, but further SRC meetings will occur approximately every 
6 months unless triggered earlier by SRC member requests or if SUSARs/AESIs are 
reported. 
The SRC will be constituted and act according to written procedures described in a 
charter. The SRC will prepare written minutes of its meetings. 
The SRC will at least comprise a sponsor medical representative, the Medical Monitor, a 
statistician, coordinating investigator, a sponsor-independent investigator, and on an 
ad hoc basis, a representative for the respective trial site depending on the trial subject in 
question. The SRC will include an independent cardiologist as an ad hoc member to 
advise on specific issues or questions in case of suspected myocarditis or pericarditis. 
10.1.6 
Dissemination of clinical trial data 
A final ICH E3 conform clinical trial report integrating the results for all defined and 
secondary outcome measures and the results for select exploratory endpoints available at 
the time of the final report drafting will be prepared by the sponsor. The results of the 
explorative research will be reported separately. 
In all cases, trial results will be reported in an objective, accurate, balanced, and complete 
manner and are reported regardless of the outcome of the trial or the country in which the 
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Clinical trial data and documentation will be disseminated as required per applicable laws 
and regulations, e.g., the EU Regulation No 536/2014, EU Regulation 1049/2001, and the 
US Final Rule, which implements Section 801 of the Food and Drug Administration 
Amendments Act (FDAAA 801). Clinical documents under such laws include protocols and 
protocol amendments, SAPs, ICH E3 clinical study reports. 
This clinical trial will be registered, and trial results publicly posted, on publicly accessible 
trial registries (e.g., ClinicalTrials.gov, the EU Clinical Trials Register, etc.) in accordance 
with the applicable regulations. 
If this clinical trial is used to support marketing authorization packages/submissions, the 
sponsor will comply with the EU Policy 0070, the proactive publication of clinical data on 
the European Medicines Agency (EMA) website. Clinical data, under Phase I of this policy, 
includes clinical overviews, clinical summaries, ICH E3 clinical study reports, and 
appendices containing the protocol and protocol amendments, sample CRFs, and 
statistical methods. Under Phase II of this policy, “clinical data” includes the publishing of 
individual patient data. 
Even if not required by applicable laws and regulations, this trial will be registered, and trial 
results be publicly posted on ClinicalTrials.gov. In addition, expert summaries of the 
outcomes for all primary and secondary outcome measures (irrespective of outcome) and 
lay summaries, will be posted on a publicly accessible website. 
The results for all primary and secondary outcome measures, irrespective of outcome, 
may be submitted for publication in academic journals (for further details, see 
Section 10.1.10). 
10.1.7 
Data quality assurance 
All trial subject data relating to the trial will be recorded in a CRF unless transmitted to the 
sponsor or designee electronically (e.g., laboratory data). The investigator is responsible 
for verifying that data entries are accurate and correct by signing the CRF. 
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF. 
The investigator must permit trial-related monitoring, audits, IEC/IRB review, and 
regulatory agency inspections and provide direct access to source data documents. 
Monitoring details describing strategy (e.g., risk-based initiatives in operations and quality, 
such as risk management and mitigation strategies and analytical risk-based monitoring), 
methods, responsibilities and requirements, including handling of non-compliance issues 
and monitoring techniques (central, remote, or on site monitoring) are provided in the 
Monitoring Plan. 
The sponsor or designee is responsible for the data management of this trial including 
quality checking of the data. 
The sponsor assumes accountability for actions delegated to other parties (e.g., contract 
research organization [CRO]). 
Trial monitors will perform ongoing source data verification to confirm that data entered 
into the CRF by authorized site personnel are accurate, complete, and verifiable from 

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source documents; that the safety and rights of trial subjects are being protected; and that 
the trial is being conducted in accordance with the currently approved protocol and any 
other trial agreements, GCP, and all applicable regulatory requirements. 
Records and documents, including signed ICFs, pertaining to the conduct of this trial must 
be retained by the investigator for 25 years after trial completion unless local regulations or 
institutional policies require a longer retention period. No records may be destroyed during 
the retention period without the written approval of the sponsor. No records may be 
transferred to another location or party without written notification to the sponsor. 
10.1.8 
Source documents 
Source documents including subject e-diaries provide evidence for the existence of the 
trial subject and substantiate the integrity of the data collected. Source documents are filed 
in the ISF. 
Source documents are original documents, data, and records (e.g., hospital records, 
clinical and office charts, laboratory notes, memoranda, subject e-diaries or evaluation 
checklists, pharmacy dispensing records, recorded data from automated instruments, 
copies or transcriptions certified after verification as being accurate copies, microfiches, 
photographic negatives, microfilm or magnetic media, x-rays, subject files, and records 
kept at the pharmacy, at the laboratories and at medico-technical departments involved in 
the clinical trial). 
Data entered in the CRF that are transcribed from source documents must be consistent 
with the source documents or the discrepancies must be explained. The investigator may 
need to request previous medical records or transfer records, depending on the trial. Also, 
current medical records must be available. 
Source data are all information in original records and certified copies of original records of 
clinical findings, observations, or other activities in a clinical trial necessary for the 
reconstruction and evaluation of the trial. Source data are contained in source documents 
(original records or certified copies). 
10.1.9 
Trial and site start and closure 
The trial start date is the date on which the trial will be open for enrollment of trial subjects 
at any site. 
The site start date is the date on which the site will be open for enrollment of trial subjects. 
The sponsor reserves the right to close the trial site or terminate the trial or a group within 
the trial at any time for any reason at the sole discretion of the sponsor. Trial sites will be 
closed upon trial completion. A trial site is considered closed when all required documents 
and trial supplies have been collected and a trial site closure visit has been performed. 
The investigator may initiate trial site closure at any time, provided there is reasonable 
cause and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a trial site by the sponsor or investigator may include but 
are not limited to: 

