A PHASE 3, RANDOMIZED, DOUBLE-BLIND TRIAL TO EVALUATE THE SAFETY AND IMMUNOGENICITY OF A 20-VALENT PNEUMOCOCCAL CONJUGATE VACCINE (20VPNC) WHEN COADMINISTERED WITH SEASONAL INACTIVATED INFLUENZA VACCINE (SIIV) IN ADULTS ≥65 YEARS OF AGE
Phase: PHASE3
Conditions: Pneumococcal Disease
Sponsor: Pfizer

20-valent Pneumococcal Conjugate Vaccine (20vPnC)
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A PHASE 3, RANDOMIZED, DOUBLE-BLIND TRIAL TO EVALUATE THE 
SAFETY AND IMMUNOGENICITY OF A 20-VALENT PNEUMOCOCCAL 
CONJUGATE VACCINE (20VPNC) WHEN COADMINISTERED WITH 
SEASONAL INACTIVATED INFLUENZA VACCINE (SIIV) IN ADULTS 
≥65 YEARS OF AGE
Study Intervention Number:
PF-06482077
Study Intervention Name:
20-valent pneumococcal conjugate vaccine 
(20vPnC)
US IND Number:
EudraCT Number:
N/A
Protocol Number:
B7471004
Phase:
3
Short Title: Safety and Immunogenicity of 20vPnC Coadministered With SIIV in 
Adults ≥65 Years of Age 
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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Protocol Amendment Summary of Changes Table
Document History
Document
Version Date
Summary and Rationale for Changes
Original protocol
15 Jun 2020
N/A

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TABLE OF CONTENTS
LIST OF TABLES.....................................................................................................................8
LIST OF FIGURES ...................................................................................................................8
1. PROTOCOL SUMMARY.....................................................................................................9
1.1. Synopsis ....................................................................................................................9
1.2. Schema ....................................................................................................................13
1.3. Schedule of Activities .............................................................................................14
2. INTRODUCTION ...............................................................................................................16
2.1. Pneumococcal Disease ............................................................................................16
2.2. Vaccines to Prevent Pneumococcal Disease ...........................................................17
2.2.1. Pneumococcal Polysaccharide Vaccines....................................................17
2.2.2. Pneumococcal Polysaccharide Conjugate Vaccines...................................17
2.3. 13vPnC and Influenza Vaccine...............................................................................19
2.4. Development of 20vPnC .........................................................................................19
2.5. Indication.................................................................................................................20
2.6. Study Rationale .......................................................................................................20
2.7. Background .............................................................................................................20
2.7.1. Clinical Overview.......................................................................................21
2.8. Benefit/Risk Assessment.........................................................................................21
2.8.1. Risk Assessment.........................................................................................22
2.8.2. Benefit Assessment.....................................................................................24
2.8.3. Overall Benefit/Risk Conclusion................................................................24
3. OBJECTIVES, ESTIMANDS, AND ENDPOINTS ...........................................................25
4. STUDY DESIGN.................................................................................................................26
4.1. Overall Design.........................................................................................................26
4.2. Scientific Rationale for Study Design.....................................................................28
4.3. Justification for Dose ..............................................................................................29
4.4. End of Study Definition ..........................................................................................29
5. STUDY POPULATION......................................................................................................29
5.1. Inclusion Criteria.....................................................................................................29
5.2. Exclusion Criteria....................................................................................................30

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5.3. Lifestyle Considerations..........................................................................................32
5.3.1. Contraception..............................................................................................32
5.4. Screen Failures ........................................................................................................32
5.5. Criteria for Temporarily Delaying Enrollment/Randomization/Study 
Intervention Administration ......................................................................................32
5.5.1. Temporary Delay Criteria...........................................................................32
5.5.1.1. Criteria for Temporarily Delaying Vaccine 
Administration...................................................................................32
6. STUDY INTERVENTION..................................................................................................33
6.1. Study Intervention(s) Administered........................................................................33
6.1.1. Concomitant Vaccines/Medications...........................................................33
6.1.2. Administration............................................................................................34
6.1.3. Medical Devices .........................................................................................34
6.2. Preparation/Handling/Storage/Accountability ........................................................34
6.2.1. Preparation and Dispensing........................................................................36
6.2.2. Preparation/Handling by Unblinded Staff ..................................................36
6.3. Measures to Minimize Bias: Randomization and Blinding.....................................36
6.3.1. Allocation to Study Intervention ................................................................36
6.3.2. Blinding of Site Personnel..........................................................................37
6.3.3. Blinding of the Sponsor..............................................................................37
6.3.4. Breaking the Blind......................................................................................38
6.4. Study Intervention Compliance...............................................................................38
6.5. Concomitant Therapy..............................................................................................38
6.5.1. Prohibited During the Study.......................................................................38
6.5.2. Permitted During the Study ........................................................................38
6.6. Recording Prior and Concomitant Vaccines and Concomitant Treatments............39
6.7. Dose Modification...................................................................................................39
6.8. Intervention After the End of the Study..................................................................39
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL...........................................................................39
7.1. Discontinuation of Study Intervention ....................................................................39
7.2. Participant Discontinuation/Withdrawal From the Study.......................................40

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7.2.1. Withdrawal of Consent...............................................................................41
7.3. Lost to Follow-up....................................................................................................42
8. STUDY ASSESSMENTS AND PROCEDURES...............................................................42
8.1. Efficacy and/or Immunogenicity Assessments .......................................................43
8.1.1. Immunogenicity Assessments ....................................................................43
8.1.2. Biological Samples.....................................................................................44
8.2. Safety Assessments .................................................................................................44
8.2.1. Participant Electronic Diary .......................................................................45
8.2.2. Grading Scale for Prompted Events ...........................................................45
8.2.2.1. Local Reactions.........................................................................45
8.2.2.2. Systemic Events – Systemic Symptoms and Fever...................46
8.2.2.3. Use of Antipyretic/Pain Medication..........................................48
8.2.3. Participant Clinical Safety Laboratory Assessments..................................48
8.2.4. Suicidal Ideation and Behavior Risk Monitoring.......................................48
8.3. Adverse Events and Serious Adverse Events..........................................................48
8.3.1. Time Period and Frequency for Collecting AE and SAE Information.......49
8.3.1.1. Reporting SAEs to Pfizer Safety...............................................49
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF...................49
8.3.2. Method of Detecting AEs and SAEs ..........................................................50
8.3.3. Follow-up of AEs and SAEs.......................................................................50
8.3.4. Regulatory Reporting Requirements for SAEs...........................................50
8.3.5. Exposure During Pregnancy or Breastfeeding, and Occupational 
Exposure ..........................................................................................................51
8.3.5.1. Exposure During Pregnancy......................................................51
8.3.5.2. Exposure During Breastfeeding ................................................52
8.3.5.3. Occupational Exposure .............................................................53
8.3.6. Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as AEs or SAEs..............................................................................53
8.3.7. Adverse Events of Special Interest.............................................................53
8.3.7.1. Lack of Efficacy........................................................................53
8.3.8. Medical Device Deficiencies (Including Malfunctions).............................53
8.3.8.1. Time Period for Detecting Medical Device Deficiencies .........53

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8.3.8.2. Follow-up of Medical Device Deficiencies...............................54
8.3.8.3. Prompt Reporting of Device Deficiencies to Sponsor ..............54
8.3.8.4. Regulatory Reporting Requirements for Device 
Deficiencies .......................................................................................54
8.3.9. Medication Errors .......................................................................................54
8.4. Treatment of Overdose............................................................................................55
8.5. Pharmacokinetics ....................................................................................................56
8.6. Pharmacodynamics..................................................................................................56
8.9. Immunogenicity Assessments.................................................................................56
8.10. Health Economics .................................................................................................56
8.11. Study Procedures...................................................................................................56
8.11.1. Visit 1 (Vaccination 1 – Day 1)................................................................57
8.11.2. Visit 2 (Vaccination 2 – 28 to 42 Days After Visit 1 [Study Days 29 
to 43])...............................................................................................................59
8.11.3. Visit 3 (Follow-up – 28 to 42 Days After Vaccination 2 [Study 
Days 57 to 85]).................................................................................................60
8.11.4. Visit 4 (6-Month Safety Collection [Telephone Contact] – 168 to 
196 Days After Last Vaccination) ...................................................................61
8.12. Unscheduled Visits................................................................................................61
9. STATISTICAL CONSIDERATIONS ................................................................................62
9.1. Estimands and Statistical Hypotheses.....................................................................63
9.1.1. Estimands....................................................................................................63
9.1.2. Statistical Hypotheses.................................................................................63
9.1.3. Multiplicity Considerations ........................................................................64
9.2. Sample Size Determination.....................................................................................64
9.3. Analysis Sets ...........................................................................................................67
9.4. Statistical Analyses .................................................................................................67
9.4.1. Immunogenicity Analysis...........................................................................67
9.4.2. Safety Analyses ..........................................................................................71
9.5. Interim Analyses .....................................................................................................72
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10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS..........................................................................................................73
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations...............73
10.1.1. Regulatory and Ethical Considerations ....................................................73
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the 
Protocol or ICH GCP.........................................................................73
10.1.2. Financial Disclosure .................................................................................74
10.1.3. Informed Consent Process ........................................................................74
10.1.4. Data Protection .........................................................................................75
10.1.5. Dissemination of Clinical Study Data ......................................................75
10.1.6. Data Quality Assurance ............................................................................77
10.1.7. Source Documents....................................................................................78
10.1.8. Study and Site Start and Closure ..............................................................78
10.1.9. Publication Policy.....................................................................................79
10.1.10. Sponsor’s Qualified Medical Personnel .................................................80
10.2. Appendix 2: Clinical Laboratory Tests .................................................................80
10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ......................................................................81
10.3.1. Definition of AE .......................................................................................81
10.3.2. Definition of an NDCMC.........................................................................82
10.3.3. Definition of SAE.....................................................................................82
10.3.4. Recording/Reporting and Follow-up of AEs and/or SAEs.......................85
10.3.5. Reporting of SAEs....................................................................................88
10.5. Appendix 5: Genetics............................................................................................92
10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-up Assessments ........92
10.7. Appendix 7: ECG Findings of Potential Clinical Concern ...................................94
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10.8. Appendix 8: Medical Device Adverse Events, Adverse Device Effects, 
Serious Adverse Events, and Device Deficiencies: Definition and Procedures 
for Recording, Evaluating, Follow-up, and Reporting..............................................94
10.8.1. Definition of AE and ADE .......................................................................95
10.8.2. Definition of SAE, SADE, and USADE ..................................................95
10.8.3. Definition of Device Deficiency...............................................................96
10.8.4. Recording/Reporting and Follow-up of AEs and/or SAEs and 
Device Deficiencies .........................................................................................97
10.8.5. Reporting of SAEs....................................................................................99
10.8.6. Reporting of SADEs...............................................................................100
10.9. Appendix 9: Country-Specific Requirements .....................................................100
10.10. Appendix 10: Abbreviations .............................................................................101
11. REFERENCES ................................................................................................................104
LIST OF TABLES
Table 1.
Grading Scales for Local Reactions .........................................................46
Table 2.
Grading Scales for Systemic Events.........................................................47
Table 3.
Ranges for Fever.......................................................................................48
 
 
LIST OF FIGURES
Figure 1.
Schema......................................................................................................13
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1. PROTOCOL SUMMARY
1.1. Synopsis
Pfizer is developing a new 20vPnC candidate to expand protection against pneumococcal 
disease beyond that covered by current pneumococcal vaccines in children and adults.  
20vPnC has the same composition as 13vPnC (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 and contains the same 
excipients as 13vPnC.  20vPnC is in late-stage clinical development, and data from Phase 3 
studies in adults 18 years of age and above provide evidence that the safety profile is 
acceptable and similar to 13vPnC, and induces immune responses that are expected to 
support licensure for an adult (≥18 years of age) indication.
Annual seasonal influenza vaccination is recommended in a number of countries around the 
world to prevent influenza in adults, particularly adults with risk factors for increased 
influenza morbidity and mortality, such as those ≥65 years of age.  Currently, 13vPnC is also 
recommended for vaccination of adults in that same age group, based on shared 
decision-making between an individual and their healthcare practitioner.  Therefore, upon 
introduction of 20vPnC for immunization of adults, it is possible that it may be administered 
with influenza vaccine during influenza season.
The purpose of this study is to assess the safety and immunogenicity of 20vPnC and SIIV 
when given together at the same visit compared to the vaccines given 1 month apart 
(SIIV followed 1 month later by 20vPnC) in adults ≥65 years of age.  Adults in this age 
group may be naïve to pneumococcal vaccine or have received prior pneumococcal vaccines,
such as PPSV23, 13vPnC, or both; this study will endeavor to enroll participants with these 
vaccine histories.
Short Title:
Safety and Immunogenicity of 20vPnC Coadministered With SIIV in Adults ≥65 Years of 
Age

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Objectives, Estimands, and Endpoints
Objectives
Estimands
Endpoints
Primary Safety Objective:
Primary Safety Estimands:
Primary Safety Endpoints:
To describe the safety profile of 
20vPnC when coadministered 
with or 1 month after SIIV
In participants receiving 1 dose of
20vPnC or SIIV or saline and having 
safety follow-up after vaccination from 
each vaccine group: 

The percentage of participants 
reporting prompted local reactions 
within 10 days after each 
vaccination 

The percentage of participants 
reporting prompted systemic events 
within 7 days after each vaccination 

The percentage of participants 
reporting AEs within 1 month after 
each vaccination

The percentage of participants 
reporting SAEs from the first 
vaccination up to 6 months after the 
last vaccination

The percentage of participants 
reporting any NDCMCs up to
6 months after the last vaccination

Prompted local reactions 
(redness, swelling, and 
pain at the injection site)

Prompted systemic events 
(fever, headache, fatigue, 
muscle pain, and joint 
pain)

AEs

SAEs

NDCMCs
Primary Pneumococcal 
Immunogenicity Objective: 
Primary Pneumococcal 
Immunogenicity Estimand:
Primary Pneumococcal 
Immunogenicity Endpoint:
To demonstrate that the OPA 
GMTs elicited by 20vPnC when 
coadministered with SIIV 
(20vPnC+SIIV) are noninferior 
to those elicited by 20vPnC 
when administered 1 month 
after SIIV
In participants in compliance with the 
key protocol criteria (evaluable 
participants):

GMR of the serotype-specific OPA 
titers 1 month after vaccination with 
20vPnC from the coadministration 
group to the serotype-specific OPA 
titers 1 month after vaccination with 
20vPnC from the separate-
administration group

Pneumococcal 
serotype-specific OPA 
titers
Primary SIIV Immunogenicity 
Objective:
Primary SIIV Immunogenicity 
Estimand:
Primary SIIV 
Immunogenicity Endpoint:
To demonstrate that the HAI 
GMTs elicited by SIIV when 
coadministered with 20vPnC 
(20vPnC+SIIV) are noninferior 
to those elicited by SIIV alone
In evaluable participants:

GMR of the strain-specific HAI 
titers 1 month after vaccination with 
SIIV from the coadministration 
group to the corresponding strain 
from the separate-administration 
group

Strain-specific HAI titers

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Objectives
Estimands
Endpoints
Secondary Pneumococcal 
Immunogenicity Objective:
Secondary Pneumococcal 
Immunogenicity Estimands:
Secondary Pneumococcal 
Immunogenicity Endpoint: 
To describe the fold rises of 
immune responses to 20vPnC 
when coadministered with or 
1 month after SIIV
In evaluable participants from each 
vaccine group:

GMFR in serotype-specific OPA 
titers from before vaccination to 
1 month after vaccination 

The percentage of participants with a
≥4-fold rise in serotype-specific 
OPA titers from before vaccination 
to 1 month after vaccination

Pneumococcal 
serotype-specific OPA 
titers 
Secondary SIIV 
Immunogenicity Objective:
Secondary SIIV Immunogenicity 
Estimands:
Secondary SIIV 
Immunogenicity Endpoint: 
To describe the fold rises of 
immune responses to SIIV when 
coadministered with 20vPnC or 
administered alone
In evaluable participants from each 
vaccine group:

GMFR in strain-specific HAI titers 
from before vaccination to 1 month 
after vaccination 

Strain-specific HAI titers
Overall Design
This Phase 3, multicenter, randomized, double-blind study with a 2-arm parallel design will 
be conducted at investigator sites in the United States.  The purpose of this study is to assess 
the safety and immunogenicity of 20vPnC and SIIV given together at the same visit 
compared to the vaccines given separately 1 month apart (SIIV followed by 20vPnC).  The
study design and assessments are modeled after prior concomitant studies of pneumococcal 
conjugate vaccine and influenza vaccine.  A single lot of SIIV is proposed for the study, and 
ideally this SIIV would be specifically indicated for use in adults ≥65 years of age; however, 
ultimately the SIIV used may be determined by supply availability.
Local reactions (redness, swelling, and pain at the injection site) occurring at the 20vPnC or 
saline injection site within 10 days and systemic events (fever, headache, fatigue, muscle 
pain, and joint pain) occurring within 7 days after each vaccination visit (Visit 1 and Visit 2) 
will be prompted for and collected daily by the participant in an e-diary device or application.  
Use of antipyretic/pain medications will also be prompted for and collected daily in the 
e-diary for 7 days after vaccination.
AEs will be collected from the signing of informed consent through Visit 3 (approximately 
1 month after Visit 2).  SAEs and NDCMCs will be collected from the signing of informed 
consent through 6 months after Visit 2.
To assess immunogenicity, blood will be collected at 3 study visits: at Visit 1 (prior to 
vaccination); at Visit 2 (prior to vaccination), 1 month after Visit 1; and at Visit 3, 1 month 
after Visit 2.

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Number of Participants
Approximately 1780 participants (890 per group) will be randomized for a total of 
approximately 1600 evaluable participants (assuming a 10% dropout rate).
Intervention Groups and Duration
Each participant will participate in the study for approximately 7 months.  Based on an 
estimated 3-month enrollment, the study duration will be approximately 10 months. All 
participants will receive SIIV, 20vPnC, and saline via intramuscular injection.
Statistical Methods
The primary pneumococcal and SIIV immunogenicity objectives will be evaluated by formal 
hypothesis tests for NI of coadministration of SIIV and 20vPnC (coadministration group) to 
administration of SIIV followed by 20vPnC 1 month later (separate-administration group), 
based on serotype-specific OPA GMTs and the strain-specific HAI GMTs 1 month after 
vaccination respectively. NI of the coadministration group to the separate-administration 
group for a pneumococcal serotype or an influenza strain will be declared if the lower bound 
of the 2-sided 95% CI for the GMR (coadministration group to separate-administration 
group) 1 month after vaccination is greater than 0.50 (2-fold criterion) or 0.67 (1.5-fold 
criterion), respectively.
 
