A PHASE 3, SINGLE-ARM TRIAL TO EVALUATE THE SAFETY AND IMMUNOGENICITY OF A 20-VALENT PNEUMOCOCCAL CONJUGATE VACCINE IN HEALTHY CHILDREN 15 MONTHS THROUGH 17 YEARS OF AGE
Phase: PHASE3
Conditions: Pneumococcal Disease
Sponsor: Pfizer

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471014
Final Protocol Amendment 1, 18 Oct 2021
PFIZER CONFIDENTIAL
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A PHASE 3, SINGLE-ARM TRIAL TO EVALUATE THE SAFETY AND 
IMMUNOGENICITY OF A 20-VALENT PNEUMOCOCCAL CONJUGATE 
VACCINE IN HEALTHY CHILDREN 15 MONTHS THROUGH 17 YEARS OF AGE
Investigational Product Number:
PF-06482077
Investigational Product Name:
20-valent pneumococcal conjugate vaccine 
(20vPnC)
United States (US) Investigational New 
Drug (IND) Number:
17980
European Clinical Trials Database 
(EudraCT) Number:
2019-003308-11
Protocol Number:
B7471014
Phase:
3
Short Title: Safety and Immunogenicity Study of 20vPnC in Healthy Children 
15 Months Through 17 Years of Age
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20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471014
Final Protocol Amendment 1, 18 Oct 2021
PFIZER CONFIDENTIAL
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Protocol Amendment Summary of Changes Table 
Document History
Document
Version Date
Summary of Changes and Rationale
Amendment 1
18 Oct 2021
•
To be consistent with the European PIP modification 
approved in August 2021 added 2 secondary 
immunogenicity endpoints.
 
•
Clarified that the primary immunogencity endpoints 
and the additional secondary endpoints are 
addressing consistencies with the approved European 
PIP modification.
Original protocol
13 Aug 2020
Not applicable (N/A)
This amendment incorporates all revision to date, including amendments made at the request 
of country health authorities and IRBs/ECs, and any protocol administrative clarification 
letter.
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20-valent Pneumococcal Conjugate Vaccine (20vPnC)
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Final Protocol Amendment 1, 18 Oct 2021
PFIZER CONFIDENTIAL
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TABLE OF CONTENTS
LIST OF TABLES.....................................................................................................................8
1. PROTOCOL SUMMARY.....................................................................................................9
1.1. Synopsis ....................................................................................................................9
1.2. Schema ....................................................................................................................13
1.3. Schedule of Activities (SoA)...................................................................................14
2. INTRODUCTION ...............................................................................................................16
2.1. Study Rationale .......................................................................................................19
2.2. Background .............................................................................................................20
2.2.1. Clinical Overview.......................................................................................20
2.3. Benefit/Risk Assessment.........................................................................................21
3. OBJECTIVES, ESTIMANDS, AND ENDPOINTS ...........................................................22
4. STUDY DESIGN.................................................................................................................24
4.1. Overall Design.........................................................................................................24
4.1.1. Approximate Duration of Participation for Each Participant .....................26
4.1.2. Approximate Number of Participants.........................................................26
4.2. Scientific Rationale for Study Design.....................................................................26
4.3. Justification for Dose ..............................................................................................27
4.4. End of Study Definition ..........................................................................................27
5. STUDY POPULATION......................................................................................................27
5.1. Inclusion Criteria.....................................................................................................27
5.1.1. Cohort 1 and Cohort 2 ................................................................................27
5.1.2. Cohort 3 and Cohort 4 ................................................................................28
5.2. Exclusion Criteria....................................................................................................29
5.2.1. Cohort 1 and Cohort 2 ................................................................................29
5.2.2. Cohort 3 and Cohort 4 ................................................................................30
5.3. Lifestyle Considerations..........................................................................................32
5.3.1. Contraception (If Applicable).....................................................................32
5.4. Screen Failures ........................................................................................................32
5.5. Temporary Delay Criteria .......................................................................................32
5.5.1. Criteria for Temporarily Delaying Vaccine Administration ......................32

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
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5.5.2. Criteria for Temporarily Delaying Immunogenicity Blood Draw..............33
6. STUDY INTERVENTION..................................................................................................33
6.1. Study Intervention(s) Administered........................................................................33
6.1.1. Administration............................................................................................33
6.1.2. Medical Devices .........................................................................................34
6.2. Preparation/Handling/Storage/Accountability ........................................................34
6.2.1. Preparation and Dispensing........................................................................35
6.3. Measures to Minimize Bias: Randomization and Blinding.....................................36
6.3.1. Allocation to Study Intervention ................................................................36
6.4. Study Intervention Compliance...............................................................................36
6.5. Concomitant Therapy..............................................................................................36
6.5.1. Prohibited Concomitant Vaccines and Treatments.....................................36
6.5.2. Permitted Concomitant Vaccines and Treatments......................................36
6.5.3. Recording Prior and Concomitant Vaccines and Treatments.....................37
6.6. Dose Modification...................................................................................................37
6.7. Intervention After the End of the Study..................................................................37
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL...........................................................................38
7.1. Discontinuation of Study Intervention ....................................................................38
7.2. Participant Discontinuation/Withdrawal From the Study.......................................38
7.3. Lost to Follow-up....................................................................................................39
8. STUDY ASSESSMENTS AND PROCEDURES...............................................................39
8.1. Efficacy Assessments..............................................................................................40
8.1.1. Immunogenicity Assessments ....................................................................40
8.1.2. Biological Samples.....................................................................................41
8.2. Safety Assessments .................................................................................................42
8.2.1. Participant Electronic Diary .......................................................................42
8.2.2. Grading Scale for Prompted Events ...........................................................43
8.2.2.1. Local Reactions.........................................................................43
8.2.2.2. Systemic Events – Symptoms and Fever ..................................44
8.2.2.3. Use of Antipyretic/Pain Medication..........................................47

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
Protocol B7471014
Final Protocol Amendment 1, 18 Oct 2021
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8.2.3. Clinical Safety Laboratory Assessments ....................................................47
8.2.4. Pregnancy Testing (If Applicable)..............................................................47
8.3. Adverse Events and Serious Adverse Events..........................................................47
8.3.1. Time Period and Frequency for Collecting AE and SAE Information.......48
8.3.1.1. Reporting SAEs to Pfizer Safety...............................................49
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF...................49
8.3.2. Method of Detecting AEs and SAEs ..........................................................49
8.3.3. Follow-up of AEs and SAEs.......................................................................49
8.3.4. Regulatory Reporting Requirements for SAEs...........................................50
8.3.5. Exposure During Pregnancy or Breastfeeding, and Occupational 
Exposure ..........................................................................................................50
8.3.5.1. Exposure During Pregnancy......................................................50
8.3.5.2. Exposure During Breastfeeding ................................................52
8.3.5.3. Occupational Exposure .............................................................52
8.3.6. Cardiovascular and Death Events...............................................................52
8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as AEs or SAEs..............................................................................53
8.3.8. Adverse Events of Special Interest.............................................................53
8.3.8.1. Lack of Efficacy........................................................................53
8.3.9. Medical Device Deficiencies......................................................................53
8.3.9.1. Time Period for Detecting Medical Device Deficiencies .........53
8.3.9.2. Follow-up of Medical Device Deficiencies...............................53
8.3.9.3. Prompt Reporting of Device Deficiencies to Sponsor ..............54
8.3.9.4. Regulatory Reporting Requirements for Medical Device 
Deficiencies .......................................................................................54
8.3.10. Medication Errors.....................................................................................54
8.4. Treatment of Overdose............................................................................................55
8.5. Pharmacokinetics ....................................................................................................55
8.6. Pharmacodynamics..................................................................................................55
8.7. Genetics...................................................................................................................56
8.8. Biomarkers ..............................................................................................................56
8.9. Health Economics ...................................................................................................56

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
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Final Protocol Amendment 1, 18 Oct 2021
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8.10. Study Procedures...................................................................................................56
8.10.1. Visit 1 (Vaccination 1, Day 1)..................................................................56
8.10.2. Visit 2 (Follow-up: 28 to 42 Days After Visit 1, ie, Study Day 29 to 
43) ....................................................................................................................58
8.10.3. Visit 3 (6-Month Safety Collection [Telephone Contact] – 168 to 
196 Days After Visit 1)....................................................................................59
8.10.4. Unscheduled Visits...................................................................................59
9. STATISTICAL CONSIDERATIONS ................................................................................61
9.1. Estimands and Statistical Hypotheses.....................................................................61
9.1.1. Estimands....................................................................................................61
9.1.2. Statistical Hypotheses.................................................................................62
9.1.2.1. Cohort 1 and Cohort 2...............................................................62
9.1.2.2. Cohort 3 and Cohort 4...............................................................62
9.1.3. Multiplicity Considerations ........................................................................62
9.2. Sample Size Determination.....................................................................................63
9.3. Populations for Analysis .........................................................................................64
9.4. Statistical Analyses .................................................................................................65
9.4.1. Immunogenicity Analyses ..........................................................................65
9.4.2. Safety Analyses ..........................................................................................68
9.5. Interim Analyses .....................................................................................................69
9.5.1. Analysis Timing..........................................................................................69
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS..........................................................................................................70
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations...............70
10.1.1. Regulatory and Ethical Considerations ....................................................70
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the 
Protocol or ICH GCP.........................................................................70
10.1.2. Financial Disclosure .................................................................................71
10.1.3. Informed Consent Process ........................................................................71
10.1.4. Data Protection .........................................................................................72
10.1.5. Dissemination of Clinical Study Data ......................................................72
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10.1.6. Data Quality Assurance ............................................................................74
10.1.7. Source Documents....................................................................................75
10.1.8. Study and Site Closure..............................................................................75
10.1.9. Publication Policy.....................................................................................76
10.1.10. Sponsor’s Qualified Medical Personnel .................................................76
10.2. Appendix 2: Clinical Laboratory Tests .................................................................77
10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ......................................................................78
10.3.1. Definition of AE .......................................................................................78
10.3.2. Definition of an NDCMC.........................................................................79
10.3.3. Definition of SAE.....................................................................................79
10.3.4. Recording/Reporting and Follow-up of AEs and/or SAEs.......................81
10.3.5. Reporting of SAEs....................................................................................84
 
10.5. Appendix 5: Genetics............................................................................................89
10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-up Assessments ........90
10.7. Appendix 7: ECG Findings of Potential Clinical Concern ...................................91
10.8. Appendix 8: Medical Device Adverse Events, Adverse Device Effects, 
Serious Adverse Events, and Device Deficiencies: Definition and Procedures 
for Recording, Evaluating, Follow-up, and Reporting..............................................92
10.8.1. Definition of AE and ADE .......................................................................92
10.8.2. Definition of SAE, SADE, and Unanticipated Serious Adverse 
Device Effect ...................................................................................................92
10.8.3. Definition of Device Deficiency...............................................................93
10.8.4. Recording/Reporting and Follow-up of AEs and/or SAEs and 
Device Deficiencies .........................................................................................94
10.8.5. Reporting of SAEs....................................................................................96
10.8.6. Reporting of SADEs.................................................................................97
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Final Protocol Amendment 1, 18 Oct 2021
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10.9. Appendix 9: Country-Specific Requirements .......................................................97
10.10. Appendix 10: Abbreviations ...............................................................................98
11. REFERENCES ................................................................................................................101
LIST OF TABLES
Table 1.
Grading Scales for Local Reactions in Study Participants .......................44
Table 2.
Grading Scales for Systemic Events - Participants Who Are 
≥15 Months to <2 Years of Age (Cohort 1) .............................................45
Table 3.
Grading Scales for Systemic Events - Participants Who Are ≥2 to 
<18 Years of Age (Cohorts 2-4)...............................................................46
Table 4.
Ranges for Fever.......................................................................................47
Table 5.
Probability of Detecting at Least 1 AE in Each of Cohorts 1 
Through 4..................................................................................................63
Table 6.
Probability (%) to Demonstrate Superiority of Immune Response of 
1 Month After 20vPnC to Before 20vPnC ...............................................64

