A Phase 3 Safety and Immunogenicity Trial of the VLP-Based Chikungunya Virus Vaccine PXVX0317 in Adults ≥65 Years of Age
Phase: PHASE3
Conditions: Chikungunya Virus
Sponsor: Bavarian Nordic

PXVX0317 
 
 
Protocol EBSI-CV-317-005, v6.0 (31 Mar 2023) 
 
 
 
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CLINICAL STUDY PROTOCOL 
A Phase 3 Safety and Immunogenicity Trial of the VLP-Based 
Chikungunya Virus Vaccine PXVX0317 in Adults ≥65 Years of Age 
EBSI-CV-317-005 
Version 6.0 
31 Mar 2023 
ClinicalTrials.gov ID: NCT05349617 
Sponsor: 
Emergent Travel Health Inc. 
 
CONFIDENTIAL 
This document is a confidential communication of the sponsor. Acceptance of this document 
constitutes an agreement by the recipient that no unpublished information contained within 
will be published or disclosed without prior written approval, except that this document may 
be disclosed to the appropriate ethics committee and regulatory authority under the condition 
that they keep it confidential. 
 

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DOCUMENT HISTORY 
Version 
Date 
Description of Change 
Brief Rationale 
1.0 
26Jul2021 
n/a 
Initial protocol 
2.0 
19Aug2021 
Added clinical relevance endpoint 
(lower bound of the two-sided 95% 
CI for the seroresponse rate in adults 
≥65 years of age must be ≥60%). 
Omitted from initial protocol 
inadvertently. 
3.0 
17Sep2021 
Changed primary immunogenicity 
objective to demonstrate superiority 
to placebo from inferiority to EBSI-
CV-317-004. Added preliminary 
group unblinded immunogenicity 
analysis. 
Change in PXVX0317 program strategy 
and allowing for earlier regulatory 
interactions prior to final database lock. 
4.0 
25Jan2022 
Removed intraarticular steroids from 
exclusion criteria 7 
Added labelling information in 
section 5.1.3 
Updated Adverse Event collection to 
begin at Day 1 
Rearranged Immunogenicity 
endpoints 
Reasons for allowing rescreening 
were expanded 
Intraarticular steroids were erroneously 
mentioned as allowed in earlier versions 
of the protocol. 
Section 5.1.3 was modified to better 
align with ICH E6(R2) GCP and 
Emergent’s updated protocol template. 
Adverse event collection was updated 
per FDA request that any event that 
begins prior to first vaccine 
administration be reported as medical 
history. 
Immunogenicity endpoints were 
reprioritized per EMA Scientific Advice. 
Rescreening was aligned with EBSI-CV-
317-004 protocol. 
5.0 
27Jul2022 
 
Added exploratory objective and 
endpoint to evaluate the ability of 
CHIKV antibodies to PXVX0317 to 
neutralize different CHIKV 
genotypes. Clarified inclusion 
criterion for participants who test 
positive for COVID-19. Clarified 
definition of MAAE. 
Addition of exploratory objective and 
endpoint to the protocol per EMA 
Scientific Advice.  
Reasons for delay of vaccination were 
updated to clarify that vaccination of 
potential participants with evidence of 
active SARS-CoV-2 virus infection 
should be delayed (or not enrolled) to 
reduce the risk of confounding safety 
and immune response data.  
MAAE definition was clarified to ensure 
consistent reporting of events, as 
intended for this clinical study.  
6.0 
See effective 
date 
Study objectives and endpoints have 
been updated and reorganized and 
GMT analysis was removed from 
hierarchical testing. 
 
 and EMA definition 
of seroresponse rate as the 
presumptive seroprotection rate. 
Simplification for global use of the 
protocol and to align with FDA and 
EMA feedback received 26Jul2022 and 
25Jan2023, respectively. 
 
 
 

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Administrative changes such as 
capitalizations, acronyms, and 
section organization. 
 
Removed Day 183 from exploratory 
endpoint. 
To align with company authoring 
guidelines for regulatory submissions, 
provide consistency across CHIK 
documents, and for clarity. 
To align with the Day 22 timepoint used 
in primary endpoints. 

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SPONSOR SIGNATORY 
 
Signatory: 
See electronic signature at end of document. 
 
 
VP, Clinical Development 
Emergent BioSolutions Inc. 
 
Date (dd/mmm/yyyy) 
 
KEY STUDY CONTACT INFORMATION 
 
Sponsor’s Medical Monitors (MM): 
 
 
Immediately Reportable Adverse Events: 
Emergent Global Pharmacovigilance 
 
For all other contact information please refer to study contact list. 

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INVESTIGATOR SIGNATORY 
Compliance Statement: This study is to be conducted in accordance with the ethical 
principles that originate from the Declaration of Helsinki and that are consistent with 
International Council for Harmonization of Technical Requirements for Pharmaceuticals for 
Human Use (ICH) Good Clinical Practice (GCP) guidelines and regulatory requirements, as 
applicable. 
 
EBSI-CV-317-005, version 6.0: 
A Phase 3 Safety and Immunogenicity Trial 
of the VLP-Based Chikungunya Virus 
Vaccine PXVX0317 in Adults ≥65 Years of 
Age 
 
 
 
My signature below verifies that I have read and agree to this protocol. I am aware of my 
responsibilities as a Principal Investigator (PI) under the current ICH GCP Guidelines, the 
Declaration of Helsinki, United States of America (US) Food and Drug Administration 
(FDA) Code of Federal Regulations (CFRs) or appropriate local regulations and applicable 
laws and regulations of the country of the investigational site for which I am responsible. I 
agree to conduct the study according to these regulations. 
I have read this protocol in its entirety and agree to conduct this study accordingly. Any 
changes in procedure will only be made, if necessary, to protect the safety, rights, and 
welfare of study participants. 
I agree to conduct in person and/or to supervise staff assigned to specific study 
responsibilities. I will ensure that all staff who assist me in the conduct of the study have 
access to the protocol and all pertinent information. I will ensure that all assigned staff are 
trained and qualified and are fully informed of their responsibilities regarding the conduct of 
the study. 
I agree to abide by the terms of the confidentiality disclosure agreement and/or contract with 
the sponsor and/or its representatives. 
Site Principal 
Investigator: 
 
 
Principal Investigator Name (print) 
Title (print) 
 
 
 
Principal Investigator Signature 
 Date (dd/mmm/yyyy) 

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PROTOCOL SYNOPSIS 
Name of Sponsor/Company:  Emergent Travel Health Inc. 
Name of Investigational Product:  PXVX0317 
Name of Active Ingredient(s):  Chikungunya virus virus-like particle (CHIKV VLP) 
Protocol No.: EBSI-CV-317-005 
Title of Study: A Phase 3 Safety and Immunogenicity Trial of the VLP-Based 
Chikungunya Vaccine PXVX0317 in Adults ≥65 Years of Age 
Study Centers: Multicenter, up to 10 sites in the US 
Study Duration for Each Participant: 7 months 
Estimated Study Duration: ~12 months 
Estimated Enrollment Period: ~6 months 
Anticipated Start Date: Q2 2022 
Estimated End Date: Q2 2023 
Phase of Development: 3 
Coprimary Objectives:  
• To compare the anti-CHIKV serum neutralizing antibody (SNA) response to 
PXVX0317 and placebo at Day 22, as measured by geometric mean titer (GMT) and 
clinically relevant difference in seroresponse rate (PXVX0317 minus placebo) in adults 
≥65 years of age.   
Note: Seroresponse rate (considered the presumptive seroprotection rate) is defined as the 
percentage of participants who achieve an anti-CHIKV SNA 
. 
• To evaluate the safety of PXVX0317 in adults ≥65 years of age. 
Secondary Objectives:  
• To compare the anti-CHIKV SNA response to PXVX0317 and placebo at Day 15 and 
Day 183, as measured by GMT and seroresponse rate.  
• To compare the anti-CHIKV SNA response to PXVX0317 and placebo in participants 
≥65 to <75 and ≥75 years of age as measured by GMT and seroresponse rate.  
Exploratory Objective: 
• To evaluate the ability of PXVX0317 vaccine-induced CHIKV antibodies to neutralize 
various CHIKV genotypes. 
Methodology/Study Design:  

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This is a phase 3, randomized, double-blind, placebo-controlled, parallel-group study with 
two treatment groups. Participants will be randomized in a 1:1 ratio to receive either a 
single intramuscular (IM) dose of PXVX0317 or placebo at Day 1. 
The target population is adults ≥65 years of age. Participants will be stratified by age 
subgroups (65 to <75 and ≥75 years of age), with a target of 25% enrollment of 
participants ≥75 years of age. With 400 participants enrolled, the treatment group totals are 
estimated as follows: 
• Group 1- PXVX0317: n=200 
• Group 2- Placebo: n=200 
An independent Safety Monitoring Committee (SMC) will provide safety oversight. The 
SMC will review aggregated, blinded safety data after the first 50 participants have 
completed seven days of safety follow-up. The remaining participants will be enrolled 
following the safety review by the SMC and based on the sponsor’s consideration of the 
SMC’s recommendation. 
Number of Participants (Planned): 400 
Study Population: Adults ≥65 years of age 
Criteria for Study Participation 
Inclusion Criteria:  
Participants must meet all the following criteria to be enrolled: 
1. Able and willing to provide informed consent voluntarily signed by participant. 
Must verbalize understanding of the general procedures of, and reason for the 
study.  
2. Males or females, ≥65 years of age. 
3. Able to complete all scheduled visits and comply with all study procedures. 
4. Women who are not of childbearing potential (CBP): surgically sterile (at least six 
weeks post bilateral tubal ligation, bilateral oophorectomy, or hysterectomy); or 
postmenopausal (defined as a history of ≥12 consecutive months without menses 
prior to randomization in the absence of other pathologic or physiologic causes, 
following cessation of exogenous post menopausal sex-hormonal treatment).  
5. Participants must be in stable health in the opinion of the investigator for at least 30 
days prior to screening (eg, no hospital admission for acute illness in the last 30 
days prior to screening). 
Exclusion Criteria:  
Participants who meet any of the following criteria cannot be enrolled: 

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1. Participation or planned participation in an investigational clinical trial (eg, 
vaccine, drug, medical device, or medical procedure) within 30 days of Day 1 and 
for the duration of the study. Note: Participation in an observational trial or 
follow-up phase of a trial may be allowed; however, these instances should be 
discussed with the sponsor’s MM prior to enrollment. 
2. Prior receipt of any CHIKV vaccine. 
3. Positive laboratory evidence of current infection with human immunodeficiency 
virus (HIV), hepatitis C virus (HCV) or hepatitis B virus (HBV).  
4. Body Mass Index (BMI) ≥35 kg/m2. 
5. History of any known or suspected allergy or history of anaphylaxis to any 
component of the investigational product (IP). 
6. History of any known congenital or acquired immunodeficiency or 
immunosuppressive condition that could impact response to vaccination (eg, 
leukemia, lymphoma, malignancy, functional or anatomic asplenia, alcoholic 
cirrhosis). Note: History of basal cell and squamous cell carcinoma of the skin or 
carcinoma in situ of the cervix considered cured would not be exclusionary. 
History of a malignancy considered cured from over five years from the date of 
screening with minimal risk of recurrence is not exclusionary. 
7. Prior or anticipated use of systemic immunomodulatory or immunosuppressive 
medications from six months prior to screening through Day 22. Note: Systemic 
corticosteroid use at a dose or equivalent dose of 20 mg of prednisone daily for 14 
days or more within 90 days of screening through Day 22 is exclusionary. The use 
of inhaled, intranasal, topical, or ocular steroids is allowed. 
8. Bleeding disorder or receipt of anticoagulants in the 21 days prior to screening, 
contraindicating IM vaccination, as judged by the investigator. 
9. Moderate or severe acute illness with or without fever (oral temperature ≥100.4°F 
[≥38.0°C]).   
10. Receipt or anticipated receipt of immunoglobulin from 180 days prior to screening 
through Day 22. 
11. Medical condition (such as dementia) that, in the opinion of the investigator, could 
adversely impact the participant’s participation in or conduct of the study. 
12. Evidence of substance abuse that, in the opinion of the investigator, could 
adversely impact the participant’s participation in or conduct of the study. 
13. Identified as an investigator or employee of an investigator or study center with 
direct involvement in the proposed study, or identified as an immediate family 
member (ie, parent, spouse) of the investigator or employee with direct 
involvement in the proposed study. 

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14. Receipt or anticipated receipt of any vaccine from 30 days prior to Day 1 through 
Day 22. 
15. Receipt or anticipated receipt of blood or blood-derived products from 90 days 
prior to screening through Day 22. 
16. Any planned elective surgery that may interfere with study participation or 
conduct. 
17. Any other medical condition that, in the opinion of the investigator, could 
adversely impact the participant’s participation in or conduct of the study. 
Reasons for Delay of Study Vaccination: 
i. 
Any fever (oral temperature ≥100.4°F [≥38.0°C]) within 24 hours of planned study 
vaccination.  
ii. 
Any condition that may interfere with assessment of reactogenicity and/or other 
safety assessments. 
iii. 
Signs and/or symptoms of an acute infectious illness. 
iv. 
Participants should not be randomized if they have tested positive for COVID-19 
(using any type of test, even if asymptomatic) for 14 days or until negative 
molecular test result eg, PCR. 
If any one of these occur at the time of the scheduled study vaccination, randomization is 
permitted later, if within the screening window (30 days), at the discretion of the 
investigator and after consultation with the MM. If randomization and vaccination cannot 
occur within the allowed screening window, rescreening will be required. 
Investigational Product, Dosage, and Mode of Administration:  
PXVX0317 vaccine is comprised of CHIKV VLP 40 μg, aluminum hydroxide, 2% 
adjuvant (Alhydrogel®), and formulation buffer supplied as a single dose of 0.8 mL in a 
single use pre-filled syringe administered via IM injection in the deltoid muscle. 
Reference Therapy, Dosage, and Mode of Administration:  
Placebo is comprised of formulation buffer supplied as a single dose of 0.8 mL in a single 
use pre-filled syringe administered via IM injection in the deltoid muscle. 
Primary Endpoints  
Coprimary Immunogenicity Endpoints: 
• Difference in anti-CHIKV SNA seroresponse rate (PXVX0317 minus placebo) and 
associated 95% CI (confidence interval) at Day 22. 
• Anti-CHIKV SNA GMT and associated 95% CIs at Day 22 for PXVX0317 and 
placebo. 

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Note: Seroresponse rate (considered the presumptive seroprotection rate) is defined as 
the percentage of participants who achieve an anti-CHIKV SNA 
. See Section 
9.6.2 for immunogenicity analysis details and Section 9.4 for success criteria and 
multiplicity controls. 
Safety Endpoints: 
• Incidence of solicited adverse events (AEs) through Day 8 for PXVX0317 and 
placebo. 
• Incidence of unsolicited AEs through Day 29 for PXVX0317 and placebo. 
• Incidence of serious adverse events (SAEs), medically attended adverse events 
(MAAEs; medically attended visits include hospital, emergency room [ER], urgent 
care clinic, or other visits to or from medical personnel), and adverse events of 
special interest (AESI; new onset or worsening arthralgia that is medically attended) 
through Day 183 for PXVX0317 and placebo. 
Secondary Immunogenicity Endpoints: 
• Key Secondary Immunogenicity Endpoints: Difference in anti-CHIKV SNA 
seroresponse rate (PXVX0317 minus placebo) with associated 95% CIs at Day 15 
and Day 183, in that order (see Section 9.6.2). 
• Anti-CHIKV SNA GMTs by study arm with associated 95% CIs at Day 15 and Day 
183.  
• Geometric mean fold increase (GMFI) from Day 1 to subsequent collection time 
points.  
• Number and percentage of participants with an anti-CHIKV SNA titer ≥15 and 
4-fold rise over baseline.  
Exploratory Immunogenicity Endpoint: 
• Geometric mean titers and associated two-sided 95% CIs for neutralizing antibodies 
against various CHIKV genotypes measured at Day 22 (and at baseline if necessary) 
for a subset of participants in the PXVX0317 group. 
Procedures and Assessments:  
Study procedures/assessments will occur at: Screening (Visit 1), to occur no more than 30 
days prior to Day 1 of IP administration; Day 1 (Visit 2, Baseline, Randomization, and IP 
Administration); Day 15 (Visit 3); Day 22 (Visit 4); Day 29 (Visit 5, telephone contact); 
Day 92 (Visit 6, telephone contact); Day 183 (Visit 7, End of Study) or Early 
Discontinuation Visit (EDV). The per-participant estimated total study duration is 212 
days (includes the 30-day screening window).  
Solicited AEs (collected from Day 1 through Day 8) will consist of local adverse reactions 
(injection site pain, redness, and swelling) and systemic adverse reactions (fever, chills, 
fatigue, headache, myalgia, arthralgia, and nausea). Unsolicited AEs will be collected from 

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Day 1 through Day 29. Serious adverse events, MAAEs, and AESI will be collected from 
Day 1 through Day 183 End of Study Visit.   
The immune response to PXVX0317 will be measured by CHIKV SNA responses up to 
182 days after dosing (Day 183). CHIKV SNA levels will be measured by a validated 
CHIKV luciferase-based assay (hereafter referred to as human SNA assay) developed by 
the sponsor (see Section 7 for human SNA assay description). 
Statistical Methods: 
Seroresponse rates: Proportions (percentages) of participants in PXVX0317 and placebo 
groups with a seroresponse at Day 15, Day 22, and Day 183 will be summarized with 
two-sided 95% CIs based on the Wilson score method. This analysis will be primarily 
based in the immunogenicity evaluable population (IEP) and repeated for the modified 
intent-to-treat (mITT) population as a measure of the robustness of the findings. The 
significance of the treatment group difference will be assessed using chi-square tests at 
each visit based on both age groups combined with a two-sided alpha=0.05. 
The difference in CHIKV SNA seroresponse rates (PXVX0317 minus placebo) among 
baseline seronegative participants will be calculated along with the two-sided 95% CI for 
the difference based on the Newcombe hybrid score method at Day 15, Day 22, and Day 
183. At Day 22, the lower bound of the two-sided 95% CI for the difference in 
seroresponse rates (PXVX0317 minus placebo) for both age strata combined must meet or 
exceed 
 for clinical relevance to be demonstrated.  
Geometric mean titers: Geometric mean titers will be derived from a linear analysis of 
variance (ANOVA) model with log10-transformed CHIKV SNA titers as the dependent 
variable and treatment group and study site as fixed effects. The adjusted least square 
means and their two-sided 95% CIs calculated based on the ANOVA model will be back 
transformed and reported as the PXVX0317 and placebo group GMT values at Day 15, 
Day 22, and Day 183. Significance testing will be carried out at a two-sided significance 
level of 0.05 using both age strata combined. 
Geometric mean fold increase: Geometric mean fold increase in CHIKV SNA titers from 
Day 1 to Day 15, Day 22, and Day 183 will be reported for PXVX0317 and placebo 
groups. 
Four-fold rise over baseline in CHIKV SNA titer: Proportions (percentages) of participants 
in PXVX0317 and placebo groups with a CHIKV SNA titer of at least 4-fold rise over 
baseline at Day 15, Day 22, and Day 183 will be summarized with two-sided 95% CIs 
based on the Wilson score method. 
Safety endpoints: The safety of PXVX0317 in adults ≥65 years of age will be evaluated 
using solicited AEs occurring from IP administration on Day 1 until Day 8, unsolicited 
AEs through Day 29, MAAEs, AESI, and SAEs though Day 183 End of Study Visit, and 
vital signs. Solicited AEs include local (pain, redness, and swelling) and systemic reactions 
(fever, chills, fatigue, headache, myalgia, arthralgia, and nausea). 

