A PHASE 3, RANDOMIZED, DOUBLE-BLIND TRIAL TO EVALUATE THE SAFETY OF A 20-VALENT PNEUMOCOCCAL CONJUGATE VACCINE IN HEALTHY INFANTS
Phase: PHASE3
Conditions: Pneumococcal Disease
Sponsor: Pfizer

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471013
Final Protocol Amendment 1, 31 Mar 2022
PFIZER CONFIDENTIAL 
Page 1
A PHASE 3, RANDOMIZED, DOUBLE-BLIND TRIAL TO EVALUATE THE 
SAFETY OF A 20-VALENT PNEUMOCOCCAL CONJUGATE VACCINE 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:
2019-003307-35
Protocol Number:
B7471013
Phase:
3
Short Title: 20-valent Pneumococcal Conjugate Vaccine Safety Study in Healthy 
Infants
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20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471013
Final Protocol Amendment 1, 31 Mar 2022
PFIZER CONFIDENTIAL 
Page 2
Protocol Amendment Summary of Changes Table
Document History
Document
Version Date
Summary of Changes and Rationale
Amendment 1
31 Mar 2022
Section 1.3, Section 8.10.5, 
Section 8.10.6, Section 8.10.7, 
Section 10.9: Amended relevant sections 
of the protocol to detail the United States 
and Puerto Rico country-specific 
amendment. Modifications impacted 
Visit 5 and Visit 7 timing, and added 
flexibility in the format of Visit 6.
Section 2.1, Section 4.1: Updated wording 
to reflect details related to the United 
States and Puerto Rico country-specific 
amendment.
Section 7.2: Clarified guidance for 
participants who are discontinued prior to 
completing all 4 doses of study 
intervention.
Original protocol
19 Feb 2020
Not applicable (N/A)

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471013
Final Protocol Amendment 1, 31 Mar 2022
PFIZER CONFIDENTIAL 
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TABLE OF CONTENTS
LIST OF TABLES.....................................................................................................................7
1. PROTOCOL SUMMARY.....................................................................................................8
1.1. Synopsis ....................................................................................................................8
1.2. Schema ....................................................................................................................10
1.3. Schedule of Activities (SoA)...................................................................................11
2. INTRODUCTION ...............................................................................................................14
2.1. Study Rationale .......................................................................................................17
2.2. Background .............................................................................................................18
2.2.1. Clinical Overview.......................................................................................18
2.3. Benefit/Risk Assessment.........................................................................................19
3. OBJECTIVES, ESTIMANDS, AND ENDPOINTS ...........................................................20
4. STUDY DESIGN.................................................................................................................21
4.1. Overall Design.........................................................................................................21
4.1.1. Approximate Duration of Participation for Each Participant .....................22
4.1.2. Approximate Number of Participants.........................................................22
4.2. Scientific Rationale for Study Design.....................................................................23
4.3. Justification for Dose ..............................................................................................23
4.4. End of Study Definition ..........................................................................................23
5. STUDY POPULATION......................................................................................................23
5.1. Inclusion Criteria.....................................................................................................23
5.2. Exclusion Criteria....................................................................................................24
5.3. Lifestyle Considerations..........................................................................................25
5.4. Screen Failures ........................................................................................................25
5.5. Temporary Delay Criteria .......................................................................................26
5.5.1. Criteria for Temporarily Delaying Vaccine Administration ......................26
6. STUDY INTERVENTION..................................................................................................26
6.1. Study Intervention(s) Administered........................................................................26
6.1.1. Administration............................................................................................26
6.1.2. Medical Devices .........................................................................................27
6.2. Preparation/Handling/Storage/Accountability ........................................................27

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471013
Final Protocol Amendment 1, 31 Mar 2022
PFIZER CONFIDENTIAL 
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6.2.1. Preparation and Dispensing........................................................................29
6.3. Measures to Minimize Bias: Randomization and Blinding.....................................29
6.3.1. Allocation to Investigational Product .........................................................29
6.3.2. Breaking the Blind......................................................................................29
6.3.3. Blinding of the Sponsor..............................................................................29
6.4. Study Intervention Compliance...............................................................................30
6.5. Concomitant Therapy..............................................................................................30
6.5.1. Prohibited Concomitant Vaccines and Treatments.....................................30
6.5.2. Permitted Concomitant Vaccines and Treatments......................................30
6.5.3. Recording Prior and Concomitant Vaccines and Treatments.....................30
6.6. Dose Modification...................................................................................................30
6.7. Intervention After the End of the Study..................................................................30
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL...........................................................................31
7.1. Discontinuation of Study Intervention ....................................................................31
7.2. Participant Discontinuation/Withdrawal From the Study.......................................31
7.3. Lost to Follow-up....................................................................................................32
8. STUDY ASSESSMENTS AND PROCEDURES...............................................................33
8.1. Efficacy Assessments..............................................................................................33
8.2. Safety Assessments .................................................................................................34
8.2.1. Participant Electronic Diary .......................................................................34
8.2.2. Grading Scale for Prompted Events ...........................................................35
8.2.2.1. Local Reactions.........................................................................35
8.2.2.2. Systemic Events – Symptoms and Fever ..................................36
8.2.2.3. Use of Antipyretic/Pain Medication..........................................38
8.2.3. Clinical Safety Laboratory Assessments ....................................................38
8.2.4. Biological Samples.....................................................................................38
8.3. Adverse Events and Serious Adverse Events..........................................................38
8.3.1. Time Period and Frequency for Collecting AE and SAE Information.......39
8.3.1.1. Reporting SAEs to Pfizer Safety...............................................39
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF...................39
8.3.2. Method of Detecting AEs and SAEs ..........................................................40

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471013
Final Protocol Amendment 1, 31 Mar 2022
PFIZER CONFIDENTIAL 
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8.3.3. Follow-up of AEs and SAEs.......................................................................40
8.3.4. Regulatory Reporting Requirements for SAEs...........................................40
8.3.5. Exposure During Pregnancy or Breastfeeding, and Occupational 
Exposure ..........................................................................................................41
8.3.5.1. Exposure During Pregnancy......................................................41
8.3.5.2. Exposure During Breastfeeding ................................................41
8.3.5.3. Occupational Exposure .............................................................41
8.3.6. Medical Device Incidents (Including Malfunctions)..................................41
8.3.6.1. Time Period for Detecting Medical Device Incidents...............42
8.3.6.2. Follow-up of Medical Device Incidents....................................42
8.3.6.3. Prompt Reporting of Medical Device Incidents to Sponsor .....42
8.3.6.4. Regulatory Reporting Requirements for Medical Device 
Incidents ............................................................................................42
8.3.7. Medication Errors .......................................................................................43
8.4. Treatment of Overdose............................................................................................44
8.5. Pharmacokinetics ....................................................................................................44
8.6. Pharmacodynamics..................................................................................................44
8.7. Genetics...................................................................................................................44
8.8. Biomarkers ..............................................................................................................44
8.9. Health Economics ...................................................................................................44
8.10. Study Procedures...................................................................................................44
8.10.1. Visit 1 (Dose 1: Day 1).............................................................................45
8.10.2. Visit 2 (Dose 2: 42 to 63 Days After Dose 1, ie, Study Day 43 to 
64) ....................................................................................................................46
8.10.3. Visit 3 (Dose 3: 42 to 63 Days After Dose 2)...........................................48
8.10.4. Visit 4 (Follow-up: 28 to 42 to Days After Dose 3).................................49
8.10.5. Visit 5 (Dose 4: 365 to 455 Days of Age) ................................................50
8.10.6. Visit 6 (Follow-up: 28 to 42 to Days After Dose 4).................................51
8.10.7. Visit 7 (Follow-up: 168 to 196 Days After Dose 4).................................52
8.10.8. Unscheduled Visits...................................................................................52
9. STATISTICAL CONSIDERATIONS ................................................................................53
9.1. Estimands and Statistical Hypotheses.....................................................................54
9.1.1. Estimands....................................................................................................54