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
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PFIZER CONFIDENTIAL
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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 pneumococcal 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, single-arm study will be conducted at investigator sites in the 
United States.  
The purpose of this study 
is to generate safety and immunogenicity data in children in the setting of a well-established 
national infant immunization program of pneumococcal conjugate vaccine (7vPnC and 
subsequently 13vPnC).  This will inform potential use of 20vPnC in children ≥15 months of 
age where direct protection against the additional 7 serotypes may offer benefit.
Approximately 800 children from ≥15 months to <18 years of age at the time of consent, 
provided by a parent/legal guardian, and assent (when age-appropriate and per local 
requirements), will be enrolled into 4 cohorts based on age (Cohort 1: ≥15 to <24 months, 
Cohort 2: ≥2 to <5 years, Cohort 3: ≥5 to <10 years, and Cohort 4: ≥10 to <18 years), 
200 participants in each cohort. Documentation of at least 3 prior doses of 13vPnC will be 
required in children <5 years of age (Cohorts 1 and 2).  Participants will receive a single dose 
of 20vPnC.
On Day 1 of the study (Visit 1), participants will be assessed for eligibility and information 
will be collected, including medical history and 13vPnC vaccination history.  Blood will be 
collected prior to vaccination for immunogenicity assessments.  Participants will receive a 
single dose of 20vPnC, which will be prepared and administered by a qualified site staff 
member or designee.  Permitted routine pediatric vaccines may be given at the same time as 
study vaccination according to local or national recommendations, if not feasible to separate 
from the 20vPnC.  Participants will be observed for 30 minutes after vaccination and any 
reactions occurring during that time will be recorded as adverse events (AEs).  The 
participant’s parent(s)/legal guardian(s) will be provided with an electronic diary (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 age-applicable 
systemic events (fever, decreased appetite, drowsiness/increased sleep, and irritability in 
Cohort 1; and fever, fatigue, headache, muscle pain, and joint pain in Cohorts 2-4) for 7 days 
following vaccination (Days 1 to 7, where Day 1 is the day of vaccination). Use of 
antipyretic/pain medications will also be prompted for and collected daily in the e-diary for 
7 days following vaccination.  The participant’s parent(s)/legal guardian(s) will be instructed 
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20-valent Pneumococcal Conjugate Vaccine (20vPnC)
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to contact the study staff if the participant experiences severe 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, approximately 1 month (28 to 42 days) after Visit 1.  
Information will be collected from the participant’s parent(s)/legal guardian(s) on AEs, 
including nonserious AEs, serious AEs (SAEs), and newly diagnosed chronic medical 
conditions (NDCMCs), and e-diary follow-up (as needed).  Concomitant medications used to 
treat SAEs or NDCMCs occurring after the previous visit will be recorded.  Information on 
vaccines given since the previous visit will also be recorded.  Blood will be collected for 
immunogenicity assessments.
Participants will have Visit 3, approximately 6 months (168 to 196 days) after Visit 1. 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 or NDCMCs since the 
previous visit.
Objectives, Estimands, and Endpoints
Objectives
Estimands
Endpoints
Primary Safety:
Primary Safety:
Primary Safety:
To describe the safety profile 
of 20vPnC 
In participants from each cohort receiving 
20vPnC and having safety data reported 
after vaccination:

The percentage of participants 
reporting prompted local reactions 
within 7 days after vaccination

The percentage of participants 
reporting prompted systemic events 
within 7 days after vaccination

The percentage of participants 
reporting AEs up to 1 month after 
vaccination

The percentage of participants 
reporting SAEs up to 6 months after 
vaccination

The percentage of participants 
reporting NDCMCs up to 6 months 
after vaccination

Prompted local reactions 
(redness, swelling, and 
pain at the injection site)

Prompted systemic events:

Cohort 1:  Fever, 
decreased appetite, 
drowsiness/ increased 
sleep, and irritability

Cohorts 2 through 4:  
Fever, fatigue,
headache, muscle 
pain, and joint pain

AEs

SAEs

NDCMCs

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
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Objectives
Estimands
Endpoints
Primary Immunogenicity:
Primary Immunogenicity:
Primary Immunogenicity:
Cohort 1 and Cohort 2: To
demonstrate that the serotype-
specific IgG concentrations
for the 7 additional serotypes
1 month after 20vPnC are
superior to the corresponding 
IgG concentrations before 
20vPnC
In participants in compliance with the key 
protocol criteria (evaluable participants):

Geometric mean fold rises
(GMFRs) of serotype-specific IgG 
concentrations for the 7 additional 
serotypes from before to 1 month 
after vaccination

Pneumococcal 
serotype-specific IgG 
concentrations
Cohort 3 and Cohort 4: To 
demonstrate that the serotype-
specific opsonophagocytic 
activity (OPA) titers for the 
7 additional serotypes 1 month 
after 20vPnC are superior to 
the corresponding OPA titers 
before 20vPnC
In participants in compliance with the key 
protocol criteria (evaluable participants):

GMFRs of serotype-specific OPA 
titers for the 7 additional serotypes
from before to 1 month after 
vaccination

Pneumococcal 
serotype-specific OPA
titers
Secondary Immunogenicity:
Secondary Immunogenicity:
Secondary Immunogenicity:
To further describe the 
immune responses to 20vPnC 
in Cohorts 1, 2, 3, and 4
In evaluable participants:

Percentage of participants with 
predefined serotype-specific IgG 
concentrations for the 7 additional 
serotypes at 1 month after vaccination 
in Cohort 1 only

Percentage of participants with 
≥4-fold rise in serotype-specific OPA 
titers for the 7 additional serotypes 
from before to 1 month after 
vaccination in Cohorts 2, 3, and 4
only

Serotype-specific IgG geometric 
mean concentrations (GMCs) for the 
20vPnC serotypes before and 
1 month after vaccination

GMFRs of serotype-specific IgG 
concentrations for the 13vPnC 
serotypes from before to 1 month 
after vaccination (in Cohorts 1 and 2)

GMFRs of serotype-specific IgG 
concentrations for the 20vPnC 
serotypes from before to 1 month 
after vaccination (in Cohorts 3 and 4)

Pneumococcal 
serotype-specific IgG 
concentrations

Pneumococcal 
serotype-specific OPA 
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20-valent Pneumococcal Conjugate Vaccine (20vPnC)
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Objectives
Estimands
Endpoints

Serotype-specific OPA geometric 
mean titers (GMTs) for the 20vPnC 
serotypes before and 1 month after 
vaccination

GMFRs of serotype-specific OPA 
titers for the 20vPnC serotypes from 
before to 1 month after vaccination
(in Cohorts 1 and 2)

GMFRs of serotype-specific OPA 
titers for the 13vPnC serotypes from 
before to 1 month after vaccination
(in Cohorts 3 and 4)
Number of Participants
Approximately 800 participants (200/cohort) will be enrolled to achieve a target of 
720 (180/cohort) evaluable participants at the follow-up time point 1 month after receipt of 
20vPnC.
The 800 participants will be enrolled into 4 cohorts based on age and, for the 2 youngest 
cohorts, documented history of 13vPnC vaccination:

Cohort 1: Approximately 200 children ≥15 months to <24 months (<2 years) of age who 
have been previously vaccinated with at least 3 doses of 13vPnC.

Cohort 2: Approximately 200 children ≥2 years to <5 years of age who have been 
previously vaccinated with at least 3 doses of 13vPnC.

Cohort 3: Approximately 200 children ≥5 years to <10 years of age regardless of 
documentation of previous vaccination with 7vPnC or 13vPnC.

Cohort 4: Approximately 200 children ≥10 years to <18 years of age regardless of
documentation of previous vaccination with 7vPnC or 13vPnC.
Duration of Participation for Each Participant
Each participant will participate in the study for approximately 6 months.

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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 age cohort.
The primary immunogenicity objectives will be evaluated by formal hypothesis tests for 
superiority of IgG concentrations for the 7 additional serotypes (8, 10A, 11A, 12F, 15B, 22F, 
and 33F) 1 month after 20vPnC to before 20vPnC in Cohorts 1 and 2, and superiority of OPA 
titers for the 7 additional serotypes 1 month after 20vPnC to before 20vPnC in Cohorts 3 
and 4. Superiority for a serotype in each cohort will be declared if the lower bound of the 
2-sided 95% confidence interval (CI) for the IgG (or OPA) GMFR from before 20vPnC to 
1 month after 20vPnC for that serotype is greater than 1.
1.2. Schema
Not applicable.
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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
Visit ID
Vaccination 
Follow-up Visit
Follow-up Phone Calla
Study Interval Visit
Day 1
1-Month Visit
6-Month Phone Call
Visit Window (Days)
28-42 Days
After Visit 1
168-196 Days After Visit 1
Obtain informed consent/assent
X
Assign participant number via IRT
X
Record demography
X
Perform clinical assessment, including medical history
X
Obtain prevaccination temperature (measured as appropriate for age)
X
Record nonstudy vaccinationsb
X
X
Record concomitant medicationsc
X
X
X
Urine pregnancy test (if applicable)
X
Contraception check (if applicable)d
X
X
Review inclusion and exclusion criteria
X
Review temporary delay criteria
X
X
Review continued eligibility
X
Obtain blood samplee
Xf
X
Assign an investigational product container number via the IRT
X
Administer investigational product into left leg (option for Cohort 1 only) or left arm
Xg
Administer and record routine pediatric vaccinations, as applicableh
X
Observe and record reactions for 30 minutes after investigational product administration
X

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Visit Number
1
2
3
Visit ID
Vaccination 
Follow-up Visit
Follow-up Phone Calla
Study Interval Visit
Day 1
1-Month Visit
6-Month Phone Call
Visit Window (Days)
28-42 Days
After Visit 1
168-196 Days After Visit 1
Provide parent(s)/legal guardian(s) with an e-diary (device or application, as appropriate), 
thermometer, and measuring device and instruct to collect prompted local reactions and 
systemic events and use of antipyretic/pain medicationsi
X
Provide a participant contact card
X
X
Review and/or collect e-diary (if applicable)j
X
Record and report adverse events
X----------------------X
Record and report SAEs and NDCMCsk
X-------------------------------------------------------X
Abbreviations: IRT = interactive response technology; NDCMC = newly diagnosed chronic medical condition.
a.
This telephone contact should occur approximately 6 months after study vaccination; this contact should be attempted for all participants who have received 
study vaccination, unless the parents/legal guardians have withdrawn consent.
b.
For Cohorts 1 and 2, information on the prior vaccination with 13vPnC will also be recorded.  For Cohorts 3 and 4, information on prior vaccination with 
7vPnC or 13vPnC will be recorded, if available.  See Section 6.5.3 for details.
c.
Record only concomitant medications used to treat SAEs and NDCMCs.
d.
The investigator or designee will inform the participant of the need to use highly effective contraception consistently and correctly until 28 days after the 
dose of investigational product and document the conversation and the participant’s affirmation in the source notes.
e.
For Cohorts 1 and 2:  ~5 mL; for Cohorts 3 and 4:  ⁓10 mL.
f.
Blood sample will be collected prior to vaccination.
g.
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).
h.
Administer permitted routine pediatric vaccinations (as applicable) after the investigational product into a limb other than the site of the 20vPnC injection.
Prohibited and permitted vaccines are described in Sections 6.5.1 and 6.5.2, respectively.
i.
The participant’s parent(s)/legal guardian(s) will record prompted local reactions and systemic events and antipyretic/pain medication in an e-diary for the 
7 days following vaccination. The participant’s parent(s)/legal guardian(s) will be instructed to contact the study staff if the participant experiences severe 
redness or swelling >14 caliper units, severe pain at the injection site (left leg [option for Cohort 1 only] or left arm), a fever >40.0°C (>104.0°F), or an 
emergency room visit or hospitalization.
j.
Designated site staff will review e-diary data online at frequent intervals (daily is optimal) for the 7 days following vaccination to evaluate participant 
compliance and as part of the ongoing safety review.
k.
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.