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Sample Size Considerations: Based on the data from the phase 2 study (protocol 
PXVX-CV-317-001), the seroresponse rate for PXVX0317 vaccine is expected to be 
approximately 
 vs <5% for the placebo participants. With an assumed 10% rate of 
nonevaluable participants, the power to show superiority over placebo with 180 
PXVX0317 vaccine and 180 placebo evaluable participants is >99.9% for the combined 
age groups.  
The difference in seroresponse rate between PXVX0317 and placebo groups that is 
considered clinically relevant is 
. With 180 PXVX0317-treated participants and a 
target seroresponse rate of 
 vs a rate of 5% for placebo, the width of a two-sided 95% 
CI would be ±5.4%. If the target PXVX0317 seroresponse is 
, the width would be 
±6.9%. Therefore, the difference in seroresponse rates must be above 
 for the lower 
bound of the 95% CI for the difference to be 
. 
Analysis Populations 
Enrolled population: All screened participants who sign the informed consent form 
(ICF), are entered in the electronic data capture (EDC) database and meet all eligibility 
criteria. 
Randomized population: All screened participants who provide informed consent and 
provide demographic and other screening measurements and are randomized. 
Exposed population: All participants in the randomized population who receive IP. 
Safety population: All participants in the exposed population who provide safety 
assessment data. Safety endpoints will utilize the safety population, analyzed as treated. 
Modified intent to treat population: All randomized participants who are vaccinated and 
have at least one postinjection CHIKV SNA titer result, analyzed as randomized. 
Immunogenicity evaluable population: All participants in the mITT population who: i) 
provide evaluable serum sample results for the Day 22 time point within the required time 
frame (Days 19 to 27); ii) have no measurable CHIKV SNA at Day 1; iii) have no 
important protocol deviation or other reason to be excluded as defined prior to unblinding. 
The IEP is the primary population for all immunogenicity analyses. 
Preliminary Analysis: There will be a safety and immunogenicity preliminary analysis on 
data for all participants through the Day 29 visit to facilitate health authority 
presubmission preparation. The analyses will be performed by a third-party vendor and 
unblinded results will be reported only at the treatment group summary level preserving 
the double-blind status on the participant level. No p-value penalty will be assessed 
because the Day 22 primary immunogenicity endpoint data will be final at the time of 
preliminary analysis and no action regarding the study will be made based on these 
findings. 

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SCHEDULE OF EVENTS 
Table 1  
Schedule of Events 
 
Screening 
Visit 1 
Day 1 
Visit 2 
Day 15 
Visit 3 
Day 22 
Visit 4 
Day 29 
Visit 5 
(phone) 
Day 92 
Visit 6 
(phone) 
Day 183/Early 
Discontinuationk 
Visit 7 
Window (days) 
Within 30 
days of Day 1 
0 
-1/+3 
-1/+3 
±1 
±3 
-14/+7 
Written informed consent 
X 
 
 
 
 
 
 
Eligibility criteria 
X 
Xa 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
Medical historyb 
X 
Xa,c 
 
 
 
 
 
Vital signsd 
X 
Xe 
 
 
 
 
 
Physical examination 
Xf 
Xa,f 
Xf 
Xf 
 
 
Xf 
Viral marker testing (HIV-1/2, anti-HCVg, 
HBsAg) 
X 
 
 
 
 
 
 
Randomization 
 
Xa 
 
 
 
 
 
Administration of IP 
 
X 
 
 
 
 
 
Diary or memory aid (electronic or paper) 
training and device distributionh 
 
Xa 
 
 
 
 
 
Acute observationi 
 
X 
 
 
 
 
 
Diary or memory aid (electronic or paper) 
collection and review 
 
 
X 
 
 
 
 
Investigator assessment of reactogenicity 
 
 
X 
 
 
 
 
Unsolicited AEs 
 
X 
X 
X 
X 
 
 
SAEs  
 
X 
X 
X 
X 
X 
X 
AESI and MAAEs 
 
X 
X 
X 
X 
X 
X 
Concomitant medications 
X 
Xa 
X 
X 
X 
Xj 
Xj 
Blood for CHIKV SNA 
 
Xa 
X 
X 
 
 
X 
Blood for testing against CHIKV genotypes 
 
Xa 
 
X 
 
 
X 

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Screening 
Visit 1 
Day 1 
Visit 2 
Day 15 
Visit 3 
Day 22 
Visit 4 
Day 29 
Visit 5 
(phone) 
Day 92 
Visit 6 
(phone) 
Day 183/Early 
Discontinuationk 
Visit 7 
a To be done prior to IP administration. 
b To include any history or current presence of joint pain. 
c To be updated if necessary. 
d Vital signs include temperature, heart rate, blood pressure, respiratory rate. Height and weight will be obtained at the screening visit only for BMI 
calculation. Vitals signs should be measured after at least five minutes of rest. Oral temperature should be measured. 
e To be taken before and after IP administration. Vital signs will be performed prevaccination and 30 minutes to one-hour postvaccination on Day 1. 
f Complete physical exam at screening and then targeted exams or per PI discretion at other visits. 
g If HCV antibody is positive HCV ribonucleic acid (RNA) testing can be performed. 
h Smart phone (e-Diary), paper diary (memory aid), digital thermometer, and ruler will be provided. 
i Participants will be monitored by study staff for signs of an acute adverse reaction for at least 30 minutes after injection. 
j Concomitant medications associated with SAEs/AESI/MAAEs only. 
k For EDV occurring within seven days postvaccination, from 7 to 21 days postvaccination, or ≥22 days postvaccination, the Visit 3, Visit 4, or Visit 7 
schedule will be followed, respectively. 

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TABLE OF CONTENTS 
1 
BACKGROUND INFORMATION ............................................................................22 
1.1 
Name and Description of Investigational Product(s) ........................................22 
1.1.1 
Indication ............................................................................................................22 
1.2 
Chikungunya Virus and Disease Background ..................................................22 
1.3 
Summary of Findings from Nonclinical Studies ...............................................23 
1.4 
Literature and Data Relevant to the Trial .........................................................24 
1.4.1 
Clinical Study VRC 311 .....................................................................................25 
1.4.2 
Clinical Study VRC 704 .....................................................................................25 
1.4.3 
Clinical Study PXVX-CV-317-001 ....................................................................26 
1.4.4 
Clinical Study EBSI-CV-317-002 ......................................................................27 
1.5 
Seroresponse Rate ................................................................................................27 
1.6 
Rationale for Dosage and Route of Administration..........................................27 
1.7 
Population to be Studied .....................................................................................27 
1.8 
Summary of Known and Potential Risks and Benefits.....................................28 
1.8.1 
Risks Related to Study Intervention ...................................................................28 
1.8.2 
Risk of Allergic Reaction....................................................................................28 
1.8.3 
Risks with Blood Draws .....................................................................................28 
1.8.4 
Risks to Pregnancy ..............................................................................................29 
1.8.5 
Risks to Confidentiality ......................................................................................29 
1.8.6 
Benefits ...............................................................................................................29 
1.9 
Hypothesis .............................................................................................................30 
2 
STUDY OBJECTIVES AND PURPOSE ...................................................................30 
2.1 
Study Purpose.......................................................................................................30 
2.2 
Coprimary Objectives .........................................................................................30 
2.3 
Secondary Objectives...........................................................................................30 
2.4 
Exploratory Objective .........................................................................................30 
3 
STUDY DESIGN ...........................................................................................................31 
3.1 
Study Description .................................................................................................31 
3.1.1 
Schematic Diagram of Study Design, Procedures, and Stages ...........................31 
3.1.2 
Study Center(s) ...................................................................................................32 
3.2 
Description of Study Assessments ......................................................................32 
3.2.1 
Review of Eligibility Criteria..............................................................................32 
3.2.2 
Medical History and Demography ......................................................................32 
3.2.3 
Physical Examination..........................................................................................32 
3.2.4 
Vital Signs ...........................................................................................................32 
3.2.5 
Laboratory Tests .................................................................................................33 
3.2.6 
Immunogenicity Samples....................................................................................33 
3.2.7 
Investigational Product Administration ..............................................................33 

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3.2.8 
Acute Observation After Investigational Product Administration......................34 
3.2.9 
Assess Solicited Adverse Events ........................................................................34 
3.2.10 Assess Unsolicited Adverse Events ....................................................................35 
3.2.11 Assess Serious Adverse Events, Medically Attended Adverse Events, and 
Adverse Events of Special Interest .....................................................................35 
3.3 
Study Endpoints ...................................................................................................35 
3.3.1 
Primary Endpoints ..............................................................................................35 
3.3.2 
Secondary Immunogenicity Endpoints ...............................................................36 
3.3.3 
Exploratory Immunogenicity Endpoint ..............................................................36 
3.4 
Measures Taken to Minimize/Avoid Bias ..........................................................36 
3.4.1 
Masking/Blinding Procedures .............................................................................36 
3.4.2 
Treatment Assignment/Randomization ..............................................................37 
3.5 
Description of Stopping Rules.............................................................................38 
3.6 
Accountability Procedures ..................................................................................38 
3.7 
Maintenance of Study Intervention Randomization ........................................38 
3.8 
Data Directly Recorded on the Electronic Case Report Form ........................38 
3.9 
End of Study .........................................................................................................38 
3.9.1 
Terminating the Study.........................................................................................39 
3.9.2 
Terminating the Study at an Individual Investigational Site ..............................39 
4 
SELECTION AND WITHDRAWAL OF PARTICIPANTS ...................................39 
4.1 
Inclusion Criteria .................................................................................................39 
4.2 
Exclusion Criteria ................................................................................................39 
4.3 
Participant Withdrawal Criteria ........................................................................41 
4.3.1 
Withdrawal of Consent .......................................................................................41 
4.3.2 
Investigator-based Participant Withdrawal .........................................................42 
4.3.3 
Follow-up for Withdrawn Participants ...............................................................42 
4.3.4 
Participant Replacement .....................................................................................42 
4.3.5 
Documentation of Withdrawal ............................................................................43 
5 
STUDY INTERVENTION ...........................................................................................43 
5.1 
Investigational Products ......................................................................................43 
5.1.1 
PXVX0317 Vaccine............................................................................................43 
5.1.2 
Placebo Pre-filled Syringe ..................................................................................43 
5.1.3 
Packaging and Labeling ......................................................................................44 
5.1.4 
Storage Conditions ..............................................................................................44 
5.1.5 
Preparation ..........................................................................................................45 
5.1.6 
Investigational Product Preparation ....................................................................45 
5.2 
Prior and Concomitant Medications ..................................................................46 
5.2.1 
Prohibited and/or Restricted Medications ...........................................................46 
5.3 
Procedures for Monitoring Participant Compliance ........................................47 
6 
STUDY PROCEDURES AND ASSESSMENTS PER VISIT ..................................47 
6.1 
Screening (Visit 1, within 30 days of Day 1) ......................................................47 

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6.2 
Rescreening ...........................................................................................................47 
6.3 
Baseline, Randomization, and IP Administration (Visit 2, Day 1) ..................48 
6.4 
Scheduled Study Visits ........................................................................................49 
6.5 
Unscheduled Visits ...............................................................................................49 
6.6 
End of Study Visit (Visit 7, Day 183 [-14/+7 days]) ..........................................49 
6.7 
Early Discontinuation Visit .................................................................................50 
7 
ASSESSMENT OF IMMUNOGENICITY ................................................................50 
7.1 
Anti-CHIKV SNA Analysis .................................................................................50 
7.2 
Cross-reactive Neutralizing Antibodies to Various CHIKV Genotypes .........50 
8 
SAFETY ASSESSMENTS AND REPORTING ........................................................51 
8.1 
Definitions .............................................................................................................51 
8.1.1 
Adverse Event .....................................................................................................51 
8.1.2 
Serious Adverse Event ........................................................................................51 
8.1.3 
Adverse Drug Reaction .......................................................................................52 
8.1.4 
Suspected Unexpected Serious Adverse Reaction ..............................................52 
8.1.5 
Adverse Events of Special Interest .....................................................................52 
8.1.6 
Solicited Adverse Event ......................................................................................52 
8.1.7 
Unsolicited Adverse Event .................................................................................53 
8.1.8 
Severity of Adverse Events .................................................................................53 
8.1.9 
Causality of Adverse Events ...............................................................................53 
8.2 
Methods and Timing for Assessing, Recording, and Analyzing Safety 
Parameters ............................................................................................................54 
8.2.1 
Safety Laboratory Tests ......................................................................................54 
8.3 
Reporting Requirements for Immediately Reportable Events ........................55 
8.3.1 
Principal Investigator’s Reporting Requirements ...............................................55 
8.3.2 
Sponsor’s Reporting Requirements ....................................................................55 
8.4 
Follow-up of Adverse Events ..............................................................................56 
8.4.1 
Follow-up of Nonserious Adverse Events ..........................................................56 
8.4.2 
Follow-up of Serious Adverse Events or Adverse Events of Special 
Interest.................................................................................................................56 
8.4.3 
Follow-up of Pregnancies ...................................................................................56 
8.4.4 
Unanticipated Problems ......................................................................................57 
8.5 
Safety Data Monitoring .......................................................................................57 
9 
STATISTICAL CONSIDERATIONS ........................................................................57 
9.1 
Sample Size Rationale..........................................................................................57 
9.2 
Analysis Populations ............................................................................................58 
9.3 
Statistical Methods ...............................................................................................58 
9.4 
Multiplicity Controls ...........................................................................................59 
9.4.1 
Coprimary Immunogenicity Endpoints...............................................................59 
9.4.2 
Key Secondary Immunogenicity Endpoints .......................................................59 
9.5 
Handling of Missing Data ....................................................................................59 

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9.6 
Planned Analyses .................................................................................................60 
9.6.1 
Study Population Characteristics ........................................................................60 
9.6.2 
Immunogenicity Analyses ..................................................................................61 
9.6.3 
Investigational Product Administration and Treatment Compliance ..................63 
9.6.4 
Safety Analyses ...................................................................................................63 
9.6.5 
Subgroup Analyses .............................................................................................64 
9.6.6 
Planned Interim Analyses and Criteria for Study Termination ..........................64 
10 
DATA HANDLING AND RECORD KEEPING .......................................................64 
10.1 
Source Documents and Access ............................................................................64 
10.2 
Data Management ................................................................................................65 
10.3 
Data Collection and Discrepancy Management ................................................65 
10.4 
Laboratory Data...................................................................................................66 
10.5 
File Management at the Investigational Site .....................................................66 
10.6 
Records Retention at the Investigational Site ...................................................66 
10.7 
Deviations from the Protocol ..............................................................................66 
11 
QUALITY CONTROL AND ASSURANCE..............................................................67 
11.1 
Monitoring ............................................................................................................67 
11.2 
Auditing ................................................................................................................67 
12 
ETHICS AND RESPONSIBILITY .............................................................................67 
12.1 
Informed Consent ................................................................................................68 
12.2 
Institutional Review Board .................................................................................68 
12.3 
Compensation for Injury .....................................................................................69 
12.4 
Documentation Required Prior to Study Initiation ..........................................69 
12.5 
Participant Confidentiality .................................................................................69 
12.6 
Future Use of Stored Samples .............................................................................70 
13 
ADMINISTRATIVE AND LEGAL REQUIREMENTS ..........................................70 
13.1 
Sponsorship ..........................................................................................................70 
13.2 
Protocol Amendments .........................................................................................70 
13.3 
Clinical Study Registration .................................................................................71 
13.4 
Publication Policy.................................................................................................71 
14 
REFERENCES ..............................................................................................................72 
15 
APPENDICES ...............................................................................................................74 
APPENDIX 
APPENDIX I 
TOXICITY GRADING SCALE TABLES .........................................74 

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LIST OF TABLES 
Table 1  
Schedule of Events..............................................................................................13 
Table 2 
Needle Length and Injection Site of Intramuscular Injections for Adults ≥19 
Years of Age (by Sex and Weight) .....................................................................34 
LIST OF FIGURES 
Figure 1 
Chikungunya Virus Global Burden (adapted from (3)) ......................................23 
Figure 2 
EBSI-CV-317-005 Schematic Diagram of Study Design...................................31 
Figure 3 
Adverse Event Period of Reporting ....................................................................54 

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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
ACIP 
Advisory Committee on Immunization Practices 
AE 
Adverse Event 
AESI 
Adverse Event of Special Interest 
ANOVA 
Analysis of Variance 
ATC 
Anatomic Therapeutic Chemical 
BMI 
Body Mass Index 
C 
Capsid 
CBP 
Childbearing Potential 
CFR 
Code of Federal Regulations 
CHIKV 
Chikungunya Virus 
CHIKV-luc 
Modified version of CHIKV containing a reporter gene that expresses a luciferase 
protein 
CI 
Confidence Interval 
DMP 
Data Management Plan 
E 
Envelope 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
EDV 
Early Discontinuation Visit 
ER 
Emergency Room 
FDA 
Food and Drug Administration 
FRNT 
Focus Reduction Neutralization Test 
GCP 
Good Clinical Practices 
GMFI 
Geometric Mean Fold Increase 
GMT 
Geometric Mean Titer 
HBsAg 
Hepatitis B Surface Antigen 
HBV 
Hepatitis B Virus 
HCV 
Hepatitis C Virus 
HIV 
Human Immunodeficiency Virus 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use 
ID 
Identification 
IEP 
Immunogenicity Evaluable Population 
IgG 
Immunoglobulin G 
IM 
Intramuscular 
IP 
Investigational Product 

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IRB 
Institutional Review Board 
LLOQ 
Lower Limit of Quantitation 
LTF 
Lost to Follow-up 
MAAE 
Medically Attended Adverse Event 
MedDRA 
Medical Dictionary of Regulatory Activities 
mITT 
Modified Intent to Treat 
MM 
Medical Monitor 
NHP 
Nonhuman Primates 
NIH 
National Institutes of Health 
nsP 
Nonstructural Proteins 
NT80 
80% Neutralization Titer 
PCR 
Polymerase Chain Reaction 
PFU 
Plaque Forming Units 
PI 
Principal Investigator 
PT 
Preferred Term 
RBC 
Red Blood Cell 
RNA 
Ribonucleic Acid 
RT-qPCR 
Reverse Transcriptase Quantitative Polymerase Chain Reaction 
RTSM 
Randomization and Trial Supply Management 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SMC 
Safety Monitoring Committee 
SNA 
Serum Neutralizing Antibody 
SOC 
System Organ Class 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
US 
United States of America 
VLP 
Virus-like Particle 
VRC 
Vaccine Research Center 
WBC 
White Blood Cell Count 
 
 

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1 
BACKGROUND INFORMATION 
1.1 
Name and Description of Investigational Product(s) 
PXVX0317 is a CHIKV VLP vaccine. The vaccine is comprised of 40 μg CHIKV VLP 
adsorbed on aluminum hydroxide 2% adjuvant (2% [w/w] aqueous suspension of aluminum 
hydroxide, Alhydrogel®) and stabilized with formulation buffer, supplied as a single dose of 
0.8 mL in a pre-filled syringe to be administered IM in the deltoid muscle.  
Placebo (diluent) is a sterile aqueous solution with the same excipient composition as the 
PXVX0317 drug product without CHIKV VLP or aluminum hydroxide components. 
For additional study vaccine information, see Section 5.1 and the PXVX0317 Investigator’s 
Brochure (IB).   
1.1.1 Indication 
The target indication for PXVX0317 vaccine is for active immunization to prevent disease 
caused by CHIKV. 
1.2 
Chikungunya Virus and Disease Background 
Chikungunya virus is an arthropod-borne alphavirus of the family Togaviridae. The CHIKV 
virion contains a positive-sense single-strand RNA genome with a long open reading frame 
coding for capsid (C) and envelope (E1, E2, E3, and 6K) structural proteins, together with 
four nonstructural proteins (nsP1, nsP2, nsP3, and nsP4) required for replication of the virus. 
Since the first case reports of CHIKV in a 1952–1953 outbreak in Tanzania (1), this disease 
has been endemic in Africa and parts of Asia with transmission occurring through Aedes 
aegypti and more recently via Aedes albopictus mosquitoes (2).  
Beginning in 2014, CHIKV disease cases were reported among US travelers returning from 
affected areas in the Americas and local transmission was identified in Florida, Puerto Rico, 
and the US Virgin Islands. According to the US Centers for Disease Control and Prevention 
approximately 117 countries or territories have documented cases of CHIKV infection 
excluding those countries where only imported cases have been documented (Figure 1 
adapted from (3)). Although mosquitoes are the primary mode of transmission of CHIKV, 
blood-borne transmission via needle stick is possible. Maternal-fetal transmission has been 
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Figure 1 
Chikungunya Virus Global Burden (adapted from (3)) 
 
