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
Phase: PHASE2
Conditions: Chikungunya Virus Infection
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Official Title: 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 
 
ClinicalTrials.gov Identifier: NCT02562482 
 
 
Document Type: 
• 
Redacted Study Protocol, including Letters of Amendment (Informed Consent 
Template located in Appendix I of the Protocol Version 2.0) 
• 
Redacted IRB-approved Version 2.0 Informed Consent from a participating 
site 
• 
Redacted Statistical Analysis Plan 
 
 
Document/Date: 
• 
Protocol Version 2.0: April 15, 2016 
• 
Protocol Version 2.0, Letter of Amendment #1: April 26, 2016 
• 
Protocol Version 2.0, Letter of Amendment #2: June 2, 2016 
• 
Version 2.0 April 15, 2016 IRB-approved Informed Consent  
• 
Statistical Analysis Plan Version 1.0: September 11, 2018 

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
Protocol VRC 704
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
Vaccine Research Center (VRC)
Bethesda, Maryland, USA
BB-IND 14907 – held by VRC, NIAID, NIH
Version 2.0
April 15, 2016
Confidentiality Statement
This document is confidential and is to be distributed for review only to investigators, potential investigators, consultants,
study staff, and applicable independent ethics committees or institutional review boards.  The contents of this document 
shall not be disclosed to others without written authorization from NIAID (or others, as applicable), unless it is necessary 
to obtain informed consent from potential study participants.

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TABLE OF CONTENTS
ABBREVIATIONS ........................................................................................................... 5 
PRÉCIS.............................................................................................................................. 6 
1. 
INTRODUCTION...................................................................................................... 7 
1.1. 
Chikungunya: Etiology, Disease Course and Epidemiology............................ 7 
1.2. 
Rationale for Development of VRC-CHKVLP059-00-VP............................... 8 
1.3. 
Previous Human Experience with VRC-CHKVLP059-00-VP......................... 9 
1.4. 
Rationale for Study Agent Dose and Schedule................................................. 9 
1.5. 
Assessment of Immunogenicity........................................................................ 9 
2. 
STUDY AGENTS .................................................................................................... 10 
2.1. 
VRC-CHKVLP059-00-VP Study Agent ........................................................ 10 
2.2. 
VRC-PBSPLA043-00-VP as Placebo............................................................. 10 
3. 
STUDY OBJECTIVES ............................................................................................ 11 
3.1. 
Primary Objective: .......................................................................................... 11 
3.2. 
Secondary Objectives:..................................................................................... 11 
3.3. 
Exploratory Objectives: .................................................................................. 11 
4. 
STUDY DESIGN AND CLINICAL PROCEDURES............................................. 11 
4.1. 
Study Population............................................................................................. 11 
4.1.1. 
Inclusion Criteria................................................................................... 12 
4.1.2. 
Exclusion Criteria.................................................................................. 12 
4.2. 
Study Schedule................................................................................................ 13 
4.2.1. 
Pre-enrollment ....................................................................................... 14 
4.2.2. 
Screening Visit(s).................................................................................. 14 
4.2.3. 
Enrollment Visit .................................................................................... 14 
4.2.4. 
Administration of Injections.................................................................. 14 
4.2.5. 
7-Day Diary Card and Follow-Up......................................................... 15 
4.2.6. 
Study Visits and Sample Collection...................................................... 15 
4.3. 
Evaluation of Chikungunya Infection during the Study ................................. 15 
4.3.1. 
Chikungunya Infection Diagnostic Visit............................................... 15 
4.3.2. 
Clinical Management and Follow-Up of Chikungunya Infection......... 16 
4.4. 
Concomitant Medications and Procedures...................................................... 16 
4.5. 
Criteria for Discontinuing Subject Participation............................................. 16 
4.5.1. 
Discontinuation of Study Injections...................................................... 16 
4.5.2. 
Discontinuation from Protocol Participation......................................... 17 
4.6. 
Criteria for Pausing the Study......................................................................... 17 
5. 
SAFETY AND ADVERSE EVENTS...................................................................... 18 
5.1. 
Adverse Events................................................................................................ 18 
5.1.1. 
Adverse Event Definition...................................................................... 18 
5.1.2. 
Adverse Event Reporting in the Study Database .................................. 18 
5.2. 
Serious Adverse Events................................................................................... 18 

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5.2.1. 
Serious Adverse Event Definition......................................................... 18 
5.2.2. 
Reporting Serious Adverse Events to the IND Sponsor........................ 19 
5.2.3. 
IND Sponsor Reporting to the FDA...................................................... 20 
5.3. 
Reporting to Site IRBs and Relevant Regulatory Agencies............................ 20 
5.3.1. 
Regulations Applicable to the French Study Sites Only ....................... 20 
5.4. 
Data and Safety Monitoring Board ................................................................. 20 
6. 
STATISTICAL CONSIDERATIONS AND SAMPLE ANALYSIS ...................... 21 
6.1. 
Overview......................................................................................................... 21 
6.2. 
Endpoints ........................................................................................................ 21 
6.2.1. 
Safety..................................................................................................... 21 
6.2.2. 
Immunogenicity..................................................................................... 21 
6.3. 
Sample Size and Accrual ................................................................................ 22 
6.3.1. 
Power Calculations for Evaluation of Safety ........................................ 22 
6.3.2. 
Power Calculations for Evaluation of Immune Responses ................... 23 
6.4. 
Statistical Analysis.......................................................................................... 24 
6.4.1. 
Baseline Demographics......................................................................... 24 
6.4.2. 
Safety Analysis...................................................................................... 25 
6.4.3. 
Analysis of Immune Responses............................................................. 25 
6.4.4. 
Analysis of Chikungunya Incidence...................................................... 25 
6.4.5. 
Interim Analyses.................................................................................... 26 
6.4.6. 
Randomization of Treatment Assignments and Unblinding Criteria.... 26 
7. 
PHARMACY AND INJECTION ADMINISTRATION PROCEDURES.............. 27 
7.1. 
Study Agents................................................................................................... 27 
7.2. 
Study Agent Presentation, Stability and Storage ............................................ 27 
7.2.1. 
Labels .................................................................................................... 27 
7.2.2. 
Storage................................................................................................... 28 
7.3. 
Preparation of Study Agent for Injection........................................................ 28 
7.3.1. 
Preparation of VRC-CHKVLP059-00-VP............................................ 28 
7.3.2. 
Preparation of VRC-PBSPLA043-00-VP ............................................. 28 
7.4. 
Study Agent Administration ........................................................................... 28 
7.5. 
Study Agent Accountability............................................................................ 29 
7.5.1. 
Documentation ...................................................................................... 29 
7.5.2. 
Disposition............................................................................................. 29 
8. 
HUMAN SUBJECTS PROTECTION ..................................................................... 29 
8.1. 
Institutional Review Board ............................................................................. 29 
8.2. 
Subject Recruitment and Enrollment .............................................................. 29 
8.2.1. 
Participation of Children ....................................................................... 29 
8.3. 
Informed Consent............................................................................................ 29 
8.4. 
Subject Confidentiality.................................................................................... 30 
8.5. 
Risks and Benefits........................................................................................... 30 
8.5.1. 
Risks of Blood Collections:................................................................... 30 
8.5.2. 
Risks of the CHIKV VLP Vaccine:....................................................... 30 

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8.5.3. 
Other Risks:........................................................................................... 31 
8.5.4. 
Benefits:................................................................................................. 31 
8.6. 
Plan for Use and Storage of Biological Samples ............................................ 31 
8.7. 
Compensation.................................................................................................. 32 
8.8. 
Safety Monitoring ........................................................................................... 32 
8.8.1. 
Protocol Safety Review Team............................................................... 32 
8.8.2. 
Data and Safety Monitoring Board........................................................ 32 
9. 
ADMINISTRATION AND LEGAL OBLIGATIONS............................................ 32 
9.1. 
Protocol Initiation, Amendments and Termination......................................... 32 
9.2. 
Study Documentation and Study Records Retention...................................... 32 
9.3. 
Data Collection and Protocol Monitoring....................................................... 33 
9.3.1. 
Data Capture Methods........................................................................... 33 
9.3.2. 
Source Documents and Access to Source Data/Documents.................. 33 
9.3.3. 
Protocol Monitoring .............................................................................. 33 
9.4. 
Language......................................................................................................... 34 
9.5. 
Policy Regarding Research-Related Injuries .................................................. 34 
9.6. 
Multi-Site Management .................................................................................. 34 
10. REFERENCES ......................................................................................................... 35 
APPENDIX I: 
TEMPLATE INFORMED CONSENT FORMS................................ 39 
APPENDIX II: 
CONTACT INFORMATION............................................................. 45 
APPENDIX III: 
SCHEDULE OF EVALUATIONS ................................................. 47 
APPENDIX IV: 
ASSESSMENT OF RELATIONSHIP TO VACCINE AND 
ADVERSE EVENT SEVERITY GRADING.......................................................... 49 

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ABBREVIATIONS
Abbreviation
Term
AE
adverse event
ALT
alanine aminotransferase
ANSM
French National Agency for Medicines and Health Products Safety
AoU
assessment of understanding
CBC
complete blood count
CDC
Center for Disease Control
CHIKV
Chikungunya virus
CRO
Contract Research Organization
DNA
deoxyribonucleic acid
DSMB
Data and Safety Monitoring Board
ELISA
enzyme-linked immunosorbent assay
EU
European Union
FDA
Food and Drug Administration
GCP
Good Clinical Practices
GMT
geometric mean titers
HIV
human immunodeficiency virus
HLA
human leukocyte antigen
ICH
International Conference on Harmonization
IM
intramuscular
IND
Investigational New Drug
IoR
Investigator of Record / Site Principle Investigator
IRB
Institutional Review Board
ITT
Intent-to-treat
MedDRA®
Medical Dictionary for Regulatory Activities
mITT
Modified intent-to-treat
NIAID
National Institute of Allergy and Infectious Diseases
NIH
National Institutes of Health
NVITAL
NIAID Vaccine Immune T-Cell and Antibody Laboratory
PBMC
peripheral blood mononuclear cells
PBS
phosphate-buffered saline
PCR
polymerase chain reaction
PP
Per-protocol
PSRT
Protocol Safety Review Team
RNA
ribonucleic acid
SAE
serious adverse event
SAP
Statistical Analysis Plan
SUSAR
serious and unexpected suspected adverse reactions
VLP
virus-like particle
VRC
Vaccine Research Center

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PRÉCIS
Protocol 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
Study Design:
This is a multicenter, randomized, placebo-controlled, double-blind 
study to evaluate the safety and immunogenicity of a 2-injection vaccine 
regimen with the Chikungunya virus (CHIKV) virus-like particle 
vaccine (CHIKV VLP, VRC-CHKVLP059-00-VP) in healthy adults. 
The hypothesis is that the vaccine regimen is safe and induces a 
neutralizing antibody response to CHIKV. The primary objectives are to 
evaluate safety and tolerability of a 2-injection investigational vaccine 
regimen of VRC-CHKVLP059-00-VP at 20 mcg compared to placebo in 
healthy adults in CHIKV endemic areas. The secondary objective is to 
evaluate neutralizing antibody response in vaccine recipients. The 
exploratory objectives relate to assessing incidence of CHIKV infection 
in vaccine and placebo recipients, as well as antigen-specific humoral 
and cellular immune responses during the study.
Product Description:
VRC-CHKVLP059-00-VP is an investigational VLP vaccine that 
consists of the E1, E2 and capsid proteins of CHIKV (strain 37997). 
VRC-PBSPLA043-00-VP is sterile phosphate-buffered saline (PBS)
prepared for human injection as a placebo.
Subjects:
Healthy adult subjects ages 18 to 60 years old that reside in CHIKV 
endemic regions. 
Study Plan:
400 subjects stratified by age groups 18-40 and 41-60 years will be 
randomized in a 1:1 ratio to vaccine or placebo.  Subjects will receive 2 
intramuscular (IM) injections via needle and syringe per the study 
schedule below:
Group
Number of 
Subjects
VRC 704 Study Injection Schedule
Day 0
Day 28(+14)
1
200
20 mcg
20 mcg
2
200
PBS
PBS
All injections will be administered IM at 0.5 mL by needle and syringe.
Study Duration:
Subjects will be evaluated at 11 clinical visits during 72 weeks of study 
participation as follows: Day 0 and Weeks 4, 8, 16, 24, 32, 40, 48, 56, 64 
and 72.

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1.
INTRODUCTION 
The Dale and Betty Bumpers Vaccine Research Center (VRC), National Institute of Allergy and 
Infectious Diseases (NIAID), National Institutes of Health (NIH) (Bethesda, MD, USA) is 
dedicated to translating the latest knowledge of disease pathogenesis and immunology into new 
vaccine strategies to provide safe and effective means to prevent and control infectious diseases.
Chikungunya virus (CHIKV) is a mosquito-borne disease causing acute infection associated with 
severe morbidity that can persist for several weeks, months or even years. Since its discovery in 
Tanzania in 1952, outbreaks of CHIKV have occurred most frequently in Africa, Asia and the 
Indian subcontinent. In recent decades, the disease has spread to Europe and the Americas. As 
of January 2015, over 1,135,000 suspected cases of CHIKV and 176 CHIKV-attributable 
deaths have been recorded in the Caribbean islands, Latin American countries and USA [1]. 
There are currently no effective vaccine or therapies against CHIKV. The rapid emergence of 
CHIKV supports the need for a safe and immunogenic vaccine. This protocol is designed as a 
Phase 2 evaluation of the investigational Chikungunya virus virus-like particle vaccine (CHIKV 
VLP), VRC-CHKVLP059-00-VP. This candidate vaccine was evaluated in a Phase 1 study as
safe and well-tolerated and observed to induce neutralizing antibody responses at levels
hypothesized to be protective against CHIKV infection [2].  
1.1.
Chikungunya: Etiology, Disease Course and Epidemiology
CHIKV (genus Alphavirus, family Togaviridae) is an arthropod-borne viral disease with a 
positive, 11.8 kilobase (kb) single-stranded RNA genome encoding structural and non-structural 
proteins [3, 4]. The virus has three distinct clades that share a high percentage of amino acid 
similarity: West African, Central/East/South African, and Asian genotypes [5-7]. 
Initial case reports of CHIKV refer to an outbreak in Tanzania in 1952-53 [8, 9] and early 
outbreaks were geographically limited [10]. Prior to 2013, CHIKV outbreaks were primarily 
detected in regions of Africa, Asia, Europe, and the Indian and Pacific Oceans. Late in 2013, the 
first local transmission of CHIKV was reported in the Americas [11-14]. The virus is 
transmitted through infected mosquitoes, predominantly Aedes aegypti, in sylvatic and human-
mosquito-human cycles [12, 13]. Genetic mutations in viral genome have enabled virus 
transmission through a new host, Aedes albopictus, altering CHIKV epidemiology and driving 
outbreaks in new regions [15-17].
CHIKV infection is associated with severe morbidity lasting 1-2 weeks, with symptoms 
persisting for weeks to months. The incubation period lasts 2-12 days [18]. Acute clinical 
manifestation involves high fever, rash, gastrointestinal complications, conjunctivitis, headache, 
arthralgia, nausea, fatigue and myalgia. The hallmark symptom of the infection, debilitating 
polyarthralgia/arthritis, is present in nearly all cases (>70%) [11, 18, 19]. Onset of alphavirus-
associated arthritis begins within 2-5 days after the infecting mosquito bite, coinciding with 
presence of virus by polymerase chain reaction (PCR) and innate immune responses against 
circulating virus. The timing and onset of arthritis is not consistent with adaptive immune 
responses that occur around day 7-14.  Persistent arthritis (3-13% of cases) has been associated 
with pro-inflammatory cytokines and detectable virus in the joint fluid and cells [20-23].  
CHIKV-associated mortality is low; the majority of fatal cases occur in older populations with 
underlying medical conditions [1, 24]. Though atypical, neurological complications including 
encephalitis and meningoencephalitis have been seen in a growing number of cases [11, 25, 26]. 

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There is currently no vaccine or anti-viral therapy available for the prevention or treatment of 
CHIKV infection. The economic losses and added stress on public health infrastructure 
experienced in areas of CHIKV outbreaks along with heightened potential for global spread 
necessitate vaccine development as a high global priority [2, 10, 27].
1.2.
Rationale for Development of VRC-CHKVLP059-00-VP
CHIKV strains have high amino acid sequence homology and are antigenically related; 
therefore, it is possible to design a vaccine that could be cross-protective against heterologous 
strains [7, 27-29]. Infection with CHIKV induces long-lasting protective immunity. Both 
humoral and cellular immunity are detected in survivors of CHIKV infection, however, their 
relative contribution to protection is unknown [21]. 
Recent changes in the epidemiology and pathogenicity of circulating CHIKV strains prompted 
close attention to genetic changes in the virus [15, 16, 30] and to viral immunobiology [21, 31-
33]. It was noted that persistent chronic inflammation and incapacitating arthralgia/arthritis 
could be observed in some infected patients for months despite a robust immune response [21]. 
Comprehensive study of the production of cytokines, chemokines and growth factors during 
acute CHIKV infection revealed a predominance of type 2 circulating cytokines, and that 
increase in interleukin (IL)-1L-6 and decrease in RANTES (regulated upon activation, normal 
T-cell expressed and secreted) expression were associated with disease severity [33].  
Development of a preventive CHIKV vaccine began in the early 1970s with investigation of 
inactivated vaccine candidates [34, 35]. Formalin-inactivated vaccine was tested in a small 
group of volunteers and reported to be safe and immunogenic [34].  Subsequently, a live-
attenuated vaccine candidate was developed and progressed into Phase 2 clinical trials. The 
attenuated vaccine induced neutralizing antibody by day 28 in 98% of evaluable vaccinees 
(n=57), which persisted at least 12 months in 85% of vaccinees. The vaccine was assessed as 
safe and well-tolerated; reactogenicity reports included transient arthralgia without arthritic signs 
in 8% of vaccinees [36]. Immunologic interference was revealed in sequential administration of 
live attenuated alphavirus vaccines [37]. Additional CHIKV vaccination strategies in preclinical 
and clinical stages include a chimeric alphavirus vaccine candidate, recombinant measles-virus-
based CHIKV vaccine, and a consensus-based DNA vaccine candidate [38-40]. 
The VRC has developed a CHIKV virus-like particle (VLP) candidate vaccine [2, 27]. VLPs are 
multi-protein structures that mimic the organization and conformation of viruses but lack the 
viral genome [41]. Compared to inactivated subunit vaccines, VLPs present conformational viral 
epitopes similar to the authentic virus [42]. VLPs are considered highly immunogenic and are 
known to elicit high neutralizing antibody titers with good durability [43-45]. The FDA has 
approved several prophylactic VLP vaccines including hepatitis B vaccines (Engerix® and 
Recombivax HB®, GlaxoSmithKline and Merck, respectively) and human papilloma virus 
(HPV) vaccines (Cervarix® and Gardasil®, GlaxoSmithKline and Merck, respectively). Several 
other VLP vaccine candidates, such as vaccines for influenza, Norwalk and parvovirus, are in 
pre-clinical testing or Phase 1 studies [41, 42]. 
Selective expression of the CHIKV structural proteins in mammalian cells results in formation of 
VLPs that resemble replication-competent alphavirus particles [27]. Immunization with CHIKV 
VLPs induced antibodies against envelope proteins that neutralized virus in vitro and protected 
against a systemic live virus challenge in non-human primates (NHP). Purified IgG from the 

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CHIKV VLP-immunized monkeys protected immune-deficient mice from a lethal virus 
challenge, suggesting that antibodies are an important component of a protective immune 
response. Preclinical animal studies demonstrate that the VLP vaccine candidate, VRC-
CHKVLP059-00-VP, has the potential to elicit protective immunity in humans.
1.3.
Previous Human Experience with VRC-CHKVLP059-00-VP
VRC-CHKVLP059-00-VP was assessed under VRC 311 (2011-2012), a Phase 1 open-label, 
dose-escalation study to evaluate safety and immunogenicity of the vaccine. Twenty-five (25)
adults, 18-50 years old, received three intramuscular (IM) injections on weeks 0, 4, and 20 via 
needle and syringe in doses of 10 mcg (n=5), 20 mcg (n=10), or 40 mcg (n=10).
All injections were well tolerated with no reported arthralgia or fever after vaccination and no
serious adverse events (SAEs).  Solicited reactogenicity parameters were either none or mild;
36% of vaccinees (n=25) reported mild local reactogenicity and 40% reported mild systemic 
reactogenicity at least once following vaccination [2].  Neutralizing antibodies were detected in 
all subjects by 4 weeks after the second vaccination.  A significant boost occurred after the third 
vaccination in all dose groups. Neutralization titers of vaccine recipients reached levels 
comparable to those reported after natural infection, suggesting a potentially durable protective 
response to the vaccine [2].  The study detected antibodies by ELISA in 80-100% of subjects in 
all three dose groups and geometric mean titers (GMT) were not significantly different between 
the groups except at week 24.  The study also found no significant difference in group GMT 4 
weeks after the second dose compared to 4 weeks after the third dose.
1.4.
Rationale for Study Agent Dose and Schedule 
Based on VRC 311 study results that all three dose levels (10 mcg, 20 mcg, and 40 mcg) were 
safe and well tolerated [2] and all dose levels elicited robust titers of CHIKV neutralizing 
antibodies as well as durable, vaccine-induced antibodies that persisted through to the final study 
visit 6 months after the last dose, VRC-CHKVLP059-00-VP will be evaluated in a 2-injection 
schedule at a dose of 20 mcg. Gaining early information about frequency, magnitude and 
durability of response to a schedule with two vaccinations will be informative to designing future 
Phase 3 efficacy studies.  
1.5.
Assessment of Immunogenicity
In protocol VRC 704, specimens to evaluate immunogenicity will be taken at baseline and at 
specified time points. The primary immunogenicity timepoint is 4 weeks after the second 
injection. Measurements of CHIKV-specific humoral immune responses will be assessed by 
neutralization antibody (NAb) assays [2]. 
ELISA and other exploratory assays to assess for humoral and cellular immune responses may be 
performed with stored samples, depending upon the most efficient use of laboratory resources to 
inform product development. Human leukocyte antigen (HLA) type may be obtained from 
stored samples if needed to assess HLA-class restricted cellular responses.
Research samples for immunogenicity assays will be processed by the NIAID Vaccine Immune 
T Cell and Antibody Laboratory (NVITAL) in Gaithersburg, MD, where many of the 
immunogenicity assays will also be performed. Immunogenicity assays may be performed by 
VRC laboratories in Bethesda, MD, contract laboratories, or by other research collaborators.

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2.
STUDY AGENTS
Study agents are manufactured under Good Manufacturing Practice.
2.1.
VRC-CHKVLP059-00-VP Study Agent
VRC-CHKVLP059-00-VP is a VLP vaccine that consists of CHIKV VLPs composed of the E1, 
E2, and capsid proteins of the CHIKV (strain 37997). VLPs are produced in the VRC293 cells 
using a transient expression system. The production process consists of upstream production 
(cell growth and antigen expression) and downstream purification. In the first step, VRC293 
cells are expanded from the working cell bank until the desired number of cells is obtained. 
Cells are then transfected with the expression plasmid VRC8900 that encodes for CHIKV
structural proteins (capsid, E3, E2, 6K, and E1). The 6K and E3 proteins have not been 
specifically detected in the VLPs of the VRC-CHKVLP059-00-VP candidate. VLPs are 
produced as the secreted product, harvested and clarified; this culture medium is used as the 
starting material for the downstream purification process. Purification includes tangential flow 
filtration, Q-Sepharose column chromatography, diafiltration, and sterile filtration.  Enveloped 
VLPs self-assemble and are released into the culture medium as ~65 nm particles. No 
replication-competent viral genetic material is incorporated in the VLP. After purification, the 
VLPs are diluted into a sucrose-containing citrate buffer, sterile-filtered, filled into single-dose 
glass vials, and stoppered to produce drug product. 
CHIKV VLP drug product is a sterile aqueous buffered solution of CHIKV VLP drug substance 
filled into single dose glass vials at 40±10 mcg/mL. The composition of drug product is 
presented in Table 1. Vials have a nominal fill of 0.8 mL to allow withdrawal of 0.5 mL. More 
details related to vaccine preparation, quality control and preclinical studies performed before the 
candidate vaccine entered Phase 1 study can be found in the Investigator’s Brochure. 
Table 1:
Quantitative Composition of the VRC-CHKVLP059-00-VP
Ingredient
Composition (per 1.0 mL)
Function
Active Substance
CHIKV VLP 
40 mcg
Antigen
Excipients
Sucrose  
74.6 mg
Buffer component
Potassium phosphate (monobasic)
0.5 mg
Buffer component
Potassium phosphate (dibasic)
1.1 mg
Buffer component
Sodium citrate (dihydrate)
7.4 mg
Buffer component
2.2.
VRC-PBSPLA043-00-VP as Placebo
VRC-PBSPLA043-00-VP, a sterile phosphate buffered saline (PBS) is the placebo for the 
CHIKV VLP vaccine.   

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3.
STUDY OBJECTIVES 
3.1.
Primary Objective:

To evaluate the safety and tolerability of VRC-CHKVLP059-00-VP in healthy adults 
that reside in CHIKV endemic areas when administered intramuscularly by needle 
and syringe at a dose of 20 mcg compared to placebo.
3.2.
Secondary Objectives:

To evaluate the immune response to VRC-CHKVLP059-00-VP by neutralization 
assay at 4 weeks after the second 20 mcg dose (Study Week 8).
3.3.
Exploratory Objectives:

To evaluate humoral and cellular responses to VRC-CHKVLP059-00-VP at 
additional time points.  CHIKV-specific responses will be assessed by antibody 
assays that include antigen-specific ELISA and neutralization assay.

To compare incidence rates of CHIKV infection in vaccine and placebo recipients.

Clinical and virus characteristics of infections will also be compared in vaccine and 
placebo recipients.
4.
STUDY DESIGN AND CLINICAL PROCEDURES
This is a Phase 2 multicenter, randomized, placebo-controlled, double-blind study to examine the 
safety and immunogenicity of a 2-injection vaccine regimen (Day 0 and 28) with the CHIKV 
VLP vaccine or PBS placebo in healthy adults.  The hypothesis is that the vaccine regimen is 
safe and induces a neutralizing antibody response to CHIKV.  The study schema is shown in 
Table 2 below.  The expected duration of time on the study per subject is approximately 72 
weeks.
Table 2:
Study Schema
Group
Number of 
Subjects
VRC 704 Study Injection Schedule
Day 0
Day 28(+14)
1
200
20 mcg
20 mcg
2
200
PBS
PBS
All injections will be administered IM at 0.5 mL by needle and syringe.
4.1.
Study Population
The study is designed for the enrollment of healthy adults.  The following eligibility criteria will 
be used.

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4.1.1.
Inclusion Criteria
A subject must meet all of the following criteria:
1. 18 to 60 years old
2. Available for clinical follow-up through Study Week 72
3. Able to provide proof of identity to the satisfaction of the study clinician completing the 
enrollment process
4. Able and willing to complete the informed consent process
5. Willing to donate blood for sample storage to be used for future research
6. ngoodgenerlhelthwthBM40wthoutclncllsgnfcntmedclhstor
and has satisfactorily completed screening
7. Physical examination and laboratory results without clinically significant findings within 
the 56 days prior to enrollment
Laboratory Criteria within 56 days prior to enrollment:
8. Hemoglobin either within institutional normal limits or accompanied by site physician 
approval as consistent with healthy adult status
9. White blood cells either within institutional normal range or accompanied by site 
physician approval as consistent with healthy adult status 
10. Platelets = 125,000 – 500,000/mm3
11. Alnnemnotrnsferse(ALT!1"2$xupperlmtofnorml('L(!
12. Serumcretnne1.1 x ULN based on site institutional normal range
13. Negative result on an HIV test that meets local standards for identification of HIV 
infection
14. Negative result on the CHIKV screening antibody assay.
Criteria applicable to women of childbearing potential:
15. Negative human chorionic gonadotropin pregnancy test (urine or serum) on day of 
enrollment 
16. Agree to use an effective means of birth control from 21 days prior to enrollment through 
12 weeks after the last study injection
4.1.2.
Exclusion Criteria
A subject will be excluded if one or more of the following conditions apply:
Women Specific:
1. Planning to become pregnant during the 16 weeks after enrollment in the study
Subject has received any of the following substances:
2. Systemic immunosuppressive medications within 2 weeks prior to enrollment

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3. Blood products within 16 weeks prior to enrollment
4. Immunoglobulin within 8 weeks prior to enrollment
5. Prior vaccinations with an  investigational CHIKV vaccine
6. Investigational research agents within 4 weeks prior to enrollment
7. Any vaccination within 2 weeks prior to enrollment
8. Current anti-TB prophylaxis or therapy
Subject has a history of any of the following clinically significant conditions:
9. A history of immune-mediated or clinically significant arthritis 
10. Serious reactions to vaccines that preclude receipt of study injections as determined by the 
investigator
11. Hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema
12. Asthma that is unstable or required emergent care, urgent care, hospitalization or 
intubation during the past two years or that is expected to require the use of oral or 
intravenous corticosteroids 
13. Diabetes mellitus (type I or II), with the exception of gestational diabetes
14. Idiopathic urticaria within the past year
15. Bleeding disorder diagnosed by a doctor (e.g. factor deficiency, coagulopathy, or platelet 
disorder requiring special precautions) or significant bruising or bleeding difficulties with 
IM injections or blood draws
16. Malignancy that is active or history of a malignancy that is likely to recur during the 
period of the study
17. Seizure in the past 3 years or treatment for a seizure disorder within the last 3 years
18. Asplenia, functional asplenia or any condition resulting in the absence or removal of the 
spleen
19. Psychiatric condition that may preclude compliance with the protocol; past or present 
psychoses; or a history of suicide plan or attempt within the five years prior to enrollment
20. Any medical or social condition that, in the judgment of the investigator, is a 
contraindication to protocol participation or impairs a volunteer’s ability to give informed 
consent
4.2.
Study Schedule 
The study schedule is presented in the Schedule of Evaluations table in Appendix III.
During or following any visit, if there is any concern about the well-being of the subject, the 
study site will conduct appropriate medical evaluations by history, physical, laboratory or other 
indicated testing. 

