VRC 705: A Phase 2/2B, Randomized Trial to Evaluate the Safety, Immunogenicity and Efficacy of a Zika Virus DNA Vaccine in Healthy Adults and Adolescents
Phase: PHASE2
Conditions: Zika Virus, Zika Virus Infection, Virus Diseases, Flavivirus Infections, Flaviviral Diseases, Flaviviridae Infections, RNA Virus Infections
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Official Title: A Phase 2/2B, Randomized Trial to Evaluate the Safety, Immunogenicity and Efficacy of a
Zika Virus DNA Vaccine in Healthy Adults and Adolescents
ClinicalTrials.gov Identifier: NCT03110770
Document Type:
• 
Redacted Study Protocol (Informed Consent Template located in Appendix I of the Protocol
Version 5.0)
• 
Redacted IRB-approved Informed Consents for Part A and Part B from a participating site
• 
Statistical Analysis Plan
Document/Date:
• 
Protocol Version 5.0: August 28, 2018
• 
Part A IRB-approved Informed Consent (Version 1.4): November 13, 2018
• 
Part B IRB-approved Informed Consent (Version 2.1): July 8, 2019
• 
Statistical Analysis Plan Version 1.0: November 11, 2019

 
 
 
 
 
A Phase 2/2B, Randomized Trial to Evaluate the Safety, Immunogenicity and 
Efficacy of a Zika Virus DNA Vaccine in Healthy Adults and Adolescents 
 
 
Protocol VRC 705 
 
Sponsored by 
National Institute of Allergy and Infectious Diseases (NIAID) 
Vaccine Research Center (VRC) 
Bethesda, Maryland, USA 
 
BB-IND 17208 – held by VRC, NIAID, NIH 
 
 
NIAID Funding Mechanism  
Contract Numbers:  
 
 
 
 
 
 
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 subjects. 
 
 
Version 5.0 
August 28, 2018

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Statement of Compliance 
The trial will be conducted in compliance with the protocol, the applicable regulatory 
requirements including but not limited to the United States (US) Code of Federal Regulations 
(CFR) applicable to clinical studies (45 CFR 46, 21 CFR including parts 50 and 56 concerning 
informed consent and Institutional Review Board (IRB)/Ethics Committee (EC) regulations, and 
21 CFR 312 concerning Investigational New Drug (IND) application), International Council for 
Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use 
(ICH) Good Clinical Practice (GCP) guidance, and the NIAID Clinical Terms of Contract 
Award.  Each site will hold a current Federal Wide Assurance (FWA) issued by the Office for 
Human Research Protections for federally funded research.  Completion of Protection of Human 
Subjects Training will be required for all study personnel in accordance with National Institutes 
of Health (NIH) policy.   
 
 

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TABLE OF CONTENTS 
 
PRINCIPAL INVESTIGATOR PROTOCOL SIGNATURE PAGE .............................................7
ABBREVIATIONS .........................................................................................................................8
DEFINITIONS ...............................................................................................................................10
PRÉCIS ..........................................................................................................................................11
1.
INTRODUCTION ..................................................................................................................13
1.1.
Zika Virus Infection: Etiology, Disease Course and Epidemiology .............................13
1.2.
Rationale for Development of VRC-ZKADNA090-00-VP ..........................................14
1.3.
Previous Human Experience with VRC DNA Vaccines ..............................................15
1.4.
Human Experience with VRC ZIKV DNA Vaccines ...................................................16
1.5.
Rationale for Study Product Dose and Administration Method ...................................18
1.6.
Rationale for the Study Population ...............................................................................19
1.7.
Assessment of Immunogenicity ....................................................................................19
1.8.
ZIKV Infection Assessment ..........................................................................................20
2.
STUDY PRODUCTS .............................................................................................................21
2.1.
VRC-ZKADNA090-00-VP, ZIKVwt DNA Vaccine ...................................................21
2.2.
VRC-PBSPLA043-00-VP, Placebo and Diluent ..........................................................21
2.3.
Preclinical Safety and Immunogenicity Studies of VRC-ZKADNA090-00-VP ..........21
3.
STUDY OBJECTIVES ..........................................................................................................22
3.1.
Primary Objectives ........................................................................................................22
3.2.
Secondary Objectives ....................................................................................................22
3.3.
Exploratory Objectives..................................................................................................22
4.
STUDY DESIGN AND CLINICAL PROCEDURES ...........................................................23
4.1.
Eligibility Criteria .........................................................................................................24
4.1.1.
Inclusion Criteria .................................................................................................24
4.1.2.
Exclusion Criteria ................................................................................................25
4.2.
Clinical Procedures and Evaluations .............................................................................26
4.2.1.
Pre-screening .......................................................................................................26
4.2.2.
Screening and Enrollment ...................................................................................26
4.2.3.
Randomization .....................................................................................................28
4.2.4.
Product Administration .......................................................................................29
4.2.5.
Diary Card and Follow-Up after Product Administration ...................................30
4.2.6.
Follow-Up Visits and Scheduling .......................................................................30
4.2.7.
Pregnancy during the Study .................................................................................31
4.3.
Evaluation of ZIKV Infection During the Study...........................................................32
4.3.1.
ZIKV Infection Definition ...................................................................................32
4.3.2.
Unscheduled Collection of Samples for Suspected ZIKV Infection ...................32
4.3.3.
Scheduled Collection of Research Samples for Asymptomatic ZIKV 
Infection (Part B only) .........................................................................................34
4.3.4.
ZIKV Infection Clinical Management and Follow-Up .......................................34
4.3.5.
Reporting of ZIKV Infections .............................................................................34

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4.3.6.
ZIKV Infection in Pregnant Women ...................................................................34
4.4.
Concomitant Medications .............................................................................................35
4.5.
Criteria for Discontinuing Product Administrations or Subject Participation ..............35
4.5.1.
Discontinuation from Receiving Study Product ..................................................35
4.5.2.
Discontinuation from Protocol Participation .......................................................36
4.6.
Criteria for Pausing and Resuming the Study ...............................................................36
5.
SAFETY AND ADVERSE EVENTS ....................................................................................37
5.1.
Adverse Events..............................................................................................................37
5.1.1.
AE Reporting Period ...........................................................................................37
5.2.
Serious Adverse Events.................................................................................................38
5.2.1.
Serious Adverse Event Definition .......................................................................38
5.2.2.
Reporting Serious Adverse Events to the IND Sponsor ......................................38
5.2.3.
IND Sponsor Reporting to the FDA ....................................................................39
5.2.4.
Serious Adverse Event Reporting to the Data and Safety Monitoring 
Board ...................................................................................................................39
5.2.5.
Serious Adverse Event Reporting to the Institutional Biosafety 
Committee ...........................................................................................................39
5.3.
Protocol Deviation ........................................................................................................39
5.4.
Unanticipated Problem ..................................................................................................39
5.5.
Reporting to Site IRBs/ECs and Relevant Regulatory Agencies ..................................40
5.6.
Data and Safety Monitoring Board ...............................................................................40
6.
STATISTICAL CONSIDERATIONS AND SAMPLE ANALYSIS ....................................41
6.1.
Overview .......................................................................................................................41
6.2.
Endpoints ......................................................................................................................41
6.2.1.
Safety ...................................................................................................................41
6.2.2.
Immunogenicity ...................................................................................................41
6.2.3.
Efficacy (Part B only) ..........................................................................................41
6.3.
Sample Size and Accrual ..............................................................................................42
6.3.1.
Sample Size Considerations: Part A ....................................................................42
6.3.2.
Sample Size Considerations: Part B ....................................................................43
6.4.
Statistical Analysis ........................................................................................................48
6.4.1.
Baseline Demographics .......................................................................................49
6.4.2.
Safety Analysis ....................................................................................................49
6.4.3.
Analysis of Immune Responses ...........................................................................50
6.4.4.
Analysis of ZIKV Incidence ................................................................................50
6.4.5.
Interim Analyses ..................................................................................................50
6.4.6.
Randomization of Treatment Assignments and Unblinding Criteria ..................51
7.
PHARMACY PROCEDURES ...............................................................................................52
7.1.
Study Products ..............................................................................................................52
7.2.
Study Product Presentation, Stability and Storage ........................................................52
7.2.1.
Labels ..................................................................................................................52
7.2.2.
Storage .................................................................................................................53

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7.2.3.
Stability ................................................................................................................53
7.3.
Preparation of Study Products for Administration ........................................................53
7.4.
Study Product Administration .......................................................................................53
7.5.
Study Product Accountability .......................................................................................54
7.5.1.
Documentation ....................................................................................................54
7.5.2.
Disposition ...........................................................................................................54
8.
HUMAN SUBJECTS PROTECTION ...................................................................................55
8.1.
Institutional Review Board/Ethics Committee..............................................................55
8.2.
Institutional Biosafety Committee ................................................................................55
8.3.
Subject Recruitment and Enrollment ............................................................................55
8.3.1.
Participation of Children .....................................................................................55
8.3.2.
Participation of Site Employees ..........................................................................56
8.4.
Informed Consent and Assent .......................................................................................56
8.5.
Subject Confidentiality..................................................................................................57
8.6.
Risks and Benefits .........................................................................................................57
8.6.1.
Risks of the ZIKVwt DNA vaccine .....................................................................57
8.6.2.
Risks of Administration with a Needle-Free Injection Device ...........................58
8.6.3.
Other Risks ..........................................................................................................58
8.6.4.
Benefits ................................................................................................................59
8.7.
Plan for Use and Storage of Biological Samples ..........................................................59
8.7.1.
Use of Samples, Specimens and Data .................................................................59
8.7.2.
Storage and Tracking of Blood Samples and Other Specimens ..........................59
8.7.3.
Disposition of Samples, Specimens and Data at Completion of the 
Protocol ................................................................................................................59
8.7.4.
Loss or Destruction of Samples, Specimens or Data ..........................................60
8.8.
Compensation ................................................................................................................60
8.9.
Safety Monitoring .........................................................................................................60
8.9.1.
Protocol Safety Review Team .............................................................................60
8.9.2.
Data and Safety Monitoring Board ......................................................................60
9.
ADMINISTRATION AND LEGAL OBLIGATIONS ..........................................................61
9.1.
Protocol Initiation, Amendments and Termination .......................................................61
9.2.
Study Documentation and Study Records Retention ....................................................61
9.3.
Data Collection, Data Sharing, and Protocol Monitoring .............................................61
9.3.1.
Data Collection ....................................................................................................61
9.3.2.
Data Sharing ........................................................................................................62
9.3.3.
Source Documents ...............................................................................................62
9.3.4.
Protocol Monitoring ............................................................................................62
9.4.
Language .......................................................................................................................62
9.5.
Policy Regarding Research-Related Injuries ................................................................62
9.6.
Multi-Site Management ................................................................................................63
10. REFERENCES .......................................................................................................................64
APPENDIX I:
 TEMPLATE INFORMED CONSENT FORM AND ASSENT FORM .........70
APPENDIX II:
PROTOCOL TEAM AND CONTACT INFORMATION .............................101

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APPENDIX III:
SCHEDULE OF EVALUATIONS .............................................................104
APPENDIX IV:
ASSESSMENT OF RELATIONSHIP TO STUDY PRODUCT 
AND ADVERSE EVENT SEVERITY GRADING ............................................................109
 
LIST OF TABLES 
Table 1:
Study Schema........................................................................................................ 23
Table 2:
Probability of Observing Safety Events within a Group (n=30)........................... 42
Table 3:
Two sided 95% CIs Based on Observed Rates of Safety Endpoints within a 
Group (n=30) ........................................................................................................ 42
Table 4: 
Power of Detecting a Range of Fold Changes from Baseline Immune Response 43
Table 5: 
Power of Detecting Between-Arm Difference over a Range of Effect Sizes ....... 43
Table 6:
Probability of Observing Safety Events within a Group (n=1200)....................... 45
Table 7:
Minimum Detectable Difference in Event Rate Assuming Type I Two-Tail 
Error Rate of 5% ................................................................................................... 45
Table 8:
Minimum Detectable Difference in the Magnitude of Immune Response (log 
transformed) between 2 Groups Assuming Type I Two-Tail Error Rate of 5% .. 46
Table 9:
Number of Cases of ZIKV Infection Required to Achieve 80% or 90% Under 
Different Vaccine Efficacies by Conditional Binomial Test with Two-sided 
TypeIErrorRateof0.05andNullVE≤20% ..................................................... 47
Table 10:
Expected Number of Cases of ZIKV Infection within 2 and 3 Years of Trial 
Initiation under Different Assumed Yearly Incidence under Placebo with 2400 
Subjects ................................................................................................................. 47
Table 11: 
Expected Number of Cases of ZIKV Infection among Seronegative Enrollees 
within 2 and 3 Years of Trial Initiation under Different Assumed Baseline 
Seropositive Rates, Yearly Incidence Rates under Placebo among 
Seronegatives, and Sample Sizes .......................................................................... 48
 
LIST OF FIGURES 
Figure 1:
Evaluation for Symptomatic ZIKV Infection in Part B ........................................ 33
 
 
 

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PRINCIPAL INVESTIGATOR PROTOCOL SIGNATURE PAGE 
 
VRC 705: A Phase 2/2B, Randomized Trial to Evaluate the Safety, Immunogenicity and 
Efficacy of a Zika Virus DNA Vaccine in Healthy Adults and Adolescents 
 
Sponsored by: 
Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases (NIAID) 
National Institutes of Health (NIH) 
 
I, the Principal Investigator for the indicated VRC 705 Study Site, agree to conduct this study in 
full accordance with the provisions of this protocol and protocol amendments.  I will comply 
with all requirements regarding the obligations of investigators as outlined in the Statement of 
Investigator (Form FDA 1572), which I have also signed.  I agree to maintain all study 
documentation pertaining to the conduct of this study, including, but not limited to, case report 
forms, source documents, consent forms, laboratory test results, and medication inventory 
records, for at least 2 years following submission of a United States Biologics License 
Application.  If no marketing application is filed, or if the application is not approved, the 
records will be retained for two years after the investigation is discontinued and the US Food and 
Drug Administration is notified.  No study records will be destroyed without prior authorization 
from VRC/NIAID.  Publication of the results of this study will be governed by the VRC/NIAID 
policies. Any presentation, abstract, or manuscript will be made available by the investigators to 
VRC Leadership and to NIAID for review prior to submission. 
 
I have read and understand the information in this protocol and the Investigator’s Brochure and 
will ensure that all associates, colleagues, and employees assisting in the conduct of the study are 
informed about the obligations incurred by their contribution to the study. 
 
__________________________________ __________________________________ 
Name/Title of Principal Investigator   
Study Site Name/Identifier 
 
__________________________________  __________________________________ 
Signature of Principal Investigator                Date 
 
 
 

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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
CFR
Code of Federal Regulations
cGMP 
current Good Manufacturing Practice
CHIKV 
chikungunya virus 
CI 
confidence interval
cm 
centimeter 
CMV
cytomegalovirus 
CRO 
contract research organization
DENV
dengue virus
DNA
deoxyribonucleic acid
DSMB 
Data and Safety Monitoring Board
EC 
Ethics Committee
ELISA 
enzyme-linked immunosorbent assay
ELISpot assay
enzyme-linked immunospot assay 
EUA 
emergency use authorization
FDA 
United States Food and Drug Administration
GBS
Guillain-Barré syndrome 
GCLP
Good Clinical Laboratory Practice
GCP
Good Clinical Practice
H0 
null hypothesis 
HF 
hemorrhagic fever 
HIV 
human immunodeficiency virus
HLA 
human leukocyte antigen
HTLV-1
Human T cell leukemia virus type 1
IB 
Investigator’s Brochure  
IBC
Institutional Biosafety Committee 
ICF 
informed consent form 
ICH 
International Council for Harmonisation of Technical Requirements 
for Registration of Pharmaceuticals for Human Use
ICS 
intracellular cytokine staining
IgM 
immunoglobulin M
IM 
intramuscular 
IND 
Investigational New Drug
IRB
Institutional Review Board
ITT
Intent-to-treat
LAR 
legally acceptable representative 
MedDRA® 
Medical Dictionary for Regulatory Activities

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Abbreviation 
Term 
mITT
Modified intent-to-treat 
NAb
neutralizing antibody
NHP 
non-human primates
NIAID 
National Institute of Allergy and Infectious Diseases
NIH 
National Institutes of Health
NVITAL
NIAID Vaccine Immune T-Cell and Antibody Laboratory 
PAHO
Pan American Health Organization
PBMC
peripheral blood mononuclear cells
PBS 
phosphate-buffered saline
PCR
polymerase chain reaction 
PDL
primary diagnostic laboratory
PI
Principal Investigator 
PP
Per-protocol 
prM 
precursor for the M transmembrane protein
PRNT
plaque reduction neutralization test
PSRT
Protocol Safety Review Team 
RBC 
red blood cells
RNA
ribonucleic acid
RT-PCR
reverse transcription-polymerase chain reaction 
RVP
reporter virus particle 
SAE
serious adverse event
SAP
Statistical Analysis Plan 
SARS
Severe acute respiratory syndrome 
SC 
subcutaneous
SUSAR
serious and unexpected suspected adverse reactions
TBD 
to be determined
ULN 
upper limit of normal 
UP 
unanticipated problem
US 
United States
VE
vaccine efficacy 
VLP
virus-like particle 
VP 
Virus particles
VRC 
Vaccine Research Center
WBC
white blood cell
WHO
World Health Organization
WNV
West Nile virus
WT
wild-type
ZIKV
Zika virus
 
 

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DEFINITIONS 
Term 
Definition 
Adolescents 
15-17 years of age.  Some countries may define adolescent age up 
to 21 years. 
Endemic 
Reported active local mosquito-borne transmission of ZIKV 
Potential endemic 
Active local mosquito-borne transmission of ZIKV may occur 
during the course of the study 
 
 

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PRÉCIS 
Study Title: 
A Phase 2/2B, Randomized Trial to Evaluate the Safety, Immunogenicity and 
Efficacy of a Zika Virus DNA Vaccine in Healthy Adults and Adolescents 
Study Design: This is a multicenter, randomized study to evaluate safety, immunogenicity, and 
efficacy of a three-dose vaccination regimen with the Zika virus (ZIKV) wild-
type (wt) DNA vaccine, VRC-ZKADNA090-00-VP, or placebo.  The 
hypotheses are that the ZIKVwt DNA vaccine will be safe and will elicit a 
ZIKV-specific immune response.  In Part A, the primary objective is to 
evaluate the safety and tolerability of the vaccine.  In Part B, the primary 
objectives are to evaluate the safety and efficacy of the vaccine compared to 
placebo.  Secondary and exploratory objectives of the study relate to 
immunogenicity and durability of immune responses. 
Product  
Description: 
VRC-ZKADNA090-00-VP was developed by the Vaccine Research Center 
(VRC), National Institute of Allergy and Infectious Diseases (NIAID), and is 
composed of a single closed-circular DNA plasmid (VRC 5283) that encodes 
the wt precursor transmembrane M (prM) and envelope (E) proteins from the 
H/PF/2013 strain of ZIKV. 
 
VRC-PBSPLA043-00-VP is sterile phosphate-buffered saline (PBS) prepared 
for human administration as a placebo. 
Subjects: 
Part A.  Healthy adults, 18-35 years of age, that reside in ZIKV endemic or 
potential endemic regions.  
 
Part B.  Healthy adults and adolescents, 15-35 years of age, that reside in ZIKV 
endemic or potential endemic regions.  Study sites may choose to enroll adults 
and adolescents, or may opt to enroll only an adult population. 
Study Plan: 
Subjects will receive study product intramuscularly (IM) in the limbs as 
specified by the group assignment.  In Part A, 90 subjects will be randomized 
to vaccine at a 1:1:1 ratio to receive a 4 mg or 8 mg dose of vaccine split 
between 2 or 4 injections. In Part B, about 2400 subjects will be randomized to 
vaccine (4 mg) or placebo in a 1:1 ratio.   
 
Vaccine safety and tolerability will be assessed by monitoring of clinical and 
laboratory parameters throughout the study.  Solicited reactogenicity symptoms 
will be collected for 7 days after each product administration.  The study 
schedule will include clinic visits with safety and immunogenicity blood 
samples collected at particular time points.   
 
The vaccine dose and administration plan for Part B was selected based on 
Part A and Phase 1 data.  Vaccine efficacy will be evaluated in Part B by 
comparing incidence of ZIKV cases between vaccine and placebo groups.  
During the study, when subjects exhibit any possible symptom of ZIKV 
infection, they will be evaluated by blood and urine ZIKV polymerase chain 
reaction (PCR).  Stored blood and urine samples will also be assessed 
retrospectively by ZIKV PCR to identify possible asymptomatic cases.  A Data 
and Safety Monitoring Board (DSMB) will oversee the study.   

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The product administration schema is as follows: 
Part A 
Group 
Subjects 
Total Dose 
Number of 
Injections per 
Dose 
Number of Limbs: 
Location of 
Injections  
Administration Schema 
Day 0 
Week 4 
Week 8 
1 
30 
4 mg 
2 
2 limbs:  
both arms 
DNA 
DNA 
DNA 
2 
30 
4 mg 
4 
4 limbs:  
both arms and legs 
DNA 
DNA 
DNA 
3 
30 
8 mg 
4 
4 limbs:  
both arms and legs 
DNA 
DNA 
DNA 
Total 
90* 
 Study product is administered IM by needle-free injection device. 
*Accrual up to a total of 100 subjects is permitted if additional subjects are needed for safety evaluations. 
Part B 
Group 
Subjects 
Total Dose 
Number of 
Injections per 
Dose 
Number of Limbs: 
Location of 
Injections†   
Administration Schema 
Day 0 
Week 4 
Week 8 
4 
1200 
4 mg 
2 
2 arms 
DNA 
DNA 
DNA 
5 
1200 
0 
2 
2 arms 
Placebo 
Placebo 
Placebo 
Total 
2400 
 Study product is administered IM by needle-free injection device. 
† Preferred location of injections is in both arms. Administration in the thighs may be allowed with IND 
Sponsor approval.  
Duration: 
Part A:  Each subject will be followed for 32 weeks. 
 
Part B:  Each subject will be followed for 96 weeks. 

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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), in Bethesda, Maryland, United 
States (US) 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.  Zika virus (ZIKV) is a mosquito-borne infection causing illness with 
mild symptoms including fever, rash, joint pain and conjunctivitis that may last for several days 
to weeks.  
Since its discovery in Uganda in 1947, outbreaks of ZIKV have been reported in Africa, 
Southeast Asia, and the Pacific Islands.  ZIKV emerged in Brazil in 2015 and then rapidly spread 
throughout the Americas [1].  In May 2015, the Pan American Health Organization (PAHO) 
issued an alert regarding the first confirmed ZIKV infection in Brazil and on February 1, 2016, 
the World Health Organization (WHO) declared ZIKV a public health emergency of 
international concern due to evidence suggesting ZIKV infection may be linked to recent clusters 
of microcephaly in babies born to infected mothers and other reported neurological disorders 
including Guillain-Barré syndrome (GBS) [2].  According to the WHO, local transmission has 
been reported in many other countries and territories and will continue to spread to new areas. 
There are currently no effective vaccines or therapies against ZIKV.  The rapid emergence of 
ZIKV supports the need for a safe and immunogenic vaccine.  This protocol is designed as a 
Phase 2/2B evaluation of the investigational ZIKV wild-type (wt) DNA vaccine, VRC-
ZKADNA090-00-VP.  This candidate vaccine is currently being evaluated in a Phase 1 study.  
This Phase 2/2B study is being advanced rapidly to follow the initiation of the Phase 1 study due 
to the significant public health need for a vaccine to prevent ZIKV.   
1.1. 
Zika Virus Infection: Etiology, Disease Course and Epidemiology 
ZIKV is an arthropod-borne virus (arbovirus) that belongs to the Flaviviridae family, genus 
Flavivirus, which also includes dengue (DENV), yellow fever, Saint Louis encephalitis, 
Japanese encephalitis and West Nile (WNV) viruses.  ZIKV is an enveloped virus with a ~10.8 
kb, positive sense, single-stranded ribonucleic acid (RNA) genome encoding for structural and 
non-structural proteins [3, 4].  
The name Zika comes from the Zika Forest in Uganda, where the virus was first isolated in 1947 
[5]. Genomic sequencing and phylogeny studies have identified three major ZIKV lineages 
including two African and one Asian [6-8].  Until recently, ZIKV remained endemic to 
equatorial Africa and parts of Asia.  In 2015, an explosive pandemic of ZIKV emerged in South 
America and spread rapidly throughout the tropical and subtropical Americas, threatening spread 
to North America [1].  The virus implicated in this current outbreak has been categorized as 
being of Asian lineage [9]. 
ZIKV is primarily transmitted to humans by infected mosquitoes, predominantly Aedes aegypti, 
but can be transmitted by other species [6].  ZIKV transmission has also been reported through 
sexual contact via semen [10], from mother to child during pregnancy or childbirth [11], and 
through blood transfusion transmission [12].  
ZIKV infection causes a fever-like disease with an incubation period (the time from exposure to 
symptoms) of 3 to 14 days.  Most people infected with ZIKV never display symptoms, which 

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makes it difficult to identify the infection.  If the disease presents, it is predominantly mild with 
symptoms resolving within a week [6, 13, 14].  Symptoms include low-grade fever, myalgia, and 
maculopapular rash accompanied by conjunctivitis, arthralgia and headache, and less often by 
edema, sore throat, and vomiting [14].  Information on laboratory changes during ZIKV infection 
is scarce but laboratory changes may include transient leukopenia, and in some cases 
thrombocytopenia and liver enzyme elevations [14, 15].  Polyfunctional T-cell activation and 
cytokine release have also been described during acute ZIKV infection [14].  Though atypical, 
neurological complications including GBS are being reported in a growing number of cases [16].  
Molecular mimicry between glycolipids and surface molecules of infectious agents may explain 
most of the cases of GBS preceded by infection; etiology of GBS associated with ZIKV infection 
is currently being investigated [17, 18].  Prenatal ZIKV infection has been associated with 
adverse pregnancy and birth outcomes, such as microcephaly and other serious neurological 
anomalies [19-21]; recent evidence shows a causal relationship between ZIKV infection during 
pregnancy and adverse outcomes in fetuses and infants, including microcephaly [22].  
Based on clinical symptoms alone, ZIKV disease cannot be reliably distinguished from 
infections with DENV, chikungunya (CHIKV) or other viruses that also cause an 
undifferentiated systemic febrile illness.  ZIKV infection diagnosis may be confirmed through 
serological testing or by viral RNA detection using reverse transcription-polymerase chain 
reaction (RT-PCR) [23].  Anti-ZIKV immunoglobulin M (IgM) is typically detectible by day 4 
through about 12 weeks post onset of symptoms [20, 23].  Serologic cross-reactivity with DENV 
and other flaviviruses has been reported, especially for subjects with a history of flavivirus 
infection and therefore background immunity [6, 20, 23].   
In February 2016, the US Food and Drug Administration (FDA) issued an emergency use 
authorization (EUA) for the ZIKV Mac-ELISA (IgM antibody capture enzyme-linked 
immunosorbent assay) diagnostic test developed by the Centers for Disease Control and 
Prevention (CDC) for diagnosis of ZIKV infection by an IgM antibody capture ELISA [20, 24].  
In July 2016, the FDA issued an EUA to authorize emergency use of Viracor-IBT Laboratories, 
Inc.'s ZIKV Real-time RT-PCR Test (Viracor-IBT) for the qualitative detection of RNA from 
Zika virus in human serum, plasma or urine [24]. 
Prolonged detection of ZIKV RNA has been observed in whole blood [25].  American Red Cross 
investigational screening of blood donations demonstrated that ZIKV RNA levels in red blood 
cells (RBC) may be detected up to 154 days after blood donation with the highest RNA copy 
levels associated with RBC [26].  ZIKV RNA can be detected by RT-PCR in serum and plasma 
within 2 to 7 days in the acute stage of infection and in urine for >10 days [27, 28].  However, 
ZIKV RNA levels in urine have been shown to degrade, making it a less viable option for 
detection compared to other methods [29].  ZIKV has also been detected in other bodily fluids 
including semen and saliva [30-32].   
1.2. 
Rationale for Development of VRC-ZKADNA090-00-VP 
ZIKV infection may induce long-lasting protective immunity.  Survivors of ZIKV infection have 
detectable humoral and cellular immunity; however, the relative contribution of these to 
protection is unknown [14, 15].  
There is no licensed vaccine or antiviral therapy available for the prevention or treatment of 
ZIKV infection.  The economic losses and added stress on public health infrastructure 

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experienced in areas of ZIKV transmission along with heightened potential for global spread 
necessitate vaccine development as a high global priority [33-35]. 
Investigators at the VRC have developed a plasmid DNA vaccine strategy that has been shown 
to elicit immune responses against the target pathogen in clinical studies [36, 37].  DNA vaccines 
have the potential to be manufactured rapidly and are known to induce balanced immune 
responses that include both humoral and cellular immunity.  The potential and experience to date 
with this vaccine platform warrants continued investigation of DNA vaccines as safe and 
efficient technology for responding to emerging infectious diseases [37]. 
The DNA vaccine platform was used in the development of two vaccines for WNV of the 
Flavivirus genus.  Similar to the VRC ZIKV DNA vaccines, the WNV investigational vaccines, 
VRC-WNVDNA017-00-VP and VRC-WNVDNA020-00-VP, express two WNV proteins: prM, 
a precursor for the M transmembrane protein, and envelope (E) protein of the virus under control 
of the cytomegalovirus (CMV) promoter and the CMV/R promoter, respectively, and result in 
the formation of noninfectious subviral particles in vitro [38, 39].  
In VRC Phase 1 trials, the WNV DNA vaccines were evaluated as safe and well tolerated, and 
provided compelling evidence that these vaccines can induce neutralizing antibody (NAb) 
against WNV in healthy adults 18-65 years of age as assessed by a reporter virus particle (RVP) 
NAb assay and plaque reduction neutralization test (PRNT) [38, 39].  
VRC ZIKV DNA vaccines using plasmids VRC 5288 (ZIKV DNA vaccine, VRC-
ZKADNA085-00-VP) and VRC 5283 (ZIKVwt DNA vaccine, VRC-ZKADNA090-00-VP) 
were developed based on prior experience with the WNV DNA vaccine platforms.  The two 
ZIKV vaccines are similar, with the ZIKVwt DNA vaccine expressing the structural prM and E 
glycoproteins of ZIKV and the ZIKV DNA vaccine expressing prM from ZIKV and a chimeric 
E protein with part of the sequence of ZIKV and part of sequence of JEV.  Expression of prM 
and E induce the formation of VLPs with antigenic properties comparable to infectious virions 
[40].   
Vaccination with either ZIKV DNA or ZIKVwt DNA elicited ZIKV-specific NAb titers in mice 
and non-human primates (NHPs).  There were no significant differences in NAb titers between 
animals that received the ZIKV DNA vaccine or animals that received the ZIKVwt DNA vaccine 
[40].  Based on data reported for WNV DNA vaccines and on animal studies with the VRC 
ZIKV DNA vaccines, it is expected that the ZIKVwt DNA vaccine will be safe and 
immunogenic.   
1.3. 
Previous Human Experience with VRC DNA Vaccines 
Cumulatively, since the first clinical trial using the VRC DNA vaccine platform in October 2001, 
more than 3,000 study subjects 6-70 years of age have received one or more injections of VRC 
DNA vaccines; all evaluated as safe and immunogenic [38, 39, 41-49].  Although a human 
efficacy study has not yet been completed with any DNA vaccine given alone, clinical trials of 
WNV DNA vaccines [38, 39], a severe acute respiratory syndrome (SARS) DNA vaccine (VRC-
SRSDNA015-00-VP) [43], and an H5 influenza DNA vaccine (VRC-AVIDNA036-00-VP) [41, 
50] have provided evidence that DNA vaccines based on the VRC plasmid backbone are safe 
and can induce NAbs against targeted pathogens.  Additionally, a seasonal influenza DNA 
vaccine (VRC-FLUDNA063-00-VP) has been shown to be safe in 44 children and adolescent 
subjects ranging in age from 6 to 17 years [unpublished data].  

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1.4. 
Human Experience with VRC ZIKV DNA Vaccines 
Phase 1 Evaluation:  A Phase 1 clinical trial VRC 319 (NCT02840487) began in August 2016 
to evaluate the safety and immunogenicity of the ZIKV DNA vaccine and a Phase 1 clinical trial 
VRC 320 (NCT02996461) began in December 2016 to evaluate the safety and immunogenicity 
of the ZIKVwt DNA vaccine.  At the time of this summary, data quality assurance and 
monitoring are ongoing, and therefore all reported data are preliminary and should not be 
considered final.  VRC 319 and VRC 320 vaccination schemas and administration routes were 
selected based on previous experience with the WNV DNA vaccines, the H5 DNA vaccine, and 
the CHIKV VLP vaccine, all developed by VRC [33, 38, 39, 51].    
VRC 319:  As of July 24, 2018, 80 subjects have enrolled and received at least one ZIKV DNA 
vaccination intramuscularly (IM) by needle and syringe.  The last study vaccination was 
administered on February 15, 2017.  There have been no serious adverse events (SAEs) related 
to study product reported in the study.  One SAE (appendicitis) was reported as unrelated to 
study product.  Overall, 60 of 80 (75.0%) subjects have had one or more unsolicited adverse 
events (AEs), with maximum severity being mild (Grade 1) for 36 (45.0%) subjects, moderate 
(Grade 2) for 18 (22.5%) subjects, severe (Grade 3) for 5 (6.3%) subjects, and life-threatening 
(Grade 4) for 1 (1.3%) subject.  Seventeen (17) mild or moderate unsolicited AEs were assessed 
as related to study product including: neutropenia (7), lymphopenia (4), leukopenia (2), 
thrombocytopenia (1); dizziness (1) and paresthesia (1) that occurred in one subject 3 days after 
vaccination and resolved that same day; and injection site pruritus (1) that occurred on day of 
vaccination and resolved that day.   
Product administrations have been generally well tolerated.  Maximum solicited local 
reactogenicity in the 7 days after product administration was reported as none by 41 of 80 
(51.3%) subjects and mild by 39 (48.8%) subjects; no moderate or severe local symptoms have 
been reported.  Mild pain at the injection site was the most common symptom after product 
administration, reported by 37 (46.3%) subjects; 5 (6.3%) subjects reported mild redness and 1 
(1.3%) subject reported mild swelling.  With regard to solicited systemic reactogenicity in the 7 
days after product administration, 47 of 80 (58.8%) subjects reported none, 29 (36.3%) subjects 
reported mild, and 4 (5.0%) subjects reported moderate systemic symptoms.  No fevers or severe 
systemic symptoms have been reported.  Mild or moderate malaise and headache were the most 
common symptoms after product administration, reported by 22 (27.5%) and 18 (22.5%) 
subjects, respectively.  Mild or moderate symptoms of myalgia (17, 21.3%), nausea (7, 8.8%), 
chills (6, 7.5%), and joint pain (4, 5.0%) were reported by subjects less frequently.  
VRC 320:  As of July 24, 2018, 45 subjects have enrolled and received at least one ZIKVwt 
DNA vaccination IM by needle and syringe or needle-free injection device, the PharmaJet 
Stratis® 0.5 mL Needle-Free Jet Injector (PharmaJet).  The last vaccination was administered on 
June 14, 2017.  There have been no SAEs related to study product reported in the study.  One 
SAE (ruptured colon) was reported as unrelated to study product.  Overall, 32 of 45 (71.1%) 
subjects have had one or more unsolicited AE with maximum severity being mild (Grade 1) for 
17 (37.8%) subjects, moderate (Grade 2) for 12 (26.7%) subjects, severe (Grade 3) for 2 (4.4%) 
subjects, and life-threatening (Grade 4) for 1 (2.2%) subject.  Three (3) AEs were assessed as 
related to study product including: mild lymphopenia, mild hypertension, and moderate 
neutropenia, all of which resolved.  

