A PHASE 3, RANDOMIZED, OPEN-LABEL TRIAL TO EVALUATE THE SAFETY AND IMMUNOGENICITY OF A 20-VALENT PNEUMOCOCCAL CONJUGATE VACCINE IN ADULTS ≥65 YEARS OF AGE WITH PRIOR PNEUMOCOCCAL VACCINATION
Phase: PHASE3
Conditions: Pneumococcal Disease
Sponsor: Pfizer

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
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A PHASE 3, RANDOMIZED, OPEN-LABEL TRIAL TO EVALUATE THE SAFETY 
AND IMMUNOGENICITY OF A 20-VALENT PNEUMOCOCCAL CONJUGATE 
VACCINE IN ADULTS ≥65 YEARS OF AGE WITH PRIOR PNEUMOCOCCAL 
VACCINATION  
Investigational Product Number:
PF-06482077
Investigational Product Name:
20-valent Pneumococcal Conjugate Vaccine 
(20vPnC)
United States (US) Investigational New 
Drug (IND) Number:
European Clinical Trials Database 
(EudraCT) Number:
2018-004278-91
Protocol Number:
B7471006
Phase:
3
This document and accompanying materials contain confidential information belonging to Pfizer.  Except as 
otherwise agreed to in writing, by accepting or reviewing these documents, you agree to hold this information in 
confidence and not copy or disclose it to others (except where required by applicable law) or use it for 
unauthorized purposes.  In the event of any actual or suspected breach of this obligation, Pfizer must be 
promptly notified.
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Document History
Document
Version Date
Summary of Changes 
Amendment 1
11 February 2019
Section 1.2.3: Added benefit-risk 
assessment (country-specific 
amendment—required for Sweden 
by the Swedish Medical Products 
Agency [MPA]).
European Clinical Trials Database 
(EudraCT) Number: Updated to 
2018-004278-91.
Original protocol
22 October 2018
Not applicable (N/A)
This country-specific amendment incorporates all revisions to date, including amendments 
made at the request of specific country health authorities and institutional review boards 
(IRBs)/ethics committees (ECs).

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TABLE OF CONTENTS
LIST OF TABLES.....................................................................................................................7
APPENDICES ...........................................................................................................................7
PROTOCOL SUMMARY.........................................................................................................8
SCHEDULE OF ACTIVITIES................................................................................................13
1. INTRODUCTION ...............................................................................................................15
1.1. Indication.................................................................................................................15
1.2. Background and Rationale ......................................................................................15
1.2.1. Pneumococcal Disease................................................................................15
1.2.2. Vaccines to Prevent Pneumococcal Disease...............................................16
1.2.2.1. Pneumococcal Polysaccharide Vaccines...................................16
1.2.2.2. Pneumococcal Polysaccharide Conjugate Vaccines .................16
1.2.2.3. Rationale for 20vPnC and Study B7471006 .............................18
1.2.3. Benefit-Risk Assessment............................................................................19
2. STUDY OBJECTIVES AND ENDPOINTS.......................................................................20
2.1. Primary Safety Objective ........................................................................................20
2.1.1. Primary Safety Endpoints...........................................................................20
2.2. Primary Immunogenicity Objective........................................................................20
2.2.1. Primary Immunogenicity Endpoint ............................................................20
2.3. Secondary Objective ...............................................................................................21
2.3.1. Secondary Endpoints ..................................................................................21
.21
21
3. STUDY DESIGN.................................................................................................................21
3.1. Duration of Subject Participation............................................................................23
3.2. Duration of Study....................................................................................................23
3.3. Number of Subjects.................................................................................................23
4. SUBJECT ELIGIBILITY CRITERIA.................................................................................23
4.1. Inclusion Criteria.....................................................................................................23
4.2. Exclusion Criteria....................................................................................................24
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4.3. Temporary Delay Criteria .......................................................................................25
4.3.1. Criteria for Temporarily Delaying Vaccine Administration ......................26
4.3.2. Criteria for Temporarily Delaying Immunogenicity Blood Draw..............26
4.4. Lifestyle Requirements ...........................................................................................26
4.4.1. Contraception..............................................................................................26
4.5. Sponsor’s Qualified Medical Personnel..................................................................26
5. INVESTIGATIONAL PRODUCTS ...................................................................................27
5.1. Allocation to Investigational Product......................................................................27
5.2. Subject Compliance.................................................................................................27
5.3. Investigational Product Supplies.............................................................................27
5.3.1. Dosage Form(s) and Packaging..................................................................28
5.3.2. Preparation and Dispensing........................................................................28
5.4. Administration.........................................................................................................29
5.5. Investigational Product Storage ..............................................................................29
5.6. Investigational Product Accountability...................................................................30
5.6.1. Destruction of Investigational Product Supplies ........................................30
5.7. Concomitant Treatment(s).......................................................................................30
5.8. Prohibited Concomitant Treatments........................................................................30
5.9. Permitted Concomitant Treatments.........................................................................31
5.10. Recording Concomitant Treatments......................................................................31
6. STUDY PROCEDURES .....................................................................................................31
6.1. Visit 1 (Vaccination – Day 1) .................................................................................31
6.2. Visit 2 (Follow-up – 28 to 42 Days After Visit 1) ..................................................33
6.3. Visit 3 (6-Month Safety Collection [Telephone Contact] – 168 to 196 Days 
After Vaccination).....................................................................................................34
6.4. Unscheduled Visits..................................................................................................34
6.5. Subject Withdrawal.................................................................................................35
7. ASSESSMENTS..................................................................................................................37
7.1. Safety Parameters....................................................................................................37
7.1.1. Subject Electronic Diary.............................................................................38
7.1.2. Grading Scale for Prompted Events ...........................................................38
7.1.2.1. Local Reactions.........................................................................38

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7.1.2.2. Systemic Events ........................................................................39
7.1.2.3. Fever..........................................................................................40
7.1.2.4. Use of Antipyretic/Pain Medication..........................................41
7.2. Immunogenicity ......................................................................................................41
7.3. Biological Samples..................................................................................................42
8. ADVERSE EVENT REPORTING......................................................................................42
8.1. Requirements...........................................................................................................42
8.1.1. Additional Details on Recording Adverse Events on the CRF...................44
8.1.2. Eliciting Adverse Event Information..........................................................44
8.1.3. Withdrawal From the Study Due to Adverse Events (see also the
Subject Withdrawal Section) ...........................................................................44
8.1.4. Time Period for Collecting AE/SAE Information......................................44
8.1.4.1. Reporting SAEs to Pfizer Safety...............................................45
8.1.4.2. Recording Nonserious AEs and SAEs on the CRF...................45
8.1.5. Causality Assessment .................................................................................45
8.1.6. Sponsor’s Reporting Requirements to Regulatory Authorities ..................45
8.2. Definitions...............................................................................................................46
8.2.1. Adverse Events...........................................................................................46
8.2.2. Abnormal Test Findings .............................................................................47
8.2.3. Serious Adverse Events ..............................................................................47
8.2.4. Hospitalization............................................................................................48
8.3. Severity Assessment................................................................................................50
8.4. Special Situations ....................................................................................................50
8.4.1. Protocol-Specified Serious Adverse Events...............................................50
8.4.2. Potential Cases of Drug-Induced Liver Injury............................................50
8.4.3. Exposure to the Investigational Product During Pregnancy or 
Breastfeeding, and Occupational Exposure.....................................................52
8.4.3.1. Exposure During Pregnancy......................................................52
8.4.3.2. Exposure During Breastfeeding ................................................52
8.4.3.3. Occupational Exposure .............................................................52
8.4.4. Medication Errors and Lack of Efficacy ....................................................53
8.4.4.1. Medication Errors......................................................................53

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8.4.4.2. Lack of Efficacy........................................................................54
8.5. Medical Device Complaint Reporting Requirements .............................................54
9. DATA ANALYSIS/STATISTICAL METHODS...............................................................54
9.1. Sample Size Determination.....................................................................................54
9.2. Analysis Populations...............................................................................................56
9.3. Analysis of Demographic and Clinical Characteristics...........................................57
9.4. Immunogenicity Analysis .......................................................................................57
9.4.1. Analysis of Primary Immunogenicity Endpoints .......................................57
9.4.2. Analysis of Secondary Immunogenicity Endpoints ...................................58
58
9.5. Safety Analysis........................................................................................................58
9.5.1. Adverse Events...........................................................................................58
9.5.2. Reactogenicity ............................................................................................59
59
59
10. QUALITY CONTROL AND QUALITY ASSURANCE.................................................59
11. DATA HANDLING AND RECORD KEEPING .............................................................60
11.1. Case Report Forms/Electronic Data Record .........................................................60
11.2. Record Retention...................................................................................................61
12. ETHICS..............................................................................................................................61
12.1. Institutional Review Board/Ethics Committee......................................................61
12.2. Ethical Conduct of the Study ................................................................................62
12.3. Subject Information and Consent..........................................................................62
12.4. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH 
GCP ...........................................................................................................................63
13. DEFINITION OF END OF TRIAL...................................................................................63
13.1. End of Trial in All Participating Countries ...........................................................63
14. SPONSOR DISCONTINUATION CRITERIA ................................................................63
15. PUBLICATION OF STUDY RESULTS..........................................................................63
15.1. Communication of Results by Pfizer ....................................................................63
15.2. Publications by Investigators ................................................................................64
16. REFERENCES ..................................................................................................................66
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LIST OF TABLES
Table 1.
Vaccine Assignment .................................................................................22
Table 2.
Grading Scales for Local Reactions .........................................................39
Table 3.
Grading Scales for Systemic Events.........................................................40
Table 4.
Ranges for Fever.......................................................................................41
Table 5.
Probability of Detecting at Least 1 AE in the 20vPnC Group in 
Cohorts A, B, and C..................................................................................55
56
APPENDICES
Appendix 1. Abbreviations......................................................................................................73
75
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PROTOCOL SUMMARY
Background and Rationale
Streptococcus pneumoniae are gram-positive encapsulated cocci that have been a leading 
cause of bacteremia, bacterial meningitis, pneumonia, and acute otitis media (AOM) and 
continue to be a major global public health concern.  Serious pneumococcal disease may 
occur at any age; however, children <5 years and adults ≥65 years of age are at particularly 
increased risk.  Individuals with certain comorbidities and immunocompromising conditions 
are also at risk.  S pneumoniae remains an important cause of serious disease in the United 
States and worldwide.  Globally, pneumococcal pneumonia was estimated to cause 
approximately 1,517,000 deaths in 2015 and, across all ages, accounted for approximately 
55% of deaths due to lower respiratory tract infections.  
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, only a subset of serotypes are more 
commonly associated with severe disease.  Pneumococcal disease can be prevented with 
polysaccharide-based vaccines that induce antibody responses with functional 
(opsonophagocytic) activity and target the capsular serotypes responsible for disease.  
Pneumococcal vaccines that contain free polysaccharides, such as the licensed 23-valent 
pneumococcal polysaccharide vaccine (PPSV23) formulated with capsular polysaccharides 
for 23 pneumococcal serotypes, elicit a T-cell–independent immune response.  These 
vaccines are poorly immunogenic for many of the serotypes contained in the vaccine in 
children less than 2 years of age, immunocompromised populations, and older adults.  They 
do not induce memory responses in any population, and have limited or no protection against 
nonbacteremic disease, including community-acquired pneumonia (CAP).  Pneumococcal 
conjugate vaccines, which contain capsular polysaccharides covalently linked to a protein 
carrier, elicit a T-cell–dependent immune response inducing protective responses in young 
children, older adults, and populations with high-risk conditions, as well as memory 
responses and protection against nonbacteremic disease. 
Prevnar/Prevenar(7-valent pneumococcal conjugate vaccine [7vPnC]), which was licensed 
in the United States in 2000, and Prevnar 13/Prevenar 13(13-valent pneumococcal 
conjugate vaccine [13vPnC]), which was licensed in the United States in 2010, are 
pneumococcal conjugate vaccines containing 7 and 13 capsular polysaccharides, 
respectively. Hereafter these will be referred to as Prevnar or Prevnar 13 (or 13vPnC).  The 
pneumococcal capsular polysaccharides in those vaccines are individually conjugated to 
cross-reactive material 197 (CRM197), a nontoxic variant of diphtheria toxin.  These vaccines 
target serotypes that caused the majority of pneumococcal disease in infants and older adults 
at the time of their introduction.  They have demonstrated efficacy/effectiveness against 
vaccine-type (VT) invasive pneumococcal disease (IPD), AOM, and pneumonia and the 
ability to reduce nasopharyngeal carriage and transmission, resulting in indirect beneficial 
effects.

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Pfizer is developing a new 20-valent pneumococcal conjugate vaccine (20vPnC) candidate to 
further expand protection against the global burden of vaccine-preventable pneumococcal
disease in children and adults over that of Prevnar 13.  20vPnC has the same composition as 
Prevnar 13, but contains an additional 7 pneumococcal conjugates to protect against 
serotypes responsible for a substantial burden of remaining pneumococcal disease.  20vPnC 
uses the same platform as Prevnar and Prevnar 13 and contains components that have 
undergone extensive clinical research.  Safety and immunogenicity data from a 20vPnC 
Phase 1 study conducted in healthy adults 18 to 49 years of age and from a Phase 2 study in 
adults 60 to 64 years of age demonstrate the vaccine induces immune responses to the 20 
vaccine serotypes and has a safety profile consistent with other pneumococcal conjugate 
vaccines.  These data support clinical development in adult and pediatric populations.  See 
the 20vPnC investigator’s brochure for additional details.  
 