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4.2.1.
Pre-enrollment
Potential study subjects who verbally agree to discuss their medical history may complete a 
scripted interview questionnaire by telephone or in person that covers protocol inclusion and 
exclusion criteria that are based on key self-reported history information to identify potential 
study volunteers. 
4.2.2.
Screening Visit(s)
Screening for this study may be completed through a general screening protocol after signing a 
site-specific IRB-approved consent form to be screened or through screening consent language 
incorporated into the VRC 704-specific consent form.  A screening segment for the study will be 
included in data collection to provide information on reasons for non-enrollment to begin study 
injections.  Evaluations will be done according to eligibility criteria and clinical assessment at 
screening. Screening evaluations for specific eligibility criteria must be completed within the 
time interval specified prior to enrollment, but may be repeated as needed to confirm eligibility.  
Samples collected during screening may be used for assay validation and site proficiency testing.  
The Assessment of Understanding (AoU) is a tool to help staff identify topics which may not be 
fully understood by study volunteers.  As part of the screening process, the AoU should be 
completed and incorrect answers discussed with the subject. The AoU may be performed one 
time or more than one time as needed with a given subject.  The timing of when to conduct the 
AoU is adaptable to the practices that work best for each clinical site, however it must be done 
within the time frame starting after initiation of screening until just prior to or during enrollment 
(prior to vaccination) on Day 0.  Each site is encouraged to develop a site standard among their 
own staff for consistency of site practices in the conduct of the consent process and deployment 
of the AoU as part of the consent process.  A subject may be re-screened prior to enrollment if 
there is a suspected change in health status.
4.2.3.
Enrollment Visit
VRC 704 enrollment is defined as the day of first study injection and is designated Day 0. 
Pregnancy test results must be confirmed as negative for women of reproductive potential on day 
of enrollment prior to the study injection.  Protocol-specific eligibility is reviewed as part of the 
enrollment process, but eligibility evaluations conducted during a prior screening visit within the 
specified window are routinely used for eligibility.  Day 0 evaluations and medical history prior 
to the first injection are the baseline for subsequent safety assessments, except that for any 
evaluation not performed on Day 0, the baseline will be the screening evaluation.  
4.2.4.
Administration of Injections
All Day 0 injections will be administered in a blinded manner according to the randomization 
assignment. Neither the clinic staff nor the subjects will know whether the injection is VRC-
CHKVLP059-00-VP or PBS placebo.  
Prior to the first study injection, staff should recheck eligibility to ensure the volunteer is still 
eligible. 
Before each injection, clinic staff must collect research and safety blood and vital signs on the 
subject.  

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All injections will be administered IM into the upper arm deltoid muscle by needle and syringe.
It is recommended, but not required, to administer the first injection into the non-dominant arm
and to alternate arms for the second injection.  When choosing an arm for the injection, clinicians 
should consider whether there is an arm injury, local skin problem or significant tattoo that 
precludes administering the injection or that will interfere with evaluating the arm after injection.
Following the study injection, the subject will remain in the clinic for observation for at least 15
minutes. After 15 minutes, blood pressure and pulse will be taken and the injection site will be 
inspected for evidence of local reaction before the subject leaves the clinic.  In keeping with 
good medical practice, acute medical care will be provided to subjects for any immediate 
reactions to a study injection. 
4.2.5.
7-Day Diary Card and Follow-Up 
Subjects will be given a “Diary Card” to use as a memory aid, on which to record the solicited 
signs and symptoms daily for 7 days following each injection.  If the solicited parameters are 
recorded directly by the subject through an electronic database, the subject’s electronic record 
will be the source for these data.  The site may use a paper diary card as a source document or 
clinician notes obtained by telephone interview as the source for the information recorded in the 
study database.  The solicited signs and symptoms on the diary card will include the following 
parameters: pain/tenderness at injection site, largest diameters of redness (erythema) and 
swelling (induration at injection site, highest measured temperature per day, unusually 
tired/feeling unwell, muscles aches (other than at injection site), arthralgia (joint pain), headache, 
chills, and nausea. 
At least one contact at about 7 days after each study injection will be conducted to complete the 
review of solicited diary card information.  Subjects will be asked to contact the clinic at any 
time following each injection if they have any concerning signs or symptoms.  Events that will 
requreclnclevlutonncludershurtcrrthrlgfeverof3-"$./(0rde 2) or higher 
lasting greater than 24 hours, or significant impairment in the activities of daily living.  
Additionally, other clinical concerns may prompt a study visit based on the judgment of a study 
clinician. 
4.2.6.
Study Visits and Sample Collection 
The schedule of visits, permitted windows for completing the visits, and evaluations performed 
at each visit is shown in the table in Appendix III.  After Day 0, deviations from the visit 
windows in completing study visits are discouraged and will be recorded as protocol deviations, 
but are permitted, at the discretion of the PI (or designee).
4.3.
Evaluation of Chikungunya Infection during the Study
4.3.1.
Chikungunya Infection Diagnostic Visit
Throughout the study if a subject reports signs and symptoms of CHIKV infection, blood 
samples should be collected for diagnostic testing by virus detection (e.g., PCR) by the 
designated diagnostic laboratories.  This may occur during a scheduled study visit or 
unscheduled visits may be conducted to complete the testing needed.  The site will be informed 
of results as soon as possible whether the subject has a CHIKV diagnosis and should share this 
information with the subject. To prevent unblinding, the site will remind subjects that all testing 

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for CHIKV infection should only be conducted as part of the study.  Unless directed by the study 
Sponsor, sites should not attempt to run the CHIKV diagnostic kit that was used to screen 
subjects for eligibility because vaccine-induced antibodies may confound this test; the diagnostic 
laboratories will perform the testing according to a specified plan for case identification that will 
not confuse vaccine-induced antibodies with infection.  Sites and the diagnostic laboratories may 
perform tests for other pathogens of concern.  Cases of CHIKV will be recorded on the CHIKV 
endpoint form.  Refer to the Manual of Procedures for instructions on documenting cases.
Repeat testing may need to be performed to confirm or to follow the course of an infection.
4.3.2.
Clinical Management and Follow-Up of Chikungunya Infection 
There is no curative treatment for CHIKV infections. However, VRC 704 study sites will have 
plans, based on CDC recommendations, by which subjects will have access to clinical care and 
management of CHIKV infection that can be implemented in parallel to VRC 704.  Study sites 
will document all signs and symptoms of infection and clinical care.
Co-enrollment of a CHIKV-infected study participant in a concurrent study of treatment and 
management of CHIKV infection is permitted with the approval of the Protocol Chair (or 
designee).  Treatment procedures and co-enrollments in treatment studies will be documented in 
the study database and available to the Protocol Safety Review Team (PSRT) through study 
reports. During the course of the study if a subject wants to enroll into other protocols, site staff 
should seek prior approval from the PSRT.
With the study participant’s permission, the results of diagnostic testing and other evaluations 
conducted as part of the VRC 704 study may be shared with clinicians providing the medical 
care in order to prevent the need for participants to undergo additional blood draws or repeat 
testing needed for general health care management. Sites will consider blood draws performed 
for clinical care or co-enrollment studies when collecting research samples to avoid exceeding 
allowable blood draw limits.
4.4.
Concomitant Medications and Procedures
Current concomitant medications are recorded in the study database at enrollment. Concomitant 
medications are updated in the study database if there is an occurrence of an adverse event (AE)
that requires expedited reporting.  If it will not endanger a subject’s health, non-investigational 
vaccines should not be administered 14 days before or until at least 28 days after a study 
injection. Licensed vaccines received by the subject within 4 weeks before the first study 
injection administration and 4 weeks after last study injection will be recorded in the study 
database.  Otherwise, a record of concomitant medication changes throughout the study will not 
be recorded in the study database.   
4.5.
Criteria for Discontinuing Subject Participation  
4.5.1.
Discontinuation of Study Injections
A subject may be discontinued from receiving study injections for the following reasons: 

Pregnancy;

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Grade 3 AE assessed as related to a study injection (with the exception that self-
limited Grade 3 solicited reactogenicity does not require discontinuation of study 
injections);

Grade 4 AE assessed as related to a study injection; 

Immediate hypersensitivity reaction associated with a study injection;

CHIKV infection or other intercurrent illness that is not expected to resolve prior to 
the scheduled study injection assessed by study clinician to require withdrawal from 
the injection schedule; 

Treatment with systemic glucocorticoids (e.g., prednisone or other glucocorticoid) or 
other immunomodulators (other than nonsteroidal anti-inflammatory drugs 
[NSAIDs]), with the exception that, study injection may continue per investigator 
discretion if the next one occurs at least 2 weeks following completion of 
glucocorticoid treatment;

The study PI assesses that it is not in the best interest of the subject to continue on the 
injection schedule.  
4.5.2.
Discontinuation from Protocol Participation
A subject may be discontinued from protocol participation for the following reasons: 

Subject voluntarily withdraws;

Subject develops a medical condition that is a contraindication to continuing study 
participation;

The Investigational New Drug (IND) sponsor or regulatory authorities stop the 
protocol; 

The study PI assesses that it is not in the best interest of the subject to continue 
participation in the study or that the subject’s compliance with the study is not 
sufficient. 
4.6.
Criteria for Pausing the Study 
The IoR for each site and IND sponsor will closely monitor and analyze study data as they 
become available and will make determinations regarding the presence and severity of AEs.  The 
administration of study injections and new enrollments will be paused and the IND Sponsor will 
be promptly notified according to the following criteria: 
One (or more) subject experience a SAE assessed by the IND Sponsor as related to study 
injection.
Two (or more) subjects experience the same Grade 4 unsolicited AE assessed by the IND 
Sponsor as related to the study injection. 
Plan for Review of Pauses and Resuming Rules:  
The IND Sponsor, with participation by the PSRT, will consult with the DSMB to conduct the 
review and make the decision to resume or close the study. As part of the pause review, the 

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reviewers will also advise on whether the study needs to be paused again for any subsequent AEs
of the same type.
The study injections and enrollments would resume only if review of the AEs that caused the 
pause resulted in a recommendation to permit further study injections and study enrollments.  
When indicated, safety data reports and changes in study status will be submitted to relevant 
regulatory authorities including the IRB in accordance with Section 5.4 and institutional policy. 
5.
SAFETY AND ADVERSE EVENTS
5.1.
Adverse Events
5.1.1.
Adverse Event Definition 
An adverse event (AE) is any untoward or unfavorable medical occurrence in a human subject, 
including any abnormal sign (e.g., abnormal physical exam or laboratory finding), symptom, or 
disease temporally associated with the use of study treatment, whether or not considered related 
to the study treatment. 
5.1.2.
Adverse Event Reporting in the Study Database
The following guidelines will be used to determine whether or not an AE is recorded in the study 
database. 
Each AE will be graded according to the table for grading severity of AEs (see Appendix IV).  
Solicited AEs will be recorded in the study database separately with data collection for 7 days 
after both the first and second study injections as detailed in Section 4.2.4; without the collection 
of attribution assessments. All unsolicited AEs will be recorded in the study database from 
receipt of first study injection through 4 weeks after the last study injection administered. At 
subsequent follow-up visits, only SAEs (as defined in Section 5.2), new chronic medical 
conditions, and CHIKV cases will be recorded through the last study visit. Laboratory 
confirmed cases of CHIKV will be recorded on a CHIKV endpoints form rather than on an AE
form without an attribution assessment.
5.2.
Serious Adverse Events
5.2.1.
Serious Adverse Event Definition
The term “Serious Adverse Event” (SAE) is defined in the 21 CFR 312.32 in terms of the   
following outcomes:  Death, a life-threatening AE, inpatient hospitalization or prolongation of 
existing hospitalization, a persistent or significant incapacity or substantial disruption of the 
ability to conduct normal life functions, or a congenital anomaly/birth defect. Important medical 
events that may not result in death, be life-threatening, or require hospitalization may be 
considered serious when, based upon appropriate medical judgment, they may jeopardize the 
patient or subject and may require medical or surgical intervention to prevent one of the 
outcomes listed in this definition. Examples of such medical events include allergic 
bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias 

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or convulsions that do not result in inpatient hospitalization, or the development of drug 
dependency or drug abuse.”
An SAE will be considered "life-threatening" if, in the view of either the investigator or sponsor, 
its occurrence places the patient or subject at immediate risk of death. It does not include an AE
or suspected adverse reaction that, had it occurred in a more severe form, might have caused 
death. 
5.2.2.
Reporting Serious Adverse Events to the IND Sponsor 
AEs that meet SAE Reporting Requirements must be reported and submitted by the clinical site 
on an expedited basis to the IND Sponsor, VRC, NIAID, NIH, according to sponsor guidelines 
as follows: 

death

life-threatening

results in persistent or significant disability/incapacity

requires unplanned inpatient hospitalization or prolongation of existing 
hospitalization

is a congenital anomaly/birth defect in the offspring of a study subject

is an important medical event that may jeopardize the patient or may require 
intervention to prevent one of the other outcomes listed above
In addition, any event, regardless of severity, which in the judgment of a site investigator 
represents a serious AE, may be reported on an expedited basis.
A site investigator will communicate an initial SAE report within 3 days of site awareness of 
occurrence to VRC (IND Sponsor) through the communication methods provided by the CRO.
Any SAE entered into the study database will generate automatic email notification to the VRC
Medical Officer. This email notification and/or a written report by the study site will be sent to 
the attention of VRC704team@nih.gov within 3 working days in order for the sponsor to comply 
with regulations mandating sponsor notification of expedited SAEs to the U.S. FDA.   
The investigator must submit additional information as it becomes available. Personal 
identifying information about the subject will be removed by the site from SAE case reports 
before submission to the IND Sponsor.
5.2.2.1
Regulations Applicable to the French Study Sites Only
This section applies only to sites in Martinique and Guadeloupe who follow regulatory oversight 
by the French National Agency for Medicines and Health Products Safety (ANSM).
A site investigator will communicate an initial SAE report within 24 hours of site awareness of 
occurrence to: 

VRC (IND Sponsor) through the communication methods provided by the IND 
Sponsor, and

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The legal representative of the sponsor in the European Union (EU) through the 
communication method provided by him/her.
5.2.3.
IND Sponsor Reporting to the FDA
It is the responsibility of the IND Sponsor to make the determination of which SAEs are “serious 
and unexpected suspected adverse reactions” (SUSARs) as defined in 21 CFR 312.32.

Suspected adverse reaction means any AE for which there is a reasonable possibility 
that the drug caused the AE.

Unexpected Adverse Event means an AE that is not listed in the Investigator’s 
Brochure or is not listed at the specificity or severity that has been observed.  
All SUSARs, as determined by the IND Sponsor, will be reported to FDA as IND Safety 
Reports; IND Safety Reports will be provided to all participating Investigators by the IND 
Sponsor or delegated CRO. 
The IND Sponsor will also submit an IND Annual Report of the progress of the investigation to 
the FDA as defined in 21 CFR 312.33.
5.3.
Reporting to Site IRBs and Relevant Regulatory Agencies
Each site IoR is responsible for reporting AEs, unanticipated problems, protocol deviations and 
non-compliance to the site IRB and other relevant country regulatory authorities in accordance 
with their institutional and country requirements for reporting.  
Site-specific data reports will be made available through the data management contractor to 
facilitate expedited and continuing review reporting requirements.  
Only the IND Sponsor will submit reports to the U.S. FDA. If the IND Sponsor submits an IND 
Safety Report to the U.S. FDA, these will be provided to all sites with instruction as to whether 
or not any actions need to be taken, such as amendment of consent.  Investigators must maintain 
documentation of compliance with actions required for IND safety reports.
5.3.1.
Regulations Applicable to the French Study Sites Only
This section applies only to sites in Martinique and Guadeloupe who follow regulatory oversight 
by the French ANSM. 
The sponsor will be responsible for reporting all Serious Adverse Reactions (SARs) to the 
ANSM and the Ethics Committee (CPP SOOM 4) in accordance with the local laws and 
regulations requirement (L. 1123-10, R. 1123-38 and following of the Public Health Code). In 
addition, SUSARs that are reported to the FDA as IND Safety Reports will be reported to the 
ANSM and the Ethics Committee (CPP SOOM 4) with 7 days or 15 days depending on the 
severity (according to Article R. 1123-47 of the Public Health Code).  The legal representative of 
the sponsor in the EU will inform the ANSM of VRC 704 study pauses and the decision to 
resume or close the study following a study pause.
5.4.
Data and Safety Monitoring Board 
The PSRT (see Section 8.8), will have the primary responsibility for the real-time oversight of 
safety data and SAE reviews.  The NIAID Intramural Data and Safety Monitoring Board 

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(DSMB) will review cumulative study data twice per year to evaluate safety, study conduct, and 
scientific validity and integrity of the trial and will be consulted if there is a study pause as 
required by Section 4.6 of the protocol.  
The DSMB members will assess the timeliness, completeness, and accuracy of the data 
submitted to them for review and whether the data are sufficient for evaluation of the safety and 
welfare of study participants.  The DSMB Executive Secretary will be provided with a sealed 
copy of the randomization codes needed for the DSMB review of the safety data.  The DSMB 
will also assess the performance of overall study operations and any other relevant issues, as 
necessary.  Following each review, the DSMB will provide its recommendations to the study 
sponsor, including whether the study should continue without change, be modified, or be 
terminated.
6.
STATISTICAL CONSIDERATIONS AND SAMPLE ANALYSIS
6.1.
Overview
This study is a multi-center trial to assess the safety and immunogenicity of a 2-injection 
schedule of VRC-CHKVLP059-00-VP or PBS placebo injections at Days 0 and 28.  The primary 
objective relates to safety and tolerability; the secondary and exploratory objectives concern 
immunogenicity and incidence of Chikungunya infection.  
6.2.
Endpoints
6.2.1.
Safety
Assessment of product safety will include clinical observation and monitoring of hematological 
and chemical parameters.  Reactogenicity will be closely monitored for 7 days after injection and 
safety evaluated by clinical visits through the study duration of 72 weeks.
The following parameters will be assessed:

Local reactogenicity signs and symptoms for 7 days after each injection

Systemic reactogenicity signs and symptoms for 7 days after each injection

Laboratory measures of safety through 4 weeks after last injection

Adverse events through 4 weeks after last injection

Serious adverse events and new chronic medical conditions throughout the study 

CHIKV infection events throughout the study
6.2.2.
Immunogenicity
The principle immunogenicity endpoints are measured at Week 0 and 8 by neutralization assay. 
Exploratory immunogenicity endpoints are measured at Week 4, 16, 24, 48, and 72 by 
neutralization assay, ELISA, and other exploratory research tests.

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6.3.
Sample Size and Accrual
The study design is to enroll 400 healthy adult participants ages 18 to 60 that reside in CHIKV 
endemic areas. Randomization will equally allocate subjects to vaccine or placebo schedules
with stratification by ages 18-40 and 41-60 years.  The enrollment plan does not include 
provision for replacing subjects with incomplete injections or visit schedules. 
Enrollments may occur rapidly at more than one site. The data management CRO will carefully 
monitor study enrollment and notify all sites and the VRC Protocol Chair when the completion 
of enrollment is near. 
The sample size for this study was not selected to test a formal null hypothesis.  It reflects the 
number of vaccine doses that are available for the study and the desire to gain maximal 
information for the conduct of possible Phase 3 follow on trials.  This latter consideration is 
particularly important as reliable estimates of CHIKV incidence in the target population, vaccine 
effects and logistical considerations in implementing future trials must be understood prior to a 
Phase III trial.  Nevertheless, power computations are provided below as an indication of the 
probability of observing results of interest.
There are not good data to estimate the loss to follow-up rate for this study.  The power 
calculations assume a 10% loss in both groups for the primary and secondary endpoints.  Loss to 
follow-up for the exploratory outcomes are likely to be larger but are not included as power 
calculations are not included for these outcomes.
6.3.1.
Power Calculations for Evaluation of Safety
The goal of the safety evaluation for this study is to identify safety concerns associated with 
injections of the investigational vaccine. Two sample size calculations for safety are expressed 
in terms of two approaches, within group and comparing two groups.
1. The ability to detect safety or reactogenicity events within each injection group:
The ability of the study to identify safety events may be expressed in terms of the probability of 
observing one or more event of interest (e.g., AEs) assuming a range of “true” but unknown 
event rates.  The power to observe one or more event in a single group of 180 subjects is 83.62% 
when the true rate is 1.0% and 97.37% when the true rate is 2.0% (Table 3).
Table 3:
Probability of Observing One or More Safety Events within a Group (n=180)
True Event Rate
Pr (1 or more events)
0.01%
1.78%
0.10%
16.48%
0.33%
45.17%
0.50%
59.43%
1.00%
83.62%
2.00%
97.37%
1. The minimum detectable difference in safety event (e.g., AEs) rates for comparing  two 
injection groups using Fisher’s exact test:

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Safety event rates may vary considerably with the type of event considered therefore a wide 
range of possible rates is considered for comparison by vaccine group (Table 4).
Table 4:
Minimum Detectable Differences in Event Rates for Power = 80% or 90% 
Assuming Type I Two-Tail Error Rate of 5% (n=180 per Group)
Power
Assumed Event Rate in 
Group 1
(n=180)
Minimum Detectable Event Rate 
Group 2
(n=180)
Difference in Rates
80%
0.1%
5.5%
5.4%
1.0%
7.5%
6.5%
5.0%
14.2%
9.2%
25%
39.3%
14.3%
90%
0.1%
6.9%
6.8%
1.0%
8.9%
7.9%
5.0%
16.0%
11.0%
25%
41.6%
16.6%
6.3.2.
Power Calculations for Evaluation of Immune Responses
A secondary objective is to evaluate the humoral immunogenicity of VRC-CHKVLP059-00-VP 
by neutralization assay at 4 weeks after the final 20 mcg dose (Week 8).  Vaccine specific 
neutralization antibodies are not anticipated in the non-vaccinated group.  Therefore, direct 
comparison between the active and placebo group is of minimal value in assessing sample size.  
Preliminary Phase 1 neutralization data suggest that neutralization results at the visit with peak 
response are log-normally distributed with a mean and standard deviation on the log-scale of
7.41 and 0.67 respectively.  This standard deviation is rounded up to 0.70 and two more 
conservative options of 1.0 and 1.5 result in 95% confidence intervals (CI) for GMT (Table 5).
Table 5:
95% Confidence Interval for GMT Neutralization among Vaccinees at Time of 
Peak Response (n=180 per Group)
Assume Standard Deviation on 
Log Scale
95% CI for GMT Neutralization 
Among Vaccinees (n=180) at Time 
of Peak Response
0.70
(1490.7, 1831.7)
1.0
(1426.6, 1914.1)
1.5
(1324.8, 2061.1)
The study is not designed to compare two groups defined by baseline covariates such as gender 
or age strata.  However, the following table is included to provide a sense of the power available 
for such comparisons.  The simple case of two groups (e.g., male and female), assuming equal 
participation (i.e., 90 subjects for each gender-vaccine group), is given in Table 6 for comparing 
response rates.
Table 6:
Detectable Geometric Mean Ratio between Two Groups for Power = 80% or 
90% Assuming Type I Two-Tail Error Rate of 5% (n=90 per Group)
Power
Standard Deviation
Detectable

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on Log Scale
Geometric Mean Ratio
(n=90 per group)
80%
0.7
1.34
1.0
1.52
1.5
1.88
90%
0.7
1.40
1.0
1.63
1.5
2.08
6.4.
Statistical Analysis 
Study enrollment is defined in this protocol as being randomized and receiving the first study 
injection. All enrolled subjects will receive at least one injection and therefore will provide some 
safety data. The safety population will include all enrolled subjects, summarized according to 
the actual vaccination received.
The Intent-to-treat (ITT) population will include all enrolled subjects, analyzed according to the 
randomized vaccine. The Per Protocol (PP) analyses will include all subjects receiving two 
vaccinations within window as assigned by the randomization schedule, and not experiencing 
any other major protocol deviations prior to their Week 8visit.  The PP analyses will also include 
subjects determined to be CHIKV infected prior to the receipt of their scheduled second 
vaccination and not experiencing any other major protocol deviations prior to their sate of 
infection.  Subjects will be censored from the immunogenicity analysis following CHIKV
infection. The Modified intent-to-treat (mITT) analyses will include all enrolled subjects with 
evaluable immunogenicity data at their week 8 visit, without exclusions for protocol deviations 
or censoring for CHIKV infection.  Additional cohorts may be defined in the Statistical Analysis 
Plan (SAP).
No formal multiple comparison adjustments will be employed.  Imputation of missing values is 
not planned.  They may be implemented for secondary or tertiary outcomes if supported by the 
data and if sufficient consequence to justify their inclusion.  Analysis variables include baseline, 
safety, reactogenicity, and immunogenicity variables for primary and secondary objective 
analyses, respectively.  Exploratory analyses will estimate CHIKV infection rates, and evaluate 
additional immunogenicity assays.
In general, descriptive statistics by vaccine group will be tabulated for all variables of interest, 
stratified by age as is appropriate.  This will include point estimates (mean, geometric mean, 
median or proportions) and their respective 95% CI or percentile spread.  Formal comparisons 
will use standard methods, contingency tables for categorical variables, t-tests or non-parametric 
analogs for comparing means or geometric means, logistic regression and analysis of covariance 
for model discrete and continuous variables respectively.
6.4.1.
Baseline Demographics
Baseline characteristics including demographics and laboratory measurements will be 
summarized by vaccine group and stratum.

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6.4.2.
Safety Analysis
Reactogenicity:  The number and percentage of subjects experiencing each type of 
reactogenicity sign or symptom will be tabulated by severity.  For a given sign or symptom, each 
subject’s reactogenicity will be counted once under the maximum severity for all assessments.
Adverse Events:  AEs will be coded into Medical Dictionary for Regulatory Activities 
(MedDRA) preferred terms. The number and percentage of subjects experiencing each specific 
AE will be tabulated by severity and relationship to treatment. For the calculations in these 
tables, each subject’s AE will be counted once under the maximum severity or strongest 
recorded causal relationship to treatment.
A complete listing of AEs for each subject will provide details including severity, relationship to 
treatment, onset, duration and outcome.
Safety Laboratory Values:  Safety laboratory values will be summarized using shift tables to 
compare baseline and follow-up values.  Shift tables will be analyzed using Generalize 
Estimating Equations to account for the longitudinal nature of these data.  The mean change from 
baseline along with 95% confidence interval at each time point measured in the study will be 
computed. Boxplots of safety laboratory values will be generated for baseline values and for 
values measured during the course of the study. Each boxplot will show the 1st quartile, the 
median, and the 3rd quartile, with values smaller than the 1st quartile or larger than the 3rd
quartiles plotted as outliers. If appropriate, horizontal lines representing boundaries for abnormal 
values will be plotted.
6.4.3.
Analysis of Immune Responses
Immunogenicity will be analyzed for a variety of cohorts defined above, and specified in the 
SAP.  At minimum these may include ITT, PP, and mITT cohorts.  Assay results will be 
examined to determine if their distributions should be analyzed as normal, lognormal, nominal or 
categorical.  It may also be appropriate to dichotomize the data into “responders” and” non-
responders”.  Immunogenicity data will be analyzed at each time point where such data is 
collected.  Longitudinal methods will be used to estimate the nature and extent of immune 
response decay over time.
6.4.4.
Analysis of Chikungunya Incidence
Incidence rates for confirmed CHIKV cases will be described by vaccine group by age stratum 
and aggregating and by combining age strata.  Results will be treated both as dichotomous 
(infection, no infection) and as a time to event (infection) variables. Time to event will be based 
on the date of blood sample with the first positive laboratory test indicating CHIKV infection. 
For each approach, infection rates in each treatment arm and vaccine efficacy along with their 
corresponding 95% CI will be computed.  Efficacy for dichotomized data will be computed by a 
simple conversion of the relative risk to efficacy.  Time to infection data, accounting for 
censoring, will be described using Kaplan Meir curves and efficacy computed using a Cox 
proportional hazards model.
Analyses of CHIKV infections are exploratory.  A number of definitions of incident cases and 
therefore efficacy will be considered.  Given the exploratory nature of these analyses, no order of 
primacy will be defined.

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Efficacy will include all cases using 2 exploratory alternatives for case inclusion:
1. all infections post vaccination 1 (Day 0),
2. all infections post vaccination 2,
Subjects not receiving vaccination 2 will be included in definition 1.  The SAP will provide any 
necessary additional specificity and/or cohort definitions such as discussed at the beginning of 
section 6.4.
6.4.5.
Interim Analyses
Independent Safety Reviews:  The PSRT will review safety data routinely throughout the 
study. The study will utilize both electronic database features and reviews by designated safety 
review personnel to identify in a timely manner if any of the safety pause rules of the study are 
met. The NIAID Intramural DSMB will provide an independent safety review at scheduled 
intervals to coincide with their biannual meeting schedule. 
In addition, the two study groups will be compared for safety, immune responses and incidence 
rates at 6 and 12 months after the study is closed to accrual.  All subjects are expected to be 
enrolled by 8 months after the study opens to accrual.  These analyses will not be used for early 
trial termination.  The 6 and 12 months reviews will be used to obtain critical data to be used in 
the event that circumstances external to the trial require a rapid initiation of a follow-up study.  
Therefore no p-value adjustments will be made for interim data analyses.
Immunogenicity Review:  An interim analysis of immunogenicity data will be performed after 
all assays up to and including Week 8 have been completed on all participants.  Reports will be 
provided to the PI and other key investigators solely for the purpose of informing future trial-
related decisions in a timely manner.  The results will remain confidential and should in no way 
influence the conduct of the VRC 704 trial in terms of early termination or later safety or 
immunogenicity endpoint assessments.
6.4.6.
Randomization of Treatment Assignments and Unblinding Criteria 
Randomizations will be done online using an electronic randomization system. The 
randomization code will be prepared by the Protocol Statistician and included in the enrollment 
module for the trial. The randomization code will link to the treatment assignment. To decrease 
the potential for subject dropouts during the period between randomization and initial injection, 
the electronic data system will assign each subject a randomization code after the eligibility to 
begin Day 0 study injections has been entered into the system. 
For each clinical site, randomization will be 1:1 allocation within each stratum to either the 
CHIKV VLP vaccine or PBS placebo. Manual back-up procedures and instructions will be 
provided for use in the event that the site temporarily loses access to the Internet or the online 
enrollment system is unavailable to a study site.
If an individual is screened but does not enroll into the clinical trial, screening records will be 
kept to document the reason the individual did not enroll. 
The injections will be prepared by an unblinded site pharmacist or otherwise qualified personnel 
who will not be involved in any subject assessments and who will not discuss randomizations 
with study clinicians. The subjects, the study personnel who perform study injections and 

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assessments, data entry personnel at the sites, and laboratory personnel performing immunologic 
assays will be blinded to the treatment assignment of all injections. Subject study injection 
assignments will be provided to the site IoR at completion of the study for communication to the 
study participant.  The DSMB may receive data in aggregate and presented by treatment group, 
but without the treatment group identified. The DSMB may be unblinded to individual study 
treatment assignments, as needed, to adequately assess safety issues.
If necessary, the IoR (or designee) and Protocol Chair may agree that management of an AE
requires emergency unblinding of an individual subject’s assignment. A designated individual at 
each site will be provided with a code list for emergency unblinding purposes, which will be kept 
in a secure place. This will be documented as a protocol deviation and the Protocol Statistician, 
the site IRB, and the DSMB will be notified that an early unblinding has occurred and provided 
with a statement explaining the medical necessity for the early unblinding.
7.
PHARMACY AND INJECTION ADMINISTRATION 
PROCEDURES
7.1.
Study Agents
This study includes one investigational vaccine and one placebo for the investigational vaccine, 
as follows:

VRC-CHIKVLP059-00-VP (CHIKV VLP vaccine), 40±10 mcg/mL in a formulation 
buffer filled to a volume of 0.8 mL vaccine in a 3 mL glass vial. Vials contain a clear 
to slightly hazy solution with some small white translucent particles that may be 
visible, which is an isotonic, sterile solution. 