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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 

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serotypes included bacteremia (49.6%), meningitis (19.1%), and pneumonia (18.8%). These 
data demonstrate the continued need for expanded serotype coverage.
Surveillance studies conducted in 2010-2012 by the Centers for Disease Control and 
Prevention (CDC) found that S pneumoniae remains among the most common pathogens 
identified in community-acquired pneumonia (CAP) requiring hospitalization in the 
United States in both children and adults.12,13 It was the most common bacterial cause in 
children <2 years of age, even in the setting of a 43% reduction in CAP hospitalizations over 
the previous decade between 1997-1999 and 2007-2009, due to the introduction to 
7vPnC.12,14 Surveillance reported in 2017 by the European Centre for Disease Prevention 
and Control (ECDC) showed that among cases of IPD for which the clinical presentation was 
known across all age groups, bacteremic pneumonia was reported in 42% of cases. The most 
common clinical presentations in children <5 years of age were septicemia and bacteremic 
pneumonia (1-4 year olds) and meningitis (<1 year old).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 

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polysaccharide-based vaccines that induce antibody responses with functional 
(opsonophagocytic) activity and target the capsular serotypes responsible for disease.19
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 IgG antibody concentrations to 7vPnC, with supportive data to demonstrate the 

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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  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 this study is to provide safety and immunogenicity 
data with 20vPnC in children ≥15 months to <18 years old in the setting of well-established 
national infant immunization program with a pneumococcal conjugate vaccine (7vPnC and 
13vPnC in the United States).  This will inform potential use of 20vPnC in children 
≥15 months of age in a setting where direct protection against the additional 7 serotypes may 
offer benefit, such as immunization campaigns intended to rapidly increase the level of 
serotype coverage in the pediatric population, or in specific individuals with risk factors.  It is 
notable that after introduction of 13vPnC in the United States in 2010, there was a short-term 
recommendation for a single supplemental dose of 13vPnC to be given to children 
14 through 59 months of age who had received the 7vPnC series, to provide protection 
against the 6 serotypes unique to 13vPnC.52
Descriptive 
immunogenicity data for all 20 vaccine serotypes will also be generated.
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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 plus 7 new serotypes (8, 10A, 11A, 12F, 
15B, 22F, and 33F) individually conjugated to CRM197.  As noted above, 20vPnC uses the 
same platform and contains the same excipients as 7vPnC and 13vPnC.  These 7 additional 
serotypes were selected based on their relative prevalence as a cause of IPD, their 
generalized geographic distribution, and other factors that would support inclusion, such as 
the presence of antibiotic resistance (11A, 15B), association with outbreaks (8, 12F), and 
greater disease severity (eg, meningitis, mortality) (10A, 11A, 22F).53,54,55,56,57,58,59,60,61,62,63,64
These 7 serotypes have a long-standing association with serious pneumococcal disease and 
are responsible for a substantial burden of remaining pneumococcal disease.
The incidence of IPD due to these 7 serotypes in children <5 years of age has remained 
relatively stable or slightly increased over the past several years, and these serotypes cause a 
significant amount of IPD in children.65,66,67,68,69,70,71  These 7 serotypes contribute to the 
burden of IPD in the United States and elsewhere. It is estimated that between 2015 and 
2016, these 7 serotypes accounted for 35% of IPD in children 5 through 17 years of age and 
39% of IPD in children <5 years of age in the United States.72 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, and serotypes 8, 12F, and 10A were among the 5 most frequent serotypes causing 
disease in 5- to 14-year-olds in the ECDC report.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 types.67
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 (IgG and OPA 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.
Additional Phase 2 and Phase 3 trials have been conducted in adults 18 years of age and 
above, with safety and immunogenicity data on over 4000 participants who received 20vPnC, 
showing it to induce an immune response to all of the 20 vaccine serotypes and to have a 
safety profile similar to 13vPnC.

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A Phase 2 study (B7471003) of 20vPnC in a pediatric population, healthy infants 
≥42 to ≤98 days of age, has been 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 was consistent with other pneumococcal conjugate 
vaccines. Immune responses of IgG after 3 doses of 20vPnC were similar to those in the 
13vPnC group. These data support continued development of 20vPnC in a pediatric 
population.
2.3. Benefit/Risk Assessment
The 20vPnC investigational product contains the same components and excipients as the 
licensed 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.  This has been the case in the clinical program to date, but additional AEs may be 
observed with the investigational 20vPnC as more clinical experience is gained.  The most 
common AEs noted in the pediatric population 15 months through 17 years of age after 
vaccination with 13vPnC are primarily related to local reactions (injection site pain or 
tenderness, redness, and swelling) and systemic events (fever, irritability, decreased appetite, 
and increased sleep).  This includes data from children with prior 7vPnC immunization.73,74
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.
Risks that may be associated with study procedures include risks from blood draws, 
including pain, swelling, bruising, and infection where blood is taken.
Safety assessments described in the protocol and ongoing review of safety data by the 
investigator and sponsor study team will serve to monitor and mitigate these risks.
 
 
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 of 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 due to the additional vaccine serotypes.
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Pfizer considers that the available information from Study B7471003 with 20vPnC, the 
available safety profile of similar pneumococcal conjugate vaccines (ie, 7vPnC and 13vPnC), 
and the limited risks from study procedures support a favorable benefit-risk profile for 
20vPnC and this study.
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of 20vPnC may be found in the 20vPnC IB, which is the single reference 
safety document (SRSD) for this study.
3. OBJECTIVES, ESTIMANDS, AND ENDPOINTS
Objectives
Estimands
Endpoints
Primary Safety
Primary Safety
Primary Safety
To describe the safety profile of 
20vPnC 
In participants from each cohort
receiving 20vPnC and having safety 
data reported after vaccination:

The percentage of participants 
reporting prompted local 
reactions within 7 days after 
vaccination

The percentage of participants 
reporting prompted systemic 
events within 7 days after 
vaccination

The percentage of participants 
reporting AEs up to 1 month 
after vaccination

The percentage of participants 
reporting SAEs up to 6 months 
after vaccination

The percentage of participants 
reporting NDCMCs up to 
6 months after vaccination

Prompted local reactions 
(redness, swelling, and pain 
at the injection site)

Prompted systemic events:

Cohort 1: Fever, 
decreased appetite, 
drowsiness/increased 
sleep, and irritability

Cohorts 2 through 4:  
Fever, fatigue, 
headache, muscle pain, 
and joint pain

AEs

SAEs

NDCMCs
Primary Immunogenicity 
Primary Immunogenicity
Primary Immunogenicity
Cohort 1 and Cohort 2: To 
demonstrate that the 
serotype-specific IgG 
concentrations for the 7 additional
serotypes 1 month after 20vPnC 
are superior to the corresponding 
IgG concentrations before 
20vPnC
In participants in compliance with 
the key protocol criteria (evaluable 
participants):

GMFRs of serotype-specific IgG 
concentrations for the
7 additional serotypes from 
before to 1 month after 
vaccination

Pneumococcal 
serotype-specific IgG 
concentrations

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Objectives
Estimands
Endpoints
Cohort 3 and Cohort 4: To 
demonstrate that the 
serotype-specific OPA titers for
the 7 additional serotypes 1 month 
after 20vPnC are superior to the 
corresponding OPA titers before 
20vPnC
In participants in compliance with 
the key protocol criteria (evaluable 
participants):

GMFRs of serotype-specific 
OPA titers for the 7 additional 
serotypes from before to 
1 month after vaccination

Pneumococcal 
serotype-specific OPA titers
Secondary Immunogenicity
Secondary Immunogenicity
Secondary Immunogenicity
To further describe the immune
responses to 20vPnC in Cohorts 1, 
2, 3, and 4
In evaluable participants:

Percentage of participants with 
predefined serotype-specific IgG 
concentrations for the 7 
additional serotypes at 1 month 
after vaccination in Cohort 1
only

Percentage of participants with 
≥4-fold rise in serotype-specific 
OPA titers for the 7 additional 
serotypes from before to 1 
month after vaccination in 
Cohorts 2, 3, and 4 only

Serotype-specific IgG GMCs for
the 20vPnC serotypes before 
and 1 month after vaccination

GMFRs of serotype-specific IgG 
concentrations for the 13vPnC 
serotypes from before to 
1 month after vaccination
(in Cohorts 1 and 2)

GMFRs of serotype-specific IgG 
concentrations for the 20vPnC 
serotypes from before to 
1 month after vaccination
(in Cohorts 3 and 4)

Serotype-specific OPA GMTs 
for the 20vPnC serotypes before 
and 1 month after vaccination

GMFRs of serotype-specific 
OPA titers for the 20vPnC 
serotypes from before to 
1 month after vaccination
(in Cohorts 1 and 2)

GMFRs of serotype-specific 
OPA titers for the 13vPnC 
serotypes from before to 
1 month after vaccination
(in Cohorts 3 and 4)

Pneumococcal 
serotype-specific IgG 
concentrations

Pneumococcal 
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Objectives
Estimands
Endpoints
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
4. STUDY DESIGN
4.1. Overall Design
This Phase 3, multicenter, single-arm study will be conducted at investigator sites in the 
United States. 
 The purpose of this study is 
to provide safety and immunogenicity data in children in the setting of a well-established 
national infant immunization program of pneumococcal conjugate vaccine (7vPnC and 
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subsequently 13vPnC).  These data will inform potential use of 20vPnC in children 
≥15 months of age where direct protection against the additional 7 serotypes may offer 
benefit.
Approximately 800 children from ≥15 months to <18 years of age at the time of consent, 
provided by a parent/legal guardian, and assent (when age-appropriate and per local 
requirements), will be enrolled into 4 cohorts based on age (Cohort 1: ≥15 to <24 months, 
Cohort 2: ≥2 to <5 years, Cohort 3: ≥5 to <10 years, and Cohort 4: ≥10 to <18 years), 
200 participants in each cohort. Documentation of at least 3 prior doses of 13vPnC will be 
required in children <5 years of age (Cohorts 1 and 2).  Participants will receive a single dose 
of 20vPnC.
On Day 1 of the study (Visit 1), participants will be assessed for eligibility and information 
will be collected including medical history and 13vPnC vaccination history 
(see Section 6.5.3).  Blood will be collected prior to vaccination for immunogenicity 
assessments.  Participants will receive a single dose of 20vPnC, which will be prepared and 
administered by a qualified site staff member or qualified designee.  Permitted routine 
pediatric vaccines (see Section 6.5.2) may be given at the same time as study vaccination 
according to local or national recommendations, if not feasible to separate from the 20vPnC.  
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 age-applicable systemic events (fever, decreased appetite, drowsiness/increased 
sleep, and irritability in Cohort 1; and fever, fatigue, headache, muscle pain, and joint pain in 
Cohorts 2-4) for 7 days following 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 severe 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, approximately 1 month (28 to 42 days) after Visit 1
(study Day 29 to 43).  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 occurring after the 
previous visit will be recorded. Information on vaccines given since the previous visit will 
also be recorded.  Blood will be collected for immunogenicity assessments.
Participants will have Visit 3, approximately 6 months (168 to 196 days) after Visit 1. 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 or NDCMCs since the 
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In the case of extreme circumstances, such as natural disasters or a pandemic, visits for 
follow-up or procedures may need to be conducted through other means (eg, telephone calls).
4.1.1. Approximate Duration of Participation for Each Participant
Each participant will participate in the study for approximately 6 months.
4.1.2. Approximate Number of Participants
Approximately 800 participants (200/cohort) will be enrolled to achieve a target of 
720 (180/cohort) evaluable participants at the follow-up time point 1 month after receipt of
20vPnC.
The 800 participants will be enrolled into 4 cohorts based on age and, for the 2 youngest 
cohorts, documented history of 13vPnC vaccination:
•
Cohort 1:  Approximately 200 children ≥15 months to <24 months (<2 years) of age 
who have been previously vaccinated with at least 3 doses of 13vPnC.
•
Cohort 2:  Approximately 200 children ≥2 years to <5 years of age who have been 
previously vaccinated with at least 3 doses of 13vPnC.
•
Cohort 3:  Approximately 200 children ≥5 years to <10 years of age regardless of 
documentation of previous vaccination with 7vPnC or 13vPnC.
•
Cohort 4:  Approximately 200 children ≥10 years to <18 years of age regardless of 
documentation of previous vaccination with 7vPnC or 13vPnC.
4.2. Scientific Rationale for Study Design
The purpose of this single-arm study is to provide safety and immunogenicity 
data in children in the setting of well-established national infant immunization programs with 
7vPnC and subsequently with 13vPnC.  Similar studies were conducted with 13vPnC in a 
population of children in the setting of 7vPnC use showing 13vPnC was well tolerated and 
elicited an immune response to all 13vPnC serotypes.73,74  Children ≥15 months of age to 
<5 years of age (Cohorts 1 and 2) will be eligible if they have been previously vaccinated 
with at least 3 prior doses of 13vPnC, and the most recent dose was received >2 months 
before enrollment. Children ≥5 to <18 years of age will be eligible regardless of previous 
vaccination status with 7vPnC or 13vPnC. Participants will be administered 1 dose of 
20vPnC at Visit 1. This is consistent with the short-term catch-up recommendations by the 
Advisory Committee on Immunization Practices (ACIP) following 13vPnC introduction.  
The recommendation was for a single dose of 13vPnC in children 12 through 59 months of 
age who received 3 doses of 13vPnC before age 12 months, administered at least 8 weeks 
after the most recent dose of 13vPnC, and it is consistent with the dosing series (1 dose) 
indicated for 13vPnC in unvaccinated children >2 years of age.31
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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. 
The design and dosing of 20vPnC in this trial are similar to previous 13vPnC trials in a 
population of children in the setting of 7vPnC use showing 13vPnC was well tolerated and 
elicited an immune response to all 13vPnC serotypes.73,74  In children 2 years of age and 
older, 1 dose of pneumococcal conjugate vaccine induces protective immune responses.  The 
population and dosing are also consistent with the ACIP recommendations after 13vPnC 
introduction noted above, for a single supplemental dose of 13vPnC for all children 
14 through 59 months of age who had received 4 doses of 7vPnC or another age-appropriate, 
complete 7vPnC schedule to induce immune responses to the additional serotypes.31
Additionally, children 12 through 23 months of age who had received 3 doses of 7vPnC 
before age 12 months were recommended to receive 1 dose of 13vPnC, given at least 
8 weeks after the last dose of 7vPnC, and a single dose of 13vPnC was to be given to all 
healthy children 24 through 59 months of age with any incomplete schedule of 7vPnC or 
13vPnC.
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:
5.1.1. Cohort 1 and Cohort 2
Age and Sex:
1. Male or female children ≥15 months to <5 years of age at the time of consent.

