A Phase 1/2, Randomized, Observer-Blind, Dose-Finding, Active-Controlled, Parallel-Group, Clinical Study to Evaluate the Safety, Tolerability, and Immunogenicity of a 31-Valent Pneumococcal Conjugate Vaccine (VAX-31) in Healthy Adults Aged 50 Years and Older
Phase: PHASE1
Conditions: Pneumococcal Vaccines
Sponsor: Vaxcyte, Inc.

 
 
 
Clinical Study Protocol VAX31-101 
Protocol Title: 
A Phase 1/2, Randomized, Observer-Blind, Dose-Finding, 
Active-Controlled, Parallel-Group, Clinical Study to 
Evaluate the Safety, Tolerability, and Immunogenicity of a 
31-Valent Pneumococcal Conjugate Vaccine (VAX-31) in 
Healthy Adults Aged 50 Years and Older 
Protocol Number: 
VAX31-101 
Investigational Product: 
VAX-31 (31-valent Pneumococcal Conjugate Vaccine) 
Sponsor: 
Vaxcyte, Inc. 
825 Industrial Road, Suite 300 
San Carlos, CA 94070 USA 
Tel: 650-837-0111 
Version: 
2.0 
Date: 
08 December 2023  
 
 
 
 
 
 
 
 
 
 
 
 
  

Protocol VAX31-101 
Version 2.0 
08 December 2023 
 
 
 
Protocol Signature Page 
Protocol Number VAX31-101 
This Clinical Study Protocol document and all information provided to you, the Principal 
Investigator, related to this protocol are the confidential and proprietary information of Vaxcyte, 
Inc. (“Sponsor”) and are subject to the terms of the Confidential Disclosure Agreement between 
you and Vaxcyte, Inc.  
By signing below, I hereby confirm the following: 
I agree to abide by the terms of the Vaxcyte, Inc. Confidential Disclosure Agreement. 
I have read this protocol entitled, A Phase 1/2, Randomized, Observer-Blind, Dose-Finding, 
Active-Controlled, Parallel-Group, Clinical Study to Evaluate the Safety, Tolerability, and 
Immunogenicity of a 31-Valent Pneumococcal Conjugate Vaccine (VAX-31) in Healthy Adults 
Aged 50 Years and Older, in its entirety, and I agree to conduct the study according to this 
protocol. Any changes in procedure will only be made if necessary to protect the safety, rights, 
or welfare of subjects. 
I agree to comply with the current International Conference on Harmonisation Tripartite 
Guideline on Good Clinical Practice in addition to the appropriate FDA Code of Federal 
Regulations (CFR) and applicable state and local regulations. 
I agree to conduct the study in person or to supervise the study. 
I agree to ensure that all who assist me in the conduct of the study have access to the study 
protocol, including any amendments thereto, and are also made aware of their responsibilities in 
meeting the foregoing obligations. 
 
 
 
 
 
Principal Investigator (Print Name) 
 
 
 
 
Title 
 
 
 
 
 
 
Signature 
Date 
Site to send signed copy to Vaxcyte, Inc. and to keep original for files.  

Protocol VAX31-101 
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Table of Contents 
Clinical Study Protocol VAX31-101 .............................................................................................1 
Vaxcyte Approvals .........................................................................................................................2 
Protocol Signature Page ................................................................................................................3 
Table of Contents ...........................................................................................................................4 
List of Tables ...........................................................................................................................8 
List of Figures ..........................................................................................................................8 
List of Abbreviations ...............................................................................................................9 
1. 
Protocol Synopsis .................................................................................................................11 
2. 
Introduction .........................................................................................................................15 
2.1 
Background and Rationale ........................................................................................15 
 
 
2.1.2 
Rationale for Dosage and Route of Administration ....................................19 
3. 
Objectives and Endpoints ...................................................................................................19 
3.1 
Primary ......................................................................................................................19 
3.2 
Secondary ..................................................................................................................20 
 
 
4. 
Study Plan ............................................................................................................................21 
4.1 
Study Design .............................................................................................................21 
4.2 
Number of Study Participants ...................................................................................23 
4.3 
Estimated Study Duration ..........................................................................................23 
4.4 
Study Population .......................................................................................................24 
4.4.1 
Inclusion Criteria .........................................................................................24 
4.4.2 
Exclusion Criteria........................................................................................24 
5. 
Study Vaccine .......................................................................................................................26 
5.1 
Investigational Vaccine (VAX-31) ............................................................................26 

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5.1.1 
Active Comparator ......................................................................................27 
5.1.2 
Ancillary Supplies .......................................................................................27 
5.2 
Dose Preparation of Study Vaccines .........................................................................27 
5.2.1 
VAX-31 .......................................................................................................27 
5.2.2 
PCV20 .........................................................................................................28 
5.2.3 
Study Vaccine Administration ....................................................................28 
5.3 
Accountability Procedures for Study Vaccines .........................................................28 
6. 
Study Procedures .................................................................................................................29 
6.1 
Informed Consent ......................................................................................................29 
6.2 
Screening ...................................................................................................................29 
6.3 
Medical History .........................................................................................................30 
6.4 
Physical Examination ................................................................................................30 
6.5 
Vital Signs .................................................................................................................30 
6.6 
Laboratory Tests ........................................................................................................31 
6.6.1 
Blood Volume .............................................................................................31 
6.6.2 
Safety Laboratory Assessments ..................................................................31 
6.6.3 
Immune Response Assessments ..................................................................32 
6.7 
Pregnancy Testing and Contraception .......................................................................33 
6.8 
Randomization ...........................................................................................................33 
6.9 
Study Vaccine Administration ..................................................................................34 
6.10 
Acute Observation .....................................................................................................34 
6.11 
Solicited Adverse Events ...........................................................................................35 
6.12 
Unsolicited Adverse Events ......................................................................................36 
6.13 
Prior and Concomitant Medications and Procedures ................................................36 
6.14 
Prohibited Medications and Therapies ......................................................................36 
6.15 
Emergency Unblinding ..............................................................................................36 

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6.16 
Protocol Deviations ...................................................................................................37 
6.17 
Dosing Errors .............................................................................................................37 
6.18 
Study Completion for Individual Subjects ................................................................37 
6.19 
Early Termination ......................................................................................................37 
6.20 
Study Completion: Overall ........................................................................................38 
7. 
Study Procedures by Visit ...................................................................................................38 
7.1 
Scheduled Study Visits ..............................................................................................38 
7.1.1 
Screening (-30 days to Day 1) .....................................................................38 
7.1.2 
Day 1 ...........................................................................................................39 
7.1.3 
Day 8 (+3 days) ...........................................................................................40 
7.1.4 
Day 15 (+3 days) .........................................................................................40 
7.1.5 
Month 1 (30 days after Day 1, ±3 days)......................................................40 
7.1.6 
Months 2, 3, 4, 5, and 6 (60 to 180 days after Day 1 [±5 days]) ................40 
7.2 
Early Termination Visit .............................................................................................41 
7.3 
Unscheduled Visits ....................................................................................................41 
8. 
Safety ....................................................................................................................................41 
8.1 
Definitions .................................................................................................................41 
8.1.1 
Adverse Event .............................................................................................41 
8.1.2 
Solicited Adverse Event ..............................................................................42 
8.1.3 
Unsolicited Adverse Event ..........................................................................43 
8.1.4 
Serious Adverse Event ................................................................................43 
8.2 
Severity Grading ........................................................................................................43 
8.3 
Causality Assessment ................................................................................................44 
8.4 
Follow-up of Adverse Events ....................................................................................45 
8.5 
Reporting of Adverse Events .....................................................................................45 
8.5.1 
Reporting Periods ........................................................................................45 
8.5.2 
Documentation ............................................................................................46 

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8.6 
SAE Reporting ...........................................................................................................46 
8.7 
Other Events Requiring Immediate Reporting ..........................................................48 
8.7.1 
Pregnancy ....................................................................................................48 
8.8 
Medical Monitor ........................................................................................................48 
8.9 
Data Monitoring Committee ......................................................................................48 
8.10 
Study Stopping Rules ................................................................................................48 
9. 
Data Handling ......................................................................................................................49 
9.1 
Source Documentation ..............................................................................................49 
9.2 
Data Monitoring ........................................................................................................50 
9.3 
Electronic Patient Reported Outcome Data ...............................................................50 
9.4 
Audit Compliance ......................................................................................................51 
9.5 
Laboratory Data .........................................................................................................51 
10. Statistical Analysis ...............................................................................................................51 
10.1 
Sample Size Calculation ............................................................................................52 
10.2 
Treatment Period .......................................................................................................52 
10.3 
Treatment Groups ......................................................................................................52 
10.4 
Populations for Analysis ............................................................................................52 
10.5 
Demographic and Baseline Characteristics Analysis ................................................53 
10.6 
Safety Analysis ..........................................................................................................53 
10.6.1 
Analysis of Extent of Exposure ..................................................................54 
10.6.2 
Solicited Adverse Events ............................................................................54 
10.6.3 
Unsolicited Adverse Events ........................................................................55 
10.6.4 
Combined Solicited and Unsolicited Adverse Events ................................55 
10.6.5 
Analysis of Other Safety Data ....................................................................56 
10.7 
Immunogenicity Analysis ..........................................................................................56 
10.7.1 
Geometric Mean Titer, Geometric Mean Concentration, and Geometric 
Mean Titer Fold Rise ..................................................................................56 

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10.7.2 
Threshold Analyses .....................................................................................57 
10.8 
Defined Safety Evaluation .........................................................................................57 
10.9 
Interim Analysis ........................................................................................................57 
11. Additional Information .......................................................................................................57 
11.1 
Ethical Conduct of the Study .....................................................................................57 
11.2 
IRB Oversight ............................................................................................................57 
11.3 
Informed Consent ......................................................................................................58 
11.4 
Subject Confidentiality ..............................................................................................58 
11.5 
Compensation for Injury ............................................................................................59 
11.6 
Clinicaltrials.gov .......................................................................................................59 
11.7 
Public Disclosure and Publication Policy ..................................................................59 
11.8 
Amendments ..............................................................................................................59 
12. Appendix A: Schedule of Events ........................................................................................60 
13. References ............................................................................................................................61 
 
 
 
 
List of Tables 
Table 1 
Blood Collections .........................................................................................31 
 
List of Figures 
Figure 1 
Study Schema for Stage 1 ............................................................................22 
Figure 2 
Study Schema for Stage 2 ............................................................................23 
Figure 3 
Safety Events Reporting Periods ..................................................................46 

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List of Abbreviations 
ACIP 
Advisory Committee on Immunization Practices 
AE 
Adverse event(s) 
ALCOA-C 
Attributable, legible, contemporaneous, original, accurate, and complete 
ALPO 
Aluminum phosphate 
ALT 
Alanine aminotransferase 
ANCOVA 
Analysis of covariance 
ANOVA 
Analysis of variance 
CBC 
Complete blood count 
CFR 
Code of Federal Regulations 
CI 
Confidence interval(s) 
CRF 
Case report form(s) 
CRO 
Contract research organization(s) 
CRP 
C-reactive protein 
CRM 
Cross-reactive material 
CSR 
Clinical Study Report 
DMC 
Data Monitoring Committee 
DP 
Drug Product(s) 
eCRF 
Electronic Case Report Form(s) 
eCRM 
Proprietary nontoxic diphtheria toxin carrier protein used in VAX-31 
EDC 
Electronic data capture 
EDTA 
Ethylenediaminetetraacetic acid 
ELISA 
Enzyme-linked immunosorbent assay 
ePRO 
Electronic patient reported outcomes 
ET 
Early Termination 
FDA 
Food and Drug Administration 
FIH 
First-in-Human 
GCP 
Good Clinical Practice 
GMC 
Geometric Mean Concentration 
GMFR 
Geometric Mean Fold Rise 
GMR 
Geometric Mean Ratio 
GMT 
Geometric Mean Titer 
HIV  
Human Immunodeficiency Virus 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 

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IEP 
Immunogenicity evaluable population 
IgG 
Immunoglobulin G 
IM 
Intramuscular 
IND 
Investigational New Drug 
IRB 
Institutional Review Board 
LLOQ 
Lower Limit of Quantitation 
MAAE 
Medically attended adverse event(s) 
MOPA 
Multiplexed opsonophagocytic assay 
MSD 
Meso Scale Discovery 
NOCI 
New onset of chronic illness(es) 
NZW 
New Zealand White (species of rabbits) 
OPA 
Opsonophagocytic assay 
pAMF 
Para-azidomethyl-L-phenylalanine 
PCV 
Pneumococcal conjugate vaccine(s) 
PCV13 
13-valent pneumococcal conjugate vaccine (Prevnar 13®) 
PCV15 
15-valent pneumococcal conjugate vaccine (Vaxneuvance™) 
PCV20 
20-valent pneumococcal conjugate vaccine (Prevnar 20®)  
PD 
Pneumococcal disease 
PFS 
Prefilled syringe(s) 
PPV 
Pneumococcal polysaccharide vaccine 
PPV23 
23-valent pneumococcal polysaccharide vaccine (Pneumovax® 23) 
PS 
Polysaccharide 
S. pneumoniae 
Streptococcus pneumoniae 
SAE  
Serious adverse event(s) 
SAP 
Statistical analysis plan 
SMMP 
Safety medical management plan 
SOC 
System organ class 
SST 
Serum Separator Tube 
SUSAR 
Suspected unexpected serious adverse reaction(s) 
TEAE 
Treatment emergent adverse event(s) 
VAX-31 
31-valent investigational pneumococcal conjugate vaccine 
US 
United States 
WHO 
World Health Organization 
WHODrug 
World Health Organization Drug (medicinal information dictionary) 
 