VRC-PBSPLA043-00-VP, phosphate buffered saline (PBS) as placebo control for the 
CHIKV VLP vaccine filled to a volume of 1.2 mL in a 3 mL glass vial. Vials contain
a clear colorless isotonic sterile solution at pH 7.2. 
The CHIKV VLP vaccine and PBS are prepared under good manufacturing practice by the VRC 
VPP and must meet lot release specifications prior to administration for use in the clinical study.  
The investigational study agents may only be shipped to the site pharmacy when the protocol is 
IRB-approved at the study site. Vials are shipped using appropriate shipping configurations.  
7.2.
Study Agent Presentation, Stability and Storage
7.2.1.
Labels
At the time of delivery of the study agent to the pharmacy, the labels for study agents VRC-
CHIKVLP059-00-VP and VRC-PBSPLA043-00-VP will have specific product information 
(e.g., part number, lot number, fill volume, storage temperature) included on the product vial 
labels. The labels will contain an Investigational Use Statement (“Caution: New Drug – Limited 
by Federal Law to Investigational Use”) and manufacturer information.

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7.2.2.
Storage
VRC-CHKVLP059-00-VP: Vials of vaccine are stored until use at -45C to -10oC in a qualified, 
continuously monitored, temperature-controlled freezer. Temperature excursions that are outside 
of the normal allowance for the storage device will be reported per pharmacy guidelines. The 
excursion must be evaluated and investigated and action must be taken to restore and maintain 
the desired temperature limits.  Pending the outcome of the investigation, the IND sponsor will 
notify the pharmacist if continued clinical use of the product is acceptable. Vials of vaccine are 
intended for single use only and should not be refrozen after thawing. 
VRC-PBSPLA043-00-VP: Vials of PBS are stored until use at -45C to -10oC in a qualified, 
continuously monitored, temperature-controlled freezer. Vials are intended for single use only, 
and thus do not contain a preservative. They should not be refrozen after thawing.
7.3.
Preparation of Study Agent for Injection
Refer to the group assignment for the study subject to select the proper vial type. The pharmacy 
will label the syringe prior to delivery to the clinic with the subject identifier and the date and 
time allowance for administration; the label on the syringe will not include the product type 
information. The injection must be administered within 8 hours after removing the vial from the 
freezer.
7.3.1.
Preparation of VRC-CHKVLP059-00-VP
Stability study conducted with VRC-CHKVLP059-00-VP show that the vaccine is stable in the 
syringe for 8 hours refrigerated or at room temperature. The following instructions apply to 
aseptic preparation of the vaccine for injection:
1. Thaw the vial containing VRC-CHKVLP059-00-VP at ambient temperature (15-25ºC).
2. Keep the material at room temperature or refrigerated during the entire preparation period 
until administration.
3. Keep the prepared injection out of direct sunlight before administration.
Preparation will be done in a clean preparation unit with limited access. The intended volume to 
administer is 0.5 mL.  Draw up vaccine into the syringe. Remove air bubbles from the syringe 
and cap it.
7.3.2.
Preparation of VRC-PBSPLA043-00-VP 
Remove a vial of VRC-PBSPLA043-00-VP from the freezer and thaw at ambient temperature 
(15-25ºC). The intended volume to administer is 0.5 mL.  Draw up VRC-PBSPLA043-00-VP 
into the syringe. Remove air bubbles from the syringe and cap it. 
7.4.
Study Agent Administration
The injection must be administered within the time allowance on the syringe label using standard 
IM injection technique.  Each study injection is 0.5 mL in volume administered intramuscularly 
into the deltoid muscle by needle and syringe. 

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7.5.
Study Agent Accountability
7.5.1.
Documentation
Each study site will be responsible for maintaining an accurate record of the codes, inventory, 
and an accountability record of the investigational study agent supplies for this study at their site. 
Electronic documentation as well as paper copies will be used.
7.5.2.
Disposition
The empty vials and the unused portion of a vial will be discarded in a biohazard containment 
bag that will be incinerated or autoclaved. Any unopened vials that remain at the end of the 
study will be discarded at the discretion of the VRC in accordance with policies that apply to 
investigational agents. Partially used vials or expired prepared doses cannot be administered to 
other subjects nor used for in vitro experimental studies and will be discarded as indicated above.
8.
HUMAN SUBJECTS PROTECTION
This research will be conducted in compliance with the protocol, Good Clinical Practices (GCP) 
guidance, and all applicable regulatory requirements.
8.1.
Institutional Review Board
A copy of the protocol, proposed informed consent and any proposed advertising material will be 
submitted to the site IRB for review and approval. 
The Site IoR will submit and, where necessary, obtain approval from the IRB for subsequent 
protocol amendments and changes to the informed consent document. The Site IoR is 
responsible for ensuring proper IRB notification of deviations from the protocol or serious AEs 
occurring at the site and other AE reports received from the VRC, NIAID, in accordance with the 
protocol and local IRB policies. The IoR will be responsible for obtaining annual IRB 
approval/renewal throughout the duration of the protocol. Documentation of the IRB approval 
and FWA number will be provided for the Sponsor’s records.
8.2.
Subject Recruitment and Enrollment
Subjects for this study will be recruited by the sites in accordance with their site IRB standard for 
recruitment practices. 
8.2.1.
Participation of Children
Children are not eligible to participate in this clinical trial because this study is designed for 
study product evaluation in adults.  If the product is assessed as safe and immunogenic, other 
protocols designed for children may be conducted in the future.
8.3.
Informed Consent
The provided template informed consent (Appendix I) will be used to guide development of the 
site-specific consent forms. Only an IRB-approved consent form will be used to consent 
subjects for participation in the study. The changes in the informed consent template by the site 

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should be approved with the VRC Program Officer before submission to respective IRB. Study 
sites needing to conduct the informed consent process in more than one language will follow the 
practices required by the site’s IRB for translation and approval of the consent(s) and provide to 
the IND sponsor all translations of documents used for consent. Before a subject’s participation 
in the protocol, it is the investigator’s responsibility to ensure that written informed consent is 
obtained from the subject after adequate explanation of the aims, methods, anticipated benefits, 
and potential hazards of the protocol.
The acquisition of informed consent should be documented in the subject’s records, as required 
by 45 CFR 46.117, and the informed consent form should be signed and personally dated by the 
subject and by the person who conducted the informed consent discussion. An original signed 
informed consent form should be retained by the site and a signed copy of the consent form 
should be provided to the subject. 
8.4.
Subject Confidentiality
The investigators at each site must ensure that the subject’s anonymity is maintained in reporting 
study results.  Subjects will not be identified in any reports of this study.  All records will be kept 
confidential to the extent provided by federal, state and local law.  Medical records will be made 
available for review when required by authorized agencies and regulatory authorities only under 
the guidelines set by the U.S. Federal Privacy Act and by relevant country-specific regulatory 
authorities.  Direct access includes examining, analyzing, verifying, and reproducing any records 
and reports that are important to the evaluation of the study.  The authorized reviewers will 
review study-related records without violating the confidentiality of the subjects.  Stored study 
research samples will be labeled by a code (such as a number) that only the site clinical study 
team can link to the subject.  The requirement to maintain subject confidentiality and inform 
subjects about review of study-related records is included in the study informed consent 
documents.
8.5.
Risks and Benefits
8.5.1.
Risks of Blood Collections:
The blood collection procedures are common in routine medical practice. The risks of blood 
sample collection are minimal and consist of mild discomfort at the sample collection site. The 
procedure may cause mild pain, bruising, fainting, and, rarely, infection at the site where the 
blood is taken.
8.5.2.
Risks of the CHIKV VLP Vaccine:
In VRC 311, the first human trial in which the CHIKV VLP vaccine was administered to 25 
subjects, the local and systemic reactogenicity was no more than mild and none of the subjects 
reported fever. It is possible that once administered to a larger number of subjects, other potential 
side effects from injection may be observed similar to those seen with other vaccines.  Although 
not previously observed with the CHIKV VLP vaccine, this includes the possibility of 
anaphylaxis. With vaccines in general, local reactogenicity may include pain, tenderness, redness 
or induration of the skin at the injection site and systemic reactogenicity may include fever, 
chills, muscle aches, joint aches, nausea, headache, and fatigue. These side effects will be 
monitored, are expected to be short term and may or may not require treatment. 

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In VRC 311, seven laboratory test AEs (occurring in four participants) were assessed as related 
to study vaccine based on temporal relationship to vaccination.  The AEs included four mild 
transient alanine aminotransferase increases and two mild and one moderate transient 
neutropenia. All resolved without clinical sequelae. There was no placebo comparison group in 
the VRC 311 study.  The comparison of AEs in placebo and vaccine recipients in the VRC 704 
study should provide a more detailed safety profile for the study vaccine.
8.5.3.
Other Risks:
There should be no unusual risks associated with the CHIKV VLP vaccine. The effect of this 
vaccine on an unborn fetus is unknown. Female subjects of child bearing potential who are 
heterosexually active will be required to agree to use birth control beginning 21 days prior to 
enrollment and continuing through 12 weeks after last study injection.  Women who are pregnant 
will be excluded from the study.  Children will not be enrolled in this study.
8.5.4.
Benefits:
Study participants may have no direct benefit from participation in this study but society may 
benefit from knowledge gained from research on the donated specimens.  This protocol is not 
designed to provide treatment for any condition. 
8.6.
Plan for Use and Storage of Biological Samples
To be eligible for this protocol, subjects must be willing to allow stored specimens to be used in 
the future for studying infectious diseases, immune function, vaccine responses and other 
medical conditions, and must also be willing to have genetic tests, including HLA typing 
performed. If tests performed at a study site show evidence of any acute or chronic condition, 
subjects will be informed of the results and advised to seek appropriate medical care for the 
condition. In general, testing performed at a research laboratory is not for diagnostic purposes 
and results will not be available to the study site or study subject.
Intended Use of the Samples/Specimens/Data:
Samples, specimens and data collected under this protocol may be used to study infectious 
diseases such as influenza, immune function, vaccine responses, genetic factors in immune 
responses, other medical conditions and for research assay validation.
Storage of Samples, Specimens and Data from Samples:
All of the stored study research samples will be labeled by a code (such as a number) that only 
the study site can link to the subject. Samples will be stored in secure facilities with controlled 
access at the sites. The NIAID Vaccine Immune T-Cell and Antibody Laboratory (NVITAL) in 
Gaithersburg, MD, under the direction of the VRC, NIAID, NIH (Bethesda, MD) will serve as a 
central repository for stored samples.  Samples collected for research may be transferred for 
testing to the VRC/NIAID/NIH, other approved collaborators or contract laboratories. Data will 
be kept secure. Only approved investigators or their designees will have access to samples and 
data.  
In the future, other investigators (both at NIH and outside) may wish to study these samples 
and/or data.  Regulatory approval through the proper human subjects protection agency will be 
sought prior to any sharing of samples that constitutes human subject research. The research use 

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of stored, unlinked or unidentified samples may be exempt from the need for IRB review and 
approval. When appropriate, exemption may be obtained through the proper regulatory 
procedures.
8.7.
Compensation
Compensation for time and inconvenience of study participation will be provided to subjects in 
accordance with the site-specific IRB approved plan. 
8.8.
Safety Monitoring
8.8.1.
Protocol Safety Review Team
Each site IoR is responsible for ensuring daily review of the site’s clinical safety data as it 
becomes available. The PSRT includes the Protocol Chair, IND Sponsor Medical Officer, and 
each site IoR or designee. The PSRT will review the summary study safety data reports weekly 
from initiation of the study until 4 weeks after all subjects have received their last study injection
and then monthly until 4 weeks after all subjects have completed the last study visit in order to 
be certain that the investigational vaccine has an acceptable safety profile. The PSRT will be 
notified and convened to review any study pauses. The Protocol Chair and IND Sponsor 
Medical Officer will continue to monitor the cumulative study safety data reports on at least a 
monthly basis through completion of the last study visit.  
8.8.2.
Data and Safety Monitoring Board
As described in Section 5.4, the DSMB will review safety data twice per year at their regularly 
scheduled meetings and will have access to the randomization code.
9.
ADMINISTRATION AND LEGAL OBLIGATIONS
9.1.
Protocol Initiation, Amendments and Termination
Each site must receive IRB approval, approval from local country regulatory agencies, as 
needed, and approval of study sponsor before initiating the study at the site.  All amendments 
will also be submitted to the site IRBs and other regulatory authorities as needed for approval.  
The VRC, NIAID, NIH, the U.S. FDA and other regulatory authorities reserve the right to 
terminate the study. Each IoR will notify the respective site IRB of the study termination in 
writing and provide documentation to the IND Sponsor.
9.2.
Study Documentation and Study Records Retention
The site IoR will maintain a list of appropriately qualified persons to whom trial duties have been 
delegated. The site IoR is responsible for ensuring that staff maintains a comprehensive and 
centralized filing system of all study-related (essential) documentation, suitable for inspection at 
any time by representatives from the VRC, IRB, designated CRO monitor and/or applicable 
regulatory authorities. Elements include but are not limited to:

Subject files containing completed informed consent forms and supporting copies of 
source documentation 

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Study files containing the protocol with all amendments, the Investigator’s Brochure,
and copies of all correspondence with the IRB
In addition, all original source documentation must be maintained and readily available.
The CRO is responsible for ensuring that records and documents pertaining to the conduct of this 
study, including CRFs, source documents, consent forms, laboratory test results, and medication 
inventory records, are managed per U.S. requirements. According to the U.S. FDA, study 
records must be retained for 2 years after the marketing application is approved for the drug; or, 
if an application is not approved for the drug, until 2 years after shipment and delivery of the 
drug for investigational use is discontinued. Therefore, VRC, NIAID may authorize transfer or 
destruction of study records. No study records will be destroyed without prior authorization 
from VRC, NIAID.
9.3.
Data Collection and Protocol Monitoring
9.3.1.
Data Capture Methods
Clinical research data will be collected and recorded by the study sites in a timely fashion in a 
secure electronic web-based clinical data management system. Immunological testing on 
collected, coded blood samples may be performed in batches at central laboratories. Extracted 
data without subject identifiers will be sent to the statisticians for statistical analysis as needed. 
The final study database and statistical evaluations will be transferred to the VRC, NIAID at the 
study completion. 
9.3.2.
Source Documents and Access to Source Data/Documents
Each participating site will maintain appropriate medical and research records for this trial, in 
compliance with ICH-GCP, regulatory and institutional requirements for the protection of 
confidentiality of subjects. As part of participating in the NIAID-sponsored study, each site will 
permit authorized representatives of the VRC, NIAID, and regulatory agencies to examine (and 
when required by applicable law, to copy) clinical records for the purposes of quality assurance 
reviews, audits and evaluation of the study safety and progress.
Source data are all information, original records of clinical findings, observations, or other 
activities in a clinical trial necessary for the reconstruction and evaluation of the trial.  Examples 
of these original documents and data records include, but are not limited to, medical records, 
laboratory reports, pharmacy records and other research records maintained for the clinical trial.
9.3.3.
Protocol Monitoring
VRC, NIAID, NIH, as the IND Sponsor, or their authorized representatives are responsible for 
ensuring study data integrity and compliance with the protocol. Routine data monitoring and 
protocol compliance will be performed by the site investigators and study coordinator on an 
ongoing basis in accordance with the Sponsor’s monitoring plan. Site investigators will allow 
the study monitors and the U.S. FDA (if requested) to inspect study documents or pertinent clinic 
records for confirmation of study data.

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9.4.
Language
All written information and other material to be used by subjects and investigative staff must use 
vocabulary and language that are readily understood. 
9.5.
Policy Regarding Research-Related Injuries
The study site will provide immediate medical care for any injury resulting from participation in 
this research. In general, the VRC, the NIH, or the Federal Government will not provide long-
term medical care or financial compensation for research-related injuries.
9.6.
Multi-Site Management
VRC, NIAID, NIH, as the IND Sponsor for the study, is responsible for overall management of 
study. Assistance in managing the study is being provided by specific Contract Research 
Organizations (CROs).
Each study site that enrolls study participants will have a site Investigator of Record (IoR), also 
referred to as Principal Investigator. An IoR is defined as an individual who is responsible for 
the conduct of the clinical investigation at a study site and under whose direction the test article 
is administered to subjects. The site IoRs have parallel roles at their respective institutions in 
conducting the study at their site in compliance with all applicable regulations and good clinical 
practices.
Publication of any study related information is governed by VRC, NIAID, NIH
policies. Specifically, neither the CROs nor site personnel may submit for public presentation 
any meeting abstract or manuscripts without prior review and approval by VRC, NIAID, NIH.

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719-26.

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APPENDIX I:
TEMPLATE INFORMED CONSENT FORMS
The sample informed consent forms are provided to guide development of a site-specific consent 
form. Only IRB-approved consent forms will be used to consent subjects for study participation.
Template Informed Consent Form for Study Participation
STUDY TITLE:  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
INTRODUCTION
We invite you to take part in a research study at the __________________________.
The study is sponsored by the National Institutes of Health (NIH) in Bethesda, MD, USA.  You 
can decide if you want to participate in this study or not. There is no penalty or loss of benefits 
for choosing not to participate. Please ask questions and discuss this study with anyone you 
want.  Take as much time as you need to decide.
[SCREENING  (delete this section if site has separate screening protocol or separate 
screening consent)]
Before you can enroll in the investigational Chikungunya virus (CHIKV) vaccine study, you will 
be screened for eligibility.  You will need to sign this consent form before we can do the 
screening.
Screening involves a physical exam and blood tests to check your general health status. If you 
are a woman, you will be asked about your birth control use and the possibility of your becoming 
pregnant while in the study.  You will be tested for pregnancy if applicable. During screening, 
we may collect some blood to store for research. We will ask you about your general health 
history.  You will have bloods test to check for past CHIKV infection and for HIV infection. We 
will ask you about medications you are taking and recent vaccinations. 
We will review the screening results with you and tell you if the results show that you are not 
eligible to join the study. You cannot be in another research study where you receive a study 
product and also enroll in this study unless you discuss this and receive approval from the study 
clinicians. 
PURPOSE OF THE VACCINE STUDY
This is a research study of an experimental vaccine.  It is called the Chikungunya Virus-Like 
Particle vaccine or “CHIKV VLP” vaccine.  The U.S. Food and Drug Administration (FDA)
allows it to be used for research only.  It is not known if the vaccine works.  The main purpose of 
this study is to see if the experimental vaccine is safe, if it causes any side effects, and if people 
who get the vaccine make an immune response. Study sites are in areas where CHIKV outbreaks
have occurred.  The study will last for about 72 weeks.

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CHIKV was first identified in Tanzania, Africa in 1952.  CHIKV outbreaks were most common 
in Africa, India and Asia until 2013, when the first cases were reported in the Americas. The 
virus is spread by mosquitoes and causes a viral infection that can lead to fever, headache, 
muscle pain, tiredness, and joint inflammation or pain.  The disease usually does not cause death; 
but the joint inflammation may be severe and may last for many months.  There is currently no 
cure for CHIKV infection or vaccine to prevent CHIKV infection.
You are eligible to participate in this study if:

you have completed the screening process,  

you are between 18 and 60 years old,

you have physical exam and blood test results that meet eligibility requirements, and 

you do not have any significant medical problems as determined by your screening. 
STUDY INJECTIONS
Vaccines are substances used to try to create resistance (or immunity) to a disease.  About 400 
people will participate in this study. About half of the participants will get two injections of the 
study vaccine and half will get two injections of an inactive solution (or placebo). 
CHIKV VLP Vaccine:  The vaccine was developed by the Vaccine Research Center (VRC) at 
the U.S. National Institutes of Health (NIH).  It was made at the VRC Vaccine Pilot Plant in
Frederick, Maryland, USA.  The vaccine is made of some CHIKV proteins that combine to make
a particle that looks like the outside of the virus. The body’s immune system may respond to this 
particle.  There is no virus in the vaccine so you cannot get CHIKV infection from the vaccine. 
Placebo Injection:  The placebo in this study is a sterile salt water solution made for injection 
into people. It has no vaccine in it.
STUDY PROCEDURES
If you agree to take part in the study, you will be randomly assigned (by chance, like flipping a 
coin) to one of two groups. Neither you nor the clinic staff will know what product you are 
receiving until the study is complete. You will receive two injections during the study. Half the 
people in this study will get the investigational CHIKV VLP vaccine and the other half will get a 
placebo injection on the day of enrollment. Four weeks later, you will get a second injection of 
the same product that you already got.  We will give all study injections with a needle and 
syringe into your upper arm muscle. If you are a woman who is able to get pregnant, we will do 
a pregnancy test before each injection.  The test must show that you are not pregnant before a
study injection is given.
The clinic staff will observe you for at least 15 minutes after each injection. We will ask you to 
complete a diary card for 7 days. For the diary card, you will need to record your temperature 
and any symptoms you feel.  You will also need to look at the injection site on your arm each 
day and record how it looks. The clinic staff is available to you by phone 24 hours a day to 
report any unexpected side effects. If you experience any concerning signs or symptoms after 
each injection, please contact the clinic. We will ask you to review your diary card with us about 
a week after each injection. 

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If you have any signs of sickness that interfere with your usual activities, you may need to come 
to the clinic for an examination before your next scheduled visit. It is very important that you 
follow the instructions we give you. 
Your participation in the study will last for about 16 months after the first injection. You will 
have about 11 planned clinic visits and 2 telephone contacts. Each clinic visit will last about [1-
2] hours [sites may edit length of visit per clinic standard]. Experimental vaccine studies follow 
a set schedule. Scheduling for your visits allows some flexibility, but it is important that you 
work with the staff to follow the schedule. You should try to not miss any visits.  
At each visit, we will check you for any health changes or problems.  We will ask how you are 
feeling and if you have taken any medications. At scheduled study visits, we will draw about 5-
12 tubes of blood from you, depending on the visit.  We may ask for urine samples. If any of 
your test results show a health problem, we will tell you about it as soon as possible.  You might 
need to have extra clinic visits and laboratory tests if you have health changes that we need to 
check. 
At any time during the study, if you think you have CHIKV infection, you must contact the study 
site and come in for a clinical evaluation and blood tests.  We will tell you the results of testing 
for CHIKV infection but it may take several weeks to learn the results. It is very important for 
the study that you get tested for CHIKV infection at our clinic only and that you do not go 
anywhere else for CHIKV testing. There is no medication that makes CHIKV infection end 
faster than naturally occurs.   We will tell you if you need testing for any other infections that 
have symptoms similar to CHIKV infection.
MONITORING OF THE STUDY
This study will be monitored by a group of physicians and scientists associated with the U.S. 
NIH. This group will review the study information and will pay close attention to harmful 
reactions.
GENETIC TESTING
Some of the blood drawn from you as part of this study will be used for genetic tests. There are 
many different types of genetic tests. In vaccine research, some genetic tests are done to see if 
immune responses to a vaccine are different in people because of genetic differences. These 
tests will be done in a research lab using your blood samples. Genetic tests done in a research 
lab will not be in your medical record. The samples used in these tests will not have your name 
them. In the future, genetic research tests to help understand how vaccines work may be done on 
your DNA using stored samples.
STORED SAMPLES
To participate in this study, you must allow us to store your blood samples for future research.
We will use some of your blood samples to study your immune response to the injection.  We 
will also use these samples for future research to learn more about CHIKV infections, vaccines, 
the immune system, and/or other medical conditions.  Results of research tests done from stored 
samples will not be in your medical record or reported to you. 
Labeling of Stored Samples
Your stored samples will be labeled by a code (such as a number) that only the study team can 
link to you. Any identifying information about you will be kept confidential to the extent 

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permitted by law. Despite protections, there is a small chance that information identifying you 
will be given to someone who should not get it.
Future Studies
In the future, other investigators at NIH or outside of NIH may wish to study your stored 
samples. When the study team shares your stored samples, they will be marked with a code, but 
will not have any identifying information on them. Some information about you, such as your 
gender, age, health history, or ethnicity may also be shared with other investigators. Any future 
research studies using your samples will be conducted in a way that protects the rights and 
privacy of study participants.
Your stored samples will be used only for research and will not be sold. The research done with 
your samples may be used to develop new products in the future but you will not receive 
payment for such products.
POSSIBLE STUDY RISKS
Possible risks from the injections:  temporary stinging, pain, redness, soreness, itchiness, 
swelling, bruising, or a cut in the arm. There is a very small chance of infection.
Possible risks of blood drawing: pain, bleeding, bruising, feeling lightheaded, or fainting.
Possible risks from genetic testing: unintended release of information that could be used by 
insurers or employers; discovering a gene or HLA type that suggests risk of disease for you or 
your family; discovering undisclosed family relationships.
Possible risks from any vaccine: fever, chills, rash, aches and pains, nausea, headache, 
dizziness, and fatigue. Some people have allergic reactions to vaccines. These types of reactions 
are usually greatest within the first 24 hours after injection and typically last 1 to 3 days. Over-
the-counter medicine, such as acetaminophen, will generally help relieve symptoms from 
injection and may be used.
Possible risks from the CHIKV VLP vaccine:  This will be the second study of this CHIKV 
VLP vaccine. In the past study, 25 people received the CHIKV VLP vaccine. The most common 
complaints were mild pain or soreness at the injection site.  About half of the people had mild 
symptoms like headache, nausea and feeling tired or unwell. A few people had a temporary 
change in a laboratory test. The vaccine does not contain any CHIKV virus. The vaccine will 
not give you CHIKV infection.  
The first 25 people to receive the CHIKV VLP vaccine did not have any fever or joint pain after 
vaccination. However, there may be side effects from the study vaccine that are not common 
which we do not yet know about. Please tell the study staff about any side effect you think you 
are having. This is important for your safety.
Possible risks during Pregnancy:  We do not know if getting the study vaccine affects a fetus.  
Therefore, women who can have children must use effective birth control starting at least 21 
days before getting the first injection until 12 weeks after the last study injection. We will 
discuss effective birth control methods with you. If you are pregnant or want to become 
pregnant in the next 16 weeks, you cannot participate.  We will ask about the outcome of any 
pregnancy that begins during the first 16 weeks on study.

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Other Risks:  It is unknown if the study injection will affect how you respond to any future 
CHIKV infection or to any other CHIKV vaccines that you may get in the future.  We will tell 
you if we learn about any important new findings or serious side effects of the vaccine during the 
study that may affect your willingness to continue participation. 
You may not donate blood while participating in an investigational vaccine study and for one 
year after the date of the last injection of an investigational vaccine.
POSSIBLE BENEFITS
This study is not designed to benefit you or protect you from CHIKV infection. You and others 
may benefit in the future from the information that we learn from the study.
COSTS OF PARTICIPATION
There are no costs to you for participating in this study. You or your health insurance will have 
to pay for all medical costs for medical care you receive outside this study. It is possible that you 
may have some expenses that are not covered by the study compensation provided.
COMPENSATION TO YOU FOR YOUR PARTICIPATION
You will be compensated [insert site IRB-approved amount] for your study participation as 
follows: [insert site plan]. This will be based on the number of study visits you attend and study 
injections you receive. 
REASONS FOR REMOVING YOU FROM THE STUDY WITHOUT YOUR CONSENT
The study doctor can take you out of this study without your permission if:

continuing in the study could harm you, 

you do not follow study instructions or keep appointments, or 

the study is stopped by the U.S. NIH, regulatory boards, the U.S. FDA or local 
regulatory authorities.  
If you agree to take part in this study, it is important for you to keep all your appointments. 
However, if you don't want to stay in the study, you can leave at any time. You will not lose any 
benefits that you would have had if you had not joined the study.  
If you receive the first injection but not the second injection, we will ask you to continue with 
your planned follow-up visits until the end of the study. It is important that we continue to 
monitor your health even if you do not receive the second injection.
ALTERNATIVES
This study is not designed to treat or prevent any disease. You may choose to not participate.
CONFIDENTIALITY
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required 
by U.S. Law.  This Web site will not include information that can identify you.  At most, the 
Web site will include a summary of the results.  You can search this Web site at any time. 
Results of NIH-supported research studies may also be reported in medical journals, on internet 
or at scientific meetings. These reports will not have information that can identify you.

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In most cases, the NIH will not release any information about your research participation without 
your written permission.  However, if you sign a release of information form, for example, for an 
insurance company, the insurance company receives information from your medical record.  This 
information might affect (either positively or negatively) if the insurance company sells 
insurance to you.
The U.S. Federal Privacy Act protects the privacy of your medical records.  However, you 
should know that the Act allows release of some information from your medical record without 
your permission, for example, if it is required by regulatory agencies that supervise the study, 
law enforcement officials, or other authorized people. [Site/country-specific information on 
confidentiality may be added.]
POLICY REGARDING RESEARCH-RELATED INJURIES
The study site will provide immediate medical care for any injury resulting from your 
participation in research here. In general, no long-term medical care or financial compensation 
for research-related injuries will be provided by the National Institutes of Health or the Federal 
Government.  However, you have the right to pursue legal remedy if you believe that your injury 
justifies such action.
Problems or Questions. If you have any problems or questions about this study, or about your 
rights as a research participant, or about any research-related injury, contact the investigator of 
record, ______________. Others you may call are the Study Coordinator 
____________at_______. You may also call the _________ Patient Representative at 
_____________.
Please keep a copy of this document in case you want to read it again.
Adult Participant Consent:
I have read the explanation about this study and have been given the opportunity to discuss it and 
ask questions. I consent to take part in this study.
Participant Name (print)
Date and Time
Signature 
Investigator name (print)
Date
Signature
Witness name (print)
Date
Signature

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APPENDIX II: CONTACT INFORMATION
 
 
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APPENDIX III: SCHEDULE OF EVALUATIONS

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APPENDIX IV: ASSESSMENT OF RELATIONSHIP TO VACCINE AND 
ADVERSE EVENT SEVERITY GRADING

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Assessment of Causality Relationship of an Adverse Event to Study Vaccine: 
The relationship between an adverse event (AE) and the vaccine will be assessed by the 
investigator on the basis of his or her clinical judgment and the definitions below.

