A PHASE 3, RANDOMIZED, DOUBLE-BLIND TRIAL TO EVALUATE THE SAFETY AND IMMUNOGENICITY OF A 20-VALENT PNEUMOCOCCAL CONJUGATE VACCINE GIVEN AS A SERIES OF 2 INFANT DOSES AND 1 TODDLER DOSE IN HEALTHY INFANTS
Phase: PHASE3
Conditions: Pneumococcal Disease
Sponsor: Pfizer

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 1
A PHASE 3, RANDOMIZED, DOUBLE-BLIND TRIAL TO EVALUATE THE 
SAFETY AND IMMUNOGENICITY OF A 20-VALENT PNEUMOCOCCAL 
CONJUGATE VACCINE GIVEN AS A SERIES OF 2 INFANT DOSES AND 
1 TODDLER DOSE IN HEALTHY INFANTS
Investigational Product Number:
PF-06482077
Investigational Product Name:
20-valent Pneumococcal Conjugate Vaccine 
(20vPnC)
United States (US) Investigational New 
Drug (IND) Number:
European Clinical Trials Database 
(EudraCT) Number:
Protocol Number:
B7471012
Phase:
3
Short Title:  20-valent Pneumococcal Conjugate Vaccine Safety and Immunogenicity 
Study of a 3-Dose Series in Healthy Infants 
CCI
CCI
CCI

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 2
Protocol Amendment Summary of Changes Table
Document History
Document
Version Date
Summary of Changes and Rationale
Amendment 2
18 June 2021
- Clarified the timing of collection of SAEs 
and NDCMCs in the safety estimands.
- Added the noninferiority of IgG GMCs 
and the percentage of participants with 
predefined thresholds after 2 infant doses as 
primary immunogenicity objectives, and 
moved the objective for IgG percentage of 
participants with predefined thresholds after 
the toddler dose to the secondary objective, 
based on Scientific Advice from the CHMP. 
The statistical sections for these objectives 
were updated accordingly.
- Removed “serotype-specific” from several 
immunogenicity estimands and endpoints.
- Deleted 2 secondary pneumococcal 
immunogenicity objectives as they were 
moved up to the primary immunogenicity 
objectives, and revised the estimands for the 
remaining objective.
- Removed a secondary objective to 
describe OPA GMTs before Dose 3, as it 
was part of the objective for OPA GMFR 
from before Dose 3 to 1 month after Dose 3. 
- Clarified wording regarding the use of 
antipyretic/pain medication.
- Updated safety language to match the 
current protocol template.
- Added a WHO reference to the reference 
list to support the table on the Russian NIP.
CCI
CCI
CCI

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 3
Document History
Document
Version Date
Summary of Changes and Rationale
- Sections 4.1 and 8: Added text regarding 
alternate options for visits due to the 
pandemic.
- Section 6.5.3: Added clarification that a 
birth dose of hepatitis B vaccine is 
permitted.
- Sections 8.3.6 and 8.3.6.1: Added sections 
to match the current protocol template.
- Section 9: Made various revisions to the 
analyses of the data and the definitions of 
the study populations.
- Section 9.1.2.1.3: Added text to describe 
hypothesis testing for IgGs 1 month after 
Dose 3.
Section 9.1.3: Clarified that this section 
relates specifically to the primary 
immunogenicity evaluations.
- Section 10.9: Added a country-specific 
appendix for Italy to clarify exclusion 
criterion 1 and the route of administration of 
concomitant study vaccines.
- Section 10.10: Added a country-specific 
appendix for a Russian cohort to add 
approximately 60 participants, and address 
comments from a national agency on the 
schedule, concomitant vaccines, and other 
study aspects, including management of 
Russian cohort data.
- Made updates throughout the protocol on 
managing the Russian cohort.
Amendment 1
13 April 2020
- Added the pneumococcal immunogenicity 
objectives comparing serotype-specific IgG 
concentrations 1 month after Dose 3 from 
the 20vPnC group to the 13vPnC group  
based on regulatory agency feedback.  The 
statistical hypotheses, sample size 
determination, and statistical analyses for 
these objectives were updated accordingly.
- Modified the concomitant administration 
of MMR and varicella vaccines (given at 

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 4
Document History
Document
Version Date
Summary of Changes and Rationale
Visit 4) to allow greater flexibility with 
accepted local practice.
- Method of body temperature measurement 
at the investigator site has been made more 
flexible (standard method beyond axillary 
measurement is also allowed).
- Name of the “Clinical Trial (CT) SAE 
Report Form was updated to “Vaccine SAE 
Reporting Form.”
- Section 1.1 Objectives, Estimands, and 
Endpoints, and Section 3: Editorial updates 
made to be consistent with other Phase 3 
studies of 20vPnC.
- Section 4.1: Minor update on wording of 
appearance of 20vPnC and 13vPnC was 
made for consistency with Section 6.1.
- Section 6.5.1: Clarification to indicate that 
a fourth dose of Infanrix hexa is not 
permitted in the study.
- Section 6.5.2:  Clarified that rotavirus 
vaccine, if given, is to be administered 
according to local or national 
recommendations.
- Section 8.1.1:  
•
Added a general description of the 
serum subsets for the concomitant 
vaccines including MMR and varicella. 
- Section 8.3.7 and Section 10.8: Mandatory 
protocol template text updates.
- Section 8.10: Added “The investigator or 
appropriately qualified designee reviews the 
e-diary data online at frequent intervals for 
the 7 days following vaccination to evaluate 
participant compliance and as part of 
ongoing safety review” to each vaccination 
visit as a reminder.
CCI

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 5
Document History
Document
Version Date
Summary of Changes and Rationale
- Section 9.3: Updated the safety population 
definitions to be consistent with other 
Phase 3 studies of 20vPnC.
Original protocol
11 February 2020
Not applicable (N/A)
This amendment incorporates all revisions to date, including amendments made at the 
request of country health authorities and IRBs/ECs.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 6
TABLE OF CONTENTS
LIST OF TABLES...................................................................................................................11
1. PROTOCOL SUMMARY...................................................................................................12
1.1. Synopsis ..................................................................................................................12
1.2. Schema ....................................................................................................................18
1.3. Schedule of Activities (SoA)...................................................................................19
2. INTRODUCTION ...............................................................................................................22
2.1. Study Rationale .......................................................................................................25
2.2. Background .............................................................................................................26
2.2.1. Clinical Overview.......................................................................................26
2.3. Benefit/Risk Assessment.........................................................................................27
3. OBJECTIVES, ESTIMANDS, AND ENDPOINTS ...........................................................28
4. STUDY DESIGN.................................................................................................................32
4.1. Overall Design.........................................................................................................32
4.1.1. Approximate Duration of Participation for Each Participant .....................35
4.1.2. Approximate Number of Participants.........................................................35
4.2. Scientific Rationale for Study Design.....................................................................35
4.3. Justification for Dose ..............................................................................................36
4.4. End of Study Definition ..........................................................................................36
5. STUDY POPULATION......................................................................................................36
5.1. Inclusion Criteria.....................................................................................................36
5.2. Exclusion Criteria....................................................................................................37
5.3. Lifestyle Considerations..........................................................................................38
5.4. Screen Failures ........................................................................................................38
5.5. Temporary Delay Criteria .......................................................................................39
5.5.1. Criteria for Temporarily Delaying Vaccine Administration ......................39
5.5.2. Criteria for Temporarily Delaying Immunogenicity Blood Draw..............39
6. STUDY INTERVENTION..................................................................................................39
6.1. Study Intervention(s) Administered........................................................................39
6.1.1. Administration............................................................................................40
6.1.2. Medical Devices .........................................................................................41

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 7
6.2. Preparation/Handling/Storage/Accountability ........................................................41
6.2.1. Preparation and Dispensing........................................................................43
6.3. Measures to Minimize Bias: Randomization and Blinding.....................................43
6.3.1. Allocation to Investigational Product .........................................................43
6.3.2. Blinding of Sponsor....................................................................................43
6.3.3. Breaking the Blind......................................................................................44
6.4. Study Intervention Compliance...............................................................................44
6.5. Concomitant Therapy..............................................................................................44
6.5.1. Prohibited Concomitant Vaccines and Treatments.....................................44
6.5.2. Permitted Concomitant Vaccines and Treatments......................................44
6.5.3. Prior Vaccines and Treatments...................................................................45
6.5.4. Recording Prior and Concomitant Vaccines and Treatments.....................45
6.6. Dose Modification...................................................................................................45
6.7. Intervention After the End of the Study..................................................................45
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL...........................................................................46
7.1. Discontinuation of Study Intervention ....................................................................46
7.2. Participant Discontinuation/Withdrawal From the Study.......................................46
7.3. Lost to Follow-up....................................................................................................47
8. STUDY ASSESSMENTS AND PROCEDURES...............................................................48
8.1. Efficacy Assessments..............................................................................................48
8.1.1. Immunogenicity Assessments ....................................................................48
8.1.2. Biological Samples.....................................................................................51
8.2. Safety Assessments .................................................................................................51
8.2.1. Participant Electronic Diary .......................................................................52
8.2.2. Grading Scale for Prompted Events ...........................................................52
8.2.2.1. Local Reactions.........................................................................52
8.2.2.2. Systemic Event Symptoms and Fever.......................................54
8.2.2.3. Use of Antipyretic/Pain Medication..........................................55
8.2.3. Clinical Safety Laboratory Assessments ....................................................55
8.3. Adverse Events and Serious Adverse Events..........................................................56
8.3.1. Time Period and Frequency for Collecting AE and SAE Information.......56

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 8
8.3.1.1. Reporting SAEs to Pfizer Safety...............................................56
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF...................57
8.3.2. Method of Detecting AEs and SAEs ..........................................................57
8.3.3. Follow-up of AEs and SAEs.......................................................................57
8.3.4. Regulatory Reporting Requirements for SAEs...........................................57
8.3.5. Exposure During Pregnancy or Breastfeeding, and Occupational 
Exposure ..........................................................................................................58
8.3.5.1. Exposure During Pregnancy......................................................58
8.3.5.2. Exposure During Breastfeeding ................................................58
8.3.5.3. Occupational Exposure .............................................................58
8.3.6. Adverse Events of Special Interest.............................................................58
8.3.6.1. Lack of Efficacy........................................................................59
8.3.7. Medical Device Deficiencies......................................................................59
8.3.7.1. Time Period for Detecting Medical Device Deficiencies .........59
8.3.7.2. Follow-up of Medical Device Deficiencies...............................59
8.3.7.3. Prompt Reporting of Medical Device Deficiencies to 
Sponsor..............................................................................................59
8.3.7.4. Regulatory Reporting Requirements for Device 
Deficiencies .......................................................................................60
8.3.8. Medication Errors .......................................................................................60
8.4. Treatment of Overdose............................................................................................61
8.5. Pharmacokinetics ....................................................................................................61
8.6. Pharmacodynamics..................................................................................................61
8.7. Genetics...................................................................................................................61
8.8. Biomarkers ..............................................................................................................62
8.9. Health Economics ...................................................................................................62
8.10. Study Procedures...................................................................................................62
8.10.1. Visit 1 (Dose 1: Day 1).............................................................................62
8.10.2. Visit 2 (Dose 2: 42 to 63 Days After Visit 1, ie, Study Day 43 
Through Study Day 64) ...................................................................................64
8.10.3. Visit 3 (Dose 2 Follow-up: 28 to 42 Days After Visit 2) .........................65
8.10.4. Visit 4 (Dose 3: 335 to 386 Days of Age) ................................................66
8.10.5. Visit 5 (Dose 3 Follow-up: 28 to 42 Days After Visit 4) .........................68

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 9
8.10.6. Unscheduled Visits...................................................................................68
9. STATISTICAL CONSIDERATIONS ................................................................................69
9.1. Estimands and Statistical Hypotheses.....................................................................70
9.1.1. Estimands....................................................................................................70
9.1.2. Statistical Hypotheses.................................................................................70
9.1.2.1. Pneumococcal Immunogenicity Hypotheses.............................70
9.1.2.2. Concomitant Immunogenicity Hypotheses ...............................72
9.1.3. Multiplicity Consideration..........................................................................73
9.2. Sample Size Determination.....................................................................................74
9.2.1. Sample Size Consideration for the Primary Pneumococcal 
Immunogenicity Objectives for the Primary Study Population.......................74
9.2.2. Sample Size Consideration for the Primary Concomitant 
Immunogenicity Objective...............................................................................76
9.2.3. Sample Size Consideration for the Primary Safety Objective....................78
9.2.4. Sample Size Consideration for the Russian Cohort....................................79
9.3. Populations for Analysis .........................................................................................79
9.4. Statistical Analyses .................................................................................................79
9.4.1. Immunogenicity Analysis...........................................................................80
9.4.2. Safety Analyses ..........................................................................................86
9.4.3. Other Analyses............................................................................................87
9.5. Interim Analyses .....................................................................................................87
9.5.1. Analysis Timing..........................................................................................87
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS..........................................................................................................89
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations...............89
10.1.1. Regulatory and Ethical Considerations ....................................................89
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the 
Protocol or ICH GCP.........................................................................89
10.1.2. Financial Disclosure .................................................................................90
10.1.3. Informed Consent Process ........................................................................90
10.1.4. Data Protection .........................................................................................91
10.1.5. Dissemination of Clinical Study Data ......................................................91
CCI

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 10
10.1.6. Data Quality Assurance ............................................................................93
10.1.7. Source Documents....................................................................................94
10.1.8. Study and Site Closure..............................................................................94
10.1.9. Publication Policy.....................................................................................95
10.1.10. Sponsor’s Qualified Medical Personnel .................................................95
10.2. Appendix 2: Clinical Laboratory Tests .................................................................97
10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ......................................................................97
10.3.1. Definition of AE .......................................................................................97
10.3.2. Definition of NDCMC..............................................................................98
10.3.3. Definition of SAE.....................................................................................98
10.3.4. Recording/Reporting and Follow-up of AEs and/or SAEs.......................99
10.3.5. Reporting of SAEs..................................................................................103
10.5. Appendix 5: Genetics..........................................................................................106
10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-up Assessments ......106
10.7. Appendix 7: ECG Findings of Potential Clinical Concern .................................108
10.8. Appendix 8: Medical Device Adverse Events, Adverse Device Effects 
(ADEs), Serious Adverse Events, and Device Deficiencies: Definition and 
Procedures for Recording, Evaluating, Follow-up, and Reporting .........................108
10.8.1. Definition of AE and ADE .....................................................................108
10.8.2. Definition of SAE, Serious Adverse Device Effect (SADE), and 
Unanticipated Serious Adverse Device Effect (USADE)..............................108
10.8.3. Definition of Device Deficiency.............................................................109
10.8.4. Recording/Reporting and Follow-up of AEs and/or SAEs and 
Device Deficiencies .......................................................................................110
10.8.5. Reporting of SAEs..................................................................................112
10.8.6. Reporting of SADEs...............................................................................113
10.9. Appendix 9: Country-Specific Appendix – Applicable to Italy Only.................114
10.9.1. Exclusion Criterion 1 Clarification.........................................................114
10.9.2. Clarification of Route of Administration of Concomitant Study 
Vaccines.........................................................................................................114
10.10. Appendix 10: Russian Cohort ...........................................................................115
CCI

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 11
10.10.1. Summary of Protocol Modification Specific to the Russian Cohort ....115
10.10.2. Schedule of Activities for Russian Cohort ...........................................116
10.10.3. Objectives, Estimands, and Endpoints for Russian Cohort ..................118
10.10.4. Notes on the Russian National Immunization Program .......................119
10.10.5. Additional Information on the Study Vaccines for Russian 
Investigators...................................................................................................121
10.11. Appendix 11: Abbreviations .............................................................................122
11. REFERENCES ................................................................................................................125
LIST OF TABLES
Table 1.
Grading Scales for Local Reactions .........................................................53
Table 2.
Grading Scales for Systemic Event Symptoms ........................................54
Table 3.
Ranges for Fever.......................................................................................55
 
Table 5.
Sample Size Required With Specified Power to Demonstrate NI 
Comparing the 20vPnC Group to the 13vPnC Group Based on 
Percentage of Participants Who Reached Prespecified Antibody 
Levels for Concomitant Antigens, With 10% NI Margin.........................76
Table 6.
Sample Size Required With Specified Power to Demonstrate NI of 
20vPnC to 13vPnC Based on GMCs of Antibody Levels to 
Concomitant Vaccine Antigens, With a 2-Fold NI Margin......................78
Table 7.
Probability of Detecting at Least 1 Adverse Event ..................................78
CCI

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 12
1. PROTOCOL SUMMARY
1.1. Synopsis
Pfizer is developing a new 20-valent pneumococcal conjugate vaccine (20vPnC) candidate to 
expand protection against pneumococcal disease beyond that covered by current 
pneumococcal vaccines in children. 20vPnC has the same composition as 13-valent 
pneumococcal conjugate vaccine (13vPnC; Prevnar 13®/Prevenar 13®), but contains an 
additional 7 polysaccharide conjugates targeting serotypes responsible for a substantial 
burden of remaining pneumococcal disease. 20vPnC uses the same platform and contains the 
same excipients as 13vPnC.  Phase 2 safety and immunogenicity data in infants support 
further development of 20vPnC in the pediatric population.
This Phase 3, multicenter, randomized, double-blind study will be conducted at investigator 
sites in the EU and Australia.  Additional sites in Russia are also being sought.
The purpose of the study is to generate data on the safety and 
immunogenicity of 20vPnC in infants when administered in a series of 2 infant doses and 
1 toddler dose.  Data will also be generated on key routine pediatric vaccines given 
concomitantly with 20vPnC or 13vPnC.  The primary study population will consist of 
approximately 1200 infants at >36 weeks of gestation and ≥42 to ≤112 days of age at the 
time of consent by a parent(s)/legal guardian(s).  Participants will be randomized in a 1:1 
ratio to receive either 20vPnC or 13vPnC (control vaccine) at 2, 4, and 11 to 12 months of 
age (Doses 1 [Visit 1], 2 [Visit 2], and 3 [Visit 4], respectively).  Participants will receive the 
same vaccine (either 20vPnC or 13vPnC) for all 3 doses. 
In order to expand the study to describe the safety and immunogenicity of 20vPnC in infants 
from Russia, approximately 60 Russian infants will be enrolled in the study, and referred to 
as the Russian cohort.  The Russian cohort will not be included in the primary study 
population.  This is a result of enrollment and subsequent visits in the primary study 
population anticipated to be complete several months before those in the Russian cohort, and 
based on some differences in concomitant vaccine schedule and visit windows in the Russian 
participants, reflecting the Russian NIP, described in Section 10.10 of this protocol.  The 
safety and immunogenicity results in the Russian cohort will be summarized in a 
supplemental CSR.
The specific vaccine containing diphtheria, tetanus, acellular pertussis, hepatitis B, 
poliovirus, and Haemophilus influenzae type b (hereafter referred to as DTaP, HBV, IPV,
and Hib or Infanrix hexa) antigens will be administered concomitantly with all doses of 
20vPnC or 13vPnC (at Visits 1, 2, and 4) into a limb other than the site of 20vPnC or 
13vPnC injection.
The specific vaccine containing measles, mumps, and rubella (MMR) antigens and the 
specific vaccine containing varicella antigen are also to be administered concomitantly with 
CCI
CCI
CCI
CCI
CCI

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 13
Dose 3 (Visit 4) into a limb other than the site of 20vPnC or 13vPnC injection.  These 
vaccines are intended to be given to all participants.  However, in case of circumstances due 
to local practice/recommendations, some sites may not administer them to their participants
at Dose 3, in which case MMR and varicella vaccines will be considered nonstudy vaccines.
Local reactions (including redness, swelling, and pain at the injection site), systemic events 
(including fever, drowsiness/increased sleep, decreased appetite, and irritability), and use of 
pain/fever medication will be prompted for and collected by the participant’s parent(s)/legal 
guardian(s) daily for 7 days after each study vaccination (where Day 1 is the day of 
vaccination) in an electronic diary (e-diary).
Adverse events (AEs) will be recorded and reported from the signing of the informed consent 
document (ICD) through approximately 1 month after Dose 2 (Visit 3) and from Dose 3 
(Visit 4) through approximately 1 month after Dose 3 (Visit 5).
Serious adverse events (SAEs) and newly diagnosed chronic medical conditions (NDCMCs) 
will be collected from the signing of the ICD through 1 month after Dose 3 (Visit 5).
Blood will be drawn from all participants for immunogenicity assessments 1 month after 
Dose 2 (5 months of age, Visit 3), prior to receipt of Dose 3 (11-12 months of age, Visit 4),
and 1 month after Dose 3 (13 months of age, Visit 5).  A subset of participants (participants 
at certain investigator sites) will also have blood drawn for immunogenicity assessments 
prior to Dose 1 and prior to Dose 2.
Objectives, Estimands, and Endpoints
Primary Safety Objective
Estimands  
Primary Safety Endpoints
To describe the safety profile of 
20vPnC
In participants receiving at least 1 dose 
of investigational product and having 
safety data reported after any 
vaccination in each vaccine group:

The percentage of participants 
reporting prompted local reactions 
within 7 days after each 
vaccination 

The percentage of participants 
reporting prompted systemic 
events within 7 days after each 
vaccination

The percentage of participants 
reporting AEs from Dose 1 to 
1 month after Dose 2 and from 
Dose 3 to 1 month after Dose 3

The percentage of participants 
reporting SAEs through 1 month 
after Dose 3 

Prompted local reactions 
(redness, swelling, and pain 
at the injection site) 

Prompted systemic events 
(fever, decreased appetite, 
drowsiness/increased sleep, 
and irritability)

AEs 

SAEs

NDCMCs

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 14

The percentage of participants 
reporting NDCMCs through 1 
month after Dose 3
Primary Pneumococcal 
Immunogenicity Objectives
Estimands
Primary Pneumococcal 
Immunogenicity Endpoints
To demonstrate that the 
percentages of participants with 
predefined serotype-specific IgG 
concentrations for the 13 
serotypes in the 20vPnC group 
are noninferior to those of the 
corresponding serotypes in the 
13vPnC group at 1 month after 
Dose 2
In evaluable participants at 1 month 
after Dose 2:

For each of the 13 matched 
serotypes: difference in the 
percentages of participants with 
predefined IgG concentrations 
between the 20vPnC group and the 
13vPnC group

Pneumococcal 
IgG concentrations
To demonstrate that the 
percentages of participants with 
predefined serotype-specific IgG 
concentrations for the 7 additional 
serotypes in the 20vPnC group 
are noninferior to the lowest 
among the 13 serotypes in the 
13vPnC group at 1 month after 
Dose 2
In evaluable participants at 1 month 
after Dose 2:

For each of the 7 additional 
serotypes in 20vPnC: difference in 
the percentages of participants with 
predefined IgG concentrations 
between the 20vPnC group and the 
lowest percentage of participants 
with predefined IgG concentrations 
among the 13 serotypes from the 
13vPnC group

Pneumococcal 
IgG concentrations
To demonstrate that the serotype-
specific IgG GMCs for the 13 
serotypes in the 20vPnC group
are noninferior to those for the 
corresponding serotypes in the 
13vPnC group at 1 month after 
Dose 2
In evaluable participants at 1 month 
after Dose 2:

For each of the 13 matched 
serotypes: GMR of IgG 
concentrations from the 20vPnC 
group to the 13vPnC group 

Pneumococcal 
IgG concentrations
To demonstrate that the serotype-
specific IgG GMCs for the 7 
additional serotypes in the 
20vPnC group are noninferior to 
the lowest among the 13 
serotypes in the 13vPnC group at 
1 month after Dose 2
In evaluable participants at 1 month 
after Dose 2:

For each of the 7 additional 
serotypes in 20vPnC: GMR of IgG 
concentration from the 20vPnC 
group to that from the serotype 
with the lowest IgG GMC among 
the 13 serotypes from the 13vPnC 
group

Pneumococcal 
IgG concentrations
To demonstrate that the serotype-
specific IgG GMCs for the 13 
serotypes in the 20vPnC group
are noninferior to those for the 
corresponding serotypes in the 
13vPnC group at 1 month after 
Dose 3
In evaluable participants at 1 month 
after Dose 3:

For each of the 13 matched 
serotypes: GMR of IgG 
concentrations from the 20vPnC 
group to the 13vPnC group 

Pneumococcal 
IgG concentrations

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 15
To demonstrate that the serotype-
specific IgG GMCs for the 7 
additional serotypes in the 
20vPnC group are noninferior to 
the lowest among the 13 
serotypes in the 13vPnC group at 
1 month after Dose 3
In evaluable participants at 1 month 
after Dose 3:

For each of the 7 additional 
serotypes in 20vPnC: GMR of IgG 
concentration from the 20vPnC 
group to that from the serotype 
with the lowest IgG GMC among 
the 13 serotypes from the 13vPnC 
group

Pneumococcal 
IgG concentrations
Primary Concomitant 
Immunogenicity Objective
Estimands
Primary Concomitant 
Immunogenicity Endpoints
To demonstrate that the immune 
responses induced by concomitant 
vaccine antigens given with 
20vPnC are noninferior to 
immune responses induced by 
concomitant vaccine antigens 
given with 13vPnC at 1 month 
after Dose 3
In evaluable participants who receive 
the appropriate concomitant vaccines: 

Differences in percentages of 
participants with prespecified 
antibody levels to diphtheria 
toxoid, tetanus toxoid, pertussis 
antigens (PT, FHA, PRN), HBsAg, 
poliovirus strains, and Hib 1 month 
after Dose 3 between the 20vPnC 
and the 13vPnC groups

GMRs of antibody levels to 
measles, mumps, rubella, and 
varicella antigens from the 20vPnC 
group to the 13vPnC group 
1 month after Dose 3

Antibody levels to 
diphtheria toxoid, tetanus 
toxoid, and pertussis 
antigens (PT, FHA, PRN)

Antibody levels to HBsAg

Antibody levels to 
poliovirus strains (types 1, 
2, and 3) 

Antibody levels to Hib

Antibody levels to measles, 
mumps, rubella, and 
varicella virus
Secondary Pneumococcal 
Immunogenicity Objective
Estimands
Secondary Pneumococcal 
Immunogenicity Endpoints
To further describe the immune 
responses induced by 20vPnC
In evaluable participants:

For each of the 13 matched 
serotypes: difference in the 
percentages of participants with 
predefined IgG concentrations 
between the 20vPnC group and the 
13vPnC group at 1 month after 
Dose 3

For each of the 7 additional 
serotypes in 20vPnC: difference in 
the percentages of participants with 
predefined IgG concentrations 
between the 20vPnC group and the 
lowest percentage of participants 
with predefined IgG concentrations 
among the 13 serotypes from the 
13vPnC group at 1 month after 
Dose 3

For each of the 20 serotypes in 
20vPnC: OPA GMTs 1 month after 

Pneumococcal IgG 
concentrations 

Pneumococcal OPA titers

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 16
Dose 2 and 1 month after Dose 3 in 
each vaccine group
•
For each of the 20 serotypes in 
20vPnC: GMFRs in IgG 
concentrations from before Dose 3 
to 1 month after Dose 3 in each 
vaccine group
Secondary Concomitant 
Immunogenicity Objective
Estimand
Secondary Concomitant 
Immunogenicity Endpoints
To further describe the immune 
responses induced by specific 
concomitant vaccine antigens 
given with 20vPnC or 13vPnC
In evaluable participants who receive 
appropriate concomitant vaccines:
•
Differences in percentages of 
participants with prespecified 
antibody levels to diphtheria 
toxoid, tetanus toxoid, pertussis 
antigens (PT, FHA, PRN), 
poliovirus strains, and Hib 1 month 
after Dose 2 between the 20vPnC 
and the 13vPnC groups
•
Antibody levels to 
diphtheria toxoid, tetanus 
toxoid, and pertussis 
antigens (PT, FHA, PRN) 
•
Antibody levels to 
poliovirus strains (types 1, 
2, and 3) 
•
Antibody levels to Hib
In addition to these objectives, estimands, and endpoints, the safety and immunogenicity of 
the pneumococcal immune responses are described for the Russian cohort (Section 10.10.3).
Number of Participants
Approximately 1200 participants will be enrolled in the primary study population.
An additional approximately 60 participants will be enrolled in the Russian cohort.
Approximate Duration of Participation for Each Participant
Each participant in the primary study population will participate in the study for 
approximately 11 months.
Participants in the Russian cohort will participate in the study for approximately 11 to
14 months (see Section 10.10 for details).
CCI

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 17
Statistical Methods
Safety Objective
The primary safety objective will be evaluated by descriptive summary statistics for local 
reactions, systemic events, and AEs, including SAEs and NDCMCs, for each vaccine group.  
A 3-tier approach will be used to summarize AEs for the primary study population.
Pneumococcal Immunogenicity Objectives
The primary pneumococcal immunogenicity objectives for the primary study population will 
be evaluated by formal hypothesis tests for noninferiority (NI) of 20vPnC to 13vPnC based 
on serotype-specific IgG results.
The NI for a serotype based on percentages of participants with predefined serotype-specific 
IgG concentrations at 1 month after Dose 2 will be declared if the lower bound of the 2-sided 
95% confidence interval (CI) for the between-group difference in percentage 
(20vPnC – 13vPnC) is greater than –10% (10% NI margin) for that serotype. The NI for a 
serotype based on serotype-specific IgG GMCs at 1 month after Dose 2 will be declared if
the lower bound of the 2-sided 95% CI for the IgG GMR of the 20vPnC group relative to the 
13vPnC group is greater than 0.5 (2-fold NI margin) for that serotype. The NI of the IgG 
GMCs at 1 month after Dose 3 will be assessed in a similar way.
Additionally, pneumococcal immunogenicity will be further characterized. 
Concomitant Immunogenicity Objectives
The primary concomitant immunogenicity objective for the primary study population will be 
evaluated by formal hypothesis tests for NI of the 20vPnC group to the 13vPnC group. At 
1 month after Dose 3, for each antigen of diphtheria toxoid, tetanus toxoid, pertussis 
(PT, FHA, PRN), HBsAg, poliovirus strains, and Hib, NI will be declared if the lower bound 
of the 2-sided 95% CI for the difference in percentage (20vPnC – 13vPnC) of participants 
with prespecified antibody levels is greater than –10% (10% NI margin).  At 1 month after 
Dose 3, NI for each of the antigens of measles, mumps, rubella, and varicella will be declared 
if the lower bound of the 2-sided 95% CI for the GMR of the 20vPnC group relative to the 
13vPnC group is greater than 0.5 (2-fold NI criterion).
CCI
CCI