Protocol VAX31-101 
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1. 
Protocol Synopsis 
Sponsor 
Vaxcyte, Inc. 
Name of Investigational Product 
VAX-31 (31-valent Pneumococcal Conjugate Vaccine) 
Names of Comparator Products 
Prevnar 20® (20-valent Pneumococcal Conjugate Vaccine; PCV20) 
Study Title 
A Phase 1/2, Randomized, Observer-Blind, Dose-Finding, Active-Controlled, Parallel-Group, Clinical 
Study to Evaluate the Safety, Tolerability, and Immunogenicity of a 31-Valent Pneumococcal 
Conjugate Vaccine (VAX-31) in Healthy Adults Aged 50 Years and Older 
Study Number VAX31-101 
Study Phase 
1/2 
Study Sites 
Approximately 25 investigative sites in the US 
Study Objectives and Endpoints 
Primary: 
The primary objectives are: 
• 
To evaluate the safety and tolerability of a single injection of VAX-31 at 3 dose levels administered 
to healthy adults aged 50 years and older. 
• 
To compare the safety of VAX-31 to that of PCV20 administered to 4 age groups: 
– Subjects 50 to 59 years of age 
– Subjects 50 years of age and older 
– Subjects 60 years of age and older 
– Subjects 65 years of age and older 
The primary endpoints are: 
• 
Percentage of subjects reporting solicited local reactions within 7 days after vaccination (redness, 
swelling, and pain at injection site) in each age group 
• 
Percentage of subjects reporting solicited systemic events within 7 days after vaccination (fever, 
headache, fatigue, muscle pain, and joint pain) in each age group 
• 
Percentage of subjects reporting unsolicited adverse event (AE) within 1 month after vaccination in 
each age group 
• 
Percentage of subjects reporting serious adverse event (SAE) within 6 months after the vaccination 
• 
Percentage of subjects reporting new onset of chronic illness (NOCI) within 6 months after the 
vaccination 
• 
Percentage of subjects reporting medically attended adverse event (MAAE) within 6 months after 
vaccination 

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Study Objectives and Endpoints cont. 
Secondary: 
The secondary objectives are: 
• 
Safety: To assess laboratory value abnormalities and/or potentially clinically significant laboratory 
values following the administration of VAX-31 at 3 dose levels compared to control groups 
receiving PCV20 for subjects 50 years and older. 
• 
Immunogenicity: To assess the induction of antibody responses to the 20 serotypes in common in 
PCV20 and VAX-31, as well as to the additional 11 non-PCV20 serotypes in VAX-31 for the 
following subpopulations: 
– Subjects 50 to 59 years of age 
– Subjects 50 years of age and older 
– Subjects 60 years of age and older 
– Subjects 65 years of age and older 
The secondary endpoints include the following: 
• 
Safety: Percentage of participants with laboratory value abnormalities and/or potentially clinically 
significant laboratory values at 1 month (30 days) after vaccination 
• 
Safety: Change from baseline in laboratory parameters at 1 month (30 days) after vaccination 
• 
Immunogenicity: 31 VAX-31 Pneumococcal serotype-specific opsonophagocytic assay (OPA) 
geometric mean titer (GMT) at 1 month (30 days) after vaccination 
• 
Immunogenicity: 31 VAX-31 Pneumococcal serotype-specific IgG geometric mean concentration 
(GMC) at 1 month (30 days) after vaccination 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Study Design 
This Phase 1/2 parallel-group, randomized, 2 stage observer-blind study is to be conducted in 
3 populations of healthy adults, aged 50 to 59, 60 to 64, and 65 years and older. Subjects will be 
randomly assigned in a 1:1:1:1 ratio to receive either VAX-31 at 1 of 3 dose levels or a single dose of 
PCV20, the active comparator. 
In Stage 1 of the study, 64 subjects (16 for each VAX-31 dose group and 16 for the comparator group) 
50 to 64 years of age will be enrolled initially. In Stage 2, approximately 736 additional adults aged 
50 to 64 years as well as a minimum of 200 adults aged 65 years and older will be concurrently 
enrolled. Subjects will have screening procedures (physical examination, vital signs, urine pregnancy 
test for females of childbearing potential), and if eligible, will be enrolled into the study. All subjects 
will have a urine sample collected as well as blood samples drawn for immunogenicity analysis (OPA 
and IgG) and safety laboratory analysis at Day 1 (predose) and Month 1 (30 days after vaccination). 
Subjects will receive VAX-31 or PCV20 on Day 1. Solicited AE will be collected for 7 days after 
vaccination and unsolicited safety information for 30 days after vaccination, with SAE, NOCI, and 
MAAE collected up to 6 months after vaccination. 
A defined safety review of data (solicited and unsolicited AE and SAE) through 7 days after vaccination 
of the 64 subjects in Stage 1 will be conducted by an independent Data Monitoring Committee (DMC) 
before proceeding with Stage 2 of the study. 
If the DMC agrees that the study may continue after reviewing data from Stage 1, Stage 2 will 
commence and approximately 736 additional adults aged 50 to 64 years as well as a minimum of 
200 adults aged 65 years and older will be concurrently enrolled. Subjects will have screening 
procedures (physical examination, vital signs, urine pregnancy test for females of childbearing 
potential), and if eligible, will be enrolled into the study. All subjects will have a urine sample collected 
as well as blood samples drawn for immunogenicity analysis (OPA and IgG) and safety laboratory 
analysis at Day 1 (predose) and Month 1 (30 days after vaccination). Subjects will be randomly 
assigned in a 1:1:1:1 ratio to receive either VAX-31 at 1 of 3 dose levels or PCV20. Solicited AE will 
be collected for 7 days post-vaccination and unsolicited safety information for 30 days post-vaccination, 
with safety data (limited to SAE, NOCI, and MAAE) collected up to 6 months post-vaccination.  
Study Population 
The study population will comprise approximately 1000 healthy US adults: up to 600 eligible subjects 
aged 50 to 59, a minimum of 200 subjects aged 60 to 64, as well as a minimum of 200 subjects aged 
65 years and older.  
Main Criteria for Inclusion 
Healthy adult subjects aged 50 years and older without a previous history of pneumococcal disease and 
who have never received a licensed or investigational pneumococcal vaccine. 
Test Product, Dose, and Mode of Administration 
VAX-31 will be administered once by intramuscular (IM) injection at 1 of 3 dose levels based on the 
amount of polysaccharide present: 1.1 mcg (Low), 2.2 mcg (Mid), and 3.3 mcg (High) for all serotypes 
with the exception of serotypes 1, 5, and 22F which will be 1.65 mcg, 3.3 mcg, and 4.4 mcg for the 
3 dose levels, respectively. 

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Reference Therapy, Dose, and Mode of Administration 
PCV20 will be administered once by IM injection at a dose of 0.5 mL. 
Treatment and Duration of Treatment 
Treatment comprises a single IM injection of VAX-31 or a single IM injection of PCV20. 
Safety Assessments 
Subjects will be evaluated for solicited and unsolicited AE, including injection site reactions following 
vaccine administration. Additionally, vital signs, changes in laboratory values, NOCI, and MAAE 
following administration of study vaccines will be evaluated.  
Statistical Methods 
Various standard statistical methods will be employed to analyze the data, including descriptive 
statistics, linear models, and graphical displays. 
Summary statistics will comprise frequencies and percentages of responses in each category for discrete 
measures and of counts, means, medians, standard deviations, 95% confidence intervals (CI), and 
minimum and maximum values for continuous measures and will be presented by study treatment. 
All calculated fields will be listed in various data listings for review. Additional analyses may be 
performed by the Sponsor to supplement these results. 
Version 9.4M6 (TS1M6) or higher of the SAS® statistical software package will be used to provide all 
statistical analyses. 

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2. 
Introduction  
2.1 
Background and Rationale 
Streptococcus pneumoniae (S. pneumoniae) is the pathogen that causes pneumococcal disease 
(PD), classified as either noninvasive (pneumonia, acute sinusitis, otitis media, and 
conjunctivitis) or invasive (meningitis, sepsis, endocarditis, and pericarditis). A persistent global 
incidence of PD, driven by emerging serotypes not covered by currently available vaccines, has 
resulted in high morbidity and mortality worldwide. Pneumococci cause over 50% of all cases of 
bacterial meningitis in the US (Gierke, 2021). Mortality rates for invasive pneumococcal disease 
in the United States (US) range from 11% to 30% in adults (CDC, 2019). The overall case-
fatality rate for pneumococcal bacteremia is approximately 20% overall, increasing to 60% in 
older adults (CDC, 2022). Pneumococcal pneumonia case fatality rates are also quite significant, 
estimated to be 5% to 7% overall with much higher rates also among older adults (Gierke, 2021). 
In a prospective population-based cohort study of adult residents in Louisville, Kentucky, from  
1 June 2014 to 31 May 2016, mortality during hospitalization for pneumonia was 6.5%, 
corresponding to an estimated 102,821 annual deaths in the US (Ramirez, 2017). 
Despite substantial reductions in PD with the availability of pneumococcal conjugate vaccines 
(PCV) as well as a pneumococcal polysaccharide vaccine (PPV), due to the diversity of 
serotypes and the phenomenon of serotype replacement, a significant burden of PD remains 
which is currently not covered by the currently available pneumococcal vaccines PCV13, 
PCV15, PCV20, and PPV23. 
For example, the invasive pneumococcal disease (IPD) incidence in 2017 in the population aged 
<5 years old was reported to be 1.7 cases per 100,000 due to PCV13 serotypes, while the 
incidence of IPD due to non-PCV13 serotypes was 5.3 cases per 100,000. Similarly, in the 
population aged 65 years and older IPD incidence in 2017 was reported to be 6.8 cases per 
100,000 due to PCV13 serotypes, while the incidence of IPD due to non-PCV13 serotypes was 
19 cases per 100,000 (Varghese, 2020). In all age groups in 2017, approximately 28.3% of IPD 
in the US was due to serotypes in PCV13, 41.3% was due to serotypes in PCV15, 59.5% was due 
to serotypes in PCV20, 69.2% was due to serotypes in VAX-24, and 93.7% was due to serotypes 
in VAX-31 (calculated from Table 1 in Varghese, 2020). 
Additionally, it is important to note that PCV have been shown to elicit T-cell-dependent 
immune response, resulting in a more robust and longer-lasting immune response in both infants 
and the elderly compared to that elicited by PPV23 (Andrews, 2014; Matanock, 2019; Richter, 
2013). Based on this information, the Advisory Committee on Immunization Practices (ACIP) 
recommended in October 2021 the use of PCV20 without a subsequent dose of PPV23 or the use 
of Vaxneuvance™ (PCV15) followed by PPV23 in adults at increased risk of pneumococcal 

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disease, including all adults ≥65 years of age. In 2023, the CDC recommended routine 
administration of PCV15 or PCV20 for all adults aged 65 years or older who have never received 
any pneumococcal conjugate vaccine or whose previous vaccination history is unknown 
(CDC, 2023). 
Developing PCV with greater serotype coverage using conventional technologies has proven to 
be difficult for 2 reasons. First, data show that as more carrier protein/polysaccharide (PS) 
conjugates are added to existing PCV, immune responses to the PS often decrease due to the 
cumulative amount of carrier protein, which immunologically competes with the PS antigens 
(Dagan, 2010), as most recently seen with PCV20 (Pfizer, 2023). Second, conjugating additional 
PS to a carrier protein molecule may mask existing T-cell epitopes that are critically important in 
eliciting an immune response. In the PCV13 carrier protein CRM197, approximately 20% of the 
39 lysine residues border relevant T-cell epitopes (Choe, 1992; Diethelm-Okita, 2000; 
Raju, 1995). Since conventional conjugation chemistry heterogeneously conjugates PS to lysine 
residues independent of their proximity to T-cell epitopes, a bound PS may block the 
presentation of a T-cell epitope to the immune system, thus preventing the induction of a T-cell 
response. Meanwhile, the B-cell epitopes of both the carrier protein and the antigen are presented 
to the immune system, increasing B-cell competition for any available T-cell help. The masking 
of these critical epitopes prevents the conversion to a T-cell dependent immune response and 
negates the benefit of the carrier protein. This competition for T-cell help diminishes the immune 
response to the PS antigen and is believed to result in the phenomenon known as carrier 
suppression (Dagan, 2010). To address this issue, Vaxcyte is developing a 24-valent PCV 
(VAX-24), and a 31-valent PCV (VAX-31) using a novel process that combines site-specific 
conjugation to the carrier protein and a highly efficient conjugation chemistry. Vaxcyte employs 
a cell-free protein synthesis platform to insert the non-native amino acid para-azidomethyl-L-
phenylalanine (pAMF) into eCRM, a recombinant version of CRM197. These pAMF residues 
serve as PS conjugation sites and are inserted in place of purposefully selected lysines, such that 
critical T-cell epitopes remain consistently exposed upon conjugation to maximize the T-cell 
dependent immune response. 
Vaxcyte’s PCV clinical development program comprises 2 vaccines for active immunization 
against S. pneumoniae: VAX-24 and VAX-31. VAX-24 has been administered as a single dose 
to adults in 2 completed Phase 1/2 clinical trials. These clinical trials demonstrated that VAX-24 
has an acceptable safety and tolerability profile similar to PCV20 and elicits an immune response 
meeting standard noninferiority criteria for all 20 serotypes shared with PCV20 and superiority 
criteria for the 4 serotypes not in PCV20. Additionally, VAX-24 reverses the historical trend of 
lower immune response with broader serotype coverage and elicits ~20% higher immune 
response across shared serotypes when compared with PCV20. 