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With regard to product administrations, maximum solicited local reactogenicity in the 7 days 
after administration was reported as none by 9 (20.0%) of 45 subjects, mild by 33 (73.3%) 
subjects, and moderate by 3 (6.7%) subjects; no severe local symptoms have been 
reported.  Mild pain at the injection site was the most common symptom after product 
administration, reported by 33 (73.3%) of 45 subjects and 3 (6.7%) subjects reported mild 
swelling.  Maximum solicited systemic reactogenicity in the 7 days after product administration 
was reported as none by 21 (46.7%) of 45 subjects, mild by 20 (44.4%) subjects, and moderate 
by 4 (8.9%) subjects; no severe systemic symptoms or fevers have been reported.  Mild or 
moderate malaise and headache were the most common symptoms after product administration, 
reported by 17 (37.8%) and 15 (33.3%) subjects, respectively.  Mild or moderate symptoms of 
myalgia (9, 20.0%), joint pain (8, 17.7%), nausea (2, 4.4%), and chills (2, 4.4%) were reported 
by subjects less frequently. 
Phase 2/2B Evaluation:  VRC 705 (NCT03110770) initiated in March 2017 with accrual into 
Part A; accrual into Part B began in July 2017.  Human experience collected in this study is 
summarized below.  At the time of this summary, data quality assurance and monitoring are 
ongoing, and therefore all reported data are preliminary and should not be considered final. 
VRC 705 Part A:  As of July 24, 2018, 90 subjects have randomized and received at least one 
ZIKVwt DNA vaccination IM by PharmaJet.  The last vaccination was administered on October 
16, 2017.  There have been no SAEs related to study product reported in this part of the study.  
Three (3) SAEs (including: bilateral urolithiasis, bipolar disorder exacerbation, and gunshot 
wound resulting in death) were reported as unrelated to study product.  Overall, 68 of 90 (75.6%) 
subjects have had one or more unsolicited AE with maximum severity being reported as mild 
(Grade 1) for 35 (38.9%), moderate (Grade 2) for 28 (31.1%), severe (Grade 3) for 4 (4.4%) 
subjects, and fatal (Grade 5) for 1 (1.1%) subject.  
Regarding product administration, maximum solicited local reactogenicity in the 7 days after 
administration was reported as none by 9 of 90 (10.0%) subjects, mild by 55 (61.1%) subjects, 
and moderate by 26 (28.9%) subjects.  Mild or moderate pain at the injection site was the most 
common symptom after product administration, reported by 81 of 90 (90.0%) subjects.  
Maximum solicited systemic reactogenicity in the 7 days after product administration was 
reported as none by 38 (42.2%), mild by 40 (44.4%), moderate by 11 (12.2%), and severe by 1 
(1.1%) subject.  Mild or moderate headache (37, 41.1%), malaise (33, 36.7%, which includes 1 
severe event), and myalgia (22, 24.4%) were the most common symptoms reported by subjects 
after product administration.  
VRC 705 Part B:  As of July 24, 2018, 1058 subjects have randomized and received at least one 
product administration with ZIKVwt DNA or PBS by PharmaJet.  There have been no SAEs 
related to study product in this part of the study.  Six (6) SAEs (including: seizure, cholelithiasis, 
ectopic pregnancy, depression, depressive episode, and rhabdomyolysis) were reported as 
unrelated to study product.  Regarding product administration, maximum solicited local 
reactogenicity in the 7 days after administration was reported as none by 354 of 905 (39.1%) 
subjects, mild by 411 (45.4%) subjects, moderate by 137 (15.1%) subjects, and severe by 1 
(0.1%) subject.  Mild or moderate pain at the injection site was the most common symptom after 
product administration reported by 543 (60.0%) subjects, and as severe by 1 (0.1%) subject.  
Maximum solicited systemic reactogenicity in the 7 days after product administration was 
reported as none by 425 (47.0%), mild by 338 (37.3%), moderate by 129 (14.3%), and severe by 

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11 (1.2%).  Mild or moderate headache (312, 34.5%), malaise (275, 30.4%), and myalgia (236, 
26.1%) were the most common symptoms reported by subjects after product administration.    
1.5. 
Rationale for Study Product Dose and Administration Method  
VRC DNA vaccines have been administered at doses of up to 8 mg, with the majority of 
injections given at 4 mg.  Data from two dose-escalation studies (VRC 004 and VRC 204) 
indicate that a 4-mg dose offers the combination of a good safety profile, greater ease of 
administration than an 8-mg dose, and reliable immunogenicity as indicated by laboratory 
measures of immune response [42, 44].  Preclinical and clinical evaluations to date of plasmid 
DNA vaccines support the safety and immunogenicity of DNA vaccines at doses up to 8 mg; 
VRC-ZKADNA090-00-VP will be evaluated at doses of 4 mg/mL and 8 mg/mL in Part A. 
Preliminary data from VRC 319, VRC 320 and VRC 705 Part A indicate that a 4 mg dose 
administered IM by PharmaJet at weeks 0, 4 and 8, offers the combination of a good safety 
profile, ease of administrations and reliable immunogenicity and as a result, this regimen was 
selected for Part B.  
In previous studies, DNA vaccines have been administered by IM, subcutaneous (SC), or 
intradermal routes using either standard needle and syringe or needle-free injection device.  The 
use of a needle-free injection system was found to be superior to needle and syringe by offering a 
significant contribution to the elicited immunogenicity [52].   
In March 2016, Biojector (Biojector 2000® needle-free injection system, Bioject Medical 
Technologies, Tigard, OR), which was used in previous VRC DNA vaccine studies, became 
unavailable.  Therefore, investigational products in this study will be administered using the 
PharmaJet, a similar needle-free injection device.   
PharmaJet is intended to deliver various medications and vaccines to adults and children either 
IM or SC by means of a narrow, high velocity fluid jet.  PharmaJet is a Class II medical device 
that holds a General Use 510(k) marketing clearance from the FDA and received the 
Performance, Quality and Safety (PQS) pre-qualified certification from the WHO (#E008/050).  
Energy to propel the fluid (“liquid needle”) is supplied by a hand-held, spring-powered injector.  
Immunogenicity studies have been conducted in rhesus macaques in which animals received 
doses of the ZIKVwt DNA vaccine via PharmaJet showed an increase in NAb production 
following immunization in both groups [40].     
In this study, ‘product administration’ describes the completion of all PharmaJet injections 
(either 2 or 4) needed to give the full dose assigned at a visit.   
In Part A, each subject will receive the ZIKVwt DNA vaccine administered by PharmaJet on 
Day 0, Week 4 and Week 8.  Group 1 will receive a total dose of 4 mg split into two 0.5 mL 
needle-free injections, with one IM injection given into each arm.  Group 2 will receive a total 
dose of 4 mg split into four 0.5 mL needle-free injections (using diluent to reach the full 0.5 mL 
volume), with one injection given IM into each arm and each leg.  Group 3 will receive a total 
dose of 8 mg split into four 0.5 mL needle-free injections, with one injection given IM into each 
arm and each leg.  These regimens will help us determine if the optimal regimen is to administer 
the full dose into one limb or to split the dose among limbs. 
In Part B, each subject will receive the ZIKVwt DNA vaccine or placebo administered by 
PharmaJet on Day 0, Week 4 and Week 8.  Group 4 will receive a total dose of 4 mg split into 

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two 0.5 mL needle-free injections, with one IM injection given into each arm and Group 5 will 
receive two 0.5 mL needle-free injections of placebo, with one IM injection given into each arm. 
1.6. 
Rationale for the Study Population  
In Part A, healthy adults 18 years of age (or the site-specific minimum age that applies to adults) 
to 35 years of age have been chosen as the target population.   
In Part B, the population will expand to include healthy adolescents 15-17 years of age.  
Therefore, healthy subjects 15-35 years of age have been chosen as the target population for Part 
B.  According to the WHO, more than 15 million of the 135 million (11%) live births worldwide 
are among girls aged 15-19 years [53].  Therefore, this study targets age groups of the highest 
reproductive potential who will likely be the initial recipients of a successful ZIKV vaccine.   
The maximum age for the study target population is 35 years of age.  This is based on data 
suggesting an increased risk of GBS with increasing age, so the study population excludes those 
who might be at higher risk for GBS [54-56]. 
1.7. 
Assessment of Immunogenicity 
In this study, specimens to evaluate immunogenicity will be collected at baseline and at specified 
time points.  The primary immunogenicity time point is 4 weeks after receipt of the last product 
administration.  ZIKV-specific humoral immune responses will be assessed at clinical visits 
through 32 weeks after receipt of the first product administration in Part A and 96 weeks after 
receipt of the first product administration in Part B.  ZIKV-specific cellular immune responses 
at baseline and select timepoints after product administration may also be assessed in Part A 
subjects and at designated sites in Part B.    
NAbs are a well-established correlate of protection against flavivirus infection.  A pseudo-
infectious ZIKV RVP NAb assay will be performed at baseline and 4 weeks after the last product 
administration for a secondary endpoint as previously described for WNV [38, 39] and possibly 
on stored samples from other study time points as an exploratory endpoint.  Use of the RVP 
approach to detect and enumerate NAbs offers several advantages as compared to the traditional 
PRNT including: increased precision, speed, and ability to perform assays under biosafety level-
2 conditions in large scale (allowing analysis in replicate using a large number of dilutions).  The 
normalization criteria used to validate assay results are derived directly from the “percentage 
law” (law of mass action) and confer a significant improvement in assay-to-assay reproducibility 
and accuracy.  Extensive analysis of the neutralization potency of several well characterized 
monoclonal antibodies [57, 58] reveal agreement with published values obtained using the PRNT 
and BHK-21 cells [59].  
Briefly, ZIKV RVPs for use in neutralization assays will be produced in HEK-293T cells by co-
transfection with plasmids encoding a green fluorescent protein (GFP)-expressing WNV replicon 
and the structural proteins of the ZIKV H/PF2013 strain [60].  ZIKV RVPs will be incubated 
with serial three-fold dilutions of heat-inactivated sera and added to Raji cells expressing the 
attachment factor DC-SIGNR.  Infected cells expressing GFP will be measured two days post-
transfection using flow cytometry or other assay readout.  The dilution of sera required to 
neutralize half the infection events (EC50) will be estimated by non-linear regression using 
Graph Pad Prism.  ZIKV NAbs elicited by immunization with VRC-ZKADNA090-00-VP have 
been recently described [51]. 

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Exploratory assays may include T-cell analyses by Intracellular Cytokine Staining (ICS) and/or 
ELISpot assay as previously described for WNV [38, 39].  Other exploratory immunogenicity 
assays may be performed with stored samples.  
To evaluate cross-reactivity of ZIKV-specific responses with responses to other flaviviruses, pre-
existing responses to DENV, yellow fever, Japanese encephalitis, and WNV at baseline may be 
evaluated retrospectively, along with cross-reactivity at 4 weeks after last product administration. 
The immunogenicity testing will be performed at the NIAID Vaccine Immune T-Cell and 
Antibody Laboratory (NVITAL, Gaithersburg, MD, US) following Good Clinical Laboratory 
Practice (GCLP) regulations and may also be performed in research laboratories at the VRC, the 
Laboratory of Viral Diseases, Viral Pathogenesis Section, NIAID, NIH, Z-Quick,  University of 
Miami Life Science and Technology Park (Miami, FL, US), or by other approved collaborators.  
New assays to characterize and quantify Zika antibodies are currently being developed and new 
collaborators and/or testing laboratories may be used in the future. 
1.8. 
ZIKV Infection Assessment 
Subjects who develop any possible sign or symptom of ZIKV infection at any time following the 
first product administration will be clinically evaluated by the trial site as soon as possible.  In 
Part A, subjects can be diagnosed at the designated primary diagnostic laboratory (PDL), the 
University of Washington (Seattle, WA, US), by PCR evaluation of blood and/or urine samples 
or by site standard procedures. 
Part B of the study is designed to evaluate the efficacy of the selected vaccine regimen 
compared to placebo.  In order to evaluate vaccine efficacy, all possible cases of ZIKV infection 
are required to be diagnosed by the PDL by PCR evaluation of blood and urine samples, except 
in the case of suspected hemorrhagic fever, in which blood and urine samples must be sent to the 
CDC’s Diagnostic and Reference Laboratory, Arbovirus Diseases Branch (Fort Collins, CO, 
US).  Additionally, sites may follow a local standard of care to diagnose suspected ZIKV 
infection by PCR testing.  Research specimens may also be collected for viral evaluation at the 
request of the Investigational New Drug (IND) Sponsor. 
In Part B, regardless of symptoms, blood will also be collected for research on a routine basis 
per the Schedule of Evaluations tables in Appendix III.  These stored samples will be 
retrospectively evaluated for ZIKV by PCR by Battelle, Biomedical Research Center (West 
Jefferson, Ohio, US).  This assessment is not intended to replace real-time evaluation of possible 
symptomatic ZIKV infections and will not provide a diagnosis nor will it guide clinical care.  
However, this assessment will be performed to aid in the evaluation of exposure to ZIKV or 
possible asymptomatic ZIKV infections throughout the trial. 

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2. 
STUDY PRODUCTS 
Study products are manufactured under current Good Manufacturing Practice (cGMP) 
regulations. 
2.1. 
VRC-ZKADNA090-00-VP, ZIKVwt DNA Vaccine  
VRC-ZKADNA090-00-VP was manufactured by the VRC Pilot Plant operated under contract 
by Leidos Biomedical Research, Inc. (Frederick, MD, US).  The VRC-ZKADNA090-00-VP 
drug substance consists of a single closed-circular plasmid DNA (VRC 5283) that encodes the 
precursor transmembrane M (prM) and envelope (E) proteins from the H/PF/2013 strain of 
ZIKV (GenBank number AHZ13508.1) derived from a French Polynesian isolate and identical 
or highly related to strains circulating in the Americas.  
The plasmid CMV/R promoter consists of translational enhancer region of the CMV immediate 
early region 1 enhancer (CMV-IE) substituted with the5′-untranslated human T cell leukemia 
virus type 1 (HTLV-1) R-U5 region of the human T cell leukemia virus type 1 HTLV-1 long 
terminal repeat (LTR), and has been shown to optimize gene expression further [61].  This 
promoter has been evaluated in preclinical safety studies as well as several clinical trials of DNA 
vaccines for HIV (BB-IND 11750), WNV (BB-IND 12933), Ebola (BB-IND 11294), SARS 
(BB-IND 11995) and avian influenza (BB-IND 13197).  
The drug product is formulated in phosphate buffered saline (PBS).  Vials are aseptically filled to 
a volume of 1.2 or 1.5 mL with 4 mg/mL of plasmid.  More details related to vaccine 
preparation, manufacturing, and preclinical studies can be found in the Investigator’s Brochure 
(IB).  
2.2. 
VRC-PBSPLA043-00-VP, Placebo and Diluent 
VRC-PBSPLA043-00-VP, sterile PBS, is the placebo and diluent for the ZIKVwt DNA vaccine.     
2.3. 
Preclinical Safety and Immunogenicity Studies of VRC-
ZKADNA090-00-VP 
Non-clinical, non-GLP immunogenicity studies in mice and NHPs were conducted at the VRC 
with the ZIKVwt DNA vaccine administered IM.  Results confirmed that the vaccine is 
immunogenic, protects against ZIKV challenge, and induces neutralizing antibodies [40].  
GLP toxicology studies are not planned for VRC-ZKADNA090-00-VP because the vector 
backbone has been extensively tested with other VRC DNA vaccines and similar inserts (WNV) 
were previously tested [38, 39, 62, 63].  
More details on the preclinical studies with VRC-ZKADNA090-00-VP can be found in the IB. 

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3. 
STUDY OBJECTIVES  
3.1. 
Primary Objectives  
Part A:  
• To evaluate the safety and tolerability of VRC-ZKADNA090-00-VP in healthy adults 
when administered IM at a dose of 4 mg IM by needle-free injection device. 
• To evaluate the safety and tolerability of VRC-ZKADNA090-00-VP in healthy adults 
when administered IM at a dose of 8 mg IM by needle-free injection device. 
Part B: 
• To evaluate the safety and tolerability of VRC-ZKADNA090-00-VP in healthy adults 
and adolescents when administered IM at a dose of 4 mg by needle-free injection device 
compared to placebo. 
• To evaluate the efficacy of VRC-ZKADNA090-00-VP by comparing incidence rates of 
virologic ZIKV cases in vaccine and placebo recipients. 
3.2. 
Secondary Objectives 
Part A:  
• To evaluate the magnitude and the frequency of ZIKV-specific antibody response as 
measured by neutralization assay at 4 weeks after the last product administration.  
Part B: 
• To evaluate the magnitude and the frequency of ZIKV-specific antibody response as 
measured by neutralization assay at 4 weeks after the last product administration.  
• To compare incidence rates of subclinical cases of ZIKV infection in vaccine and placebo 
recipients. 
3.3. 
Exploratory Objectives 
Part A: 
• To characterize ZIKV-specific antibody and T cell responses at specified time points. 
• To evaluate the durability of ZIKV-specific immune responses. 
• To evaluate the immunogenicity of split dose injections administered to 2 or 4 limbs. 
Part B: 
• To evaluate the magnitude and duration of ZIKV viruria or viremia.  
• To characterize ZIKV-specific antibody and T cell responses at specified time points 
throughout the study. 
• To evaluate the durability of ZIKV-specific immune responses. 
• To compare the incidence of DENV disease in the vaccine and placebo recipients. 
• To compare incidence rates of symptomatic cases of ZIKV infection in vaccine and 
placebo recipients.  

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4. 
STUDY DESIGN AND CLINICAL PROCEDURES 
This is a Phase 2/2B multicenter, randomized study of the ZIKVwt DNA vaccine in healthy 
adults and adolescents.  The hypotheses are that the vaccine regimen is safe and induces a 
neutralizing antibody response to ZIKV.  Part A will target healthy adults only.  Part B includes 
adolescents in the study population.  Therefore, Part B study sites will have the option to enroll 
adolescents and adults, or sites may choose to enroll only an adult population.   
This study will be conducted at trial sites that are located in areas of confirmed or projected 
active transmission of ZIKV infection.  The allotted randomization slots per site for Part A will 
be defined per site capability to enroll rapidly.  The allotted randomization slots per site for Part 
B will be assigned based on site capacity and local epidemiological data, the number of site slots 
may be increased or decreased as the epidemic shifts.  All sites participating in Part B will be 
asked to monitor their local epidemiologic data as reported by regional or other authorities and 
be prepared to report this data to the IND Sponsor, when applicable and requested.  Each subject 
will be on study for about 32 weeks in Part A and 96 weeks in Part B.  The study schema is in 
Table 1.   
Table 1: 
Study Schema 
Part A 
Group 
Subjects 
Total  
Dose 
Number of 
Injections per 
Dose 
Number of Limbs: 
Location of 
Injections  
Administration Schema 
Day 0 
Week 4 
Week 8 
1 
30 
4 mg 
2 
2 limbs:  
both arms 
DNA 
DNA 
DNA 
2 
30 
4 mg 
4 
4 limbs:  
both arms and legs 
DNA 
DNA 
DNA 
3 
30 
8 mg 
4 
4 limbs:  
both arms and legs 
DNA 
DNA 
DNA 
Total 
90* 
Study product is administered IM by needle-free injection device. 
*Accrual up to a total of 100 subjects is permitted if additional subjects are needed for safety evaluations. 
Part B 
Group 
Subjects 
Total  
Dose 
Number of 
Injections per 
Dose 
Number of Limbs: 
Location of 
Injections†  
Administration Schema 
Day 0 
Week 4 
Week 8 
4 
1200 
4 mg 
2 
2 arms 
DNA 
DNA 
DNA 
5 
1200 
0 
2 
2 arms 
Placebo 
Placebo 
Placebo 
Total 
2400 
Study product is administered IM by needle-free injection device. 
† Preferred location of injections is in both arms. Administration in the thighs may be allowed with IND 
Sponsor approval.  

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4.1. 
Eligibility Criteria 
The study is designed for the participation of healthy adults and adolescents.  All inclusion and 
exclusion criteria must be met for eligibility. 
4.1.1. 
Inclusion Criteria 
A subject must meet all of the following criteria: 
1. Part A: 18 to 35 years of age;   
Part B: 15 to 35 years of age 
2. Part A: Available for clinical follow-up through Study Week 32;  
Part B: Available for clinical follow-up through Study Week 96 
3. Able to provide proof of identity to the satisfaction of the clinician completing the 
enrollment process 
4. Able and willing to complete the informed consent/assent process 
5. Able and willing to complete the Assessment of Understanding and to verbalize 
understanding of all questions answered incorrectly prior to signing consent/assent 
6. Willing to donate blood and urine to be stored and used for future research 
7. In good general health without clinically significant medical history 
8. Physical examination and laboratory results without clinically significant findings within 
the 56 days prior to randomization 
9. Weight > 30 kg 
10. Agree not to receive any licensed or investigational flavivirus vaccines through 4 weeks 
after the last product administration  
11. Part A: Accessible injection sites on each limb as follows: 1 injection site in the deltoid 
muscle of each arm and 1 injection site in the vastus lateralis muscle of each anterolateral 
thigh. 
Part B: Accessible injection sites on the deltoid muscle of each arm.  Injection sites on the 
vastus lateralis muscle of the anterolateral thighs may be allowed with IND Sponsor 
approval if an injection site on each deltoid muscle is not available. 
Laboratory criteria within 56 days prior to randomization: 
12. Hemoglobin within site institutional normal limits  
13. Absolute neutrophil count (ANC) within site institutional normal limits  
14. Totallymphocytecount≥800cells/mm3 
15. Platelets = 125,000 – 510,000 cells/mm3 
16. Alanine aminotransferase (ALT) ≤1.5xupperlimitofnormal(ULN) based on site 
institutional normal range for respective age group 

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17. Serumcreatinine≤1.2 x ULN based on site institutional normal range for respective age 
group 
18. Negative result on an HIV test that meets local standards for identification of HIV 
infection 
Criteria applicable to women and adolescents of childbearing potential: 
19. Negative result on a human chorionic gonadotropin pregnancy test (urine or serum) on day 
of randomization before receiving study product 
20. Agree to use effective means of birth control from at least 21 days before randomization 
through 12 weeks after the last product administration 
Criteria applicable to adolescents: 
21. Capability of the parent/guardian of the minor to understand and comply with planned 
study procedures. 
22. Capability of the minor and their parent/guardian to provide assent/informed consent  
4.1.2. 
Exclusion Criteria 
A subject will be excluded if one or more of the following conditions apply: 
Criteria applicable to women and adolescents of childbearing potential: 
1. Breast-feeding or planning to become pregnant while participating through 12 weeks after 
the last product administration 
Subject has received any of the following: 
2. More than 10 days of systemic immunosuppressive medications or cytotoxic medications 
within the 4 weeks prior to randomization  
3. Any systemic immunosuppressive medications or cytotoxic medications within the 14 
days prior to randomization 
4. Blood products within 16 weeks prior to randomization 
5. Immunoglobulin within 8 weeks prior to randomization 
6. Investigational research agents within 4 weeks prior to randomization or planning to 
receive investigational products while on the study 
7. Any vaccination within 2 weeks prior to randomization  
8. Any live attenuated vaccination within 4 weeks prior to randomization 
9. Current anti-TB prophylaxis or therapy 
Subject has any of the following: 
10. Confirmed history of ZIKV infection (as reported by subject) 
11. Serious reactions to vaccines  
12. Chronic angioedema or chronic urticaria 
13. Asthma that is not well-controlled  

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14. Diabetes mellitus (type I or II) 
15. Clinically significant autoimmune disease or immunodeficiency  
16. Hypertension that is not well controlled  
17. Bleeding disorder diagnosed by a doctor (e.g. factor deficiency, coagulopathy, or platelet 
disorder requiring special precautions)  
18. Significant bruising or bleeding difficulties with IM injections or blood draws 
19. Malignancy that is active or history of a malignancy that is likely to recur during the 
period of the study 
20. Seizure or treatment for a seizure disorder within the last 3 years 
21. Asplenia, functional asplenia or any condition resulting in the absence or removal of the 
spleen 
22. History of Guillain-Barré Syndrome 
23. Psychiatric condition that may preclude compliance with the protocol; past or present 
psychoses; or a history of suicide plan or attempt within 5 years prior to randomization 
24. Any medical, psychiatric, or social condition that, in the judgment of the investigator, is a 
contraindication to protocol participation or impairs a subject’s ability to give informed 
consent. 
4.2. 
Clinical Procedures and Evaluations  
Evaluation of this investigational vaccine will include laboratory tests, medical history, physical 
examination by clinicians and subject self-assessment.  The schedule of study visits is shown in 
the Schedule of Evaluations tables in Appendix III.  As per NIH Clinical Center guidelines, total 
blood volume drawn from adult subjects (who weigh at least 50 kg) will not exceed 550 mL in 
any 8-week period; total blood volume from each adolescent subject will not exceed 9.5 mL/kg 
in any 8-week period.  Sites must also follow institutional policy for blood collection from adults 
and adolescents as applicable.   
4.2.1. 
Pre-screening 
Subjects will be recruited through Institutional Review Board (IRB)/ Ethics Committee (EC) -
approved advertising.   
To identify potential study subjects, study staff may discuss the VRC 705 clinical trial with those 
who express interest.  Study staff may use an interview questionnaire to obtain self-reported 
medical history in order to determine if the subject may be eligible based on protocol inclusion 
and exclusion criteria.  Potential study subjects who appear to be eligible may continue to screen 
for this study.  No study-specific interventions may be done during pre-screening. 
4.2.2. 
Screening and Enrollment 
The screening process may occur over one visit or multiple visits in order for the site to fully 
assess each subject’s eligibility to participate in this study.  Table A: Schedule of Evaluations – 
Screening is available in Appendix III.  Screening procedures must be completed within the 56-
day screening window.  The informed consent form (ICF)/ assent form may be signed more than 

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56 days before study randomization and does not need to be re-signed if outside of this window, 
unless required by local regulations or an updated form becomes available.   
Assessment of Understanding:  The Assessment of Understanding (AoU) is a tool to help study 
staff confirm the subject’s understanding of the consent/assent information.  The AoU must be 
completed before the subject signs the consent/assent form.  For adolescent subjects, the AoU 
will be completed with the parent/guardian present.  Incorrect answers on the AoU must be 
reviewed with the subject.   
Informed Consent:  In clinical research, informed consent is a process in which a competent 
individual is fully informed about the nature, benefits and risks of a clinical trial and makes an 
informed decision on his/her study participation.  Informed consent will be presented and 
discussed in a language and at a level that is understandable to the potential subject (and parent/ 
guardian, if applicable).   
Appropriately trained and delegated study staff must review the ICF with each potential subject 
(and parent/guardian, if applicable).  Before screening procedures can be performed, informed 
consent must be obtained, and the form must be signed by the subject.   
Template main and parental ICFs are provided in Appendix I.  Per Section 8.4, sites must use the 
templates to develop site-specific forms as needed, adding relevant information as required by 
site institutional/local/national regulations.   
Assent of Adolescents:  Adolescents are expected to be able to provide informed consent.  
However, if the adolescent’s age is below the legal age of consent per country regulations, the 
parent/guardian must also provide consent and sign the ICF (or both parents if required by site 
regulatory authorities) or the site may use an assent form.   
A template assent form is provided in Appendix I.  Per Section 8.4, sites must use the template to 
develop site-specific forms as needed, adding relevant information as required by site 
institutional/local/national regulations.   
Enrollment:  All subjects who sign the consent or assent forms must be enrolled in the database 
following completion of the informed consent/assent process. 
During Screening: 
• Medical History and Physical Examination:  The PI or designee must obtain a medical 
history and perform a physical examination including collection of vital signs, height and 
weight within 56 days before randomization.    
• Injection Site Assessment: Clinical staff should assess potential injection sites in the 
deltoid muscle of each arm and in the vastus lateralis muscle of each anterolateral thigh, 
as applicable.  Clinical staff should avoid administering an injection in an area that has an 
injury, local skin problem or significant tattoo that interferes with evaluation of the 
injection site after product administration.   
• Pregnancy Prevention Counseling and Pregnancy Testing:  Clinical staff must 
perform pregnancy prevention counseling on female subjects of childbearing potential to 
evaluate if subjects are able to meet the birth control eligibility criteria.  Pregnancy test 
results must also be confirmed as negative for these subjects during screening. 

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• HIV Prevention Counseling:  During screening, HIV counseling must be performed on 
all subjects being tested for HIV to ensure the subject is aware of how to reduce risk of 
and avoid HIV infection.  Every attempt must be made to provide the HIV test results to 
the subjects. 
• Blood Sample Collection:   
− Samples for clinical evaluation of eligibility criteria must be completed no more than 
56 days before randomization.  Tests may be repeated as needed based on clinical 
judgment to confirm eligibility or if there is a suspected change in health status.   
− Samples for research must be collected during screening.  However, research samples 
obtained more than 56 days before randomization do not need to be repeated.  Some 
samples collected during screening may be used for assay validation and site 
proficiency testing.   
• Eligibility Review:  Based on results from the physical examination, medical history 
evaluation, blood tests and any additional health assessments performed during screening, 
the PI or designee will determine if subjects qualify to participate in this study and 
confirm by documenting on the applicable data collection forms and in the database.  For 
subjects who are not eligible, the reason(s) must be recorded.  
4.2.3. 
Randomization 
Visit 02 (Day 0) is defined as the day of study randomization and first product administration.  
Table B: Schedule of Evaluations – Part A and Table C: Schedule of Evaluations – Part B are 
available in Appendix III.   
Before Randomization:  
• Pregnancy Prevention Counseling and Pregnancy Testing:  Pregnancy prevention 
counseling must be conducted, and pregnancy test results must be confirmed negative for 
females of childbearing potential.   
• Medical History Review and Targeted Physical Examination:  Review health status 
and current medications including recent vaccinations, measure vital signs, re-assess 
potential injection sites, and verify all eligibility criteria. 
If a subject presents with fever or other signs of illness during the first product 
administration visit, do not randomize the subject and do not order or administer study 
product.  Instead, review the subject’s medical history and conduct a targeted physical 
examination, as needed.  If there are no exclusionary findings or significant illness and 
the subject becomes well, the randomization visit may be rescheduled within the 56-day 
allowable screening period.  If Visit 02 cannot be rescheduled within the 56-day window, 
re-test and re-evaluate all required screening parameters in order to ensure eligibility 
prior to rescheduling the subject for randomization.   
• Eligibility Confirmation:  Eligibility criteria must be reviewed prior to randomization in 
the study database.   

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Randomization:  Subjects are electronically randomized in the database based on a 
randomization plan prepared in advance by the Protocol Statistician.  Randomization and product 
administration must both occur on the same day at Visit 02 (Day 0).  
Baseline Values for Future Health Assessments:  Visit 02 evaluations and medical history that 
were obtained prior to the first product administration will be used as the baseline for all future 
safety assessments.  If a blood test was not performed at Visit 02 or if results were not obtained 
due to an error, the values that were obtained during screening evaluations may be used as the 
baseline for all future safety assessments.  
4.2.4. 
Product Administration  
Before Ordering Study Product:  Pregnancy prevention counseling must be conducted, and 
pregnancy test results must be confirmed negative for females of childbearing potential.  
Subjects must be clinically evaluated with a medical history review and injection site assessment.  
Blood samples must be collected after randomization but prior to product administration per 
Tables B and C in Appendix III for Part A and Part B, respectively.     
For the Second and Third Product Administrations:  If a subject presents with fever or other 
signs of significant illness on the day of the product administration visit, do not order or 
administer study product.  Unscheduled visits may be used to evaluate the subject’s condition 
and the administration visit should be rescheduled within the allowable visit window.   
If a subject is undergoing evaluation and/or treatment for a medical condition at the time of the 
second or third scheduled administration visit, then the visit should be delayed and discussed 
with the IND Sponsor.   
To schedule a product administration visit outside of the allowable visit window, the site must 
obtain IND Sponsor approval.   
Ordering Study Products:  Sites must follow their standard operating procedures to order study 
products from the Pharmacy. 
4.2.4.1. 
Product Administration Procedures 
All subjects in Part A will receive the ZIKVwt DNA vaccine.  Therefore, Part A of the study is 
open-label and blinding of treatment assignment is not required. 
In Part B, subjects will receive either the ZIKVwt DNA vaccine or placebo.  Therefore, all 
injections will be administered in a blinded manner according to the randomization assignment.  
Neither the study staff nor the subjects will know if the injections are vaccine or placebo.   
Administer injections to the subject as soon as possible after the syringes are filled.  All 2 or 4 
PharmaJet injections per dose should be administered consecutively, one given immediately after 
the other and so forth.  The maximum allowable time between all 2 or 4 injections is 1 hour (60 
minutes).  If all injections per dose are not given within 1 hour, administration of any remaining 
injections must be approved by the IND Sponsor before proceeding. 
Both the staff administering study product and the subject receiving study product must wear 
safety glasses during product administration.  The PharmaJet apparatus should be pressed firmly 
against the subject’s skin, in the area over the lateral deltoid muscle of the arm or the vastus 
lateralis muscle of the anterolateral thigh.  This technique compresses the SC space, bringing the 

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skin and muscle into close proximity, to deliver the vaccine or placebo to the muscle.  Even in 
obese subjects, these areas have comparatively little SC fat accumulation; thus, they are reliable 
sites to achieve IM fluid penetration.  Refer to the IB for more information and instructions for 
use of the PharmaJet device.  
Study staff must practice universal precautions and dispose of the syringes and the needle-free 
device disposable components in accordance with the site policy and practices.  
4.2.5. 
Diary Card and Follow-Up after Product Administration 
Immediately after Product Administration:  After each completed product administration (the 
required sets of 2 or 4 injections are given), subjects must be observed for at least 15 minutes.  
After 15 minutes, vital signs including temperature, blood pressure, and pulse must be measured 
and recorded.  The injection sites must be inspected for evidence of local reaction and the subject 
must be assessed for any signs or symptoms of an immediate reaction before leaving the clinic.  
Acute medical care will be provided to subjects for any significant adverse reactions to study 
product. 
Diary Card:  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 after each product administration.  The site may 
use the paper diary card as a source document, or clinical staff notes obtained by telephone or in-
person interview may be used as the source for the information that is recorded in the database.   
The solicited signs and symptoms on the diary card will include the following parameters: 
unusually tired/feeling unwell, muscles aches (other than at injection sites), headache, chills, 
nausea, joint pain, and pain/tenderness at the injection sites.  Subjects will also record the highest 
measured temperature per day and measurement per day of the largest diameter for redness and 
swelling at the injection sites, if applicable.  Subjects should be instructed to record the greatest 
symptom or measurement overall when evaluating multiple injection sites.  Subjects will be 
provided with devices to measure temperature and diameter. 
Follow-Up after Product Administration:  Subjects are informed to contact the clinic or seek 
immediate medical attention, if necessary, at any time during the study if they experience any 
concerning signs or symptoms.  Follow-up on subject well-being will be performed by telephone 
or in-person between 7 to 10 days after each product administration.  At this time, clinical staff 
will also review the solicited diary card information. 
Events that should prompt clinical evaluation include rash, urticaria, skin changes at the injection 
site,feverof38˚C(Grade1) or higher, or any concerning systemic symptom.  Subjects should be 
counseled to report these symptoms as soon as they occur.  These symptoms could indicate an 
injection site reaction or potential ZIKV infection and therefore must carefully be evaluated by 
the PI or designee. 
4.2.6. 
Follow-Up Visits and Scheduling 
Study follow-up will continue via clinical visits after the first product administration through 32 
weeks in Part A and 96 weeks in Part B.  Clinical visits may include a health status review, 
vital signs and/or blood collection.  The scheduled visits are based on intervals of time after each 
product administration visit.  If study product is not given as scheduled, then the follow-up visits 
should be scheduled based on the date that the last study product was given.  When product is 
not given, the corresponding follow-up phone contact (A visit) may be omitted. 

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The schedule of visits, allowable windows (range of consecutive days) for completing the visits, 
terms of rescheduling visits, and evaluations performed at each visit are shown in the tables in 
Appendix III.  After Visit 02, deviations from the visit windows are discouraged and will be 
recorded as protocol deviations but are permitted, at the discretion of the IND Sponsor. 
As of protocol version 5.0 approval, study visits 15, 17, 19, 21, 23, and 25 will not be performed.  
The applicable study visits have been removed from the Schedule of Evaluations table for Part B 
(Appendix III).  
4.2.6.1. 
Important Information about Shifting Study Visits 
Study visits are scheduled a specific number of days apart in order to obtain blood samples for 
safety and research data at critical time points after each product administration.  Note that these 
days are calendar days and not working business days.  Therefore, the “Day of Study” is 
important to consider when scheduling or rescheduling a subject visit.  All study visits are 
scheduled based on the date of the most recent product administration.  Below is further 
explanation on scheduling. 
Visit 02 (Day 0) = first product administration visit.  Study Visits 02A and 03 must be scheduled 
based on the date of the first product administration.  
Visit 03 = second product administration visit.  Study Visits 03A through 04 must be scheduled 
based on the date of Visit 03.  For example, if Visit 03 occurs +15 calendar days outside of the 
visit window, then Visits 03A and 04 must also be moved ahead +15 calendar days.  If the 
second product administration does not occur, then schedule all follow-up visits based on the 
date of the first product administration. 
Visit 04 = third product administration visit.  Study Visits 04A through 26 must be scheduled 
based on the date of Visit 04.  For example, if Visit 04 occurs +20 calendar days outside of the 
visit window, then visits 04A through 26 must also shift (or be moved forward) +20 calendar 
days.  If the third product administration does not occur, then schedule all follow-up visits based 
on the date of the second product administration. 
4.2.7. 
Pregnancy during the Study 
Female subjects of childbearing potential will receive pregnancy prevention counseling 
throughout the study.  Women will be asked to notify the site immediately if they suspect or 
learn they are pregnant during this study.  In case of pregnancy, subjects will be removed from 
the product administration schedule but may have limited clinic contacts and blood draws at the 
discretion of the site PI and IND Sponsor.   
Each site will have a prepared list of resources for any woman who becomes pregnant during the 
study.  Sites will also refer pregnant women to the CDC guidance on how to protect themselves 
from getting ZIKV infection (https://www.cdc.gov/zika/pregnancy/protect-yourself.html).   
All pregnancies that begin during the study will be recorded.  The site must contact the subject to 
learn the outcome of a pregnancy that begins during the study. 

