Final Full Clinical Study Report
Protocol B7471016

CLINICAL STUDY REPORT SYNOPSISSYNOPSIS
Study Title: Final Report: A Phase 3, Randomized, Double-Blind, Third-Party Unblind Trial
to Evaluate the Safety and Immunogenicity of a 20-valent Pneumococcal Conjugate Vaccine
in Healthy Japanese Infants
Study Number: B7471016
Regulatory Agency or Public Disclosure Identifier Number: 2022-001146-38
Study Phase: 3
Name of Study Intervention: 20-valent Pneumococcal Conjugate Vaccine (20vPnC),
Compound Number: PF-06482077
Name of Sponsor/Company: Pfizer Inc.
CSR Version and Report Date: Final CSR Version 1.0, 05 October 2022
Number of Study Center(s) and Investigator(s):A total of 668 participants were enrolled at 38 centers in Japan.
A list of study centers and investigators involved in this study is provided inAppendix 16.1.4.1.
Publications:Not applicable.
Study Period:
Study Initiation Date: 16 September 2020
Primary Completion Date: 02 April 2022
This study was neither discontinued nor interrupted.
Rationale:
In Japan, 7-valent pneumococcal conjugate vaccine (7vPnC) and 13-valent pneumococcal
conjugate vaccine (13vPnC) have been administered to infants by subcutaneous (SC)injection on a 4-dose vaccination schedule (3 doses for infant series and 1 dose for toddlerdose).

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Final Full Clinical Study Report
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CLINICAL STUDY REPORT SYNOPSIS
The purpose of this study was to provide key safety and comparative immunogenicity data inJapanese infants to support licensure in this population in Japan. The targeted age of thepopulation for this study, infants ≥2 to ≤6 months of age, has been selected as the routinelyrecommended vaccination schedule for pneumococcal conjugate vaccines and other vaccines
in infants starts at approximately 2 months of age. The participants were administered either
20vPnC (SC or IM injection) or 13vPnC SC by the same injection route for all 4 doses.
Objectives, Endpoints, and Statistical Methods:
Study objectives, estimands, and endpoints are provided in Table S1.

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Table S1. Study Objectives, Estimands, and Endpoints
Primary Safety Objective

Estimands

Primary Safety Endpoints

 To describe the safety profile of 20vPnC byboth SC injection and IM injection

In participants receiving at least 1 dose ofinvestigational product and having safety datareported after any vaccination:

 Prompted local reactions (redness,swelling, and pain at the injection site) Prompted systemic events (fever,decreased appetite, drowsiness/increasedsleep, and irritability)
 AEs
 SAEs NDCMCs The percentage of participants reporting
prompted local reactions at injection site ofinvestigational product within 7 days after eachvaccination in each group
 The percentage of participants reporting
prompted systemic events within 7 days aftereach vaccination in each group
 The percentage of participants reporting AEs
from Dose 1 to 1 month after Dose 3 in eachgroup
 The percentage of participants reporting AEs
from Dose 4 to 1 month after Dose 4 in eachgroup
 The percentage of participants reporting SAEs
up to 1 month after Dose 4 in each group
 The percentage of participants reporting
NDCMCs up to 1 month after Dose 4 in eachgroup

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Table S1. Study Objectives, Estimands, and Endpoints
Primary Immunogenicity Objectives

Estimands

Primary Immunogenicity Endpoints

 To demonstrate the percentage of participants
with predefined serotype-specific IgG
concentrations for the 13 serotypes in the20vPnC SC group are noninferior to thepercentage of the corresponding serotypes inthe 13vPnC SC group at 1 month after Dose 3

In participants in compliance with the key protocolcriteria (evaluable participants) at 1 month after
Dose 3:

 Pneumococcal serotype-specific IgG
concentration

 To demonstrate the percentage of participants
with predefined serotype-specific IgG
concentrations for the 7 additional serotypes in
the 20vPnC SC group are noninferior to thelowest percentage among the 13 serotypes in
the 13vPnC SC group at 1 month after Dose 3