 
 
Strain-specific HAI GMFR from before vaccination to 1 month after vaccination, 
The primary safety objective will be evaluated by descriptive summary statistics for local 
reactions, systemic events, and AEs (including SAEs and NDCMCs) for each vaccine group. 
A 3-tier approach will be used to summarize AEs.
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1.2. Schema
Figure 1.
Schema

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1.3. Schedule of Activities
The SoA table provides an overview of the protocol visits and procedures.  Refer to the STUDY ASSESSMENTS AND
PROCEDURES section of the protocol for detailed information on each procedure and assessment required for compliance with the 
protocol.
The investigator may schedule visits (unplanned visits) in addition to those listed in the SoA table, in order to conduct evaluations or 
assessments required to protect the well-being of the participant.
Visit Number
1
2
3
4
Visit Description
Vaccination 1
Vaccination 2
Follow-up After 
Vaccination 2
6-Month Safety 
Collection
Visit Type
Clinic Visit
Clinic Visit
Clinic Visit
Telephone Contact
Visit Window (Days)
Day 1
28 to 42 Days
After Vaccination 1
28 to 42 Days
After Vaccination 2
168 to 196 Days After 
Vaccination 2
Obtain informed consent
X
Assign participant number via the IRT
X
Record demography
X
Perform clinical assessment, including medical history 
and smoking history
X
Record pneumococcal vaccine historya
X
Record nonstudy vaccinations
X
X
Record concomitant medicationsb
X
X
X
X
Obtain prevaccination oral temperature
X
X
Contraception check, if applicablec
X
X
Review inclusion and exclusion criteria
X
Review temporary delay criteria
X
X
Review continued eligibility
X
X
Assign randomization number
X

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Visit Number
1
2
3
4
Obtain blood sample for immunogenicity (~30 mL)
Xd
Xd
X
Administer investigational product(s)e
X
X
Observe and record acute reactions for 30 minutes after 
investigational product administration
X
X
Provide a participant contact card
X
Provide participant with an e-diary (device or 
application), thermometer, and measuring device and 
instruct to collect prompted local reactions, systemic 
events, and use of pain/antipyretic medicationsf
X
Review e-diaryg
X
X
Record and report AEsh
                    X------------------------------------------------------------X
Record and report SAEs and NDCMCsi,j
               X------------------------------------------------------------------------------------X
Abbreviations: e-diary = electronic diary; IRT = interactive response technology; NDCMC = newly diagnosed chronic medical condition.
a.
The name and date of administration of any prior pneumococcal vaccines will be collected and recorded in the CRF.  The names and dates must be 
obtained from sources, such as vaccination cards or medical records.
b.
Record concomitant medications used to treat SAEs or NDCMCs.
c.
The investigator or designee will inform the participant of the need to use highly effective contraception consistently and correctly until 28 days after the 
last dose of investigational product and document the conversation and the participant’s affirmation in the participant’s chart.
d.
Blood sample will be collected prior to vaccination.
e.
Remind the participant that the use of prophylactic antipyretic/pain medication, while permitted, is not recommended on the day of investigational product 
administration (before or after vaccination).
f.
Participants will record prompted local reactions and systemic events in an e-diary 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. Participants will be instructed to 
contact the study staff or investigator if they experience redness or swelling measuring ≥20 measuring device units or severe pain at the 20vPnC/saline 
injection site or any Grade 4 prompted systemic event.
g.
Designated site staff will review e-diary data online at frequent intervals (daily is optimal) for the 10 days following each vaccination to evaluate 
participant compliance and reported events as part of the ongoing safety review. Any e-diary devices given to participants are to be collected no later than
Visit 3.
h.
AEs include nonserious AEs, SAEs, and NDCMCs.
i.
An NDCMC is defined as a disease or medical condition, not previously identified, that is expected to be persistent or otherwise long-lasting in its effects.
j.
If the participant consents, participants withdrawn from the study will receive a 6-month telephone safety follow-up after their last vaccination for 
collection of any SAEs and NDCMCs.

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2. INTRODUCTION
2.1. Pneumococcal Disease
Streptococcus pneumoniae are gram-positive encapsulated cocci that have been a leading 
cause of bacteremia, bacterial meningitis, pneumonia, and 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 and adults ≥65 years of age are at particularly increased risk.4  
Individuals with certain comorbidities and immunocompromising conditions are also at 
increased risk, including persons with chronic heart, lung, liver, and renal disease, and those 
with functional asplenia.
Surveillance studies conducted in 2010 to 2012 by the CDC found that S pneumoniae were 
among the most common bacterial pathogens identified in CAP requiring hospitalization in 
both children and adults in the United States.5,6  Bacteremic pneumococcal pneumonia 
(accounting for the majority of IPD in adults) is less common than nonbacteremic 
pneumococcal pneumonia (an estimated 3 to 10 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.1,7 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 aged ≥65 years from 2011 through 2012 corresponded to an incidence 
rate of 1347/100,000 population.8  Incidence rates were higher in adults ≥85 years of age 
(3507/100,000).  Pneumococcal pneumonia accounted for 20.6% of hospitalization with an 
incidence of 274/100,000 population.8 In a study of the global burden of LRIs using data 
from 195 countries, it was estimated that in 2016, LRIs were among the leading causes of 
death in people of all ages and pneumococcal LRIs accounted for approximately 50% of LRI 
deaths (1.2 million deaths) across all ages in 2016.9  The CDC estimated that in 2017, there 
were 31,000 cases and 3590 deaths due to IPD in the United States.10  As these numbers 
suggest, S pneumoniae remains an important cause of serious disease in the United States and 
worldwide.
S pneumoniae has been identified as one of the main pathogens in influenza-related 
secondary bacterial pneumonia. A review of Emerging Infections Network data identified 
S pneumoniae in 16% of both pediatric and adult patients with laboratory-confirmed 
influenza and secondary bacterial infection.11 Coinfection with influenza and S pneumoniae
may cause more severe disease than infection with either alone.12,13 Both pneumococcal 
pneumonia and IPD (eg, S pneumoniae isolated from a normally sterile site) have been 
associated with severe and fatal cases of influenza during influenza pandemics, including the 
influenza A(H1N1)pdm09 pandemic in 2009.14,15,16,17,18
In addition to the burden of pneumococcal pneumonia among adults, influenza is an
important contributor to adult morbidity and mortality.19 In the United States, annual
influenza vaccination is recommended for adults as the primary method for preventing
influenza illness and its complications (which may include bacterial pneumonia).20

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2.2. Vaccines to Prevent Pneumococcal Disease
2.2.1. Pneumococcal Polysaccharide Vaccines
The polysaccharide capsule has been identified as an important virulence factor for this 
pathogen.  While more than 95 pneumococcal serotypes, differentiated by their capsular 
polysaccharide composition, have been identified, serious disease is generally caused by a 
smaller subset of serotypes.21,22  Anticapsular antibodies, directed against the specific 
serotype, bind to the capsule and promote complement-mediated opsonophagocytic killing 
and clearance of the organism.23  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.24
Vaccines containing free polysaccharides have been licensed since the 1970s.  One such 
vaccine, PPSV23, has been licensed in the United States since 1983.25  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), nor do they 
generate immunologic memory, so their protective effect wanes over 2 to 5 years.4,26,27,28  
Moreover, their ability to prevent nonbacteremic pneumonia and AOM is limited or 
lacking.24,28,29,30 They also do not have an impact on nasopharyngeal carriage and, therefore,
do not afford herd protection.31 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.32,33,34  Such “hyporesponsiveness” 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 VT pneumococcus.35  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.35,36,37
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.27,38 Prevnar® (7vPnC) was the first 
pneumococcal conjugate vaccine to be licensed (2000) and was indicated for prevention of 
pneumococcal disease in infants and young children on the basis of efficacy studies.  7vPnC 
contained capsular polysaccharide conjugates for 7 pneumococcal serotypes (4, 6B, 9V, 14, 
18C, 19F, and 23F), each covalently linked to CRM197, a nontoxic variant of diphtheria toxin.  
These 7 serotypes were responsible for approximately 80% to 90% of IPD in children 
<5 years of age in the United States and approximately 60% to 80% of IPD in the same age 
group in Europe at that time (1998-2000).39,40,41,42,43  These serotypes also accounted for a 
high proportion of antibiotic-resistant strains.44  7vPnC demonstrated efficacy against 

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VT IPD, pneumonia, and AOM in large, randomized controlled efficacy studies in 
infants.45,46 The 7vPnC components contained in a related pneumococcal conjugate vaccine 
also were demonstrated to be efficacious against clinically/radiographically-defined 
pneumonia.47,48  Following the introduction of 7vPnC, a reduction of nasopharyngeal 
carriage and transmission has resulted in indirect herd effects, with a 92% reduction of 
7vPnC VT IPD in older adults ≥65 years of age.49
Prevnar 13® (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.38,42,50  The 
vaccine was licensed for use in infants and young children based on comparisons of 
serotype-specific 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 OPA responses to 
PPSV23, followed by traditional approval based on demonstration of efficacy against VT 
CAP in CAPiTA, a randomized controlled study of adults ≥65 years of age.51  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 the evidence that 
protection against IPD wanes significantly over time.26 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.52,53,54,55  It has also been prequalified by WHO for use in 
national infant immunization programs in lower- and middle-income countries.56,57
Surveillance data from several countries following the introduction of 13vPnC into the 
routine infant immunization program have demonstrated vaccine effectiveness against VT 
IPD in the vaccinated population.58,59,60
Prevnar 13 was licensed for adults ≥50 years of age in 2011 and recommended by the ACIP 
for use in adults with immunocompromising conditions in 2012.37,61,62,63  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 13 into the routine infant immunization schedule, suggesting potential value in 
direct immunization of adults rather than reliance solely on the herd effect.64  13vPnC is 
currently recommended for adults ≥65 years of age, based on shared decision-making 
between the individual and their healthcare practitioner. 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.65,66,67  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.

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2.3. 13vPnC and Influenza Vaccine
Because 13vPnC and influenza vaccine have similar target populations and might be given at 
the same visit, 3 Pfizer-sponsored trials previously evaluated the safety and immunogenicity
of 13vPnC coadministered with SIIV.68,69,70 One trial evaluated the safety and 
immunogenicity of 13vPnC coadministered with TIV among healthy adults 50 to 59 years of 
age naïve to PPSV23.68 Another trial evaluated the safety and immunogenicity of 13vPnC 
coadministered with TIV among healthy adults ≥65 years of age who were PPSV23-naïve.69
A third trial evaluated the safety and immunogenicity of 13vPnC coadministered with QIV 
among adults ≥50 years of age who received at least 1 dose of PPSV23 before study 
enrollment.70
The safety profile of 13vPnC when coadministered with SIIV was generally consistent with 
the known safety profile of 13vPnC.  Serotype-specific pneumococcal antibody responses 
generally appeared to be slightly lower when 13vPnC was coadministered with SIIV 
compared to 13vPnC administered alone, but NI was demonstrated for all (2 studies),68,70 or 
almost all (12 of 13 serotypes in 1 study),69 vaccine serotypes in the studies.  The immune 
responses to the influenza vaccine strains were comparable whether 13vPnC was 
coadministered or given separately.68,69,70
See Section 2.4 for more details about the safety and immunogenicity results for the 
13vPnC+SIIV studies.
2.4. Development of 20vPnC
The 20vPnC candidate is modeled after 7vPnC and 13vPnC.  20vPnC contains the 
polysaccharides of capsular serotypes present in 13vPnC and 7 new capsular polysaccharides 
(for serotypes 8, 10A, 11A, 12F, 15B, 22F, and 33F) individually conjugated to CRM197.  
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 (11A, 15B), association with outbreaks (8, 12F), and 
greater disease severity (eg, meningitis, mortality) (10A, 11A, and 
22F).71,72,73,74,75,76,77,78,79,80,81,82,83,84 These 7 serotypes have a long-standing association with 
serious pneumococcal disease and are responsible for a substantial burden of remaining 
pneumococcal disease.
The 20vPnC clinical development program in adults has included several trials, including: 
2 Phase 1 trials in healthy adults; 1 Phase 2 trial in adults 60 through 64 years of age; and, 
3 Phase 3 trials in adults ≥18 years of age.
In Phase 1 and Phase 2 trials, 20vPnC induced immune responses to the pneumococcal 
serotypes in the vaccine. The Phase 3 pivotal trial (B7471007) met its primary 
immunogenicity objectives of NI for all serotypes in common with licensed Prevnar 13 and 
6 of the 7 additional serotypes when compared PPSV23; 1 of the new 7 serotypes missed NI 
criteria by a small margin. Secondary immunogenicity objectives for adults 18 to 59 years of 
age compared to those 60 to 64 years of age met NI for all 20 serotypes. This suggests that 
protective antibodies against all 20 serotypes were elicited by 20vPnC, and that protection 

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against pneumococcal disease will be similar to 13vPnC. The safety objectives were met in 
adults ≥18 years of age, demonstrating that the safety and tolerability of 20vPnC were 
comparable to licensed pneumococcal vaccines.
Additionally, the Phase 3 program has demonstrated equivalence of immunogenicity among 
3 different lots of 20vPnC in a clinical lot consistency trial, and 20vPnC has acceptable 
safety and elicits immune responses to the 20 vaccine serotypes in adults previously 
vaccinated with pneumococcal vaccines.
Additional description of the clinical trial results, epidemiology of the 7 serotypes, and 
clinical (and nonclinical) program are described in the 20vPnC IB.
2.5. Indication
20vPnC is being developed in adults for the prevention of pneumococcal disease (including 
pneumonia and invasive disease) caused by S pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 8, 
9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, and 33F in adults ≥18 years of age.
2.6. Study Rationale
When an individual interacts with a healthcare provider to obtain an influenza vaccination, 
there may also be an opportunity to administer other recommended vaccines for which the 
individual may be eligible, such as pneumococcal conjugate vaccine.  Therefore, assessing 
the safety and immunogenicity of coadministration with the influenza vaccine will help 
inform potential use of 20vPnC.
The purpose of this study is to assess the safety and immunogenicity of 20vPnC and SIIV 
when given together at the same visit compared to the vaccines given 1 month apart 
(SIIV followed 1 month later by 20vPnC) in adults ≥65 years of age.  Adults in this age 
group may be naïve to pneumococcal vaccine or have received prior pneumococcal vaccines,
such as PPSV23, 13vPnC, or both. Therefore, this study will enroll participants with these 
diverse vaccine histories, although no specific proportions will be targeted. The study 
described in this protocol uses a similar design, and will perform similar assessments, as in 
prior studies of SIIV coadministration with other pneumococcal conjugate vaccines.68,69,70
2.7. Background
20vPnC is being developed to further expand protection beyond 13vPnC against the global 
burden of vaccine-preventable pneumococcal disease in children and adults.  The clinical 
development program in adults has been generally modeled on the 13vPnC program.  The 
clinical program is currently in late-stage development. To date, 2 Phase 1, 1 Phase 2, and 
3 Phase 3 studies in adults have been conducted to support licensure for an adult indication.
These are all safety and immunogenicity studies.  An application to support licensure of 
20vPnC in adults 18 years of age and above is anticipated to be submitted in late 2020.

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Upon introduction of 20vPnC in adults, healthcare providers may seek the opportunity during 
influenza season to provide 20vPnC when individuals present for their influenza vaccination.  
Therefore, data on the safety and immunogenicity of coadministration of these 2 vaccines 
will be helpful for that situation.  This Phase 3 study is designed to provide data on the safety 
profile and immunogenicity of 20vPnC and SIIV when administered at the same visit.
2.7.1. Clinical Overview
Data from Phase 1 and Phase 2 studies in adults 18 to 64 years of age found that 20vPnC 
induces immune responses to the 20 vaccine serotypes and had a safety profile consistent 
with other pneumococcal conjugate vaccines.  Additionally, safety data from 3 Phase 3 adult 
studies (B7471006, B7471007, and B7471008) have shown safety profiles consistent with 
other pneumococcal conjugate vaccines. Immunogenicity data from the pivotal Phase 3 
studies demonstrated that 20vPnC induces OPA GMTs that are noninferior to 13vPnC for the 
13 matched serotypes and noninferior to PPSV23 for 6 of the 7 additional serotypes.  The 
remaining serotype demonstrated strong immune responses.  See the 20vPnC IB for 
additional details.
2.8. Benefit/Risk Assessment
The safety profile of 20vPnC is expected to be similar to 13vPnC, but AEs may be different 
with the investigational 20vPnC. The safety profiles are expected to be similar because 
20vPnC contains the same components and excipients as 13vPnC, along with the 
polysaccharide conjugates for 7 additional pneumococcal serotypes, and to date, 20vPnC has 
demonstrated a safety profile similar to 13vPnC in clinical trials. The most common AEs 
noted in adults after vaccination are primarily related to local reactions (injection site pain, 
redness, and swelling) and systemic events (fever, headache, fatigue, joint pain, and muscle 
pain). Safety review of data from the 3 completed Phase 3 adult trials have not revealed any 
unexpected safety concerns.  See the 20vPnC IB for additional details.
As with any vaccine, an allergic reaction can occur.  The allergic reaction can vary from skin 
rash to swelling of the face or lips, wheezing, and/or shortness of breath.  A severe allergic 
reaction (anaphylactic shock, collapse, or shock-like state [hypotonic-hyporesponsive 
episode]) may also occur.  There may also be additional risks related to the vaccines 
administered in the study that are not known at this time.
Additional potential risks of clinical significance are presented in the table in Section 2.8.1
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of 20vPnC may be found in the IB, which is the SRSD for this study.  The 
SRSD for the SIIV agent is the USPI.