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471013
Final Protocol Amendment 1, 31 Mar 2022
PFIZER CONFIDENTIAL 
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9.2. Sample Size Determination.....................................................................................54
9.3. Populations for Analysis .........................................................................................54
9.4. Statistical Analyses .................................................................................................55
9.4.1. Safety Analyses ..........................................................................................55
9.5. Interim Analyses .....................................................................................................55
9.5.1. Analysis Timing..........................................................................................56
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS..........................................................................................................57
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations...............57
10.1.1. Regulatory and Ethical Considerations ....................................................57
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the 
Protocol or ICH GCP.........................................................................57
10.1.2. Financial Disclosure .................................................................................58
10.1.3. Informed Consent Process ........................................................................58
10.1.4. Data Protection .........................................................................................59
10.1.5. Dissemination of Clinical Study Data ......................................................59
10.1.6. Data Quality Assurance ............................................................................61
10.1.7. Source Documents....................................................................................62
10.1.8. Study and Site Closure..............................................................................62
10.1.9. Publication Policy.....................................................................................63
10.1.10. Sponsor’s Qualified Medical Personnel .................................................63
10.2. Appendix 2: Clinical Laboratory Tests .................................................................64
10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ......................................................................64
10.3.1. Definition of AE .......................................................................................64
10.3.2. Definition of an NDCMC.........................................................................65
10.3.3. Definition of SAE.....................................................................................65
10.3.4. Recording/Reporting and Follow-up of AEs and/or SAEs.......................67
10.3.5. Reporting of SAEs....................................................................................70
10.5. Appendix 5: Genetics............................................................................................72
10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-up Assessments ........72
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20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471013
Final Protocol Amendment 1, 31 Mar 2022
PFIZER CONFIDENTIAL 
Page 7
10.7. Appendix 7: ECG Findings of Potential Clinical Concern ...................................74
10.8. Appendix 8: Medical Device Incidents: Definition and Procedures for 
Recording, Evaluating, Follow-up, and Reporting....................................................74
10.9. Appendix 9: Amendment 1 Country-Specific Requirements – Applicable to 
United States and Puerto Rico Only..........................................................................76
10.10. Appendix 10: Abbreviations ...............................................................................77
11. REFERENCES ..................................................................................................................79
LIST OF TABLES
Table 1.
Grading Scales for Local Reactions .........................................................36
Table 2.
Grading Scales for Systemic Events.........................................................37
Table 3.
Ranges for Fever.......................................................................................38
Table 4.
Probability of Detecting at Least 1 AE in the 20vPnC and 13vPnC 
Groups.......................................................................................................54

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471013
Final Protocol Amendment 1, 31 Mar 2022
PFIZER CONFIDENTIAL 
Page 8
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 7-valent pneumococcal conjugate vaccine (7vPnC; Prevnar®) and 
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 with a 2-arm parallel design will 
be conducted at investigator sites in the United States and potentially other countries to be 
determined. 
 
 The purpose of this study is to describe the safety 
of 20vPnC. 
Approximately 1500 infants ≥42 to ≤98 days of age will be randomized (2:1) to receive 
either 20vPnC or 13vPnC at 2, 4, and 6 months of age (Doses 1 through 3) and 12 to 
15 months of age (Dose 4).  
Other routine pediatric vaccines are permitted according to official local 
recommendations/regulations at any time throughout study participation.  The targeted age of 
the population for this study, infants ≥42 to ≤98 days of age, has been selected as this is the 
routinely recommended age for initial vaccination with pneumococcal conjugate vaccines 
and other vaccines in infants.
Local reactions (redness, swelling, and pain at the injection site) and systemic events 
(fever, decreased appetite, drowsiness/increased sleep, and irritability) will be prompted for 
and collected by an electronic diary (e-diary) device or application, for 7 days following 
vaccination (Days 1 to 7, where Day 1 is the day of vaccination).
Adverse events (AEs) will be collected from the time the participant’s parent(s)/legal 
guardian(s) provides informed consent through 1 month after Dose 3 (Visit 4) and from 
Dose 4 (Visit 5) through 1 month after Dose 4 (Visit 6).  Serious adverse events (SAEs) and 
newly diagnosed chronic medical conditions (NDCMCs) will be collected from informed 
consent through 6 months after Dose 4 (Visit 7).
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20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471013
Final Protocol Amendment 1, 31 Mar 2022
PFIZER CONFIDENTIAL 
Page 9
Objectives, Estimands, and Endpoints
Objectives
Estimands
Endpoints
Primary Safety: 
Primary Safety:
Primary Safety: 
•
To describe the safety profile 
of 20vPnC.
In participants receiving at least 1 
dose of investigational product and 
who have safety data reported after 
any vaccination:
•
The percentage of participants 
reporting prompted local 
reactions within 7 days after 
each dose in each group.
•
The percentage of participants 
reporting prompted systemic 
events within 7 days after each 
dose in each group.
•
The percentage of participants 
reporting AEs from Dose 1 
through 1 month after Dose 3 
in each group.
•
The percentage of participants 
reporting AEs from Dose 4 
through 1 month after Dose 4 
in each group.
•
The percentage of participants 
reporting SAEs up to 6 months 
after Dose 4 in each group.
•
The percentage of participants 
reporting NDCMCs up to 
6 months after Dose 4 in each 
group.
•
Prompted local reactions 
(redness, swelling, and pain 
at the injection site).
•
Prompted systemic events 
(fever, decreased appetite, 
irritability, and 
drowsiness/increased sleep).
•
AEs.
•
SAEs.
•
NDCMCs.
Number of Participants
Approximately 1500 participants will be randomized (approximately 1000 in the 20vPnC 
group and approximately 500 in the 13vPnC group).
Duration of Participation for Each Participant
Each participant will participate in the study for approximately 16 months.
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20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471013
Final Protocol Amendment 1, 31 Mar 2022
PFIZER CONFIDENTIAL 
Page 10
Statistical Methods
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. 
1.2. Schema
Not applicable.
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20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471013
Final Protocol Amendment 1, 31 Mar 2022
PFIZER CONFIDENTIAL 
Page 11
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. 
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
5a
6a
7a
Visit Description
Dose 1
Visit
Dose 2
Visit
Dose 3
Visit
Dose 3 
Follow-up
Visit
Dose 4
Visit
Dose 4 
Follow-up Visit
Dose 4 
6-Month 
Telephone 
Contact
Visit Window (Days)
Day 1
42 to 63 Days 
After Visit 1
42 to 63 Days 
After Visit 2
28 to 42 Days 
After Visit 3
365 to 455 Days 
of Age
28 to 42 Days 
After Visit 5
168 to 196 Days 
After Visit 5
Obtain informed consent
X
Assign participant number via IRT
X
Record demography 
X
Perform clinical assessment including 
medical history
X
Record vaccine history
X
Record concomitant medicationsb
X
X
X
X
X
X
X
Obtain prevaccination temperature 
(measured as appropriate for age)
X
X
X
X
Review inclusion and exclusion 
criteria
X
Review temporary delay criteria
X
X
X
X
Review continued eligibility
X
X
X
X
X
Assign randomization number
X
Administer investigational product 
(20vPnC or 13vPnC) into the left thigh 
Xc
Xc
Xc
Xc