Protocol VAX31-101 
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Safety data in adults are available from the VAX-24 clinical program, in which a total of 
779 adults have received at least 1 dose of VAX-24. Two clinical studies of VAX-24 have been 
completed: VAX24-101, a Phase 1/2 study in adults 18 to 64 years of age and VAX24-102, a 
Phase 2 study in adults 65 years of age and older. The control vaccine in these studies was 
PCV20. In both studies, the safety and tolerability profile of VAX-24 was generally similar to 
that of licensed PCV. In both studies, the most commonly reported solicited adverse event (AE) 
in >10% of PCV20 recipients were pain at injection site (~70%), muscle pain (~50%), fatigue 
(~40%), headache (~30%), and arthralgia (~20%). All solicited AE were similarly distributed 
among the study groups. These events were typically mild to moderate and self-limiting. 
The safety profile of VAX-24 was consistent across study groups with no apparent dose 
dependence, and the incidence of events was similar to that for the PCV20 control. In the 
VAX-24 groups, 12.3% of subjects experienced a Treatment Emergent Adverse Event (TEAE) 
within 1 month post-vaccination, 11.3% experienced a MAAE, 1.9% experienced NOCI, and 
1.2% experienced SAE through 6 months post-vaccination. No NOCI or SAE were reported by 
the Investigators as related to VAX-24 and no clinically relevant abnormalities were observed in 
vital signs or laboratory parameters during either study. Additionally, protocol-specified safety 
laboratory assessments in the first-in-human study of VAX-24, VAX24-101, including baseline 
and Day 29 serum chemistry, hematology, and urinalysis panels, showed no clinically relevant 
post-vaccination changes or differences between treatment groups. Based on the favorable results 
from the VAX-24 clinical studies and the continued unmet need for vaccine-induced protection 
against additional serotypes not represented in currently approved PCV or VAX-24, Vaxcyte has 
initiated development of VAX-31. 
VAX-31 vaccine is a sterile liquid suspension of capsular pneumococcal polysaccharide antigens 
of S. pneumoniae serotypes 1, 2, 3, 4, 5, 6A, 6B, 7C, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15A, 
15B, 16F, 17F, 18C, 19A, 19F, 20B, 22F, 23A, 23B, 23F, 31, 33F and 35B, each individually 
conjugated in a site-specific manner to a carrier protein referred to as eCRM, which is an amino 
acid variant of the detoxified version of the diphtheria toxin known as CRM197. 
VAX-31 contains the same 24 conjugated polysaccharides as VAX 24, plus 7 additional 
serotypes. The same manufacturing processes are used for VAX-31 and VAX-24, and they are 
supplied in the same formulation (295 mcg succinate, 4385 mcg sodium chloride, 1175 mcg 
sodium phosphate, 500 mcg polysorbate 80 at pH 5.8, with 0.125 mg of aluminum phosphate 
added per 0.5 mL dose). Each vial is filled to deliver a single 0.5 mL dose of vaccine for IM 
administration, with no preservative. 

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2.1.2 
Rationale for Dosage and Route of Administration 
VAX-31 will be administered at 1 of 3 dose levels based on the amount of polysaccharide 
present: 1.1 mcg (Low), 2.2 mcg (Mid), and 3.3 mcg (High) for all serotypes with the exception 
of serotypes 1, 5, and 22F, which will be 1.65 mcg, 3.3 mcg, and 4.4 mcg for the 3 dose levels, 
respectively. This dose range was informed by the polysaccharide dose in PCV20 and the results 
of dose-ranging studies with VAX-24. Each Mid dose is formulated to contain a similar quantity 
of S. pneumoniae polysaccharides as that of PCV20, the current standard of care. Serotypes 1, 5, 
and 22F are increased in each of the dose levels because these 3 serotypes had the lowest 
immune responses in VAX24-101. Site-specific conjugation to the eCRM protein carrier 
increases the PS-to-eCRM ratio, enhancing overall T-cell epitope exposure. Consequently, 
VAX-31 Mid dose is consistent with current dosing of licensed PCV, such as PCV15 and 
PCV20. Vaxcyte implemented a Low dose and a High dose to characterize the dose response to 
VAX-31. Safety data from VAX-24 clinical studies support including the High dose in the initial 
dose-finding study for VAX-31. 
 
 
 
 
3. 
Objectives and Endpoints 
3.1 
Primary 
The primary objectives are: 
• 
To evaluate the safety and tolerability of a single injection of VAX-31 at 3 dose levels 
administered to healthy adults 50 years of age and older. 
• 
To compare the safety of VAX-31 to that of PCV20 administered to 4 age groups: 
− Subjects 50 to 59 years of age 
− Subjects 50 years of age and older 
− Subjects 60 years of age and older 
− Subjects 65 years of age and older 
Safety and tolerability will be assessed by measuring the incidence of solicited local and 
systemic AE, unsolicited AE, serious adverse events (SAE), new onset of chronic illness 
(NOCI), and medically attended adverse events (MAAE): 

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• 
Percentage of subjects reporting solicited local reactions within 7 days after vaccination 
(redness, swelling, and pain at injection site) in each age group 
• 
Percentage of subjects reporting solicited systemic events within 7 days after vaccination 
(fever, headache, fatigue, muscle pain, and joint pain) in each age group 
• 
Percentage of subjects reporting unsolicited AE within 1 month (30 days) after vaccination 
in each age group 
• 
Percentage of subjects reporting SAE within 6 months after the vaccination 
• 
Percentage of subjects reporting NOCI within 6 months after the vaccination 
• 
Percentage of subjects reporting MAAE within 6 months after vaccination 
3.2 
Secondary  
The secondary objectives are: 
• 
Safety: To assess laboratory value abnormalities and/or potentially clinically significant 
laboratory values following administration of VAX-31 at 3 dose levels compared to control 
groups receiving PCV20 for subjects 50 years and older. 
• 
Immunogenicity: To assess the induction of antibody responses to the 20 serotypes in 
common in PCV20 as well as to the additional 11 non-PCV20 serotypes in VAX-31 for the 
following subpopulations: 
− Subjects 50 to 59 years of age 
− Subjects 50 years of age and older 
− Subjects 60 years of age and older 
− Subjects 65 years of age and older 
The secondary endpoints include the following: 
• 
Safety: Percentage of participants with laboratory value abnormalities and/or potentially 
clinically significant laboratory values at 1 month (30 days) after vaccination 
• 
Safety: Change from baseline in laboratory parameters at 1 month (30 days) after 
vaccination 
• 
Immunogenicity: 31 VAX-31 Pneumococcal serotype-specific OPA geometric mean titer 
(GMT) at 1 month (30 days) after vaccination. 
• 
Immunogenicity: 31 VAX-31 Pneumococcal serotype-specific IgG geometric mean 
concentration (GMC) at 1 month (30 days) after vaccination 

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Figure 1 
Study Schema for Stage 1 
 
* VAX-31 doses are as follows: 1.1 mcg (Low), 2.2 mcg (Mid), and 3.3 mcg (High) for all serotypes with the 
exception of serotypes 1, 5, and 22F, which are 1.65 mcg, 3.3 mcg, and 4.4 mcg for the 3 dose levels, 
respectively. 
After the safety data in the Stage 1 group is evaluated by the DMC and approved to proceed as 
planned, Stage 2 of the study will start enrollment and the remainder of the 800 subjects aged 
50 to 64 years old (approximately 736 subjects with a minimum of 200 subjects aged 60 to 64) 
along with a minimum of 200 subjects aged 65 years and older will be concurrently enrolled in 
the study across the 4 treatment arms (Figure 2).  
Solicited AE will be collected for 7 days post-vaccination and unsolicited safety information 
for 30 days post-vaccination, with SAE, NOCI, and MAAE collected up to 6 months post-
vaccination. Females of childbearing potential will take a urine pregnancy test at screening and 
immediately prior to vaccination. All subjects in Stage 2 will also have a urine sample collected 
as well as blood samples drawn for safety labs and immunogenicity analysis (OPA and IgG) at 
Day 1 (predose) and Month 1 (refer to Section 6.6.3). 

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Figure 2 
Study Schema for Stage 2 
 
* VAX-31 doses are as follows: 1.1 mcg (Low), 2.2 mcg (Mid), and 3.3 mcg (High) for all serotypes with the 
exception of serotypes 1, 5, and 22F, which are 1.65 mcg, 3.3 mcg, and 4.4 mcg for the 3 dose levels, 
respectively. 
** Minimum of 200 total subjects aged 60 to 64 years (enrolled in Stage 1 and Stage 2) and minimum of 
200 subjects aged 65 years and older. 
4.2 
Number of Study Participants 
The study population will comprise approximately 1000 healthy US adults who meet the 
eligibility criteria listed in Section 4.4.  
Approximately 800 eligible subjects aged 50 to 64 years (with a minimum of 200 subjects aged 
60 to 64 years) and a minimum of 200 subjects aged 65 years and older will be enrolled. 
4.3 
Estimated Study Duration 
The Screening period is 30 days, the Treatment and Observation period is from Day 1 to 
Month 1 (30 days after vaccination), and the Follow-Up period is through Month 6 (180 days 
after study vaccination). The maximum possible study duration for an individual is 7 months 
(210 days). 

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4.4 
Study Population 
4.4.1 
Inclusion Criteria 
Subjects must meet all of the following criteria to be enrolled: 
1) 
Male or female aged 50 to 64 years (inclusive) for Stage 1, or 50 years and older (inclusive) 
for Stage 2 at the time of randomization into the study. 
2) 
Able and willing to complete the informed consent process. 
3) 
Available for clinical follow-up through the last study visit at 6 months after the study 
vaccination. 
4) 
In good general health as determined by medical history, vital signs, physical examination, 
and clinical judgment of the Investigator. 
5) 
Willing to have blood samples collected, stored indefinitely, and used for research 
purposes. 
6) 
Able to provide proof of identity to the satisfaction of the study staff completing the 
enrollment process. 
7) 
Women of childbearing potential, defined as premenopausal females capable of becoming 
pregnant, must have a negative urine pregnancy test immediately prior to randomization 
and agree to use acceptable contraception, defined as: condoms, male or female, with or 
without a spermicide; diaphragm or cervical cap with spermicide; intrauterine device; 
contraceptive pills or patch, Norplant, Depo-Provera; or a female with a male partner that 
has previously undergone a vasectomy. Subjects must agree to consistently practice 
contraception if sexually active at least 7 days prior to enrollment and throughout the 
duration of the study. 
8) 
Able to access and use a smartphone, tablet, computer, or other device connected to Wi-Fi 
or cellular network for completion of an electronic diary.  
4.4.2 
Exclusion Criteria 
Subjects who meet any of the following criteria cannot be enrolled: 
1) 
Previous pneumococcal disease (either confirmed or self-reported). 
2) 
Previous receipt of a licensed or investigational pneumococcal vaccine. 
3) 
Receipt of any investigational study product within 30 days prior to enrollment into the 
study, currently participating in another interventional investigational study, or having plans 
to receive another investigational product(s) while on study.  