 The purpose of the study is to describe 
the safety and immunogenicity of 20vPnC administered to adults ≥65 years of age who have 
been previously vaccinated with various pneumococcal vaccines to provide data in this 
population.
Study Design
This Phase 3, multicenter, randomized, open-label study will be conducted at investigator 
sites in the United States and at least 1 European country. A total of ~875 adults ≥65 years 
of age will be enrolled into 3 different cohorts based on their prior pneumococcal vaccination 
history.  
Subjects who have received PPSV23 ≥1 to ≤5 years previously, but have not been vaccinated 
with 13vPnC, will be assigned to Cohort A and will be randomized (2:1) to receive either 
20vPnC or 13vPnC.
Subjects who have received 13vPnC ≥6 months previously, but have not been vaccinated 
with PPSV23, will be assigned to Cohort B and will be randomized (2:1) to receive either 
20vPnC or PPSV23.  
Subjects who have previously received 13vPnC followed by PPSV23 (PPSV23 vaccination 
must have been given ≥1 year prior to vaccination in this study) will be assigned to Cohort C 
and will receive 20vPnC.  
On Day 1 (Visit 1), subjects will be assessed for eligibility, have blood drawn for 
immunogenicity assessments in the 20vPnC group and for vaccine research in all subjects, 
and receive the study vaccination.  Subjects will be observed for at least 30 minutes after 
vaccination and adverse events (AEs) occurring during that time (immediate AEs) will be 
recorded.  Subjects will also receive safety follow-up and electronic diary (e-diary) 
instructions at the visit.  Prompted systemic events (fever, headache, fatigue, muscle pain, 
and joint pain) occurring within 7 days after vaccination, and prompted local reactions 
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(redness, swelling, and pain at the injection site) occurring at the assigned vaccine (20vPnC, 
13vPnC, or PPSV23) injection site within 10 days after vaccination, will be collected daily in 
the e-diary.  Use of antipyretic/pain medications will also be prompted for and collected daily 
in the e-diary for 7 days after vaccination.  
Subjects will return for Visit 2 (28 to 42 days after Visit 1).  Information will be collected 
from the subjects on AEs, serious AEs (SAEs), newly diagnosed chronic medical conditions 
(NDCMCs), and e-diary follow-up (as needed).  Blood will be drawn for immunogenicity 
assessments in the 20vPnC group and for purposes of vaccine research in all subjects.
At Visit 3 (approximately 6 months [168 to 196 days] after Visit 1), the sites will contact the 
subject via telephone to inquire about SAEs and NDCMCs, concomitant medications used to 
treat SAEs or NDCMCs, and receipt of nonstudy vaccines.  
 
 
 
Objectives and Endpoints
Primary Safety Objective 
•
To describe the safety profile of 20vPnC.
Primary Safety Endpoints 
•
Reported prompted local reactions (redness, swelling, and pain at the injection site) 
within 10 days after vaccination.
•
Reported prompted systemic events (fever, headache, fatigue, muscle pain, and joint 
pain) within 7 days after vaccination.
•
Reported AEs within 1 month after vaccination.
•
Reported SAEs and NDCMCs within 6 months after vaccination.
Primary Immunogenicity Objective 
•
To describe the immune responses to 20vPnC in adults previously vaccinated with 
PPSV23, previously vaccinated with 13vPnC, or previously vaccinated with both 13vPnC 
and PPSV23.
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Primary Immunogenicity Endpoint 
•
Pneumococcal serotype-specific opsonophagocytic activity (OPA) titers 1 month after 
vaccination.
Secondary Objective 
•
To further describe the immune responses to 20vPnC in adults previously vaccinated with 
PPSV23, previously vaccinated with 13vPnC, or previously vaccinated with both 13vPnC 
and PPSV23.
Secondary Endpoints  
•
Fold rise in serotype-specific OPA titers from before to 1 month after vaccination.
•
≥4-Fold rise in serotype-specific OPA titers from before to 1 month after vaccination. 
•
Serotype-specific OPA titers greater than or equal to the lower limit of quantitation 
(≥LLOQ) 1 month after vaccination.
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Statistical Methods
The study size in each cohort is not based on any formal hypothesis test for a safety or 
immunogenicity endpoint. Statistical analyses of safety and immunogenicity will be 
descriptive in general.  Safety and immunogenicity results from each cohort will be analyzed 
separately from other cohorts.  AEs will be summarized by vaccine group within each cohort.  
Local reactions and systemic events will also be summarized by vaccine group within each 
cohort.  Immunogenicity summary statistics will include geometric mean titers, geometric 
mean fold rises, percentage of subjects with ≥4-fold rises, and percentage of subjects with 
OPA titer ≥LLOQ.

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SCHEDULE OF ACTIVITIES
The schedule of activities table provides an overview of the protocol visits and procedures.  Refer to the Study Procedures and 
Assessments sections 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 on the schedule of activities table, in order to 
conduct evaluations or assessments required to protect the well-being of the subject.
Visit Number
1
2
3
Visit Description
Vaccination
Follow-up After 
Vaccination
6-Month Safety Collection
Visit Type
Clinic Visit
Clinic Visit
Telephone Contact
Visit Window (Days)
Day 1
28 to 42 Days
After Vaccination
168 to 196 Days After 
Vaccination
Obtain informed consent
X
Assign subject number 
X
Record demography 
X
Conduct clinical assessment, including collecting medical history data and 
smoking history
X
Record nonstudy vaccinations and concomitant medicationsa
X
X
X
Measure height and weight 
X
Measure prevaccination oral temperature
X
Contraception check, if applicableb
X
X
Review inclusion and exclusion criteria
X
Review temporary delay criteria
X
X
Review continued eligibility
X
Assign randomization number
X
Obtain blood sample for immunogenicity (~30 mL) 
Xc
X
Administer investigational product(s)
X
Assess and record acute (immediate)  reactions for at least 30 minutes after 
investigational product administration
X

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Visit Number
1
2
3
Visit Description
Vaccination
Follow-up After 
Vaccination
6-Month Safety Collection
Visit Type
Clinic Visit
Clinic Visit
Telephone Contact
Visit Window (Days)
Day 1
28 to 42 Days
After Vaccination
168 to 196 Days After 
Vaccination
Provide subject with an e-diary, thermometer, and measuring device and 
instruct how to collect prompted local reactions, systemic events, and use of 
pain/antipyretic medicationsd
X
Review e-diarye
X
Collect e-diary
X
Record and report adverse events
X-------------------------X
Record and report serious adverse events and newly diagnosed chronic medical 
conditionsf
X-----------------------------------------------------------X
Abbreviation: e-diary = electronic diary.
a.
Record nonstudy vaccinations as well as concomitant medications used to treat SAEs or newly diagnosed chronic medical conditions.
b.
If appropriate, the investigator or designee will inform the subject 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 subject’s affirmation in the subject’s chart.
c.
Blood sample will be collected prior to vaccination.
d.
Subjects will record in an e-diary prompted local reactions and systemic events occurring within 10 and 7 days, respectively, after vaccination. Use of 
antipyretic/pain medications will also be prompted for and collected daily in an e-diary for 7 days after vaccination.  Subjects will be instructed to contact the 
study staff if they experience redness or swelling measuring >20 measuring device units or severe pain at the injection site or any Grade 4 prompted 
systemic event.
e.
Designated site staff will review e-diary data online at frequent intervals for the 10 days following vaccination to evaluate subject compliance and reported 
events as part of the ongoing safety review and will collect the e-diary at Visit 2.
f.
A newly diagnosed chronic medical condition 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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1. INTRODUCTION
1.1. Indication
20-valent pneumococcal conjugate vaccine (20vPnC) is being developed for: 

Active immunization to prevent disease caused by the Streptococcus pneumoniae
serotypes in the vaccine.
1.2. Background and Rationale
1.2.1. Pneumococcal Disease
S pneumoniae are gram-positive encapsulated cocci that have been 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 increased risk.  Surveillance studies conducted in 2010-2012 by the Centers for Disease 
Control and Prevention (CDC) found that S pneumoniae remains among the most common 
bacterial pathogens identified in community-acquired pneumonia (CAP) requiring 
hospitalization in the United States in both children and adults.5,6  Bacteremic pneumococcal 
pneumonia (accounting for the majority of invasive pneumococcal disease [IPD] in adults) is 
less common than nonbacteremic pneumococcal pneumonia (an estimated 3 or more cases of 
nonbacteremic pneumococcal pneumonia occur for every 1 case of bacteremic pneumonia).  
Both bacteremic and nonbacteremic pneumococcal pneumonia are associated with significant 
morbidity and mortality in all age groups.1  Pneumococcal disease in older adults represents a 
high clinical and economic healthcare burden.  In Australia, the incidence of hospitalization 
for all-cause pneumonia in adults ≥65 years of age from 2011-2012 corresponded to an 
incidence rate of 1347/100,000 population.  Incidence rates were higher in adults ≥85 years 
of age (3507/100,000).  Pneumococcal pneumonia accounted for 20.6% of pneumonia 
hospitalizations, with an incidence of 274/100,000 population.7  In a study of the global 
burden of disease using data from 195 countries, it was estimated that in 2015 lower 
respiratory tract infections (LRIs) were the leading infectious cause of death and the fifth 
leading cause of death overall, causing 2.74 million deaths globally.  Pneumococcal 
pneumonia caused 55.4% of LRI deaths in all ages, totaling 1,517,388 deaths; of those,
approximately 400,000 deaths were in children younger than 5 years and approximately 
700,000 deaths were in adults ≥70 years of age.8  The CDC estimated that in 2016 there were 
30,400 cases and 3690 deaths due to IPD in the United States.9  As these numbers suggest, 
S pneumoniae remains an important cause of serious disease in the United States and 
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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, only a subset of serotypes are more 
commonly associated with severe disease.10,11  Anticapsular antibodies directed against the 
specific serotype bind to the capsule and promote complement-mediated opsonophagocytic 
killing and clearance of the organism.12  Pneumococcal disease can be prevented with 
polysaccharide-based vaccines that induce antibody responses with functional 
(opsonophagocytic) activity and target the capsular serotypes responsible for disease.13
1.2.2. Vaccines to Prevent Pneumococcal Disease
1.2.2.1. Pneumococcal Polysaccharide Vaccines
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 1983.14,15 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).  PPSV23 elicits a T-cell–independent immune response.  
Unconjugated polysaccharide vaccines do not induce robust responses in certain populations 
(eg, immunocompromised persons, children <2 years of age, and adults ≥65 years of age), 
nor do they generate immunologic memory, so their protective effect wanes over 2 to 
5 years.4,15,16,17  Moreover, their ability to prevent nonbacteremic pneumonia and AOM is 
limited or lacking.13,17,18,19 They also do not have an impact on nasopharyngeal carriage, and 
therefore do not afford herd protection.20 Another limitation is that in several studies,
individuals vaccinated with pneumococcal polysaccharide vaccine had lower functional
antibody responses following subsequent vaccination with either another dose of
pneumococcal polysaccharide vaccine or a dose of pneumococcal conjugate vaccine,
compared to the first dose of polysaccharide vaccine.21,22,23  Such ͆hyporesponsiveness͇
has been observed with other polysaccharide vaccines as well, and raises concern regarding 
the quality of response after revaccination or natural exposure to an invading vaccine-type 
(VT) pneumococcus.24 Despite waning immunity, these concerns of hyporesponsiveness, as 
well as other factors, have led most recommending bodies to restrict PPSV23 to a single 
lifetime dose in adults ≥65 years of age and 1 to 2 doses in most other high-risk
populations.24,25,26
1.2.2.2. 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 and also induce memory responses.16,27 Prevnar®
(7-valent pneumococcal conjugate vaccine [7vPnC]) was the first pneumococcal conjugate 
vaccine to be licensed (in the United States in 2000) and was indicated for prevention of 
pneumococcal disease in infants and young children.  7vPnC contained 7 pneumococcal 
capsular polysaccharides each conjugated to cross-reactive material 197 (CRM197), a 
nontoxic variant of diphtheria toxin.  