Following an incubation period of 2 to 12 days, acute clinical manifestations include high 
fever, rash, gastrointestinal complications, headache, muscle pain, nausea, fatigue, myalgia, 
and joint pain (5, 6, 7). The most classic symptom of chikungunya is a debilitating 
polyarthralgia that is present in greater than 90% of cases (8). This acute phase resolves 
within several weeks, but joint pain and arthritis may persist for months or years in over 25% 
to 40% of infected individuals (9). The frequency and severity of arthritic sequelae are higher 
in older adults (10). 
Currently there are no approved vaccines to prevent CHIKV infection or disease. However, 
protection against subsequent infection has been shown to correlate with the presence of 
CHIKV antibodies that neutralize the virus in vitro (11, 12).  
1.3 
Summary of Findings from Nonclinical Studies 
The sponsor conducted a study in mice that demonstrated comparability between the immune 
responses induced by the VRC-CHKVLP059-00-VP (discussed in Section 1.4) and 
PXVX0317 vaccines. Following this, the sponsor conducted a pilot challenge study in 
cynomolgus macaques nonhuman primates (NHP) to determine the CHIKV challenge dose 
required to induce signs of arthritis, as quantified by degree of inflammation of the joints and 
surrounding tissues in infected animals. A scoring system was developed to measure the 
degree of joint infiltration and a challenge dose of 107 plaque forming units (PFUs) of 
CHIKV La Reunion outbreak strain LR2006-OPY1 was selected as the optimal dose to 

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induce signs of arthritis in NHPs. An NHP active vaccination and challenge study with the 
PVXV0317 vaccine followed. Nonhuman primates received two IM immunizations (on 
study Days 0 and 28) with VLP (1.25, 6, or 20 µg) adjuvanted with alum (300 µg), VLP 
alone (20 µg), or alum alone, followed by challenge with 107 (PFU) of CHIKV strain 
LR2006-OPY1.   
Data from the study demonstrate that all three dose levels of the PXVX0317 vaccine, 
including 20 µg without alum, induced a robust immune response as measured by CHIKV 
luciferase serum neutralizing antibody assay for NHP serum (NHP SNA Assay), even after a 
single immunization. Importantly, the addition of alum increased the prechallenge SNA titers 
compared to the VLP vaccine without alum. Furthermore, vaccination completely protected 
NHPs from viremia, as measured by plaque assay on serum from challenged animals. Joint 
pathology scores in the active vaccination study demonstrate that vaccination with 
PXVX0317 protects NHPs from joint infiltration in a dose-dependent manner. Quantitative 
reverse transcriptase polymerase chain reaction (RT-qPCR) analysis (by NHP RT-qPCR 
assay) of joint tissues showed significantly lower levels of viral RNA in tissues of vaccinated 
animals, which rarely had detectable RNA, compared with animals that had received only 
alum. Taken together, these data suggest that vaccination induced CHIKV SNA protects 
cynomolgus macaques from developing CHIKV disease following viral challenge.  
In addition, Emergent conducted a passive transfer and challenge study in cynomolgus 
macaque NHPs. Human Immunoglobulin G (IgG) purified from plasma of volunteers 
vaccinated with PXVX0317 was passively transferred to NHPs at three dose levels (5, 15, 
and 100 mg/kg, resulting in SNA titers at time of challenge of 1:38, 1:101, and 1:644, 
respectively) followed by CHIKV (strain LR2006-OPY1) challenge. All three dose levels of 
IgG purified from plasma of PXVX0317 vaccinated participants protected NHPs from 
viremia as measured by plaque assay. Human IgG administration also appears to protect 
NHPs from joint pathology in a dose-dependant manner. Results indicate that purified human 
IgG at an SNA titer of 1:38 is sufficient to protect NHPs against viremia as measured by 
plaque assay following CHIKV challenge. 
1.4 
Literature and Data Relevant to the Trial 
The National Institutes of Health (NIH) Vaccine Research Center (VRC) initiated the 
development of the CHIKV VLP vaccine, designated VRC-CHKVLP059-00-VP. The VRC 
completed phase 1 (VRC 311) (13, 14) and phase 2 (VRC 704) (15, 16) clinical studies. 
PaxVax Inc. then manufactured the vaccine as PXVX0317, conducted a mouse 
immunogenicity study showing comparability to the VRC-CHKVLP059-00-VP vaccine, and 
proceeded to a phase 2 study (PXVX-CV-317-001) (17). PaxVax Inc. was acquired by 
Emergent BioSolutions, Inc. in October 2018, and has been renamed Emergent Travel Health 
Inc. (Emergent) as the sponsor of two phase 2 studies (PXVX-CV-317-001 and 
EBSI-CV-317-002), a phase 3 study (EBSI-CV-317-004) and this phase 3 study.  

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1.4.1 Clinical Study VRC 311 
The safety and immunogenicity of VRC-CHKVLP059-00-VP were evaluated under BB-IND 
14907 in VRC 311, a phase 1 open-label, dose-escalation study (13, 14). Healthy adult 
participants 18 to 50 years of age were assigned to sequential dose level groups to receive IM 
injections of 10 µg, 20 µg, or 40 µg (without adjuvant) on Weeks 0, 4, and 20, with 
follow-up for 44 weeks after enrollment. The primary endpoints were safety and tolerability 
of the vaccine. Secondary endpoints were CHIKV-specific immune responses assessed by 
neutralizing antibody assay and enzyme linked immunosorbent assay (13, 14).   
All injections were well tolerated, with no SAEs reported. The most common local reaction 
was mild injection site pain (36%) and the most common systemic reaction was mild malaise 
(24%). No moderate or severe reactogenicity was observed (13, 14). 
Neutralizing antibodies were detected in all dose groups after the second vaccination. The 
GMT of the half maximum inhibitory concentration (IC50) was 2688 in the 10 µg group, 
1775 in the 20 µg group, and 7246 in the 40 µg group, and a significant boost occurred after 
the third vaccination in all dose groups (10 µg group p=0.0197, 20 µg group p<0.0001, and 
40 µg group p<0.0001). Four weeks after the third vaccination, the GMT of the IC50 was 
8745 for the 10 µg group, 4525 for the 20 µg group, and 5390 for the 40 µg group (13, 14). 
These findings were confirmed by both a plaque reduction assay and the sponsor’s 
luciferase-based assay (human SNA assay) (18), confirming both the immunogenicity of the 
VLP and the suitability of human SNA assay for future studies (see Section 7 for assay 
details).  
1.4.2 Clinical Study VRC 704 
The NIH VRC 704 was a phase 2 study conducted at multiple CHIKV-endemic sites in the 
Caribbean (15, 16). The study was a double-blind, placebo-controlled study with 200 
participants (planned) receiving 20 µg of CHIKV VLP and 200 receiving placebo in a 
two-dose series at Weeks 0 and 4. The study was initiated in 2016 and completed in 2018. 
Approximately 20% of participants demonstrated detectable CHIKV neutralizing antibodies 
at baseline using the focus reduction neutralization test (FRNT) reported as EC50 values. 
EC50 is the dilution of sera that inhibits 50% infection in viral neutralization assay. 
Chikungunya virus VLP appeared safe and well tolerated in participants who were followed 
through Week 72, with no related SAEs or other safety concerns (15, 16). Chikungunya virus 
VLP appeared highly immunogenic, with a GMT of 2004.5 and 99.5% of recipients having 
neutralizing antibodies at Week 8. A boosting effect of SNA after administration of CHIKV 
VLP was also observed in participants with baseline CHIKV neutralizing antibodies (15, 16). 
Specimens from VRC 704 were also analyzed ad hoc by the sponsor, using the human SNA 
assay. A subgroup analysis was performed on participants without baseline CHIKV 
neutralizing activity. Using a more stringent 80% neutralization cut-off (NT80), the GMT was 
123 at Week 4 and 1701 at Week 8. After Week 8, antibody levels declined by about 1 log 
but remained elevated above baseline, with GMTs of 213 at Week 24, 115 at Week 48, and 
100 at Week 72, indicating that long-term protection can potentially be achieved without the 

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need for booster dose(s). These results demonstrated that CHIKV VLP was safe and 
immunogenic in adults in CHIKV-endemic areas, including those with serologic evidence of 
previous CHIKV exposure. The most frequently reported local AE was pain/tenderness at the 
injection site reported as mild by 58 of 197 (29%) vaccine recipients who received at least 
one study injection and as moderate by 3/197 vaccine recipients (2.0%). The most frequently 
reported systemic AEs were mild or moderate headache reported by 54 of 197 (27.4%) 
vaccine recipients, malaise (53/197, 26.9%), and myalgia (46/197, 23.4%) (15, 16). Placebo 
recipients reported these systemic reactogenicity symptoms at similar frequencies. One 
vaccine recipient (0.5%) experienced a headache graded as severe following the second 
vaccination. A total of 16 SAEs in 15 (3.8%) participants were reported, all were assessed as 
unrelated to the IP (ie, CHIKV VLP or placebo). All potentially related AEs resolved without 
clinical sequelae (15, 16). 
Taken together, the findings from VRC 311 and VRC 704 suggest that 
VRC-CHKVLP059-00-VP is well-tolerated and immunogenic in both CHIKV-exposed and 
CHIKV-naïve adults. 
1.4.3 Clinical Study PXVX-CV-317-001 
The sponsor’s phase 2 clinical study (PXVX-CV-317-001) conducted in the US compared 
multiple dose and dosing regimens of CHIKV VLP in healthy adults 18 to <46 years of age 
(17). The dosages of CHIKV VLP ranged from 6 µg to 40 µg, adjuvanted or unadjuvanted. 
These doses were below or approximately equivalent to those used in the NIH’s VRC 311 
and VRC 704 clinical studies using the non-adjuvanted CHIKV VLP (VRC-CHKVLP059-
00-VP) vaccine. PXVX0317 vaccine was immunogenic across all dose groups as measured 
by human SNA assay. Immunogenicity data reported as 80% antibody neutralization titer 
(NT80) values supported the benefit of adjuvant was evident after one dose but not two doses. 
There was a clear dose-response relationship in GMT. Participants receiving 20 µg on the 
standard schedule (Days 1 and 29), either unadjuvanted (as the NIH reference dose) or 
adjuvanted, had the highest Day 57 GMT at 1946 and 1884 respectively, similar to those of 
CHIKV VLP recipients in the VRC 704 study. Participants receiving the single 40 µg dose 
demonstrated only slightly lower GMT levels (1712 at Day 57, ie, 28 days after vaccination); 
all other dose groups demonstrated a GMT range of 914 to 1613 at Day 57. Seroconversion 
rates (titer ≥15) showed that with a single dose administered, up to 98% of study participants 
produced a neutralizing antibody response by Day 8. Further, the immune response was 
shown to be persistent through the 24-month visit, including in the one dose 40 µg CHIKV 
VLP regimen. There was a clear dose-response relationship in GMT, with the Group 8 40 µg 
CHIKV VLP + 300 µg alum adjuvant single dose resulting in 86% seroresponse (titers ≥40) 
7 days post vaccination as well as the highest GMTs at Day 182. Seroresponse was well 
maintained at 760 days in Group 8 participants. Based on these data the 40 µg CHIKV VLP 
+ 300 µg alum adjuvant single dose regimen was selected going forward in the PXVX0317 
clinical development.  

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1.4.4 Clinical Study EBSI-CV-317-002 
The phase 2 clinical study (EBSI-CV-317-002) conducted at two sites in the US compared 
the safety and immunogenicity of a 40 µg CHIKV VLP + 300 µg alum adjuvant single dose 
in prior recipients of other alphavirus vaccines vs alphavirus vaccine-naïve controls (19).  
The 30 prior alphavirus vaccine recipients and 30 gender and age-matched vaccine-naïve 
controls were vaccinated and followed for six months. There were no differences between the 
groups in CHIKV neutralizing antibody GMTs at Day 22 and no new safety signals were 
identified.  
For more information refer to the IB. 
1.5 
Seroresponse Rate 
In historical studies, a human SNA assay threshold titer of  ≥40 was used, however after 
additional analysis of protective efficacy data from animal studies and discussions with 
regulatory agencies, an anti-CHIKV SNA titer 
 (seroresponse rate, also considered the 
presumptive seroprotection rate) will be used in the present and future studies.  
1.6 
Rationale for Dosage and Route of Administration 
The regimen of PXVX0317 selected for this study is 40 µg of CHIKV VLP with alum 
adjuvant administered in a single IM dose on Day 1. The alum dose of 300 µg is within the 
range of doses of alum adjuvants used in many licensed vaccines, including VLP-based 
vaccines. This dose also creates a concentration ratio to PXVX0317 that achieves high 
(~90%) levels of adsorption, thought to enhance immunogenicity. The IM route of 
administration is consistent with that in previous clinical studies (VRC 311, VRC 704, 
PXVX-CV-317-001, and EBSI-CV-317-002). This regimen was selected by an interim 
analysis of the PXVX-CV-317-001 study data. All regimens tested were given to groups of 
50 to 53 healthy adults and all resulted in 100% seroconversion by Day 57. The group 
receiving a single dose of 40 µg plus alum showed the highest CHIKV SNA GMT at Day 
182 and Day 365. Similar findings were observed in EBSI-CV-317-002. 
The PXVX0317 vaccine (40 µg CHIKV VLP + 300 µg aluminum hydroxide adjuvant) single 
dose was selected for further development by the sponsor in this phase 3 clinical study 
(EBSI-CV-317-005). 
1.7 
Population to be Studied 
The target population is adults ≥65 years of age. This study will generate safety and 
immunogenicity data in elderly adults, in whom PXVX0317 has not been previously 
evaluated. This study is important due to the high relative disease burden in older adults, as 
well as potential concerns about immunosenescence and attendant hyporesponsiveness to 
vaccination in this age group. 

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1.8 
Summary of Known and Potential Risks and Benefits 
1.8.1 Risks Related to Study Intervention 
The injection of PXVX0317, like other injections, can cause pain, redness, or swelling at the 
injection site. These types of reactions are generally mild. Less commonly, it can cause 
itching, bruising, or infection. 
Most solicited AEs reported by participants enrolled in study PXVX-CV-317-001 were mild 
to moderate in severity. The percentage of participants who reported ≥Grade 3 AEs for the 
following categories were as follows: any AEs (7.9%), any solicited AE (6.1%), any 
systemic solicited AE (5.9%), any local solicited AE (0.2%), any unsolicited AE through 
Day 57 (2.9%), any treatment-related solicited AE (3.6%), any treatment-related systemic 
solicited AE (3.4%), any treatment-related local solicited AE (0.2%). There were no reports 
of ≥Grade 3 treatment-related unsolicited AEs through Day 57. No participants had a 
treatment-related SAE, and no participants permanently discontinued study due to AE or died 
during the study.  
Among participants from PXVX-CV-317-001 Group 8 (n=50) participants who received the 
40 µg adjuvanted dose selected for further development, 48.0% reported solicited AEs 
occurring within seven days postvaccination with active vaccine at Day 29. Approximately 
22% of participants reported solicited systemic AEs and 40.0% reported solicited local AEs. 
Solicited local AEs reported included only injection site pain; no injection site redness or 
swelling was reported after receipt of the active dose. Solicited systemic AEs reported 
included malaise (4.0%), fatigue (4.0%), headache (8.0%), myalgia (12.0%), nausea (4.0%), 
and joint pain (2.0%). 
There were 13 unrelated SAEs reported for 10 participants in study PXVX-CV-317-001 and 
study EBSI-CV317-002. One case of anaphylaxis occurred on study Day 309 in a participant 
that was suspected to be due to a nut allergy. No participants had a treatment-related SAE, 
and no participants permanently discontinued study due to AE or died during the study. 
1.8.2 Risk of Allergic Reaction 
With any vaccine, there is a risk of severe allergic reaction. Although such reactions have not 
been reported as related to this vaccine, they have occurred with other vaccines containing 
some of the same ingredients. Symptoms of allergic reaction may include, but are not limited 
to, rash, wheezing and difficulty breathing, difficulty swallowing, dizziness and fainting, 
swelling around the mouth, throat or eyes, a fast pulse, and/or sweating. Participants will be 
directed to inform study staff immediately if experiencing any of these symptoms. 
1.8.3 Risks with Blood Draws 
Blood drawing may cause pain, bruising, feeling faint, fainting, needle site infections, 
swelling, and rarely other infections. Bruising at the site of blood drawing can be prevented 

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by applying pressure for several minutes. To reduce the risk of infection, the area will be 
wiped clean with alcohol and sterile equipment will be used. 
1.8.3.1 
Risks of Positive Screening Test for HIV, Hepatitis B, and Hepatitis C 
At the Screening Visit, participants will be tested for HBV, HCV, and HIV. Receiving 
information that any health screening tests are abnormal or that tests for HIV and HBV or 
HCV are positive may upset participants. The study doctors will discuss their health results 
face-to-face (and notify their primary doctor at their request). Counseling will be available to 
the study participant if they wish. A positive HIV status could limit a participant’s ability to 
obtain future life and health insurance. In rare circumstances, a positive HIV test has led to 
discrimination in employment and housing, etc. Participants will be advised of this in the 
ICF. 
1.8.4 Risks to Pregnancy 
PXVX0317 has not been thoroughly evaluated for potential risks to unborn or nursing 
children. 
1.8.5 Risks to Confidentiality 
Efforts will be made to keep participants’ personal health information confidential. To 
maintain confidentiality, paper study records will be stored in a secure location such as a 
locked office or locked cabinet. Electronic data will be password protected. Electronic study 
records and samples taken will be coded with a number, not the participants’ names. Records 
will only be shared with authorized personnel and only in connection with carrying out the 
obligations related to the study. 
Although efforts are made to protect the research study records, there is always a risk that 
someone could get access to the personal information in research records or other 
information researchers have stored about participants. 
1.8.6 Benefits 
There is no expected benefit to participants from this study. A potential benefit of 
participation in this clinical trial might be protection against CHIKV disease; however, the 
clinical efficacy of this vaccine for that indication has not yet been proven. This study will 
accumulate additional safety data on this vaccine and uniquely provide a first glimpse at the 
safety and immunogenicity of this vaccine in the context of elderly adults. This data will be 
important to the design of field studies. If, for example, the vaccine is less immunogenic in 
the elderly, this should be considered for determining any potential modified dosing/dose 
regimen recommendations. 

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1.9 
Hypothesis 
The study hypothesis being tested is that the immune response to PXVX0317 is superior to 
that of placebo in adults ≥65 years of age at Day 22, that the immune response to PXVX0317 
in adults ≥65 years of age at Day 22 is clinically relevant, and that the safety profile in adults 
≥65 years of age is comparable to that in individuals 18 to <65 years of age. A clinically 
relevant immune response in adults ≥65 years of age is defined as the lower bound of the 
two-sided 95% CI for the Day 22 seroresponse rate 
. 
Note: Seroresponse rate (considered the presumptive seroprotection rate) is defined as the 
percentage of participants who achieve an anti-CHIK SNA titer 
. 
2 
STUDY OBJECTIVES AND PURPOSE 
2.1 
Study Purpose 
The purpose of this phase 3, randomized, double-blind, placebo-controlled study is to 
evaluate the safety and immunogenicity to PXVX0317 in adults ≥65 years of age. 
2.2 
Coprimary Objectives 
• To compare the anti-CHIKV SNA response to PXVX0317 and placebo at Day 22, as 
measured by GMT and clinically relevant difference in seroresponse rate (PXVX0317 
minus placebo) in adults ≥65 years of age.   
Note: Seroresponse rate (considered the presumptive seroprotection rate) is defined as the 
percentage of participants who achieve an anti-CHIKV SNA titer 
. 
• To evaluate the safety of PXVX0317 in adults ≥65 years of age. 
2.3 
Secondary Objectives 
• To compare the anti-CHIKV SNA response to PXVX0317 and placebo at Day 15 and 
Day 183, as measured by GMT and seroresponse rate.  
• To compare the anti-CHIKV SNA response to PXVX0317 and placebo in participants 
≥65 to <75 and ≥75 years of age as measured by GMT and seroresponse rate. 
2.4 
Exploratory Objective 
To evaluate the ability of PXVX0317 vaccine-induced CHIKV antibodies to neutralize 
various CHIKV genotypes. 