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 18
Concomitant immunogenicity for the primary study population will be further described 
using summary statistics for the percentages of participants with prespecified antibody levels 
to diphtheria toxoid, tetanus toxoid, pertussis antigens (PT, FHA, PRN), poliovirus strains,
and Hib 1 month after Dose 2.
The Russian cohort data will be summarized descriptively and separately from the primary 
study population data (see Section 10.10.3).
1.2. Schema
Not applicable.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 19
1.3. Schedule of Activities (SoA)
The SoA table provides an overview of the protocol visits and procedures.  Refer to the Study Assessments and Procedures section of 
the protocol for detailed information on each procedure and assessment required for compliance with the protocol.  
Please see Section 10.10.2 for the SoA for the Russian cohort.
The investigator may schedule visits (unplanned visits) in addition to those listed in the SoA table, in order to conduct evaluations or 
assessments required to protect the well-being of the participant.
Visit Number
1
2
3
4
5
Visit Description
Dose 1 Visit
Dose 2 Visit
Dose 2 
Follow-up Visit
Dose 3 Visit
Dose 3 
Follow-up Visit
Visit Window (Days)
≥42 to ≤112 
Days After
Birth
42 to 63 Days
After Visit 1
28 to 42 Days 
After Visit 2
335 to 386 Days 
of Age
28 to 42 Days 
After Visit 4
Obtain informed consent
X
Assign participant number via the IRT
X
Review inclusion and exclusion criteria
X
Record demography
X
Perform clinical assessment, including 
medical history
X
Record vaccine history
X
Provide parent(s)/legal guardian(s) with a 
contact card
X
Obtain prevaccination temperature
(measured as appropriate for age)
X
X
X
Record nonstudy vaccinations and 
concomitant medicationsa
X
X
X
X
X

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 20
Visit Number
1
2
3
4
5
Visit Description
Dose 1 Visit
Dose 2 Visit
Dose 2 
Follow-up Visit
Dose 3 Visit
Dose 3 
Follow-up Visit
Visit Window (Days)
≥42 to ≤112 
Days After
Birth
42 to 63 Days
After Visit 1
28 to 42 Days 
After Visit 2
335 to 386 Days 
of Age
28 to 42 Days 
After Visit 4
Record vaccines administered during 
pregnancy and intrapartum antibiotic use 
(yes/no) (if available)
Xb
Review temporary delay criteria
X
X
X
X
X
Review continued eligibility
X
X
X
X
Assign randomization number
X
Obtain ~5-mL blood sample
X
Xc
X
Administer investigational product in the 
left thighe
X
X
X
Administer specific concomitant vaccines as 
applicable for visit
Xf
Xf
Xf,g
Observe and record any reactions for 
30 minutes after investigational vaccine 
administration
X
X
X
Provide parent(s)/legal guardian(s) with an 
e-diary (device or application, as 
appropriate), digital thermometer, and 
measuring device and instruct to collect 
prompted local reactions and systemic 
events 7 days after vaccinationh
X
X
X
Review e-diaryi
X
X
X
Collect e-diary (if applicable)
X
X
CCI
CCI

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 21
Visit Number
1
2
3
4
5
Visit Description
Dose 1 Visit
Dose 2 Visit
Dose 2 
Follow-up Visit
Dose 3 Visit
Dose 3 
Follow-up Visit
Visit Window (Days)
≥42 to ≤112 
Days After
Birth
42 to 63 Days
After Visit 1
28 to 42 Days 
After Visit 2
335 to 386 Days 
of Age
28 to 42 Days 
After Visit 4
Record and report AEsj
X-----------------------------------------X
X -------------------X
Record and report SAEs and NDCMCsj,k
X-------------------------------------------------------------------------------------X
Abbreviations: DTaP = diphtheria, tetanus, and acellular pertussis vaccine; e-diary = electronic diary; HBV = hepatitis B virus; Hib = Haemophilus influenzae
type b; IPV = inactivated poliovirus vaccine; IRT = interactive response technology; NDCMC = newly diagnosed chronic medical condition.
a.
Record concomitant medications used to treat SAEs and NDCMCs from the signing of the ICD to the final visit (Visit 5) .
b.
Vaccines administered during pregnancy and intrapartum antibiotic use (yes or no) will be collected at Visit 1 only (if available).
c.
Blood sample will be collected prior to vaccination.
e.
Remind the participant’s parent(s)/legal guardian(s) that the use of prophylactic antipyretic/pain medication, while permitted, is not recommended on the 
day of investigational product administration (before or after vaccination).  If symptoms develop, the use of antipyretic/pain medication is allowed.  
f.
The participant will receive a specific vaccine containing DTaP, HBV, IPV, and Hib antigens at approximately 2, 4, and 11 to 12 months of age (Visit 1, 
Visit 2, and Visit 4, respectively). This vaccine(s) will be given in a limb other than the site of administration of 20vPnC or 13vPnC.
g.
Specific concomitant vaccines containing measles, mumps, rubella (MMR) and varicella antigens are also to be administered at approximately 11 to 12 
months of age with Dose 3 (Visit 4).  These vaccines will be administered in a limb other than the site of administration of 20vPnC or 13vPnC and are 
intended to be given to all participants.  However, in case of circumstances due to local practice/recommendations, some sites may not administer them to 
their participants with Dose 3, in which case MMR and varicella vaccines will be considered nonstudy vaccines.
h.
The participant’s parent(s)/legal guardian(s) will record prompted local reactions and systemic events in an e-diary for the 7 days following each dose of 
20vPnC or 13vPnC. Use of antipyretic/pain medications will also be prompted for and collected daily in the e-diary for 7 days after vaccination.  The 
participant’s parent(s)/legal guardian(s) will be instructed to contact the study staff if the participant experiences redness or swelling >14 caliper units, 
severe pain at the 20vPnC or 13vPnC injection site, a fever >40.0°C (>104.0°F), an emergency room visit, or hospitalization.
i.
Designated site staff will review e-diary data online at frequent intervals (daily is optimal) for the 7 days following each dose of 20vPnC or 13vPnC to 
evaluate participant compliance and reported events as part of the ongoing safety review.
j.
If the parent(s)/legal guardian(s) consents, participants withdrawn from the study will have any new AEs, SAEs, and NDCMCs collected for 1 month after 
their last study vaccination.
k.
An NDCMC is a significant disease or medical condition, not previously identified, that is expected to be persistent or is otherwise long-lasting in its 
effects.
CCI

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 22
2. INTRODUCTION
Pneumococcal Disease
Streptococcus pneumoniae are gram-positive encapsulated cocci that are a leading cause of 
bacteremia, bacterial meningitis, pneumonia, and acute otitis media (AOM) and continue to 
be a major global public health concern.1,2,3 Serious pneumococcal disease may occur at any 
age; however, children <5 years and adults ≥65 years of age are at particularly increased 
risk.4  Individuals with certain comorbidities and immunocompromising conditions are also 
at risk, especially persons with chronic heart, lung, liver, and renal disease, as well as those 
who are functionally asplenic.  The global burden of pneumococcal disease has been 
substantially impacted by pneumococcal conjugate vaccines.  S pneumoniae caused an 
estimated 14.5 million cases of serious disease and 826,000 deaths annually in children 
<5 years of age prior to introduction of pneumococcal conjugate vaccines.2 It has been 
estimated that in 2015, several years following introduction of pneumococcal conjugate 
vaccines into the national infant immunization programs of more than 100 countries, the 
global disease burden had declined, but S pneumoniae still accounted for 2.6 million cases of 
severe pneumococcal disease, 332,000 deaths in children <5 years of age, and 11% of deaths 
in children between the ages of 1 and 5 years.5
The overall invasive pneumococcal disease (IPD) burden was estimated in 2013 to have 
decreased approximately 90% in the population <5 years of age in the United States since the 
introduction of pneumococcal conjugate vaccines; however, there was a slight increase in the 
proportions of IPD cases associated with hospitalization (63% to 71%), and the IPD case 
fatality rate was also slightly but statistically significantly increased (2% to 3%) in that age 
group.6  This is due to the decrease in disease due to the serotypes in 7-valent pneumococcal 
conjugate vaccine (7vPnC; Prevnar®/Prevenar®) and 13vPnC.  However, disease due to 
serotypes not covered by those vaccines remains and causes significant morbidity and 
mortality.
National IPD surveillance data in England and Wales for the epidemiological year 
2016-2017, approximately 10 years after the introduction of 7vPnC in the national infant 
immunization program and 6 years after the introduction of 13vPnC, the overall incidence of 
IPD was 9.87 per 100,000 population, with an incidence of 13.90 per 100,000 population 
<2 years of age.7 The data for England and Wales are consistent with the patterns observed 
in data from the European Union (EU) for 2017, which showed an overall IPD incidence of 
6.2 cases per 100,000 population, with an incidence of 14.5 per 100,000 infants under 1 year 
of age.8  Pediatric surveillance studies conducted between 2007 and 2013 in 8 US children’s 
hospitals, and between 1997 and 2010 in a referral center in Utah, found case fatality rates of 
10% and 13% with pneumococcal meningitis, respectively.  These studies also found that 
between 52% and 63% of children surviving pneumococcal meningitis experience neurologic 
sequelae.9,10  More recent pediatric surveillance conducted between 2014 and 2017 in 8 US 
children’s hospitals following 13vPnC introduction in 2010 showed that 76.1% of residual 
IPD was caused by non-13vPnC serotype isolates. Serotypes 10A, 12F, 15B/15C, 22F, and 
33F accounted for 36% of isolates causing IPD.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 23
The most common clinical presentations of IPD due to non-13vPnC serotypes included 
bacteremia (49.6%), meningitis (19.1%), and pneumonia (18.8%).11  These data demonstrate 
the continued need for expanded serotype coverage.
Surveillance studies conducted in 2010-2012 by the Centers for Disease Control and 
Prevention (CDC) found that S pneumoniae remains among the most common pathogens 
identified in community-acquired pneumonia (CAP) requiring hospitalization in the United 
States in both children and adults.12,13 It was the most common bacterial cause in children 
<2 years of age, even in the setting of a 43% reduction in CAP hospitalizations over the 
previous decade between 1997-1999 and 2007-2009, due to the introduction to 7vPnC.12,14
Surveillance reported in 2017 by the European Centre for Disease Prevention and Control 
(ECDC) showed that among cases of IPD for which the clinical presentation was known 
across all age groups, septicemia was reported in 35%, bacteremic pneumonia in 42%, 
meningitis in 19%, meningitis and septicemia in 1%, and other clinical syndromes in 3% of 
cases. The most common clinical presentations in children <5 years of age were septicemia 
and bacteremic pneumonia equally (1-4 year olds), and meningitis (<1 year olds).8  Data 
from nationwide surveillance networks in France for the year 2012 showed the rate of IPD 
among children <2 years of age to be 17.2 per 100,000 population, with the incidence of 
pneumococcal meningitis among children <2 years of age to be 4.5 per 100,000 population. 
Of note, meningitis comprised 26.4%, 7.8%, and 19.6% of all cases of IPD in children <2 
years of age, 2 through 4 years of age, and 5 through 15 years of age, respectively.15 The 
relatively high rates of meningitis among these pediatric populations are of particular concern 
not only because of the severity of the acute disease, but also because of the neurological 
sequelae that are frequently associated with meningitis. These data suggest that 
S pneumoniae remains an important cause of serious disease in the United States and 
worldwide.
AOM is a common childhood illness, with 2011 visit rates of 0.82 and 0.81 visits for 
AOM/child-year in children <2 years of age and 2 to 6 years of age, respectively, and 
represents a significant medical burden.16  S pneumoniae is one of the common bacterial 
causes of AOM, and accounted for an estimated 850,000 outpatient and 125,000 emergency 
room visits in the United States in 2004 in children <5 years of age, representing a significant 
burden on the healthcare system.3 While AOM is generally not considered a serious disease, 
it does carry the risk of more serious complications.  These complications can range from the 
development of chronic or recurrent otitis media necessitating surgical intervention 
(tympanostomy tube placement), and accompanied by hearing losses with potential 
developmental and language delays, to invasive extension leading to mastoiditis and 
meningitis.
Although the introduction of pneumococcal conjugate vaccines into the United States and 
other national infant immunization programs has brought about substantial reductions in the 
various manifestations of pneumococcal disease in pediatric (infants and children) 
populations, a substantial burden of pneumococcal disease remains. Serotypes not included 
in existing vaccines continue to contribute significantly to morbidity and mortality.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 24
Vaccines to Prevent Pneumococcal Disease
Pneumococcal Polysaccharide Vaccines
The polysaccharide capsule has been identified as an important virulence factor for this 
pathogen.  While more than 95 pneumococcal serotypes, differentiated by their capsular 
polysaccharide composition, have been identified, serious disease is generally caused by a 
smaller subset of serotypes.17,18  Anticapsular antibodies directed against the specific 
serotype bind to the capsule and promote complement-mediated opsonophagocytic killing 
and clearance of the organism.19  Pneumococcal disease can be prevented with 
polysaccharide-based vaccines that induce antibody responses with functional 
(opsonophagocytic) activity and target the capsular serotypes responsible for disease.20
Vaccines containing free polysaccharides have been licensed since the 1970s.  One such 
vaccine, the 23-valent pneumococcal polysaccharide vaccine (PPSV23), has been licensed in 
the United States since 1983.21,22  PPSV23 contains capsular polysaccharides for 
23 serotypes (1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19F, 19A, 
20, 22F, 23F, and 33F).  Pneumococcal vaccines containing free polysaccharides such as 
PPSV23 elicit a T-cell–independent immune response.  Unconjugated polysaccharide 
vaccines do not induce robust responses in certain populations (eg, immunocompromised 
persons, and children <2 years of age), nor do they generate immunologic memory, so that 
their protective effect wanes over 2 to 5 years.4,22,23,24  Moreover, their ability to prevent 
nonbacteremic pneumonia, CAP, and AOM is limited or lacking.20,24,25,26,27  In addition, 
polysaccharide vaccines do not reduce vaccine-type (VT) nasopharyngeal carriage, which is 
important for herd immunity.27  PPSV23 is not recommended for children <2 years of age 
and only recommended in children >2 years of age who are at high risk for IPD to provide 
some degree of protection from disease caused by serotypes not covered by existing 
pneumococcal conjugate vaccines.20
Pneumococcal Polysaccharide Conjugate Vaccines
Pneumococcal conjugate vaccines contain polysaccharides that are covalently linked 
(conjugated) to an immunogenic protein.  This modification results in T-cell–dependent 
immune responses, which have been shown to be protective in young children, older adults, 
and populations with high-risk conditions.23,28  7vPnC was the first pneumococcal conjugate 
vaccine to be licensed (2000) and was indicated for prevention of pneumococcal disease in 
infants and young children on the basis of efficacy studies.  7vPnC contained capsular 
polysaccharide conjugates for 7 pneumococcal serotypes (4, 6B, 9V, 14, 18C, 19F, and 23F), 
each covalently linked to cross-reactive material 197 (CRM197), a nontoxic variant of 
diphtheria toxin.  These 7 serotypes were responsible for approximately 80% to 90% of IPD 
in children <5 years of age in the United States and approximately 60% to 80% of IPD in the 
same age group in Europe at that time (1998-2000).29,30,31,32,33  These serotypes also 
accounted for a high proportion of antibiotic-resistant strains.34  7vPnC demonstrated 
efficacy against VT IPD, pneumonia, and AOM in large randomized, controlled efficacy 
studies in infants.35,36

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 25
The 7vPnC components contained in a related pneumococcal conjugate vaccine also were 
demonstrated to be efficacious against clinically/radiographically defined pneumonia.37,38,39,40  
Following introduction of 7vPnC, reduction of nasopharyngeal carriage and transmission has 
resulted in indirect herd effects, with a 92% reduction of 7vPnC VT IPD in older adults 
≥65 years of age.41
13vPnC was developed to expand serotype coverage and was licensed in the United States in 
2010.  In the EU, 13vPnC was initially indicated for use in infants from 6 weeks to 5 years of 
age, but the indication was later expanded to include children and adolescents up to 17 years 
of age.  13vPnC includes the same S pneumoniae serotypes as 7vPnC and an additional 
6 polysaccharide conjugates for serotypes 1, 3, 5, 6A, 7F, and 19A.28,32,42  The vaccine was 
licensed for use in infants and young children based on comparisons of serotype-specific 
serum IgG antibody concentrations to 7vPnC, with supportive data to demonstrate the 
functional activity of the immune responses.  13vPnC was later licensed in adults based on 
demonstration of efficacy against CAP due to serotypes contained in 13vPnC in adults 
65 years of age and older.43  13vPnC has replaced 7vPnC and is licensed in the United States 
and many other countries, with national recommendations for use in children and older 
adults.44,45,46,47  It has also been prequalified by the World Health Organization (WHO) for 
use in national infant immunization programs in lower- and middle-income countries.48,49  
Surveillance data from several countries following introduction of 13vPnC into the routine 
infant immunization program have demonstrated vaccine effectiveness against 13vPnC VT 
IPD in the vaccinated population.50,51,52
Development of 20vPnC
The 20vPnC candidate is modeled after 7vPnC and 13vPnC, and contains polysaccharides of 
capsular serotypes of S pneumoniae, each covalently linked to CRM197. The amount of 
polysaccharide (2.2 μg/dose) selected for each new serotype (8, 10A, 11A, 12F, 15B, 22F, 
and 33F) contained in the 20vPnC candidate mirrors the approach taken for the addition of 
the 6 new serotypes when developing 13vPnC.  The 20vPnC candidate contains the same 
components as 13vPnC, including the 13 polysaccharide conjugates, excipients 
(polysorbate 80, succinate buffer, sodium chloride), and aluminum phosphate, in addition to 
the 7 new polysaccharide conjugates.  Additional epidemiology data of the 7 serotypes and 
the preclinical program are described in the 20vPnC investigator’s brochure (IB).  The 
vaccine is being developed for use in pediatric and adult populations.
2.1. Study Rationale
 The targeted age of the 
population for this study, infants born at >36 weeks of gestation and ≥42 to ≤112 days of age, 
has been selected as the routinely recommended vaccination schedule for pneumococcal 
conjugate vaccines and other vaccines in infants, starting at approximately 2 months of age.
CCI
CCI

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 26
The participants will be administered either 20vPnC or 13vPnC in a series of 2 infant doses 
and 1 toddler dose (at 2, 4, and 11-12 months of age).  Data will also be generated on key 
routine pediatric vaccines given concomitantly with 20vPnC or 13vPnC.
2.2. Background
20vPnC is being developed to further expand protection against the global burden of 
vaccine-preventable pneumococcal disease in children and adults over that of 13vPnC.  
20vPnC contains the serotypes present in 13vPnC, and 7 new serotypes (8, 10A, 11A, 12F, 
15B, 22F, and 33F) individually conjugated to CRM197.  As noted above, 20vPnC uses the 
same platform and contains the same excipients as 7vPnC and 13vPnC.  These 7 additional 
serotypes were selected based on their relative prevalence as a cause of IPD, their 
generalized geographic distribution, and other factors that would support inclusion, such as 
the presence of antibiotic resistance (11A, 15B), association with outbreaks (8, 12F), and 
greater disease severity (eg, meningitis, mortality) (10A, 11A, 22F).53,54,55,56,57,58,59,60,61,62,63,64  
These 7 serotypes have a long-standing association with serious pneumococcal disease and 
are responsible for a substantial burden of remaining pneumococcal disease.
The incidence of IPD due to these 7 serotypes in children <5 years of age has remained 
relatively stable or slightly increased over the past several years, and these serotypes cause a 
significant amount of IPD in children.65,66,67,68,69,70,71  These 7 serotypes contribute to the 
burden of IPD in the United States and elsewhere. It is estimated that between 2015 and 
2016, these 7 serotypes accounted for 34% to 39% of IPD in children in the United States.72
In the EU, according to the ECDC annual IPD epidemiological report, in 2017, 
approximately 75% of cases in children <5 years of age were caused by a serotype not in 
13vPnC, increased from 63% in 2013.  Five of the 10 most common serotypes included 
serotypes 8, 10A, 11A, 12F, and 22F, with serotypes 8, 10A, 12F, and 24F being among the 
most common in children in this age group.8
A meta-analysis of serotypes causing IPD in children <5 years of age in regions of the world 
that have introduced higher-valent pneumococcal conjugate vaccines (such as 13vPnC) 
showed that, overall, these 7 serotypes accounted for approximately 70% of disease not due 
to the 13vPnC vaccine types.67
2.2.1. Clinical Overview
Safety and immunogenicity data from a 20vPnC Phase 1 study (B7471001) conducted in 
healthy adults 18 to 49 years of age demonstrated that the vaccine induces immune responses 
to the 20 vaccine serotypes and has a safety profile consistent with other pneumococcal 
conjugate vaccines.  These data supported clinical development in other populations, 
including pediatrics.
A Phase 2 study (B7471003) of 20vPnC in healthy infants was started in April 2018. In the 
study, 460 US participants ≥42 to ≤98 days of age were randomized to receive either blinded 
20vPnC or 13vPnC. The study is currently ongoing, but safety and immunogenicity data are 
available from the study.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 27
20vPnC was well tolerated in the infants and the safety profile was similar to that of the 
13vPnC group in the study and consistent with other pneumococcal conjugate vaccines. 
Immune responses (either IgG GMCs or percentages of participants meeting a predefined 
IgG concentration) after 3 doses of 20vPnC were similar to those in the 13vPnC group.  
These data support continued development of 20vPnC in the pediatric population.
2.3. Benefit/Risk Assessment
13vPnC is a licensed vaccine and the most common AEs noted in children <5 years of age 
after vaccination are primarily related to local reactions (injection site pain or tenderness, 
redness, and swelling) and systemic events (fever, irritability, decreased appetite, and 
increased sleep).
The 20vPnC investigational product contains the same components and excipients as 
13vPnC, along with the polysaccharide conjugates for the 7 additional pneumococcal 
serotypes.  Thus, the AE profile of 20vPnC is expected to be similar to 13vPnC, but AEs may 
be different with the investigational 20vPnC.
In a randomized, active-controlled, double-blind study with a 2-arm parallel design 
(B7471003), 20vPnC was administered to 460 infants ≥42 to ≤98 days of age naïve to 
pneumococcal vaccine. The vaccine was well tolerated and the AE profile was consistent 
with events commonly seen in this age group.  The most common AEs after 20vPnC 
administration were local reactions (pain, redness, and swelling at the injection site) and 
systemic events (irritability, drowsiness/increased sleep, and decreased appetite).
As with any vaccine, an allergic reaction can occur. The allergic reaction can vary from skin 
rash to swelling of the face or lips, wheezing, and/or shortness of breath. A severe allergic 
reaction (anaphylactic shock, collapse, or shock-like state [hypotonic-hyporesponsive 
episode]) may also occur. There may also be additional risks related to the vaccines 
administered in the study that are not known at this time.
The most common adverse reactions observed after administration of a specific vaccine 
containing DTaP, HBV, IPV, and Hib antigens were loss of appetite, abnormal crying, 
irritability, restlessness, fever, fatigue, and injection site reactions including swelling, pain,
and redness.
The most common adverse reactions observed after administration of a specific MMR 
vaccine were fever, injection site reactions including pain, swelling, bruising, and redness,
rash, and upper respiratory tract infection.
The most common adverse reactions observed after administration of a specific varicella 
vaccine were injection site pain, redness, and swelling, fever, rash, upper respiratory tract 
infection, and irritability.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 28
Risks that may be associated with study procedures include risks from blood draws, 
including pain, swelling, bruising, and infection where blood is taken. Safety assessments 
described in the protocol and ongoing review of safety data by the investigator and sponsor 
study team will serve to monitor and mitigate these risks.
13vPnC is approved for the prevention of pneumococcal disease due to the serotypes in the 
vaccine, and may provide a clinical benefit to those receiving it.
In the B7471003 study, 20vPnC induced immune responses to the pneumococcal serotypes 
in the vaccine.  This suggests that protection against pneumococcal disease will be similar to 
13vPnC.  If 20vPnC is successful in Phase 3 studies, and approved, it is anticipated to 
provide a public health benefit by reducing the burden of pneumococcal disease (invasive 
and noninvasive) due to vaccine serotypes.
Pfizer considers that the available information from Study B7471003 with 20vPnC, the 
available safety profile of similar pneumococcal conjugate vaccines (ie, 7vPnC and 13vPnC), 
and the limited risks from study procedures support a favorable benefit-risk profile for 
20vPnC and this study.
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of 20vPnC may be found in the IB, which is the single reference safety 
document (SRSD) for this study. The SRSD for the 13vPnC active comparator vaccine is the 
EU summary of product characteristics (SmPC).  The SRSD for the vaccine containing 
DTaP, HBV, IPV, and Hib, the MMR vaccine, and the varicella vaccine is the EU SmPC.
3. OBJECTIVES, ESTIMANDS, AND ENDPOINTS
Primary Safety Objective
Estimands
Primary Safety Endpoints
To describe the safety profile of 
20vPnC
In participants receiving at least 1 dose 
of investigational product and having 
safety data reported after any 
vaccination in each vaccine group:
•
The percentage of participants 
reporting prompted local reactions 
within 7 days after each 
vaccination 
•
The percentage of participants 
reporting prompted systemic 
events within 7 days after each 
vaccination
•
The percentage of participants 
reporting AEs from Dose 1 to 
1 month after Dose 2 and from 
Dose 3 to 1 month after Dose 3
•
The percentage of participants 
reporting SAEs through 1 month 
after Dose 3
•
Prompted local reactions 
(redness, swelling, and pain 
at the injection site) 
•
Prompted systemic events 
(fever, decreased appetite, 
drowsiness/increased sleep, 
and irritability)
•
AEs 
•
SAEs
•
NDCMCs
CCI
CCI

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 29

The percentage of participants 
reporting NDCMCs through 1 
month after Dose 3
Primary Pneumococcal 
Immunogenicity Objectives
Estimands
Primary Pneumococcal 
Immunogenicity Endpoints
To demonstrate that the 
percentages of participants with 
predefined serotype-specific IgG 
concentrations for the 13 
serotypes in the 20vPnC group 
are noninferior to those of the 
corresponding serotypes in the 
13vPnC group at 1 month after 
Dose 2
In evaluable participants at 1 month 
after Dose 2:

For each of the 13 matched 
serotypes: difference in the 
percentages of participants with 
predefined IgG concentrations 
between the 20vPnC group and the 
13vPnC group

Pneumococcal 
IgG concentrations
To demonstrate that the 
percentages of participants with 
predefined serotype-specific IgG 
concentrations for the 7 additional 
serotypes in the 20vPnC group 
are noninferior to the lowest 
among the 13 serotypes in the 
13vPnC group at 1 month after 
Dose 2
In evaluable participants at 1 month 
after Dose 2:

For each of the 7 additional 
serotypes in 20vPnC: difference in 
the percentages of participants with 
predefined IgG concentrations 
between the 20vPnC group and the 
lowest percentage of participants 
with predefined IgG concentrations 
among the 13 serotypes from the 
13vPnC group

Pneumococcal 
IgG concentrations
To demonstrate that the 
serotype-specific IgG GMCs for 
the 13 serotypes in the 20vPnC 
group are noninferior to those for 
the corresponding serotypes in the 
13vPnC group at 1 month after 
Dose 2
In evaluable participants at 1 month 
after Dose 2:

For each of the 13 matched 
serotypes: GMR of IgG 
concentrations from the 20vPnC 
group to the 13vPnC group 

Pneumococcal 
IgG concentrations
To demonstrate that the 
serotype-specific IgG GMCs for
the 7 additional serotypes in the 
20vPnC group are noninferior to 
the lowest among the 13 
serotypes in the 13vPnC group at 
1 month after Dose 2
In evaluable participants at 1 month 
after Dose 2:

For each of the 7 additional 
serotypes in 20vPnC: GMR of IgG 
concentration from the 20vPnC 
group to that from the serotype 
with the lowest IgG GMC among 
the 13 serotypes from the 13vPnC 
group

Pneumococcal 
IgG concentrations
To demonstrate that the 
serotype-specific IgG GMCs for
the 13 serotypes in the 20vPnC
group are noninferior to the 
GMCs for the corresponding 
serotypes in the 13vPnC group at 
1 month after Dose 3
In evaluable participants at 1 month 
after Dose 3:

For each of the 13 matched 
serotypes: GMR of IgG 
concentrations from the 20vPnC 
group to the 13vPnC group 

Pneumococcal 
IgG concentrations

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 30
To demonstrate that the 
serotype-specific IgG GMCs for
the 7 additional serotypes in the 
20vPnC group are noninferior to 
the lowest among the 13 
serotypes in the 13vPnC group at 
1 month after Dose 3
In evaluable participants at 1 month 
after Dose 3:

For each of the 7 additional 
serotypes in 20vPnC: GMR of IgG 
concentration from the 20vPnC 
group to that from the serotype 
with the lowest IgG GMC among 
the 13 serotypes from the 13vPnC 
group

Pneumococcal 
IgG concentrations
Primary Concomitant 
Immunogenicity Objective
Estimands
Primary Concomitant 
Immunogenicity Endpoints
To demonstrate that the immune 
responses induced by concomitant 
vaccine antigens given with 
20vPnC are noninferior to 
immune responses induced by 
concomitant vaccine antigens 
given with 13vPnC at 1 month 
after Dose 3
In evaluable participants who receive 
the appropriate concomitant vaccines: 

Differences in percentages of 
participants with prespecified 
antibody levels to diphtheria 
toxoid, tetanus toxoid, pertussis 
antigens (PT, FHA, PRN), HBsAg, 
poliovirus strains, and Hib 1 month 
after Dose 3 between the 20vPnC 
and the 13vPnC groups

GMRs of antibody levels to 
measles, mumps, rubella, and 
varicella antigens from the 20vPnC 
group to the 13vPnC group 
1 month after Dose 3