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• Failure of the investigator to comply with the protocol, the requirements of the 
IEC/IRB or local health authorities, the sponsor’s procedures, or GCP guidelines. 
• Inadequate recruitment of trial subjects by the investigator. 
• Discontinuation of further trial treatment development. 
If the trial is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the IECs/IRBs, the regulatory authorities, and any CROs used in the trial of 
the reason for termination or suspension, as specified by the applicable regulatory 
requirements. The investigator shall promptly inform the trial subject and should assure 
appropriate follow-up. 
10.1.10 Publication policy 
The results for all primary and secondary outcome measures, irrespective of outcome, will 
be submitted by the sponsor for publication in academic journals. The results of this trial 
may also be presented by the sponsor at scientific meetings. 
The results of this trial may be published or presented at scientific meetings by the 
investigator. If this is foreseen, the investigator agrees to submit all manuscripts or 
abstracts to the sponsor before submission. This will allow the sponsor to protect 
proprietary information and to provide comments. 
The investigator will, on request, remove any previously undisclosed confidential 
information before disclosure, except for any trial treatment-related information necessary 
for the appropriate scientific presentation or understanding of the trial results. 
Unless agreed in advance otherwise, site- or subpopulation-specific analyses may only be 
published after the outcomes of the primary endpoint analyses have been published. 
The sponsor will comply with the requirements for the publication of trial results. In 
accordance with standard editorial and ethical practice, the sponsor will generally support 
publication of multi-site trials only in their entirety and not as individual site data. In this 
case, a coordinating investigator will be designated by mutual agreement. 
Authorship will be determined by mutual agreement and in line with International 
Committee of Medical Journal Editors (ICMJE) authorship requirements. 
10.1.11 Protocol preparation and approval 
This protocol has been prepared, reviewed and approved, including wet ink sign-off by the 
sponsor’s responsible person, in accordance with the sponsor’s standard operating 
procedures. Documentation of this process is filed in the TMF. 
10.2 
Clinical laboratory tests 
Blood and urine will be collected for clinical laboratory tests at the times given in the SoA 
(Section 1.3). The below list is the required minimum, but local sites may include additional 
parameters. 

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Hematology 
Hemoglobin, hematocrit, red blood cell count, white blood cell count and differential 
(neutrophils, lymphocytes, monocytes, eosinophils, basophils), platelet count. 
Clinical chemistry 
Alkaline phosphatase, creatinine, ferritin, C-reactive protein, albumin, alanine 
aminotransferase, amylase, aspartate aminotransferase, gamma glutamyl transpeptidase, 
total bilirubin, blood urea nitrogen, glucose, lipase, sodium, potassium, calcium. 
Follicle stimulating hormone: Only in women who are not considered WOCBP. 
Urinalysis 
Dipstick: glucose, bilirubin, ketone, specific gravity (1 mL ≙ 1 g), blood, pH, protein, 
urobilinogen, nitrite, and leukocytes. 
Microscopic urinalysis: If warranted by dipstick results, urine sediment will be 
microscopically examined for presence of red blood cells, white blood cells, casts, crystals, 
epithelial cells, and bacteria. 
10.3 
Adverse events: Definitions and procedures for recording, 
evaluating, follow-up, and reporting 
10.3.1 
Definition of AE, TEAE, and AESIs 
• An AE is any untoward medical occurrence in a trial subject, temporally associated 
with the use of trial treatment, whether or not considered related to the IMP. 
NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding that is clinically significant), symptom, or disease (new 
or exacerbated) temporally associated with the use of IMP. 
• A TEAE is defined as any AE with an onset after the first IMP injection or worsened 
after the first IMP injection (if the AE was present before the first administration of 
IMP). 
• For a definition of AESIs, see Section 8.3.8. 
10.3.1.1 
Events meeting the AE definition 
• Any abnormal laboratory test results or other safety assessments (e.g., vital signs 
measurements), including those that worsen from baseline, and which are 
considered clinically significant in the medical and scientific judgment of the 
investigator, may be considered as AEs. 
• New conditions or (at the discretion of the investigator) any worsening of a pre-
existing condition detected or diagnosed after Visit 0. 
• Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 