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3 
STUDY DESIGN 
3.1 
Study Description 
This is a phase 3, randomized, double-blind, placebo-controlled, parallel-group study with 
two treatment groups. 
At least 400 healthy US elderly participants ≥65 years of age and older will be enrolled, 
stratified in two age subgroups (≥65 to <75 and ≥75 years of age). Participants will be 
randomized in a 1:1 ratio to receive either a single IM dose of PXVX0317 or placebo at Day 
1, respectively. 
The per participant estimated total study duration is 212 days (including screening). The 
screening window will be no greater than 30 days prior to Day 1 (randomization and 
administration of IP). The immune response to PXVX0317 will be measured by anti-CHIKV 
SNA up to the Day 183 End of Study Visit. For details on schedule of events, refer to Table 1 
An independent SMC will provide safety oversight. The SMC will review aggregated, 
blinded safety data after the first 50 participants have completed seven days of safety 
follow-up. The remaining participants will be enrolled following the safety review by the 
SMC and based on the sponsor’s consideration of the SMC’s recommendation. The need for 
any further reviews will be determined by the SMC. 
3.1.1 Schematic Diagram of Study Design, Procedures, and Stages 
Figure 2 
EBSI-CV-317-005 Schematic Diagram of Study Design 
 
Note: Days 29 and 92 are phone call follow-ups. 

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3.1.2 Study Center(s) 
This will be a multicenter study conducted in the US with up to 10 sites. 
3.2 
Description of Study Assessments 
The underlying subsections (Section 3.2.1 through Section 3.2.11) describe the planned study 
procedures and assessments. For the per visit timing of these procedures and assessments 
refer to Section 6 and the study schedule of events (Table 1). Information on participant 
consent is described in Section 12.1. 
3.2.1 Review of Eligibility Criteria 
Review of inclusion and exclusion criteria should be completed, and participant eligibility 
confirmed prior to planned IP administration. Refer to Sections 4.1 and Section 4.2 for the 
eligibility criteria. 
3.2.2 Medical History and Demography 
Medical history information will be collected from participants at the Screening Visit and 
confirmed at the Day 1 Visit (at baseline ie, prior to IP administration) and will include (but 
not be limited to) demographic information (date of birth, race, ethnicity, and sex of 
participant), current and past medical conditions (including presence of joint pain), prior and 
concomitant medications (see Section 5.2) taken within 30 days of Screening Visit (or within 
90 days for blood products, or within six months for immunosuppressive/immunomodulatory 
medications). 
3.2.3 Physical Examination 
A complete physical examination will be performed on participants during the Screening 
Visit. The examination should include, general appearance, eyes-ears-nose-throat, head-neck, 
lungs-chest, heart, abdomen, musculoskeletal, lymph nodes, skin, extremities, and 
neurological assessment.  
A targeted physical examination may be performed on participants at additional time points 
if indicated by AE, SAE, or AESI reports or at the investigator’s discretion. 
3.2.4 Vital Signs 
Vital signs collected from participants will include blood pressure, heart rate, respiratory rate, 
and temperature. Vital signs should be measured after the participant has been at rest for at 
least five minutes. The first set of screening vitals are to be collected and transcribed into the 
screening electronic case report form (eCRF) for inclusion of the participant into the study. 
Repeat measurements on abnormal vital parameters are allowed twice for confirmation of 
eligibility for IP administration. Vital signs will be taken prior to vaccination and 30 minutes 
to one hour after IP administration.  

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Measurement of body weight and height for BMI calculations will be obtained at the 
Screening Visit. 
3.2.5 Laboratory Tests 
At the Screening Visit, blood samples will be collected for serum testing for hepatitis B 
surface antigen (HBsAg), HCV antibody (HCV RNA polymerase chain reaction (PCR), if 
needed), HIV-1/HIV-2.  
For additional information on sample collection, processing, storage, and shipment refer to 
the study Laboratory Manual.  
3.2.6 Immunogenicity Samples 
3.2.6.1 
Immunogenicity Sample for Human SNA Assay  
Chikungunya virus SNA levels will be assessed using a validated human SNA assay that 
measures NT80 titer. Blood (serum) samples will be taken on Day 1 (prior to IP 
administration), Day 15, Day 22, and Day 183 End of Study Visit (or at Early 
Discontinuation/Withdrawal).  
For additional information on sample collection, processing, storage, shipment, and retention 
refer to the study Laboratory Manual. 
3.2.6.2 
Immunogenicity Sample for Various CHIKV Genotypes 
Neutralizing antibodies against various CHIKV genotypes will be measured for a subset of 
participants in the PXVX0317 group using FRNT50. Blood (serum) samples will be 
collected on Day 1, Day 22, and Day 183 End of Study Visit. 
3.2.7 Investigational Product Administration 
Investigational product is 0.8 mL in volume and administered by IM injection into the deltoid 
muscle with a pre-filled syringe attached to 25 gauge 1” (or 1.5”) needle, using universal 
precautions and sterile technique in accordance with General Best Practice Guidelines for 
Immunization: Best Practices Guidance of the Advisory Committee on Immunization 
Practices (ACIP) (20) per Table 2. Investigational product is to be administered only under 
the direct supervision of the investigator or a qualified subinvestigator identified on the FDA 
Form 1572. 

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Table 2 
Needle Length and Injection Site of Intramuscular Injections for Adults ≥19 Years of Age 
(by Sex and Weight) 
Sex, Weight 
Needle length 
Injection Site 
Men and women, <60 kg (<130 lbs) 
1 inch (25 mm)1 
Deltoid muscle of arm 
Men and women, 60–70 kg (130–152 lbs) 
1 inch (25 mm) 
Men, 70–118 kg (152–260 lbs) 
1–1.5 inches (25–38 mm) 
Women, 70–90 kg (152–200 lbs) 
Men, >118 kg (260 lbs) 
1.5 inches (38 mm) 
Women, >90 kg (200 lbs) 
Source: Adapted from Table 6-2, General Best Practice Guidelines for Immunization: Best Practices 
Guidance of the Advisory Committee on Immunization Practices (ACIP) (20). 
1Some experts recommend a 5/8-inch needle for men and women who weigh <60 kg, if used, skin must be 
stretched tightly (do not bunch subcutaneous tissue).  
Under no circumstances will the investigator allow PXVX0317 vaccine to be used other than 
as specified in the protocol. 
For further details on the IP refer to Section 5.1.  
3.2.8 Acute Observation After Investigational Product Administration 
The participant will be monitored by study staff for signs of an acute adverse reaction for at 
least 30 minutes after injection and vital signs will be obtained 30 minutes to one hour after 
vaccination. 
3.2.9 Assess Solicited Adverse Events 
Electronic or paper diaries (memory aids) will be used to collect solicited AEs following 
vaccination. Participants will record events in their diary daily, for at least seven days after 
vaccination. Solicited AEs to be assessed in this study are local events of pain, redness, and 
swelling at the injection site and systemic events of oral temperature ≥38.0°C (≥100.4°F), 
chills, fatigue, headache, myalgia, arthralgia, and nausea.  
Participants will be trained to complete a diary (electronic or paper) to observe, measure, and 
record these solicited AEs daily. A digital thermometer will be provided to the participants to 
measure their temperature each day. The highest temperature measured each day should be 
recorded in the participant’s diary or memory aid (electronic or paper). To record injection 
site local reactions, a ruler will be provided to the participant to measure and record the 
diameter of redness and swelling at the largest point of the reaction each day.  
Study staff will review the signs and symptoms recorded in the diary or memory aid 
(electronic or paper) daily and will follow-up with participants if any data is missing. The 
investigator will then assess all solicited AEs for severity (Section 8.1.8) and the action 
taken, and causality (Section 8.1.9). The results of the investigator’s assessment will be 
recorded as a separate source document and will be entered on the solicited AE eCRF. 

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Symptoms continuing beyond the solicited AE collection period will be collected and 
recorded on the AE eCRF. 
Details on safety definition, evaluation, reporting periods and documentation are outlined in 
Section 8. 
3.2.10 Assess Unsolicited Adverse Events 
Unsolicited AEs (AEs not listed in the diary or memory aid [electronic or paper]) will be 
collected from Day 1 through 28 days post vaccination. 
Details on safety definition, evaluation, reporting periods and documentation are outlined in 
Section 8. 
3.2.11 Assess Serious Adverse Events, Medically Attended Adverse Events, and 
Adverse Events of Special Interest 
Serious Adverse Events, AESI, and MAAE will be collected for all participants from Day 1 
through Day 183 End of Study Visit. 
Details on safety definition, evaluation, reporting periods, and documentation are outlined in 
Section 8. 
3.3 
Study Endpoints 
3.3.1 Primary Endpoints 
Coprimary Immunogenicity Endpoints 
• Difference in anti-CHIKV SNA seroresponse rate (PXVX0317 minus placebo) and 
associated 95% CI at Day 22.  
Success criterion: Lower bound of the two-sided 95% CI on the difference in 
seroresponse rates between PXVX0317 and placebo groups 
 (equivalent to a 
difference >0 using a two-sided chi-square test). 
• Anti-CHIKV SNA GMT and associated 95% CIs at Day 22 for PXVX0317 and placebo.  
Success criterion: Significant difference in the IEP across all age groups combined 
using an ANOVA model with logarithmically transformed anti-CHIKV SNA titers 
(log10) as the dependent variable and treatment group and study site as the fixed 
effects with a two-sided significance level of 0.05. 
Note: Seroresponse rate (considered the presumptive seroprotection rate) is defined as the 
percentage of participants who achieve an anti-CHIK SNA 
. See Section 9.6.2 
for immunogenicity analysis details and Section 9.4 for success criteria and multiplicity 
controls. 

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Safety Endpoints 
• Incidence of solicited AEs through Day 8 for PXVX0317 and placebo. 
• Incidence of unsolicited AEs through Day 29 for PXVX0317 and placebo. 
• Incidence of SAEs, MAAEs, and AESI through Day 183 for PXVX0317 and placebo. 
3.3.2 Secondary Immunogenicity Endpoints 
• Key Secondary Immunogenicity Endpoints: Difference in anti-CHIKV SNA 
seroresponse rate (PXVX0317 minus placebo) with associated 95% CIs at Day 15 and 
Day 183, in that order (see Section 9.6.2). 
• Anti-CHIKV SNA GMTs by study arm with associated 95% CIs at Day 15 and Day 183.  
• Geometric mean fold increase from Day 1 to subsequent collection time points.  
• Number and percentage of participants with an anti-CHIKV SNA titer ≥15 and 4-fold 
rise over baseline.  
3.3.3 Exploratory Immunogenicity Endpoint 
Geometric mean titers and associated two-sided 95% CIs for neutralizing antibodies against 
various CHIKV genotypes measured at Day 22 (and at baseline if necessary) for a subset of 
participants in the PXVX0317 group. 
3.4 
Measures Taken to Minimize/Avoid Bias 
3.4.1 Masking/Blinding Procedures 
Study participants, the investigator, and study site personnel will remain blinded to all 
randomization assignments throughout the study. Sponsor’s MM and personnel, who are in 
regular contact with the study site and/or involved with documentation associated with the 
study will remain blinded to all participant randomization assignments. 
The following safeguards will be employed to reduce the risk of inadvertent unblinding: 
• Use of a standardized pre-filled syringe and injection volume for all injections. 
• All PXVX0317 and placebo syringes have a semi-transparent barrel cover to mask 
any difference in appearance between placebo and PXVX0317. 
• No sponsor personnel will have access to the randomization schedule. No site 
personnel will have access to treatment assignments. The Randomization and Trial 
Supply Management (RTSM) system allows for unblinding in an emergency (see 
Section 3.4.1.1). 

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• Assays will be run in a blinded manner. The assay titer results will not be delivered to 
the sponsor data management and analysis teams until after database lock, as they are 
potentially unblinding.  
• Should any participant or staff member become inadvertently unblinded, the 
investigator will promptly (within 24 hours of their awareness of the error) disclose 
the event to the sponsor’s MM in a blinded fashion (disclosing only participant 
number, not treatment) so that corrective action can be initiated. The unblinding 
sequence of events will be documented and retained as source documents. A protocol 
deviation will be entered in the eCRF. 
Members of the SMC may have access to unblinded data as defined in the SMC Charter for 
safety/other data review.   
Under certain circumstances (eg, safety reasons, required reporting to regulatory agencies), 
unblinding of IP for a particular participant will be allowed. This safety unblinding will be 
documented as a protocol deviation. Otherwise, unblinding of the study will only occur after 
the clinical database has been locked.  
Refer to the Pharmacy Manual for procedures in case of accidental unblinding of 
study-affiliated personnel.  
3.4.1.1 
Breaking the Blind for Individual Participants 
If the PI determines that knowledge of a participant’s treatment assignment is urgently 
needed to guide treatment or ensure the participant’s safety, the PI may perform emergency 
unblinding via the RTSM system. The PI must attempt to notify the sponsor MM prior to 
unblinding and must notify the sponsor MM within 24 hours after unblinding at the latest. 
If a participant’s study treatment assignment is unblinded for safety reasons, or if a 
participant becomes accidentally unblinded for any reason, the participant will be requested 
to remain in the study for safety follow-up.  
Documentation of breaking the blind must be entered in the study participants’ source 
documents with the following information recorded: (i) date and time the blind was broken; 
(ii) the rationale behind the unblinding decision/occurrence; (iii) the names of the personnel 
involved; and (iv) date of contact with the sponsor MM(s). The unblinding will be 
documented as a protocol deviation. 
3.4.2 Treatment Assignment/Randomization 
Participant eligibility will be confirmed and documented by the investigator immediately 
prior to randomization of each participant on Day 1. Study staff will indicate on a 
randomization eCRF within the EDC system that they want to generate a randomization 
number for the participant. When they agree to proceed, a randomization number will be 
generated from the EDC randomization module but hidden from study staff. The EDC 
randomization module will match the randomization number to an IP kit available at the site 

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and inform the study staff of the assigned kit. Study staff will use the appropriate kit for 
planned administration to the participant. 
Participants will be considered enrolled once a randomization number has been assigned 
within the EDC system. Participants will be stratified by age subgroups (65 to <75 years and 
≥75 years of age), with a target of 25% enrollment of participants ≥75 years of age. 
Participants will be randomized to PXVX0317 or placebo in a 1:1 ratio. 
The study will be conducted as a double-blind study through Day 183 End of Study Visit. 
Neither participants nor clinical site personnel, including the PI, nor the sponsor will know 
participants' individual treatment assignments until all participants have either prematurely 
discontinued or completed their participation in the study through the Day 183 End of Study 
Visit and the database has been cleaned and locked. 
3.5 
Description of Stopping Rules 
There are no specific predefined stopping rules for this study; however, an independent SMC 
will provide safety oversight. The SMC will review aggregated, blinded safety data after the 
first 50 participants have completed seven days of safety follow-up. The remaining 
participants will be enrolled following the safety review by the SMC and based on the 
sponsor’s consideration of the SMC’s recommendation. The need for any further reviews 
will be determined by the SMC. 
3.6 
Accountability Procedures 
The PI (or designee) is responsible for maintaining accurate inventory records of the IP and 
placebo. 
3.7 
Maintenance of Study Intervention Randomization 
Please see Section 3.4. 
3.8 
Data Directly Recorded on the Electronic Case Report Form 
Data recorded directly from the e-Diary will be considered source data. 
3.9 
End of Study 
A participant is considered to have completed this study if he/she has been dosed with IP and 
completed the final planned study visit at Day 183. Participants who do not complete the Day 
183 visit are considered to have been withdrawn from the study. For participants that 
terminate early, efforts should be made to conduct an EDV. 
The End of Study Date is defined as the date of the participant’s last study visit on Day 183 
or EDV. 

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3.9.1 Terminating the Study 
The sponsor reserves the right to stop or terminate the study at any time for clinical or 
administrative reasons.  
Any decision to voluntarily suspend or terminate a clinical study will be carefully reviewed 
and fully justified. The sponsor will notify the applicable regulatory authority of any 
suspension or termination, along with justification for terminating the study. 
The sponsor will notify the investigators, FDA, and central institutional review board (IRB) 
of study’s completion or early termination. The investigators will notify local IRBs in writing 
of the study’s completion or early termination. The sponsor must receive a copy of the 
notification letter from the IRB indicating receipt of the completion or early termination 
letter. 
3.9.2 Terminating the Study at an Individual Investigational Site 
An investigational site may be terminated from the study at the discretion of the sponsor or 
IRB for reasons such as noncompliance, lack of recruitment, fraud or blacklisting by the 
regulatory authorities, relocation of the investigator, etc.  
The sponsor may decide to replace a terminated investigational site.  
4 
SELECTION AND WITHDRAWAL OF PARTICIPANTS 
4.1 
Inclusion Criteria 
Participants must meet all the following criteria to be enrolled: 
1. 
Able and willing to provide informed consent voluntarily signed by participant. Must 
verbalize understanding of the general procedures of, and reason for the study.  
2. 
Males or females, ≥65 years of age. 
3. 
Able to complete all scheduled visits and comply with all study procedures. 
4. 
Women who are not of CBP: surgically sterile (at least six weeks post bilateral tubal 
ligation, bilateral oophorectomy or hysterectomy); or postmenopausal (defined as a 
history of ≥12 consecutive months without menses prior to randomization in the 
absence of other pathologic or physiologic causes, following cessation of exogenous 
post menopausal sex-hormonal treatment).  
5. 
Participants must be in stable health in the opinion of the investigator for at least 30 
days prior to screening (eg, no hospital admission for acute illness in the last 30 days 
prior to screening). 
4.2 
Exclusion Criteria 
Participants who meet any of the following criteria cannot be enrolled: 

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1. 
Participation or planned participation in an investigational clinical trial (eg, vaccine, 
drug, medical device, or medical procedure) within 30 days of Day 1 and for the 
duration of the study. Note: Participation in an observational trial or follow-up phase 
of a trial may be allowed; however, these instances should be discussed with the 
sponsor’s MM prior to enrollment. 
2. 
Prior receipt of any CHIKV vaccine. 
3. 
Positive laboratory evidence of current infection with HIV, HCV, or HBV.  
4. 
Body Mass Index ≥35 kg/m2. 
5. 
History of any known or suspected allergy or history of anaphylaxis to any 
component of the IP. 
6. 
History of any known congenital or acquired immunodeficiency or 
immunosuppressive condition that could impact response to vaccination (eg, 
leukemia, lymphoma, malignancy, functional or anatomic asplenia, alcoholic 
cirrhosis). Note: History of basal cell and squamous cell carcinoma of the skin or 
carcinoma in situ of the cervix considered cured would not be exclusionary. History 
of a malignancy considered cured from over five years from the date of screening 
with minimal risk of recurrence is not exclusionary. 
7. 
Prior or anticipated use of systemic immunomodulatory or immunosuppressive 
medications from six months prior to screening through Day 22. Note: For systemic 
corticosteroid use at a dose or equivalent dose of 20 mg of prednisone daily for 14 
days or more within 90 days of screening through Day 22 is exclusionary. The use of 
inhaled, intranasal, topical, or ocular steroids is allowed. 
8. 
Bleeding disorder or receipt of anticoagulants in the 21 days prior to screening, 
contraindicating IM vaccination, as judged by the investigator. 
9. 
Moderate or severe acute illness with or without fever (oral temperature ≥100.4°F 
[≥38.0°C]).  
10. Receipt or anticipated receipt of immunoglobulin from 180 days prior to screening 
through Day 22. 
11. Medical condition (such as dementia) that, in the opinion of the investigator, could 
adversely impact the participant’s participation in or conduct of the study. 
12. Evidence of substance abuse that, in the opinion of the investigator, could adversely 
impact the participant’s participation in or conduct of the study. 
13. Identified as an investigator or employee of an investigator or study center with direct 
involvement in the proposed study, or identified as an immediate family member (ie, 
parent, spouse) of the investigator or employee with direct involvement in the 
proposed study. 