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2.8.1. Risk Assessment
Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Study Intervention(s): Vaccinations with 20vPnC and SIIV
20vPnC
The relevant key risks associated with 20vPnC
include: local reactions (injection site pain, 
redness, and swelling); systemic events (fever,
headache, fatigue, joint pain, and muscle 
pain); and allergic reactions, including skin 
rash, face or lip swelling, wheezing, shortness 
of breath, or severe allergic reaction 
(eg, anaphylactic shock).
The risks are based on the 20vPnC IB.
Eligibility criteria have been selected to ensure that only appropriate 
participants are included in the study (see Section 5).
E-diary and AE data will be monitored by the investigator 
(or designee) and sponsor.
Participants who develop exclusionary conditions during study 
conduct or participants with significant reactions after Visit 1 
vaccination or AEs considered by the investigator to present 
increased risk to the participant if he/she received additional study 
vaccinations will be excluded from further vaccinations.
SIIV
The relevant key risks associated with SIIV 
include: injection site pain, tenderness at the 
injection site, headache, fatigue, myalgia, and 
malaise.
The risks are based on the SIIV USPI.
Eligibility criteria have been selected to ensure that only appropriate 
participants are included in the study (see Section 5).
Participants who develop exclusionary conditions during study 
conduct or participants with significant reactions after Visit 1 
vaccinations or AEs considered by the investigator to present 
increased risk to the participant if he/she received additional study 
vaccinations will be excluded from further vaccinations.
Conjugate pneumococcal vaccine 
coadministered with SIIV.
Anticipated risks of coadministration of 
20vPnC and SIIV are based on risks of 
coadministration of 13vPnC and SIIV and 
include: possible increased incidence of local 
reactions at the 20vPnC injection site 
compared with placebo, higher proportion of 
participants reporting systemic events 
(eg, fatigue, headache, muscle pain, chills, 
rash, decreased appetite).
The risks are based on 3 clinical 
trials.68,69,70
E-diary and AE data will be monitored by the investigator 
(or designee) and sponsor.
Participants who develop exclusionary conditions during study 
conduct or participants with significant reactions after Visit 1 
vaccinations or AEs considered by the investigator to present 
increased risk to the participant if he/she received additional study 
vaccinations will be excluded from further vaccinations.

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Study Procedure: Venipuncture
There is the risk of fainting, and pain, 
swelling, bruising, and infection at the 
venipuncture site.
Venipuncture is required to collect 
immunogenicity data from participants.
Only qualified nurses, physicians, nurse practitioners, physician 
assistants, phlebotomists, or medical assistants certified or otherwise 
authorized to draw blood per the standards and procedures of the 
investigative site, as allowed by institutional, local, and country 
guidance, will be allowed to draw blood to minimize local 
complications.
Other: N/A

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2.8.2. Benefit Assessment
As described in Section 2, adults ≥65 years of age are at particularly increased risk of 
pneumococcal disease, and pneumococcal conjugate vaccines have been shown to elicit 
T-cell–dependent immune responses, which have been shown to be protective in older adults.
A safe and immunogenic pneumococcal conjugate vaccine with expanded pneumococcal 
serotype coverage would fulfill an unmet need for expanded protection against 
pneumococcal disease.
If 20vPnC is successful in Phase 3 studies and is approved, it is anticipated to provide a 
benefit to a participant in the prevention of pneumonia and invasive disease caused by 
vaccine serotypes.
The SIIV in this study is licensed by the FDA for the prevention of influenza disease due to 
the influenza strains; therefore, administration of this vaccine may help protect against 
influenza disease.
2.8.3. Overall Benefit/Risk Conclusion
Taking into account the measures taken to minimize risk to participants participating in this 
study, the potential risks of vaccination with 20vPnC or SIIV (eg, transient, mild-to-moderate 
local reactions and systemic events and risks of minor complications from intramuscular 
injections or venipuncture) are justified by the anticipated benefits that participants might 
receive (eg, possible protective immunity against vaccine-serotype S pneumoniae and 
influenza).
Pfizer considers that the available information in clinical studies conducted to date with 
20vPnC, the available safety profile of similar pneumococcal conjugate vaccines (ie, Prevnar 
and Prevnar 13), and the limited risks from study procedures support a favorable benefit-risk 
profile for 20vPnC and this study.

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3. OBJECTIVES, ESTIMANDS, AND ENDPOINTS
Objectives
Estimands
Endpoints
Primary Safety Objective:
Primary Safety Estimands:
Primary Safety Endpoints:
To describe the safety profile of 
20vPnC when coadministered 
with or 1 month after SIIV
In participants receiving 1 dose of
20vPnC or SIIV or saline and having 
safety follow-up after vaccination from 
each vaccine group: 

The percentage of participants 
reporting prompted local reactions 
within 10 days after each vaccination

The percentage of participants 
reporting prompted systemic events 
within 7 days after each vaccination

The percentage of participants 
reporting AEs within 1 month after 
each vaccination

The percentage of participants 
reporting SAEs up to 6 months after 
the last vaccination

The percentage of participants 
reporting any NDCMCs up to
6 months after the last vaccination

Prompted local reactions 
(redness, swelling, and 
pain at the injection site)

Prompted systemic events 
(fever, headache, fatigue, 
muscle pain, and joint 
pain)

AEs

SAEs

NDCMCs
Primary Pneumococcal 
Immunogenicity Objective: 
Primary Pneumococcal 
Immunogenicity Estimand:
Primary Pneumococcal 
Immunogenicity Endpoint:
To demonstrate that the OPA 
GMTs elicited by 20vPnC when 
coadministered with SIIV 
(20vPnC+SIIV) are noninferior 
to those elicited by 20vPnC 
when administered 1 month 
after SIIV
In participants in compliance with the 
key protocol criteria (evaluable 
participants):

GMR of the serotype-specific OPA 
titers 1 month after vaccination with 
20vPnC from the coadministration 
group to the serotype-specific OPA 
titers 1 month after vaccination with 
20vPnC from the separate-
administration group

Pneumococcal 
serotype-specific OPA 
titers
Primary SIIV Immunogenicity 
Objective:
Primary SIIV Immunogenicity 
Estimand:
Primary SIIV 
Immunogenicity Endpoint:
To demonstrate that the HAI 
GMTs elicited by SIIV when 
coadministered with 20vPnC 
(20vPnC+SIIV) are noninferior 
to those elicited by SIIV alone
In evaluable participants:

GMR of the strain-specific HAI 
titers 1 month after vaccination with 
SIIV from the coadministration 
group to the corresponding strain 
from the separate-administration 
group.

Strain-specific HAI titers

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Objectives
Estimands
Endpoints
Secondary Pneumococcal 
Immunogenicity Objective:
Secondary Pneumococcal 
Immunogenicity Estimands:
Secondary Pneumococcal 
Immunogenicity Endpoint: 
To describe the fold rises of 
immune responses to 20vPnC 
when coadministered with or 
1 month after SIIV
In evaluable participants from each 
vaccine group:
•
GMFR in serotype-specific OPA
titers from before vaccination to 
1 month after vaccination 
•
The percentage of participants with a 
≥4-fold rise in serotype-specific 
OPA titers from before vaccination 
to 1 month after vaccination
•
Pneumococcal 
serotype-specific OPA 
titers 
Secondary SIIV 
Immunogenicity Objective:
Secondary SIIV Immunogenicity 
Estimand:
Secondary SIIV 
Immunogenicity Endpoint: 
To describe the fold rises of 
immune responses to SIIV when 
coadministered with 20vPnC or 
administered alone
In evaluable participants from each 
vaccine group:
•
GMFR in strain-specific HAI titers 
from before vaccination to 1 month 
after vaccination 
•
Strain-specific HAI titers
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
4. STUDY DESIGN
4.1. Overall Design
This Phase 3, multicenter, randomized, double-blind study, with a 2-arm parallel design, will 
be conducted at investigator sites in the United States.  The purpose of this study is to assess 
the safety and immunogenicity of 20vPnC and SIIV when given together at the same visit 
([SIIV+20vPnC]/saline group) compared to 20vPnC given 1 month after SIIV 
([SIIV+saline]/20vPnC group).  The study design and assessments are modeled from prior 
studies of pneumococcal conjugate vaccine coadministered with influenza vaccine.68,69,70  
 
CCI
CCI

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Approximately 1780 healthy adults ≥65 years of age will be stratified by prior pneumococcal 
vaccine status (no previous pneumococcal vaccine [naïve], receipt of at least 1 dose of 
PPSV23 only, receipt of at least 1 dose of 13vPnC only, or receipt of at least 1 dose each of 
PPSV23 and 13vPnC) and randomized in 1:1 ratio to 1 of 2 groups by center-based 
randomization. The coadministration group ([SIIV+20vPnC]/saline) will receive SIIV and 
20vPnC at the same visit (Visit 1), followed 1 month later by administration of saline 
(Visit 2).  The separate-administration group ([SIIV+saline]/20vPnC) will receive SIIV and 
saline at Visit 1, followed 1 month later with 20vPnC administered at Visit 2.
Refer to Section 4.2 for the rationale behind this stratification.
If participants have received prior pneumococcal vaccination(s), the most recent dose must 
have been given ≥6 months prior to the first study vaccination.  Information on any prior 
pneumococcal vaccines will be collected at enrollment. 
 
 
 
On Day 1 (Visit 1), participants will be assessed for eligibility (including medical history and 
pneumococcal vaccine history).  If eligible, participants will have blood drawn for 
immunogenicity assessments and be randomized to receive either SIIV and 20vPnC 
([SIIV+20vPnC]/saline) or SIIV and saline ([SIIV+saline]/20vPnC). The 20vPnC and saline 
will be prepared and administered by an unblinded investigator site staff member.
Participants will be observed for 30 minutes after vaccination by blinded investigator site 
staff, and any reactions occurring during that time will be recorded as AEs.
At Visit 2, (28 to 42 days after Visit 1 [Study Days 29 to 43]), participants will return to the 
investigator site and be assessed for continued eligibility. Participants will be asked to 
provide information on any AEs (including nonserious AEs, SAEs, and NDCMCs), and on 
any needed e-diary follow-up.  Participants will also be asked for information on concomitant 
medications used to treat any SAEs or NDCMCs and on any nonstudy vaccines they received 
since Visit 1. Blood will be drawn for immunogenicity assessments. Participants will 
receive a vaccination with either saline (if the participant was in the [SIIV+20vPnC]/saline
group) or 20vPnC (if the participant was in the [SIIV+saline]/20vPnC group) and be 
observed for 30 minutes after vaccination by blinded investigator site staff; any reactions 
occurring during this time will be recorded as AEs.
At Visit 1, participants will receive an e-diary (device or mobile-device application), 
thermometer, and measuring device (caliper) and will be instructed at each vaccination visit 
(Visit 1 and Visit 2) to record prompted local reactions (redness, swelling, and pain at the 
injection site) occurring at the 20vPnC/saline injection site within 10 days after vaccination 
(Days 1 through 10, where Day 1 is the day of vaccination) and prompted systemic events 
(fever, headache, fatigue, muscle pain, and joint pain) occurring within 7 days after 
vaccination (Days 1 through 7, where Day 1 is the day of vaccination) daily in the e-diary.
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Participants will also be instructed to record any use of antipyretic/pain medications in the 
e-diary daily for 7 days after vaccination.  Participants will be instructed to contact the study 
staff if the participant experiences redness or swelling at the 20vPnC/saline injection site 
measuring >20 measuring device units (>10 cm) or severe injection site pain (prevents daily 
activity) in the 10 days after vaccination or has an emergency room visit or hospitalization.
AEs (nonserious AEs, SAEs, and NDCMCs) will be collected for each participant from the 
time informed consent is obtained through and including Visit 3.
At Visit 3 (28 to 42 days after Visit 2), participants will return to the investigator site and be 
assessed for continued eligibility.  Information will be collected from the participants on 
AEs, SAEs, NDCMCs, and e-diary follow-up (as needed). Blood will be drawn for 
immunogenicity assessment.
At Visit 4 (approximately 6 months [168 to 196 days] after Visit 2), the site will contact the 
participant via telephone to inquire about SAEs and NDCMCs and concomitant medications 
used to treat SAEs or NDCMCs since the last visit.
In the case of extreme circumstances, such as natural disasters or a pandemic, visits for 
follow-up or procedures may need to be conducted through other means (eg, telephone, home 
visits).
4.2. Scientific Rationale for Study Design
The purpose of this study is to assess the safety and immunogenicity of 20vPnC and SIIV 
given together at the same visit compared to the vaccines given separately.  This study uses a
similar design and includes similar assessments as in prior studies of SIIV coadministration 
with other pneumococcal conjugate vaccines (13vPnC and an investigational 15-valent 
pneumococcal conjugate vaccine).68,69,70,85
Additionally, this study design accounts for potential effect of prior pneumococcal vaccine 
on subsequent pneumococcal responses.  Adults ≥65 years of age may be naïve to 
pneumococcal vaccines or have been vaccinated with PPSV23 or 13vPnC in the past.  
Previous studies have found lower pneumococcal responses to pneumococcal conjugate 
vaccines among individuals vaccinated with PPSV23 compared to naïve individuals, and 
variable responses after a second dose of 13vPnC compared to naïve individuals were also 
observed.68,86
 
 
 
 
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4.3. Justification for Dose
The 20vPnC candidate is modeled after 7vPnC and 13vPnC, and contains capsular 
polysaccharides from pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 
14, 15B, 18C, 19A, 19F, 22F, 23F, and 33F individually conjugated to CRM197.  The vaccine 
formulation contains 2.2 µg of each saccharide, except for 4.4 µg of 6B, per 0.5-mL dose.  In
adults, administration of 1 dose of pneumococcal conjugate vaccine induces immune 
responses.  The SIIV will be a licensed vaccine, provided in a commercially available 
presentation, and the indicated dose will be administered.
For these products the term “dose” refers to an injection of a vaccine.
4.4. End of Study Definition
The end of the study is defined as the date of the last visit of the last participant in the study.
5. STUDY POPULATION
This study can fulfill its objectives only if appropriate participants are enrolled.  The 
following eligibility criteria are designed to select participants for whom participation in the 
study is considered appropriate.  All relevant medical and nonmedical conditions should be 
taken into consideration when deciding whether a particular participant is suitable for this 
protocol.
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted.
5.1. Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria apply:
Age and Sex:
1. Male or female participants ≥65 years of age at the time of consent.
Type of Participant and Disease Characteristics:
2. Participants who are willing and able to comply with all scheduled visits, treatment plan, 
laboratory tests, lifestyle considerations, and other study procedures.
3. 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.
4. Expected to be available for the duration of the study and can be contacted by telephone 
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5. Male participant who is able to father children and willing to use a highly effective 
method of contraception, as outlined in this protocol, for at least 28 days after the dose of 
investigational product; or female participant not of childbearing potential; or male 
participant not able to father children.  Refer to Appendix 4 for reproductive criteria for 
male (Section 10.4.1) and female (Section 10.4.2) participants.
 
6. Adults who have no history of ever receiving a pneumococcal vaccine (ie, pneumococcal
vaccine–naïve), or have a history of receiving a licensed pneumococcal vaccination 
≥6 months prior to the first vaccination in the study.
Note: For participants with a history of receiving a licensed pneumococcal vaccination,
documentation of date(s) and type(s) of prior pneumococcal vaccination(s) will be 
obtained.
Informed Consent:
7. Capable of giving signed informed consent, as described in Appendix 1, which includes 
compliance with the requirements and restrictions listed in the ICD and in this protocol.
5.2. Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions:
1. History of severe adverse reaction associated with a vaccine and/or severe allergic 
reaction (eg, anaphylaxis) to any component of 20vPnC, any other diphtheria toxoid–
containing vaccine, or SIIV.
2. Allergy to egg proteins (egg or egg products) or chicken proteins.
3. Serious chronic disorder, including metastatic malignancy, severe COPD requiring 
supplemental oxygen, end-stage renal disease with or without dialysis, cirrhosis of the 
liver, clinically unstable cardiac disease, or any other disorder that in the investigator’s 
opinion would make the participant inappropriate for entry into the study.
4. History of Guillain-Barré syndrome.
5. History of microbiologically proven invasive disease caused by S pneumoniae.
6. Known or suspected immunodeficiency or other conditions associated with 
immunosuppression, including, but not limited to, immunoglobulin class/subclass 
deficiencies, generalized malignancy, HIV infection, leukemia, lymphoma, or organ or 
bone marrow transplant.
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7. Bleeding diathesis or condition associated with prolonged bleeding that would, in the 
opinion of the investigator, contraindicate intramuscular injection.
8. Congenital, functional, or surgical asplenia.
9. Other medical or psychiatric condition, including recent (within the past year) or active 
suicidal ideation/behavior, or laboratory abnormality that may increase the risk of study 
participation or, in the investigator’s judgment, make the participant inappropriate for the 
study.
Prior/Concomitant Therapy:
10. Previous vaccination with any investigational pneumococcal vaccine, or planned receipt 
of any licensed or investigational pneumococcal vaccine through study participation.
11. Vaccination with any influenza vaccine <6 months before investigational product 
administration, or planned receipt of any licensed or investigational nonstudy influenza 
vaccine during study participation.
12. Currently receives treatment with immunosuppressive therapy, including cytotoxic agents 
or systemic corticosteroids, or planned receipt through the last blood draw (Visit 3).  If 
systemic corticosteroids have been administered short term (<14 days) for treatment of an 
acute illness, participants should not be enrolled into the study until corticosteroid 
therapy has been discontinued for at least 28 days before investigational product 
administration.  Inhaled/nebulized, intraarticular, intrabursal, or topical (skin, eyes, or 
ears) corticosteroids are permitted.
13. Receipt of blood/plasma products or immunoglobulin within the 60 days before 
investigational product administration, or planned receipt through the last planned blood 
draw in the study (through Visit 3).
Prior/Concurrent Clinical Study Experience:
14. Participation in other studies involving investigational drugs, investigational vaccines, or 
investigational devices within 28 days prior to study entry and/or during study 
participation. Participation in purely observational studies is acceptable.
Diagnostic Assessments:
Not applicable.
Other Exclusions:
15. Investigator site staff or Pfizer employees directly involved in the conduct of the study, 
site staff otherwise supervised by the investigator, and their respective family members.