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4) 
Planned or actual administration of any licensed vaccine during the period starting 30 days 
before enrollment into the study through Month 1. 
5) 
Physical examination indicating any clinically significant medical condition. 
6) 
Body Temperature >38.0°C (>100.4°F) or acute illness within 3 days prior to study 
vaccination (subject may be rescheduled). 
7) 
Previous or existing diagnosis of HIV, Hepatitis B, or Hepatitis C. 
8) 
History of severe allergic reaction with generalized urticaria, angioedema, or anaphylaxis. 
9) 
Female who is pregnant, breastfeeding, or planning to become pregnant during study 
participation. 
10) Bleeding disorder diagnosed by a doctor (e.g., factor deficiency, coagulopathy, or platelet 
disorder requiring special precautions) resulting in clinically significant bruising or 
bleeding difficulties with IM injections or blood draws. 
11) Any other chronic or clinically significant medical condition that, in the opinion of the 
Investigator, would jeopardize the safety or rights of the subject or confound evaluation of 
the study vaccine, including but not limited to diabetes mellitus type I, untreated 
hypertension, chronic hepatitis or clinically significant forms of drug or alcohol abuse, 
asthma, autoimmune disease, psychiatric disorders, heart disease, pulmonary disease, 
neurologic disease, cancer, or any known or suspected impairment of immune function. 
12) Any medical, psychiatric, or social condition that in the judgment of the Investigator is a 
contraindication to protocol participation or impairs a subject’s ability to give informed 
consent. 
13) Received blood or blood product (including Immune Globulin IV) within 90 days prior to 
enrollment into the study. 
14) Received systemic corticosteroids (except for inhaled, topical, intra-articular) for 
≥14 consecutive days and has not completed treatment ≤30 days prior to enrollment into the 
study. 
15) Receiving immunosuppressive therapy, including chemotherapeutic agents used to treat 
cancer or other conditions, immunostimulants, and treatments associated with organ or 
bone marrow transplantation, or autoimmune disease. 
16) History of malignancy ≤5 years before enrollment, except for adequately treated basal cell 
or squamous cell skin cancer or in situ cervical cancer. 

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5. 
Study Vaccine 
5.1 
Investigational Vaccine (VAX-31) 
VAX-31 is the Sponsor’s research name for a 31-valent pneumococcal conjugate vaccine. 
VAX-31 comprises capsular polysaccharide antigens of S. pneumoniae serotypes 1, 2, 3, 4, 5, 
6A, 6B, 7C, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15A, 15B, 16F, 17F, 18C, 19A, 19F, 20B, 22F, 
23A, 23B, 23F, 31, 33F, and 35B, with each of the 31 polysaccharides (1 from each serotype) 
individually conjugated in a site-specific manner to a proprietary non-toxic diphtheria carrier 
protein referred to as eCRM. 
 
 
 Each vial is filled to deliver a single 0.5 mL dose of VAX-31 vaccine for IM 
administration, with no preservative.VAX-31 is manufactured by Laboratoire Baccinex 
(Switzerland) and will be supplied at 3 strengths in single-use 2 mL glass vials. The vial is sealed 
with a 13 mm bromo butyl rubber stopper with FluroTec® coating on the side in contact with 
VAX-31 DP. The stopper is capped with a 13 mm crimped aluminum seal with a flip-off white 
cap for the Low dose level, a blue cap for the Mid dose level, and a natural colored cap for the 
High dose level. 
The 3 different dose levels of VAX-31 will be identified as: 
• 
Low, 1.1 mcg of Polysaccharide (PS)/dose per serotype 
• 
Mid, 2.2 mcg of PS/dose per serotype 
• 
High, 3.3 mcg of PS/dose per serotype. 
Conjugate Drug Substance serotypes 1, 5, and 22F are present at 1.65 mcg for Low, 3.3 mcg for 
Mid, and 4.4 mcg for High dose levels. 
The amount of eCRM also varies by dose level.  The Low dose level contains ~30 mcg of 
eCRM, the Mid dose level contains ~60 mcg of eCRM, and the High dose level contains 
~90 mcg of eCRM.  
VAX-31 must be stored in a temperature-controlled refrigerator at 2°C to 8°C with controlled, 
limited access to authorized personnel only. The temperature should be monitored by checking 
and recording current and maximum/minimum temperature readings inside the vaccine storage 
unit at least once each working day and/or before dosing subjects that day.  

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5.1.1 
Active Comparator 
Prevnar 20 (PCV20), 20-valent pneumococcal conjugate vaccine, is a sterile suspension of 
saccharides of the capsular antigens of S. pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 
10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, and 33F individually linked to nontoxic 
diphtheria CRM197 protein. PCV20 is manufactured by Wyeth Pharmaceuticals, LLC (subsidiary 
of Pfizer Inc.) and is commercially available in the US. Each 0.5 mL dose of the vaccine is 
formulated to contain approximately 2.2 mcg of each S. pneumoniae serotypes 1, 3, 4, 5, 6A, 7F, 
8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, and 33F; 4.4 mcg of the 
polysaccharide from serotype 6B; 51 mcg CRM197 carrier protein; and 100 mcg polysorbate 80, 
295 mcg succinate buffer, 4.4 mg sodium chloride, and 125 mcg aluminum as aluminum 
phosphate adjuvant. PCV20 prefilled syringes (PFS) are to be stored at 2°C to 8°C (36°F to 
46°F), as required by the manufacturer.  
Refer to the PCV20 Package Insert for clinical dosage and administration, storage and handling, 
contraindications, warnings and precautions, and summary of clinical study results. 
5.1.2 
Ancillary Supplies  
The following supplies are provided by the Sponsor for preparation and administration of study 
vaccine: 
• 
1 mL BD Luer-Lok™ Syringe sterile, single use polycarbonate 
• 
1-1/2 inch 25 Gauge Safety Hypodermic Needle Eclipse BD™ single use, sterile 
5.2 
Dose Preparation of Study Vaccines 
A central supply depot(s) will provide study vaccines and ancillary supplies. 
Unblinded site personnel will manage all aspects of the vaccine inventory; prepare the vaccine 
for administration; administer the vaccine and active comparator to study subjects; and store and 
monitor the vaccine in a secure area and maintain all accountability documentation. All study 
site personnel who complete subject assessments will be blinded to the vaccines being 
administered to study subjects. Unblinded site personnel will be trained in all aspects of vaccine 
management, preparation, and administration, and will be provided a Pharmacy Manual 
regarding such procedures. 
5.2.1 
VAX-31 
VAX-31 should be inspected visually for particulate matter and discoloration prior to 
administration. The product should not be used, and the Sponsor should be notified if particulate 
matter or discoloration is found. VAX-31 is a suspension containing ALPO and should be 

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shaken vigorously (for at least 15 seconds) immediately prior to use to obtain a homogenous, 
white suspension in the vaccine container. The vaccine should not be used if it cannot be 
resuspended. All VAX-31 doses are to be withdrawn into Sponsor-provided syringes using 
sterile technique. No dilution or reconstitution is necessary. VAX-31 vials must be stored upright 
and brought to room temperature (≥10 minutes) and administered between 10 to 60 minutes, 
inclusive, from the time the vaccine is removed from the refrigerator. Detailed instructions on 
packaging, preparation, administration, and accountability are found in the VAX31-101 
Pharmacy Manual. 
5.2.2 
PCV20 
PCV20 prefilled syringes (PFS) should be inspected visually for particulate matter and 
discoloration prior to administration. The vaccine should not be used and the Sponsor should be 
notified if particulate matter or discoloration is found. PCV20 is a suspension containing ALPO 
and should be shaken vigorously immediately prior to use to obtain a homogenous, white 
suspension in the vaccine container. The vaccine should not be used if it cannot be resuspended. 
PCV20 will be supplied to the clinical sites as single-use PFS packaged by the manufacturer and 
should be stored horizontally. PCV20 should be administered by IM injection as soon as possible 
after being removed from refrigeration. Preparation and administration instructions are found in 
the PCV20 Prescribing Information (manufacturer’s package insert) and should be adhered to. 
5.2.3 
Study Vaccine Administration 
Each vaccine (VAX-31 or PCV20) is to be administered IM as a single dose in the deltoid 
muscle of the upper arm. 
5.3 
Accountability Procedures for Study Vaccines 
It is the responsibility of the Investigator to supervise accurate monitoring of the receipt, storage, 
dispensing, and accounting of all study vaccines according to accepted industry practice. Sites 
must maintain and retain accurate, original site records of study vaccine inventory as well as all 
shipping documentation, including temperature data, invoices of shipments and records of study 
vaccine distribution. 
Vaccine accountability information will be collected on paper source documents for tracking 
study vaccines (e.g., date material was received, dispensed to individual subjects, and amount 
used and unused on site etc.). 
Each site must keep all used study vaccine cartons until the unblinded CRA has performed 
vaccine accountability and arranges return of unused study vaccines to the central repository 

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vendor. Expired vaccine should be separately quarantined until the unblinded CRA has 
completed accountability monitoring. 
Detailed instructions on packaging, preparation, administration, and accountability are found in 
the VAX31-101 Pharmacy Manual. 
6. 
Study Procedures 
Source documents and source data should meet the elements of data quality and integrity 
(ALCOA-C: attributable, legible, contemporaneous, original, accurate, and complete). 
6.1 
Informed Consent 
The Investigator must obtain informed consent from study subjects at the Screening visit prior to 
starting any study-related activities. All prospective subjects must sign and date an Institutional 
Review Board (IRB)-approved ICF. For further details on informed consent, refer to 
Section 11.3. 
6.2 
Screening 
Screening procedures are listed in the Schedule of Events (Appendix A). 
Each subject who signs an ICF will receive a sequential 3-digit identification number unique to 
the site (e.g., 001, 002, etc.). Upon entry of a subject into the Screening Form within the 
electronic data capture (EDC) system, Zelta, each subject will be automatically assigned a 
unique Subject identifier. This Subject ID will be in the following format: 
 
Study Number – 2-digit site number – 3-digit identification number: VAX31-101-01-001 
Subject numbers will also be sequential since screen-failed subjects will be entered into the EDC 
system. 
Each site is required to record the reason(s) for screen failure for all subjects who receive a 
subject identification number within the EDC system. Sites may elect to use a prescreening 
consent form and maintain a prescreening log for those subjects contacted for the study and will 
provide that log to the Sponsor or designee on request. 
Rescreening: A subject who meets exclusion criterion of having a current acute febrile illness at 
the time of scheduled enrollment may be rescreened after resolution of the acute illness. A 
subject who has taken any prohibited medication within the exclusionary window may be 
rescreened after the appropriate duration has passed. If an eligible subject is not able to be 
randomized and treated within 30 days of the screening period, all screening procedures must be 

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conducted again, including reconsenting and assigning a new subject ID number. A subject may 
be rescreened once only. Rescreening is not otherwise permitted. 
If a subject is rescreened outside of the initial 30-day screening window, a new subject number 
will be assigned as they are entered into the EDC for a new Screening visit and the previous 
subject number will be captured in the source file of the newly assigned subject number. 
6.3 
Medical History 
Medical history information will be collected from subjects at the Screening Visit and confirmed 
at the Day 1 (Baseline) Visit. Medical history will include but not be limited to demographic 
information, current and past medical conditions, and prior and concomitant medications taken 
within 30 days prior to Day 1, including history of vaccinations. 
In consideration of the availability of commercial pneumococcal vaccines and ongoing 
investigational vaccine clinical research, the history of pneumococcal vaccination must be 
collected and, if the subject’s medical records and/or state-mandated vaccine registry are 
available, the site is required to maintain this documentation as part of the eligibility review. 
6.4 
Physical Examination 
A complete physical examination will be performed on subjects during the Screening visit. The 
examination should include: 
• 
Height 
• 
Body weight 
• 
Vital signs 
• 
General appearance 
• 
Eyes-ears-nose-throat 
• 
Head-neck 
• 
Lungs-chest 
• 
Heart 
• 
Abdomen 
• 
Musculoskeletal 
• 
Lymph nodes 
• 
Skin 
• 
Extremities 
• 
Neurological 
A physical exam may be performed on subjects at additional time points if indicated by AE 
reporting. 
6.5 
Vital Signs 
Vital signs collected from subjects will include blood pressure, heart rate, respiratory rate, and 
oral temperature. The first set of Screening vitals are to be collected for inclusion of the subject 
into the study. Repeat measurements on abnormal vital parameters are allowed 1 additional time 

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for inclusion into the study. After Day 1, abnormal vital signs can be repeated for confirmation 
of clinical significance. Vital signs should be taken after at least 5 minutes in supine position. 
6.6 
Laboratory Tests 
6.6.1 
Blood Volume 
Blood is collected by venipuncture, in the appropriate blood container tubes according to the 
schedule of sample collection shown in Appendix A and Table 1. The maximum volume of 
blood taken from a subject is 43 mL. Phlebotomy will observe the American Red Cross limit of 
no more than 450 mL in any 8-week period. 
Table 1 
Blood Collections 
Study Day 
Blood Volume 
(mL) 
Laboratory Tests 
Tube Type/Volume 
Minimum No. 
of 1 mL 
Cryovials 
Day 1 
21.5 mL 
Hematology 
Clinical Chemistry 
Immunogenicity 
1 EDTA 2 mL 
1 SST 2.5 mL 
2 SST 8.5 mL 
Not applicable 
Not applicable 
12 
Month 1 
21.5 mL 
Hematology 
Clinical Chemistry 
Immunogenicity  
1 EDTA 2 mL 
1 SST 2.5 mL 
2 SST 8.5 mL 
Not applicable 
Not applicable 
12 
Note: All cryovials should be frozen and stored at -20C or colder and shipped on dry ice. 
Samples are obtained during the trial according to Appendix A. At each time point, blood is 
collected in the appropriate blood tube(s). 
To minimize the impact of lost or damaged shipments, the frozen serum samples will be sent in 
separate consignments (on different days to minimize risk of transport delays or loss) to the 
central laboratory. 
Further details regarding specimen collection, processing, and shipping will be provided in the 
Central Laboratory Manual. 
6.6.2 
Safety Laboratory Assessments 
Biological samples will be collected for the following clinical laboratory tests and shipped to the 
central laboratory for analysis: 
• 
Hematology: Hemoglobin, White blood cell count (absolute), Neutrophils (absolute), 
Eosinophils (absolute), Platelet count, Blood Film Review, Manual Differential (Panel) 