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• Signs, symptoms, or the clinical sequelae of a suspected overdose of either trial 
treatment or a concomitant medication. Overdose per se will not be reported as an 
AE/SAE. 
10.3.1.2 
Events not meeting the AE definition 
• Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that 
leads to the procedure is the AE. 
• Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
10.3.1.3 
Suspected adverse reaction 
All untoward and unintended responses to an IMP-related to any dose administered. 
• The definition also covers medication errors and uses outside what is foreseen in 
the protocol, including misuse and abuse of the IMP. 
• The definition implies a reasonable possibility of a causal relationship between the 
event and the IMP. This means that there are facts (evidence) or arguments to 
suggest a causal relationship and an alternative etiology is not apparent. 
10.3.1.4 
Definition of SAE 
An SAE is defined as any untoward medical occurrence that, at any dose: 
• Results in death. 
• Is life-threatening. 
• The term “life-threatening” in the definition of “serious” refers to an event in which 
the trial subject was at risk of death at the time of the event. It does not refer to an 
event which hypothetically might have caused death if it were more severe. 
• Requires trial subject hospitalization or prolongation of existing hospitalization. 
• In general, hospitalization signifies that the trial subject has been detained (usually 
involving at least an overnight stay) at the hospital or emergency ward for 
observation and/or treatment that would not have been appropriate in the 
physician’s office or out trial subject setting. Complications that occur during 
hospitalization are AEs. If a complication prolongs hospitalization or fulfills any 
other serious criteria, the event is serious. When in doubt as to whether 
“hospitalization” occurred or was necessary, the AE should be considered serious. 
• Results in persistent disability/incapacity. 
This definition is not intended to include cases of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, 
influenza, and accidental trauma (e.g., sprained ankle) which may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption. 
• Is a congenital anomaly or is a birth defect. 
• Other situations: 

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o Medical or scientific judgment should be exercised in deciding whether 
SAE reporting is appropriate in other situations such as important 
medical events that may not be immediately life-threatening or result in 
death or hospitalization but may jeopardize the trial subject or may 
require medical or surgical treatment to prevent one of the other 
outcomes listed in the above definition. These events should usually be 
considered serious. 
10.3.1.5 
Suspected unexpected serious adverse reactions 
All suspected adverse reactions related to an IMP that occur in this trial and that are both 
unexpected and serious are SUSARs. SUSARs are subject to expedited reporting. 
10.3.1.6 
Use of the terms “severe” and “serious” 
Severity (intensity or grade) and seriousness need to be assessed independently for each 
AE and be recorded in the CRF. For a definition of the terms “severe” and “serious” for 
AEs, see: 
• Section 10.3.1.7 for AEs. 
• Section 10.3.1.4 for SAEs (see Section 10.3.1.10 for SAE reporting instructions). 
10.3.1.7 
Recording and follow-up of AE and/or SAE 
AE and SAE recording 
The investigator needs to assess and document any AE regardless of association with the 
use of the trial treatment during the period of observation as defined in Section 8.3.1. 
Data pertaining to AEs will be collected during each trial visit and the clinical significance 
of any sign or symptom needs to be evaluated by the investigator. 
• Clinically significant findings need to be documented as AEs in the source data and 
CRF. Findings that are evaluated and documented in the source data as not 
clinically significant (e.g., an abnormal laboratory value without any clinical 
manifestation), should not be documented as AE. 
• AEs that are related to one clinical event should be subsumed under that event 
when recorded on the CRF. For example, elevated creatinine, nausea, vomiting, 
hypercalcemia should be subsumed under renal failure if that explains the etiology 
for the subsumed signs and symptoms. 
• The investigator will then record AE information in the CRF and perform an 
assessment on: 
• Intensity, see the section “Assessment of AE and/or SAE intensity” for guidance on 
the assessment of intensity, 
• Seriousness, 
• Outcome, 
• Causal relationship of the AE to the trial treatment, 

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• Any trial treatment action and/or any other action taken. 
• All assessments as well as AE term (diagnosis/description), start date and time of 
onset, end date and time need to be documented in the CRF. 
• There may be instances when copies of medical records for certain cases are 
requested by the sponsor. In this case, all trial subject identifiers, with the exception 
of the trial subject number, will be redacted on the copies of the medical records 
before submission to the sponsor. 
• To avoid colloquial expressions, the AE should be reported in standard medical 
terminology. The investigator will attempt to establish a diagnosis of the event 
based on signs, symptoms, and/or other clinical information. Whenever possible, 
the diagnosis (not the individual signs/symptoms) will be documented as the AE. If 
a definitive diagnosis is not possible, the individual signs and symptoms should be 
recorded. 
Assessment of AE and/or SAE intensity 
The assessment of AE and/or SAE intensity should be done consistently for all subjects 
treated with the same treatment and dose. In case of doubt, the Medical Monitor should be 
consulted. 
The intensity of AEs or SAEs will be graded by the investigator. For further guidance refer 
to the FDA Guidance for Industry “Toxicity Grading Scale for Healthy Adult and Adolescent 
Volunteers Enrolled in Preventive Vaccine Clinical Trials”. Where specific guidance for an 
adverse event term is not provided, the following general approach should be followed: 
• Grade 1 - Mild; does not interfere with the subject’s usual function. 
• Grade 2 - Moderate; interferes to some extent with the subject’s usual function. 
• Grade 3 - Severe; interferes significantly with the subject’s usual function. 
• Grade 4 - Potentially life-threatening; life-threatening consequences, urgent 
intervention required. 
Actions taken by the investigator 
Actions taken by the investigator as a result of an AE must be documented. 
Action(s) taken with trial treatment (IMPs) by the investigator: 
• Dose not changed (= continuation of trial treatment administration according to the 
trial protocol) 
• Drug withdrawn 
• Not applicable (e.g., in case treatment with trial treatment has not yet started or 
event starts after last trial treatment administration) 
Other action(s) that may be taken by the investigator include: 
• None 