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The pneumococcal capsular polysaccharide conjugates represented the serogroups/serotypes 
(4, 6B, 9V, 14, 18C, 19F, and 23F) responsible for most of the IPD and AOM in young 
children in the United States (80%-90% of IPD) and much of the world at the time (1998 to 
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 Following introduction of 7vPnC, 
reduction of nasopharyngeal carriage and transmission has resulted in indirect herd effects, 
with a 92% reduction of VT IPD in older adults ≥65 years of age.38,39
Prevnar 13(13-valent pneumococcal conjugate vaccine [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.27,31,40  The vaccine was licensed for use in infants and 
young children based on comparisons of serotype-specific immunoglobulin G (IgG) to 
7vPnC, with supportive data to demonstrate the functional activity of the immune responses.  
13vPnC was subsequently licensed in adults based on an accelerated approval pathway 
demonstrating comparable serotype-specific opsonophagocytic activity (OPA) responses to 
PPSV23, followed by traditional approval based on demonstration of efficacy against VT 
CAP in the Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA), a 
randomized controlled study of adults 65 years of age and older.41 Prevention of 
nonbacteremic VT CAP in this older adult population was also demonstrated and protection 
was observed through 4 years of follow-up.  This is notable given the lack of definitive data 
showing that PPSV23 prevents nonbacteremic disease in older adults, and evidence that 
protection against IPD wanes significantly over time.15  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.42,43,44,45  It has also been prequalified by the World Health 
Organization (WHO) for use in national infant immunization programs in lower- and middle-
income countries.46,47  Surveillance data from several countries following introduction of
13vPnC into the routine infant immunization program have demonstrated vaccine 
effectiveness against VT IPD in the vaccinated population.48,49,50
Prevnar 13 was licensed for adults ≥50 years of age in 2011, and recommended by the
Advisory Committee on Immunization Practices (ACIP) for use in adults with 
immunocompromising conditions in 2012. In July 2016, it was also licensed for use in adults 
18 to 49 years of age. The potential burden of VT CAP in adults in the United States was 
demonstrated by a study conducted well after the introduction of Prevnar into the routine 
infant immunization schedule, suggesting potential value in direct immunization of adults 
rather than reliance solely on the herd effect.51 The data on disease burden, combined with 
the results of the CAPiTA study, led to the August 2014 ACIP recommendation for all adults 
≥65 years of age to receive Prevnar 13, followed by PPSV23.26,52 The recommendation for 
Prevnar 13 was made based on the potential added benefit in protecting against disease, 
particularly nonbacteremic pneumonia caused by the vaccine serotypes. 

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The continued recommendation for PPSV23 was intended to provide expanded protection 
against IPD for serotypes not in Prevnar 13. However, the prevalence of IPD due to most of 
the serotypes contained only in PPSV23 has remained stable or slightly increased in the 
United States and other countries despite continued recommendation and use of PPSV23 in
adults ≥65 years of age and high-risk adults.53,54,55  These serotypes account for a significant 
amount of pneumococcal disease, and their continued presence highlights the need for a 
better vaccine than PPSV23 to expand protection.
1.2.2.3. Rationale for 20vPnC and Study B7471006
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).  The 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 and greater disease 
severity (eg, meningitis, mortality).56,57,58,59,60,61,62,63,64,65,66,67,68,69  These 7 serotypes are also 
present in PPSV23.70 Adding these 7 additional serotypes to the 13 serotypes in 13vPnC is 
anticipated to further reduce the global burden of pneumococcal disease and provide 
protection comparable to, or greater than, that of PPSV23.  
The 20vPnC candidate is modeled after 7vPnC and 13vPnC, and contains polysaccharides of 
capsular serotypes of S pneumoniae, each covalently linked to CRM197. 
 
 
 
 
 
 
 
Safety and immunogenicity data from a Phase 1 study (B7471001) conducted in healthy 
adults 18 through 49 years of age and from a Phase 2 study (B7471002) in adults 60 through
64 years of age demonstrate the vaccine induces immune responses to the 20 vaccine 
serotypes and has a safety profile consistent with other pneumococcal conjugate vaccines.  
These data support clinical development in adult and pediatric populations.  See the 20vPnC 
IB for additional details.
As noted earlier, 20vPnC is intended for use in adults from age 18 years and above.  
Both PPSV23 and 13vPnC are recommended vaccines in adults ≥65 years of age in various 
parts of the world, and many adults have received either one or both of the vaccines.26,71
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 This study is part of the clinical 
development program and the purpose of the study is to describe the safety and 
immunogenicity of 20vPnC administered to adults ≥65 years of age who have been 
previously vaccinated with various pneumococcal vaccines (PPSV23, 13vPnC, or both 
13vPnC and PPSV23) to provide data in this population.  Generation of safety and 
immunogenicity data for 20vPnC in these populations will help inform potential efforts to 
protect individuals with 20vPnC, and provide safety and immunogenicity information for 
vaccination of persons previously vaccinated. The subjects receiving licensed vaccines in 
this study serve as controls for safety. Immunogenicity will not be measured in the control 
groups, but blood will be collected for vaccine research (see Section 7.2).  
 
 
Additional information for these compounds may be found in the summary of product 
characteristics (for 13vPnC and PPSV23) and the single reference safety document (SRSD).
The SRSD for 20vPnC is the IB. The SRSD for 13vPnC is the US package insert (USPI). 
The SRSD for PPSV23 is the USPI.
1.2.3. Benefit-Risk Assessment
20vPnC has been administered to 33 adults 18 through 49 years of age in the Phase 1 Study 
B7471001 and to 221 adults 60 through 64 years of age in the Phase 2 Study B7471002.  The 
vaccine was well tolerated and the adverse event (AE) profile reflected events that may be 
observed in subjects in these age groups.  The most common AEs after 20vPnC 
administration were primarily related to local reactions (pain, redness, swelling) and systemic 
events (fever, fatigue, headache, muscle pain, joint pain).  20vPnC has not been evaluated in 
adults 65 years of age or older prior to this study.  
 
Both 13vPnC and PPSV23 are licensed vaccines, and the most common AEs noted after 
vaccination are primarily related to local reactions and systemic events.  Injection with saline 
(placebo) may produce pain and redness at the injection site. 
As with any vaccine, an allergic reaction can occur. The allergic reaction can vary from skin 
rash to swelling of the face or lips and/or shortness of breath.  A severe allergic reaction
(anaphylactic shock) may also occur. There may also be additional risks related to the 
vaccines administered in the study that are unknown at this time.  
Risks that may be associated with study procedures include risk from blood sampling, such 
as feeling faint, fainting, pain, swelling, bruising, and infection where blood is taken.
 
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In the B7471001 and B7471002 studies, 20vPnC induced antibodies with functional 
(opsonophagocytic) activity to the pneumococcal serotypes in the vaccine; these antibodies 
may provide clinical benefit.  If 20vPnC is successful in Phase 3 studies and approved, it is 
anticipated to provide a public health benefit by reducing the burden of pneumococcal 
disease (invasive and noninvasive) due to vaccine serotypes.
13vPnC and PPSV23 are vaccines approved for the prevention of pneumococcal disease due 
to the serotypes in the vaccines, and may provide a clinical benefit to those receiving them.  
Pfizer considers that the available information from Studies B7471001 and B7471002 with 
20vPnC, the available safety profile of similar pneumococcal conjugate vaccines (ie, 
13vPnC), and the limited risks from study procedures support a favorable benefit-risk profile 
for 20vPnC and this study.  
The current IB provides additional details on the B7471001 and B7471002 studies and the 
potential risks and benefits of 20vPnC.  Please refer to the respective summary of product 
characteristics/USPI for potential risks of licensed vaccines 13vPnC and PPSV23.
2. STUDY OBJECTIVES AND ENDPOINTS
2.1. Primary Safety Objective 

To describe the safety profile of 20vPnC.
2.1.1. Primary Safety Endpoints 

Reported prompted local reactions (redness, swelling, and pain at the injection site) 
within 10 days after vaccination.

Reported prompted systemic events (fever, headache, fatigue, muscle pain, and joint 
pain) within 7 days after vaccination.

Reported adverse events (AEs) within 1 month after vaccination.

Reported serious adverse events (SAEs) and newly diagnosed chronic medical conditions 
(NDCMCs) within 6 months after vaccination.
2.2. Primary Immunogenicity Objective 

To describe the immune responses to 20vPnC in adults previously vaccinated with 
PPSV23, previously vaccinated with 13vPnC, or previously vaccinated with both 13vPnC 
and PPSV23.
2.2.1. Primary Immunogenicity Endpoint 

Pneumococcal serotype-specific OPA titers 1 month after vaccination.

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2.3. Secondary Objective 
•
To further describe the immune responses to 20vPnC in adults previously vaccinated with 
PPSV23, previously vaccinated with 13vPnC, or previously vaccinated with both 13vPnC 
and PPSV23.
2.3.1. Secondary Endpoints  
•
Fold rise in serotype-specific OPA titers from before to 1 month after vaccination.
•
≥4-Fold rise in serotype-specific OPA titers from before to 1 month after vaccination. 
•
Serotype-specific OPA titers greater than or equal to the lower limit of quantitation 
(≥LLOQ) 1 month after vaccination.
3. STUDY DESIGN
This Phase 3, multicenter, randomized, open-label study will be conducted at investigator 
sites in the United States and at least 1 European country.  The purpose of the study is to 
describe the safety and immunogenicity of 20vPnC administered to adults ≥65 years of age 
who have been previously vaccinated with various pneumococcal vaccines to provide data in 
this population.   
A total of ~875 adults ≥65 years of age will be enrolled into 3 different cohorts based on their 
prior pneumococcal vaccination history.  Subjects will be randomized to receive either 
20vPnC or control vaccine (13vPnC in Cohort A, or PPSV23 in Cohort B) by site-based 
randomization within each cohort (see Table 1).  In 2 of the 3 cohorts, a control group is 
included; the purpose is to serve as a control for safety assessments.  
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Subjects who have received PPSV23 ≥1 to ≤5 years previously, but have not been vaccinated 
with 13vPnC, will be assigned to Cohort A and will be randomized (2:1) to receive either 
20vPnC or 13vPnC.
Subjects who have received 13vPnC ≥6 months previously, but have not been vaccinated 
with PPSV23, will be assigned to Cohort B and will be randomized (2:1) to receive either 
20vPnC or PPSV23.  
Subjects who have previously received 13vPnC followed by PPSV23 (PPSV23 vaccination 
must have been given ≥1 year prior to vaccination in this study) will be assigned to Cohort C 
and will receive 20vPnC.  
Table 1.
Vaccine Assignment
Cohort 
Prior Vaccination History
Vaccine 
Assignment
Sample 
Size
A
Received PPSV23a vaccination in prior ≥1 to ≤5 years
20vPnC
250
13vPnC
125
B
Received 13vPnCb vaccination in prior ≥6 months 
20vPnC
250
PPSV23
125
C
Received 13vPnC followed by PPSV23 vaccination (PPSV23 
vaccination ≥1 year prior) 
20vPnC
125
a.
Vaccinated with PPSV23 and no prior 13vPnC.
b.
Vaccinated with 13vPnC but no prior PPSV23.
On Day 1 (Visit 1), subjects will be assessed for eligibility, have blood drawn for 
immunogenicity assessments in the 20vPnC group and for purposes of vaccine research in all 
subjects (see Section 7.2), and receive the study vaccination.  Subjects will be observed for at 
least 30 minutes after vaccination, and AEs occurring during that time (immediate AEs) will 
be recorded. Subjects will also receive safety follow-up and electronic diary (e-diary) 
instructions at the visit.  Prompted systemic events (fever, headache, fatigue, muscle pain, 
and joint pain) occurring within 7 days after vaccination, and prompted local reactions 
(redness, swelling, and pain at the injection site) occurring at the assigned vaccine (20vPnC, 
13vPnC, or PPSV23) injection site within 10 days after vaccination, will be collected daily in 
the e-diary.  Use of antipyretic/pain medications will also be prompted for and collected daily 
in the e-diary for 7 days after vaccination.  
Subjects will return for Visit 2 (28 to 42 days after Visit 1).  Information will be collected 
from the subjects on AEs, SAEs, NDCMCs, and e-diary follow-up (as needed).  Blood will 
also be drawn at this visit for immunogenicity assessments in the 20vPnC group and for 
purposes of vaccine research in all subjects.
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At Visit 3 (approximately 6 months [168 to 196 days] after Visit 1), the sites will contact the 
subjects via telephone to inquire about SAEs, NDCMCs, concomitant medications used to 
treat SAEs or NDCMCs, and receipt of nonstudy vaccines. 
3.1. Duration of Subject Participation
Each subject will participate in the study for approximately 6 months.
3.2. Duration of Study 
Based on a 5-month enrollment period, the study duration will be approximately 11 months.
3.3. Number of Subjects
Enrollment of approximately 875 subjects will result in ~790 evaluable subjects (assuming a 
10% dropout rate). 
Subjects who withdraw or are withdrawn from the study after randomization will not be 
replaced, regardless of the reason for withdrawal.
4. SUBJECT ELIGIBILITY CRITERIA
This study can fulfill its objectives only if appropriate subjects are enrolled.  The following 
eligibility criteria are designed to select subjects 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 subject is suitable for this protocol.  
Subject eligibility should be reviewed and documented by an appropriate member of the 
investigator’s study team before subjects are included in the study.  
4.1. Inclusion Criteria
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the 
study:
1. Evidence of a personally signed and dated informed consent document (ICD) indicating 
that the subject has been informed of all pertinent aspects of the study.  
2. Willing and able to comply with scheduled visits, treatment plan, and other study 
procedures.
3. Expected to be available for the duration of the study and can be contacted by telephone 
during study participation.
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4. Male or female adults ≥65 years of age. 
5. Adults determined by clinical assessment, including medical history and clinical 
judgment, to be eligible for the study, including adults with preexisting stable disease, 
defined as disease not requiring significant change in therapy in the previous 6 weeks or 
hospitalization for worsening disease within 12 weeks before receipt of investigational 
product. 
6. Female subject of nonchildbearing potential; male subject not able to father children; 
male subject who is able to father children and willing to use a highly effective method of
contraception as outlined in this protocol until at least 28 days after the last dose of 
investigational product.
 