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• 
Clinical Chemistry: Albumin, Alkaline phosphatase, Alanine aminotransferase (ALT), 
aspartate aminotransferase (AST), Bilirubin (total and direct), Blood urea nitrogen, 
Calcium, Carbon dioxide, Chloride, Cholesterol and triglycerides, Creatinine, Glucose 
(random), Gamma-glutamyl transferase (GGT), Lactate dehydrogenase, Phosphate, 
Potassium, Sodium, Total serum protein, Uric acid 
• 
Urinalysis: Specific gravity, pH, Glucose, Protein (Total), Ketones, Bilirubin, 
Urobilinogen, Hemoglobin, Leucocyte esterase, Nitrite 
Urine pregnancy tests will be conducted at the site using a dipstick before vaccination. 
Unscheduled laboratory tests will be performed if indicated by a change in medical condition 
(including clinically significant abnormal values). The volume to be collected will be appropriate 
to the tests performed. The toxicity grading scales for clinical laboratory values (FDA, 2007) 
must be used when assigning severity to an out-of-range laboratory value; however, not all out of 
range laboratory values are considered AE and need to be evaluated according to Section 8.1.1. 
Further details regarding specimen collection, processing, and shipping will be provided in the 
Central Laboratory Manual. 
6.6.3 
Immune Response Assessments 
Immunogenicity samples should be collected for all subjects randomized in the study. Serum 
antibody responses to pneumococcal polysaccharides induced by vaccination will be measured 
using 2 standard assays, OPA and multiplexed Meso Scale Discovery (MSD). 
The OPA assay has been developed and qualified by Nexelis, a GCP-compliant central 
laboratory, to analyze the functional responses to 31 polysaccharide antigens contained in 
VAX-31. The OPA assay has been consistently used as the method for measuring the functional 
capacity of pneumococcal antibodies, as antibodies to pneumococcal PS protect the host by 
opsonizing pneumococci (marking pneumococci for destruction) for phagocytosis 
(Burton, 2012). 
The MSD assay has been developed and qualified by Nexelis to measure IgG responses against 
the 31 polysaccharide antigens contained in VAX-31. The MSD multiplex electrochemi-
luminescent assay is an immunoassay platform that allows simultaneous measurement of 
responses against multiple antigens and has been used to evaluate responses to various PCV 
(Feyssaguet, 2019; Goldblatt, 2011; Marchese, 2009; Nolan, 2020). 
The immune responses (as assessed by OPA and MSD assays) against the 20 polysaccharide 
antigens common to PCV20 and VAX-31 (1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 

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18C, 19A, 19F, 22F, 23F and 33F) will be compared in the various treatment groups (VAX-31 at 
3 different dose levels, and the comparator vaccine), and the 11 additional polysaccharide 
antigens contained in VAX-31 (2, 7C, 9N, 15A, 16F,17F, 20B, 23A, 23B, 31 and 35B) will be 
evaluated separately. 
6.7 
Pregnancy Testing and Contraception 
Female subjects of childbearing potential, defined as premenopausal females capable of 
becoming pregnant, will undergo a urine pregnancy test at Screening and immediately prior to 
vaccination. The subject must have a negative pregnancy test prior to study vaccine 
administration. The Investigator must report any pregnancies as described in Section 8.7.1. 
Female subjects of childbearing potential must also use an acceptable method of contraception 
from prior to Day 1 through Month 6 (throughout the study). The Investigator must confirm that 
contraception methods were initiated prior to Day 1 (e.g., hormonal contraception) to be 
considered fully effective. 
For reporting a pregnancy, refer to Section 8.7.1. 
6.8 
Randomization 
Subject eligibility will be confirmed and documented by the Investigator immediately prior to 
randomization of each subject. 
Blinded study staff will indicate on a Randomization electronic Case Report Form (eCRF) within 
the EDC system that they want to generate a randomization number for the subject. When they 
indicate yes, a randomization number will be generated from EDC. The randomization number is 
separate from, and does not replace, the subject identification number which is assigned at 
Screening. The unblinded designee will receive information from the Zelta EDC with treatment 
assigned for VAX-31 (1.1/1.65 mcg, 2.2/3.3 mcg, or 3.3/4.4 mcg dose) or treatment assigned 
PCV20 PFS. The unblinded designee may then prepare the treatment assigned for administration. 
Randomization will be 1:1:1:1 for the 4 treatment groups across the sample size (1000 subjects). 
For Stage 1, there were no stratification factors. For Stage 2, randomization will be stratified by 
each of the 25 clinical sites. See Section 10.3 for further details on the sample sizes within each 
age group. 
A subject will be considered enrolled once a randomization number has been assigned within the 
EDC system. The study will be conducted as an observer-blind study. No one except specific 
predesignated unblinded staff (at sites and CRO) will know subjects’ individual treatment 
assignments until all subjects have completed their participation in the study and the database has 
been cleaned and locked. 

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The following safeguards will be employed to reduce the risk of inadvertent unblinding: 
• 
Each clinical site is required to have a blinding plan that outlines its process on blinding the 
subject in situations such as administration of IM injection with different syringe types, 
transport of study vaccine to the clinic room for administration, providing initial training 
and reminders to the subjects on how to maintain the study blind. 
• 
No Sponsor personnel other than the designated unblinded monitor(s), Sponsor unblinded 
Oversight Representative, third-party unblinded biostatistics and programming staff, and 
the Sponsor Medical Director, if necessary, will have access to the randomization treatment 
assignments. If Sponsor personnel are unblinded, they will not provide input on data for the 
specific subject they were unblinded to. 
• 
Should any subject or blinded staff member become inadvertently unblinded, the 
Investigator will promptly (within 24 hours of the Investigator’s awareness of the error) 
disclose the event to the Sponsor clinical study manager and medical monitor in a blinded 
fashion (disclosing only subject number, not treatment) so that corrective action can be 
initiated. The unblinding sequence of events will be documented as a protocol deviation and 
retained as source documents. See Section 6.15 for details on Emergency Unblinding. 
6.9 
Study Vaccine Administration 
On Day 1 before randomization, the medical history, including physical exam (if indicated by 
updated medical history) and vital signs, and concomitant medications will be collected, females 
of childbearing potential must have a negative urine pregnancy test, and information updated in 
the subject file to recheck subject eligibility. Immediately prior to study vaccine administration, 
the following biological samples will be collected: blood for hematology and chemistry, urine for 
urinalysis (and if applicable, pregnancy test), and serum for immunogenicity. Once these 
procedures are performed, study vaccine will be administered. All doses of study vaccine are 
0.5 mL in volume and are administered by IM injection with a Sponsor-provided 1 mL syringe 
and Safety Hypodermic Needle Eclipse 1.5 inch 25 gauge as described above or PCV20 PFS, 
using universal precautions and sterile technique. All injections will be administered into the 
deltoid muscle. Injections will be administered by an unblinded staff member delegated by the 
Investigator. 
6.10 
Acute Observation 
The subject will be monitored by blinded study staff for signs of an acute adverse reaction for at 
least 30 minutes after the injection and the blinded study staff will document any AE. Vital signs 
will also be obtained at least 30 minutes after the injection. 

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Allergic reactions to the study vaccine are possible; therefore, appropriate drugs and medical 
equipment to treat acute anaphylactic reactions must be immediately available and a medically 
qualified study team member trained to recognize and treat anaphylaxis must be present in the 
clinic during the entire post-dosing monitoring period. 
6.11 
Solicited Adverse Events 
Solicited AE will be collected for 7 days after vaccine administration, starting on Day 1. 
Solicited AE for this study are local events of pain, erythema (redness) and edema (swelling) at 
the injection site, and systemic events of oral temperature ≥100.4ºF, fatigue, headache, muscle 
pain, and joint pain. 
Subjects will be trained to complete an electronic diary (eDiary) via Zelta’s electronic Patient 
Reported Outcomes (ePRO) system. The eDiary collects the primary safety endpoint data. This 
system is accessed via a secure URL and will be used to observe, measure, and record these 
solicited AE. A digital thermometer will be provided to the subject to measure oral temperature 
each day, and it is to be recorded daily in the diary. To record injection site local reaction, a ruler 
will be provided to the subject to measure the diameter of redness and swelling at the largest 
point of the reaction each day; it is to be recorded daily in the diary. Study staff will be provided 
with a Reference Guide for instructing subjects on accessing the Zelta ePRO system. Each user 
will be provided with login credentials and a temporary password. The Zelta ePRO system is 
web-based and accessed via a secure URL. 
Study staff will review the signs and symptoms recorded in the diary and the action taken for the 
event during the subject’s clinic visit. The electronic diary will serve as the primary source 
document and data will be automatically integrated into the subject visit Solicited AE form in the 
EDC platform for site staff view-only access. The Investigator will then assess all recorded 
solicited events for severity and relatedness. Severity will be graded according to the FDA 
Toxicity Grading Scale (FDA, 2007). The results of the Investigator’s assessment, if different 
from the subject’s entry, will be recorded in a separate eCRF specified for Investigators. For 
solicited injection site reactions, the relationship to study vaccine will be automatically recorded 
to be probably related, however, the Investigator will determine the relationship for each 
systemic solicited reaction. 
Symptoms continuing beyond the solicited AE collection period (7 days following injection) will 
be collected and recorded as unsolicited AE in the source document. The start date of unsolicited 
AE will be equal to the date of onset of the solicited AE. 

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6.12 
Unsolicited Adverse Events 
Unsolicited AE (any AE not listed in the diary) will be collected for this study. Details regarding 
definitions, evaluation, reporting periods, and documentation are outlined in Section 8. 
6.13 
Prior and Concomitant Medications and Procedures 
At the Screening visit, the details of prior and concomitant medications and procedures (through 
30 days prior to Day 1) usage will be collected, including history of vaccinations. From Day 1 
through Month 1, the details of all concomitant medications and procedures including those 
associated with solicited AE and unsolicited AE, not qualifying as SAE, NOCI or MAAE, will 
be collected. 
Concomitant medications and procedures associated with an SAE, NOCI, and MAAE will be 
collected through the end of the study. 
6.14 
Prohibited Medications and Therapies 
Subjects must not have received or be planning to receive: 
• 
Licensed or investigational pneumococcal vaccine. 
• 
Investigational agents or study product from 30 days prior to Day 1 through the duration of 
the study. 
• 
Other (non-pneumococcal) licensed vaccines from 30 days prior to Day 1 through Month 1. 
• 
Blood or blood product (including IGIV) from 90 days prior to Day 1 through the duration 
of the study. 
• 
Systemic immunosuppressant therapy (e.g., chemotherapeutics) and immunostimulants. 
• 
Immunomodulatory medications (e.g., oral corticosteroids, allergy shots) from 30 days 
prior to Day 1 through Month 1 or received systemic corticosteroids (except for inhaled, 
topical, intra-articular) exceeding physiologic replacement doses from 14 days prior to 
Day 1 through Month 1. 
The history of all prohibited medications at any time during study participation (regardless of 
association with an AE) will be collected. 
6.15 
Emergency Unblinding 
The Investigator may obtain a treatment assignment for a study subject only in the case of a 
medical emergency in which knowledge of the treatment is necessary for management of an AE. 