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• Remedial drug therapy 
• Other specific treatment(s) of AE (to be specified) 
Outcome 
The investigator has to assess the outcome of an AE (and not the trial subject’s outcome) 
at the time of documentation based on the following criteria: 
• Recovered/resolved * (= complete resolution of the AE) 
• Recovering/resolving (= AEs which are improving but not yet resolved completely, 
e.g., decrease in an intensity grade) 
• Not recovered/not resolved (= AEs which are ongoing without improving or still 
present when the trial subject deceases due to another cause) 
• Recovered/resolved with sequelae * (= trial subject recuperated but retained 
pathological conditions resulting from the AE; the sequelae should be indicated) 
• Fatal ** (= death due to the AE) 
• Unknown (e.g., in case the trial subject is lost to follow-up) 
* Generally, an AE is defined as recovered/resolved if all symptoms have ceased, no 
medication for treatment of the event is taken anymore and no other measures (e.g., 
hospitalization) are ongoing. 
If the trial subject has developed permanent or chronic symptoms or if the event 
requires long term medication(s), the AE is defined as recovered/resolved with 
sequelae as soon as no changes of symptoms and/or medication(s) are expected 
anymore. 
An AE that is documented as a worsening of a medical condition already known at 
baseline, is defined as recovered as soon as the medical condition has returned to 
baseline status. 
** In case of a fatal event, the event term should not be “death” but the underlying 
event which led to death (death = outcome). If there is more than one AE in a fatal 
case, only the AE leading to death will be attributed with the outcome “fatal”. All other 
AEs ongoing at the time of death will be attributed with the outcome “not recovered/not 
resolved”. A copy of an autopsy report should be submitted if available. 
Assessment of causality 
The investigator is obligated to assess the relationship between trial treatment/trial 
procedure and each occurrence of each AE/SAE. 
The investigator will use clinical judgment to determine the relationship. 
Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to trial treatment administration 
will be considered and investigated. 
It is sufficient to document the causality in the source data and CRF as: 

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• Related (= there is a reasonable possibility of a causal relationship) or 
• Not related (= there is no reasonable possibility of a causal relationship) 
Relationship to trial treatment 
• The relationship or association of an AE or SAE to a trial treatment will be made by 
the investigator after having evaluated all accessible data and, if necessary, he/she 
will re-evaluate the case as new information becomes available. 
• Events caused by the procedure of trial treatment administration should be 
differentiated from events caused by the trial treatment itself. Only events 
suspected to be caused by the IMPs itself should be documented as suspected. 
Relationship to trial procedures including trial treatments 
• In this trial, it cannot be excluded that during the course of the trial some 
procedures give rise to AEs which are related to the trial procedure and not to the 
trial treatment. Procedure-related AEs can occur on the site of injection of the trial 
treatment e.g., redness, swelling, hematoma, or itching or during or after trial-
specific procedure, e.g., discomfort after blood drawing. 
• There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to the sponsor. However, it is very 
important that the investigator always makes an assessment of causality for every 
event before the initial transmission of the SAE data to the sponsor. 
• The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality 
assessment. 
• The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. 
10.3.1.8 
SAE exemptions 
In general, SAEs are defined according to ICH Topic E2A (CPMP/ICH/377/95), 
EU Directive 2001/20/EC, and ENTR/CT-3 (see Section 10.3.1.4). 
In the present trial, some events are excluded from the SAE definition. The following 
events do not need to be reported as SAEs: 
• AEs and SAEs occurring after trial subject discharge from the trial must only be 
reported by the investigator to the sponsor if a relationship to trial treatment or trial 
procedure is suspected. 
• Planned hospitalizations required by the protocol will not be considered as 
reportable SAEs. 

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10.3.1.9 
Documentation of particular situations 
AEs that are secondary to other events: 
In general, AEs that are secondary to other events (e.g., cascade events or clinical 
sequelae) should be identified by their primary cause, with the exception of severe or 
serious secondary events. A medically significant secondary AE that is separated in time 
from the initiating event should be documented as an independent AE in source data and 
CRF. For example: 
• If vomiting results in mild dehydration with no additional treatment in a healthy 
adult, only vomiting should be documented as AE. 
• If vomiting results in severe dehydration, both events should be documented as 
AEs separately. 
Abnormal clinical laboratory results and vital signs values: 
Not every laboratory or vital signs abnormality needs to be documented as AE. For 
clinically significant laboratory/vital signs abnormalities the following definitions and 
documentation rules apply: 
• If a laboratory/vital signs abnormality is a sign of a disease or syndrome, the 
laboratory/vital signs abnormality is clinically significant and only the diagnosis of 
the causing disease or syndrome needs to be documented as AE. 
• If a clinical laboratory/vital signs abnormality results in specific symptoms but no 
diagnosis of a disease or syndrome can be made, the laboratory/vital signs 
abnormality is clinically significant and only the symptoms need to be documented 
as AEs. 
• If a clinical laboratory/vital signs abnormality is not a sign of a disease or syndrome 
and does not result in specific symptoms but leads to a change in trial treatment or 
in a medical intervention, the laboratory/vital signs abnormality is clinically 
significant and must be documented as AE. 
• If a clinical laboratory/vital signs abnormality is not considered clinically significant 
by the investigator, then an AE does not need to be documented. 
AEs associated with an overdose or error in drug administration: 
• An overdose or incorrect administration of a drug is not itself an AE, but it may 
result in an AE. For a definition of an overdose, see Section 8.4. 
• All AEs associated with an overdose or incorrect administration should be 
documented as AE in source data and CRF and reported as SAE if applicable. 
10.3.1.10 
Reporting of SAEs and AESIs 
All SAEs and AESIs (even if non-serious) which occur in a trial subject during the 
observation period, whether considered to be associated with trial medication or not, must 
be reported by the investigator to the sponsor within 24 h following knowledge of the 
event. 