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4.3. 
Evaluation of ZIKV Infection During the Study 
4.3.1. 
ZIKV Infection Definition  
A virologic case of ZIKV infection will be defined as a virologically confirmed ZIKV infection 
irrespective of symptoms. 
A subclinical case of ZIKV infection will be defined as a virologically confirmed ZIKV infection 
without clinical signs or symptoms of ZIKV.  Subclinical cases of ZIKV infection will be 
identified by retrospective PCR testing of stored whole blood samples.  
A symptomatic case of ZIKV infection will be defined as a virologically confirmed ZIKV 
infection in conjunction with at least one clinical sign and/or symptom.  According to the CDC, 
the most common symptoms of ZIKV are fever, rash, joint pain, or conjunctivitis (red eyes).  
Other common symptoms include muscle pain and headache.  
4.3.2. 
Unscheduled Collection of Samples for Suspected ZIKV Infection 
At any time during the study, if a subject exhibits any sign or symptom possibly consistent with a 
ZIKV infection, PI or designee must attempt to diagnose the infection rapidly.  PCR testing must 
be used to test for ZIKV infection because vaccine-induced antibodies could be detected by 
antibody-based diagnostic tests and even mimic the antibody profile of acute or remote ZIKV 
infection.   
Sample collection for diagnostic testing may occur during a scheduled study visit or an 
unscheduled visit may be conducted.  All samples sent to the PDL will be tested using the 
RealStar® Zika Virus RT-PCR to test for ZIKV specific RNA.  Upon site request, the PDL will 
also run the TrioPlex Real-time RT-PCR for the differentiation of ZIKV, DENV and CHIKV 
RNA.  The site should request TrioPlex when there is suspicion of DENV and/or CHIKV based 
on clinical symptoms or local epidemiology in order to differentiate from ZIKV infection.   
Because diagnostic testing based on ZIKV-specific antibody tests could lead to inadvertent 
unblinding, study staff will remind subjects that it is preferable that no testing for ZIKV infection 
be done outside of the trial during study participation unless required to provide care to the 
subject, such as if needed while traveling.  If this occurs, virologic (PCR-only) test results should 
be provided to the study team as available so that proper documentation of ZIKV infection can 
occur.  In addition to laboratory testing, subjects should always be evaluated using clinical 
judgment, local requirements, and the current CDC or WHO definitions of ZIKV infection: 
https://wwwn.cdc.gov/nndss/conditions/zika-virus-disease-and-zika-virus-congenital-
infection/case-definition/2016/ or http://www.who.int/csr/disease/zika/case-definition/en/ 
respectively.   
In Part A, diagnostic testing of suspected ZIKV infections by virus detection (e.g., PCR) may be 
done through the PDL or by the site’s local standard testing procedures.  It is recommended that 
serum and urine be collected for laboratory testing but there is no requirement for the type or 
number of samples that should be collected and tested.  Note that only samples collected on one 
day are recorded in the database if collected, additional samples must be recorded and tracked in 
the subject study file. 
In Part B, diagnostic testing of suspected ZIKV infections by virus detection (e.g., PCR) must 
be done through the PDL.  When possible, sites may also use local standard testing procedures 

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using PCR only to diagnose suspected ZIKV infections.  As shown in Figure 1, up to 3 blood 
samples for serum (8 mL each) and up to 3 samples of urine (minimum of 10 mL) should be 
collected as soon as possible after the onset of a sign or symptom, preferably within 3 days of the 
onset of the sign or symptom.  Study clinicians should attempt to collect blood and urine on 3 
different dates within the first 13 days after illness onset.  The collection dates do not need to be 
consecutive.  Any samples collected within the first 13 days of illness should be sent for testing, 
even if all 3 samples of biological type were not collected.  Sites may collect additional blood 
and other bodily fluids if instructed by the IND Sponsor.  
Figure 1: Evaluation for Symptomatic ZIKV Infection in Part B 
 
Test Results:  Subjects will be informed of all diagnostic test results from the PDL as soon as 
the results are available.  Any one positive PCR result, even in the event of discrepant results 
between the PDL and local laboratory, should be treated as a positive for the purposes of clinical 
care and reporting requirements.  Repeat testing may need to be performed to confirm or follow 
the course of an infection. 
4.3.2.1. 
Suspected Hemorrhagic Fever 
If at any time a subject exhibits possible signs of hemorrhagic fever (HF), including hypotension 
and purpura, the subject should be evaluated as soon as possible.  Once symptoms of HF are 
known, diagnostic testing of samples must first occur through testing at the CDC, and samples 
must not be sent to the PDL until instructed by the IND Sponsor or Sponsor’s contract research 
organization (CRO) to do so.  Collection procedures for subjects with suspected HF are the same 
as they are for suspected ZIKV infections as follows: Part A: collect blood and urine as soon as 
possible; Part B: collect 3 blood samples for serum (8 mL each) and 3 samples of urine 
(minimum of 10 mL) as soon as possible after the onset of a sign or symptom within the first 13 
days.  
Backup samples should be retained by the site until the evaluation for HF is complete.  Only if 
reported as negative for HF and notified by the IND Sponsor or sponsor representatives to 
proceed may backup samples be sent to the PDL for further testing.  

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4.3.3. 
Scheduled Collection of Research Samples for Asymptomatic ZIKV Infection 
(Part B only) 
The purpose of routine research sample collections is to retrospectively identify possible cases of 
ZIKV infection in the viremic phase, since many ZIKV infections are often subclinical with mild 
to no symptoms.  Subjects will not receive the results of these evaluations.   
• Blood Collection:  All sites will collect blood samples for research, obtained at scheduled 
follow up visits as noted in Appendix III, Table C: Schedule of Evaluations – Part B. 
• Urine Collection:  As of protocol version 5.0, collection of urine samples for research is 
discontinued.    
4.3.4. 
ZIKV Infection Clinical Management and Follow-Up  
There is no curative treatment for ZIKV infection.  In both Part A and Part B, study sites should 
have plans for subjects to have access to clinical care and management of ZIKV infection based 
on recommendations by CDC, WHO, and/or site local authority.  Subjects should continue to 
participate in VRC 705 follow-up visits while under care.  Study staff must document all signs 
and symptoms of infection and all clinical care provided.  
Any subject with a positive ZIKV result must be discontinued from receiving study product.  In 
addition, pregnancy testing and pregnancy prevention counseling must be added to all study 
visits for female subjects of childbearing potential following a ZIKV diagnosis, as shown on 
Tables B and C in the Schedule of Evaluations.   
In areas where there is an option, per PI discretion, it is acceptable for a ZIKV-infected study 
subject to co-enroll in a concurrent study of treatment or management of ZIKV infection to allow 
for optimal care of the subject.  The IND Sponsor should be notified if co-enrollment occurs.  
Treatment procedures and co-enrollments will be documented in the study database and available 
to the Protocol Safety Review Team (PSRT) through study reports.  With permission from the 
subject, the results of diagnostic testing and other evaluations conducted for this study may be 
shared with the clinician(s) providing the medical care to minimize the need for the subject to 
have extra blood draws or repeat testing.   
4.3.5. 
Reporting of ZIKV Infections 
All confirmed cases of ZIKV infection will be reported to the IND Sponsor through data entry in 
the database.  Test results for DENV, CHIKV and hemorrhagic fever must be reported as an AE, 
according to the corresponding AE reporting period as noted in protocol Section 5.1.1.  Sites 
must also comply with local regulatory requirements for reporting ZIKV infections and other 
reportable infections of interest, such as DENV and CHIKV, as applicable. 
4.3.6. 
ZIKV Infection in Pregnant Women  
Per Section 4.2.7, in case of pregnancy, subjects will be removed from the product 
administration schedule but may have limited clinic contacts and blood draws at the discretion of 
the site PI and IND Sponsor.  Pregnant women will also be advised about reducing risks of 
becoming infected with ZIKV.  However, if a pregnant woman becomes infected with ZIKV, she 
will be referred for care based on the site’s prepared list of resources.  All pregnancies that begin 

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during the study will be recorded.  The site must contact the subject to learn the outcome of any 
pregnancy that begins during the study. 
4.4. 
Concomitant Medications  
Only routine medications should be entered in the database at the time of study randomization.  
All approved vaccinations for routine health care must be entered in the database throughout the 
study.  Concomitant medications will be updated in the study database if there is an occurrence 
of an AE that requires expedited reporting or development of a new chronic medical condition 
that requires ongoing medical management.  Otherwise, concomitant medications taken during 
the study, including those for DENV infection, must be recorded in the subject study file. 
Vaccines during the Study:  As stated above, subjects may receive routine vaccinations 
throughout the study as needed for standard healthcare practice.  Product administrations must be 
scheduled such that: 
• No inactivated vaccine is received within 2 weeks before or after each product 
administration  
• No live attenuated vaccine is received within 4 weeks before or after each product 
administration 
4.5. 
Criteria for Discontinuing Product Administrations or Subject 
Participation  
Decisions to discontinue giving the second or third product administrations or to discontinue 
protocol participation for a subject will be made by the site PI or designee.   
4.5.1. 
Discontinuation from Receiving Study Product 
Subjects who receive at least one product administration are expected to continue with planned 
follow-up visits until the end of the study.  If the second product administration is not given, then 
the subject should be discontinued from the third product administration. 
A subject may be discontinued from getting study product for the following reasons:  
• Pregnancy; 
• Grade 3 AE assessed as related to study product (except that self-limited Grade 3 
solicited reactogenicity does not require discontinuation of product administrations); 
• Grade 4 AE assessed as related to study product; 
• Immediate hypersensitivity reaction associated with study product; 
• Confirmed ZIKV infection; 
• Clinically significant intercurrent illness that is not expected to resolve before the next 
scheduled product administration; 
• 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 product administration may continue per site PI discretion if 
the next one occurs at least 2 weeks following completion of glucocorticoid treatment; or, 

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• The IND Sponsor and/or PI assess that it is not in the best interest of the subject to 
continue receiving study product.   
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 on study; 
• The IND Sponsor or regulatory authorities stop the protocol; or, 
• The IND Sponsor and/or PI assess that it is not in the best interest of the subject to 
continue participation or that the subject’s compliance with the study is not sufficient.  
4.6. 
Criteria for Pausing and Resuming the Study 
The PI for each site, study team, 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.  
Product administrations, new enrollments, and randomizations will be paused and the IND 
Sponsor will be promptly notified according to the following criteria:  
• One (or more) subject experiences a Serious Adverse Event (SAE) assessed by the PI as 
related to study product. 
• Two (or more) subjects experience the same Grade 4 unsolicited AE assessed by the PI 
as related to the study product.  
Plan for Review of Pauses and Resuming Rules:   
The IND Sponsor, with participation by the PSRT, will conduct the review and consult with the 
Data and Safety Monitoring Board (DSMB) to make the decision to resume, amend or close the 
study.  As part of the pause review, the reviewers will also advise on whether the study needs to 
be paused again for any subsequent AEs of the same type. 
Product administrations, new enrollments, and randomizations would resume only if review of 
the AEs that caused the pause result in a recommendation to permit further product 
administrations, enrollments, and randomizations.  When indicated, safety data reports and 
changes in study status will be submitted to relevant regulatory authorities including the site 
IRB/EC in accordance with Section 5.5 and site institutional policy.  
 

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5. 
SAFETY AND ADVERSE EVENTS 
5.1. 
Adverse Events 
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.  AEs will be graded according to the Table for Grading Severity of AEs 
(Appendix IV).   
All AEs will be followed until they have resolved or are considered stable during the course of 
the study.  If the event has a resolution date, this date must be recorded on the Adverse Event 
form, regardless of whether or not it falls within the AE reporting period. 
5.1.1. 
AE Reporting Period  
The following guidelines will be used to determine if an AE should be recorded in the database: 
• Solicited AEs (i.e. reactogenicity parameters) will be recorded in the study database for 7 
days after each product administration without the collection of their relationship to study 
product.   
• Unsolicited AEs and their relationship to study product must be recorded in the study 
database immediately after the first product administration at Visit 02 through the one 
month visit that follows the last product administration.  Therefore, the following rules 
apply: 
− If a subject receives all 3 study product administrations, then the AE Reporting Period 
for unsolicited AEs and their relationship to study product is immediately after Visit 
02 through Visit 05. 
− If a subject only receives the first product administration at Visit 02 but not the 
second or third, then the AE Reporting Period for unsolicited AEs and their 
relationship to study product is immediately after Visit 02 through Visit 03. 
− If a subject receives the first and second product administrations at Visit 02 and Visit 
03, respectively, but not the third, then the AE Reporting Period for unsolicited AEs 
and their relationship to study product is immediately after Visit 02 through Visit 04. 
• Only SAEs (as defined in Section 5.2), new chronic medical conditions, and confirmed 
cases of DENV infection, diagnosed locally or by the PDL, are recorded as AEs through 
the last study visit.   
• Confirmed cases of ZIKV infection are not recorded as an AE unless the infection meets 
the definition of a SAE.  ZIKV infections must be recorded on the ZIKV Endpoints Form 
throughout the full duration of the study.   

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5.2. 
Serious Adverse Events 
5.2.1. 
Serious Adverse Event Definition 
The term “serious adverse event” (SAE) as defined in US 21 Code of Federal Regulations (CFR) 
312.32 as follows: “an adverse event or suspected adverse reaction is considered "serious" if, in 
the view of either the investigator or sponsor, it results in any of the following outcomes:  Death, 
a life-threatening adverse event, 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 or convulsions that do 
not result in inpatient hospitalization, or the development of drug dependency or drug abuse.”   
“Life threatening” refers to an AE that, at occurrence, represented an immediate risk of death to 
the subject.  An event that hypothetically may cause death if it occurs in a more severe form is 
not considered life-threatening.  Similarly, a hospital admission for an elective procedure is not 
considered a SAE.  
5.2.2. 
Reporting Serious Adverse Events to the IND Sponsor  
AEs that meet the definition of a SAE must be reported from the time that the subject signs the 
informed consent/assent form through the last study visit by the study site and submitted on an 
expedited basis to the IND Sponsor, according to sponsor guidelines as follows:  
• results in death; 
• is 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; or, 
• is an important medical event that may jeopardize the subject or may require intervention 
to prevent one of the other outcomes listed above. 
Additionally, any event, regardless of severity, which in the judgment of a site PI represents a 
SAE, may be reported on an expedited basis. 
Reporting to the IND Sponsor: Within 3 calendar days of site awareness of the SAE 
occurrence, the site PI or designee will communicate an initial SAE report to the IND Sponsor 
through the communication methods provided by VRC’s CRO.  The site will remove personal 
identifying information about the subject from SAE case reports before submission to the IND 
Sponsor. 
Any SAE entered into the study database will generate an automatic email notification to the 
IND Sponsor.  A written event summary by the study site should be sent to the IND Sponsor 
within 7 calendar days and sooner, if possible, in case of death.  Additional information should 

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be submitted as it becomes available.  The IND Sponsor will use this information to comply with 
FDA regulations mandating notification of expedited SAEs.    
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 IB 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 the FDA as IND Safety 
Reports.  All IND Safety Reports will be provided to all participating site PIs by the IND 
Sponsor and should be submitted to site local or national regulatory authorities as required.  
The IND Sponsor will also submit an IND Annual Report of the progress of the investigation to 
the FDA as defined in US 21 CFR 312.33. 
5.2.4. 
Serious Adverse Event Reporting to the Data and Safety Monitoring Board  
SAEs that occur during the study will be reported to the DSMB by the IND Sponsor or sponsor 
representative on a monthly basis.  However, any SAE that is reported to the FDA as a IND 
Safety Report will be reported to the DSMB as soon as possible. 
5.2.5. 
Serious Adverse Event Reporting to the Institutional Biosafety Committee  
In keeping with Institutional Biosafety Committee (IBC) requirements, sites will follow their 
IBC reporting regulations per institutional policy. 
5.3. 
Protocol Deviation 
A Protocol Deviation is defined as any change, divergence, or departure from the IRB/EC-
approved study procedures in a research protocol.  This includes but is not limited to:   
• Those that occur because a member of the research team deviates from the protocol. 
• Those that are identified before they occur, but cannot be prevented. 
• Those that are discovered after they occur. 
5.4. 
Unanticipated Problem 
A serious Unanticipated Problem (UP) is defined as any incident, experience, or outcome that 
meets all three of the following criteria: 
• unexpected in nature, severity, or frequency in relation to the research risks that are 
described in the protocol, informed consent, IB, other study documents or in 
consideration of the characteristics of the subject population being studied; and 
• related to participation in the research; and 

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• suggests that the research places subjects or others at a greater risk of harm (including 
physical, psychological, economic, or social harm) than was previously known or 
recognized. 
Non-serious UP:  An UP that is not an Adverse Event (UPnonAE) is an unanticipated problem 
that does not fit the definition of an AE, but which may, in the opinion of the investigator, 
involve risk to the subject, affect others in the research study, or significantly impact the integrity 
of research data.  Such events would be considered a non-serious UP.  For example, we will 
report occurrences of breaches of confidentiality, accidental destruction of study records or 
samples, or unaccounted-for study drug. 
5.5. 
Reporting to Site IRBs/ECs and Relevant Regulatory Agencies 
Each site PI is responsible for reporting study information to the site IRB/EC per the IRB/EC 
requirements for reporting and to other relevant regulatory authorities in accordance with their 
institutional and country requirements for reporting.   
Site-specific data reports will be made available through the data management CRO to facilitate 
expedited and continuing review reporting requirements.   
Only the IND Sponsor will submit reports to the FDA.  Any IND Safety Report that is submitted 
to the FDA will also be provided to all sites, with instructions on whether or not any action needs 
to be taken.  Investigators must maintain documentation of compliance with actions required for 
IND Safety Reports. 
5.6. 
Data and Safety Monitoring Board  
The PSRT (Section 8.9.1) will have the primary responsibility for the regularly scheduled 
oversight of safety data and SAE reviews.  The NIAID DSMB will review cumulative study data 
at least twice per year or as often as recommended by the DSMB 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.   
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 subjects.  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 IND 
Sponsor, including whether the study should continue without change, be modified, or be 
terminated. 
In addition, SAEs will be reported to the DSMB as outlined in Section 5.2.4. 

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6. 
STATISTICAL CONSIDERATIONS AND SAMPLE ANALYSIS 
6.1. 
Overview 
This is a multicenter, randomized, study to evaluate the safety, immunogenicity, and efficacy of 
VRC-ZKADNA90-00-VP (ZIKVwt DNA vaccine) or placebo.  The hypotheses are that the 
ZIKVwt DNA vaccine will be safe and will elicit a ZIKV-specific immune response.  In Part A, 
the primary objective is to evaluate the safety and tolerability of the vaccine.  In Part B, the 
primary objectives are to evaluate the safety, tolerability, and efficacy of the vaccine compared 
to placebo.  In Part A and Part B, secondary and exploratory objectives relate to 
immunogenicity/durability of immune responses, incidence of subclinical and symptomatic 
ZIKV infection, and ZIKV viremia/viruria following 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 each product 
administration and safety evaluated by clinical visits through the study duration of 32 or 96 
weeks in Part A or Part B, respectively. 
The following parameters will be assessed: 
• Local reactogenicity signs and symptoms;  
• Systemic reactogenicity signs and symptoms;  
• Laboratory measures of safety;  
• Adverse events;  
• Serious adverse events, new chronic medical conditions, and confirmed cases of DENV; 
and, 
• ZIKV infection events (Part B only). 
6.2.2. 
Immunogenicity 
The principal immunogenicity endpoints are 4 weeks after the last product administration 
compared to Day 0 as measured by neutralization assay.  Exploratory immunogenicity endpoints 
are measured by neutralization assay, ELISA, and other research tests as described in Section 
1.7. 
6.2.3. 
Efficacy (Part B only) 
The primary efficacy endpoint is the ZIKV incidence defined as virologically confirmed 
infection by PCR virus detection.  The secondary efficacy endpoint is the incidence of 
subclinical virologic cases.   

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6.3. 
Sample Size and Accrual 
6.3.1. 
Sample Size Considerations: Part A  
Part A of the study targets healthy adults (age 18-35).  Since the risk of GBS has been shown to 
increase with age, the study population excludes those who might be at higher perceived risk for 
GBS [54-56].  Ninety subjects will be randomized 1:1:1 to three vaccination arms.  The sample 
size decision is based on the evaluation of vaccine safety and immunogenicity.  Accrual up to 
100 subjects is permitted if additional subjects are needed for safety and immunogenicity 
evaluations. 
6.3.1.1. 
Power Calculations for Evaluation of Safety 
The ability of the study to identify safety events can be expressed in terms of the probability of 
observing one or more event of interest (e.g., AEs) within each group assuming a range of 
underlying true event rates.  With 30 subjects per group, assuming the true event rate of 0.3%, 
there is a probability of 8.6% to observe at least one event and a probability of 0.4% to observe 
more than one event (Table 2). 
Table 2: 
Probability of Observing Safety Events within a Group (n=30) 
True Event Rate 
 (%) 
Pr (0 event)  
(%) 
Pr (more than one event)  
(%) 
0.1 
97.0
<0.1 
0.3 
91.4
0.4 
0.5 
86.0
1.0 
1.0
74.0
3.6 
3.0
40.1
22.7 
5.0
21.5
44.6 
Table 3 shows the 95% confidence intervals (CIs) of the true event rate based on the observed 
safety data.  Calculations are done using exact binomial test.  For a given arm with sample size 
n=30, if none of the subjects experience a safety event, the 95% CI has upper bound as 0.116. 
Table 3: 
Two sided 95% CIs Based on Observed Rates of Safety Endpoints within a 
Group (n=30) 
Observed 
event rate 
95% CI 
Lower bound 
Upper bound 
0/30 
0 
0.116 
1/30 
0.001 
0.172 
2/30 
0.008 
0.221 
3/30 
0.021 
0.265 
4/30 
0.038 
0.307 
5/30 
0.056 
0.347 

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6.3.1.2. 
Power Calculations for Evaluation of Immunogenicity 
The evaluation of immunogenicity includes the magnitude of the immune response as well as the 
positive response rate.  The primary endpoint is the immune response measured by neutralization 
assay at 4 weeks after the last product administration.  Table 2 provides the probability of 
observing zero or more than one positive responses within a group of size 30 and Table 3 
provides the 95% CIs of the positive response rate in the vaccinated population.  Neutralization 
assay data are close to being log-normally distribution.  The magnitude of immune response due 
to the study vaccine can be evaluated by the fold change from baseline.  Table 4 shows the 
power of detecting a range of fold changes, assuming normal distribution after log 
transformation with standard deviation=1, within a group of size 30.  Table 5 presents the power 
of detecting between-arm differences over a range of effect sizes, assuming normal distribution 
after log transformation with common standard deviation.  The calculations are done using t-tests 
in log scales.  With 30 subjects per group, the study is capable of detecting with over 80% power 
the fold change of 0.75 and above within a group, and over 80% power the between-arm 
difference of 0.80 standard deviation and above in log scale. 
Table 4:  Power of Detecting a Range of Fold Changes from Baseline Immune Response 
Fold change 
Power 
 (%) 
0.25 
22 
0.50 
57 
0.75 
84 
1.00 
96 
Table 4 is based on assuming normal distribution after natural log transformation with standard 
deviation=1, by one sample two-sided t-test with type I error rate of 5%, within a group (n=30). 
Table 5:  Power of Detecting Between-Arm Difference over a Range of Effect Sizes  
Effect size of 
between-arm 
difference 
Power 
(%) 
0.5 
48
0.6 
63
0.7 
76
0.8 
86
0.9 
93
Table 5 is based on assuming normal distribution after log transformation, by two-sample two-
sided t-test with type I error rate of 5% (n=30). 
6.3.2. 
Sample Size Considerations: Part B  
Part B of the study targets healthy adults and adolescents ages 15 to 35 years who reside in 
ZIKV endemic or potential endemic regions.  This age range is considered to be the range of the 
highest reproductive potential and therefore, this age group will likely be the initial target for a 
successful ZIKV vaccine.  Additionally, the risk of GBS has been shown to increase with age, so 

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this study population excludes those who might be at higher perceived risk for GBS [54-56].  
Randomization at each study site will equally allocate subjects to vaccine or placebo schedules.  
The randomization plan does not include provisions for replacing subjects with incomplete 
product administration or visit schedules.  
A total of 2400 subjects will be randomized 1:1 to receive either the study vaccine or placebo. 
The study sample size was determined primarily based on the evaluation of vaccine efficacy 
(VE).  The study also has ample sample size for detecting AEs, therefore meeting the primary 
endpoints.   
To detect a VE of 61%, the trial aims to achieve 90 cases of naturally acquired virologic ZIKV 
infection within 2 to 3 years.  If it appears this target is unlikely to be met, the study may be 
expanded to achieve this target.  Prior to the completion of randomization, the combined vaccine 
and placebo incidence rate of subclinical ZIKV cases will be calculated.  At each site, the 
blinded site-specific baseline seropositivity rate may be calculated and used to adjust the needed 
sample size and to aid in allocation of enrollment slots.  Both types of rates will be used to help 
decide if the enrollment should be extended to allow for the target to be achieved.  For planning 
purposes, we will allow for a total sample size of up to 15,000.  Such a sample size could achieve 
our target number of virologic ZIKV cases within 3 years, assuming full accrual within 12 
months, even if the placebo incidence rate is as low as 0.50% and the seropositive rate is as high 
as 30% among enrollees. 
Sample size will be re-evaluated prior to the end of the randomization period to estimate if we 
will achieve 90 cases of virologic ZIKV infection in 2 to 3 years.  This calculation will explicitly 
take into account the accrual rate, the dropout rate, the baseline seropositive rate, and the 
incidence rate.  Values for these rates will be based on within trial data augmented by other 
information (e.g., historical dropout rates in other studies, epidemiologic projections of incidence 
from other sources).  If this calculation suggests the sample size of 2400 is inadequate to achieve 
90 cases of virologic ZIKV infection in 2 to 3 years, the sample size may be increased.   
Accrual may occur rapidly at more than one site.  The data managers will carefully monitor 
study accrual and notify the sites and Protocol Chairs when completion of accrual is near.  
6.3.2.1. 
Power Calculations for Evaluation of Safety 
The goal of the safety evaluation for this study is to identify safety concerns associated with 
administration of the investigational vaccine.  Two sample size calculations for safety are 
expressed in terms of two approaches, within group and comparing two groups. 
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) within each group assuming a range of 
underlying true event rates.  With 1200 subjects per group and the true event rate of 0.3%, there 
is a probability of 97.3% to observe at least one event and a probability of 87.5% to observe 
more than one event (Table 6). 
Safety event rates may vary considerably with the type of event considered.  Safety will be 
evaluated within each arm and additionally stratified by baseline ZIKV status, pre-exposed or 
not.   
 

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Table 6: 
Probability of Observing Safety Events within a Group (n=1200) 
True Event Rate 
(%) 
Pr (0 event)  
(%) 
Pr (more than one event)  
(%) 
0.01 
88.7 
0.7 
0.05 
54.9 
12.2 
0.10 
30.1 
33.7 
0.30 
2.7 
87.5 
0.50 
0.2 
98.3 
Table 7 provides the minimum detectable difference by two-sided chi-square test between the 
vaccine and placebo groups over a range of possible event rates and sample sizes as follows: 
1200 samples per group, 960 samples per group to account for 20% early drop out, 480 and 240 
samples per group for comparisons within a stratum defined by baseline ZIKV status. 
Table 7: 
Minimum Detectable Difference in Event Rate Assuming Type I Two-Tail 
Error Rate of 5% 
Sample size 
within each 
group (#) 
Event rate 
(in placebo) 
(%) 
Detectable with 80% power 
Detectable with 90% power 
Difference (%) 
Event rate (in 
vaccine) (%) 
Difference (%) 
Event rate (in 
vaccine) (%) 
1200 
0.1 
0.81 
0.91 
1.04 
1.14 
0.5 
1.19 
1.69 
1.46 
1.96 
1.0 
1.50 
2.50 
1.80 
2.80 
5.0 
2.80 
7.80 
3.29 
8.29 
10.0 
3.69 
13.69 
4.32 
14.32 
25.0 
5.11 
30.11 
5.93 
30.93 
960 
0.1 
0.98 
1.08 
1.26 
1.36 
0.5 
1.39 
1.89 
1.71 
2.21 
1.0 
1.73 
2.73 
2.09 
3.09 
5.0 
3.17 
8.17 
3.74 
8.74 
10.0 
4.16 
14.16 
4.88 
14.88 
25.0 
5.73 
30.73 
6.66 
31.66 
480 
0.1 
1.79 
1.89 
2.33 
2.43 
0.5 
2.30 
2.80 
2.88 
3.38 
1.0 
2.75 
3.75 
3.38 
4.38 
5.0 
4.72 
9.72 
5.60 
10.60 
10.0 
6.08 
16.08 
7.15 
17.15 
25.0 
8.20 
33.20 
9.55 
34.55 
240 
0.1 
3.38 
3.48 
4.43 
4.53 
0.5 
3.97 
4.47 
5.04 
5.54 
1.0 
4.54 
5.54 
5.65 
6.65 
5.0 
7.14 
12.14 
8.55 
13.55 
10.0 
8.98 
18.98 
10.61 
20.61 
25.0 
11.79 
36.79 
13.73 
38.73 

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6.3.2.2. 
Power Calculations for Evaluation of Immunity 
The evaluation of immunogenicity includes the magnitude of the immune response as well as the 
positive response rate.  The primary endpoint is the immune response measured by neutralization 
assay at 4 weeks after the third product administration.  Neutralization assay data are close to 
being log-normally distribution.  Table 7 provides the minimum detectable between-group 
difference with respect to positive response rate.  Table 8 presents the minimum detectable effect 
size of the between-group difference in log scale with respect to the magnitude of immune 
response by two-sided t-test.  With 1200 subjects per group, the study is capable of detecting the 
between-group difference with 80% power if the mean of the between-group difference is 0.11 
and the standard deviation is 1 on the log scale.  If the standard deviation is 0.30, the study is 
capable of detecting a 0.03 between-group difference with 80% power and 1200 per group.   
Table 8: 
Minimum Detectable Difference in the Magnitude of Immune Response (log 
transformed) between 2 Groups Assuming Type I Two-Tail Error Rate of 5% 
Standard Deviation 
Subjects within each group  
(#) 
Minimum detectable effect size 
With 80% power 
With 90% 
power 
1 
1200 
0.11 
0.13 
960 
0.13 
0.15 
480 
0.18 
0.21 
240 
0.26 
0.30 
0.30 
1200 
0.03 
0.04 
960 
0.04 
0.04 
480 
0.05 
0.06 
240 
0.08 
0.09 
 
6.3.2.3. 
Power Calculations for Evaluation of Efficacy 
This trial is designed as an event driven study to test the null hypothesis that VE ≤ 20%.  The 
efficacy endpoint will be evaluated once a fixed number of ZIKV cases have occurred.  Table 9 
provides the number of cases that are required to achieve 80% and 90% power for the test of the 
null hypothesis (VE ≤ 20%) for various assumed VEs using the R function binom.power.  For 
this calculation, we note that conditional on the total number of cases, the probability a case 
comes from the vaccine group is equal to (1-VE)/(2-VE).  Thus, the null probability that a case 
comes from the vaccine is given by (1-0.2)/(2-0.2) = 4/9.  Simulations show that power from this 
conditional binomial calculation is an excellent approximation to the power from a Cox 
regression model which will be used for analysis.  With ninety cases of virologic ZIKV 
infection, the study is capable of detecting a vaccine efficacy of 61% with 90% power.  While 
these calculations assume there is no interim monitoring and the study will be monitored using 
an O’Brien-Fleming boundary for efficacy, such monitoring has a negligible impact on power. 

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Table 9: 
Number of Cases of Virologic ZIKV Infection Required to Achieve 80% or 90% 
Under Different Vaccine Efficacies by Conditional Binomial Test with Two-
sided Type I Error Rate of 0.05 andNullVE≤20%   
Vaccine Efficacy 
Cases of ZIKV infection  
for 80% power (#) 
Cases of ZIKV infection  
for 90% power (#) 
0.80 
20 
27 
0.70 
37 
50 
0.61 
66 
89 
0.60 
71 
95 
0.50 
150 
201 
While the study is designed to achieve 90 cases of virologic ZIKV infection, the sample size 
required to achieve this goal will depend on the duration of the study and the yearly incidence 
rate in the placebo group.  Table 10 provides the expected number of cases of virologic ZIKV 
infection with 2 or 3 years of follow-up from the start of accrual under different assumptions 
about the placebo yearly incidence rate while assuming a VE of 61% and a total sample size of 
2400.  For this calculation, we assume that the 2400 subjects are accrued within 6 months. 
Table 10: Expected Number of Cases of Virologic ZIKV Infection within 2 and 3 Years of 
Trial Initiation under Different Assumed Yearly Incidence under Placebo with 
2400 Subjects   
Yearly Incidence 
of cases of ZIKV 
infection (under placebo) 
Cases of ZIKV 
infection within 2 
years (#) 
Cases of ZIKV 
infection within 3 
years (#) 
0.005 
14 
23 
0.010 
29 
45 
0.020 
57 
91 
0.030 
86 
136 
0.040 
114 
181 
Therefore, we see that if the placebo incidence rate is 3%, the target of 90 infections will take 
about 2 years to achieve.  If the placebo incidence rate is 2%, the target of 90 infections will take 
about 3 years to achieve.    
The annual incidence of virologic ZIKV cases is uncertain and may be lower than 2%.  In 
addition, at ZIKV endemic sites, some enrollees in the study may have been pre-exposed to 
ZIKV and are therefore unlikely to become virologic ZIKV cases.  To compensate for low 
incidence and/or baseline seropositive subjects, we may need to expand the sample size.  Table 
11 gives the expected number of virologic ZIKV cases by 2 or 3 years from a potentially 
expanded study that accounts for 0% to 30% seropositive enrollees at baseline over a range of 
annual incidence rates that can be as low as 0.25% under placebo.  In these calculations, we 
assume baseline seropositives will not become infected with ZIKV and the incidence rate applies 
to the baseline seronegatives and a VE of 61%.  We also assume that enrollment is completed 
within 12 months. 

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Table 11:  Expected Number of Cases of Virologic ZIKV Infection among Seronegative 
Enrollees within 2 and 3 Years of Trial Initiation under Different Assumed 
Baseline Seropositive Rates, Yearly Incidence Rates under Placebo among 
Seronegatives, and Sample Sizes  
Seropositive 
rate at baseline 
(%) 
Total 
sample size 
(#) 
Yearly 
incidence 
(under placebo) 
Cases of ZIKV 
infections 
within 2 years 
(#) 
Cases of ZIKV 
infections 
within 3 years 
(#) 
0 
7500 
0.0100 
78 
130 
12500 
0.0050 
65 
108 
15000 
0.0050 
78 
130 
15000 
0.0025 
39 
65 
10 
7500 
0.0100 
70 
117 
12500 
0.0050 
58 
97 
15000 
0.0050 
70 
117 
15000 
0.0025 
35 
58 
20000 
0.0025 
47 
78 
30 
7500 
0.0100 
54 
91 
12500 
0.0050 
45 
76 
15000 
0.0050 
54 
91 
15000 
0.0250 
27 
45 
25000 
0.0250 
45 
76 
If the seropositive rate at baseline is no more than 30% and the yearly incidence for cases of 
virologic ZIKV infection is 0.005, i.e., 0.5% under placebo, then with VE of 61%, an expanded 
study of size 15000 reaches the targeted 90 cases of ZIKV infections within 3 years if enrollment 
is completed within 12 months.  
6.4. 
Statistical Analysis  
Study accrual is defined in this protocol as being randomized to a treatment group and receiving 
the first administration of study product.  All accrued subjects will receive at least one product 
administration and therefore will provide some safety data.  The safety population will include 
all enrolled subjects, summarized according to the actual vaccination dose received. 
In Part B, all subjects will be tested for baseline ZIKV serostatus based on samples collected at 
Visit 02 prior to the first product administration.  Since those with prior exposure to ZIKV may 
respond differently to the vaccine from those naïve subjects, safety, immunogenicity and efficacy 
will be analyzed within each stratum defined by baseline ZIKV status in addition to overall strata 
combined.  Part A of the study is to be conducted at endemic or potentially endemic sites with 
baseline ZIKV serostatus tested, then safety and immunogenicity analyses will be similarly run 
by stratum in addition to overall strata combined. 
Three types of analysis cohorts are defined.  The Intent-to-treat (ITT) cohort will include all 
accrued subjects according to group assignment.  The Per Protocol (PP) cohort will include all 
subjects receiving all planned vaccinations within window as assigned by the randomization 
schedule, and not experiencing any other major protocol deviations prior to the visit of 

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evaluation.  The Modified intent-to-treat (mITT) analyses will include all accrued subjects who 
remain event-free one week after all planned product administration, where event is the primary 
efficacy event of a positive ZIKV PCR test result.   
No multiple comparison adjustment will be employed for safety, immunogenicity, or efficacy 
analyses.  Missing data will be primarily considered as missing completely at random in safety 
and immunogenicity analysis provided missing data is modest (e.g. <5-10%).  For completeness, 
we will examine the missing data completely at random assumption and perform sensitivity 
analyses which weaken the missing completely at random assumption if the missing data is 
>10% or if the missing at random assumption is questionable.  For efficacy, missing at random 
will be assumed and methods for handling missingness, such as multiple imputation and inverse 
propensity weighting, will be considered.  
In general, descriptive statistics by vaccine group will be tabulated for all variables of interest, 
stratified by baseline ZIKV testing results.  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. 
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% CI 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. 

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6.4.3. 
Analysis of Immune Responses 
Immunogenicity will be analyzed for a variety of cohorts defined above, and specified in the 
SAP (Statistical Analysis Plan).  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.  Immunogenicity will be assessed by group.  To 
account for preexisting immunogenicity due to prior ZIKV exposure, immunogenicity will also 
be assessed according to baseline serostatus as a secondary analysis. 
6.4.4. 
Analysis of ZIKV Incidence 
Efficacy evaluation with respect to ZIKV incidence will be performed in Part B.  Incidence rates 
for ZIKV cases will be described by vaccine group and by baseline ZIKV stratum for each 
group.  Results will be treated both as dichotomous (infection, no infection) and as a time to 
event (infection) variables.  The primary analysis will be based on the time to case of virologic 
ZIKV infection, i.e., when a subject is positive for ZIKV based on a PCR test.  The time to ZIKV 
case data, accounting for censoring, will be described using Kaplan-Meier curves and efficacy 
computed using a Cox proportional hazards model.  VE will be estimated by the hazard ratio 
from the Cox proportional hazards model stratified by baseline ZIKV exposure status. 
The primary efficacy analysis is a test of the null hypothesis (H0): the study vaccine has VE no 
more than 20% in preventing ZIKV infection, i.e., VE ≤ 20%, where ZIKV infection is defined 
as virologically confirmed infection by PCR virus detection.  The alternative hypothesis is that 
VE > 20%.  The criterion for success will be that a one-sided test of H0 has p-value ≤ 0.025.  
This primary analysis will be based on the mITT cohort stratified by baseline serostatus (prior 
exposed to ZIKV or not).  If the null VE ≤20% is not rejected, an additional test of H0*: VE = 0 
will be conducted using a one-sided type I error rate of 0.025.   
The secondary efficacy analyses include the testing of this hypothesis over the two stratum 
combined.  Another secondary analysis will test the above hypothesis H0, where ZIKV infection 
is defined as PCR virus detection irrespective of symptoms.  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 DSMB will provide an 
independent safety review at scheduled intervals to coincide with their biannual meeting 
schedule.  