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5.3. Lifestyle Considerations
5.3.1. 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 SoA, the investigator or 
designee will inform the participant of the need to use highly effective contraception 
consistently and correctly and document the conversation and the participant’s affirmation in 
the participant’s chart (participants need to affirm their consistent and correct use of at least 1 
of the selected methods of contraception).  In addition, the investigator or designee will 
instruct the participant to call immediately if the selected contraception method is 
discontinued or if pregnancy is known or suspected in the participant or partner.
5.4. Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study but 
are not subsequently randomly assigned to study intervention/enrolled in the study.  A 
minimal set of screen failure information is required to ensure transparent reporting of screen 
failure participants to meet the CONSORT publishing requirements and to respond to queries 
from regulatory authorities.  Minimal information includes demography, screen failure 
details, eligibility criteria, and any AEs and SAEs.
Individuals who do not meet the criteria for participation in this study (screen failures) may 
not be rescreened.
5.5. Criteria for Temporarily Delaying Enrollment/Randomization/Study Intervention 
Administration
The following conditions may allow a participant to be vaccinated once the conditions have 
resolved and the participant is otherwise eligible:
5.5.1. Temporary Delay Criteria
The following conditions are temporary or self-limiting and a participant may be vaccinated 
in the study once the condition(s) has/have resolved and no other exclusion criteria are met.
The Visit 1 and Visit 2 blood draws prior to vaccination should take place on the same day as 
the vaccination.
5.5.1.1. Criteria for Temporarily Delaying Vaccine Administration
•
Current febrile illness (body temperature ≥100.4°F [≥38.0°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.
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•
Receipt of short-term (<14 days) systemic corticosteroids. Investigational product 
administration should be delayed until systemic corticosteroid use has been discontinued 
for at least 28 days.  Inhaled/nebulized, intraarticular, intrabursal, or topical (skin, eyes, 
or ears) corticosteroids are permitted.
6. STUDY INTERVENTION
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, medical device(s), or study procedure(s) intended to be administered to a study 
participant according to the study protocol.
For the purposes of this protocol, the term investigational product may be used 
synonymously with study intervention.
6.1. Study Intervention(s) Administered
20vPnC and saline will be provided by the sponsor to the study sites (see Section 6.1.1 for 
SIIV supply).
20vPnC and saline will be packed and labeled as investigational product in accordance with 
current guidelines and applicable local and legal regulatory requirements.  The formulations 
of the investigational products are described below.
20vPnC is a sterile liquid suspension formulation containing saccharides from pneumococcal 
serotypes 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, 
and 33F individually conjugated to CRM197. 
 
 
20vPnC will be supplied to the site as packaged, single-use prefilled syringes.
The saline control will consist of a sterile normal saline solution for injection (0.9% sodium 
chloride injection) and will be supplied to the site as packaged single-use prefilled syringes.
6.1.1. Concomitant Vaccines/Medications
Licensed SIIV containing strains of influenza viruses that are antigenically equivalent to the 
annually recommended strains will be supplied to the site as packaged, single-use prefilled 
syringes after required regulatory and legal documents have been received by the sponsor. 
Pfizer will provide this vaccine.
 
Administration of SIIV will be recorded in the CRF.
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6.1.2. Administration
At Visit 1, all participants will receive a single dose of SIIV injected intramuscularly into the 
right deltoid.  The SIIV will be administered in an open-label fashion. Participants 
randomized to the (SIIV+20vPnC)/saline group will receive 0.5 mL of 20vPnC injected 
intramuscularly into the left deltoid, and participants randomized to the 
(SIIV+saline)/20vPnC group will receive 0.5 mL of saline injected intramuscularly into the 
left deltoid.
At Visit 2, participants randomized to the (SIIV+20vPnC)/saline group will receive 0.5 mL 
of saline intramuscularly into the left deltoid, and participants randomized into the 
(SIIV+saline)/20vPnC group will receive 0.5 mL of 20vPnC injected intramuscularly into the 
left deltoid.
The 20vPnC and saline vaccines will be administered by an unblinded third-party site staff 
member at Visit 1 and Visit 2.
Standard vaccination practices must be observed, and the vaccine must not be injected into 
the 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 study interventions should be performed by an appropriately qualified, 
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.
Study intervention administration details will be recorded on the CRF.
6.1.3. Medical Devices
In this study, medical devices being deployed are the prefilled syringes containing 20vPnC, 
saline, or SIIV.  Instructions for medical device use are provided in the IP manual or in the 
package insert.
Medical device incidents, including those resulting from malfunctions of the device, must be 
detected, documented, and reported by the unblinded study personnel throughout the study.  
6.2. Preparation/Handling/Storage/Accountability
The investigator or an approved representative, eg, pharmacist, will ensure that all 
investigational 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.
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6.2.1. Preparation and Dispensing
See the IP manual or applicable SRSD for instructions on how to prepare the study 
intervention for administration.  Study interventions 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.  The 20vPnC and saline will be prepared 
and administered by an unblinded staff member (see Section 6.2.2).
6.2.2. Preparation/Handling by Unblinded Staff
The 20vPnC and saline will be prepared by qualified unblinded site personnel according to 
the IP manual and will be administered by an unblinded site staff member at Visit 1 and 
Visit 2.  All other site staff members, including the PI, and the participant will be blinded.  
The PI will assign the responsibility of administering 20vPnC and saline to unblinded 
persons who will not participate in the evaluation of any study participant.  More than 
1 unblinded site staff member will be assigned.  A site staff member or clinic pharmacy 
should fulfill this role and must be an appropriately qualified and experienced member of the 
study staff as described in Section 6.2.1.  Contact between the unblinded site staff member 
who will administer 20vPnC and saline and study participants should be kept to a minimum.
6.3. Measures to Minimize Bias: Randomization and Blinding
As the appearances of 20vPnC and saline are different, the investigational products will be 
prepared and administered by a designated third-party unblinded site staff member. All other 
study personnel, including the PI, and the participant will be blinded. The unblinded site 
staff member(s) will not participate in participant assessments. Because all participants will 
receive SIIV at Visit 1, SIIV will be an open-label vaccination but can still be prepared and 
administered by the same designated third-party unblinded site staff member. See
Section 6.3.2 and Section 6.3.3 for more details on blinding of site staff members and 
sponsor.
6.3.1. Allocation to Study Intervention
Allocation (randomization) of participants to vaccine groups will proceed through the use of
an IRT system (IWR).  The site staff (study coordinator or specified designee) will be 
required to enter or select information, including, but not limited to, the user’s ID and 
password, the protocol number, and the participant number.  The site staff will then be 
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provided with a vaccine assignment, randomization number, and DU or container number 
when the investigational product is being supplied via the IRT system.  The IRT system will 
provide a confirmation report containing the participant number, randomization number, and 
DU or container number assigned.  The confirmation report must be stored in the site’s files.
The study-specific IRT reference manual and IP manual will provide the contact information 
and further details on the use of the IRT system.
Participants will be stratified by prior pneumococcal vaccine status (no previous 
pneumococcal vaccine [naïve], receipt of at least 1 dose of PPSV23 only or at least 1 dose of 
13vPnC only, or receipt of at least 1 dose of both PPSV23 and 13vPnC) and randomized in a 
1:1 ratio to each of the 2 vaccine groups, either the coadministration group 
([SIIV+20vPnC]/saline) or the separate-administration group ([SIIV+saline]/20vPnC group),
by center-based randomization.  Investigators will remain blinded to each participant’s 
assigned study intervention throughout the course of the study.  In order to maintain this 
blind, an otherwise uninvolved third party will be responsible for the preparation and 
dispensing of all study intervention and will endeavor to ensure that there are no differences 
in time or effort taken to administer the study intervention and no blinded site staff are able 
to view the administration.
This third party will instruct the participant to avoid discussing the packaging of the study 
intervention with the investigator.
In the event of a Quality Assurance audit, the auditor(s) will be allowed access to unblinded 
study intervention records at the site(s) to verify that randomization/dispensing has been done 
accurately.
6.3.2. Blinding of Site Personnel
Site staff taking part in any participant randomization, assessments, interviews, data 
collection, or CRF data entry, including the investigator and investigator staff, will be 
blinded to investigational product assignments during the study.
The investigational products will be prepared and administered by a designated third-party 
unblinded site staff member (see Section 6.2.2 for details).
6.3.3. Blinding of the Sponsor
Sponsor personnel directly involved in evaluating participant data will be blinded to vaccine 
assignment 
 following the principles 
outlined in the ICH E9 Statistical Principles for Clinical Trials.87  A data blinding plan will 
be created to describe the blinding requirements and unblinding events.  Laboratory 
personnel performing the immunologic assays will be blinded until all assays have been 
completed and assay results finalized.  As noted in Section 6.3.4, the investigator site staff 
will remain blinded for the duration of the study.
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6.3.4. Breaking the Blind
The study will be participant- and investigator-blinded through the duration of the study.
The IRT will be programmed with blind-breaking instructions.  In case of an emergency, the 
investigator has the sole responsibility for determining if unblinding of a participant’s 
vaccine assignment is warranted.  Participant safety must always be the first consideration in 
making such a determination.  If the investigator decides that unblinding is warranted, the 
investigator should make every effort to contact the sponsor prior to unblinding a 
participant’s vaccine assignment unless this could delay further management of the 
participant.  If a participant’s vaccine assignment is unblinded, the sponsor must be notified 
within 24 hours after breaking the blind.  The date and reason that the blind was broken must 
be recorded in the source documentation and CRF.
6.4. Study Intervention Compliance
The date and time of each dose administered will be recorded in the source documents and 
recorded in the CRF.  The blinded study intervention and study participant ID will be 
confirmed at the time of dosing by a member of the study site staff other than the person 
administering the study intervention.
6.5. Concomitant Therapy
6.5.1. Prohibited During the Study

Receipt of any investigational vaccines, drugs, or medical devices is prohibited during 
study participation.

Receipt of nonstudy pneumococcal or influenza vaccine is prohibited during study 
participation.

Receipt of any other licensed nonstudy vaccine is prohibited until after Visit 3, unless 
medically necessary, in which case every effort should be made to separate inactivated 
vaccines by 14 days and live vaccines by 28 days from the study vaccination visits.

Receipt of blood/plasma products, immunoglobulins, and/or immunosuppressive therapy 
(including a ≥14-day course of systemic corticosteroids) is prohibited through Visit 3.
6.5.2. Permitted During the Study

Prescription and nonprescription medications, vitamins, minerals, and herbal remedies 
are permitted during participation in the study.

The use of prophylactic antipyretic/pain medication, while permitted, is not 
recommended on the day of investigational product administration (before or after 
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
Inhaled/nebulized, topical (eg, skin, eyes, or ears), or localized injections of 
corticosteroids (eg, intraarticular or intrabursal administration) are permitted during study 
participation.
6.6. Recording Prior and Concomitant Vaccines and Concomitant Treatments
The name and date of administration of any prior pneumococcal vaccines will be collected 
and recorded in the CRF. The name(s) and date(s) of administration are to be obtained from 
sources, such as medical records or vaccination cards.
The name and date of administration for all nonstudy vaccinations received from the time of 
signing of the ICD to Visit 3 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 4 
will be recorded in the CRF.
6.7. Dose Modification
Not applicable.
6.8. Intervention After the End of the Study
There is no intervention at the end of the study.
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL
7.1. Discontinuation of Study Intervention
Participant eligibility must be confirmed prior to each vaccination in order to continue in the 
study.
If a participant no longer meets the eligibility criteria during the vaccination period of the 
study, further vaccinations should be discontinued, but the participant may remain in the 
study.  If a participant is discontinued from vaccination and the participant consents, safety 
follow-up will be conducted as per Section 8.3 (AEs will be collected for 1 month after the 
last study vaccination and SAEs will be collected for 6 months after the last study 
vaccination).
In rare instances, it may be necessary for a participant to permanently discontinue study 
intervention (definitive discontinuation).  Reasons for definitive discontinuation of study 
intervention include the following: participant no longer meets eligibility criteria, specific 
protocol deviations, withdrawal by participant, and certain AEs or SAEs.
Note that discontinuation of study intervention does not represent withdrawal from the study.  
Per the study estimands, if study intervention is discontinued, the participant will remain in 
the study to be evaluated for safety.  See the SoA for data to be collected at the time of 
discontinuation of study intervention and follow-up for any further evaluations that need to 
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In the event of discontinuation of study intervention, it must be documented on the 
appropriate CRF/in the medical records whether the participant is only discontinuing further 
receipt of study intervention or also withdrawing from study procedures, postvaccination 
study follow-up, and/or future collection of additional information.
7.2. Participant Discontinuation/Withdrawal From the Study
A participant may withdraw from the study at any time at his/her own request.  Reasons for 
withdrawal from the study include the following:

Refused further follow-up;

Lost to follow-up;

Death;

Study terminated by sponsor;

AE;

Physician decision;

Pregnancy;

Protocol deviation;

Screen failure;

Withdrawal by participant;

Medication error without associated AE;

No longer meets eligibility criteria;

Other.
A participant may withdraw from the study at any time at his/her own request, or may be 
withdrawn at any time at the discretion of the investigator or sponsor for safety, behavioral, 
compliance, or administrative reasons.
If a participant does not return for a scheduled visit, every effort should be made to contact 
the participant.  All attempts to contact the participant and information received during 
contact attempts must be documented in the participant’s source document.  In any 
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At the time of discontinuing, please refer to the ISF and SoA for assessments to be collected 
at the time of study discontinuation and follow-up and for any further evaluations that need 
to be completed.
Participants should ideally notify the investigator in writing of the decision to withdraw 
consent from future follow-up, whenever possible.  Participants should be questioned 
regarding their reason for withdrawal. The investigator or his or her designee should capture 
the reason for withdrawal in the CRF for all participants.
The participant should be requested to return for a final visit, if applicable, and the 
investigator will perform the procedures indicated for the next visit, agreed to by the 
participant.  Any AEs or SAEs that are continuing at the time of withdrawal from the study 
should be followed until resolution or, in case of permanent impairment, until the condition 
stabilizes.
A final telephone contact 6 months after the last vaccination (Section 8.3) for the collection 
of safety information should be completed for all participants who have been withdrawn after 
administration of investigational product, unless consent for further contact has been 
withdrawn, or the participant is lost to follow-up. Participant withdrawal should be 
explained in the source documents and should include whether the withdrawal is only from 
further receipt of investigational product or also from study procedures and/or 
postvaccination study follow-up.
If a participant withdraws from the study, he/she may request destruction of any remaining 
samples taken and not tested, but data already generated from the samples will continue to be 
available and may be used to protect the integrity of existing analyses; the investigator must 
document any such requests in the site study records and notify the sponsor accordingly.
If the participant withdraws from the study and also withdraws consent (see Section 7.2.1) 
for disclosure of future information, no further evaluations should be performed and no 
additional data should be collected.  The sponsor may retain and continue to use any data 
collected before such withdrawal of consent.
When a participant is withdrawn from the study because of an SAE, the SAE must be 
recorded on the CRF and reported on the Vaccine SAE Reporting Form. If a participant is 
withdrawn due to an AE, the AE must be recorded on the CRF.
Lack of completion of all or any of the withdrawal/early termination procedures will not be 
viewed as protocol deviations so long as the participant’s safety was preserved.
7.2.1. Withdrawal of Consent
Participants who request to discontinue receipt of study intervention will remain in the study 
and must continue to be followed for protocol-specified follow-up procedures.  The only 
exception to this is when a participant specifically withdraws consent for any further contact 
with him or her or persons previously authorized by the participant to provide this 
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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 study intervention 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 participant 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.
7.3. Lost to Follow-up
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit or fails to respond to the 6-month safety follow-up telephone call:

The site must attempt to contact the participant and reschedule the missed visit as soon as 
possible and counsel the participant on the importance of maintaining the assigned visit 
schedule and ascertain whether or not the participant wishes to and/or should continue in 
the study;

Before a participant is deemed lost to follow-up, the investigator or designee must make 
every effort to regain contact with the participant (where possible, 3 telephone calls and, 
if necessary, a certified letter to the participant’s last known mailing address or local 
equivalent methods).  These contact attempts should be documented in the participant’s 
medical record;

Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study.
Discontinuation of specific sites or of the study as a whole is handled as part of
Section 10.1.8 (Appendix 1).
8. STUDY ASSESSMENTS AND PROCEDURES
The investigator (or an appropriate delegate at the investigator site) must obtain a signed and 
dated ICD before performing any study-specific procedures.
The date of birth will be collected to critically evaluate the immune response and safety
profile by age.
Study procedures and their timing are summarized in Section 8.11 and in the SoA.  Protocol
waivers or exemptions are not allowed.
Safety issues should be discussed with the sponsor immediately upon occurrence or 
awareness to determine whether the participant should continue or discontinue study 
intervention.

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Adherence to the study design requirements, including those specified in Section 4 and in the 
SoA, is essential and required for study conduct.
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria.  The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable.
Every effort should be made to ensure that protocol-required tests and procedures are 
completed as described.  However, it is anticipated that from time to time there may be 
circumstances outside the control of the investigator that may make it unfeasible to perform 
the test.  In these cases, the investigator must take all steps necessary to ensure the safety and 
well-being of the participant.  When a protocol-required test cannot be performed, the 
investigator will document the reason for the missed test and any corrective and preventive 
actions that he or she has taken to ensure that required processes are adhered to as soon as 
possible.  The study team must be informed of these incidents in a timely manner.
For samples being collected and shipped, detailed collection, processing, storage, and 
shipment instructions and contact information will be provided to the investigator site prior 
to initiation of the study. See the laboratory manual for details.
The total blood-sampling volume for individual participants in this study is approximately 
90 mL.
8.1. Efficacy and/or Immunogenicity Assessments
8.1.1. Immunogenicity Assessments
Blood samples (approximately 30 mL) will be collected from all participants at Visit 1 
(prior to administration of SIIV and blinded vaccine), Visit 2 (1 month [28 to 42 days] after 
administration of vaccines at Visit 1, and prior to blinded vaccine at Visit 2), and Visit 3 
(1 month [28 to 42 days] after vaccination at Visit 2).  Sample collection, processing, storage, 
and shipping information can be found in the SRM or equivalent manual.
Pneumococcal Responses
OPA Responses to the 20vPnC Serotypes
OPA titers for the 20vPnC serotypes will be measured in sera collected at Visits 1, 2, and 3.
SIIV Responses
HAI titers to the influenza strains in the SIIV administered will be determined on sera 
collected at Visits 1 and 2 (prior to and 1 month [28 to 42 days] after SIIV administration).

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8.1.2. Biological Samples
Serum samples will be used only for scientific research.  Each sample will be labeled with a 
code so that the laboratory personnel testing the samples will not know the participant’s 
identity.  Samples that remain after performing assays outlined in the protocol may be stored 
by Pfizer.  Unless a time limitation is required by local regulations or ethical requirements, 
the samples will be stored for up to 15 years after the end of the study and then destroyed. 
 