Definitely Related. The AE and administration of study agent are related in time, and 
a direct association can be demonstrated.

Probably Related. The AE and administration of study agent are reasonably related 
in time, and the AE is more likely explained by study agent than other causes. 

Possibly Related. The AE and administration of study agent are reasonably related in 
time, but the AE can be explained equally well by causes other than study agent.

Not Related. There is not a reasonable possibility that the AE is related to the study 
agent. 
For purposes of preparing data reports in which AE attributions are limited to “Related” or “Not 
Related”, in this protocol, the “Definitely, Probably and Possibly” attributions  will be  mapped 
to the “Related” category.  The definitions that apply when these two categories alone are used 
are as follows:

Related – There is a reasonable possibility that the AE may be related to the study 
agent.

Not Related – There is not a reasonable possibility that the AE is related to the study 
agent.
Grading the Severity of Adverse Events:
The FDA Guidance for Industry (September 2007): “Toxicity Grading Scale for Healthy Adult 
and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials” is the basis for the 
severity grading of AEs in this protocol. Several modifications were made to the table as follows:

“Emergency room visit” is not automatically considered a life-threatening event; 
these words have been removed from any “grade 4’ definition where they appear in 
the table copied from the guidance document.

Any laboratory value shown as a “graded” value in the table that is within the 
institutional normal range will not be severity graded or recorded as an AE.

Severity grading for hemoglobin decrease on the basis of the magnitude of decrease 
from baseline is not applicable at the grade 1 level; only absolute hemoglobin will be 
used to define grade 1 decrease.  Increases in hemoglobin are AEs only for values 
above the upper limit of normal and are graded by the systemic illness clinical 
criteria.

Severity grading definition for Grade 4 local reaction to injectable product 
(Erythema/Redness and Induration/Swelling) included added text “requiring medical 
attention”.

1 X ULN was removed from the definition for PT increase.

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When not otherwise specified in the table, the following guidance will be used to assign a 
severity grade:
Grade 1 (Mild):  No effect on activities of daily living
Grade 2 (Moderate): Some interference with activity not requiring medical intervention 
Grade 3 (Severe): Prevents daily activity and requires medical intervention 
Grade 4 (Life-threatening): Hospitalization; immediate medical intervention or therapy 
required to prevent death.
Grade 5 (Death): Death is assigned a Grade 5 severity. 
Only the single AE that is assessed as the primary cause of death should be assigned “grade 5” 
severity.

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Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in 
Preventive Vaccine Clinical Trials
FDA Guidance - September 2007
A. Tables for Clinical Abnormalities 
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 
Hospitalization 
Tenderness 
Mild discomfort to 
touch 
Discomfort with 
movement 
Significant 
discomfort at rest 
Hospitalization 
1Erythema/Redness  
2.5 – 5 cm 
5.1 – 10 cm 
> 10 cm 
Necrosis or 
exfoliative 
dermatitis requiring 
medical attention 
2 Induration/Swelling  
2.5 – 5 cm and does 
not interfere 
with activity 
5.1 – 10 cm or 
interferes with 
activity 
> 10 cm or 
prevents daily 
activity 
Necrosis requiring 
medical attention 
3 Vital Signs
Mild
(Grade 1)
Moderate
(Grade 2)
Severe
(Grade 3)
Potentially Life
Threatening
(Grade 4)
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 
Hospitalization for 
arrhythmia 
5 Bradycardia - beats per 
Minute
50 – 54 
45 – 49 
< 45 
Hospitalization for 
arrhythmia 
Hypertension (systolic) -
mm Hg 
141 – 150 
151 – 155 
> 155 
Hospitalization for 
malignant 
hypertension 
Hypertension (diastolic) -
mm Hg 
91 – 95 
96 – 100 
> 100 
Hospitalization for 
malignant 
hypertension 
Hypotension (systolic) –
mm Hg 
85 – 89 
80 – 84 
< 80 
Hospitalization for 
hypotensive shock 
Respiratory Rate – breaths 
per minute 
17 – 20 
21 – 25 
> 25 
Intubation 
1.
In addition to grading the measured local reaction at the greatest single diameter, the measurement should be recorded as 
a continuous variable. 
2.
Induration/Swelling should be evaluated and graded using the functional scale as well as the actual measurement.
3.
Subject should be at rest for all vital sign measurements. 
4.
Oral temperature; no recent hot or cold beverages or smoking. 
5.
When resting heart rate is between 60 – 100 beats per minute. Use clinical judgment when characterizing 
Bradycardia among some healthy subject populations, for example, conditioned athletes.



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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 
Hospitalization for 
hypotensive shock 
Diarrhea 
2 – 3 loose stools or
< 400 gms/24 hours
4 – 5 stools or 
400 – 800 gms/24 
hours 
6 or more watery 
stools or 
> 800gms/24 hours 
or requires 
outpatient IV 
hydration 
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 
Hospitalization 
Fatigue 
No interference 
with
activity 
Some interference 
with activity 
Significant; 
prevents daily 
activity 
Hospitalization 
Myalgia 
No interference 
with
activity 
Some interference 
with activity 
Significant; 
prevents daily 
activity 
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 not 
requiring medical 
intervention 
Prevents daily 
activity and 
requires medical 
intervention 
Hospitalization 
B. Tables for Laboratory Abnormalities 
The laboratory values provided in the tables below serve as guidelines and are dependent upon 
institutional normal parameters.  Institutional normal reference ranges should be provided to 
demonstrate that they are appropriate.
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 

V R C 7 0 4, Versi o n 2. 0
A pril 1 5, 2 0 1 6
P a ge 5 4 of 5 5
Ser u m *
Mil d
( Gr a de 1)
M o der ate
( Gr a de 2)
Se vere
( Gr a de 3)
P ot e nti all y Life
T hre ate ni n g
( Gr a de 4) * *
P otassi u m –  H y p o kale mia 
m E q/ L 
3. 5 – 3. 6 
3. 3 – 3. 4 
3. 1 – 3. 2 
< 3. 1 
Gl u c ose –  H y p o gl yce mia 
m g/ d L 
6 5 – 6 9 
5 5 – 6 4 
4 5 – 5 4 
< 4 5 
Gl u c ose –  H y per gl yce mia 
Fasti n g –  m g/ d L 
Ra n d o m –  m g/ d L 
1 0 0 – 1 1 0 
1 1 0 – 1 2 5 
1 1 1 – 1 2 5 
1 2 6 – 2 0 0 
> 1 2 5 
> 2 0 0 
I ns uli n 
re q uire me nts or 
h y per os m olar c o ma 
Bl o o d  Urea Nitr o ge n 
B U N m g/ d L 
2 3 – 2 6 
2 7 – 3 1 
> 3 1 
Re q uires dial ysis 
C reati ni ne –  m g/ d L  
1. 5 – 1. 7 
1. 8 – 2. 0 
2. 1 – 2. 5 
> 2. 5 or re q uires 
dial ysis 
C alci u m – h y p ocalce mia 
m g/ d L 
8. 0 – 8. 4 
7. 5 – 7. 9 
7. 0 – 7. 4 
< 7. 0 
C alci u m – h y percalce mia 
m g/ d L 
1 0. 5 – 1 1. 0  
1 1. 1 – 1 1. 5  
1 1. 6 – 1 2. 0  
> 1 2. 0 
Ma g nesi u m –
h y p o ma g nese mia m g/ d L 
1. 3 – 1. 5 
1. 1 – 1. 2 
0. 9 – 1. 0 
< 0. 9 
P h os p h or o us –
h y p o p h os p hate mia m g/ d L 
2. 3 – 2. 5 
2. 0 – 2. 2 
1. 6 – 1. 9 
< 1. 6 
C P K –  m g/ d L 
1. 2 5 – 1. 5 x 
U L N * * * 
1. 6 – 3. 0 x U L N  
3. 1 – 1 0 x U L N  
> 1 0 x U L N 
A l b u mi n –
H y p o al b u mi ne mia g/ d L 
2. 8 – 3. 1 
2. 5 – 2. 7 
< 2. 5 
--
T otal Pr otei n –
H y p o pr otei ne mia g/ d L 
5. 5 – 6. 0 
5. 0 – 5. 4 
< 5. 0 
--
A l kali ne p h os p hate –
i ncrease b y fact or 
1. 1 – 2. 0 x U L N  
2. 1 – 3. 0 x U L N 
3 . 1 – 1 0  x U L N  
> 1 0 x U L N 
L i ver F u ncti o n Tests –
A L T, A S T 
i ncrease b y fact or 
1. 1 – 2. 5 x U L N  
2. 6 – 5. 0 x U L N  
5. 1 – 1 0 x U L N  
> 1 0 x U L N 
Bil ir u bi n –  w he n 
acc o m pa nie d 
b y a n y i ncrease i n Li ver 
F u ncti o n T est 
i ncrease b y fact or 
1. 1 – 1. 2 5 x U L N  
1. 2 6 – 1. 5 x U L N  
1. 5 1 – 1. 7 5 x U L N  
> 1. 7 5 x U L N 
Bil ir u bi n –  w he n Li ver 
F u ncti o n T est is n or mal; 
i ncrease b y fact or 
1. 1 – 1. 5 x U L N  
1. 6 – 2. 0 x U L N  
2. 0 – 3. 0 x U L N  
> 3. 0 x U L N 
C h olester ol 
2 0 1 – 2 1 0 
2 1 1 – 2 2 5  
> 2 2 6 
---
P a ncreatic e nz y mes –
a m ylase, li pase 
1. 1 – 1. 5 x U L N  
1. 6 – 2. 0 x U L N  
2. 1 – 5. 0 x U L N  
> 5. 0 x U L N 
*  T he la b orat or y val ues pr o vi de d i n t he ta bles ser ve as g ui deli nes a n d are de p e n de nt u p o n i nstit uti o nal n or mal 
para meters. I nstit uti o nal n or mal refere nce r a n ges s h o ul d b e pr o vi de d t o de m o nstrate t hat t he y are a p pr o priate. 
* * T he cli nical si g ns or s y m pt o ms ass ociate d wit h la b orat or y a b n or malities mi g ht res ult i n c haracterizati o n of 
t he la b orat or y a b n or malities as P ote ntiall y Life T hreate ni n g ( Gra de 4). F or e xa m ple, a l o w s o di u m val ue t hat 
falls wit hi n a gra de 3 para meter ( 1 2 5- 1 2 9 m E/ L) s h o ul d be rec or de d as a gra de 4 h y p o natre mia e ve nt if t he 
s u bj ect ha d a ne w seiz ure ass ociate d wit h t he l o w s o di u m val ue. 
* * * U L N” is t he u p p er li mit of t he n or mal ra n ge.

VRC 704, Version 2.0
April 15, 2016
Page 55 of 55
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) 
decrease from baseline 
value - gm/dL 
not applicable
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) 
decrease from baseline 
value – gm/dL 
not applicable 
1.6 – 2.0 
2.1 – 5.0 
> 5.0 
WBC Increase - cell/mm
3
10,800 – 15,000 
15,001 – 20,000 
20,001 – 25, 000 
> 25,000 
WBC Decrease - cell/mm
3
2,500 – 3,500 
1,500 – 2,499 
1,000 – 1,499 
< 1,000 
Lymphocytes Decrease -
cell/mm
3
750 – 1,000 
500 – 749 
250 – 499 
< 250 
Neutrophils Decrease -
cell/mm
3
1,500 – 2,000 
1,000 – 1,499 
500 – 999 
< 500 
Eosinophils - cell/mm
3
650 – 1500 
1501 - 5000 
> 5000 
Hypereosinophilic 
Platelets Decreased -
cell/mm
3
125,000 – 140,000 
100,000 – 124,000 
25,000 – 99,000 
< 25,000 
PT – increase by factor 
(prothrombin time) 
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) 
1.10 – 1.20 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) 
* 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.

DATE:
April 26, 2016
TO:
VRC 704 Study Investigators
FROM:
Julie Ledgerwood, D.O, VRC 704 Protocol Chair
SUBJECT:
VRC 704, Version 2.0 (April 15, 2016), Letter of Amendment #1
This Letter of Amendment (LoA) affects the VRC 704 Version 2.0 (April 15, 2016) protocol 
and must be approved by the IRB prior to implementation. 
This letter and any IRB correspondence with regard to this letter will be filed in the protocol 
regulatory file and other pertinent files. 
Purpose: The purpose of this LoA is to add (1) Dr. Grace Chen as a Protocol Co-Chair to VRC 
704 and (2) 
 as a Scientific and Laboratory Collaborator to VRC 704 for 
use of study samples and stored specimens for flavivirus-related research. 
Contact information is as follows:
-
-
This LoA has no substantive effect on the protocol plan and does not result in a change in the 
protocol informed consent. This update will be included in the next version of the protocol if it is 
amended at a future date.

DATE:
June 2, 2016
TO:
VRC 704 Study Investigators
FROM:
Julie Ledgerwood, D.O, VRC 704 Protocol Chair
SUBJECT:
VRC 704, Protocol Version 2.0 (April 15, 2016), Letter of Amendment #2
This Letter of Amendment (LoA) affects the VRC 704 protocol Version 2.0 (April 15, 2016) 
and must be approved by the IRB prior to implementation. This letter and any IRB 
correspondence with regard to this letter will be filed in the protocol regulatory file and other 
pertinent files. 
Purpose: The purpose of this LoA is to (1) amend the Schedule of Evaluations footnote regarding 
the reference for scheduling study visits and (2) add a Scientific and Laboratory Collaborator.  
(1) The Schedule of Evaluations footnote reads: “Schedule Visits 02A through 04 with 
respect to the last prior injection day and subsequent visits with respect to Day 0.”  With 
this amendment, we are changing this footnote to read: “Schedule Visits 02A through 12 
with respect to the last prior injection date. Therefore, if Visit 03 does not occur exactly on 
Day 28, schedule all subsequent visits (03A through 12) based on the actual Visit 03 date.”  
This amendment is to ensure that all follow up visits are conducted in respect to the last 
study injection given.  Therefore, if only one study injection is given, use the date of that 
injection to schedule all study visits.
(2) With this amendment, we are also adding
 as a Scientific and 
Laboratory Collaborator to VRC 704 for use of study samples and stored specimens for 
flavivirus-related research. Contact information is as follows:
This LoA has no substantive effect on the protocol plan and does not result in a change in the 
protocol informed consent. This update will be included in the next version of the protocol if it is 
amended at a future date.

STATISTICAL ANALYSIS PLAN 
Protocol 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 
ClinicalTrials.gov Identifier: NCT02562482
Version 1.0 
DATE: 11 SEP 2018 
Prepared and distributed by: 
The Emmes Corporation 
Rockville, Maryland USA 
THIS COMMUNICATION IS PRIVILEGED AND CONFIDENTIAL

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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 
Protocol Number Code: 
VRC 704 
Development Phase: 
Phase 2 
Products:
VRC-CHKVLP059-00-VP, 
VRC-PBSPLA043-00-VP (Phosphate Buffered Saline) 
Form/Route:
IM injection 
Indication Studied: 
Chikungunya 
Sponsor:
Vaccine Research Center  
National Institute of Allergy and Infectious Diseases 
National Institutes of Health 
Protocol Chair: 
 
Medical Monitor: 
Biostatistician:
 
Clinical Trial Initiation Date: 
18 November 2015 
Clinical Trial Completion Date: 
06 March 2018 
Date of the Analysis Plan: 
11 September 2018 
Version Number: 
1.0 

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SIGNATURE PAGE 
SPONSOR:  
Vaccine Research Center 
National Institute of Allergy and Infectious Diseases 
National Institutes of Health 
STUDY TITLE:                          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
PROTOCOL NUMBER:
VRC 704
Protocol Chair: 
Signed: 
 
The Emmes Corporation:  
Signed: 
 

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TABLE OF CONTENTS 
1
PREFACE ..............................................................................................................................3
2
INTRODUCTION ...................................................................................................................4
2.1
Purpose of the Analyses .................................................................................................... 4
3
STUDY OBJECTIVES AND ENDPOINTS ..............................................................................5
3.1
Study Objectives .............................................................................................................. 5
3.2
Endpoints ........................................................................................................................ 5
3.2.1
Primary Endpoints ................................................................................................... 5
3.2.2
Secondary Endpoints................................................................................................ 5
3.2.3
Exploratory Endpoints.............................................................................................. 6
3.3
Study Definitions and Derived Variables ............................................................................ 6
4
INVESTIGATIONAL PLAN ...................................................................................................7
4.1
Overall Study Design and Plan........................................................................................... 7
4.2
Study Design Issues .......................................................................................................... 7
4.3
Selection of Study Population ............................................................................................ 8
4.4
Treatments ..................................................................................................................... 10
4.4.1
Treatments Administered........................................................................................ 10
4.4.2
Method of Assigning Subjects to Treatment Groups (Randomization)......................... 11
4.4.3
Blinding and Conditions for Unblinding................................................................... 11
4.5
Safety and Immunogenicity Variables and Chikungunya Infection Incidence ....................... 11
5
SAMPLE SIZE CONSIDERATIONS .....................................................................................13
6
GENERAL STATISTICAL CONSIDERATIONS ...................................................................16
6.1
General Principles .......................................................................................................... 16
6.2
Timing of Analyses ........................................................................................................ 16
6.3
Analysis Populations....................................................................................................... 17
6.4
Covariates and Subgroups ............................................................................................... 17
6.5
Missing Data .................................................................................................................. 17
6.6
Interim Analyses and Data Monitoring ............................................................................. 17
6.7
Multicenter Studies ......................................................................................................... 18
6.8
Multiple Comparisons/Multiplicity................................................................................... 18
7 ￿
Study Subjects ........................................................................

7.1
Subject Disposition ......................................................................................................... 19
7.2
Protocol Deviations ........................................................................................................ 19

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8
SAFETY EVALUATION ......................................................................................................20
8.1
Demographic and Other Baseline Characteristics ............................................................... 20
8.1.1
Concurrent Illnesses and Medical Conditions ........................................................... 20
8.1.2
Prior and Concurrent Medications ................
8.2
Measurements of Treatment Compliance ...............
8.3
Adverse Events .............................................................................................................. 21
8.3.1
Solicited Events and Symptoms .............................................................................. 21
8.3.2
Unsolicited Adverse Events .................................................................................... 22
8.4
Deaths, Serious Adverse Events and other Significant Adverse Events ................................ 23
8.5
Pregnancies .................................................................................................................... 23
8.6
Clinical Laboratory Evaluations ....................................................................................... 23
8.7
Vital Signs and Physical Evaluations ................................................................................ 25
9
IMMUNOGENICITY EVALUATION ...................................................................................26
10
ANALYSES OF CHIKUNGUNYA INFECTION INCIDENCE AND TIME TO EVENT ...........27
10.1
Description of Observed Events: ...................................................................................... 27
10.2
Analysis of Vaccine Efficacy: .......................................................................................... 27
10.3
Sample SAS Code for Analysis: ....................................................................................... 28
11
REPORTING CONVENTIONS .............................................................................................30
12
TECHNICAL DETAILS ........................................................................................................31
13
REFERENCES .....................................................................................................................31
14
LISTING OF TABLES, LISTINGS AND FIGURES ................................................................31

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APPENDICES: 
APPENDIX I - TABLE MOCK-UPS - See separate document 
APPENDIX II - FIGURE MOCK-UPS- See separate document
APPENDIX III - DATA LISTING MOCK-UPS - See separate document

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ABBREVIATIONS 
Abbreviation 
Term 
AE 
adverse event 
ALT 
alanine aminotransferase 
AoU 
assessment of understanding 
CBC 
complete blood count 
CDC 
Centers for Disease Control and Prevention 
CHIKV 
Chikungunya virus 
CRO 
Contract Research Organization 
DNA 
deoxyribonucleic acid 
DSMB 
Data and Safety Monitoring Board 
ELISA 
enzyme-linked immunosorbent assay 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practices 
GMT 
geometric mean titers 
HIV 
human immunodeficiency virus 
HLA 
human leukocyte antigen 
ICH 
International Conference on Harmonization 
IM 
Intramuscular 
IND 
Investigational New Drug 
IoR 
Investigator of Record 
IRB 
Institutional Review Board 
ITT 
Intent-to-treat 
MedDRA® 
Medical Dictionary for Regulatory Activities 
mITT 
Modified intent-to-treat 

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Abbreviation 
Term 
NIAID 
National Institute of Allergy and Infectious Diseases 
NIH 
National Institutes of Health 
NVITAL 
NIAID Vaccine Immune T-Cell and Antibody Laboratory 
PBMC 
peripheral blood mononuclear cells 
PBS 
phosphate-buffered saline 
PCR 
polymerase chain reaction 
PDL 
Primary Diagnostic Laboratory 
PI 
Principal Investigator 
PP 
Per-protocol 
PSRT 
Protocol Safety Review Team 
RNA 
ribonucleic acid 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SDCC 
Statistical Data Coordinating Center 
SUSAR 
serious and unexpected suspected adverse reaction 
VLP 
virus-like particle 
VRC 
Vaccine Research Center 

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1
PREFACE
This Statistical Analysis Plan (SAP) for “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” describes and expands upon the statistical information presented in protocol VRC 
704. 
This document describes all planned analyses and provides reasons and justifications for these analyses. 
It also includes sample tables, listings, and figures planned for the final analyses. Regarding the final 
analyses and Clinical Study Report (CSR), this SAP follows the International Conference on 
Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) 
Guidelines, as indicated in Topic E3 (Structure and Content of Clinical Study Reports), and more 
generally is consistent with Topic E8 (General Considerations for Clinical Trials) and Topic E9 
(Statistical Principles for Clinical Trials). The structure and content of the SAP provides sufficient detail 
to meet the requirements identified by the FDA and ICH, while all work planned and reported for this 
SAP will follow internationally accepted guidelines published by the American Statistical Association 
and the Royal Statistical Society for statistical practice.  
This document contains four sections: (1) a review of the study design, (2) general statistical 
considerations, (3) comprehensive statistical analysis methods for efficacy and safety outcomes, and (4) 
a list of proposed tables and figures. Any deviation from this SAP will be described and justified in 
protocol amendments and/or in the CSR, as appropriate. The reader of this SAP is encouraged to also 
review the study protocol for details on conduct of the study and the operational aspects of clinical 
assessments. 

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2
INTRODUCTION
The Dale and Betty Bumpers Vaccine Research Center (VRC), National Institute of Allergy and 
Infectious Diseases (NIAID), National Institutes of Health (NIH) (Bethesda, MD, USA) is dedicated to 
translating the latest knowledge of disease pathogenesis and immunology into new vaccine strategies to 
provide safe and effective means to prevent and control infectious diseases.  Chikungunya virus 
(CHIKV) is a mosquito-borne disease causing acute infection associated with severe morbidity that can 
persist for several weeks, months or even years.  Since its discovery in Tanzania in 1952, outbreaks of 
CHIKV have occurred most frequently in Africa, Asia and the Indian subcontinent.  In recent decades, 
the disease has spread to Europe and the Americas.  In January 2015, over 1,135,000 suspected cases of 
CHIKV and 176 CHIKV-attributable deaths had been recorded in the Caribbean islands, Latin 
American countries and USA [1].  There are currently no effective vaccines or therapies against CHIKV.  
The rapid emergence of CHIKV supports the need for a safe and immunogenic vaccine.  This protocol 
is designed as a Phase 2 evaluation of the investigational Chikungunya virus virus-like particle vaccine 
(CHIKV VLP), VRC-CHKVLP059-00-VP.  This candidate vaccine was evaluated in a Phase 1 study 
as safe and well-tolerated and observed to induce neutralizing antibody responses at levels hypothesized 
to be protective against CHIKV infection [2]. 
2.1
Purpose of the Analyses 
This is a Phase 2 multicenter, randomized, placebo-controlled, double-blind study to examine the safety 
and immunogenicity of a 2-injection vaccine regimen (Day 0 and 28) with the CHIKV VLP vaccine or 
PBS placebo in healthy adults. Note, not all analyses for endpoints included in the protocol are detailed 
in this plan. This statistical analysis plan details the analyses pertaining to the primary and secondary 
outcomes. The exploratory immunogenicity endpoint of humoral and cellular immune response as 
measured by NAb, ELISA and other assays at Week 4, 16, 24, 48, and 72 may not be performed. The 
only immunogenicity data expected is humoral and cellular immune response as measured by NAb at 
Week 0 and 8 and ELISA at screening. Also, interim analyses included in the protocol are not detailed 
in this plan, including the analysis of immune responses and CHIKV incidence rates at 6 and 12 months 
after the study is closed to accrual. 

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3
STUDY OBJECTIVES AND ENDPOINTS 
3.1
Study Objectives
Primary Objective: 
To evaluate the safety and tolerability of VRC-CHKVLP059-00-VP in healthy adults that 
reside in CHIKV endemic areas when administered intramuscularly by needle and syringe 
at a dose of 20 mcg compared to placebo. 
Secondary Objectives: 
To evaluate the immune response to VRC-CHKVLP059-00-VP by neutralization assay at 
4 weeks after the second 20 mcg dose (Study Week 8). 
Exploratory Objectives: 
To evaluate humoral and cellular responses to VRC-CHKVLP059-00-VP at additional time 
points.  CHIKV-specific responses will be assessed by antibody assays that include antigen-
specific ELISA and neutralization assay. 
To compare incidence rates of CHIKV infection in vaccine and placebo recipients. 
To compare clinical and virus characteristics of infections in vaccine and placebo recipients. 
3.2
Endpoints
3.2.1
Primary Endpoints  
Safety
Assessment of product safety will include clinical observation and monitoring of hematological and 
chemical parameters.  Reactogenicity will be closely monitored for 7 days after injection and safety 
evaluated by clinical visits through the study duration of 72 weeks. 
The following parameters will be assessed: 
Local reactogenicity signs and symptoms for 7 days after each injection 
Systemic reactogenicity signs and symptoms for 7 days after each injection 
Laboratory measures of safety through 4 weeks after last injection 
Adverse events through 4 weeks after last injection 
Serious adverse events and new chronic medical conditions throughout the study   
CHIKV infection events throughout the study 
3.2.2
Secondary Endpoints

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Immunogenicity
Humoral immune response as measured by neutralization antibody (NAb) assay at baseline 
(Day 0) and at 4 weeks after second injection (Week 8). 
3.2.3
Exploratory Endpoints  
Immunogenicity
Humoral responses to VRC-CHKVLP059-00-VP at additional time points assessed by 
antibody assays that include antigen-specific ELISA and neutralization assay. 
Chikungunya Infection Incidence
Confirmed Chikungunya infections by positive PCR results for CHIKV at the end of the 
study. 
Cases of illness clinically consistent with Chikungunya infection confirmed or not by a 
positive PCR at the end of the study.  
Clinical characteristics of infections based on standard of care parameters for CHIKV 
disease. Virus characteristics of infections measured by signs and symptoms.  
3.3
Study Definitions and Derived Variables 
The baseline value will be defined as the last value obtained prior to the first injection of study product 
on Day 0.  
Individual neutralization antibody (NAb) assay results will be reported as a titer. The lower limit of 
detection for the NAb assay is 15 reciprocal serum dilution and the lower limit of confidence is 30 
reciprocal serum dilution. Values below the limit of detection will be imputed as 15 if not already 
imputed prior to analysis. For analysis, the arithmetic mean of repeated results for each sample will be 
computed and used as the response for all subsequent calculations.  
Fold-rise (NAb) is a measure that describes how much the NAb titer changes from an initial to a final 
value. The fold-rise is calculated as the ratio of the final value to the initial value. 
Positive response rate (NAb) will be measured as the proportion of subjects with a positive response, 
defined as a reciprocal serum dilution  30.  

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4
INVESTIGATIONAL PLAN 
4.1
Overall Study Design and Plan 
VRC 704 is a Phase 2 multicenter, randomized, placebo-controlled, double-blind parallel group study 
as summarized in Table 1 below.  It examines the safety and immunogenicity of a 2-injection vaccine 
regimen (Day 0 and 28) with the CHIKV VLP vaccine or PBS placebo in healthy adults (N=200 per 
group).  Subjects will be randomly assigned in a 1:1 allocation to active vaccine or placebo control using 
a randomized block design stratified by age within each study site. The expected duration of time on the 
study per subject is approximately 72 weeks. 
Table 1: 
Study Schema 
Group 
Number of 
Subjects
VRC 704 Study Injection Schedule 
Day 0 
Day 28(+14) 
1 
200 
20 mcg CHIKV VLP 
20 mcg CHIKV VLP 
2 
200 
PBS 
PBS 
All injections will be administered IM at 0.5 mL by needle and syringe. 
The Protocol Safety Review Team (PSRT) will review safety data routinely throughout the study.  The 
study will utilize both electronic database features and reviews by designated safety review personnel 
to identify in a timely manner if any of the safety pause rules of the study are met.  The NIAID Intramural 
DSMB will provide an independent safety review at scheduled intervals to coincide with their biannual 
meeting schedule.  
No formal statistical interim analysis intended to terminate the trial early for futility or efficacy is 
planned.  Therefore, no p-value adjustments will be made. 
4.2
Study Design Issues 
The design for this study is a simple parallel group double-blind randomized control using PBS as the 
control.  Following screening, eligible subjects are enrolled; enrollment includes subject randomized to 
a treatment assignment and administration of the first injection based on the randomization assignment.  
Subjects who are randomized but whom do not receive a study injection  (for example a subject who is 
randomized but then decides not to participate prior to receiving the Day 0 injection) will not contribute 
to the analysis cohorts. 