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Immunogenicity Reviews: 
Part A:  The data in Part A will be used in an ongoing manner to help select the regimen to be 
used in Part B.  
Part B:  An interim analysis of immunogenicity data may be performed after the NAb assays up 
to and including Week 12 have been completed on a subset of subjects.  Reports will be provided 
to the Protocol Chairs 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 705 trial in terms of early termination or later safety or 
immunogenicity endpoint assessments. 
Efficacy Reviews (Part B only):   
The final efficacy analysis will occur when the total number of virologic ZIKV cases in Part B 
of the study reaches 90.  Interim efficacy analysis will be performed when the total number of 
virologic ZIKV cases in the mITT cohort reaches 30 and 60.   To preserve a one-sided type I 
error rate of 2.5%, the Lan-DeMets spending function will be adopted.  The Lan-DeMets analog 
of the O’Brien-Fleming boundary, or equivalently, the nominal significance of 0.0001, 0.006, 
and 0.023 will be used in the two interim analyses and the final analysis, respectively, for 
declaring efficacy.  These tests will be of the null H0: VE ≤ 20%.   
To examine for harm (i.e., a greater rate of ZIKV cases in the vaccine arm) a 95% nominal CI for 
the hazard ratio will be calculated.  A guideline for stopping is met if this CI excludes 0 in the 
direction of harm.  Harm will be monitored after 15, 30, 45, 60, and 75 cases have accrued.  
Harm will be monitored using both the ITT and mITT cohorts.   
Incidence Reviews (Part B only): 
The study will be regularly monitored using the combined (blinded) incidence rates for ZIKV 
disease and for ZIKV infections.  These rates will be monitored at each site and over all sites 
combined.  Such monitoring will allow for enrollment to be expanded or curtailed at different 
sites.   
The trial will periodically evaluate the expected time to achieve 90 cases of virologic ZIKV 
disease and may be stopped for lack of feasibility if this expected time is deemed excessive.    
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.  The 
electronic data system will assign each subject a randomization code after eligibility has been 
confirmed in the system.  
In Part A, randomization will be performed with 1:1:1 allocation to the three vaccination arms at 
each study site.  In Part B, randomization will be performed with 1:1 allocation to the ZIKV 
DNA vaccine and placebo at each study site.   
Part A will be open-label and no unblinding will be needed.  In Part B, the injections will be 
prepared by an unblinded site pharmacist, designee, or otherwise qualified personnel who will 
not be involved in any subject assessments and who will not discuss randomizations with blinded 
study staff.  The subjects, the study personnel who perform product administrations 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 product administrations.  Product 
assignments will be provided to the site PI at completion of the study per the Study Blinding 
Plan for communication to the study subjects.  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. 
The IND Sponsor intends to unblind treatment assignments for Part B of the study once 90 cases 
of ZIKV infection are detected.  The DSMB will be consulted prior to unblinding. 
If necessary, the site PI or designee and Protocol Chair may agree that an event, such as 
management of an AE or pregnancy, requires emergency unblinding of an individual subject’s 
assignment.  If early unblinding occurs for any reason, it will be documented as a protocol 
deviation.  The Protocol Statistician, the site IRB/EC (as required), 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 PROCEDURES 
7.1. 
Study Products 
The study products are prepared under cGMP by the VRC Pilot Plant and must meet lot release 
specifications prior to release for use in the clinical study.  This study includes one 
investigational vaccine and one placebo (and diluent) as follows: 
• VRC-ZKADNA090-00-VP (ZIKVwt DNA vaccine) is supplied as a 3-mL glass vial 
containing a clear, colorless, isotonic, PBS-buffered (pH 7.2) sterile solution.  Each vial 
contains a total fill volume of either 1.2 mL (+/- 0.1 mL) or 1.5 mL (+/- 0.1 mL), at a 
concentration of 4 mg/mL.  Vials are intended for single use only and do not contain a 
preservative.  Vials must not be refrozen or reused after thawing.    
• VRC-PBSPLA043-00-VP, phosphate buffered saline (PBS), placebo control and diluent, 
is a clear, colorless, sterile solution at pH 7.2 aseptically filled to a volume of 1.2 mL or 
1.5 mL in 3-mL glass vials.  Vials are intended for single use only and do not contain a 
preservative.  Vials must not be refrozen or reused after thawing.   
Both study products are clear, colorless solutions and there is no difference in appearance.  Study 
products may only be shipped to the site pharmacy per IND Sponsor approval.  Vials are shipped 
using appropriate shipping configurations.   
7.2. 
Study Product Presentation, Stability and Storage 
7.2.1. 
Labels 
At the time of study product delivery to the pharmacy, labels on study products, VRC-
ZKADNA090-00-VP and VRC-PBSPLA043-00-VP, will have specific product information 
(e.g., product description, VRC product number, lot number, fill volume, concentration, fill date, 

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storage condition).  Labels will contain an Investigational Use Statement (“Limited by Federal 
Law to Investigational Use”) and manufacturer information. 
7.2.2. 
Storage 
VRC-ZKADNA090-00-VP:  Vaccine vials will be shipped to the study pharmacy at the 
recommended temperature range using appropriate shipping configurations.  Vaccine vials will 
be stored until use at the target temperature of -35°C to -15°C in a qualified, continuously-
monitored, temperature-controlled freezer.  As freezer temperatures may fluctuate, a temperature 
range of -45°C to -10°C is acceptable based upon historic stability data from studies of similar 
products.  Storage below -45ºC is not permitted because of stopper temperature limitation.  
If deviations in storage temperature occur from the normal allowance for the pharmacy freezer, 
the site pharmacist or designee must quarantine affected product(s) and report the storage 
temperature excursion within 48 hours to the site PI and IND Sponsor.  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 
site pharmacist or designee if clinical use of the affected product is acceptable and the affected 
product may be removed from quarantine. 
VRC-PBSPLA043-00-VP: Vials of PBS are stored until use at the target temperature of -35°C to 
-15°C in a qualified, continuously monitored, temperature-controlled freezer.  As freezer 
temperatures may fluctuate, a temperature range of -45°C to -10°C is acceptable based upon 
historic stability data from studies of similar products.   
7.2.3. 
Stability 
Study product vials must equilibrate to room temperature after removal from the freezer for use.  
Keep filled syringes at room temperature and out of direct sunlight until the product is 
administered.  Vaccine and placebo are stable for up to 8 hours after being removed from the 
freezer and therefore, must be administered within those 8 hours. 
7.3. 
Preparation of Study Products for Administration 
Refer to the IB for information on study products preparation and use.  Refer to the group 
assignment for the study subject to select the proper product type.   
Label all Part A syringes with “VRC 705 Study Product for IM administration” and all Part B 
syringes with “VRC 705 Study Product or Placebo for IM administration.”  In addition, all Part 
A and Part B labels must include the subject identifier, group number (Part A only), treatment 
number (Part B only), time removed from freezer, time of expiration, and preparer’s initials and 
date. 
Site staff should practice universal precautions and dispose of syringes and the needle-free 
device disposable components in keeping with the site policy and practices. 
7.4. 
Study Product Administration 
All injections will be administered using PharmaJet.  The PharmaJet syringes are single use, 
auto-disabling, disposable containers designed to hold 0.5 mL fluid volume.  Reference the 
instructions in the IB to fill the PharmaJet syringes.   

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Additional product administration instructions are listed in protocol Section 4.2.6.1. 
7.5. 
Study Product Accountability 
7.5.1. 
Documentation 
Each study site will be responsible for maintaining an accurate record of the treatment codes, 
inventory and an accountability record of the investigational study product supplies for this 
study.   
7.5.2. 
Disposition 
Empty vials and the unused portion of a vial must be discarded on the day of use in a biohazard 
container that will be incinerated or autoclaved in accordance with site policy.  Any unopened 
vials that remain at the end of the study will be discarded at the discretion of the IND Sponsor in 
accordance with policies that apply to investigational products.  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. 
 

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8. 
HUMAN SUBJECTS PROTECTION 
This research will be conducted in compliance with the protocol, Good Clinical Practice (GCP) 
guidances, and all applicable regulatory requirements. 
8.1. 
Institutional Review Board/Ethics Committee 
A copy of the protocol, proposed consent/assent forms, and any proposed advertising material 
must be submitted to the site IRB/EC for review and approval.  
The site PI must submit and, where necessary, obtain approval from the IRB/EC for subsequent 
protocol amendments and changes to the consent/assent forms.  The site PI is responsible for 
ensuring proper IRB/EC notification of protocol deviations or SAEs occurring at the site and 
other AE reports received from the VRC, in accordance with the protocol and local IRB/EC and 
regulatory policies.  The PI will be responsible for obtaining annual IRB/EC approval/renewal 
throughout the duration of the protocol.  Documentation of the IRB/EC approval and FWA 
number must be provided to the IND Sponsor. 
8.2. 
Institutional Biosafety Committee  
Institutional Biosafety Committees (IBCs) are the cornerstone of institutional oversight of 
recombinant DNA research.  Research with recombinant or synthetic (or both) nucleic acid 
molecules that is performed at or sponsored by an institution that receives any NIH funding for 
such research is required to adhere to IBC guidelines.  Documentation of IBC approval for the 
study must be provided to the IND Sponsor. 
8.3. 
Subject Recruitment and Enrollment 
Subjects for this study will be recruited by the sites in accordance with their IRB/EC standards 
for recruitment practices.  
8.3.1. 
Participation of Children 
This study meets the US Department of Health and Human Services regulations (45 CFR 46, 
Subpart D, 401-409) for inclusion and protections for children/minors who participate in 
research. Healthy minors can participate in research studies considered as "not greater than 
minimal risk" and can participate in research with greater than minimal risk only when it 
presents the prospect of direct benefit to the individual minor or is likely to yield generalizable 
knowledge about the child's condition and meets the criteria in 45 CFR 46, Subpart D.  
Participation in this study will not provide any benefits directly to individual minors; however, 
this study is likely to yield generalizable knowledge that is considered necessary for the 
development of a ZIKV vaccine regimen that would provide durable immune responses and be 
protective.  In accordance to the 45 CFR 46, Subpart D, research involving greater than minimal 
risk and no prospect of direct benefit to the individual subjects should be scientifically sound and 
significant, and have the following conditions met to be approved:  
a. The risk represents a minor increase over minimal risk; 

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b. The intervention or procedure presents experiences to subjects that are reasonably 
commensurate with those inherent in their actual or expected medical, dental, 
psychological, social, or educational situations; 
c. The intervention or procedure is likely to yield generalizable knowledge about the 
subjects' disorder or condition which is of vital importance for the understanding or 
amelioration of the subjects' disorder or condition; and 
d. Adequate provisions are made for soliciting assent of the children and permission of their 
parents or guardians, as set forth in 45 CFR 46.408. 
The conditions listed above have been considered and incorporated in this protocol for 
minimization of risk to adolescents who may participate. 
Children ages 14 years and younger are not eligible to participate in this clinical trial because this 
study is designed for study product evaluation in adults and adolescents of reproductive age.  If 
the product is assessed as safe and immunogenic, other protocols designed for younger children 
may be conducted in the future. 
8.3.2. 
Participation of Site Employees 
Each study site will follow institutional policies related to study participation of site employees.  
Neither participation nor refusal to participate will have an effect, either beneficial or adverse, on 
the subject’s employment or work situation. 
8.4. 
Informed Consent and Assent 
Before a subject’s participation in the protocol, it is the site PI or designee’s responsibility to 
ensure that written informed consent is obtained from the subject (and parent/guardian if 
applicable) after adequate explanation of the purpose, methods, anticipated benefits, and 
potential hazards of the protocol.  The ICF must be signed and personally dated by the subject, 
and by the person who conducted the informed consent discussion.  The subject must also record 
the time of his or her signature.  
As of protocol version 4.0, the Sponsor-required witness, for the sole purpose of verifying and 
attesting to the subject’s signing of the informed consent/assent form, is no longer required.  
However, an impartial witness, defined as a person who is independent of the trial, who cannot 
be unfairly influenced by people involved with the trial, who attends the informed consent/assent 
process, and who reads the informed consent/assent form and any other written information 
supplied to the subject, is required if a subject or subject’s legally acceptable representative 
(LAR) is unable to read.  In the case of an impartial witness, he/she should be present during the 
entire informed consent/assent discussion.  After the written informed consent/assent form and 
any other written information provided to subjects is read and explained to the subject or the 
subject’s LAR, and after the subject or subject’s LAR has orally consented to the subject’s 
participation in the trial and, if capable of doing so, has signed and personally dated the informed 
consent/assent form, the witness should sign and personally date the form.  By signing the 
consent/assent form, the witness attests that the information in the consent form and any other 
written information was accurately explained to, and apparently understood by, the subject or the 
subject's LAR, and that informed consent/assent was freely given by the subject or subject’s 

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LAR.  Sites must also follow local regulations for the use of a LAR or witness to consent 
subjects who are unable to read, as needed. 
Per site regulations for adolescents, sites may use an assent form in conjunction with an ICF 
signed by the parent/guardian, or sites can use only a consent form, provided that both the 
subject and the parent/guardian consent is obtained on the form. 
The acquisition of informed consent/assent must be documented in the subject’s records, as 
required by 45 CFR 46.117.  The original signed consent/assent form must be retained by the site 
with the subject’s study records and a copy of the signed form must be provided to the subject.  
The provided template study informed consent and assent forms (Appendix I) will be used to 
guide development of the site-specific forms.  Only IRB/EC-approved informed consent/assent 
forms will be used to consent and re-consent subjects for study participation.   
All changes made to the templates by the site must be approved by the IND Sponsor before 
submission to the respective IRB/EC and other regulatory authorities.   
Study sites that need to conduct the informed consent/assent process in more than one language 
will follow the practices required by their IRB/EC for translation and approval of the consent(s).  
All translated and English back-translated consent/assent documents must be provided to the 
IND Sponsor.   
8.5. 
Subject Confidentiality 
Site investigators must ensure that the subject’s anonymity is maintained and will ensure that no 
information identifying the subject will be released to any unauthorized party.  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 US 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.  Subject confidentiality will not be violated.  Stored 
study research samples will be labeled by a code (such as a number) that only the 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. 
8.6. 
Risks and Benefits 
8.6.1. 
Risks of the ZIKVwt DNA vaccine 
The investigational ZIKV DNA vaccine, VRC-ZKADNA085-00-VP, which is similar to the 
ZIKVwt DNA vaccine, VRC-ZKADNA090-00-VP, is being tested in a Phase 1 study, VRC 319.  
As of July 24, 2018, 80 subjects have enrolled into VRC 319 and received at least 2 or 3 
injections of the ZIKV DNA vaccine by needle and syringe; 45 subjects have enrolled into VRC 
320 and received at least one injection of the ZIKVwt DNA vaccine by PharmaJet.  Both 
products have been well tolerated based on early findings, as reported in Section 1.3. 
Subjects may exhibit general signs and symptoms associated with administration of a vaccine 
including fever, chills, rash, aches and pains, nausea, headache, dizziness and fatigue.  These 

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side effects will be monitored, but are generally short term, mild to moderate in severity and 
usually do not require treatment. 
In previous VRC DNA vaccine studies, placebo and vaccine recipients were noted to have 
occasional asymptomatic and self-limited changes in laboratory tests such as temporary decrease 
in white blood cell count.  Urticaria has been reported as an AE possibly related to DNA 
vaccines.  
Neurological complications including GBS have been reported in people diagnosed with ZIKV 
infection.  While GBS has not been observed with other DNA vaccines or vaccines developed 
against other flaviviruses, we cannot rule out all concern for GBS.  The cause of GBS associated 
with ZIKV disease is still under investigation.  To minimize the risk of GBS, which has been 
shown to increase with age, the study population is limited to healthy adults and adolescents 15-
35 years of age.  
It is unknown if the study vaccine will affect how subjects respond to a future ZIKV infection or 
ZIKV vaccine that may be available in the future.  There may be side effects from the study 
products, which may be serious or life threatening, that we do not yet know about. 
8.6.2. 
Risks of Administration with a Needle-Free Injection Device 
Investigational DNA vaccines administered via Biojector have been associated with mild skin 
lesions (0.5-1.0 cm diameter) at the injection site.  In these cases, a small scab formed within 1-2 
weeks and then came off after a few days.  The skin healed without treatment within a few 
weeks.   
Potential side effects resulting from IM injection by needle-free devices include stinging, arm 
discomfort, redness of the skin, mild bruising, or a small laceration at the injection sites.   
Product administrations with PharmaJet have been ongoing in VRC 705 Part A and B since 
March 29, 2017 and July 19, 2017, respectively.  As of July 24, 2018, 0.54% of injections have 
involved a device malfunction.  The malfunctions have included the syringe breaking and in rare 
cases, study product spraying during product administration.  This has resulted in some subjects 
not receiving the full dose of study product.  However, no study subjects experienced adverse 
events due to these malfunctions.  The potential for spray due to syringe breakage has led to the 
determination that staff administering the PharmaJet device and subjects receiving the product 
administration must both wear safety glasses during the procedure. 
8.6.3. 
Other Risks 
Blood drawing may cause pain, bruising, fainting, and, rarely, infection at the site where the 
blood is taken. 
We do not know the possible effects of the study vaccine on the fetus or nursing infant.  
Therefore, females of childbearing potential will be tested for pregnancy prior to each product 
administration.   
It is possible that the standard medical tests performed as part of this research protocol will result 
in new diagnoses.  Depending on the medical findings and consequences of being provided with 
the new medical information about health status, the study subject may view this aspect of study 
participation as either a risk or a benefit.  Any such information will be shared and discussed 

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with the subject and, if requested by the subject, will be forwarded to the subject’s primary 
health care provider for further workup and management.  
8.6.4. 
Benefits 
Study subjects will not receive direct health benefit from study participation.  This protocol is not 
designed to provide treatment for any condition.  Others may benefit from knowledge gained in 
this study that may aid in the development of a ZIKV vaccine.  The investigational vaccine is not 
expected to provide protection from ZIKV infection.  
8.7. 
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.  Samples from vaccinated individuals will be critical to development of new 
antibody detection assays for ZIKV diagnosis and for characterization of antibody as well as T- 
and B-cell responses.  These samples will be required for case-control analysis of breakthrough 
ZIKV infections in vaccine versus placebo recipients. 
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.  
Research tests performed at a research laboratory are not for diagnostic purposes and results will 
generally not be available to the study site or study subject. 
8.7.1. 
Use of Samples, Specimens and Data 
Samples, specimens and data collected under this protocol may be used by the protocol team to 
conduct protocol-related safety and immune response evaluations, exploratory laboratory 
evaluations related to ZIKV infection, exploratory laboratory evaluations related to vaccine or 
infectious disease research in general, and for research assay validation.   
8.7.2. 
Storage and Tracking of Blood Samples and Other Specimens 
All of the stored study research samples are labeled by a code that only the site can link to the 
subject.  Coded (de-identified) samples are stored at secure facilities with limited access 
including NVITAL, Gaithersburg, MD, and VRC Laboratories in Bethesda, MD or other 
approved CRO facilities.  Data will be kept in password-protected computers.  Only investigators 
or their designees will have access to the samples and data.  Samples will be tracked in 
GlobalTraceSM and may be transferred to other approved databases as needed for analysis. 
8.7.3. 
Disposition of Samples, Specimens and Data at Completion of the Protocol  
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 subjects research.  The research 
use of stored, unlinked or unidentified samples may be exempt from the need for IRB/EC review 
and approval.  When appropriate, exemption may be obtained through the proper regulatory 
procedures. 
At the time of protocol termination, samples will remain in the contracted central repository, the 
NVITAL facility, or VRC laboratories; or, after IRB/EC approval, samples may be transferred to 

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another repository.  Regulatory oversight of the stored samples and data may be transferred to a 
stored samples protocol as part of the IRB/EC-approved termination plan.  Data will be archived 
by the IND Sponsor in compliance with requirements for retention of research records, or after 
the IRB/EC and the IND Sponsor approval, it may be either destroyed or transferred to another 
repository. 
8.7.4. 
Loss or Destruction of Samples, Specimens or Data 
The NIH Intramural Protocol Deviation definition related to loss of or destruction of samples or 
data will be followed.  Any loss or unanticipated destruction of samples (for example, due to 
freezer malfunction) or data (for example, misplacing a printout of data with identifiers) that 
compromises the scientific integrity of the study will be reported to the site IRB/EC in 
accordance with institutional policies.  The site PI will also notify the site IRB/EC if the decision 
is made to destroy the remaining samples. 
8.8. 
Compensation 
Compensation for time and inconvenience of study participation will be provided to subjects in 
accordance with the site-specific IRB/EC approved plan.  This includes scheduled visits and 
unscheduled visits, such as for evaluation of possible ZIKV infection. 
Suggested compensation rates per visit include: $25-$75 for clinic visits, $50-$100 for product 
administration visits, $5-$20 for phone contacts, $15-$25 for returning the completed diary card, 
and $10-$100 bonus for completion of the study as appropriate.  Site-specific compensation rates 
will be determined based on site SOPs and regional rates of compensation for participation in 
clinical trials for healthy subjects.   
8.9. 
Safety Monitoring 
8.9.1. 
Protocol Safety Review Team 
Each site PI is responsible for ensuring daily review of the site’s clinical safety data as it 
becomes available.  The PSRT includes the Protocol Chairs and IND Sponsor Medical Officers.  
The summary study safety data reports will be reviewed weekly and the PSRT will meet as 
needed (generally weekly) by teleconference to review any safety issues requiring discussion 
from initiation of the study until 4 weeks after all subjects have received their last product 
administration.  After that, the PSRT will meet monthly (or more/less frequently as needed) until 
4 weeks after all subjects have completed the last study visit to be certain that the investigational 
vaccine has an acceptable safety profile.  The PSRT will be notified and convened to review any 
study pauses.   
8.9.2. 
Data and Safety Monitoring Board 
As described in Section 4.6, the DSMB will be consulted to make a decision to resume, amend or 
close the study following a safety pause.  As described in Section 5.6, the DSMB will review 
safety data at least twice per year at their regularly scheduled meetings and will have access to 
the randomization code. 

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9. 
ADMINISTRATION AND LEGAL OBLIGATIONS 
9.1. 
Protocol Initiation, Amendments and Termination 
Each site must receive IRB/EC approval, approval from local country regulatory agencies, as 
needed, and approval of IND Sponsor before initiating the study at the site.   
Protocol amendments must be made only with the prior approval of the IND Sponsor.  
Agreement from the investigator must be obtained for all protocol amendments and amendments 
to the informed consent document.  All amendments will also be submitted to the site IRBs/ECs 
and other regulatory authorities as needed for approval.   
The VRC, NIAID, NIH, FDA and other regulatory authorities reserve the right to terminate the 
study.  Each site PI will notify the respective site IRB/EC of the study termination in writing and 
provide documentation to the IND Sponsor. 
9.2. 
Study Documentation and Study Records Retention 
The site PI will maintain a list of appropriately qualified persons to whom trial duties have been 
delegated.  The site PI 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 IND Sponsor, site IRB/EC, designated CRO monitor and/or 
applicable regulatory authorities.  Elements include but are not limited to: 
• Subject files containing completed informed consent/assent forms and copies of 
supporting source documentation, and,  
• Study files containing the protocol with all amendments, the IB, and copies of all 
correspondence with the IRB/EC and local regulatory authorities, when applicable. 
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/assent forms, laboratory test results, and study 
product inventory records, are managed per US requirements.  The CRO will request financial 
disclosure forms from applicable site personnel at the beginning of the trial.  Financial disclosure 
information must be kept current and must be promptly updated if any relevant changes occur 
during the period of time the investigator participated in the study and for one year following 
study participation.  According to the FDA, study records must be retained for 2 years after the 
marketing application is approved for the product; or, if an application is not approved for the 
product, until 2 years after shipment and delivery of the product for investigational use is 
discontinued.  Study sites are also responsible for ensuring local regulations for record retention 
are followed, as applicable.  The IND Sponsor may authorize transfer or destruction of study 
records and none will be destroyed without prior authorization. 
9.3. 
Data Collection, Data Sharing, and Protocol Monitoring 
9.3.1. 
Data Collection 
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 

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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 IND Sponsor at 
study completion.  
9.3.2. 
Data Sharing 
Data generated in this study will be shared as de-identified data in the government-funded public 
repository, www.ClinicalTrials.gov.  Data may be shared prior to publication at approved public 
presentations or for collaborative development and will be shared at the time of publication or 
within 1 year thereafter. 
9.3.3. 
Source Documents  
Each participating study site will maintain appropriate medical and research records for this trial, 
in compliance with International Conference on Harmonisation of Technical Requirements for 
Registration of Pharmaceuticals for Human Use (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, 
designated CROs 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 original documents and data records include but are not limited to: medical records, diary 
cards, laboratory reports, pharmacy records and other research records for the clinical trial. 
9.3.4. 
Protocol Monitoring 
The IND Sponsor, VRC, or their authorized representatives are responsible for ensuring integrity 
of study data 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 IND Sponsor’s monitoring plan.  Site investigators will allow the study 
monitors, IND Sponsor, the US FDA, and/or other regulatory authorities (if requested) to inspect 
study documents or pertinent clinic records for confirmation of study data. 
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 
Each study site will provide immediate medical care for any injury resulting from participation in 
this research.  In general, the VRC, NIAID, NIH, or US Government will not provide long-term 
medical care or financial compensation for research-related injuries. 

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9.6. 
Multi-Site Management 
The IND Sponsor is responsible for overall study management.  Assistance in managing the 
study is being provided by specific CROs. 
Each study site that enrolls study subjects will have a site PI.  A PI is defined as an individual 
who actually conducts a clinical investigation at a study site and under whose immediate 
direction the test article is administered to subjects.  The site PIs 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 by VRC. 
 

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Inserts. Toxicol Sci, 2006. 91(2): p. 620-630. 
 
63. 
Sheets, R.L., J. Stein, T.S. Manetz, C. Duffy, M. Nason, et al., Biodistribution of DNA 
Plasmid Vaccines against HIV-1, Ebola, Severe Acute Respiratory Syndrome, or West 
Nile Virus Is Similar, without Integration, despite Differing Plasmid Backbones or Gene 
Inserts. Toxicol Sci, 2006. 91(2): p. 610-619. 
 

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APPENDIX I: TEMPLATE INFORMED CONSENT FORM AND ASSENT FORM 
The sample informed consent and assent forms are provided to guide development of a site-
specific documents.  Only IRB/EC-approved forms will be used to consent/assent subjects for 
study participation. 

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Template: Study Informed Consent Form – Part A 
 
STUDY TITLE:  VRC 705: A Phase 2/2B, Randomized Trial to Evaluate the Safety, 
Immunogenicity and Efficacy of a Zika Virus DNA Vaccine in Healthy Adults and Adolescents 
INTRODUCTION 
We invite you to take part in a research study conducted at the [insert site name]. 
The study is sponsored by the National Institutes of Health (NIH) in Bethesda, MD, US.  You 
can choose if you want to take part in this study or not.  There is no penalty or loss of benefits for 
choosing not to take part in this study.  Please ask questions and discuss this study with anyone 
you want.  Take as much time as you need to decide.  You will be given a copy of this consent 
form. 
SCREENING  
Before you can take part in this experimental Zika DNA vaccine study, your health will be 
checked so we can decide if you qualify.  You will need to sign this consent form before 
screening.  If you qualify, then you may take part in the vaccine study. 
Screening includes a physical exam and blood tests to check your health.  We will ask you 
about your health history.  If you are a female who is able to have children, you will be asked 
about the possibility of you becoming pregnant while in the study.  You will be tested for 
pregnancy.  During screening, we will collect some blood to store for research.  We will 
review the test results with you and tell you if the results show that you are eligible to join the 
study.   
PURPOSE OF THIS STUDY 
This is a research study of an experimental vaccine against Zika virus infection. “Experimental” 
means that the study vaccine has not been approved by the US Food and Drug Administration 
(FDA).  The FDA allows this vaccine to be used for research purposes only.  This vaccine has 
been given to people in a Phase 1 study.  We do not know if the vaccine works.  The main 
purpose of this study is to see if the experimental vaccine is safe and if there are any side effects.  
We also want to study immune responses to the vaccine including cells that may recognize and 
fight Zika virus.  This study will take place in areas where Zika outbreaks are happening or may 
happen.   
BACKGROUND ON ZIKA VIRUS  
Zika virus was discovered in 1947.  It is named after the Zika Forest in Uganda where it was 
found.  Until recently, Zika infections happened in parts of Africa and Asia.  Recent outbreaks 
have been reported in North, Central and South America, the Caribbean, the Pacific Islands, and 
Africa.   
Zika is passed from human to human by infected mosquitos.  Zika can also be passed through 
sex from a person who has Zika to his or her partners, and from a mother to her child during 
pregnancy.  Zika infection causes symptoms that are usually mild and may include fever, rash, 
joint pain, and conjunctivitis (red eyes).  Many times, there are no symptoms at all, so many 

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people do not know that they have been infected.  Symptoms usually last from 2 to 7 days.  
People usually don’t get sick enough to go to the hospital, and they very rarely die.  A person 
who has been infected once is not likely to get Zika infection again.   
Recently, some cases of microcephaly (abnormally small head and brain) and other birth defects 
were found in babies that were born to mothers who had a Zika infection.  Some people who had 
Zika infection also had rare cases of a severe muscle weakness called Guillain-Barré syndrome.  
We do not know why some people who get Zika infection develop Guillain-Barré syndrome.  
Most people who develop Guillain-Barré syndrome recover over time.  If you have ever had this 
condition, you will not qualify for this study.  
There is currently no cure for or vaccine to prevent Zika infection. 
We will tell you if we learn anything new during this study that might cause you to change your 
mind about staying in the study.  At the end of the study, we will tell you when study results may 
be available and how to learn about them.  
STUDY PLAN 
This study has 2 parts, Part A and Part B.  Part A of the study has 3 groups with a total of 90 
people.  We will test the vaccine at doses of 4 milligrams (mg) or 8 mg split into either 2 or 4 
injections.  Part A will last for 32 weeks or about 8 months.  Part B of the study has 2 groups 
with a total of about 2400 people.  We will test the vaccine in comparison to the placebo, 
which is a salt-water solution that has no vaccine in it.  Part B will last for 96 weeks or about 
24 months. 
By signing this form, you are agreeing to take part in Part A.  The plan for Part A is below: 
VRC 705 – Part A 
Group 
Subjects 
Dose 
Number of 
Injections  
Location of 
Injections  
Product Administration 
Day 0 
Week 4 
Week 8 
1 
30 
4 mg 
2 
each arm 
vaccine 
vaccine 
vaccine 
2 
30 
4 mg 
4 
each arm and 
each leg 
vaccine 
vaccine 
vaccine 
3 
30 
8 mg 
4 
each arm and 
each leg 
vaccine 
vaccine 
vaccine 
Total 
90 
 Study product is given into the muscle by needle-free injection device. 
STUDY PRODUCT 
The study product being tested in this study is VRC-ZKADNA090-00-VP, which is called the 
‘Zika DNA vaccine’ or ‘Zika vaccine’.  The Zika vaccine was developed by the Vaccine 
Research Center (VRC) at the US NIH.  It was made at the VRC Pilot Plant in Frederick, 
Maryland, US   
Vaccines are given to help the body fight off an infection.  When you get a dose of this vaccine, 
it should cause your body to make a small amount of Zika protein.  Your body may use this 
protein to build an immune response against Zika.   

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There is no Zika virus in this vaccine. You cannot get Zika infection from this vaccine. 
You should not expect this experimental Zika vaccine to protect you from Zika infection.  You 
must take steps to protect yourself if you think you might be exposed to Zika in your 
environment.  You should avoid mosquitos, use mosquito repellant, wear long sleeves and pants, 
and use bed nets at night.  If you have any side effects that seem like Zika infection (including 
fever, rash, eye pain, red eyes, muscle aches, headache, or joint pain) while on the study, tell the 
study team right away so we can check you as soon as possible. 
ELIGIBILITY 
You may qualify to take part in this study if: 
• you are between 18 [or insert site-specific age that applies to adults] and 35 years of 
age,  
• you agree not to become pregnant for at least 12 weeks after you get the last product 
administration, which is about 5 months after the study begins, 
• you have physical exam and blood test results that meet study requirements, and  
• you do not have any serious medical problems as determined by your screening.  
STUDY PROCEDURES 
About 90 people will take part in Part A of this study.  If you agree to join Part A, you will be 
assigned to one of the three study groups by chance (like flipping a coin).  Once you are on the 
study, you will know which group you are in.   
You will get a total of 3 product administrations.  A product administration will be given at 3 
separate visits that are each about 4 weeks apart.  Depending on which study group you are in, 
you will get either 2 or 4 injections at each product administration visit.  We will give all 
injections using the needle-free injection device called the PharmaJet Stratis® Needle Free Jet 
Injector (PharmaJet).  In all study groups, PharmaJet injections will be given into the deltoid 
muscle on the arms.  In some study groups, PharmaJet injections will also be given into the 
muscle on the upper thighs.  
PharmaJet injects the vaccine into your body without using a needle.  Instead of a needle, 
PharmaJet uses high pressure to push the vaccine through your skin into the muscle. Even though 
there is no needle, it may still cause pain.  Needle-free devices have been used to give vaccines 
and other medications since the 1940s.  This device has been cleared by the FDA for giving 
vaccine injections into the muscle.  Studies have shown that some people who get injections with 
PharmaJet have more local reactions at the injection site than people who get injections with 
needle and syringe.  However, the local reactions were mild. 
If you are a female who is able to get pregnant, you will be given a pregnancy test before you get 
each product administration.  The test must show that you are not pregnant before we can give 
you the study product. 
We will watch you for at least 15 minutes after you get each full dose of study product, which is 
after you get all 2 or 4 injections.   

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We will ask you to complete a diary card for 7 days after each product administration.  You will 
use the diary card to write down your highest temperature each day and any side effects that you 
feel.  You will also need to look at the injection sites each day and write down how it looks and 
any side effects that you see.  We will give you a thermometer and a measuring device to do this.  
We will ask you to review your diary card with us about a week later.   
The clinic staff is available to you by phone 24 hours a day to report any unexpected side effects.  
If you have any concerning side effects or if you feel sick, you should tell the clinic right away.  
We may ask you to come into the clinic for an examination before your next scheduled visit.  It 
is very important that you follow the instructions we give you.  
Follow-Up Visits 
You will be in the study for about 8 months after you get the first product administration.  You 
will have about 11 clinic visits and 3 telephone contacts.  Each clinic visit will last about [insert 
site standard length of clinic visit].  
At each visit, we will ask you about 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 4 
to 11 tubes of blood from you, depending on the visit.  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.  
Experimental vaccine studies like this one follow a set schedule.  The study schedule for your 
visits allows some flexibility, but it is important that you work with the staff to follow the set 
schedule as much as possible.  You should try to not miss any visits.   
Sample Collection for Zika Diagnosis  
At any time during the study, if you think you have Zika infection, you must contact our clinic 
right away.  We will ask you to come in for a clinical examination and we may collect blood and 
urine so that we can test you for Zika infection.  If you have a rash or another sign or symptom of 
illness that could possibly be a Zika infection, we may take a photograph of the affected area 
with your permission.  These photographs will not identify you in any way and will only be used 
by the study team to evaluate your illness.  We may also test for other infections that have 
symptoms similar to Zika infection.   
These samples will be shipped to either the Primary Diagnostic Laboratory at the University of 
Washington (Seattle, WA, US) or the Diagnostic and Reference Laboratory Arbovirus Diseases 
Branch, Centers for Disease Control and Prevention (CDC), Fort Collins, CO, US for testing. 
We will tell you the results of your test(s) as soon as possible but it may take several weeks to 
get the results.  It is very important that you get tested for Zika infection at our clinic only and 
that you do not get tested elsewhere unless it is necessary for your health, for example, while 
traveling. 
VOLUNTARY PARTICIPATION  
Your participation in this study is completely voluntary.  You can choose to stop taking part in 
the study at any time during the study.  There is no penalty or loss of benefits for choosing to 
leave the study at any time. 

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MONITORING OF THE STUDY 
This study will be monitored by a group of physicians and scientists associated with the US NIH.  
This group will review the study information and will pay close attention to any reactions that 
people have to the study product. 
STORED SAMPLES 
We will collect blood and other bodily fluids such as urine from you during this study.  We will 
keep these samples to study your immune response to the study product and for future research 
to learn more about Zika, vaccines, the immune system or other related medical conditions.  The 
urgency of the Zika epidemic has accelerated the development of Zika tests and assays.  Samples 
from study subjects may be an important part in the development of new assays to diagnose and 
to study Zika infections.  No genetic research (deoxyribonucleic acid [DNA] testing) will be 
done on these samples. 
[Add as required per local/national regulations]:  Research samples will be shipped to the 
Fisher BioServices (Germantown, MD, US) storage facility.  Research samples may be stored for 
up to 20 years.  Stored samples may be sent for testing by any of the following laboratories: 
• VRC/NIAID Vaccine Immune T-Cell and Antibody Laboratory (NVITAL; Rockville, 
MD, US) 
• NIAID Laboratory of Infectious Diseases (LID; Bethesda, MD, US) 
• Battelle, Biomedical Research Center (West Jefferson, OH, US) 
• Z-Quick/University of Miami Life Science and Technology Park (Miami, FL, US) 
• Blood Systems Research Institute (BSRI, San Francisco, CA, US) 
• PaxVax (San Diego, CA, US)  
As new tests are developed, additional laboratories may use your stored samples for testing.  
These laboratories are unknown at this time.  
Results from the research done with your stored samples are not for diagnostic purposes or 
medical care.  Therefore, the results will not be part of your medical record.  
Labeling of Stored Samples:  Your stored samples will be labeled by a special code or number 
that only the study team can link to you.  Any identifying information about you, like your name 
or date of birth, will be kept as confidential as allowable 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 researchers at NIH or outside of NIH may wish to study 
your stored samples.  When the study team shares your samples, they will be marked with a 
code.  Your samples will not have any information on them that could identify you.  Some 
information about you, such as your gender, age, health history, or ethnicity may be shared.  Any 
future research done with your samples will be done in a way that protects the rights and privacy 
of study subjects. 
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 get payment for 
these products. 