In evaluable participants at 1 month after Dose 3:

For 20vPnC SC group: For each of the 13 matched serotypes:
difference in the percentage of participants withpredefined serotype-specific IgG concentrations
between the 20vPnC SC group and the 13vPnCSC group
 For each of the 7 additional serotypes in
20vPnC: difference in the percentage ofparticipants with predefined serotype-specificIgG concentrations, between the 20vPnC SCgroup and the lowest percentage of participants
with predefined serotype-specific IgG
concentrations among the 13 serotypes from the13vPnC SC group

 Pneumococcal serotype-specific IgG
concentration

For 20vPnC IM group: To describe the immune responses to20 serotypes induced by 20vPnC given by IMinjection at 1 month after Dose 3

In evaluable participants at 1 month after Dose 3:
 For each of the serotypes in 20vPnC: differencein the percentage of participants with predefined
serotype-specific IgG concentrations between
the 20vPnC IM group and the 20vPnC SC group

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 Pneumococcal serotype-specific IgG
concentration

Final Full Clinical Study Report
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CLINICAL STUDY REPORT SYNOPSIS
Table S1. Study Objectives, Estimands, and Endpoints
Secondary Immunogenicity Objectives

Estimands

Secondary Immunogenicity Endpoints

 To demonstrate the serotype-specific IgG
GMCs for the 13 serotypes in the 20vPnC SC
group are noninferior to the GMCs for thecorresponding serotypes in the 13vPnC SC
group at 1 month after Dose 3

In evaluable participants at 1 month after Dose 3:

 Pneumococcal serotype-specific IgG
concentrations

 To demonstrate the serotype-specific IgG GMCs
for the 7 additional serotypes in the 20vPnC SC
group are noninferior to the lowest IgG GMC
among the 13 serotypes induced by the 13vPnC
SC group at 1 month after Dose 3In evaluable participants at 1 month after Dose 3:

 To further describe the immunogenicity of20vPnC by both SC and IM injection

In evaluable participants at 1 month after Dose 3:

 For each of the 13 matched serotypes: GMR ofserotype-specific IgG concentrations from the20vPnC SC group to the 13vPnC SC group

 For each of the 7 additional serotypes in Pneumococcal serotype-specific IgG
concentrations

 20vPnC: GMR of serotype-specific IgG
concentration from the 20vPnC SC group to theserotype with the lowest IgG GMC among the13 serotypes from the 13vPnC SC group
 For each of the serotypes in 20vPnC: GMR ofserotype-specific IgG concentrations from the20vPnC IM group to the 20vPnC SC group
In evaluable participants at 1 month after Dose 4:
 For each of the serotypes in 20vPnC: Serotypespecific IgG GMCs at 1 month after Dose 4 ineach group
In evaluable participants at 1 month after Dose 3
and 1 month after Dose 4:

 Pneumococcal serotype-specific IgG
concentrations

 Pneumococcal serotype-specific IgG
concentrations

 Pneumococcal serotype-specific OPA titers Serotype-specific OPA GMTs at 1 month after
Dose 3, prior to Dose 4, and 1 month after Dose
4 in each group
In evaluable participants at 1 month after Dose 4:

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 Pneumococcal serotype-specific IgG
concentrations

Final Full Clinical Study Report
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CLINICAL STUDY REPORT SYNOPSIS
Table S1. Study Objectives, Estimands, and Endpoints
 For each of the serotypes in 20vPnC: percentageof participants with the predefined serotypespecific IgG concentration in each group
In evaluable participants:
 GMFRs in serotype-specific IgG concentrations
from 1 month after Dose 3 to before Dose 4,
from before Dose 4 to 1 month after Dose 4, andfrom 1 month after Dose 3 to 1 month after Dose
4 in each group
Exploratory Immunogenicity Objectives