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471013
Final Protocol Amendment 1, 31 Mar 2022
PFIZER CONFIDENTIAL 
Page 12
Visit Number
1
2
3
4
5a
6a
7a
Visit Description
Dose 1
Visit
Dose 2
Visit
Dose 3
Visit
Dose 3 
Follow-up
Visit
Dose 4
Visit
Dose 4 
Follow-up Visit
Dose 4 
6-Month 
Telephone 
Contact
Visit Window (Days)
Day 1
42 to 63 Days 
After Visit 1
42 to 63 Days 
After Visit 2
28 to 42 Days 
After Visit 3
365 to 455 Days 
of Age
28 to 42 Days 
After Visit 5
168 to 196 Days 
After Visit 5
If applicable, administer and record 
routine pediatric vaccinationsd
X
X
X
X
Observe and record acute (immediate) 
reactions for 30 minutes after 
investigational product administration
X
X
X
X
Provide a participant contact card
X
Provide parent(s)/legal guardian(s) 
with an e-diary (device or application, 
as appropriate), digital thermometer, 
and measuring device and instruct how 
to collect prompted local reactions, 
systemic events, and use of 
antipyretic/pain medicationse
X
X
Review e-diaryf
X
X
X
X
Collect e-diary (if applicable)
X
X

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471013
Final Protocol Amendment 1, 31 Mar 2022
PFIZER CONFIDENTIAL 
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Visit Number
1
2
3
4
5a
6a
7a
Visit Description
Dose 1
Visit
Dose 2
Visit
Dose 3
Visit
Dose 3 
Follow-up
Visit
Dose 4
Visit
Dose 4 
Follow-up Visit
Dose 4 
6-Month 
Telephone 
Contact
Visit Window (Days)
Day 1
42 to 63 Days 
After Visit 1
42 to 63 Days 
After Visit 2
28 to 42 Days 
After Visit 3
365 to 455 Days 
of Age
28 to 42 Days 
After Visit 5
168 to 196 Days 
After Visit 5
Record and report adverse events
X----------------------------------------------------------------X
X----------------------------X
Record and report SAEs and 
NDCMCsg,h
X-----------------------------------------------------------------------------------------------------------------------------------------X
Abbreviations: e-diary = electronic diary; IRT = interactive response technology; NDCMC = newly diagnosed chronic medical condition.
a.
Per Protocol Amendment 1: For the United States and Puerto Rico country-specific amendment details, pertaining to Visits 5, 6, and 7, please refer to 
Section 10.9 (Appendix 9: Amendment 1 Country-Specific Requirements – Applicable to United States and Puerto Rico Only).
b.
Collect and record only concomitant medications used to treat SAEs and NDCMCs.
c.
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).
d.
If applicable, administer routine pediatric vaccinations after the investigational product into a limb other than the site of 20vPnC or 13vPnC injection.  
The name, date of administration, and site of administration for all vaccinations given on the same day as investigational product administration at Visits 1, 
2, 3, and 5 will be recorded.
e.
The participant’s parent(s)/legal guardian(s) will record in an e-diary prompted local reactions and systemic events occurring within 7 days following each 
dose of 20vPnC or 13vPnC.  Use of antipyretic/pain medications will also be prompted for and collected daily in an 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 measuring 
>14 device units, severe pain at the 20vPnC or 13vPnC injection site, or a fever >40.0°C (>104.0°F), or has an emergency room visit or hospitalization.
f.
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.
g.
An NDCMC is defined as a disease or medical condition, not previously identified, that is expected to be persistent or otherwise long-lasting in its effects.
h.
If the parent(s)/legal guardian(s) consents, participants withdrawn from the study will receive a 6-month telephone safety follow-up after their last dose of 
study vaccination for collection of any SAEs and NDCMCs.

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
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Final Protocol Amendment 1, 31 Mar 2022
PFIZER CONFIDENTIAL 
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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 7vPnC 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, showed that 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.11  Serotypes 10A, 12F, 15B/15C, 22F, and 33F accounted for 
36% of isolates causing IPD.  The most common clinical presentations of IPD due to 
non-13vPnC serotypes included bacteremia (49.6%), meningitis (19.1%), and pneumonia 
(18.8%).  These data demonstrate the continued need for expanded serotype coverage.  

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
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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, bacteremic pneumonia was reported in 42% 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  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 the 2011 visit rates of 0.82 and 0.81 visits per 
AOM/child-year in children <2 years of age and 2 to 6 years of age, respectively, and 
represents a significant medical burden.15  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.
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.16,17  Anticapsular antibodies directed against the specific 
serotype bind to the capsule and promote complement-mediated opsonophagocytic killing 
and clearance of the organism.18  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.19

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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 1983.20,21  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.4,21,22,23  Moreover, their ability to prevent 
nonbacteremic pneumonia, CAP, and AOM is limited or lacking.19,23,24,25,26  In addition, 
polysaccharide vaccines do not reduce vaccine-type (VT) nasopharyngeal carriage, which is 
important for herd immunity.26  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.19
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.22,27  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).28,29,30,31,32  These serotypes also 
accounted for a high proportion of antibiotic-resistant strains.33  7vPnC demonstrated 
efficacy against VT IPD, pneumonia, and AOM in large randomized, controlled efficacy 
studies in infants.34,35  The 7vPnC components contained in a related pneumococcal 
conjugate vaccine also were demonstrated to be efficacious against 
clinically/radiographically defined pneumonia.36,37,38,39  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.40
13vPnC was developed to expand serotype coverage and was licensed in the United States in 
2010.  13vPnC includes the same S pneumoniae serotypes as 7vPnC and an additional 6 
polysaccharide conjugates for serotypes 1, 3, 5, 6A, 7F, and 19A.27,31,41  The vaccine was 
licensed for use in infants and young children based on comparisons of serotype-specific 
serum immunoglobulin G (IgG) antibody concentrations to 7vPnC, with supportive data to 
demonstrate the functional activity of the immune responses.  13vPnC has also been licensed 
in adults based on demonstration of efficacy against CAP due to serotypes contained in 
13vPnC in adults 65 years of age and older.42   