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4.3
Selection of Study Population 
The study is designed for the enrollment of healthy adults.  The following eligibility criteria will be 
used. 
Inclusion Criteria 
A subject must meet all of the following criteria: 
1.
18 to 60 years old 
2.
Available for clinical follow-up through Study Week 72 
3.
Able to provide proof of identity to the satisfaction of the study clinician completing the 
enrollment process 
4.
Able and willing to complete the informed consent process 
5.
Willing to donate blood for sample storage to be used for future research 
6.
In good general health, with a BMI 40, without clinically significant medical history, and has 
satisfactorily completed screening 
7.
Physical examination and laboratory results without clinically significant findings within the 56 
days prior to enrollment 
Laboratory Criteria within 56 days prior to enrollment: 
8.
Hemoglobin either within institutional normal limits or accompanied by site physician 
approval as consistent with healthy adult status 
9.
White blood cells either within institutional normal range or accompanied by site physician 
approval as consistent with healthy adult status  
10. Platelets = 125,000 – 500,000/mm3
11. Alanine aminotransferase (ALT)  1.25 x upper limit of normal (ULN) 
12. Serum creatinine  1.1 x ULN based on site institutional normal range 
13. Negative result on an HIV test that meets local standards for identification of HIV infection 
14. Negative result on the CHIKV screening antibody assay. 
Criteria applicable to women of childbearing potential: 
15. Negative human chorionic gonadotropin pregnancy test (urine or serum) on day of enrollment  
16. Agree to use an effective means of birth control from 21 days prior to enrollment through 12 
weeks after the last study injection 

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Exclusion Criteria 
A subject will be excluded if one or more of the following conditions apply: 
Women Specific: 
1.
Planning to become pregnant during the 16 weeks after enrollment in the study 
Subject has received any of the following substances: 
2.
Systemic immunosuppressive medications within 2 weeks prior to enrollment 
3.
Blood products within 16 weeks prior to enrollment 
4.
Immunoglobulin within 8 weeks prior to enrollment 
5.
Prior vaccinations with an investigational CHIKV vaccine 
6.
Investigational research agents within 4 weeks prior to enrollment 
7.
Any vaccination within 2 weeks prior to enrollment 
8.
Current anti-TB prophylaxis or therapy 
Subject has a history of any of the following clinically significant conditions: 
9.
A history of immune-mediated or clinically significant arthritis  
10. Serious reactions to vaccines that preclude receipt of study injections as determined by the 
investigator 
11. Hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema 
12. Asthma that is unstable or required emergent care, urgent care, hospitalization or intubation 
during the past two years or that is expected to require the use of oral or intravenous 
corticosteroids  
13. Diabetes mellitus (type I or II), with the exception of gestational diabetes 
14. Idiopathic urticaria within the past year 
15. Bleeding disorder diagnosed by a doctor (e.g. factor deficiency, coagulopathy, or platelet 
disorder requiring special precautions) or significant bruising or bleeding difficulties with IM 
injections or blood draws 
16. Malignancy that is active or history of a malignancy that is likely to recur during the period of 
the study 
17. Seizure in the past 3 years or treatment for a seizure disorder within the last 3 years 
18. Asplenia, functional asplenia or any condition resulting in the absence or removal of the spleen 
19. Psychiatric condition that may preclude compliance with the protocol; past or present 
psychoses; or a history of suicide plan or attempt within the five years prior to enrollment 

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20. Any medical or social condition that, in the judgment of the investigator, is a contraindication 
to protocol participation or impairs a volunteer’s ability to give informed consent 
4.4  Subject Discontinuations
A subject may be discontinued from receiving study injections for the following reasons:  
Pregnancy; 
Grade 3 AE assessed as related to a study injection (with the exception that self-limited 
Grade 3 solicited reactogenicity does not require discontinuation of study injections); 
Grade 4 AE assessed as related to a study injection;  
Immediate hypersensitivity reaction associated with a study injection; 
CHIKV infection or other intercurrent illness that is not expected to resolve prior to the 
scheduled study injection assessed by study clinician to require withdrawal from the 
injection schedule;  
Treatment with systemic glucocorticoids (e.g., prednisone or other glucocorticoid) or other 
immunomodulators (other than nonsteroidal anti-inflammatory drugs [NSAIDs]), with the 
exception that, study injection may continue per investigator discretion if the next one 
occurs at least 2 weeks following completion of glucocorticoid treatment; 
The study PI assesses that it is not in the best interest of the subject to continue on the 
injection schedule. 
A subject may be discontinued from protocol participation for the following reasons:  
Subject voluntarily withdraws; 
Subject develops a medical condition that is a contraindication to continuing study 
participation; 
The Investigational New Drug (IND) sponsor or regulatory authorities stop the protocol;  
The study PI assesses that it is not in the best interest of the subject to continue participation 
in the study or that the subject’s compliance with the study is not sufficient.  
4.5
Treatments 
4.5.1
Treatments Administered 
The active vaccine under study is 20 mcg dose of VRC-CHKVLP059-00-VP, an investigational VLP 
vaccine that consists of the E1, E2 and capsid proteins of CHIKV (strain 37997).  The control is VRC-
PBSPLA043-00-VP, sterile phosphate-buffered saline (PBS) prepared for human injection.   Subjects 
will receive 2 intramuscular (IM) injections via needle and syringe.  

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4.5.2
Method of Assigning Subjects to Treatment Groups (Randomization)  
For each clinical site, randomization will be 1:1 allocation within each stratum of age group to either 
the CHIKV VLP vaccine or PBS placebo.  The randomization sequence was generated in SAS using 
permuted blocked randomization with randomly selected block sizes of two or four.
Randomizations will be done online using an electronic randomization system.  The randomization code 
was prepared by the Protocol Statistician and included in the enrollment module for the trial.  The 
randomization code will link to the treatment assignment.  To decrease the potential for subject dropouts 
during the period between randomization and initial injection, the electronic data system will assign 
each subject a randomization code on Day 0 after confirmation of eligibility to begin Day 0 study 
injections has been entered into the system. Manual randomization back-up procedures and instructions 
will be provided for use in the event that the site temporarily loses access to the Internet or the online 
enrollment system is unavailable to a study site. 
If an individual is screened but does not enroll into the clinical trial, screening records will be kept to 
document the reason the individual did not enroll.  
4.5.3
Blinding and Conditions for Unblinding 
The injections will be prepared by an unblinded site pharmacist or otherwise qualified personnel who is 
not involved in any subject assessments and who will not discuss randomizations with blinded study 
staff.  The subjects, study personnel who perform study injections and assessments, data entry personnel 
at the sites, and laboratory personnel performing immunologic assays will be blinded to the treatment 
assignment of all injections.  Subject study injection assignments will be provided to the site Principal 
Investigator (PI) at completion of the study for communication to the study participants.  The DSMB 
may receive data in aggregate and presented by treatment group during the study, but without the 
treatment group identified.  The DSMB may be unblinded to individual study treatment assignments, as 
needed, to adequately assess safety issues. 
If necessary, the site PI (or designee) and Protocol Chair may agree that management of an AE requires 
emergency unblinding of an individual subject’s assignment following the first injection.  This will be 
documented as a protocol deviation and the Protocol Statistician, the site IRB, and the DSMB will be 
notified that an early unblinding has occurred and provided with a statement explaining the medical 
necessity for the early unblinding. For further details on unblinding in the study, consult the Study 
Blinding Plan. 
4.6
Safety and Immunogenicity Variables and Chikungunya Infection Incidence 
4.6.1
Safety
Solicited AEs will be recorded in the study database with data collection for 7 days after both the first 
and second study injections. All unsolicited AEs will be recorded separately in the database from receipt 
of first study injection through 4 weeks after the last study injection administered. At subsequent follow-
up visits, only serious adverse events (SAEs) and new chronic medical conditions will be recorded 
through the last study visit.  

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4.6.2
Immunogenicity
The principle immunogenicity endpoint is  measured 4 weeks post second injection (Week 8) by 
neutralization assay.   
4.6.3
Chikungunya Infection Incidence
The primary variable for this analysis is PCR-confirmed CHIKV illness.  Reports of clinical illness with 
or without PCR confirmation will also be provided. Throughout the study if a subject reports signs and 
symptoms of CHIKV infection, blood samples should be collected for diagnostic testing by virus 
detection (e.g., PCR) by the Primary Diagnostic Laboratory (PDL).  This may occur during a scheduled 
study visit or unscheduled visits may be conducted to complete the testing needed. CHIKV cases will 
be recorded through the last study visit.  Laboratory confirmed cases of CHIKV will be recorded on a 
CHIKV endpoints form rather than on an AE form without an attribution assessment. 

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5
SAMPLE SIZE CONSIDERATIONS 
The study design is to enroll 400 healthy adult participants ages 18 to 60 that reside in CHIKV endemic 
areas.  Randomization will equally allocate subjects to vaccine or placebo schedules with electronic 
stratification by ages 18-40 and 41-60 years.  The enrollment plan does not include provision for 
replacing subjects with incomplete injections or visit schedules.  
Enrollments may occur rapidly at more than one site.  The sample size for this study was not selected to 
test a formal null hypothesis, rather it reflects the number of vaccine doses that are available for the 
study and the desire to gain maximal information for the possible conduct of Phase 3 follow on trials.  
There are not good data to estimate the loss to follow-up rate for this study.  The power calculations 
assume a 10% loss in both groups for the primary and secondary endpoints.  
5.1 Power Calculations for Evaluation of Safety 
The goal of the safety evaluation for this study is to identify safety concerns associated with injections 
of the investigational vaccine.  Two sample size calculations for safety are expressed in terms of two 
approaches, within group and comparing two groups. 
1.
The ability to detect safety or reactogenicity events within each injection group: 
The ability of the study to identify safety events may be expressed in terms of the probability of 
observing one or more event of interest (e.g., AEs) assuming a range of “true” but unknown event rates.  
The power to observe one or more event in a single group of 180 subjects is 83.62% when the true rate 
is 1.0% and 97.37% when the true rate is 2.0% (Table ). 
Table 2: 
Probability of Observing One or More Safety Events within a Group (n=180) 
True Event Rate 
Pr (1 or more events) 
0.01% 
1.78% 
0.10% 
16.48% 
0.33% 
45.17% 
0.50% 
59.43% 
1.00% 
83.62% 
2.00% 
97.37% 
2.
The minimum detectable difference in safety event (e.g., AEs) rates for comparing two injection 
groups using Fisher’s exact test: 
Safety event rates may vary considerably with the type of event considered therefore a wide range of 
possible rates is considered for comparison by vaccine group (Table ). 

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Table 3: 
Minimum Detectable Differences in Event Rates for Power = 80% or 90% Assuming 
Type I Two-Tail Error Rate of 5% (n=180 per Group) 
Power 
Assumed Event Rate 
in Group 1 
(n=180) 
Minimum Detectable 
Event Rate Group 2 
(n=180) 
Difference in 
Rates 
80% 
0.1% 
5.5% 
5.4% 
1.0% 
7.5% 
6.5% 
5.0% 
14.2% 
9.2% 
25% 
39.3% 
14.3% 
90% 
0.1% 
6.9% 
6.8% 
1.0% 
8.9% 
7.9% 
5.0% 
16.0% 
11.0% 
25% 
41.6% 
16.6% 
5.2 Power Calculations for Evaluation of Immune Responses 
A secondary objective is to evaluate the humoral immunogenicity of VRC-CHKVLP059-00-VP by 
neutralization assay at 4 weeks after the second 20 mcg dose (Week 8).  Vaccine specific neutralization 
antibodies are not anticipated in the non-vaccinated group.  Therefore, direct comparison between the 
active and placebo group is of minimal value in assessing sample size.  Preliminary Phase 1 
neutralization data suggest that neutralization results at the visit with peak response are log-normally 
distributed with a mean and standard deviation on the log-scale of 7.41 and 0.67 respectively.  This 
standard deviation is rounded up to 0.70 and two more conservative options of 1.0 and 1.5 result in 95% 
confidence intervals (CI) for geometric mean titers (GMT) (Table ). 
Table 4: 
95% CI for GMT Neutralization among Vaccinees at Time of Peak Response (n=180 
per Group) 
Assume Standard Deviation 
on Log Scale 
95% CI for GMT 
Neutralization Among 
Vaccinees (n=180) at Time 
of Peak Response 
0.70 
(1490.7, 1831.7) 
1.0 
(1426.6, 1914.1) 
1.5 
(1324.8, 2061.1) 
The study is not designed to compare two groups defined by baseline covariates such as gender or age 
strata.  However, the following table is included to provide a sense of the power available for such 
comparisons.  The simple case of two groups (e.g., male and female), assuming equal participation (i.e., 
90 subjects for each gender-vaccine group), is given in Table  for comparing response rates. 

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Table 5: 
Detectable Geometric Mean Ratio between Two Groups for Power = 80% or 90% 
Assuming Type I Two-Tail Error Rate of 5% (n=90 per Group) 
Power 
Standard Deviation on 
Log Scale 
Detectable 
Geometric Mean Ratio 
(n=90 per group) 
80% 
0.7 
1.34 
1.0 
1.52 
1.5 
1.88 
90% 
0.7 
1.40 
1.0 
1.63 
1.5 
2.08 

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6
GENERAL STATISTICAL CONSIDERATIONS 
6.1
General Principles 
All continuous variables will be summarized using the following descriptive statistics: n (non-missing 
sample size), mean, standard deviation, median, maximum and minimum. The frequency and 
percentages (based on the non-missing sample size) of observed levels will be reported for all categorical 
measures. In general, all data will be listed, sorted by site, treatment and subject, and when appropriate 
by visit number within subject. All summary tables will be structured with a column for each treatment 
in the order (Experimental, Control) and will be annotated with the total population size relevant to that 
table/treatment, including any missing observations. 
 
Summary statistics for discrete data will include estimates and confidence intervals for binomial data; 
contingency tables, along with summary analyses such as tests of independence.  Two-by-two tables 
may also include summaries of risk differences or risk ratios as is appropriate along with their confidence 
intervals.  
Tabulations will be used extensively to summarize the data and will include summary statistics.  For 
continuous data, tables will include measures of central tendency such as the mean, geometric mean, or 
median, and measures of dispersion such as the standard deviation or inter-quartile range.  Tables of 
discrete data will include proportions and their confidence intervals.   
Unless noted, statistical analyses will use standard methods as described below. 
6.2
Timing of Analyses 
This study is addressing an emerging and potentially expanding epidemic of Chikungunya.  Therefore, 
at any time during the study an unplanned analysis may be required.  There is no intention to use such 
an analysis to modify the study design.  The extent of unblinding (e.g., group versus individual level 
and parameters examined) and the distribution of results will be limited to the maximal extent 
compatible with necessary use of the results.  For example, site investigators will not receive interim 
results without an explicit request from the PI. Absent any possible safety concerns in a blinded review 
of the results, unblinded analyses will focus on immune responses and CHIKV incidence.  The PSRT 
may also request an unblinding of the safety data at any time if, in their opinion, data internal or external 
to the trial requires such a review. 
If any interim analyses are conducted, a separate analysis plan will be established to further describe the 
nature of the analyses and presentation of data. While these interim results may be used for design of 
future trials they will not be used to modify the design of this protocol.  
Final analyses and the production of a CSR will occur when all subjects have completed their follow-
up or have otherwise been prematurely censored, their data is cleaned within the limitations of practical 
follow-up and the database is locked.   

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6.3
Analysis Populations 
The Safety population will include all enrolled subjects, summarized according to the actual vaccination 
received. 
The Per Protocol (PP) analyses will include all subjects receiving two injections within window as 
assigned by the randomization schedule, and not experiencing any other major protocol deviations prior 
to their week 8 visit. Major protocol deviations include ineligibility, product administration deviations, 
and primary endpoint missing data. The subjects will be analyzed based on product actually received, 
regardless of randomization assignment.  If subjects receive study vaccine for one visit and placebo for 
the other, then they will be included in the PP population until they receive the second injection or are 
otherwise removed from the PP population.  The PP analyses will also include subjects determined to 
be CHIKV infected prior to the receipt of their scheduled second injection and not experiencing any 
other major protocol deviations prior to their state of infection.  Subjects will be censored from the 
immunogenicity analysis following PCR-confirmed CHIKV infection.  Immunogenicity and infection 
rates will both be examined for the PP population. 
The Intent-to-treat (ITT) population will include all enrolled subjects, analyzed according to the 
randomized treatment. The ITT population will be used to analyze immunogenicity and infection rates. 
The Modified intent-to-treat (mITT) analyses will include all enrolled subjects that received at least 
one product administration with non-missing immunogenicity data at their Week 8 visit, analyzed 
according to the study product(s) received. This definition will exclude subjects with protocol deviations 
related to possible dosing errors.   The mITT population will only be used for immunogenicity analyses. 
Subjects excluded from Immunogenicity (or CHIKV Incidence) analyses are listed in Appendix III, 
Listing 16.2.3.
6.4
Covariates and Subgroups 
This study is not powered to perform formal subgroup analyses.   Age stratum (18-40,  41-60 years) and 
site will be used to define subgroup analyses for descriptive purposes. 
6.5
Missing Data 
Imputation of missing values is not planned.  Imputation may be implemented for secondary or tertiary 
outcomes if supported by the data and if sufficient consequence to justify their inclusion.  
6.6
Interim Analyses and Data Monitoring 
The PSRT will review safety data routinely throughout the study. The NIAID Intramural DSMB will 
provide an independent safety review at scheduled intervals to coincide with their biannual meeting 
schedule.  
Interim analyses are mentioned above in Section 6.2 and are also covered and detailed elsewhere in the 
VRC 704 Interim Analysis Plan dated 19 January 2018. 
Note that these analyses will not be used for early trial termination. Therefore, final p-values will not be 
adjusted for interim analyses.  

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6.7
Multicenter Studies 
Data will be pooled across all clinical sites.  Center effects are not anticipated because the sites are using 
standardized procedures for vaccination and assessment of solicited and unsolicited adverse events, and 
the study relies on central laboratories for the assessment of immunogenicity and clinical efficacy 
endpoints. 
Nevertheless, to guard against the potential for regional differences, the primary analysis will also be 
presented by site.  
6.8
Multiple Comparisons/Multiplicity  
This study is not designed to test a specific hypothesis.  Rather it is intended to obtain sufficient data to 
design and implement future efficacy trials.  Absent the testing of a formal primary hypothesis there is 
no requirement for multiple comparison adjustments. 

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7
STUDY SUBJECTS 
7.1 Subject Disposition 
Table 14.1.1 (Appendix I), will present a summary of the reasons that subjects were screened but not 
enrolled. 
The composition of analysis populations, including reasons for subject exclusion, by treatment arm, is 
presented in Table 14.1.2, Appendix I.
The disposition of subjects in the study will be tabulated by site and treatment group (Table 14.1.3, 
Appendix I).  The table shows the total number of subjects screened, enrolled, receiving at least 1 dose, 
receiving at least 2 doses, discontinued dosing or terminated from study follow-up and the number 
completing the study.  CHIKV infection status and subject disposition will be tabulated by site and 
treatment group (Table 14.1.4, Appendix I). The table shows the number and percentages of subjects 
who had a PCR-confirmed CHIKV infection, those with a clinical CHIKV infection (both further split 
by when infection occurred), and those uninfected. 
A flowchart showing the disposition of study subjects, adapted from the CONSORT Statement [3] will 
be included (Figure 14.1.1, Appendix II). This figure will present the number of subjects screened, 
enrolled, lost to follow-up, and analyzed, by treatment arm where applicable. 
A listing of subjects who discontinued dosing or terminated from study follow-up and the reason will 
be included in Listing 16.2.1 (Appendix III).
7.2
Protocol Deviations 
A summary of subject-specific protocol deviations will be presented by the reason for the deviation, the 
deviation category, and treatment group for all subjects (Table 14.1.5). Deviations that are considered 
major in the categories of ineligibility, product administration, and primary endpoint missing data will 
be reviewed for possible subject exclusion from the per protocol population. All subject-specific 
protocol deviations and non-subject-specific protocol deviations will be included in Appendix III as data 
listings (Listings 16.2.2.1 and 16.2.2.2, respectively). 
 

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8
SAFETY EVALUATION 
8.1
Demographic and Other Baseline Characteristics 
Summaries of age, gender, ethnicity, and race will be presented by treatment group overall and by site 
(Tables 14.1.6.1-14.1.6.4, Appendix I). Ethnicity is categorized as Hispanic or Latino, Not Hispanic or 
Latino, or Unknown/Not reported. 
In accordance with NIH reporting policy, subjects may self-designate as belonging to more than one 
race or may refuse to identify a race, the latter reflected in the eCRF as “No” to each racial option.  The 
race categories to be used are: American Indian or Alaska Native; Asian; Native Hawaiian or Other 
Pacific Islander; Black or African American; White; Unknown. Individual subject listings (Appendix 
III) will be presented for all demographics (Listing 16.2.4.1); pre-existing medical conditions (Listing 
16.2.4.2); vital signs and oral temperature (Listing 16.2.9.1); and concomitant medications (Listing 
16.2.10).  
8.1.1
Concurrent Illnesses and Medical Conditions 
All current illnesses and past pre-existing medical conditions will be Medical Dictionary for Regulatory 
Activities (MedDRA®) coded using MedDRA dictionary version 19.1 or higher.   
Summaries of subjects’ pre-existing medical conditions will be presented by treatment group and age 
stratum (Table 14.1.7, Appendix I).  
Individual subject listings will be presented for all medical conditions (Listing 16.2.4.2, Appendix III). 
8.1.2
Prior and Concurrent Medications 
Current concomitant prescription medications are recorded in the study database at enrollment. 
Concomitant medications are updated in the study database if there is an occurrence of an adverse event 
(AE) that requires expedited reporting. If it will not endanger a subject’s health, non-investigational 
vaccines should not be administered 14 days before or until at least 28 days after a study injection. 
Licensed vaccines received by the subject within 4 weeks before the first study injection administration 
and 4 weeks after last study injection will be recorded in the study database. Otherwise, a record of 
concomitant medication changes throughout the study will not be recorded in the study database.  
All concomitant medications taken during the study will be recorded on the source documentation. 
A by-subject listing of concomitant medication for the safety population use will be presented in Table
14.3.6, Appendix I.
Individual subject listings will be presented for all concomitant medications (Listing 16.2.10, Appendix 
III). 
8.2
Measurements of Treatment Compliance 
All subjects were to receive two doses of study product administered in the clinic. The number of doses 
of study product administered to subjects will be presented by treatment group and by site as part of the 
subject disposition table (Table 14.1.3, Appendix I).

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Table 14.1.8 (Appendix I) presents compliance with the dosing schedule, i.e., the number of subjects 
who received first dose, by treatment arm and by site. Listing 16.2.5 (Appendix III) presents individual 
subject listings for treatment compliance and dosage administration.
8.3
Adverse Events 
The severity of an adverse event (AE) is defined as: Grade 1 (Mild), Grade 2 (Moderate), Grade 3 
(Severe), Grade 4 (Life-threatening), and Grade 5 (Death). Only the single AE that is assessed as the 
primary cause of death should be assigned “Grade 5” severity. 
Relation of an AE to the study product is defined as Definitely Related, Probably Related, Possibly 
Related, and Not Related. For purposes of preparing data reports in which AE attributions are limited to 
“Related” or “Not Related”, in this protocol, the “Definitely, Probably and Possibly” attributions will 
be mapped to the “Related” category. 
AEs will be coded into MedDRA preferred terms. 
When calculating the incidence of AEs (i.e., on a per subject basis), each subject will only be counted 
once and any repetitions of AEs within a subject will be ignored; the denominator will be the total 
population size.  All AEs reported will be included in the summaries and analyses.  
8.3.1
Solicited Events and Symptoms 
Solicited AEs will be recorded in the study database with data collection for 7 days after both the first 
and second study injections, without the collection of attribution assessments. 
Following the study injection, the subject will remain in the clinic for observation for at least 15 minutes. 
After 15 minutes, blood pressure and pulse will be taken and the injection site will be inspected for 
evidence of local reaction before the subject leaves the clinic. 
Subjects will be given a diary card to use as a memory aid, on which to record the solicited signs and 
symptoms daily for 7 days following each injection. The site may use a paper diary card as a source 
document or clinician notes obtained by telephone interview as the source for the information recorded 
in the study database. The solicited signs and symptoms on the diary card will include the following 
parameters: pain/tenderness at injection site, largest diameters of redness (erythema) and swelling 
(induration) at injection site, highest measured temperature per day, unusually tired/feeling unwell, 
muscle/body aches (other than at injection site), arthralgia (joint pain), headache, chills, and nausea.  
At least one contact at about 7 days after each study injection will be conducted to complete the review 
of solicited diary card information. Subjects will be asked to contact the clinic at any time following 
each injection if they have any concerning signs or symptoms. Events that will require clinical evaluation 
include rash, urticaria, arthralgia, fever of 38.5 C (Grade 2) or higher lasting more than 24 hours, or 
significant impairment in the activities of daily living. Additionally, other clinical concerns may prompt 
a study visit based on the judgment of a study clinician.  
The proportion of subjects reporting at least one solicited AE will be summarized by dose, treatment 
group and age stratum for each solicited adverse event, any systemic symptom, any local symptom, and 
any symptom.  The 95% CI calculated using Clopper-Pearson methodology from a binomial distribution 
will be presented (Table 14.3.1.1, Appendix I).

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For each solicited systemic and local event, any systemic event, any local event, and any solicited event, 
the maximum severity over 7 days after each dose will be summarized for the safety population by 
treatment group and age stratum. The number and percentage of subjects reporting each event will be 
summarized by the maximum severity and treatment group, separately for each dose and over all doses. 
For each event the denominator is the number of subjects with non-missing data for the specific event
(Table 14.3.1.2, Appendix I).  
The number and proportion of subjects reporting a solicited AE will be summarized pre-dose and for 
each day post-dose for each injection and for all injections combined both in a summary table by 
treatment group and age stratum (Table 14.3.1.3, Appendix I) and graphically in a bar chart (Figure 
14.3.1.1, Appendix II).   A comparison of the event rate of solicited adverse events for each treatment 
group between dose 1 and dose 2 will be presented by age stratum (Tables 14.3.1.4-14.3.1.5, Appendix 
I). 
Solicited AEs by subject will be presented in Listing 16.2.7.1, Appendix III.
8.3.2
Unsolicited Adverse Events 
All unsolicited AEs will be recorded in the study database from receipt of first study injection through 
4 weeks after the last study injection administered. At subsequent follow-up visits, only SAEs and new 
chronic medical conditions will be recorded through the last study visit. 
The proportion of subjects reporting at least one unsolicited AE will be summarized by MedDRA system 
organ class and preferred term for each injection, age stratum, and treatment group and over all 
injections. Denominators for percentages are the number of subjects who received the injection being 
summarized.  A 95% CI will be presented along with a Fisher's exact test comparing the treatment 
groups and testing the difference in the proportion of subjects reporting an unsolicited AE for each 
MedDRA system organ class and preferred term (Table 14.3.1.6, Appendix I).
Unsolicited AEs by subject will be presented in Listing 16.2.7.2, Appendix III.
The following summaries for unsolicited AEs will be presented by MedDRA system organ class (SOC), 
preferred term, dose, age stratum, treatment group, and site: 
Subject level summary of severity and relationship to study product (Tables 14.3.1.7.1-
14.3.1.7.2, Appendix I);
Subject incidence of AEs over time (Days 1-7, Days > 7) (Tables 14.3.1.8.1-14.3.1.8.2, 
Appendix I);
Total frequency of AEs over time (Days 1-7, Days > 7) (Table 14.3.1.9, Appendix I);
Subject listing of non-serious AEs of moderate or greater severity (Table 14.3.2.2, 
Appendix I);
Bar chart of non-serious AEs by severity and MedDRA SOC (Figure 14.3.1.2, Appendix 
II);
Bar chart of non-serious AEs by severity (Figure 14.3.1.3, Appendix II);
Bar chart of non-serious AEs by relationship to study product and MedDRA SOC (Figure
14.3.1.4, Appendix II);

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Bar chart of non-serious AEs by relationship to study product (Figure 14.3.1.5, Appendix 
II).
8.4
Deaths, Serious Adverse Events and other Significant Adverse Events 
For reported deaths, SAEs, and new onset chronic medical conditions, the following listings will be 
presented:  
Deaths and SAEs (Table 14.3.2.1, Appendix I);
New Onset Chronic Medical Conditions (Table 14.3.2.3, Appendix I). 
These tables will be presented in terms of the following variables: Subject ID, Age (years), AE 
Description, Severity, AE Onset Date/End Date, Last Dose Received/Days Post Dose, Effect on 
Injection Schedule, Reason Reported as an SAE, Relationship to Treatment, Outcome, and Duration of 
Event (days). 
8.5
Pregnancies
For subjects who become pregnant during the first 16 weeks on study, every attempt will be made to 
follow them to completion of pregnancy to document the outcome, including information regarding any 
complications with pregnancy and/or delivery.  The pregnancy outcomes are captured by the pregnancy 
eCRF. Pregnant subjects are discontinued from receiving the study injections.  
A table summarizing the total pregnancies, number of live births, and number of spontaneous abortions, 
elective abortions or stillbirths by treatment will be presented (Table 14.3.7, Appendix I). In addition, 
a listing of pregnancies and outcomes will be presented (Listing 16.2.11, Appendix III).
8.6
Clinical Laboratory Evaluations 
Safety laboratory parameters evaluated from serum will include only the liver function test measuring 
ALT. Hematology parameters include hemoglobin, white blood cells (WBC), red blood cells (RBC), 
hematocrit, mean corpuscular volume (MCV), platelets, and absolute values for lymphocytes, 
neutrophils, eosinophils, monocytes and basophils. Sites enter the absolute values for the laboratory 
parameters and the system calculates percentage values. Laboratory safety evaluations are scheduled at 
week 4, 8, 16, 24, 32, 40, 48, 56, 64, and 72. Clinical laboratory results by subject will be presented in 
Listings 16.2.8.1 – 16.2.8.2, Appendix III. 
As a note, the lab data for site PRCTRC were initially entered as percentage values but, in June 2016, 
the site switched to reporting absolute values with their respective units. This caused some discrepancy 
between calculated values in the database and data collection forms at the site. This could influence 
precision and will be considered as lab data are reported. 
Only results for scheduled routine visits will be included in these analyses.  In particular, laboratory 
results obtained at visits other than Week 4 and 8 for diagnosis of AEs will not be included.   
Safety laboratory evaluations will be graded as follows: mild (grade 1), moderate (grade 2), severe 
(grade 3), or life-threatening (grade 4).  

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Safety laboratory results will be tabulated for each measure by study visit, treatment group, age stratum 
and grade (Table 14.3.4.1, Appendix I).  The mean change from baseline along with 95% CI at each 
time point measured in the study will be computed (Table 14.3.4.2, Appendix I).  Boxplots of safety 
laboratory values will be generated for baseline values and for values measured during the course of the 
study.  Each boxplot will show the 1st quartile, the median, and the 3rd quartile, with values smaller 
than the 1st quartile or larger than the 3rd quartiles plotted as outliers.  If appropriate, horizontal lines 
representing boundaries for abnormal values will be plotted.  
Post dose 1 measures may also be summarized using shift tables to compare baseline and follow-up 
values (Tables 14.3.4.4.x – 14.3.4.5.x, Appendix I).  Shift tables may be analyzed using Generalized 
Estimating Equations to account for the longitudinal nature of these data, as follows: 
1)
For laboratory parameters with two categories: Normal and abnormal (Binary 
response)  
a.
For each parameter, the shift table displays the number of subjects who are categorized 
as normal or abnormal at baseline cross tabulated with normal or abnormal results at 
the post-vaccination visit. 
b.
A GEE for the binary responses above is fitted and used for parameter estimation 
Observation 
 for each subject 
 and repeated measurement time 
point 
dependent 
variable 
, 
independent 
variable 
; 
probability of abnormal is 
; 
model: 
 using the logit link; 
GEE: 
=0 where 
 is the working covariance 
matrix; 
 Implementation: PROC GENMOD (SAS) using SUBJECT option in the 
REPEATED statement to identify the cluster variable 
Output: point estimates and 95% CI for the individual levels of the GROUP, TIME 
and GROUP*TIME variables, and Type-3 SAS output for the parameter 
significance; 
Other analysis and outputs: Odds ratio with associated 95% CI of observing 
abnormality (from the fitted logistic model). Implemented with LSMEANS 
statement in PROC GENMOD. 
2)
For laboratory parameters with four categories: Grade 1, Grade 2, Grade 3, and 
Grade 4 (Ordinal response)  
a.
For each parameter the shift table displays the number of subjects who are categorized 
as grade 1, grade 2, grade 3, or grade 4 at baseline cross tabulated with grade 1, grade 
2, grade 3, or grade 4 results at the post-vaccination visit. 