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All SAEs occurring after the end of the observation period only have to be reported to the 
sponsor if the investigator suspects a relationship to trial medication or the trial procedure. 
SAE and AESI reporting to sponsor 
For the period of observation, see Section 8.3.1. 
For every SAE and AESI (even in the AESI is non-serious), the investigator needs to 
complete the applicable paper report form which must be sent to the sponsor via one of 
the following reporting methods: 
• Safety Report Fax No.:   
 
 
• Safety Report E-mail Address:  
 
Information for final description and evaluation of a case report may not be available within 
the required time frames for reporting. Nevertheless, for regulatory purposes, initial reports 
should be submitted if the following minimal information is available: 
• An identifiable trial subject (trial subject number) 
• A suspected medicinal product 
• An identifiable reporting source (investigator/trial site identification) 
• An event or outcome that can be identified as serious 
All SAE/AESI follow-up information should be sent to the sponsor (indicating that this is a 
“follow-up” report using the SAE Form or the Additional Information and Follow-Up Form) 
without delay as described above and accompanied by appropriate anonymous supporting 
documentation (e.g., discharge letters, medical reports or death certificates), until a final 
outcome and date are available. All confidential information (name, address, full day of 
birth) needs to be blackened before sending. In addition to a medical record, the 
investigator should complete an Additional Information and Follow-Up Form, which 
contains the SAE term and trial subject number. 
A copy of the submitted SAE/AESI report must be retained on file by the investigator. If 
explicitly required according to national legislation, the investigator must submit copies of 
the SAEs to the IECs/IRBs or authority and retain documentation of these submissions in 
the ISF. 
In case an investigator or any other trial team member has questions on safety reporting 
the sponsor may be contacted via: E-mail: 
 
For medical questions, the sponsor’s Medical Monitor for this trial should be contacted. 
10.4 
Contraceptive guidance and collection of pregnancy information 
The following guidance is based on the Clinical Trial Facilitation Group (CTFG) 
recommendations related to contraception and pregnancy testing in clinical trials issued in 
2020 (CTFG 2020). 
CCI
CCI
CCI

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10.4.1 
Definitions 
Women of childbearing potential 
For the purpose of this document, a woman is considered fertile following menarche and 
until becoming post-menopausal unless permanently sterile (see below). 
If fertility is unclear (e.g., amenorrhea in adolescents or athletes) and a menstrual cycle 
cannot be confirmed before first dose of trial treatment, additional evaluation should be 
considered. 
Women in the following categories are not considered WOCBP: 
• Premenarchal 
• Premenopausal female with one of the following: 
• Documented hysterectomy 
• Documented bilateral salpingectomy 
• Documented bilateral oophorectomy 
For trial subjects with permanent infertility due to an alternate medical cause other than the 
above (e.g., mullerian agenesis, androgen insensitivity), investigator discretion should be 
applied to determining trial entry. 
Note: Documentation can come from the site personnel review of the trial subject’s 
medical records, medical examination, or medical history interview. 
Post-menopausal female 
For the purpose of this document, a post-menopausal state is defined as no menses for 
12 months without an alternative medical cause. 
A high follicle stimulating hormone level in the post-menopausal range may be used to 
confirm a post-menopausal state in women not using hormonal contraception or hormonal 
replacement therapy. However, in the absence of 12 months of amenorrhea, confirmation 
with more than one follicle stimulating hormone measurement is required. 
Females on hormonal replacement therapy and whose menopausal status is in doubt will 
be required to use one of the non-estrogen hormonal highly effective contraception 
methods if they wish to continue their hormonal replacement therapy during the trial. 
Otherwise, they must discontinue hormonal replacement therapy to allow confirmation of 
post-menopausal status before trial enrollment. 
Male trial subjects 
Male trial subjects with previous successful bilateral vasectomy or orchidectomy, or those 
who are truly abstinent or exclusively homosexual are deemed as being “not of 
reproductive potential”. 

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10.4.2 
Contraception guidance 
Trial subjects must meet the “Reproductive status” inclusion criteria, including 
contraception requirements, as listed in Section 5.1. 
The investigator or delegate should advise the subject how to achieve highly effective 
contraception. The following birth control methods may be considered as highly effective: 
• Combined estrogen and progestogen-based contraception hormonal contraception 
associated with inhibition of ovulation a, i.e., established use of: 
• oral, 
• intravaginal, or 
• transdermal hormonal methods of contraception. 
• Progesterone-only based contraception associated with inhibition of ovulation a, i.e., 
established use of: 
• oral, 
• injected, or 
• implanted hormonal methods of contraception. b 
• Intrauterine device. b 
• Intrauterine hormone-releasing system. b 
• Bilateral tubal occlusion. b 
• Vasectomy (for a male subject or male partner of a female subject). b, c 
• Sexual abstinence. d 
a Hormonal contraception may be susceptible to interaction with the IMP, which may reduce the efficacy of the 
contraception method. 
b Contraception methods that in the context of this guidance are considered to have low user dependency. 
c 
Vasectomized partner is a highly effective birth control method provided that partner is the sole sexual partner of 
the WOCBP trial subjects and that the vasectomized partner has received medical assessment of the surgical 
success. 
d In the context of this guidance sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated with the trial treatments. The 
reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the 
preferred and usual lifestyle of the subject. 
 