7. Male or female adults who meet 1 of the following:
a.
Vaccination with PPSV23 ≥1 year and ≤5 years prior to vaccination in the study, and 
no prior 13vPnC vaccination (Cohort A).
b. Vaccination with 13vPnC ≥6 months prior to vaccination in the study, and no prior 
PPSV23 vaccination (Cohort B).
c.
Vaccination with 13vPnC followed by PPSV23 (PPSV23 vaccination ≥1 year prior to 
vaccination in the study) (Cohort C).
4.2. Exclusion Criteria
Subjects with any of the following characteristics/conditions will not be included in the 
study:
1. Investigator site staff members directly involved in the conduct of the study and their 
family members, site staff members otherwise supervised by the investigator, or subjects
who are Pfizer employees, including their family members, directly involved in the 
conduct of the study.
2. 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.
3. History of severe adverse reaction associated with a vaccine and/or severe allergic 
reaction (eg, anaphylaxis) to any component of 20vPnC, 13vPnC, or any other diphtheria 
toxoid–containing vaccine, or PPSV23.
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4. Serious chronic disorder including metastatic malignancy, severe chronic obstructive 
pulmonary disease (COPD) requiring supplemental oxygen, end-stage renal disease with 
or without dialysis, clinically unstable cardiac disease, or any other disorder that, in the 
investigator’s opinion, excludes the subject from participating in the study.
5. 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 subject inappropriate for entry into this study.
6. History of microbiologically proven invasive disease caused by S pneumoniae.
7. Subjects who receive 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, subjects 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 or eyes) corticosteroids are 
permitted.
8. Subjects with known or suspected immunodeficiency or other conditions associated with 
immunosuppression, including, but not limited to, immunoglobulin class/subclass 
deficiencies, generalized malignancy, human immunodeficiency virus (HIV) infection, 
leukemia, lymphoma, or organ or bone marrow transplant.
9. Bleeding diathesis or condition associated with prolonged bleeding that would, in the 
opinion of the investigator, contraindicate intramuscular injection.
10. Receipt of blood/plasma products or immunoglobulin, from 60 days before 
investigational product administration, or planned receipt through study participation.
4.3. Temporary Delay Criteria
The following conditions are temporary or self-limiting and a subject 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.  

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4.3.1. Criteria for Temporarily Delaying Vaccine Administration 
•
Current febrile illness (body temperature ≥100.4°F [≥38°C]) or other acute illness within 
48 hours before investigational product administration.
•
Receipt of any inactivated or otherwise nonlive vaccine within 14 days or any live 
vaccine within 28 days before investigational product administration.
•
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.
4.3.2. Criteria for Temporarily Delaying Immunogenicity Blood Draw
•
Receipt of antibiotic therapy within 72 hours before blood draw.
4.4. Lifestyle Requirements
4.4.1. Contraception
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 
 and will confirm that the participant has been instructed in its consistent 
and correct use.  At time points indicated in the schedule of activities, 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 (subjects 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. 
4.5. 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 supporting study 
documentation/team SharePoint site/study portal].
To facilitate access to appropriately qualified medical personnel on study-related medical 
questions or problems, subjects are provided with a contact card. The contact card contains, 
at a minimum, protocol and investigational product identifiers, subject study numbers, 
contact information for the investigator site, and contact details for a contact center in the 
event that the investigator site staff cannot be reached to provide advice on a medical 
question or problem originating from another healthcare professional not involved in the 
subject’s participation in the study.  
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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 subject directly, and if a subject calls that 
number, he or she will be directed back to the investigator site.
5. INVESTIGATIONAL PRODUCTS 
For the purposes of this study, and per International Council for Harmonisation (ICH) 
guidelines, investigational product is defined as a pharmaceutical form of an active 
ingredient or placebo being tested or used as a reference/comparator in a clinical trial, 
including a product with a marketing authorization when used or assembled (formulated or 
packaged) in a way different from the approved form, or when used for an unapproved 
indication, or when used to gain further information about an approved use (ICH E6 1.33). 
For this study, the investigational products are 20vPnC, 13vPnC, and PPSV23. 
5.1. Allocation to Investigational Product
The investigator’s knowledge of the investigational product should not influence the decision 
to enroll a particular subject or affect the order in which subjects are enrolled.
Allocation of subjects to vaccine groups will proceed through the use of an interactive 
response technology (IRT) system (interactive Web-based response [IWR]).  The site 
personnel (study coordinator or specified designee) will be required to enter or select 
information including but not limited to the user’s identification (ID) and password, the 
protocol number, and the subject number. The site personnel will then be provided with a 
vaccine assignment, randomization number, and dispensable unit (DU) or container number 
when investigational product is being supplied via the IRT system.  The IRT system will 
provide a confirmation report containing the subject number, randomization number, and DU 
or container number assigned. The confirmation report must be stored in the site’s files.
The study-specific IRT reference manual will provide the contact information and further 
details on the use of the IRT system. 
5.2. Subject Compliance
All doses of investigational product will be administered by the appropriately designated 
study staff at the investigator site.
5.3. Investigational Product Supplies
20vPnC, 13vPnC, and PPSV23 will be provided by the sponsor to the study sites.

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Study vaccines will be packed and labeled as investigational product in accordance with 
current guidelines and applicable local and legal regulatory requirements.  The formulation 
of the investigational products is described below. 
5.3.1. Dosage Form(s) and Packaging
20vPnC contains saccharides from pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 
10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, and 33F individually conjugated to 
CRM197. 
 
13vPnC contains saccharides from pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 
18C, 19A, 19F, and 23F individually conjugated to CRM197.  
 
20vPnC and 13vPnC will be supplied to the site as packaged, single-use prefilled syringes 
and labeled according to local regulatory requirements.
PPSV23 is a licensed commercial product and is a clear, sterile solution consisting of a 
mixture of purified capsular polysaccharides from 23 types of S pneumoniae: 1, 2, 3, 4, 5, 
6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19F, 19A, 20, 22F, 23F, and 33F.  
The vaccine is formulated to contain 25 μg of each of the 23 purified polysaccharide 
serotypes per 0.5-mL dose of vaccine in an isotonic saline solution containing 0.25% phenol 
as a preservative.  PPSV23 will be supplied by the sponsor to the site as packaged vials or 
prefilled syringes and labeled according to local regulatory requirements.
5.3.2. Preparation and Dispensing
See the Investigational Product Manual (IP manual) or package insert for instructions on how 
to prepare the investigational product for administration.  Investigational product should be 
prepared and dispensed by an appropriately qualified and experienced member of the study 
staff (eg, physician, nurse, physician’s assistant, nurse practitioner, pharmacy 
assistant/technician, or pharmacist) as allowed by local, state, and institutional guidance.  
Investigational product will be prepared by qualified site personnel according to the IP 
manual.  
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5.4. Administration
A 0.5-mL dose of 13vPnC, 20vPnC, or PPSV23 will be administered intramuscularly in the 
deltoid muscle of the nondominant arm at Visit 1. Standard vaccination practices must be 
observed and vaccine must not be injected into blood vessels.  Appropriate medication and 
other supportive measures for management of an acute hypersensitivity reaction should be 
available in accordance with local guidelines for standard immunization practices.
Administration of investigational products should be performed by an appropriately 
qualified, Good Clinical Practice (GCP)-trained, and vaccine-experienced member of the 
study staff (eg, physician, nurse, physician’s assistant, nurse practitioner, pharmacist, or 
medical assistant) as allowed by local, state, and institutional guidance. 
Investigational product administration details will be recorded on the case report form (CRF).
5.5. Investigational Product Storage 
The investigator or an approved representative, eg, pharmacist, will ensure that all 
investigational products, including any comparator and/or marketed products, are stored in a 
secured area with controlled access under required storage conditions and in accordance with 
applicable regulatory requirements.
Investigational products should be stored in their original containers and in accordance with 
the labels.  
20vPnC, 13vPnC, and PPSV23 will be shipped to the study site after required regulatory and 
legal documents have been received by the sponsor.
Any storage conditions stated in the SRSD (20vPnC IB, 13vPnC USPI, and PPSV23 USPI) 
will be superseded by the storage conditions stated on the product label.
Site systems must be capable of measuring and documenting (for example, via a log), at a 
minimum, daily minimum and maximum temperatures for all site storage locations 
(as applicable, including frozen, refrigerated, and/or room-temperature products).  This 
should be captured from the time of investigational product receipt throughout the study.  
Even for continuous-monitoring systems, a log or site procedure that ensures active 
evaluation for excursions should be available.  The intent is to ensure that the minimum and 
maximum temperature is checked each business day to confirm that no excursion occurred 
since the last evaluation and to provide the site with the capability to store or view the 
minimum/maximum temperature for all nonworking days upon return to normal operations.  
The operation of the temperature monitoring device and storage unit (for example, 
refrigerator), as applicable, should be regularly inspected to ensure they are maintained in 
working order.  
CCI

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Any excursions from the product label storage conditions should be reported to Pfizer upon 
discovery.  The site should actively pursue options for returning the product to the storage 
conditions described in the labeling, as soon as possible.  Deviations from the storage 
requirements, including any actions taken, must be documented and reported to Pfizer.  
Once an excursion is identified, the investigational product must be quarantined and not used 
until Pfizer provides permission to use the investigational product.  It will not be considered a 
protocol deviation if Pfizer approves the use of the investigational product after the 
temperature excursion. Use of the investigational product prior to Pfizer approval will be 
considered a protocol deviation. Specific details regarding information the site should report 
for each excursion will be provided to the site.
Receipt of materials, door opening and closing, and other routine handling operations where 
the products are briefly out of the temperature range described in the labeling are not 
considered excursions.
5.6. Investigational Product Accountability 
The investigator site must maintain adequate records documenting the receipt, use, loss, or 
other disposition of the investigational product supplies.  All investigational products will be 
accounted for using a drug accountability form/record.
Used needles and syringes should be disposed of according to local practice.  Empty outer 
investigational product containers must be retained until reviewed by the sponsor's 
representative and then may be destroyed after the sponsor’s representative has performed 
accountability.  Investigational product return/destruction must be documented on the 
accountability log.
5.6.1. Destruction of Investigational Product Supplies 
The sponsor or designee will provide guidance on the destruction of unused investigational 
product (eg, at the site).  If destruction is authorized to take place at the investigator site, the 
investigator must ensure that the materials are destroyed in compliance with applicable 
environmental regulations, institutional policy, and any special instructions provided by 
Pfizer, and all destruction must be adequately documented.
5.7. Concomitant Treatment(s)
5.8. Prohibited Concomitant Treatments 

Receipt of any investigational vaccines, drugs, or medical devices is prohibited during 
subject participation in the study.

Receipt of nonstudy pneumococcal vaccine is prohibited during subject participation in 
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
Receipt of blood/plasma products, immunoglobulins, and/or immunosuppressive therapy 
(including a ≥14-day course of systemic corticosteroids) is prohibited during study 
participation.  
5.9. Permitted Concomitant Treatments 

Prescription and nonprescription medications, vitamins, minerals, and herbal remedies 
are permitted during subject participation in the study.

Licensed inactivated influenza vaccine may be given >14 days prior to or >14 days after 
investigational product administration (Visit 1).  If medically necessary (eg, pandemic), 
influenza vaccine may be given at any time.

Receipt of other licensed nonstudy vaccine is permitted after Visit 2 (except 
pneumococcal [prohibited] or influenza vaccine [permitted] as described above).

The use of prophylactic antipyretic medication, while permitted, is not recommended on 
the day prior to vaccination or the day of investigational product administration.

Inhaled/nebulized, topical (skin, eyes, or ears), or localized injections of corticosteroids 
(eg, intra-articular or intrabursal administration) are permitted during subject 
participation in the study.
5.10. Recording Concomitant Treatments
The name and date of administration for any nonstudy vaccinations received from the time of 
signing of the ICD to the final visit will be collected and recorded in the CRF.
Medications taken to treat SAEs or NDCMCs from the time of signing of the ICD to Visit 3 
will be recorded in the CRF.
6. STUDY PROCEDURES 
The study procedures are summarized in the schedule of activities. The day of vaccination is 
considered to be Day 1.
6.1. Visit 1 (Vaccination – Day 1)
Prior to Vaccination:

Obtain written informed consent before performing any study-specific procedures. 

Assign a subject number via the IRT.

Obtain and record the subject demography (sex, date of birth, ethnicity, and race). The 
complete date of birth (ie, DD-MMM-YYYY) will be collected to provide the specific 
demographics to critically evaluate the immune response and safety profile by age.