 No testing of the participant’s genetic material will be performed.
The participant 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 participant’s genetic material is performed.
8.2. Safety Assessments
A clinical assessment, including medical history and measurement of oral temperature, will 
be performed on all participants prior to any vaccination at Visit 1 to determine participant 
eligibility and to establish a clinical baseline.  Significant medical history and significant 
findings from any physical examination (if performed) will be recorded as medical history in 
the CRF.  Temperature measurement prior to vaccination at Visits 1 and 2 will be 
documented and recorded in the CRF.
The participant will be observed for 30 minutes after each study vaccination and any 
reactions occurring during that time will be recorded as AEs.
Prompted e-diary events, including local reactions (redness, swelling, and pain at the 
injection site) at the site of the 20vPnC or saline injection and systemic events (fever, 
headache, fatigue, muscle pain, and joint pain) that occur 10 and 7 days, respectively, after 
each vaccination at Visit 1 and Visit 2 (where Day 1 is the day of vaccination), are graded as 
described in Section 8.2.2.1 and Section 8.2.2.2.  Furthermore, AEs, SAEs, and NDCMCs 
will be collected as defined in Section 8.3.
Planned time points for all safety assessments are provided in the SoA.  Unscheduled clinical 
laboratory measurements may be obtained at any time during the study to assess any 
perceived safety issues.
CCI
CCI

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8.2.1. Participant Electronic Diary
Participants will be asked to monitor and record local reactions and systemic events using an 
e-diary (in a provisioned device or an application on a personal device).  Use of 
antipyretic/pain medication will also be collected. This allows recording of these 
assessments only within a fixed time window, thus providing the accurate representation of 
the participant’s experience.  Data reported in 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 participant is 
withdrawn because of prompted events reported in the e-diary, the event(s) should be 
recorded on the AE page of the CRF, regardless of whether the investigator considers the 
event(s) to be clinically significant.
The investigator or designee must obtain stop dates for any local reactions and specific 
systemic events that were ongoing on the last day that the e-diary was completed.  The stop 
dates should be entered in the CRF.  Because chronic use of antipyretic/pain medication is 
very common in this population and is not being used as a surrogate for an adverse 
sign/symptom, a stop date will not be sought if antipyretic/pain medication use is present on 
the last day that the e-diary was completed.
Investigators (or an appropriately qualified designee) are required to review the e-diary data 
online at frequent intervals (daily is optimal) to evaluate participant compliance and reported 
events as part of the ongoing safety review.
8.2.2. Grading Scale for Prompted Events
The grading scales used in this study to assess prompted events as described below are based 
on concepts outlined in the FDA CBER guidelines on toxicity grading scales for healthy 
adult volunteers enrolled in preventive vaccine clinical trials.88
8.2.2.1. Local Reactions
For the first 10 days following each study vaccination (Days 1 through 10, where Day 1 is 
the day of vaccination), the participants will be asked to assess redness, swelling, and pain at 
the blinded vaccine (20vPnC or saline) injection site and to record the symptoms in the 
e-diary in the evening.  Redness and swelling will be measured and recorded in measuring 
device (caliper) units (range: 1 to 21+) and then categorized during analysis as mild, 
moderate, or severe based on the grading scale in Table 1.  Measuring device units can be 
converted to centimeters according to the following scale: 1 measuring device unit = 0.5 cm.  
Pain at the vaccine injection site will be assessed by the participant as mild, moderate, or 
severe according to the grading scale in Table 1.  The participant will be prompted to contact 
the investigator if he/she experiences a severe (Grade 3 or above) local reaction 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 participant’s local reaction as Grade 4, after physical 
examination of the participant or documentation from another medically qualified source 
(eg, emergency room or hospital record).  If a participant experiences a Grade 4 local 
reaction, the investigator must immediately notify the sponsor.  Site staff will educate the 
participants 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 10.3.4).
The procedure for notification of the sponsor is provided in the ISF or equivalent.
Table 1.
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.
Participants experiencing Grade 3 local reactions are required to contact the investigator site.  In the event 
that the participant does not call, the investigator will call the participant.
b.
Grade 4 assessment should be made by the investigator; Grade 4 local reactions will not be collected in 
the e-diary but will be collected as AEs on the CRF.  The severity of the local reaction should be graded 
using the AE severity grading scale in Section 10.3.4.
c.
Prevents daily activity, eg, results in missed days of work or is otherwise incapacitating.
8.2.2.2. Systemic Events – Systemic Symptoms and Fever
From Day 1 through Day 7 following vaccination at Visit 1 and Visit 2, where Day 1 is the 
day of vaccination, participants 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 participant as mild, moderate, or severe according to the grading scale in 
Table 2 below.  Participants 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) 

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within 7 days after vaccination.  Study staff may also contact the participant to obtain 
additional information on Grade 3 events entered into the e-diary.
Only an investigator is able to classify a participant’s systemic event as Grade 4, after 
physical examination of the participant or documentation from another medically qualified 
source (eg, emergency room or hospital record) or telephone contact with the participant.  If 
a participant 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 (See Section 10.3.4).
The procedure for notification of the sponsor is provided in the SRM or equivalent.
Table 2.
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 is otherwise incapacitating; includes 
use of narcotics for analgesia.
b.
Grade 4 assessment should be made by the investigator; Grade 4 systemic events will not be collected in 
the e-diary but will be collected as AEs on the CRF.  The severity of the systemic event should be graded 
using the AE severity grading scale in Section 10.3.4.
8.2.2.2.1. Fever
In order to record information on fever, a digital thermometer will be given to the participant 
with instructions on how to measure oral temperature at home.  Temperature will be 
collected in the evening daily for 7 days following each vaccination (Days 1 through 7, 
where Day 1 is the day of vaccination) and at any time during the 7 days that fever is 
suspected.  Fever is defined as an oral temperature of ≥100.4°F (≥38.0°C).  The highest 

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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 the fever has resolved (1 day of temperature 
<100.4°F [<38.0°C]) in order to collect a stop date in the CRF.  Participants reporting a fever 
>40.0°C will be prompted to contact the study site. Study staff may also contact the 
participant to obtain additional information if a temperature of >102.0°F is entered into an 
e-diary.  Temperature will be measured and recorded to 1 decimal place.
Temperatures reported in degrees Fahrenheit will be programmatically converted to degrees 
Celsius for reporting. Fever will be grouped into ranges for the analysis according to 
Table 3.
Table 3.
Ranges for Fever
38.0°C to 38.4°C
>38.4°C to 38.9°C
>38.9°C to 40.0°C
>40.0°Ca
Note: Fever is defined as a temperature of ≥38.0°C.
a.
Participants reporting a fever >40.0°C will be prompted to contact the study site.
8.2.2.3. Use of Antipyretic/Pain Medication
The participant 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 each vaccination (Days 1 through 7, where 
Day 1 is the day of vaccination).  Antipyretic/pain medication includes chronic use of 
NSAIDs; however, use of low-dose aspirin (<325 mg) should not be recorded in the e-diary.
8.2.3. Participant Clinical Safety Laboratory Assessments
Clinical safety laboratory assessments will not be collected in this study.
8.2.4. Suicidal Ideation and Behavior Risk Monitoring
Not applicable.
8.3. Adverse Events and Serious Adverse Events
The definitions of an AE and an SAE can be found in Section 10.3.
AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, or 
the participant's legally authorized representative).
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible to pursue 
and obtain adequate information both to determine the outcome and to assess whether the 
event meets the criteria for classification as an SAE or caused the participant to discontinue 
the study intervention (see Section 7.1).

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Each participant will be questioned about the occurrence of AEs in a nonleading manner.
In addition, the investigator may be requested by Pfizer Safety to obtain specific follow-up 
information in an expedited fashion.
8.3.1. Time Period and Frequency for Collecting AE and SAE Information
The time period for actively eliciting and collecting AEs and SAEs (“active collection 
period”) for each participant begins from the time the participant provides informed consent, 
which is obtained before the participant’s participation in the study (ie, before undergoing 
any study-related procedure and/or receiving study intervention), through and including 
Visit 3.  At Month 7 (Visit 4, final telephone contact), the participant will be contacted by 
telephone to inquire about SAEs, including hospitalizations and NDCMCs, since Visit 3.
Follow-up by the investigator continues throughout and after the active collection period and 
until the AE or SAE or its sequelae resolve or stabilize at a level acceptable to the 
investigator and Pfizer concurs with that assessment.
For participants who are screen failures, the active collection period ends when screen failure 
status is determined.
If the participant withdraws from the study and also withdraws consent for the collection of 
future information, the active collection period ends when consent is withdrawn.
If a participant definitively discontinues or temporarily discontinues study intervention 
because of an AE or SAE, the AE or SAE must be recorded on the CRF and the SAE 
reported using the Vaccine SAE Reporting Form.
Investigators are not obligated to actively seek AEs or SAEs after the participant has 
concluded study participation.  However, if the investigator learns of any SAE, including a 
death, at any time after a participant has completed the study, and he/she considers the event 
to be reasonably related to the study intervention, the investigator must promptly report the 
SAE to Pfizer using the Vaccine SAE Reporting Form.
8.3.1.1. Reporting SAEs to Pfizer Safety
All SAEs occurring in a participant during the active collection period, as described in 
Section 8.3.1, are reported to Pfizer Safety on the Vaccine SAE Reporting Form immediately 
upon awareness and under no circumstance should this exceed 24 hours, as indicated in 
Appendix 3.  The investigator will submit any updated SAE data to the sponsor within 
24 hours of it being available.
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF
All nonserious AEs and SAEs occurring in a participant during the active collection period, 
which begins after obtaining informed consent as described in Section 8.3.1, will be recorded 
on the AE section of the CRF.

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The investigator is to record on the CRF all directly observed and all spontaneously reported 
AEs and SAEs reported by the participant.
8.3.2. Method of Detecting AEs and SAEs
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix 3.
Care will be taken not to introduce bias when detecting AEs and/or SAEs.  Open-ended and 
nonleading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences.
8.3.3. Follow-up of AEs and SAEs
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts.  For each event, the investigator must pursue and 
obtain adequate information until resolution, stabilization, the event is otherwise explained, 
or the participant is lost to follow-up (as defined in Section 7.3).
In general, follow-up information will include a description of the event in sufficient detail to 
allow for a complete medical assessment of the case and independent determination of 
possible causality.  Any information relevant to the event, such as concomitant medications 
and illnesses, must be provided.  In the case of a participant death, a summary of available 
autopsy findings must be submitted as soon as possible to Pfizer Safety.
Further information on follow-up procedures is given in Appendix 3.
8.3.4. Regulatory Reporting Requirements for SAEs
Prompt notification by the investigator to the sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities toward the safety of participants and the safety of a 
study intervention under clinical investigation are met.
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation.  The 
sponsor will comply with country-specific regulatory requirements relating to safety 
reporting to the regulatory authority, IRBs/ECs, and investigators.
Investigator safety reports must be prepared for SUSARs according to local regulatory 
requirements and sponsor policy and forwarded to investigators, as necessary.
An investigator who receives SUSARs or other specific safety information (eg, summary or 
listing of SAEs) from the sponsor will review and then file it along with the SRSD(s) for the 
study and will notify the IRB/EC, if appropriate, according to local requirements.

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8.3.5. Exposure During Pregnancy or Breastfeeding, and Occupational Exposure
Exposure to the study intervention under study during pregnancy or breastfeeding and 
occupational exposure are reportable to Pfizer Safety within 24 hours of investigator 
awareness.
8.3.5.1. Exposure During Pregnancy
An EDP occurs if:

A female participant is found to be pregnant while receiving or after discontinuing study 
intervention.

A male participant who is receiving or has discontinued study intervention exposes a 
female partner prior to or around the time of conception.

A female is found to be pregnant while being exposed or having been exposed to study 
intervention due to environmental exposure.  Below are examples of environmental EDP:

A female family member or healthcare provider reports that she is pregnant after 
having been exposed to the study intervention by injection.
The investigator must report EDP to Pfizer Safety within 24 hours of the investigator’s 
awareness, irrespective of whether an SAE has occurred.  The initial information submitted 
should include the anticipated date of delivery (see below for information related to 
termination of pregnancy).

If EDP occurs in a participant or a participant’s partner, the investigator must report this 
information to Pfizer Safety on the Vaccine SAE Reporting Form and EDP Supplemental 
Form, regardless of whether an SAE has occurred.  Details of the pregnancy will be 
collected after the start of study intervention and until the final telephone contact 
(Visit 4).

If EDP occurs in the setting of environmental exposure, the investigator must report 
information to Pfizer Safety using the Vaccine SAE Reporting Form and EDP 
Supplemental Form.  Since the exposure information does not pertain to the participant 
enrolled in the study, the information is not recorded on a CRF; however, a copy of the 
completed Vaccine SAE Reporting Form is maintained in the ISF.
Follow-up is conducted to obtain general information on the pregnancy and its outcome for 
all EDP reports with an unknown outcome.  The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify Pfizer Safety of the outcome as a 
follow-up to the initial EDP Supplemental Form.  In the case of a live birth, the structural 
integrity of the neonate can be assessed at the time of birth.  In the event of a termination, the 
reason(s) for termination should be specified and, if clinically possible, the structural 
integrity of the terminated fetus should be assessed by gross visual inspection (unless 

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preprocedure test findings are conclusive for a congenital anomaly and the findings are 
reported).
Abnormal pregnancy outcomes are considered SAEs.  If the outcome of the pregnancy meets 
the criteria for an SAE (ie, ectopic pregnancy, spontaneous abortion, intrauterine fetal 
demise, neonatal death, or congenital anomaly), the investigator should follow the procedures 
for reporting SAEs.  Additional information about pregnancy outcomes that are reported to 
Pfizer Safety as SAEs follows: 

Spontaneous abortion, including miscarriage and missed abortion;

Neonatal deaths that occur within 1 month of birth should be reported, without regard to 
causality, as SAEs.  In addition, infant deaths after 1 month should be reported as SAEs 
when the investigator assesses the infant death as related or possibly related to exposure 
to the study intervention.
Additional information regarding the EDP may be requested by the sponsor.  Further 
follow-up of birth outcomes will be handled on a case-by-case basis (eg, follow-up on 
preterm infants to identify developmental delays).  In the case of paternal exposure, the 
investigator will provide the participant with the Pregnant Partner Release of Information 
Form to deliver to his partner.  The investigator must document in the source documents that 
the participant was given the Pregnant Partner Release of Information Form to provide to his 
partner.
8.3.5.2. Exposure During Breastfeeding
An exposure during breastfeeding occurs if: 

A female participant is found to be breastfeeding while receiving or after discontinuing 
study intervention.

A female is found to be breastfeeding while being exposed or having been exposed to 
study intervention (ie, environmental exposure).  An example of environmental exposure 
during breastfeeding is a female family member or healthcare provider who reports that 
she is breastfeeding after having been exposed to the study intervention by inhalation or 
skin contact.
The investigator must report exposure during breastfeeding to Pfizer Safety within 24 hours 
of the investigator’s awareness, irrespective of whether an SAE has occurred.  The 
information must be reported using the Vaccine SAE Reporting Form.  When exposure
during breastfeeding occurs in the setting of environmental exposure, the exposure 
information does not pertain to the participant enrolled in the study, so the information is not 
recorded on a CRF.  However, a copy of the completed Vaccine SAE Reporting Form is 
maintained in the ISF.

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An exposure during breastfeeding report is not created when a Pfizer drug specifically 
approved for use in breastfeeding women (eg, vitamins) is administered in accord with 
authorized use.  However, if the infant experiences an SAE associated with such a drug, the 
SAE is reported together with the exposure during breastfeeding.
8.3.5.3. Occupational Exposure
An occupational exposure occurs when a person receives unplanned direct contact with the 
study intervention, which may or may not lead to the occurrence of an AE.  Such persons 
may include healthcare providers, family members, and other roles that are involved in the 
trial participant’s care.
The investigator must report occupational exposure to Pfizer Safety within 24 hours of the 
investigator’s awareness, regardless of whether there is an associated SAE.  The information 
must be reported using the Vaccine SAE Reporting Form.  Since the information does not 
pertain to a participant enrolled in the study, the information is not recorded on a CRF; 
however, a copy of the completed Vaccine SAE Reporting Form is maintained in the ISF.
8.3.6. Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as AEs 
or SAEs
Not applicable.
8.3.7. Adverse Events of Special Interest
Not applicable.
8.3.7.1. Lack of Efficacy
Lack of efficacy in an approved indication should be reported as an SAE to Pfizer Safety.
8.3.8. Medical Device Deficiencies (Including Malfunctions)
Medical devices are being provided for use in this study for the purposes of administering the 
investigational product and the SIIV in prefilled syringes.  In order to fulfill regulatory 
reporting obligations worldwide, the investigator or unblinded site staff is responsible for the 
detection and documentation of events meeting the definitions of device deficiency that occur 
during the study with such devices.
The definition of a medical device deficiency can be found in Appendix 8.
Note: Deficiencies fulfilling the definition of an AE/SAE will also follow the processes 
outlined in Section 8.3.1 through 8.3.4 and Appendix 3 of the protocol.
8.3.8.1. Time Period for Detecting Medical Device Deficiencies
Medical device deficiencies or malfunctions of the device will be detected, documented, and 
reported during all periods of the study in which the medical device is used.

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If the investigator learns of any device deficiency at any time after a participant has been 
discharged from the study, and such incident is considered reasonably related to a medical 
device provided for the study, the investigator will promptly notify the sponsor.
The method of documenting medical device deficiencies is provided in Appendix 8.
8.3.8.2. Follow-up of Medical Device Deficiencies
All medical device incidents involving an AE will be followed and reported in the same 
manner as other AEs (see Section 8.3.3).  Follow-up applies to all participants, including 
those who discontinue study intervention.
The investigator is responsible for ensuring that follow-up includes any supplemental 
investigations as indicated to elucidate the nature and/or causality of the deficiency.
New or updated information will be recorded on a follow-up form with all changes signed 
and dated by the investigator.
8.3.8.3. Prompt Reporting of Device Deficiencies to Sponsor
Device deficiencies will be reported to the sponsor within 1 day after the investigator 
determines that the event meets the protocol definition of a medical device deficiency.  
Information will be provided to the sponsor as described in the IP manual.
Any device deficiency that is associated with an SAE must be reported to Pfizer Safety 
within 24 hours upon the investigator’s awareness as outlined in Section 8.3.1.1 and 8.3.1.2.
The sponsor will be the contact for the receipt of device deficiency information.
8.3.8.4. Regulatory Reporting Requirements for Device Deficiencies
The investigator will promptly report all device deficiencies occurring with any medical 
device provided for use in the study in order for the sponsor to fulfill the legal responsibility 
to notify appropriate regulatory authorities and other entities about certain safety information 
relating to medical devices being used in clinical studies.
The investigator, or responsible person according to local requirements (eg, the head of the 
medical institution), will comply with the applicable local regulatory requirements relating to 
the reporting of device deficiencies to the IRB/EC.
8.3.9. Medication Errors
Medication errors may result from the administration or consumption of the study 
intervention by the wrong participant, or at the wrong time, or at the wrong dosage strength.