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HUMAN DATA SHARING 
To advance science, it is helpful for researchers to share information they get from studying 
humans by putting it into shared scientific databases.  Researchers can then study the information 
combined from many studies to learn even more about health and diseases.  
If you agree to take part in this study, some of your data will be placed into one or more 
scientific databases.  We will remove identifying information like your name, address, and birth 
date.  The data may then be used for future research and shared broadly for research purposes. 
Only researchers who are approved to access the database may be able to see and use your 
information.  You will not get any direct benefits from future research that uses your data and 
information.   
You may stop participating in this study at any time and withdraw permission for your individual 
data, specimens, and health information to be used for additional or future research.  You may 
ask to have your research data destroyed.  However, it may not be possible to withdraw or delete 
data once they have been shared with other researchers. 
POSSIBLE STUDY RISKS 
Possible risks from the injections:  Temporary stinging, pain, redness, soreness, itchiness, 
swelling, or bruising.  Injections given with the needle-free device have been shown to cause a 
small cut at the injection site.  A small scab may form within 1 to 2 weeks after the injection is 
given.  There is a very small chance of infection. 
There is also a small chance that the needle-free device could not work properly.  As of July 
2018, 0.54% of VRC 705 injections involved a PharmaJet device malfunction.  This includes the 
syringe breaking and study product spraying during administration.  No study subjects were 
harmed because of these malfunctions.  However, because there is the possibility of a 
malfunction, we ask that you wear safety glasses while we give you the injections. 
Possible risks of blood drawing:  Pain, bleeding, bruising, feeling lightheaded, or fainting, and 
rarely, infection at the site where blood is taken. 
Possible risks from any vaccine:  Fever, chills, rash, aches and pains, nausea, headache, 
dizziness, and feeling tired or unwell.  Some people have allergic reactions to vaccines.  These 
types of reactions are usually greatest within the first 24 hours after an injection and typically last 
1 to 3 days.  Medicines, such as acetaminophen, may be used to help relieve these symptoms. 
Very rarely, a serious allergic reaction with symptoms such as hives, trouble breathing, or 
sudden weakness may happen shortly after any vaccination.  This is called “anaphylaxis” and 
may be life-threatening.  While you are waiting in the clinic after the injections, we will monitor 
you for anaphylaxis.  Treatment for anaphylaxis will be given right away if it happens.   
Possible risks of DNA vaccines:  Temporary drop in white blood cell count, sore arm, skin rash 
or hives, some people get a small red bump and then a scab for a few days where the injection is 
given.  The NIH has tested many similar vaccines made by the VRC and these vaccines were 
found to be safe and well-tolerated.  We expect this vaccine to be like the ones tested before. 
Possible risks of the Zika DNA vaccine:  As of July 2018, this Zika vaccine has been tested in 
45 subjects in the Phase 1 study, VRC 320.  So far, the most common complaints after injection 

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by PharmaJet are mild or moderate headache and feeling tired or unwell, and mild pain at the 
injection site. 
A very similar Zika vaccine has been tested in 80 subjects in the Phase 1 study, VRC 319.  As of 
July 2018, that experimental vaccine was found to be safe for additional studies in humans.  So 
far, the most common complaints after injection by needle and syringe have been mild pain at 
the injection site, and mild or moderate headache, muscle aches and feeling tired or unwell. 
This Zika vaccine does not contain Zika virus.  Guillain-Barré syndrome has not been seen with 
similar vaccines or vaccines made against similar viruses.  We do not know if there is a risk of 
Guillain-Barré syndrome from the study vaccine.  However, we have to be very cautious and 
observant with a Zika vaccine.  This is because natural Zika infection seems to be associated 
with Guillain-Barré syndrome and we don’t know how Zika might cause Guillain-Barré 
syndrome.  You should tell the study team if you develop weakness or tingling in your arms or 
any other unusual symptoms.  
Possible risks during Pregnancy:  We do not know if getting the study product will affect a 
fetus.  Therefore, women and adolescents who can get pregnant must agree to use an effective 
method of birth control starting at least 21 days before getting the first product administration 
until 12 weeks after the last product administration.  We will discuss effective birth control 
methods with you.  If you are pregnant or want to become pregnant in the next 20 weeks, you 
cannot participate.   
During the study, if you think you might be pregnant, you must tell the clinic staff right away.  
If you are pregnant, you will not get any more study product.  We will give you resources you 
can use to learn about protecting yourself from getting Zika infection.  You will be asked to 
continue with some follow-up visits.  We will ask you about the outcome of the pregnancy. 
Unknown risks:  We do not know if the study product will affect how you respond to any future 
Zika infection or Zika vaccine that you may get in the future.  There may be side effects from the 
study product, even serious or life threatening ones, that we do not yet know about.  We will tell 
you if we learn about any important new findings or serious side effects of the vaccine during the 
study that may change your mind about your willingness to continue participation.  
You may not donate blood while taking part in this study.  You may not donate blood for one 
year after the date of your last product administration. 
POSSIBLE BENEFITS 
This study is not designed to benefit you or to protect you from Zika 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 taking part in this study.  You or your health insurance will have to 
pay for all medical costs for medical care that you get outside of this study.  It is possible that 
you may have some costs that are not covered by the study compensation we give you. 

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COMPENSATION TO YOU FOR TAKING PART IN THE STUDY 
You will be compensated [insert site IRB/EC-approved amount] for taking part in this study 
as follows: [insert site plan].  Total compensation will be based on the number of study visits 
you attend and the number of product administrations you get [or insert site plan].   
REASONS FOR REMOVING YOU FROM THE STUDY WITHOUT YOUR CONSENT 
The study doctor can take you out of this study without your consent if: 
• continuing in the study could hurt you,  
• you do not follow study instructions or keep your appointments, or  
• the study is stopped by the US NIH, FDA, or regulatory authorities.   
If you agree to take part in this study, it is important for you to keep all of your appointments. 
However, if you do not 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 get at least one product administration, 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 check your health 
even if you do not get the second or third product administrations. 
ALTERNATIVES 
This study is not designed to treat or prevent any disease.  You may choose not to take part. 
CONFIDENTIALITY 
[Site/country-specific information on confidentiality may be added to this section.] 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required 
by US law.  This website will not include information that can identify you.  At most, the 
website will include a summary of the study results.  You can search this website at any time.  
Results of US NIH-supported research studies may also be reported in medical journals, on the 
internet or at scientific meetings.  These reports will not have information that can identify you.   
In most cases, the US 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 gets information from your medical 
record.  This information might affect (either positively or negatively) if the insurance company 
sells insurance to you. 
POLICY REGARDING RESEARCH-RELATED INJURIES 
The study site will provide immediate medical care for any injury resulting from you being in 
research here.  In general, no long-term medical care or financial compensation for research-
related injuries will be provided by the US NIH or the US Federal Government.  However, you 
have the right to seek legal action if you think that your injury has a good reason for such action. 

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PROBLEMS OR QUESTIONS 
If you have any problems or questions about this study, about your rights as a research subject, 
or about any research-related injury, call the Principal Investigator [insert site PI information].  
You may also call the Study Coordinator [insert site SC information] or the Patient 
Representative at [insert site Patient Representative, as applicable] 
Please keep a copy of this form in case you want to read it again. 
 

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SUBJECT CONSENT 
I have read the explanation about this study and have been given the opportunity to discuss it 
and to ask questions.  All my questions have been answered to my satisfaction.  I consent to 
take part in this study. 
 
 
 
Subject Name (print): 
 
Date and Time: 
Signature: 
 
 
 
Investigator Name (print): 
 
Date: 
Signature: 
 

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Template: Study Informed Consent Form – Part B 
 
STUDY TITLE:  VRC 705: A Phase 2/2B, Randomized Trial to Evaluate the Safety, 
Immunogenicity and Efficacy of a Zika Virus DNA Vaccine in Healthy Adults and Adolescents 
INTRODUCTION 
We invite you to take part in a research study conducted at the [insert site name].  
The study is sponsored by the National Institutes of Health (NIH) in Bethesda, MD, US.  You 
can choose if you want to take part in this study or not.  There is no penalty or loss of benefits for 
choosing not to take part in this study.  Please ask questions and discuss this study with anyone 
you want.  Take as much time as you need to decide.  You will be given a copy of this consent 
form. 
SCREENING  
Before you can take part in this experimental Zika DNA vaccine study, your health will be 
checked so we can decide if you qualify.  You will need to sign this consent form before 
screening.  If you qualify, then you may take part in the vaccine study. 
Screening includes a physical exam and blood tests to check your health.  We will ask you 
about your health history.  If you are a female who is able to have children, you will be asked 
about the possibility of you becoming pregnant while in the study.  You will be tested for 
pregnancy.  During screening, we will collect some blood to store for research.  We will 
review the test results with you and tell you if the results show that you are eligible to join the 
study.   
PURPOSE OF THIS STUDY 
This is a research study of an experimental vaccine against Zika virus infection. 
“Experimental” means that the study vaccine has not been approved by the US Food and Drug 
Administration (FDA).  The FDA allows this vaccine to be used for research purposes only.  
This vaccine has been given to people in a Phase 1 study.  We do not know if the vaccine 
works.  The main purpose of this study is to see if the experimental vaccine is safe and if there 
are any side effects.  We also want to study immune responses to the vaccine including cells 
that may recognize and fight Zika virus.  This study will take place in areas where Zika 
outbreaks are happening or may happen.   
BACKGROUND ON ZIKA VIRUS  
Zika virus was discovered in 1947.  It is named after the Zika Forest in Uganda where it was 
found.  Until recently, Zika infections happened in parts of Africa and Asia.  Recent outbreaks 
have been reported in North, Central and South America, the Caribbean, the Pacific Islands, and 
Africa.   
Zika is passed from human to human by infected mosquitos.  Zika can also be passed through 
sex from a person who has Zika to his or her partners, and from a mother to her child during 
pregnancy.  Zika infection causes symptoms that are usually mild and may include fever, rash, 
joint pain, and conjunctivitis (red eyes).  Many times, there are no symptoms at all, so many 

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people do not know that they have been infected.  Symptoms usually last from 2 to 7 days.  
People usually don’t get sick enough to go to the hospital, and they very rarely die.  A person 
who has been infected once is not likely to get Zika infection again.   
Recently, some cases of microcephaly (abnormally small head and brain) and other birth defects 
were found in babies that were born to mothers who had a Zika infection.  Some people who had 
Zika infection also had rare cases of a severe muscle weakness called Guillain-Barré syndrome.  
We do not know why some people who get Zika infection develop Guillain-Barré syndrome.  
Most people who develop Guillain-Barré syndrome recover over time.  If you have ever had this 
condition, you will not qualify for this study.  
There is currently no cure for or vaccine to prevent Zika infection. 
We will tell you if we learn anything new during this study that might cause you to change your 
mind about staying in the study.  At the end of the study, we will tell you when study results may 
be available and how to learn about them.  
STUDY PLAN 
This study has 2 parts, Part A and Part B.  Part A of the study has 3 groups with a total of 90 
people.  We are testing the vaccine at doses of 4 milligrams (mg) or 8 mg split into either 2 or 
4 injections.  Part A will last for 32 weeks or about 8 months.  Part B of the study has 2 groups 
with a total of about 2400.  We will test the vaccine in comparison to the placebo, which is a 
salt-water solution that has no vaccine in it.  Part B will last for 96 weeks or about 24 months. 
By signing this form, you are agreeing to take part in Part B.  The plan for Part B is below: 
VRC 705 – Part B 
Group 
Subjects 
Dose 
Number of 
Injections  
Location of 
Injections  
Product Administration 
Day 0 
Week 4 
Week 8 
4 
1200 
4 mg 
2 
both arms 
vaccine 
vaccine 
vaccine 
5 
1200 
0 
2 
both arms 
placebo 
placebo 
placebo 
Total 
2400 
Study products are given into the muscle by needle-free injection device. 
STUDY PRODUCTS 
There are two study products in Part B of this study, the Zika vaccine and the salt water solution 
(or placebo).  Half of the people in the study will get the vaccine and half will get the placebo.   
1. Vaccine:  In this study, the vaccine being tested is VRC-ZKADNA090-00-VP, which is 
called the ‘Zika DNA vaccine’ or ‘Zika vaccine’.  The Zika vaccine was developed by 
the Vaccine Research Center (VRC) at the US NIH.  It was made at the VRC Pilot Plant 
in Frederick, Maryland, US.   

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Vaccines are given to help the body fight off an infection.  When you get a dose of this 
vaccine, it should cause your body to make a small amount of Zika protein.  Your body 
may use this protein to build an immune response against Zika.   
There is no Zika virus in this vaccine. You cannot get Zika infection from this vaccine. 
You should not expect this experimental Zika vaccine to protect you from Zika infection.  
You must take steps to protect yourself if you think you might be exposed to Zika in your 
environment.  You should avoid mosquitos, use mosquito repellant, wear long sleeves 
and pants, and use bed nets at night.  If you have any side effects that seem like Zika 
infection (including fever, rash, eye pain, red eyes, muscle aches, headache, or joint pain) 
while on the study, tell the study team right away so we can check you as soon as 
possible. 
2. Placebo:  The placebo in this study is a sterile salt water solution made for injection into 
people.  It has no vaccine in it.  We use the placebo as a control for the vaccine, so we 
can compare to the vaccine and see how it works. 
ELIGIBILITY 
You may qualify to take part in this study if: 
• you are between [insert site-specific age that applies] and 35 years of age,  
• you agree not to become pregnant for at least 12 weeks after you get the last product 
administration, which is about 5 months after the study begins, 
• you have physical exam and blood test results that meet study requirements, and  
• you do not have any serious medical problems as determined by your screening.  
STUDY PROCEDURES 
About 2400 people will take part in Part B of this study.  If you agree to join Part B, you will be 
assigned to one of the two study groups by chance (like flipping a coin).  You and the clinic staff 
will not know which study product you are getting until after the study is over.   
You will get a total of 3 product administrations.  A product administration will be given at 3 
separate visits that are each about 4 weeks apart.  You will get 2 injections at each product 
administration visit.  We will give all injections using the needle-free injection device called the 
PharmaJet Stratis® Needle Free Jet Injector (PharmaJet).  PharmaJet injections will be given into 
the deltoid muscle on each arm.  In special cases, PharmaJet injections may also be given into 
the muscle on the upper thigh. 
PharmaJet injects the vaccine into your body without using a needle.  Instead of a needle, 
PharmaJet uses high pressure to push the vaccine through your skin into the muscle. Even though 
there is no needle, it may still cause pain.  Needle-free devices have been used to give vaccines 
and other medications since the 1940s.  This device has been cleared by the FDA for giving 
vaccine injections into the muscle.  Studies have shown that some people who get injections with 
PharmaJet have more local reactions at the injection site than people who get injections with 
needle and syringe.  However, the local reactions were mild. 

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If you are a female who is able to get pregnant, you will be given a pregnancy test before you get 
each product administration.  The test must show that you are not pregnant before we can give 
you the study product. 
We will watch you for at least 15 minutes after you get each full dose of study product, which is 
after you get both injections.   
We will ask you to complete a diary card for 7 days after each product administration.  You will 
use the diary card to write down your highest temperature each day and any side effects that you 
feel.  You will also need to look at the injection sites each day and write down how it looks and 
any side effects that you see.  We will give you a thermometer and a measuring device to do this.  
We will ask you to review your diary card with us about a week later.   
The clinic staff is available to you by phone 24 hours a day to report any unexpected side effects.  
If you have any concerning side effects or if you feel sick, you should tell the clinic right away.  
We may ask you to come into the clinic for an examination before your next scheduled visit.  It 
is very important that you follow the instructions we give you.  
Follow-Up Visits 
You will be in the study for about 2 years after you get the first product administration.  You will 
have about 19 to 25 clinic visits and 3 telephone contacts.  Each clinic visit will last about [insert 
site standard length of clinic visit].  
At each visit, we will ask you about 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 2 
to 9 tubes of blood from you, depending on the visit.  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.  
Experimental vaccine studies like this one follow a set schedule.  The study schedule for your 
visits allows some flexibility, but it is important that you work with the staff to follow the set 
schedule as much as possible.  You should try to not miss any visits.   
Sample Collection for Zika Diagnosis  
At any time during the study, if you think you have Zika infection, you must contact our clinic 
right away.  We will ask you to come in for a clinical examination and we may collect blood, and 
urine so that we can test you for Zika infection.  If you have a rash or another sign or symptom of 
illness that could possibly be a Zika infection, we may take a photograph of the affected area 
with your permission.  These photographs will not identify you in any way and will only be used 
by the study team to evaluate your illness.  We may also test for other infections that have 
symptoms similar to Zika infection.   
These samples will be shipped to either the Primary Diagnostic Laboratory at the University of 
Washington (Seattle, WA, US) or the Diagnostic and Reference Laboratory Arbovirus Diseases 
Branch, Centers for Disease Control and Prevention (CDC), Fort Collins, CO, US for testing. 
We will tell you the results of your test(s) as soon as possible but it may take several weeks to 
get the results.  It is very important that you get tested for Zika infection at our clinic only and 
that you do not get tested elsewhere unless it is necessary for your health, for example, while 
traveling. 

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Sample Collection for Zika Research 
Many people who have Zika infection do not feel sick even when there is virus in their blood, 
urine, or other bodily fluids.  As part of this study, we will collect blood samples from you about 
once a month for the first year and then every two months for the whole study (which is 96 
weeks) so we can test for Zika infection.  The sample collection plans may change if you get 
Zika infection.  We will collect these samples for research purposes only. 
VOLUNTARY PARTICIPATION  
Your participation in this study is completely voluntary.  You can choose to stop taking part in 
the study at any time during the study.  There is no penalty or loss of benefits for choosing to 
leave the study at any time. 
MONITORING OF THE STUDY 
This study will be monitored by a group of physicians and scientists associated with the US NIH.  
This group will review the study information and will pay close attention to any reactions that 
people have to the study products. 
STORED SAMPLES 
We will collect blood and other bodily fluids such as urine from you during this study.  We will 
keep these samples to study your immune response to the study product and for future research 
to learn more about Zika, vaccines, the immune system or other related medical conditions.  The 
urgency of the Zika epidemic has accelerated the development of Zika tests and assays.  Samples 
from study subjects may be an important part in the development of new assays to diagnose and 
to study Zika infections.  No genetic research (deoxyribonucleic acid [DNA] testing) will be 
done on these samples. 
[Add as required per local/national regulations]:  Research samples will be shipped to the 
Fisher BioServices (Germantown, MD, US) storage facility.  Research samples may be stored for 
up to 20 years.  Stored samples may be sent for testing by any of the following laboratories: 
• VRC/NIAID Vaccine Immune T-Cell and Antibody Laboratory (NVITAL; Rockville, 
MD, US) 
• NIAID Laboratory of Infectious Diseases (LID; Bethesda, MD, US) 
• Battelle, Biomedical Research Center (West Jefferson, OH, US) 
• Z-Quick/University of Miami Life Science and Technology Park (Miami, FL, US) 
• Blood Systems Research Institute (BSRI, San Francisco, CA, US) 
• PaxVax (San Diego, CA, US)  
As new tests are developed, additional laboratories may use your stored samples for testing.  
These laboratories are unknown at this time.  
Results from the research done with your stored samples are not for diagnostic purposes or 
medical care.  Therefore, the results will not be part of your medical record.  
Labeling of Stored Samples:  Your stored samples will be labeled by a special code or number 
that only the study team can link to you.  Any identifying information about you, like your name 
or date of birth, will be kept as confidential as allowable by law.  Despite protections, there is a 
small chance that information identifying you will be given to someone who should not get it. 

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Future Studies:  In the future, other researchers at NIH or outside of NIH may wish to study 
your stored samples.  When the study team shares your samples, they will be marked with a 
code.  Your samples will not have any information on them that could identify you.  Some 
information about you, such as your gender, age, health history, or ethnicity may be shared.  Any 
future research done with your samples will be done in a way that protects the rights and privacy 
of study subjects. 
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 get payment for 
these products. 
HUMAN DATA SHARING 
To advance science, it is helpful for researchers to share information they get from studying 
humans by putting it into shared scientific databases.  Researchers can then study the information 
combined from many studies to learn even more about health and diseases.  
If you agree to take part in this study, some of your data will be placed into one or more 
scientific databases.  We will remove identifying information like your name, address, and birth 
date.  The data may then be used for future research and shared broadly for research purposes. 
Only researchers who are approved to access the database may be able to see and use your 
information.  You will not get any direct benefits from future research that uses your data and 
information.   
You may stop participating in this study at any time and withdraw permission for your individual 
data, specimens, and health information to be used for additional or future research.  You may 
ask to have your research data destroyed.  However, it may not be possible to withdraw or delete 
data once they have been shared with other researchers. 
POSSIBLE STUDY RISKS 
Possible risks from the injections:  Temporary stinging, pain, redness, soreness, itchiness, 
swelling, or bruising.  Injections given with the needle-free device have been shown to cause a 
small cut at the injection site.  A small scab may form within 1 to 2 weeks after the injection is 
given.  There is a very small chance of infection. 
There is also a small chance that the needle-free device could not work properly.  As of July 
2018, 0.54% of VRC 705 injections involved a PharmaJet device malfunction.  This includes the 
syringe breaking and study product spraying during administration.  No study subjects were 
harmed because of these malfunctions.  However, because there is the possibility of a 
malfunction, we ask that you wear safety glasses while we give you the injections. 
Possible risks of blood drawing:  Pain, bleeding, bruising, feeling lightheaded, or fainting, and 
rarely, infection at the site where blood is taken. 
Possible risks from any vaccine:  Fever, chills, rash, aches and pains, nausea, headache, 
dizziness, and feeling tired or unwell.  Some people have allergic reactions to vaccines.  These 
types of reactions are usually greatest within the first 24 hours after an injection and typically last 
1 to 3 days.  Medicines, such as acetaminophen, may be used to help relieve these symptoms. 
Very rarely, a serious allergic reaction with symptoms such as hives, trouble breathing, or 
sudden weakness may happen shortly after any vaccination.  This is called “anaphylaxis” and 

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may be life-threatening.  While you are waiting in the clinic after the injections, we will monitor 
you for anaphylaxis.  Treatment for anaphylaxis will be given right away if it happens.   
Possible risks of DNA vaccines:  Temporary drop in white blood cell count, sore arm, skin rash 
or hives, some people get a small red bump and then a scab for a few days where the injection is 
given.  The NIH has tested many similar vaccines made by the VRC and these vaccines were 
found to be safe and well-tolerated.  We expect this vaccine to be like the ones tested before. 
Possible risks of the Zika DNA vaccine:  As of July 2018, this Zika vaccine has been tested in 
45 subjects in the Phase 1 study, VRC 320.  The most common complaints after injection by 
PharmaJet are mild or moderate headache and feeling tired or unwell, and mild pain at the 
injection site. 
A very similar Zika vaccine has been tested in 80 subjects in the Phase 1 study, VRC 319.  As of 
July 2018, that experimental vaccine was found to be safe for additional studies in humans.  So 
far, the most common complaints after injection by needle and syringe have been mild pain at 
the injection site, and mild or moderate headache, muscle aches and feeling tired or unwell. 
This Zika vaccine does not contain Zika virus.  Guillain-Barré syndrome has not been seen with 
similar vaccines or vaccines made against similar viruses.  We do not know if there is a risk of 
Guillain-Barré syndrome from the study vaccine.  However, we have to be very cautious and 
observant with a Zika vaccine.  This is because natural Zika infection seems to be associated 
with Guillain-Barré syndrome and we don’t know how Zika might cause Guillain-Barré 
syndrome.  You should tell the study team if you develop weakness or tingling in your arms or 
legs or any other unusual symptoms.  
Possible risks during Pregnancy:  We do not know if getting the study products will affect a 
fetus.  Therefore, women and adolescents who can get pregnant must agree to use an effective 
method of birth control starting at least 21 days before getting the first product administration 
until 12 weeks after the last product administration.  We will discuss effective birth control 
methods with you.  If you are pregnant or want to become pregnant in the next 20 weeks, you 
cannot participate.   
During the study, if you think you might be pregnant, you must tell the clinic staff right away.  
If you are pregnant, you will not get any more study product.  We will give you resources you 
can use to learn about protecting yourself from getting Zika infection.  You will be asked to 
continue with some follow-up visits.  We will ask you about the outcome of the pregnancy. 
Unknown risks:  We do not know if the study product will affect how you respond to any future 
Zika infection or Zika vaccine that you may get in the future.  There may be side effects from the 
study products, even serious or life threatening ones, that we do not yet know about.  We will tell 
you if we learn about any important new findings or serious side effects of the vaccine during the 
study that may change your mind about your willingness to continue participation.  
You may not donate blood while taking part in this study.  You may not donate blood for one 
year after the date of your last product administration. 
POSSIBLE BENEFITS 
This study is not designed to benefit you or to protect you from Zika infection.  You and others 
may benefit in the future from the information that we learn from the study. 

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COSTS OF PARTICIPATION 
There are no costs to you for taking part in this study.  You or your health insurance will have to 
pay for all medical costs for medical care that you get outside of this study.  It is possible that 
you may have some costs that are not covered by the study compensation we give you. 
COMPENSATION TO YOU FOR TAKING PART IN THE STUDY 
You will be compensated [insert site IRB/EC-approved amount] for taking part in this study 
as follows: [insert site plan].  Total compensation will be based on the number of study visits 
you attend and the number of product administrations you get [or insert site plan].   
REASONS FOR REMOVING YOU FROM THE STUDY WITHOUT YOUR CONSENT 
The study doctor can take you out of this study without your consent if: 
• continuing in the study could hurt you,  
• you do not follow study instructions or keep your appointments, or  
• the study is stopped by the US NIH, FDA, or regulatory authorities.   
If you agree to take part in this study, it is important for you to keep all of your appointments. 
However, if you do not 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 get at least one product administration, 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 check your health 
even if you do not get the second or third product administrations. 
ALTERNATIVES 
This study is not designed to treat or prevent any disease.  You may choose not to take part. 
CONFIDENTIALITY 
[Site/country-specific information on confidentiality may be added to this section.] 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required 
by US law.  This website will not include information that can identify you.  At most, the 
website will include a summary of the study results.  You can search this website at any time.  
Results of US NIH-supported research studies may also be reported in medical journals, on the 
internet or at scientific meetings.  These reports will not have information that can identify you.   
In most cases, the US 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 gets information from your medical 
record.  This information might affect (either positively or negatively) if the insurance company 
sells insurance to you. 
POLICY REGARDING RESEARCH-RELATED INJURIES 
The study site will provide immediate medical care for any injury resulting from you being in 
research here.  In general, no long-term medical care or financial compensation for research-

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related injuries will be provided by the US NIH or the US Federal Government.  However, you 
have the right to seek legal action if you think that your injury has a good reason for such action. 
PROBLEMS OR QUESTIONS 
If you have any problems or questions about this study, about your rights as a research subject, 
or about any research-related injury, call the Principal Investigator [insert site PI information].  
You may also call the Study Coordinator [insert site SC information] or the Patient 
Representative at [insert site Patient Representative, as applicable] 
Please keep a copy of this form in case you want to read it again. 

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SUBJECT CONSENT 
I have read the explanation about this study and have been given the opportunity to discuss it 
and to ask questions.  All my questions have been answered to my satisfaction.  I consent to 
take part in this study. 
 
Subject Name (print): 
 
Date and Time: 
Signature: 
 
PARENT/GUARDIAN CONSENT 
I/we have read the explanation about this study and have been given the opportunity to 
discuss it and to ask questions.  All my/our questions have been answered to my/our 
satisfaction.  I/we hereby give permission for my child to take part in this study.   
Parent/Guardian (1) permission for minor patient, if applicable (print): 
 
Date: 
Signature:  
 
Parent/Guardian (2, if applicable per site/country regulations) permission 
for minor patient, if applicable (print): 
 
Date: 
Signature:  
 
 
 
Investigator Name (print): 
 
Date: 
Signature: 
 

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Template: Study Assent Form – Part B 
STUDY TITLE:  VRC 705: A Phase 2/2B, Randomized Trial to Evaluate the Safety, 
Immunogenicity and Efficacy of a Zika Virus DNA Vaccine in Healthy Adults and Adolescents 
 
INTRODUCTION 
We invite you to take part in a research study conducted at the [insert site name].  
The study is sponsored by the National Institutes of Health (NIH) in Bethesda, MD, US.  You 
can choose if you want to take part in this study or not.  There is no penalty or loss of benefits for 
choosing not to take part in this study.  Please ask questions and discuss this study with anyone 
you want.  Take as much time as you need to decide.  You will be given a copy of this assent 
form. 
SCREENING  
Before you can take part in this experimental Zika DNA vaccine study, your health will be 
checked so we can decide if you qualify.  You will need to sign this assent form before 
screening.  If you qualify, then you may take part in the vaccine study. 
Screening includes a physical exam and blood tests to check your health.  We will ask you 
about your health history.  If you are a female who is able to have children, you will be asked 
about the possibility of you becoming pregnant while in the study.  You will be tested for 
pregnancy.  During screening, we will collect some blood to store for research.  We will 
review the test results with you and tell you if the results show that you are eligible to join the 
study.   
PURPOSE OF THIS STUDY 
This is a research study of an experimental vaccine against Zika virus infection. 
“Experimental” means that the study vaccine has not been approved by the US Food and Drug 
Administration (FDA).  The FDA allows this vaccine to be used for research purposes only.  
This vaccine has been given to people in a Phase 1 study.  We do not know if the vaccine 
works.  The main purpose of this study is to see if the experimental vaccine is safe and if there 
are any side effects.  We also want to study immune responses to the vaccine including cells 
that may recognize and fight Zika virus.  This study will take place in areas where Zika 
outbreaks are happening or may happen.   
BACKGROUND ON ZIKA VIRUS  
Zika virus was discovered in 1947.  It is named after the Zika Forest in Uganda where it was 
found.  Until recently, Zika infections happened in parts of Africa and Asia.  Recent outbreaks 
have been reported in North, Central and South America, the Caribbean, the Pacific Islands, and 
Africa.   
Zika is passed from human to human by infected mosquitos.  Zika can also be passed through 
sex from a person who has Zika to his or her partners, and from a mother to her child during 
pregnancy.  Zika infection causes symptoms that are usually mild and may include fever, rash, 
joint pain, and conjunctivitis (red eyes).  Many times, there are no symptoms at all, so many 

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people do not know that they have been infected.  Symptoms usually last from 2 to 7 days.  
People usually don’t get sick enough to go to the hospital, and they very rarely die.  A person 
who has been infected once is not likely to get Zika infection again.   
Recently, some cases of microcephaly (abnormally small head and brain) and other birth defects 
were found in babies that were born to mothers who had a Zika infection.  Some people who had 
Zika infection also had rare cases of a severe muscle weakness called Guillain-Barré syndrome.  
We do not know why some people who get Zika infection develop Guillain-Barré syndrome.  
Most people who develop Guillain-Barré syndrome recover over time.  If you have ever had this 
condition, you will not qualify for this study.  
There is currently no cure for or vaccine to prevent Zika infection. 
We will tell you if we learn anything new during this study that might cause you to change your 
mind about staying in the study.  At the end of the study, we will tell you when study results may 
be available and how to learn about them.  
STUDY PLAN 
This study has 2 parts, Part A and Part B.  Part A of the study has 3 groups with a total of 90 
people.  We will test the vaccine at doses of 4 milligrams (mg) or 8 mg split into either 2 or 4 
injections.  Part A will last for 32 weeks or about 8 months.  Part B of the study has 2 groups 
with a total of about 2400 people.  We will test the vaccine in comparison to the placebo, 
which is a salt-water solution that has no vaccine in it.  Part B will last for 96 weeks or about 
24 months. 
By signing this form, you are agreeing to take part in Part B.  The plan for Part B is below: 
VRC 705 – Part B 
Group 
Subjects 
Dose 
Number of 
Injections  
Location of 
Injections  
Product Administration 
Day 0 
Week 4 
Week 8 
4 
1200 
4 mg 
2 
both arms 
vaccine 
vaccine 
vaccine 
5 
1200 
0 
2 
both arms 
placebo 
placebo 
placebo 
Total 
2400 
Study products are given into the muscle by needle-free injection device. 
STUDY PRODUCTS 
There are two study products in Part B of this study, the Zika vaccine and the salt water solution 
(or placebo).  Half of the people in the study will get the vaccine and half will get the placebo.   
1. Vaccine:  In this study, the vaccine being tested is VRC-ZKADNA090-00-VP which is 
called the ‘Zika DNA vaccine’ or ‘Zika vaccine’.  The Zika vaccine was developed by 
the Vaccine Research Center (VRC) at the US NIH.  It was made at the VRC Pilot Plant 
in Frederick, Maryland, US.   

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Vaccines are given to help the body fight off an infection.  When you get a dose of this 
vaccine, it should cause your body to make a small amount of Zika protein.  Your body 
may use this protein to build an immune response against Zika.   
There is no Zika virus in this vaccine. You cannot get Zika infection from this vaccine. 
You should not expect this experimental Zika vaccine to protect you from Zika infection.  
You must take steps to protect yourself if you think you might be exposed to Zika in your 
environment.  You should avoid mosquitos, use mosquito repellant, wear long sleeves 
and pants, and use bed nets at night.  If you have any side effects that seem like Zika 
infection (including fever, rash, eye pain, red eyes, muscle aches, headache, or joint pain) 
while on the study, tell the study team right away so we can check you as soon as 
possible. 
2. Placebo:  The placebo in this study is a sterile salt water solution made for injection into 
people.  It has no vaccine in it.  We use the placebo as a control for the vaccine, so we 
can compare to the vaccine and see how it works. 
ELIGIBILITY 
You may qualify to take part in this study if: 
• you are between [insert site-specific age range that applies to minors] years of age,  
• you agree not to become pregnant for at least 12 weeks after you get the last product 
administration, which is about 5 months after the study begins, 
• you have physical exam and blood test results that meet study requirements, and  
• you do not have any serious medical problems as determined by your screening.  
STUDY PROCEDURES 
About 2400 people will take part in Part B of this study.  If you agree to join Part B, you will be 
assigned to one of the two study groups by chance (like flipping a coin).  You and the clinic staff 
will not know which study product you are getting until after the study is over.   
You will get a total of 3 product administrations.  A product administration will be given at 3 
separate visits that are each about 4 weeks apart.  You will get 2 injections at each product 
administration visit.  We will give all injections using the needle-free injection device called the 
PharmaJet Stratis® Needle Free Jet Injector (PharmaJet).  PharmaJet injections will be given into 
the upper muscle on each arm.  In special cases, PharmaJet injections may also be given into the 
muscle on the upper thigh. 
PharmaJet injects the vaccine into your body without using a needle.  Instead of a needle, 
PharmaJet uses high pressure to push the vaccine through your skin into the muscle. Even though 
there is no needle, it may still cause pain.  Needle-free devices have been used to give vaccines 
and other medications since the 1940s.  This device has been cleared by the FDA for giving 
vaccine injections into the muscle.  Studies have shown that some people who get injections with 
PharmaJet have more local reactions at the injection site than people who get injections with 
needle and syringe.  However, the local reactions were mild. 