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
Obtain and record the medical history including the presence of chronic conditions 
(eg, diabetes, asthma, cardiac disease, COPD) and/or medical history of significance such 
as relevant surgical procedures.  

Assess and record smoking history.

Record nonstudy vaccinations and concomitant medications as described in Section 5.10.

Measure and record the subject’s height, weight, and oral temperature (F/C).

Conduct a clinical assessment.  If the clinical assessment indicates that a physical 
examination is necessary to comprehensively evaluate the subject, perform a physical 
examination and record any findings in the source documents and, if significant, record 
on the medical history CRF.

The investigator or designee will inform the subject of the need to use highly effective
contraceptives consistently and correctly until 28 days after vaccination, if applicable, 
and document the conversation and the subject’s affirmation in the subject’s chart.

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 a randomization number and an investigational product container number via the 
IRT.  This must be the last step before proceeding.  A site staff member will prepare the 
investigational product according to the IP manual.
After Randomization:

Collect a blood sample of approximately 30 mL for immunogenicity assessments prior to 
vaccination.

Administer a single 0.5-mL injection of investigational product into the deltoid muscle of 
the nondominant arm. 

Site staff will observe the subject for at least 30 minutes after investigational product 
administration for any acute (immediate) reactions.  Record any acute (immediate) 
reactions on the AE CRF and on an SAE form as applicable.

Issue the subject a measuring device to measure injection site reactions and a digital 
thermometer and provide instructions on their use.

Issue the subject an e-diary and provide instructions on its use and completion.  Ask the 
subject to complete the e-diary from Day 1 to Day 10, with Day 1 being the day of 
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
Ask the subject to contact the site staff or investigator immediately during the 10 days 
after vaccination if he or she experiences redness or swelling at the injection site 
measuring 20 measuring device units (10.0 cm) or severe injection site pain (prevents 
daily activity) to determine if the event requires further assessment by the investigator. 

Subjects will also be instructed to contact site staff or the investigator if they experience 
any possible Grade 4 prompted local reaction or systemic event (refer to Section 6.4).

Inform the subject that use of prophylactic antipyretic/pain medication, while permitted, 
is not recommended on the day of investigational product administration (before or after 
vaccination).

Ask the subject to contact the site staff or investigator immediately if any significant 
illness or medical event (eg, emergency room visit or hospitalization) occurs during the 
study period.

Remind the subject to use appropriate contraceptives until 28 days after vaccination, if 
applicable.

Record AEs, SAEs, and NDCMCs as described in Section 8.

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 10 days following vaccination to evaluate subject compliance 
and as part of the ongoing safety review.
6.2. Visit 2 (Follow-up – 28 to 42 Days After Visit 1)

Record nonstudy vaccinations as described in Section 5.10.

Perform a contraception check (see Section 4.4.1), if applicable. 

Review the subject's e-diary data and collect the e-diary.  Collect stop dates of any 
e-diary events ongoing on the last day that the e-diary was completed and record stop 
dates in the CRF.

Determine if any AEs, SAEs, or NDCMCs have occurred since Visit 1, collect 
medications as applicable (as described in Sections 5.10), and follow up on any 
previously reported ongoing AEs, SAEs, or NDCMCs to determine the outcome 
(ie, record stop dates or confirm if they are still continuing) and record as described in 
Section 8.1.4.

Ensure and document that the subject continues to be eligible for the study and that none 
of the temporary blood draw delay criteria are met.

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
Collect a blood sample of approximately 30 mL for immunogenicity assessments.

Remind the subject to contact the site staff or investigator immediately if any significant 
illness or medical event (eg, emergency room visit or hospitalization) occurs during the 
study period.

The investigator or an authorized designee completes the CRF.
6.3. Visit 3 (6-Month Safety Collection [Telephone Contact] – 168 to 196 Days After 
Vaccination)

Record nonstudy vaccinations as described in Section 5.10.

Determine whether any NDCMCs or SAEs have occurred since Visit 2, collect 
medications as applicable (as described in Section 5.10), and follow up on any previously 
reported ongoing AEs, SAEs, or NDCMCs to determine the outcome (ie, record stop 
dates or confirm if they are still continuing) and record as described in Section 8.1.4.

The investigator or an authorized designee completes the CRF.
6.4. Unscheduled Visits 
Following vaccination, if the subject reports any redness or swelling at the injection site 
measuring >20 measuring device units (>10.0 cm) or severe pain at the injection site during 
the 10 days following vaccination, a telephone contact must occur as soon as possible 
between the investigator or medically qualified designee and subject to assess if an 
unscheduled site visit is required.  A site visit must be scheduled as soon as possible to assess 
the extent of the reaction unless any of the following is true:

The subject is unable to attend the unscheduled visit.

The reaction is no longer present at the time of the telephone contact.

The subject 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 subject’s source documentation and the CRF.
If the subject is unable to attend the unscheduled visit, or the PI or authorized designee 
determined it was not needed, any ongoing reactions must be assessed at the next study visit.

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During the unscheduled 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 oral temperature (F/C).

Measure minimum and maximum diameters of redness (if present).

Measure minimum and maximum diameters of swelling (if present).

Assess injection site pain (if present) in accordance with the grades provided in 
Section 7.1.2.1.

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.
Subjects will also be instructed to contact site staff or the investigator if they experience any 
possible Grade 4 prompted systemic event (ie, emergency room visit or hospitalization for 
headache, fatigue, muscle pain, or joint pain) or local reaction (ie, necrosis, exfoliative 
dermatitis, or emergency room visit/hospitalization for injection site pain) within 7 or 
10 days, respectively, after vaccination.  Lastly, subjects will be instructed to contact site 
staff or the investigator to report any significant illness, medical event, or hospitalization that 
occurs during the study period.  The site should determine if an unscheduled visit to further 
evaluate the event is warranted in all such cases.
6.5. Subject Withdrawal
An investigator and/or sponsor can withdraw a subject from the study if deemed appropriate.  
In addition, if a subject fails to continue to meet the inclusion criteria, new information 
becomes available that would exclude the subject, or the subject develops a condition or 
situation that would meet exclusion criteria, the subject may be considered for withdrawal.
Reasons why a subject may discontinue or be withdrawn from the study by the investigator 
or sponsor include, but are not limited to, failure to meet entrance criteria (screening failure), 
AE, death, pregnancy, protocol deviation, lost to follow-up, no longer willing to participate 
in the study, study terminated by the sponsor, or any other reason.  Subjects who have 
received the investigational product will not be replaced, regardless of the reason for 
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The investigator should capture the reason for withdrawal in the database for all subjects and 
a follow-up telephone contact 6 months after vaccination for the collection of safety 
information should be completed for all subjects who have been withdrawn after 
administration of investigational product unless consent for further contact has been 
withdrawn.
Subjects may withdraw from the study at any time at their own request, or they may be 
withdrawn at any time at the discretion of the investigator or sponsor for safety 
(see Section 8.1.3) or behavioral reasons, or the inability of the subject to comply with the 
protocol-required schedule of study visits or procedures at a given study site. 
If a subject does not return for a scheduled visit, every effort should be made to contact the 
subject.  All attempts to contact the subject and information received during contact attempts 
must be documented in the subject’s medical record.  In any circumstance, every effort 
should be made to document subject outcome, if possible.  The investigator should inquire 
about the reason for withdrawal, request that the subject return for a final visit, if applicable, 
and follow up with the subject regarding any unresolved AEs.
If the subject withdraws from the study, and 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.
Withdrawal of Consent:
Subjects who request to discontinue will remain in the study and must continue to be 
followed for protocol specified follow-up procedures through 6 months after vaccination.  
The only exception to this is when a subject specifically withdraws consent for any further 
contact with him or her or persons previously authorized by the subject to provide this 
information.  Subjects should notify the investigator in writing of the decision to withdraw 
consent from future follow-up, whenever possible.  The withdrawal of consent should be 
explained in detail in the medical records by the investigator, as to whether the withdrawal is 
only from further receipt of investigational product or also from study procedures and/or 
postvaccination study follow-up, and entered on the appropriate CRF page.  In the event that 
vital status (whether the subject is alive or dead) is being measured, publicly available 
information should be used to determine vital status only as appropriately directed in 
accordance with local law.
Lost to Follow-up: 
All reasonable efforts must be made to locate subjects to determine and report their ongoing 
status.  This includes follow-up with persons authorized by the subject as noted above.  Lost 
to follow-up is defined by the inability to reach the subject after a minimum of 2 documented 
phone calls, faxes, or emails as well as lack of response by the subject to 1 registered mail 
letter.  All attempts should be documented in the subject’s medical records.  

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If it is determined that the subject has died, the site will use locally permissible methods to 
obtain the date and cause of death.  If the investigator’s use of a third-party representative to 
assist in the follow-up portion of the study has been included in the subject’s informed 
consent, then the investigator may use a sponsor-retained third-party representative to assist 
site staff with obtaining the subject’s contact information or other public vital status data 
necessary to complete the follow-up portion of the study.  The site staff and representative
will consult publicly available sources, such as public health registries and databases, in 
order to obtain updated contact information.  If, after all attempts, the subject remains lost to 
follow-up, then the last-known-alive date as determined by the investigator should be 
reported and documented in the subject’s medical records.
7. ASSESSMENTS
Every effort should be made to ensure that the protocol-required tests and procedures are 
completed as described.  However, it is anticipated that from time to time there may be 
circumstances outside of the control of the investigator that may make it unfeasible to 
perform the test.  In these cases the investigator will take all steps necessary to ensure the 
safety and well-being of the subject.  When a protocol-required test cannot be performed, the 
investigator will document the reason for this and any corrective and preventive actions that 
he or she has taken to ensure that normal processes are adhered to as soon as possible.  The 
study team will 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.
7.1. Safety Parameters
Safety parameters will be assessed as described in the schedule of activities, Section 8, and 
below.
A clinical assessment, including medical history and measurement of oral temperature, will 
be performed on all subjects prior to vaccination to determine subject eligibility and to 
establish a clinical baseline.  Significant medical history, significant findings from any 
physical examination, if performed, and temperature measurements will be documented and 
recorded in the CRF.  
Acute reactions (immediate events) within the first 30 minutes after investigational product 
administration will be assessed and documented as an AE or SAE, as appropriate, in the 
CRF.
Prompted e-diary events, including local reactions and systemic events that occur within
10 and 7 days, respectively, after investigational product administration, are graded as 
described in Section 7.1.2. Furthermore, AEs, SAEs, and NDCMCs will be collected as 
defined in Section 8.1.4.

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7.1.1. Subject Electronic Diary
The subject will be asked to monitor and record local reactions for 10 days and systemic 
events, fever, and antipyretic/pain medication usage for 7 days, each evening following 
vaccination (Day 1 through Day 10 or Day 7, where Day 1 is the day of vaccination) using an 
e-diary.  This allows recording of these assessments only within a fixed time window, thus 
providing the accurate representation of the subject’s experience at that time.  Data on local 
reactions, specific systemic events, fever, and antipyretic/pain medication usage reported on 
the e-diary will be transferred electronically to the e-diary vendor, where they will be 
available for review by investigators, their appropriately 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 subject withdraws 
because of prompted events reported in the e-diary, the event(s) should be recorded on the 
AE page of the CRF, regardless of whether the investigator considers the event(s) to be 
clinically significant.
The investigators (or appropriately qualified designees) are required to review the e-diary 
data online at frequent intervals to evaluate subject compliance and reported events as part of 
the ongoing safety review.
The investigator or designee must obtain stop dates for any reactions ongoing on the last day 
that the e-diary was completed.  The stop dates should be entered in the CRF.
7.1.2. Grading Scale for Prompted Events
The grading scales used in this study to assess AEs 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 healthy adult volunteers enrolled 
in preventive vaccine clinical trials.72
7.1.2.1. Local Reactions 
From Day 1 to Day 10 after vaccination, where Day 1 is the day of vaccination, subjects will 
be asked to assess redness, swelling, and pain at the injection site and to record the symptoms 
in the e-diary in the evening.  Redness and swelling will be measured and recorded in 
measuring device units (range: 1 to 21 and >21), and then categorized during analysis as 
mild, moderate, or severe based on the grading scale in Table 2 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 subject as mild, 
moderate, or severe according to the grading scale in Table 2. A subject with a severe 
(Grade 3 or above) local reaction will be prompted to contact the investigator to assess the 
reaction and perform an unscheduled assessment or visit as appropriate.