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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.43,44,45,46  It has also been 
prequalified by the World Health Organization (WHO) for use in national infant 
immunization programs in lower- and middle-income countries.47,48 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.49,50,51
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 purpose of the study is to assess the safety of 20vPnC in 
infants, and to provide key safety data to support licensure in this population.  The targeted 
age of the population for this study, infants ≥42 to ≤98 days of age, has been selected as this 
is the routinely recommended age for initial vaccination with pneumococcal conjugate 
vaccines and other vaccines in infants.  The participants will be administered either 20vPnC 
or 13vPnC at 2, 4, 6, and 12 to 15 months of age.
Amendment 1 is a United States and Puerto Rico country-specific amendment, which is 
being implemented to complete the vaccination schedule in a timely manner, as all 
participants are age-eligible for their final dose (Dose 4) as of the amendment date. There is 
no benefit to the participant to delay completion of the series. Delaying vaccination and 
in-person study visits in the trial also carries a risk of even further delays in vaccination and 
exposure risks that may occur with a potential resurgence of coronavirus disease in the near 
future. Finally, the 20vPnC pediatric program has been granted Breakthrough Therapy 
designation by the Food and Drug Administration (FDA), indicating that it has the potential 
to meet an unmet medical need to prevent serious disease in the pediatric population. 
Therefore, avoiding further delays in study completion will support our shared goal of 
generating the key data with 20vPnC in this vulnerable population and, if successful, allow 
this vaccine to be licensed and available to help protect young children as soon as possible. 
The modifications in this amendment impact only a very small overall proportion of 
participants who have not yet received Dose 4 and those who received Dose 4 after a certain 
date, and do not adversely affect the safety, scientific integrity, or management of the study.
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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).52,53,54,55,56,57,58,59,60,61,62,63  
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.64,65,66,67,68,69,70  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.71
In the EU, according to the ECDC annual IPD epidemiological report for 2017, 
approximately 75% of cases of IPD 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.66
2.2.1. Clinical Overview
Safety and immunogenicity data from a 20vPnC Phase 1 study (B7471001) conducted in 
healthy adults 18 through 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 support clinical development in other 
populations, including pediatrics. 
A Phase 2 study (B7471003) of 20vPnC in healthy infants ≥42 to ≤98 days of age was also 
conducted.  The study randomized 460 US participants to receive either blinded 20vPnC or 
13vPnC.  Safety and immunogenicity data are available from the study.  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 geometric mean concentrations 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 a pediatric population. 

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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, but also contains the polysaccharide conjugates for the 7 additional pneumococcal 
serotypes.  Thus, the AE profile of 20vPnC is expected to be similar to that of 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. 
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 
that with 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, Prevnar® and 
Prevnar 13®), and the limited risks from study procedures support a favorable benefit-risk 
profile for 20vPnC and this study. 
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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 control vaccine is the US 
package insert (USPI). 
3. OBJECTIVES, ESTIMANDS, AND ENDPOINTS
Objectives
Estimands
Endpoints
Primary Safety: 
Primary Safety:
Primary Safety: 
•
To describe the safety profile 
of 20vPnC.
In participants receiving at least 1 
dose of investigational product and 
who have safety data reported after 
any vaccination:
•
The percentage of participants 
reporting prompted local 
reactions within 7 days after 
each dose in each group.
•
The percentage of participants 
reporting prompted systemic 
events within 7 days after each 
dose in each group.
•
The percentage of participants 
reporting AEs from Dose 1 
through 1 month after Dose 3 
in each group.
•
The percentage of participants 
reporting AEs from Dose 4 
through 1 month after Dose 4 
in each group.
•
The percentage of participants 
reporting SAEs up to 6 months 
after Dose 4 in each group.
•
The percentage of participants 
reporting NDCMCs up to 6 
months after Dose 4 in each 
group.
•
Prompted local reactions 
(redness, swelling, and pain 
at the injection site).
•
Prompted systemic events 
(fever, decreased appetite, 
irritability, and 
drowsiness/increased sleep).
•
AEs.
•
SAEs.
•
NDCMCs.
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4. STUDY DESIGN
4.1. Overall Design
This Phase 3, multicenter, randomized, double-blind study with a 2-arm parallel design will 
be conducted at investigator sites in the United States and potentially other countries to be 
determined.  
 
 The purpose of this study is to describe the safety of 
20vPnC. 
Approximately 1500 infants ≥42 to ≤98 days of age will be randomized (2:1) to receive 
either 20vPnC or 13vPnC at 2, 4, and 6 months of age (Doses 1 through 3) and 12 to 
15 months of age (Dose 4).  Other routine pediatric vaccines are permitted according to 
official local recommendations/regulations at any time throughout study participation.
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.  
Participants will receive 20vPnC or 13vPnC Dose 1.  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), 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 
within 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 injection site, or fever 
>40.0°C (>104.0°F), or has an emergency room visit or hospitalization.
Participants will return for Visit 2 (42 to 63 days after Visit 1, study Day 43 to 64) and 
Visit 3 (42 to 63 days after Visit 2).  Information will be collected from the participant’s 
parent(s)/legal guardian(s) on AEs, including nonserious AEs, SAEs, and NDCMCs, and 
e-diary follow-up (as needed).  Concomitant medications used to treat SAEs or NDCMCs 
will be recorded.  Dose 2 will be given at Visit 2 and Dose 3 will be given at Visit 3.  
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 instructed to collect prompted local reactions and systemic events occurring within 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 injection site, or fever >40.0°C (>104.0°F), 
or has an emergency room visit or hospitalization.  
Participants will return for Visit 4, approximately 1 month (28 to 42 days) after Visit 3.  
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.
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Participants will return for Visit 5 (365 to 455 days of age).  Information will be collected 
from the participant’s parent(s)/legal guardian(s) on SAEs, NDCMCs, and e-diary follow-up 
(as needed).  Concomitant medications used to treat SAEs or NDCMCs will be recorded.  
Dose 4 will 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 instructed to collect prompted local 
reactions and systemic events occurring within 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 injection site, or fever >40.0°C (>104.0°F), or has an 
emergency room visit or hospitalization.  
All participants will return for Visit 6, approximately 1 month (28 to 42 days) after Visit 5.  
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.
All participants will have Visit 7, approximately 6 months (168 to 196 Days) after Visit 5.  
The sites will contact the participant’s parent(s)/legal guardian(s) via telephone to inquire 
about SAEs and NDCMCs and concomitant medications used to treat SAEs and NDCMCs.
Amendment 1 applies to the small number of participants in this study who have not received 
Dose 4 of study intervention (these participants are solely from investigator sites in the
United States and Puerto Rico and all are age-eligible for Dose 4), and for participants who 
received Dose 4 after 16 Feb 2022. The following modifications are being introduced as part 
of a United States and Puerto Rico country-specific amendment: 1) the window for Visit 5 
(time-based rather than age-based, as all participants are now age-eligible), 2) an option of 
conducting Visit 6 by telephone, and 3) Visit 7 windows for a small number of participants 
will be modified slightly (see Section 10.9 – Appendix 9).  The modified follow-up windows 
are consistent with the original protocol, as they will still allow for approximately 6 months 
of follow-up after the final vaccination in the series.
4.1.1. Approximate Duration of Participation for Each Participant
Each participant will participate in the study for approximately 16 months.
4.1.2. Approximate Number of Participants
Approximately 1500 participants will be randomized (approximately 1000 in the 20vPnC 
group and approximately 500 in the 13vPnC group). 