Antibody levels to 
diphtheria toxoid, tetanus 
toxoid, and pertussis 
antigens (PT, FHA, PRN)

Antibody levels to HBsAg

Antibody levels to 
poliovirus strains (types 1, 
2, and 3) 

Antibody levels to Hib

Antibody levels to measles, 
mumps, rubella, and 
varicella virus
Secondary Pneumococcal 
Immunogenicity Objective
Estimands
Secondary Pneumococcal 
Immunogenicity Endpoints
To further describe the immune 
responses induced by 20vPnC
In evaluable participants:

For each of the 13 matched 
serotypes: difference in the 
percentages of participants with 
predefined IgG concentrations 
between the 20vPnC group and the 
13vPnC group at 1 month after 
Dose 3

For each of the 7 additional 
serotypes in 20vPnC: difference in 
the percentages of participants with 
predefined  IgG concentrations 
between the 20vPnC group and the 
lowest percentage of participants
with predefined IgG concentrations 
among the 13 serotypes from the 
13vPnC group at 1 month after 
Dose 3

For each of the 20 serotypes in 
20vPnC: serotype-specific OPA 
GMTs 1 month after Dose 2 and 

Pneumococcal  IgG 
concentrations 

Pneumococcal  OPA titers

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 31
1 month after Dose 3 in each 
vaccine group
•
For each of the 20 serotypes in 
20vPnC: GMFRs in IgG 
concentrations from before Dose 3 
to 1 month after Dose 3 in each 
vaccine group
Secondary Concomitant 
Immunogenicity Objective
Estimand
Secondary Concomitant 
Immunogenicity Endpoints
To further describe the immune 
responses induced by specific 
concomitant vaccine antigens 
given with 20vPnC or 13vPnC
In evaluable participants who receive 
appropriate concomitant vaccines:
•
Differences in percentages of 
participants with prespecified 
antibody levels to diphtheria 
toxoid, tetanus toxoid, pertussis 
antigens (PT, FHA, PRN), 
poliovirus strains, and Hib 1 month 
after Dose 2 between the 20vPnC 
and the 13vPnC groups
•
Antibody levels to 
diphtheria toxoid, tetanus 
toxoid, and pertussis 
antigens (PT, FHA, PRN) 
•
Antibody levels to 
poliovirus strains (types 1, 
2, and 3) 
•
Antibody levels to Hib
CCI

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 32
(For Russian cohort–specific objectives, estimands, and endpoints, please see 
Section 10.10.3)
4. STUDY DESIGN
4.1. Overall Design
This Phase 3, multicenter, randomized, double-blind study will be conducted at investigator 
sites in the EU and Australia. Additional sites in Russia are also being sought to generate 
data in infants from that country.
The purpose 
of the study is to generate data on the safety and immunogenicity of 20vPnC in infants when 
administered in a series of 2 infant doses and 1 toddler dose (at 2, 4, and 11-12 months of 
age).  Data will also be generated on key routine pediatric vaccines given concomitantly with 
20vPnC or 13vPnC.  13vPnC will serve as an active comparator.
Approximately 1200 infants >36 weeks of gestation and ≥42 to ≤112 days of age at the time 
of consent by a parent(s)/legal guardian(s) will be enrolled in the primary study population
of the study.  Participants will be randomized in a 1:1 ratio to receive either 20vPnC or 
13vPnC (control vaccine) by site-based randomization. At 2, 4, and 11 to 12 months of age 
(Doses 1 [Visit 1], 2 [Visit 2], and 3 [Visit 4], respectively), participants will receive the 
CCI
CCI
CCI

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 33
same vaccine (either 20vPnC or 13vPnC) for all 3 doses. Blood will be drawn from all 
participants for immunogenicity assessments 1 month after Dose 2 (5 months of age), prior to 
receipt of Dose 3 (11-12 months of age), and 1 month after Dose 3 (13 months of age).  A 
subset of participants (participants at certain investigator sites) will also have blood drawn 
for immunogenicity assessments prior to Dose 1 and prior to Dose 2.
The Russian cohort will not be included in the primary study population, as the enrollment 
and subsequent visits in the primary study population are anticipated to be complete several 
months before the Russian cohort, and the concomitant vaccine schedule and visit windows 
are slightly different, reflecting the Russian NIP; these details are described in Section 10.10
of this protocol.  The safety and immunogenicity results in the Russian cohort will be 
summarized in a supplemental CSR.
On Day 1 (Visit 1, Dose 1 vaccination) of the study, participants will be assessed for 
eligibility and information will be collected, including medical history and vaccine history.  
Vaccines administered during pregnancy and intrapartum antibiotic use (yes/no) will also be 
collected (if available).  In a subset of participants (participants at selected investigator sites),
blood will be drawn prior to Dose 1.  All participants will receive Dose 1 of 20vPnC or 
13vPnC.  The 13vPnC and 20vPnC will be matched in appearance and will be prepared and 
administered by a site staff member or designee.  Specific concomitant vaccination
containing DTaP, HBV, IPV, and Hib antigens (Infanrix hexa) will also be administered at 
this visit.  Participants will be observed for 30 minutes after vaccination, and any reactions 
occurring during that time will be recorded as AEs. 
The participant’s parent(s)/legal guardian(s) will be provided with an e-diary (or e-diary 
application), digital thermometer, and measuring device and instructed to collect prompted 
local reactions (redness, swelling, and pain at the injection site) and systemic events (fever, 
decreased appetite, drowsiness/increased sleep, and irritability) occurring 7 days after each 
vaccination.  Use of antipyretic/pain medications will also be prompted for and collected 
daily in the e-diary for 7 days after vaccination.  The participant’s parent(s)/legal guardian(s) 
will be instructed to contact the study staff if the participant experiences redness or swelling 
>14 caliper units, severe pain at the 20vPnC or 13vPnC injection site, or fever >40.0°C 
(>104.0°F) in the 7 days after vaccination, or has an emergency room visit or hospitalization.
Participants will return for Visit 2 (42 to 63 days after Visit 1).  Participants will be assessed 
for continued eligibility and information will be collected from the participant’s 
parent(s)/legal guardian(s) on AEs, including nonserious AEs, SAEs, NDCMCs, and e-diary 
follow-up (as needed).  Concomitant medications used to treat SAEs and NDCMCs will be 
recorded, as will information on nonstudy vaccinations given since the last visit.  An 
NDCMC is defined as a significant disease or medical condition, not previously identified, 
that is expected to be persistent or is otherwise long-lasting in its effects.  A subset of 
participants will have blood drawn for immunogenicity assessment at this visit prior to 
Dose 2.  Dose 2 of 20vPnC or 13vPnC will be administered.  Specific concomitant 
vaccination containing DTaP, HBV, IPV, and Hib antigens will also be administered at this 
visit.  Participants will be observed for 30 minutes after vaccination and any reactions 

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 34
occurring during that time will be recorded as AEs.  The participant’s parent(s)/legal 
guardian(s) will be instructed to collect prompted local reactions and systemic events 
occurring 7 days after vaccination.  Use of antipyretic/pain medications will also be 
prompted for and collected daily in the e-diary for 7 days after vaccination.  The participant’s 
parent(s)/legal guardian(s) will be instructed to contact the study staff if the participant 
experiences redness or swelling >14 caliper units, severe pain at the 20vPnC or 13vPnC 
injection site, or fever >40.0°C (>104.0°F) in the 7 days after vaccination or has an 
emergency room visit or hospitalization.
Participants will return for Visit 3 (28 to 42 days after Visit 2).  Participants will be assessed 
for continued eligibility and information will be collected from the participant’s 
parent(s)/legal guardian(s) on AEs, SAEs, NDCMCs, and e-diary follow-up (as needed).  The 
e-diary will be collected (if applicable).  Concomitant medications used to treat SAEs and 
NDCMCs will be recorded, as will information on nonstudy vaccinations given since the last 
visit.  Blood will be taken for immunogenicity assessment.
Participants will return for Visit 4 (335 to 386 days of age).  Participants will be assessed for 
continued eligibility and information will be collected from the participant’s parent(s)/legal 
guardian(s) on SAEs and NDCMCs.  Concomitant medications used to treat SAEs and 
NDCMCs will be recorded, as will information on nonstudy vaccinations given since the last 
visit.  Blood will be taken for immunogenicity assessment prior to vaccination.  Dose 3 will 
be administered at this visit.  Specific concomitant vaccine containing DTaP, HBV, IPV, and 
Hib antigens will also be administered.  
Specific vaccines containing MMR and varicella antigens are also to be administered at this 
visit.  The MMR and varicella vaccines are intended to be given to all participants.  
However, in case of circumstances due to local practice/recommendations, some sites may 
not administer them to their participants at Dose 3, in which case MMR and varicella 
vaccines will be considered nonstudy vaccines. Participants will be observed for 30 minutes 
after vaccination and any reactions occurring during that time will be recorded as AEs.  The 
participant’s parent(s)/legal guardian(s) will be reissued an e-diary (if applicable).  The 
participant’s parent(s)/legal guardian(s) will be instructed to collect prompted local reactions 
and systemic events occurring 7 days after vaccination.  Use of antipyretic/pain medications 
will also be prompted for and collected daily in the e-diary for 7 days after vaccination.  The 
participant’s parent(s)/legal guardian(s) will be instructed to contact the study staff if the 
participant experiences redness or swelling >14 caliper units, severe pain at the 20vPnC or
13vPnC injection site, or fever >40.0°C (>104.0°F) in the 7 days after vaccination, or has an 
emergency room visit or hospitalization.
All participants will return for Visit 5 (28 to 42 days after Visit 4).  Information will be 
collected from the participant’s parent(s)/legal guardian(s) on AEs, SAEs, NDCMCs, and 
e-diary follow-up (as needed).  Concomitant medications used to treat SAEs or NDCMCs 
will be recorded, as will information on nonstudy vaccinations given since the last visit.  
Blood will be taken for immunogenicity assessment.  Other licensed nonstudy vaccines may 
be administered after the blood draw at this visit.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 35
In the case of extreme circumstances, such as natural disasters or a pandemic, visits for 
follow-up or procedures may need to be conducted through other means (eg, telephone calls).
(For Russian cohort–specific differences, please see Section 10.10.1.)
4.1.1. Approximate Duration of Participation for Each Participant
Each participant in the primary study population will participate in the study for 
approximately 11 months.
Participants in the Russian cohort will participate in the study for approximately 11 to 
14 months (see Section 10.10).
4.1.2. Approximate Number of Participants
Approximately 1200 participants will be enrolled in the primary study population.
Approximately 60 additional participants will be enrolled in the Russian cohort.
4.2. Scientific Rationale for Study Design
Infants born at >36 weeks of gestation and ≥42 to 
≤112 days of age will be eligible if they are naïve to pneumococcal vaccination. This study 
population has been selected as this is the historical population studied for licensure of 
7vPnC and 13vPnC in infants.  The participants will be administered either 20vPnC or 
13vPnC at 2, 4, and 11 to 12 months of age. This is consistent with the current 
pneumococcal vaccine recommendations for infants in the EU.32 13vPnC will serve as the 
comparator to 20vPnC for assessment of safety and immunogenicity.
In order to expand the study to describe the safety and immunogenicity of 20vPnC in infants 
from Russia, approximately 60 Russian infants will be enrolled in the study, and referred to 
as the Russian cohort.  The Russian cohort will not be included in the primary study 
population.  This is a result of enrollment and subsequent visits in the primary study 
population anticipated to be complete several months before those in the Russian cohort, and 
based on differences in concomitant vaccine schedule and visit windows in the Russian 
participants, reflecting the Russian NIP, described in Section 10.10 of this protocol. The 
safety and immunogenicity results in the Russian cohort will be summarized in a 
supplemental CSR.
CCI
CCI
CCI

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 36
4.3. Justification for Dose
The 20vPnC candidate is modeled after 7vPnC and 13vPnC, and contains capsular 
polysaccharides from pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 
14, 15B, 18C, 19A, 19F, 22F, 23F, and 33F individually conjugated to CRM197. The vaccine 
is formulated to contain 2.2 µg of each saccharide, except for 4.4 µg of 6B, per 0.5-mL dose. 
In infants, administration of 2 doses of pneumococcal conjugate vaccine given in infancy at 
2 and 4 months of age, and 1 dose given at 11 to 12 months of age, induces protective 
immune responses.
4.4. End of Study Definition

Primary study population: The end of the study is defined as the date of the last visit of 
the last participant in the primary study population.

Russian cohort: The end of the study is defined as the date of the last visit of the last 
participant in this cohort.
5. STUDY POPULATION
This study can fulfill its objectives only if appropriate participants are enrolled.  The 
following eligibility criteria are designed to select participants for whom participation in the 
study is considered appropriate.  All relevant medical and nonmedical conditions should be 
taken into consideration when deciding whether a particular participant is suitable for this 
protocol.
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted.
5.1. Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria apply:
Age and Sex:
1. Male or female infants born at >36 weeks of gestation and 2 months of age (≥42 to 
≤112 days) at the time of consent (the day of birth is considered day of life 1).
Type of Participant and Disease Characteristics:
2. Participants whose parent(s)/legal guardian(s) are willing and able to comply with all 
scheduled visits, treatment plan, and other study procedures.
3. Healthy infants determined by clinical assessment, including medical history and 
clinical judgment, to be eligible for the study.
4. Expected to be available for the duration of the study and whose parents(s)/legal 
guardian can be contacted by telephone during study participation.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 37
Informed Consent:
5. Participants whose parent(s)/legal guardian(s) is capable of giving signed informed 
consent as described in Appendix 1, which includes compliance with the 
requirements and restrictions listed in the ICD and in this protocol.
(See Section 10.10 for the Russian cohort enrollment age window.)
5.2. Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions:
1. History of severe adverse reaction associated with a vaccine and/or severe allergic 
reaction (eg, anaphylaxis) to any component of investigational product or any 
diphtheria toxoid–containing vaccine.
2. Significant neurological disorder or history of seizure including febrile seizure or 
significant stable or evolving disorders such as cerebral palsy, encephalopathy, 
hydrocephalus, or other significant disorders. Does not include resolving syndromes 
due to birth trauma, such as Erb’s palsy and/or hypotonic-hyporesponsive episodes.
3. Major known congenital malformation or serious chronic disorder.
4. History of microbiologically proven invasive disease caused by S pneumoniae.
5. Known or suspected immunodeficiency or other conditions associated with 
immunosuppression, including, but not limited to, immunoglobulin class/subclass 
deficiencies, DiGeorge syndrome, generalized malignancy, human immunodeficiency 
virus (HIV) infection, leukemia, lymphoma, or organ or bone marrow transplant.
6. Bleeding diathesis or condition associated with prolonged bleeding that would, in the 
opinion of the investigator, contraindicate intramuscular injection.
7. Congenital, functional, or surgical asplenia.
8. Other acute or chronic medical or psychiatric condition or laboratory abnormality that 
may increase the risk associated with study participation or investigational product 
administration or may interfere with the interpretation of study results and, in the 
judgment of the investigator, would make the participant inappropriate for entry into 
this study.
Prior/Concomitant Therapy:
9. Previous vaccination with any licensed or investigational pneumococcal vaccine, or 
planned receipt through study participation.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 38
10. Prior receipt of diphtheria, tetanus, pertussis, poliomyelitis, and/or Hib vaccine.
11. Currently receives treatment with immunosuppressive therapy, including cytotoxic 
agents or systemic corticosteroids, or planned receipt through the last blood draw.  If 
systemic corticosteroids have been administered short term (<14 days) for treatment 
of an acute illness, participants should not be enrolled into the study until 
corticosteroid therapy has been discontinued for at least 28 days before 
investigational product administration.  Inhaled/nebulized, intra-articular, intrabursal, 
or topical (skin, eyes, or ears) corticosteroids are permitted.
12. Receipt of blood/plasma products or immunoglobulins (including hepatitis B 
immunoglobulin) since birth or planned receipt through the last planned blood draw 
in the study (Visit 5, 1 month after Dose 3).
Prior/Concurrent Clinical Study Experience:
13. Participation in other studies involving investigational drug(s), investigational 
vaccines, or investigational devices within 28 days prior to study entry and/or during 
study participation or intrauterine exposure to investigational vaccines.  Participation 
in purely observational studies is acceptable.
Diagnostic Assessments:
Not applicable.
Other Exclusions:
14. Children or grandchildren who are direct descendants of investigator site staff 
members or Pfizer employees who are directly involved in the conduct of the study.
5.3. Lifestyle Considerations
No restrictions are required.
5.4. Screen Failures
Screen failures are defined as participants whose parent(s)/legal guardian(s) have consented 
for them to participate in the clinical study but are not subsequently randomly assigned to 
investigational product/entered in the study.  A minimal set of screen failure information is 
required to ensure transparent reporting of screen failure participants to meet the 
Consolidated Standards of Reporting Trials (CONSORT) publishing requirements and to 
respond to queries from regulatory authorities.  Minimal information includes demography, 
screen failure details, eligibility criteria, and any AEs and SAEs.
Individuals who do not meet the criteria for participation in this study (screen failure) will 
not be rescreened.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 39
5.5. Temporary Delay Criteria
The following conditions are temporary or self-limiting and a participant may be vaccinated 
and/or have blood drawn in the study once the condition(s) has/have resolved and no other 
exclusion criteria are met.
The blood draws prior to vaccination should take place on the same day as the vaccination.
5.5.1. Criteria for Temporarily Delaying Vaccine Administration

Current febrile illness (temperature ≥38.0°C [≥100.4°F]) or other acute illness within 
48 hours before investigational product administration.

Receipt of any inactivated or otherwise nonlive vaccine within 14 days or any live 
vaccine within 28 days before investigational product administration (with the exception 
of licensed inactivated influenza vaccine, which may be given at any time during the 
study per national recommendations).

Receipt of short-term (<14 days) systemic corticosteroids. Investigational product 
administration should be delayed until systemic corticosteroid use has been discontinued 
for at least 28 days.  Inhaled/nebulized, intra-articular, intrabursal, or topical (skin, eyes, 
or ears) corticosteroids are permitted.
5.5.2. Criteria for Temporarily Delaying Immunogenicity Blood Draw

Receipt of antibiotic therapy within 72 hours before blood draw. Topical antibiotics are 
permitted.
6. STUDY INTERVENTION
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study participant according to 
the study protocol.
For the purposes of this protocol, the term investigational product may be used 
synonymously with study intervention.
For additional information for the Russian cohort, please see Section 10.10.4.
6.1. Study Intervention(s) Administered
20vPnC is a sterile liquid suspension formulation containing saccharides from pneumococcal 
serotypes 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, 
and 33F individually conjugated to CRM197. The vaccine is formulated to contain 2.2 µg of 
each saccharide, except for 4.4 µg of 6B, per 0.5-mL dose. The vaccine contains 5 mM 
succinate buffer, 150 mM sodium chloride, 0.02% polysorbate 80, and 125 µg aluminum as 
aluminum phosphate, per 0.5-mL dose.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 40
13vPnC is a sterile liquid suspension formulation containing saccharides from pneumococcal 
serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F individually conjugated to 
CRM197.  The vaccine is formulated to contain 2.2 μg of each saccharide, except for 4.4 μg 
of 6B, per 0.5-mL dose.  The vaccine contains 295 μg succinate buffer, 0.85% sodium 
chloride, 100 μg polysorbate 80, and 125 μg aluminum as aluminum phosphate, per 0.5-mL 
dose.
20vPnC and 13vPnC, supplied as syringes, are both white suspensions and have a matching
appearance.
DTaP, HBV, IPV, and Hib vaccine, Infanrix hexa (supplied as a vial and a prefilled syringe),
is a vaccine indicated for active immunization against diphtheria, tetanus, pertussis, hepatitis 
B caused by all known subtypes of hepatitis B virus, poliomyelitis, and Hib infection, 
respectively.  See the investigational product manual (IP manual) and applicable SRSD.
MMR vaccine (supplied as a vial and prefilled syringe with solvent) is a live virus vaccine 
for vaccination against measles (rubeola), mumps, and rubella (German measles).  See the IP 
manual and applicable SRSD provided.
Varicella vaccine (supplied as a vial and prefilled syringe with solvent) is a live virus vaccine 
for vaccination against varicella.  See the IP manual and applicable SRSD.
Investigational product will be supplied by Pfizer as prefilled syringes or vials.  Each 
syringe/vial will be packaged in a carton with a label and a tamper-evident seal, and will be 
labeled as required per country requirement (refer to the IP manual).
6.1.1. Administration
Participants will receive 1 dose of 20vPnC or 13vPnC at each vaccination visit (Visits 1, 2, 
and 4) in accordance with the study’s SoA.
Participants will also receive 1 dose of DTaP, HBV, IPV, and Hib vaccine at Visits 1, 2, and 
4.  Participants are also to receive MMR and varicella vaccines at Visit 4 in accordance with 
the study’s SoA. The MMR and varicella vaccines are intended to be given to all 
participants.  However, in case of circumstances due to local practice/recommendations, 
some sites may not administer them to their participants at Dose 3, in which case MMR and 
varicella vaccines will be considered nonstudy vaccines.  If MMR and varicella vaccines are 
not given with Dose 3, and administered based on local practice/recommendations, they are 
not to be given during the interval <28 days before Dose 3 through the Visit 5 blood draw 
after Dose 3.
20vPnC and 13vPnC should be administered intramuscularly by injecting 0.5 mL into the 
anterolateral thigh muscle of the left leg at the vaccination visits.
CCI

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 41
The DTaP, HBV, IPV, and Hib vaccine will be administered concomitantly with 20vPnC or 
13vPnC and must be given in a limb other than the site of administration of 20vPnC or 
13vPnC, as appropriate for the age of the child and the route of administration (ie, 
intramuscular or subcutaneous).
The MMR and varicella vaccines will be administered concomitantly with 20vPnC or 
13vPnC and must be given in a limb other than the site of administration of 20vPnC or 
13vPnC, as appropriate for the age of the child and the route of administration 
(ie, intramuscular or subcutaneous).
Standard vaccination practices must be observed and vaccine must not be injected into blood 
vessels.  Appropriate medication and other supportive measures for management of an acute 
hypersensitivity reaction should be available in accordance with local guidelines for standard 
immunization practices.
Administration of investigational products should be performed by an appropriately 
qualified, Good Clinical Practice (GCP)-trained, and vaccine-experienced member of the 
study staff (eg, physician, nurse, physician’s assistant, nurse practitioner, pharmacist, or 
medical assistant) as allowed by local, state, and institutional guidance.
Investigational product administration details will be recorded on the case report form (CRF).
6.1.2. Medical Devices
In this study, medical devices being deployed are the 20vPnC and 13vPnC, DTaP, HBV
vaccine, IPV, and Hib vaccine prefilled syringes, and the MMR and varicella vaccine 
prefilled syringes.
Instructions for medical device use are provided in the IP manual or in the package insert.
Medical device incidents, including those resulting from malfunctions of the device, must be 
detected, documented, and reported by the study personnel throughout the study.  Please refer 
to Section 8.3.7 for details.
6.2. Preparation/Handling/Storage/Accountability
1. The investigator or designee must confirm appropriate temperature conditions have 
been maintained during transit for all study interventions received and any 
discrepancies are reported and resolved before use of the study intervention, as 
applicable for temperature-monitored shipments.
CCI

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 42
CCI

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 43
Additional details about accountability, storage, destruction, and excursion reporting can be 
found in the IP manual.
6.2.1. Preparation and Dispensing
See the IP manual or package insert for instructions on how to prepare the investigational 
product for administration.  Investigational product should be prepared and dispensed by an 
appropriately qualified and experienced member of the study staff (eg, physician, nurse, 
physician’s assistant, nurse practitioner, pharmacy assistant/technician, or pharmacist) as 
allowed by local, state, and institutional guidance.
6.3. Measures to Minimize Bias: Randomization and Blinding
6.3.1. Allocation to Investigational Product
All eligible participants will be randomized in a 1:1 ratio to receive either 20vPnC or 13vPnC 
(control vaccine).
Allocation of participants to vaccine groups will proceed through the use of an interactive 
response technology (IRT) system (interactive Web-based response [IWR]).  The site 
personnel (study coordinator or specified designee) will be required to enter or select 
information including but not limited to the user’s identification (ID) and password, the 
protocol number, and the participant number.  The site personnel will then be provided with a 
vaccine assignment, randomization number, and dispensable unit (DU) or container numbers 
when investigational product is being supplied via the IRT system.  The IRT system will 
provide a confirmation report containing the participant number, randomization number, and 
DU or container numbers assigned.  The confirmation report must be stored in the site’s files.
The study-specific IRT reference manual and IP manual will provide the contact information 
and further details on the use of the IRT system.
6.3.2. Blinding of Sponsor
Sponsor personnel involved in evaluating participant data in the primary study population 
will be blinded to vaccine assignment until the final analysis at the completion of
participation of the primary study population, following the principles outlined in 
International Council for Harmonisation (ICH) E9 guideline on Statistical Principles for 
Clinical Trials.73 The study team will remain blinded to the vaccine assignments of the 
Russian cohort until that cohort has completed the study. A data blinding plan will be created 
to describe the blinding requirements and unblinding events. Laboratory personnel 
CCI

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 44
performing the immunologic assays will be blinded until all assays have been completed and 
assay results finalized.
6.3.3. Breaking the Blind
The study will be participant- and investigator-blinded.
At the initiation of the study, the investigator site will be instructed on the method for 
breaking the blind for an individual participant.  The method will be an electronic process.  
Blinding codes should be broken only in exceptional circumstances when knowledge of the 
actual treatment code is absolutely essential for further management of the participant.  
Investigators are encouraged to discuss with a member of the study team if they believe that 
unblinding is necessary.  When the blinding code is broken, the reason must be recorded in 
the source documentation and entered on the CRF.
6.4. Study Intervention Compliance
All doses of investigational product will be administered by the appropriately designated 
study staff at the investigator site.
6.5. Concomitant Therapy
6.5.1. Prohibited Concomitant Vaccines and Treatments

Receipt of any investigational vaccines, drugs, or medical devices is prohibited during 
study participation.

Receipt of nonstudy pneumococcal vaccine is prohibited during study participation.

No additional doses of the study concomitant vaccines are allowed during the study 
except as prescribed by the protocol (eg, only 2 infant and 1 toddler dose of Infanrix hexa 
can be given, and should be given consistent with the protocol).

Receipt of blood/plasma products, immunoglobulins, and/or immunosuppressive therapy 
(including a ≥14-day course of systemic corticosteroids) is prohibited during study 
participation.
6.5.2. Permitted Concomitant Vaccines and Treatments

Licensed inactivated influenza vaccine may be given at any time during the study per 
national recommendations.

Rotavirus vaccine may be given at any time during the study, and according to local or 
national recommendations.

Meningitis B vaccine may be given during the study as per national recommendations.  It 
must be given at least 2 weeks before and/or 2 weeks after scheduled study vaccinations, 
and in accordance with local recommendations.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 45

Receipt of meningococcal conjugate vaccines is permitted after the blood draw at Visit 5.

Receipt of other licensed nonstudy vaccines is permitted after the Visit 5 blood draw.

Use of topical anesthetic is permitted during the study per local practice.

The use of prophylactic antipyretic/pain medication, while permitted, is not 
recommended on the day of investigational product administration (before or after 
vaccination). If symptoms develop, the use of antipyretic/pain medication is allowed.

Inhaled/nebulized, topical (skin, eyes, or ears), or localized injections of corticosteroids 
(eg, intra-articular or intrabursal administration) are permitted during participant 
participation in the study.

Prescription and nonprescription medications, vitamins, minerals, and herbal remedies 
are permitted during the study.
6.5.3. Prior Vaccines and Treatments

A birth dose of bacille Calmette-Guérin (BCG) vaccine may be given at least 28 days 
before vaccination with the first dose of investigational product.