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The Investigator must notify the Medical Monitor (and as backup, Medical Director) no later 
than 24 hours following unblinding. Additional details for this unblinding process are provided 
in the Pharmacy Manual. 
6.16 
Protocol Deviations 
The Investigator and delegated staff are responsible for conducting the study in accordance with 
the protocol. Any deviation from the protocol must be documented in the study file. Unblinded 
study personnel will document protocol deviations in a blinded manner for the blinded study 
personnel to record in the EDC. In addition, deviations must be reported to the IRB as 
applicable. Subject-specific deviations must be recorded in the subject’s source documents. The 
Sponsor will review all protocol deviations on an ongoing basis and will be responsible for 
categorizing protocol deviations. 
6.17 
Dosing Errors 
The Investigator or designee must report any error in the dosing of study vaccine to the 
site-assigned unblinded CRA and Sponsor Medical Monitor or designee within 24 hours of the 
Investigator’s awareness of the error. Additional information regarding the dosing error may be 
provided as a follow-up report. A dosing error without signs or symptoms is not considered an 
AE but may be determined to be an important protocol deviation and investigated further. 
6.18 
Study Completion for Individual Subjects 
An individual subject is considered to complete study participation after completion of the 
Month 6 visit (180 days after study vaccine administration) and completion of any required 
safety follow-up. 
6.19 
Early Termination 
An individual subject is considered to undergo Early Termination if the subject stops study 
participation before the Month 6 visit. 
An enrolled subject may voluntarily withdraw consent for further participation at any time before 
the Month 6 visit. The Investigator will request (but cannot require) such subjects to provide the 
reason(s) for withdrawal of consent and to undergo an Early Termination visit. 
In addition, the Investigator, at his or her discretion, may withdraw a subject from further 
participation in the study. Criteria for withdrawal by the Investigator include: 
• 
Noncompliance with the protocol 
• 
Pregnancy 
• 
Immediate hypersensitivity reaction associated with a study injection 

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• 
Lost to follow-up status requires documentation of at least 3 unsuccessful attempts to 
contact the subject. Lost to follow-up will be determined after the date of the subject’s 
projected last visit. 
• 
Other reason(s) which, in the opinion of the Investigator, indicate that continued 
participation in the study is not in the best interest of the subject. 
The Investigator or designee must report any early termination for safety reasons to the Sponsor 
Medical Monitor or designee within 24 hours of discontinuation. Additional information 
regarding ongoing AE may be provided as a follow-up report. 
6.20 
Study Completion: Overall 
The study is planned to be completed after all subjects have completed the Month 6 visit (or 
Early Termination, as appropriate), all necessary safety follow-up has been completed, and all 
data have been monitored and queries have been resolved. The Sponsor reserves the right to 
terminate the study prior to the planned study completion. 
7. 
Study Procedures by Visit 
The overall summary of procedures and assessments by visit is provided in the Schedule of 
Events (Appendix A). All visits are relative to the day of vaccine administration, Day 1. 
Acceptable time windows for the visit schedule are indicated. 
7.1 
Scheduled Study Visits 
7.1.1 
Screening (-30 days to Day 1) 
The following will take place during the Screening visit, which will occur within 30 days prior to 
Day 1, or the visit may be combined with Day 1 (preferred): 
• 
Informed consent 
• 
Demographics  
• 
Review of eligibility criteria 
• 
Medical history  
• 
Physical exam  
• 
Vital signs 
• 
Urine pregnancy test for females of childbearing potential  
• 
Prior and concomitant medications review 

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Screening and Day 1 Visits are encouraged to be combined into the same day to complete 1 set 
of procedures.  
7.1.2 
Day 1 
If the subject had a separate Screening visit, the following procedures will take place during the 
Day 1 visit and before study vaccine administration: 
• 
Updated medical history 
• 
Confirm Inclusion/Exclusion criteria are met 
• 
Targeted physical examination, if indicated by updated medical history 
• 
Vital signs 
• 
Biological specimen collection for clinical laboratory tests: 
− Blood for hematology and chemistry 
− Urine for urinalysis 
− Serum for immunogenicity 
• 
Urine pregnancy test for females of childbearing potential 
• 
Prior and concomitant medications review 
• 
Randomization 
All eligible, consented, and randomized subjects will be vaccinated at the Day 1 Baseline visit. 
• 
Study vaccine administration, either VAX-31 or PCV20 
The following procedures will take place during the visit and after study vaccine administration: 
• 
Acute observation for at least 30 minutes after vaccine administration 
• 
Vital signs collected at least 30 minutes after vaccine administration 
• 
AE (solicited and unsolicited) and SAE evaluation 
• 
Review of concomitant medications taken after vaccination 
• 
Instructions on completion of a diary (login to new account for electronic diary), use of a 
ruler and thermometer  

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7.1.3 
Day 8 (+3 days) 
The following procedures will take place at this visit: 
• 
Visual inspection of injection site location 
• 
Review of diary data with the subject; Investigator’s assessment of severity and relationship 
to study vaccine 
• 
Review of concomitant medications 
• 
AE (solicited and unsolicited) and SAE evaluation 
7.1.4 
Day 15 (+3 days) 
This visit is a follow-up phone call for safety evaluation. The following procedures will take 
place at this visit: 
• 
Review of concomitant medications 
• 
AE (unsolicited) and SAE evaluation 
7.1.5 
Month 1 (30 days after Day 1, ±3 days) 
The following procedures will take place during this visit: 
• 
Review of concomitant medications 
• 
AE (unsolicited) and SAE evaluation 
• 
Biological specimen collection for clinical laboratory tests: 
− Blood for hematology and chemistry 
− Urine for urinalysis 
− Serum for immunogenicity  
7.1.6 
Months 2, 3, 4, 5, and 6 (60 to 180 days after Day 1 [±5 days]) 
These visits are follow-up phone calls for safety evaluation. The following procedures will take 
place at each visit: 
• 
SAE, NOCI, and MAAE evaluation 
• 
Review of concomitant medications or vaccines potentially related to SAE, NOCI, MAAE, 
or prohibited medications 

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7.2 
Early Termination Visit 
All subjects who discontinue study participation before the Month 6 visit will be requested to 
undergo an Early Termination (ET) visit. 
• 
Review of diary data with the subject; Investigator’s assessment of severity and relationship 
to study vaccine (if ET is within 7 days) 
• 
Review of unsolicited AE and SAE 
• 
Review of concomitant medications associated with new or ongoing AE and any SAE 
• 
Biological specimen collection for clinical laboratory tests (if ET is after Day 8 and before 
Month 1) 
− Blood for hematology and chemistry 
− Urine for urinalysis 
− Serum for immunogenicity 
7.3 
Unscheduled Visits 
Any study procedure, excluding study vaccination, may be conducted at an unscheduled visit as 
needed. Examples include repeat specimen collection and additional safety follow-up for an AE. 
8. 
Safety 
8.1 
Definitions 
8.1.1 
Adverse Event 
An AE is any untoward medical occurrence in a study subject, regardless of the suspected causal 
relationship with study vaccine. The definition of an AE includes: 
• 
A new-onset symptom or disease 
• 
An exacerbation of a pre-existing symptom or disease 
• 
A new-onset clinical laboratory abnormality considered by the Investigator to be clinically 
significant 
• 
A new-onset symptom or disease that occurs as a result of a protocol-specified procedure 
The definition of an AE does not include: 
• 
A pre-existing symptom or disease that does not worsen during the study (even if first 
disclosed by the subject after the start of the study) 

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• 
A medical or surgical intervention such as surgery, endoscopy, tooth extraction, or 
transfusion (although the condition leading to the procedure or a complication from the 
procedure may be an AE) 
• 
An uncomplicated pregnancy 
• 
A dosing error without any resulting signs or symptoms 
• 
Any other situation where an untoward medical occurrence has not occurred (e.g., 
hospitalization for cosmetic elective surgery or social admissions) 
The definition of a treatment emergent adverse event (TEAE) is an event that occurs after 
vaccination and within 30 days after vaccination (i.e., excluding those after a subject has given 
informed consent, but before vaccination). 
The definition of a medically attended adverse event (MAAE) includes: 
• 
A new onset or worsening of a condition that prompts the subject to seek unplanned 
medical advice at a physician’s office, urgent care center, or Emergency Department 
The definition of a new onset of chronic illness (NOCI) includes: 
• 
A new onset of a disease or condition that requires ongoing medical attention and/or limits 
activity of daily living, e.g., heart disease, cancer, diabetes 
The Investigator will attempt to establish a diagnosis based on signs, symptoms, and other 
clinical information. Whenever possible, the Investigator will report an AE as a diagnosis rather 
than 1 or more signs or symptoms. If a clinically significant laboratory abnormality meets the 
definition of an AE, a diagnosis or clinical signs and symptoms rather than the abnormal clinical 
laboratory finding should be reported if possible. If no diagnosis is known and clinical signs and 
symptoms are not present, but the laboratory abnormality is clinically significant by itself, then it 
should be reported as the AE. 
8.1.2 
Solicited Adverse Event 
A solicited AE is a protocol-specified AE about which the Investigator or designee proactively 
asks the subject during a protocol-specified time period. Solicited AE for this study are local 
events of pain, erythema (redness), and edema (swelling) at the injection site, and systemic 
events of fever (oral temperature ≥100.4ºF), fatigue, headache, muscle pain, and joint pain. 

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8.1.3 
Unsolicited Adverse Event 
An unsolicited AE is an AE that is spontaneously reported by the subject or discovered by the 
Investigator. New onset of chronic illness(es) would be recorded as part of the collection of 
unsolicited AE as specified in the visit procedures. Unsolicited AE will be collected separately 
from solicited AE. Solicited AE occurring or persisting beyond the solicitation period or which 
meet SAE/NOCI/MAAE criteria are also recorded as unsolicited AE. 
8.1.4 
Serious Adverse Event 
An SAE is an AE (either solicited or unsolicited) which meets any of the following criteria: 
• 
Results in death 
• 
Is life-threatening 
• 
Requires hospitalization or prolongs an existing hospitalization 
• 
Results in a persistent or significant incapacity or substantial disruption of the ability to 
conduct normal life functions 
• 
Is a congenital anomaly or birth defect 
• 
Important medical event that may jeopardize the patient or subject and/or may require 
medical or surgical intervention to prevent any of the above outcomes 
The Investigator will evaluate all AE for seriousness using the above criteria. 
“Life-threatening” means that in the opinion of the Investigator the subject was at immediate risk 
of death from the event as it occurred. It does not mean that the event might have caused death 
had it occurred in a more severe form. 
Hospitalization for observation or for elective treatment of a pre-existing condition that did not 
worsen during the study is not considered an SAE. 
Important medical events may be considered serious at the discretion of the Investigator. 
These seriousness criteria also apply to the Study Stopping Rules in Section 8.10. 
8.2 
Severity Grading 
The Investigator will grade all AE for severity. AE listed in the Guidance for Industry, Toxicity 
Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine 
Clinical Trials (FDA, 2007) will be graded according to the criteria in the table. AE not listed in 
the Toxicity Grading Scale will be graded as follows: 

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• 
Mild (Grade 1): 
No interference with activity 
• 
Moderate (Grade 2): 
Some interference with activity 
• 
Severe (Grade 3): 
Significant; prevents daily activity 
• 
Potentially Life-Threatening (Grade 4): ER visit or hospitalization 
8.3 
Causality Assessment 
The Investigator will assess all AE, including solicited AE, for causality (relationship to study 
vaccine), assigning 1 of these 3 categories: Not Related, Possibly Related, or Probably Related. 
An AE will be considered “Not Related” to study vaccine if any of the following conditions are 
met: 
• 
An unreasonable temporal relationship between administration of the study vaccine and the 
onset of the AE (e.g., the event occurred either before or too long after administration of the 
study vaccine for it to be considered related). 
• 
A causal relationship between the study vaccine and the AE is biologically implausible 
(e.g., injury as a passenger in an automobile accident). 
• 
A clear alternative causality for the AE is present (e.g., typical adverse reaction to a 
concomitant medication). 
An AE will be considered “Possibly Related” if there is a reasonable possibility that the AE may 
have been caused by the study vaccine. 
• 
A single occurrence of an event that is uncommon and known to be strongly associated 
with vaccine exposure (e.g., angioedema, hepatic injury, Stevens-Johnson Syndrome). 
• 
One or more occurrences of an event that is not commonly associated with vaccine 
exposure but is otherwise uncommon in the population exposed to the vaccine (e.g., tendon 
rupture). 
• 
An aggregate analysis of specific events observed in a clinical study (such as known 
consequences of the underlying disease or condition under investigation or other events that 
commonly occur in the study population independent of vaccine administration) that 
indicates those events occur more frequently in the vaccine treatment group than in a 
concurrent or historical control group. 
An AE will be considered “Probably Related” if there is evidence that the AE was caused by the 
study vaccine. 

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8.4 
Follow-up of Adverse Events 
The Investigator must follow all AE until resolution, until the condition stabilizes or is no longer 
clinically significant, or until no further information is likely to be obtained. 
The Investigator is responsible for ensuring the conduct of any supplemental investigations 
considered necessary to evaluate the AE. These may include unscheduled clinical laboratory 
tests or investigations, histopathological examinations, or consultation with other health care 
professionals. 
In the event of a non-fatal SAE, subjects will be instructed to contact the Investigator (or 
designee) immediately. All subjects experiencing an SAE will be evaluated by the Investigator or 
designee as soon as is feasible following the report of the SAE by the subject. In the event of a 
fatal SAE, the Investigator must provide the Sponsor with any available post-mortem findings, 
including histopathology. 
Additionally, the Sponsor may request that the Investigator perform or arrange for the conduct of 
supplemental investigations for 1 or more AE. 
8.5 
Reporting of Adverse Events 
8.5.1 
Reporting Periods 
The reporting period for solicited AE begins immediately after study vaccine administration and 
continues for 7 days after the injection. The reporting period for unsolicited AE is immediately 
after study vaccine administration on Day 1, continuing through Month 1. AE that correspond to 
solicited AE terms but occur outside of (or continue past) the solicited AE collection periods are 
also collected through the unsolicited AE reporting periods. The reporting period for SAE begins 
at the time of informed consent and continues for the duration of study participation. A summary 
of the reporting periods is presented in Figure 3. 