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If you are a female who is able to get pregnant, you will be given a pregnancy test before you get 
each product administration.  The test must show that you are not pregnant before we can give 
you the study product. 
We will watch you for at least 15 minutes after you get each full dose of study product, which is 
after you get both injections.   
We will ask you to complete a diary card for 7 days after each product administration.  You will 
use the diary card to write down your highest temperature each day and any side effects that you 
feel.  You will also need to look at the injection sites each day and write down how it looks and 
any side effects that you see.  We will give you a thermometer and a measuring device to do this.  
We will ask you to review your diary card with us about a week later.   
The clinic staff is available to you by phone 24 hours a day to report any unexpected side effects.  
If you have any concerning side effects or if you feel sick, you should tell the clinic right away.  
We may ask you to come into the clinic for an examination before your next scheduled visit.  It 
is very important that you follow the instructions we give you.  
Follow-Up Visits 
You will be in the study for about 2 years after you get the first product administration.  You will 
have about 19 to 25 clinic visits and 3 telephone contacts.  Each clinic visit will last about [insert 
site standard length of clinic visit].   
At each visit, we will ask you about 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 1-
13 tubes of blood from you, depending on the visit.  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.  
Experimental vaccine studies like this one follow a set schedule.  The study schedule for your 
visits allows some flexibility, but it is important that you work with the staff to follow the set 
schedule as much as possible.  You should try to not miss any visits.   
Sample Collection for Zika Diagnosis  
At any time during the study, if you think you have Zika infection, you must contact our clinic 
right away.  We will ask you to come in for a clinical examination and we may collect blood and 
urine so that we can test you for Zika infection.  If you have a rash or another sign or symptom of 
illness that could possibly be a Zika infection, we may take a photograph of the affected area 
with your permission.  These photographs will not identify you in any way and will only be used 
by the study team to evaluate your illness.  We may also test for other infections that have 
symptoms similar to Zika infection.   
We will tell you the results of your test for Zika infection but it may take several weeks to get the 
results.  It is very important that you get tested for Zika infection at our clinic only and that you 
do not get tested elsewhere unless it is necessary for your health, for example, while traveling. 
Sample Collection for Zika Research 
Many people who have Zika infection do not feel sick even when there is virus in their blood, 
urine, or other bodily fluids.  As part of this study, we will collect blood samples from you about 
once a month for the first year and then every two months for the whole study (which is 96 

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weeks) so we can test for Zika infection.  The sample collection plans may change if you get 
Zika infection.  We will collect these samples for research purposes only. 
VOLUNTARY PARTICIPATION  
Your participation in this study is completely voluntary.  You can choose to stop taking part in 
the study at any time during the study.  There is no penalty or loss of benefits for choosing to 
leave the study at any time. 
MONITORING OF THE STUDY 
This study will be monitored by a group of physicians and scientists associated with the US NIH.  
This group will review the study information and will pay close attention to any reactions that 
people have to the study products. 
STORED SAMPLES 
We will collect blood and other bodily fluids such as urine from you during this study.  We will 
keep these samples to study your immune response to the study product and for future research 
to learn more about Zika, vaccines, the immune system or other related medical conditions.  The 
urgency of the Zika epidemic has accelerated the development of Zika tests and assays.  Samples 
from study subjects may be an important part in the development of new assays to diagnose and 
to study Zika infections.  No genetic research (deoxyribonucleic acid [DNA] testing) will be 
done on these samples. 
[Add as required per local/national regulations]:  Research samples will be shipped to the 
Fisher BioServices (Germantown, MD, US) storage facility.  Research samples may be stored for 
up to 20 years.  Stored samples may be sent for testing by any of the following laboratories: 
• VRC/NIAID Vaccine Immune T-Cell and Antibody Laboratory (NVITAL; Rockville, 
MD, US) 
• NIAID Laboratory of Infectious Diseases (LID; Bethesda, MD, US) 
• Battelle, Biomedical Research Center (West Jefferson, OH, US) 
• Z-Quick/University of Miami Life Science and Technology Park (Miami, FL, US) 
• Blood Systems Research Institute (BSRI, San Francisco, CA, US) 
• PaxVax (San Diego, CA, US)  
As new tests are developed, additional laboratories may use your stored samples for testing.  
These laboratories are unknown at this time.  
Results from the research done with your stored samples are not for diagnostic purposes or 
medical care.  Therefore, the results will not be part of your medical record.  
Labeling of Stored Samples:  Your stored samples will be labeled by a special code or number 
that only the study team can link to you.  Any identifying information about you, like your name 
or date of birth, will be kept as confidential as allowable 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 researchers at NIH or outside of NIH may wish to study 
your stored samples.  When the study team shares your samples, they will be marked with a 
code.  Your samples will not have any information on them that could identify you.  Some 
information about you, such as your gender, age, health history, or ethnicity may be shared.  Any 

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future research done with your samples will be done in a way that protects the rights and privacy 
of study subjects. 
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 get payment for 
these products. 
HUMAN DATA SHARING 
To advance science, it is helpful for researchers to share information they get from studying 
humans by putting it into shared scientific databases.  Researchers can then study the information 
combined from many studies to learn even more about health and diseases.  
If you agree to take part in this study, some of your data will be placed into one or more 
scientific databases.  We will remove identifying information like your name, address, and birth 
date.  The data may then be used for future research and shared broadly for research purposes. 
Only researchers who are approved to access the database may be able to see and use your 
information.  You will not get any direct benefits from future research that uses your data and 
information.   
You may stop participating in this study at any time and withdraw permission for your individual 
data, specimens, and health information to be used for additional or future research.  You may 
ask to have your research data destroyed.  However, it may not be possible to withdraw or delete 
data once they have been shared with other researchers. 
POSSIBLE STUDY RISKS 
Possible risks from the injections:  Temporary stinging, pain, redness, soreness, itchiness, 
swelling, or bruising.  Injections given with the needle-free device have been shown to cause a 
small cut at the injection site.  A small scab may form within 1 to 2 weeks after the injection is 
given.  There is a very small chance of infection. 
There is also a small chance that the needle-free device could not work properly.  This includes 
the syringe breaking and study product spraying during administration.  No subjects were 
harmed when the device did not work.  As a result, we ask that you wear safety glasses while we 
give the injections. 
Possible risks of blood drawing:  Pain, bleeding, bruising, feeling lightheaded, or fainting, and 
rarely, infection at the site where blood is taken. 
Possible risks from any vaccine:  Fever, chills, rash, aches and pains, nausea, headache, 
dizziness, and feeling tired or unwell.  Some people have allergic reactions to vaccines.  These 
types of reactions are usually greatest within the first 24 hours after an injection and typically last 
1 to 3 days.  Medicines, such as acetaminophen, may be used to help relieve these symptoms. 
Very rarely, a serious allergic reaction with symptoms such as hives, trouble breathing, or 
sudden weakness may happen shortly after any vaccination.  This is called “anaphylaxis” and 
may be life-threatening.  While you are waiting in the clinic after the injections, we will monitor 
you for anaphylaxis.  Treatment for anaphylaxis will be given right away if it happens.   
Possible risks of DNA vaccines:  Temporary drop in white blood cell count, sore arm, skin rash 
or hives, some people get a small red bump and then a scab for a few days where the injection is 

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given.  The NIH has tested many similar vaccines made by the VRC and these vaccines were 
found to be safe and well-tolerated.  We expect this vaccine to be like the ones tested before. 
Possible risks of the Zika DNA vaccine:  As of July 2018, this Zika vaccine has been tested in 
45 subjects in the Phase 1 study, VRC 320.  The most common complaints after injection by 
PharmaJet are mild headache, feeling tired or unwell, and mild pain and bruising at the injection 
site. 
A very similar Zika vaccine has been tested in 80 subjects in the Phase 1 study, VRC 319.  As of 
July 2018, that experimental vaccine was found to be safe for additional studies in humans.  The 
most common complaints after injection by needle and syringe have been arm soreness, 
headache, muscle aches and feeling tired or unwell. 
This Zika vaccine does not contain Zika virus.  Guillain-Barré syndrome has not been seen with 
similar vaccines or vaccines made against similar viruses.  We do not know if there is a risk of 
Guillain-Barré syndrome from the study vaccine.  However, we have to be very cautious and 
observant with a Zika vaccine.  This is because natural Zika infection seems to be associated 
with Guillain-Barré syndrome and we don’t know how Zika might cause Guillain-Barré 
syndrome.  You should tell the study team if you develop weakness or tingling in your arms or 
legs or any other unusual symptoms.  
Possible risks during Pregnancy:  We do not know if getting the study products will affect a 
fetus.  Therefore, women and adolescents who can get pregnant must agree to use an effective 
method of birth control starting at least 21 days before getting the first product administration 
until 12 weeks after the last product administration.  We will discuss effective birth control 
methods with you.  If you are pregnant or want to become pregnant in the next 20 weeks, you 
cannot participate.   
During the study, if you think you might be pregnant, you must tell the clinic staff right away.  
If you are pregnant, you will not get any more study product.  We will give you resources you 
can use to learn about protecting yourself from getting Zika infection.  You will be asked to 
continue with some follow-up visits.  We will ask you about the outcome of the pregnancy. 
Unknown risks:  We do not know if the study product will affect how you respond to any future 
Zika infection or Zika vaccine that you may get in the future.  There may be side effects from the 
study products, even serious or life threatening ones, that we do not yet know about.  We will tell 
you if we learn about any important new findings or serious side effects of the vaccine during the 
study that may change your mind about your willingness to continue participation.  
You may not donate blood while taking part in this study.  You may not donate blood for one 
year after the date of your last product administration. 
POSSIBLE BENEFITS 
This study is not designed to benefit you or to protect you from Zika 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 taking part in this study.  You or your health insurance will have to 
pay for all medical costs for medical care that you get outside of this study.  It is possible that 
you may have some costs that are not covered by the study compensation we give you. 

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COMPENSATION TO YOU FOR TAKING PART IN THE STUDY 
You will be compensated [insert site /EC-approved amount] for taking part in this study as 
follows: [insert site plan].  Total compensation will be based on the number of study visits you 
attend and the number of product administrations you get [or insert site plan].   
REASONS FOR REMOVING YOU FROM THE STUDY WITHOUT YOUR CONSENT 
The study doctor can take you out of this study without your consent if: 
• continuing in the study could hurt you,  
• you do not follow study instructions or keep your appointments, or  
• the study is stopped by the US NIH, FDA, or regulatory authorities.   
If you agree to take part in this study, it is important for you to keep all of your appointments. 
However, if you do not 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 get at least one product administration, 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 check your health 
even if you do not get the second or third product administrations. 
ALTERNATIVES 
This study is not designed to treat or prevent any disease.  You may choose not to take part. 
CONFIDENTIALITY 
[Site/country-specific information on confidentiality may be added to this section.] 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required 
by US law.  This website will not include information that can identify you.  At most, the 
website will include a summary of the study results.  You can search this website at any time.  
Results of US NIH-supported research studies may also be reported in medical journals, on the 
internet or at scientific meetings.  These reports will not have information that can identify you.   
In most cases, the US 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 gets information from your medical 
record.  This information might affect (either positively or negatively) if the insurance company 
sells insurance to you. 
POLICY REGARDING RESEARCH-RELATED INJURIES 
The study site will provide immediate medical care for any injury resulting from you being in 
research here.  In general, no long-term medical care or financial compensation for research-
related injuries will be provided by the US NIH or the US Federal Government.  However, you 
have the right to seek legal action if you think that your injury has a good reason for such action. 

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PROBLEMS OR QUESTIONS 
If you have any problems or questions about this study, about your rights as a research subject, 
or about any research-related injury, call the Principal Investigator [insert site PI information].  
You may also call the Study Coordinator [insert site SC information] or the Patient 
Representative at [insert site Patient Representative, as applicable]. 
Please keep a copy of this form in case you want to read it again. 
 

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SUBJECT ASSENT 
I have had this study explained to me in a way that I understand, and I have had the chance to 
ask questions.  All my questions have been answered to my satisfaction.  I agree to take part in 
this study. 
 
Subject Name (print): 
 
Date and Time: 
Signature: 
 
PARENT/GUARDIAN CONSENT 
I/we have read the explanation about this study and have been given the opportunity to 
discuss it and to ask questions.  All my/our questions have been answered to my/our 
satisfaction. I/we hereby give permission for my/our child to take part in this study.   
Parent/Guardian (1) permission for minor patient, if applicable (print): 
 
Date: 
Signature:  
 
Parent/Guardian (2, if applicable per site/country regulations) permission 
for minor patient, if applicable (print): 
 
Date: 
Signature:  
 
 
 
Investigator Name (print): 
 
Date: 
Signature: 
 

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APPENDIX II: 
PROTOCOL TEAM AND CONTACT INFORMATION  
 

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APPENDIX III: 
SCHEDULE OF EVALUATIONS

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TABLE A:  SCHEDULE OF EVALUATIONS – SCREENING (PART A and PART B) 
Visit Number 
 
01 
Week of Study 
 
Week -8 to Day 0 
1Day of Study 
 
Day -56 to Day 0 
Screening  
4Tube 
Screen 
Assessment of Understanding (AoU) 
 
X 
Informed Consent 
 
X 
Enrollment  
 
X 
Pregnancy Prevention Counseling 
 
X 
HIV Prevention Counseling 
 
X 
Screening Laboratory Tests 
 
 
Pregnancy Test (urine or serum) 
 
2X 
CBC with differential 
EDTA 
3 
ALT, Creatinine 
SST 
4 
HIV Test 
SST 
4 
Clinical Evaluations 
 
 
Medical History 
 
X 
3Physical Examination 
 
X 
4Research Samples 
 
 
Serum for storage 
SST 
32 
PBMC and plasma for storage 
EDTA 
5[20] 
Total Blood Volume (mL) 
 
63 
 
1 Screening evaluations may be repeated or completed over more than one visit, if needed. Screening research blood 
draw and consent obtained more than 56 days prior to enrollment are not required to be repeated. 
2 A pregnancy test is not required for women determined to be of non-childbearing potential or for men.  
3 Physical examination assesses eligibility criteria and includes measurement of vital signs and height/weight.   
4 Tube types/volumes are shown to estimate blood volumes in mL.  Different tubes for clinical evaluations 
may be used to meet site requirements but research sample tubes must be used as shown or as instructed 
by the IND Sponsor.  
5 Brackets [ ] indicate that only approved sites will collect the samples for PBMC and plasma storage. 
 

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Visit windows: Visits 02A, 03A, 04A (+3 days); Visits 03B and 04B (±2 days); Visits 03, 05, 06, 07, 08, 09, 10 (±7 days); Visit 04 (-7 days/+14 days; product 
administrations must be at least 21 days apart).   Schedule Visit 02A relative to Visit 02, Visit 03A and 03B relative to Visit 03, Visits 04A through 10 relative to Visit 04, if 
all product administrations are given as scheduled.  Refer to Section 4.2.6.1 for scheduling instructions if all product administrations are not given as scheduled. 
1 Targeted physical examination is only performed as needed, based on subject report or other indications of illness; brackets [ ] indicate optional, as needed. 
2 Pregnancy prevention counseling and pregnancy testing are to be added to every visit, as shown in brackets [ ], for any subject of childbearing potential with confirmed ZIKV 
infection.  A pregnancy test and pregnancy prevention counseling are not required for women determined to be of non-reproductive potential or for men throughout the study.  
3 Brackets [ ] indicate that only approved sites will collect samples for PBMC and plasma storage. Tube types/volumes are shown to estimate blood volumes in mL. 
4 Different tubes for clinical evaluations may be used to meet site requirements but research sample tubes must be used as shown or as instructed by the IND Sponsor. 
TABLE B:  SCHEDULE OF EVALUATIONS – PART A 
Visit Number 
 
02 
02A 
03 
03A 
03B 
04 
04A 
04B 
05 
06 
07 
08 
09 
10 
Week of Study 
 
W0 
W1 
W4 
W5 
W6 
W8 
W9 
W10 
W12 
W16 
W20 
W24 
W28 
W32 
Day of Study 
 
D0 
D7 
D28 
D35 
D42 
D56 
D63 
D70 
D84 
D112 
D140 D168 D196 
D224 
Clinical Evaluations 
4Tube 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical History Review 
 
X 
 
X 
 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
Vital Signs 
 
X 
 
X 
 
X 
X 
 
X 
X 
X 
 
 
 
 
1Targeted Physical Examination 
 
[X] 
 
[X] 
 
[X] 
[X] 
 
[X] 
[X] 
[X] 
[X] 
[X] 
[X] 
[X] 
2Pregnancy Prevention Counseling  
 
X 
 
X 
 
[X] 
X 
 
[X] 
[X] 
X 
X 
[X] 
[X] 
[X] 
2Pregnancy Test 
 
[X] 
 
X 
 
[X] 
X 
 
[X] 
[X] 
X 
X 
[X] 
[X] 
[X] 
Eligibility Confirmation  
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization  
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Product Administration 
 
X 
 
X 
 
 
X 
 
 
 
 
 
 
 
 
Begin Diary Card 
 
X 
 
X 
 
 
X 
 
 
 
 
 
 
 
 
Phone Contact (clinic visit if needed) 
 
 
X 
 
X 
 
 
X 
 
 
 
 
 
 
 
CBC with differential 
EDTA 
3 
 
3 
 
3 
3 
 
3 
3 
3 
 
 
 
 
ALT 
SST 
4 
 
4 
 
4 
4 
 
4 
4 
4 
 
 
 
 
Research Samples  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum 
SST 
40 
 
16 
 
16 
16 
 
16 
16 
16 
16 
16 
16 
16 
3PBMC and plasma  
EDTA 
[40] 
 
[40] 
 
[40] 
[40] 
 
[40] 
[40] 
[40] 
[40] 
[40] 
[40] 
[40] 
Daily Volume (mL) 
 
87 
- 
63 
- 
63 
63 
- 
63 
63 
63 
56 
56 
56 
56 
Cumulative Volume (mL) 
 
87 
87 
150 
150 
213 
276 
276 
339 
402 
465 
521 
577 
633 
689 

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Visit windows: Visits 02A, 03A, 04A (+3 days); Visits 03, 05, 06, 07, 08, 09, 10, 11, 12 (±7 days); Visit 04 (-7 days/+14 days; product administrations must 
be at least 21 days apart).  Schedule Visit 02A relative to Visit 02, Visit 03A relative to Visit 03, Visits 04A through 26 relative to Visit 04, if all product 
administrations are given as scheduled.  Refer to Section 4.2.6.1 for scheduling instructions if all product administrations are not given as scheduled. 
1 Full medical history review at screening, then perform an interim medical history review from V02 through end of study. 
2 Targeted physical examination is only performed as needed, based on subject report or other indications of illness; brackets [ ] indicate optional, as needed. 
3 A pregnancy test and pregnancy prevention counseling are not required for females of non-childbearing potential or for men throughout the study.  Pregnancy prevention 
counseling and pregnancy testing are to be added to every visit, as shown in brackets [ ], for any subject of childbearing potential with ZIKV infection.   
4 Brackets [ ] indicate that only approved sites will collect samples for PBMC and plasma. 
5 Scheduled collection of whole blood and serum research samples to evaluate asymptomatic ZIKV infection can occur outside of visit windows without permission but should be 
recorded as a protocol deviation.  Every effort should be made to obtain these samples once a month.  
6 Tube types/volumes are shown to estimate blood volumes in mL.  Different tubes for clinical evaluations may be used to meet site requirements but research sample tubes must 
be used as shown or as instructed by the IND Sponsor.  
TABLE C:  SCHEDULE OF EVALUATIONS – PART B 
Visit Number 
 
02 
02A 
03 
03A 
04 
04A 
05 
06 
07 
08 
09 
10 
11 
12 
Week of Study 
 
W0 
W1 
W4 
W5 
W8 
W9 
W12 
W16 
W20 
W24 
W28 
W32 
W36 
W40 
Day of Study 
 
D0 
D7 
D28 
D35 
D56 
D63 
D84 
D112 
D140 
D168 
D196 
D224 
D252 
D280 
Clinical Evaluations 
6Tube 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1Medical History Review 
 
X 
 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Vital Signs 
 
X 
 
X 
 
X 
 
 
X 
 
 
 
 
 
 
2Targeted Physical Examination 
 
[X] 
 
[X] 
 
[X] 
 
[X] 
[X] 
[X] 
[X] 
[X] 
[X] 
[X] 
[X] 
3Pregnancy Prevention Counseling  
 
X 
 
X 
 
X 
 
[X] 
[X] 
X 
[X] 
[X] 
[X] 
[X] 
[X] 
3Pregnancy Test 
 
X 
 
X 
 
X 
 
[X] 
[X] 
X 
[X] 
[X] 
[X] 
[X] 
[X] 
Eligibility Confirmation  
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization  
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Product Administration 
 
X 
 
X 
 
X 
 
 
 
 
 
 
 
 
 
Begin Diary Card 
 
X 
 
X 
 
X 
 
 
 
 
 
 
 
 
 
Phone Contact (clinic visit if needed) 
 
 
X 
 
X 
 
X 
 
 
 
 
 
 
 
 
CBC with differential 
EDTA 
3 
 
3 
 
3 
 
 
3 
 
 
 
 
 
 
ALT 
SST 
4 
 
4 
 
4 
 
 
4 
 
 
 
 
 
 
Research Samples  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum 
SST 
32 
 
16 
 
16 
 
16 
16 
8 
8 
8 
8 
8 
8 
4PBMC and plasma  
EDTA 
[40] 
 
[40] 
 
[40] 
 
[40] 
[40] 
 
 
 
 
 
 
5Whole blood (red blood cells and plasma) 
EDTA 
10 
 
10 
 
10 
 
10 
10 
10 
10 
10 
10 
10 
10 
Daily Volume (mL) 
 
89 
- 
73 
- 
73 
- 
66 
73 
18 
18 
18 
18 
18 
18 
Cumulative Volume (mL) 
 
89 
89 
162 
162 
235 
235 
301 
374 
392 
410 
428 
446 
464 
482 

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TABLE C:  SCHEDULE OF EVALUATIONS – PART B (continued) 
Visit Number 
 
13 
14 
16 
18 
20 
22 
24 
26 
Week of Study  
 
W44 
W48 
W56 
W64 
W72 
W80 
W88 
W96 
Day of Study 
 
D308 
D336 
D392 
D448 
D504 
D560 
D616 
D672 
Clinical Evaluations 
6Tube 
 
 
 
 
 
 
 
 
1Medical History Review 
 
X 
X 
X 
X 
X 
X 
X 
X 
2Targeted Physical Examination 
 
[X] 
[X] 
[X] 
[X] 
[X] 
[X] 
[X] 
[X] 
3Pregnancy Prevention Counseling  
 
[X] 
[X] 
[X] 
[X] 
[X] 
[X] 
[X] 
[X] 
3Pregnancy Test 
 
[X] 
[X] 
[X] 
[X] 
[X] 
[X] 
[X] 
[X] 
CBC with differential 
EDTA 
3 
 
 
 
 
 
 
 
ALT 
SST 
4 
 
 
 
 
 
 
 
Research Samples  
 
 
 
 
 
 
 
 
 
Serum 
SST 
16 
8 
8 
8 
16 
8 
8 
16 
4PBMC and plasma  
EDTA 
[40] 
 
 
 
[40] 
 
 
[40] 
5Whole blood (red blood cells and plasma) 
EDTA 
10 
10 
10 
10 
10 
10 
10 
10 
Daily Volume (mL) 
 
73 
18 
18 
18 
66 
18 
18 
66 
Cumulative Volume (mL) 
 
555 
573 
591 
609 
675 
693 
711 
777 
Visit windows: Visits 13 through 26 (±7 days). 
1  Perform an interim medical history review from V02 through end of study. 
2 Targeted physical examination is only performed as needed, based on subject report or other indications of illness; brackets [ ] indicate optional, as needed. 
3 A pregnancy test is not required for females of non-childbearing potential or men throughout the study. Pregnancy prevention counseling and pregnancy testing are to be added to 
every visit, as shown in brackets [ ], for any subject of childbearing potential with ZIKV infection.   
4 Brackets [ ] indicate that only approved sites will collect samples for PBMC and plasma storage. 
5 Scheduled collection of research blood samples to evaluate asymptomatic ZIKV infection can occur outside of visit windows without permission but should be recorded as a 
protocol deviation.  Every effort should be made to obtain these samples once a month.  
6 Tube types/volumes are shown to estimate blood volumes.  Different tubes for clinical evaluations may be used to meet site requirements but research sample tubes must be used 
as shown or as instructed by the IND Sponsor. 
* As of protocol version 5.0 approval at site, study visits 15, 17, 19, 21, 23, and 25 are not required.  If the visit is scheduled to occur for the subject prior to V5.0 approval, then 
the visit should be conducted.   

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

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Assessment of Causality Relationship of an Adverse Event to Study Product:  
The relationship between an adverse event (AE) and the product will be assessed by the 
investigator on the basis of his or her clinical judgment and the definitions below. 
• Definitely Related. The AE and study product are related in time and a direct association 
can be demonstrated. 
• Probably Related. The AE and study product are reasonably related in time and the AE 
is more likely explained by study product than other causes.  
• Possibly Related. The AE and study product are reasonably related in time but the AE 
can be explained equally well by causes other than study product. 
• Not Related. There is not a reasonable possibility that the AE is related to the study 
product.  
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 
product. 
• Not Related – There is not a reasonable possibility that the AE is related to the study 
product. 
Grading the Severity of Adverse Events: 
The FDA Guidance for Industry (September 2007): “Toxicity Grading Scale for Healthy Adult 
and Adolescent Volunteers [Subjects] 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 potentially 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 (Potentially 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 [Subjects] 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  

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

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Hematology* 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially Life 
Threatening 
(Grade 4) 
Hemoglobin (Female) - 
gm/dL  
11.0 – 12.0  
9.5 – 10.9  
8.0 – 9.4  
< 8.0  
Hemoglobin (Female)  
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. 
 

 
 
STATISTICAL ANALYSIS PLAN 
for 
Protocol VRC 705 
Study Title: 
A Phase 2/2B, Randomized Trial to Evaluate the 
Safety, Immunogenicity and Efficacy of a Zika Virus 
DNA Vaccine in Healthy Adults and Adolescents 
 
 
ClinicalTrials.gov Registration: 
NCT03110770 
 
 
Version 1.0 
DATE: November 11, 2019 
 
 
 
 
 
 
 
 
THIS COMMUNICATION IS PRIVILEGED AND CONFIDENTIAL. 
 

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Version 1.0 
 
 
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STUDY TITLE 
Protocol Number Code: 
Protocol VRC 705 
Development Phase: 
Phase 2/2B 
Products: 
VRC-ZKADNA090-00-VP (ZIKVwt DNA vaccine) 
VRC-PBSPLA043-00-VP (sterile phosphate-buffered saline) 
Form/Route: 
IM administration via PharmaJet Stratis® 0.5 mL Needle-
Free Jet Injector (PharmaJet) 
Indication Studied: 
Zika virus 
Sponsor: 
Vaccine Research Center 
Clinical Trial Initiation Date: 
Part A: March 29, 2017 
Part B: July 19, 2017 
Clinical Trial Completion Date: TBD 
Date of the Analysis Plan: 
November 11, 2019 
Version Number: 
1.0 
 

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TABLE OF CONTENTS 
STUDY TITLE ............................................................................................................................... II
LIST OF ABBREVIATIONS ......................................................................................................... V
1.
PREFACE .....................................................................................................................1
2.
INTRODUCTION ........................................................................................................2
2.1.
Purpose of the Analyses ................................................................................................2
3.
STUDY OBJECTIVES AND ENDPOINTS ................................................................4
3.1.
Study Objectives ...........................................................................................................4
3.2.
Endpoints ......................................................................................................................4
3.2.1.
Study Definitions and Derived Variables .....................................................................4
4.
INVESTIGATIONAL PLAN .......................................................................................4
4.1.
Overall Study Design and Plan .....................................................................................4
4.2.
Discussion of Design, Including the Choice of Control Group ....................................4
4.3.
Selection of Study Population ......................................................................................4
4.4.
Study Product Administrations .....................................................................................4
4.4.1.
Study Product................................................................................................................4
4.4.2.
Vaccine Dose and Administration Method ...................................................................4
4.4.3.
Method of Assigning Subjects to Study Groups (Randomization) ..............................4
4.4.4.
Blinding and Conditions for Unblinding ......................................................................5
5.
SAMPLE SIZE CONSIDERATIONS .........................................................................5
6.
GENERAL STATISTICAL CONSIDERATIONS ......................................................6
6.1.
General Principles .........................................................................................................6
6.2.
Timing of Analyses .......................................................................................................7
6.3.
Analysis Populations ....................................................................................................7
6.4.
Covariates and Subgroups ............................................................................................9
6.5.
Missing Data .................................................................................................................9
6.6.
Interim Analyses and Data Monitoring ........................................................................9
6.6.1.
Independent Safety Reviews.........................................................................................9
6.6.2.
Immunogenicity Reviews: ..........................................................................................10
6.6.3.
Incidence Reviews (Part B only): ...............................................................................10
6.7.
Multicenter Studies .....................................................................................................10
7.
STUDY SUBJECTS ...................................................................................................11

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7.1.
Disposition of Subjects ...............................................................................................11
7.2.
Protocol Deviations ....................................................................................................11
8.
SAFETY EVALUATION ..........................................................................................12
8.1.
Demographic and Other Baseline Characteristics ......................................................12
8.1.1.
Concurrent Illnesses and Medical Conditions ............................................................12
8.1.2.
Prior and Concomitant Therapy ..................................................................................12
8.2.
Measurements of Treatment Compliance ...................................................................13
8.3.
Adverse Events ...........................................................................................................13
8.3.1.
Solicited Events and Symptoms .................................................................................13
8.3.2.
Unsolicited Adverse Events ........................................................................................14
8.4.
Deaths, Serious Adverse Events and other Significant Adverse Events ....................15
8.4.1.
Deaths and Serious Adverse Events ...........................................................................15
8.4.2.
New Chronic Medical Conditions ..............................................................................16
8.4.3.
Confirmed Cases of DENV (Part B) ..........................................................................16
8.5.
Pregnancies .................................................................................................................16
8.6.
Clinical Laboratory Evaluations .................................................................................16
8.7.
Vital Signs and Physical Evaluations .........................................................................18
9.
IMMUNOGENICITY EVALUATION .....................................................................20
10.
EFFICACY ANALYSIS ............................................................................................21
10.1.
Analysis of ZIKV Incidence .......................................................................................21
10.2.
Analysis of vaccine efficacy: ......................................................................................22
10.2.1.
Sample SAS code for time to event analysis: .............................................................23
10.3.
Analysis of Clinical Signs and Symptoms of ZIKV Illness .......................................23
11.
REPORTING CONVENTIONS ................................................................................24
12.
TECHNICAL DETAILS ............................................................................................24
13.
REFERENCES ...........................................................................................................24
14.
LISTING OF TABLES, FIGURES AND LISTINGS ...............................................24
APPENDIX 1: TABLES .............................................................................................................25
APPENDIX 2: FIGURES .........................................................................................................111
APPENDIX 3: LISTINGS ........................................................................................................138
 

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LIST OF ABBREVIATIONS 
Abbreviation 
Term 
AE 
adverse event 
ALT 
alanine aminotransferase 
ATC 
Anatomical Therapeutic Classification 
CI 
confidence interval 
DENV 
dengue virus 
DNA 
deoxyribonucleic acid 
DSMB 
Data and Safety Monitoring Board 
eCRF 
Electronic case report form 
ELISA 
enzyme-linked immunosorbent assay 
ELISpot assay 
enzyme-linked immunospot assay 
FDA 
United States Food and Drug Administration 
GBS 
Guillain-Barré syndrome 
GEE 
generalized estimating equation 
GMFI 
geometric mean fold increase 
GMT 
geometric mean titer 
H0 
null hypothesis 
HIV 
human immunodeficiency virus 
HR 
Hazard ratio 
ICH 
International Council for Harmonisation of Technical Requirements 
for Registration of Pharmaceuticals for Human Use 
ICS 
intracellular cytokine staining 
IM 
intramuscular 
IND 
investigational new drug 
ITT 
Intent-to-treat 
MedDRA® 
Medical Dictionary for Regulatory Activities 
MCV 
mean corpuscular volume 
mITT 
modified intent-to-treat 
NAb 
neutralizing antibody 
NIAID 
National Institute of Allergy and Infectious Diseases 
NIH 
National Institutes of Health 
NCMC 
new chronic medical condition 
NVITAL 
NIAID Vaccine Immune T-Cell and Antibody Laboratory 
PAHO 
Pan American Health Organization 
PBS 
phosphate-buffered saline 
PCR 
polymerase chain reaction 

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List of Abbreviations (continued) 
 
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Abbreviation 
Term 
PDL 
primary diagnostic laboratory 
PI 
Principal Investigator 
PP 
per protocol 
PSRT 
Protocol Safety Review Team 
PT 
preferred term 
RNA 
ribonucleic acid 
RVP 
reporter virus particle  
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SOC 
System organ class 
TBD 
to be determined 
TFL 
tables, figures, and listings 
US 
United States 
VE 
vaccine efficacy 
VRC 
Vaccine Research Center 
WBC 
white blood cell 
WHO 
World Health Organization 
WNV 
West Nile virus 
ZIKV 
Zika virus 
ZIKVwt 
Zika virus wild-type 
 

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1. 
PREFACE 
The Statistical Analysis Plan (SAP) for “A Phase 2/2B, Randomized Trial to Evaluate the Safety, 
Immunogenicity and Efficacy of a Zika virus DNA Vaccine in Healthy Adults and Adolescents” 
(VRC 705) describes and expands upon the statistical information presented in the protocol. 
This document describes all planned analyses that will be conducted by the VRC 705 Data Center 
and provides reasons and justifications for these analyses. It also includes sample tables, figures, 
and listings (TFL) planned for the final analyses. Regarding the final analyses, 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 Food and Drug Administration (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 endpoints, 
and (4) a list of proposed TFLs (Appendices 1, 2, and 3).  
Following any protocol amendment, this SAP will be reviewed and revised to address any changes 
in the protocol impacting analysis. Any deviation from the final SAP will be described and 
justified. 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. 
Zika virus (ZIKV) is a mosquito-borne infection causing illness with mild symptoms including 
fever, rash, joint paint and conjunctivitis that may last for several days to weeks.  
Since its discovery in Uganda in 1947, outbreaks of ZIKV have been reported in Africa, Southeast 
Asia, and the Pacific Islands. ZIKV emerged in Brazil in 2015 and then rapidly spread throughout 
the Americas [1]. In May 2015, the Pan American Health Organization (PAHO) issued an alert 
regarding the first confirmed ZIKV infection in Brazil and on February 1, 2016, the World Health 
Organization (WHO) declared ZIKV a public health emergency of international concern due to 
evidence suggesting ZIKV infection may be linked to recent clusters of microcephaly in babies 
born to infected mothers and other reported neurological disorders including Guillain-Barré 
syndrome (GBS) [2]. According to the WHO, local transmission has now been reported in many 
other countries and territories and will continue to spread to new areas. 
There are currently no effective vaccines or therapies against ZIKV. The rapid emergence of ZIKV 
supports the need for a safe and immunogenic vaccine. This protocol is designed as a Phase 2B 
evaluation of the investigational ZIKV DNA vaccine, VRC-ZKADNA090-00-VP. This candidate 
vaccine was evaluated in a Phase 1 study (VRC 320, NCT02996461).  
VRC 705 is a multicenter, randomized, clinical trial evaluating the safety, immunogenicity, and 
efficacy of a three-dose vaccination regimen with the Zika virus (ZIKV) wild-type (ZIKVwt) DNA 
vaccine, VRC-ZKADNA090-00-VP. This Phase 2/2B study is being advanced rapidly to follow 
the initiation of the Phase 1 studies due to the significant public health need for a vaccine to prevent 
ZIKV. The study includes two Parts: Part A is an open-label evaluation of 90 subjects randomized 
to one of 3 groups to receive a 4 mg or 8mg dose of vaccine split between 2 or 4 injections; Part 
B is a double-blinded evaluation of 2400 subjects randomized to receive ZIKV vaccine or placebo. 
2.1. 
Purpose of the Analyses 
Note, not all analyses for endpoints included in the protocol are detailed in this plan. The 
exploratory endpoint analyses are not included in this SAP. 
In Part A, the primary objective is to evaluate the safety and tolerability of the vaccine. In Part 
B, the primary objectives are to evaluate the safety and efficacy of the vaccine compared to the 
placebo. Secondary and exploratory objectives of the study relate to immunogenicity and 
durability of immune responses. 
The VRC 705 protocol calls for multiple planned interim analyses. During Part A of the study 
immunogenicity may be analyzed in an ongoing fashion. During Part B of the study the following 
interim analyses will be performed:  

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1. Interim immunogenicity analyses may be performed after the neutralizing antibody 
(NAb) assays up to and including Week 12 have been completed on a subset of subjects.  
2. Interim efficacy analysis may be performed when the total number of ZIKV cases in the 
modified Intent-to-treat (mITT) cohort reaches 30 and 60.  
For Part B, the final efficacy analysis will occur when the total number of virologic ZIKV cases 
in the mITT cohort reaches 90 or study completion. The final analysis of Part A and Part B will 
be performed and completed when all primary and secondary safety, efficacy, and immunogenicity 
endpoint data are available, and the study database has been locked. The study clinical database 
and immunogenicity/efficacy database will be locked separately; the final analysis of Part A and 
Part B safety data will follow the clinical database lock and the final analysis of Part A and Part 
B immunogenicity and efficacy data will follow the second database lock once all lab data are 
received and validated. 

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3. 
STUDY OBJECTIVES AND ENDPOINTS 
3.1. 
Study Objectives 
Refer to Protocol Section 3, “Study Objectives.” 
3.2. 
Endpoints 
Refer to Protocol Section 6.2, “Endpoints.” 
3.2.1. 
Study Definitions and Derived Variables 
The baseline value will be defined as the last value obtained prior to the receipt of the first product 
administration on Day 0 (Visit 02). 
Individual neutralization antibody (NAb) assay results will be reported as a titer. 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. Subjects will be tested for 
baseline ZIKV serostatus based on serum samples collected at screening, Visit 01.  
4. 
INVESTIGATIONAL PLAN 
4.1. 
Overall Study Design and Plan 
Refer to Protocol Precis. 
4.2. 
Discussion of Design, Including the Choice of Control Group  
Refer to Protocol Section 4, “Study Design and Clinical Procedures.” 
4.3. 
Selection of Study Population 
Refer to Protocol Precis. 
4.4. 
Study Product Administrations 
4.4.1. 
Study Product 
Refer to Protocol Section 2, “Study Products”. 
4.4.2. 
Vaccine Dose and Administration Method 
Refer to Protocol Section 1.5, “Rationale for Study Product Dose and Administration Method.” 
4.4.3. 
Method of Assigning Subjects to Study Groups (Randomization) 
Refer to Protocol Section 6.4.6, “Randomization of Treatment Assignments and Unblinding 
Criteria.” 

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4.4.4. 
Blinding and Conditions for Unblinding 
Refer to Protocol Section 6.4.6, “Randomization of Treatment Assignments and Unblinding 
Criteria.” 
Please refer to the Study Blinding Plan for additional details on blinding and processes for planned 
and unplanned unblinding events. 
5. 
SAMPLE SIZE CONSIDERATIONS 
Refer to Protocol Section 6.3, “Sample Size and Accrual.” 

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6. 
GENERAL STATISTICAL CONSIDERATIONS 
6.1. 
General Principles 
Summary tables will be presented separately for Part A and Part B, and will mostly be structured 
with columns summarizing the groups as follows:  
Part A 
• Group 1: 4 mg ZIKVwt DNA, 2 injections 
• Group 2: 4 mg ZIKVwt DNA, 4 injections 
• Group 3: 8 mg ZIKVwt DNA, 4 injections 
• All Part A Subjects. 
Since the primary safety objective indicates assessing the 4mg dose regardless of the number of 
injections, safety data will be tabulated with the following columns.  
• Group 1: 4 mg ZIKVwt DNA, 2 injections 
• Group 2: 4 mg ZIKVwt DNA, 4 injections 
• Groups 1 + 2: 4mg ZIKVwt DNA, 2 or 4 injections 
• Group 3: 8 mg ZIKVwt DNA, 4 injections 
• All Part A Subjects. 
Part B 
• Group 4: 4 mg ZIKVwt DNA 
• Group 5: Placebo 
• All Part B Subjects.  
The total sample size for each summary group for the applicable analysis population being 
tabulated will be displayed in all tables. 
All continuous variables will be summarized using the following descriptive statistics: n (non-
missing sample size), mean (or geometric mean, as appropriate), standard deviation, median, 
minimum and maximum. The frequency and percentages (denominators based on the non-missing 
sample size) of observed levels will be reported for all categorical measures. Unless otherwise 
specified, Clopper-Pearson exact methodology will be used to calculate CIs for proportions. All 
logarithmic transformations will be done using the natural log. 
In presenting statistical inferences, the statistical claim (i.e. null and alternative hypotheses) will 
be clearly stated, the method used for hypothesis testing or CI estimation will be described and 
appropriately referenced, and the assumptions underlying the methods will be validated. 