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4.2. Scientific Rationale for Study Design
 
  The Phase 3 study described in this protocol will provide key 
safety data of 20vPnC in infants to support licensure in this population.  Infants born at 
>34 weeks of gestation and 2 months of age (≥42 to ≤98 days of age) at the time of consent 
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, 6, and 
12 to 15 months of age.  This is consistent with the current pneumococcal vaccine 
recommendations for infants in the United States.  13vPnC will serve as the comparator to 
20vPnC for assessment of safety.31
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, 3 doses of pneumococcal conjugate vaccine given in infancy at 2, 4, and 6 months 
of age and 1 dose given at 12 to 15 months of age induces protective immune responses.
4.4. End of Study Definition
The end of the study is defined as the date of the last visit of the last participant in the study.
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 ≥34 weeks of gestation and who are 2 months of age 
(≥42 to ≤98 days) at the time of consent (the day of birth is considered day of life 1).
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Type of Participant and Disease Characteristics:
2. Participants whose parent(s)/legal guardian(s) is willing and able to comply with 
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 parent(s)/legal 
guardian(s) can be contacted by telephone during study participation.
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 informed consent document (ICD) and in 
this protocol.
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 13vPnC, 20vPnC, or any other 
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. 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.
5. Bleeding diathesis or condition associated with prolonged bleeding that would, in the 
opinion of the investigator, contraindicate intramuscular injection.
6. 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 
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Prior/Concomitant Therapy:
7. Previous vaccination with any licensed or investigational pneumococcal vaccine, or 
planned receipt through study participation.
8. Currently receives treatment with immunosuppressive therapy, including cytotoxic 
agents or systemic corticosteroids, or planned receipt through the visit occurring 
1 month after Dose 4 (Visit 6).  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.
Prior/Concurrent Clinical Study Experience:
9. 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.  Participation in purely observational studies is acceptable. 
Diagnostic Assessments:
Not applicable.
Other Exclusions:
10. 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.  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 recorded from signing the informed consent until the time of 
determination of screen failures.
Individuals who do not meet the criteria for participation in this study (screen failure) may 
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5.5. Temporary Delay Criteria
The following conditions are temporary or self-limiting and a participant may be vaccinated 
at the visit once the condition(s) has/have resolved and no other exclusion criteria are met.  
5.5.1. Criteria for Temporarily Delaying Vaccine Administration
•
Current febrile illness (eg, body temperature ≥38.0°C [≥100.4°F]) or other acute illness 
within 48 hours before investigational product administration. 
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.
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. 
 
 
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 are both white suspensions and are identical in appearance. 
Investigational product will be supplied by Pfizer as prefilled syringes.  Each syringe 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 investigational product manual [IP manual]).
6.1.1. Administration
Participants will receive 1 dose of 20vPnC or 13vPnC at each vaccination visit (Visits 1, 2, 3, 
and 5) in accordance with the study’s SoA.
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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.
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 prefilled syringes.
Instructions for medical device use are provided in the IP manual.
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 8.3.6 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. 
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6.2.1. Preparation and Dispensing
See the IP manual 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
Allocation (randomization) 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 number 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 number 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. 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.
6.3.3. Blinding of the Sponsor
Sponsor personnel directly involved in evaluating participant data will be blinded to vaccine 
assignment until the analysis of available data through 1 month after Dose 4, following the 
principles outlined in the International Council for Harmonisation E9 guideline on Statistical 
Principles for Clinical Trials.72 A data blinding plan will be created to describe the blinding 
requirements and unblinding events.

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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 
participant participation in the study.

Receipt of any nonstudy pneumococcal vaccine is prohibited during participant 
participation in the study.
6.5.2. Permitted Concomitant Vaccines and Treatments

Other routine pediatric vaccines, including influenza vaccine, are permitted at any time 
throughout study participation, given according to official local 
recommendations/regulations.

The use of prophylactic antipyretic/pain medication, while permitted, is not 
recommended on the day of investigational product administration (before or after 
vaccination).

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 participant participation in the study.
6.5.3. Recording Prior and Concomitant Vaccines and Treatments
The name, date of administration, and site of administration for all vaccinations given on the 
same day as investigational product administration (Visits 1, 2, 3 and 5) will be recorded in 
the CRF.  At Visit 1, information on prior vaccinations received by the participant will be 
recorded in the CRF. 
Concomitant medications used to treat an NDCMC or SAE should be collected from the 
signing of informed consent through 6 months after Dose 4 (Visit 7 telephone call) and will 
be recorded in 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.

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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 7.2.
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 please refer to the study reference manual (SRM) 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 participant will be permanently discontinued both from the study 
intervention and from the study at that time.  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.
For participants who are discontinued prior to completing all 4 doses of study intervention, 
the parent(s)/legal guardian(s) should be encouraged to follow up with their primary care 
physician to have the participant complete the pneumococcal conjugate vaccine series as part 
of their recommended standard of care.

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A final telephone contact 6 months after the last vaccination (similar to Section 8.10.7) for 
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. 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 
postvaccination study follow-up.
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 VaccineCT 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 or fails to respond to the 6-month safety follow-up telephone call:

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 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. 

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Discontinuation of specific sites or of the study as a whole is handled as part of Appendix 1.
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.
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.
8.1. Efficacy Assessments
Not applicable.

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8.2. Safety Assessments
A clinical assessment, including medical history and measurement of temperature as 
appropriate for the age of the child, according to routine local practice, 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 observed during 
physical examination (if performed) will be recorded in the medical history CRF.  
Temperature measurement prior to vaccination will be documented and recorded in the CRF.
The participant will be observed for 30 minutes after each vaccination and any reactions 
during the visit will be assessed and recorded.
Prompted e-diary events, including local reactions (redness, swelling, and pain at the 
injection site) and systemic events (fever, decreased appetite, drowsiness/increased sleep, and 
irritability) that occur within 7 days following investigational product administration (Days 1 
to 7, where Day 1 is the day of vaccination) are graded as described in Section 8.2.2.  
Furthermore, AEs, SAEs, and NDCMCs will be collected as defined in Section 10.3.
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.
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 medications taken for 7 days, each 
evening following each vaccination using an e-diary (in a provisioned device or application 
on a personal device), which 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 medications 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 is 
withdrawn 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 local reactions and specific 
systemic events ongoing on the last day that the e-diary was completed.  The stop dates 
should be entered in the CRF.
Investigators (or an appropriately qualified designee) are required to review the e-diary data 
online at frequent intervals (daily is optimal) to evaluate participant compliance and reported 
events as part of the ongoing safety review.

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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 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.73
8.2.2.1. Local Reactions
For the first 7 days following each vaccination from Day 1 through Day 7, 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 will denote >14), and then categorized during analysis as 
mild, moderate, or severe based on the grading scale in Table 1 below.  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 below.  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 investigator site file (ISF) or 
equivalent.

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Table 1.
Grading Scales for Local Reactions
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.
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.
a.
Parents/legal guardians 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 in the CRF.  The severity of the local reaction should be graded using the AE 
severity grading scale provided in the protocol.
8.2.2.2. Systemic Events – Symptoms and Fever
8.2.2.2.1. Symptoms
For the first 7 days following each vaccination from Day 1 through Day 7, 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 below.  
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 ISF or equivalent.