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Figure 3 
Safety Events Reporting Periods 
 
8.5.2 
Documentation 
The Investigator or designee will document all AE in the subject’s source documents and 
solicited AE in the source document file within 24 hours of awareness. All AE should include: 
• 
Event term 
• 
Start and stop date 
• 
Severity 
• 
Seriousness (Yes/No) and if Yes, which seriousness criteria were met 
• 
Relationship to study vaccine 
• 
Action taken in response to the AE 
• 
Action taken with study vaccine 
8.6 
SAE Reporting 
The Investigator or designee must report all SAE to the contract research organization (CRO) 
Drug Safety Group within 24 hours of becoming aware of the event, using the SAE Report Form. 
The Investigator or designee must also enter SAE into the source document. 
The CRO will provide safety support for SAE report processing. Email transmission of the CRO 
SAE Report Form is the preferred method to transmit this information to the CRO Drug Safety 
group. If initial notification is provided via telephone, this does not replace the need for the 

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8.7 
Other Events Requiring Immediate Reporting 
8.7.1 
Pregnancy 
The Investigator or designee must report all pregnancies to the Vaxcyte Clinical Safety Team 
within 24 hours of becoming aware of the pregnancy, using the Pregnancy Report Form. All 
pregnancies will be followed to outcome. Additional information regarding the pregnancy may 
be provided as a follow-up report. 
An uncomplicated pregnancy is not considered an AE. Complications of pregnancy may qualify 
as AE or SAE and would therefore be documented and reported as specified above. 
8.8 
Medical Monitor 
The Medical Monitor will be the first point of contact regarding safety and eligibility questions 
and will assess AE and SAE that trigger the stopping rules and address all other safety related 
questions from the sites. 
 
 
8.9 
Data Monitoring Committee 
The DMC will comprise 2 or more persons (independent Subject Matter Experts) and an 
unblinded statistician to compile the data and present to the members. The DMC will 
independently review the 7 days post-vaccination unblinded safety data for the Stage 1 subjects 
aged 50 to 64 years before advancing the study into Stage 2, enrolling the remaining adult 
population aged 50 to 64 years and 65 years and older. Stopping rules will be observed during 
the active study vaccine administration periods (see Section 8.10) and the DMC will conduct 
ad hoc reviews if the study is paused, triggered by one of the Stopping Rules, in order to identify 
any emerging safety concerns. 
The DMC will refer to the DMC Charter for procedures. 
8.10 
Study Stopping Rules 
The rules governing the stopping of the study vaccine administration at any time during the study 
are defined by the Stage 1 and Stage 2 segments of the clinical study. During the vaccination 
period(s), if any of the stopping rules are triggered, no further administration of study vaccine(s) 
will occur until safety data are reviewed by the DMC in communication with the Medical 
Director and the Investigator at the site where the event occurred, as needed. The DMC may 
recommend resumption of enrollment after stopping if the DMC determines it is safe to proceed 

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with no modifications or with modifications to the protocol plans. Vaxcyte must approve the 
recommendation to resume enrollment.  
Stage 1: 
• 
1 SAE assessed as at least possibly related to study vaccine 
• 
1 subject with a Grade 4 (potentially life-threatening) assessed as at least possibly related to 
study vaccine 
• 
2 subjects with the same or similar Grade 3 (severe) AE assessed as at least possibly related 
to study vaccine 
• 
Any concern from the Investigator or study team that warrants a study halt 
Stage 2: 
• 
1 SAE assessed as at least possibly related to study vaccine 
• 
1 subject with a Grade 4 (potentially life threatening) AE assessed as at least possibly 
related to study vaccine 
• 
2 subjects with the same or similar Grade 3 (severe) unsolicited AE assessed as at least 
possibly related to study vaccine other than solicited events 
• 
Thirteen (13) subjects with the same or similar Grade 3 (severe) solicited AE 
• 
Any concern from the Investigator or study team that warrants a study halt 
The appropriate regulatory authority will be informed in writing when either of the following 
occurs: 
• 
Study dosing is stopped. 
• 
DMC has decided to resume or discontinue study activities. 
Enrollment may be resumed following review of available safety data by the Sponsor. 
Vaxcyte’s clinical safety team will refer to the VAX31-101 Safety Medical Monitoring Plan for 
detailed procedures on stopping rule reporting and safety oversight for the study. 
9. 
Data Handling 
9.1 
Source Documentation 
Source documents and source data will meet elements of data quality and integrity (ALCOA-C: 
attributable, legible, contemporaneous, original, accurate, and complete). 

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The Investigator must maintain source documentation of all study conduct data and observations 
relevant to the study. This source documentation includes but is not limited to ICF, original 
medical records, progress notes from the Investigator and study staff, laboratory reports, eDiary 
for solicited AE, and documentation of study vaccine accountability. 
The Investigator will maintain all study documentation, including copies of ICF, source 
documents, and documentation of study vaccine accountability, for either 2 years following FDA 
or other regulatory approval of VAX-31 or 2 years after clinical development of VAX-31 is 
discontinued, unless a longer period is required by applicable law or regulation. The Investigator 
will destroy study documentation only on instruction by the Sponsor and must notify the Sponsor 
on completion of such destruction. Subject identity information will be maintained for 15 years 
unless a longer period is required by applicable law or regulation. 
These source data will be verified by the Clinical Research Associate (CRA) and the location of 
the source data documented before the start of the study. Remote monitoring of original source 
records may be performed, but on-site monitoring would occur for review of any paper source 
documents and their transcription into the system, etc. 
9.2 
Data Monitoring 
The Sponsor or designee will monitor completed source documents at regular intervals 
throughout the study to verify adherence to the protocol; completeness, accuracy, and 
consistency of the data; and adherence to local regulations on the conduct of clinical research. 
The Investigator must make source documentation accessible to the Sponsor or designee as 
needed to verify the information in the source documents. The Investigator agrees to cooperate 
with the Sponsor or designee to ensure that any problems detected during data monitoring are 
resolved. 
9.3 
Electronic Patient Reported Outcome Data 
This study will employ electronic transfers of external eDiary data generated from the subjects 
recording of solicited AE and actions taken for 7 days post-vaccination within a validated system 
that is 21 CFR Part 11 compliant. The eDiary is integrated into the EDC (Zelta) system and 
subject-reported outcome data are available as soon as the subject submits data. The eDiary is 
considered source documentation and should be limited to the subject’s recording. The 
Investigator is responsible for the adequacy and accuracy of data associated with severity and 
relationship to study vaccine, and this is recorded on a separate source document from the 
eDiary. 

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9.4 
Audit Compliance 
The Investigator must permit the Sponsor and/or designee, regulatory agencies, and/or the IRB 
direct access to facilities and study documentation for the purpose of auditing study conduct. 
Direct access includes examining, analyzing, verifying, and reproducing any records and reports 
that are needed for the evaluation of the study. 
9.5 
Laboratory Data 
This study will employ electronic transfers of external laboratory data generated from clinical 
specimens collected by the Investigator. The Investigator is responsible for the adequacy and 
accuracy of these specimens, and for determining clinical significance for all out-of-range 
values. 
10. Statistical Analysis 
This Phase 1/2 study is designed to achieve both safety and immunogenicity objectives. 
The primary objectives are to evaluate the safety of a single injection of VAX-31 at 3 dose levels 
and to compare the safety of VAX-31 to that of PCV20 administered to 4 groups:  
• 
Subjects aged 50 to 59 years receiving PCV20 
• 
Subjects aged 50 years and older receiving PCV20 
• 
Subjects aged 60 years and older receiving PCV20 
• 
Subjects aged 65 years and older receiving PCV20 
The secondary immunogenicity objectives are to assess the induction of OPA and MSD antibody 
responses by VAX-31 at 3 dose levels compared to the 20 PCV20 serotypes (1, 3, 4, 5, 6A, 6B, 
7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F and 33F), as measured at 30 days 
after the injection (Month 1) and 11 non-PCV20 serotypes (2, 7C, 9N, 15A, 16F,17F, 20B, 23A, 
23B, 31 and 35B), as compared to the standard regulatory criteria for efficacy (e.g., lower bound 
of the 2-sided 95% CI for the geometric mean ratio GMR for a given serotype greater than 0.5 
for noninferiority of shared serotypes and the lower bound of the 2-sided 95% CI for the 
geometric mean ratio GMR for a given serotype greater than 2.0 for superiority of the novel 
serotypes), measured at 30 days after the injection (Month 1) for subjects aged 50 to 59 years, 
50 years and older, 60 years and older, and 65 years and older. 
A statistical analysis plan (SAP) will be generated and approved prior to the interim analysis and 
treatment group unblinding for the primary safety and secondary immunogenicity endpoints 
through Month 1 visits. Individual treatment unblinding will occur after the data are cleaned 

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through the last Month 6 visits and final database lock. A single completed Clinical Study Report 
(CSR) will summarize safety and immunogenicity findings through Month 6 for all 
1000 subjects. 
10.1 
Sample Size Calculation 
For subjects enrolled in Stage 1 of the study, comprising 64 subjects 50 to 64 years of age, 
sample size is not driven by statistical assumptions for formal hypothesis testing but is based on 
the safety objective for the study. With 16 subjects, events that occur at a frequency of 15% or 
more will be detected with at least 92% probability and events that occur at a frequency of 10% 
or more will be detected with 81% probability. Therefore 16 subjects in each treatment group are 
proposed as the basis for the number of subjects in whom to conduct the first safety assessment. 
For subjects enrolled in Stage 2 of the study, comprising approximately 736 subjects aged 50 to 
64 years as well as a minimum of 200 subjects aged 65 years and older, sample size is not based 
on statistical justification. A total of approximately 800 subjects aged 50 to 64 (with a minimum 
of 200 subjects aged 60 to 64), as well as a minimum of 200 subjects aged 65 years and older, 
should provide sufficient information to assess safety and immunogenicity in the older age 
groups. The sample size will also be adequate to plan future studies. 
10.2 
Treatment Period 
The Treatment period begins at the time of study vaccine administration and extends through the 
Month 1 visit. The Follow-up period spans the time following the Month 1 visit through Month 6 
(180 days after study vaccine administration). 
10.3 
Treatment Groups 
Subjects will be randomized into 4 treatment groups: 
• 
250 subjects will receive VAX-31 Low Dose 
• 
250 subjects will receive VAX-31 Mid Dose 
• 
250 subjects will receive VAX-31 High Dose 
• 
250 subjects will receive PCV20 
For Stage 1, there were no stratification factors. For Stage 2, randomization will be stratified by 
clinical site. 
10.4 
Populations for Analysis 
Randomized Population: All screened subjects who have informed consent, provide 
demographic and other baseline measurements, are randomized, and are assigned a study subject 

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ID (number). Each subject will be analyzed as randomized (i.e., according to the vaccine 
regimen to which the subject was randomized). 
Exposed Population: All subjects who receive 1 study vaccination. 
Safety Population: All subjects in the Exposed Population who provide safety assessment data. 
This generally includes any subject in the Exposed Population that is not lost to follow-up at 
Day 1, as they will be at risk for reporting an SAE. Each subject will be analyzed as treated (i.e., 
according to the vaccine regimen a subject received, rather than the vaccine regimen to which the 
subject may have been randomized). 
Immunogenicity Evaluable Population: For this Phase 1/2 study, the immunogenicity 
population will be analyzed as treated (i.e., according to the vaccine regimen a subject receives, 
which may be different from the vaccine regimen to which the subject is randomized in the case 
of treatment errors). 
The Immunogenicity Evaluable Population (IEP) includes all subjects in the Exposed Population 
who: 
• 
Have no major protocol deviation that would impact immunogenicity assessment or other 
reason to be excluded as defined prior to unblinding or analysis. 
• 
Have not received a prohibited medication or vaccine. 
• 
Provide evaluable serum sample results for baseline, the relevant post-vaccination time 
points, and within the required time frames: 
− Baseline: Day 1 or within 30 days before study vaccine administration 
− Month 1: 30 days after vaccination ±5 days, inclusive 
10.5 
Demographic and Baseline Characteristics Analysis 
The demographic and baseline characteristics will be summarized descriptively according to age 
group, treatment group, and overall. Age, height, weight, and body mass index at enrollment will 
be summarized by reporting the mean, standard deviation, median, minimum, and maximum. 
The frequencies and percentages of subjects by sex, race, and ethnicity will be presented. 
Demographic data will be tabulated for the Randomized, Immunogenicity Evaluable, and Safety 
Populations. 
10.6 
Safety Analysis 
All safety analyses will be based on the Safety Population. 