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14. Receipt or anticipated receipt of any vaccine from 30 days prior to Day 1 through 
Day 22. 
15. Receipt or anticipated receipt of blood or blood-derived products from 90 days prior 
to screening through Day 22. 
16. Any planned elective surgery that may interfere with study participation or conduct. 
17. Any other medical condition that, in the opinion of the investigator, could adversely 
impact the participant’s participation in or conduct of the study. 
Reasons for Delay of Study Vaccination: 
i. 
Any fever (oral temperature ≥100.4°F [≥38.0°C]) within 24 hours of planned study 
vaccination.  
ii. 
Any condition that may interfere with assessment of reactogenicity and/or other 
safety assessments. 
iii. 
Signs and/or symptoms of an acute infectious illness. 
iv. 
Participants should not be randomized if they have tested positive for COVID-19 
(using any type of test, even if asymptomatic) for 14 days or until negative molecular 
test result eg, PCR. 
If any one of these occur at the time of the scheduled study vaccination, randomization is 
permitted later, if within the screening window (30 days), at the discretion of the investigator 
and after consultation with the MM. If randomization and vaccination cannot occur within 
the allowed screening window, rescreening will be required. 
4.3 
Participant Withdrawal Criteria 
The participants must be available, without coercion, for all parts of the study. If continued 
participation jeopardizes the participant’s health, the participant should be withdrawn from 
the study. The investigator is encouraged to consult the sponsor prior to the withdrawal of 
any participant, except in the event of a medical emergency. The reason for withdrawal of 
any participant must be clearly documented on the study source documents and the 
appropriate eCRF. 
All participants have the right to withdraw at any time during the study without prejudice. 
4.3.1 Withdrawal of Consent 
All participants are free to withdraw from participation in this study at any time, for any 
reason, specified or unspecified, and without penalty or loss of benefits to which the 
participant is otherwise entitled. The investigator will ask (but cannot require) such 
participants to provide the reason(s) for withdrawal of consent.  
For information on safety follow-up for withdrawn participants see Section 4.3.3. 

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4.3.2 Investigator-based Participant Withdrawal 
The investigator may withdraw a participant from further participation in the study, at their 
discretion, if medically necessary or for reasons of noncompliance. The reason for 
withdrawal of any participant must be clearly documented on the study source documents 
and the appropriate eCRF. The investigator is encouraged to consult the sponsor prior to the 
withdrawal of any participant, except in the event of a medical emergency.  
The investigator (and/or sponsor) may withdraw a participant from the study for any of, but 
not limited to, the following reasons: 
• Noncompliance with the protocol. If the participant is noncompliant with protocol 
requirement, the issue should be discussed with the participant and, if not resolved, 
consideration given to withdrawing the participant. 
• Lost to follow-up (LTF); requires documentation of at least three unsuccessful 
attempts to contact participants, one of which must be a registered letter. Lost to 
follow-up will be determined after the date of the participant’s projected last visit. 
Study disposition date will be the last date of contact with the participant prior to 
LTF. 
• Other reason(s) which, in the opinion of the investigator, indicates that continued 
participation in the study is not in the best interest of the participant.  
Safety follow-up for AEs should occur for all participants. For information on safety 
follow-up for withdrawn participants see Section 4.3.3. 
Reasons for withdrawal of individual participants from the study prior to the final protocol 
required visit and/or final safety follow-up are to be recorded on the eCRF and participant 
source documents. 
4.3.3 Follow-up for Withdrawn Participants 
Outreach will be made to ensure that participants who are withdrawn, or who withdraw from 
the study, during the active observation or follow-up period will complete all safety and 
available assessments for the EDV as outlined in this protocol. The investigator should 
inform the participant that these assessments are for their own well-being and, if possible, for 
study purposes. The participant must first agree to the collection of early withdrawal and 
safety assessments prior to the assessments, and this agreement must be documented in the 
source documents. Additional information regarding ongoing AEs may be provided as a 
follow-up report. 
4.3.4 Participant Replacement   
Participants withdrawn from the study or who withdraw consent prior to or after dosing will 
not be replaced. Data from participants withdrawn from the study or who withdraw consent 
after dosing will be kept in the exposed population (all enrolled participants who received 
IP). 

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4.3.5 Documentation of Withdrawal 
Reasons for withdrawal of individual participants from the study prior to final protocol 
required visit and/or safety follow-up are to be recorded on the eCRF. The reason for 
withdrawal from the study will be recorded as one of the following: 
• Lost to follow-up (Note: requires documentation of at least three unsuccessful 
attempts to contact participants, LTF will be determined after the date of the 
participant’s projected last visit) 
• Adverse event 
• Death 
• Physician (ie, investigator) decision 
• Other 
Safety follow-up for AEs should occur for all participants, for information on safety 
follow-up for withdrawn participants see Section 4.3.3. 
5 
STUDY INTERVENTION 
5.1 
Investigational Products 
5.1.1 PXVX0317 Vaccine 
The PXVX0317 vaccine is comprised of CHIKV VLP adsorbed on aluminum hydroxide 
adjuvant 2%, and formulation buffer supplied as a single dose in a pre-filled glass syringe. 
Chikungunya virus VLP refers to the virus-like particle component of PXVX0317 produced 
by transient transfection of human embryonic kidney (HEK293) cells with a DNA expression 
plasmid encoding C and E (E3, E2, 6K, and E1) proteins. After expression of the 
plasmid-encoded proteins, VLPs self-assemble and are released into the cell culture medium 
as ~70 nm particles. The 6K and E3 proteins have not been specifically detected in the VLPs. 
No replication-capable viral genetic material is incorporated into the VLPs. Virus-like 
particles are then concentrated from the cell supernatant purified, and buffer exchanged. The 
VLPs are then formulated with excipients and aluminum hydroxide adjuvant, mixed, and 
filled into 1 mL glass syringes with a 0.85 mL fill volume to allow for 0.8 mL of deliverable 
volume. The glass syringe is sealed with a rubber closure and plastic cap. The rubber closure 
does not contain natural latex.  
See the Pharmacy Manual and the IB for additional information, including composition of 
PXVX0317 vaccine.  
5.1.2 Placebo Pre-filled Syringe 
The placebo is a sterile aqueous solution with the same excipient composition as the drug 
product without CHIKV VLP and aluminum hydroxide adjuvant. The placebo is filled into 

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1 mL glass syringes with a 0.85 mL fill volume to allow for 0.8 mL of deliverable volume. 
The placebo is stored at 2.0 to 8.0°C. The glass syringe is sealed with a rubber closure and 
plastic cap. The rubber closure does not contain natural latex. 
See the Pharmacy Manual for additional information, including composition of the placebo.  
5.1.3 Packaging and Labeling 
Investigational product (PXVX0317 and placebo) will be shipped in kits containing labelled 
pre-filled syringes. Kits and syringes will be labelled with the following information: 
• “Caution: New Drug – Limited by Federal Law to Investigational Use Only” 
• Investigational product name – PXVX0317 or placebo (to maintain the blind both 
names will be included) 
• Dose volume and container – single dose of 0.8 mL in pre-filled single-dose syringe 
• Route of administration – IM 
• Randomization kit number (in lieu of lot numbers and manufacture date and/or expiry 
date to maintain the blind) 
• Protocol number – EBSI-CV-317-005 
• Recommended storage temperature/conditions – stored refrigerated at 2.0 to 8.0°C 
• Sponsor – Emergent Travel Health Inc. 
5.1.4 Storage Conditions 
Investigational product syringes must be stored at 2.0 to 8.0°C in a secured area until ready 
for use. The temperature in the storage area must be monitored by checking and recording 
current, maximum/minimum temperature readings inside the vaccine storage unit once daily. 
Any excursions must be promptly reported to the sponsor; product should be quarantined by 
the site and may be released for use by the sponsor only after investigation and confirmation 
of continued stability. Accountability will be maintained in accordance with GCP to include 
dates on which IP kit was received, administered to participants, returned to the sponsor, or 
destroyed at the site. The study monitors will periodically check supplies held at the clinical 
sites to verify accountability. Templates for accountability records are included in the 
Pharmacy Manual. 
The investigator will only approve administration of the IP to participants enrolled in this 
study according to the procedures described in this protocol. At the end of the study all 
unused IP and containers will either be destroyed on site with appropriate documentation or 
returned to the sponsor. 

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5.1.5 Preparation 
Investigational product (PXVX0317 vaccine and placebo) will be supplied as a single dose of 
0.8 mL in a pre-filled single-dose syringe shipped in kits.  
5.1.6 Investigational Product Preparation 
On Day 1 before IP administration, the interim medical history (ie, from Screening Visit to 
Day 1) will be reviewed and updated in the participant file, a targeted physical exam may be 
performed, and blood samples will be collected. Immediately prior to IP administration, staff 
will verify that the participant is still eligible and randomize the participant in the EDC 
(Section 3.4.2). Once these procedures are performed and if the participant is still eligible, IP 
will be administered. 
All doses of IP are 0.8 mL in volume and are administered by IM injection in the deltoid 
muscle with a 1 mL syringe and 25 gauge 1” (or 1.5”, at the investigator’s discretion) needle 
using universal precautions and sterile technique; see Table 2 for more details. 
Investigational product is to be administered only under the direct supervision of the PI or a 
qualified subinvestigator identified on the FDA Form 1572. The injection will be 
administered into the deltoid muscle by a staff member delegated by the investigator. Right 
or left deltoid muscle may be used at the discretion of the administering staff member with 
consideration for participant preference and features that may obscure interpretation of any 
local AEs such as tattoos, scars, or other lesions. 
For further details see the Pharmacy Manual. 
The investigator is responsible for maintaining accurate inventory records of IP (PXVX0317 
or placebo). The investigator or designee will inventory all IP kit shipments upon receipt, 
acknowledge possession by signing all required documentation, and returning these to the 
sponsor. The investigator must ensure that all drug supplies are kept in a secure location in 
the site pharmacy in accordance with recommended storage conditions. Inventory and 
ongoing record of test material supplies using the Drug Accountability Form provided within 
the Clinical Trial Material Tracking Module of the sponsor’s RTSM system. This inventory 
record for the IP will include: 
• Protocol name, number, and sponsor 
• Kit number 
• Study site and investigator name 
• Use-by/Expiry/Retest date 
• Name and title of qualified individual administering IP. 
These records will be reviewed by representatives of the sponsor and may be reviewed by 
regulatory agencies. 

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5.1.6.1 
Investigational Product Resupply 
Investigational product will be automatically resupplied via the sponsor’s RTSM system. 
5.1.6.2 
Used or Partially Used Investigational Product 
Remaining unused IP kits will either be returned to sponsor or destroyed according to written 
investigational site procedures with a record of disposition maintained, per sponsor 
instructions. 
5.2 
Prior and Concomitant Medications 
At the Screening Visit, the details of prior and concomitant medications taken within 30 days 
of the Screening Visit (or within 90 days for blood products, or within six months for 
immunosuppressive/immunomodulatory medications) will be collected. Concomitant 
medications will be collected at each onsite study visit or by phone interview (or EDV) for 
all groups. The details of all concomitant medications including those associated with 
solicited AEs and unsolicited AEs through Day 29 will be collected. Concomitant 
medications associated with SAEs, MAAEs, and/or AESI will be collected through the end 
of the study. 
5.2.1 Prohibited and/or Restricted Medications 
The history of all prohibited medications used at any time during study participation 
(regardless of association with an AE) will be collected. The sponsor MM should be 
consulted for any questions about prohibited or restricted medication usage. 
Participants must not have received or be planning to receive: 
• Systemic immunomodulatory or immunosuppressive medications from six months prior 
to screening through Day 22.   
• Systemic corticosteroid use at a dose or equivalent dose of 20 mg of prednisone or more 
daily for 14 days or more within 90 days of screening through Day 22. The use of 
inhaled, intranasal, topical, or ocular, is allowed. 
• Any vaccine from 30 days prior to Day 1 through Day 22. 
• Blood or blood-derived products from 90 days prior to screening through Day 22. 
• Receipt or anticipated receipt of immunoglobulin from 180 days prior to screening 
through Day 22. 
• Investigational agents from 30 days prior to Day 1 through the duration of study 
participation. 
Medically required concomitant medications should be used for the treatment of AEs 
regardless of whether their use will need to be documented as a protocol deviation (Section 
10.7). 

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5.3 
Procedures for Monitoring Participant Compliance 
All participants will be administered the IP by qualified site study staff. Compliance with the 
study protocol and procedures will be monitored on an ongoing basis by study staff.  
6 
STUDY PROCEDURES AND ASSESSMENTS PER VISIT 
6.1 
Screening (Visit 1, within 30 days of Day 1) 
Within 30 days prior to Day 1 of IP administration, eligible participants will first undergo 
informed consent counseling. Once written informed consent has been obtained, participants 
will undergo a screening visit to ascertain their eligibility in this study. The screening visit 
assessments will include: 
• Informed consent (Section 12.1). 
• Review of eligibility criteria (Section 3.2.1). 
• Medical history including demographics (Section 3.2.2). 
• Prior and current medications (Section 5.2).  
• Vital signs: blood pressure, heart rate, respiratory rate, and temperature (Section 3.2.4). 
• Complete physical examination including height and weight (general appearance, eyes-
ears-nose-throat, head-neck, lungs-chest, heart, abdomen, musculoskeletal, lymph nodes, 
skin, extremities, and neurological assessment) (Section 3.2.3). 
• Blood collection for laboratory testing for HIV, HBV, and HCV (Section 3.2.5). 
Each participant who signs the ICF will receive a sequential identification (ID) number 
unique to the site number and the participant. When screening information is entered into the 
EDC system a participant will be assigned a participant ID number with the following 
format: 4-digit site number and 4-digit ID number, eg, 1111-1111. Participant numbers will 
be sequential since screen failed participants will be entered into the EDC system. Each site 
will maintain a screening enrollment log to record the enrollment or the reason(s) for screen 
failure for all participants who receive a participant ID number. Reason for screen failure will 
also be captured in the EDC disposition eCRF. Screening procedures are listed in the 
schedule of events (Table 1). 
6.2 
Rescreening 
Rescreening may occur given the following circumstances: 
• If the participant has an acute febrile illness at the time of their scheduled enrollment, 
they may be rescreened 14 days after resolution of their acute illness. 
• If the participant tests positive for COVID-19 (using any type of test, even if 
asymptomatic) the participant can be rescreened after 14 days or after a negative 

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molecular test, eg, PCR, if outside of the initial screening window (within 30 days of 
Day 1). 
• Participants who have received vaccines within 30 days of Day 1 may be rescreened 
provided no additional doses are anticipated up to Day 22. 
• Participants who have received blood products or IP from participation in another 
clinical study that has ended may be rescreened after the appropriate duration has 
passed (90 days for blood products; 30 days for IP; six months prior to screening for 
systemic immunomodulatory or immunosuppressive medications). 
• Eligible participants who are not able to be vaccinated within 30 days of their 
screening period may be rescreened. 
Any other request for rescreening should be discussed with the sponsor MM. 
Rescreening will involve undergoing all screening procedures again, including reconsenting 
and use of the same participant ID number. Participants may be rescreened one time only. 
Rescreening is not otherwise permitted.   
6.3 
Baseline, Randomization, and IP Administration (Visit 2, Day 1)  
The following will take place during the visit and prior to IP administration: 
• Reverification of eligibility criteria 
• Review medical history 
• Review prior and concomitant medications 
• Vital signs 
• Targeted physical examination (as needed) 
• Blood collection for anti-CHIKV SNA and CHIKV antibodies to neutralize strains 
representing all CHIKV genotypes (Section 3.2.6) 
• Randomization (Section 3.4.2) 
• Confirm and review any AEs that may have occurred after ICF signing 
• Diary or memory aid (electronic or paper) training, ruler and thermometer distribution 
and training (Section 3.2.9) 
• IP administration (Section 3.2.7) 
The following will take place during the visit and after IP administration: 
• In-clinic acute observation (Section 3.2.8) 
• Vital signs (Section 3.2.4) 
• Solicited AEs, unsolicited AEs, MAAEs, SAEs and AESI evaluation (Sections 3.2.9, 
3.2.10, 3.2.11) 

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6.4 
Scheduled Study Visits 
Visit 3, Day 15 (-1/+3 days): 
• Review diary or memory aid (electronic or paper) 
• PI assessment of reactogenicity (Sections 8.1.8, 8.1.9) 
• Solicited AEs, unsolicited AEs, MAAEs, SAEs, and AESI evaluation (Sections 3.2.9, 
3.2.10, 3.2.11) 
• Review concomitant medications 
• Targeted physical examination (as needed) 
• Blood collection for anti-CHIKV SNA 
Visit 4, Day 22 (-1/+3 days) 
• Unsolicited AEs, MAAEs, SAEs, and AESI evaluation 
• Review concomitant medications 
• Targeted physical examination (as needed) 
• Blood collection for anti-CHIKV SNA and CHIKV antibodies to neutralize strains 
representing all CHIKV genotypes 
Visit 5, Day 29 (±1 day) (Telephone Contact) 
• Unsolicited AEs, MAAEs, SAEs, and AESI evaluation 
• Review concomitant medications 
Visit 6, Day 92 (±3 days) (Telephone Contact) 
• MAAEs, SAEs, and AESI evaluation 
• Review concomitant medications (only if associated with MAAEs/SAEs/AESI) 
6.5 
Unscheduled Visits 
Any study procedure, excluding study vaccination, may be conducted at an unscheduled visit 
as needed and recorded on the unscheduled visit eCRF. Examples include repeat specimen 
collection and additional safety follow-up for an AE. 
6.6 
End of Study Visit (Visit 7, Day 183 [-14/+7 days]) 
• MAAEs, SAEs, and AESI evaluation 
• Review concomitant medications (only if associated with MAAEs/SAEs/AESI) 
• Targeted physical examination (as needed) 
• Blood collection for anti-CHIKV SNA and CHIKV antibodies to neutralize strains 
representing all CHIKV genotypes 

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6.7 
Early Discontinuation Visit 
For EDV occurring within seven days postvaccination, from seven to 21 days 
postvaccination, or ≥22 days postvaccination, the Visit 3, Visit 4, or Visit 7 schedule will be 
followed, respectively.  
7 
ASSESSMENT OF IMMUNOGENICITY  
7.1 
Anti-CHIKV SNA Analysis 
The immune response to PXVX0317 will be measured by anti-CHIKV SNA analysis, for 
which serum samples will be collected on Day 1 predose, Day 15, Day 22, and Day 183 End 
of Study Visit (or at EDV). 
The immunogenicity analysis will be performed using the validated human SNA assay, a 
high-throughput in vitro infectivity assay developed by the sponsor for assessing titers of 
neutralizing antibodies against CHIKV in serum samples. The induction of the humoral 
immune response (immunogenicity) by PXVX0317 vaccine, specifically anti-CHIKV SNA 
levels, will be measured by a bioluminescence assay that uses a modified version of CHIKV 
containing a reporter gene that expresses a luciferase protein (CHIKV-luc) in infected Vero 
cells in vitro. Reduction of luciferase activity (ie, reduced bioluminescence) occurs in 
infected cultures of cells following treatment of CHIKV-luc with test serum containing 
anti-CHIKV SNA. The quantitation of reporter gene expression, a correlate of the level of 
virus infection of cells, is determined by detection of luciferase using a micro-plate 
luminometer. The anti-CHIKV SNA titer 80 (NT80) is the reciprocal of the serum dilution 
that provides 80% protection of Vero cells from CHIKV-luc infection, or an 80% reduction 
of luciferase activity compared to virus only control.  
7.2 
Cross-reactive Neutralizing Antibodies to Various CHIKV Genotypes 
Cross-reactive neutralizing antibodies to various CHIKV genotypes will be measured using 
FRNT50, as an exploratory objective. Foci from infected cells are enumerated following 
exposure to mixtures of virus and immune serum. The foci are identified by examining 
stained cells with antiviral antibodies and detected with a colorimetric substrate to horse 
radish peroxidase. Reduction of stained foci are quantitated using a plate reader and 
neutralizing data analyzed using GraphPad prism analysis software. Anti-CHIKV 
neutralization antibody titer is the reciprocal of the antibody dilution that protects a 
percentage of cells from infection compared to virus only control. 