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All data will be included in listings, sorted by study group and subject, and when appropriate by 
administration number and/or visit number within subject. Listings will be presented with Part A 
and Part B data separated. 
6.2. 
Timing of Analyses 
1. Interim immunogenicity analyses for Part A may be performed on an ongoing basis, per 
sponsor directive. 
a) The first interim immunogenicity analysis will be performed when 10 subjects in each 
group have data available through Visit 05 
2. Interim immunogenicity analyses for Part B may be performed on a subset of subjects 
after the NAb assays up to and including Week 12 have been completed for the subset of 
subjects.  
3. Final Efficacy Analysis will occur when the total number of mITT virologic ZIKV cases 
(primary efficacy endpoint) in Part B of the study reaches 90 or study completion.  
4. The Final Analysis of safety data for both Part A and Part B will be performed after 
clinical database lock when all subjects have been followed through 32 weeks after the 
last product administration for Part A and at least 6 months after the first product 
administration for Part B. Final analysis of the efficacy and immunogenicity endpoint 
data will follow the database lock of the immunogenicity and efficacy data once all lab 
data are received and validated.  
5. Exploratory Immunogenicity Analyses may be completed following database lock as 
assay results become available. 
For all analyses completed prior to database lock, individual subjects’ study group assignments 
will not be unblinded with the possible exception of a review of selected AEs or episodes of ZIKV 
disease for safety monitoring requirements, as described in the Study Blinding Plan.  
6.3. 
Analysis Populations 
The two parts of the study share the following definition for each type of analysis population: 
All Enrolled Subjects: all subjects who enrolled in the screening segment. This population will 
be used for summaries of subject disposition, eligibility, demographics and the serious adverse 
event listing. 
Safety population: all randomized subjects in the study who receive at least one study product 
administration, and have at least one post-administration safety assessment, analyzed according to 
the study product received. If it is unknown what study product was received, subjects will be 
summarized according to the randomized treatment assignment. This population will be used for 
analysis of all safety endpoints.  

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The Intent-to-treat (ITT) population will include all randomized subjects, analyzed according to 
the randomized study product. The ITT population will be used to analyze immunogenicity and 
efficacy analyses. 
The Modified intent-to-treat (mITT) analyses will include all randomized subjects who remain 
event-free one week after all planned product administrations, where event is the primary efficacy 
event of a positive ZIKV PCR or other Zika test result with or without symptoms, analyzed 
according to the randomized study product. The mITT population will be used for immunogenicity 
and efficacy analyses (Part B only).  
The Per Protocol (PP) analyses will include all subjects receiving three administrations within 
window as assigned by the randomization schedule, and not experiencing any other major protocol 
deviations prior to their week 12 visit. Safety, immunogenicity, and efficacy analyses will all be 
examined for the PP population. The following subjects will be excluded from the PP population: 
- 
Subjects who do not receive 3 administrations of study product. 
- 
Subjects who acquire confirmed ZIKV infection on or before 1 week after third 
administration. 
- 
Subjects missing baseline ZIKV serostatus. 
- 
Subjects who received a study product administration different from the randomization 
assignment. 
- 
Subjects who receive the second or third administration out of the protocol-defined windows: 
- 
Subjects who did not meet all inclusion/exclusion criteria at the time of enrollment. 
- 
Subjects whose study group assignment is unblinded during study follow-up (Part B). 
- 
Subjects who receive study product via incorrect route or incomplete administration. 
- 
For efficacy analyses – subjects who do not have at least one post-administration efficacy 
assessment (at least one visit or PCR (or other Zika) result) following product administration 
3. 
- 
For immunogenicity analyses – subjects who do not have NAb results 4 weeks post product 
administration 3 (Visit 05) or at baseline. 
- 
For immunogenicity analyses – subjects with serum sample for 4 weeks post product 
administration 3 (Visit 05) collected outside the protocol specified window (Day 77 to Day 
91). 
Subjects may be censored from the Per-Protocol Analysis for any of the following: 
- 
Receipt of any non-study inactivated vaccination within 2 weeks of any study product 
administration. 
- 
Receipt of any live attenuated vaccination within 4 of any study product administration. 

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- 
Receipt of any other investigational research agent at any time during the trial.  
- 
Receipt of any concomitant medication that may interfere with immune response, including 
but not limited to:  
o Any systemic immunosuppressive or cytotoxic medical blood products within 16 
weeks prior to randomization. 
o Immunoglobulin within 8 weeks prior to randomization. 
o Current anti-TB prophylaxis or therapy.  
- 
Confirmed or suspected immunosuppressive or immunodeficient condition, including HIV 
infection.  
All exclusions from analysis populations and censoring events will be reviewed by the Protocol 
Statistician, Protocol Chairs, and Lead Medical Officer and others on the Protocol Safety Review 
Team.  
6.4. 
Covariates and Subgroups 
All immunogenicity analyses will be conducted overall and stratified by baseline ZIKV 
seroprevalance for all Part A and Part B subjects. Additional summaries may be tabulated by 
clinical site, but the study is not powered for any additional subgroup analyses. 
6.5. 
Missing Data 
Missing data will be primarily considered as missing completely at random in safety and 
immunogenicity analyses provided missing data is modest (e.g. <10%).  For completeness, we will 
examine the missing data completely at random assumption and perform sensitivity analyses 
which weaken the missing completely at random assumption if the missing data is >10% or if the 
missing at random assumption is questionable. Data will be presented as available; no imputation 
is planned. For efficacy, missing at random will be assumed and imputation may be implemented 
if supported by the data and if sufficient consequence to justify their inclusion. 
6.6. 
Interim Analyses and Data Monitoring 
6.6.1. 
Independent Safety Reviews 
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 Data and Safety Monitoring Board (DSMB) will provide an independent safety review at 
scheduled intervals to coincide with their biannual meeting schedule.  

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6.6.2. 
Immunogenicity Reviews:  
Part A: The data in Part A will be used in an ongoing manner to help select the regimen to be used 
in Part B. Analyses will be performed as described in Section 9. 
Part B: An interim analysis of immunogenicity data may be performed after the NAb assays up 
to and including Week 12 have been completed on a subset of subjects. Analyses will be performed 
as described in Section 9. Reports will be provided to the Protocol Chairs and other key 
investigators as described in the study blinding plan solely for the purpose of informing future 
trial-related decisions in a timely manner. Results will be provided summarized by treatment arm, 
and to prevent inadvertent unblinding, no individual subject data will be released that would 
indicate study group. The results will remain confidential and should in no way influence the 
conduct of the VRC 705 trial in terms of early termination or later safety or immunogenicity 
endpoint assessments.  
6.6.3. 
Incidence Reviews (Part B only): 
The study will be regularly monitored using the combined (blinded) incidence rates for ZIKV 
disease and for ZIKV infections. These rates will be monitored at each site and over all sites 
combined. Such monitoring will allow for enrollment to be expanded or curtailed at different sites.  
Prior to completion of enrollment of the 2400 Part B subjects, calculations using the blinded 
incidence rates will be performed to estimate the expected time to achieve 90 cases of ZIKV 
disease. Based on these calculations, the sample size may remain fixed at 2400, be increased up to 
15,000, or the trial may be stopped for lack of feasibility if this expected time is deemed excessive.  
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 study product administration and assessment of solicited and 
unsolicited AEs, and the study relies on central laboratories for the assessment of immunogenicity 
and clinical efficacy endpoints.  

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7. 
STUDY SUBJECTS 
7.1. 
Disposition of Subjects 
A summary of the reasons why subjects were screened but not randomized will be presented 
overall in Table 1 and by site in Table 2 (Appendix 1). The disposition of subjects in the study 
will be tabulated by study group (Table 3 for Part A and Table 4 for Part B, Appendix 1) and by 
site (Table 5 for Part A and Table 6 for Part B, Appendix 1). The tables will display the total 
number and percentage of subjects screened, randomized, received the first administration, 
received the second administration, received the third administration, terminated from study 
follow-up, and completed the protocol.  
The number of subjects included in each analysis population, and the number meeting each 
population exclusion criterion, will be presented in Table 7 for Part A and in Table 8 for Part B 
(Appendix 1). 
A flowchart showing the disposition of study subjects, adapted from the CONSORT Statement [3] 
will be included (Figure 1 for Part A and Figure 2 for Part B, Appendix 2). This figure will 
present the number of subjects screened, randomized, vaccinated, and included in the mITT and 
PP analysis populations by study group. 
A listing of subjects who discontinued dosing or terminated from study follow-up and the reason 
will be included in Listing 1 and Listing 2 (Appendix 3).  
A listing of subjects who were unblinded during study follow-up will be included in Listing 4. 
7.2. 
Protocol Deviations 
A summary of subject-specific protocol deviations will be presented by the reason for the deviation 
and the deviation category for all enrolled subjects (Table 9 for Part A, Table 10 for Part B, 
Table 11 for Screening Segment, Appendix 1). Deviations will be reviewed for possible subject 
exclusion from the per protocol population including those defined in Section 6.3. All subject-
specific protocol deviations, non-subject-specific protocol deviations, and unanticipated problem 
reports will be included in in data listings (Listing 3, Listing 4, Listing 5, Listing 6, Listing 7, 
Appendix 3). 

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8. 
SAFETY EVALUATION 
8.1. 
Demographic and Other Baseline Characteristics 
Summaries of age, gender, ethnicity, race, and language will be presented by study group for all 
enrolled subjects, the mITT population, and the ITT population (Table 13 - Table 14 , for Part A 
and Table 15 - Table 16, Part B, Appendix 1), and by site for all enrolled subjects (Table 17 for 
Part A and Table 18 for Part B, Appendix 1).  
Ethnicity is self-reported by subjects as Mexican, Mexican-American, or Chicano/a; Puerto Rican; 
Cuban; Another Hispanic, Latinola, or Spanish origin; Not of Hispanic, Latinola or Spanish 
Origin; Unknown/Not Reported. Ethnicity will be summarized as categories of Any Hispanic, 
Latinola, or Spanish Origin, or Not of Hispanic, Latinola or Spanish Background. 
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 CRF as “No” to each racial 
option. The race categories collected on the eCRF: White; Black or African American; American 
Indian or Alaskan Native; Asian Indian; Chinese; Filipino; Japanese; Korean; Vietnamese; Other 
Asian; Native Hawaiian; Guamanian or Chamorro; Samoan; Other Pacific Islander. Race may also 
be presented with categories aggregated such that any categories reported by <5% of subjects are 
reported as “Other”. 
Individual subject listings will be presented for all demographics (Listing 10 - Listing 11 , 
Appendix 3).  
8.1.1. 
Concurrent Illnesses and Medical Conditions 
All current illnesses and past or pre-existing medical conditions will be MedDRA coded using 
MedDRA dictionary version 20.0 or higher.  
Summaries of subjects’ pre-existing medical conditions will be tabulated by system organ class 
(SOC) and preferred term (PT) (Table 19 for Part A and Table 20 for Part B, Appendix 1).  
Individual subject listings will be presented for all medical conditions (Listing 12 - Listing 13, 
Appendix 3). 
8.1.2. 
Prior and Concomitant Therapy 
Only routine prescription medications will be entered in the database at the time of study 
randomization. All approved vaccinations for routine health care will be entered in the database 
throughout the study. Concomitant medications will be updated in the study database if there is an 
occurrence of an AE that requires expedited reporting or development of a new chronic medical 
condition that requires ongoing medical management. Otherwise, concomitant medications taken 
throughout the study will be recorded in the subject’s chart, including any medication taking for 
DENV infection.  

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Individual subject listings will be presented for all concomitant medications (Listing 38 - Listing 
39, Appendix 3). 
8.2. 
Measurements of Treatment Compliance 
In both parts of the study, all subjects are to receive 3 doses of study product administered in the 
clinic. The number of doses of study product administered to subjects will be presented by study 
group and by site as part of the subject disposition table as described in Section 7.1.  
8.3. 
Adverse Events 
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.  
8.3.1. 
Solicited Events and Symptoms 
Solicited AEs will be recorded in the study database separately with data collection on the day of 
administration and for 7 days after each product administration, graded on a scale of 0 (none), 1 
(mild), 2 (moderate) and 3 (severe), without the collection of attribution assessments. The solicited 
signs and symptoms on the diary card will include the following parameters: malaise (unusually 
tired/feeling unwell), myalgia (muscles aches (other than at injection sites), headache, chills, 
nausea, joint pain, and pain/tenderness at the injection sites. Subjects will also record the highest 
measured temperature per day and measurement per day of the largest diameter for redness and 
swelling at the injection sites, if applicable. Subjects are instructed to record the greatest local 
symptoms or measurement when evaluating multiple injection sites. Subjects will be provided with 
devices to measure temperature and diameter. 
The number and percentage of subjects reporting at least one solicited event of any severity 
following any administration will be summarized for each solicited symptom, any systemic 
symptom, any local symptom, and any solicited symptom. The denominator is the number of 
subjects in the Safety Analysis Population with non-missing data for the symptom being 
summarized. The 95% CI along with p-values from a Chi-square test comparing treatment groups 
will be presented (Table 60 for Part A and Table 61 for Part B, Appendix 1). In cases where 
there is a small sample size (e.g. Part A), Fisher’s exact 2-tailed test will be presented.  
For each type of reactogenicity sign and symptom, the maximum severity (none, mild, moderate, 
severe, or missing) reported on Day 0 through Day 7 after each administration will be summarized. 
Similarly, the maximum severity across all systemic events and across all local events will be 
summarized. The number and percentage of subjects reporting each type of event, any systemic 
event, and any local event will be summarized by the maximum severity for each study group 
separately for each administration and over all administrations. (Table 62 for Part A and Table 63 
for Part B, Appendix 1).   

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The number of subjects reporting each type of solicited adverse event will be summarized for each 
day post administration by study group for each administration graphically in a bar chart (Figure 45 
and Figure 47 for Part A and Figure 46 and Figure 48 for Part B, Appendix 2).  
Solicited adverse events reported for each subject who reported at least one mild or greater event 
will be presented in Listing 22 - Listing 23 for systemic adverse events and Listing 24 - Listing 25 
for local adverse events, Appendix 3. 
8.3.2. 
Unsolicited Adverse Events 
Unsolicited AEs and their relationship to study product are recorded in the study immediately after 
the first product administration at Visit 02 through the one month visit that follows the last product 
administration. If a subject only receives the first product administration at Visit 02 but not the 
second or third, then the AE Reporting Period for unsolicited AEs and their relationship to study 
product is immediately after Visit 02 through Visit 03. If a subject only receives the first and 
second product administrations at Visit 02 and Visit 03, respectively, but not the third, then the 
AE Reporting Period for unsolicited AEs and their relationship to study product is immediately 
after Visit 02 through Visit 04. After this period, only SAEs, new chronic medical conditions, and 
confirmed cases of DENV will be recorded as an AE through the last study visit. SAEs are recorded 
from the time the informed consent is signed (Visit 01) through the end of the study. 
The severity of an adverse event (AE) is reported on the eCRF as: Grade 1 (Mild), Grade 2 
(Moderate), Grade 3 (Severe), Grade 4 (Life-threatening), and Grade 5 (Death). For any subject, 
only the single AE that is assessed as the primary cause of death should be assigned “Grade 5” 
severity. Following conventions of Clinical Data Interchange Standards Consortium (CDISC), 
conventions the severity data will be mapped to categories of Grade 1 (Mild), Grade 2 (Moderate), 
Grade 3 (Severe), where any AEs reported on the eCRF as Grade 4 (Life-threatening) or Grade 5 
(Death) will be coded as Grade 3 (Severe). The CDISC compliant severity grading scale will be 
used for all summaries and analysis for the final analysis.  
Relation of an AE to the study product is defined as Definitely Related, Probably Related, Possibly 
Related, and Not Related. Following CDISC conventions the AE attributions will be mapped to 
“Related” or “Not Related”, where any AEs reported on the eCRF as “Definitely, Probably and 
Possibly” attributions will be mapped to the “Related” category. The CDISC compliant 
relationship will be used for all summaries and analysis for the CSR. 
AEs will be coded into Medical Dictionary for Regulatory Activities (MedDRA) system organ 
class and preferred terms. 
Any SAEs reported before the first study product administration receipt at Visit 02 will be listed 
in Table 72, Table 78, Table 84, Appendix 1. All other tables and figures of unsolicited AEs will 
include only AEs reported following the first study product administration. 
The number and proportion of subjects reporting at least one unsolicited adverse event will be 
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over all study product administrations. Denominators for percentages are the number of subjects 
in the Safety Analysis Population who received the administration being summarized (Table 73, 
Table 74, Table 75 for Part A and Table 76, Table 77 for Part B, Appendix 1). For each 
MedDRA system organ class and preferred term a 95% CI will be presented, along with the p-
value for the comparison of study groups from a Fisher’s exact test for Part A and a Chi-square 
test for Part B (Table 64, Table 65, Table 66, Table 67 for Part A and Table 68, Table 69, 
Table 70, Table 71 for Part B, Appendix 1). 
The following summaries for unsolicited adverse events will be presented by MedDRA system 
organ class, preferred term for each administration and overall administrations, for all subjects: 
• Proportion of subjects reporting adverse events by severity (Table 64 through Table 78, 
Appendix 1); 
• Proportion of subjects reporting related adverse events by severity (Table 79 through 
Table 84, Appendix 1); 
• Proportion of subjects reporting related adverse events by dose (Table 85 through Table 89, 
Appendix 1); 
• Number of adverse events by dose (Table 90 through Table 94, Appendix 1); 
• Number and proportion of subjects experiencing adverse events above 5% frequency 
threshold by MedDRA SOC and PT (Table 95 - Table 96, Appendix 1);  
• Bar chart of the proportion of subjects reporting any adverse events by severity (Figure 49 
- Figure 50, Appendix 2); 
• Bar chart of adverse events by severity and MedDRA SOC for SOCs reported by 5% or 
more of subjects (Figure 53 - Figure 54, Appendix 2); 
• Bar chart of adverse events by relationship to study product (Figure 51 - Figure 52, 
Appendix 2); 
Unsolicited AEs by subject will be presented in Listing 26 through Listing 28, Appendix 3. 
8.4. 
Deaths, Serious Adverse Events and other Significant Adverse 
Events 
8.4.1. 
Deaths and Serious Adverse Events 
A listing of Deaths will be presented including Subject ID, Age (years), Baseline ZIKV serostatus, 
Adverse Event Description, SOC, PT, Adverse Event Onset Date/End Date, Last Dose 
Received/Days Post Dose, Reason Reported as an SAE, Relationship to Treatment, Alternate 
Etiology if not Related, Outcome, and Duration of Event (days). 
A listing of SAEs will be presented including Subject ID, Age (years), Baseline ZIKV serostatus, 
Adverse Event Description, SOC, PT, Adverse Event Onset Date/End Date, Last Dose 

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Received/Days Post Dose, Reason Reported as an SAE, Relationship to Treatment, Alternate 
Etiology if not Related, Outcome, and Duration of Event (days) (Table 99 for Part A; Table 100 
for Part B; Table 101 for Screening Segment, Appendix 1). The number and proportion of 
subjects reporting at least one SAE will be summarized by MedDRA SOC and PT for each over 
all administrations (Table 98, Appendix 1).  
8.4.2. 
New Chronic Medical Conditions  
NCMC will be recorded on the AE form through the full duration of the study. These events will 
be identified from the database as any event without an end date and a date of onset greater than 
28 days after the last product administration or any SAE at the time of trial completion. A blinded 
listing will be reviewed by the Protocol Lead Medical Officer prior to database lock. A listing of 
NCMC will be presented including Subject ID, Age (years), Baseline ZIKV serostatus, Adverse 
Event Description, SOC, PT, Adverse Event Onset Date/End Date, Last Dose Received/Days Post 
Dose, Relationship to Treatment, Alternate Etiology if not Related, Outcome, and Duration of 
Event (days) (Table 104 for Part A and Table 105 for Part B, Appendix 1).  
8.4.3. 
Confirmed Cases of DENV (Part B) 
For Part B, confirmed cases of DENV will be recorded on an AE Form throughout the full duration 
of the study. The incidence of DENV will be summarized as the number and percentage of subjects 
tabulated by treatment arm overall and stratified by baseline ZIKV Status. 95% CIs will be 
included along with p-values from Chi-Square test (Table 107, Appendix 1). 
8.5. 
Pregnancies 
Female subjects of childbearing potential will receive pregnancy prevention counseling throughout 
the study. Women will be asked to notify the site immediately if they suspect or learn they are 
pregnant during this study. In case of pregnancy, subjects will be removed from the product 
administration schedule but may have limited clinic contacts and blood draws at the discretion of 
the site PI and IND Sponsor. The pregnancy outcomes are captured by the Pregnancy eCRF.  
A table summarizing the total pregnancies, number of live births, miscarriages, elective abortions, 
ectopic pregnancies, still births, congenital anomalies, and neonatal deaths by treatment will be 
presented (Table 108 for Part A, Table 109 for Part B, Appendix 1). In addition, a listing of 
pregnancies and outcomes will be presented (Listing 40 for Part A and Listing 41 for Part B, 
Appendix 3). 
8.6. 
Clinical Laboratory Evaluations 
Planned safety laboratory parameters include: alanine aminotransferase (ALT), white blood cells 
(WBC), red blood cells (RBC), hemoglobin, hematocrit, mean corpuscular volume (MCV), 
platelets, neutrophils, lymphocytes, monocytes, eosinophils, and basophils. Laboratory safety 
evaluations are scheduled at baseline and weeks 4, 6, 8, 10, 12, 16 for Part A, and at baseline and 
weeks 4, 8, 16, 20, for Part B. 

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Only results for planned parameters and scheduled visits will be included in summaries. Safety 
laboratory evaluations are graded as follows: mild (grade 1), moderate (grade 2), severe (grade 3), 
or partially life threatening (grade 4) following the grading criteria in Protocol Appendix IV. Any 
abnormal laboratory results are reported as unsolicited AEs, and thus summarized as described in 
Section 8.3.2. 
Safety laboratory results will be summarized for each parameter by study visit and study group. 
Continuous summary statistics for each parameter along with standard deviation for the mean will 
be presented in Table 117 through Table 119 for Part A and Table 120 - Table 121 for Part B 
(Appendix 1). Box plots for each parameter will be included in Figure 55 through Figure 66 for 
Part A and Figure 67 through Figure 78 for Part B (Appendix 2). 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.  
Continuous summary statistics for the change from baseline for each parameter along with 
standard deviation for the mean will be presented in Table 117 through Table 119 for Part A and 
Table 120 - Table 121 for Part B (Appendix 1). Each Safety laboratory parameter will be 
summarized using shift tables to compare baseline and follow-up values (Table 122 through 
Table 147 for Part A and Table 148 through Table 166 for Part B, Appendix 1). Shift tables will 
be analyzed using Generalized Estimating Equations (GEE) 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 categorized as 
normal and abnormal at baseline cross tabulated with normal and abnormal results at 
the post-product administration 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: ∑


 
!
=1
$
−1&' ( )=0 where $& is the working covariance 
matrix; 
•  Implementation: PROC GENMOD (SAS) using SUBJECT option in the 
REPEATED statement to identify the cluster variable 

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• 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 three categories: Low, Normal and High (Ordinal 
response)  
a. For each parameter the shift table displays the number of subjects who are 
categorized as low, normal, or high at baseline cross tabulated with low, normal or 
high results at the post-vaccination visit. 
b. A GEE model for the ordinal responses above is fitted and used for parameter 
estimation 
• Observation '  for each subject       at time point     . 
'  1 2is the ordinal response variable with 3 ordered categories; 
• Cumulative probability +  	
+   ,-.
 
	
' ≤- -  ; 
• Proportional Odds model0
1  11  
′ 
2  12  
′  using the logit link; 
• 
′   1  2  3 ∗ 
• GEE: ∑


 
!
=1
$
−1&' ( )=0 where)  3' $& is the working 
covariance matrix; 
• Output: estimates 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 study group, therefore the absence of statistically 
significant differences should not be interpreted as no such differences exist.   
Individual clinical laboratory results will be presented for subjects with abnormal results of Grade 
2 or higher for at least one parameter from at least one visit, including planned parameters collected 
at scheduled visits as well as any other parameters collected, and any results for unscheduled visits 
in Table 167 for Part A and Table 168 for Part B, Appendix 1. 
8.7. 
Vital Signs and Physical Evaluations 
Vital signs measurements include oral temperature, pulse, systolic and diastolic blood pressure, 
and respiratory rate. The assessment of vital signs is planned at baseline and weeks 4, 6, 8, 18, 12, 
and 16 for Part A, and at baseline and weeks 4, 8, 16, 44, 72, and 96 for Part B. Vitals are collected 

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pre- and post-study product administration. Vitals are also captured on the Visit Documentation 
eCRF at visits 6, 13, 20 and 26. A targeted physical exam is conducted at the same time points as 
the vital signs assessment and recorded in the subject’s chart but not reported in the study database.  
Vital signs will be summarized for each parameter by study visit, assessment (pre- or post-
administration, if applicable), severity grading and study group (Table 174 through Table 176 for 
Part A and Table 177 - Table 178 for Part B, Appendix 1). Box plots for each parameter will be 
included in Figure 103 through Figure 106 for Part A and Figure 107 through Figure 110 for Part 
B (Appendix 2). 

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9. 
IMMUNOGENICITY EVALUATION 
The principal immunogenicity endpoints are measured at Day 0 (Visit 02) and 4 weeks after the 
third administration (Visit 05) by NAb. We assume NAb results will follow a log-normal 
distribution.  
The following summaries will be presented by study group and study visit separately for Part A 
and Part B for all subjects in each of the ITT, PP and mITT analysis populations. Summaries are 
presented over all subjects and stratified by baseline ZIKV serostatus. 
• ThenumberandpercentageofsubjectswithpositiveNAbresponse,definedasatiter≥30,
along with their exact 95% CIs and p-values from a Chi-squared test comparing study 
groups. (Table 19 through Table 24, Appendix 1) 
• GMTs and their CIs, p-values from a t-test comparing log-NAb titers between study 
groups. (Table 25 through Table 30, Appendix 1) 
• Geometric mean fold rise (GMFR) in NAb from baseline with the corresponding 
confidence interval and (1) p-value from a paired t-test comparing the log-NAb titers 
between baseline and post-administration within each treatment arm, and (2) p-value from 
t-test comparing log-transformed fold increases in NAb between study groups.  Non-
parametric tests will be considered if the normality assumption is not realized. (Table 25 
through Table 30, Appendix 1) 
• Boxplots of NAb titers. (Figure 15 through Figure 26, Appendix 2) 
• Reverse cumulative distribution curves of NAb titers. (Figure 3 through Figure 14, 
Appendix 2) 
Exploratory analysis of NAb for other visits will be presented in a similar fashion as data are 
available. 
A listing of individual NAb titer levels, whether positive and the corresponding planned and actual 
collection dates are presented in Listing 16 - Listing 17, Appendix 3. For any immunogenicity 
reports released prior to database lock and study unblinding, a coded subject identifier will be 
included in listings to prevent unblinding any subject’s study product assignment.  

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10. 
EFFICACY ANALYSIS  
As one of the primary and secondary objectives of Part B, an efficacy evaluation with respect to 
ZIKV incidence will be performed. Tables providing efficacy data analysis (Table 45 through 
Table 56, Appendix 1) may be excluded if there are only a nominal number of Zika cases.  
For primary analysis: 
• Case of ZIKV infection: Virologically confirmed infection by PCR or other virus 
detection method in blood or in urine. 
The final efficacy analysis will occur when the total of 90 ZIKV cases have been reported in the 
mITT population or following database lock and receipt of PCR or other virus detection assay 
results. If additional cases are reported following the data cut-off for this analysis and before the 
database lock, this analysis will be repeated and will include all cases reported during the study 
for inclusion in the final analyses.  
For secondary analysis: 
• Subclinical case of ZIKV infection: PCR virus detection in blood or in urine with no 
signs or symptoms. Subclinical cases of ZIKV infection will be identified by retrospective 
PCR or other virus testing methods. 
For exploratory analysis: 
• Symptomatic case of ZIKV infection: PCR or other virus detection method in blood or 
in urine in conjunction with at least one clinical sign and/or symptom. 
The analyses requiring retrospective assessment of stored samples, will be conducted after 
database lock and Zika results are available for all subjects for inclusion in the final analysis. 
 
For all subjects with suspected ZIKV infection a listing of all signs/and symptoms, PCR or other 
Zika results, and for confirmed cases, neurological symptoms, severity, and outcome are included 
in Listing 20 - Listing 21 for Part B, Appendix 3. Of note, Listing 18 - Listing 19 will include 
ZIKV data collected in Part A, which does not contribute to the efficacy analysis.  
10.1. 
Analysis of ZIKV Incidence  
For Part B, incidence will be summarized for each ZIKV endpoint as the number and percentage 
of subjects along with 95% CI and be described by study group, and stratified by baseline ZIKV 
seroprevalence. Incidence summaries will be presented for the ITT, mITT, and PP populations, 
Table 45 through Table 47, Appendix 1. Incidence for each ZIKV endpoint will also be 
summarized in a similar presentation by clinical site Table 48 through Table 50, Appendix 1.  

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10.2. 
Analysis of vaccine efficacy: 
The time of ZIKV events is defined as the illness onset date recorded on the ZIKV Endpoints 
eCRF (for clinical cases) or date first specimen was collected with a positive PCR or other Zika 
result, whichever is earliest. Time to event for analysis will be as follows: 
• For subjects with infection: time of ZIKV event minus date of first administration (Visit 
02) + 1.  
• For subjects with no infection: date of protocol completion/termination as recorded on the 
study status eCRF minus date of first administration (Visit 02) + 1. These subjects will be 
censored at their date of study completion or date of early termination. 
• Subjects with or without infection may be censored from the analysis for the PP population 
as described in Section 6.3. 
For subjects who were randomized but did not receive any product, date of randomization will be 
used in place of date of first administration in the definitions above. 
The cumulative incidence of ZIKV cases will be presented graphically as 1 – Kaplan-Meier curves. 
Curves will be presented by study group and baseline ZIKV stratum and by study group combined 
over all subjects (Figure 27 through Figure 44, Appendix 2). Similar presentations will be 
displayed for virologic ZIKV cases and subclinical ZIKV cases). 
Vaccine efficacy will be estimated as 1 - Hazard Ratio estimated from a Cox proportional hazard 
model. The primary efficacy analysis for ZIKV infection will use the following test: 
H0:VE≤20% 
H1: VE >20% 
The criterion for success will be that a one-sided test of H0 has p-value≤0.025. Success will be 
met if the lower bound of the 95.0% confidence interval for VE estimated for the mITT population 
using a Cox proportional hazards model stratified by baseline ZIKV status is >20 (Table 51 
through Table 53, Appendix 1).  
IfthenullhypothesisVE≤20%isnotrejected,thenthefollowingwillbetestedusingaone-sided 
type I error rate of 0.025. 
H*0: VE =0% 
H*1: VE >0% 
As secondary analyses of vaccine efficacy this hypothesis will be tested for:  
• ZIKV cases without stratification for baseline ZIKV serostatus  
• virologic ZIKV cases stratified by baseline ZIKV serostatus  
• subclinical ZIKV cases stratified by baseline ZIKV serostatus  
• subclinical ZIKV cases without stratification for baseline ZIKV serostatus 

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All analyses will be included in Table 51 through Table 53, Appendix 1. All efficacy analyses 
will be conducted for ITT, mITT, and PP populations. For all analyses the assumptions of 
proportional hazards and non-informative censoring will be evaluated.  
10.2.1. 
Sample SAS code for time to event analysis: 
Notations 
Timevar = the variable that gives the time to occurrence 
Censorvar = the variable indicating whether timevar is censored, where 1 = censored, 0 = 
not censored (event) 
Trtmnt = study product (placebo or ZIKVwt DNA) 
Stratavar = variable indicating baseline ZIKV serostatus 
Cox Proportional Hazard 
SAS Code for stratified Cox Regression [4] to obtain Vaccine Efficacy and 95% CI for Vaccine 
Efficacy: 
Proc phreg; 
CLASS trtmnt (ref = ‘placebo’) / param = ref; 
STRATA stratavar; 
MODEL timevar*censorvar(1)=trtmnt (and any covariates)/rl; 
ODS OUTPUT ParameterEstimates=ests (keep=HazardRatio HRUpperCL 
HRLowerCL); 
RUN; 
Calculate the following from the estimates obtained from the PROC PHREG output: 
Vaccine Efficacy = 1 – HazardRatio  
Lower 95% CI= 1 – HRUpperCL  
Upper 95% CI= 1 – HRLowerCL  
Similar code will be used to fit the cox regression combined across ZIKV serostatus stratum by 
removing the STRATA statement on PROC PHREG. 
10.3. 
Analysis of Clinical Signs and Symptoms of ZIKV Illness 
For confirmed ZIKV cases (primary endpoint), the number and percentage of subjects reporting 
each sign/symptom collected on the ZIKV Endpoint eCRF will be presented by study group in 
Table 51 through Table 53, Appendix 1. Continuous summary statistics for the duration of ZIKV 
illness, defined as date of resolution or death minus illness onset date plus 1 will be shown in 
Table 57 through Table 59, Appendix 1. 

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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, including VE, will be 
reported to the nearest tenth. Estimated parameters, not on the same scale as raw observations (e.g. 
regression coefficients) will be reported to 3 significant figures.  
12. 
TECHNICAL DETAILS 
SAS version 9.3 or above will be used to generate all tables, figures and listings. 
13. 
REFERENCES 
1. Fauci, A.S. and D.M. Morens, Zika Virus in the Americas--Yet Another Arbovirus Threat. 
N Engl J Med, 2016. 374(7): p. 601-4. 
2. WHO Director-General summarizes the outcome of the Emergency Committee regarding 
clusters of microcephaly and Guillain-Barré syndrome. 2016. 
3. Drummond R. CONSORT Revised: Improving the Reporting of Randomized Clinical 
Trials. JAMA. 2001; 285(15):2006-2007. 
4. Allison, P. Survival Analysis Using SAS. 2010 
14. 
LISTING OF TABLES, FIGURES AND LISTINGS 
Table, figure, and listing shells are presented in Appendices 1, 2, and 3, respectively. 