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Only an investigator is able to classify a subject’s local reaction as Grade 4, after physical 
examination of the subject or documentation from another medically qualified source 
(eg, emergency room or hospital record) or, in the case of pain at the injection site only, 
telephone contact with the subject.  If a subject experiences a Grade 4 local reaction, the 
investigator must immediately notify the sponsor.  Site staff will educate the subject 
regarding signs and symptoms that would prompt site contact.  Grade 4 reactions will be 
collected as an AE on the CRF. The event will be graded using the AE severity grading scale 
(Section 8.3).
The procedure for notification of the sponsor is provided in the study reference manual 
(SRM) or equivalent.
Table 2.
Grading Scales for Local Reactions
Mild 
Grade 1
Moderate
Grade 2
Severe
Grade 3a
Grade 4b
Redness
5 to 10 measuring 
device units
=
>2.0 to 5.0 cm
11 to 20 measuring 
device units
=
>5.0 to 10.0 cm
>20 measuring 
device units
=
>10.0 cm
Necrosis or 
exfoliative  
dermatitis
Swelling
5 to 10 measuring 
device units
=
>2.0 to 5.0 cm
11 to 20 measuring 
device units
=
>5.0 to 10.0 cm
>20 measuring 
device units
=
>10.0 cm
Necrosis
Pain at injection site
Does not interfere 
with activity
Interferes with 
activity
Prevents daily 
activityc
Emergency room 
visit or 
hospitalization for 
severe injection site 
pain
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.
Subjects experiencing Grade 3 local reactions are required to contact the investigator site. In the event that 
the subject does not call, the investigator will call the subject.
b.
Grade 4 assessment should be made by the investigator; Grade 4 will not be collected in the e-diary but will 
be collected as an AE on the CRF.  The severity of the local reaction should be graded using the AE 
severity grading scale.
c.
Prevents daily activity, eg, results in missed days of work or school or is otherwise incapacitating.
7.1.2.2. Systemic Events
From Day 1 to Day 7 after vaccination, where Day 1 is the day of vaccination, subjects will 
be asked to assess headache, fatigue, muscle pain, and joint pain and to record the symptoms 
in the e-diary in the evening.  The symptoms will be assessed by the subject as mild, 
moderate, or severe according to the grading scale in Table 3 below.  Subjects will also be 
instructed to contact site staff or the investigator if they experience any possible Grade 4 
prompted systemic event (ie, emergency room visit or hospitalization for severe headache, 
severe fatigue, severe muscle pain, or severe joint pain) within 7 days after vaccination.  

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Study staff may also contact the subject to obtain additional information on Grade 3 events 
entered into the e-diary.
Only an investigator is able to classify a subject’s systemic event as Grade 4, after physical 
examination of the subject or documentation from another medically qualified source 
(eg, emergency room or hospital record) or telephone contact with the subject.  If a subject 
experiences a Grade 4 systemic event, the investigator must immediately notify the sponsor.  
Grade 4 events will be collected as an AE on the CRF. The event will be graded using the 
AE severity grading scale (Section 8.3).
The procedure for notification of the sponsor is provided in the SRM or equivalent.
Table 3.
Grading Scales for Systemic Events
Mild
Grade 1
Moderate
Grade 2
Severe
Grade 3a
Grade 4b
Fatigue 
(tiredness)
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 on the CRF. The severity of the systemic event should be graded using the AE 
severity grading scale in Section 8.3.
7.1.2.3. Fever
In order to record information on fever, a digital thermometer will be given to the subject 
with instructions on how to measure oral temperature at home.  Temperature will be 
collected in the evening daily for 7 days following vaccination (Days 1 to 7, where Day 1 is 
the day of vaccination) and at any time during the 7 days that fever is suspected.  Fever is 
defined as an oral temperature of ≥100.4F (≥38.0C).  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 <100.4F [<38.0C]) in order to 
collect a stop date in the CRF.  Temperature will be measured and recorded to 1 decimal 
place and then grouped into ranges for the analysis according to Table 4 below. 

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Temperatures reported in degrees Fahrenheit will be programmatically converted to degrees 
Celsius for reporting.  
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.
7.1.2.4. Use of Antipyretic/Pain Medication
The subject will be asked to record the use of antipyretic/pain medication (yes/no) in the 
e-diary in the evening daily for 7 days following vaccination.  The use of prophylactic 
antipyretic/pain medication, while permitted, is not recommended on the day prior to 
vaccination or the day of investigational product administration (before or after vaccination).
7.2. Immunogenicity
Blood samples (approximately 30 mL per sample) will be collected from all subjects at 
Visit 1 (prior to administration of 20vPnC, 13vPnC, or PPSV23) and at Visit 2 
(1 month [28 to 42 days] after vaccination). 
The total volume of blood collected from each subject completing participation through 
Visit 3 will be approximately 60 mL.  
Sample collection, processing, storage, and shipping information can be found in the SRM or 
equivalent manual.
Immunogenicity assays will be performed at Pfizer Vaccine Research & Development 
Laboratory located at 401 North Middletown Road, Pearl River, NY 10965, and/or at an 
external contract laboratory designated by Pfizer. 
Pneumococcal Antibody Response
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 on all sera collected prior to 
study vaccination and 1 month after vaccination from 20vPnC recipients.  
 
 
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7.3. 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 subject’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 subject’s genetic material will be performed.  
The subject may request that his or her samples, if still identifiable, be destroyed at any time; 
however, any data already collected from those samples will still be used for this research.  
The biological samples may be shared with other researchers as long as confidentiality is 
maintained and no testing of the subject’s genetic material is performed.
8. ADVERSE EVENT REPORTING
8.1. Requirements
The table below summarizes the requirements for recording safety events on the CRF and for 
reporting safety events on the Clinical Trial (CT) Serious Adverse Event (SAE) Report 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.  
Safety Event
Recorded on the CRF
Reported on the CT SAE 
Report Form to Pfizer 
Safety Within 24 Hours of 
Awareness
SAE
All
All
Nonserious AE
All
None
Exposure to the 
investigational product 
under study during 
pregnancy or breastfeeding, 
and occupational exposure
All (regardless of whether 
associated with an AE), except 
occupational exposure
Exposure during pregnancy, 
exposure via breastfeeding, 
occupational exposure 
(regardless of whether 
associated with an AE)
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All observed or volunteered events regardless of vaccine group or suspected causal 
relationship to the investigational product(s) will be reported as described in the following 
paragraphs.
Events listed in the table above that require reporting to Pfizer Safety on the CT SAE Report 
Form within 24 hours of awareness of the event by the investigator are to be reported 
regardless of whether the event is determined by the investigator to be related to an 
investigational product under study.  In particular, if the SAE is fatal or life-threatening, 
notification to Pfizer Safety must be made immediately, irrespective of the extent of available 
event information.  This time frame also applies to additional new (follow-up) information on 
previously forwarded reports.  In the rare situation that the investigator does not become 
immediately aware of the occurrence of an event, the investigator must report the event 
within 24 hours after learning of it and document the time of his/her first awareness of the 
event.
In addition to the reporting requirements to Pfizer Safety (above) the investigator must 
contact the Pfizer study physician or sponsor designee directly as soon as possible after 
becoming aware of an SAE occurring within 30 days after vaccination. Additional 
information regarding such events and the reporting requirements can be found in the SRM 
or equivalent.
For each event, the investigator must pursue and obtain adequate information both to 
determine the outcome and to assess whether it meets the criteria for classification as an SAE 
(see the Serious Adverse Events section below).  In addition, the investigator may be 
requested by Pfizer Safety to obtain specific follow-up information in an expedited fashion.  
This information is more detailed than that recorded on the CRF.  In general, this 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 
subject death, a summary of available autopsy findings must be submitted as soon as possible 
to Pfizer Safety.  Any pertinent additional information must be reported on the CT SAE 
Report Form; additional source documents (eg, medical records, CRF, laboratory data) are to 
be sent to Pfizer Safety ONLY upon request.
As part of ongoing safety reviews conducted by the sponsor, any nonserious AE that is 
determined by the sponsor to be serious will be reported by the sponsor as an SAE.  To assist 
in the determination of case seriousness, further information may be requested from the 
investigator to provide clarity and understanding of the event in the context of the clinical 
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8.1.1. Additional Details on Recording Adverse Events on the CRF
All events detailed in the table above will be recorded on the AE page(s) of the CRF.  It 
should be noted that the CT SAE Report 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 CT SAE Report 
Form for reporting of SAE information.
8.1.2. Eliciting Adverse Event Information
The investigator is to record on the CRF all directly observed AEs and all AEs spontaneously 
reported by the study subject.  In addition, each study subject will be questioned about the 
occurrence of AEs in a nonleading manner.
8.1.3. Withdrawal From the Study Due to Adverse Events (see also the Subject 
Withdrawal Section)
Withdrawal due to AEs should be distinguished from withdrawal due to other causes, 
according to the definition of AE noted below, and recorded on the CRF.  
When a subject withdraws from the study because of an SAE, the SAE must be recorded on 
the CRF and reported, as appropriate, on the CT SAE Report Form, in accordance with the 
Requirements section above.
8.1.4. Time Period for Collecting AE/SAE Information
The time period for actively eliciting and collecting AEs and SAEs and NDCMCs (“active 
collection period”) for each subject begins from the time the subject provides informed 
consent, which is obtained before the subject’s participation in the study (ie, before 
undergoing any study-related procedure and/or receiving investigational product), through 
and including Visit 2 (approximately 1 month after Visit 1).
For all subjects, SAEs and NDCMCs will be recorded and reported from the signing of the 
ICD until the final visit (approximately 6 months after Visit 1).  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.  
For subjects who are screen failures, the active collection period ends when screen failure 
status is determined.

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8.1.4.1. Reporting SAEs to Pfizer Safety
All SAEs occurring in a subject during the active collection period are reported to Pfizer 
Safety on the CT SAE Report Form.
SAEs occurring in a subject 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.
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.
8.1.4.2. Recording Nonserious AEs and SAEs on the CRF
During the active collection period, both nonserious AEs and SAEs are recorded on the CRF.
Follow-up by the investigator may be required until the event or its sequelae resolve or 
stabilize at a level acceptable to the investigator, and Pfizer concurs with that assessment.
8.1.5. Causality Assessment
The investigator’s assessment of causality must be provided for all AEs (serious and 
nonserious); the investigator must record the causal relationship on the CRF, and report such 
an assessment in accordance with the SAE reporting requirements, if applicable.  An 
investigator’s causality assessment is the determination of whether there exists a reasonable 
possibility that the investigational product caused or contributed to an AE; generally the facts 
(evidence) or arguments to suggest a causal relationship should be provided.  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.  If the investigator's causality assessment is “unknown but not 
related” to investigational product, this should be clearly documented on study records.  
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 CT SAE Report Form and in 
accordance with the SAE reporting requirements.
8.1.6. Sponsor’s Reporting Requirements to Regulatory Authorities
AE reporting, including suspected unexpected serious adverse reactions, will be carried out 
in accordance with applicable local regulations.

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8.2. Definitions
8.2.1. Adverse Events
An AE is any untoward medical occurrence in a study subject administered a product or 
medical device; the event need not necessarily have a causal relationship with the treatment 
or usage.  Examples of AEs include, but are not limited to: 

Abnormal test findings;

Clinically significant signs and symptoms;

Changes in physical examination findings;

Hypersensitivity;

Progression/worsening of underlying disease;

Drug abuse;

Drug dependency.
Additionally, AEs may include signs and symptoms resulting from:

Drug overdose;

Drug withdrawal;

Drug misuse; 

Drug interactions;

Extravasation;

Exposure during pregnancy (EDP);

Exposure via breastfeeding;

Medication error;

Occupational exposure.

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8.2.2. Abnormal Test Findings
Abnormal objective test findings should be recorded as AEs when any of the following 
conditions are met: 

Test result is associated with accompanying symptoms; and/or

Test result requires additional diagnostic testing or medical/surgical intervention; 
and/or

Test result leads to a change in study dosing (outside of any protocol-specified 
dose adjustments) or discontinuation from the study, significant additional 
concomitant drug treatment, or other therapy; and/or

Test result is considered to be an AE by the investigator or sponsor.
Merely repeating an abnormal test, in the absence of any of the above conditions, does not 
constitute an AE.  Any abnormal test result that is determined to be an error does not require 
recording as an AE.
8.2.3. Serious Adverse Events
A serious adverse event is any untoward medical occurrence at any dose that:

Results in death;

Is life-threatening (immediate risk of death);

Requires inpatient hospitalization or prolongation of existing hospitalization;

Results in persistent or significant disability/incapacity (substantial disruption of 
the ability to conduct normal life functions);

Results in congenital anomaly/birth defect.
Or that is considered to be:

An important medical event.
Medical and scientific judgment is exercised in determining whether an event is an important 
medical event.  An important medical event may not be immediately life-threatening and/or 
result in death or hospitalization.  However, if it is determined that the event may jeopardize 
the subject or may require intervention to prevent one of the other AE outcomes, the 
important medical event should be reported as serious.