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b.
A GEE model for the ordinal responses above are fitted and used for parameter 
estimation 
Observation 
 for each subject 
 at time point
. 
is the ordinal response variable with 3 ordered categories; 
Cumulative probability 
; 
Proportional Odds model
 using the logit link;
GEE: 
=0 where
 is the working 
covariance matrix;
Output: estimated of two intercepts from the two fitted logistic models; point 
estimates and 95% CI for the individual levels of the GROUP, TIME and 
GROUP*TIME variables, and Type-3 SAS output for the parameter significance 
(chi-Square test);
The study is not powered to detect differences by vaccine group, therefore the absence of statistically 
significantly differences should not be interpreted that no such differences exist.   
Individual clinical laboratory results for hematology and chemistry will be presented in Listing 16.2.8.1 
– 16.2.8.2, Appendix III. Laboratory summary statistics are presented in Table 14.3.4.2, Appendix I.  
Box plots for laboratory results are presented in Figures 14.5.1 -- 14.5.x, Appendix II. A listing of 
abnormal laboratory results is presented in Table 14.3.4.3, Appendix I. 
8.7 Vital Signs and Physical Evaluations 
Vital signs measurements include temperature, pulse, and systolic and diastolic blood pressure. The 
assessment of vital signs is planned at week 0, 4, 8, 16, 24, 32, 40, 48, 56, 64 and 72. The physical exam 
is only required at the screening visit and may be performed at subsequent visits if needed based on 
interim history. These optional physical exam evaluations are not captured in the data system.  
Vital signs are tabulated by visit, age stratum, and treatment group. Vital signs will be summarized over 
time graphically using box plots for subjects in the Safety population (Table 14.3.5, Appendix I, Figure
14.4.1-14.4.x, Appendix II, Listing 16.2.9, Appendix III). 

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9
IMMUNOGENICITY EVALUATION 
Specimens to evaluate immunogenicity will be taken at baseline and at specified time points. The 
primary immunogenicity timepoint is 4 weeks after the second injection. Measurements of CHIKV-
specific humoral immune responses will be assessed by neutralization antibody (NAb) assays. A listing 
of individual titer levels and the corresponding planned and actual collection dates are presented in 
Appendix III, Listing 16.2.6.  
At some sites, positive baseline Week 0 neutralization antibody assay results were reported. ELISA 
response data, captured as part of the screening eligibility process, have been received by the Sponsor 
from the laboratory. When raw ELISA data is received, baseline ELISA responses will be assessed in 
relation to neutralization antibody data and results will be reported. For further information, a separate 
analysis plan will be created to elaborate on specific analyses to be performed. 
The principle immunogenicity endpoint is  measured at Week 8 by neutralization assay.  
Descriptive analyses will be presented by study day, age group, and treatment group, aggregated over 
all study sites and by site.  If none or a very small number of placebo group subjects have a neutralization 
response, their results will only be reported for the positive response rate summaries and omitted from 
other analyses.  This approach is taken to achieve brevity and easier understanding of results when the 
control group has no meaningful responses.  
Summaries include: 
GMT and their confidence intervals (Table 14.2.1, Appendix I)
Geometric mean ratio (GMR) of results obtained at baseline (Week 0) to results obtained at 
Week 8 and its 95% CI. (Table 14.2.1, Appendix I)
Positive response rates, as defined by an assay-specific post dose response, and their exact 
95% CI (Table 14.2.1, Appendix I)
Reverse cumulative distribution of the neutralization assay results (Figure 14.2.1, 
Appendix II) 
Boxplots of titer values (Figure 14.2.2, Appendix II).
These summaries will be repeated for all exploratory research tests used to measure exploratory 
immunogenicity endpoints at the timepoints for which there are data. 

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10
ANALYSES OF CHIKUNGUNYA INFECTION INCIDENCE AND TIME TO EVENT 
Analyses of CHIKV infections are exploratory. A few definitions of incident cases exist and therefore 
efficacy will be considered in: 
cases for which CHIKV is confirmed by a positive PCR 
cases with symptoms consistent with CHIKV but not necessarily confirmed by a positive PCR 
Efficacy will include all cases using 2 exploratory alternatives for case inclusion:  
1. all infections post dose 1 (Day 0),  
2. all infections post dose 2.  
Subjects not receiving dose 2 will be included in definition 1. 
The analysis of efficacy is divided into two parts which are described below, using the intent-to-treat 
cohort.  
Clinical cases as well as PCR confirmed cases are listed in Listing 16.3.1, Appendix III. Individual 
time to event data post dose one and post dose two are listed in Listing 16.3.2 -16.3.3, Appendix III.
10.1
Description of Observed Events: 
Incidence and number of clinical cases of CHIKV 
o
Inclusion 1: All cases post dose 1 (Day 0) 
o
Inclusion 2: All cases post dose 2. Subjects not receiving dose 2 will be considered for 
inclusion 1.  
Incidence and number of PCR confirmed cases of CHIKV  
o
Inclusion 1: All cases post dose 1 (Day 0) 
o
Inclusion 2: All cases post dose 2. Subjects not receiving dose 2 will be considered for 
inclusion 1.  
For each scenario, incidence rates and number of cases will be described by treatment group by age 
stratum and aggregating and by combining age strata. Results are presented in Tables 15.1.1-15.1.4 in 
Appendix I.
10.2
Analysis of Vaccine Efficacy: 
Time to occurrence of clinical CHIKV infection 
o
Inclusion 1: All cases post dose 1 (Day 0) 
o
Inclusion 2: All cases post dose 2. Subjects not receiving dose 2 will be considered for 
inclusion 1.  
Time to occurrence of PCR confirmed CHIKV infection 
o
Inclusion 1: All cases post dose 1 (Day 0) 
o
Inclusion 2: All cases post dose 2. Subjects not receiving dose 2 will be considered for 
inclusion 1.  
Time to event will be based on the date of onset of the clinical symptom (for clinical cases) or on blood 
sample with the first positive laboratory test indicating CHIKV infection (for PCR confirmed cases). 

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Time to occurrence post dose one and post dose two will be calculated for clinical CHIKV infections as 
well as PCR confirmed CHIKV infections as follows: 
Post first injection: 
For subjects with infection: First date of diagnosis of clinical CHIKV infection minus date of 
first injection + 1.  These subjects will not be censored. 
For subjects with no infection: Date of study completion or date of early termination minus 
date of first injection + 1.   These subjects will be censored at their date of study completion 
or date of early termination. 
Post second injection: 
For subjects with infection: First date of diagnosis of clinical CHIKV infection minus date of 
second injection + 1.  These subjects will not be censored. 
For subjects with no infection: Date of study completion or date of early termination minus 
date of second injection + 1.   These subjects will be censored at their date of study 
completion or date of early termination. 
Subjects that do not receive the second dose are excluded. 
Subjects that develop CHIKV before second dose are excluded. 
The principal exploratory analysis consists of a comparison between the vaccine and placebo groups of 
the time to occurrence of infection after first dose and after second dose. The magnitude of vaccine 
effect will be estimated in terms of vaccine efficacy (95% CI) obtained from Cox proportional hazard 
model. Statistical testing will be performed using Log-rank test. (Tables 15.2.1-15.2.4, Appendix I)  
The secondary exploratory analysis consists of an adjusted survival for age and site using a Log-rank 
test. In addition to univariate adjustments, multivariate adjustment will be performed in a single model 
using Cox regression for time to infection after first dose and after second dose. Estimates of vaccine 
efficacy adjusting for baseline characteristics will be displayed in Tables 15.3.1-15.3.4, Appendix I. 
Kaplan-Meier survival curves will be plotted by group, as presented in Figures 15.1.1-15.1.4 Appendix 
III. 
10.3
Sample SAS Code for Analysis: 
Notations 
    Timevar = the variable that gives the time to occurrence 
    Censor_var = the variable defining whether timevar is censored 
    Trtmnt_group = treatment group where 0 = Placebo and 1=VRC-CHIKVLP059-00-VP; 
Cox Proportional Hazard 
SAS Code for Cox Regression to obtain Vaccine Efficacy and 95% CI for Vaccine Efficacy: 
Proc phreg; 
Model timevar*censor_var(0)=trtmnt_group (and any covariates)/rl; 
Ods output parameterestimates=ests(keep=HazardRatio HRUpperCL HRLowerCL); 
Run; 

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Ods output RiskDiffCol1=rdc1; 
Run;
Calculate the following from the hazard ratios/estimates obtained from SAS 
Vaccine Efficacy = 1 – Hazardratio;  
Lower 95% CI= 1 – HRUpperCL which is the same as 1 – exp(estimate + 1.96*stderr) 
Upper 95% CI= 1 – HRLowerCL which is the same as 1 - exp(estimate – 1.96*stderr)
Log-Rank Test 
SAS Code for Log-Rank Test to obtain p-value: 
Proc lifetest; 
time timevar*censor_var(0); 
strata trtmnt_group;  
id pid; 
Ods output homtests = tests(where=(test=”Log-Rank”) keep=test probchisq); 
Run; 
Obtain p-value from SAS:  p-value=probchisq; 

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11
REPORTING CONVENTIONS 
P-values 0.001 and 0.999 will be reported to 3 decimal places; p-values less than 0.001 will be 
reported as “<0.001”; p-values greater than 0.999 will be reported as “> 0.999“. The mean, standard 
deviation, and any other statistics other than quantiles, will be reported to one decimal place greater than 
the original data. Quantiles, such as median, or minimum and maximum will use the same number of 
decimal places as the original data. Proportions will be presented as two decimal places; values <0.01 
will be presented as “<0.01”. Percentages will be reported to the nearest whole number; values < 1% 
will be presented as “<1”. Estimated parameters, not on the same scale as raw observations (e.g. 
regression coefficients), will be reported to 3 significant figures.  

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12
TECHNICAL DETAILS 
SAS version 9.3 or above will be used to generate all tables, figures and listings. 
13
REFERENCES 
1.
WHO. 
Chikungunya. 
2015 
[cited; 
Available 
from: 
http://www.who.int/mediacentre/factsheets/fs327/en/.] 
2.
Chang, L.J., K.A. Dowd, F.H. Mendoza, J.G. Saunders, S. Sitar, et al., Safety and 
tolerability of chikungunya virus-like particle vaccine in healthy adults: a phase 1 dose-
escalation trial. Lancet, 2014. 384(9959): p. 2046-52. 
3.
Schulz Kenneth F, Altman Douglas G, Moher David. CONSORT 2010 Statement: 
updated 
guidelines 
for 
reporting 
parallel 
group 
randomised 
trials. BMJ
2010; 340:c332 
14
LISTING OF TABLES, LISTINGS AND FIGURES 
Table, figure, and listing shells are presented in Appendices I, II and III respectively.

Statistical Analysis Plan 
Appendix I: Table Mock - Ups
for
Protocol 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 
Version 1.0 
Prepared and distributed by: 
The Emmes Corporation 
Rockville, Maryland 
THIS COMMUNICATION IS PRIVILEGED AND CONFIDENTIAL

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Table of Contents
TABLE 14.1.1: Ineligibility Summary of Screen Failures by Site......................................................... 1
TABLE 14.1.2: Analysis Populations by Treatment Group ................................................................... 2
TABLE 14.1.3: Subject Disposition by Site and Treatment Group ....................................................... 3
TABLE 14.1.4: Chikungunya Infection Subject Status by Site and Treatment Group .......................... 4
TABLE 14.1.5: Distribution of Subject-Specific Protocol Deviations by Category and Treatment 
Group ...................................................................................................................................................... 6
TABLE 14.1.6.1: Distribution of Sex, Ethnicity, Race, and Language by Site ..................................... 7
TABLE 14.1.6.2: Age Statistics (in Years) by Site ................................................................................ 8
TABLE 14.1.6.3: Distribution of Sex, Ethnicity, Race, and Language by Treatment Group ................ 9
TABLE 14.1.6.4: Age Statistics (in Years) by Treatment Group ........................................................ 10
TABLE 14.1.7: Distribution of Subjects with Pre-Existing Medical Conditions by MedDRA® System 
Organ Class and Treatment Group by Age Stratum ............................................................................. 11
TABLE 14.1.8: Dates of First Treatment by Site and Treatment Group ............................................. 12
TABLE 14.2.1: Geometric Mean Titer (GMT), Geometric Mean Ratio, and Positive Response Rates 
of the [specific strain/assay] Results with 95% Confidence Intervals at Baseline and Week 8 by Site 
and Treatment Group <<Age Stratum>> ............................................................................................. 13
TABLE 14.3.1.1: Number and Percentage of Subjects Experiencing Solicited Events with 95% 
Confidence Intervals by Symptom, Dose, Treatment Group, and Site <<Age Stratum>> .................. 14
TABLE 14.3.1.2: Number and Percentage of Subjects Experiencing Solicited Events by Symptom, 
Maximum Severity, Dose, Treatment Group, and Site <<Age Stratum>> .......................................... 16
TABLE 14.3.1.3: Number and Percentage of Subjects Experiencing Solicited Events by Symptom, 
Severity, Dose, Day Post Dosing, Treatment Group, and Site <<Age Stratum>> ............................... 19
TABLE 14.3.1.4: Number and Percentage of Subjects Experiencing Solicited Events for Dose 1 
Compared with Dose 2 by Treatment Group ....................................................................................... 22
TABLE 14.3.1.5: Comparison of the Proportion of Subjects Experiencing Solicited Events by 
Treatment Group and Site <<Age Stratum>> ...................................................................................... 24
TABLE 14.3.1.6: Number and Percentage of Subjects Experiencing Unsolicited Adverse Events with 
95% Confidence Intervals by MedDRA® System Organ Class, Preferred Term, Treatment Group and 
Dose Number <<Age Stratum>> ......................................................................................................... 25

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TABLE 14.3.1.7.1: Number and Percentage of Subjects Experiencing Unsolicited Adverse Events by 
MedDRA® System Organ Class and Preferred Term, Severity, Relationship, Treatment Group, and 
Site <<Age Stratum>> ......................................................................................................................... 26
TABLE 14.3.1.7.2: Number and Percentage of Subjects Experiencing Related Unsolicited Adverse 
Events by MedDRA® System Organ Class and Preferred Term, Severity, Treatment Group, and Site 
<<Age Stratum>> ................................................................................................................................. 27
TABLE 14.3.1.8.1: Number and Percentage of Subjects Experiencing Unsolicited Adverse Events by 
MedDRA® System Organ Class and Preferred Term, Day Post Dosing, Treatment Group, and Site 
<<Age Stratum>> ................................................................................................................................. 28
TABLE 14.3.1.8.2: Number and Percentage of Subjects Experiencing Related Unsolicited Adverse 
Events Within 7 Days Post Dosing by MedDRA® System Organ Class and Preferred Term, Dose, 
Treatment Group, and Site <<Age Stratum>> ..................................................................................... 29
TABLE 14.3.1.9: Number of Unsolicited Adverse Events by MedDRA® System Organ Class and 
Preferred Term, Day Post Dosing, Treatment Group, and Site <<Age Stratum, Overall/Site>> ........ 30
TABLE 14.3.2.1: Listing of Deaths and Serious Adverse Events........................................................ 31
TABLE 14.3.2.2: Listing of Non-Serious, Unsolicited, Moderate or Severe Adverse Events ............ 32
TABLE 14.3.2.3: Listing of New Onset Chronic Medical Conditions ................................................ 33
TABLE 14.3.4.1: Distribution of Laboratory Results by Parameter, Severity, Study Day, and 
Treatment Group <<Age Stratum, Overall/Site>> ............................................................................... 34
TABLE 14.3.4.2: Laboratory Summary Statistics by Parameter, Study Day, and Treatment Group 
<<Age Stratum, Overall/Site>> ........................................................................................................... 40
TABLE 14.3.4.3: Listing of Abnormal Laboratory Results ................................................................. 47
TABLE 14.3.4.4.x: Shift Table for <<binary-graded laboratory parameter>> by Treatment Group 
Comparing Pre-Dose One Measure to Post-Dose One Measures <<Overall/Site>> ........................... 48
TABLE 14.3.4.5.x: Shift Table for <<ordinal-graded laboratory parameter>> by Treatment Group 
Comparing Pre-Dose One Measure to Post-Dose One Measures <<Overall/Site>> ........................... 49
TABLE 14.3.5: Distribution of Vital Signs by Day Post Dosing, Grade, and Treatment Group <<Age 
Stratum, Overall/Site>> ........................................................................................................................ 50
TABLE 14.3.6: Number and Percentage of Subjects with Concurrent Medications by Treatment 
Group <<Age Stratum>> ..................................................................................................................... 52
TABLE 14.3.7: Number of Pregnancies by Outcome and Treatment Group ...................................... 53
TABLE 15.1.1: Incidence of Clinical Cases of CHIKV Post Dose One by Treatment Group and 
Stratified by Age .................................................................................................................................. 54

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TABLE 15.1.2: Incidence of Clinical Cases of CHIKV Post Dose Two by Treatment Group and 
Stratified by Age .................................................................................................................................. 55
TABLE 15.1.3: Incidence of PCR Confirmed Cases of CHIKV Post Dose One by Group and 
Stratified by Age .................................................................................................................................. 55
TABLE 15.1.4: Incidence of PCR Confirmed Cases of CHIKV Post Dose Two by Group and 
Stratified by Age .................................................................................................................................. 55
TABLE 15.2.1: Primary Exploratory Analysis – Vaccine Efficacy for Time to Occurrence of Clinical 
CHIKV Infection Post Dose One ......................................................................................................... 56
TABLE 15.2.2: Primary Exploratory Analysis – Vaccine Efficacy for Time to Occurrence of Clinical 
CHIKV Infection Post Dose Two ......................................................................................................... 57
TABLE 15.2.3: Primary Exploratory Analysis – Vaccine Efficacy for Time to Occurrence of PCR 
Confirmed CHIKV Infection Post Dose One ....................................................................................... 57
TABLE 15.2.4: Primary Exploratory Analysis – Vaccine Efficacy for Time to Occurrence of PCR 
Confirmed CHIKV Infection Post Dose Two ...................................................................................... 57
TABLE 15.3.1: Secondary Exploratory Analysis - Vaccine Efficacy for Time to Occurrence of 
Clinical CHIKV Infection Post Dose One with Adjustment for Baseline Characteristics ................... 58
TABLE 15.3.2: Secondary Exploratory Analysis - Vaccine Efficacy for Time to Occurrence of 
Clinical CHIKV Infection Post Dose Two with Adjustment for Baseline Characteristics .................. 59
TABLE 15.3.3: Secondary Exploratory Analysis – Vaccine Efficacy for Time to Occurrence of PCR 
Confirmed CHIKV Infection Post Dose One with Adjustment for Baseline Characteristics .............. 59
TABLE 15.3.4: Secondary Exploratory Analysis – Vaccine Efficacy for Time to Occurrence of PCR 
Confirmed CHIKV Infection Post Dose Two with Adjustment for Baseline Characteristics .............. 59

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Section 14.1 Demographic Data 
TABLE 14.1.1: 
Ineligibility Summary of Screen Failures by Site
Inclusion/Exclusion Criterion 
Number of Times Item Marked Ineligible* 
Site 1 Site 2 Site 3 Site 4 Site 5 Site 6 All Sites
Number of subjects failing  
any eligibility criterion 
x
Laboratory findings 
x
        CHIKV Positive or Indeterminate
x
Physical exam findings 
x
Medical history 
x
Other
x
*More than one criterion may be marked per subject. 
Note: If subject is positive or indeterminate for at least one result from the IgG and IgM CHIKV tests, 
then they will be counted as CHIKV Positive or Indeterminate.  

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TABLE 14.1.2: 
Analysis Populations by Treatment Group 
[Implementation note: All percentages should use N as the denominator, where N is the total number 
of subjects defined in column headers. 
More than one criterion may be marked per subject.] 
Analysis Populations 
CHIKV
(N=X) 
Placebo
(N=X) 
All Subjects 
(N=X) 
n
%
n
%
n
%
Population 1, Per Protocol 
Subjects included in PP 
x
x.x 
x
x.x 
x
x.x 
Any reason for exclusion 
    Vaccination out of window 
    Major protocol deviation prior     
to Week 8 visit 
    Error in second vaccination 
Immunogenicity Only 
PCR-confirmed CHIKV infection 
Population 2, Intent to 
Treat 
Immunogenicity
Subjects included in ITT 
Immunogenicity data not available 
Infection Rates 
Subjects included in ITT (no 
exclusions) 
Population 3, Modified 
Intent to Treat 
Immunogenicity Only 
Subjects included in mITT 
Any reason for exclusion 
Immunogenicity data not available 
at Week 8 visit 
Received no product 
administrations
Protocol deviation related to 
dosing error 

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TABLE 14.1.3: 
Subject Disposition by Site and Treatment Group 
Subject 
Disposition
Site 1 
CHIKV
(N=X) 
Site 1 
Placebo
(N=X) 
Site 2 
CHIKV
(N=X) 
Site 2 
Placebo
(N=X) 
Site 3 
CHIKV
(N=X) 
Site 3 
Placebo
(N=X) 
Site 4 
CHIKV
(N=X) 
Site 4 
Placebo
(N=X) 
Site 5 
CHIKV
(N=X) 
Site 5 
Placebo
(N=X) 
Site 6 
CHIKV
(N=X) 
Site 6 
Placebo
(N=X) 
All Sites 
CHIKV
(N=X) 
All Sites 
Placebo
(N=X) 
All Sites All 
Subjects 
(N=X) 
n
%
n
%
n
%
n
%
n
%
n
%
n
%
n
%
n
%
n
%
n
%
n
%
n
%
n
%
n
%
Screened 
x
x.x 
x
x.x 
x
x.x
x
x.x
x
x.x
x
x.x 
x
x.x 
x
x.x
x
x.x 
x
x.x
x
x.x 
x
x.x 
x
x.x 
x
x.x 
x
x.x 
Enrolled and 
Received First 
Vaccination  
Received Second 
Vaccination 
Remaining In PP 
Population a
Completed- Per 
Protocolb
Lost to Per Protocol 
Before Vaccination 
Two
Lost to Per Protocol 
At or After the Time 
of Vaccination 2 
Completed ITT 
Cohort
aRefer to Listing 16.2.1 for reasons subjects discontinued or terminated early. 
bRefer to Listing 16.2.3 for reasons subjects are excluded from the per protocol population. 

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TABLE 14.1.4: 
Chikungunya Infection Subject Status by Site and Treatment Group 
Subject 
Disposition
Site 1 
CHIKV
(N=X) 
Site 1 
Placebo
(N=X) 
Site 2 
CHIKV
(N=X) 
Site 2 
Placebo
(N=X) 
Site 3 
CHIKV
(N=X) 
Site 3 
Placebo
(N=X) 
Site 4 
CHIKV
(N=X) 
Site 4 
Placebo
(N=X) 
Site 5 
CHIKV
(N=X) 
Site 5 
Placebo
(N=X) 
Site 6 
CHIKV
(N=X) 
Site 6 
Placebo
(N=X) 
All Sites 
CHIKV
(N=X) 
All Sites 
Placebo
(N=X) 
All Sites All 
Subjects 
(N=X) 
n
%
n
%
n
%
n
%
n
%
n
%
n
%
n
%
n
%
n
%
n
%
n
%
n
%
n
%
n
%
Enrolled 
x
x.x 
x
x.x 
x
x.x
x
x.x
x
x.x
x
x.x
x
x.x
x
x.x
x
x.x
x
x.x 
x
x.x
x
x.x 
x
x.x 
x
x.x 
x
x.x 
ChikV infection confirmed by PCR 
ChikV infection prior to 
second injection   
Received second injection 
and not ChikV infected 
ChikV infected post 
second injection 
Completed follow-up in 
PP Cohort without 
infection 
Lost to follow-up and not 
known to be infected 
Completed ITT Cohort 
without ChikV infection 
Clinical ChikV infection (confirmed or not by PCR) 
ChikV infection prior to 
second injection   
Received second injection 
and not ChikV infected 
ChikV infected post 
second injection 

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Subject 
Disposition
Site 1 
CHIKV
(N=X) 
Site 1 
Placebo
(N=X) 
Site 2 
CHIKV
(N=X) 
Site 2 
Placebo
(N=X) 
Site 3 
CHIKV
(N=X) 
Site 3 
Placebo
(N=X) 
Site 4 
CHIKV
(N=X) 
Site 4 
Placebo
(N=X) 
Site 5 
CHIKV
(N=X) 
Site 5 
Placebo
(N=X) 
Site 6 
CHIKV
(N=X) 
Site 6 
Placebo
(N=X) 
All Sites 
CHIKV
(N=X) 
All Sites 
Placebo
(N=X) 
All Sites All 
Subjects 
(N=X) 
n
%
n
%
n
%
n
%
n
%
n
%
n
%
n
%
n
%
n
%
n
%
n
%
n
%
n
%
n
%
Completed follow-up in 
PP Cohort without 
infection 
Lost to follow-up and not 
known to be infected 
Completed ITT Cohort 
without ChikV infection 

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TABLE 14.1.5: 
Distribution of Subject-Specific Protocol Deviations by Category and Treatment Group 
Category
CHIKV
(N=X) 
Placebo
(N=X) 
All Subjects 
(N=X) 
# of 
Subj. 
# of 
Dev.
# of 
Subj. 
# of 
Dev.
# of 
Subj. 
# of 
Dev.
Eligibility/enrollment 
Product administration schedule 
Follow-up visit schedule 
Protocol procedure/assessment 
Product administration 
Blinding policy/procedure 

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TABLE 14.1.6.1: 
Distribution of Sex, Ethnicity, Race, and Language by Site
Demographic
Category
Characteristic
Site 1
(N=X)
Site 2
(N=X)
Site 3
(N=X)
Site 4 
(N=X) 
Site 5 
(N=X) 
Site 6 
(N=X) 
All
Subjects
(N=X) 
n
%
n
%
n
%
n
%
n
%
n
%
n
%
Sex
Male 
x
x.x x x.x x
x.x x x.x x x.x x
x.x 
x
x.x 
Female 
Unknown or Not Reported 
Ethnicity  
Hispanic or Latino 
x
x.x x x.x x
x.x x x.x x x.x x
x.x 
x
x.x 
Not Hispanic or Latino 
Unknown or Not Reported 
Race  
American Indian or Alaska Native 
x
x.x x x.x x
x.x x x.x x x.x x
x.x 
x
x.x 
Asian
Native Hawaiian or Other Pacific Islander 
Black or African American 
White 
Unknown 
Language 
English 
x
x.x x x.x x
x.x x x.x x x.x x
x.x 
x
x.x 
French 
Spanish 
Haitian Creole 
Antillean Creole 

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TABLE 14.1.6.2: 
Age Statistics (in Years) by Site
Statistic 
[Site 1] 
(N=X) 
[Site 2] 
(N=X) 
[Site 3] 
(N=X) 
[Site 4] 
(N=X) 
[Site 5] 
(N=X) 
[Site 6] 
(N=X) 
All Subjects 
(N=X) 
Mean 
x.x 
x.x 
x.x 
Standard Deviation 
x.x 
x.x 
x.x 
Median 
x.x 
x.x 
x.x 
Minimum
X
X
x
Maximum 
X
X
x

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TABLE 14.1.6.3: 
Distribution of Sex, Ethnicity, Race, and Language by Treatment Group 
Demographic
Category
Characteristic
CHIKV
(N=X) 
Placebo
(N=X) 
All Subjects 
(N=X) 
n
%
n
%
n
%
Sex
Male 
x
x.x 
x
x.x 
x
x.x 
Female 
Unknown or Not Reported 
Ethnicity  
Hispanic or Latino 
x
x.x 
x
x.x 
x
x.x 
Not Hispanic or Latino 
Unknown or Not Reported 
Race  
American Indian or Alaska Native 
x
x.x 
x
x.x 
x
x.x 
Asian
Native Hawaiian or Other Pacific 
Islander 
Black or African American 
White 
Unknown 
Language 
English 
x
x.x 
x
x.x 
x
x.x 
French 
Spanish 
Haitian Creole 
Antillean Creole 

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TABLE 14.1.6.4: 
Age Statistics (in Years) by Treatment Group 
Statistic 
CHIKV
(N=X) 
Placebo
(N=X) 
All Subjects 
(N=X) 
Mean 
x.x 
x.x 
x.x 
Standard Deviation 
x.x 
x.x 
x.x 
Median 
x
X
x
Minimum
x
X
x
Maximum 
x
X
x

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TABLE 14.1.7: 
Distribution of Subjects with Pre-Existing Medical Conditions by MedDRA® 
System Organ Class and Treatment Group by Age Stratum
Age Stratum 
 (years) 
MedDRA® System Organ Class 
CHIKV
(N=X) 
Placebo
(N=X) 
All Subjects 
(N=X) 
n
%
n
%
n
%
18-40
Any SOC 
x
x.x 
x
x.x 
x
x.x 
[SOC 1] 
[SOC 2] 
41-60
Any SOC 
[SOC 1] 
[SOC 2] 
Note: This table presents number and percentage of subjects.  A subject is only counted once per SOC. 