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8 
SAFETY ASSESSMENTS AND REPORTING 
8.1 
Definitions 
8.1.1 Adverse Event 
An AE is any untoward medical occurrence in a patient or clinical investigation participant 
administered a medicinal product and that does not necessarily have a causal relationship 
with this treatment. An AE can therefore be any unfavorable and unintended sign (including 
an abnormal laboratory finding), symptom, or disease temporally associated with the use of a 
medicinal (investigational) product, whether or not considered related to the medicinal 
(investigational) product. 
Notes:  
• A diagnosis should be captured as an AE term and signs and symptoms should be 
captured only in the absence of a unifying diagnosis. If a diagnosis is ultimately 
made, it should replace the previous report based on signs and symptoms.  
• In the event that there are multiple diagnoses, then all diagnoses should be captured.  
• The worsening of an existing sign, symptom or disease is also considered to be an 
AE.  
• An abnormal laboratory finding deemed by the PI (or designee) as not clinically 
significant will not be captured as an AE, but an abnormal laboratory finding that 
worsens after dosing with the IP, from not clinically significant to clinically 
significant, is considered an AE.  
• Surgical procedures are not AEs. They are the action taken to treat a medical 
condition. The medical condition that was treated with surgery may be the AE 
depending on whether it occurred prior to IP treatment. Interventions that were 
planned prior to study entry for medical conditions that started prior to study entry 
but did not worsen during the clinical study are not reported as AEs. 
• Medically attended adverse events: medically attended visits include hospital, ER, 
urgent care clinic, or other visits to or from medical personnel for any reason. 
Routine scheduled study visits will not be considered medically attended visits. 
8.1.2 Serious Adverse Event 
An SAE is any untoward medical occurrence that: results in death, is life threatening, 
requires inpatient hospitalization or prolongation of existing hospitalization, results in 
persistent or significant disability/incapacity or substantial disruption of the ability to conduct 
normal life functions, or is a congenital anomaly/birth defect. 
Important medical events which may not result in death, be life threatening, or require 
hospitalization may be considered an SAE when, based upon appropriate medical judgment, 

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they may jeopardize the patient or participant and may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition. 
Notes:  
• Death is an outcome and not an event. The condition leading to death is the event. If 
no other information regarding the cause of death is available, the event will be 
considered “Unspecified Adverse Event”/Death not otherwise specified (Death NOS).  
• Overnight stays at hospital/clinic that occurs during a trial for social reasons (eg, 
transportation difficulties, respite care) is not considered to be a hospitalization 
event. 
8.1.3 Adverse Drug Reaction 
A response to a medicinal product which is noxious and unintended. Response in this context 
means that a causal relationship between a medicinal product and an AE is at least a 
reasonable possibility.   
8.1.4 Suspected Unexpected Serious Adverse Reaction 
Suspected Unexpected Serious Adverse Reaction (SUSAR) is a serious, unexpected AE that 
is suspected of being related to the IP and occurring during the clinical study.   
8.1.5 Adverse Events of Special Interest 
An AESI is a noteworthy event for the particular product or class of products that a sponsor 
may wish to monitor carefully. It could be serious or nonserious and could include events 
that might be potential precursors or prodromes for more serious medical conditions in 
susceptible individuals. 
In this study, new onset or worsening arthralgia that is medically attended will be included as 
an AESI. The occurrence of new onset or worsening arthralgia that is medically attended will 
be monitored throughout the study for all participants. Medically attended visits include 
hospital, ER, urgent care clinic, or other visits to or from medical personnel. Routine 
scheduled study visits will not be considered medically attended visits. 
8.1.6 Solicited Adverse Event   
A solicited AE is a protocol-specified AE about which the investigator (or designee) 
proactively asks the participants during a protocol-specified time period. Solicited AEs to be 
assessed for this study are local injection site events of pain, redness, and swelling at the 
injection site and systemic events of fever with oral temperature ≥38.0°C (≥100.4°F; if more 
than one temperature reading is taken, the highest reading obtained each day should be 
recorded), fatigue, chills, headache, myalgia, arthralgia, and nausea. 

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Solicited AEs will be recorded by the participants using a diary (electronic or paper) for 
seven days postvaccination.    
8.1.7 Unsolicited Adverse Event 
An unsolicited AE is an AE that is spontaneously reported by the participant or discovered 
by the PI. 
8.1.8 Severity of Adverse Events 
The investigator will grade all AEs for severity. For the study Grading Scale see Appendix I.  
Adverse events not listed in the Grading Scale will be graded as follows: 
• 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) – as determined at ER visit or 
hospitalization 
• For solicited AEs, the severity of redness and swelling recorded as diameters (mm) will 
be summarized according to categories based on the largest diameter linear measurement 
when the local reaction is present. 
• Events reported as not present (0 mm is entered) will be reported as Grade 0. 
8.1.9 Causality of Adverse Events  
The investigator is responsible for the assessment of the causality of an AE and the sponsor’s 
MM will also assess SAE causality, independent of the PI. 
The following guidelines are provided for this assessment: 
• Unrelated: No relationship between the IP and the reported event. The event will be 
considered “not related” to the IP. 
• Possibly related: The event follows a reasonable temporal sequence from the time of 
administration of IP and/or follows a known response pattern to the IP but could also 
have been produced by other factors. 
• Probably related: A reasonable temporal sequence of the event with administration of IP 
exists and based on the known response to the IP, known or previously reported adverse 
reactions to the IP or similar products, or in the PI’s (or designee) clinical judgment the 
association of the event with the IP seems likely. 
• Definitely related: A clinical event, including laboratory test abnormality, occurring in a 
plausible time relationship to IP administration, and which cannot be explained by 
concurrent disease or other drugs or chemicals.  

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If the relationship between the AE and the IP is determined to be “possible” “probable,” or 
“definitely”, the event will be considered to be “related” to the IP. 
8.2 
Methods and Timing for Assessing, Recording, and Analyzing Safety 
Parameters 
For reporting of solicited AEs, unsolicited AEs, SAEs/AESI/MAAEs please see Sections 
8.1.1, 8.1.5 – 8.1.7. 
Figure 3 
Adverse Event Period of Reporting  
 
Occurrence of SAEs will be monitored throughout the study and will cover all participating 
individuals. Study participants will be provided with a 24-hour telephone number to contact 
study personnel in case of an untoward reaction. 
8.2.1 Safety Laboratory Tests 
Not applicable. 
8.2.1.1 
Drug Screen 
Not applicable. 
8.2.1.2 
Alcohol Screen 
Not applicable. 
8.2.1.3 
Viral Testing 
At the Screening Visit, blood samples will be collected for serum testing for HBsAg, HCV 
antibody, and HIV-1/HIV-2 antigen/antibodies. If HCV antibody is positive HCV RNA 
testing can be performed. 

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8.3 
Reporting Requirements for Immediately Reportable Events 
8.3.1 Principal Investigator’s Reporting Requirements 
The following events must be reported within 24 hours of awareness by the PI (or designee) 
to the sponsor:  
• Any SAE regardless of causal association with the IP.  
• Any AESI regardless of causal association with the IP. 
Applicable events must be entered into the validated EDC system. In the event of a system 
failure, the appropriate forms (listed below) will be completed and sent by email to the 
following address: 
Global Pharmacovigilance Department 
Emergent BioSolutions Inc. 
 
The paper reported SAEs and AESI should be entered in EDC once the system is available. 
For SAEs/AESIs, the Serious Adverse Event/Adverse Event of Special Interest Report Form 
will be completed (abbreviated hereafter SAE/AESI Report Form). The SAE/AESI Report 
Form is NOT the same as the AE eCRF. Participant identifiers (eg, name, address, telephone 
number, social security number, medical record number, or hospital/laboratory number) must 
be redacted from the source documentation.  
All SAEs that are unexpected (eg, adverse drug reactions) must be reported to the IRB by the 
PI (or designee) as required by ICH GCP E6(R2). 
The PI is responsible to notify their IRB according to their policy. 
8.3.2 Sponsor’s Reporting Requirements 
As specified in 21 CFR 312.32, SUSARs will be reported by the sponsor of the IP to the 
FDA and to all participating investigators in an individual case safety report as soon as 
possible, no later than 15 calendar days after the sponsor becomes aware of the suspected 
adverse reaction (21 CFR 312.32(c)(1)). In addition, any unexpected fatal or life-threatening 
suspected adverse reaction will be reported to the FDA no later than seven days after the 
sponsor’s initial receipt of the information in accordance with 21 CFR 312.32(c)(2). All 
SAEs that are unexpected (e.g., adverse drug reactions) must be reported to the IRB as 
required by ICH GCP E6(R2).  

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8.4 
Follow-up of Adverse Events 
All AEs, MAAEs, SAEs, and AESI will be followed until resolution, stabilization, or up to 
30 days after the last study visit. 
8.4.1 Follow-up of Nonserious Adverse Events 
Nonserious AEs that are identified from the time IP administration through the 28-day 
post-IP administration period and are still ongoing on the last scheduled visit must be 
recorded on the AE eCRF with the current status noted. All nonserious events that are 
ongoing at this time will be recorded as “Not Recovered/Not Resolved” on the AE eCRF. 
The status of ongoing, previously reported AEs will be subject to active follow-up. 
8.4.2 Follow-up of Serious Adverse Events or Adverse Events of Special Interest 
This study requires that participants be monitored for SAE/AESI up to Day 183 End of Study 
Visit.  
The PI will provide or arrange appropriate care for participants for whom SAEs or a potential 
AESI are experienced. Withdrawal of participants from the study to treat SAEs/AESI is at 
the discretion of the treating PI. See Section 4.3 Participant Withdrawal Criteria. 
All SAEs/AESI will be followed by the PI until at least one of the following conditions is 
met:  
• The SAE/AESI is resolved or stable if expected to remain chronic. 
• The participant is referred to a specialist or other physician for treatment and follow-up. 
The PI (or designee) will follow the participant’s condition even if the participant is seen 
by another physician, to obtain information about the diagnosis and outcome and any 
treatments and medications administered for the event. 
The following will be considered acceptable reasons for discontinuation of follow-up of 
ongoing SAEs/AESI: 
• Participant withdraws consent 
• Participant is referred to appropriate long-term medical care 
• Participant is considered LTF 
It is expected that the investigational site will obtain supporting medical records from 
appropriate physicians and record this information on the SAE/AESI Report Form and AE 
eCRF. Additional information received related to any SAE/AESI must be forwarded within 
24 hours of awareness to the Emergent Global Pharmacovigilance Department. 
8.4.3 Follow-up of Pregnancies 
Not applicable, as study population is ≥65 years of age. 

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8.4.4 Unanticipated Problems  
For investigational sites in the US, as outlined by the Office for Human Research Protection, 
unanticipated problems must be reported to the IRB according to the requirements of 45 CFR 
Part 46. Unanticipated problems are considered to include any incident, experience, or 
outcome that meets ALL the following criteria: 
• Unexpected (in terms of nature, severity, or frequency) given: 
• Procedures that are described in the study-related documents, such as the IRB 
approved research protocol and informed consent document. 
• The characteristics of the participant population being entered into the study. 
• Related or possibly related to participation in the study which means there is a reasonable 
possibility that the incident, experience, or outcome may have been caused by the sample 
collection. 
• Suggests that the study places participants or others at a greater risk of harm (including 
physical, psychological, economic, or social harm) than was previously known or 
recognized. 
An incidence, experience, or outcome that meets the three criteria above generally will 
warrant consideration of substantive changes in the study or informed consent 
process/document or other corrective actions in order to protect the safety, welfare, or rights 
of participants or others.  
The PI should promptly notify the IRB when an unanticipated problem involving risks to 
participants or others is identified. Also, the PI should notify the sponsor of unanticipated 
problem(s). 
8.5 
Safety Data Monitoring 
An independent SMC will provide safety oversight. The SMC will review aggregated, 
blinded safety data after the first 50 participants have completed at least seven days of safety 
follow-up. The remaining participants will be enrolled following the safety review by the 
SMC and based on the sponsor’s consideration of the SMC’s recommendation. Any further 
safety reviews will be at the discretion of the SMC and per the SMC Charter. 
9 
STATISTICAL CONSIDERATIONS 
This section is a summary of the planned statistical analyses. The details are described in the 
study Statistical Analysis Plan (SAP). 
9.1 
Sample Size Rationale 
Based on the data from the phase 2 study (protocol PXVX-CV-317-001), the seroresponse 
rate for PXVX0317 vaccine is expected to be approximately 
 vs <5% for the placebo 
participants. With an assumed 10% rate of nonevaluable participants, the power to show 

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superiority over placebo with 180 PXVX0317 vaccine and 180 placebo evaluable 
participants is >99.9% for the combined age groups.  
The difference in seroresponse rate between PXVX0317 and placebo groups that is 
considered clinically relevant is 
. With 180 baseline seronegative PXVX0317-treated 
participants and a target seroresponse rate of 
 vs a rate of 5% for placebo, the width of a 
two-sided 95% CI would be ±5.4%. If the target PXVX0317 seroresponse is 
, the width 
would be ±6.9%. Therefore, the difference in seroresponse rates must be above 
 for the 
lower bound of the 95% CI for the difference to be 
. 
9.2 
Analysis Populations 
Analysis will be based on the following study populations: 
Enrolled Population: All screened participants who sign an ICF, are entered in the EDC 
database, and meet all eligibility criteria. 
Randomized Population: All screened participants who provide informed consent and 
provide demographic and other screening measurements and are randomized in the EDC. 
Exposed Population: All participants in the randomized population who receive IP. 
Safety Population: All participants in the exposed population who provide safety 
assessment data. Safety endpoints will utilize the safety population, analyzed as treated. 
Modified Intent-to-Treat population: All randomized participants who are vaccinated and 
have at least one postinjection anti-CHIKV SNA titer result, analyzed as randomized. 
Immunogenicity Evaluable Population: All participants in the mITT population who: i) 
provide evaluable serum sample results for the Day 22 time point within the required time 
frame of Day 19 through Day 27, inclusive, ii) have no measurable anti-CHIKV SNA at Day 
1, iii) have no important protocol deviation or other reason to be excluded as defined prior to 
unblinding. The IEP is the primary population for all immunogenicity analyses. 
9.3 
Statistical Methods 
Tables will be displayed by treatment group (PXVX0317 and placebo) columns for the 
analysis populations described in Section 9.6. 
Continuous endpoints will be summarized by descriptive statistics including number of 
nonmissing observations (n), mean, standard deviation, median, minimum, and maximum. In 
the analysis of the human SNA assay data as a continuous variable, anti-CHIKV SNA NT80 
values will be logarithmically transformed (base10), and the GMTs and associated 95% CIs 
for each treatment group will be computed by exponentiating the corresponding 
log-transformed means and two-sided 95% CIs. Categorical variables will be summarized by 
frequency counts (n) and percentages of participants (%) in each category, including missing 
or unknown when appropriate. 

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9.4 
Multiplicity Controls 
9.4.1 Coprimary Immunogenicity Endpoints 
The familywise error rate will be fixed at a two-sided alpha of 0.05 by the requirement that 
both coprimary immunogenicity endpoints must be met for a successful outcome: 
1. 
Day 22 seroresponse in the IEP across all age groups combined, including superiority to 
placebo and the success criterion of the lower bound of the two-sided Newcombe hybrid 
score method 95% CI on the difference in seroresponse rates between PXVX0317 and 
placebo 
. 
2. 
Day 22 GMTs significantly different between PXVX0317 and placebo in the IEP across 
both age groups combined using an ANOVA model with logarithmically transformed 
anti-CHIKV SNA titers (log10) as the dependent variable and treatment group and study 
site as the fixed effects with a two-sided significance level of 0.05. 
9.4.2 Key Secondary Immunogenicity Endpoints 
A prespecified hierarchical approach will be employed for the key secondary 
immunogenicity endpoint hypothesis testing to preserve the type I error rate without the need 
for further multiplicity adjustment. If the null hypotheses are rejected for both coprimary 
endpoints, only then will the key secondary endpoints be formally tested in sequential order. 
If a nonsignificant test is reached formal testing will stop, and the remaining endpoints will 
be reported for information only. The seroresponse rates and rate differences at Days 15 and 
183 will be tested sequentially in order, each for the IEP across both age groups combined, as 
follows: 
1. 
Day 15 seroresponse superior to placebo. 
2. 
Day 183 seroresponse superior to placebo. 
After testing the coprimary immunogenicity endpoints and, if both met, the hierarchical key 
secondary immunogenicity endpoints, no other formal hypothesis testing will be carried out. 
The remaining secondary immunogenicity endpoints including GMTs, GMFI, other titers, 
the exploratory endpoint, and all safety endpoints will be evaluated and reported for 
information only, thus no further multiplicity adjustment is needed. 
9.5 
Handling of Missing Data 
Participants with missing immunogenicity data at Days 15, 22, or 183 will be excluded from 
the corresponding analysis; missing immunogenicity data will not be imputed. Human SNA 
assay anti-CHIKV SNA NT80 values below the lower limit of quantitation (LLOQ) will be 
replaced by LLOQ/2 in the immunogenicity analyses. Imputation rules for partial or missing 
dates and for missing AE relatedness and/or severity will be described in the study SAP. 

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9.6 
Planned Analyses 
9.6.1 Study Population Characteristics 
9.6.1.1 
Participant Disposition 
Participant disposition will be summarized for all screened participants who sign and date the 
ICF. Randomized participants will be displayed by treatment group, including number and 
percentages of participants still in the study at each scheduled visit, those competing the 
study and reason for not completing the study. Screen failure reasons will be listed by 
participant. The number and percentage of participants enrolled by site will be provided by 
treatment group for all randomized participants. 
Randomization details including site, stratum, date and time of randomization, kit number, 
randomized treatment group assignment and actual treatment received will be listed by 
participant. Participants randomized but not treated and those receiving the wrong treatment 
will be listed. Participants who were randomized despite not meeting entry criteria and those 
who received an excluded concomitant medication will be listed. 
9.6.1.2 
Protocol Deviations 
Protocol deviations will be categorized as important or not important and evaluated for 
exclusion of participants from analysis populations prior to database lock and unblinding. 
Important protocol deviations will be tabulated by category and by treatment group for the 
randomized population as well as listed by participant. 
9.6.1.3 
Populations Analyzed 
The number and percentage of participants in each analysis population (see Section 9.2; 
randomized, exposed, safety, mITT, IEP) will be summarized by treatment group for all 
randomized participants. Reasons for exclusion from analysis populations will be 
summarized by treatment group for all randomized participants and listed by participant. 
9.6.1.4 
Demographics and Baseline Characteristics 
Demographic and baseline characteristics including age, age stratum, sex, race, ethnicity, 
baseline height, weight, and BMI will be tabulated by treatment group for the randomized, 
safety, mITT, and IEP populations. 
9.6.1.5 
Medical History 
Medical history will be coded to the MedDRA dictionary system organ class (SOC) and 
preferred term (PT). A summary table and a listing of medical history will be supplied by 
treatment group for the randomized population. 