Receipt of hepatitis B vaccine at birth is permitted but must be at least 28 days before the 
first vaccination of investigational product.
6.5.4. Recording Prior and Concomitant Vaccines and Treatments
The name and date of administration for all vaccinations should be collected from the time of 
signing of the ICD to Visit 5 and will be recorded in the CRF.  At Visit 1, information on 
prior vaccinations will also be recorded in the CRF. Vaccines required by the protocol, as 
well as those not stipulated, will be recorded throughout study participation.  Information on 
vaccines given to the mother during pregnancy and any intrapartum antibiotic use will also 
be collected (at Visit 1 only), if available.
Medications taken to treat SAEs and NDCMCs from the signing of the ICD to the final visit 
(Visit 5) will be recorded on the CRF.
6.6. Dose Modification
Not applicable.
6.7. Intervention After the End of the Study
No intervention will be provided to study participants at the end of the study.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 46
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL
7.1. Discontinuation of Study Intervention
Participant eligibility must be confirmed prior to each vaccination in order to continue in the 
study.
If a participant no longer meets the eligibility criteria during the vaccination period of the 
study, further vaccinations should be discontinued, but the participant may remain in the 
study.  If a participant is discontinued from vaccination and the participant’s parent(s)/legal 
guardian(s) consents, safety follow-up will be conducted as per Section 8.3. AEs, SAEs, and 
NDCMCs will be collected for 1 month after the last study vaccination.
See the SoA for data to be collected at the time of intervention discontinuation and follow-up 
and for any further evaluations that need to be completed.
7.2. Participant Discontinuation/Withdrawal From the Study
A participant may be withdrawn from the study at any time at the request of his/her 
parent(s)/legal guardian(s), or may be withdrawn at any time at the discretion of the 
investigator for safety, behavioral, compliance, or administrative reasons.
If a participant does not return for a scheduled visit, every effort should be made to contact 
the participant’s parent(s)/legal guardian(s).  All attempts to contact the participant’s 
parent(s)/legal guardian(s) and information received during contact attempts must be 
documented in the participant’s source document.  In any circumstance, every effort should 
be made to document participant outcome, if possible.
At the time of discontinuing from the study, please refer to the investigator site file (ISF) and 
SoA for assessments to be collected at the time of study discontinuation and follow-up and 
for any further evaluations that need to be completed.
The participant’s parent(s)/legal guardian(s) should ideally notify the investigator in writing 
of the decision to withdraw consent from future follow-up, whenever possible. The 
participant’s parent(s)/legal guardian(s) should be questioned regarding their reason for 
withdrawal.  The investigator or his or her designee should capture the reason for withdrawal 
in the CRF for all participants.
The participant should be requested to return for a final visit, if applicable, and the 
investigator will perform the procedures indicated for the next visit.  Any AEs or SAEs that 
are continuing at the time of withdrawal from the study should be followed until resolution 
or, in case of permanent impairment, until the condition stabilizes.
The collection of safety information should be completed for all participants who have been 
withdrawn after administration of investigational product, unless consent for further contact 
has been withdrawn, or the participant is lost to follow-up.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 47
Participant withdrawal should be explained in the source documents and should include 
whether the withdrawal is only from further receipt of investigational product or also from 
study procedures and/or posttreatment study follow-up.  The participant will be monitored 
for AEs, SAEs, and NDCMCs for 1 month after the last study vaccination.
If a participant is withdrawn from the study, his/her parent(s)/legal guardian(s) may request 
destruction of any remaining samples, but data already generated from the samples will 
continue to be available, and may be used to protect the integrity of existing analyses.  The 
investigator must document any such requests in the site study records.
If the participant is withdrawn from the study and his/her parent(s)/legal guardian(s) also 
withdraws consent (see below) for disclosure of future information, no further evaluations 
should be performed and no additional data should be collected.  The sponsor may retain and 
continue to use any data collected before such withdrawal of consent.
When a participant is withdrawn from the study because of an SAE, the SAE must be 
recorded on the CRF and reported on the Vaccine SAE Reporting Form.
Lack of completion of all or any of the withdrawal/early termination procedures will not be 
viewed as protocol deviations so long as the participant’s safety was preserved.
7.3. Lost to Follow-up
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and the participant’s parent(s)/legal guardian(s) is unable to be contacted by 
the study site.
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit:

The site must attempt to contact the participant’s parent(s)/legal guardian(s) and 
reschedule the missed visit as soon as possible and counsel the participant’s 
parent(s)/legal guardian(s) on the importance of maintaining the assigned visit 
schedule and ascertain whether or not the participant’s parent(s)/legal guardian(s) 
wishes for the participant to and/or should continue in the study;

Before a participant is deemed lost to follow-up, the investigator or designee must 
make every effort to regain contact with the participant’s parent(s)/legal guardian(s) 
(where possible, 3 telephone calls and, if necessary, a certified letter to the 
participant’s last known mailing address or local equivalent methods).  These contact 
attempts should be documented in the participant’s medical record;

Should the participant’s parent(s)/legal guardian(s) continue to be unreachable, the 
participant will be considered to have been withdrawn from the study.
Discontinuation of specific sites or of the study as a whole is handled as part of Appendix 1.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 48
8. STUDY ASSESSMENTS AND PROCEDURES
The investigator (or an appropriate delegate at the investigator site) must obtain a signed and 
dated ICD before performing any study-specific procedures.
Study procedures and their timing are summarized in the SoA.  Protocol waivers or 
exemptions are not allowed.
In the case of extreme circumstances, such as natural disasters or a pandemic, visits for 
follow-up or procedures may need to be conducted through other means (eg, telephone calls).
Immediate safety concerns should be discussed with the sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or discontinue study 
intervention.
Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct.
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria.  The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable.
Every effort should be made to ensure that protocol-required tests and procedures are 
completed as described.  However, it is anticipated that from time to time there may be 
circumstances outside the control of the investigator that may make it unfeasible to perform 
the test.  In these cases, the investigator must take all steps necessary to ensure the safety and 
well-being of the participant.  When a protocol-required test cannot be performed, the 
investigator will document the reason for the missed test and any corrective and preventive 
actions that he or she has taken to ensure that required processes are adhered to as soon as 
possible.  The study team must be informed of these incidents in a timely manner.
For samples being collected and shipped, detailed collection, processing, storage, and 
shipment instructions and contact information will be provided to the investigator site prior 
to initiation of the study.
The total blood sampling volume for individual participants in this study is approximately 
15 to 25 mL,
8.1. Efficacy Assessments
8.1.1. Immunogenicity Assessments
Blood samples (approximately 5 mL per sample) will be collected from all participants at 
Visits 3 (1 month after Dose 2), 4 (prior to Dose 3), and 5 (1 month after Dose 3). These are 
CCI
CCI

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 49
the immunogenicity time points. OPA titers will be determined for a randomly selected 
subset of participants.
Pneumococcal Responses
IgG Responses to the 20 Serotypes Contained in 20vPnC
IgG antibody concentrations for serotypes present in 20vPnC (1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 
10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, and 33F) will be determined on all sera 
collected at the 5 immunogenicity time points (prior to Dose 1, prior to Dose 2, 1 month after 
Dose 2, prior to Dose 3, and 1 month after Dose 3).  The serotype-specific IgG 
concentrations will be measured by Pfizer’s multiplex Luminex immunoassay.
OPA Responses to the 20 Serotypes Contained in 20vPnC
OPA titers for serotypes present in 20vPnC (1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 
15B, 18C, 19A, 19F, 22F, 23F, and 33F) will be determined in subsets of sera for the 3 key 
immunogenicity time points (1 month after Dose 2, prior to Dose 3, and 1 month after Dose 
3) in a randomly selected subset of the study participants.  These subsets will be randomly 
selected, by an unblinded third party, to ensure that each subset has equal representation of 
both vaccine groups. Further details will be described in the clinical specimen assessment 
plan (CSAP).
Concomitant Vaccine Antigens
Concomitant vaccine responses to the following antigens will be assessed.  The randomly 
selected serum subsets to be assayed will be based on minimum sample sizes needed to 
demonstrate the objectives of the study balanced with the serum volume required and 
available for testing. These subsets will be randomly selected, by an unblinded third party, to 
ensure that each subset has equal representation of both vaccine groups. Further details will 
be described in the CSAP. The serum subsets for MMR and varicella response will be 
randomly selected from participants who receive MMR and varicella vaccines at Dose 3.
Diphtheria toxoid: Concentration of antibody (in international units [IU]) to diphtheria toxoid 
(prespecified level ≥0.1 IU/mL) will be determined on the subsets of sera collected at the 
2 immunogenicity time points (1 month after Dose 2 and 1 month after Dose 3). 
CCI
CCI
CCI
CCI

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 50
Tetanus toxoid: Concentration of antibody (in IU) to tetanus toxoid (prespecified level 
≥0.1 IU/mL) will be determined on the subsets of sera collected at the 2 immunogenicity 
time points (1 month after Dose 2 and 1 month after Dose 3). 
Acellular pertussis: Concentration of IgG antibodies to pertussis antigens PT, FHA, and PRN
(prespecified level ≥ the observed antipertussis antibody concentration achieved by 95% of 
13vPnC recipients) will be determined on the subsets of sera collected at the 
2 immunogenicity time points (1 month after Dose 2 and 1 month after Dose 3). 
Hepatitis B: Concentration of hepatitis B antibody (in milli-international units per mL 
[mIU/mL]) (prespecified level ≥10 mIU/mL) will be determined on the subsets of sera 
collected at 1 immunogenicity time point (1 month after Dose 3). 
Poliomyelitis: Neutralizing antibody (NA) titers to poliovirus types 1, 2, and 3 (prespecified 
level NA titer ≥1:8) will be determined on the subsets of sera collected at the 2 
immunogenicity time points (1 month after Dose 2 and 1 month after Dose 3). 
Hib: Concentration of antibody to Hib (polyribosylribitol phosphate [PRP]) in μg/mL 
(prespecified level ≥0.15 μg/mL anti-PRP; alternative prespecified level ≥1.0 μg/mL 
anti-PRP) will be determined on the subsets of sera collected at the 2 immunogenicity time 
points (1 month after Dose 2 and 1 month after Dose 3). 
Measles: Concentration of antimeasles antibody will be determined on the subsets of sera 
collected at 1 immunogenicity time point (1 month after Dose 3). 
Mumps: Concentration of antimumps antibody will be determined on the subsets of sera 
collected at 1 immunogenicity time point (1 month after Dose 3). 
Rubella: Concentration of antirubella antibody will be determined on the subsets of sera 
collected at 1 immunogenicity time point (1 month after Dose 3). 
Varicella: Concentration of antivaricella antibody will be determined on the subsets of sera 
collected at 1 immunogenicity time point (1 month after Dose 3). 
For Russian cohort–specific differences, please see Section 10.10.1.
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 51
8.1.2. Biological Samples
Blood samples will be used only for scientific research.  Each sample will be labeled with a 
code so that the laboratory personnel testing the samples will not know the participant’s 
identity.  Samples that remain after performing assays outlined in the protocol may be stored 
by Pfizer.  Unless a time limitation is required by local regulations or ethical requirements, 
the samples will be stored for up to 15 years after the end of the study and then destroyed. 
No testing of the participant’s genetic material will be performed.
The participant’s parent(s)/legal guardian(s) may request the participant’s samples, if still 
identifiable, be destroyed at any time; however, any data already collected from those 
samples will still be used for this research.  The biological samples may be shared with other 
researchers as long as confidentiality is maintained and no testing of the participant’s genetic 
material is performed.
8.2. Safety Assessments
Planned time points for all safety assessments are provided in the SoA.  Unscheduled clinical 
laboratory measurements may be obtained at any time during the study to assess any 
perceived safety concerns.
A clinical assessment, including medical history and measurement of temperature, will be 
performed on all participants prior to vaccination to determine participant eligibility and to 
establish a clinical baseline.  Significant medical history and significant findings from any 
physical examination (if performed) will be recorded as medical history on the CRF.  
Temperature measurement prior to vaccination will be documented and recorded on the CRF.
The participant will be observed for 30 minutes after each study vaccination and any 
reactions occurring during that time will be recorded as AEs.
Local reactions (including redness, pain, and swelling at the injection site), systemic events 
(including fever, drowsiness/increased sleep, decreased appetite, and irritability), and use of 
pain/fever medication will be prompted for and collected by the participant’s parent(s)/legal 
guardian(s) daily for 7 days after each study vaccination (where Day 1 is the day of 
vaccination) in an e-diary.  These prompted e-diary events are graded as described in 
Section 8.2.  AEs, SAEs, and NDCMCs will be collected as defined in Section 8.3.
CCI
CCI
CCI
CCI

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 52
AEs will be recorded and reported from the signing of the ICD through Visit 3 and from 
Visit 4 through Visit 5.
SAEs and NDCMCs will be recorded and reported from the signing of the ICD through the 
final visit (Visit 5).
Causality and severity of AEs and SAEs will be assessed for all participants.
8.2.1. Participant Electronic Diary
The participant’s parent(s)/legal guardian(s) will be asked to monitor and record local 
reactions, specific systemic events, and antipyretic/pain medication taken for 7 days, each 
evening, following each vaccination using an e-diary (in a provisioned device or application 
on a personal device).  This allows recording of these assessments only within a fixed time 
window, thus providing the accurate representation of the participant’s experience.  Data on 
local reactions, specific systemic events, and antipyretic/pain medication reported in the 
e-diary will be transferred electronically to the e-diary vendor, where they will be available 
for review by investigators, their qualified designees, and sponsor staff at all times via an 
internet-based portal.  At intervals agreed to by the vendor and Pfizer, these data will be 
transferred electronically to Pfizer for analysis and reporting.
The daily e-diary data will not be captured in the CRF.  However, if a participant withdraws 
because of prompted events reported in the e-diary, the event(s) should be recorded on the 
AE page of the CRF, regardless of whether the investigator considers the event(s) to be 
clinically significant.
The investigator or designee must obtain stop dates for any reactions ongoing on the last day 
that the e-diary was completed.  The stop dates should be entered in the CRF.
Designated site staff will review the e-diary data online at frequent intervals (daily is 
optimal) for the 7 days following each dose of 20vPnC or 13vPnC to evaluate participant 
compliance and reported events as part of the ongoing safety review.
8.2.2. Grading Scale for Prompted Events
The grading scales used in this study to assess prompted events as described below are based 
on concepts outlined in the Food and Drug Administration (FDA) Center for Biologics 
Evaluation and Research (CBER) guidelines on toxicity grading scales for adults and 
adolescent volunteers enrolled in preventive vaccine clinical trials, but have been adapted for 
applicability to healthy infants.74
8.2.2.1. Local Reactions
For the first 7 days following each vaccination (Days 1 through Day 7, where Day 1 is the 
day of vaccination), the participant’s parent(s)/legal guardian(s) will be asked to assess 
redness, swelling, and pain at the 20vPnC or 13vPnC injection site and to record the 
symptoms in the e-diary in the evening.  Redness and swelling will be measured and 
recorded in measuring device (caliper) units (range: 1 to >14; an entry in the e-diary of 15 

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 53
will denote >14), and then categorized during analysis as mild, moderate, or severe based on 
the grading scale in Table 1.  Measuring device units can be converted to centimeters 
according to the following scale: 1 measuring device unit = 0.5 cm.  Pain at the vaccine 
injection site will be assessed by the participant’s parent(s)/legal guardian(s) as mild, 
moderate, or severe according to the grading scale in Table 1.  The participant’s 
parent(s)/legal guardian(s) will be prompted to contact the investigator if the participant 
experiences a severe (Grade 3) or above local reaction to assess the reaction and perform an 
unscheduled assessment or visit as appropriate.
Only an investigator is able to classify a participant’s local reaction as Grade 4, after physical 
examination of the participant or documentation from another medically qualified source 
(eg, emergency room or hospital record).  If a participant experiences a Grade 4 local 
reaction, the investigator must immediately notify the sponsor. Site staff will educate the 
participant’s parent(s)/legal guardian(s) regarding signs and symptoms that would prompt 
site contact.
The procedure for notification of the sponsor is provided in the study reference manual 
(SRM) or equivalent.
Table 1.
Grading Scales for Local Reactions
Local Reaction
GRADE 1
Mild
GRADE 2 
Moderate
GRADE 3a
Severe
GRADE 4b
Redness
1 to 4 caliper units
(or measuring 
device units)
=
>0 to 2.0 cm
5 to 14 caliper units
(or measuring 
device units)
=
>2.0 to 7.0 cm
>14 caliper units 
(or measuring 
device units)
=
>7 cm
Necrosis or 
exfoliative dermatitis
Swelling
1 to 4 caliper units
(or measuring 
device units)
=
>0 to 2.0 cm
5 to 14 caliper units
(or measuring 
device units)
=
>2.0 to 7.0 cm
>14 caliper units 
(or measuring 
device units)
=
>7 cm
Necrosis
Pain at injection 
site
(tenderness)
Hurts if gently 
touched
(eg, whimpers, 
winces, protests,
or withdraws)
Hurts if gently 
touched with crying
Causes limitation of 
limb movement
Emergency room 
visit or 
hospitalization for 
severe pain 
(tenderness) at 
injection site
Abbreviations: CRF = case report form; e-diary = electronic diary.
a.
Parent(s)/legal guardian(s) of the participants experiencing local reactions >14 caliper units (>7.0 cm) are 
to be contacted by the study site. An unscheduled visit may be required.
b.
Grade 4 assessment should be made by the investigator. Grade 4 will not be collected in the e-diary but 
will be collected as an AE on the CRF (see Section 10.3.4).
Note: If the size of the redness and/or swelling falls between 2 measuring device units, the higher measuring 
device unit number will be recorded in the e-diary.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 54
8.2.2.2. Systemic Event Symptoms and Fever
8.2.2.2.1. Systemic Event Symptoms
For the first 7 days following each vaccination (Day 1 through Day 7, where Day 1 is the day 
of vaccination), the participant’s parent(s)/legal guardian(s) will be asked to assess decreased 
appetite, drowsiness/increased sleep, and irritability and to record the symptoms in the 
e-diary (in a provisioned device or application on a personal device) in the evening.  The 
symptoms will be assessed by the participant’s parent(s)/legal guardian(s) as mild, moderate, 
or severe according to the grading scale in Table 2.  The participant’s parent(s)/legal 
guardian(s) will also be instructed to contact site staff if the participant experiences any 
possible Grade 4 prompted systemic event (ie, emergency room visit or hospitalization for 
severe decreased appetite, severe drowsiness/increased sleep, or severe irritability) within 
7 days after vaccination.  Study staff may also contact the participant’s parent(s)/legal 
guardian(s) to obtain additional information on Grade 3 events entered into the e-diary.
Only an investigator is able to classify a participant’s systemic event as Grade 4, after 
physical examination of the participant or documentation from another medically qualified 
source (eg, emergency room or hospital record) or telephone contact with the participant’s 
parent(s)/legal guardian(s).  If a participant experiences a Grade 4 systemic event, the 
investigator must immediately notify the sponsor.
The procedure for notification of the sponsor is provided in the SRM or equivalent.
Table 2.
Grading Scales for Systemic Event Symptoms
Systemic Event
GRADE 1
Mild
GRADE 2 
Moderate
GRADE 3
Severe
GRADE 4a
Decreased appetite 
(loss of appetite)
Decreased interest in 
eating
Decreased oral 
intake
Refusal to feed
Emergency room visit or 
hospitalization for severe 
decreased appetite 
(loss of appetite)
Drowsiness
(increased sleep)
Increased or 
prolonged sleeping 
bouts
Slightly subdued 
interfering with 
daily activity
Disabling not 
interested in 
usual daily 
activity
Emergency room visit or 
hospitalization for severe 
drowsiness 
(increased sleep)
Irritability
(fussiness)
(synonymous with 
restless sleep; 
decreased sleep)
Easily consolable
Requiring 
increased attention
Inconsolable; 
crying cannot be 
comforted
Emergency room visit or 
hospitalization for severe 
irritability (fussiness)
Abbreviations: CRF = case report form; e-diary = electronic diary.
a.
Grade 4 assessment should be made by the investigator. Grade 4 will not be collected in the e-diary but 
will be collected as an AE on the CRF (see Section 10.3.4).

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 55
8.2.2.2.2. Fever
In order to record information on fever, a digital thermometer will be given to the 
participant’s parent(s)/legal guardian(s) with instructions on how to measure axillary
temperature at home.  Temperature will be collected in the evening, daily, for 7 days 
following vaccination (Days 1 to 7, where Day 1 is the day of vaccination) and at any time 
during the 7 days that fever is suspected.  Fever is defined as an axillary temperature of 
≥38.0°C (≥100.4°F).  The highest temperature for each day will be recorded in the e-diary.  
In the event of a fever on the last day of diary collection, temperature will be collected daily 
until fever has resolved (1 day of temperature less than 38.0°C [100.4°F]) in order to collect 
a stop date in the CRF.  A participant’s parent(s)/legal guardian(s) will be prompted to 
contact the investigator if the participant experiences a fever >40.0°C (>104.0°F) within the 
7 days following vaccination to assess the fever and perform an unscheduled assessment, as 
applicable (see Section 8.10.6).  Study staff may also contact the participant’s parent(s)/legal 
guardian(s) to obtain additional information if a temperature of >38.9°C (>102.0°F) is 
entered into an e-diary.  Temperature will be measured and recorded to 1 decimal place and 
then grouped into ranges for the analysis; see Table 3.
Table 3.
Ranges for Fever
≥38.0°C to 38.4°C
>38.4°C to 38.9°C
>38.9°C to 40.0°C
>40.0°C
Note: Fever is defined as temperature ≥38.0°C. 
8.2.2.3. Use of Antipyretic/Pain Medication
The participant’s parent(s)/legal guardian(s) will be asked to record the use of 
antipyretic/pain medication (yes/no) in the e-diary (in a provisioned device or application on 
a personal device) in the evening, daily, for 7 days after each dose of investigational product.
The use of prophylactic antipyretic/pain medication, while permitted, is not recommended on 
the day of investigational product administration (before or after vaccination).  If symptoms 
develop, the use of antipyretic/pain medication is allowed.
8.2.3. Clinical Safety Laboratory Assessments
Clinical safety laboratory tests are not required by this protocol.
If laboratory values from non–protocol-specified laboratory assessments performed at the 
institution’s local laboratory require a change in participant management or are considered 
clinically significant by the investigator (eg, SAE or AE or dose modification), then the 
results must be recorded in the CRF.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 56
8.3. Adverse Events and Serious Adverse Events
The definitions of an AE and an SAE can be found in Appendix 3.
AEs will be reported by the participant’s parent(s)/legal guardian(s).  Events that, in the 
clinical judgment of the investigator, are 1) consistent with normal growth and development 
and 2) do not differ significantly in frequency or severity from expected are not generally to 
be considered AEs. Examples may include, but are not limited to, teething, contact diaper 
rash, spitting up, colic, or typical fussiness/crying in infants and children.  
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible to pursue 
and obtain adequate information both to determine the outcome and to assess whether it 
meets the criteria for classification as an SAE or caused the participant to discontinue from
the study (see Section 7).
In addition, the investigator may be requested by Pfizer Safety to obtain specific follow-up 
information in an expedited fashion.
8.3.1. Time Period and Frequency for Collecting AE and SAE Information
The time period for actively eliciting and collecting AEs and SAEs (“active collection 
period”) for each participant begins from the time the participant’s parent(s)/legal guardian(s) 
provides informed consent, which is obtained before the participant’s participation in the 
study (ie, before undergoing any study-related procedure and/or receiving investigational 
product), through and including Visit 3, and from Visit 4 through Visit 5.  SAEs and 
NDCMCs will be recorded and reported from the signing of the ICD through the final visit 
(Visit 5).  At Visit 5, the participant’s parent(s)/legal guardian(s) will be asked to report any 
AEs and SAEs, including hospitalizations and NDCMCs, that have occurred since Visit 4.
Follow-up by the investigator continues throughout and after the active collection period and 
until the event or its sequelae resolve or stabilize at a level acceptable to the investigator, and 
Pfizer concurs with that assessment.
Investigators are not obligated to actively seek AEs or SAEs after conclusion of the study 
participation.  However, if the investigator learns of any SAE, including a death, at any time 
after a participant has completed or withdrawn early from the study, and he/she considers the 
event to be reasonably related to the study intervention or study participation, the investigator 
must promptly notify the sponsor.
8.3.1.1. Reporting SAEs to Pfizer Safety
All SAEs occurring in a participant during the active collection period are reported to Pfizer 
Safety on the Vaccine SAE Reporting Form immediately upon awareness and under no 
circumstance should this exceed 24 hours, as indicated in Appendix 3.  The investigator will 
submit any updated SAE data to the sponsor within 24 hours of it being available.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 57
SAEs occurring in a participant after the active collection period has ended are reported to 
Pfizer Safety if the investigator becomes aware of them; at a minimum, all SAEs that the 
investigator believes have at least a reasonable possibility of being related to investigational 
product must be reported to Pfizer Safety.
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF
During the active collection period, both nonserious AEs and SAEs are recorded on the CRF.
8.3.2. Method of Detecting AEs and SAEs
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix 3.
Care will be taken not to introduce bias when detecting AEs and/or SAEs.  Open-ended and 
nonleading verbal questioning of the participant’s parent(s)/legal guardian(s) is the preferred 
method to inquire about AE occurrences.
8.3.3. Follow-up of AEs and SAEs
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts.  For each event, the investigator must pursue and 
obtain adequate information until resolution, stabilization, the event is otherwise explained, 
or the participant is lost to follow-up (as defined in Section 7.3).
In general, follow-up information will include a description of the event in sufficient detail to 
allow for a complete medical assessment of the case and independent determination of 
possible causality.  Any information relevant to the event, such as concomitant medications 
and illnesses, must be provided.  In the case of a participant death, a summary of available 
autopsy findings must be submitted as soon as possible to Pfizer Safety.
Further information on follow-up procedures is given in Appendix 3.
8.3.4. Regulatory Reporting Requirements for SAEs
Prompt notification by the investigator to the sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a 
study intervention under clinical investigation are met.
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation.  The 
sponsor will comply with country-specific regulatory requirements relating to safety 
reporting to the regulatory authority, institutional review boards (IRBs)/ethics committees 
(ECs), and investigators.
Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions (SUSARs) according to local regulatory requirements and sponsor policy and 
forwarded to investigators as necessary.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 58
An investigator who receives an investigator safety report describing an SAE or other 
specific safety information (eg, summary or listing of SAEs) from the sponsor will review 
and then file it along with the IB and will notify the IRB/EC, if appropriate according to local 
requirements.
8.3.5. Exposure During Pregnancy or Breastfeeding, and Occupational Exposure
Exposure to the investigational product under study during pregnancy or breastfeeding and 
occupational exposure are reportable to Pfizer Safety within 24 hours of investigator 
awareness.
8.3.5.1. Exposure During Pregnancy
Details of all pregnancies in females (via occupational exposure) will be collected after the 
start of study intervention and until delivery.
Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, ectopic pregnancy) are considered SAEs.
8.3.5.2. Exposure During Breastfeeding
Scenarios of exposure during breastfeeding (via occupational exposure) must be reported, 
irrespective of the presence of an associated SAE, to Pfizer Safety within 24 hours of the 
investigator’s awareness, using the Vaccine SAE Reporting Form.  An exposure during 
breastfeeding report is not created when a Pfizer drug specifically approved for use in 
breastfeeding women (eg, vitamins) is administered in accord with authorized use.  However, 
if the infant experiences an SAE associated with such a drug’s administration, the SAE is 
reported together with the exposure during breastfeeding.
8.3.5.3. Occupational Exposure
An occupational exposure occurs when, during the performance of job duties, a person 
(whether a healthcare professional or otherwise) gets in unplanned direct contact with the 
product, which may or may not lead to the occurrence of an AE.
An occupational exposure is reported to Pfizer Safety within 24 hours of the investigator’s 
awareness, using the Vaccine SAE Reporting Form, regardless of whether there is an 
associated SAE.  Since the information does not pertain to a participant enrolled in the study, 
the information is not recorded on a CRF; however, a copy of the completed Vaccine SAE 
Reporting Form is maintained in the ISF.
8.3.6. Adverse Events of Special Interest
Not applicable.
CCI

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 59
8.3.6.1. Lack of Efficacy
This section is not applicable because efficacy is not expected to be detected (vaccine is 
expected to be efficacious) in the study population.
8.3.7. Medical Device Deficiencies
Medical devices are being provided for use in this study for the purposes of administering the 
investigational product.  In order to fulfill regulatory reporting obligations worldwide, the 
investigator is responsible for the detection and documentation of events meeting the 
definitions of device deficiency that occur during the study with such devices.
The definition of a medical device deficiency can be found in Appendix 8.
NOTE: Deficiencies fulfilling the definition of an AE/SAE will also follow the processes 
outlined in Section 8.3.3 and Appendix 3 of the protocol.
8.3.7.1. Time Period for Detecting Medical Device Deficiencies
Medical device deficiencies or malfunctions of the device  will be detected, documented, and 
reported during all periods of the study in which the medical device is used.
If the investigator learns of any device deficiency at any time after a participant has been 
discharged from the study, and such incident is considered reasonably related to a medical 
device provided for the study, the investigator will promptly notify the sponsor.
The method of documenting medical device deficiencies is provided in Appendix 8.
8.3.7.2. Follow-up of Medical Device Deficiencies
All medical device incidents involving an AE will be followed and reported in the same 
manner as other AEs (see Section 8.3.3).  This applies to all participants, including those who 
discontinue study intervention.
The investigator is responsible for ensuring that follow-up includes any supplemental 
investigations as indicated to elucidate the nature and/or causality of the deficiency.
New or updated information will be recorded on the follow-up form with all changes signed 
and dated by the investigator.
8.3.7.3. Prompt Reporting of Medical Device Deficiencies to Sponsor
Device deficiencies will be reported to the sponsor within 1 day after the investigator 
determines that the event meets the protocol definition of a medical device deficiency.  
Information will be provided to the sponsor as described in the IP manual.
Any device deficiency that is associated with an SAE must be reported to Pfizer Safety 
within 24 hours upon the investigator’s awareness as outlined in Section 8.3.1.1 and 
Section 8.3.1.2.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 60
The sponsor will be the contact for the receipt of device deficiency information.
8.3.7.4. Regulatory Reporting Requirements for Device Deficiencies
The investigator will promptly report all device deficiencies occurring with any medical 
device provided for use in the study in order for the sponsor to fulfill the legal responsibility 
to notify appropriate regulatory authorities and other entities about certain safety information 
relating to medical devices being used in clinical studies.
The investigator, or responsible person according to local requirements (eg, the head of the 
medical institution), will comply with the applicable local regulatory requirements relating to 
the reporting of device deficiencies to the IRB/EC.
8.3.8. Medication Errors
Medication errors may result from the administration or consumption of the investigational 
product by the wrong participant, or at the wrong time, or at the wrong dosage strength.
Exposures to the investigational product under study may occur in clinical trial settings, such 
as medication errors.
Safety Event
Recorded on the CRF
Reported on the Vaccine SAE 
Reporting Form to Pfizer Safety 
Within 24 Hours of Awareness
Medication errors 
All (regardless of whether 
associated with an AE)
Only if associated with an SAE
Medication errors include:

Medication errors involving participant exposure to the investigational product;

Potential medication errors or uses outside of what is foreseen in the protocol that do 
or do not involve the study participant.
Such medication errors occurring to a study participant are to be captured on the medication 
error page of the CRF, which is a specific version of the AE page.
In the event of a medication dosing error, the sponsor should be notified within 24 hours.
Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error is recorded on the medication error page of the CRF and, if 
applicable, any associated AE(s), serious and nonserious, are recorded on an AE page of the 
CRF.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 61
Medication errors should be reported to Pfizer Safety within 24 hours on a Vaccine SAE
Reporting Form only when associated with an SAE.
Other examples include, but are not limited to:

The administration of expired investigational product;

The administration of an incorrect investigational product;

The administration of an incorrect dosage;

The administration of investigational product that has undergone temperature 
excursion from the specified storage range, unless it is determined by the sponsor that 
the investigational product under question is acceptable for use.
8.4. Treatment of Overdose
For this study, any dose of investigational product greater than 0.5 mL within a 24-hour time 
period will be considered an overdose.
Pfizer does not recommend specific treatment for an overdose.
In the event of an overdose, the investigator should:
1. Contact the medical monitor within 24 hours.
2. Closely monitor the participant for any AEs/SAEs.
3. Document the quantity of the excess dose as well as the duration of the overdose in 
the CRF.
4. Overdose is reportable to Safety only when associated with an SAE.
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the medical monitor based on the clinical evaluation of the participant.
8.5. Pharmacokinetics
Pharmacokinetic parameters are not evaluated in this study.
8.6. Pharmacodynamics
Pharmacodynamic parameters are not evaluated in this study.
8.7. Genetics
Genetics (specified analyses) are not evaluated in this study.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 62
8.8. Biomarkers
Biomarkers are not evaluated in this study.
8.9. Health Economics
Health economics/medical resource utilization and health economics parameters are not 
evaluated in this study.
8.10. Study Procedures
The study procedures are summarized in the SoA. The day of Dose 1 is considered to be 
Day 1.  The timing of visit procedures (ie, prior to vaccination and after vaccination) must be 
maintained; however, there is flexibility in the order in which the procedures can be 
conducted at each visit. The only exception is that at Visit 1, the ICD must be signed prior to 
the start of any study procedure.
8.10.1. Visit 1 (Dose 1: Day 1)
Prior to vaccination:

Obtain a personally signed and dated ICD indicating the participant’s parent(s)/legal 
guardian(s) has been informed of all pertinent aspects of the study before performing any 
study-specific procedures.