Unless practicing true sexual abstinence, the following birth control methods may be 
considered as acceptable but potentially not highly effective methods: 
• Male or female condom with a spermicidal agent; both female and male condom 
should not be used together. e 
• Cap diaphragm or sponge with a spermicidal agent. e 
e A combination of male condom with either cap, diaphragm or sponge with spermicide (double barrier methods) 
are also considered acceptable, but not highly effective, birth control methods. 
 

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10.4.3 
Collection of pregnancy information 
Pregnancy information will be recorded at the times listed in the SoA (Section 1.3). 
Pregnancy information will only be collected after obtaining written informed consent from 
the pregnant female subject (or if a male subject’s partner becomes pregnant, written 
informed consent from the pregnant partner). 
The initial and follow-up information must be documented on the paper-based Pregnancy 
Reporting Form and submitted to the sponsor within 24 h of learning of a trial subject’s 
pregnancy/partner’s pregnancy. The completed form needs to be sent to the Safety Report 
Fax number or E-mail given in Section 10.3.1.10. Completed pregnancy forms must be 
signed by an investigator before faxing/mailing them to the sponsor. Blank reporting forms 
are provided to the investigator during the site initiation visit and are filed in the ISF. 
The investigator will collect follow-up information on the trial subject/trial subject’s partner 
and the neonate and the information will be forwarded to the sponsor. Pregnancy follow-up 
should describe the outcome of the pregnancy, including any voluntary or spontaneous 
termination, details of the birth, the presence or absence of any congenital abnormalities, 
birth defects, maternal or newborn complications and their presumed relation to the IMP. 
Generally, the follow-up will be of a duration determined in consultation with the 
pediatrician. 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication 
or elective termination of a pregnancy will be reported as an AE or SAE. 
A spontaneous abortion is always considered to be an SAE and will be reported as such. 
Any post-trial pregnancy related SAE considered reasonably related to the trial 
intervention by the investigator will be reported to the sponsor. While the investigator is not 
obligated to actively seek this information in former trial subjects, he or she may learn of 
an SAE through spontaneous reporting. 
10.4.4 
Sperm donation 
Trial subjects must comply with the inclusion criteria prohibiting sperm donation listed in 
Section 5.1. 
10.5 
Genetics 
Not applicable. 
10.6 
Liver safety: Suggested actions and follow-up assessments 
Not applicable. 
10.7 
Investigators and trial administrative structure 
10.7.1 
Investigators and trial site personnel 
There must be an investigator at each trial site. 

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If the trial is conducted by a team of individuals at the trial site, the investigator leading and 
responsible for the team is called the principal investigator. 
All persons assigned responsibility as principal investigator must sign a declaration of their 
responsibilities and their agreement to this protocol before any trial-related procedure is 
performed. 
Curriculum vitae and/or other relevant documents confirming the current qualification of 
the investigators must be provided to the sponsor. This should include any previous 
training in the principles of GCP, experience obtained from work with clinical trials, and 
experience with trial subject care. 
Documentation of all involved investigators must be maintained according to GCP and 
applicable regulatory requirements. 
10.7.2 
Trial site personnel assigned trial-related duties 
The principal investigator or deputy may define appropriately qualified personnel at a trial 
site to perform significant trial-related procedures and/or to make trial-related decisions 
under his/her supervision. In this case, the principal investigator must maintain a signed 
list of the persons to whom they delegate significant trial-related duties/responsibilities; the 
delegated trial-related duties/responsibilities must be specified in the list. 
When personnel or responsibility changes are made, the principal investigator or deputy 
must ensure that the relevant documentation is updated before any trial-related activities 
are performed. 
Documentation of all involved trial site personnel performing significant trial-related 
procedures and/or making trial-related decisions must be maintained according to GCP 
and applicable regulatory requirements. 
10.7.3 
Contract research organizations 
Documentation of all involved CROs must be maintained by the sponsor according to GCP 
and applicable regulatory requirements. This includes documentation of any delegation of 
responsibilities to CROs. 
10.7.4 
The sponsor and sponsor’s personnel 
The trial sponsor listed on the title page accepts the responsibilities of the sponsor 
according to GCP and applicable regulatory requirements. 
The sponsor must designate appropriately qualified personnel to advise on trial-related 
topics. The trial site will be provided with contact details for these personnel before any 
trial-related procedure is performed. 
A list of key sponsor personnel involved in the preparation of this protocol and the conduct 
of the trial, including their full names, titles, roles, and responsibilities, must be maintained. 
10.8 
Country-specific requirements 
Not applicable. 