Estimands

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 Pneumococcal serotype-specific IgG
concentrations

Exploratory Immunogenicity Endpoints

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CLINICAL STUDY REPORT SYNOPSIS
Table S1. Study Objectives, Estimands, and Endpoints
Abbreviations: 13vPnC =13-valent pneumococcal conjugate vaccine; 20vPnC = 20-valent pneumococcal conjugate vaccine; AE = adverse event;
GMC = geometric mean concentration; GMFR = geometric mean fold rise; GMR = geometric mean ratio; IgG = immunoglobulin G; IM = intramuscular;; NDCMC = newly diagnosed chronic medical condition; OPA = opsonophagocytic activity; SAE = serious adverseevent; SC = subcutaneous.

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CLINICAL STUDY REPORT SYNOPSIS
Methodology:
This Phase 3, multicenter, randomized, double-blinded, third party unblinded study wasconducted at investigator sites in Japan.
Thepurpose of this study was to describe safety and conduct the pivotal immunogenicity
comparison of 20vPnC administered by SC injection to the licensed pneumococcal conjugate
vaccine, 13vPnC, administered by the currently indicated SC injectionin Japan. Data was generated from 20vPnC administered by IM injection, with the20vPnC administered by SC as a control.
This study planned to enroll approximately 666 infants between 2 through 6 months of age at
the time of consent by their parent(s)/legal guardian(s). Participants were randomized equallyto 1 of the following vaccine groups: (1) 20vPnC SC group, (2) 13vPnC SC group (controlvaccine), or (3) 20vPnC IM group. Participants received the same vaccine (20vPnC or13vPnC) by the same injection method (SC or IM injection) for all 4 doses at Visits 1, 2, 3,and 5 (refer to the protocol Schedule of Activities table for the timing of the visits; FigureS1). All vaccine groups were blinded to all members of the site involved in the study except
unblinded staff who administered 20vPnC or 13vPnC.
Local reactions (redness, swelling, and pain at the injection site), systemic events (fever,decreased appetite, drowsiness/increased sleep, and irritability), and use of antipyretic/pain
medication were prompted for and collected by the participant’s parent(s)/legal guardian(s)in an e-diary, via device or application, from Day 1 through Day 7 after each vaccination(where Day 1 is the day of vaccination).
Adverse events (AEs)were collected from the time the participant’s parent(s)/legalguardian(s) provided informed consent through 1 month after Dose 3 (Visit 4) and from Dose4 (Visit 5) through 1 month after Dose 4 (Visit 6). SAEs and NDCMCs were collected frominformed consent through 1 month after Dose 4 (Visit 6).
Blood was collected 1 month after Dose 3 (Visit 4), immediately prior to Dose 4 (Visit 5),
and 1 month after Dose 4 (Visit 6) to assess immunogenicity.

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Figure S1. Study Design Overview
CCI