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Type of Participant and Disease Characteristics:
2. Participants’ parent(s)/legal guardian(s) and participants, as age-appropriate, who are 
willing and able to comply with all scheduled visits and study procedures.
3. Healthy children 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.
5. Written documentation of receipt of at least 3 doses of 13vPnC.  The last dose of 13vPnC
must have been administered >2 months before enrollment into the study.
Informed Consent:
6. 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.
5.1.2. Cohort 3 and Cohort 4
Age and Sex:
1. Male or female children ≥5 years to <18 years of age at the time of consent.
Type of Participant and Disease Characteristics:
2. Participants’ parent(s)/legal guardian(s) and participants, as age-appropriate, who are 
willing and able to comply with all scheduled visits and study procedures.
3. Healthy children 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.
5. Negative urine pregnancy test for female participants who are menstruating.
6. Female participant of childbearing potential or male participant able to father children 
who is willing to use a highly effective method of contraception as outlined in this 
protocol for at least 28 days after the last dose of investigational product if at risk of 
pregnancy with her/his partner; or female participant not of childbearing potential or male 
participant not able to father children.
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Informed Consent:
7. Participants whose parent(s)/legal guardian(s) is capable of giving signed informed 
consent as described in Appendix 1, which includes compliance with the requirements 
and restrictions listed in the ICD and in this protocol.  Depending on the age of the 
participant and according to local requirements, participants will also be asked to provide 
assent as appropriate (verbal or written).
5.2. Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
5.2.1. Cohort 1 and Cohort 2
Medical Conditions:
1. History of severe adverse reaction associated with a vaccine and/or severe allergic 
reaction (eg, anaphylaxis) to any component of the investigational product, or any 
diphtheria toxoid–containing vaccine.
2. Significant neurological disorder or history of seizure (excluding febrile seizure) or 
significant stable or evolving disorders such as cerebral palsy, encephalopathy, 
hydrocephalus, or other significant disorders.
3. Major known congenital malformation or serious chronic disorder.
4. History of microbiologically proven invasive disease caused by S pneumoniae.
5. Known or suspected immunodeficiency or other conditions associated with 
immunosuppression, including, but not limited to, immunoglobulin class/subclass 
deficiencies, DiGeorge syndrome, generalized malignancy, human immunodeficiency 
virus (HIV) infection, leukemia, lymphoma, or organ or bone marrow transplant.
6. Bleeding diathesis or condition associated with prolonged bleeding that would, in the 
opinion of the investigator, contraindicate intramuscular injection.
7. Congenital, functional, or surgical asplenia.
8. Other acute or chronic medical or psychiatric condition including recent (within the past 
year) or active suicidal ideation or behavior or laboratory abnormality that may increase 
the risk associated with study participation or investigational product administration or 
may interfere with the interpretation of study results and, in the judgment of the 
investigator, would make the participant inappropriate for entry into this study.

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Prior/Concomitant Therapy:
9. Previous vaccination with any investigational pneumococcal vaccine or with PPSV23, or 
planned receipt through study participation.
10. Currently receives treatment with immunosuppressive therapy, including cytotoxic agents 
or systemic corticosteroids, or planned receipt through the last blood draw.  If systemic 
corticosteroids have been administered short term (<14 days) for treatment of an acute 
illness, participants should not be enrolled into the study until corticosteroid therapy has 
been discontinued for at least 28 days before investigational product administration.  
Inhaled/nebulized, intra-articular, intrabursal, or topical (skin, eyes, or ears) 
corticosteroids are permitted.
11. Receipt of blood/plasma products or immunoglobulins (including hepatitis B 
immunoglobulin) or planned receipt through the last planned blood draw in the study 
(through Visit 2).
Prior/Concurrent Clinical Study Experience:
12. 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:
13. 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.
5.2.2. Cohort 3 and Cohort 4
Medical Conditions:
1. History of severe adverse reaction associated with a vaccine and/or severe allergic 
reaction (eg, anaphylaxis) to any component of the investigational product, or any 
diphtheria toxoid–containing vaccine.
2. Significant neurological disorder or history of seizure (excluding febrile seizure) or 
significant stable or evolving disorders such as cerebral palsy, encephalopathy, 
hydrocephalus, or other significant disorders.
3. Major known congenital malformation or serious chronic disorder.

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4. History of microbiologically proven invasive disease caused by S pneumoniae.
5. Known or suspected immunodeficiency or other conditions associated with 
immunosuppression, including, but not limited to, immunoglobulin class/subclass 
deficiencies, DiGeorge syndrome, generalized malignancy, HIV infection, leukemia, 
lymphoma, or organ or bone marrow transplant.
6. Bleeding diathesis or condition associated with prolonged bleeding that would, in the 
opinion of the investigator, contraindicate intramuscular injection.
7. Congenital, functional, or surgical asplenia.
8. Other acute or chronic medical or psychiatric condition including recent (within the past 
year) or active suicidal ideation or behavior or laboratory abnormality that may increase 
the risk associated with study participation or investigational product administration or 
may interfere with the interpretation of study results and, in the judgment of the 
investigator, would make the participant inappropriate for entry into this study.
9. Pregnant or breastfeeding female participants.
Prior/Concomitant Therapy:
10. Previous vaccination with any investigational pneumococcal vaccine or with PPSV23, or 
planned receipt through study participation.
11. Currently receives treatment with immunosuppressive therapy, including cytotoxic agents 
or systemic corticosteroids, or planned receipt through the last blood draw.  If systemic 
corticosteroids have been administered short term (<14 days) for treatment of an acute 
illness, participants should not be enrolled into the study until corticosteroid therapy has 
been discontinued for at least 28 days before investigational product administration.  
Inhaled/nebulized, intra-articular, intrabursal, or topical (skin, eyes, or ears) 
corticosteroids are permitted.
12. Receipt of blood/plasma products or immunoglobulins (including hepatitis B 
immunoglobulin) or planned receipt through the last planned blood draw in the study 
(through Visit 2).
Prior/Concurrent Clinical Study Experience:
13. Participation in other studies involving investigational drug(s), investigational vaccines, 
or investigational devices within 28 days prior to study entry and/or during study 
participation.  Participation in purely observational studies is acceptable.
Diagnostic Assessments:
Not applicable.

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Other Exclusions:
14. Children or grandchildren who are direct descendants of investigator site staff members 
or Pfizer employees who are directly involved in the conduct of the study.
5.3. Lifestyle Considerations
5.3.1. Contraception (If Applicable)
The investigator or his or her designee, in consultation with the participant, will confirm that 
the participant has selected an appropriate method of contraception for the individual 
participant and his or her partner(s) from the permitted list of contraception methods
(Section 10.4) and will confirm that the participant has been instructed in its consistent and 
correct use.  At time points indicated in the SoA, the investigator or designee will inform the 
participant of the need to use highly effective contraception consistently and correctly and 
document the conversation and the participant’s affirmation in the participant’s chart 
(participants need to affirm their consistent and correct use of at least 1 of the selected 
methods of contraception).  In addition, the investigator or designee will instruct the 
participant to call immediately if the selected contraception method is discontinued or if 
pregnancy is known or suspected in the participant or partner.
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 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 AE or SAE recorded from signing the informed consent until the 
time of determination of screen failure.
Individuals who do not meet the criteria for participation in this study (screen failure) may 
not be rescreened.
5.5. Temporary Delay Criteria
The following conditions are temporary or self-limiting and a participant may be vaccinated 
and/or have blood drawn in the study once the condition(s) has/have resolved and no other 
exclusion criteria are met.
The blood draw prior to vaccination should take place on the same day as the vaccination.
5.5.1. Criteria for Temporarily Delaying Vaccine Administration 

Current febrile illness (body temperature ≥38.0°C [≥100.4°F]) or other acute illness 
within 48 hours before investigational product administration.

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•
Receipt of short-term (<14 days) systemic corticosteroids. Investigational product 
administration should be delayed until systemic corticosteroid use has been discontinued 
for at least 28 days.  Inhaled/nebulized, intra-articular, intrabursal, or topical (skin or 
eyes) corticosteroids are permitted.
5.5.2. Criteria for Temporarily Delaying Immunogenicity Blood Draw
•
Receipt of antibiotic therapy within 72 hours before blood draw. Topical antibiotics are 
permitted.
6. STUDY INTERVENTION
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study participant according to 
the study protocol.
For the purposes of this protocol, the term investigational product may be used 
synonymously with study intervention.
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. 
 
 
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
All participants will receive a single dose of 20vPnC at Visit 1.
The 0.5-mL dose of 20vPnC will be administered intramuscularly into the left leg (option for 
Cohort 1 only) or left arm by a designated site staff member. All other vaccinations 
(if given) should be administered into a limb other than the site of 20vPnC injection.  The 
location of the injection of each vaccine administered (investigational product and other) will 
be recorded.
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.
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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 prefilled syringes.
Instructions for medical device use are provided in the IP manual.
Medical device deficiencies, including those resulting from malfunctions of the device, must 
be detected, documented, and reported by the investigator throughout the study. Please refer 
to Section 8.3.9 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.
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6.3. Measures to Minimize Bias: Randomization and Blinding
Since all participants will receive 20vPnC at Visit 1, this will be an open-label vaccination 
and will be prepared and administered by a site staff member or designee.
6.3.1. Allocation to Study Intervention
Laboratory personnel performing the immunologic assays will be blinded to the visit 
information until all assays have been completed and assay results finalized.
Each participant will receive a single dose of 20vPnC; however, the investigational product 
will be assigned using 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 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 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.
6.4. Study Intervention Compliance
All doses of investigational product will be administered by the appropriately designated 
study staff at the investigator site.
6.5. Concomitant Therapy
6.5.1. Prohibited Concomitant Vaccines and Treatments 

Receipt of any investigational vaccines, drugs, or medical devices is prohibited during 
study participation.