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Exposures to the study intervention under study may occur in clinical trial settings, such as 
medication errors.
Safety Event
Recorded on the CRF
Reported on the Vaccine SAE
Reporting Form to Pfizer Safety 
Within 24 Hours of Awareness
Medication errors 
All (regardless of whether 
associated with an AE)
Only if associated with an SAE
Medication errors include:

Medication errors involving participant exposure to the investigational product;

Potential medication errors or uses outside of what is foreseen in the protocol that do 
or do not involve the study participant.
Such medication errors occurring to a study participant are to be captured on the medication 
error page of the CRF, which is a specific version of the AE page.
In the event of a medication dosing error, the sponsor should be notified immediately.
Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error is recorded on the medication error page of the CRF and, if 
applicable, any associated AE(s), serious and nonserious, are recorded on the AE page of the 
CRF.
Medication errors should be reported to Pfizer Safety within 24 hours on a Vaccine SAE
Reporting Form only when associated with an SAE.
Other examples include, but are not limited to:

The administration of expired investigational product;

The administration of an incorrect investigational product;

The administration of an incorrect dosage;

The administration of investigational product that has undergone temperature excursion 
from the specified storage range, unless it is determined by the sponsor that the 
investigational product under question is acceptable for use.
8.4. Treatment of Overdose
For this study, any dose of investigational product greater than 1 dose within a 24-hour time 
period will be considered an overdose.

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Pfizer does not recommend specific treatment for an overdose.
In the event of an overdose, the investigator should:
1. Contact the medical monitor immediately.
2. Closely monitor the participant for any AEs/SAEs.
3. Document the quantity of the excess dose as well as the duration of the overdose in 
the CRF.
4. Overdose is reportable to Safety only when associated with an SAE.
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the medical monitor based on the clinical evaluation of the participant.
8.5. Pharmacokinetics
Pharmacokinetic parameters are not evaluated in this study.
8.6. Pharmacodynamics
Pharmacodynamic parameters are not evaluated in this study.
8.9. Immunogenicity Assessments
Immunogenicity assessments are described in Section 8.1.
8.10. Health Economics
Health economics/medical resource utilization and health economics parameters are not 
evaluated in this study.
8.11. Study Procedures
The study procedures are summarized in the SoA. The day of Dose 1 is considered to be
Day 1. The timing of visit procedures (ie, prior to vaccination and after vaccination) must be
maintained; however, there is flexibility in the order in which the procedures can be
conducted at each visit. The only exception is that at Visit 1, the ICD must be signed prior to
the start of any study procedure.
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8.11.1. Visit 1 (Vaccination 1 – Day 1)
Prior to randomization:

Obtain a personally signed and dated ICD indicating that the participant has been 
informed of all pertinent aspects of the study before performing any study-specific 
procedures.

Assign a participant number via the IRT.

Obtain and record the participant’s demographic information (including date of birth, sex, 
race, and ethnicity).  The complete date of birth (ie, DD-MMM-YYYY) will be collected 
to critically evaluate the immune response and safety profile by age.

Obtain and record significant 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.

Perform a clinical assessment. If the clinical assessment indicates that a physical 
examination is necessary to comprehensively evaluate the participant, perform a physical 
examination and record any findings in the source documents and, if significant, record 
such findings on the medical history CRF.

Record pneumococcal vaccine history, including name(s) of the vaccine(s) received and 
date(s) given (dates may be approximate but minimally sufficient to confirm eligibility
and appropriate stratification).

Assess and record smoking history.

If applicable, instruct the participant to use appropriate contraceptives until 28 days after 
administration of the last dose of investigational product, and document the conversation 
and the participant’s affirmation in the participant’s source document.

Measure and record the participant’s oral temperature (°F/°C).

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.  An unblinded site staff member will 
prepare the investigational product according to the IP manual.

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After randomization:

Collect a blood sample of approximately 30 mL for immunogenicity assessments prior to 
vaccination.

Administer a single 0.5-mL injection of SIIV into the right deltoid muscle.

An unblinded site staff member will administer a single 0.5-mL injection of 20vPnC or 
saline into the left deltoid muscle.

Blinded site staff will observe the participant for 30 minutes after administration of 
20vPnC or saline for any reactions.  Record any AEs on the CRF and on the Vaccine 
SAE Reporting Form, as applicable.  Record concomitant medications used to treat SAEs 
and NDCMCs.

Issue the participant a measuring device to measure 20vPnC or saline injection site 
reactions and a digital thermometer and provide instructions on their use.

Issue the participant an e-diary (device or application) and provide instructions on its use 
and completion.  Ask the participant to complete the e-diary from Day 1 to Day 10, with 
Day 1 being the day of vaccination.

Ask the participant to contact the investigator site staff or investigator as soon as possible 
during the 10-day postvaccination period if the participant has redness and/or swelling at 
the 20vPnC or saline injection site measuring >20 measuring device units (>10 cm), or 
severe 20vPnC or saline injection site pain (prevents daily activity) to determine if the 
event requires further assessment by the investigator (refer to Section 8.2).

Ask the participant to contact the investigator site staff or the investigator as soon as 
possible if they experience any possible Grade 4 prompted local reaction in their left arm 
within 10 days, or systemic event within 7 days, after vaccination (refer to Section 8.2).

Ask the participant to contact the site staff or investigator immediately if any significant 
illness or medical event (eg, emergency room visit or hospitalization) occurs.

Provide the participant with the participant contact card containing the study and 
investigator information (see Section 10.1.10).

Inform the participant that they may be contacted by site staff to obtain additional 
information on reports of fever >102.0°F or Grade 3 events entered into the e-diary.

Inform the participant that the use of prophylactic antipyretic/pain medication, while 
permitted, is not recommended on the day of investigational product administration 
(before or after vaccination).

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
Remind the participant to use appropriate contraceptives until 28 days after vaccination, 
if applicable.

The investigator or an authorized designee completes the CRF and the source documents 
and updates the investigational product accountability records.

The investigator or appropriately qualified designee reviews the e-diary data online at 
frequent intervals (daily is optimal) for the 10 days (Day 1 is the day of vaccination) 
following vaccination to evaluate participant compliance and as part of the ongoing 
safety review.
8.11.2. Visit 2 (Vaccination 2 – 28 to 42 Days After Visit 1 [Study Days 29 to 43])
Prior to vaccination:

Ensure and document that the participant continues to be eligible for the study 
(see Section 7 for participant discontinuation/withdrawal) and that none of the temporary 
delay criteria are met.

Record nonstudy vaccinations as described in Section 6.6.

Perform a contraception check (see Section 10.4), if applicable.

Review the participant’s e-diary data.  Collect stop dates of any e-diary events (local 
reactions or systemic events) ongoing on the last day that the e-diary was completed and 
record stop dates in the CRF.

Determine if any AEs (includes nonserious AEs, SAEs, and NDCMCs) have occurred 
since the previous visit, follow up on any previously reported events to determine the 
outcome (ie, record stop dates or confirm if they are still continuing), record as described 
in Section 8.2, and record concomitant medications used to treat NDCMCs and SAEs.

Measure and record the participant’s oral temperature (°F/°C).

Collect a blood sample of approximately 30 mL for immunogenicity assessments prior to 
vaccination.
After vaccination (including investigational product administration):

An unblinded site staff member will administer a single 0.5-mL injection of 20vPnC or 
saline into the deltoid muscle of the left arm.

Blinded site staff will observe the participant for 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.

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
Confirm that the e-diary is working and review instructions, if necessary.  Ask the 
participant to complete the e-diary from Day 1 to Day 10, with Day 1 being the day of 
vaccination.  Provide thermometer or measuring device, if needed.

Ask the participant to contact the investigator site staff or investigator as soon as possible 
during the 10-day postvaccination period if the participant has redness and/or swelling at 
the 20vPnC or saline injection site measuring >20 measuring device units (>10.0 cm), or 
severe 20vPnC or saline injection site pain (prevents daily activity) to determine if the 
event requires further assessment by the investigator (refer to Section 10.3).

Ask the participant to contact the investigator site staff or the investigator as soon as 
possible if they experience any possible Grade 4 prompted local reaction in their left arm 
within 10 days, or systemic event within 7 days, after vaccination (refer to Section 8.3).

Ask the participant to contact the site staff or investigator immediately if any significant 
illness or medical event (eg, emergency room visit or hospitalization) occurs.

Inform the participant that they may be contacted by site staff to obtain additional 
information on reports of fever >102.0°F or Grade 3 events entered into the e-diary.

Inform the participant that use of prophylactic antipyretic/pain medication, while 
permitted, is not recommended on the day of investigational product administration 
(before or after vaccination).

Remind the participant to use appropriate contraceptives until 28 days after vaccination, 
if applicable.

The investigator or an authorized designee completes the CRF and the source documents 
and updates the investigational product accountability records.

The investigator or appropriately qualified designee reviews the e-diary data online at 
frequent intervals (daily is optimal) for the 10 days (Day 1 is the day of vaccination) 
following vaccination to evaluate participant compliance and as part of the ongoing 
safety review.
8.11.3. Visit 3 (Follow-up – 28 to 42 Days After Vaccination 2 [Study Days 57 to 85])

Ensure and document that the participant continues to be eligible for the study 
(see Section 7 for participant discontinuation/withdrawal).

Record nonstudy vaccinations as described in Section 6.6.

Review the participant’s e-diary data.  Collect stop dates of any e-diary events (local 
reactions or systemic events) ongoing on the last day that the e-diary was completed and 
record stop dates in the CRF.

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
Collect the e-diary (if applicable).

Determine if any AEs (includes nonserious AEs, SAEs, and NDCMCs) have occurred 
since the previous visit, follow up on any previously reported events to determine the 
outcome (ie, record stop dates or confirm if they are still continuing), record as described 
in Section 8.3, and record concomitant medications used to treat NDCMCs and SAEs.

Collect a blood sample of approximately 30 mL for immunogenicity assessments.

Ask the participant to contact the site staff or investigator immediately if any significant 
illness or medical event (eg, emergency room visit or hospitalization) occurs.

The investigator or an authorized designee completes the CRF and the source documents.
8.11.4. Visit 4 (6-Month Safety Collection [Telephone Contact] – 168 to 196 Days After 
Last Vaccination)

Contact the participant by telephone approximately 6 months after the last study 
vaccination; this contact should be attempted for all participants who have received at 
least 1 study vaccination, unless the participant has withdrawn consent.

Determine whether any SAEs and NDCMCs have occurred since the previous visit,
follow up on any previously reported events to determine the outcome (ie, record stop 
dates or confirm if they are still continuing), record as described in Section 8.3, and 
record concomitant medications used to treat NDCMCs and SAEs.

The investigator or an authorized designee completes the CRF and the source documents.
8.12. Unscheduled Visits
If the participant reports redness or swelling at the 20vPnC or saline injection site measuring 
20 measuring device units (10.0 cm) or severe injection site pain during the 10 days 
following vaccination, a telephone contact must occur as soon as possible between the 
investigator or medically qualified designee and the participant to assess if an unscheduled 
investigator site visit is required.  A site visit should be scheduled as soon as possible to 
assess the extent of the injection site reaction unless any of the following is true:

The participant is unable to attend the unscheduled visit.

The reaction is no longer present at the time of the telephone contact.

The participant recorded an incorrect value in the e-diary (confirmation of an e-diary data 
entry error).

The PI or authorized designee determined it was not needed.

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This telephone contact will be recorded in the participant’s source documentation and the 
CRF.
If the participant 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.
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 8.2.2.1.

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.
Participants 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 fever >104.0°F (>40.0°C) within 7 days, 
or local reaction in the 20vPnC/saline injection site (ie, necrosis, exfoliative dermatitis, or 
emergency room visit/hospitalization for injection site pain) within 10 days after vaccination.
Participants 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 
investigator site staff should determine if an unscheduled visit to further evaluate the event is 
warranted in all such cases.
Additionally, site staff may contact the participant to obtain additional information on fever 
>102.0°F or Grade 3 events entered into the e-diary.
9. STATISTICAL CONSIDERATIONS
Methodology for summary and statistical analyses of the data collected in this study is 
described here and further detailed in a 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 
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9.1. Estimands and Statistical Hypotheses
9.1.1. Estimands
The estimands corresponding to each primary, secondary,
 objective are
described in the table in Section 3. The estimands to evaluate the immunogenicity objectives 
for NI) are based on the evaluable populations (see Section 9.3 for definition). The 
estimands estimate the vaccine effect in the hypothetical setting where participants follow the 
study schedules and protocol requirements as directed. The estimands address the objective 
of estimating the maximum potential difference between 2 groups, since the impact of 
noncompliance is likely to diminish the observed difference between the 2 groups. Missing 
serology results will not be imputed. Immunogenicity results that are below the LLOQ will 
be set to 0.5 × LLOQ in the analysis. In the primary safety objective evaluations, missing 
e-diary data will not be imputed. Missing AE dates will be imputed according to Pfizer 
Safety rules. No other missing information will be imputed in the safety analysis.
9.1.2. Statistical Hypotheses
There are 2 primary immunogenicity objectives (Section 3). Hypothesis testing will be used 
to assess those 2 NI objectives.
The null hypotheses (H01) for each pneumococcal serotype is:
H01: ln(μA) – ln(μB) ≤ ln(0.5)  
where ln(0.5) corresponds to a 2-fold margin for the assessment of NI with respect to the
immune responses to 20vPnC and
•
ln(μA) is the natural log of the serotype-specific OPA GMT 1 month after 
coadministration of SIIV and 20vPnC for the (SIIV+20vPnC)/saline group;
•
ln(μB) is the natural log of the serotype-specific OPA GMT 1 month after 20vPnC
administration for the (SIIV+saline)/20vPnC group.
NI for serotype-specific OPA titers will be formally evaluated by a 2-sided 95% CI for the 
ratio of serotype-specific OPA GMTs (SIIV+20vPnC)/saline group over 
(SIIV+saline)/20vPnC group. The null hypothesis (H01) will be rejected and NI for a 
serotype will be declared if the lower bound of the 2-sided 95% CI for the GMR of the 
coadministration group to the separate-administration group is greater than 0.5 (2-fold 
criterion). 
 
 
 
 
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The null hypotheses (H02) for each influenza strain-specific antibody is:
H02: ln(μC) – ln(μD) ≤ ln(0.67)
where ln(0.67) corresponds to a 1.5-fold margin for assessment of NI with respect to the
immune responses to SIIV and  
•
ln(μC) is the natural log of the strain-specific HAI GMT 1 month after 
coadministration of SIIV and 20vPnC for the (SIIV+20vPnC)/saline group; 
•
ln(μD) is the natural log of the strain-specific HAI GMT 1 month after SIIV 
administration for the (SIIV+saline)/20vPnC group.
NI for strain-specific HAI titers will be formally evaluated by a 2-sided 95% CI for the ratio 
of strain-specific HAI GMTs ([SIIV+20vPnC]/saline group over [SIIV+saline]/20vPnC 
group). The null hypothesis (H02) will be rejected and NI for strain-specific HAI will be 
declared if the lower bound of the 2-sided 95% CI for the GMR of the coadministration 
group to the separate-administration group is greater than 0.67 (1.5-fold criterion).
 
9.1.3. Multiplicity Considerations
For the primary immunogenicity assessment of NI of coadministration of SIIV and 20vPnC 
([SIIV+20vPnC]/saline group) to administration of SIIV followed by 20vPnC 1 month later 
([SIIV+saline]/20vPnC group) for all 20 OPA serotypes in 20vPnC and all the HAI strains in 
SIIV, a 2-sided test for each of the 20 OPA serotypes and each of the HAI strains is 
performed only once at an alpha level of 0.05. The primary immunogenicity objectives of 
the study will be achieved if the 2-fold NI criterion is met for each of the 20 OPA serotypes 
and the 1.5-fold NI criterion is met for each of the HAI strains. Therefore, the type I error 
rate for the immunogenicity assessments is well controlled.
9.2. Sample Size Determination
 
Sample size and power are based on simulations with assumptions supported by the OPA
results from a Phase 3 pivotal study (B7471007) of 20vPnC and a Phase 4 study (B1851138) 
of 13vPnC evaluating the immune response when 13vPnC was given concomitantly and 
separately. With 800 evaluable participants in each vaccine group, the study has
approximately 99%, 95%, and 75% power to demonstrate NI for at least 18 out of 20, for at 
least 19 out of 20, and for all 20 serotypes, respectively. Assuming a nonevaluable rate of 
10%, the study will randomize approximately 1780 participants to achieve 800 evaluable 
participants in each group.
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 Assuming the GMR of 
the (SIIV+20vPnC)/saline group to the (SIIV+saline)/20vPnC group is 0.9 for each HAI 
strain and standard deviations are the same as those observed in Study B1851138, 
800 evaluable participants in each vaccine group provide approximately 99% power to 
demonstrate NI for all HAI strains.
 
 
 
 
 
 
 
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9.3. Analysis Sets
Participant Analysis Set
Description
Enrolled
All participants who sign the ICD.
Randomized
All participants who are assigned a randomization number in 
the IWR system.
Evaluable pneumococcal 
immunogenicity
All randomized participants who receive the assigned 
investigational products at Visit 1 for the 
(SIIV+20vPnC)/saline group or receive the assigned 
investigational products at both Visit 1 and Visit 2 for 
the (SIIV+saline)/20vPnC group; have the blood collection 
within an appropriate window 1 month after 20vPnC 
(Visit 2 for [SIIV+20vPnC]/saline group, Visit 3 for 
[SIIV+saline]/20vPnC group); have at least 1 valid and 
determinate OPA result from 1 month after vaccination with 
20vPnC; and have no other major protocol deviations as 
determined by the clinician.
Evaluable HAI 
immunogenicity
All randomized participants who receive the assigned 
investigational products at Visit 1, have Visit 2 blood 
collection within an appropriate window for Visit 2, have at 
least 1 valid and determinate HAI titer for any of the HAI 
strains in SIIV at Visit 2, and have no other major protocol 
deviations as determined by the clinician.
 