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9.6.1.6 
Prior and Concomitant Medications 
Prior and concomitant medications and vaccines will be coded to the World Health 
Organization Drug Global Dictionary anatomic therapeutic chemical (ATC) classification 
and preferred drug name. All prior and concomitant medications and vaccines will be 
tabulated together by ATC classification, preferred drug name and treatment group for the 
safety population. A participant data listing of all prior and concomitant medications will be 
generated. 
9.6.2 Immunogenicity Analyses 
Summary statistics for immunogenicity results by scheduled visit for each treatment group 
will be provided for the IEP and mITT populations. Chikungunya virus SNA GMT will be 
tabulated by visit for each treatment group. Chikungunya virus SNA GMT will also be 
plotted over time for each treatment group for the IEP. 
In the analysis of the human SNA assay data as a continuous variable, anti-CHIKV SNA 
NT80 values will be logarithmically transformed (base10), and the GMTs and associated 95% 
CI for each treatment group will be computed by exponentiating the corresponding 
log-transformed means and two-sided 95% CIs. Results will be presented for both age groups 
combined as well as separately. Geometric mean fold increase will also be displayed by 
postvaccination scheduled visit for each treatment group. 
Proportions of participants with human SNA assay titer 
 and secondary response rates at 
other titers (eg, 15 and 4-fold rise over baseline) will be reported with associated two-sided 
95% Wilson method CIs by scheduled visit for each treatment group. 
Reverse cumulative distribution plots of human SNA assay vs proportion of participants in 
each treatment group will be generated by scheduled visit. Geometric mean titer will also be 
plotted over time for each treatment group. 
9.6.2.1 
Coprimary Immunogenicity Analysis 
9.6.2.1.1 
Day 22 Seroresponse Rate Analysis  
The superiority of the immune response to PXVX0317 vaccine over that to placebo will be 
demonstrated at Day 22 by comparing seroresponse rates between the two treatment groups 
(the proportion of participants with a human SNA assay 
; considered the presumptive 
seroprotection rate). The difference in seroresponse rates between the PXVX0317 and 
placebo groups will be calculated, along with the 95% CI for the difference based on the 
Newcombe hybrid score method. The lower bound of the two-sided 95% CI on the difference 
in seroresponse rates between PXVX0317 and placebo groups must be 
. Additionally, 
the null hypothesis of no difference between seroresponse rate proportions will be tested 
using a chi-square test with alpha=0.05. No multiplicity adjustment will be employed (see 
Section 9.4) and no covariate adjustment will be performed. 

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The primary comparison will be in the IEP across all age groups combined. Tests will be 
repeated in the mITT population as a measure of robustness, along with tests for each 
population in the separate age strata. No multiplicity adjustment will be made for the analysis 
of the separate age strata as the primary population will be the combined age groups. 
9.6.2.1.2 
Day 22 Geometric Mean Titer Analysis 
In addition, Day 22 GMTs will be compared between PXVX0317 and placebo treatment 
groups and will be analyzed via a linear model based on an alpha=0.05. The primary model is 
an ANOVA, with logarithmically transformed anti-CHIKV SNA titers (log10) as the 
dependent variable and treatment group and study site as the fixed effects in the model. The 
adjusted least square means and their 95% CIs calculated based on the ANOVA will be back 
transformed and reported as the group GMT values. All tests will be carried out at a 
two-sided significance level of 0.05 and no adjustment for multiplicity will be applied.  
The primary comparison will be in the IEP across both age groups combined. Tests will be 
repeated in the mITT population as a measure of robustness, along with tests for each 
population in the separate age strata. No multiplicity adjustment will be made for the analysis 
of the separate age strata as the primary population will be the combined age groups. 
9.6.2.2 
Secondary Immunogenicity Analysis 
9.6.2.2.1 
Key Secondary Immunogenicity Analyses: Seroresponse Rate and 
Seroresponse Rate Difference at Days 15 and 183, in that Order 
Seroresponse rates and seroresponse rate differences (PXVX0317 minus placebo) with 
associated 95% CIs based on antibody titers measured at Days 15 and 183 will be analyzed 
as described above for Day 22. For each time point, the null hypothesis of no difference 
between seroresponse rate proportions in the PXVX0317 vs placebo group will be tested 
using a chi-square test with alpha=0.05. 
9.6.2.2.2 
Geometric Mean Titer at Days 15 and 183 
For the comparison of PXVX0317 to placebo, GMTs based on antibody titers measured at 
Days 15 and 183 will be analyzed as described above for Day 22. Geometric mean fold 
increases for increase over Day 1 titer will be analysed as described for GMTs for each 
postvaccination time point.  
9.6.2.2.3 
Seroconversion at Other Titers 
As described above, secondary response rates at other titers (eg, 15 and 4-fold rise over 
baseline) will be reported with associated two-sided 95% Wilson method CIs by scheduled 
visit for each treatment group using the IEP. The significance of the treatment group 
difference will be assessed using chi-square tests at each visit for the IEP based on both age 
groups combined with an alpha=0.05. 

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9.6.2.3 
Geometric Mean Titer for Different CHIKV Genotypes at Day 22 for 
PXVX0317 Group 
This exploratory endpoint will be evaluated in the CHIKV genotype subset population for 
both age strata combined.   
9.6.3 Investigational Product Administration and Treatment Compliance 
Investigational product administration data will be summarized for the randomized 
population and listed by participant. 
Treatment compliance is not applicable since this study involves a single, in-clinic IP 
administration. 
9.6.4 Safety Analyses 
The safety of PXVX0317 in adults ≥65 years of age will be evaluated using solicited AEs 
occurring from IP administration on Day 1 until Day 8 and unsolicited AEs from Day 1 
through Day 29, AESI, MAAEs, and SAEs though Day 183 End of Study Visit, and vital 
signs. 
9.6.4.1 
Adverse Events 
Adverse events will be coded to the MedDRA dictionary SOC and PT. They will be graded 
for severity according to Section 8.1.8. Only treatment-emergent AEs will be collected (ie, 
those after the start of IP administration). Adverse events will be reported using both age 
strata pooled, but selected AE analyses will be repeated for the separate age strata. All AE 
tabulations and participant listings will be based on the safety population. 
Solicited AEs, unsolicited AEs, MAAEs, AESI, and SAEs will be summarized separately by 
treatment group and SOC, PT, and maximum severity for the safety population for both age 
strata combined. Only participants with at least one solicited AE observation (ie, any 
nonmissing values but excluding “not done/unknown”) will be summarized. Solicited AEs 
continuing beyond seven days after IP administration will be combined with the unsolicited 
AEs; a combined summary table of solicited and unsolicited AEs by treatment group and 
SOC, PT, and maximum severity will also be provided for the safety population for both age 
strata pooled. 
Additional AE displays will include the following: 
• Solicited AEs ≥Grade 3 
• Treatment-related (“possibly”, “probably” or “definitely”) solicited AEs 
• Solicited AEs: day of first onset, duration, day postinjection, and occurrence of at 
least one solicited AE by category (local, systemic) 
• Unsolicited AEs ≥Grade 3 
• Treatment-related (“possibly”, “probably” or “definitely”) unsolicited AEs 

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• Medically attended AEs 
• Treatment-related MAAEs 
• AEs leading to study discontinuation 
• Fatal AEs, if any 
• Treatment-related (“possibly”, “probably” or “definitely”) SAEs 
Separate participant data listings of solicited and unsolicited AEs sorted by participant 
identifier and AE start date will be generated. Diary compliance will not be summarized. 
9.6.4.2 
Vital Signs 
Pre- and post-IP administration vital signs data will be listed by participant, visit, and time 
point for each treatment group for the safety population. 
9.6.5 Subgroup Analyses 
Subgroup analyses of key safety and immunogenicity endpoints may be performed by age 
subgroups (65 to <75 and ≥75 years of age), sex, race, ethnicity, and baseline serostatus (if 
more than 10% of participants are seropositive at baseline). 
9.6.6 Planned Interim Analyses and Criteria for Study Termination 
The SMC (Sections 3.5 and 8.5) will review aggregated, blinded safety data after the first 50 
participants have completed seven days of safety follow-up and periodically thereafter as per 
SMC recommendation according to the SMC Charter.  
There will be a safety and immunogenicity preliminary analysis on data for all participants 
through the Day 29 Visit to facilitate health authority presubmission preparation. The 
analyses will be performed by a third-party vendor and results will be reported only at the 
treatment group summary level preserving the double-blind status on the participant level. 
No p-value penalty will be assessed because the Day 22 primary immunogenicity endpoint 
data will be final at the time of preliminary analysis and no action regarding the study will be 
made based on these findings. 
10 DATA HANDLING AND RECORD KEEPING 
10.1 
Source Documents and Access 
Source data are all information, original records of clinical findings, and observations in a 
clinical trial necessary for the reconstruction and evaluation of the trial. The source 
documentation requirements described below apply to all source documentation and study 
records in any form, including those maintained in the institution’s electronic health record 
system, if applicable. 

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The PI/Institution will maintain adequate and accurate source documents and study records 
that include all pertinent information related to participants’ participation in the study, 
including details but not limited to signed and dated notes on consenting, eligibility, medical 
history, study assessments, IP administration, AEs, concomitant medications, participant 
follow-up information, and other relevant observations. 
Source data should be attributable, legible, contemporaneous, original, accurate, and 
complete. Changes to source data should be traceable, should not obscure the original entry 
and should be explained if necessary (eg, via an audit trail). 
The PI/Institution shall permit study-related monitoring, audits, IRB review, and regulatory 
inspection(s), providing direct access to source data/documents.  
Records from the study that identify the participant will be confidential except that they may 
be given to and inspected by the sponsor (or designee), the IRB, the FDA, EMA, other 
government agencies as appropriate and will not otherwise be released except as required by 
law. Refer to Section 12.5 Participant Confidentiality. All information provided to the PI by 
the sponsor is to be considered confidential unless otherwise stated. 
10.2 
Data Management 
A validated, EDC system will be used during the study. Data management activities to be 
performed for the study will be described in detail in the Data Management Plan (DMP).  
10.3 
Data Collection and Discrepancy Management 
Data collected during the study will be recorded in the eCRFs designed for this study. 
Investigational sites will have the responsibility for capturing and maintaining accurate eCRF 
data, records, and relevant source documentation, as well as conforming to procedures 
established by the sponsor around system access/security and ensuring a data audit/edit trail 
for data corrections. All source documents will be verified by the study monitor for accuracy. 
Information from external sources such as laboratory data, images, etc, as defined in this 
protocol will be collected and maintained outside the EDC and reconciled with the eCRF 
data periodically (as applicable). As data are entered into the eCRF, automated edit checks 
will validate data. Additionally, manual reviews will be performed for data discrepancy by 
the monitor and queries will be generated into the EDC system. After clinical sites respond to 
queries and data corrections are made and reviewed by the monitor, the investigator will 
review and electronically sign the eCRF for each participant. The sponsor will review data 
for accuracy, completeness, and consistency during the conduct of the study and prior to 
database lock. 
For further information on eCRFs, refer to the CRF Completion Guidelines. Details on data 
handling will be described in the DMP. 

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10.4 
Laboratory Data 
No external laboratory data transfers will be done. Sites will manually enter results of 
HBsAg/HCV antibody/HIV-1/HIV-2 into applicable eCRFs. Chikungunya virus SNA titer 
results will be handled by the sponsor. 
10.5 
File Management at the Investigational Site 
The PI will ensure that the essential study documents are maintained in accordance with the 
ICH GCP Guidelines and as required by applicable local and federal regulations. The 
PI/institution will take measures to prevent accidental or premature destruction of these 
documents. 
10.6 
Records Retention at the Investigational Site 
Per ICH guidelines, study documents will be retained for one of the following periods: 
• A period of at least two years after the date of the last approval of a marketing application 
in an ICH region until there are no pending or contemplated marketing applications. 
• A period of at least two years after the sponsor has notified the regulatory authority(ies) 
that clinical investigation with this product is discontinued. 
The PI must not dispose of any records relevant to this study without either (1) written 
permission from the sponsor or (2) provision of an opportunity for the sponsor to collect such 
records. The PI will be responsible to maintain adequate and accurate electronic or hard copy 
source documents of all observations and data generated during this study, including any data 
queries received from the sponsor (or designee). Such documentation is subject to inspection 
by the sponsor (or its designee[s]) and relevant regulatory agencies. If the PI withdraws from 
the study (eg, due to relocation or retirement), all study-related records will be transferred to 
a mutually agreed upon designee within the sponsor’s specified timeframe. Notice of such 
transfer will be given to the sponsor in writing. 
10.7 
Deviations from the Protocol 
The PI agrees to conduct the clinical study in compliance with the protocol agreed to by the 
sponsor and approved by the investigational site’s IRB. 
A protocol deviation is any change, divergence, or departure from the study design or 
procedures defined in the protocol. 
The PI or investigational site staff may not deviate from the protocol, except, in rare 
circumstances, as necessary to eliminate immediate hazards to study participants. In such 
event, both the sponsor and IRB will be immediately notified.  
The occurrence of protocol deviations will be routinely monitored for by evaluation of PI 
compliance with the protocol, GCP, and regulatory requirements. The sponsor will review all 
protocol deviations on an ongoing basis and will be responsible for determining if the 

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deviation should be categorized as an important protocol deviation. Important protocol 
deviations may require additional documentation as requested by the sponsor. 
Continued protocol deviations despite re-education of investigational site personnel, or 
persistent protocol deviations that are reportable to regulatory agencies may result in 
discontinued shipment of IP and termination of further enrollment at the investigational site, 
or termination of the investigational site from the study. 
11 QUALITY CONTROL AND ASSURANCE 
11.1 
Monitoring 
The assigned clinical study monitor will verify eCRF entries against source documentation at 
regular intervals throughout the study to verify adherence to the protocol; completeness, 
accuracy, and consistency of the data; and adherence to ICH GCP Guidelines and local and 
federal regulations applicable to the conduct of the clinical study. The PI must make source 
documentation accessible to the study monitor as needed to verify the information in the 
eCRFs. The PI agrees to meet with the study monitor at regular intervals to discuss study 
progress and ensure that any problems detected in the course of data monitoring are resolved 
appropriately. 
11.2 
Auditing 
The sponsor’s Quality Assurance Department (or designee) may conduct investigational site 
audits before study initiation, during the study, or after study completion. Audits will include, 
but are not limited to, review of source documents, verification of eCRFs against source 
documents and review of essential documents to ensure compliance with protocol and 
applicable local and federal regulations. The PI agrees to participate in site audits and assist 
in the prompt resolution of any issues found during audits. 
In the event the PI is contacted by a regulatory agency in relation to this study, the PI and 
investigational site staff must be available to respond to reasonable requests and inspection 
queries made during the inspection process. The PI must provide the sponsor with copies of 
all correspondence that may affect the review of the current study (eg, Form FDA 483, 
inspectional observations, warning letters). The sponsor will provide any needed assistance 
in responding to regulatory inspections. 
12 ETHICS AND RESPONSIBILITY 
This study must be conducted in accordance with the ethical principles described in the 
current Declaration of Helsinki, and in compliance with the protocol, current ICH GCP 
Guidelines, and applicable local and federal regulations, and all other applicable local laws. 
Each investigational site will seek approval by an IRB according to regional requirements. 
The IRB will evaluate the ethical, scientific, and medical appropriateness of the study. 
Further, in collecting and handling participant data and completing eCRFs, the PI and 

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investigational site staff will take measures to ensure adequate care in protecting participant 
privacy. To this end, a participant ID number will be used to identify each participant. 
12.1 
Informed Consent 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate 
in the study and continues throughout their study participation.  
The sponsor (or designee) will generate and provide a master ICF template to each 
investigational site for development of a site-specific ICF.  
All site-specific ICFs must be in compliance with ICH GCP Guidelines, local regulatory 
requirements, and legal requirements and must be approved by the sponsor (or designee) and 
the IRB. The sponsor (or designee) will advise the investigational site of required changes to 
the master ICF template during the study. 
The participant will be asked to read and review the document. The PI will explain the 
research study to the participant and answer any questions that may arise. A verbal 
explanation will be provided in terms suited to the participant’s comprehension of the 
purposes, procedures, and potential risks of the study and of their rights as research 
participants. Participants will have the opportunity to carefully review the written consent 
form and ask questions prior to signing. The participants should have the opportunity to 
discuss the study with their family or think about it prior to agreeing to participate. The 
participant will sign the informed consent document prior to any procedures being done 
specifically for the study. Participants must be informed that participation is voluntary and 
that they may withdraw from the study at any time, without prejudice. A copy of the 
informed consent document will be given to the participants for their records. The informed 
consent process will be conducted and documented in the source document (including the 
date), and the form signed, before the participant undergoes any study-specific procedures. 
The rights and welfare of the participants will be protected by emphasizing to them that the 
quality of their medical care will not be adversely affected if they decline to participate in 
this study. 
12.2 
Institutional Review Board 
Before the start of the study, the protocol, the IB, proposed ICF(s), participant compensation 
(if any), sponsor-approved study materials and advertisements, and any other written 
information to be provided to the participant, and applicable amendments, will be submitted 
to a properly constituted IRB for review. The sponsor must receive a copy of the written 
approval from the IRB for all of the above applicable documents prior to recruitment of 
participants and shipment of PXVX0317.  
The PI (or designee) is responsible for informing and obtaining appropriate approval from 
the IRB of any amendment to the protocol or ICF in accordance with local requirements.  

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The PI (or designee) is also responsible for providing the IRB with reports of any reportable 
serious adverse drug reactions from any other study conducted with the IP, if required by the 
IRB. The sponsor will provide this information to the PI. 
Initial IRB approval, and all materials approved by the IRB for the study including the ICF 
and recruitment materials, must be maintained by the PI and made available for inspection.  
All correspondence between the PI and the IRB will be available for review by the sponsor 
and applicable regulatory authority(ies). 
12.3 
Compensation for Injury 
The sponsor will adhere to local regulations and guidelines regarding clinical study 
compensation to participants whose health is adversely affected by taking part in the study. 
Compensation for injury will be described in the ICF. 
12.4 
Documentation Required Prior to Study Initiation  
The PI (or designee) is responsible for forwarding the following documents to the sponsor for 
review prior to study initiation: 
• Signed protocol signature page, form FDA 1572 (or equivalent, depending on applicable 
local and federal regulations), financial disclosure form (principal and subinvestigators), 
Clinical Trial Agreement, and any other required regulatory documents. 
• Copy of IRB-approved ICF and assent form (as applicable). 
• Copy of the written IRB approval for the following documents: protocol, IB, ICF, 
participant compensation (if any), any study materials and advertising, and any other 
written information or tools (including diaries) to be provided to the participant. 
• Current signed and dated Curriculum Vitae and a copy of medical license (if applicable) 
of the PI and subinvestigator, and other investigational site personnel as required by the 
sponsor. 
• Written statement that the IRB is properly constituted and operates according to ICH 
GCP Guidelines and applicable local and federal regulations. Investigators participating 
in this study, if IRB members, should state in writing that they have abstained from 
voting in regard to this protocol.  
• Laboratory normal ranges and documentation of laboratory certification (as applicable). 
12.5 
Participant Confidentiality 
The PI must ensure the anonymity of each participant is maintained at all times. Participants 
should only be identified by their Participant Study ID number on the eCRF or on any other 
study documents provided to the sponsor (or designee(s)). Biospecimens should only be 
identified by sample numbers/codes as specified in the Laboratory Manual. Any documents 
that identify the participant should be kept in strict confidence by the investigational site.  

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Based on ICH GCP Guidelines and regulatory requirements, the PI is required to allow 
authorized personnel of the sponsor (or its designee), the IRB, and members of the 
appropriate regulatory authority(ies) to review participant’s files that are related to study 
EBSI-CV-317-005. Participants must be informed that their records may be reviewed by the 
sponsor, its designee(s), the IRB and the appropriate regulatory authority(ies) through direct 
access to the participant’s original medical records. 
Redacted copies of participant medical records that are related to study EBSI-CV-317-005 
may be collected by the sponsor for the purposes of AE follow-up and reporting, and/or 
monitoring. Redacted copies of medical records may be transferred via encrypted email 
(AES or triple DES); via secure fax line; or uploaded to a secure, encrypted 
password-protected environment hosted by a third-party service provider to which only 
assigned site personnel and monitors have access, with a list of users maintained for the 
duration of the study and audit trails available on all activities.  
Copies of redacted medical records related to monitoring will be permanently destroyed at 
study closure. 
12.6 
Future Use of Stored Samples 
Any remnant (leftover) blood samples collected for the anti-CHIKV SNA analysis will be 
retained for future testing. Specimens will be identified by sample numbers/codes, thereby 
maintaining blinding while in storage. Participants will be asked to consent to the future use 
of these samples as part of the informed consent process.  
Samples may be retained for at least two years after the last approval of a marketing 
application in an ICH region and until there are no pending or contemplated marketing 
applications in an ICH region or until at least two years have elapsed since the formal 
discontinuation of clinical development. 
13 ADMINISTRATIVE AND LEGAL REQUIREMENTS 
13.1 
Sponsorship 
This clinical study is sponsored by Emergent Travel Health Inc., 
 
 who is the manufacturer of PXVX0317. 
13.2 
Protocol Amendments 
Protocol amendments will only be made by the sponsor. In general, any change to the 
protocol must be made in the form of a formal amendment to the protocol and must be 
approved in writing by the PI, the sponsor, and the IRB prior to implementation. The PI must 
receive written IRB approval for all protocol amendments prior to implementing protocol 
amendments at the investigational site; copies of IRB correspondence including 
approval/disapproval letters from the IRB must be provided to the sponsor. 