Receipt of nonstudy pneumococcal vaccine is prohibited during study participation.

Receipt of blood/plasma products, immunoglobulins, and/or immunosuppressive therapy 
(including a ≥14-day course of systemic corticosteroids) is prohibited through Visit 2.
6.5.2. Permitted Concomitant Vaccines and Treatments

Influenza vaccine is permitted at any time during influenza season in this study.  
However, if feasible, it is recommended that influenza vaccine be administered at least 
14 days before or after 20vPnC administration.

Receipt of quadrivalent meningococcal conjugate vaccine is permitted only after the 
blood sample is collected at Visit 2.

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
Receipt of other licensed nonstudy vaccines (except pneumococcal vaccine as described 
above) is permitted.  However, if feasible, it is recommended that licensed nonstudy 
vaccines be administered at least 14 days (for nonlive vaccines) or at least 28 days 
(for live vaccines) before or after 20vPnC administration.

Use of topical anesthetic is permitted.

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 the study.
6.5.3. Recording Prior and Concomitant Vaccines and Treatments
The name, location, and date of administration for any nonstudy vaccinations received from 
the time of signing of the ICD to Visit 2 will be collected and recorded in the CRF.
For Cohorts 1 and 2, confirmation in the source documents of 3 or more prior doses of 
13vPnC with the date of administration of the most recent (third or fourth) dose of 13vPnC is
to be recorded on the CRF.  For Cohorts 3 and 4, the date of administration of the most 
recent dose of 7vPnC or 13vPnC will be recorded on the CRF, if available.
Only medications taken to treat SAEs or NDCMCs from the time of signing of the ICD to the 
final visit (approximately 6 months after vaccination at Visit 1) will be collect and 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
Since this is a single-dose study, this section is not applicable.
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 own 
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 investigator site file (ISF) and SoA for 
assessments to be collected at the time of study discontinuation and follow-up and for any 
further evaluations that need to be completed.
The participant’s parent(s)/legal guardian(s) should ideally notify the investigator in writing 
of the decision to withdraw consent from future follow-up, whenever possible. The 
participant’s parent(s)/legal guardian(s) should be questioned regarding their reason for 
withdrawal. The investigator or his or her designee should capture the reason for withdrawal 
in the CRF for all participants.
The participant should be requested to return for a final visit, if applicable, and the 
investigator will perform the procedures indicated for the next visit. Any AEs or SAEs that 
are continuing at the time of withdrawal from the study should be followed until resolution 
or, in case of permanent impairment, until the condition stabilizes.
A final telephone contact 6 months after vaccination (Section 8.10.3) for the collection of 
safety information should be completed for all participants who withdraw or 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 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.

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If the participant is withdrawn from the study and his/her parent(s)/legal guardian(s) also 
withdraws consent for disclosure of future information, no further evaluations should be 
performed and no additional data should be collected. The sponsor may retain and continue 
to use any data collected before such withdrawal of consent.
When a participant is withdrawn from the study because of an SAE, the SAE must be 
recorded on the CRF and reported on the Vaccine SAE Reporting Form.
Lack of completion of all or any of the withdrawal/early termination procedures will not be 
viewed as protocol deviations so long as the participant’s safety was preserved.
7.3. Lost to Follow-up
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and the participant’s parent(s)/legal guardian(s) is unable to be contacted by 
the study site.
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit 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 have been considered to have withdrawn from the study.
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.

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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.
In the case of extreme circumstances, such as natural disasters or a pandemic, visits for 
follow-up or procedures may need to be conducted through other means (eg, telephone, home 
visits).
8.1. Efficacy Assessments
8.1.1. Immunogenicity Assessments
Blood samples (Cohorts 1 and 2: approximately 5 mL per sample; Cohorts 3 and 4: 
approximately 10 mL per sample) will be collected from all participants prior to vaccination 
at Visit 1 and at Visit 2 (1 month after vaccination).  These are the immunogenicity time 
points.
The total blood sampling volume for individual participants in this study is approximately 
10 mL in children ≥15 months to <5 years of age (Cohorts 1 and 2), and 20 mL in children 
and adolescents ≥5 to <18 years of age (Cohorts 3 and 4).

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Pneumococcal Responses
IgG Responses to the 20 Pneumococcal Serotypes Contained in 20vPnC
IgG antibody concentrations for serotypes present in 20vPnC (1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 
10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, and 33F) will be determined on all sera 
collected at the 2 immunogenicity time points (Visits 1 and 2).  The serotype-specific IgG 
concentrations will be measured by Pfizer’s multiplex Luminex immunoassay.
OPA Responses to the 20 Pneumococcal Serotypes Contained in 20vPnC
OPA titers for serotypes present in 20vPnC (1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 
15B, 18C, 19A, 19F, 22F, 23F, and 33F) will be determined in randomly selected subsets of 
sera for the immunogenicity time points (Visits 1 and 2). These subsets will be randomly
selected, by an unblinded third party, to ensure that each subset has equal representation of
both vaccine groups. Further details will be described in the clinical specimen assessment 
plan (CSAP).  The serotype-specific OPA titers will be measured by Pfizer’s OPA assay.
 
 
8.1.2. Biological Samples
Blood samples will be used only for scientific research.  Each sample will be labeled with a 
code so that the laboratory personnel testing the samples will not know the participant’s 
identity.  Samples that remain after performing assays outlined in the protocol may be stored 
by Pfizer.  Unless a time limitation is required by local regulations or ethical requirements, 
the samples will be stored for up to 15 years after the end of the study and then destroyed. 
 
 
 No testing of the participant’s genetic material will be performed.
The participant’s parent(s)/legal guardian(s) may request that the participant’s samples, if 
still identifiable, be destroyed at any time (depending on the age of the participant and 
according to local requirements, participants may also request that their samples be
destroyed); however, any data already collected from those samples will still be used for this 
research. The biological samples may be shared with other researchers as long as 
confidentiality is maintained and no testing of the participant’s genetic material is performed.
C
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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 from any physical 
examination (if performed) will be recorded as medical history in the CRF.  Temperature 
measurement prior to vaccination will be documented and recorded in the CRF.
The participant will be observed for 30 minutes after study 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 (Cohort 1: fever, decreased appetite, drowsiness/increased 
sleep, and irritability; Cohorts 2-4: fever, fatigue, headache, muscle pain, and joint pain) 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, fever, and antipyretic/pain medication taken for 7 days, 
each evening following the study vaccination using an e-diary (in a provisioned device or 
application on a personal device). This allows recording of these assessments only within a 
fixed time window, thus providing an accurate representation of the participant’s experience.  
Data on local reactions, specific systemic events, fever, and use of antipyretic/pain 
medication reported in the e-diary will be transferred electronically to the e-diary vendor, 
where they will be available for review by investigators, their qualified designees, and 
sponsor staff at all times via an internet-based portal.  At intervals agreed to by the vendor 
and Pfizer, these data will be transferred electronically to Pfizer for analysis and reporting.
The daily e-diary data will not be captured in the CRF.  However, if a participant 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 or specific 
systemic events ongoing on the last day that the e-diary was completed.  The stop dates 
should be entered in the CRF.

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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.
8.2.2. Grading Scale for Prompted Events
The grading scales used in this study to assess prompted events as described below are based 
on concepts outlined in the Food and Drug Administration (FDA) Center for Biologics 
Evaluation and Research (CBER) guidelines on toxicity grading scales for adults and 
adolescent volunteers enrolled in preventive vaccine clinical trials,75 but have been adapted 
for applicability to healthy infants.
8.2.2.1. Local Reactions
For the first 7 days following the study vaccination (Days 1 through 7, where Day 1 is the 
day of vaccination), the participant’s parent(s)/legal guardian(s) will be asked to assess 
redness, swelling, and pain at the injection site (left leg [option for Cohort 1 only] or left 
arm) 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 scales 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 scales 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 ISF or equivalent.

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Table 1.
Grading Scales for Local Reactions in Study Participants
Local Reaction
GRADE 1
Mild
GRADE 2 
Moderate
GRADE 3a
Severe
GRADE 4b
Redness
1 to 4 caliper units
(or measuring device 
units)
=
>0 to 2.0 cm
5 to 14 caliper units
(or measuring device 
units)
=
>2.0 to 7.0 cm
>14 caliper units 
(or measuring device 
units)
=
>7.0 cm
Necrosis or 
exfoliative 
dermatitisb
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)
=
>7.0 cm
Necrosisb
Pain at injection site 
(tenderness)
Cohort 1: Hurts if 
gently touched
(eg, whimpers, 
winces, protests, or 
withdraws)
Cohorts 2-4:  Does 
not interfere with 
activity
Cohort 1: Hurts if 
gently touched with 
crying
Cohorts 2-4: 
Interferes with 
activity
Cohort 1: Causes 
limitation of limb 
movement
Cohorts 2-4: 
Prevents daily 
activityc
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.
Parent(s)/legal guardian(s) of the participants experiencing local reactions >14 caliper units (>7.0 cm) are 
to be contacted by the study site. An unscheduled visit may be required.
b.
Grade 4 assessment should be made by the investigator. Grade 4 will not be collected in the e-diary but 
will be collected as an AE in the CRF. The severity of the local reaction should be graded using the AE 
grading scale in Section 10.3.4.
c.
Prevents daily activity, eg, results in missed days of work or school or is otherwise incapacitating.
8.2.2.2. Systemic Events – Symptoms and Fever
8.2.2.2.1. Symptoms
For the first 7 days following the study vaccination (Days 1 through 7, where Day 1 is the 
day of vaccination), the participant’s parent(s)/legal guardian(s) will be asked to assess
decreased appetite, drowsiness/increased sleep, and irritability in Cohort 1, and fatigue, 
headache, muscle pain, and joint pain in Cohorts 2 through 4, 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 scales in Table 2 and Table 3 below.  The participant’s 
parent(s)/legal guardian(s) will also be instructed to contact site staff if the participant 

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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) for 7 days following 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 study reference manual
(SRM) or equivalent.
Table 2.
Grading Scales for Systemic Events - Participants Who Are ≥15 Months to 
<2 Years of Age (Cohort 1)
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 Section 10.3.4.

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Table 3.
Grading Scales for Systemic Events - Participants Who Are ≥2 to 
<18 Years of Age (Cohorts 2-4)
Systemic Event
GRADE 1
Mild
GRADE 2 
Moderate
GRADE 3
Severea
GRADE 4b
Fatigue
(= tiredness in 
diaries)
Does not interfere 
with activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room visit 
or hospitalization for 
severe fatigue
Headache
Does not interfere 
with activity
Some interference 
with activity
Prevents daily
routine activity
Emergency room visit 
or hospitalization for 
severe headache
Muscle pain
Does not interfere 
with activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room visit 
or hospitalization for 
severe muscle pain
Joint pain
Does not interfere 
with activity
Some interference
with activity
Prevents daily 
routine activity
Emergency room visit 
or hospitalization for 
severe joint pain
Abbreviations: CRF = case report form; e-diary = electronic diary.
a.
Prevents daily routine activity, eg, results in missed days of work or school or is otherwise incapacitating; 
includes use of narcotics for analgesia.
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 systemic event should be graded using the AE 
severity grading scale provided in Section 10.3.4.
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 at 
home.  Temperature will be collected in the evening, daily, for 7 days following the study 
vaccination (Days 1 through 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 fever >40.0°C (>104.0°F) to assess the fever and perform an unscheduled 
assessment, as applicable (see Section 8.10.4).  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 4 below.

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Table 4.
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 following vaccination, where Day 1 is the 
day of vaccination.
8.2.3. Clinical Safety Laboratory Assessments
Clinical safety laboratory tests are not required by this protocol.
If laboratory values from non–protocol-specified laboratory assessments performed at the 
institution’s local laboratory require a change in participant management or are considered 
clinically significant by the investigator (eg, SAE or AE or dose modification), then the 
results must be recorded in the CRF.
8.2.4. Pregnancy Testing (If Applicable)
Urine pregnancy tests will have a sensitivity of at least 25 mIU/mL.  Pregnancy tests will be 
performed in women of childbearing potential (WOCBP) at the times listed in the SoA, 
immediately before the administration of the vaccine. A negative pregnancy test result will 
be required prior to the participant’s receiving the investigational product.  Pregnancy tests 
may also be repeated if requested by institutional review boards (IRBs)/ethics committees 
(ECs) or if required by local regulations. In the case of a positive confirmed pregnancy, the 
participant will be withdrawn from administration of investigational product and from the 
study.
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 adverse events. Examples may include, but are not limited 
to, teething, contact diaper rash, spitting up, colic, or typical fussiness/crying in infants and 
children.