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Examples of such events are 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.
Medical device complaints may meet the SAE reporting requirement criteria (see the Medical 
Device Complaint Reporting Requirements section).  An incident is any malfunction (ie, the 
failure of a device to meet its performance specifications or to perform as intended; 
performance specifications include all claims made in the labeling for the device) that, 
directly or indirectly, might lead to or might have led to the death of a subject, or user, or of 
other persons, or to a serious deterioration in their state of health.  
A serious injury that can cause a serious deterioration in state of health can include:

A life-threatening illness, even if temporary in nature;

A permanent impairment of a body function or permanent damage to a body 
structure; 

A condition necessitating medical or surgical intervention to prevent the above 
2 bulleted items;
Examples: clinically relevant increase in the duration of a surgical procedure; a 
condition that requires hospitalization or significant prolongation of existing 
hospitalization;

Any indirect harm as a consequence of an incorrect diagnostic or in vitro 
diagnostic device test results when used within the manufacturer’s instructions for 
use;

Fetal distress, fetal death, or any congenital abnormality or birth defects.
8.2.4. Hospitalization
Hospitalization is defined as any initial admission (even less than 24 hours) in a hospital or 
equivalent healthcare facility, or any prolongation of an existing admission.  Admission also 
includes transfer within the hospital to an acute/intensive care unit (eg, from the psychiatric 
wing to a medical floor, medical floor to a coronary care unit, or neurological floor to a 
tuberculosis unit).  An emergency room visit does not necessarily constitute a hospitalization; 
however, the event leading to the emergency room visit is assessed for medical importance.
Hospitalization does not include the following:

Rehabilitation facilities;

Hospice facilities;

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
Respite care (eg, caregiver relief);

Skilled nursing facilities;

Nursing homes;

Same-day surgeries (as outpatient/same-day/ambulatory procedures).
Hospitalization or prolongation of hospitalization in the absence of a precipitating clinical 
AE is not in itself an SAE.  Examples include:

Admission for treatment of a preexisting condition not associated with the 
development of a new AE or with a worsening of the preexisting condition 
(eg, for workup of a persistent pretreatment laboratory abnormality);

Social admission (eg, subject has no place to sleep);

Administrative admission (eg, for yearly physical examination);

Protocol-specified admission during a study (eg, for a procedure required by the 
study protocol);

Optional admission not associated with a precipitating clinical AE 
(eg, for elective cosmetic surgery);

Hospitalization for observation without a medical AE;

Preplanned treatments or surgical procedures.  These should be noted in the 
baseline documentation for the entire protocol and/or for the individual subject.
Diagnostic and therapeutic noninvasive and invasive procedures, such as surgery, should not 
be reported as SAEs.  However, the medical condition for which the procedure was 
performed should be reported if it meets the definition of an SAE.  For example, an acute 
appendicitis that begins during the reporting period should be reported if the SAE 
requirements are met, and the resulting appendectomy should be recorded as treatment of the 
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8.3. Severity Assessment
If required on the AE page of the CRF, the investigator will use the adjectives MILD, MODERATE, SEVERE
to describe the maximum intensity of the AE. For purposes of consistency, these intensity grades are defined as 
follows:
MILD
Does not interfere with subject's usual function.
MODERATE
Interferes to some extent with subject's usual function.
SEVERE
Interferes significantly with subject's usual function.
Note the distinction between the severity and the seriousness of an AE.  A severe event is not 
necessarily an SAE.  For example, a headache may be severe (interferes significantly with 
the subject's usual function) but would not be classified as serious unless it met one of the 
criteria for SAEs, listed above.
8.4. Special Situations
8.4.1. Protocol-Specified Serious Adverse Events
There are no protocol-specified SAEs in this study.  All SAEs will be reported to Pfizer 
Safety by the investigator as described in previous sections, and will be handled as SAEs in 
the safety database. 
8.4.2. 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 subjects, transaminase elevations are a harbinger of a more 
serious potential outcome.  These subjects fail to adapt and therefore are "susceptible" to 
progressive and serious liver injury, commonly referred to as drug-induced liver injury 
(DILI).  Subjects 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 subject 
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 

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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 subject’s 
individual baseline values and underlying conditions.  Subjects 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:

Subjects 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 subjects 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:
o
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).
o
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 subject 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, 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, alkaline phosphatase, and acetaminophen drug and/or protein adduct levels.  
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 

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collected.  Further testing for acute hepatitis A, B, C, D, and E infection and liver imaging 
(eg, biliary tract) 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.
8.4.3. Exposure to the Investigational Product 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.
8.4.3.1. Exposure During Pregnancy
Details of all pregnancies in female subjects and female partners of male subjects will be 
collected after the start of study intervention and until the end of the subject’s participation.
If a pregnancy is reported, the investigator should inform the sponsor within 24 hours of 
learning of the pregnancy 
.
Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, ectopic pregnancy) are considered SAEs.
8.4.3.2. Exposure During Breastfeeding
Scenarios of exposure during breastfeeding must be reported, irrespective of the presence of 
an associated SAE, to Pfizer Safety within 24 hours of the investigator’s awareness, using the 
CT SAE Report Form.  An exposure during breastfeeding report is not created when a Pfizer 
drug specifically approved for use in breastfeeding women (eg, vitamins) is administered in 
accord with authorized use.  However, if the infant experiences an SAE associated with such 
a drug’s administration, the SAE is reported together with the exposure during breastfeeding.
8.4.3.3. 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.
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An occupational exposure is reported to Pfizer Safety within 24 hours of the investigator’s 
awareness, using the CT SAE Report Form, regardless of whether there is an associated 
SAE.  Since the information does not pertain to a subject enrolled in the study, the 
information is not recorded on a CRF; however, a copy of the completed CT SAE Report 
Form is maintained in the investigator site file.
8.4.4. Medication Errors and Lack of Efficacy
Other exposures to the investigational product under study may occur in clinical trial settings, 
such as medication errors and lack of efficacy.
Safety Event
Recorded on the CRF
Reported on the CT SAE 
Report Form to Pfizer 
Safety Within 24 Hours of 
Awareness
Medication errors and lack of 
efficacy
All (regardless of whether 
associated with an AE)
Only if associated with an 
SAE
8.4.4.1. Medication Errors
Medication errors may result from the administration or consumption of the investigational 
product by the wrong subject, or at the wrong time, or at the wrong dosage strength.  
Medication errors include:

Medication errors involving subject 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 participating subject;

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.
Such medication errors occurring to a study participant are to be captured on the medication 
error page of the CRF, which is a specific version of the AE page.
In the event of a medication dosing error, the sponsor should be notified immediately.

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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 CT SAE Report 
Form only when associated with an SAE.
8.4.4.2. Lack of Efficacy
Lack of efficacy in an approved indication should be reported as an SAE to Pfizer Safety.
8.5. Medical Device Complaint Reporting Requirements
All medical device complaints (prefilled syringes at Visit 1), regardless of whether the 
medical device complaint is associated with an AE, will be recorded on the applicable pages 
within the CRF.  This includes potential incidents or malfunctions associated with the use of 
a medical device product.  An incident or malfunction is an event that might have led to 
death or serious deterioration in health, or if it occurred again might lead to death or serious 
deterioration in health.
Pfizer is to be notified of all medical device complaints within 24 hours of the investigator’s 
awareness of the event. 
Medical device complaints should be forwarded to Pharmaceutical Sciences.
9. DATA ANALYSIS/STATISTICAL METHODS
Methodology for summary and statistical analyses of the data collected in this study is 
outlined here and will be 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. Sample Size Determination
The study size in each cohort is not based on any formal hypothesis test for a safety or 
immunogenicity endpoint. All statistical analyses of safety and immunogenicity will be 
descriptive.
Safety Endpoints
The primary safety objective includes the endpoint of reported AEs within 1 month after
vaccination. The number of subjects receiving 20vPnC is 250 in each of Cohorts A and B.  
The number of subjects receiving 20vPnC is 125 in Cohort C. There is a greater than 90% 
chance of observing at least 1 AE in the 20vPnC group in each of Cohorts A and B, assuming 
the true rate is at least 1%.  There is a greater than 90% chance of observing at least 1 AE in 
the 20vPnC group in Cohort C, assuming the true rate is at least 2% (Table 5).

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Table 5.
Probability of Detecting at Least 1 AE in the 20vPnC Group in Cohorts A, 
B, and C
Cohort
20vPnC Sample Size
True Rate of AEs
Probability of Observing at Least 1 AE
A, B
250 per cohort
0.1%
22.1%
0.5%
71.4%
1%
91.9%
2%
99.4%
C
125
0.1%
11.8%
0.5%
46.6%
1%
71.5%
2%
92.0%
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
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9.2. Analysis Populations
Safety Population
The safety population will include all subjects who receive 1 dose of 20vPnC, 13vPnC, or 
PPSV23 and have any reported safety data.  Subjects will be included in the vaccine group 
corresponding to the vaccine actually received.  The safety population will be the only 
analysis population for safety results.  
Evaluable Immunogenicity Population 
The evaluable immunogenicity population will be the primary population for the evaluation 
of immunogenicity results. Subjects will be included in the vaccine group as randomized in 
the evaluable immunogenicity analyses.  The evaluable immunogenicity population will 
generally include any subject who:
1. receives 20vPnC as randomized,
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2. is enrolled in the appropriate cohort based on prior pneumococcal vaccination history,  
3. has Visit 2 blood collection within an appropriate window for Visit 2, 
4. has at least 1 valid and determinate OPA titer for any serotype for Visit 2, 
5. does not receive any prohibited vaccinations after vaccination and before Visit 2, and 
6. has no other major protocol deviations as determined by the clinician.
 
 
 
 
9.3. Analysis of Demographic and Clinical Characteristics
The demographic characteristics, which will include sex, race, ethnicity, smoking history, 
and age at the time of randomization, will be summarized using descriptive statistics for each 
vaccine group within each cohort.  Age at randomization will also be categorized into 65
through 69 years, 70 through 79 years, and 80 years and older for each cohort. 
9.4. Immunogenicity Analysis
Immunogenicity results from the 20vPnC group will be descriptively summarized separately 
for each cohort.  
Missing assay results will not be replaced or imputed. 
OPA LLOQ values and conventions to handle OPA titers below the LLOQ or below the limit 
of quantitation will be described in the SAP. 
All statistical analyses for serotype-specific OPA titers will be performed on the natural log 
scale.  OPA results will be reported on the original scale after back transformation. 
9.4.1. Analysis of Primary Immunogenicity Endpoints 
Serotype-specific OPA GMTs will be calculated before study vaccination and 1 month after 
vaccination.  Geometric means and their 2-sided 95% CIs will be derived by calculating 
means and CIs on the natural log scale, then exponentiating the results.  CIs will be 
calculated based on the t-distribution.
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9.4.2. Analysis of Secondary Immunogenicity Endpoints
Serotype-specific OPA geometric mean fold rises (GMFRs) will be summarized for each 
vaccine serotype from before to 1 month after vaccination.  GMFRs will be limited to 
subjects with nonmissing values both before and after vaccination.  
The percentage of subjects with ≥4-fold rise in serotype-specific OPA titer from before to 
1 month after vaccination will be provided for each serotype.  The associated 95% CIs will 
be obtained using the Clopper-Pearson method.  
The percentage of subjects with OPA titer ≥LLOQ will also be provided for each serotype at 
Visits 1 and 2.  The associated 95% CIs will be obtained using the Clopper-Pearson method.  
  
9.5. Safety Analysis 
Safety and reactogenicity results will be summarized separately for each cohort.  
9.5.1. Adverse Events
AEs will be categorized according to the Medical Dictionary for Regulatory Activities 
(MedDRA) and will be summarized by vaccine group within each cohort.  A 3-tier approach 
will be used to summarize AEs. Under this approach, AEs are classified into 1 of 3 tiers:
•
Tier 1 events (Cohorts A and B only): These are prespecified events of clinical 
importance and are identified in a list in the product’s safety review plan. p-Values and 
95% CIs for between-group comparisons (risk differences) will be provided for Tier 1 
events only for Cohorts A and B. At this development stage for 20vPnC, no Tier 1 
events have been identified.
•
Tier 2 events (Cohorts A and B only): These are events that are not Tier 1, but are 
considered “relatively common.”  A MedDRA preferred term is defined as a Tier 2 event 
if there are at least 4 events in any vaccine group in Cohort A or B. 95% CIs for 
between-group comparisons (risk differences) will be provided for Tier 2 events only for 
Cohorts A and B.
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•
Tier 3 events (all cohorts): These are events that are neither Tier 1 nor Tier 2 events. 
Counts and percentages for each group will be provided for Tier 3 events.
The Miettinen and Nurminen method73 will be used to derive the 95% CI for the risk 
difference between vaccine groups.  
9.5.2. Reactogenicity
Descriptive statistics will be provided by cohort for each reactogenicity endpoint for each 
vaccine group.  In each group, local reactions from Day 1 through Day 10 and systemic 
events from Day 1 through Day 7 after vaccination will be presented by severity and 
cumulatively across severity levels.  Descriptive statistics will include proportions of subjects
with the indicated endpoint and the associated Clopper-Pearson 95% CIs.
 