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Table 2.
Grading Scales for Systemic Events
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 in the CRF.  The severity of the systemic event should be graded using the AE 
severity grading scale provided in the protocol.
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 temperature 
(as appropriate for the age of the child) 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 a 
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 Day 7, 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 temperature >40.0C (>104.0F) to assess the 
fever and perform an unscheduled assessment, as applicable (see unscheduled assessments in 
Section 8.10.8).  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 below.

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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, 
where Day 1 is the day of vaccination.
The use of prophylactic antipyretic/pain medication, while permitted, is not recommended on 
the day of investigational product administration (before or after vaccination).
8.2.3. Clinical Safety Laboratory Assessments
Clinical safety laboratory assessments 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.
8.2.4. Biological Samples
Collection of biological samples are not required by this protocol.
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 that caused the participant to discontinue 
from the study (see Section 7). 

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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 4, and from Visit 5 to Visit 6.  Between Visit 4 and 
Visit 5, only SAEs and NDCMCs will be reported.  At Visit 7 (final telephone contact), the 
participant’s parent(s)/legal guardian(s) will be contacted by telephone to inquire about 
SAEs, including hospitalizations and NDCMCs, since Visit 6.
AEs that begin before the start of study intervention but after obtaining informed consent will 
be recorded on the Medical History/Current Medical Conditions section of the CRF, not the 
AE section.
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.
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.

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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.
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.

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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 is 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 at least 6 months after exposure.
If a pregnancy is reported, the investigator should inform the sponsor within 24 hours of 
learning of the pregnancy and should follow the procedures outlined in 
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. Medical Device Incidents (Including Malfunctions)
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 incident or malfunction that occur during the study with such devices.
The definition of a medical device incident can be found in Appendix 8.
NOTE: Incidents fulfilling the definition of an AE/SAE will also follow the processes
outlined in Section 8.3.3 and Appendix 3 of the protocol.
CCI

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8.3.6.1. Time Period for Detecting Medical Device Incidents
Medical device incidents or malfunctions of the device that result in an incident 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 incident 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 incidents is provided in Appendix 8.
8.3.6.2. Follow-up of Medical Device Incidents
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 incident.
New or updated information will be recorded on the originally completed form with all 
changes signed and dated by the investigator.
8.3.6.3. Prompt Reporting of Medical Device Incidents to Sponsor
Medical device incidents will be reported to the sponsor within 24 hours after the investigator 
determines that the event meets the protocol definition of a medical device incident.
Refer to the IP manual for instructions on reporting medical device incidents. 
The same individual will be the contact for the receipt of medical device reports and SAEs.
8.3.6.4. Regulatory Reporting Requirements for Medical Device Incidents
The investigator will promptly report all incidents 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 incidents to the IRB/EC.

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8.3.7. 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:
a.
Medication errors involving participant exposure to the investigational product;
b. 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 immediately.
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.
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.

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8.4. Treatment of Overdose
For this study, any dose of investigational product greater than 0.5 mL of investigational 
product 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 immediately.
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.
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.
Unless specified in the sections below, the order of key procedures within a given visit may 
have some flexibility.

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8.10.1. Visit 1 (Dose 1: Day 1)
Prior to vaccination:

Obtain a personally signed and dated ICD indicating that 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 safety profile by age.

Perform a clinical assessment including medical history (including significant birth 
history); record any findings on the medical history CRF.

Record vaccine history.

Measure and record the participant’s prevaccination temperature using a method 
appropriate for the age of the child, according to routine local practice (F/C).

Ensure that all inclusion criteria, none of the exclusion criteria, and none of the temporary 
delay criteria are met.

Assign a randomization number and investigational product container number via the 
IRT.  This must be the last step before proceeding.  A blinded site staff member will 
prepare the investigational product according to the IP manual.
After randomization:

Administer a single 0.5-mL injection of 20vPnC or 13vPnC into the left anterolateral 
thigh.

If applicable, administer routine pediatric vaccinations into a limb other than the site of 
20vPnC or 13vPnC injection and capture all details of the concomitant vaccine given on 
the same day as investigational product administration, including the name, date of 
administration, and site of administration, 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 injection 
site reactions and a digital thermometer and provide instructions on their use.

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
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 injection site measuring 
>14 measuring device units (>7 cm), or severe 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 a participant contact card with the study and investigator information 
(see Section 10.1.10).

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).

The investigator or an authorized designee completes the CRF 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.
8.10.2. Visit 2 (Dose 2: 42 to 63 Days After Dose 1, ie, Study Day 43 to 64)

Ensure and document that the participant continues to be eligible for the study 
(see Section 7.2 for participant withdrawal information) 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.

Review the participant’s e-diary data with the participant’s parent(s)/legal guardian(s); 
collect stop dates of any e-diary 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, and record concomitant medications used to treat 
NDCMCs and SAEs.

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
Measure and record the participant’s prevaccination temperature using a method 
appropriate for the age of the child, according to routine local practice (F/C).

Administer a single 0.5-mL injection of 20vPnC or 13vPnC into the left anterolateral 
thigh.

If applicable, administer routine pediatric vaccinations into a limb other than the site of 
20vPnC or 13vPnC injection and capture all details of the concomitant vaccine given on 
the same day as investigational product administration, including the name, date of 
administration, and site of administration, 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 
medication used to treat NDCMCs and SAEs.

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 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 
experiences fever >40.0C (>104.0F), redness or swelling at the injection site measuring 
>14 measuring device units (>7 cm), or severe 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).

The investigator or an authorized designee completes the CRF 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.

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8.10.3. Visit 3 (Dose 3: 42 to 63 Days After Dose 2)

Ensure and document that the participant continues to be eligible for the study 
(see Section 7.2 for participant withdrawal information) 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.

Review the participant’s e-diary data with the participant’s parent(s)/legal guardian(s); 
collect stop dates of any e-diary 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, and record concomitant medications used to treat 
NDCMCs and SAEs.

Measure and record the participant’s prevaccination temperature using a method 
appropriate for the age of the child, according to routine local practice (F/C).

Administer a single 0.5-mL injection of 20vPnC or 13vPnC into the left anterolateral 
thigh.

If applicable, administer routine pediatric vaccinations into a limb other than the site of 
20vPnC or 13vPnC injection and capture all details of the concomitant vaccine given on 
the same day as investigational product administration, including the name, date of 
administration, and site of administration, 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.

Confirm that the e-diary is working appropriately and review instructions if needed. 
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 thermometer and/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 
experiences fever >40.0C (>104.0F), redness or swelling at the injection site measuring 
>14 measuring device units (>7 cm), or severe injection site pain (causes limitation of 
limb movement) to determine if the event requires further assessment by the investigator.

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
Remind the participant’s parent(s)/legal guardian(s) to contact the investigator or 
investigator site staff immediately 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).

The investigator or an authorized designee completes the CRF 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.
8.10.4. Visit 4 (Follow-up: 28 to 42 to Days After Dose 3)

Ensure and document that the participant continues to be eligible for the study 
(see Section 7.2 for participant withdrawal information).

Confirm whether the parent(s)/legal guardian(s) still possesses the participant contact 
card.