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The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible to pursue 
and obtain adequate information both to determine the outcome and to assess whether it 
meets the criteria for classification as an SAE or caused the participant to discontinue from 
the study (see Section 7).
Each parent/legal guardian will be questioned about the occurrence of AEs in a nonleading 
manner. 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 2.  At Month 6 (final telephone contact), the 
participant’s parent(s)/legal guardian(s) will be contacted by telephone to collect information 
about SAEs, including hospitalizations and NDCMCs, since Visit 2.
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.
For participants who are screen failures, the active collection period ends when screen failure 
status is determined.
If the participant is withdrawn from the study and their parent(s)/legal guardian(s) also 
withdraws consent for the collection of future information, the active collection period ends 
when consent is withdrawn.
If a participant definitively discontinues or temporarily discontinues study intervention 
because of an AE or SAE, the AE or SAE must be recorded on the CRF and the SAE 
reported using the Vaccine SAE Reporting Form.
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.

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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
All nonserious AEs and SAEs occurring in a participant during the active collection period, 
which begins after obtaining informed consent as described in Section 8.3.1, will be recorded 
on the AE section of the CRF.
The investigator is to record on the CRF all directly observed and all spontaneously reported 
AEs and SAEs reported by the participant.
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 (Section 10.3).

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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, IRBs/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.
8.3.5. Exposure During Pregnancy or Breastfeeding, and Occupational Exposure
Exposure to the investigational product under study during pregnancy or breastfeeding and 
occupational exposure are reportable to Pfizer Safety within 24 hours of investigator 
awareness.
8.3.5.1. Exposure During Pregnancy
An EDP occurs if: 

A female participant is found to be pregnant while receiving or after discontinuing 
study intervention.

A male participant who is receiving or has discontinued study intervention exposes a 
female partner prior to or around the time of conception.

A female is found to be pregnant while being exposed or having been exposed to 
study intervention due to environmental exposure.  Below are examples of 
environmental exposure during pregnancy:  

A female family member or healthcare provider reports that she is pregnant after 
having been exposed to the study intervention by ingestion, inhalation, or skin 
contact.

A male family member or healthcare provider who has been exposed to the study 
intervention by ingestion, inhalation, or skin contact then exposes his female 
partner prior to or around the time of conception.

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The investigator must report EDP to Pfizer Safety within 24 hours of the investigator’s 
awareness, irrespective of whether an SAE has occurred.  The initial information submitted 
should include the anticipated date of delivery (see below for information related to 
termination of pregnancy).

If EDP occurs in a participant or a participant’s partner, the investigator must report 
this information to Pfizer Safety on the Vaccine SAE Reporting Form and an EDP 
Supplemental Form, regardless of whether an SAE has occurred.  Details of the 
pregnancy will be collected after the start of study intervention and until study end.

If EDP occurs in the setting of environmental exposure, the investigator must report 
information to Pfizer Safety using the Vaccine SAE Reporting Form and EDP 
Supplemental Form.  Since the exposure information does not pertain to the 
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 
investigator site file.
Follow-up is conducted to obtain general information on the pregnancy and its outcome for 
all EDP reports with an unknown outcome.  The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify Pfizer Safety of the outcome as a 
follow-up to the initial EDP Supplemental Form.  In the case of a live birth, the structural 
integrity of the neonate can be assessed at the time of birth.  In the event of a termination, the 
reason(s) for termination should be specified and, if clinically possible, the structural 
integrity of the terminated fetus should be assessed by gross visual inspection (unless 
preprocedure test findings are conclusive for a congenital anomaly and the findings are 
reported).
Abnormal pregnancy outcomes are considered SAEs.  If the outcome of the pregnancy meets 
the criteria for an SAE (ie, ectopic pregnancy, spontaneous abortion, intrauterine fetal 
demise, neonatal death, or congenital anomaly in a live-born baby, a terminated fetus, an 
intrauterine fetal demise, or a neonatal death), the investigator should follow the procedures 
for reporting SAEs.  Additional information about pregnancy outcomes that are reported to 
Pfizer Safety as SAEs follows: 

Spontaneous abortion including miscarriage and missed abortion;

Neonatal deaths that occur within 1 month of birth should be reported, without regard 
to causality, as SAEs.  In addition, infant deaths after 1 month should be reported as 
SAEs when the investigator assesses the infant death as related or possibly related to 
exposure to the study intervention.
Additional information regarding the EDP may be requested by the sponsor.  Further 
follow-up of birth outcomes will be handled on a case-by-case basis (eg, follow-up on 
preterm infants to identify developmental delays).  In the case of paternal exposure, the 
investigator will provide the participant with the Pregnant Partner Release of Information 

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Form to deliver to his partner.  The investigator must document in the source documents that 
the participant was given the Pregnant Partner Release of Information Form to provide to his 
partner.
8.3.5.2. Exposure During Breastfeeding
An exposure during breastfeeding occurs if: 

A female participant is found to be breastfeeding while receiving or after 
discontinuing study intervention.

A female is found to be breastfeeding while being exposed or having been exposed to 
study intervention (ie, environmental exposure).  An example of environmental 
exposure during breastfeeding is a female family member or healthcare provider who 
reports that she is breastfeeding after having been exposed to the study intervention 
by inhalation or skin contact.
The investigator must report exposure during breastfeeding to Pfizer Safety within 24 hours 
of the investigator’s awareness, irrespective of whether an SAE has occurred.  The 
information must be reported using the Vaccine SAE Reporting Form.  When exposure 
during breastfeeding occurs in the setting of environmental exposure, the exposure 
information does not pertain to the participant enrolled in the study, so the information is not 
recorded on a CRF.  However, a copy of the completed Vaccine SAE Reporting Form is 
maintained in the investigator site file.
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, 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. Cardiovascular and Death Events
Not applicable

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8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as AEs 
or SAEs
Not applicable
8.3.8. Adverse Events of Special Interest
Not applicable
8.3.8.1. Lack of Efficacy
This section is not applicable because efficacy is not expected in the study population.
8.3.9. Medical Device Deficiencies
Medical devices are being provided for use in this study for the purposes of administering the 
investigational product.  In order to fulfill regulatory reporting obligations worldwide, the 
investigator is responsible for the detection and documentation of events meeting the 
definitions of deficiencies that occur during the study with such devices.
The definition of a medical device deficiency can be found in Appendix 8.
NOTE: Deficiencies fulfilling the definition of an AE/SAE will also follow the processes 
outlined in Section 8.3.3 and Section 10.3 of the protocol.
8.3.9.1. Time Period for Detecting Medical Device Deficiencies
Medical device deficiencies 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 device deficiency at any time after a participant has been 
discharged from the study, and such incident is considered reasonably related to a medical 
device provided for the study, the investigator will promptly notify the sponsor.
The method of documenting medical device deficiencies is provided in Appendix 8.
8.3.9.2. Follow-up of Medical Device Deficiencies
All medical device deficiencies involving an AE will be followed and reported in the same 
manner as other AEs (see Section 8.3.3). This applies to all participants, including those who 
discontinue study intervention. The investigator is responsible for ensuring that follow-up 
includes any supplemental investigations as indicated to elucidate the nature and/or causality 
of the deficiency.
New or updated information will be recorded on a follow-up form with all changes signed 
and dated by the investigator.

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8.3.9.3. Prompt Reporting of Device Deficiencies to Sponsor
Device deficiencies will be reported to the sponsor within 1 day after the investigator 
determines that the event meets the protocol definition of a medical device deficiency.
Any device deficiency that is associated with an SAE must be reported to Pfizer Safety 
within 24 hours upon the investigator’s awareness as outlined in Section 8.3.1.1 and 
Section 8.3.1.2.
The sponsor will be the contact for the receipt of device deficiency information.
Information will be provided to the sponsor as described in the IP manual.
8.3.9.4. Regulatory Reporting Requirements for Medical Device Deficiencies
The investigator will promptly report all device deficiencies occurring with any medical 
device provided for use in the study in order for the sponsor to fulfill the legal responsibility 
to notify appropriate regulatory authorities and other entities about certain safety information 
relating to medical devices being used in clinical studies.
The investigator, or responsible person according to local requirements (eg, the head of the 
medical institution), will comply with the applicable local regulatory requirements relating to 
the reporting of device deficiencies to the IRB/EC.
8.3.10. Medication Errors
Medication errors may result from the administration or consumption of the investigational 
product by the wrong participant, or at the wrong time, or at the wrong dosage strength.
Exposures to the investigational product under study may occur in clinical trial settings, such 
as medication errors.
Safety Event
Recorded on the CRF
Reported on the Vaccine SAE Reporting
Form to Pfizer Safety Within 24 Hours of 
Awareness
Medication errors 
All (regardless of whether 
associated with an AE)
Only if associated with an SAE
Medication errors include:

Medication errors involving participant exposure to the investigational product;

Potential medication errors or uses outside of what is foreseen in the protocol that do or 
do not involve the study participant.
Such medication errors occurring to a study participant are to be captured on the medication 
error page of the CRF, which is a specific version of the AE page.

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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.
8.4. Treatment of Overdose
For this study, any dose of investigational product greater than 1 dose 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 within 24 hours.
2. Closely monitor the participant for any AEs/SAEs.
3. Document the quantity of the excess dose as well as the duration of the overdose in the 
CRF.
4. Overdose is reportable to Safety only when associated with an SAE.
8.5. Pharmacokinetics
Pharmacokinetic parameters are not evaluated in this study.
8.6. Pharmacodynamics
Pharmacodynamic parameters are not evaluated in this study.

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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 (Section 1.3). 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 a visit may 
have some flexibility.
8.10.1. Visit 1 (Vaccination 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 
as permitted per local regulations to critically evaluate the immune response and safety 
profile by age.

Perform a clinical assessment including medical history; record any findings on the 
medical history CRF.

Measure and record the participant’s temperature as appropriate for the age of the child, 
according to routine local practice (°F/°C).

Confirm receipt of 3 or more prior doses of 13vPnC and record the date of prior 
administration of the most recent (third or fourth) dose of 13vPnC for Cohorts 1 and 2 
only.  Record the date of administration of the most recent dose of 7vPnC or 13vPnC for 
Cohorts 3 and 4, if available.

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
Perform urine pregnancy test for female participants of childbearing potential 
(see Section 8.2.4).

For participants of childbearing potential, instruct the participant to use appropriate 
contraceptives until 28 days after administration of investigational product and document 
the conversation and the participant’s affirmation in the participant’s source document.

Ensure and document that all of the inclusion criteria and none of the exclusion criteria 
are met and that none of the temporary delay criteria are met.

Assign an investigational product container number via the IRT.  This must be the last 
step before proceeding.  A site staff member will prepare the investigational product 
according to the IP manual.
After investigational product container number assignment:

Collect a blood sample of approximately 5 mL for Cohorts 1 and 2, and approximately 
10 mL for Cohorts 3 and 4, for immunogenicity assessments prior to vaccination.

Administer a single 0.5-mL injection of 20vPnC into the left leg (option for Cohort 1 
only) or left arm.

Permitted routine pediatric vaccines may be given at the same time as study vaccination 
according to local or national recommendations (to be administered into a limb other than 
the site of 20vPnC). However, if feasible, it is recommended that licensed nonstudy 
vaccines be administered at least 14 days or 28 days (see Section 6.5.2) before or after 
20vPnC administration. The location of the injection of each vaccine administered at 
Visit 1 (20vPnC and other, if applicable) will be recorded 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) a measuring device (caliper) to measure 
injection site reactions in the participant’s limb that received the 20vPnC and a digital 
thermometer to measure temperature, and provide instructions on their use.