Number of Participants (Planned and Analyzed):
Approximately 666 participants were planned to be enrolled. A total of 668 participants wererandomized, 659 (98.7%) participants completed the Dose 3 follow-up visit, and 649 (97.2%)
completed all visits per protocol.
A total of 667 participants were included in the safety population. One (1) participant
randomized to the 20vPnC IM was excluded from the safety population due to not receiving
any study treatment.
A total of 659 (98.7%) participants were included in the all-available immunogenicity
population, with the primary reason for exclusion being no valid immunogenicity results. The
primary reason for exclusion from the Dose 3 or Dose 4 evaluable immunogenicity
populations was not receiving the assigned vaccine, as randomized, for first 3 or all 4 doses,respectively. Of those vaccinated, 654 (97.9%) participants received all 3 infant doses and648 (97.0%) participants received all 4 doses.
Diagnosis and Main Criteria for Inclusion and Exclusion:
Participants included healthy Japanese male or female infants ≥2 months to ≤6 months(defined as the first day the participant is 2 months of age to the last day the participant is
6 months of age) at the time of consent.
Participants were excluded from the study if they had a history of severe adverse reaction
associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any componentof the investigational product, the specified concomitant vaccines, or any diphtheria toxoidcontaining vaccine. Additional exclusion criteria included any contraindication to vaccination
with pneumococcal conjugate vaccine or the specified concomitant vaccines, significant
neurological disorder or history of seizure, major known congenital malformation or serious
chronic disorders, history of microbiologically proven invasive disease caused by
Streptococcus pneumoniae, known or suspected immunodeficiency or other conditions
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acute or chronic medical or psychiatric condition or laboratory abnormality that mightincrease the risk associated with study participation. Participants were excluded from thestudy if they had a history of previous vaccination with any licensed or investigational
pneumococcal vaccine, prior receipt of Haemophilus influenzae type b, Hepatitis B (Hep B),
rotavirus, diphtheria, tetanus, acellular pertussis, and/or poliovirus vaccines, currently
receiving treatment with immunosuppressive therapy, or receipt of blood/plasma products or
immunoglobulins (including Hep B immunoglobulin and monoclonal antibodies) since birthor planned receipt through the last planned blood sample collection in the study (throughVisit 6).
Study Interventions, Dose, Mode of Administration, and Batch Number(s):Participants received 1 dose of 20vPnC or 13vPnC at each vaccination visit (Visits 1, 2, 3,and 5 with Doses 1, 2, 3, and 4, respectively). Doses 1 to 3 were preferred to be administeredat 2, 3, and 4 months of age consistent with the vaccination schedule recommended by theJapan Pediatric Society. In addition, Dose 3 was to be completed by 12 months of age andDose 4 was to be administered ≥60 days after Dose 3.
In the 20vPnC SC and 13vPnC SC groups, 20vPnC or 13vPnC was administeredsubcutaneously by injecting 0.5 mL into the anterolateral thigh (preferably into the leftanterolateral thigh) at the vaccination visits. In the 20vPnC IM group, 20vPnC wasadministered intramuscularly by injecting 0.5 mL into the anterolateral thigh muscle of theleg (preferably of the left leg) at the vaccination visits.
The manufacturing lot numbers for the study intervention(s) dispensed in this study areprovided in Table S2.
Table S2. Investigational Product Lot Numbers
Investigational
Product20vPnC
13vPnC

Manufacturer

Lot Numbera (Pfizer)

PfizerVendor Lot Number(Manufacturer)
DW163620-002030

Pfizer

DN380620-001731

a. Lot number assigned to the investigational product by Pfizer Global Clinical Supply.
Protocol B7471016 Investigational Product Lot Numbers Table – Final, Version 1.0, 05Aug2022.

Duration of Study Intervention:
Each participant participated in the study for approximately 7 to 14 months depending on theage of enrollment in the study.
Summary of Results:
Demographic and Other Baseline Characteristics:
Demographic and baseline characteristics of sex, race, ethnicity, and age for the safety
population were balanced across the vaccine groups. Across the vaccine groups, allPFIZER CONFIDENTIAL
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participants were Asian (Japanese), 49.4% were males, and median age at first dose was2.3 months.
Exposure:
Of the 668 participants enrolled in the study, 659 participants (98.7%) were vaccinatedthrough Dose 3 and 651 (97.5%) participants received Dose 4.
Immunogenicity Results:
Response to 20vPnC compared to 13vPnC
The percentage of participants with predefined serotype-specific IgG concentrations 1 monthafter Dose 3 of 20vPnC SC was noninferior to 13vPnC SC for 11 of the 13 matched
serotypes (all but serotypes 6A and 6B), and to the lowest serotype in the 13vPnC SC groupfor 5 of 7 additional serotypes (all but serotypes 10A and 12F). Out of the 13 matched
serotypes, 6A and 6B missed this endpoint by a small margin. The totality of data supportsthat the immune responses elicited by 20vPnC are expected to be effective against diseasecaused by the 20 vaccine serotypes, including those that missed NI.