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However, a protocol change intended to eliminate an apparent immediate hazard to 
participants will be implemented immediately, followed by IRB notification within five 
working days. The sponsor will submit protocol amendments to the applicable regulatory 
authority(ies). 
13.3 
Clinical Study Registration 
The sponsor is responsible for clinical trial registration and reporting to Clinicaltrials.gov and 
other registries in accordance with applicable regulations. 
13.4 
Publication Policy 
Following the completion of the study, the data may be considered for reporting at a 
scientific meeting or for publication in a scientific journal. In these cases, the sponsor will be 
responsible for these activities and may work with a PI (or a number of PIs) to determine 
how the manuscript is written and edited, the number and order of authors, the publication to 
which it will be submitted and other related issues. The sponsor has final approval authority 
over all such issues.  
Any proposed publication will be subject to review conditions and timelines agreed between 
the sponsor and the investigational site(s) PI(s) and detailed in the agreements with these 
parties prior to the start of the study. The sponsor will also post the results of the clinical 
study on ClinicalTrials.gov (or other applicable registries) in a period no greater than 12 
months from the completion of the study, defined as the time the final participant was 
examined or received an intervention for purposes of final collection of data for the primary 
outcome. 
Data are the property of the sponsor and cannot be published without prior authorization 
from the sponsor, but data and publication thereof will not be unduly withheld. 
All publication rights are delineated in the Clinical Trial Agreement. 

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14 REFERENCES 
1. 
Ross RW. The Newala epidemic. III. The virus: isolation, pathogenic properties and 
relationship to the epidemic. J Hyg (Lond). 1956;54(2):177-191. 
2. 
Powers AM, Logue CH. Changing patterns of chikungunya virus: re-emergence of a zoonotic 
arbovirus. J Gen Virol. 2007;88(Pt 9):2363-2377. 
3. 
CDC. Geographic Distribution: countries and territories where chikungunya cases have been 
reported [Internet]. Centers for Disease Control and Prevention (US); 2020Oct30 [cited 
2021Jul13]. Available from: https://www.cdc.gov/chikungunya/geo/.  
4. 
Staples JE, Hills SL, Powers AM. CDC yellow book [Internet]. Centers for Disease Control 
and Prevention (US); revised 2020Jan10. Chapter 4, Travel-related infectious diseases: 
chikungunya; [cited 2019 Sep 26]; p.78. Available from: 
https://wwwnc.cdc.gov/travel/yellowbook/2020/travel-related-infectious-
diseases/chikungunya.  
5. 
Borgherini G, Poubeau P, Staikowsky F, Lory M, Le Moullec N, Becquart JP, et al. Outbreak 
of chikungunya on Reunion Island: early clinical and laboratory features in 157 adult 
patients. Clin Infect Dis. 2007;44(11):1401-1407. 
6. 
Pialoux G, Gauzere BA, Jaureguiberry S, Strobel M. Chikungunya, an epidemic arbovirosis. 
Lancet Infect Dis. 2007;7(5):319-327. 
7. 
Taubitz W, Cramer JP, Kapaun A, Pfeffer M, Drosten C, Dobler G, et al. Chikungunya fever 
in travelers: clinical presentation and course. Clin Infect Dis. 2007;45(1):e1-4. 
8. 
Schilte C, Staikowsky F, Couderc T, Madec Y, Carpentier F, Kassab S, et al. Chikungunya 
virus-associated long-term arthralgia: a 36-month prospective longitudinal study. PLoS Negl 
Trop Dis. 2013;7(3):e2137. 
9. 
Amaral JK, Bilsborrow JB, Schoen RT. Brief report: the disability of chronic chikungunya 
arthritis. Clin Rheumatol. 2019;38(7):2011-2014. 
10. Gérardin P, Fianu A, Malvy D, Mussard C, Boussaïd K, Rollot O, et al. Perceived morbidity 
and community burden after a chikungunya outbreak: the TELECHIK survey, a population-
based cohort study [Internet]. BMC Med. 2011;9(5). Available from: 
https://doi.org/10.1186/1741-7015-9-5.  
11. EBSI, Emergent BioSolutions Inc. PXVX-EPI-CV-001 Pediatric Dengue Cohort Study in 
Nicaragua 2019. 

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12. Yoon IK, Alera MT, Lago CB, Tac-An IA, Villa D, Fernandez S, et al. High rate of 
subclinical chikungunya virus infection and association of neutralizing antibody with 
protection in a prospective cohort in the Philippines. PLoS Negl Trop Dis. 
2015;9(5):e0003764. 
13. Ledgerwood J. VRC 311: a phase 1 open label, dose-escalation clinical trial to evaluate the 
safety and immunogenicity of a virus-like particle (VLP) chikungunya vaccine, VRC-
CHKVLP059-00-VP, in healthy adults. ClinicalTrials.gov Identifier: NCT01489358. 2016 
[cited 2019 September 26]. Available from: 
https://clinicaltrials.gov/ct2/show/record/NCT01489358. 
14. Chang LJ, Dowd KA, Mendoza FH, Saunders JG, Sitar S, Plummer SH, et al. VRC 311: 
safety and tolerability of chikungunya virus-like particle vaccine in healthy adults: a phase 1 
dose-escalation trial. Lancet. 2014;384(9959):2046-52. 
15. Chen G, Ledgerwood J. VRC 704 phase 2 randomized, placebo-controlled trial to evaluate 
the safety and immunogenicity of a chikungunya virus-like particle vaccine, VRC-
CHKVLP059-00-VP, in healthy adults. 2019 [cited 2019 September 26]. Available from: 
https://clinicaltrials.gov/ct2/show/record/NCT02562482?term=VRC+704&rank=1. 
16. Chen GL, Coates EE, Plummer SH, Carter CA, Berkowitz N, Conan-Cibotti M, et al. VRC 
704: effect of a chikungunya virus-like particle vaccine on safety and tolerability outcomes: a 
randomized clinical trial. JAMA. 2020;323(14):1369-77. 
17. Bennett S. PXVX-CV-317-001 a phase 2 parallel-group, randomized, double-blind study to 
assess the safety and immunogenicity of PXVX0317 (chikungunya virus virus-like particle 
vaccine [CHIKV VLP], unadjuvanted or alum-adjuvanted). ClinicalTrials.gov Identifier: 
NCT03483961. 2018 [cited 2019 September 26]. Available from: 
https://clinicaltrials.gov/ct2/show/NCT03483961. 
18. Mendy J. Poster: Development of a high-throughput luciferase-based chikungunya 
neutralization assay (CHIKV-luc). ASTMH 2018. Emergent Travel Health Inc. 
19. Bennett S. EBSI-CV-317-002 a phase 2 open-label study to assess the safety and 
immunogenicity of an alum-adjuvanted chikungunya virus-like particle vaccine (PXVX0317) 
in prior recipients of other alphavirus vaccines (WRAIR). ClinicalTrials.gov Identifier: 
NCT03992872. 2020. Available from: 
https://www.clinicaltrials.gov/ct2/show/NCT03992872. 
20. CDC. Vaccine Recommendations and Guidelines of the ACIP: Centers for Disease Control 
and Prevention. 2020 [TABLE 6-2. Needle length and injection site of IM injections for 
children aged ≤18 years (by age) and adults aged ≥9 years (by sex and weight)]. Available 
from: https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/administration.html. 

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15 APPENDICES 
APPENDIX I 
TOXICITY GRADING SCALE TABLES 
Local Reaction to 
Injectable Product 
Mild  
(Grade 1) 
Moderate  
(Grade 2) 
Severe  
(Grade 3) 
Potentially Life 
Threatening 
(Grade 4) 
Pain 
Does not interfere 
with activity 
Repeated use of 
non-narcotic pain 
reliever >24 hours 
or interferes with 
activity 
Any use of 
narcotic pain 
reliever or 
prevents daily 
activity 
Emergency room 
(ER) visit or 
hospitalization 
Tenderness 
Mild discomfort to 
touch 
Discomfort with 
movement 
Significant 
discomfort at rest 
ER visit or 
hospitalization 
Erythema/Redness* 
25 – 50 mm*** 
51 – 100 mm*** 
>100 mm*** 
Necrosis or 
exfoliative 
dermatitis 
Induration/Swelling** 
25 – 50 mm*** 
and does not 
interfere with 
activity 
51 – 100 mm*** 
or interferes with 
activity 
>100 mm*** or 
prevents daily 
activity 
Necrosis 
*In addition to grading the measured local reaction at the greatest single diameter, the measurement should 
be recorded as a continuous variable. 
**Induration/Swelling should be evaluated and graded using the functional scale as well as the actual 
measurement. 
***Revised by sponsor. 
 
Vital Signs* 
Mild  
(Grade 1) 
Moderate  
(Grade 2) 
Severe 
(Grade 3) 
Potentially Life 
Threatening 
(Grade 4) 
Fever (°C)** 
          (°F)** 
38.0 – 38.4 
100.4 – 101.1 
38.5 – 38.9 
101.2 – 102.0 
39.0 – 40 
102.1 – 104 
>40 
>104 
Tachycardia – 
beats per minute 
101 – 115 
116 – 130 
>130 
ER visit or 
hospitalization for 
arrhythmia 
Bradycardia – 
beats per 
minute*** 
50 – 54 
45 – 49 
<45 
ER visit or 
hospitalization for 
arrhythmia 
Hypertension 
(systolic) – mmHg 
141 – 150 
151 – 155 
>155 
ER visit or 
hospitalization for 
malignant 
hypertension 
Hypertension 
(diastolic) – mmHg 
91 – 95 
96 – 100 
>100 
ER visit or 
hospitalization for 
malignant 
hypertension 

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Vital Signs* 
Mild  
(Grade 1) 
Moderate  
(Grade 2) 
Severe 
(Grade 3) 
Potentially Life 
Threatening 
(Grade 4) 
Hypotension 
(systolic) – mmHg 
85 – 89 
80 – 84 
<80 
ER visit or 
hospitalization for 
hypotensive shock 
Respiratory Rate – 
breaths per minute 
17 – 20 
21 – 25 
>25 
Intubation 
*Participant should be at rest for all vital sign measurements. 
**Oral temperature; no recent hot or cold beverages or smoking. 
***When resting heart rate is between 60 – 100 beats per minute. Use clinical judgement when 
characterizing bradycardia among some healthy participant populations, for example, conditioned athletes. 
 
Systemic 
(General) 
Mild  
(Grade 1) 
Moderate  
(Grade 2) 
Severe 
 (Grade 3) 
Potentially Life 
Threatening 
(Grade 4) 
Nausea/vomiting 
No interference 
with activity or 1 – 
2 episodes/24 
hours 
Some interference 
with activity or >2 
episodes/24 hours 
Prevents daily 
activity, requires 
outpatient IV 
hydration 
ER visit or 
hospitalization for 
hypotensive shock 
Diarrhea 
2 – 3 loose stools 
or <400 g/24 hours 
4 – 5 stools or 400 
– 800 g/24 hours 
6 or more watery 
stools or >800 g/24 
hours or requires 
outpatient IV 
hydration 
ER visit or 
hospitalization 
Headache 
No interference 
with activity 
Repeated use of 
non-narcotic pain 
reliever >24 hours 
or some 
interference with 
activity 
Significant; any 
use of narcotic pain 
reliever or prevents 
daily activity 
ER visit or 
hospitalization 
Fatigue 
No interference 
with activity 
Some interference 
with activity 
Significant; 
prevents daily 
activity 
ER visit or 
hospitalization 
Myalgia 
No interference 
with activity 
Some interference 
with activity 
Significant; 
prevents daily 
activity 
ER visit or 
hospitalization 
 
Systemic Illness 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially Life 
Threatening 
(Grade 4) 
Illness or clinical 
adverse event (as 
defined according 
to applicable 
regulations) 
No interference 
with activity 
Some interference 
with activity 
Prevents daily 
activity and 
requires medical 
intervention 
ER visit or 
hospitalization 

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Serum* 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially Life 
Threatening 
(Grade 4)** 
Sodium – Hyponatremia mEq/L 
132 – 134 
130 – 131 
125 – 129 
<125 
Sodium – Hypernatremia mEq/L 
144 – 145 
146 – 147 
148 – 150 
>150 
Potassium – Hyperkalemia mEq/L 
5.1 – 5.2 
5.3 – 5.4 
5.5 – 5.6 
>5.6 
Potassium – Hypokalemia mEq/L 
3.5 – 3.6 
3.3 – 3.4 
3.1 – 3.2 
<3.1 
Glucose – Hypoglycemia mg/dL 
65 – 69 
55 – 64 
45 – 54 
<45 
Glucose – Hyperglycemia 
Fasting – mg/dL 
Random – mg/dL 
 
100 – 110 
110 – 125 
 
111 – 125 
126 – 200 
 
>125 
>200 
Insulin requirements 
or hyperosmolar 
coma 
Blood Urea Nitrogen BUN mg/dL 
23 – 26 
27 – 31 
>31 
Requires dialysis 
Creatinine – mg/dL 
1.5 – 1.7 
1.8 – 2.0 
2.1 – 2.5 
>2.5 or requires 
dialysis 
Calcium – hypocalcemia mg/dL 
8.0 – 8.4 
7.5 – 7.9 
7.0 – 7.4 
<7.0 
Calcium – hypercalcemia mg/dL 
10.5 – 11.0 
11.1 – 11.5 
11.6 – 12.0 
>12.0 
Magnesium – hypomagnesemia mg/dL 
1.3 – 1.5 
1.1 – 1.2 
0.9 – 1.0 
<0.9 
Phosphorous – hypophosphatemia mg/dL 
2.3 – 2.5 
2.0 – 2.2 
1.6 – 1.9 
<1.6 
CPK – mg/dL 
1.25 – 1.5 x 
ULN*** 
1.6 – 3.0 
ULN 
3.1 – 10 x 
ULN 
>10 x ULN 
Albumin – Hypoalbuminemia g/dL 
2.8 – 3.1 
2.5 – 2.7 
<2.5 
-- 
Total Protein – Hypoproteinemia g/dL 
5.5 – 6.0 
5.0 – 5.4 
<5.0 
-- 
Alkaline phosphate – increase by factor 
1.1 – 2.0 x 
ULN 
2.1 – 3.0 x 
ULN 
3.1 – 10 x 
ULN 
>10 x ULN 
Liver Function Tests – ALT, AST 
increase by factor 
1.1 – 2.5 x 
ULN 
2.6 - 5.0 x 
ULN 
5.1 – 10 x 
ULN 
>10 x ULN 
Bilirubin – when accompanied by any 
increase in Liver Function Test increase 
by factor 
1.1 – 1.25 x 
ULN 
1.26 – 1.5 x 
ULN 
1.51 – 1.75 
x ULN 
>1.75 x ULN 
Bilirubin – when Liver Function Test is 
normal; increase by factor 
1.1 – 1.5 x 
ULN 
1.6 – 2.0 x 
ULN 
2.0 – 3.0 x 
ULN 
>3.0 x ULN 
Cholesterol 
201 – 210 
211 – 225 
>226 
-- 
Pancreatic enzymes – amylase, lipase 
1.1 – 1.5 x 
ULN 
1.6 – 2.0 x 
ULN 
2.1 – 5.0 x 
ULN 
>5.0 x ULN 
*The laboratory values provided in the tables serve as guidelines and are dependent upon institutional normal 
parameters. Institutional normal reference ranges should be provided to demonstrate that they are 
appropriate. 
**The clinical signs or symptoms associated with laboratory abnormalities might result in characterization of 
the laboratory abnormalities as Potentially Life Threatening (Grade 4). For example. a low sodium value that 
falls within a grade 3 parameter (125-129 mE/L) should be recorded as a grade 4 hyponatremia event if the 
participant had a new seizure associated with the low sodium value. 
***“ULN” is the upper limit of the normal range. 
 

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Hematology* 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially Life 
Threatening 
(Grade 4) 
Hemoglobin (Female) - gm/dL 
11.0 – 12.0 
9.5 – 10.9 
8.0 – 9.4 
<8.0 
Hemoglobin (Female) 
change from baseline value - 
gm/dL 
Any decrease 
– 1.5 
1.6 – 2.0 
2.1 – 5.0 
>5.0 
Hemoglobin (Male) - gm/dL 
12.5 – 13.5 
10.5 – 12.4 
8.5 – 10.4 
<8.5 
Hemoglobin (Male) 
change from baseline value – 
gm/dL 
Any decrease 
– 1.5 
1.6 – 2.0 
2.1 – 5.0 
>5.0 
WBC Increase - cell/mm3 
10,800 – 
15,000 
15,001 – 
20,000 
20,001 – 
25,000 
>25,000 
WBC Decrease - cell/mm3 
2,500 – 3,500 
1,500 – 2,499 
1,000 – 1,499 
<1,000 
Lymphocytes Decrease - cell/mm3 
750 – 1,000 
500 – 749 
250 – 499 
<250 
Neutrophils Decrease - cell/mm3 
1,500 – 2,000 
1,000 – 1,499 
500 – 999 
<500 
Eosinophils - cell/mm3 
650 – 1,500 
1,501 – 5,000 
>5,000 
Hypereosinophilic 
Platelets Decreased - cell/mm3 
125,000 – 
140,000 
100,000 – 
124,000 
25,000 – 
99,000 
<25,000 
PT – increase by factor 
(prothrombin time) 
1.0 – 1.10 x 
ULN** 
1.11 – 1.20 x 
ULN 
1.21 – 1.25 x 
ULN 
>1.25 ULN 
PTT – increase by factor 
(partial thromboplastin time) 
1.0 – 1.2 x 
ULN 
1.21 – 1.4 x 
ULN 
1.41 – 1.5 x 
ULN 
>1.5 x ULN 
Fibrinogen increase - mg/dL 
400 – 500 
501 – 600 
>600 
-- 
Fibrinogen decrease - mg/dL 
150 – 200 
125 – 149 
100 – 124 
<100 or 
associated with 
gross bleeding or 
disseminated 
intravascular 
coagulation (DIC) 
WBC - White blood cell count 
*The laboratory values provided in the tables serve as guidelines and are dependent upon institutional normal 
parameters. Institutional normal reference ranges should be provided to demonstrate that they are 
appropriate. 
**“ULN” is the upper limit of the normal range. 

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Urine* 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially Life 
Threatening 
(Grade 4) 
Protein 
Trace 
1+ 
2+ 
Hospitalization or 
dialysis 
Glucose 
Trace 
1+ 
2+ 
Hospitalization 
for hyperglycemia 
Blood (microscopic) – red blood 
cells per high power field (rbc/hpf) 
1 – 10 
11 – 50 
>50 and/or 
gross blood 
Hospitalization or 
packed red blood 
cells (PRBC) 
transfusion 
*The laboratory values provided in the tables serve as guidelines and are dependent upon institutional normal 
parameters. Institutional normal reference ranges should be provided to demonstrate that they are 
appropriate. 
 

Document Approvals
Approved Date: 31 Mar 2023
Document Approval Task
Verdict:  Approve
 Scientist, Clinical Research
Document Approval Task
Verdict:  Approve
 Sr Director, Biostatistics & Data Sciences
Document Approval Task
Verdict:  Approve
 Sr. Director, Clinical Development
Document Approval Task
Verdict:  Approve
 VP, Clinical Development