 
Safety
All randomized participants who receive 1 dose of 20vPnC or 
SIIV or saline and have safety follow-up after vaccination.
9.4. Statistical Analyses
The SAP will be developed and finalized before any planned analyses (Section 9.5.1) are 
performed. The SAP will describe the analyses and procedures for accounting for missing, 
unused, and spurious data.  This section is a summary of the planned statistical analyses of 
the primary, secondary,
 endpoints.
9.4.1. Immunogenicity Analysis
The statistical analysis of immunogenicity results will be primarily based on the evaluable 
immunogenicity populations as defined in Section 9.3.
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Missing serology results will not be imputed. Titers below LLOQ or denoted as BLQ will be 
set to 0.5 × LLOQ for analysis.
Endpoint
Statistical Analysis Methods
Primary 
pneumococcal 
immunogenicity
•
For the 20 serotypes in 20vPnC, 1 month after vaccination refers 
to 1 month after vaccination with 20vPnC and SIIV (Visit 2) for 
the (SIIV+20vPnC)/saline group and 1 month after vaccination 
with 20vPnC (Visit 3) for the (SIIV+saline)/20vPnC group.
•
For each of the 20 serotype-specific OPA titers, the GMRs of 
the (SIIV+20vPnC)/saline group GMT to 
the (SIIV+saline)/20vPnC group GMT at 1 month after 
vaccination will be provided.
•
GMRs and their 2-sided 95% CIs will be derived by calculating 
differences in means and CIs on the natural log scale, then 
exponentiating the results. The difference in means, on the 
natural log scale, will be the (SIIV+20vPnC)/saline group at 
Visit 2 minus the (SIIV+saline)/20vPnC group at Visit 3 for the 
20 serotypes in 20vPnC.
As the primary approach to calculate the GMR and CI for each 
serotype of OPA titer, a linear regression model that includes 
terms for prior pneumococcal vaccine status, age (at the time of 
randomization), corresponding baseline OPA titer, sex, smoking 
status, and vaccine group will be used to calculate the 
serotype-specific OPA GMR and 95% CI, along with the 
model-based least squares GMTs and associated 2-sided 95% CIs 
for each vaccine group. NI for a serotype will be declared if the 
lower bound of the 2-sided 95% CI for the GMR of the
(SIIV+20vPnC)/saline group over the (SIIV+saline)/20vPnC 
group exceeds 0.5. 
 
 
 
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This analysis will be based on the evaluable pneumococcal 
immunogenicity populations in order to provide a comparison that 
has the greatest chance of identifying a difference between the 
groups with respect to immunogenicity, if a meaningful 
difference in vaccine effect actually exists.
Primary SIIV 
immunogenicity
•
For the HAI strains in SIIV, 1 month after vaccination refers to 
1 month after vaccination with SIIV (Visit 2) for both vaccine 
groups.
•
For each of the HAI strains, the GMRs of the
(SIIV+20vPnC)/saline group GMT to the (SIIV+saline)/20vPnC 
group GMT at 1 month after vaccination will be provided. GMRs 
and their 2-sided 95% CIs will be derived by calculating 
differences in means and CIs on the natural log scale, then 
exponentiating the results. The difference in means, on the 
natural log scale, will be the (SIIV+20vPnC)/saline group at Visit 
2 minus the (SIIV+saline)/20vPnC group at Visit 2 for all HAI 
strains in SIIV.
As the primary approach to calculate the GMR and CI for each 
strain of HAI titer, a linear regression model that includes terms 
for prior pneumococcal vaccine status, age (at the time of 
randomization), corresponding baseline HAI titer, sex, smoking 
status, and vaccine group will be used to calculate the 
strain-specific HAI GMR and 95% CI, along with the model-
based least squares GMTs and associated 2-sided 95% CIs for 
each vaccine group. NI for a strain will be declared if the lower 
bound of the 2-sided 95% CI for the GMR of the 
(SIIV+20vPnC)/saline group over the (SIIV+saline)/20vPnC 
group exceeds 0.67.
 
 
This analysis will be based on the evaluable HAI immunogenicity 
populations in order to provide a comparison that has the greatest 
chance of identifying a difference between the groups with 
respect to immunogenicity, if a meaningful difference in vaccine 
effect actually exists.
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Secondary 
pneumococcal 
immunogenicity
•
GMFRs and associated 2-sided 95% CIs will be provided for each 
OPA serotype from before vaccination to 1 month after 
vaccination for each vaccine group.  GMFRs will be limited to 
participants with nonmissing values both before and after 
vaccination. The GMFR will be calculated as the mean of the 
difference of logarithmically transformed serotype-specific OPA 
titer (after vaccination minus before vaccination for each 
participant) and transformed back to the original units. 2-Sided 
95% CIs will be obtained by exponentiating CIs using Student’s 
t distribution for the mean difference of measures on the 
logarithmically transformed assay results.
•
The point estimate and exact 2-sided 95% CI will be calculated 
for each vaccine group using the Clopper-Pearson method for the 
percentage of participants with a ≥4-fold rise in serotype-specific 
OPA titers from before vaccination to 1 month after vaccination.
Secondary SIIV 
immunogenicity
•
HAI GMFRs and associated 2-sided 95% CIs will be provided for 
each HAI strain from before vaccination to 1 month after 
vaccination for each vaccine group, using the same method 
described above for serotype-specific OPA GMFRs and CIs.
 
 
 
 
 
 
 
 
 
 
 
CCI

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9.4.2. Safety Analyses
Endpoint
Statistical Analysis Methods
Primary

Descriptive statistics will be provided for each reactogenicity endpoint 
for each vaccine group. In each vaccine group, prompted local 
reactions from Day 1 through Day 10 and prompted systemic events 
from Day 1 through Day 7 after each vaccination will be presented by 
severity and cumulatively across severity levels. Descriptive summary 
statistics will include counts and percentages of participants with the 
indicated endpoint and the associated 2-sided Clopper-Pearson 95% 
CIs.

AEs, SAEs, and NDCMCs will be categorized according to MedDRA 
terms. A 3-tier approach will be used to summarize AEs. Under this 
approach, AEs are classified into 1 of 3 tiers: 
(1) Tier 1 events are prespecified events of clinical importance and are 
identified in a list in the product’s safety review plan; 
(2) Tier 2 events are those that are not Tier 1 but are considered 
“relatively common”; a MedDRA preferred term is defined as a Tier 2 
event if there are at least 1% of participants in at least 1 vaccine group 
reporting the event; 
(3) Tier 3 events are those that are neither Tier 1 nor Tier 2 events.
For both Tier 1 and Tier 2 events, the 2-sided 95% CIs for the 
difference in percentage of participants reporting the events between 
the (SIIV+20vPnC)/saline group and the (SIIV+saline)/20vPnC group 
will be calculated using the Miettinen and Nurminen method. In 
addition, for Tier 1 events, the asymptotic p-values will also be 
presented for the difference in percentage of participants reporting the 
events, based on the same test statistic and under the assumption that 
the test statistic is asymptotically normally distributed.
There is no Tier 1 event identified for 20vPnC at this stage. For Tier 2 
AEs, the between-group difference and 95% CIs will be calculated for 
1 month after vaccination with SIIV and 20vPnC for the 
(SIIV+20vPnC)/saline group vs 1 month after vaccination with SIIV 
and saline for the (SIIV+saline)/20vPnC group, and for 1 month after 
vaccination with SIIV and 20vPnC for the (SIIV+20vPnC)/saline 
group vs 1 month after vaccination with 20vPnC for the 
(SIIV+saline)/20vPnC group.  Descriptive summary statistics (counts 
and percentages and associated 2-sided Clopper-Pearson 95% CIs) will 
be provided for Tier 3 events, SAEs, and NDCMCs for each vaccine 
group.

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•
The safety analyses are based on the safety population. Participants 
will be summarized by vaccine group according to the investigational
products they actually received. Missing e-diary data will not be 
imputed. Missing AE dates will be handled according to the Pfizer 
safety rules.
Secondary
N/A
9.5. Interim Analyses
No interim analysis is planned in this study.
 
 
 
 
 
 
 
 
 
 
 
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10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations
10.1.1. Regulatory and Ethical Considerations
This study will be conducted in accordance with the protocol and with the following:

Consensus ethical principles derived from international guidelines, including the 
Declaration of Helsinki and CIOMS International Ethical Guidelines;

Applicable ICH GCP guidelines;

Applicable laws and regulations, including applicable privacy laws.
The protocol, protocol amendments, ICD, SRSD(s), and other relevant documents 
(eg, advertisements) must be reviewed and approved by the sponsor and submitted to an 
IRB/EC by the investigator and reviewed and approved by the IRB/EC before the study is 
initiated.
Any amendments to the protocol will require IRB/EC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants.
The investigator will be responsible for the following:

Providing written summaries of the status of the study to the IRB/EC annually or more 
frequently in accordance with the requirements, policies, and procedures established by 
the IRB/EC;

Notifying the IRB/EC of SAEs or other significant safety findings as required by IRB/EC 
procedures;

Providing oversight of the conduct of the study at the site and adherence to requirements 
of 21 CFR, ICH guidelines, the IRB/EC, European regulation 536/2014 for clinical 
studies (if applicable), and all other applicable local regulations.
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
regulatory authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the study 
intervention, Pfizer should be informed immediately.
In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study participants against any immediate hazard, and 
of any serious breaches of this protocol or of ICH GCP that the investigator becomes aware 
of.

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10.1.2. Financial Disclosure
Investigators and subinvestigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities.  Investigators 
are responsible for providing information on financial interests during the course of the study 
and for 1 year after completion of the study.
10.1.3. Informed Consent Process
The investigator or his/her representative will explain the nature of the study to the 
participant and answer all questions regarding the study.  The participant should be given 
sufficient time and opportunity to ask questions and to decide whether or not to participate in 
the trial.
Participants must be informed that their participation is voluntary.  Participants will be 
required to sign a statement of informed consent that meets the requirements of 21 CFR 50, 
local regulations, ICH guidelines, HIPAA requirements, where applicable, and the IRB/EC 
or study center.
The investigator must ensure that each study participant is fully informed about the nature 
and objectives of the study, the sharing of data related to the study, and possible risks 
associated with participation, including the risks associated with the processing of the 
participant’s personal data.
The participant must be informed that his/her personal study-related data will be used by the 
sponsor in accordance with local data protection law.  The level of disclosure must also be 
explained to the participant.
The participant must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB/EC members, and by inspectors from regulatory authorities.
The investigator further must ensure that each study participant is fully informed about his or 
her right to access and correct his or her personal data and to withdraw consent for the 
processing of his or her personal data.
The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date the written consent was obtained.  
The authorized person obtaining the informed consent must also sign the ICD.
Participants must be reconsented to the most current version of the ICD(s) during their 
participation in the study.
A copy of the ICD(s) must be provided to the participant.

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Unless prohibited by local requirements or IRB/EC decision, the ICD will contain a separate 
section that addresses the use of samples for optional additional research.  The optional 
additional research does not require the collection of any further samples.  The investigator 
or authorized designee will explain to each participant the objectives of the additional 
research.  Participants will be told that they are free to refuse to participate and may 
withdraw their consent at any time and for any reason during the storage period.
10.1.4. Data Protection
All parties will comply with all applicable laws, including laws regarding the implementation 
of organizational and technical measures to ensure protection of participant data.
Participants’ personal data will be stored at the study site in encrypted electronic and/or paper 
form and will be password-protected or secured in a locked room to ensure that only 
authorized study staff have access.  The study site will implement appropriate technical and 
organizational measures to ensure that the personal data can be recovered in the event of
disaster.  In the event of a potential personal data breach, the study site will 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 participants with regard to the processing of personal 
data, participants will be assigned a single, participant-specific numerical code.  Any 
participant records or data sets that are transferred to the sponsor will contain the numerical 
code; participant names will not be transferred.  All other identifiable data transferred to the 
sponsor will be identified by this single, participant-specific code.  The study site will 
maintain a confidential list of participants who participated in the study, linking each 
participant’s numerical code to his or her actual identity and medical record ID.  In case of 
data transfer, the sponsor will protect the confidentiality of participants’ personal data 
consistent with the CSA and applicable privacy laws.
10.1.5. Dissemination of Clinical Study Data
Pfizer fulfills its commitment to publicly disclose clinical study results through posting the 
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov), the EudraCT, and/or 
www.pfizer.com, and other public registries in accordance with applicable local 
laws/regulations.  In addition, Pfizer reports study results outside of the requirements of local 
laws/regulations pursuant to its SOPs.
In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country in 
which the study was conducted.

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www.clinicaltrials.gov
Pfizer posts clinical trial results on www.clinicaltrials.gov for Pfizer-sponsored interventional 
studies (conducted in patients) that evaluate the safety and/or efficacy of a product, 
regardless of the geographical location in which the study is conducted.  These results are 
submitted for posting in accordance with the format and timelines set forth by US law.
EudraCT
Pfizer posts clinical trial results on EudraCT for Pfizer-sponsored interventional studies in 
accordance with the format and timelines set forth by EU requirements.
www.pfizer.com
Pfizer posts public disclosure synopses (CSR synopses in which any data that could be used 
to identify individual participants have been removed) on www.pfizer.com for 
Pfizer-sponsored interventional studies at the same time the corresponding study results are 
posted to www.clinicaltrials.gov.
Documents within marketing authorization packages/submissions
Pfizer complies with the EMA Policy 0070, the proactive publication of clinical data to the 
EMA website.  Clinical data, under Phase 1 of this policy, includes clinical overviews, 
clinical summaries, CSRs, and appendices containing the protocol and protocol amendments, 
sample CRFs, and statistical methods.  Clinical data, under Phase 2 of this policy, includes 
the publishing of individual participant data.  Policy 0070 applies to new marketing 
authorization applications submitted via the centralized procedure since 01 January 2015 and 
applications for line extensions and for new indications submitted via the centralized 
procedure since 01 July 2015.
Data sharing
Pfizer provides researchers secure access to patient-level data or full CSRs for the purposes 
of “bona-fide scientific research” that contributes to the scientific understanding of the 
disease, target, or compound class.  Pfizer will make available data from these trials 
24 months after study completion.  Patient-level data will be anonymized in accordance with 
applicable privacy laws and regulations.  CSRs will have personally identifiable information 
redacted.
Data requests are considered from qualified researchers with the appropriate competencies to 
perform the proposed analyses.  Research teams must include a biostatistician.  Data will not 
be provided to applicants with significant conflicts of interest, including individuals 
requesting access for commercial/competitive or legal purposes.

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

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The investigator(s) will notify the sponsor or its agents immediately of any regulatory 
inspection notification in relation to the study.  Furthermore, the investigator will cooperate 
with the sponsor or its agents to prepare the investigator site for the inspection and will allow 
the sponsor or its agent, whenever feasible, to be present during the inspection.  The 
investigator site and investigator will promptly resolve any discrepancies that are identified 
between the study data and the participant's medical records.  The investigator will promptly 
provide copies of the inspection findings to the sponsor or its agent.  Before response 
submission to the regulatory authorities, the investigator will provide the sponsor or its 
agents with an opportunity to review and comment on responses to any such findings.
10.1.7. Source Documents
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected.  Source documents are filed at the investigator site.
Data reported on the CRF or entered in the eCRF that are from source documents must be 
consistent with the source documents or the discrepancies must be explained.  The 
investigator may need to request previous medical records or transfer records, depending on 
the study.  Also, current medical records must be available.
A definition of what constitutes source data can be found in the ISF.
A description of the use of computerized systems is documented in the Data Management 
Plan.
10.1.8. Study and Site Start and Closure
The study start date is the date on which the clinical study will be open for recruitment of 
participants.
The first act of recruitment is the date of the first participant’s first visit and will be the study 
start date.
The sponsor designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor.  Study sites will be closed upon 
study completion.  A study site is considered closed when all required documents and study 
supplies have been collected and a study-site closure visit has been performed.
The investigator may initiate study-site closure at any time upon notification to CRO if 
requested to do so by the responsible IRB/EC or if such termination is required to protect the 
health of study participants.

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Reasons for the early closure of a study site by the sponsor may include but are not limited 
to:

Failure of the investigator to comply with the protocol, the requirements of the IRB/EC 
or local health authorities, the sponsor's procedures, or GCP guidelines;

Inadequate recruitment of participants by the investigator;

Discontinuation of further study intervention development.
If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the ECs/IRBs, the regulatory authorities, and any CRO(s) used in the study of 
the reason for termination or suspension, as specified by the applicable regulatory 
requirements.  The investigator shall promptly inform the participant and should assure 
appropriate participant therapy and/or follow-up.
Study termination is also provided for in the CSA.  If there is any conflict between the 
contract and this protocol, the contract will control as to termination rights.
10.1.9. Publication Policy
The results of this study may be published or presented at scientific meetings by the 
investigator after publication of the overall study results or 1 year after the end of the study 
(or study termination), whichever comes first.
The investigator agrees to refer to the primary publication in any subsequent publications,
such as secondary manuscripts, and submits all manuscripts or abstracts to the sponsor 
30 days before submission.  This allows the sponsor to protect proprietary information and to 
provide comments, and the investigator will, on request, remove any previously undisclosed 
confidential information before disclosure, except for any study- or Pfizer 
intervention-related information necessary for the appropriate scientific presentation or 
understanding of the study results.
For all publications relating to the study, the investigator will comply with recognized ethical 
standards concerning publications and authorship, including those established by the 
International Committee of Medical Journal Editors.
The sponsor will comply with the requirements for publication of the overall study results 
covering all investigator sites.  In accordance with standard editorial and ethical practice, the 
sponsor will support publication of multicenter studies only in their entirety and not as 
individual site data.  In this case, a coordinating investigator will be designated by mutual 
agreement.
Authorship of publications for the overall study results will be determined by mutual 
agreement and in line with International Committee of Medical Journal Editors authorship 
requirements.

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If publication is addressed in the CSA, the publication policy set out in this section will not 
apply.
10.1.10. Sponsor’s Qualified Medical Personnel
The contact information for the sponsor's appropriately qualified medical personnel for the 
study is documented in the study contact list located in the ISF.  To facilitate access to 
appropriately qualified medical personnel on study-related medical questions or problems, 
participants are provided with a contact card at the time of informed consent.  The contact 
card contains, at a minimum, protocol and study intervention identifiers, participant numbers, 
contact information for the investigator site, and contact details for a contact center in the 
event that the investigator site staff cannot be reached to provide advice on a medical 
question or problem originating from another healthcare professional not involved in the 
participant’s participation in the study.  The contact number can also be used by investigator 
staff if they are seeking advice on medical questions or problems; however, it should be used 
only in the event that the established communication pathways between the investigator site 
and the study team are not available.  It is therefore intended to augment, but not replace, the 
established communication pathways between the investigator site and the study team for 
advice on medical questions or problems that may arise during the study.  The contact 
number is not intended for use by the participant directly, and if a participant calls that 
number, he or she will be directed back to the investigator site.
10.2. Appendix 2: Clinical Laboratory Tests
Not applicable.

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10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting
10.3.1. Definition of AE
AE Definition

An AE is any untoward medical occurrence in a patient or clinical study participant, 
temporally associated with the use of study intervention, whether or not considered 
related to the study intervention.

NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of study intervention.
Events Meeting the AE Definition

Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (eg, ECG, radiological scans, vital sign measurements), 
including those that worsen from baseline, considered clinically significant in the 
medical and scientific judgment of the investigator.  Any abnormal laboratory test 
results that meet any of the conditions below must be recorded as an AE:

Is associated with accompanying symptoms.

Requires additional diagnostic testing or medical/surgical intervention.