Issue the participant’s parent(s)/legal guardian(s) an e-diary (device or application).  
Provide instructions on use and completion of the e-diary.  Ask the participant’s 
parent(s)/legal guardian(s) to complete the e-diary from Day 1 to Day 7, with Day 1 
being the day of vaccination.

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
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 (left leg 
[option for Cohort 1 only] or left arm) 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 or the participant’s parent(s)/legal guardian(s) to contact the 
investigator or investigator site staff as soon as possible if any significant illness or 
medical event (eg, emergency room visit or hospitalization) occurs.

Provide the parent(s)/legal guardian(s) with the participant contact card containing the 
study and investigator information (see Section 10.1.10).

Inform the participant’s parent(s)/legal guardian(s) that the use of prophylactic 
antipyretic/pain medication, while permitted, is not recommended on the day of 20vPnC 
administration (before or after vaccination).

Record AEs, SAEs, and NDCMCs during the visit as described in Section 8.3 and record 
concomitant medications as described in Section 6.5.3.

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 the ongoing safety review.
8.10.2. Visit 2 (Follow-up: 28 to 42 Days After Visit 1, ie, Study Day 29 to 43)

Record nonstudy vaccinations administered since Visit 1, as described in Section 6.5.3.

Perform a contraception check (see Section 10.4), if applicable (Cohort 3 and Cohort 4 
only).

Ensure and document that the participant continues to be eligible for the study 
(see Section 7.2 for participant discontinuation/withdrawal) and that the temporary delay 
criteria for the immunogenicity blood draw are not met.

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).

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
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.

Collect a blood sample of approximately 5 mL for Cohorts 1 and 2, and approximately 
10 mL for Cohorts 3 and 4, for immunogenicity (a topical anesthetic is permitted).

Remind the participant or 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.

Confirm whether the parent(s)/legal guardian(s) still possesses the participation contact 
card.

The investigator or an authorized designee completes the CRF and the source documents.
8.10.3. Visit 3 (6-Month Safety Collection [Telephone Contact] – 168 to 196 Days After 
Visit 1)

Contact the participant’s parent(s)/legal guardian(s) by telephone approximately 
6 months after the study vaccination; this contact should be attempted for all participants 
who have received 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 NDCMCs and SAEs.

The investigator or an authorized designee completes the CRF and the source documents.
8.10.4. Unscheduled Visits
If the participant’s parent(s)/legal guardian(s) reports redness or swelling at the injection site 
(left leg [option for Cohort 1 only] or left arm) 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.  An investigator site visit should be scheduled as soon as possible to assess the extent 
of the injection site reaction, unless any of the following is true:

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
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.
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, and/or irritability in Cohort 1, or fatigue, headache, 
muscle pain, and/or joint pain in Cohorts 2 through 4, or for a local reaction (all groups) in 
the 7 days following vaccination.

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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
Methodology for summary and statistical analyses of the data collected in this study is 
described here and further detailed in a statistical analysis plan (SAP), which will be 
maintained by the sponsor.  The SAP may modify what is outlined in the protocol where 
appropriate; however, any major modifications of the primary endpoint definitions or their 
analyses will also be reflected in a protocol amendment.
9.1. Estimands and Statistical Hypotheses
9.1.1. Estimands
The estimands corresponding to each primary, secondary
 objective are
described in the table in Section 3.
The estimands for evaluating the immunogenicity objectives are based on the evaluable 
population (see Section 9.3 for definition) and estimate the vaccine effect in the hypothetical 
setting where participants follow the study schedule and protocol requirements. The 
estimand addresses the objective of estimating the true difference in the immune response 
between the 2 time points within each cohort, since noncompliance may obscure the true
difference in immune response between the 2 time points in each cohort.  Missing serology 
results will not be imputed. Immunogenicity results that are below the LLOQ will be set to 
0.5 × LLOQ in the analysis.
In the safety evaluation, missing e-diary data will not be imputed.  A missing AE start date
will be imputed according to Pfizer standard rules following a conservative principle to 
characterize the AE in the safety analysis, with details further described in the study SAP. 
No other missing information will be imputed in the safety analysis.
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9.1.2. Statistical Hypotheses
9.1.2.1. Cohort 1 and Cohort 2
For the primary immunogenicity objective, hypothesis testing will be used to assess 
superiority of the IgG concentrations for the 7 additional pneumococcal serotypes 1 month 
after 20vPnC to the IgG concentrations before 20vPnC within each cohort.  The null 
hypothesis (H0) for a serotype is
H0: µfold-rise ≤1.0
where

µfold-rise is the geometric mean of the fold rise in IgG concentration from before to 
1 month after vaccination;
The null hypothesis (H0) will be rejected for a serotype if the lower bound of the 2-sided 
95% CI for the IgG GMFR is greater than 1.0.
9.1.2.2. Cohort 3 and Cohort 4
For the primary immunogenicity objective, hypothesis testing will be used to assess 
superiority of the OPA titers for the 7 additional pneumococcal serotypes 1 month after 
20vPnC to the OPA titers before 20vPnC within each cohort in a randomly selected subset of 
participants.  The null hypothesis (H0) for a serotype is
H0: µfold-rise ≤1.0
where

µfold-rise is the geometric mean of the fold change in OPA titer from before to 1 month 
after vaccination;
The null hypothesis (H0) will be rejected for a serotype if the lower bound of the 2-sided 
95% CI for the OPA GMFR is greater than 1.0.
9.1.3. Multiplicity Considerations
The primary immunogenicity objectives for superiority are evaluated separately for each
cohort. Within each cohort, superiority of the immune response 1 month after 20vPnC to 
before vaccination (serotype-specific IgG concentrations for Cohorts 1 and 2;
serotype-specific OPA titers for Cohorts 3 and 4) is assessed by the hypothesis tests as 
described in Section 9.1.2.1 or Section 9.1.2.2, each hypothesis test at an alpha level of 0.05 
for each serotype. The primary immunogenicity objectives will be achieved if the superiority 
of the immune response 1 month after 20vPnC to before 20vPnC is established for all 
7 additional serotypes in a given cohort.  Therefore, the overall type I error rate for 
immunogenicity evaluation is well controlled at the 0.05 level for each cohort.

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9.2. Sample Size Determination
The study size is based on considerations of 1) the evaluations of safety, tolerability, and 
immunogenicity of a single dose of 20vPnC in the population in each cohort, 2) operational 
constraints of available serum volumes from individual study participants, and 
3) contribution to the overall safety database for the 20vPnC pediatric clinical development 
program.
Safety Endpoints
The primary safety objective includes the endpoint of reported AEs within 1 month after 
vaccination. The number of participants receiving 20vPnC is 200 in each of Cohorts 1 
through 4. There is a greater than 90% chance of observing at least 1 AE in each of the 
groups, assuming the true rate is at least 2% (Table 5).
Table 5.
Probability of Detecting at Least 1 AE in Each of Cohorts 1 Through 4
Sample Size
True Rate of AEs
Probability (%) of Observing at Least 1 AE
200 per Cohort
0.1%
18
200 per Cohort
0.5%
63
200 per Cohort
1%
87
200 per Cohort
2%
98
Immunogenicity Endpoints
Table 6 provides information on the probability of demonstrating superiority of IgG 
concentrations (Cohorts 1 and 2) and OPA titers (Cohorts 3 and 4) 1 month after 20vPnC 
compared with before 20vPnC based on data from the B7471003 Phase 2 20vPnC study in 
infants and the B7471007 Phase 3 20vPnC study in adults, respectively.
For IgG concentrations with 180 evaluable participants in each cohort (Cohort 1 or 
Cohort 2), there is a >99% probability that superiority will be declared for all 7 additional 
serotypes, if the true GMFRs from before 20vPnC to 1 month after 20vPnC are at least 50% 
of the observed GMFRs from before to 1 month after Dose 4 in the B7471003 study.  For 
OPA titers with 90 evaluable participants in each cohort (Cohort 3 or Cohort 4), the 
probability that superiority will be declared for the 7 additional serotypes ranges from 
64% (11A) to ≥99% (all other serotypes except 33F) if the true GMFRs from before 20vPnC 
to 1 month after 20vPnC are 75% of the observed GMFRs from before 20vPnC to 1 month 
after 20vPnC from participants 18 through 29 years of age in the B7471007 study.  If the 
assumed evaluable participants are increased to 180 and GMFR assumptions are unchanged,
the probability to demonstrate superiority for 11A increases to 91%.

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Table 6.
Probability (%) to Demonstrate Superiority of Immune Response of 
1 Month After 20vPnC to Before 20vPnC
Serotype
IgGa
(Cohorts 1 and 2)
OPAb
(Cohorts 3 and 4)
Assumption 1
Assumption 2
Assumption 3
8
>99
>99
>99
>99
10A
>99
>99
>99
>99
11A
>99
64
95
91
12F
>99
>99
>99
>99
15B
>99
>99
>99
>99
22F
>99
>99
>99
>99
33F
>99
98
>99
>99
Overall
>99
63
95
91
Abbreviations: GMFR = geometric mean fold rise; IgG = immunoglobulin G; OPA = opsonophagocytic 
activity.
Note: The probability calculation assumes the variabilities for IgG concentration and OPA titers are the same 
as observed in infant study B7471003 and adult study B7471007 (18 through 29 years of age), respectively, 
using the t-distribution. Additional assumptions in the calculation:
a.
The true IgG GMFR from before to 1 month after 20vPnC for each serotype to be 50% of the observed 
IgG GMFR from before to 1 month after Dose 4 of 20vPnC in Study 7471003, 180 evaluable participants 
in each cohort.
b.
For Assumption 1, 2, or 3, respectively, the true OPA GMFR from before to 1 month after 20vPnC for 
each serotype to be 75%, 100%, or 75% of the observed OPA GMFR from before to 1 month after 
20vPnC from participants 18 through 29 years of age in Study B7471007, and 90, 90, or 180 evaluable 
participants in each cohort.
9.3. Populations for Analysis
For purposes of analysis, the following populations are defined:
Population
Description
Enrolled
All participants who have a signed ICD.
Evaluable immunogenicity
All eligible participants who receive 1 dose of 20vPnC, have at least 
1 valid immunogenicity result collected within the appropriate window
1 month after vaccination, and have no other major protocol deviations as 
determined by the clinician.
 
Safety 
All participants who receive 1 dose of the investigational product and 
have safety data reported after vaccination.
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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 and will describe the participant populations to be included in the analyses, 
and procedures for accounting for missing, unused, and spurious data.  This section is a 
summary of the planned statistical analyses of the primary, secondary
endpoints.
Immunogenicity and safety results will be analyzed separately for each cohort.
9.4.1. Immunogenicity Analyses
The statistical analysis of pneumococcal immunogenicity results will be primarily based on 
the evaluable immunogenicity population as defined in Section 9.3.
 
Participants will be summarized according to the vaccine group as randomized.
Missing serology data will not be imputed.
Endpoint
Statistical Analysis Methods
Primary
•
Pneumococcal serotype-specific IgG GMFRs from before to 
1 month after 20vPnC
For each of the 20 serotypes in each cohort, GMFRs and the associated 
95% CIs for serotype-specific IgG concentrations from before to 
1 month after vaccination will be provided. The GMFR will be 
calculated by exponentiating the mean of the difference of 
logarithmically transformed assay results (1 month after vaccination –
before vaccination for each participant).  Two-sided CIs will be 
obtained by calculating the CIs using Student’s t-distribution for the 
mean difference of measures on the logarithmically transformed assay 
results and exponentiating the limits.
In Cohort 1 and Cohort 2, for each of the 7 additional serotypes, the 
lower limit of the 2-sided 95% CI of the IgG GMFR for a serotype will 
be used in the hypothesis test for superiority of IgG concentrations
1 month after 20vPnC to before 20vPnC for that serotype, as detailed in 
Section 9.1.2.1.
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Endpoint
Statistical Analysis Methods

Pneumococcal serotype-specific OPA GMFRs from before to 
1 month after 20vPnC
For each of the 20 serotypes in each cohort, GMFRs of OPA titers from 
before vaccination to 1 month after vaccination will be analyzed the 
same way as the IgG GMFRs.
In Cohort 3 and Cohort 4, for each of the 7 additional serotypes, the 
lower limit of the 2-sided 95% CI of the OPA GMFR for a serotype will 
be used in the hypothesis test for superiority of OPA titers 1 month after 
20vPnC to before 20vPnC for that serotype, as detailed in 
Section 9.1.2.2.
Secondary

Percentages of participants with predefined pneumococcal 
serotype-specific IgG concentrations for the 7 additional serotypes 
at 1 month after 20vPnC
Percentages (and 2-sided 95% CIs) of participants with serotype-specific
IgG concentrations ≥the predefined level will be provided for each of 
the 7 additional serotypes in Cohort 1. The Clopper-Pearson method 
will be used to calculate the CIs.