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10.9 
Protocol amendments and updates 
A comparison of every new sponsor approved protocol version with the next approved 
version is filed together with the protocol in the TMF for all protocol amendments and 
updates. 
Also, changes made to the protocol during the protocol amendments or updates are 
described in the document Protocol Amendment History which is available upon request. 
This Protocol Amendment History is filed together with the respective protocol in the TMF. 
10.9.1 
Amendment 1.0 (update from protocol version 1.0 to 2.0) 
The amendment implements updates in response to Center for Biologics Evaluation and 
Research (CBER) comments (dated 07 AUG 2021) on protocol version 1.0. 
10.9.2 
Amendment 2.0 (update from protocol version 2.0 to 3.0) 
The amendment implements updates for clarification, updates reflecting the decision to 
perform SAR-CoV-2 viral genome sequencing for all subjects (and not just if triggered), 
and adaptions to the statistical analysis reflecting discussion of booster data analysis with 
the FDA which requires the exclusion of certain protocol deviations from the primary 
analysis and thereby makes the Per Protocol Set redundant. 
10.9.3 
Amendment 3.0 (update from protocol version 3.0 to 4.0) 
This amendment implements three additional cohorts (Cohorts 7, 8, and 9) within Part C, 
comprising an additional ~410 subjects who: 
• have received two or three doses of any authorized COVID-19 RNA-based vaccine, 
e.g., 30 µg BNT162b2 (Comirnaty) or the Moderna vaccine (Spikevax), and 
• had a breakthrough SARS-CoV-2 infection from January 2022 on (limited to a 
period when there was a high prevalence of SARS-CoV-2 Omicron infections). 
Subjects in Part C will receive either 30 µg of the monovalent BNT162b2 (B.1.1.529) as a 
third or fourth dose, 30 µg BNT162b2 as a third or fourth dose, or no vaccination within 
3 months of Visit 1. 
In addition, a third dose of the multivariant vaccine has been added for Cohort 6, Parts A 
and B comprising BNT162b2-naïve subjects, with planned visits at pre-Dose 3, 1-week 
post-Dose 3, and 1-month post-Dose 3. 
For subjects who receive non-trial SARS-CoV-2 vaccinations, blood samples for humoral 
immunogenicity and T-cell and B-cell response assessments will not be collected, and 
they will be discontinued from the BNT162-17 trial. 
The amendment also includes updates for clarification and an updated Table 8, which 
following the request of the IEC in Germany now includes information on the SARS-CoV-2 
Omicron variant. 
10.9.4 
Amendment 4.0 (update from protocol version 4.0 to 5.0) 
This update implements a change in eligibility criteria for Part C. Eligibility criteria were 
updated to correspond to the existing regulatory guidance, clarifying the required time 

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10.10.3 Data management 
The CRO (see the title page) will be responsible for data management of this trial, 
including quality checking of the data. 
Data entered manually will be submitted to the sponsor through use of an EDC system, 
data extracts, and reports. Trial sites will be responsible for data entry into the EDC 
system. In the event of discrepant data, the data management service provider will request 
data clarification from the trial sites, which the trial sites will resolve electronically in the 
EDC system. 
The data management service provider will produce a Trial Data Validation Specification 
document that describes the quality checking to be performed on the data. CRFs and 
correction documentation will be maintained in the EDC system’s audit trail. 
Central laboratory data will be sent directly to the data management service provider. 
System backups for data stored by the sponsor and records retention for the trial data will 
be in accordance with regulatory requirements. 
10.10.4 Investigator’s Site File and the TMF 
The principal investigator or deputy is responsible for the filing of all essential documents 
in an ISF. The sponsor or a delegated CRO is responsible for the timely filing of all 
essential documents in the TMF. As applicable, these files must be available at monitoring 
visits and during audits or regulatory inspections. 
After trial completion, the principal investigator or deputy must ensure that all source data 
and documentation related to the trial is recorded, handled, and stored in a way that allows 
its accurate reporting, interpretation, and verification. The principal investigator or deputy 
must take measures to prevent accidental or premature destruction of these documents. 
The principal investigator or deputy must keep the ISF, the source data/documentation 
arising from the trial according to the prescribed record retention period in the country 
and/or according to the hospital policy, but at least until informed by the sponsor that the 
trial-related records are no longer required. 
11 
REFERENCES 
BNT162 investigator’s brochure, current edition. 
Abdool Karim SS, de Oliveira T. New SARS-CoV-2 variants - clinical, public health, and 
vaccine implications. N Engl J Med. 2021 May 13;384(19):1866-1868. 
doi:10.1056/NEJMc2100362. 
Abu-Raddad LJ, Chemaitelly H, Butt AA; National Study Group for COVID-19 Vaccination. 
Effectiveness of the BNT162b2 Covid-19 Vaccine against the B.1.1.7 and B.1.351 
Variants. N Engl J Med. 2021;385(2):187-189. doi:10.1056/NEJMc2104974. 
BNT162-02 / C4591001 (NCT04368728). Study to describe the safety, tolerability, 
immunogenicity, and efficacy of RNA vaccine candidates against COVID-19 in healthy 
individuals. Ongoing BioNTech clinical trial. 