Review the participant’s e-diary data with the participant’s parent(s)/legal guardian(s); 
collect stop dates of any e-diary 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, and record concomitant medications used to treat 
NDCMCs and SAEs.

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). 

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.

The investigator or an authorized designee completes the CRF.

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8.10.5. Visit 5 (Dose 4: 365 to 455 Days of Age)
NOTE: For the United States and Puerto Rico country-specific amendment related to Visit 5, 
please refer to Section 10.9.

Ensure and document that the participant continues to be eligible for the study 
(see Section 7.2 for participant withdrawal information) 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.

Determine whether any 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, and 
record concomitant medications used to treat NDCMCs and SAEs.  Measure and record 
the participant’s prevaccination temperature using a method appropriate for the age of the 
child, according to routine local practice (F/C).

Administer a single 0.5-mL injection of investigational product (20vPnC or 13vPnC) into 
the anterolateral left thigh.

If applicable, administer routine pediatric vaccinations into a limb other than the site of 
20vPnC or 13vPnC injection and capture all details of the concomitant vaccine given on 
the same day as investigational product administration, including the name, date of 
administration, and site of administration, 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.

Issue the participant’s parent(s)/legal guardian(s) an e-diary (device or application).  
Review and 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 investigational product vaccination.  Provide the 
participant’s parent(s)/legal guardian(s) with a thermometer or measuring device if 
needed.

Ask the participant’s parent(s)/legal guardian(s) to contact the investigator site staff or 
investigator immediately during the 7-day postvaccination period if the participant 
experiences fever >40.0C (>104.0F), redness or swelling at the injection site measuring 
>14 measuring device units (>7 cm), or severe injection site pain (causes limitation of 
limb movement) to determine if the event requires further assessment by the investigator.

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
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.

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).

The investigator or an authorized designee completes the CRF 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.
8.10.6. Visit 6 (Follow-up: 28 to 42 to Days After Dose 4)
NOTE: For the United States and Puerto Rico country-specific amendment related to Visit 6, 
please refer to Section 10.9.

Ensure and document that the participant continues to be eligible for the study 
(see Section 7.2 for participant withdrawal information).

Confirm whether the parent(s)/legal guardian(s) still possesses the participant contact 
card.

Review the participant’s e-diary data with the participant’s parent(s)/legal guardian(s); 
collect stop dates of any e-diary 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, and record concomitant medications used to treat 
NDCMCs and SAEs.

Remind the participant’s parent(s)/legal guardian(s) to contact the investigator or 
investigator site staff immediately if any significant illness or medical event 
(eg, emergency room visit or hospitalization) occurs.

The investigator or an authorized designee completes the CRF.

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8.10.7. Visit 7 (Follow-up: 168 to 196 Days After Dose 4)
NOTE: For the United States and Puerto Rico country-specific amendment related to Visit 7, 
please refer to Section 10.9.

Contact the participant’s parent(s)/legal guardian(s) by telephone approximately 
6 months after the last study vaccination; this contact should be attempted for all 
participants who have received at least 1 study vaccination, unless the participant’s 
parent(s)/legal guardian(s) has withdrawn consent.

Determine whether any 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, and 
record concomitant medications used to treat SAEs and NDCMCs.

The investigator or an authorized designee completes the CRF and the source documents. 
8.10.8. 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) or 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 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 needed.  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 principal investigator (PI) or authorized designee determined it was not needed.
This telephone contact will be recorded in the participant’s source documentation and the 
CRF.
If the participant’s parent(s)/legal guardian(s) is unable to bring the participant to an 
unscheduled visit, or the PI or authorized designee determined it was not needed, any 
ongoing reactions must be assessed at the next study visit.

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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 (as appropriate for the age of the child, according to routine local 
practice [F/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. 
9. STATISTICAL CONSIDERATIONS
Detailed methodology for summary and statistical analyses of the data collected in this study 
is outlined 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 
appropriate; however, any major modifications of the primary endpoint definitions or their 
analyses will also be reflected in a protocol amendment.

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9.1. Estimands and Statistical Hypotheses
9.1.1. Estimands
The primary objective of the study is to describe the safety profile of 20vPnC in healthy 
infants.  Estimands to address the primary objective are provided in Section 3.  In the safety 
evaluation, 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.
There is no formal hypothesis test for any safety results.
9.2. Sample Size Determination
The study size in each vaccine group is not based on any formal hypothesis test for any 
safety endpoints.  All statistical analyses will be descriptive. 
The primary safety objectives include the endpoints for AEs reported between Dose 1 and 
1 month after Dose 3 and also between Dose 4 and 1 month after Dose 4.  The number of 
participants receiving 20vPnC is 1000, which provides a greater than 95% chance of 
observing at least 1 AE in this group, assuming a true rate of at least 0.3% (Table 4).
Table 4.
Probability of Detecting at Least 1 AE in the 20vPnC and 13vPnC Groups
Group
Sample Size
True Rate of AEs
Probability of Observing 
at Least 1 AE
20vPnC
1000
0.1%
63.2%
0.2%
86.5%
0.3%
95.0%
0.4%
98.2%
0.5%
99.3%
13vPnC
500
0.1%
39.4%
0.2%
63.2%
0.3%
77.7%
0.4%
86.5%
0.5%
91.8%
9.3. Populations for Analysis
For purposes of analysis, the following populations are defined:
Population
Description
Enrolled 
All participants who have a signed ICD.
Randomized
All participants who are assigned a randomization number in the IWR system. 
Safety
All randomized participants who receive at least 1 dose of the investigational 
product and have safety data after any dose.

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9.4. Statistical Analyses
The SAP will be developed and finalized before database lock for any of the planned analysis 
in Section 9.5.1 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 
 endpoints, as 
applicable.
9.4.1. Safety Analyses
All safety analyses will be performed on the safety population.
Endpoint
Statistical Analysis Methods
Primary 
•
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 dose 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 Clopper-Pearson 95% confidence intervals 
(CIs).  Between-group differences (20vPnC – 13vPnC) in percentage and 2-sided 95% 
CIs will 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; (3) Tier 3 events are those 
that are neither Tier 1 nor Tier 2 events.  For both Tier 1 and Tier 2 events, the 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 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 and percentages and the associated Clopper-Pearson 95% 
CIs) will be provided for Tier 3 events for each vaccine group.
•
SAEs will be categorized according to MedDRA terms. Counts, percentages, and the 
associated Clopper-Pearson 95% CIs of SAEs and NDCMCs from Dose 1 to 6 months 
after Dose 4 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
•
There are no secondary endpoints in the study.
9.5. Interim Analyses 
There is no interim analysis planned for the study. 
CCI
CCI

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9.5.1. Analysis Timing
Safety data through the visit occurring 1 month after Dose 4 from all participants may be 
analyzed (Primary Analysis 1) by the study team when available (at which time the study 
team will be unblinded).  Safety data from 1 month after Dose 4 through 6 months after 
Dose 4 will be analyzed (Primary Analysis 2) and reported after the final visit.
The investigator site staff will remain blinded to participant vaccine group until the last 
participant completes the final visit telephone call.
CCI

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10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations
10.1.1. Regulatory and Ethical Considerations
This study will be conducted in accordance with the protocol and with the following:

Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences (CIOMS) International Ethical Guidelines;

Applicable International Council for Harmonisation (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. 