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TABLE 14.1.8: 
Dates of First Treatment by Site and Treatment Group 
Month and Year 
[Site 1] 
CHIKV
(N=X) 
[Site 1] 
Placebo
(N=X) 
[Site 2]
CHIKV
(N=X) 
[Site 2]
Placebo
(N=X) 
[Site 3]
CHIKV
(N=X) 
[Site 3]
Placebo
(N=X) 
[Site 4]
CHIKV
(N=X) 
[Site 4]
Placebo
(N=X) 
[Site 5] 
CHIKV
(N=X) 
[Site 5]
Placebo
(N=X) 
[Site 6]
CHIKV
(N=X) 
[Site 6]
Placebo
(N=X) 
All Sites
CHIKV
(N=X) 
All Sites
Placebo
(N=X) 
All Sites 
All Subjects
(N=X) 
November 2015 
x
x
x
x
x
x
x
x
x
x
X
x
x
x
x
December 2015 
…

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Section 14.2 Immunogenicity Data 
TABLE 14.2.1: 
Geometric Mean Titer (GMT), Geometric Mean Ratio, and Positive Response Rates of the [specific strain/assay] Results with 
95% Confidence Intervals at Baseline and Week 8 by Site and Treatment Group <<Age Stratum>>
Baseline 
Week 8 
Treatment Group 
N
GMT (95% CI)
N
GMT (95% CI) 
Comparison of 
GMT at Week 
8 (p-value) 
Geometric
Mean 
Ratio 
(95% CI) 
P-value 
comparison of 
GMR
Positive Response 
Rates (%) at Week 8
(95% CI)^ 
P-value 
comparison of
Positive 
Response 
Rates* 
Overall 
CHIKV VLP 20 mcg 
x
xx.x (xx.x, 
xx.x) 
x
xx.x (xx.x, xx.x) 
x.xxx 
x.xx (x.xx, x.xx) 
x.xxx 
xx.x (xx.x, xx.x) 
x.xxx 
PBS 
Site 1 [repeat for all sites]
CHIKV VLP 20 mcg 
PBS 
GMT = Geometric Mean Titer, CI = Confidence Interval, GMR = Geometric Mean Ratio 
^Positive immune response defined as [positivity criteria here] 
*p-value from Fisher's exact test 

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Section 14.3 Safety Data 
TABLE 14.3.1.1: 
Number and Percentage of Subjects Experiencing Solicited Events with 95% Confidence Intervals by Symptom, 
Dose, Treatment Group, and Site <<Age Stratum>> 
[Implementation note: Repeat rows for each site like the example at the end of the table for Site 1]
Symptom 
Post Dose 1 
CHIKV
(N=X) 
Post Dose 1 
Placebo
(N=X) 
Post Dose 2 
CHIKV
(N=X) 
Post Dose 2 
Placebo
(N=X) 
Post Either Dose 
CHIKV
(N=X) 
Post Either Dose 
Placebo
(N=X) 
n
%
95% CI
n
%
95% CI
n
%
95% CI
n
%
95% CI
n
%
95% CI
n
%
95% CI
Overall 
Any Symptom 
x
x.x 
x.x, x.x 
x
x.x 
x.x, x.x 
x
x.x 
x.x, x.x 
x
x.x 
x.x, x.x 
x
x.x 
x.x, x.x 
x
x.x 
x.x, x.x 
Any Systemic 
Symptom 
Nausea
Chills 
Headache 
Malaise [Unusually 
Tired/Feeling 
Unwell]
Myalgia 
[Muscle/Body 
Aches]

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TABLE 14.3.1.1: Number and Percentage of Subjects Experiencing Solicited Symptoms with 95% Confidence Intervals by 
Symptom, Dose and Treatment Group (continued)
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Symptom 
Post Dose 1 
CHIKV
(N=X) 
Post Dose 1 
Placebo
(N=X) 
Post Dose 2 
CHIKV
(N=X) 
Post Dose 2 
Placebo
(N=X) 
Post Either Dose 
CHIKV
(N=X) 
Post Either Dose 
Placebo
(N=X) 
Joint Pain 
Temperature 
Any Local 
Symptom 
Pain/Tenderness 
Erythema/Redness 
Induration/Swelling 
Site 1 
Any Symptom 
…[continue for all 
symptoms and 
sites]

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TABLE 14.3.1.2: 
Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Maximum Severity, Dose, 
Treatment Group, and Site <<Age Stratum>>
Any Symptom 
Symptom 
Severity 
Post Dose 1 
CHIKV
(N=X) 
Post Dose 1 
Placebo
(N=X) 
Post Dose 2 
CHIKV
(N=X) 
Post Dose 2 
Placebo
(N=X) 
Post Either Dose
CHIKV
(N=X) 
Post Either Dose
Placebo
(N=X) 
n
%
n
%
n
%
n
%
n
%
n
%
Overall 
Any Symptom None
x
x.x 
x
x.x 
x
x.x 
x
x.x 
x
x.x 
x
x.x 
Mild
Moderate
Severe
Site 1 [repeat for all sites]
Any Symptom None
Mild
Moderate
Severe
Severity is the maximum severity reported post dosing for each subject. 

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Systemic Symptoms <<Age Stratum>>
Symptom 
Severity
Post Dose 1 
CHIKV
(N=X) 
Post Dose 1 
Placebo
(N=X) 
Post Dose 2 
CHIKV
(N=X) 
Post Dose 2 
Placebo
(N=X) 
Post Either Dose
CHIKV
(N=X) 
Post Either Dose
Placebo (N=X) 
n
%
n
%
n
%
n
%
n
%
n
%
Overall 
Any Systemic Symptom 
None
x
x.x 
x
x.x 
x
x.x 
x
x.x 
x
x.x 
x
x.x 
Mild
Moderate
Severe
[Systemic Symptom 1] 
None
Mild
Moderate
Severe
[Systemic Symptom 2] 
None
Mild
Moderate
[continue for all systemic symptoms] Severe
Site 1 [repeat for all sites]
Any Systemic Symptom 
None
Mild
Moderate
Severe
Severity is the maximum severity reported post dosing for each subject. 

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Local Symptoms <<Age Stratum>>
Symptom 
Severity
Post Dose 1 
CHIKV
(N=X) 
Post Dose 1 
Placebo
(N=X) 
Post Dose 2 
CHIKV
(N=X) 
Post Dose 2 
Placebo
(N=X) 
Post Either Dose
CHIKV
(N=X) 
Post Either Dose
Placebo
(N=X) 
n
%
n
%
n
%
n
%
n
%
n
%
Overall 
Any Local Symptom 
None
x
x.x 
x
x.x 
x
x.x 
x
x.x 
x
x.x 
x
x.x 
Mild
Moderate
Severe
[Local Symptom 1] 
None
Mild
Moderate
Severe
[Local Symptom 2] 
None
Mild
Moderate
[continue for all local symptoms] Severe
Site 1 [repeat for all sites]
Any Local Symptom 
None
Mild
Moderate
Severe
Severity is the maximum severity reported post dosing for each subject. 

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TABLE 14.3.1.3: 
Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Severity, Dose, Day Post 
Dosing, Treatment Group, and Site <<Age Stratum>>
[Implementation Note: If there are more than 7 days of solicited symptom data, then you may want to group together days, for example: Pre-Dose, 
Post-Dose through Day 2, Days 3-5, Days 6+.] 
Any Symptom 
[CHIKV, Post Dose 1] [Repeat this table for each group, each dose]
Symptom 
Severity 
Day 1 
(N=X) 
Day 2 
(N=X) 
Day 3 
(N=X) 
Day 4 
(N=X) 
Day 5 
(N=X) 
Day 6 
(N=X) 
Day 7+ 
(N=X) 
 
 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Overall 
Any Symptom 
None 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Not Reported 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Site 1 [repeat for all sites] 
Any Symptom 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Not Reported 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severity is the maximum severity reported post dosing for each subject for each day. 

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Systemic Symptoms <<Age Stratum>>
[CHIKV, Post Dose 1] [Repeat this table for each group, each dose]
Symptom 
Severity 
Day 1 
(N=X) 
Day 2 
(N=X) 
Day 3 
(N=X) 
Day 4 
(N=X) 
Day 5 
(N=X) 
Day 6 
(N=X) 
Day 7+ 
(N=X) 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Overall
Any Systemic 
Symptom 
None 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Not Reported 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[Systemic 
Symptom 1] 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Not Reported 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[Systemic 
Symptom 2] 
None
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[continue for all 
sys. symptoms] 
Not Reported 
 
Site 1 [repeat for all sites] 
Any Systemic 
Symptom 
None 
 
Severity is the maximum severity reported post dosing for each subject for each day. 

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Local Symptoms <<Age Stratum>>
[CHIKV, Post Dose 1] [Repeat this table for each group, each dose]
Symptom 
Severity 
Day 1 
(N=X) 
Day 2 
(N=X) 
Day 3 
(N=X) 
Day 4 
(N=X) 
Day 5 
(N=X) 
Day 6 
(N=X) 
Day 7+ 
(N=X) 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Overall 
Any Local 
Symptom 
None 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Not Reported 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[Local Symptom 
1]
None 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Not Reported 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[Local Symptom 
2]
None 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[continue for all 
local symptoms] Not Reported 
 
Site 1 [repeat for all sites] 
Any Local 
Symptom 
None 
 
Severity is the maximum severity reported post dosing for each subject for each day.

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TABLE 14.3.1.4: 
Number and Percentage of Subjects Experiencing Solicited Events for Dose 1 Compared with Dose 2 by Treatment Group 
Systemic Symptoms <<Overall/Site, Age Stratum>>
Treatment Group 
Dose 1 
Dose 2 – No Symptoms 
(N=X) 
Dose 2 – Mild or Greater Symptom 
(N=X)
Dose 2 – Total 
(N=X) 
CHIKV
No Symptoms (N=X) 
x (x.xx)
x (x.xx)
x (x.xx)
Mild or Greater Symptom (N=X) 
Total (N=X) 
Placebo 
No Symptoms (N=X) 
Mild or Greater Symptom (N=X) 
Total (N=X) 

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Local Symptoms <<Overall/Site, Age Stratum>>
Treatment Group 
Dose 1 
Dose 2 – No Symptoms 
(N=X) 
Dose 2 – Mild or Greater Symptom 
(N=X)
Dose 2 – Total 
(N=X) 
CHIKV
No Symptoms (N=X) 
x
x
x
Mild or Greater Symptom (N=X) 
Total (N=X) 
Placebo 
No Symptoms (N=X) 
Mild or Greater Symptom (N=X) 
Total (N=X) 

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TABLE 14.3.1.5: 
Comparison of the Proportion of Subjects Experiencing Solicited Events by Treatment Group and Site <<Age Stratum>>
Symptom 
Statistic 
CHIKV
Post Either Dose 
(N=X) 
Placebo
Post Either Dose 
(N=X) 
Overall 
Any Symptom 
Proportion 
x.xx 
x.xx 
 
95% CI (for proportion) 
x.xx, x.xx 
x.xx, x.xx 
 
Difference 
x.xx 
x.xx 
 
95% CI (for difference) 
x.xx, x.xx 
x.xx, x.xx  
[Symptom 1] 
Proportion 
 
 
 
95% CI (for proportion) 
 
 
 
Difference 
 
 
[continue for all symptoms] 
95% CI (for difference) 
 
 
Site 1 [repeat for all sites] 
Any Symptom 
Proportion 
 
 
 
95% CI (for proportion) 
 
 
 
Difference 
 
 
 
95% CI (for difference) 
 
 

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TABLE 14.3.1.6: 
Number and Percentage of Subjects Experiencing Unsolicited Adverse Events with 95% Confidence Intervals by 
MedDRA® System Organ Class, Preferred Term, Treatment Group and Dose Number <<Age Stratum>>
Post Dose 1 [Repeat for Dose 2 and Either Dose] 
MedDRA® System Organ Class
MedDRA® Preferred 
Term 
CHIKV
(N=X) 
Placebo
(N=X) 
Comparison of % subjects 
experiencing event (p-
value)1
n
%
95% CI
n
%
95% CI
Overall 
Any SOC 
Any PT 
x
x.x 
x.x, x.x 
x
x.x 
x.x, x.x 
x.xxx 
[SOC 1] 
Any PT 
[PT 1] 
[PT 2] 
[SOC 2] 
Any PT 
[PT 1] 
[continue for all SOC/PT] 
[PT 2] 
Site 1 [repeat for all sites] 
Any SOC 
Any PT 
Note: This table presents number and percentage of subjects.  A subject is only counted once per PT/time point. 
1. p-values from Fisher’s exact test. 

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TABLE 14.3.1.7.1: 
Number and Percentage of Subjects Experiencing Unsolicited Adverse Events by MedDRA® System 
Organ Class and Preferred Term, Severity, Relationship, Treatment Group, and Site <<Age Stratum>>
CHIKV [Repeat for Placebo] (N=X) 
MedDRA® System Organ Class 
MedDRA® Preferred Term 
Any Incidence 
Severity 
Relationship to Treatment 
Mild 
Moderate 
Severe 
Not Related 
Related
n
%
n
%
n
%
n
%
n
%
n
%
Overall 
Any SOC 
Any PT 
x
x.x 
x
x.x 
x
x.x 
x
x.x 
x
x.x 
x
x.x 
[SOC 1] 
Any PT 
[PT 1] 
[PT 2] 
[SOC 2] 
Any PT 
[PT 1] 
[continue for all SOC/PT] 
[PT 2] 
Site 1 [repeat for all sites] 
Any SOC 
Any PT 
Note: This table presents number and percentage of subjects.  A subject is only counted once per PT and is summarized according to their highest severity and closest relationship. 

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TABLE 14.3.1.7.2: 
Number and Percentage of Subjects Experiencing Related Unsolicited Adverse Events by MedDRA®
System Organ Class and Preferred Term, Severity, Treatment Group, and Site <<Age Stratum>>
CHIKV [Repeat for Placebo] (N=X) 
MedDRA® System Organ Class 
MedDRA® Preferred Term 
Any Incidence 
Severity 
Mild 
Moderate 
Severe 
n
%
n
%
n
%
n
%
Overall 
Any SOC 
Any PT 
x
x.x 
x
x.x 
x
x.x 
x
x.x 
[SOC 1] 
Any PT 
[PT 1] 
[PT 2] 
[SOC 2] 
Any PT 
[PT 1] 
[continue for all SOC/PT] 
[PT 2] 
Site 1 [repeat for all sites] 
Any SOC 
Any PT 
Note: This table presents number and percentage of subjects.  A subject is only counted once per PT and is summarized according to their highest severity.

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TABLE 14.3.1.8.1: 
Number and Percentage of Subjects Experiencing Unsolicited Adverse Events by MedDRA® System 
Organ Class and Preferred Term, Day Post Dosing, Treatment Group, and Site <<Age Stratum>>
CHIKV [Repeat for Placebo] (N=X) 
[Implementation Note: Day x-y interval should correspond to period of collection for solicited symptoms, in this case Day 1-7.  Day y-z interval 
should be up until subsequent dose, in this case Days > 7.] 
[Day 1-7] 
Post Dose 1 
[Day 8-28] 
Post Dose 1 
[Day 1-7] 
Post Dose 2 
[Day 8-28] 
Post Dose 2 
Anytime Post 
Either Dose
MedDRA® System Organ Class 
MedDRA® Preferred Term 
n
%
n
%
n
%
n
%
n
%
Overall 
Any SOC 
Any PT 
x
x.x 
x
x.x 
x
x.x 
x
x.x 
x
x.x 
[SOC 1] 
Any PT 
[PT 1] 
[PT 2] 
[SOC 2] 
Any PT 
[PT 1] 
[continue for all SOC/PT] 
[PT 2] 
Site 1 [repeat for all sites] 
Any SOC
Any PT 
Note: This table presents number and percentage of subjects.  A subject is only counted once per PT/Time point. 

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TABLE 14.3.1.8.2: 
Number and Percentage of Subjects Experiencing Related Unsolicited Adverse Events Within 7 Days Post 
Dosing by MedDRA® System Organ Class and Preferred Term, Dose, Treatment Group, and Site <<Age
Stratum>>
CHIKV [Repeat for Placebo] (N=X) 
[Implementation Note: Day x-y interval should correspond to period of collection for solicited symptoms, if applicable. In this case, that is Days 1-
7.] 
[Day 1-7] 
Post Dose 1 
[Day 1-7] 
Post Dose 2 
Within y Days 
Post Either Dose
MedDRA® System Organ Class 
MedDRA® Preferred Term 
n
%
n
%
n
%
Overall 
Any SOC 
Any PT 
x
x.x 
x
x.x 
x
x.x 
[SOC 1] 
Any PT 
[PT 1] 
[PT 2] 
[SOC 2] 
Any PT 
[PT 1] 
[continue for all SOC/PT] 
[PT 2] 
Site 1 [repeat for all sites] 
Any SOC
Any PT 
Note: This table presents number and percentage of subjects.  A subject is only counted once per PT/Time point. 

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TABLE 14.3.1.9: 
Number of Unsolicited Adverse Events by MedDRA® System Organ Class and Preferred Term, Day 
Post Dosing, Treatment Group, and Site <<Age Stratum, Overall/Site>>
CHIKV [Repeat for Placebo] (N=X) 
[Implementation Note: Day x-y interval should correspond to period of collection for solicited symptoms, if applicable.  Day y-z interval should be 
up until subsequent dose.] 
[Day 1-7] 
Post Dose 1 
[Day 8-28] 
Post Dose 1 
[Day 1-7] 
Post Dose 2 
[Day 8-28] 
Post Dose 2 
Anytime Post 
Either Dose
MedDRA® System Organ Class 
MedDRA® Preferred Term 
# of Events 
# of Events 
# of Events 
# of Events 
# of Events 
Overall 
Any SOC 
Any PT 
x
x
x
x
x
[SOC 1] 
Any PT 
[PT 1] 
[PT 2] 
[SOC 2] 
Any PT 
[PT 1] 
[continue for all SOC/PT] 
[PT 2] 
Site 1 [repeat for all sites] 
Any SOC
Any PT 
Note: This table presents number of events. 

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TABLE 14.3.2.1: 
Listing of Deaths and Serious Adverse Events 
[Implementation note: If event is ongoing at end of study, indicate as “Ongoing” in the “Duration” column. 
If there are no comments for an event, populated “Comments” row with “None.”] 
Part 1
Subject 
ID 
Age
(Years) 
Treatment 
Group 
AE
Number 
Adverse 
Event
Adverse 
Event
Onset
Date
Associated 
with Dose # 
# of Days 
Post
Associated 
Dose
Adverse 
Event
End
Date
Duration
(Days) 
Reason
Reported 
as an SAE 
Severity 
Part 2
Subject ID 
Adverse 
Event
Relationship
to Study 
Treatment 
Effect on 
Injection 
Schedule 
Subject 
Discontinued 
Due to AE 
Outcome 
Comments 

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TABLE 14.3.2.2: 
Listing of Non-Serious, Unsolicited, Moderate or Severe Adverse Events  
[Implementation note: If there are no comments for an event, populated “Comments” row with “None.”] 
Part 1  
Subject 
ID 
Age
(Years) 
Treatment 
Group 
AE
Number 
Adverse 
Event
Adverse 
Event
Onset
Date
Associated 
with Dose # 
# of Days 
Post
Associated 
Dose
Adverse 
Event
End
Date
Duration
(Days) 
Severity 
Relationship
to Study 
Treatment 
Part 2  
Subject ID 
Adverse 
Event
Effect on 
Injection 
Schedule 
Subject 
Discontinued 
Due to AE 
Outcome 
Comments 

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TABLE 14.3.2.3: 
Listing of New Onset Chronic Medical Conditions  
[Implementation note: These conditions are met when AD12SAEA = ‘3’ (Persistent/significant disability/incapacity) and/or AD12OTCM = ‘3’ 
(Ongoing/persistent condition)] 
Part 1  
Subject 
ID 
Age
(Years) 
Treatment 
Group 
AE
Number 
Adverse 
Event
Adverse 
Event
Onset
Date
Associated 
with Dose # 
# of Days 
Post
Associated 
Dose
Adverse 
Event
End
Date
Duration
(Days) 
Severity 
Relationship
to Study 
Treatment 
Part 2  
Subject ID 
Adverse 
Event
Effect on 
Injection 
Schedule 
Subject 
Discontinued 
Due to AE 
Outcome 
Comments 

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TABLE 14.3.4.1: 
Distribution of Laboratory Results by Parameter, Severity, Study Day, and Treatment Group <<Age Stratum, Overall/Site>> 
[Implementation: Repeat this table for the Placebo group]
Lab.  Param 
Severity
Baseline
CHIKV 
(N=X) 
Week 4 
CHIKV 
(N=X) 
Week 8 
CHIKV 
(N=X) 
Week 16 
CHIKV 
(N=X) 
Week 24 
CHIKV 
(N=X) 
Week 32 
CHIKV 
(N=X) 
Week 40
CHIKV
(N=X) 
Week 48
CHIKV
(N=X) 
Week 56
CHIKV
(N=X) 
Week 64
CHIKV
(N=X) 
Week 72
CHIKV
(N=X) 
Max
Severity
Post 
Baseline
CHIKV 
(N=X) 
n
%
n
%
n
%
n
%
n
%
n
%
n
%
n
%
n
%
n
%
n
%
n
%
Any parameter 
Normal 
x
x.x 
x
x.x 
x
x.x 
x
x.x 
x
x.x 
x
x.x 
x
x.x 
x
x.x 
x
x.x 
x
x.x 
x
x.x 
x
x.x 
Outside
Normal 
Range
Grade 1 
Grade 2 
Grade 3 
Grade 4 
ALT 
Normal 
Outside
Normal 
Range
Grade 1 
Grade 2 
Grade 3 
Grade 4 
WBC 
Normal 

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Lab.  Param 
Severity
Baseline
CHIKV 
(N=X) 
Week 4 
CHIKV 
(N=X) 
Week 8 
CHIKV 
(N=X) 
Week 16 
CHIKV 
(N=X) 
Week 24 
CHIKV 
(N=X) 
Week 32 
CHIKV 
(N=X) 
Week 40
CHIKV
(N=X) 
Week 48
CHIKV
(N=X) 
Week 56
CHIKV
(N=X) 
Week 64
CHIKV
(N=X) 
Week 72
CHIKV
(N=X) 
Max
Severity
Post 
Baseline
CHIKV 
(N=X) 
Outside
Normal 
Range
Grade 1 
Grade 2 
Grade 3 
Grade 4 
RBC
Normal 
Outside
Normal 
Range
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Hemoglobin 
Normal 
Outside
Normal 
Range
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Hematocrit 
Normal 

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Lab.  Param 
Severity
Baseline
CHIKV 
(N=X) 
Week 4 
CHIKV 
(N=X) 
Week 8 
CHIKV 
(N=X) 
Week 16 
CHIKV 
(N=X) 
Week 24 
CHIKV 
(N=X) 
Week 32 
CHIKV 
(N=X) 
Week 40
CHIKV
(N=X) 
Week 48
CHIKV
(N=X) 
Week 56
CHIKV
(N=X) 
Week 64
CHIKV
(N=X) 
Week 72
CHIKV
(N=X) 
Max
Severity
Post 
Baseline
CHIKV 
(N=X) 
Outside
Normal 
Range
Grade 1 
Grade 2 
Grade 3 
Grade 4 
MCV 
Normal 
Outside
Normal 
Range
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Platelets 
Normal 
Outside
Normal 
Range
Grade 1 
Grade 2 
Grade 3 
Grade 4 

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Lab.  Param 
Severity
Baseline
CHIKV 
(N=X) 
Week 4 
CHIKV 
(N=X) 
Week 8 
CHIKV 
(N=X) 
Week 16 
CHIKV 
(N=X) 
Week 24 
CHIKV 
(N=X) 
Week 32 
CHIKV 
(N=X) 
Week 40
CHIKV
(N=X) 
Week 48
CHIKV
(N=X) 
Week 56
CHIKV
(N=X) 
Week 64
CHIKV
(N=X) 
Week 72
CHIKV
(N=X) 
Max
Severity
Post 
Baseline
CHIKV 
(N=X) 
Neutrophil 
Normal 
Outside
Normal 
Range
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Lymphocyte 
Normal 
Outside
 Normal 
Range
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Monocyte 
Normal 
Outside
Normal 
Range
Grade 1 
Grade 2 
Grade 3 

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Lab.  Param 
Severity
Baseline
CHIKV 
(N=X) 
Week 4 
CHIKV 
(N=X) 
Week 8 
CHIKV 
(N=X) 
Week 16 
CHIKV 
(N=X) 
Week 24 
CHIKV 
(N=X) 
Week 32 
CHIKV 
(N=X) 
Week 40
CHIKV
(N=X) 
Week 48
CHIKV
(N=X) 
Week 56
CHIKV
(N=X) 
Week 64
CHIKV
(N=X) 
Week 72
CHIKV
(N=X) 
Max
Severity
Post 
Baseline
CHIKV 
(N=X) 
Grade 4 
Eosinophil 
Normal 
Outside
Normal 
Range
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Basophil 
Normal 
Outside
Normal 
Range
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Other 
Normal 
Outside
Normal 
Range
Grade 1 
Grade 2 

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Lab.  Param 
Severity
Baseline
CHIKV 
(N=X) 
Week 4 
CHIKV 
(N=X) 
Week 8 
CHIKV 
(N=X) 
Week 16 
CHIKV 
(N=X) 
Week 24 
CHIKV 
(N=X) 
Week 32 
CHIKV 
(N=X) 
Week 40
CHIKV
(N=X) 
Week 48
CHIKV
(N=X) 
Week 56
CHIKV
(N=X) 
Week 64
CHIKV
(N=X) 
Week 72
CHIKV
(N=X) 
Max
Severity
Post 
Baseline
CHIKV 
(N=X) 
Grade 3 
Grade 4 
Note: The “Max Post Baseline” column includes the maximum severity experienced by each subject at any time point post baseline, including unscheduled assessments. 
All subjects will be counted once per symptom by time point at the maximum severity.

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TABLE 14.3.4.2: 
Laboratory Summary Statistics by Parameter, Study Day, and Treatment Group <<Age Stratum, Overall/Site>>
[Implementation Note: For calculated fields (Mean, SD, Median), decimal place should be the format in which the data were collected + 1 extra 
place.  For Min, Max, decimal place should be in the same format in which the data were collected. 
Repeat this table for the Placebo group] 
Laboratory Parameter 
Statistic 
Baseline
CHIKV 
(N=X) 
Week 4 
CHIKV 
(N=X) 
Week 8
CHIKV
(N=X) 
Week 16
CHIKV 
(N=X) 
Week 24
CHIKV 
(N=X) 
Week 32
CHIKV 
(N=X) 
Week 40
CHIKV 
(N=X) 
Week 48
CHIKV 
(N=X) 
Week 56
CHIKV 
(N=X) 
Week 64
CHIKV 
(N=X) 
Week 72
CHIKV 
(N=X) 
ALT 
N
x
Mean 
xx.x 
Standard
Deviation
xx.x 
Median 
xx.x 
Min, Max 
xx.x, xx.x
ALT Change from Baseline 
N
N/A
x
Mean (95% CI) 
N/A
xx.x 
Standard
Deviation
N/A
xx.x 
Median 
N/A
xx.x 
Min, Max 
N/A
xx.x, xx.x
WBC 
N
x
Mean 
xx.x 
Standard
Deviation
xx.x 
Median 
xx.x 

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Min, Max 
xx.x, xx.x
WBC Change from Baseline  N
N/A
x
Mean (95% CI) 
N/A
xx.x 
Standard
Deviation
N/A
xx.x 
Median 
N/A
xx.x 
Min, Max 
N/A
xx.x, xx.x
RBC
N
x
Mean 
xx.x 
Standard
Deviation
xx.x 
Median 
xx.x 
Min, Max 
xx.x, xx.x
RBC Change from Baseline 
N
N/A
x
Mean (95% CI) 
N/A
xx.x 
Standard
Deviation
N/A
xx.x 
Median 
N/A
xx.x 
Min, Max 
N/A
xx.x, xx.x
Hemoglobin 
N
x
Mean 
xx.x 
Standard
Deviation
xx.x 
Median 
xx.x 
Min, Max 
xx.x, xx.x

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Hemoglobin Change from 
Baseline
N
N/A
x
Mean (95% CI) 
N/A
xx.x 
Standard
Deviation
N/A
xx.x 
Median 
N/A
xx.x 
Min, Max 
N/A
xx.x, xx.x
Hematocrit 
N
x
Mean 
xx.x 
Standard
Deviation
xx.x 
Median 
xx.x 
Min, Max 
xx.x, xx.x
Hematocrit Change from 
Baseline
N
N/A
x
Mean (95% CI) 
N/A
xx.x 
Standard
Deviation
N/A
xx.x 
Median 
N/A
xx.x 
Min, Max 
N/A
xx.x, xx.x
MCV 
N
x
Mean 
xx.x 
Standard
Deviation
xx.x 
Median 
xx.x 
Min, Max 
xx.x, xx.x

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MCV Change from Baseline 
N
N/A
x
Mean (95% CI) 
N/A
xx.x 
Standard
Deviation
N/A
xx.x 
Median 
N/A
xx.x 
Min, Max 
N/A
xx.x, xx.x
Platelets 
N
x
Mean 
xx.x 
Standard
Deviation
xx.x 
Median 
xx.x 
Min, Max 
xx.x, xx.x
Platelets Change from 
Baseline
N
N/A
x
Mean (95% CI) 
N/A
xx.x 
Standard
Deviation
N/A
xx.x 
Median 
N/A
xx.x 
Min, Max 
N/A
xx.x, xx.x
Neutrophil 
N
x
Mean 
xx.x 
Standard
Deviation
xx.x 
Median 
xx.x 
Min, Max 
xx.x, xx.x

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Neutrophil Change from 
Baseline
N
N/A
x
Mean (95% CI) 
N/A
xx.x 
Standard
Deviation
N/A
xx.x 
Median 
N/A
xx.x 
Min, Max 
N/A
xx.x, xx.x
Lymphocyte 
N
x
Mean 
xx.x 
Standard
Deviation
xx.x 
Median 
xx.x 
Min, Max 
xx.x, xx.x
Lymphocyte Change from 
Baseline
N
N/A
x
Mean (95% CI) 
N/A
xx.x 
Standard
Deviation
N/A
xx.x 
Median 
N/A
xx.x 
Min, Max 
N/A
xx.x, xx.x
Monocyte 
N
x
Mean 
xx.x 
Standard
Deviation
xx.x 
Median 
xx.x 
Min, Max 
xx.x, xx.x

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Monocyte Change from 
Baseline
N
N/A
x
Mean (95% CI) 
N/A
xx.x 
Standard
Deviation
N/A
xx.x 
Median 
N/A
xx.x 
Min, Max 
N/A
xx.x, xx.x
Eosinophil 
N
x
Mean 
xx.x 
Standard
Deviation
xx.x 
Median 
xx.x 
Min, Max 
xx.x, xx.x
Eosinophil Change from 
Baseline
N
N/A
x
Mean (95% CI) 
N/A
xx.x 
Standard
Deviation
N/A
xx.x 
Median 
N/A
xx.x 
Min, Max 
N/A
xx.x, xx.x
Basophil 
N
x
Mean 
xx.x 
Standard
Deviation
xx.x 
Median 
xx.x 
Min, Max 
xx.x, xx.x

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Basophil Change from 
Baseline
N
N/A
x
Mean (95% CI) 
N/A
xx.x 
Standard
Deviation
N/A
xx.x 
Median 
N/A
xx.x 
Min, Max 
N/A
xx.x, xx.x
Hematocrit 
N
x
Mean 
xx.x 
Standard
Deviation
xx.x 
Median 
xx.x 
Min, Max 
xx.x, xx.x
Hematocrit Change from 
Baseline
N
N/A
x
Mean (95% CI) 
N/A
xx.x 
Standard
Deviation
N/A
xx.x 
Median 
N/A
xx.x 
Min, Max 
N/A
xx.x, xx.x

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TABLE 14.3.4.3: 
Listing of Abnormal Laboratory Results  
[Implementation Note: This listing is included in the table shells document, as it is included in the body of the CSR.   
This listing only includes abnormal laboratory results.  A complete listing of all laboratory results is included in the listings document. 
In the Laboratory Parameter column, indicate the units after the parameter, e.g., Hemoglobin (g/dL). 
This listing is not color-coded, but the severity should be included in parentheses after the result, e.g., 16.2 (mild).] 
Subject 
ID 
Treatment 
Group 
Sex 
Age
(years)
Date
Specimen 
Collected
Laboratory 
Parameter 
(Units) 
Result
(Severity) 
Relationship to 
Treatment 
Action
Taken with 
Study 
Treatment 
Subject 
Discontinued 
Due to Result?