 
 
 
 
  
 
 
10. QUALITY CONTROL AND QUALITY ASSURANCE
Pfizer or its agent will conduct periodic monitoring visits during study conduct to ensure that 
the protocol and GCPs are being followed.  The monitors may review source documents to 
confirm that the data recorded on CRFs are accurate.  The investigator and institution will 
allow Pfizer monitors/auditors or its agents and appropriate regulatory authorities direct 
access to source documents to perform this verification.  This verification may also occur 
after study completion.
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During study conduct and/or after study completion, the investigator site may be subject to 
review by the institutional review board/ethics committee (IRB/EC), and/or to quality 
assurance audits performed by Pfizer, or companies working with or on behalf of Pfizer, 
and/or to inspection by appropriate regulatory authorities.
The investigator(s) will notify Pfizer or its agents immediately of any regulatory inspection 
notification in relation to the study.  Furthermore, the investigator will cooperate with Pfizer 
or its agents to prepare the investigator site for the inspection and will allow Pfizer 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 subject's medical records.  The investigator will promptly provide copies of the 
inspection findings to Pfizer or its agent.  Before response submission to the regulatory 
authorities, the investigator will provide Pfizer or its agents with an opportunity to review 
and comment on responses to any such findings.
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.
11. DATA HANDLING AND RECORD KEEPING
11.1. Case Report Forms/Electronic Data Record
As used in this protocol, the term CRF should be understood to refer to either a paper form or 
an electronic data record or both, depending on the data collection method used in this study.
A CRF is required and should be completed for each included subject.  The completed 
original CRFs are the sole property of Pfizer and should not be made available in any form to 
third parties, except for authorized representatives of Pfizer or appropriate regulatory 
authorities, without written permission from Pfizer. The investigator shall ensure that the 
CRFs are securely stored at the study site in encrypted electronic form and will be password 
protected to prevent access by unauthorized third parties.
The investigator has ultimate responsibility for the collection and reporting of all clinical, 
safety, and laboratory data entered on the CRFs and any other data collection forms (source 
documents) and ensuring that they are accurate, authentic/original, attributable, complete, 
consistent, legible, timely (contemporaneous), enduring, and available when required.  The 
CRFs must be signed by the investigator or by an authorized staff member to attest that the 
data contained on the CRFs are true.  Any corrections to entries made in the CRFs or source 
documents must be dated, initialed, and explained (if necessary) and should not obscure the 
original entry. 
In most cases, the source documents are the hospital or the physician subject chart.  In these 
cases, data collected on the CRFs must match the data in those charts. 

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In some cases, the CRF may also serve as the source document.  In these cases, a document 
should be available at the investigator site and at Pfizer that clearly identifies those data that 
will be recorded on the CRF, and for which the CRF will stand as the source document.
11.2. Record Retention
To enable evaluations and/or inspections/audits from regulatory authorities or Pfizer, the 
investigator agrees to keep records, including the identity of all participating subjects
(sufficient information to link records, eg, CRFs and hospital records), all original signed 
ICDs, copies of all CRFs, safety reporting forms, source documents, and detailed records of 
treatment disposition, and adequate documentation of relevant correspondence (eg, letters, 
meeting minutes, and telephone call reports).  The records should be retained by the 
investigator according to the ICH guidelines, according to local regulations, or as specified in 
the clinical study agreement (CSA), whichever is longer.  The investigator must ensure that 
the records continue to be stored securely for so long as they are retained.
If the investigator becomes unable for any reason to continue to retain study records for the 
required period (eg, retirement, relocation), Pfizer should be prospectively notified.  The 
study records must be transferred to a designee acceptable to Pfizer, such as another 
investigator, another institution, or an independent third party arranged by Pfizer.  
Investigator records must be kept for a minimum of 15 years after completion or 
discontinuation of the study or for longer if required by applicable local regulations.
The investigator must obtain Pfizer's written permission before disposing of any records, 
even if retention requirements have been met.
12. ETHICS
12.1. Institutional Review Board/Ethics Committee
It is the responsibility of the investigator to have prospective approval of the study protocol, 
protocol amendments, informed consent documents, and other relevant documents, 
eg, recruitment advertisements, if applicable, from the IRB/EC.  All correspondence with the 
IRB/EC should be retained in the investigator file.  Copies of IRB/EC approvals should be 
forwarded to Pfizer.
The only circumstance in which an amendment may be initiated prior to IRB/EC approval is 
where the change is necessary to eliminate apparent immediate hazards to the subjects.  In 
that event, the investigator must notify the IRB/EC and Pfizer in writing immediately after 
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12.2. Ethical Conduct of the Study
The study will be conducted in accordance with the protocol, legal and regulatory 
requirements, and the general principles set forth in the International Ethical Guidelines for 
Biomedical Research Involving Human Subjects (Council for International Organizations of 
Medical Sciences 2002), ICH Guideline for Good Clinical Practice, and the Declaration of 
Helsinki.
12.3. Subject Information and Consent
All parties will comply with all applicable laws, including laws regarding the implementation 
of organizational and technical measures to ensure protection of subject personal data. Such 
measures will include omitting subject names or other directly identifiable data in any 
reports, publications, or other disclosures, except where required by applicable laws. 
The personal data will be stored at the study site in encrypted electronic form and will be 
password protected 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, when study data are compiled for transfer to Pfizer and other authorized 
parties, subject names will be removed and will be replaced by a single, specific, numerical
code, based on a numbering system defined by Pfizer.  All other identifiable data transferred 
to Pfizer or other authorized parties will be identified by this single, subject-specific code.  
The investigator site will maintain a confidential list of subjects who participated in the 
study, linking each subject’s numerical code to his or her actual identity.  In case of data 
transfer, Pfizer will maintain high standards of confidentiality and protection of subjects’ 
personal data consistent with the CSA and applicable privacy laws.
The informed consent documents and any subject recruitment materials must be in 
compliance with ICH GCP, local regulatory requirements, and legal requirements, including 
applicable privacy laws.
The informed consent documents used during the informed consent process and any subject 
recruitment materials must be reviewed and approved by Pfizer, approved by the IRB/EC 
before use, and available for inspection.
The investigator must ensure that each study subject is fully informed about the nature and 
objectives of the study, the sharing of data relating to the study and possible risks associated 
with participation, including the risks associated with the processing of the subject’s personal 
data.  The investigator further must ensure that each study subject is fully informed about his 
or her right to access and correct his or her personal data and to withdraw consent for the 
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The investigator, or a person designated by the investigator, will obtain written informed 
consent from each subject before any study-specific activity is performed.  The investigator 
will retain the original of each subject's signed consent document.
12.4. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
regulatory authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the investigational 
product, Pfizer should be informed immediately.  
In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study subjects against any immediate hazard, and of 
any serious breaches of this protocol or of ICH GCP that the investigator becomes aware of.
13. DEFINITION OF END OF TRIAL
13.1. End of Trial in All Participating Countries 
End of trial in all participating countries is defined as last subject last visit (LSLV). After 
this time, sites will be closed out, the IRB/EC will be informed, and no further Council for 
International Organizations of Medical Sciences (CIOMS) reports will be sent.
14. SPONSOR DISCONTINUATION CRITERIA
Premature termination of this study may occur because of a regulatory authority decision, 
change in opinion of the IRB/EC, or investigational product safety problems, or at the 
discretion of Pfizer.  In addition, Pfizer retains the right to discontinue development of 
20vPnC at any time.
If a study is prematurely terminated, Pfizer will promptly notify the investigator.  After 
notification, the investigator must contact all participating subjects and the hospital pharmacy 
(if applicable) within 30 days.  As directed by Pfizer, all study materials must be collected 
and all CRFs completed to the greatest extent possible.
15. PUBLICATION OF STUDY RESULTS
15.1. Communication of Results by Pfizer
Pfizer fulfills its commitment to publicly disclose clinical trial 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 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 
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www.clinicaltrials.gov
Pfizer posts clinical trial US Basic Results on www.clinicaltrials.gov for Pfizer-sponsored 
interventional studies (conducted in patients) that evaluate the safety and/or efficacy of a 
Pfizer product, regardless of the geographical location in which the study is conducted.  US 
Basic Results are submitted for posting within 1 year of the primary completion date (PCD) 
for studies in adult populations or within 6 months of the PCD for studies in pediatric 
populations.
PCD is defined as the date that the final subject was examined or received an intervention for 
the purposes of final collection of data for the primary outcome, whether the clinical study 
concluded according to the prespecified protocol or was terminated.
EudraCT
Pfizer posts European Union (EU) Basic Results on EudraCT for all Pfizer-sponsored 
interventional studies that are in scope of EU requirements.  EU Basic Results are submitted 
for posting within 1 year of the PCD for studies in adult populations or within 6 months of 
the PCD for studies in pediatric populations.
www.pfizer.com
Pfizer posts Public Disclosure Synopses (clinical study report synopses in which any data 
that could be used to identify individual patients has been removed) on www.pfizer.com for 
Pfizer-sponsored interventional studies at the same time the US Basic Results document is 
posted to www.clinicaltrials.gov.
15.2. Publications by Investigators
Pfizer supports the exercise of academic freedom and has no objection to publication by the 
PI of the results of the study based on information collected or generated by the PI, whether 
or not the results are favorable to the Pfizer product.  However, to ensure against inadvertent 
disclosure of confidential information or unprotected inventions, the investigator will provide 
Pfizer an opportunity to review any proposed publication or other type of disclosure of the
results of the study (collectively, “publication”) before it is submitted or otherwise disclosed.
The investigator will provide any publication to Pfizer at least 30 days before it is submitted 
for publication or otherwise disclosed.  If any patent action is required to protect intellectual 
property rights, the investigator agrees to delay the disclosure for a period not to exceed an 
additional 60 days.
The investigator will, on request, remove any previously undisclosed confidential 
information before disclosure, except for any study- or Pfizer product-related information 
necessary to the appropriate scientific presentation or understanding of the study results.

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If the study is part of a multicenter study, the investigator agrees that the first publication is 
to be a joint publication covering all investigator sites, and that any subsequent publications 
by the PI will reference that primary publication.  However, if a joint manuscript has not 
been submitted for publication within 12 months of completion or termination of the study at 
all participating sites, the investigator is free to publish separately, subject to the other 
requirements of this section.
For all publications relating to the study, the institution will comply with recognized ethical 
standards concerning publications and authorship, including Section II - “Ethical 
Considerations in the Conduct and Reporting of Research” of the Uniform Requirements for 
Manuscripts Submitted to Biomedical Journals, http://www.icmje.org/index.html#authorship, 
established by the International Committee of Medical Journal Editors.
Publication of study results is also provided for in the CSA between Pfizer and the 
institution.  In this section entitled Publications by Investigators, the defined terms shall have 
the meanings given to them in the CSA.
If there is any conflict between the CSA and any attachments to it, the terms of the CSA 
control.  If there is any conflict between this protocol and the CSA, this protocol will control 
as to any issue regarding treatment of study subjects, and the CSA will control as to all other 
issues.

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pneumococcal conjugate vaccine received market authorization in Europe. Expert Rev 
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against pneumococcal pneumonia in adults. N Engl J Med. 2015;372(12):1114-1125.
42. Centers for Disease Control and Prevention. Licensure of a 13-valent pneumococcal 
conjugate vaccine (PCV13) and recommendations for use among children -- Advisory 
Committee on Immunization Practices (ACIP), 2010.  MMWR Morbid Mortal Wkly 
Rep. 2010;59(9):258-261.
43. Centers for Disease Control and Prevention. Licensure of 13-valent pneumococcal 
conjugate vaccine for adults aged 50 years and older.  MMWR Morb Mortal Wkly Rep. 
2012;61(21):394-395.
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Appendix 1. 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
AE
adverse event
ALT
alanine aminotransferase
AOM
acute otitis media
AST
aspartate aminotransferase
CAP
community-acquired pneumonia
CAPiTA
Community-Acquired Pneumonia Immunization Trial in Adults
CBER
Center for Biologics Evaluation and Research
CDC
Centers for Disease Control and Prevention
CI
confidence interval
CIOMS
Council for International Organizations of Medical Sciences
CK
creatine kinase
COPD
chronic obstructive pulmonary disease
CRF
case report form
CRM197
cross-reactive material 197
CSA
clinical study agreement
CT
clinical trial
DILI
drug-induced liver injury
DU
dispensable unit
EC
ethics committee
e-diary
electronic diary
EDP
exposure during pregnancy
EU
European Union
EudraCT
European Clinical Trials Database
FDA
Food and Drug Administration
FSH
follicle-stimulating hormone
GCP
Good Clinical Practice
GGT
gamma-glutamyl transferase
GMFR
geometric mean fold rise
GMT
geometric mean titer
HIV
human immunodeficiency virus
HRT
hormone replacement therapy
IB
investigator’s brochure
ICD
informed consent document
ICH
International Council for Harmonisation
ID
identification
IgG
immunoglobulin G
IND
investigational new drug application
INR
international normalized ratio
IP manual
Investigational Product Manual
IPD
invasive pneumococcal disease
IRB
institutional review board
CCI

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Abbreviation
Term
IRT
interactive response technology
IUD
intrauterine device
IWR
interactive Web-based response
LFT
liver function test
LLOQ
lower limit of quantitation
LRI
lower respiratory tract infection 
LSLV
last subject last visit 
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
PPSV23
23-valent pneumococcal polysaccharide vaccine
PT
prothrombin time
SAE
serious adverse event
SAP
statistical analysis plan
SRM
study reference manual
SRSD
single reference safety document
TBili
total bilirubin
ULN
upper limit of normal
US
United States
USPI
US package insert
VT
vaccine-type
WHO
World Health Organization
WOCBP
woman/women of childbearing potential 
CCI

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CCI

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CCI

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CCI

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CCI

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CCI

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