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10.6.1 
Analysis of Extent of Exposure 
The frequencies and percentages of subjects with vaccinations will be summarized by age group 
and treatment group for the Randomized Population. 
10.6.2 
Solicited Adverse Events 
With the exception of redness and swelling, all solicited AE (local and systemic) will be 
summarized according to severity grading scales defined in Section 8.2, from “mild” to 
“potentially life-threatening.” 
Solicited AE will be recorded daily until 7 days post-injection within an eDiary. The analyses of 
solicited AE (any event, after any injection, and after each injection) will be performed by 
maximum severity and by treatment group. In addition, solicited AE ongoing after the 
solicitation period (7 days post-injection) will also be recorded as unsolicited AE. 
Frequencies and percentages of subjects experiencing each solicited AE will be presented by 
maximum severity. Summary tables showing the occurrence of any local or systemic solicited 
AE overall and at each time point will also be presented. 
The severity of redness and swelling recorded as diameters (cm) will be summarized according 
to categories based on the largest diameter linear measurement when the local reaction is present: 
• 
Grade 0/absent: 
0–2.4 cm. 
• 
Grade 1/mild: 
>2.5–5.0 cm. 
• 
Grade 2/moderate: >5.1–10.0 cm. 
• 
Grade 3/severe: 
>10.0 cm. 
The following summaries of subjects will be performed: 
• 
Solicited events by day post-injection, for each event and for any event. 
• 
Time of first onset of solicited AE, after injection, for each event and any event. 
• 
Solicited AE by maximum event severity, after injection, for each event and for any event. 
• 
Duration of solicited AE, after injection, for each event and maximum duration of any 
event. 
• 
Solicited AE, occurrence of at least 1 event by category (local, systemic), after injection. 

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For each of the time points or time intervals presented in the summaries, only subjects with at 
least 1 observation (i.e., any non-missing values but excluding “Not done/unknown”) for the 
solicited AE will be summarized. 
10.6.3 
Unsolicited Adverse Events 
All the unsolicited AE occurring during the study will be recorded, regardless of their assessment 
of relatedness by the Investigator. 
The original verbatim terms used by Investigators to identify AE will be mapped to preferred 
terms using the MedDRA dictionary. The unsolicited AE will then be grouped by MedDRA 
preferred terms into frequency tables according to system organ class (SOC). All reported AE, as 
well as AE judged by the Investigator as at least possibly related to study vaccine, will be 
summarized by treatment group, according to SOC and preferred term within SOC. When an 
unsolicited AE occurs more than once for a subject, the maximum severity reported and 
strongest reported relationship to the treatment group will be counted. 
Only TEAE will be summarized as defined in Section 8.1.1. The selection of unsolicited AE and 
their assignment to time intervals will be done by day of onset and not by days 
ongoing/persisting. 
Unsolicited AE will be summarized by alphabetic SOC and preferred term as follows: 
• 
Any unsolicited TEAE 
• 
Possibly or probably related unsolicited TEAE 
• 
SAE 
• 
Possibly or probably related SAE 
• 
NOCI 
• 
MAAE 
• 
Unsolicited TEAE leading to withdrawal 
• 
Any AE leading to death 
Listings of all TEAE will be provided by subject. 
10.6.4 
Combined Solicited and Unsolicited Adverse Events 
Solicited AE continuing beyond 7 days after an injection will be coded by MedDRA and 
combined with the unsolicited AE. An overall summary of subjects with all combined solicited 
and unsolicited AE, by SOC and preferred term, will be provided as well. 

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10.6.5 
Analysis of Other Safety Data 
The frequencies and percentages of concomitant medications will be tabulated by age group, 
treatment group, and overall. Medications will be coded using the WHODrug dictionary. 
10.7 
Immunogenicity Analysis  
10.7.1 
Geometric Mean Titer, Geometric Mean Concentration, and Geometric Mean 
Titer Fold Rise 
Immunogenicity analyses will be performed by age group (50 to 59, 60 years and older, 65 years 
and older) and overall (50 years and older). Analyses will be performed for both OPA titers 
(log10) and IgG titers (mcg/mL). All immunogenicity analyses will be based on the IEP and 
Exposed Population. 
The Geometric Mean Titer (GMT) and Geometric Mean Concentration (GMC) will be analyzed 
via linear models. The primary model is an analysis of variance (ANOVA), with logarithmically-
transformed titers (log10) as the dependent variable and treatment group and study site as the 
fixed effects in the model. The results included in the main tables of the report will be based on 
this basic ANOVA model. As a secondary analysis, in order to remove the effect of baseline 
concentration on the GMT, an analysis of covariance (ANCOVA) will also be performed. The 
ANCOVA includes treatment group and study site as the fixed effects and log10 baseline titer as 
the covariate in the model. The rationale for including baseline values as a covariate is that prior 
data have shown vaccine response is correlated with baseline antibody levels. 
The least squares means and their 95% confidence intervals (CI) calculated based on the 
ANOVA and ANCOVA will be back transformed and reported as the group GMT and GMC 
values (adjusted for the mean baseline in the case of the ANCOVA). GMR will also be 
calculated from the ANCOVA and ANOVA models. 
Comparisons between relevant groups will be based on the estimated adjusted GMT measured at 
Month 1 for 31 serotypes in VAX-31 (of those 20 in PCV20), and mean square error calculated 
from the basic ANOVA model using contrast statements. The analysis of GMFR relative to 
Day 1 will also be computed using similar models. 
The main comparison of interest will be the 3 VAX-31 dose level groups vs the PCV20 
(20 serotypes) group. However, the 3 VAX-31 dose level groups will also be compared in a 
pairwise fashion on a serotype-by-serotype basis. No adjustment for multiplicity will be applied, 
and missing data will not be imputed. 

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10.7.2 
Threshold Analyses 
For the 11 non-PCV20 serotypes that are in VAX-31, the % of subjects with a ≥4-fold increase 
in OPA titer will be evaluated using a logistic regression model, with an indicator variable for 
achieving a ≥4-fold increase in OPA titer as the dependent variable, and treatment group and 
study site as fixed effects and log10 baseline titer as a covariate. The difference in proportions 
achieving a ≥4-fold increase in OPA titer in each of the 3 VAX-31 dose levels group vs the 
PCV20 and the corresponding 95% CI will be calculated. If the lower bound of the 95% CI is 
>0.1, the VAX-31 dose will be deemed statistically superior to PCV20. 
The percentage of subjects achieving specified thresholds (e.g., GMFR ≥4 in serotype-specific 
OPA and IgG, achieving OPA titer of at least serotype-specific LLOQ of the assay), and 
associated Wilson (score) 95% CI, will be calculated for the Month 1 visit data for each 
treatment group. A reverse cumulative distribution curve will be provided. Differences between 
pair-wise treatment groups may be determined via Fisher’s exact tests. 
10.8 
Defined Safety Evaluation 
A defined safety evaluation will be conducted for the Stage 1 cohort of subjects aged 50 to 
64 years, based on the safety data collected through Day 8. The results will be reported to the 
DMC by treatment group preserving the double-blind status on the subject level, unless the 
DMC requests unblinded individual treatments. If the DMC concludes that no safety concerns 
exist, the study will resume enrollment of the remaining subjects aged 50 to 64 years 
(approximately 736 subjects) as well as all subjects 65 years and older. 
10.9 
Interim Analysis 
There will be a safety and immunogenicity interim analysis based on the data collected through 
Month 1. The results will be reported by treatment group preserving the double-blind status on 
the subject level. 
For further information, please refer to the VAX31-101 Statistical Analysis Plan (SAP). 
11. Additional Information 
11.1 
Ethical Conduct of the Study 
The study will be performed in accordance with the protocol and consistent with ICH GCP 
Guidelines and applicable local regulatory requirements and laws. 
11.2 
IRB Oversight 
The study (protocol, informed consent form, recruiting materials, and any documents seen by the 
subject) will be reviewed and approved by an IRB appropriate to each study site. Subjects will 

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not be recruited, consented, screened, or enrolled until the IRB has approved the required 
documentation. In addition, the IRB will review amendments to the protocol before their 
implementation. 
The Investigator will retain all correspondence with the IRB in the trial master file and forward 
copies of all IRB approvals to the Sponsor. 
11.3 
Informed Consent 
The Sponsor or designee will provide a master ICF template to each site for development of a 
site-specific ICF. At the Investigator’s discretion, the site may develop a separate ICF for 
prescreening as described in Section 6.2. 
All site-specific ICF must be approved by the Sponsor or designee and the IRB and must be in 
compliance with ICH GCP, local regulatory requirements, and legal requirements. The Sponsor 
or designee will advise the site of required changes to the master ICF template during the course 
of the study. 
The Investigator will ensure that each potential study subject is fully informed about the nature 
and objectives of the study and possible risks associated with participation. Before informed 
consent is obtained, the Investigator, or a qualified person designated by the Investigator, will 
provide the potential study subject with ample time and opportunity to inquire about the details 
of the study, and will answer all relevant questions to the potential study subject’s satisfaction. 
The potential study subject will then decide whether or not to participate in the study. The 
Investigator, or a qualified person designated by the Investigator, will obtain written informed 
consent from each study subject before any study-specific activity is performed. 
The Investigator will retain the original and any amended signed and dated ICF at the study site 
and provide a copy to each study subject. 
11.4 
Subject Confidentiality 
The Investigator will ensure that each subject’s anonymity is maintained. In all documents 
submitted to the Sponsor and/or its designee, subjects can be identified by subject ID number and 
initials. Documents not intended for submission to the Sponsor and/or its designee (e.g., signed 
ICF) must be maintained by the Investigator securely and must be in compliance with all federal 
laws and regulations and ICH GCP Guidelines. 

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11.5 
Compensation for Injury 
The Sponsor will adhere to local regulations and guidelines regarding clinical study 
compensation to subjects whose health is adversely affected by taking part in the study. The 
applicable policy for compensation for injury will be described in the master ICF template. 
11.6 
Clinicaltrials.gov 
For purposes of reporting to clinicaltrials.gov, the Sponsor is the responsible party and will 
provide information regarding this study in accordance with applicable regulations. 
11.7 
Public Disclosure and Publication Policy 
All publication rights are delineated in the Clinical Study Agreement with the Investigator(s). 
11.8 
Amendments 
The protocol may be amended only by the Sponsor. 
The IRB must generally be informed of all amendments prior to implementation. In addition, the 
Investigator must obtain IRB approval for any amendments likely to affect the safety of study 
subjects prior to implementation. 
The Sponsor may implement an amendment prior to IRB notification or approval only to 
eliminate an apparent, immediate hazard to study subjects. In that event, the Sponsor will notify 
the IRB in writing within 7 calendar days after the implementation. 
Amendments, including descriptions and rationales, will be documented in this section of the 
protocol. 
 

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12. Appendix A: Schedule of Events 
Study Event 
Screening Visit 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
to Visit 9 
Early  
Termination 
Screeninga 
(-30 days) 
Day 1a 
Day 8 
(+3 days) 
Day 15 – 
Phone 
(+3 days) 
Month 1 
(±3 days) 
Months 2, 3, 4, 
5, 6 –Phone 
(±5 days) 
Informed Consent 
X 
 
 
 
 
 
Refer to 
Section 7.2 for 
Procedures 
Demographics, Medical History 
X 
Xb 
 
 
 
 
Concomitant Medications 
X 
X 
X 
X 
Xd 
Xd 
Physical Exam(s), targeted 
X 
Xb 
 
 
 
 
Vital Signs 
X 
Xc 
 
 
 
 
Confirmation of Eligibility 
X 
X 
 
 
 
 
 
Randomization 
 
X 
 
 
 
 
 
Study Vaccine Administration 
 
X 
 
 
 
 
 
Post-vaccination Observation (at least 30 minutes) 
 
X 
 
 
 
 
 
Issue eDiary instructions, Ruler, Thermometer; 
Conduct Training/Retraining 
 
X 
 
 
 
 
 
Review eDiary Data 
 
 
X 
 
 
 
 
AE Evaluation (Solicited and/or Unsolicited) 
 
X 
X 
X 
X 
Xd 
 
Clinical Labs 
 
 
 
 
 
 
 
Hematology, Chemistry, Urinalysis  
 
Xb 
 
 
X 
 
Urine Pregnancy    
Xb 
Xb 
 
 
  
 
Serum for Immunogenicity 
 
Xb 
 
 
X 
 
a) Screening and Day 1 Visit are encouraged to be combined; however, subjects may screen for up to 30 days prior to randomizing into the study, and a separate Screening visit 
may be conducted.  
b) Conduct or collect prior to study vaccination (if indicated by updated medical history or change in health status, as applicable). 
c) Vitals to be taken before and ≥30 minutes after study vaccine administration.  
d) Only NOCI, MAAE, SAE, and associated concomitant medications collected after Month 1. 

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Feyssaguet M, Bellanger A, Nozay F, Friel D, Merck E, Verlant V, et al. Comparison between a 
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