BioNTech SE 
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BNT162-17 
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Version: 7.0 
Date: 28 JUN 2023 
 
 
BNT162-07 / C4591007 (NCT048166443). A Phase 1, open-label, dose-finding study to 
evaluate safety, tolerability, and immunogenicity and Phase 2/3 placebo-controlled 
observer-blinded safety, tolerability, and immunogenicity study of a SARS-CoV-2 RNA 
vaccine candidate against COVID-19 in healthy children and young adults. Ongoing 
BioNTech clinical trial. 
CTFG 2020. Clinical Trial Facilitation Group (CTFG) Recommendations related to 
contraception and pregnancy testing in clinical trials. Version 1.1, issued September 2020. 
Dan JM, Mateus J, Kato Y, et al. Immunological memory to SARS-CoV-2 assessed for up 
to 8 months after infection. Science. 2021;371(6529):eabf4063. 
doi:10.1126/science.abf4063. 
FDA Guidance 2007. FDA Guidance for Industry. Toxicity Grading Scale for Healthy Adult 
and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials. 
FDA Guidance 2020. FDA Guidance for Industry. Development and Licensure of Vaccines 
to Prevent COVID-19. 
Feldman RA, Fuhr R, Smolenov I, et al. mRNA vaccines against H10N8 and H7N9 
influenza viruses of pandemic potential are immunogenic and well tolerated in healthy 
adults in phase 1 randomized clinical trials. Vaccine. 2019;37(25):3326-3334. 
doi:10.1016/j.vaccine.2019.04.074. 
Ferguson N, Ghani A, Cori A, et al. Growth, population distribution and immune escape of 
Omicron in England. Imperial College London. Published 16 DEC 2021. Accessed 
19 FEB 2022, doi:https://doi.org/10.25561/93038. 
Goel RR, Apostolidis SA, Painter MM, et al. Distinct antibody and memory B cell 
responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination. 
Sci Immunol. 2021 Apr 15; 6(58): eabi6950. doi:10.1126/sciimmunol.abi6950. 
Liu Y, Liu J, Xia H, et al. Neutralizing Activity of BNT162b2-Elicited Serum. N Engl J Med. 
2021;384(15):1466-1468. doi:10.1056/NEJMc2102017. 
Mulligan M, Lyke KE, Kitchin N, et al. Phase I/II study of COVID-19 RNA vaccine 
BNT162b1 in adults. [published correction appears in Nature. 2021 Feb;590(7844):E26]. 
Nature. 2020;586(7830):589-593. doi:10.1038/s41586-020-2639-4. 
Payne RP, Longet S, Austin JA, et al. Immunogenicity of standard and extended dosing 
intervals of BNT162b2 mRNA vaccine. Cell. 2021;184(23):5699-5714.e11. 
doi:10.1016/j.cell.2021.10.011. 
Polack FP, Thomas SJ, Kitchin N, et al. Safety and Efficacy of the BNT162b2 mRNA 
Covid-19 Vaccine. N Engl J Med. 2020 Dec 31; 383(27): 2603-2615. 
doi:10.1056/NEJMoa2034577. 
Rauch S, Jasny E, Schmidt KE, Petsch B. New Vaccine Technologies to Combat 
Outbreak Situations. Front Immunol. 2018;9:1963. doi:10.3389/fimmu.2018.01963. 
Sahin U, Karikó K, Türeci Ö. mRNA-based therapeutics - developing a new class of drugs. 
Nat Rev Drug Discov. 2014;13(10):759-780. doi:10.1038/nrd4278. 

BioNTech SE 
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Clinical Trial Protocol 
BNT162-17 
Page 125 of 125 
Version: 7.0 
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Schmidt F, Muecksch F, Weisblum Y, et al. Plasma Neutralization of the SARS-CoV-2 
Omicron Variant [published online ahead of print, 2021 Dec 30]. N Engl J Med. 
2021;NEJMc2119641. doi:10.1056/NEJMc2119641. 
Tauzin A, Gong SY, Beaudoin-Bussières G, et al. Strong humoral immune responses 
against SARS-CoV-2 Spike after BNT162b2 mRNA vaccination with a 16-week interval 
between doses. Cell Host Microbe. 2022;30(1):97-109.e5. 
doi:10.1016/j.chom.2021.12.004. 
UK Health Security Agency. SARS-CoV-2 variants of concern and variants under 
investigation in England: Technical briefing 34. Published 14 JAN 2022. 
US Centers for Disease Control and Prevention (CDC) webpage “COVID Data Tracker – 
Variant Proportions” https://covid.cdc.gov/covid-data-tracker/#variant-proportions. 
Accessed 09 FEB 2022. 
Walsh EE, Frenck RW Jr, Falsey AR, et al. Safety and Immunogenicity of Two RNA-Based 
Covid-19 Vaccine Candidates. N Engl J Med. 2020;383(25):2439-2450. 
doi:10.1056/NEJMoa2027906. 
WHO webpage “Coronavirus disease (COVID-19) Weekly Epidemiological Update”. 
https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports. 
Accessed 09 FEB 2022. 
WHO webpage “Tracking SARS-CoV-2 variants”. 
https://www.who.int/en/activities/tracking-SARS-CoV-2-variants/. Accessed 26 JUL 2022. 
WHO webpage “Update on Omicron”. https://www.who.int/news/item/28-11-2021-update-
on-omicron. Published 29 NOV 2021. Accessed 07 JAN 2022.