Percentages of participants with ≥4-fold rise in predefined 
pneumococcal serotype-specific OPA titers for the 7 additional 
serotypes from before to 1 month after 20vPnC
Percentages (and 2-sided 95% CIs) of participants with ≥4-fold rise in 
serotype-specific OPA titers from before to 1 month after 20vPnC will 
be provided for each of the 7 additional serotypes in Cohorts 2, 3, and 4. 
The Clopper-Pearson method will be used to calculate the CIs.

Pneumococcal serotype-specific IgG GMCs before and 1 month
after 20vPnC
GMCs and 2-sided 95% CIs for serotype-specific IgG concentrations 
before and 1 month after vaccination will be provided for each serotype 
in each age cohort. Geometric means and the associated 2-sided CIs 
will be obtained by calculating means and CIs on the natural log scale 
based on the t-distribution and then exponentiating the results.

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Endpoint
Statistical Analysis Methods
•
Pneumococcal serotype-specific OPA GMTs
OPA GMTs before and 1 month after 20vPnC for each serotype in each 
cohort will be analyzed the same way as IgG GMCs.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CCI
CCI
CCI
C
C
I
C
C
I

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Endpoint
Statistical Analysis Methods
 
 
 
 
 
 
9.4.2. Safety Analyses
The safety analyses are based on the safety population. Participants will be summarized by 
vaccine group as administered. Missing AE start dates will be imputed according to Pfizer 
standard rules following a conservative principle to characterize the AE in the safety 
analysis, with details further described in the study SAP. No other missing information will 
be imputed in the safety analysis.
Endpoint
Statistical Analysis Methods
Primary
•
Descriptive statistics will be provided for each reactogenicity endpoint 
for each age cohort. Local reactions and systemic events from Day 1 
after vaccination through Day 7 will be presented by severity 
cumulatively across severity levels. Descriptive summary statistics will 
include counts and percentages of participants with the indicated 
endpoint and the associated 2-sided Clopper-Pearson 95% CIs.
•
AEs will be categorized according to Medical Dictionary for Regulatory 
Activities (MedDRA) terms. Descriptive summary statistics (counts and 
percentages and the associated 2-sided Clopper-Pearson 95% CIs) for 
AEs from vaccination to 1 month after vaccination will be provided for 
each age cohort.
•
SAEs and NDCMCs will be categorized according to MedDRA terms.  
Descriptive summary statistics (counts, percentages, and the associated 
2-sided Clopper-Pearson 95% CIs) for SAEs and NDCMCs from 
C
C
I
C
C
I

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Endpoint
Statistical Analysis Methods
vaccination to 6 months after vaccination will be provided for each age 
cohort.
Secondary
Not applicable.
9.5. Interim Analyses
There is no interim analysis planned for the study.
9.5.1. Analysis Timing
Safety data through the visit occurring 1 month after the dose from all participants may be 
analyzed by the study team when available. All results will be analyzed and reported after 
the completion of the study.
 
 
 
CCI
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 their 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.

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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.
A copy of the ICD(s) must be provided to the participant’s parent(s)/legal guardian(s).
If a participant reaches the age at which he or she is legally able to provide consent 
(eg, 18 years old) during the study, his or her consent must be obtained. Since the participant 
is no longer a minor, the consent of the parent(s)/legal guardian(s) is no longer valid. Once 
the participant provides consent, the participant then becomes responsible to directly 
participate in study procedures and assessments. This is expected for a minority of 
participants in the study, and therefore any references in the protocol to parent(s)/legal 
guardian(s) may, in certain cases, be directly applicable to the participant.
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).

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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 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.  These results are 
submitted for posting in accordance with the format and timelines set forth by US law.
EudraCT
Pfizer posts clinical trial results on EudraCT for Pfizer-sponsored interventional studies in 
accordance with the format and timelines set forth by EU requirements.
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 
corresponding study results are 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.

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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.
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 

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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.
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;

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
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.
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 

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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 
investigator site and the study team for advice on medical questions or problems that may 
arise during the study.  The contact number is not intended for use by the participant’s 
parent(s)/legal guardian(s) directly, and if the 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.

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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 adverse events. 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).

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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.
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.

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
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.

Suspected transmission via a Pfizer product of an infectious agent, pathogenic or 
non-pathogenic, is considered serious.  The event may be suspected from clinical 
symptoms or laboratory findings indicating an infection in a patient exposed to a Pfizer 
product.  The terms “suspected transmission” and “transmission” are considered 
synonymous.  These cases are considered unexpected and handled as serious expedited 
cases by pharmacovigilance personnel.  Such cases are also considered for reporting as 
product defects, if appropriate.
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 SAEs 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

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Exposure to the 
investigational product 
under study during 
pregnancy or 
breastfeeding, and 
occupational exposure
All AEs/SAEs associated 
with exposure during 
pregnancy or breastfeeding
Occupational exposure is 
not recorded.
All (and EDP supplemental 
form for EDP)
Note:  Include all SAEs 
associated with exposure 
during pregnancy or 
breastfeeding. Include all 
AEs/SAEs associated with 
occupational exposure.

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.
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.

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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.

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.

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
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.
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.

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

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
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 
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.

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10.8. Appendix 8: Medical Device Adverse Events, Adverse Device Effects, Serious 
Adverse Events, and Device Deficiencies: Definition and Procedures for Recording, 
Evaluating, Follow-up, and Reporting
Definitions of a Medical Device Incident
The definitions and procedures detailed in this appendix are in accordance with ISO 14155.
Both the investigator and the sponsor will comply with all local medical device reporting 
requirements.
The detection and documentation procedures described in this protocol apply to all sponsor 
medical devices provided for use in the study (see Section 6.1.2 for the list of sponsor 
medical devices).
10.8.1. Definition of AE and ADE
AE and ADE Definition

An AE is defined as any untoward medical occurrence, unintended disease or 
injury, or untoward clinical signs (including abnormal laboratory finding) in study 
participants, users, or other persons, whether or not related to the investigational 
medical device.  This definition includes events related to the investigational 
medical device or comparator for study participants, users, and other persons.  This 
definition also includes events considered related to  procedures for study 
participants only.

An ADE is defined as an adverse event related to the use of an investigational 
medical device.  This definition includes any adverse events resulting from 
insufficient or inadequate instructions for use, deployment, implantation, 
installation, or operation, or any malfunction of the investigational medical device 
as well as any event resulting from use error or from intentional misuse of the 
investigational medical device.
10.8.2. Definition of SAE, SADE, and Unanticipated Serious Adverse Device Effect
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).

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

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

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
Severe: An event that prevents normal everyday activities.  An AE that is assessed 
as severe should not be confused with an SAE.  Severe is a category utilized for 
rating the intensity of an event; and both AEs and SAEs can be assessed as severe.

An event is defined as “serious” when it meets at least 1 of the predefined 
outcomes as described in the definition of an SAE, NOT when it is rated as severe.
Assessment of Causality

The investigator is obligated to assess the relationship between study intervention 
and each occurrence of each AE/SAE/device deficiency.

A “reasonable possibility” of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot 
be ruled out.

The investigator will use clinical judgment to determine the relationship.

Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated.

The investigator will also consult the IB and/or product information, for marketed 
products, in his/her assessment.

For each AE/SAE/device deficiency, the investigator must document in the 
medical notes that he/she has reviewed the AE/SAE/device deficiency and has 
provided an assessment of causality.

There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to the sponsor. However, it is 
very important that the investigator always make an assessment of causality for 
every event before the initial transmission of the SAE data to the sponsor.

The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality 
assessment.

The causality assessment is one of the criteria used when determining regulatory 
reporting requirements.

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Follow-up of AE/SAE/Device Deficiency

The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by the 
sponsor to elucidate the nature and/or causality of the AE/SAE/device deficiency as 
fully as possible.  This may include additional laboratory tests or investigations, 
histopathological examinations or consultation with other healthcare providers.

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.
10.8.5. Reporting of SAEs
SAE Reporting to Pfizer Safety via an Electronic Data Collection Tool

The primary mechanism for reporting an SAE to Pfizer Safety will be the 
electronic data collection tool.

If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) in order to report the event within 24 hours.

The site will enter the SAE data into the electronic system as soon as the data 
become available.

After the study is completed at a given site, the electronic data collection tool will 
be taken off-line to prevent the entry of new data or changes to existing data.

If a site receives a report of a new SAE from a study participant or receives updated 
data on a previously reported SAE after the electronic data collection tool has been 
taken off-line, then the site can report this information on a paper SAE form 
(see next section) or to Pfizer Safety by telephone.

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SAE Reporting to Pfizer Safety via Vaccine SAE Reporting Form

Facsimile transmission of the Vaccine SAE Reporting Form is the preferred 
method to transmit this information to Pfizer Safety.

In circumstances when the facsimile is not working, notification by telephone is 
acceptable with a copy of the Vaccine SAE Reporting Form sent by overnight mail 
or courier service.

Initial notification via telephone does not replace the need for the investigator to 
complete and sign the Vaccine SAE Reporting Form pages within the designated 
reporting time frames.
10.8.6. Reporting of SADEs
SADE Reporting to Pfizer Safety
NOTE: There are additional reporting obligations for medical device incidents that are 
potentially related to SAEs that must fulfill the legal responsibility to notify appropriate 
regulatory authorities and other entities about certain safety information relating to medical 
devices being used in clinical studies.

Any device deficiency that is associated with an SAE must be reported to the 
sponsor within 24 hours after the investigator determines that the event meets the 
definition of a device deficiency.

The sponsor shall review all device deficiencies and determine and document in 
writing whether they could have led to an SAE.  These shall be reported to the 
regulatory authorities and IRBs/ECs as required by national regulations.
10.9. Appendix 9: Country-Specific Requirements
Not applicable.

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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
ACIP
Advisory Committee on Immunization Practices
ADE
adverse device effect
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
CSAP
clinical specimen assessment plan
CSR
clinical study report
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
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Abbreviation
Term
GMC
geometric mean concentration
GMFR
geometric mean fold rise
GMT
geometric mean titer 
HIPAA
Health Insurance Portability and Accountability Act
HIV
human immunodeficiency virus
IB
investigator’s brochure
ICD
informed consent document
ICH
International Council for Harmonisation
ID
identification
IgG
immunoglobulin G
IND
investigational new drug 
INR
international normalized ratio
IP manual
investigational product manual
IPD
invasive pneumococcal disease
IRB
institutional review board
IRT
interactive response technology
ISF
investigator site file
ISO
International Organization for Standardization
IUD
intrauterine device
IUS
intrauterine hormone-releasing system
IWR
interactive Web-based response
LFT
liver function test
LLOQ
lower limit of quantitation
MedDRA
Medical Dictionary for Regulatory Activities
N/A
not applicable
NDCMC
newly diagnosed chronic medical condition
OPA
opsonophagocytic activity
PCD
primary completion date
PI
principal investigator
PIP
pediatric investigation plan
PPSV23
23-valent pneumococcal polysaccharide vaccine
PT
prothrombin time
SADE
serious adverse device effect
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
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Abbreviation
Term
TBili
total bilirubin
ULN
upper limit of normal
US
United States
USADE
unanticipated serious adverse device effect
VT
vaccine-type
WHO
World Health Organization
WOCBP
woman of childbearing potential

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

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10
Stockmann C, Ampofo K, Byington CL, et al. Pneumococcal meningitis in children:  
epidemiology, serotypes, and outcomes from 1997-2010 in Utah. Pediatrics 
2013;132(3):421-8.
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