Post hoc analysis with alternative defined level of ≥0.15 μg/mL for IgG
concentrations at this time point showed that serotype 6A would have met NI of20vPnC SC to 13vPnC SC at this level with the same NI criterion.

The majority of participants (90.0% for serotype 6A and 87.8% for serotype 6B) in
the 20vPnC SC group had predefined IgG concentrations for those serotypes 1 monthafter Dose 3, with increases at 1 month after Dose 4 of 20vPnC SC (100% forserotypes 6A and 6B) comparable to 13vPnC SC.

The majority of participants (60.2% for serotype 10A and 74.7% for serotype 12F) inthe 20vPnC SC group had predefined IgG concentrations at this time point withincreases at 1 month after Dose 4 of 20vPnC SC (>98.4% for all of the 7 additionalserotypes).

The IgG GMCs 1 month after Dose 3 of 20vPnC SC were noninferior to 13vPnC SC for
10 of the 13 matched serotypes and to 6 of the 7 additional serotypes compared to thelowest in the 13vPnC SC group. Serotypes 5, 6A, 6B, and 10A missed NI; serotypes 5,6A, and 10A missed the statistical criterion by a small margin.


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Following 3 infant doses of 20vPnC SC, infants were primed for memory responses tothe 13 matched vaccine serotypes, similar to the 13vPnC SC. This was shown by IgG
GMFRs from 1 month after Dose 3 to 1 month after Dose 4 >1.0 for all serotypes except
serotype 3. The IgG GMFRs in the 20vPnC SC group for the serotypes that missed NI for
the primary objective (serotypes 6A, 6B, 10A, and 12F) were 3.4 or higher 1 month afterDose 4. Boosting from before Dose 4 to 1 month after Dose 4 was also observed for all
serotypes.

Observed IgG and OPA responses for all 7 additional serotypes were much higher in the20vPnC SC group (consistent with superior, statistically significantly higher antibodylevels) when compared with the corresponding serotype responses in the 13vPnC SC
group. Therefore, 20vPnC elicits potentially protective antibody responses in infants thatare not available in existing vaccines.

Safety Results:
The percentages of participants with prompted local reactions and systemic events weregenerally similar in the 20vPnC SC and 13vPnC SC groups after each dose. The
proportion of reported swelling and redness in the 20vPnC IM group was lower than in
the 20vPnC SC and 13vPnC SC groups. Injection site redness was the most frequent local
reaction reported in all groups. Most local reactions and systemic events were mild or
moderate in severity.

Rates of AEs within 1 month after Dose 3 or from Dose 4 to 1 month after Dose 4 of20vPnC SC, 13vPnC SC, or 20vPnC IM were similar across vaccine groups. No safetyconcerns were identified.

The percentages of participants with NDCMCs after Dose 1 were low (≤10.7%) andsimilar across the 20vPnC SC, 13vPnC SC, and 20vPnC IM groups.

The proportion of participants with reported SAEs was low (≤7.4%) and similar acrossthe 20vPnC SC, 13vPnC SC, and 20vPnC IM groups. Most SAEs reported wereconsistent with medical events that may occur in this population. One death occurred inPFIZER CONFIDENTIAL
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the 20vPnC IM group; this event and all reported SAEs were not considered related tostudy intervention.
Conclusions
20vPnC SC was observed to have a similar tolerability and safety profile to 13vPnC SC. The
4-dose series of 20vPnC SC elicits immune responses that are expected to help expand
protection against pneumococcal disease due to the 7 additional serotypes, while maintaining
existing protection currently controlled by 13vPnC in Japanese infants.
The 2 modes of administration were observed to have a similar safety and tolerability
profile with the exception of injection site swelling and redness, which were lower when
20vPnC was administered IM.

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