Assign a participant number via the IRT.

Obtain and record the participant’s demographic information (including date of birth, sex, 
race, and ethnicity).  The complete date of birth (ie, DD-MMM-YYYY) will be collected 
to critically evaluate the immune response and safety profile by age.

Perform a clinical assessment that includes medical history, including significant birth 
history; record any findings on the medical history CRF.

Record vaccination history.

Record vaccines administered during pregnancy and intrapartumn antibiotic use (yes/no)
(if available).

Measure and record the participant’s temperature (°C) as appropriate for age.

Ensure that all inclusion criteria, none of the exclusion criteria, and none of the temporary 
delay criteria are met.

Assign a randomization number and an investigational product container number via the 
IRT.  This must be the last step before proceeding.  A site staff member will prepare the 
investigational product according to the IP manual.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 63
After randomization:
 
•
Administer a single 0.5-mL injection of 20vPnC or 13vPnC into the left anterolateral 
thigh.
•
Administer concomitant vaccine containing DTaP, HBV, IPV, and Hib antigens and 
other permitted vaccines (must be given in a limb other than the site of 20vPnC or 
13vPnC administration, as appropriate for the age of the child and the route of 
administration [ie, intramuscular, subcutaneous, or oral]).  The site of administration will 
be captured on the CRF.
•
Site staff will observe the participant for 30 minutes after vaccination for any reactions.  
Record any AEs on the CRF and on an SAE form as applicable.  Record concomitant 
medications used to treat SAEs and NDCMCs.
•
Issue the participant’s parent(s)/legal guardian(s) a measuring device to measure 20vPnC 
or 13vPnC injection site reactions and a digital thermometer and provide instructions on 
their use.
•
Issue the participant’s parent(s)/legal guardian(s) an e-diary (device or application).  
Provide instructions on use and completion of the e-diary.  Ask the participant’s 
parent(s)/legal guardian(s) to complete the e-diary from Day 1 to Day 7, with Day 1 
being the day of vaccination.
•
Ask the participant’s parent(s)/legal guardian(s) to contact the investigator site staff or 
investigator as soon as possible during the 7-day postvaccination period if the participant 
has a fever >40.0°C (>104.0°F), redness and/or swelling at the 20vPnC or 13vPnC 
injection site measuring >14 measuring device units (>7 cm), or severe 20vPnC or 
13vPnC injection site pain (causes limitation of limb movement) to determine if the event 
requires further assessment by the investigator.
•
Ask the participant’s parent(s)/legal guardian(s) to contact the investigator or investigator 
site staff as soon as possible if any significant illness or medical event (eg, emergency 
room visit or hospitalization) occurs.
•
Provide the parent(s)/legal guardian(s) with the participant contact card containing the 
study and investigator information (see Section 10.1.10).
•
Inform the participant’s parent(s)/legal guardian(s) that the use of prophylactic 
antipyretic/pain medication, while permitted, is not recommended on the day of 
investigational product administration (before or after vaccination).  If symptoms 
develop, the use of antipyretic/pain medication is allowed.
CCI

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 64
•
The investigator or an authorized designee completes the CRFs and updates the 
investigation product accountability records.
•
The investigator or appropriately qualified designee reviews the e-diary data online at 
frequent intervals for the 7 days following vaccination to evaluate participant compliance 
and as part of ongoing safety review.
8.10.2. Visit 2 (Dose 2: 42 to 63 Days After Visit 1, ie, Study Day 43 Through Study 
Day 64)
•
Ensure and document that the participant continues to be eligible for the study 
(see Section 7 for participant discontinuation/withdrawal) and none of the temporary 
delay criteria are met (Section 5.5).
•
Confirm whether the parent(s)/legal guardian(s) still possesses the participant contact 
card.
•
Record nonstudy vaccinations administered since Visit 1, as described in Section 6.5.4.
•
Review the participant’s e-diary data with the participant’s parent(s)/legal guardian(s); 
collect stop dates of any local and systemic events ongoing on the last day that the e-diary 
was completed and record stop dates in the CRF.
•
Determine whether any AEs (includes nonserious AEs, SAEs, and NDCMCs) have 
occurred since the previous visit and follow up on any previously reported events to 
determine the outcome (ie, record stop dates or confirm if they are still continuing) and 
record as described in Section 10.3.4, and record concomitant medications used to treat 
NDCMCs and SAEs.
•
Measure and record the participant’s temperature (°C).
 
•
Administer a single 0.5-mL injection of 20vPnC or 13vPnC into the left anterolateral 
thigh.
•
Administer concomitant vaccine containing DTaP, HBV, IPV, and Hib antigens and 
other permitted vaccines (must be given in a limb other than the site of 20vPnC or 
13vPnC administration, as appropriate for the age of the child and the route of 
administration [ie, intramuscular, subcutaneous, or oral]).  The site of administration will 
be captured on the CRF.
CCI

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 65
After vaccination:

Site staff will observe the participant for 30 minutes after vaccination for any reactions.  
Record any AEs on the CRF and on an SAE form as applicable.  Record concomitant 
medications used to treat SAEs and NDCMCs.

Confirm that the e-diary is working and review instructions if necessary.  Remind the 
participant’s parent(s)/legal guardian(s) to complete the e-diary from Day 1 to Day 7, 
with Day 1 being the day of vaccination.  Provide a digital thermometer or measuring 
device if needed.

Ask the participant’s parent(s)/legal guardian(s) to contact the investigator site staff or 
investigator as soon as possible during the 7-day postvaccination period if the participant 
has a fever >40.0°C (>104.0°F), redness and/or swelling at the 20vPnC or 13vPnC 
injection site measuring >14 measuring device units (>7 cm), or severe 20vPnC or 
13vPnC injection site pain (causes limitation of limb movement), to determine if the 
event requires further assessment by the investigator.

Remind the participant’s parent(s)/legal guardian(s) to contact the investigator or 
investigator site staff as soon as possible if any significant illness or medical event 
(eg, emergency room visit or hospitalization) occurs during the study period.

Remind the participant’s parent(s)/legal guardian(s) that use of prophylactic 
antipyretic/pain medication, while permitted, is not recommended on the day of 
investigational product administration (before or after vaccination).  If symptoms 
develop, the use of antipyretic/pain medication is allowed.

The investigator or an authorized designee completes the CRF and the source documents 
and updates the investigational product accountability records.

The investigator or appropriately qualified designee reviews the e-diary data online at 
frequent intervals for the 7 days following vaccination to evaluate participant compliance 
and as part of ongoing safety review.
8.10.3. Visit 3 (Dose 2 Follow-up: 28 to 42 Days After Visit 2)

Ensure and document that the participant continues to be eligible for the study (see 
Section 7 for participant discontinuation/withdrawal) and none of the temporary delay 
criteria are met (Section 5.5).

Confirm whether the parent(s)/legal guardian(s) still possesses the participant contact 
card.

Record nonstudy vaccinations administered since Visit 2, as described in Section 6.5.4.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 66

Review the participant’s e-diary data with the participant’s parent(s)/legal guardian(s); 
collect stop dates of any local and systemic events ongoing on the last day that the e-diary 
was completed and record stop dates in the CRF.

Collect the e-diary (if applicable).

Determine whether any AEs (includes nonserious AEs, SAEs, and NDCMCs) have 
occurred since the previous visit and follow up on any previously reported events to 
determine the outcome (ie, record stop dates or confirm if they are still continuing) and 
record as described in Section 10.3.4, and record concomitant medications used to treat 
NDCMCs and SAEs.

Collect a blood sample of approximately 5 mL for immunogenicity (a topical anesthetic 
is permitted).

The investigator or an authorized designee completes the CRF and the source documents 
and updates the investigational product accountability records.
8.10.4. Visit 4 (Dose 3: 335 to 386 Days of Age)

Ensure and document that the participant continues to be eligible for the study (see 
Section 7 for participant discontinuation/withdrawal) and none of the temporary delay 
criteria are met (Section 5.5).

Confirm whether the parent(s)/legal guardian(s) still possesses the participant contact 
card.

Record nonstudy vaccinations administered since Visit 3, as described in Section 6.5.4.

Determine whether any SAEs or NDCMCs have occurred since the previous visit and 
follow up on any previously reported events to determine the outcome (ie, record stop 
dates or confirm if they are still continuing) and record as described in Section 10.3.4, 
and record concomitant medications used to treat NDCMCs and SAEs.  Any AEs that 
have occurred since the last visit will be documented in the participant’s source 
documents; however, they will not be captured on the CRF.

Measure and record the participant’s temperature (°C).

Collect a blood sample of approximately 5 mL for immunogenicity (a topical anesthetic 
is permitted).

Administer a single 0.5-mL injection of 20vPnC or 13vPnC into the left anterolateral 
thigh.

Administer concomitant vaccine containing DTaP, HBV, IPV, and Hib antigens and 
other permitted vaccines.  These vaccines must be given in a limb other than the site of 

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 67
20vPnC or 13vPnC administration, as appropriate for the age of the child and the route of 
administration (ie, intramuscular, subcutaneous, or oral).  The sites of administration will 
be captured on the CRF.

MMR and varicella vaccines are intended to be given to all participants.  However, in  
case of circumstances due to local practice/recommendations, some sites may not 
administer them to their participants, in which case MMR and varicella vaccines will be 
considered nonstudy vaccines. These vaccinations must be given in a limb other than the 
site of administration of 20vPnC or 13vPnC, as appropriate for the age of the child and 
the route of administration (ie, intramuscular or subcutaneous).  The sites of 
administration will be captured on the CRF.
After vaccination:

Site staff will observe the participant for 30 minutes after vaccination for any reactions.  
Record any AEs on the CRF and on an SAE form as applicable.  Record concomitant 
medications used to treat SAEs and NDCMCs.

Reissue the participant’s parent(s)/legal guardian(s) an e-diary (device or application).  
Provide instructions on use and completion of the e-diary.  Ask the participant’s 
parent(s)/legal guardian(s) to complete the e-diary from Day 1 to Day 7, with Day 1 
being the day of vaccination.

Ask the participant’s parent(s)/legal guardian(s) to contact the investigator site staff or 
investigator as soon as possible during the 7-day postvaccination period if the participant 
has a fever >40.0°C (>104.0°F), redness and/or swelling at the 20vPnC or 13vPnC 
injection site measuring >14 measuring device units (>7 cm), or severe 20vPnC or 
13vPnC injection site pain (causes limitation of limb movement), to determine if the 
event requires further assessment by the investigator.

Remind the participant’s parent(s)/legal guardian(s) to contact the investigator or 
investigator site staff as soon as possible if any significant illness or medical event 
(eg, emergency room visit or hospitalization) occurs during the study period.

Remind the participant’s parent(s)/legal guardian(s) that use of prophylactic 
antipyretic/pain medication, while permitted, is not recommended on the day of 
investigational product administration (before or after vaccination).  If symptoms 
develop, the use of antipyretic/pain medication is allowed.  

The investigator or an authorized designee completes the CRF and the source documents 
and updates the investigational product accountability records.

The investigator or appropriately qualified designee reviews the e-diary data online at 
frequent intervals for the 7 days following vaccination to evaluate participant compliance 
and as part of ongoing safety review.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 68
8.10.5. Visit 5 (Dose 3 Follow-up: 28 to 42 Days After Visit 4)

Ensure and document that the participant continues to be eligible for the study 
(see Section 7 for participant discontinuation/withdrawal) and none of the temporary 
delay criteria are met (Section 5.5).

Record nonstudy vaccinations administered since Visit 4, as described in Section 6.5.4.

Review the participant’s e-diary data with the participant’s parent(s)/legal guardian(s); 
collect stop dates of any local and systemic events ongoing on the last day that the e-diary 
was completed and record stop dates in the CRF.

Collect the e-diary (if applicable).

Determine whether any AEs (includes nonserious AEs, SAEs, and NDCMCs) have 
occurred since the previous visit and follow up on any previously reported events to 
determine the outcome (ie, record stop dates or confirm if they are still continuing) and 
record as described in Section 10.3.4, and record concomitant medications used to treat 
NDCMCs and SAEs.

Collect a blood sample of approximately 5 mL for immunogenicity (a topical anesthetic 
is permitted).

The investigator or an authorized designee completes the CRF and the source documents 
and updates the investigational product accountability records.
8.10.6. Unscheduled Visits
If the participant’s parent(s)/legal guardian(s) reports redness or swelling at the injection site 
measuring >14 measuring device units (>7 cm), severe injection site pain, or a fever >40.0°C 
(>104.0°F) during the 7-day postvaccination period, a telephone contact must occur as soon 
as possible between the investigator or medically qualified designee and the participant’s 
parent(s)/legal guardian(s) to assess if an unscheduled investigator site visit is required.  Note 
that for a fever >40.0°C (>104.0°F), the participant’s parent(s)/legal guardian(s) should be 
instructed not to delay seeking medical care, as appropriate, while arranging for an 
unscheduled visit, if applicable.  A visit should be scheduled as soon as possible to assess the 
extent of the injection site reaction, unless any of the following is true:

The participant’s parent(s)/legal guardian(s) is unable to bring the participant to the 
unscheduled visit.

The reaction is no longer present at the time of the telephone contact.

The participant’s parent(s)/legal guardian(s) recorded an incorrect value in the e-diary 
(confirmation of an e-diary data entry error).

The investigator or authorized designee determined it was not needed.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 69
This telephone contact will be recorded in the participant’s source documentation and the 
CRF.
If the participant’s parent(s)/legal guardian(s) is unable to bring the participant to an 
unscheduled visit, or the principal investigator or authorized designee determined it was not 
needed, any ongoing reactions must be assessed at the next study visit.
During the investigator site visit, the reactions should be assessed by the investigator or a 
medically qualified member of the study staff such as a study physician or a study nurse, as 
applicable to the investigator’s local practice, who will:

Measure temperature (°C).

Measure minimum and maximum diameters of redness (if present).

Measure minimum and maximum diameters of swelling (if present).

Assess injection site pain in accordance with the grades provided in Section 8.2.2
(if present).

Assess for other findings associated with the reaction and record on the AE page of the 
CRF, if appropriate.
The investigator or an authorized designee will complete the unscheduled visit assessment 
page of the CRF.
The participant’s parent(s)/legal guardian(s) will also be instructed to contact investigator site 
staff if the participant experiences any emergency room visit or hospitalization for decreased 
appetite, drowsiness/increased sleep, irritability, or local reaction within 7 days of 
vaccination.
The participant’s parent(s)/legal guardian(s) will also be instructed to contact the investigator 
site to report any significant illness, medical event, or hospitalization that occurs during the 
study period.  The investigator site should determine if an unscheduled visit to further 
evaluate the event is warranted in all such cases.
Additionally, study staff may contact the participant’s parent(s)/legal guardian(s) to obtain 
additional information on Grade 3 events entered into the e-diary.
For specific modifications of visit windows, blood sample collection, and concomitant 
vaccine administration in the Russian cohort, please see Sections 10.10.1 and 10.10.2.
9. STATISTICAL CONSIDERATIONS
Methodology for summary and statistical analyses of the data collected in this study is 
described here and further detailed in a statistical analysis plan (SAP), which will be 
maintained by the sponsor.  The SAP may modify what is outlined in the protocol where 

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 70
appropriate; however, any major modifications of the primary endpoint definitions or their 
analyses will also be reflected in a protocol amendment.
9.1. Estimands and Statistical Hypotheses
9.1.1. Estimands
The estimands corresponding to each objective are described in the table in Section 3. The 
estimands to evaluate the immunogenicity objectives for NI are based on evaluable 
populations (see Section 9.3 for definition). These estimands estimate vaccine effect in the 
hypothetical setting where participants follow the study schedules and protocol requirements 
as directed. The estimand addresses the objective of estimating the maximum potential 
difference between 2 groups, since the impact of noncompliance is likely to diminish the 
observed difference between the 2 groups. Missing serology results will not be imputed. 
Immunogenicity results that are below the LLOQ will be set to 0.5 × LLOQ in the analysis.
In the primary safety objective evaluations, missing e-diary data will not be imputed. Missing 
AE dates will be imputed according to Pfizer safety rules.  No other missing information will 
be imputed in the safety analysis.
The endpoints and estimands corresponding to the objectives for the Russian cohort can be 
found in Section 10.10.3. All the statistical analysis for the Russian cohort will be 
descriptive.
9.1.2. Statistical Hypotheses
All hypothesis testing will be performed on the data from the primary study population.
9.1.2.1. Pneumococcal Immunogenicity Hypotheses
9.1.2.1.1. Percentage of Participants With Predefined Pneumococcal Serotype-Specific 
IgG Concentrations 1 Month After Dose 2
Hypothesis testing will be used to assess the NI of 20vPnC to 13vPnC for the percentage of 
participants with predefined pneumococcal serotype-specific IgG concentrations 1 month 
after Dose 2.  The null hypothesis (H0A) for a serotype is
H0A: π20vPnC – π13vPnC ≤–10%,
with a 10% margin for NI, where

π20vPnC is the percentage of participants achieving an IgG antibody concentration of 
predefined level in the 20vPnC group for the serotype 1 month after Dose 2;

If the serotype is from the 13 matched serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 
19A, 19F, 23F) in 13vPnC, π13vPnC is the percentage of participants achieving a 
predefined IgG concentration for the serotype from the 13vPnC group 1 month after 
Dose 2;

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 71

If the serotype is from the 7 additional serotypes (8, 10A, 11A, 12F, 15B, 22F, 33F) in 
20vPnC, π13vPnC is the percentage of participants achieving a predefined IgG 
concentration from the serotype with the lowest percentage among the 13 serotypes from 
the 13vPnC group 1 month after Dose 2, provided that the lowest percentage is not from 
serotype 3.  If the lowest percentage in the 13vPnC group is from serotype 3, the next 
lowest percentage in the 13vPnC group will be used in the comparison.  Historical data
suggest that serotype 3 behaves somewhat differently from the other serotypes in 
13vPnC; therefore, IgG results from serotype 3 will not be used in the comparison to 
assess the NI of the 7 additional serotypes;

The predefined levels for serotype-specific IgG concentrations are 0.35 µg/mL for all 
serotypes in 20vPnC except that the predefined levels are 0.23 µg/mL, 0.10 µg/mL, and 
0.12 µg/mL for serotypes 5, 6B, and 19A, respectively.
The null hypothesis (H0A) will be rejected and NI of 20vPnC to 13vPnC for the percentage of 
participants with predefined IgG concentration for a serotype will be declared if the lower 
bound of the 2-sided 95% CI for the difference (20vPnC – 13vPnC) in percentages, 
computed using the Miettinen and Nurminen method, is greater than –10% (10% NI margin).
9.1.2.1.2. Pneumococcal Serotype-Specific IgG GMCs 1 Month After Dose 2
Hypothesis testing will be used to assess the NI of 20vPnC to 13vPnC for pneumococcal
serotype-specific IgG GMCs 1 month after Dose 2.  The null hypothesis (H0B) for a serotype 
is
H0B: ln(µ20vPnC) – ln(µ13vPnC) ≤ln(0.5)
where ln(0.5) corresponds to a 2-fold margin for NI and

ln(μ20vPnC) is the natural log of the geometric mean IgG concentration in the 20vPnC
group for that serotype 1 month after Dose 2;

If the serotype is from the 13 matched serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 
19A, 19F, 23F), ln(μ13vPnC) is the natural log of the geometric mean IgG concentration in 
the 13vPnC group 1 month after Dose 2;

If the serotype is from the 7 additional serotypes (8, 10A, 11A, 12F, 15B, 22F, 33F) in 
20vPnC, ln(μ13vPnC) is the natural log of the geometric mean IgG concentration for the 
serotype with the lowest IgG GMC among the 13 serotypes from the 13vPnC group
1 month after Dose 2, provided that the lowest GMC is not from serotype 3.  If the lowest 
GMC in the 13vPnC group is from serotype 3, the next lowest GMC in the 13vPnC group 
will be used in the comparison.  As stated in Section 9.1.2.1.1, historical data suggest that 
serotype 3 behaves somewhat differently from the other serotypes in 13vPnC; therefore, 
IgG results from serotype 3 will not be used in the comparison to assess the NI of the
7 additional serotypes.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 72
The null hypothesis (H0B) will be rejected and NI of 20vPnC to 13vPnC for the 
pneumococcal serotype-specific IgG GMC will be declared for a serotype if the lower bound 
of the 2-sided 95% CI for the IgG GMR of 20vPnC to 13vPnC is greater than 0.5 (2-fold NI
margin).
9.1.2.1.3. Pneumococcal Serotype-Specific IgG GMCs 1 Month After Dose 3
Hypothesis testing to assess the NI of 20vPnC to 13vPnC for pneumococcal serotype-specific 
IgG GMCs 1 month after Dose 3 will be performed similarly to that for IgG GMCs 1 month 
after Dose 2, as described in Section 9.1.2.1.2, with ln(μ20vPnC) and ln(μ13vPnC) being the 
natural log of the geometric mean IgG concentrations 1 month after Dose 3 from the 20vPnC 
and 13vPnC groups, respectively, except for the 7 additional serotypes in 20vPnC, where 
ln(μ13vPnC) is the natural log of the geometric mean IgG concentration for the serotype with 
the lowest IgG GMC among the 13 serotypes from the 13vPnC group, provided that the 
lowest GMC is not from serotype 3. If the lowest GMC in the 13vPnC group is from 
serotype 3, the next lowest GMC in the 13vPnC group will be used in the hypothesis testing.
The null hypothesis (H0C: ln[µ20vPnC] – ln[µ13vPnC] ≤ ln[0.5]) will be rejected and NI of 
20vPnC to 13vPnC for the pneumococcal serotype-specific IgG GMC will be declared for a 
serotype if the lower bound of the 2-sided 95% CI for the IgG GMR of 20vPnC to 13vPnC 
for the serotype is greater than 0.5 (2-fold NI margin). 
9.1.2.2. Concomitant Immunogenicity Hypotheses
9.1.2.2.1. Noninferiority for Percentage of Participants With a Prespecified Antibody 
Level to Each Concomitant Vaccine Antigen 1 Month After Dose 3
Hypothesis testing will be used to assess the NI of the 20vPnC group to the 13vPnC group 
for the percentage of participants with a prespecified antibody level to each concomitant 
vaccine antigen at 1 month after Dose 3. The null hypothesis (H0C) for each concomitant 
vaccine antigen is 
H0C: π20vPnC – π13vPnC ≤-10%
with a 10% margin for NI, where π20vPnC and π13vPnC are the percentages of participants with 
prespecified antibody levels to diphtheria toxoid, tetanus toxoid, pertussis antigens (PT, 
FHA, PRN), HBsAg, poliovirus strains, or Hib at 1 month after Dose 3, from the 20vPnC 
group and the 13vPnC group, respectively.
The following are the prespecified antibody thresholds for the concomitant vaccine antigens:
Antigen
Prespecified Level
Diphtheria
≥0.1 IU/mL
Tetanus
≥0.1 IU/mL
Acellular pertussis (PT, FHA, PRN)
≥ the observed antipertussis antibody 
concentration achieved by 95% of 13vPnC 
recipients

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 73
Antigen
Prespecified Level
Hepatitis B
≥10 mIU/mL
Poliomyelitis (types 1, 2 and 3)
≥1:8
Hib
≥0.15 µg/mL anti-PRP
Alternative: ≥1.0 µg/mL anti-PRP
The null hypothesis (H0C) testing for NI will be rejected for a concomitant vaccine antigen if 
the lower bound of the 2-sided 95% CI for the difference (20vPnC – 13vPnC) in percentages, 
computed using the Miettinen and Nurminen method, is greater than –10% (10% NI margin).
9.1.2.2.2. Noninferiority for GMCs of Antibody Levels to Concomitant Vaccine 
Antigens 1 Month After Dose 3
Hypothesis testing will be used to assess the NI of the 20vPnC group to the 13vPnC group 
for GMCs of antibody levels to each concomitant vaccine antigen 1 month after Dose 3. The 
null hypothesis (H0D) for each concomitant vaccine antigen is
H0D: ln(µ20vPnC) – ln(µ13vPnC) ≤ln(0.5)
where ln(0.5) corresponds to a 2-fold margin for NI, and ln(µ20vPnC) and ln(µ13vPnC) are the 
natural log of the GMCs for antibody levels to measles, mumps, rubella, and varicella virus 
at 1 month after Dose 3 from the 20vPnC group and the 13vPnC group, respectively.
The null hypothesis (H0D) testing for NI will be rejected for a concomitant vaccine antigen if 
the lower bound of the 2-sided 95% CI for the GMR of GMCs (20vPnC over 13vPnC) is 
greater than 0.5 (2-fold NI margin).
9.1.3. Multiplicity Consideration
Primary Pneumococcal Immunogenicity Evaluation
For the primary pneumococcal immunogenicity objectives comparing serotype-specific IgG 
concentrations from the 20vPnC group to that from the 13vPnC group, NI of the immune 
response for each serotype is assessed by the hypothesis tests as described in 
Section 9.1.2.1.1 and Section 9.1.2.1.2, each at an alpha level of 0.05.  The primary 
pneumococcal immunogenicity objectives will be achieved if NI of the immune response 
induced by 20vPnC compared to 13vPnC based on both percentages of participants with 
predefined IgG levels and IgG GMCs at 1 month after Dose 2, as well as the IgG GMCs at 1 
month after Dose 3, is established for all 20 serotypes, a total of 60 NI evaluations.  
Therefore, the overall type I error rate for the primary immunogenicity assessment of the 
pneumococcal immune response of 20vPnC 1 month after Dose 3 is well controlled at the 
0.05 level.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 74
Primary Concomitant Immunogenicity Evaluation
All the primary concomitant immunogenicity endpoints/estimands are considered coprimary 
in the study. For the primary concomitant immunogenicity objective comparing immune 
responses induced by concomitant vaccine antigens from the 20vPnC group to that from the 
13vPnC group, NI is assessed by hypothesis tests as stated in Section 9.1.2.2, at a 
significance level of 0.05 for each of the concomitant vaccine antigens, including diphtheria 
toxoid, tetanus toxoid, PT, FHA, PRN, HBsAg, poliovirus strains, Hib, measles, mumps, 
rubella, and varicella. The primary concomitant immunogenicity objective will be met if NI
is achieved for each concomitant vaccine antigen. Therefore, the type I error rate for the 
concomitant immunogenicity assessment is well controlled at the 0.05 level.
9.2. Sample Size Determination
The sample size of the study is determined primarily based on considerations of
1) accumulating a sufficient overall safety database for the 20vPnC infant clinical 
development program, 2) providing robust assessment of the pneumococcal immune 
responses induced by 20vPnC and 13vPnC, 3) ensuring robust assessment to demonstrate 
that the immune responses induced by concomitant vaccine antigens given with 20vPnC are 
noninferior to immune responses induced by concomitant vaccine antigens given with 
13vPnC, and 4) practical constraints of available serum volumes from individual study 
participants with all planned immunogenicity assessments.
9.2.1. Sample Size Consideration for the Primary Pneumococcal Immunogenicity 
Objectives for the Primary Study Population
The study power for the primary pneumococcal immunogenicity objectives is assessed based 
on simulations of multivariate log-normal distributed random numbers with assumptions 
supported by IgG results after 2 and/or 3 infant doses from historical 13vPnC and 7vPnC
infant studies, and IgG results after 3 infant doses and the toddler dose of an internal Phase 2 
infant study of 20vPnC (B7471003).
For the immune response 1 month after 2 infant doses of 20vPnC, serotype-specific IgG 
GMCs and the variance-covariance matrix are assumed to be the same as those estimated 
from Study B7471003 1 month after 3 infant doses of 20vPnC, after adjustments made based 
on the observed relationship between IgG results after 2 infant doses and after 3 infant doses 
in the historical studies. To accommodate the uncertainties in the assumptions, 3 different 
assumed GMRs of the 20vPnC to the 13vPnC group 1 month after Dose 2 are explored to 
evaluate the study power in the simulation
For the immune response 1 month after Dose 3 (toddler dose), the true GMCs and 
variance-covariance matrices for the 20 serotype-specific IgG concentrations from both the 
20vPnC and 13vPnC groups are assumed to be the same as the IgG results 1 month after 
Dose 4 from Study B7471003 (3 infant doses and a toddler dose).
With approximately 1200 enrolled participants using a 1:1 randomization ratio, assuming a 
10% nonevaluable rate at 1 month after Dose 2, and a 17% nonevaluable rate at 1 month after
CCI

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 75
Dose 3, the study will result in approximately 540 and 500 evaluable participants for each 
vaccine group at 1 month after Dose 2 and 1 month after Dose 3, respectively. Under the 
3 IgG GMR assumptions, the study has approximately 99%, 97%, and 85% probability, 
respectively, to show NI of 20vPnC to 13vPnC for at least 47 (out of 60 total) positive NI
assessments comparing IgG results CCI
CCI
CCI
CCI
CCI
CCI