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TABLE 14.3.4.4.x:
Shift Table for <<binary-graded laboratory parameter>> by Treatment Group Comparing Pre-Dose One Measure to Post-
Dose One Measures <<Overall/Site>> 
CHIKV 
(N=X) 
Baseline 
Placebo
(N=X) 
Baseline 
Pre- Dose One1 
Normal 
Abnormal 
Total 
Normal 
Abnormal 
Total 
<<Post Dose One Visit 1>> 
Normal 
x 
x 
x [row 
total] 
x 
x 
x 
Abnormal 
Total 
[column total] 
 
[sum of 4 
blocks, 
should be 
N] 
<<Post Dose One Visit 2>>
Normal 
Abnormal 
Total 
Continue for all Post Dose One visits
1. Footnote defines when pre-dose measurement was taken 

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TABLE 14.3.4.5.x:
Shift Table for <<ordinal-graded laboratory parameter>> by Treatment Group Comparing Pre-Dose One Measure to Post-
Dose One Measures <<Overall/Site>> 
CHIKV 
(N=X) 
Baseline
Placebo
(N=X) 
Baseline
Pre-Dose 
One1
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Total 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Total 
Grade 1 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Grade 2 
 
 
 
 
 
 
 
 
 
 
Grade 3 
 
 
 
 
 
 
 
 
 
 
Grade 4 
 
 
 
 
 
 
 
 
 
 
Total 
 
 
 
 
 
 
 
 
 
 
Continue for all Post Dose One visits 
1. Footnote defines when pre-dose measurement was taken 

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TABLE 14.3.5: 
Distribution of Vital Signs by Day Post Dosing, Grade, and Treatment Group <<Age Stratum, Overall/Site>>
[Implementation Note: If an assessment has a grading scale that includes grading for both high and low, then include one row for each severity for 
high and low. 
If data is not collected, enter ‘N/A’ for entry. (For example, Temperature at Post-Injection) 
Repeat this table for Placebo group] 
Vital Signs 
Assessment 
Severity
Pre-
injection 
(Baseline)
CHIKV 
(N=X) 
Post-
injection
CHIKV
(N=X) 
Week 4 
CHIKV
(N=X) 
Week 8 
CHIKV
(N=X) 
Week 16
CHIKV
(N=X) 
Week 24
CHIKV
(N=X) 
Week 
32 
CHIKV 
(N=X) 
Week 
40 
CHIKV
(N=X) 
Week 
48 
CHIKV
(N=X) 
Week 
56 
CHIKV
(N=X) 
Week 
64 
CHIKV
(N=X) 
Week 
72 
CHIKV
(N=X) 
Max
Severity
Post 
Baseline
CHIKV 
(N=X) 
n
%
n
%
n
%
n
%
n
%
n
%
n
%
n
%
n
%
n
%
Any Assessment 
Normal 
x
x.x 
x
x.x 
x
x.x 
x
x.x 
x
x.x 
x
x.x 
x
x.x 
x
x.x 
x
x.x 
x
x.x 
Mild
Moderate 
Severe 
Potentially
Life 
Threatening
Systolic BP 
Normal 
Mild
Moderate 
Severe 
Potentially
Life 
Threatening

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Vital Signs 
Assessment 
Severity
Pre-
injection 
(Baseline)
CHIKV 
(N=X) 
Post-
injection
CHIKV
(N=X) 
Week 4 
CHIKV
(N=X) 
Week 8 
CHIKV
(N=X) 
Week 16
CHIKV
(N=X) 
Week 24
CHIKV
(N=X) 
Week 
32 
CHIKV 
(N=X) 
Week 
40 
CHIKV
(N=X) 
Week 
48 
CHIKV
(N=X) 
Week 
56 
CHIKV
(N=X) 
Week 
64 
CHIKV
(N=X) 
Week 
72 
CHIKV
(N=X) 
Max
Severity
Post 
Baseline
CHIKV 
(N=X) 
Diastolic BP 
Normal 
Mild
Moderate 
Severe 
Potentially
Life 
Threatening
Pulse
Normal 
Mild
Moderate 
Severe 
Potentially
Life 
Threatening
Temperature (°C) Normal 
Mild
Moderate 
Severe 
Potentially
Life 
Threatening

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TABLE 14.3.6: 
Number and Percentage of Subjects with Concurrent Medications by 
Treatment Group <<Age Stratum>>
Medication 
CHIKV
(N=X) 
Placebo
(N=X) 
All Subjects 
(N=X) 
n
%
n
%
n
%
x
x.x 
x
x.x 
x
x.x 

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TABLE 14.3.7: 
Number of Pregnancies by Outcome and 
Treatment Group
CHIKV
(N=X) 
Placebo
(N=X) 
All Subjects 
(N=X) 
Total pregnancies 
x
x
x
Live births 
Spontaneous abortions 
Elective abortions 
Ectopic pregnancies 
Stillbirths 

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TABLE 15.1.1:
Incidence of Clinical Cases of CHIKV Post Dose One by Treatment Group and Stratified by Age 
Age Stratum 
CHIKV 
Placebo 
n 
% 
95%CI 
n 
% 
95%CI 
18-40 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
41-60 
 
 
 
 
 
 
Aggregate
(18-60)
Note: Subjects not receiving dose two are included in this table.  
n = number of subjects with CHIKV symptoms (clinical cases) 
% = n divided by the number of subjects receiving dose one 
95%CI = 95% Clopper-Pearson confidence interval. 

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TABLE 15.1.2:
Incidence of Clinical Cases of CHIKV Post Dose Two by Treatment Group and Stratified by Age 
Age Stratum 
CHIKV 
Placebo 
n 
% 
95%CI 
n 
% 
95%CI 
18-40 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
41-60 
 
 
 
 
 
 
Aggregate
(18-60)
n = number of subjects with CHIKV symptoms (clinical cases) 
% = n divided by the number of subjects receiving dose two and free of infection when receiving dose two 
95%CI = 95% Clopper-Pearson confidence interval. 
Additional Tables using the same format as 15.1.1 and 15.1.2 
TABLE 15.1.3: 
 Incidence of PCR Confirmed Cases of CHIKV Post Dose One by Group and Stratified by Age 
TABLE 15.1.4:
Incidence of PCR Confirmed Cases of CHIKV Post Dose Two by Group and Stratified by Age 

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TABLE 15.2.1: 
 Primary Exploratory Analysis – Vaccine Efficacy for Time to Occurrence of Clinical CHIKV Infection Post Dose One 
 
CHIKV N= 
Placebo N= 
 
V.E. 
95% CI for V.E. 
p-value 
Primary Analysis: 
Unadjusted
x.xx 
xx.xx - xx.xx 
x.xxx 
N=number of subjects in the specific treatment group that received first dose 
V.E. =Vaccine efficacy obtained from Cox Proportional Hazard model 
95%CI = 95% confidence interval obtained from Cox Proportional Hazard model 
p-value = result of comparison of Kaplan-Meier survival curves between groups by Log-rank test. 

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TABLE 15.2.2:
Primary Exploratory Analysis – Vaccine Efficacy for Time to Occurrence of Clinical CHIKV Infection Post Dose Two 
 
CHIKV N= 
Placebo N= 
 
V.E. 
95% CI for V.E. 
p-value 
Primary Analysis: 
Unadjusted
x.xx 
xx.xx - xx.xx 
x.xxx 
N=number of subjects in the specific treatment group that received second dose 
V.E. =Vaccine efficacy obtained from Cox Proportional Hazard model 
95%CI = 95% confidence interval obtained from Cox Proportional Hazard model 
p-value = result of comparison of Kaplan-Meier survival curves between groups by Log-rank test. 
Additional Tables using the same format as 15.2.1 and 15.2.2 
TABLE 15.2.3:
Primary Exploratory Analysis – Vaccine Efficacy for Time to Occurrence of PCR Confirmed CHIKV Infection Post Dose One 
TABLE 15.2.4: 
 Primary Exploratory Analysis – Vaccine Efficacy for Time to Occurrence of PCR Confirmed CHIKV Infection Post Dose Two

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TABLE 15.3.1:
Secondary Exploratory Analysis - Vaccine Efficacy for Time to Occurrence of Clinical CHIKV Infection Post Dose One with 
Adjustment for Baseline Characteristics 
 
CHIKV N= 
Placebo N= 
 
V.E. 
95% CI for V.E. 
p-value 
Secondary Analysis: 
    Multivariate adjustment for age, race, site 
xx.x 
xx.x – xx.x 
x.xxx 
Univariate Adjustments 
    Age (18-40, 41-60) 
    Race (White/Non-White) 
    Site (1-6) 
xx.x 
xx.x 
xx.x 
xx.x – xx.x 
xx.x - xx.x 
xx.x – x.xx 
x.xxx 
x.xxx 
x.xxx 
N=number of subjects in the specific treatment group that received first dose 
V.E. =Vaccine efficacy obtained from Cox Proportional Hazard model 
95%CI = 95% confidence interval obtained from Cox Proportional Hazard model 
p-value = for the multivariate adjustment, it is the result of comparison of Kaplan-Meier survival curves between groups by Log-rank test. 
For univariate adjustment, it is the result of comparison of Kaplan-Meier survival curves between groups stratified by the adjusted variables by 
Log-Rank test. 

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TABLE 15.3.2: 
 Secondary Exploratory Analysis - Vaccine Efficacy for Time to Occurrence of Clinical CHIKV Infection Post Dose Two with 
Adjustment for Baseline Characteristics 
 
CHIKV N= 
Placebo N= 
 
V.E. 
95% CI for V.E. 
p-value 
Secondary Analysis: 
    Multivariate adjustment for age, race, site 
xx.x 
xx.x – xx.x 
x.xxx 
Univariate Adjustments 
    Age (18-40, 41-60) 
    Race (White/Non-White) 
    Site (1-6) 
xx.x 
xx.x 
xx.x 
xx.x – xx.x 
xx.x - xx.x 
xx.x – x.xx 
x.xxx 
x.xxx 
x.xxx 
N=number of subjects in the specific treatment group that received second dose 
V.E. =Vaccine efficacy obtained from Cox Proportional Hazard model 
95%CI = 95% confidence interval obtained from Cox Proportional Hazard model 
p-value = for the multivariate adjustment, it is the result of comparison of Kaplan-Meier survival curves between groups by Log-rank test. 
For univariate adjustment, it is the result of comparison of Kaplan-Meier survival curves between groups stratified by the adjusted variables by 
Log-Rank test.
Additional Tables using the same format as 15.3.1 and 15.3.2 
TABLE 15.3.3:
Secondary Exploratory Analysis – Vaccine Efficacy for Time to Occurrence of PCR Confirmed CHIKV Infection Post Dose One 
with Adjustment for Baseline Characteristics 
TABLE 15.3.4:
Secondary Exploratory Analysis – Vaccine Efficacy for Time to Occurrence of PCR Confirmed CHIKV Infection Post Dose Two 
with Adjustment for Baseline Characteristics

Statistical Analysis Plan
Appendix II: Figure Mock- Ups
for
VRC 704 
Study Title: 
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 
Version 1.0 
Prepared and distributed by: 
The Emmes Corporation 
Rockville, Maryland 
THIS COMMUNICATION IS PRIVILEGED AND CONFIDENTIAL

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Table of Contents 
FIGURE 14.1.1: CONSORT Flow Diagram By Age Stratum ............................................................... 2
FIGURE 14.2.1: Reverse Cumulative Distribution of the Assay by Study Day, Site, and Treatment 
Group ...................................................................................................................................................... 3
FIGURE 14.2.2: Boxplots with Overlaid Scatter Plots Summarizing the Assay by Study Day, Site, 
and Treatment Group .............................................................................................................................. 4
FIGURE 14.3.1.1: Maximum Severity per Subject by Days Post Treatment ........................................ 5
FIGURE 14.3.1.2: Number and Severity of Non-Serious Adverse Events by MedDRA® System 
Organ Class ............................................................................................................................................ 6
FIGURE 14.3.1.3: Non-Serious Adverse Events by Severity ................................................................ 7
FIGURE 14.3.1.4: Number and Relationship of Non-Serious Adverse Events by MedDRA® System 
Organ Class ............................................................................................................................................ 8
FIGURE 14.3.1.5: Non-Serious Adverse Events by Relationship to Treatment .................................. 10
FIGURE 14.3.4.1: Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Laboratory Parameter and Treatment Group ........................................................................................ 11
FIGURE 14.4.1-14.4.x: Boxplot of Vital Signs by Scheduled Visits .................................................. 12
FIGURE 14.5.1-14.5.x: Boxplot of Laboratory Results by Scheduled Visits ...................................... 13
FIGURE 15.1.1: Kaplan-Meier Curves for Time to Occurrence of Clinical CHIKV Infection Post 
Dose One .............................................................................................................................................. 14
FIGURE 15.1.2: Kaplan-Meier Curves for Time to Occurrence of Clinical CHIKV Infection Post 
Dose Two ............................................................................................................................................. 14
FIGURE 15.1.3: Kaplan-Meier Curves for Time to Occurrence of PCR Confirmed CHIKV Infection 
Post Dose One ...................................................................................................................................... 14
FIGURE 15.1.4: Kaplan-Meier Curves for Time to Occurrence of PCR Confirmed CHIKV Infection 
Post Dose Two ...................................................................................................................................... 14

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FIGURE 14.1.1: 
CONSORT Flow Diagram By Age Stratum 
[Implementation Note: In the SAP, include a blank diagram with the possible reasons why subjects may 
be excluded from analyses.  The reasons for exclusion should be in line with the SAP text.] 

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FIGURE 14.2.1: 
Reverse Cumulative Distribution of the [specific assay] by Study Day, Site, and 
Treatment Group <<Age Stratum>>
Note: These are illustrative curves.  The actual curves compare CHIKV vaccine and placebo. For 
neutralization (the primary immunogenicity endpoint), the time periods to be used are Days 0, 28 and 56. 

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FIGURE 14.2.2: 
Boxplots with Overlaid Scatter Plots Summarizing the [specific assay] by Study Day, Site, 
and Treatment Group <<Age Stratum>> 
Note: Y-axis label will change with specific assay and x-axis will change based on time points available 
in the data. 
Baseline
Week 8
1
2
3
4
PBS
CHIKV VLP 20 mcg
Treatment Group

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FIGURE 14.3.1.1: 
Maximum Severity per Subject by Days Post Treatment 
CHIKV, Dose 1 [Repeat for Placebo Group and Dose 2] (N=X) 

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FIGURE 14.3.1.2:
Number and Severity of Non-Serious Adverse Events by MedDRA® System Organ Class  

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FIGURE 14.3.1.3: 
Non-Serious Adverse Events by Severity 
CHIKV [Repeat for Placebo Group] (N=X) 
[Implementation Note: This figure includes all unsolicited adverse events.] 

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FIGURE 14.3.1.4: 
Number and Relationship of Non-Serious Adverse Events by MedDRA® System Organ 
Class
CHIKV [Repeat for Placebo Group] (N=X) 
[Implementation Note: This figure includes all unsolicited adverse events.] 
Or …. 

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FIGURE 14.3.1.4: Number and Relationship of Non-Serious Adverse Events by 
MedDRA® System Organ Class (continued)
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FIGURE 14.3.1.5: 
Non-Serious Adverse Events by Relationship to Treatment 
CHIKV [Repeat for Placebo Group] (N=X) 
[Implementation Note: This figure includes all unsolicited adverse events.] 

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FIGURE 14.3.4.1: 
Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Laboratory Parameter and Treatment Group <<for Age Strata>> 
CHIKV [Repeat for Placebo Group] (N=X) 

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FIGURE 14.4.1-14.4.x: 
Boxplot of Vital Signs by Scheduled Visits – Pulse 
[Implementation Note: There will be only two treatment groups and not 4, and the visits will be 
updated based on available data; the box-plot will be repeated for each recorded vital sign] 

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FIGURE 14.5.1-14.5.x: 
Boxplot of Laboratory Results by Scheduled Visits – Hemoglobin 
[Implementation Note: There will be only two treatment groups and the visits will be updated 
based on available data; the box-plot will be repeated for each recorded laboratory measure] 

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FIGURE 15.1.1: 
 Kaplan-Meier Curves for Time to Occurrence of Clinical CHIKV Infection Post Dose One 
[Implementation notes: there will be two lines, one for each treatment group; x-axis is the time variable 
for time to occurrence of infection, y-axis is survival estimate from Kaplan-Meier curves; all subjects that 
received first dose will be considered] 
FIGURE 15.1.2:
Kaplan-Meier Curves for Time to Occurrence of Clinical CHIKV Infection Post Dose Two 
[Implementation notes: there will be two lines, one for each treatment group; x-axis is the time 
variable for time to occurrence of infection, y-axis is survival estimate from Kaplan-Meier 
curves; all subjects that received second dose will be considered] 
FIGURE 15.1.3:
Kaplan-Meier Curves for Time to Occurrence of PCR Confirmed CHIKV Infection Post 
Dose One 
FIGURE 15.1.4:
Kaplan-Meier Curves for Time to Occurrence of PCR Confirmed CHIKV Infection Post 
Dose Two 

Statistical Analysis Plan
Appendix III: Listing Mock- Ups
for
Protocol VRC 704 
Study Title: 
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 
Version 1.0 
Prepared and distributed by: 
The Emmes Corporation 
Rockville, Maryland 

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Table of Contents 
LISTING 16.2.1: Early Terminations or Discontinued Subjects ........................................................... 1
LISTING 16.2.2.1: Subject-Specific Protocol Deviations ..................................................................... 2
LISTING 16.2.2.2: Non-Subject-Specific Protocol Deviations ............................................................. 3
LISTING 16.2.3: Subjects Excluded from the Efficacy/Immunogenicity Analysis .............................. 4
LISTING 16.2.4.1: Demographics Data ................................................................................................. 5
LISTING 16.2.4.2: Pre-Existing Medical Conditions ............................................................................ 6
LISTING 16.2.5: Compliance and/or Drug Concentration Data ............................................................ 7
LISTING 16.2.6: Individual Immunogenicity Response Data ............................................................... 8
LISTING 16.2.7.1: Solicited Events ...................................................................................................... 9
LISTING 16.2.7.2: Unsolicited Adverse Events .................................................................................. 10
LISTING 16.2.8.1: Individual Clinical Laboratory Results – Hematology ......................................... 11
LISTING 16.2.8.2: Individual Clinical Laboratory Results – Biochemistry ....................................... 12
LISTING 16.2.9: Vital Signs................................................................................................................ 13
LISTING 16.2.10: Concomitant Medications ...................................................................................... 14
LISTING 16.2.11: Pregnancy Reports ................................................................................................. 15
LISTING 16.3.1: Chikungunya Endpoints Evaluations Performed ..................................................... 16
LISTING 16.3.2: Individual Time to Occurrence of Clinical CHIKV Infection Efficacy Data .......... 17
LISTING 16.3.3: Individual Time to Occurrence of PCR Confirmed CHIKV Infection Efficacy Data18

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LISTING 16.2.1: 
Early Terminations and/or Discontinued Subjects 
Subject ID 
Treatment Group 
Category
Reason for Early Termination or Treatment Discontinuation 
Date of Termination or Discontinuation

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LISTING 16.2.2.1: 
Subject-Specific Protocol Deviations 
[Implementation note: sort by Treatment Group, Subject ID, then Deviation Number.] 
Treatment 
Group 
Subject 
ID 
Deviation
Number 
Deviation
Deviation
Date
Reason for
Deviation
Deviation
Resulted
in AE? 
Deviation
Resulted in 
Subject 
Termination? 
Deviation
Affected
Product
Stability?
Deviation
Category
Deviation
Resolution
Meet IRB 
Reporting
Requirements? If 
Yes, Date IRB 
Notified
Comments

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LISTING 16.2.2.2: 
Non-Subject-Specific Protocol Deviations 
[Implementation note: sort by site, start date.] 
Site 
Deviation
Deviation
Date
Reason for
Deviation
Deviation
Resulted in 
Adverse 
Event?
Deviation
Resulted in 
Subject 
Termination? 
Deviation
Affected 
Product 
Stability? 
Deviation
Category
Deviation
Resolution
Meet IRB Reporting 
Requirements? If 
Yes, Date IRB 
Notified
Comments
.

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LISTING 16.2.3: 
Subjects Excluded from the Efficacy/Immunogenicity Analysis 
[Implementation Note: This data in this listing should be congruent with the “Analysis Populations by Treatment Group” table (Table 14.1.2, 
Appendix I). The reasons included here should match the SAP text that describes who will be excluded from analyses.] 
Treatment Group 
Subject ID 
Analyses in which 
Subject is Included 
Analyses from which  
Subject is Excluded 
Results Available? 
Reason Subject Excluded 
[e.g., Safety, ITT, mITT, PP] 
[e.g., Safety, ITT, mITT, PP] 
Note: “Yes” in the “Results available” column indicates that available data were removed from the analysis.  “No” indicates that no data were available for inclusion in the 
analysis. 

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LISTING 16.2.4.1: 
Demographics Data 
[Implementation Note: If a subject is multi-racial, in “Race” column, note “Multiple: (list races, separated by a comma).”] 
Subject ID 
Treatment Group 
Sex 
Age at Enrollment (years) 
Ethnicity 
Race
Language

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LISTING 16.2.4.2: 
Pre-Existing Medical Conditions 
Subject ID 
Treatment 
Group 
MH Number 
Medical History Term MedDRA® System Organ Class
MedDRA® Preferred Term 

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LISTING 16.2.5: 
Compliance and/or Drug Concentration Data 
[Implementation note: only use if these cases exist. Data will come from either UVD (if subject missed product administration) or
special cases excel spreadsheet (not eCRFs).] 
Scenario 1
Treatment Group  
Subject ID  
Dose Number  
Actual [Dosage/Concentration] Administered 
Scenario 2 
Treatment Group  
Subject ID  
Dose(s) Missed 
[e.g., Day 3, Day 3 AM, etc.] 

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LISTING 16.2.6: 
Individual Immunogenicity Response Data 
Subject ID
Treatment Group
Assay 
Collection Date 
Titer

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LISTING 16.2.7.1: 
Solicited Events 
[Implementation Note: This listing is not color-coded.  To indicate severity for quantitative symptoms (e.g., temperature, measurements), include 
the grade in parentheses after the number, e.g., 100.7 (Mild). 
We are not indicating the “side” or arm assessed.  If the arm assessed was wrong (not the arm that received treatment), then note this error in a 
footnote in the Local Symptoms listing. 
This listing includes baseline assessments in addition to post-treatment assessments. 
MA uses DCA, Clinic uses VTL (only for temperature).] 
Systemic Symptoms 
Subject ID Treatment Group Dose Number 
Post Dose Day Assessment*
[Symptom 1] [Symptom 2]
[Symptom 3]
[Symptom 4]
MA 
Clinic 
* MA = Data reported by subject on the Memory Aid and reviewed by clinic staff and reported in Solicited Events eCRF. 
Clinic = Data collected by clinic staff during physical exam or symptom assessment (treatment administration record, in-clinic assessment, etc.) 
Local Symptoms 
Subject ID Treatment Group Dose Number 
Post Dose Day Assessment*
[Symptom 1] [Symptom 2]
[Symptom 3]
[Symptom 4]
MA 
* MA = Data reported by subject on the Memory Aid and reviewed by clinic staff and reported in Solicited Events eCRF. 

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LISTING 16.2.7.2: 
Unsolicited Adverse Events 
[Implementation Note: This listing includes all unsolicited adverse events.] 
Part 1  
Subject 
ID 
Treatment 
Group 
AE
Number 
Adverse 
Event
MedDRA
Preferred 
Term 
Number of 
Administrations
Days 
Since Last 
Admin 
Severity 
SAE? 
Relationship
to Study 
Treatment 
Admin
Date
AE
Onset
Date
Date of 
Resolution
Part 2  
Subject ID 
Adverse 
Event
Action Taken 
with Study 
Treatment 
Subject 
Discontinued 
Due to AE 
Outcome 
Comments 
Note: For additional details about SAEs, see Table: 14.3.2.1. 

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LISTING 16.2.8.1: 
Individual Clinical Laboratory Results – Hematology 
[Implementation Note: These listings (for hematology and biochemistry) include all laboratory results, scheduled and unscheduled.   
These listings are not color-coded, but the severity should be included in parentheses after the result for abnormal results, e.g., 16.2 (Mild). 
The “extra” fields that are completed for abnormal results are not included in this listing; they are included in the listing of abnormal laboratory 
results that is included in the table shells document.] 
Subject ID Treatment Group 
Sex 
Age
(years) 
Date Specimen 
Collected 
[Laboratory Parameter 1 
(Units)] 
[Laboratory Parameter 2
(Units)] 
[Laboratory Parameter 3
(Units)] 

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LISTING 16.2.8.2: 
Individual Clinical Laboratory Results – Biochemistry 
Subject ID Treatment Group 
Sex 
Age
(years) 
Date Specimen 
Collected 
[Laboratory Parameter 1 
(Units)] 
[Laboratory Parameter 2
(Units)] 
[Laboratory Parameter 3
(Units)] 

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LISTING 16.2.9: 
Vital Signs 
[Implementation Note: This listing includes all vital sign assessments, scheduled and unscheduled.   
These listings are not color-coded, but the severity should be included in parentheses after the result for abnormal assessments, e.g., 100.7 (Mild).] 
Subject ID Treatment Group  
Date
Temperature
(°C)
Systolic Blood 
Pressure 
(mmHg) 
Diastolic Blood 
Pressure 
(mmHg) 
Heart Rate
(beats/min)
Weight
(kg)
Height
(cm) 
BMI

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LISTING 16.2.10: 
Concomitant Medications 
[Implementation Note: “Medication Start Day” and “Medication End Day” are relative to enrollment (which is Day 1, day before enrollment is 
Day -1).  For medication start dates that are > 30 days prior to enrollment, rather than use exact study days, categorize as follows:
> 5 years prior to enrollment 
1-5 years prior to enrollment 
1-12 months prior to enrollment 
If ongoing, display “Ongoing” in the “Medication End Day” column. 
If taken for an AE, display “Yes” with the AE Number in parentheses, e.g., “Yes (7)”.] 
Subject 
ID 
Treatment 
Group 
Medication 
Number 
Medication 
Medication Start 
Date
Medication End 
Date
Indication 
Taken for an AE?
(AE Number) 
Comments

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LISTING 16.2.11: 
Pregnancy Reports 
[Implementation Note: Only include the “Pregnancy Number” column if a subject has more than 1 pregnancy.] 
Subject 
ID 
Treatment 
Group 
Pregnancy 
Number 
Start Date 
of Last 
Menstrual 
Period
Date Site 
Notified
Date of 
Last Study 
Injection 
Date of 
Delivery or 
Pregnancy 
Termination 
Pregnancy 
Outcome 
If Live or 
Still Birth, 
Congenital
Anomalies
or Birth 
Defects? 
If Live 
Birth,
Neonatal
Death?
Clinical
History of 
Pregnancy 
Therapeutic 
Management
of Pregnancy 
Hospitaliz-
ations
Relevant
to this 
Pregnancy 
Note: Medications taken during pregnancy are included in the Concomitant Medications Listing. 

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LISTING 16.3.1:
Chikungunya Endpoints Evaluations Performed 
Subject 
ID 
Illness Onset 
Date
Number 
of PCR 
Test
Number 
of Positive
PCR
Clinical 
CHIKV
Case?
Fever 
Severity
Grade 
Arthritis/
Arthralgia
Severity 
Grade 
Atypical 
Case? 
Hospitalized? 
SAE? 
Illness 
Resolution Date 
Duration of
CHIK Illness
(days) 

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LISTING 16.3.2:
Individual Time to Occurrence of Clinical CHIKV Infection Efficacy Data 
Subject ID
Treatment Group
Date of Dose One 
Date of Dose Two 
Date of CHIKV 
Symptoms 
Time from Dose 
One
Time from Dose 
Two 
xx.xx 
xx.xx 
Censored
Censored
N/A
Time from dose one represents the time from dose one to CHIKV infection. This can be either censored (if the subject does not develop CHIKV during the study period) or have 
an actual value (time from first dose to event).  
Time from dose two represents the time from dose two to CHIKV infection. This can be either censored (if the subject does not develop CHIKV during the study period), have an 
actual value (time from second dose to event) or not applicable if the subject did not receive second dose/developed CHIKV before dose two. Subjects with N/A are not included in 
the analysis of this outcome.   

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LISTING 16.3.3:
Individual Time to Occurrence of PCR Confirmed CHIKV Infection Efficacy Data 
Subject ID
Treatment Group
Date of Dose One 
Date of Dose Two 
Date of CHIKV 
PCR confirmation 
Time from Dose 
One
Time from Dose 
Two 
xx.xx 
xx.xx 
Censored
Censored
NA 
Time from dose one represents the time from dose one to CHIKV infection. This can be either censored (if the subject does not develop CHIKV during the study period) or have 
an actual value (time from first dose to event).  
Time from dose two represents the time from dose two to CHIKV infection. This can be either censored (if the subject does not develop CHIKV during the study period), have an 
actual value (time from second dose to event) or not applicable if the subject did not receive second dose/developed CHIKV before dose two. Subjects with NA are not included in 
the analysis of this outcome.