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In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study participants against any immediate hazard, and 
of any serious breaches of this protocol or of ICH GCP that the investigator becomes aware 
of.
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.

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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.

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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.

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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.

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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 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.

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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 available.  It is therefore 
intended to augment, but not replace, the established communication pathways between the 
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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.
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.

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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 an NDCMC
An NDCMC is defined as a 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.

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An SAE is defined as any untoward medical occurrence that, at any dose:
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.

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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. 
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.

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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.

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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.

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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.

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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.  
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Therefore, abnormal elevations in either AST OR ALT in addition to TBili that meet the 
criteria outlined below are considered potential DILI (assessed per Hy’s law criteria) cases 
and should always be considered important medical events, even before all other possible 
causes of liver injury have been excluded.
The threshold of laboratory abnormalities for a potential DILI case depends on the 
participant’s individual baseline values and underlying conditions.  Participants who present 
with the following laboratory abnormalities should be evaluated further as potential DILI 
(Hy’s law) cases to definitively determine the etiology of the abnormal laboratory values:

Participants with AST/ALT and TBili baseline values within the normal range who 
subsequently present with AST OR ALT values >3 × ULN AND a TBili value 
>2 × ULN with no evidence of hemolysis and an alkaline phosphatase value 
<2 × ULN or not available.

For participants with baseline AST OR ALT OR TBili values above the ULN, the 
following threshold values are used in the definition mentioned above, as needed, 
depending on which values are above the ULN at baseline:

Preexisting AST or ALT baseline values above the normal range: AST or ALT 
values >2 times the baseline values AND >3 × ULN; or >8 × ULN (whichever is 
smaller).

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 (PT)/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 

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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.
10.7. Appendix 7: ECG Findings of Potential Clinical Concern
Not applicable.
10.8. Appendix 8: Medical Device Incidents: Definition and Procedures for Recording, 
Evaluating, Follow-up, and Reporting
Definitions of a Medical Device Incident
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).
Medical Device Incident Definition

A medical device incident is any malfunction or deterioration in the characteristics 
and/or performance of a device as well as any inadequacy in the labeling or the 
instructions for use which, directly or indirectly, might lead to or might have led to the 
death of a participant/user/other person or to a serious deterioration in his/her state of 
health.

Not all incidents lead to death or serious deterioration in health.  The nonoccurrence of 
such a result might have been due to other fortunate circumstances or to the 
intervention of healthcare personnel.
It is sufficient that:

An incident associated with a device happened.
AND

The incident was such that, if it occurred again, might lead to death or a serious 
deterioration in health.

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A serious deterioration in state of health can include any of the following:

Life-threatening illness;

Permanent impairment of body function or permanent damage to body structure;

Condition necessitating medical or surgical intervention to prevent one of the above;

Fetal distress, fetal death, or any congenital abnormality or birth defects.
Examples of Incidents

A participant, user, caregiver, or healthcare professional is injured as a result of a 
medical device failure or its misuse.

A participant’s study intervention is interrupted or compromised by a medical device 
failure.

A misdiagnosis due to medical device failure leads to inappropriate treatment.

A participant’s health deteriorates due to medical device failure.
Documenting Medical Device Incidents
Medical Device Incident Documentation

Any medical device incident occurring during the study will be documented in the 
participant’s medical records, in accordance with the investigator’s normal clinical 
practice, and on the appropriate form.

For incidents fulfilling the definition of an AE or an SAE, the appropriate AE/SAE 
CRF page will be completed as described in Appendix 3.

The CRF will be completed as thoroughly as possible and signed by the investigator 
before transmittal to the sponsor or designee.

It is very important that the investigator provides his/her assessment of causality 
(relationship to the medical device provided by the sponsor) at the time of the initial 
AE or SAE report and 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 an incident.  
This includes any amendment to the device design to prevent recurrence.

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10.9. Appendix 9: Amendment 1 Country-Specific Requirements – Applicable to United 
States and Puerto Rico Only
Per Protocol Amendment 1, the following list summarizes the modifications of the protocol 
that are specific to sites in the United States and Puerto Rico only.  The modifications impact 
Visit 5 and Visit 7 timing, and add flexibility in the format of Visit 6 as follows:

Per Protocol Amendment 1: The last day to be eligible for Dose 4 (Visit 5) is 
20 Apr 2022. Participants who have not received Dose 4 by this date are ineligible 
and will be discontinued per Section 7 of the protocol.

Per Protocol Amendment 1: Visit 6 may be conducted by telephone.

Per Protocol Amendment 1: The window for Visit 7 is modified for participants who 
have Visit 5 (receive Dose 4) after 16 Feb 2022:
o
Visit 5 performed on 17 Feb 2022 through 14 Mar 2022: the target Visit 7 
window remains 168 to 196 days after Visit 5, but Visit 7 is to be completed by 
31 Aug 2022, whichever is earlier.
o
Visit 5 performed on 15 Mar 2022 through 01 Apr 2022: the window is 145 to 
168 days after Visit 5, or until 31Aug 2022, whichever is earlier.
o
Visit 5 performed on 02 Apr 2022 through 20 Apr 2022: the window is 126 to 145 
days after Visit 5, or until 31Aug 2022, whichever is earlier.

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10.10. Appendix 10: 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
ALT
alanine aminotransferase
AOM
acute otitis media
AST
aspartate aminotransferase
CAP
community-acquired pneumonia
CBER
Center for Biologics Evaluation and Research
CDC
Centers for Disease Control and Prevention
CFR
Code of Federal Regulations
CI
confidence interval
CIOMS
Council for International Organizations of Medical Sciences
CK
creatine kinase
CONSORT
Consolidated Standards of Reporting Trials
CRF
case report form
CRM197
cross-reactive material 197
CRO
contract research organization
CSR
clinical study report
CT
clinical trial
DILI
drug-induced liver injury
DU
dispensable unit
EC
ethics committee
ECDC
European Centre for Disease Prevention and Control
ECG
electrocardiogram
eCRF
electronic case report form
e-diary
electronic diary
 
EDP
exposure during pregnancy
EMA
European Medicines Agency
EU
European Union
EudraCT
European Clinical Trials Database
FDA
Food and Drug Administration
GCP
Good Clinical Practice
GGT
gamma-glutamyl transferase
HIPAA
Health Insurance Portability and Accountability Act
HIV
human immunodeficiency virus
IB
investigator’s brochure
ICD
informed consent document
ICH
International Council for Harmonisation
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Abbreviation
Term
ID
identification
IgG
immunoglobulin G
IND
investigational new drug application
INR
international normalized ratio
IPD
invasive pneumococcal disease
IP manual
investigational product manual
IRB
institutional review board
IRT
interactive response technology
ISF
investigator site file
IWR
interactive Web-based response
LFT
liver function test
MedDRA
Medical Dictionary for Regulatory Activities
N/A
not applicable
NDCMC
newly diagnosed chronic medical condition
PCD
primary completion date
PI
principal investigator
PPSV23
23-valent pneumococcal polysaccharide vaccine
PT
prothrombin time
SAE
serious adverse event
SAP
statistical analysis plan
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
USPI
United States package insert
VT
vaccine-type
WHO
World Health Organization

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