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.

Exacerbation of a chronic or intermittent preexisting condition, including either an 
increase in frequency and/or intensity of the condition.

New conditions detected or diagnosed after study intervention administration, even 
though it may have been present before the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication.  Overdose per se will not be reported as an 
AE/SAE unless it is an intentional overdose taken with possible suicidal/self-harming 
intent.  Such overdoses should be reported regardless of sequelae.

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
The signs, symptoms, and/or clinical sequelae resulting from lack of efficacy will be 
reported as an AE or SAE if they fulfill the definition of an AE or SAE and meet the 
requirements as per Section 8.3.7.1.  Also, “lack of efficacy” or “failure of expected 
pharmacological action” does constitute an AE or SAE.
Events NOT Meeting the AE Definition

Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments that are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition.

The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the participant’s 
condition.

Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that leads 
to the procedure is the AE.

Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).

Anticipated day-to-day fluctuations of preexisting disease(s) or condition(s) present or 
detected at the start of the study that do not worsen.
10.3.2. Definition of an NDCMC
An NDCMC is defined as a significant disease or medical condition, not previously 
identified, that is expected to be persistent or is otherwise long-lasting in its effects.
10.3.3. Definition of SAE
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (eg, hospitalization for signs/symptoms of the disease under study, death 
due to progression of disease).

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An SAE is defined as any untoward medical occurrence that, at any dose:
a. Results in death
b. Is life-threatening
The term “life-threatening” in the definition of “serious” refers to an event in which the 
participant was at risk of death at the time of the event.  It does not refer to an event that 
hypothetically might have caused death if it were more severe.
c.
Requires inpatient hospitalization or prolongation of existing hospitalization
In general, hospitalization signifies that the participant has been detained (usually 
involving at least an overnight stay) at the hospital or emergency ward for observation 
and/or treatment that would not have been appropriate in the physician’s office or 
outpatient setting.  Complications that occur during hospitalization are AEs.  If a 
complication prolongs hospitalization or fulfills any other serious criteria, the event is 
serious.  When in doubt as to whether “hospitalization” occurred or was necessary, the AE 
should be considered serious.
Hospitalization for elective treatment of a preexisting condition that did not worsen from 
baseline is not considered an AE.
d. Results in persistent disability/incapacity

The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions.

This definition is not intended to include experiences of relatively minor medical 
significance, such as uncomplicated headache, nausea, vomiting, diarrhea, 
influenza, and accidental trauma (eg, sprained ankle), that may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption.
e.
Is a congenital anomaly/birth defect
f.
Other situations:

Medical or scientific judgment should be exercised in deciding whether SAE 
reporting is appropriate in other situations such as important medical events that 
may not be immediately life-threatening or result in death or hospitalization but 
may jeopardize the participant or may require medical or surgical intervention to 
prevent one of the other outcomes listed in the above definition.  These events 
should usually be considered serious.

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
Examples of such events include invasive or malignant cancers, intensive treatment 
in an emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization, or development of drug 
dependency or drug abuse.

Suspected transmission via a Pfizer product of an infectious agent, pathogenic or 
non-pathogenic, is considered serious.  The event may be suspected from clinical 
symptoms or laboratory findings indicating an infection in a patient exposed to a 
Pfizer product.  The terms “suspected transmission” and “transmission” are 
considered synonymous.  These cases are considered unexpected and handled as 
serious expedited cases by pharmacovigilance personnel.  Such cases are also 
considered for reporting as product defects, if appropriate.

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10.3.4. Recording/Reporting and Follow-up of AEs and/or SAEs
AE and SAE Recording/Reporting
The table below summarizes the requirements for recording AEs on the CRF and for 
reporting SAEs on the Vaccine SAE Reporting Form to Pfizer Safety.  These requirements 
are delineated for 3 types of events: (1) SAEs; (2) nonserious AEs; and (3) exposure to the 
study intervention under study during pregnancy or breastfeeding, and occupational 
exposure.
It should be noted that the Vaccine SAE Reporting Form for reporting of SAE information 
is not the same as the AE page of the CRF.  When the same data are collected, the forms 
must be completed in a consistent manner.  AEs should be recorded using concise medical 
terminology and the same AE term should be used on both the CRF and the Vaccine SAE
Reporting Form for reporting of SAE information.
Safety Event
Recorded on the CRF
Reported on the Vaccine 
SAE Reporting Form to 
Pfizer Safety Within 
24 Hours of Awareness
SAE
All
All
Nonserious AE
All
None
Exposure to the study 
intervention under study 
during pregnancy or 
breastfeeding, and 
occupational exposure.
All AEs/SAEs associated 
with EDP or breastfeeding.
Occupational exposure is not 
recorded.
All (and EDP Supplemental 
Form for EDP)
Note: Include all SAEs 
associated with EDP or 
breastfeeding. Include all 
AEs/SAEs associated with 
occupational exposure.

When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (eg, hospital progress notes, laboratory reports, and diagnostic reports) 
related to the event.

The investigator will then record all relevant AE/SAE information in the CRF.

It is not acceptable for the investigator to send photocopies of the participant’s medical 
records to Pfizer Safety in lieu of completion of the Vaccine SAE Reporting
Form/AE/SAE CRF page.

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
There may be instances when copies of medical records for certain cases are requested 
by Pfizer Safety.  In this case, all participant identifiers, with the exception of the 
participant number, will be redacted on the copies of the medical records before 
submission to Pfizer Safety.

The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information.  Whenever possible, the diagnosis (not the 
individual signs/symptoms) will be documented as the AE/SAE.
Assessment of Intensity
The investigator will make an assessment of intensity for each AE and SAE reported during 
the study and assign it to 1 of the following categories: 

Mild: An event that is easily tolerated by the participant, causing minimal discomfort 
and not interfering with everyday activities.

Moderate: An event that causes sufficient discomfort and interferes with normal 
everyday activities.

Severe: An event that prevents normal everyday activities.  An AE that is assessed as 
severe should not be confused with an SAE.  Severe is a category utilized for rating the 
intensity of an event; and both AEs and SAEs can be assessed as severe.
An event is defined as “serious” when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as severe.
GRADE If required on the AE page of the CRF, the investigator will use the 
adjectives MILD, MODERATE, SEVERE, or LIFE-THREATENING to 
describe the maximum intensity of the AE. For purposes of consistency, 
these intensity grades are defined as follows:
1
MILD
Does not interfere with participant's usual 
function.
2
MODERATE
Interferes to some extent with participant's usual 
function.
3
SEVERE
Interferes significantly with participant's usual 
function.
4
LIFE-THREATENING
Life-threatening consequences; urgent 
intervention indicated.

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Assessment of Causality

The investigator is obligated to assess the relationship between study intervention and 
each occurrence of each AE/SAE.

A “reasonable possibility” of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot be 
ruled out.

The investigator will use clinical judgment to determine the relationship.

Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study intervention 
administration, will be considered and investigated.

The investigator will also consult the IB and/or product information, for marketed 
products, in his/her assessment.

For each AE/SAE, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality.

There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to the sponsor.  However, it is very 
important that the investigator always make an assessment of causality for every 
event before the initial transmission of the SAE data to the sponsor.

The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality assessment.

The causality assessment is one of the criteria used when determining regulatory 
reporting requirements.

If the investigator does not know whether or not the study intervention caused the 
event, then the event will be handled as “related to study intervention” for reporting 
purposes, as defined by the sponsor.  In addition, if the investigator determines that an 
SAE is associated with study procedures, the investigator must record this causal 
relationship in the source documents and CRF, and report such an assessment in the 
dedicated section of the Vaccine SAE Reporting Form and in accordance with the SAE 
reporting requirements.

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

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SAE Reporting to Pfizer Safety via the Vaccine SAE Reporting Form
•
Facsimile transmission of the Vaccine SAE Reporting Form is the preferred method to 
transmit this information to Pfizer Safety.
•
In circumstances when the facsimile is not working, notification by telephone is 
acceptable with a copy of the Vaccine SAE Reporting Form sent by overnight mail or 
courier service.
•
Initial notification via telephone does not replace the need for the investigator to 
complete and sign the Vaccine SAE Reporting Form pages within the designated 
reporting time frames.
 
 
 
 
 
CCI

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CCI
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10.5. Appendix 5: Genetics
Not applicable.
10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-up Assessments
Potential Cases of Drug-Induced Liver Injury
Humans exposed to a drug who show no sign of liver injury (as determined by elevations in 
transaminases) are termed “tolerators,” while those who show transient liver injury but adapt 
are termed “adaptors.”  In some participants, transaminase elevations are a harbinger of a 
more serious potential outcome.  These participants fail to adapt and therefore are 
"susceptible" to progressive and serious liver injury, commonly referred to as DILI.  
Participants who experience a transaminase elevation above 3 × ULN should be monitored 
more frequently to determine if they are “adaptors” or are “susceptible.”
LFTs are not required as a routine safety monitoring procedure in this study.  However, 
should an investigator deem it necessary to assess LFTs because a participant presents with 
clinical signs/symptoms, such LFT results should be managed and followed as described 
below.
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In the majority of DILI cases, elevations in AST and/or ALT precede TBili elevations 
(>2 × ULN) by several days or weeks.  The increase in TBili typically occurs while 
AST/ALT is/are still elevated above 3 × ULN (ie, AST/ALT and TBili values will be 
elevated within the same laboratory sample).  In rare instances, by the time TBili elevations 
are detected, AST/ALT values might have decreased.  This occurrence is still regarded as a 
potential DILI.  Therefore, abnormal elevations in either AST OR ALT in addition to TBili 
that meet the criteria outlined below are considered potential DILI (assessed per Hy’s law 
criteria) cases and should always be considered important medical events, even before all 
other possible causes of liver injury have been excluded.
The threshold of laboratory abnormalities for a potential DILI case depends on the 
participant’s individual baseline values and underlying conditions.  Participants who present 
with the following laboratory abnormalities should be evaluated further as potential DILI 
(Hy’s law) cases to definitively determine the etiology of the abnormal laboratory values:

Participants with AST/ALT and TBili baseline values within the normal range who 
subsequently present with AST OR ALT values >3 × ULN AND a TBili value >2 × ULN 
with no evidence of hemolysis and an alkaline phosphatase value <2 × ULN or not 
available.

For participants with baseline AST OR ALT OR TBili values above the ULN, the 
following threshold values are used in the definition mentioned above, as needed, 
depending on which values are above the ULN at baseline:

Preexisting AST or ALT baseline values above the normal range: AST or ALT values 
>2 times the baseline values AND >3 × ULN; or >8 × ULN (whichever is smaller).

Preexisting values of TBili above the normal range: TBili level increased from 
baseline value by an amount of at least 1 × ULN or if the value reaches >3 × ULN 
(whichever is smaller).
Rises in AST/ALT and TBili separated by more than a few weeks should be assessed 
individually based on clinical judgment; any case where uncertainty remains as to whether it 
represents a potential Hy’s law case should be reviewed with the sponsor.
The participant should return to the investigator site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the abnormal results.  This evaluation should 
include laboratory tests, detailed history, and physical assessment.
In addition to repeating measurements of AST and ALT and TBili for suspected cases of 
Hy’s law, additional laboratory tests should include albumin, CK, direct and indirect 
bilirubin, GGT, PT/INR, total bile acids, and alkaline phosphatase.  Consideration should 
also be given to drawing a separate tube of clotted blood and an anticoagulated tube of blood 
for further testing, as needed, for further contemporaneous analyses at the time of the 
recognized initial abnormalities to determine etiology.  A detailed history, including relevant 
information, such as review of ethanol, acetaminophen/paracetamol (either by itself or as a 

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coformulated product in prescription or over-the-counter medications), recreational drug, 
supplement (herbal) use and consumption, family history, sexual history, travel history, 
history of contact with a jaundiced person, surgery, blood transfusion, history of liver or 
allergic disease, and potential occupational exposure to chemicals, should be collected.  
Further testing for acute hepatitis A, B, C, D, and E infection and liver imaging (eg, biliary 
tract) and collection of serum samples for acetaminophen/paracetamol drug and/or protein 
adduct levels may be warranted.
All cases demonstrated on repeat testing as meeting the laboratory criteria of AST/ALT and 
TBili elevation defined above should be considered potential DILI (Hy’s law) cases if no 
other reason for the LFT abnormalities has yet been found.  Such potential DILI (Hy’s law) 
cases are to be reported as SAEs, irrespective of availability of all the results of the 
investigations performed to determine etiology of the LFT abnormalities.
A potential DILI (Hy’s law) case becomes a confirmed case only after all results of 
reasonable investigations have been received and have excluded an alternative etiology.
10.7. Appendix 7: ECG Findings of Potential Clinical Concern
Not applicable.
10.8. Appendix 8: Medical Device Adverse Events, Adverse Device Effects, Serious 
Adverse Events, and Device Deficiencies: Definition and Procedures for Recording, 
Evaluating, Follow-up, and Reporting
Definitions of a Medical Device Incident
The definitions and procedures detailed in this appendix are in accordance with ISO 14155.
Both the investigator and the sponsor will comply with all local medical device reporting 
requirements.
The detection and documentation procedures described in this protocol apply to all sponsor 
medical devices provided for use in the study (see Section 6.1.3 for the list of sponsor 
medical devices).

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10.8.1. Definition of AE and ADE
AE and ADE Definition

An AE is defined as any untoward medical occurrence, unintended disease or injury, or 
untoward clinical signs (including abnormal laboratory finding) in study participants, 
users, or other persons, whether or not related to the investigational medical device.  
This definition includes events related to the investigational medical device or 
comparator for study participants, users, and other persons.  This definition also 
includes events considered related to procedures for study participants only.

An ADE is defined as an AE related to the use of an investigational medical device.  
This definition includes any AEs resulting from insufficient or inadequate instructions 
for use, deployment, implantation, installation, or operation, or any malfunction of the 
investigational medical device as well as any event resulting from use error or from 
intentional misuse of the investigational medical device.
10.8.2. Definition of SAE, SADE, and USADE
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (eg, hospitalization for signs/symptoms of the disease under study, death 
due to progression of disease).

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

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

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

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

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

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10.10. Appendix 10: Abbreviations
The following is a list of abbreviations that may be used in the protocol.
Abbreviation
Term
7vPnC
7-valent pneumococcal conjugate vaccine
13vPnC
13-valent pneumococcal conjugate vaccine
20vPnC
20-valent pneumococcal conjugate vaccine
ACIP
Advisory Committee on Immunization Practices
ADE
adverse device effect
AE
adverse event
ALT
alanine aminotransferase
AOM
acute otitis media
AST
aspartate aminotransferase
BLQ
below the limit of quantitation
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
CFR
Code of Federal Regulations
CI
confidence interval
CIOMS
Council for International Organizations of Medical Sciences
CK
creatine kinase
CONSORT
Consolidated Standards of Reporting Trials
COPD
chronic obstructive pulmonary disease
CRF
case report form
CRM197
cross-reactive material 197
CRO
contract research organization
CSA
clinical study agreement
DILI
drug-induced liver injury
DU
dispensable unit
EC
ethics committee
ECG
electrocardiogram
e-diary
electronic diary
EDP
exposure during pregnancy
EMA
European Medicines Agency
EU
European Union
EudraCT
European Clinical Trials Database
FDA
Food and Drug Administration
FSH
follicle-stimulating hormone
GCP
Good Clinical Practice
GGT
gamma-glutamyl transferase
GMFR
geometric mean fold rise
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Abbreviation
Term
GMR
geometric mean ratio
GMT
geometric mean titer
HAI
hemagglutination inhibition assay
HIPAA
Health Insurance Portability and Accountability Act
HIV
human immunodeficiency virus
HRT
hormone replacement therapy
IB
investigator’s brochure
ICD
informed consent document
ICH
International Council for Harmonisation
ID
identification
IND
investigational new drug application
INR
international normalized ratio
IP manual
investigational product manual
IPAL
Investigational Product Accountability Log
IPD
invasive pneumococcal disease
IRB
institutional review board
IRT
interactive response technology
ISO
International Organization for Standardization
ISF
investigator site file
IWR
interactive Web-based response
LFT
liver function test
LLOQ
lower limit of quantitation
LRI
lower respiratory tract infection
MedDRA
Medical Dictionary for Regulatory Activities
N/A
not applicable
NDCMC
newly diagnosed chronic medical condition
NI
noninferiority
NSAID
nonsteroidal antiinflammatory drug
OPA
opsonophagocytic activity
PI
principal investigator
PPSV23
23-valent pneumococcal polysaccharide vaccine
PT
prothrombin time
QIV
quadrivalent inactivated influenza vaccine
SADE
serious adverse device effect
SAE
serious adverse event
SAP
statistical analysis plan
SD
standard deviation
SIIV
seasonal inactivated influenza vaccine
SoA
Schedule of Activities
SOP
standard operating procedure
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Abbreviation
Term
SRM
study reference manual
SRSD
single reference safety document
SUSAR
suspected unexpected serious adverse reaction
TBili
total bilirubin
TIV
trivalent inactivated influenza vaccine
ULN
upper limit of normal
US
United States
USADE
unanticipated serious adverse device effect
USPI
US package insert
VT
vaccine-type
WHO
World Health Organization
WOCBP
woman/women of childbearing potential

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11. REFERENCES
1.
Said MA, Johnson HL, Nonyane BAS, et al. Estimating the burden of pneumococcal 
pneumonia among adults: a systematic review and meta-analysis of diagnostic 
techniques. PLoS ONE 2013;8(4):e60273.
2.
O'Brien KL, Wolfson LJ, Watt JP, et al. Burden of disease caused by 
Streptococcus pneumoniae in children younger than 5 years: global estimates. Lancet 
2009;374(9693):893-902.
3.
Huang SS, Johnson KM, Ray GT, et al. Healthcare utilization and cost of pneumococcal 
disease in the United States. Vaccine 2011;29(18):3398-412.
4.
Iyer AS, Ohtola JA, Westerink MAJ. Age-related immune response to pneumococcal 
polysaccharide vaccination: lessons for the clinic. Expert Rev 
Vaccines 2015;14(1):85-97.
5.
Jain S, Williams DJ, Arnold SR, et al. Community-acquired pneumonia requiring 
hospitalization among U.S. children. N Engl J Med 2015;372(9):835-45.
6.
Jain S, Self WH, Wunderink RG, et al. Community-acquired pneumonia requiring 
hospitalization among U.S. adults. N Engl J Med 2015;373(5):415-27.
7.
McLaughlin JM, Jiang Q, Isturiz RE, et al. Effectiveness of 13-valent pneumococcal 
conjugate vaccine against hospitalization for community-acquired pneumonia in older 
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