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 76
9.2.2. Sample Size Consideration for the Primary Concomitant Immunogenicity 
Objective
For the primary concomitant immunogenicity objective, the size of the subset of study 
participants for each assay will be determined based on the serum volume required and 
available samples for testing, in addition to the statistical power for each concomitant 
antigen.
Table 5 provides the minimum evaluable sample size required to demonstrate NI with the 
specified power for percentage of participants with prespecified antibody level to each 
concomitant vaccine antigen at 1 month after Dose 3. A 10% NI margin is used for each 
concomitant vaccine antigen. The estimates of response rates for the concomitant antigens 
were taken from a Pfizer infant study of 13vPnC.  With a target power of 99% for each 
concomitant antigen, the number of evaluable participants in each vaccine group needed 
ranges from 36 to 502. If the target power for each concomitant antigen is 95%, the 
evaluable sample size per group reduces to a range of 36 to 362 per group.
Table 5.
Sample Size Required With Specified Power to Demonstrate NI 
Comparing the 20vPnC Group to the 13vPnC Group Based on Percentage 
of Participants Who Reached Prespecified Antibody Levels for 
Concomitant Antigens, With 10% NI Margin
Antigen
Antibody Level 
Threshold
Assumed Percentagea of 
Participants Achieving
Prespecified Threshold
Evaluable Sample Size per
Vaccine Group
With at Least
20vPnC
13vPnC
95% Power
99% Power
Diphtheria
≥0.1 IU/mL
100
100
36
36
Tetanus 
≥0.1 IU/mL
97
97
116
154
PT
≥ Concentration achieved 
by 95% of 13vPnC group 
92
95
362
502
FHA
≥ Concentration achieved 
by 95% of 13vPnC group 
95
95
155
212
PRN
≥ Concentration achieved 
by 95% of 13vPnC group 
94
95
201
276
Hepatitis B
≥10 mIU/mL
97
98
127
167
Polio 1
≥1:8
100
100
36
36
Polio 2
≥1:8
100
100
36
36
Polio 3
≥1:8
100
100
36
36
CCI

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 77
Table 5.
Sample Size Required With Specified Power to Demonstrate NI 
Comparing the 20vPnC Group to the 13vPnC Group Based on Percentage 
of Participants Who Reached Prespecified Antibody Levels for 
Concomitant Antigens, With 10% NI Margin
Antigen
Antibody Level 
Threshold
Assumed Percentagea of 
Participants Achieving
Prespecified Threshold
Evaluable Sample Size per
Vaccine Group
With at Least
20vPnC
13vPnC
95% Power
99% Power
Haemophilus 
influenzae type B
≥0.15 µg/mL
99
99
72
90
Abbreviations: FHA = filamentous hemagglutinin; NI = noninferiority; PRN = pertactin; PT = pertussis toxin.
Note: NI criterion for each concomitant antigen: the lower bound of the 2-sided 95% CI for the difference 
(20vPnC – 13vPnC) in percentages of participants who reached the prespecified threshold is above -10%, 
calculated using the Miettinen and Nurminen method.
a.
The differences between 20vPnC and 13vPnC are assumed to be similar to those observed between 
13vPnC and 7vPnC from Phase 3 Prevnar 13 Study 6096A1-500.  Percentages of participants who 
reached specified thresholds from 13vPnC are assumed to be the same as those observed in 13vPnC 
groups from Phase 3 Prevnar 13 Study 6096A1-500 with a similar design.
Table 6 presents the minimum evaluable sample size required to demonstrate NI with 
specified power for GMC comparisons of the 20vPnC group to the 13vPnC group for 
antibody levels to measles, mumps, rubella, and varicella antigens 1 month after Dose 3. A 
2-fold NI margin is used for each concomitant vaccine antigen. The GMRs of antibody 
levels to each concomitant vaccine antigen from the 20vPnC group to that from the 13vPnC 
group and their standard deviations are assumed to be similar to those observed from a Pfizer 
Phase 3 13vPnC study in the power calculations (Table 6). With a target power of 99% for 
each of the measles, mumps, rubella, and varicella antigens, the evaluable sample size for 
each group ranges from 20 to 240. The evaluable sample size per group lowers to 15 to 171 
for a target power of 95% per antigen.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 78
Table 6.
Sample Size Required With Specified Power to Demonstrate NI of 20vPnC 
to 13vPnC Based on GMCs of Antibody Levels to Concomitant Vaccine 
Antigens, With a 2-Fold NI Margin
Antigen
Assumed GMRa for 
20vPnC vs 13vPnC
Assumed Standard 
Deviation GMRa
(on the Natural Log 
Scale)
Evaluable Sample Size per
Vaccine Group With at Least
95% Power
99% Power
Measles
0.98
0.654
26
36
Mumps
1.00
0.743
31
44
Rubella
0.83
1.294
171
240
Varicella Ig
1.00
0.497
15
20
Abbreviations: GMC = geometric mean concentration; GMR = geometric mean ratio; Ig = immunoglobulin; 
NI = noninferiority.
Note: NI criterion for each serotype: lower bound of the 2-sided 95% CI for GMR (20vPnC over 13vPnC) is 
greater than 0.5, calculated using a t-distribution.
a.
The GMR of the 20vPnC group to the 13vPnC group and the standard deviations are assumed to be 
similar to those observed from the 13vPnC and 7vPnC groups in Study 6096A1-004.
9.2.3. Sample Size Consideration for the Primary Safety Objective
The primary safety objective includes the endpoints for AEs, local reactions, and systemic 
events.  The number of participants in each vaccine group is 600, which provides a greater 
than 90% chance of observing at least 1 AE, local reaction, or systemic event in a group, 
assuming a true rate of at least 0.4% (Table 7).
Table 7.
Probability of Detecting at Least 1 Adverse Event
Sample Size per Group
True Rate of AEs
Probability of Observing at Least 1 AE
600
0.1%
45.1%
0.2%
69.9%
0.3%
83.5%
0.4%
91.0%
0.5%
95.1%
CCI

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 79
9.2.4. Sample Size Consideration for the Russian Cohort
The sample size for the Russian cohort is not driven by statistical power.  There is no 
hypothesis test for the data in the Russian cohort. The safety and pneumococcal 
immunogenicity data from the Russian cohort will be descriptively summarized.
9.3. Populations for Analysis
For purposes of analysis, the following participant populations are defined:
Population
Description
Enrolled 
All participants who have a signed ICD.
Randomized
All participants who are assigned a randomization number in 
the IRT system. 
Dose 2 evaluable 
immunogenicity 
All eligible randomized participants who are within the 
protocol-defined age window on the day of first vaccination, 
receive the vaccines to which they are randomly assigned at 
the first 2 doses, have at least 1 valid immunogenicity result 
from the 1-month-after-Dose 2 visit, have blood collection 
within an appropriate window for this visit, and have no 
other major protocol deviations as determined by the 
clinician.
Dose 3 evaluable 
immunogenicity
All eligible randomized participants who are within the 
protocol-defined age window on the day of first vaccination, 
receive all 3 randomized vaccinations, with Dose 3 received 
within the protocol-defined age window, have at least 1 valid 
immunogenicity result from the 1-month-after-Dose 3 visit, 
have blood collection within an appropriate window at this 
visit, and have no other major protocol deviations as 
determined by the clinician. 
Safety
All participants who receive at least 1 dose of the 
investigational product and have safety data assessed after 
any dose.
9.4. Statistical Analyses
The SAP will be developed and finalized before database lock for the final analysis and will 
describe the participant populations to be included in the analyses, and procedures for 
accounting for missing, unused, and spurious data.  This section is a summary of the planned 
statistical analyses of the primary, secondary, 
endpoints.
CCI
CCI

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 80
9.4.1. Immunogenicity Analysis
The statistical analysis of the pneumococcal immunogenicity results will be primarily based 
on the evaluable immunogenicity populations as defined in Section 9.3. The statistical 
analysis of concomitant immunogenicity results will be primarily based on the evaluable 
immunogenicity populations among those who receive the appropriate concomitant vaccines.
Participants will be summarized according to the vaccine group to which they were 
randomized.
Endpoint
Statistical Analysis Methods
Primary 
pneumococcal 
immunogenicity
•
Percentages of participants with predefined pneumococcal IgG 
concentrations 1 month after Dose 2
For each of the 20 serotypes, the difference between groups 
(20vPnC – 13vPnC) and its 2-sided 95% CI for the percentage of 
participants with predefined IgG concentrations 1 month after Dose 
2 will be provided.  If a serotype is from the 
13 matched serotypes, the percentage of participants with the 
predefined IgG level for the serotype in the 20vPnC group will be 
compared with the percentage for that serotype in the 13vPnC 
group.  If a serotype is from the 7 additional serotypes, the 
percentage of participants with the predefined IgG level in the 
20vPnC group will be compared with the lowest percentage among 
the 13 serotypes from the 13vPnC group, provided that the lowest 
percentage is not from serotype 3.  If the lowest percentage in the 
13vPnC group is from serotype 3, the next lowest percentage in the 
13vPnC group will be used in the comparison.  The Miettinen and 
Nurminen method will be used to derive the CI for the difference in 
percentages between vaccine groups.  The lower limit of the CI will 
be used in the hypothesis test for NI of 20vPnC to 13vPnC as 
detailed in Section 9.1.2.1.1.
In addition, for each of the 7 additional serotypes, the difference 
between groups (20vPnC – 13vPnC) with the comparator being the 
percentage of participants achieving predefined IgG concentrations 
for that corresponding serotype from the 13vPnC group will be 
calculated. The 2-sided 95% CI for the difference will also be 
based on the Miettinen and Nurminen method.
The analysis will be based on the Dose 2 evaluable immunogenicity 
population. 
CCI
CCI
CCI

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 81
Endpoint
Statistical Analysis Methods
Participants will be summarized according to the 
vaccine group to which they were randomized.  Missing serology 
data will not be imputed.
•
GMRs of pneumococcal IgG concentrations from the 20vPnC 
group to the 13vPnC group 1 month after Dose 2
For each of the 20 serotypes, the GMR of 20vPnC to 13vPnC at 
1 month after Dose 2 will be provided.  If a serotype is from the 
13 matched serotypes, the IgG GMC for the serotype in the 20vPnC 
group will be compared with the IgG GMC for that serotype in the 
13vPnC group.  If the serotype is from the 7 additional serotypes, 
the IgG GMC in the 20vPnC group will be compared with the 
lowest IgG GMC among the 13 serotypes from the 13vPnC group, 
provided that the lowest GMC is not from serotype 3.  If the lowest 
GMC in the 13vPnC group is from serotype 3, the next lowest 
GMC in the 13vPnC group will be used in the comparison.  GMRs 
and their 2-sided 95% CIs will be derived by calculating 
differences in means and CIs on the natural log scale of the 
concentration based on the t-distribution, and then exponentiating 
the results.  The difference in means, on the natural log scale, will 
be 20vPnC minus 13vPnC.  The lower limit of the CI will be used 
in the hypothesis test for NI of 20vPnC to 13vPnC as detailed in 
Section 9.1.2.1.2.
In addition, for each of the 7 additional serotypes, the GMR of 
20vPnC to 13vPnC at 1 month after Dose 2 with the comparator 
being the IgG GMC of that serotype in the 13vPnC group will be 
calculated. GMRs and their 2-sided 95% CIs will be derived in the 
same way as described above. 
The analyses will be based on the Dose 2 evaluable 
immunogenicity population. 
Participants will be summarized according to the 
vaccine group to which they were randomized. Missing serology 
data will not be imputed.
CCI
CCI
CCI
CCI
CCI

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 82
Endpoint
Statistical Analysis Methods

GMRs of pneumococcal IgG concentrations from the 20vPnC 
group to the 13vPnC group 1 month after Dose 3
The IgG GMRs at 1 month after Dose 3 will be analyzed the same 
way as the IgG GMRs at 1 month after Dose 2. The lower limit of 
the CI of the GMR will be used in the hypothesis test for NI of 
20vPnC to 13vPnC as detailed in Section 9.1.2.1.3.
Primary 
concomitant 
immunogenicity

Percentages of participants with prespecified antibody levels to 
specific concomitant vaccine antigens (diphtheria, tetanus, 
pertussis, HBsAg, polio, and Hib) at 1 month after Dose 3
For each of the concomitant vaccine antigens, 
a.
Antibody levels to diphtheria toxoid, tetanus toxoid, and 
pertussis antigens (PT, FHA, PRN), 
b. Antibody levels to HBsAg,
c.
Antibody levels to poliovirus strains (types 1, 2, and 3), and
d. Antibody levels to Hib.
The difference between the groups (20vPnC – 13vPnC) and its 
2-sided 95% CI for the percentage of participants with prespecified 
antibody levels 1 month after Dose 3 will be provided. The 
Miettinen and Nurminen method will be used to derive the CI for 
the difference in percentages between vaccine groups. The lower 
limit of the CI will be used in the hypothesis test for NI of 20vPnC 
group to 13vPnC group as detailed in Section 9.1.2.2.1.

GMRs in antibody levels to measles, mumps, rubella, and 
varicella viruses at 1 month after Dose 3
For each antibody level to measles, mumps, rubella, and varicella 
viruses, the GMR of the 20vPnC group to the 13vPnC group at 
1 month after Dose 3 will be provided. GMRs and their 2-sided 
95% CIs will be derived by calculating differences in means and 
CIs on the natural log scale of the concentrations based on the 
t-distribution, and then exponentiating the results. The difference in 
means, on the natural log scale, will be 20vPnC minus 13vPnC. 
The lower limit of the CI will be used in the hypothesis test for NI 
of 20vPnC to 13vPnC as detailed in Section 9.1.2.2.2.
The analysis will be based on the Dose 3 evaluable 
immunogenicity population, restricted to those who also receive 
the corresponding concomitant vaccines. An additional analysis 
will be performed based on the Dose 3 all-available 
immunogenicity population among those who also receive the 
corresponding concomitant vaccine, if there is a large enough 
difference in sample size between the all-available immunogenicity 

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 83
Endpoint
Statistical Analysis Methods
population and the evaluable immunogenicity population. 
Participants will be summarized according to the vaccine group to 
which they were randomized. Missing serology data will not be 
imputed.
Secondary 
pneumococcal 
immunogenicity

Percentages of participants with predefined pneumococcal IgG 
concentrations 1 month after Dose 3
This endpoint will be analyzed in the same way as the percentages 
of participants with predefined pneumococcal IgG concentrations 
1 month after Dose 3, except that no hypothesis test for NI will be 
performed.

GMTs of OPA 1 month after Dose 2 and 1 month after Dose 3
For each of the 20 serotypes in 20vPnC, the GMTs and 2-sided 
95% CIs for the OPA titers at each time point will be provided for 
each vaccine group. Geometric means and the associated 2-sided 
95% CIs will be derived by calculating means and CIs on the 
natural log scale based on the t-distribution, and then 
exponentiating the results.

GMFRs of pneumococcal IgG concentrations from before Dose 
3 to 1 month after Dose 3 in each vaccine group
For each of the 20 serotypes in 20vPnC, the GMFR and 2-sided 
95% CI for IgG concentrations from before Dose 3 to 1 month 
after Dose 3 will be provided for each vaccine group. GMFRs will 
be limited to participants with nonmissing values at both time 
points. The GMFR will be calculated as the mean of the difference 
of logarithmically transformed assay results (1 month after Dose 3 
– before Dose 3) and transformed back to the original scale. Two 
(2)-sided 95% CIs will be obtained by calculating the CIs using 
Student’s t-distribution for the mean difference of the 
logarithmically transformed assay results and exponentiating the 
limits back to the original scale.
Secondary 
concomitant 
immunogenicity 

Percentages of participants with prespecified antibody levels to 
specific concomitant vaccine antigens (diphtheria, tetanus, 
pertussis, polio, and Hib) 1 month after Dose 2
Percentages of participants with prespecified antibody levels to 
diphtheria toxoid, tetanus toxoid, pertussis antigens (PT, FHA, 
PRN), poliovirus strains, and Hib 1 month after Dose 2 will be 
provided for each vaccine group, along with 2-sided 
Clopper-Pearson 95% CIs. The differences between the groups 

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 84
Endpoint
Statistical Analysis Methods
(20vPnC – 13vPnC) in these percentages and the associated 
2-sided Miettinen and Nurminen 95% CIs will be calculated.
CCI

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 85
CCI

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 86
9.4.2. Safety Analyses
All safety analyses will be performed on the safety population.
Endpoint
Statistical Analysis Methods
Primary 
safety 
•
Descriptive statistics will be provided for each reactogenicity endpoint 
for each dose and vaccine group. Local reactions and systemic events 
from Day 1 through Day 7 after each vaccination will be presented by 
severity cumulatively across severity levels. Descriptive summary 
statistics will include counts and percentages of participants with the 
indicated endpoint and the associated 2-sided Clopper-Pearson 95% CIs. 
Between-group differences (20vPnC – 13vPnC) in these percentages
and their 2-sided 95% CIs will also be provided.  The Miettinen and 
Nurminen method will be used to derive the 95% CI for the difference 
in percentages between vaccine groups.
•
AEs will be categorized according to Medical Dictionary for Regulatory 
Activities (MedDRA) terms. A 3-tier approach will be used to 
summarize AEs. Under this approach AEs are classified into 1 of 
3-tiers: (1) Tier 1 events are prespecified events of clinical importance 
and are identified in a list in the product’s safety review plan; (2) Tier 2 
events are those that are not Tier 1 but are considered “relatively 
common”; a MedDRA preferred term is defined as a Tier 2 event if 
there are at least 1% of participants in at least 1 vaccine group reporting 
the event; and (3) Tier 3 events are those that are neither Tier 1 nor Tier 
2 events. For both Tier 1 and Tier 2 events, the 2-sided 95% CIs for the 
difference in percentage of participants reporting the events between the 
20vPnC and 13vPnC groups will be calculated using the Miettinen and 
CCI

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 87
Endpoint
Statistical Analysis Methods
Nurminen method. In addition, for Tier 1 events, the asymptotic 
p-values will also be presented for the difference in percentage of 
participants reporting the events, based on the same test statistic and 
under the assumption that the test statistic is asymptotically normally 
distributed. There is no Tier 1 event identified for 20vPnC at this stage. 
Descriptive summary statistics (counts, percentages, and associated 
2-sided Clopper-Pearson 95% CIs) will be provided for Tier 3 events for 
each vaccine group.
•
SAEs and NDCMCs will be categorized according to MedDRA terms. 
Counts, percentages, and the associated 2-sided Clopper-Pearson 95% 
CIs for SAEs and NDCMCs will be provided for each vaccine group.
The safety analyses are based on the safety population. Participants will 
be summarized by vaccine group according to the investigational 
products they actually received. Missing e-diary data will not be 
imputed; missing AE dates will be handled according to the Pfizer 
safety rules.
Secondary
•
Not applicable (N/A)
9.4.3. Other Analyses 
The safety and pneumococcal immunogenicity data from the Russian cohort will be 
descriptively summarized separately.
9.5. Interim Analyses
No interim analysis is planned in this study.
9.5.1. Analysis Timing
The safety and immunogenicity results in this study will be analyzed and reported when the 
safety and immunogenicity data 1 month after Dose 3 are available from all participants in 
the primary study population.
The safety and pneumococcal immunogenicity results of the Russian cohort will be analyzed 
and reported when safety and pneumococcal immunogenicity data are available from all 
participants in the Russian cohort.
Sponsor personnel involved in evaluating participant data in the primary study population 
will be blinded to vaccine assignment until the analysis at the completion of the primary 
study population. The study team will remain blinded to the vaccine assignments of the 
Russian cohort until that cohort has completed the study. Laboratory personnel performing 
CCI

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 88
the assays will remain blinded until all assays are completed and assay results of each 
population/cohort are finalized.
CCI

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 89
10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations
10.1.1. Regulatory and Ethical Considerations
This study will be conducted in accordance with the protocol and with the following:

Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and CIOMS International Ethical Guidelines;

Applicable ICH GCP guidelines;

Applicable laws and regulations, including applicable privacy laws.
The protocol, protocol amendments, ICD, IB, and other relevant documents 
(eg, advertisements) must be reviewed and approved by the sponsor and submitted to an 
IRB/EC by the investigator and reviewed and approved by the IRB/EC before the study is 
initiated.
Any amendments to the protocol will require IRB/EC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants.
The investigator will be responsible for the following:

Providing written summaries of the status of the study to the IRB/EC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/EC;

Notifying the IRB/EC of SAEs or other significant safety findings as required by 
IRB/EC procedures;

Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 Code of Federal Regulations (CFR), ICH guidelines, the IRB/EC, 
European regulation 536/2014 for clinical studies (if applicable), and all other 
applicable local regulations.
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
regulatory authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the investigational 
product, Pfizer should be informed immediately.
In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study participants against any immediate hazard, and 

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 90
of any serious breaches of this protocol or of ICH GCP that the investigator becomes aware 
of.
10.1.2. Financial Disclosure
Investigators and subinvestigators 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 study 
and for 1 year after completion of the study.
10.1.3. Informed Consent Process
The investigator or his/her representative will explain the nature of the study to the 
participant’s parent(s)/legal guardian(s) and answer all questions regarding the study.
The participant’s parent(s)/legal guardian(s) must be informed that participation is voluntary.  
The participant’s parent(s)/legal guardian(s) will be required to sign a statement of informed 
consent that meets the requirements of 21 CFR 50, local regulations, ICH guidelines, Health 
Insurance Portability and Accountability Act (HIPAA) requirements, where applicable, and 
the IRB/EC or study center.
The investigator must ensure that each study participant’s parent(s)/legal guardian(s) is fully 
informed about the nature and objectives of the study, the sharing of data related to the study, 
and possible risks associated with participation, including the risks associated with the 
processing of the participant’s personal data.
The participant’s parent(s)/legal guardian(s) must be informed that the participant’s personal 
study-related data will be used by the sponsor in accordance with local data protection law.  
The level of disclosure must also be explained to the participant’s parent(s)/legal guardian(s).
The participant’s parent(s)/legal guardian(s) must be informed that the participant’s medical 
records may be examined by Clinical Quality Assurance auditors or other authorized 
personnel appointed by the sponsor, by appropriate IRB/EC members, and by inspectors 
from regulatory authorities.
The investigator further must ensure that each study participant’s parent(s)/legal guardian(s) 
is fully informed about his or her right to access and correct the participant’s personal data 
and to withdraw consent for the processing of the participant’s personal data.
The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date the written consent was obtained.  
The authorized person obtaining the informed consent must also sign the ICD.
The participant’s parent(s)/legal guardian(s) must be reconsented to the most current version 
of the ICD(s) during the participant’s participation in the study.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 91
A copy of the ICD(s) must be provided to the participant’s parent(s)/legal guardian(s).
10.1.4. Data Protection
All parties will comply with all applicable laws, including laws regarding the implementation 
of organizational and technical measures to ensure protection of participant data.
Participants’ personal data will be stored at the study site in encrypted electronic and/or paper 
form and will be password protected or secured in a locked room to ensure that only 
authorized study staff have access.  The study site will implement appropriate technical and 
organizational measures to ensure that the personal data can be recovered in the event of 
disaster.  In the event of a potential personal data breach, the study site shall be responsible 
for determining whether a personal data breach has in fact occurred and, if so, providing 
breach notifications as required by law.
To protect the rights and freedoms of natural persons with regard to the processing of 
personal data, participants will be assigned a single, participant-specific numerical code.  
Any participant records or data sets that are transferred to the sponsor will contain the 
numerical code; participant names will not be transferred.  All other identifiable data 
transferred to the sponsor will be identified by this single, participant-specific code.  The 
study site will maintain a confidential list of participants who participated in the study, 
linking each participant’s numerical code to his or her actual identity.  In case of data 
transfer, the sponsor will protect the confidentiality of participants’ personal data consistent 
with the clinical study agreement and applicable privacy laws.
10.1.5. Dissemination of Clinical Study Data
Pfizer fulfills its commitment to publicly disclose clinical study results through posting the 
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov), the European Clinical Trials 
Database (EudraCT), and/or www.pfizer.com, and other public registries in accordance with 
applicable local laws/regulations.  In addition, Pfizer reports study results outside of the 
requirements of local laws/regulations pursuant to its standard operating procedures (SOPs).
In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country in 
which the study was conducted.
www.clinicaltrials.gov
Pfizer posts clinical trial US Basic Results on www.clinicaltrials.gov for Pfizer-sponsored 
interventional studies (conducted in patients) that evaluate the safety and/or efficacy of a 
product, regardless of the geographical location in which the study is conducted.  US Basic 
Results are generally submitted for posting within 1 year of the primary completion date 
(PCD) for studies in adult populations or within 6 months of the PCD for studies in pediatric 
populations.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 92
PCD is defined as the date that the final participant was examined or received an intervention 
for the purposes of final collection of data for the primary outcome, whether the clinical 
study concluded according to the prespecified protocol or was terminated.
EudraCT
Pfizer posts EU Basic Results on EudraCT for all Pfizer-sponsored interventional studies that 
are in scope of EU requirements.  EU Basic Results are submitted for posting within 1 year 
of the PCD for studies in adult populations or within 6 months of the PCD for studies in 
pediatric populations.
www.pfizer.com
Pfizer posts public disclosure synopses (clinical study report [CSR] synopses in which any 
data that could be used to identify individual participants have been removed) on 
www.pfizer.com for Pfizer-sponsored interventional studies at the same time the US Basic 
Results document is posted to www.clinicaltrials.gov.
Documents within marketing authorization packages/submissions
Pfizer complies with the European Union Policy 0070, the proactive publication of clinical 
data to the European Medicines Agency (EMA) website.  Clinical data, under Phase 1 of this 
policy, includes clinical overviews, clinical summaries, CSRs, and appendices containing the 
protocol and protocol amendments, sample CRFs, and statistical methods.  Clinical data, 
under Phase 2 of this policy, includes the publishing of individual participant data.  Policy 
0070 applies to new marketing authorization applications submitted via the centralized 
procedure since 01 January 2015 and applications for line extensions and for new indications 
submitted via the centralized procedure since 01 July 2015.
Data Sharing
Pfizer provides researchers secure access to patient-level data or full CSRs for the purposes 
of “bona-fide scientific research” that contribute to the scientific understanding of the 
disease, target, or compound class.  Pfizer will make available data from these trials 
24 months after study completion.  Patient-level data will be anonymized in accordance with 
applicable privacy laws and regulations.  CSRs will have personally identifiable information 
redacted.
Data requests are considered from qualified researchers with the appropriate competencies to 
perform the proposed analyses.  Research teams must include a biostatistician.  Data will not 
be provided to applicants with significant conflicts of interest, including individuals 
requesting access for commercial/competitive or legal purposes.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 93
10.1.6. Data Quality Assurance
All participant data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (eg, laboratory data).  The investigator is 
responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the CRF.
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF.
The investigator must ensure that the CRFs are securely stored at the study site in encrypted 
electronic and/or paper form and are password protected or secured in a locked room to 
prevent access by unauthorized third parties.
The investigator must permit study-related monitoring, audits, IRB/EC review, and 
regulatory agency inspections and provide direct access to source data documents.  This 
verification may also occur after study completion.  It is important that the investigator(s) 
and their relevant personnel are available during the monitoring visits and possible audits or 
inspections and that sufficient time is devoted to the process.
Monitoring details describing strategy (eg, risk-based initiatives in operations and quality 
such as risk management and mitigation strategies and analytical risk-based monitoring), 
methods, responsibilities, and requirements, including handling of noncompliance issues and 
monitoring techniques (central, remote, or on-site monitoring), are provided in the
monitoring plan.
The sponsor or designee is responsible for the data management of this study, including 
quality checking of the data.
Study monitors will perform ongoing source data verification to confirm that data entered 
into the CRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements.
Records and documents, including signed ICDs, pertaining to the conduct of this study must 
be retained by the investigator for 15 years after study completion unless local regulations or 
institutional policies require a longer retention period.  No records may be destroyed during 
the retention period without the written approval of the sponsor.  No records may be 
transferred to another location or party without written notification to the sponsor.  The 
investigator must ensure that the records continue to be stored securely for as long as they are 
maintained.
When participant data are to be deleted, the investigator will ensure that all copies of such 
data are promptly and irrevocably deleted from all systems.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 94
The investigator(s) will notify the sponsor or its agents immediately of any regulatory 
inspection notification in relation to the study.  Furthermore, the investigator will cooperate 
with the sponsor or its agents to prepare the investigator site for the inspection and will allow 
the sponsor or its agent, whenever feasible, to be present during the inspection.  The 
investigator site and investigator will promptly resolve any discrepancies that are identified 
between the study data and the participant's medical records.  The investigator will promptly 
provide copies of the inspection findings to the sponsor or its agent.  Before response 
submission to the regulatory authorities, the investigator will provide the sponsor or its 
agents with an opportunity to review and comment on responses to any such findings.
10.1.7. Source Documents
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected.  Source documents are filed at the investigator site.
Data reported on the CRF or entered in the electronic CRF (eCRF) 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 study.  Also, current medical records must be available.
Definition of what constitutes source data can be found in the ISF.
10.1.8. Study and Site Closure
The sponsor designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor.  Study sites will be closed upon 
study completion.  A study site is considered closed when all required documents and study 
supplies have been collected and a study-site closure visit has been performed.
The investigator may initiate study-site closure at any time upon notification to the contract 
research organization (CRO) if requested to do so by the responsible IRB/EC or if such 
termination is required to protect the health of study participants.
Reasons for the early closure of a study site by the sponsor may include but are not limited 
to:

Failure of the investigator to comply with the protocol, the requirements of the 
IRB/EC or local health authorities, the sponsor's procedures, or GCP guidelines;

Inadequate recruitment of participants by the investigator;

Discontinuation of further study intervention development;

Study completion of the applicable population or cohort.
Study termination is also provided for in the clinical study agreement.  If there is any conflict 
between the contract and this protocol, the contract will control as to termination rights.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 95
10.1.9. Publication Policy
The results of this study may be published or presented at scientific meetings by the 
investigator after publication of the overall study results or 18 months after end of the study 
(or study termination), whichever comes first.
The investigator agrees to refer to the primary publication in any subsequent publications 
such as secondary manuscripts, and submits all manuscripts or abstracts to the sponsor 
30 days before submission.  This allows the sponsor to protect proprietary information and to 
provide comments and the investigator will, on request, remove any previously undisclosed 
confidential information before disclosure, except for any study- or Pfizer 
intervention-related information necessary for the appropriate scientific presentation or 
understanding of the study results.
For all publications relating to the study, the investigator will comply with recognized ethical 
standards concerning publications and authorship, including those established by the 
International Committee of Medical Journal Editors.
The sponsor will comply with the requirements for publication of the overall study results 
covering all investigator sites.  In accordance with standard editorial and ethical practice, the 
sponsor will support publication of multicenter studies only in their entirety and not as 
individual site data.  In this case, a coordinating investigator will be designated by mutual 
agreement.
Authorship of publications for the overall study results will be determined by mutual 
agreement and in line with International Committee of Medical Journal Editors authorship 
requirements.
If publication is addressed in the clinical study agreement, the publication policy set out in 
this section will not apply.
10.1.10. Sponsor’s Qualified Medical Personnel
The contact information for the sponsor's appropriately qualified medical personnel for the 
study is documented in the study contact list located in the ISF.
To facilitate access to appropriately qualified medical personnel on study-related medical 
questions or problems, the participant’s parent(s)/legal guardian(s) are provided with a 
contact card.  The contact card contains, at a minimum, protocol and investigational product 
identifiers, participant numbers, contact information for the investigator site, and contact 
details for a contact center in the event that the investigator site staff cannot be reached to 
provide advice on a medical question or problem originating from another healthcare 
professional not involved in the participant’s participation in the study.
The contact number can also be used by investigator staff if they are seeking advice on 
medical questions or problems; however, it should be used only in the event that the 
established communication pathways between the investigator site and the study team are not 

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 96
available.  It is therefore intended to augment, but not replace, the established communication 
pathways between the investigator site and the study team for advice on medical questions or 
problems that may arise during the study.  The contact number is not intended for use by the 
participant’s parent(s)/legal guardian(s) directly, and if a participant’s parent(s)/legal 
guardian(s) calls that number, he or she will be directed back to the investigator site.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 97
10.2. Appendix 2: Clinical Laboratory Tests
Not applicable.
10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting
10.3.1. Definition of AE
AE Definition

An AE is any untoward medical occurrence in a patient or clinical study participant, 
temporally associated with the use of study intervention, whether or not considered 
related to the study intervention.

NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of study intervention.
Events Meeting the AE Definition

Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) 
or other safety assessments (eg, electrocardiogram [ECG], radiological scans, vital 
sign measurements), including those that worsen from baseline, considered 
clinically significant in the medical and scientific judgment of the investigator 
(ie, not related to progression of underlying disease).

Exacerbation of a chronic or intermittent preexisting condition including either an 
increase in frequency and/or intensity of the condition.

New conditions detected or diagnosed after study intervention administration even 
though it may have been present before the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication.  Overdose per se will not be reported as 
an AE/SAE unless it is an intentional overdose taken with possible 
suicidal/self-harming intent.  Such overdoses should be reported regardless of 
sequelae.

The signs, symptoms, and/or clinical sequelae resulting from lack of efficacy will be 
reported as an AE or SAE if they fulfill the definition of an AE or SAE.  Also, “lack 
of efficacy” or “failure of expected pharmacological action” constitutes an AE or 
SAE.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 98
Events NOT Meeting the AE Definition

Events that, in the clinical judgment of the investigator, are 1) consistent with 
normal growth and development and 2) do not differ significantly in frequency or 
severity from expected, are not generally to be considered AEs. Examples may 
include, but are not limited to, teething, contact diaper rash, spitting up, colic, or 
typical fussiness/crying in infants and children.

Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition.

The disease/disorder being studied or expected progression, signs, or symptoms of 
the disease/disorder being studied, unless more severe than expected for the 
participant’s condition.

Medical or surgical procedure (eg, 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).

Anticipated day-to-day fluctuations of preexisting disease(s) or condition(s) present 
or detected at the start of the study that do not worsen.
10.3.2. Definition of NDCMC
An NDCMC is defined as a significant disease or medical condition, not previously 
identified, that is expected to be persistent or is otherwise long-lasting in its effects.
10.3.3. Definition of SAE
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (eg, hospitalization for signs/symptoms of the disease under study, death 
due to progression of disease).
An SAE is defined as any untoward medical occurrence that, at any dose:
a. Results in death
b. Is life-threatening
The term “life-threatening” in the definition of “serious” refers to an event in which the 
participant was at risk of death at the time of the event.  It does not refer to an event that 
hypothetically might have caused death if it were more severe.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 99
c.
Requires inpatient hospitalization or prolongation of existing hospitalization
In general, hospitalization signifies that the participant 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 outpatient 
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.
Hospitalization for elective treatment of a preexisting condition that did not worsen from 
baseline is not considered an AE.
d. Results in persistent disability/incapacity

The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions.

This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, 
and accidental trauma (eg, sprained ankle), which may interfere with or prevent 
everyday life functions but do not constitute a substantial disruption.
e.
Is a congenital anomaly/birth defect
f.
Other situations:

Medical or scientific judgment should be exercised in deciding whether SAE 
reporting is appropriate in other situations such as important medical events that 
may not be immediately life-threatening or result in death or hospitalization but may 
jeopardize the participant or may require medical or surgical intervention to prevent 
one of the other outcomes listed in the above definition.  These events should 
usually be considered serious.

Examples of such events include invasive or malignant cancers, intensive treatment 
in an emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization, or development of drug dependency 
or drug abuse.
10.3.4. Recording/Reporting and Follow-up of AEs and/or SAEs
AE and SAE Recording/Reporting
The table below summarizes the requirements for recording adverse events on the CRF and 
for reporting serious adverse events on the Vaccine SAE Reporting Form to Pfizer Safety.  
These requirements are delineated for 3 types of events: (1) SAEs; (2) nonserious AEs; and 
(3) exposure to the investigational product under study during pregnancy or breastfeeding, 
and occupational exposure.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 100
It should be noted that the Vaccine SAE Reporting Form for reporting of SAE information 
is not the same as the AE page of the CRF.  When the same data are collected, the forms 
must be completed in a consistent manner.  AEs should be recorded using concise medical 
terminology and the same AE term should be used on both the CRF and the Vaccine SAE 
Reporting Form for reporting of SAE information.
Safety Event
Recorded on the CRF
Reported on the Vaccine 
SAE Reporting Form to 
Pfizer Safety Within 24 
Hours of Awareness
SAE
All
All
Nonserious AE
All
None
Exposure to the 
investigational product 
under study during 
pregnancy or 
breastfeeding, and 
occupational exposure
None
All (and exposure during 
pregnancy [EDP] 
supplemental form for EDP)  

When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (eg, hospital progress notes, laboratory reports, and diagnostic 
reports) related to the event.

The investigator will then record all relevant AE/SAE information in the CRF.

It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to Pfizer Safety in lieu of completion of the Vaccine SAE Reporting
Form/AE/SAE CRF page.

There may be instances when copies of medical records for certain cases are 
requested by Pfizer Safety.  In this case, all participant identifiers, with the 
exception of the participant number, will be redacted on the copies of the medical 
records before submission to Pfizer Safety.

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/SAE.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 101
Assessment of Intensity
The investigator will make an assessment of intensity for each AE and SAE reported during 
the study and assign it to 1 of the following categories: 

Mild: An event that is easily tolerated by the participant, causing minimal 
discomfort and not interfering with everyday activities.

Moderate: An event that causes sufficient discomfort and interferes with normal 
everyday activities.

Severe: An event that prevents normal everyday activities.  An AE that is assessed 
as severe should not be confused with an SAE. Severe is a category utilized for 
rating the intensity of an event; and both AEs and SAEs can be assessed as severe.
An event is defined as “serious” when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as severe.
GRADE 
If required on the AE page of the CRF, the investigator will use the 
adjectives MILD, MODERATE, or SEVERE to describe the maximum 
intensity of the AE. For purposes of consistency, these intensity grades 
are defined as follows:
1
MILD
Does not interfere with participant's usual 
function.
2
MODERATE
Interferes to some extent with participant's usual 
function.
3
SEVERE
Interferes significantly with participant's usual 
function.
Assessment of Causality

The investigator is obligated to assess the relationship between study intervention 
and each occurrence of each AE/SAE.

A “reasonable possibility” of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot 
be ruled out.

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 study intervention 
administration will be considered and investigated.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 102
Assessment of Causality

The investigator will also consult the IB and/or product information, for marketed 
products, in his/her assessment.

For each AE/SAE, the investigator must document in the medical notes that he/she 
has reviewed the AE/SAE and has provided an assessment of causality.

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 make 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.

If the investigator does not know whether or not the investigational product caused 
the event, then the event will be handled as “related to investigational product” for 
reporting purposes, as defined by the sponsor.  In addition, if the investigator 
determines that an SAE is associated with study procedures, the investigator must 
record this causal relationship in the source documents and CRF, and report such an 
assessment in the dedicated section of the Vaccine SAE Reporting Form and in 
accordance with the SAE reporting requirements.
Follow-up of AEs and SAEs

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.

If a participant dies during participation in the study or during a recognized 
follow-up period, the investigator will provide Pfizer Safety with a copy of any 
postmortem findings, including histopathology.

New or updated information will be recorded in the originally completed CRF.

The investigator will submit any updated SAE data to the sponsor within 24 hours of 
receipt of the information.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 103
10.3.5. Reporting of SAEs
SAE Reporting to Pfizer Safety via an Electronic Data Collection Tool

The primary mechanism for reporting an SAE to Pfizer Safety will be the electronic 
data collection tool.

If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) in order to report the event within 24 hours.

The site will enter the SAE data into the electronic system as soon as the data 
become available.

After the study is completed at a given site, the electronic data collection tool will be 
taken off-line to prevent the entry of new data or changes to existing data.

If a site receives a report of a new SAE from a study participant or receives updated 
data on a previously reported SAE after the electronic data collection tool has been 
taken off-line, then the site can report this information on a paper SAE form 
(see next section) or to Pfizer Safety by telephone.
SAE Reporting to Pfizer Safety via Vaccine SAE Reporting Form

Facsimile transmission of the Vaccine SAE Reporting Form is the preferred method 
to transmit this information to Pfizer Safety.

In circumstances when the facsimile is not working, notification by telephone is 
acceptable with a copy of the Vaccine SAE Reporting Form sent by overnight mail 
or courier service.

Initial notification via telephone does not replace the need for the investigator to 
complete and sign the Vaccine SAE Reporting Form pages within the designated 
reporting time frames.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 104
CCI

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 105
CCI

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 106
10.5. Appendix 5: Genetics
Not applicable.
10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-up Assessments 
Potential Cases of Drug-Induced Liver Injury
Humans exposed to a drug who show no sign of liver injury (as determined by elevations in 
transaminases) are termed “tolerators,” while those who show transient liver injury, but adapt 
are termed “adaptors.”  In some participants, transaminase elevations are a harbinger of a 
more serious potential outcome.  These participants fail to adapt and therefore are 
"susceptible" to progressive and serious liver injury, commonly referred to as drug-induced 
liver injury (DILI).  Participants who experience a transaminase elevation above 3 times the 
upper limit of normal (× ULN) should be monitored more frequently to determine if they are 
an “adaptor” or are “susceptible.”
Liver function tests (LFTs) are not required as a routine safety monitoring procedure in this 
study.  However, should an investigator deem it necessary to assess LFTs because a 
participant presents with clinical signs/symptoms, such LFT results should be managed and 
followed as described below.
In the majority of DILI cases, elevations in aspartate aminotransferase (AST) and/or alanine 
aminotransferase (ALT) precede total bilirubin (TBili) elevations (>2 × ULN) by several 
days or weeks.  The increase in TBili typically occurs while AST/ALT is/are still elevated 
above 3 × ULN (ie, AST/ALT and TBili values will be elevated within the same laboratory 
sample).  In rare instances, by the time TBili elevations are detected, AST/ALT values might 
have decreased.  This occurrence is still regarded as a potential DILI.  Therefore, abnormal 
elevations in either AST OR ALT in addition to TBili that meet the criteria outlined below 
are considered potential DILI (assessed per Hy’s law criteria) cases and should always be 
considered important medical events, even before all other possible causes of liver injury 
have been excluded.
The threshold of laboratory abnormalities for a potential DILI case depends on the 
participant’s individual baseline values and underlying conditions.  Participants who present 
with the following laboratory abnormalities should be evaluated further as potential DILI 
(Hy’s law) cases to definitively determine the etiology of the abnormal laboratory values:

Participants with AST/ALT and TBili baseline values within the normal range who 
subsequently present with AST OR ALT values >3 × ULN AND a TBili value 
>2 × ULN with no evidence of hemolysis and an alkaline phosphatase value 
<2 × ULN or not available.

For participants with baseline AST OR ALT OR TBili values above the ULN, the 
following threshold values are used in the definition mentioned above, as needed, 
depending on which values are above the ULN at baseline:

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 107

Preexisting AST or ALT baseline values above the normal range: AST or ALT 
values >2 times the baseline values AND >3 × ULN; or >8 × ULN (whichever is 
smaller).

Preexisting values of TBili above the normal range: TBili level increased from 
baseline value by an amount of at least 1 × ULN or if the value reaches 
>3 × ULN (whichever is smaller).
Rises in AST/ALT and TBili separated by more than a few weeks should be assessed 
individually based on clinical judgment; any case where uncertainty remains as to whether it 
represents a potential Hy’s law case should be reviewed with the sponsor.
The participant should return to the investigator site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the abnormal results.  This evaluation should 
include laboratory tests, detailed history, and physical assessment.
In addition to repeating measurements of AST and ALT and TBili for suspected cases of 
Hy’s law, additional laboratory tests should include albumin, creatine kinase (CK), direct and 
indirect bilirubin, gamma-glutamyl transferase (GGT), prothrombin time/international 
normalized ratio (INR), total bile acids, and alkaline phosphatase.  Consideration should also 
be given to drawing a separate tube of clotted blood and an anticoagulated tube of blood for 
further testing, as needed, for further contemporaneous analyses at the time of the recognized 
initial abnormalities to determine etiology.  A detailed history, including relevant 
information, such as review of ethanol, acetaminophen (either by itself or as a coformulated 
product in prescription or over-the-counter medications), recreational drug, supplement 
(herbal) use and consumption, family history, sexual history, travel history, history of contact 
with a jaundiced person, surgery, blood transfusion, history of liver or allergic disease, and 
potential occupational exposure to chemicals, should be collected.  Further testing for acute 
hepatitis A, B, C, D, and E infection and liver imaging (eg, biliary tract) and collection of 
serum sample for acetaminophen drug and/or protein adduct levels may be warranted.
All cases demonstrated on repeat testing as meeting the laboratory criteria of AST/ALT and 
TBili elevation defined above should be considered potential DILI (Hy’s law) cases if no 
other reason for the LFT abnormalities has yet been found.  Such potential DILI (Hy’s law) 
cases are to be reported as SAEs, irrespective of availability of all the results of the 
investigations performed to determine etiology of the LFT abnormalities.
A potential DILI (Hy’s law) case becomes a confirmed case only after all results of 
reasonable investigations have been received and have excluded an alternative etiology.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 108
10.7. Appendix 7: ECG Findings of Potential Clinical Concern
Not applicable.
10.8. Appendix 8: Medical Device Adverse Events, Adverse Device Effects (ADEs), 
Serious Adverse Events, and Device Deficiencies: Definition and Procedures for 
Recording, Evaluating, Follow-up, and Reporting
Definitions of a Medical Device Incident
The definitions and procedures detailed in this appendix are in accordance with ISO 14155.
Both the investigator and the sponsor will comply with all local medical device reporting 
requirements.
The detection and documentation procedures described in this protocol apply to all sponsor 
medical devices provided for use in the study (see Section 6.1.2 for the list of sponsor 
medical devices).
10.8.1. Definition of AE and ADE
AE and ADE Definition

An AE is defined as any untoward medical occurrence, unintended disease or injury, 
or untoward clinical signs (including abnormal laboratory finding) in study 
participants, users, or other persons, whether or not related to the investigational 
medical device.  This definition includes events related to the investigational 
medical device or comparator and events related to the procedures involved except 
for events in users or other persons, which only include events related to 
investigational devices.

An ADE is defined as an adverse event related to the use of an investigational 
medical device.  This definition includes any adverse events resulting from 
insufficient or inadequate instructions for use, deployment, implantation, 
installation, or operation, or any malfunction of the investigational medical device as 
well as any event resulting from use error or from intentional misuse of the 
investigational medical device.
10.8.2. Definition of SAE, Serious Adverse Device Effect (SADE), and Unanticipated 
Serious Adverse Device Effect (USADE)

If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (eg, hospitalization for signs/symptoms of the disease under study, 
death due to progression of disease).

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 109
An SAE is an AE that:
a.
Led to death. 
b. Led to serious deterioration in the health of the participant, that either resulted in:

A life-threatening illness or injury.  The term “life-threatening” in the definition of 
serious refers to an event in which the participant was at risk of death at the time of 
the event.  It does not refer to an event, that hypothetically might have caused death, 
if it were more severe.

A permanent impairment of a body structure or a body function.

Inpatient or prolonged hospitalization.  Planned hospitalization for a preexisting 
condition, or a procedure required by the protocol, without serious deterioration in 
health, is not considered an SAE.

Medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function.
c.
Led to fetal distress, fetal death, or a congenital abnormality or birth defect.
SADE Definition

An SADE is defined as an adverse device effect that has resulted in any of the 
consequences characteristic of a serious adverse event.
USADE Definition

A USADE is a serious adverse device effect which by its nature, incidence, severity, 
or outcome has not been identified in the current version of the risk analysis 
management file.
10.8.3. Definition of Device Deficiency
Device Deficiency Definition

A device deficiency is an inadequacy of a medical device with respect to its identity, 
quality, durability, reliability, safety, or performance.  Device deficiencies include 
malfunctions, use errors, and inadequate labeling.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 110
10.8.4. Recording/Reporting and Follow-up of AEs and/or SAEs and Device 
Deficiencies
AE, SAE, and Device Deficiency Recording

When an AE/SAE/device deficiency occurs, it is the responsibility of the 
investigator to review all documentation (eg, hospital progress notes, laboratory 
reports, and diagnostic reports) related to the event.

The investigator will then record all relevant AE/SAE/device deficiency information 
in the participant’s medical records, in accordance with the investigator’s normal 
clinical practice and on the appropriate form of the CRF.

It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to Pfizer Safety in lieu of following the reporting process described 
in the IP manual.

There may be instances when copies of medical records for certain cases are 
requested by Pfizer Safety.  In this case, all participant identifiers, with the 
exception of the participant number, will be redacted on the copies of the medical 
records before submission to Pfizer Safety.

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/SAE.

For device deficiencies, it is very important that the investigator describes any 
corrective or remedial actions taken to prevent recurrence of the incident.

A remedial action is any action other than routine maintenance or servicing of a 
medical device where such action is necessary to prevent recurrence of a device 
deficiency.  This includes any amendment to the device design to prevent 
recurrence.
Assessment of Intensity
The investigator will make an assessment of intensity for each AE/SAE/device deficiency 
reported during the study and assign it to 1 of the following categories: 

Mild: An event that is easily tolerated by the participant, causing minimal 
discomfort and not interfering with everyday activities.

Moderate: An event that causes sufficient discomfort and interferes with normal 
everyday activities.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 111

Severe: An event that prevents normal everyday activities.  An AE that is assessed 
as severe should not be confused with an SAE.  Severe is a category utilized for 
rating the intensity of an event; and both AEs and SAEs can be assessed as severe.

An event is defined as “serious” when it meets at least 1 of the predefined outcomes 
as described in the definition of an SAE, NOT when it is rated as severe.
Assessment of Causality

The investigator is obligated to assess the relationship between study intervention 
and each occurrence of each AE/SAE/device deficiency.

A “reasonable possibility” of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot 
be ruled out.

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 study intervention 
administration will be considered and investigated.

The investigator will also consult the IB and/or product information, for marketed 
products, in his/her assessment.

For each AE/SAE/device deficiency, the investigator must document in the medical 
notes that he/she has reviewed the AE/SAE/device deficiency and has provided an 
assessment of causality.

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 make 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.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 112
Follow-up of AE/SAE/Device Deficiency

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/SAE/device deficiency as 
fully as possible.  This may include additional laboratory tests or investigations, 
histopathological examinations, or consultation with other healthcare providers.

New or updated information will be recorded in the originally completed CRF.

The investigator will submit any updated SAE data to the sponsor within 24 hours of 
receipt of the information.
10.8.5. Reporting of SAEs
SAE Reporting to Pfizer Safety via an Electronic Data Collection Tool

The primary mechanism for reporting an SAE to Pfizer Safety will be the electronic 
data collection tool.

If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) in order to report the event within 24 hours.

The site will enter the SAE data into the electronic system as soon as the data 
become available.

After the study is completed at a given site, the electronic data collection tool will be 
taken off-line to prevent the entry of new data or changes to existing data.

If a site receives a report of a new SAE from a study participant or receives updated 
data on a previously reported SAE after the electronic data collection tool has been 
taken off-line, then the site can report this information on a paper SAE form 
(see next section) or to Pfizer Safety by telephone.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 113
SAE Reporting to Pfizer Safety via Vaccine SAE Reporting Form

Facsimile transmission of the Vaccine SAE Reporting Form is the preferred method 
to transmit this information to Pfizer Safety.

In circumstances when the facsimile is not working, notification by telephone is 
acceptable with a copy of the Vaccine SAE Reporting Form sent by overnight mail 
or courier service.

Initial notification via telephone does not replace the need for the investigator to 
complete and sign the Vaccine SAE Reporting Form pages within the designated 
reporting time frames.
10.8.6. Reporting of SADEs
SADE Reporting to Pfizer Safety 
NOTE: There are additional reporting obligations for medical device incidents that are 
potentially related to SAEs that must fulfill the legal responsibility to notify appropriate 
regulatory authorities and other entities about certain safety information relating to medical 
devices being used in clinical studies.

Any device deficiency that is associated with an SAE must be reported to the 
sponsor within 24 hours after the investigator determines that the event meets the 
definition of a device deficiency.

The sponsor shall review all device deficiencies and determine and document in 
writing whether they could have led to an SAE.  These shall be reported to the 
regulatory authorities and IRBs/ECs as required by national regulations.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 114
10.9. Appendix 9: Country-Specific Appendix – Applicable to Italy Only
The following supplementary text should be read in conjunction with the applicable sections 
of the protocol.
10.9.1. Exclusion Criterion 1 Clarification
Exclusion criterion 1 (Section 5.2) reads, "History of severe adverse reaction associated with 
a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of 
investigational product or any diphtheria toxoid–containing vaccine”. As specified in 
Section 6, the concomitant study vaccines (DTaP, HBV, IPV, and Hib vaccine, MMR 
vaccine, and varicella vaccine), which are provided by Pfizer, are considered to be 
investigational product when administered as part of the study and are described as such in 
the IP manual. The authorized product SmPCs should be referenced for contraindications for 
the DTaP, HBV, IPV and Hib vaccine, MMR vaccine, and varicella vaccine (the 
vaccine-specific SRSDs referred to in Section 2.3). The SmPC for each of the vaccines is 
provided in the ISF.
10.9.2. Clarification of Route of Administration of Concomitant Study Vaccines
Section 6.1 describes the study interventions, including the concomitant study vaccines, and 
refers to the IP manual and SRSDs (ie, SmPC) for each of the vaccines. Section 6.1.1
describes the route of administration of concomitant study vaccines, and the wording allows 
for flexibility of supply or sourcing of vaccines that might have different routes of 
administration. The IP manual is referred to in the protocol and is provided to all 
investigator sites. It is also referred to during investigator site training as the document to 
guide preparation and administration of study vaccines. The IP manual, along with the 
SRSDs, should be referenced for the specific routes of administration for the concomitant 
vaccines being used in the study, which are as follows:

DTaP, HBV, IPV, and Hib vaccine is to be administered intramuscularly.

MMR vaccine is to be administered intramuscularly or subcutaneously.

Varicella vaccine is to be administered subcutaneously.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 115
10.10. Appendix 10: Russian Cohort
10.10.1. Summary of Protocol Modification Specific to the Russian Cohort 
The following list summarizes the modifications of the protocol that are specific to the  
Russian cohort.
•
The Russian cohort will consist of approximately 60 participants randomized in a 1:1 
ratio to receive either 20vPnC or 13vPnC.  Enrollment of the Russian cohort is 
projected to commence after enrollment of the primary study population is complete.
•
The inclusion criterion for age is ≥42 to ≤70 days of age (within the range, but a 
slightly more narrow window than the primary study population).
•
The parents/legal guardians of Russian cohort participants
but 
the blood draws at Visits 3, 4, and 5 are required (see the SoA in Section 10.10.2).
•
Participants in the Russian cohort will not receive MMR and varicella vaccinations as 
part of the study. Instead, they will receive MMR and varicella as per local 
requirements/NIP.
•
The timing of visits for participants has been slightly modified for the Russian cohort, 
to align with the Russian NIP (see the SoA for the Russian cohort below, 
Section 10.10.2) and the age range for Dose 3 vaccination is wider (with an older 
upper age limit of 15 months).  This also results in the potentially longer duration of 
study participation than the primary study population noted in Section 4.1.1 of the 
protocol.
•
Concomitant vaccine antigen responses will not be assessed.
•
The Russian cohort data will be summarized separately and descriptively. No formal 
hypothesis test is planned.
CCI
CCI

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 116
10.10.2. Schedule of Activities for Russian Cohort
Visit Number
1
2
3
4
5
Visit Description
Dose 1 Visit Dose 2 Visit
Dose 2 
Follow-up 
Visit
Dose 3 Visit
Dose 3 
Follow-up 
Visit
Visit Window (Days)
≥42 to ≤70 
Days After 
Birth
60 to 90 
Days
After Visit 1
28 to 42 Days 
After Visit 2
335 to 455 
Days of Age
28 to 42 Days 
After Visit 4
Obtain informed consent
X
Assign participant number via the 
IRT
X
Review inclusion and exclusion 
criteria
X
Record demography
X
Perform clinical assessment, 
including medical history
X
Record vaccine history
X
Provide parent(s)/legal guardian(s) 
with a contact card
X
Obtain prevaccination temperature 
(measured as appropriate for age)
X
X
X
Record nonstudy vaccinations and 
concomitant medicationsa
X
X
X
X
X
Record vaccines administered 
during pregnancy and intrapartum 
antibiotic use (yes/no) 
(if available)
Xb
Review temporary delay criteria
X
X
X
X
X
Review continued eligibility
X
X
X
X
Assign randomization number
X
Obtain ~5-mL blood sample
X
Xc
X
Administer investigational product 
in the left thighd
X
X
X
Administer specific concomitant 
vaccine
Xe
Xe
Xe
Observe and record any reactions 
for 30 minutes after investigational 
vaccine administration
X
X
X
Provide parent(s)/legal guardian(s) 
with an e-diary (device or 
application, as appropriate), digital 
thermometer, and measuring 
device and instruct to collect 
prompted local reactions and
systemic events 7 days after 
vaccinationf
X
X
X
Review e-diaryg
X
X
X
Collect e-diary (if applicable)
X
X

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 117
Visit Number
1
2
3
4
5
Visit Description
Dose 1 Visit Dose 2 Visit
Dose 2 
Follow-up 
Visit
Dose 3 Visit
Dose 3 
Follow-up 
Visit
Visit Window (Days)
≥42 to ≤70 
Days After 
Birth
60 to 90 
Days
After Visit 1
28 to 42 Days 
After Visit 2
335 to 455 
Days of Age
28 to 42 Days 
After Visit 4
Record and report AEsh
X-----------------------------------------X
X -------------------X
Record and report SAEs and 
NDCMCsh,i
X-------------------------------------------------------------------------------------X
Abbreviations: DTaP = diphtheria, tetanus, and acellular pertussis vaccine; e-diary = electronic diary; HBV = 
hepatitis B virus; Hib = Haemophilus influenzae type b; ICD = informed consent document; IPV = inactivated 
poliovirus vaccine; IRT = interactive response technology; NDCMC = newly diagnosed chronic medical 
condition.
a.
Record concomitant medications used to treat SAEs and NDCMCs from the signing of the ICD to the final 
visit (Visit 5).
b.
Vaccines administered during pregnancy and intrapartum antibiotic use (yes or no) will be collected at 
Visit 1 only (if available).
c.
Blood sample will be collected prior to vaccination.
d.
Remind the participant’s parent(s)/legal guardian(s) that the use of prophylactic antipyretic/pain 
medication, while permitted, is not recommended on the day of investigational product administration 
(before or after vaccination). If symptoms develop, the use of antipyretic/pain medication is allowed.    
e.
The participant will receive a specific vaccine containing DTaP, HBV, IPV, and Hib antigens at 2, 4.5, and 
11 to 15 months of age (Visit 1, Visit 2, and Visit 4, respectively). This vaccine(s) will be given in a limb 
other than the site of administration of 20vPnC or 13vPnC. 
f.
The participant’s parent(s)/legal guardian(s) will record prompted local reactions and systemic events in an 
e-diary for the 7 days following each dose of 20vPnC or 13vPnC. Use of antipyretic/pain medications will 
also be prompted for and collected daily in the e-diary for 7 days after vaccination.  The participant’s 
parent(s)/legal guardian(s) will be instructed to contact the study staff if the participant experiences 
redness or swelling >14 caliper units, severe pain at the 20vPnC or 13vPnC injection site, a fever >40.0°C 
(>104.0°F), an emergency room visit, or hospitalization.
g.
Designated site staff will review e-diary data online at frequent intervals (daily is optimal) for the 7 days 
following each dose of 20vPnC or 13vPnC to evaluate participant compliance and reported events as part 
of the ongoing safety review.
h.
If the parent(s)/legal guardian(s) consents, participants withdrawn from the study will have any new AEs, 
SAEs, and NDCMCs collected for 1 month after their last study vaccination.
i.
An NDCMC is a significant disease or medical condition, not previously identified, that is expected to be 
persistent or is otherwise long-lasting in its effects.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 118
10.10.3. Objectives, Estimands, and Endpoints for Russian Cohort
Safety Objective
Estimands
Safety Endpoints
To describe the safety profile of 
20vPnC 
In participants (primary study 
population and Russian cohort 
combined) receiving at least 1 dose of 
investigational product and having 
safety data reported after any 
vaccination in each vaccine group:

The percentage of participants 
reporting prompted local reactions 
within 7 days after each 
vaccination

The percentage of participants 
reporting prompted systemic 
events within 7 days after each 
vaccination 

The percentage of participants 
reporting AEs from Dose 1 to 
1 month after Dose 2 and from 
Dose 3 to 1 month after Dose 3

The percentage of participants 
reporting SAEs through 1 month 
after Dose 3

The percentage of participants 
reporting NDCMCs through 
1 month after Dose 3

Prompted local reactions 
(redness, swelling, and pain 
at the injection site) 

Prompted systemic events 
(fever, decreased appetite, 
drowsiness/increased sleep, 
and irritability)

AEs 

SAEs

NDCMCs
Primary Pneumococcal
Immunogenicity Objective
Estimands
Primary Pneumococcal 
Immunogenicity Endpoints
To describe the IgG responses 
induced by 20vPnC in the 
Russian cohort
In evaluable Russian participants for 
each of the 20 serotypes in 20vPnC for 
each vaccine group:

Percentages of participants with 
predefined IgG concentrations at 
1 month after Dose 2

IgG GMCs at 1 month after Dose 2

IgG GMCs at 1 month after Dose 3 

Pneumococcal 
IgG concentrations

Pneumococcal OPA titers
Secondary Pneumococcal
Immunogenicity Objective
Estimands
Secondary Pneumococcal 
Immunogenicity Endpoints
To further describe immune
responses induced by 20vPnC in 
the Russian cohort
In evaluable Russian participants for 
each of the 20 serotypes in 20vPnC for 
each vaccine group:

Percentages of participants with 
predefined IgG concentrations at 
1 month after Dose 3

OPA GMTs at 1 month after 
Dose 2 

OPAs GMTs at 1 month after 
Dose 3 

Pneumococcal 
IgG concentrations

Pneumococcal OPA titers

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 119
10.10.4. Notes on the Russian National Immunization Program
The following table includes information about the National Immunization Schedule of the 
Russian Federation for children 0 through 18 months of age:
NATIONAL IMMUNIZATION SCHEDULE (Partial)75
List of amending documents
(as amended by Orders of the Ministry of Health of Russia No. 370н dated 16 June 2016,
No. 175н dated 13 April 2017, No. 243н dated 24 April 2019, No. 967н dated 14 September 2020)
Categories and age of citizens subject to 
compulsory vaccination
Immunization name
Newborns in the first 24 hours of life
First vaccination against hepatitis B virusa
Newborns, on the 3rd - 7th day of age
Vaccination against tuberculosisb
Children of 1 month of age
Second vaccination against hepatitis B virusa
Children of 2 months of age
Third vaccination against hepatitis B virus (risk groups)c
First vaccination against pneumococcal infection
Children of 3 months of aged
First vaccination against diphtheria, pertussis, tetanus
First vaccination against poliomyelitise
First vaccination against Haemophilus influenzae (risk groups)f
(as amended by Order of the Ministry of Health of Russia of No. 175н dated 13 April 2017)
Children of 4.5 months of aged
Second vaccination against diphtheria, pertussis, tetanus
Second vaccination against Haemophilus influenzae (risk groups)f
Second vaccination against poliomyelitise
Second vaccination against pneumococcal infection
(as amended by Order of the Ministry of Health of Russia of No. 175н dated 13 April 2017)
CCI

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 120
NATIONAL IMMUNIZATION SCHEDULE (Partial)75
List of amending documents
(as amended by Orders of the Ministry of Health of Russia No. 370н dated 16 June 2016,
No. 175н dated 13 April 2017, No. 243н dated 24 April 2019, No. 967н dated 14 September 2020)
Categories and age of citizens subject to 
compulsory vaccination
Immunization name
Children of 6 months of aged
Third vaccination against diphtheria, pertussis, tetanus
Third vaccination against hepatitis B virusa
Third vaccination against poliomyelitisg
Third vaccination against Haemophilus influenzae (risk group)f
(as amended by Order of the Ministry of Health of Russia of No. 175н dated 13 April 2017)
Children of 12 months of age
Vaccination against measles, rubella, mumps
Fourth vaccination against hepatitis B virus (risk groups)c
Children of 15 months of age
Revaccination against pneumococcal infection
Children of 18 months of aged
First revaccination against poliomyelitisg
First revaccination against diphtheria, pertussis, tetanus
Revaccination against Haemophilus influenzae (risk groups)
(as amended by Order of the Ministry of Health of Russia of No. 175н dated 13 April 2017)
a.
First, second, and third vaccinations are carried out according to the 0-1-6 schedule (1st dose - at the start 
of vaccination, 2nd dose - one month after the 1st vaccination, 3rd dose - 6 months after the start of 
vaccination), with the exception of children belonging to risk groups, for whom the vaccination against 
hepatitis B virus is carried out according to the 0-1-2-12 schedule (1st dose - upon start of the vaccination, 
2nd dose - one month after the 1st vaccination, 3rd dose - 2 months after the start of vaccination, 
4th dose - 12 months after the start of vaccination).
b.
Vaccination is carried out with a tuberculosis vaccine for attenuated primary vaccination (BCG-M, ie, 
modified BCG vaccine); in the constituent entities of the Russian Federation with morbidity rates 
exceeding 80 per 100,000 population, as well as in the presence of tuberculosis patients in the environment 
of a newborn - a tuberculosis vaccine (BCG vaccine).
c.
Vaccination is carried out for children belonging to risk groups (born from mothers carrying HBsAg, HBV 
or who have had HBV in the third trimester of pregnancy, who do not have blood test results for hepatitis B 
markers, who use narcotic drugs or psychotropic substances, from families with a carrier of HBsAg or a 
patient with acute HBV and chronic viral hepatitis).
d.
Vaccination and revaccination of children at risk can be carried out with immunobiological drugs for 
immunoprophylaxis of infectious diseases, containing combinations of vaccines to be used at appropriate 
age periods. 
(footnote introduced by Order of the Ministry of Health of Russia No. 175н dated 13 April 2017)
e.
First and second vaccinations are carried out with the polio vaccine (inactivated).
f.
Vaccination is carried out for children belonging to risk groups (with diseases of the nervous system, 
immunodeficiency disorders, or anatomical defects leading to a sharply increased risk of hemophilic 
infection; with intestinal malformations; with oncological diseases and/or receiving immunosuppressive 
therapy for a long time; children born to mothers with HIV infection; children with HIV infection; 
premature and low-birth-weight children; children in orphanages). 
(footnote as amended by Order of the Ministry of Health of Russia of No. 243н dated 24 April 2019)
g.
Third vaccination and subsequent revaccinations of children against poliomyelitis are carried out with the 
polio vaccine (live); children belonging to risk groups (with diseases of the nervous system, 
immunodeficiency disorders, or anatomical defects leading to a sharply increased risk of hemophilic 
infection; with intestinal malformations; with oncological diseases and/or receiving long-term 
immunosuppressive therapy; children born to mothers with HIV infection; children with HIV infection; 
premature and low-birth-weight children; children in orphanages) - with the polio vaccine (inactivated).
(footnote as amended by Order of the Ministry of Health of Russia of No. 243н dated 24 April 2019)

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 121
The use of Infanrix hexa will provide the concomitant vaccine antigens of diphtheria, tetanus, 
acellular pertussis, hepatitis B, poliovirus, and Haemophilus influenzae type b (DTaP, HBV, 
IPV, and Hib) and be administered at approximately 2, 4.5, and 11 to 15 months of age with 
the blinded study vaccine (20vPnC or 13vPnC [control vaccine]). Although the 
administration of Infanrix hexa will be given on a slightly different schedule than the 
National Immunization Schedule of the Russian Federation noted above, numerous studies of 
Infanrix hexa have demonstrated that an immunization schedule of 2 infant doses and a 
toddler dose will provide protection against the diseases covered by the vaccine.  Based on 
data in the Russian Infanrix hexa SmPC, the 2-dose and 3-dose primary vaccination 
schedules have similar overall seroprotective or seropositive antibody levels against each of 
the vaccine antigens.
Therefore, Infanrix hexa use in this study in accordance with a 2-dose primary and booster 
schedule is consistent with the manufacturer’s label for providing appropriate and adequate 
protection of the infant against the aforementioned diseases.
CCI

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 122
10.11. Appendix 11: Abbreviations
The following is a list of abbreviations that may be used in the protocol.
Abbreviation
Term
7vPnC
7-valent pneumococcal conjugate vaccine
13vPnC
13-valent pneumococcal conjugate vaccine
20vPnC
20-valent pneumococcal conjugate vaccine
AE
adverse event
ADE
adverse device effect
ADL
activity(ies) of daily living
ALT
alanine aminotransferase
AOM
acute otitis media
AST
aspartate aminotransferase
BCG
bacille Calmette-Guérin 
CAP
community-acquired pneumonia
CBER
Center for Biologics Evaluation and Research
CDC
Centers for Disease Control and Prevention
CFR
Code of Federal Regulations
CHMP
Committee for Medicinal Products for Human Use
CI
confidence interval
CIOMS
Council for International Organizations of Medical Sciences
CK
creatine kinase
CLIA
chemiluminescent immunoassay 
CONSORT
Consolidated Standards of Reporting Trials
CRF
case report form
CRM197
cross-reactive material 197
CRO
contract research organization
CSAP
clinical specimen assessment plan
CSR
clinical study report
DILI
drug-induced liver injury
DTaP
diphtheria, tetanus, and acellular pertussis vaccine
DU
dispensable unit
EC
ethics committee
ECDC
European Centre for Disease Prevention and Control
ECG
electrocardiogram
eCRF
electronic case report form
EDB
exposure during breastfeeding
e-diary
electronic diary
EDB
exposure during breastfeeding
EDP
exposure during pregnancy
ELISA
enzyme-linked immunosorbent assay
CCI

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 123
Abbreviation
Term
EMA
European Medicines Agency
EU
European Union
EudraCT
European Clinical Trials Database
FDA
Food and Drug Administration
FHA
filamentous hemagglutinin
GCP
Good Clinical Practice
GGT
gamma-glutamyl transferase
GMC
geometric mean concentration
GMFR
geometric mean fold rise
GMR
geometric mean ratio
GMT
geometric mean titer
HBsAg
hepatitis B surface antigen
HBV
hepatitis B virus
Hib
Haemophilus influenzae type b
HIPAA
Health Insurance Portability and Accountability Act
HIV
human immunodeficiency virus
IB
investigator's brochure
ICD
informed consent document
ICH
International Council for Harmonisation
ID
identification
IgG
immunoglobulin G
IND
investigational new drug application
INR
international normalized ratio
IP manual
investigational product manual
IPD
invasive pneumococcal disease
IPV
inactivated poliovirus vaccine
IRB
institutional review board
IRT
interactive response technology
ISF
investigator site file
IU
international unit(s)
IWR
interactive Web-based response
LFT
liver function test
LLOQ
lower limit of quantitation
MedDRA
Medical Dictionary for Regulatory Activities
MMR
measles, mumps, and rubella vaccine
N/A
not applicable
NA
neutralizing antibody
NDCMC
newly diagnosed chronic medical condition
NI
noninferiority
NIP
national immunization program
OPA
opsonophagocytic activity

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 124
Abbreviation
Term
PCD
primary completion date
PPSV23
23-valent pneumococcal polysaccharide vaccine
PRN
pertactin
PRP
polyribosylribitol phosphate
PT
pertussis toxin
SADE
serious adverse device effect
SAE
serious adverse event
SAP
statistical analysis plan
SmPC
summary of product characteristics
SoA
schedule of activities
SOP
standard operating procedure
SRM
study reference manual
SRSD
single reference safety document
SUSAR
suspected unexpected serious adverse reaction
TBili
total bilirubin
ULN
upper limit of normal
US
United States
USADE
unanticipated serious adverse device effect
VT
vaccine-type
WHO
World Health Organization
CCI

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 125
11. REFERENCES
1
Said MA, Johnson HL, Nonyane BA, et al. Estimating the burden of pneumococcal 
pneumonia among adults: a systematic review and meta-analysis of diagnostic 
techniques. PLoS One 2013;8(4):e60273.
2
O'Brien KL, Wolfson LJ, Watt JP, et al. Burden of disease caused by Streptococcus 
pneumoniae in children younger than 5 years: global estimates. Lancet
2009;374(9693):893-902.
3
Huang SS, Johnson KM, Ray GT, et al. Healthcare utilization and cost of pneumococcal 
disease in the United States. Vaccine 2011;29(18):3398-412.
4
Iyer AS, Ohtola JA, Westerink MAJ. Age-related immune response to pneumococcal 
polysaccharide vaccination: lessons for the clinic. Expert Rev Vaccines 2015;14(1):85-
97.
5
Wahl B, O’Brien KL, Greenbaum A, et al. Global burden of Streptococcus pneumoniae
in children younger than 5 years in the pneumococcal conjugate vaccines (PCV) era: 
2000-2015. 10th International Symposium on Pneumococci & Pneumococcal Diseases 
(ISPPD-10); 26-30 Jun 2016; Glasgow, Scotland.
6
Moore MR, Link-Gelles R, Schaffner W, et al. Effect of use of 13-valent pneumococcal 
conjugate vaccine in children on invasive pneumococcal disease in children and adults 
in the USA: analysis of multisite, population-based surveillance. Lancet Infect Dis
2015;15(3):301-9.
7
Ladhani SN, Collins S, Djennad A, et al. Rapid increase in non-vaccine serotypes 
causing invasive pneumococcal disease in England and Wales, 2000–17: a prospective 
national observational cohort study. Lancet Infect Dis 2018;18:441-51.
8
European Centre for Disease Prevention and Control. Invasive pneumococcal disease. 
In: ECDC. Annual epidemiological report for 2017. Stockholm: ECDC; 2018. Available 
from: https://www.ecdc.europa.eu/sites/portal/files/documents/AER_for_2017-invasive-
pneumococcal-disease.pdf. Accessed: 26 Aug 2019.
9
Olarte L, Barson WJ, Barson RM, et al. Impact of the 13-valent pneumococcal 
conjugate vaccine on pneumococcal meningitis in US children. Clin Infect Dis 
2015;61(5):767-75.
10
Stockmann C, Ampofo K, Byington CL, et al. Pneumococcal meningitis in children:  
epidemiology, serotypes, and outcomes from 1997-2010 in Utah. Pediatrics 
2013;132(3):421-8.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 126
11
Kaplan SL, Barson WJ, Lin PL, et al. Invasive pneumococcal disease in children’s 
hospitals: 2014–2017. Pediatrics 2019;144(3):e20190567.
12
Jain S, Williams DJ, Arnold SR, et al. Community-acquired pneumonia requiring 
hospitalization among U.S. children. N Engl J Med 2015;372(9):835-45.
13
Jain S, Self WH, Wunderink RG, et al. Community-acquired pneumonia requiring 
hospitalization among U.S. adults. N Engl J Med 2015;373(5):415-27.
14
Griffin MR, Zhu Y, Moore MR, et al. U.S. hospitalizations for pneumonia after a decade 
of pneumococcal vaccination. N Engl J Med 2013;369(2):155-63.
15
Lepoutre A, Varon E, Georges S, et al. Impact of the pneumococcal conjugate vaccines 
on invasive pneumococcal disease in France, 2001–2012. Vaccine 2015;33(2):359-66.
16
Marom T, Tan A, Wilkinson GS, et al. Trends in otitis media–related health care use in 
the United States, 2001-2011. JAMA Pediatr 2014;168(1):68-75.
17
Geno KA, Gilbert GL, Song JY, et al. Pneumococcal capsules and their types: past, 
present, and future. Clin Microbiol Rev 2015;28(3):871-99.
18
Hausdorff WP, Hanage WP. Interim results of an ecological experiment—conjugate 
vaccination against the pneumococcus and serotype replacement. Hum Vaccin
Immunother 2016;12(2):358-74.
19
AlonsoDeVelasco E, Verheul AFM, Verhoef J, et al. Streptococcus pneumoniae: 
virulence factors, pathogenesis, and vaccines. Microbiol Rev 1995;59(4):591-603.
20
Centers for Disease Control and Prevention. Prevention of pneumococcal disease: 
recommendations of the Advisory Committee on Immunization Practices (ACIP). 
MMWR Recomm Rep 1997;46(RR-8):1-24.
21
Austrian R. A brief history of pneumococcal vaccines. Drugs Aging 1999;15(suppl 1):1-
10.
22
Shapiro ED, Berg AT, Austrian R, et al. The protective efficacy of polyvalent 
pneumococcal polysaccharide vaccine. N Engl J Med 1991;325(21):1453-60.
23
Stein KE. Thymus-independent and thymus-dependent responses to polysaccharide 
antigens. J Infect Dis 1992;165 suppl 1:S49-S52.
24
Borrow R, Health PT, Siegrist CA. Use of pneumococcal polysaccharide vaccine in 
children: what is the evidence? Curr Opin Infect Dis 2012;25(3):292-303.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 127
25
Jackson LA, Neuzil KM, Yu O, et al. Effectiveness of pneumococcal polysaccharide 
vaccine in older adults. N Engl J Med 2003;348(18):1747-55.
26
Leventer-Roberts M, Feldman BS, Brufman I, et al. Effectiveness of 23-valent 
pneumococcal polysaccharide vaccine against invasive disease and hospital-treated 
pneumonia among people aged ≥65 years: a retrospective case-control study. Clin Infect
Dis 2015;60(10):1472-80.
27
Wright PF, Sell SH, Vaughn WK, et al. Clinical studies of pneumococcal vaccines in 
infants. II. Efficacy and effect on nasopharyngeal carriage. Rev Infect Dis 1981;3 
suppl:S108-S112.
28
Torres A, Bonanni P, Hryniewicz W, et al. Pneumococcal vaccination: what have we 
learnt so far and what can we expect in the future? Eur J Clin Microbiol Infect Dis
2015;34(1):19-31.
29
Robinson KA, Baughman W, Rothrock G, et al. Epidemiology of invasive 
Streptococcus pneumoniae infections in the United States, 1995-1998: opportunities for 
prevention in the conjugate vaccine era. JAMA 2001;285(13):1729-35.
30
Hausdorff WP, Bryant J, Paradiso PR, et al. Which pneumococcal serogroups cause the 
most invasive disease: implications for conjugate vaccine formulation and use, part I. 
Clin Infect Dis 2000;30(1):100-121.
31
Hausdorff WP, Bryant J, Kloek C, et al. The contribution of specific pneumococcal 
serogroups to different disease manifestations: implications for conjugate vaccine 
formulation and use, part II. Clin Infect Dis 2000;30(1):122-40.
32
Nuorti JP, Whitney CG. Prevention of pneumococcal disease among infants and 
children - use of 13-valent pneumococcal conjugate vaccine and 23-valent 
pneumococcal polysaccharide vaccine - recommendations of the Advisory Committee 
on Immunization Practices (ACIP). MMWR Recomm Rep 2010;59(RR-11):1-18.
33
Johnson HL, Deloria-Knoll M, Levine OS, et al. Systematic evaluation of serotypes 
causing invasive pneumococcal disease among children under five: the Pneumococcal 
Global Serotype Project. PLoS Med 2010;7(10):1-13.
34
Richter SS, Heilmann KP, Dohrn CL, et al. Pneumococcal serotypes before and after 
introduction of conjugate vaccines, United States, 1999-2011. Emerg Infect Dis
2013;19(7):1074-83.
35
Black SB, Shinefield HR, Ling S, et al. Effectiveness of heptavalent pneumococcal 
conjugate vaccine in children younger than five years of age for prevention of 
pneumonia. Pediatr Infect Dis J 2002;21(9):810-5.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 128
36
Hansen J, Black S, Shinefield H, et al. Effectiveness of heptavalent pneumococcal 
conjugate vaccine in children younger than 5 years of age for prevention of pneumonia: 
updated analysis using World Health Organization standardized interpretation of chest 
radiographs. Pediatr Infect Dis J 2006;25(9):779-81.
37
Cutts FT, Zaman SM, Enwere G, et al. Efficacy of nine-valent pneumococcal conjugate 
vaccine against pneumonia and invasive pneumococcal disease in The Gambia: 
randomised, double-blind, placebo-controlled trial. Lancet 2005;365(9465):1139-46.
38
Eskola J, Kilpi T, Palmu A, et al. Efficacy of a pneumococcal conjugate vaccine against 
acute otitis media. N Engl J Med 2001;344(6):403-9.
39
O'Brien KL, Moulton LH, Reid R, et al. Efficacy and safety of seven-valent conjugate 
pneumococcal vaccine in American Indian children: group randomised trial. Lancet
2003;362(9381):355-61.
40
Klugman KP, Madhi SA, Huebner RE, et al. A trial of a 9-valent pneumococcal 
conjugate vaccine in children with and those without HIV infection. N Engl J Med
2003;349(14):1341-8.
41
Pilishvili T, Lexau C, Farley MM, et al. Sustained reductions in invasive pneumococcal 
disease in the era of conjugate vaccine. J Infect Dis 2010;201(1):32-41.
42
Reinert RR, Paradiso P, Fritzell B. Advances in pneumococcal vaccines: the 13-valent 
pneumococcal conjugate vaccine received market authorization in Europe. Expert Rev
Vaccines 2010;9(3):229-36.
43
Bonten MJM, Huijts SM, Bolkenbaas M, et al.  Polysaccharide conjugate vaccine 
against pneumococcal pneumonia in adults. N Engl J Med 2015;372(12):1114-25.
44
Centers for Disease Control and Prevention. Licensure of a 13-valent pneumococcal 
conjugate vaccine (PCV13) and recommendations for use among children -- Advisory 
Committee on Immunization Practices (ACIP), 2010.  MMWR Morb Mortal Wkly Rep
2010;59(9):258-61.
45
Centers for Disease Control and Prevention. Licensure of 13-valent pneumococcal 
conjugate vaccine for adults aged 50 years and older.  MMWR Morb Mortal Wkly Rep
2012;61(21):394-5.
46
Prevenar 13 summary of product characteristics. European Medicines Agency website. 
Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/prevenar-13. 
Published: 01 Aug 2010. Updated: 10 Aug 2019.  Accessed: 12 Nov 2019.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 129
47
European Medicines Agency. Prevenar 13 assessment report. 22 Jan 2015.  Available 
from: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-
_Assessment_Report_-_Variation/human/001104/WC500186805.pdf. Accessed: 12 Sep 
2016.
48
World Health Organization. WHO prequalified vaccines. Pneumococcal 
(conjugate). Prevenar 13. Available from: 
https://extranet.who.int/gavi/PQ_Web/PreviewVaccine.aspx?nav=0&ID=
221. Effective: 20 Aug 2010. Accessed: 12 Sep 2016.
49
World Health Organization. WHO prequalified vaccines. Pneumococcal (conjugate). 
Prevenar 13 multidose vial. Available from: 
https://extranet.who.int/gavi/PQ_Web/PreviewVaccine.aspx?nav=0&ID=317. Effective: 
14 Jul 2016. Accessed: 12 Sep 2016.
50
Harboe ZB, Dalby T, Weinberger DM, et al. Impact of 13-valent pneumococcal 
conjugate vaccination in invasive pneumococcal disease incidence and mortality 
[erratum appears in Clin Infect Dis 2014;59(12):1812]. Clin Infect Dis 2014;59(8):1066-
73. 
51
Steens A, Bergsaker MA, Aaberge IS, et al. Prompt effect of replacing the 7-valent 
pneumococcal conjugate vaccine with the 13-valent vaccine on the epidemiology of 
invasive pneumococcal disease in Norway. Vaccine 2013;31(52):6232-8.
52
Miller E, Andrews NJ, Waight PA, et al. Effectiveness of the new serotypes in the 13-
valent pneumococcal conjugate vaccine. Vaccine 2011;29(49):9127-31.
53
Cohen R, Biscardi S, Levy C. The multifaceted impact of pneumococcal conjugate 
vaccine implementation in children in France between 2001 to 2014. Hum Vaccin
Immunother 2016;12(2):277-84.
54
Cohen R, Levy C, Bingen E, et al. Impact of 13-valent pneumococcal conjugate vaccine 
on pneumococcal nasopharyngeal carriage in children with acute otitis media. Pediatr
Infect Dis J 2012;31(3):297-301.
55
Flasche S, Van Hoek AJ, Sheasby E, et al. Effect of pneumococcal conjugate 
vaccination on serotype-specific carriage and invasive disease in England: a cross-
sectional study. PLoS Med 2011;8(4):e1001017.
56
Williams SR, Mernagh PJ, Lee MHT, Tan JT. Changing epidemiology of invasive 
pneumococcal disease in Australian children after introduction of a 7-valent 
pneumococcal conjugate vaccine. Med J Aust 2011;194(3):116-20.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 130
57
Munoz-Almagro C, Ciruela P, Esteva C, et al. Serotypes and clones causing invasive 
pneumococcal disease before the use of new conjugate vaccines in Catalonia, Spain. J 
Infect 2011;63(2):151-62.
58
Norton NB, Stanek RJ, Mufson MA. Routine pneumococcal vaccination of children 
provokes new patterns of serotypes causing invasive pneumococcal disease in adults and 
children. Am J Med Sci 2013;345(2):112-20.
59
Adam HJ, Karlowsky JA, Nichol KA, et al. Baseline epidemiology of Streptococcus 
pneumoniae serotypes in Canada prior to the introduction of the 13-valent 
pneumococcal vaccine. Microb Drug Resist 2012;18(2):176-82.
60
Harboe ZB, Thomsen RW, Riis A, et al. Pneumococcal serotypes and mortality 
following invasive pneumococcal disease: a population-based cohort study. PLoS Med
2009;6(5):e1000081.
61
Wroe PC, Lee GM, Finkelstein JA, et al. Pneumococcal carriage and antibiotic 
resistance in young children before 13-valent conjugate vaccine. Pediatr Infect Dis J
2012;31(3):249-54.
62
Cohen R, Varon E, Doit C, et al. A 13-year survey of pneumococcal nasopharyngeal 
carriage in children with acute otitis media following PCV7 and PCV13 
implementation. Vaccine 2015;33(39):5118-26.
63
Tomczyk S, Lynfield R, Schaffner W, et al. Prevention of antibiotic-nonsusceptible 
invasive pneumococcal disease with the 13-valent pneumococcal conjugate vaccine. 
Clin Infect Dis 2016;62(9):1119-25.
64
Richter SS, Diekema DJ, Heilmann KP, et al. Changes in pneumococcal serotypes and 
antimicrobial resistance after introduction of the 13-valent conjugate vaccine in the 
United States. Antimicrob Agents Chemother 2014;58(11):6484-9. 
65
Demczuk WHB, Martin I, Griffith A, et al. Serotype distribution of invasive 
Streptococcus pneumoniae in Canada after the introduction of the 13-valent 
pneumococcal conjugate vaccine, 2010–2012. Can J Microbiol 2013;59(12):778-88.
66
Cohen R, Cohen JF, Chalumeau M, et al. Impact of pneumococcal conjugate vaccines 
for children in high- and non-high-income countries. Expert Rev Vaccines
2017;16(6):625-40.
67
Balsells E, Guillot L, Nair H, et al. Serotype distribution of Streptococcus pneumoniae
causing invasive disease in children in the post-PCV era: a systematic review and meta-
analysis. PloS One 2017;12(5):e0177113.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471012
Final Protocol Amendment 2, 18 June 2021 
PFIZER CONFIDENTIAL
Page 131
68
Golden AR, Adam HJ, Zhanel GG. Invasive Streptococcus pneumoniae in Canada, 
2011–2014: characterization of new candidate 15-valent pneumococcal conjugate 
vaccine serotypes 22F and 33F. Vaccine 2016;34(23):2527-30.
69
Metcalf BJ, Gertz RE Jr, Gladstone RA, et al. Strain features and distributions in 
pneumococci from children with invasive disease before and after 13-valent conjugate 
vaccine implementation in the USA. Clin Microbiol Infect 2016;22(1):60.e9-.e29.
70
Waight PA, Andrews NJ, Ladhani SN, et al. Effect of the 13-valent pneumococcal 
conjugate vaccine on invasive pneumococcal disease in England and Wales 4 years after
its introduction: an observational cohort study. Lancet Infect Dis 2015;15(5):535-43.
71
van der Linden M, Falkenhorst G, Perniciaro S, et al. Effects of infant pneumococcal 
conjugate vaccination on serotype distribution in invasive pneumococcal disease among 
children and adults in Germany. PLoS One 2015;10(7):e0131494.
72
Beall B, Chochua S, Gertz RE Jr, et al. A population-based descriptive atlas of invasive 
pneumococcal strains recovered within the U.S. during 2015-2016 [online 
supplementary material]. Front Microbiol 2018;9:2670. Available from: 
https://www.frontiersin.org/articles/10.3389/fmicb.2018.02670/full#supplementary-
material. Accessed: 03 Oct 2019.
73
International Committee on Harmonisation. Statistical Principles for Clinical Trials. ICH 
Harmonised Tripartite Guideline E9, February 1998.
74
US Food and Drug Administration. Guidance for industry: toxicity grading scale for 
healthy adult and adolescent volunteers enrolled in preventive vaccine clinical trials. 
Rockville, MD: Center for Biologics Evaluation and Research; September 2007.
75
Order of the Ministry of Health of the Russia Federation. [On approval of the national 
immunization schedule and the immunization schedule for epidemic indications] 
[Russian]. Available from: https://docs.cntd.ru/document/499086215#64U0IK. Dated 
21 Mar 2014 (as amended on 03 Feb 2021). Accessed: 16 Jun 2021.

'RFXPHQW $SSURYDO 5HFRUG
'RFXPHQW 1DPH
	
    
   
	

'RFXPHQW 7LWOH
  ! " #$%&'()!% %&*+!,+($% -#(+ -& !.+*-!
-!  /!-0 $% (''*$&1!$((-0 &/  
	,.+!$- $!*'&
&+ &$*1-! .($! 1(.!$    !#(! &/ 
 ($/$-
%& ! $%  -&%%+!# %& ! ($ !+-0 ($/$- 
6LJQHG %\
'DWH*07
6LJQLQJ &DSDFLW\
,,
	
 
44"
/ 5
,,
	
 

4
84""
/ 5
PPD
PPD