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APPENDIX 1: 
TABLES 
Table 1:
Summary of Screen Failures, All Enrolled Subjects ..................................................36
Table 2:
Summary of Screen Failures by Site, All Enrolled Subjects ......................................36
Table 3:
Subject Disposition by Study Group– Part A .............................................................38
Table 4:
Subject Disposition by Study Group– Part B .............................................................38
Table 5:
Subject Disposition by Site, All Enrolled Subject – Part A .......................................39
Table 6:
Subject Disposition by Site, All Enrolled Subjects – Part B ......................................39
Table 7:
Analysis Populations by Study Group, All Randomized Subjects – Part A ...............40
Table 8:
Analysis Populations by Study Group, All Randomized Subjects – Part B ...............40
Table 9:
Summary of Subject-Specific Protocol Deviations by Category, Reason, and 
Study Group, ITT Population – Part A .......................................................................41
Table 10: Summary of Subject-Specific Protocol Deviations by Category, Reason, and 
Study Group, ITT Population – Part B .......................................................................46
Table 11: Summary of Subject-Specific Protocol Deviations by Category and Reason – 
Screening Segment .....................................................................................................46
Table 12: Summary of Non-Subject Specific Protocol Deviations by Category, Reason, 
and Site – Parts A and B .............................................................................................46
Table 13: Summary of Demographic Characteristics, by Study Group, ITT population– 
Part A ..........................................................................................................................51
Table 14: Summary of Demographic Characteristics, by Study Group, mITT 
Population – Part A .....................................................................................................53
Table 15: Summary of Demographic Characteristics, by Study Group, ITT Population 
– Part B .......................................................................................................................53
Table 16: Summary of Demographic Characteristics, by Study Group, mITT 
Population – Part B .....................................................................................................53
Table 17: Summary of Demographic Characteristics, by Site, All Enrolled Subjects – 
Part A ..........................................................................................................................53
Table 18: Summary of Demographic Characteristics, by Site, All Enrolled Subjects – 
Part B ..........................................................................................................................53
Table 19: Summary of Pre-Existing Medical Conditions by MedDRA® System Organ 
Class and Study Group, ITT Population – Part A ......................................................54
Table 20: Summary of Pre-Existing Medical Conditions by MedDRA® System Organ 
Class and Study Group, ITT Population – Part B .......................................................54

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Table 21: Summary of Subjects with Positive Response to ZIKV Neutralizing 
Antibody (EC50) by Study Visit, Study Group and Baseline Zika Serostatus, 
ITT Population – Part A .............................................................................................55
Table 22: Summary of Subjects with Positive Response to ZIKV Neutralizing 
Antibody (EC50) by Study Visit, Study Group and Baseline Zika Serostatus, 
mITT Population – Part A ..........................................................................................56
Table 23: Summary of Subjects with Positive Response to ZIKV Neutralizing 
Antibody (EC50) by Study Visit and Study Group, Per Protocol Population – 
Part A ..........................................................................................................................56
Table 24: Summary of Subjects with Positive Response to ZIKV Neutralizing 
Antibody (EC80) by Study Visit, Study Group and Baseline Zika Serostatus, 
ITT Population – Part A .............................................................................................56
Table 25: Summary of Subjects with Positive Response to ZIKV Neutralizing 
Antibody (EC80) by Study Visit, Study Group and Baseline Zika Serostatus, 
mITT Population – Part A ..........................................................................................56
Table 26: Summary of Subjects with Positive Response to ZIKV Neutralizing 
Antibody (EC80) by Study Visit and Study Group, Per Protocol Population – 
Part A ..........................................................................................................................56
Table 27: Summary of Subjects with Positive Response to ZIKV Neutralizing 
Antibody (EC50) by Study Visit, Study Group and Baseline Zika Serostatus, 
ITT Population – Part B ..............................................................................................56
Table 28: Summary of Subjects with Positive Response to ZIKV Neutralizing 
Antibody (EC50) by Study Visit, Study Group and Baseline Zika Serostatus, 
mITT Population – Part B...........................................................................................56
Table 29: Summary of Subjects with Positive Response to ZIKV Neutralizing 
Antibody (EC50) by Study Visit and Study Group, Per Protocol Population – 
Part B ..........................................................................................................................56
Table 30: Summary of Subjects with Positive Response to ZIKV Neutralizing 
Antibody (EC80) by Study Visit, Study Group and Baseline Zika Serostatus, 
ITT Population – Part B ..............................................................................................56
Table 31: Summary of Subjects with Positive Response to ZIKV Neutralizing 
Antibody (EC80) by Study Visit, Study Group and Baseline Zika Serostatus, 
mITT Population – Part B...........................................................................................56
Table 32: Summary of Subjects with Positive Response to ZIKV Neutralizing 
Antibody (EC80) by Study Visit and Study Group, Per Protocol Population – 
Part B ..........................................................................................................................56
Table 33: Geometric Mean Titers of ZIKV Neutralizing Antibody (EC50) by Study 
Visit, Study Group and Baseline Zika Serostatus, ITT Population – Part A ..............57
Table 34: Geometric Mean Titers of ZIKV Neutralizing Antibody (EC50) by Study 
Visit, Study Group and Baseline Zika Serostatus, mITT Population – Part A ...........58

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Table 35: Geometric Mean Titers of ZIKV Neutralizing Antibody (EC50) by Study 
Visit, Study Group and Baseline Zika Serostatus, Per Protocol Population – 
Part A ..........................................................................................................................58
Table 36: Geometric Mean Titers of ZIKV Neutralizing Antibody (EC80) by Study 
Visit, Study Group and Baseline Zika Serostatus, mITT Population – Part A ...........58
Table 37: Geometric Mean Titers of ZIKV Neutralizing Antibody (EC80) by Study 
Visit, Study Group and Baseline Zika Serostatus, mITT Population – Part A ...........58
Table 38: Geometric Mean Titers of ZIKV Neutralizing Antibody (EC80) by Study 
Visit, Study Group and Baseline Zika Serostatus, Per Protocol Population – 
Part A ..........................................................................................................................58
Table 39: Geometric Mean Titers of ZIKV Neutralizing Antibody (EC50) by Study 
Visit, Study Group and Baseline Zika Serostatus, ITT Population – Part B ..............58
Table 40: Geometric Mean Titers of ZIKV Neutralizing Antibody (EC50) by Study 
Visit, Study Group and Baseline Zika Serostatus, mITT Population – Part B ...........58
Table 41: Geometric Mean Titers of ZIKV Neutralizing Antibody (EC50) by Study 
Visit, Study Group and Baseline Zika Serostatus, Per Protocol Population – 
Part B ..........................................................................................................................58
Table 42: Geometric Mean Titers of ZIKV Neutralizing Antibody (EC80) by Study 
Visit, Study Group and Baseline Zika Serostatus, mITT Population – Part B ...........58
Table 43: Geometric Mean Titers of ZIKV Neutralizing Antibody (EC80) by Study 
Visit, Study Group and Baseline Zika Serostatus, mITT Population – Part B ...........58
Table 44: Geometric Mean Titers of ZIKV Neutralizing Antibody (EC80) by Study 
Visit, Study Group and Baseline Zika Serostatus, Per Protocol Population – 
Part B ..........................................................................................................................58
Table 45: Incidence of ZIKV Cases by Serostatus and Study Group, ITT Population - 
Part B ..........................................................................................................................59
Table 46: Incidence of ZIKV Cases by Serostatus and Study Group, mITT Population - 
Part B ..........................................................................................................................59
Table 47: Incidence of ZIKV Cases by Serostatus and Study Group, PP Population - 
Part B ..........................................................................................................................59
Table 48: Incidence of ZIKV Cases by Site and Study Group, ITT Population – Part B ..........60
Table 49: Incidence of ZIKV Cases by Site and Study Group, mITT Population – Part 
B ..................................................................................................................................60
Table 50: Incidence of ZIKV Cases by Site and Study Group, PP Population – Part B ............60
Table 51: Number and Percentage of Subjects Reporting ZIKV Signs/Symptoms by 
Study Group, ITT Population – Part B .......................................................................61
Table 52: Number and Percentage of Subjects Reporting ZIKV Signs/Symptoms by 
Study Group, mITT Population – Part B ....................................................................62

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Table 53: Number and Percentage of Subjects Reporting ZIKV Signs/Symptoms by 
Study Group, PP Population – Part B .........................................................................62
Table 54: Vaccine Efficacy for Time to Occurrence of ZIKV Cases by Serostatus and 
Study Group, ITT Population - Part B ........................................................................63
Table 55: Vaccine Efficacy for Time to Occurrence of ZIKV Cases by Serostatus and 
Study Group, mITT Population - Part B .....................................................................63
Table 56: Vaccine Efficacy for Time to Occurrence of ZIKV Cases by Serostatus and 
Study Group, PP Population - Part B..........................................................................63
Table 57: Duration of ZIKV Illness, ITT Population - Part B ....................................................64
Table 58: Duration of ZIKV Illness, mITT Population - Part B .................................................64
Table 59: Duration of ZIKV Illness, PP Population - Part B......................................................64
Table 60: Number and Percentage of Subjects Experiencing Solicited Events, Safety 
Analysis Population – Part A ......................................................................................65
Table 61: Number and Percentage of Subjects Experiencing Solicited Events, Safety 
Analysis Population – Part B ......................................................................................65
Table 62: Number and Percentage of Subjects Experiencing Solicited Events by 
Symptom, Maximum Severity, Administration, and Study Group, Safety 
Analysis Population – Part A ......................................................................................66
Table 63: Number and Percentage of Subjects Experiencing Solicited Events by 
Symptom, Maximum Severity, Administration, and Study Group, Safety 
Analysis Population – Part B ......................................................................................70
Table 64: Number and Percentage of Subjects Experiencing Unsolicited Adverse 
Events with 95% Confidence Intervals by MedDRA® System Organ Class 
and Preferred Term, and Study Group, Safety Analysis Population Post Any 
Administration– Part A ...............................................................................................70
Table 65:  Number and Percentage of Subjects Experiencing Unsolicited Adverse 
Events with 95% Confidence Intervals by MedDRA® System Organ Class 
and Preferred Term, and Study Group, Safety Analysis Population Post First 
Administration– Part A ...............................................................................................71
Table 66: Number and Percentage of Subjects Experiencing Unsolicited Adverse 
Events with 95% Confidence Intervals by MedDRA® System Organ Class 
and Preferred Term, and Study Group, Safety Analysis Population Post 
Second Administration– Part A ..................................................................................72
Table 67: Number and Percentage of Subjects Experiencing Unsolicited Adverse 
Events with 95% Confidence Intervals by MedDRA® System Organ Class 
and Preferred Term, and Study Group, Safety Analysis Population Post 
Third Administration– Part A .....................................................................................72
Table 68: Number and Percentage of Subjects Experiencing Unsolicited Adverse 
Events with 95% Confidence Intervals by MedDRA® System Organ Class 

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and Preferred Term, and Study Group, Safety Analysis Population Post Any 
Administration– Part B ...............................................................................................72
Table 69: Number and Percentage of Subjects Experiencing Unsolicited Adverse 
Events with 95% Confidence Intervals by MedDRA® System Organ Class 
and Preferred Term, and Study Group, Safety Analysis Population Post First 
Administration– Part B ...............................................................................................72
Table 70: Number and Percentage of Subjects Experiencing Unsolicited Adverse 
Events with 95% Confidence Intervals by MedDRA® System Organ Class 
and Preferred Term, and Study Group, Safety Analysis Population Post 
Second Administration– Part B ..................................................................................72
Table 71: Number and Percentage of Subjects Experiencing Unsolicited Adverse 
Events with 95% Confidence Intervals by MedDRA® System Organ Class 
and Preferred Term, and Study Group, Safety Analysis Population Post 
Third Administration– Part B .....................................................................................72
Table 72: Number and Percentage of Subjects Experiencing Unsolicited Adverse 
Events with 95% Confidence Intervals by MedDRA® System Organ Class 
and Preferred Term, All Enrolled Subjects, Pre-First Administration .......................72
Table 73: Number and Percentage of Subjects Experiencing Unsolicited Adverse 
Events by MedDRA® System Organ Class and Preferred Term, Severity, 
Relationship, and Study Group – Part A, Group 1 (N=X) ..........................................72
Table 74: Number and Percentage of Subjects Experiencing Unsolicited Adverse 
Events by MedDRA® System Organ Class and Preferred Term, Severity, 
Relationship, and Study Group – Part A, Group 2 (N=X) ..........................................73
Table 75: Number and Percentage of Subjects Experiencing Unsolicited Adverse 
Events by MedDRA® System Organ Class and Preferred Term, Severity, 
Relationship, and Study Group – Part A, Group 3 (N=X) ..........................................73
Table 76: Number and Percentage of Subjects Experiencing Unsolicited Adverse 
Events by MedDRA® System Organ Class and Preferred Term, Severity, 
Relationship, and Study Group – Part B, Group 4 (N=X) ..........................................74
Table 77: Number and Percentage of Subjects Experiencing Unsolicited Adverse 
Events by MedDRA® System Organ Class and Preferred Term, Severity, 
Relationship, and Study Group – Part B, Group 5 (N=X) ..........................................74
Table 78: Number and Percentage of Subjects Experiencing Unsolicited Adverse 
Events by MedDRA® System Organ Class and Preferred Term, Severity, 
Relationship, and Study Group – Screening Segment (N=X) ....................................74
Table 79: Number and Percentage of Subjects Experiencing Related Unsolicited 
Adverse Events by MedDRA® System Organ Class and Preferred Term, 
Severity, and Study Group – Part A, Group 1 (N=X) ................................................75
Table 80: Number and Percentage of Subjects Experiencing Related Unsolicited 
Adverse Events by MedDRA® System Organ Class and Preferred Term, 
Severity, and Study Group – Part A, Group 2 (N=X) ................................................75

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Table 81: Number and Percentage of Subjects Experiencing Related Unsolicited 
Adverse Events by MedDRA® System Organ Class and Preferred Term, 
Severity, and Study Group – Part A, Group 3 (N=X) ................................................75
Table 82: Number and Percentage of Subjects Experiencing Related Unsolicited 
Adverse Events by MedDRA® System Organ Class and Preferred Term, 
Severity, and Study Group – Part B, Group 4 (N=X) .................................................76
Table 83: Number and Percentage of Subjects Experiencing Related Unsolicited 
Adverse Events by MedDRA® System Organ Class and Preferred Term, 
Severity, and Study Group – Part B, Group 5 (N=X) .................................................76
Table 84: Number and Percentage of Subjects Experiencing Related Unsolicited 
Adverse Events by MedDRA® System Organ Class and Preferred Term, 
Severity, and Study Group – Screening Segment (N=X) ...........................................76
Table 85: Number and Percentage of Subjects Experiencing Related Unsolicited 
Adverse Events Post Dosing by MedDRA® System Organ Class and 
Preferred Term, Dose, and Study Group – Part A, Group 1 .......................................77
Table 86: Number and Percentage of Subjects Experiencing Related Unsolicited 
Adverse Events Post Dosing by MedDRA® System Organ Class and 
Preferred Term, Dose, and Study Group – Part A, Group 2 .......................................77
Table 87: Number and Percentage of Subjects Experiencing Related Unsolicited 
Adverse Events Post Dosing by MedDRA® System Organ Class and 
Preferred Term, Dose, and Study Group – Part A, Group 3 .......................................77
Table 88: Number and Percentage of Subjects Experiencing Related Unsolicited 
Adverse Events Post Dosing by MedDRA® System Organ Class and 
Preferred Term, Dose, and Study Group – Part B, Group 4 .......................................78
Table 89: Number and Percentage of Subjects Experiencing Related Unsolicited 
Adverse Events Post Dosing by MedDRA® System Organ Class and 
Preferred Term, Dose, and Study Group – Part B, Group 5 .......................................78
Table 90: Number of Unsolicited Adverse Events by MedDRA® System Organ Class 
and Preferred Term, Dose, and Study Group – Part A, Group 1 ................................78
Table 91: Number of Unsolicited Adverse Events by MedDRA® System Organ Class 
and Preferred Term, Dose, and Study Group – Part A, Group 2 ................................79
Table 92: Number of Unsolicited Adverse Events by MedDRA® System Organ Class 
and Preferred Term, Dose, and Study Group – Part A, Group 3 ................................79
Table 93: Number of Unsolicited Adverse Events by MedDRA® System Organ Class 
and Preferred Term, Dose, and Study Group – Part B, Group 4 ................................79
Table 94: Number of Unsolicited Adverse Events by MedDRA® System Organ Class 
and Preferred Term, Dose, and Study Group – Part B, Group 5 ................................79
Table 95: Number and Percentage of Subjects Experiencing Adverse Events Above 
5% Frequency Threshold by MedDRA System Organ Class, Preferred Term, 
and Study Group – Part A ...........................................................................................80

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Table 96: Number and Percentage of Subjects Experiencing Adverse Events Above 
5% Frequency Threshold by MedDRA System Organ Class, Preferred Term, 
and Study Group – Part B ...........................................................................................80
Table 97: Overall Summary of Adverse Events .........................................................................81
Table 98: Number and Percentage of Subjects Experiencing Serious Adverse Events 
by MedDRA System Organ Class, Preferred Term, and Study Group ......................82
Table 99: Listing of Serious Adverse Events – Part A ...............................................................83
Table 100: Listing of Serious Adverse Events – Part B ...............................................................84
Table 101: Listing of Serious Adverse Events – Screening Segment ..........................................85
Table 102: Listing of Non-Serious, Unsolicited, Moderate or Severe Adverse Events – 
Part A ..........................................................................................................................86
Table 103: Listing of Non-Serious, Unsolicited, Moderate or Severe Adverse Events – 
Part B ..........................................................................................................................87
Table 104: Listing of New Onset Chronic Medical Conditions – Part A .....................................88
Table 105: Listing of New Onset Chronic Medical Conditions – Part B .....................................88
Table 106: Narratives of Deaths, Other Serious and Significant Adverse Events- All 
Enrolled Subjects ........................................................................................................89
Table 107: Confirmed Cases of DENV, Safety Population – Part B ............................................89
Table 108: Number of Pregnancies by Outcome and Study Group – Part A ...............................89
Table 109: Number of Pregnancies by Outcome and Study Group – Part B ...............................90
Table 110: Distribution of Laboratory Results (Binary-Graded) by Parameter, Severity, 
Study Day, and Study Group – Part A ........................................................................90
Table 111: Distribution of Laboratory Results (Ordinal-Graded) by Parameter, Severity, 
Study Day, and Study Group – Part A, Group 1 ........................................................91
Table 112: Distribution of Laboratory Results (Ordinal-Graded) by Parameter, Severity, 
Study Day, and Study Group – Part A, Group 2 ........................................................93
Table 113: Distribution of Laboratory Results (Ordinal-Graded) by Parameter, Severity, 
Study Day, and Study Group – Part A, Group 3 ........................................................93
Table 114: Distribution of Laboratory Results (Binary-Graded) by Parameter, Severity, 
Study Day, and Study Group – Part B ........................................................................93
Table 115: Distribution of Laboratory Results (Ordinal-Graded) by Parameter, Severity, 
Study Day, and Study Group – Part B, Group 4 .........................................................93
Table 116: Distribution of Laboratory Results (Ordinal-Graded) by Parameter, Severity, 
Study Day, and Study Group – Part B, Group 5 .........................................................93
Table 117: Laboratory Summary Statistics by Parameter, Study Day, and Study Group – 
Part A, Group 1 ...........................................................................................................93

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Table 118: Laboratory Summary Statistics by Parameter, Study Day, and Study Group – 
Part A, Group 2 ...........................................................................................................95
Table 119: Laboratory Summary Statistics by Parameter, Study Day, and Study Group – 
Part A, Group 3 ...........................................................................................................95
Table 120: Laboratory Summary Statistics by Parameter, Study Day, and Study Group – 
Part B, Group 4 ...........................................................................................................96
Table 121: Laboratory Summary Statistics by Parameter, Study Day, and Study Group – 
Part B, Group 5 ...........................................................................................................97
Table 122: Shift Table for RBC by Study Group Comparing Baseline to Post-Baseline 
Measures – Part A .......................................................................................................98
Table 123: Shift Table for Hematocrit by Study Group Comparing Baseline to Post-
Baseline Measures – Part A ........................................................................................99
Table 124: Shift Table for MCV by Study Group Comparing Baseline to Post-Baseline 
Measures – Part A .......................................................................................................99
Table 125: Shift Table for Monocytes by Study Group Comparing Baseline to Post-
Baseline Measures – Part A ........................................................................................99
Table 126: Shift Table for Basophils by Study Group Comparing Baseline to Post-
Baseline Measures – Part A ........................................................................................99
Table 127: Shift Table for ALT by Study Group Comparing Baseline to Post-Baseline 
Measures – Part A, Group 1 .....................................................................................100
Table 128: Shift Table for ALT by Study Group Comparing Baseline to Post-Baseline 
Measures – Part A, Group 2 .....................................................................................102
Table 129: Shift Table for ALT by Study Group Comparing Baseline to Post-Baseline 
Measures – Part A, Group 3 .....................................................................................102
Table 130: Shift Table for WBC by Study Group Comparing Baseline to Post-Baseline 
Measures – Part A, Group 1 .....................................................................................102
Table 131: Shift Table for WBC by Study Group Comparing Baseline to Post-Baseline 
Measures – Part A, Group 2 .....................................................................................102
Table 132: Shift Table for WBC by Study Group Comparing Baseline to Post-Baseline 
Measures – Part A, Group 3 .....................................................................................102
Table 133: Shift Table for Hemoglobin by Study Group Comparing Baseline to Post-
Baseline Measures – Part A, Group 1 .......................................................................102
Table 134: Shift Table for Hemoglobin by Study Group Comparing Baseline to Post-
Baseline Measures – Part A, Group 2 .......................................................................102
Table 135: Shift Table for Hemoglobin by Study Group Comparing Baseline to Post-
Baseline Measures – Part A, Group 3 .......................................................................102
Table 136: Shift Table for Platelets by Study Group Comparing Baseline to Post-
Baseline Measures – Part A, Group 1 .......................................................................102

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Table 137: Shift Table for Platelets by Study Group Comparing Baseline to Post-
Baseline Measures – Part A, Group 2 .......................................................................102
Table 138: Shift Table for Platelets by Study Group Comparing Baseline to Post-
Baseline Measures – Part A, Group 3 .......................................................................102
Table 139: Shift Table for Neutrophils by Study Group Comparing Baseline to Post-
Baseline Measures – Part A, Group 1 .......................................................................102
Table 140: Shift Table for Neutrophils by Study Group Comparing Baseline to Post-
Baseline Measures – Part A, Group 2 .......................................................................102
Table 141: Shift Table for Neutrophils by Study Group Comparing Baseline to Post-
Baseline Measures – Part A, Group 3 .......................................................................102
Table 142: Shift Table for Lymphocytes by Study Group Comparing Baseline to Post-
Baseline Measures – Part A, Group 1 .......................................................................102
Table 143: Shift Table for Lymphocytes by Study Group Comparing Baseline to Post-
Baseline Measures – Part A, Group 2 .......................................................................102
Table 144: Shift Table for Lymphocytes by Study Group Comparing Baseline to Post-
Baseline Measures – Part A, Group 3 .......................................................................102
Table 145: Shift Table for Eosinophils by Study Group Comparing Baseline to Post-
Baseline Measures – Part A, Group 1 .......................................................................102
Table 146: Shift Table for Eosinophils by Study Group Comparing Baseline to Post-
Baseline Measures – Part A, Group 2 .......................................................................102
Table 147: Shift Table for Eosinophils by Study Group Comparing Baseline to Post-
Baseline Measures – Part A, Group 3 .......................................................................102
Table 148: Shift Table for RBC by Study Group Comparing Baseline to Post-Baseline 
Measures – Part B .....................................................................................................103
Table 149: Shift Table for Hematocrit by Study Group Comparing Baseline to Post-
Baseline Measures – Part B ......................................................................................103
Table 150: Shift Table for MCV by Study Group Comparing Baseline to Post-Baseline 
Measures – Part B .....................................................................................................103
Table 151: Shift Table for Monocytes by Study Group Comparing Baseline to Post-
Baseline Measures – Part B ......................................................................................103
Table 152: Shift Table for Basophils by Study Group Comparing Baseline to Post-
Baseline Measures – Part B ......................................................................................103
Table 153: Shift Table for ALT by Study Group Comparing Baseline to Post-Baseline 
Measures – Part B, Group 4 ......................................................................................103
Table 154: Shift Table for ALT by Study Group Comparing Baseline to Post-Baseline 
Measures – Part B, Group 5 ......................................................................................103
Table 155: Shift Table for WBC by Study Group Comparing Baseline to Post-Baseline 
Measures – Part B, Group 4 ......................................................................................103

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Table 156: Shift Table for WBC by Study Group Comparing Baseline to Post-Baseline 
Measures – Part B, Group 5 ......................................................................................103
Table 157: Shift Table for Hemoglobin by Study Group Comparing Baseline to Post-
Baseline Measures – Part B, Group 4 .......................................................................103
Table 158: Shift Table for Hemoglobin by Study Group Comparing Baseline to Post-
Baseline Measures – Part B, Group 5 .......................................................................103
Table 159: Shift Table for Platelets by Study Group Comparing Baseline to Post-
Baseline Measures – Part B, Group 4 .......................................................................103
Table 160: Shift Table for Platelets by Study Group Comparing Baseline to Post-
Baseline Measures – Part B, Group 5 .......................................................................103
Table 161: Shift Table for Neutrophils by Study Group Comparing Baseline to Post-
Baseline Measures – Part B, Group 4 .......................................................................103
Table 162: Shift Table for Neutrophils by Study Group Comparing Baseline to Post-
Baseline Measures – Part B, Group 5 .......................................................................103
Table 163: Shift Table for Lymphocytes by Study Group Comparing Baseline to Post-
Baseline Measures – Part B, Group 4 .......................................................................103
Table 164: Shift Table for Lymphocytes by Study Group Comparing Baseline to Post-
Baseline Measures – Part B, Group 5 .......................................................................103
Table 165: Shift Table for Eosinophils by Study Group Comparing Baseline to Post-
Baseline Measures – Part B, Group 4 .......................................................................103
Table 166: Shift Table for Eosinophils by Study Group Comparing Baseline to Post-
Baseline Measures – Part B, Group 5 .......................................................................103
Table 167: Listing of Abnormal Laboratory Results- Part A .....................................................103
Table 168: Listing of Abnormal Laboratory Results- Part B .....................................................105
Table 169: Distribution of Abnormal Laboratory Results (Ordinal-Graded) Related to 
Study Treatment by Parameter, Severity, Study Day, and Study Group – Part 
A, Group 1 ................................................................................................................105
Table 170: Distribution of Abnormal Laboratory Results (Ordinal-Graded) Related to 
Study Treatment by Parameter, Severity, Study Day, and Study Group – Part 
A, Group 2 ................................................................................................................107
Table 171: Distribution of Abnormal Laboratory Results (Ordinal-Graded) Related to 
Study Treatment by Parameter, Severity, Study Day, and Study Group – Part 
A, Group 3 ................................................................................................................107
Table 172: Distribution of Abnormal Laboratory Results (Ordinal-Graded) Related to 
Study Treatment by Parameter, Severity, Study Day, and Study Group – Part 
B, Group 4 ................................................................................................................107
Table 173: Distribution of Abnormal Laboratory Results (Ordinal-Graded) Related to 
Study Treatment by Parameter, Severity, Study Day, and Study Group – Part 
B, Group 5 ................................................................................................................107

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Table 174: Distribution of Vital Signs by Day Post Dosing, Grade, and Study Group – 
Part A, Group 1 .........................................................................................................108
Table 175: Distribution of Vital Signs by Day Post Dosing, Grade, and Study Group – 
Part A, Group 2 .........................................................................................................109
Table 176: Distribution of Vital Signs by Day Post Dosing, Grade, and Study Group – 
Part A, Group 3 .........................................................................................................109
Table 177: Distribution of Vital Signs by Day Post Dosing, Grade, and Study Group – 
Part B, Group 4 .........................................................................................................110
Table 178: Distribution of Vital Signs by Day Post Dosing, Grade, and Study Group – 
Part B, Group 5 .........................................................................................................110
 
 

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Table 1: 
Summary of Screen Failures, All Enrolled Subjects  
Reason for Screen Failure1 
All Subjects 
(N = XX) 
n 
% 
Not Eligible 
x 
x.x 
Laboratory finding(s) 
x 
x.x 
Physical exam finding(s) 
x 
x.x 
Medical history 
x 
x.x 
Other 
x 
x.x 
Eligible but not Randomized 
x 
x.x 
Time commitment 
x 
x.x 
Concern of potential risks 
x 
x.x 
Number of procedures/blood draws 
x 
x.x 
Unable to contact subject 
x 
x.x 
Study closed out 
x 
x.x 
Other 
x 
x.x 
1Subjects may be counted under multiple criteria 
N = number of subjects screened 
Note, there was only a single segment of the protocol for screening subjects into both Part 
A and Part B  
 
Table 2: 
Summary of Screen Failures by Site, All Enrolled Subjects 
Reason for Screen 
Failure1 
Site 1 
(N = XX) 
Site 2 
(N = XX) 
[Repeat for all sites] 
n 
% 
n 
% 
n 
% 
Not Eligible 
 
 
 
 
 
 
Laboratory 
finding(s) 
 
 
 
 
 
 
Physical exam 
finding(s) 
 
 
 
 
 
 
Medical history 
 
 
 
 
 
 
Other 
 
 
 
 
 
 
Eligible but not 
Randomized 
 
 
 
 
 
 
Time commitment 
 
 
 
 
 
 
Concern of 
potential risks 
 
 
 
 
 
 

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Reason for Screen 
Failure1 
Site 1 
(N = XX) 
Site 2 
(N = XX) 
[Repeat for all sites] 
n 
% 
n 
% 
n 
% 
Number of 
procedures/blood 
draws 
 
 
 
 
 
 
Unable to contact 
subject 
 
 
 
 
 
 
Study closed out 
 
 
 
 
 
 
Other 
 
 
 
 
 
 
1.Subjects may be counted under multiple criteria 
N = number of subjects screened 
Note, there was only a single segment of the protocol for screening subjects into both Part A and 
Part B  
 
 
 

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Table 3: 
Subject Disposition by Study Group– Part A 
Subject 
Disposition  
Group 1: 4 mg 
ZIKVwt DNA, 2 
injections 
(N=X) 
Group 2: 4 mg 
ZIKVwt DNA, 4 
injections 
(N=X) 
Group 3: 8 mg 
ZIKVwt DNA, 4 
injections 
(N=X) 
All Subjects 
(N=X) 
n 
% 
n 
% 
n 
% 
n 
% 
Randomized 
 
 
 
 
 
 
 
 
Received First Administration  
 
 
 
 
 
 
 
 
Received Second Administration 
 
 
 
 
 
 
 
 
Received Third Administration 
 
 
 
 
 
 
 
 
Early Termination 
 
 
 
 
 
 
 
 
Completed Per Protocol Population1 
 
 
 
 
 
 
 
 
Completed mITT Population1 
 
 
 
 
 
 
 
 
1 Subjects removed from the per protocol population and mITT are listed in Listing 8. 
N = number of subjects randomized 
 
Table with similar format: 
Table 4: 
Subject Disposition by Study Group– Part B 
 

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Table 5: 
Subject Disposition by Site, All Enrolled Subject – Part A 
Subject 
Disposition  
Site 1 
(N = XX) 
Site 2 
(N = XX) 
All Subjects 
(N=X) 
n 
% 
n 
% 
n 
% 
Screened 
x 
x.x 
x 
x.x 
x 
x.x 
Randomized 
 
 
 
 
 
 
Received First Administration  
 
 
 
 
 
 
Received Second Administration 
 
 
 
 
 
 
Received Third Administration 
 
 
 
 
 
 
Early Termination 
 
 
 
 
 
 
Lost to Per Protocol Before Administration 3 
 
 
 
 
 
 
 
Table with similar format: 
Table 6: 
Subject Disposition by Site, All Enrolled Subjects – Part B 
 
 

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Table 7: 
Analysis Populations by Study Group, All Randomized Subjects – Part A 
Analysis Population/ 
Reasons for Exclusion 
Group 1: 4 mg 
ZIKVwt DNA, 2 
injections 
(N=X) 
Group 2: 4 mg 
ZIKVwt DNA, 4 
injections 
(N=X) 
Group 3: 8 mg 
ZIKVwt DNA, 4 
injections 
(N=X) 
All Subjects 
(N=X) 
n 
% 
n 
% 
n 
% 
n 
% 
Safety Population/ 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
No study product administered 
 
 
 
 
 
 
 
 
No post administration safety assessments 
 
 
 
 
 
 
 
 
Intent-to-treat 
 
 
 
 
 
 
 
 
Modified intent-to-treat/  
 
 
 
 
 
 
 
 
Not all 3 study product administrations received 
 
 
 
 
 
 
 
 
PCR confirmed symptomatic ZIKV infection on or 
before 1 week after third administration. 
 
 
 
 
 
 
 
 
Per Protocol/ 
 
 
 
 
 
 
 
 
All 3 study product administrations not received 
 
 
 
 
 
 
 
 
PCR confirmed symptomatic ZIKV infection on or 
before 1 week after third administration. 
 
 
 
 
 
 
 
 
<Additional per protocol population exclusion 
categories will be defined following the examination of 
the protocol deviations> 
 
 
 
 
 
 
 
 
N = Number of Randomized Subjects 
Table with similar format: 
Table 8: 
Analysis Populations by Study Group, All Randomized Subjects – Part B  

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Table 9: 
Summary of Subject-Specific Protocol Deviations by Category, Reason, and Study Group, ITT Population – 
Part A  
Category 
Reason for Deviation 
Group 1: 4 mg 
ZIKVwt DNA, 2 
injections  
(N=X) 
Group 2: 4 mg 
ZIKVwt DNA, 4 
injections 
(N=X) 
Group 3: 8 mg 
ZIKVwt DNA, 4 
injections 
(N=X) 
All Subjects 
(N=X) 
n 
Subj. 
n 
Dev. 
n Subj. 
n 
Dev. 
n 
Subj. 
n 
Dev. 
n 
Subj. 
n 
Dev. 
Eligibility 
Any type 
 
 
 
 
 
 
 
 
 
Subject illness 
x 
x 
x 
x 
x 
x 
x 
x 
 
Subject unable to comply 
 
 
 
 
 
 
 
 
 
Subject refusal 
 
 
 
 
 
 
 
 
 
Clinic error 
 
 
 
 
 
 
 
 
 
Pharmacy error 
 
 
 
 
 
 
 
 
 
PharmaJet malfunction 
 
 
 
 
 
 
 
 
 
Laboratory error 
 
 
 
 
 
 
 
 
 
Investigator/study decision 
 
 
 
 
 
 
 
 
 
Other 
 
 
 
 
 
 
 
 
Product administration schedule 
Any type 
 
 
 
 
 
 
 
 
 
Subject illness 
 
 
 
 
 
 
 
 
 
Subject unable to comply 
 
 
 
 
 
 
 
 
 
Subject refusal 
 
 
 
 
 
 
 
 
 
Clinic error 
 
 
 
 
 
 
 
 
 
Pharmacy error 
 
 
 
 
 
 
 
 
 
PharmaJet malfunction 
 
 
 
 
 
 
 
 
 
Laboratory error 
 
 
 
 
 
 
 
 
 
Investigator/study decision 
 
 
 
 
 
 
 
 

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Category 
Reason for Deviation 
Group 1: 4 mg 
ZIKVwt DNA, 2 
injections  
(N=X) 
Group 2: 4 mg 
ZIKVwt DNA, 4 
injections 
(N=X) 
Group 3: 8 mg 
ZIKVwt DNA, 4 
injections 
(N=X) 
All Subjects 
(N=X) 
n 
Subj. 
n 
Dev. 
n Subj. 
n 
Dev. 
n 
Subj. 
n 
Dev. 
n 
Subj. 
n 
Dev. 
 
Other 
 
 
 
 
 
 
 
 
Follow-up visit schedule 
Any type 
 
 
 
 
 
 
 
 
 
Subject illness 
 
 
 
 
 
 
 
 
 
Subject unable to comply 
 
 
 
 
 
 
 
 
 
Subject refusal 
 
 
 
 
 
 
 
 
 
Clinic error 
 
 
 
 
 
 
 
 
 
Pharmacy error 
 
 
 
 
 
 
 
 
 
PharmaJet malfunction 
 
 
 
 
 
 
 
 
 
Laboratory error 
 
 
 
 
 
 
 
 
 
Investigator/study decision 
 
 
 
 
 
 
 
 
 
Other 
 
 
 
 
 
 
 
 
Protocol procedure/assessment 
Any type 
 
 
 
 
 
 
 
 
 
Subject illness 
 
 
 
 
 
 
 
 
 
Subject unable to comply 
 
 
 
 
 
 
 
 
 
Subject refusal 
 
 
 
 
 
 
 
 
 
Clinic error 
 
 
 
 
 
 
 
 
 
Pharmacy error 
 
 
 
 
 
 
 
 
 
PharmaJet malfunction 
 
 
 
 
 
 
 
 
 
Laboratory error 
 
 
 
 
 
 
 
 
 
Investigator/study decision 
 
 
 
 
 
 
 
 
 
Other 
 
 
 
 
 
 
 
 
Product administration 
Any type 
 
 
 
 
 
 
 
 

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Category 
Reason for Deviation 
Group 1: 4 mg 
ZIKVwt DNA, 2 
injections  
(N=X) 
Group 2: 4 mg 
ZIKVwt DNA, 4 
injections 
(N=X) 
Group 3: 8 mg 
ZIKVwt DNA, 4 
injections 
(N=X) 
All Subjects 
(N=X) 
n 
Subj. 
n 
Dev. 
n Subj. 
n 
Dev. 
n 
Subj. 
n 
Dev. 
n 
Subj. 
n 
Dev. 
 
Subject illness 
 
 
 
 
 
 
 
 
 
Subject unable to comply 
 
 
 
 
 
 
 
 
 
Subject refusal 
 
 
 
 
 
 
 
 
 
Clinic error 
 
 
 
 
 
 
 
 
 
Pharmacy error 
 
 
 
 
 
 
 
 
 
PharmaJet malfunction 
 
 
 
 
 
 
 
 
 
Laboratory error 
 
 
 
 
 
 
 
 
 
Investigator/study decision 
 
 
 
 
 
 
 
 
 
Other 
 
 
 
 
 
 
 
 
Blinding policy/procedure 
Any type 
 
 
 
 
 
 
 
 
 
Subject illness 
 
 
 
 
 
 
 
 
 
Subject unable to comply 
 
 
 
 
 
 
 
 
 
Subject refusal 
 
 
 
 
 
 
 
 
 
Clinic error 
 
 
 
 
 
 
 
 
 
Pharmacy error 
 
 
 
 
 
 
 
 
 
PharmaJet malfunction 
 
 
 
 
 
 
 
 
 
Laboratory error 
 
 
 
 
 
 
 
 
 
Investigator/study decision 
 
 
 
 
 
 
 
 
 
Other 
 
 
 
 
 
 
 
 
Informed consent/assent 
Any type 
 
 
 
 
 
 
 
 
 
Subject illness 
 
 
 
 
 
 
 
 
 
Subject unable to comply 
 
 
 
 
 
 
 
 

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Category 
Reason for Deviation 
Group 1: 4 mg 
ZIKVwt DNA, 2 
injections  
(N=X) 
Group 2: 4 mg 
ZIKVwt DNA, 4 
injections 
(N=X) 
Group 3: 8 mg 
ZIKVwt DNA, 4 
injections 
(N=X) 
All Subjects 
(N=X) 
n 
Subj. 
n 
Dev. 
n Subj. 
n 
Dev. 
n 
Subj. 
n 
Dev. 
n 
Subj. 
n 
Dev. 
 
Subject refusal 
 
 
 
 
 
 
 
 
 
Clinic error 
 
 
 
 
 
 
 
 
 
Pharmacy error 
 
 
 
 
 
 
 
 
 
PharmaJet malfunction 
 
 
 
 
 
 
 
 
 
Laboratory error 
 
 
 
 
 
 
 
 
 
Investigator/study decision 
 
 
 
 
 
 
 
 
 
Other 
 
 
 
 
 
 
 
 
Study product dispensation 
Any type 
 
 
 
 
 
 
 
 
 
Subject illness 
 
 
 
 
 
 
 
 
 
Subject unable to comply 
 
 
 
 
 
 
 
 
 
Subject refusal 
 
 
 
 
 
 
 
 
 
Clinic error 
 
 
 
 
 
 
 
 
 
Pharmacy error 
 
 
 
 
 
 
 
 
 
PharmaJet malfunction 
 
 
 
 
 
 
 
 
 
Laboratory error 
 
 
 
 
 
 
 
 
 
Investigator/study decision 
 
 
 
 
 
 
 
 
 
Other 
 
 
 
 
 
 
 
 
Clinical endpoint 
Any type 
 
 
 
 
 
 
 
 
 
Subject illness 
 
 
 
 
 
 
 
 
 
Subject unable to comply 
 
 
 
 
 
 
 
 
 
Subject refusal 
 
 
 
 
 
 
 
 
 
Clinic error 
 
 
 
 
 
 
 
 

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Category 
Reason for Deviation 
Group 1: 4 mg 
ZIKVwt DNA, 2 
injections  
(N=X) 
Group 2: 4 mg 
ZIKVwt DNA, 4 
injections 
(N=X) 
Group 3: 8 mg 
ZIKVwt DNA, 4 
injections 
(N=X) 
All Subjects 
(N=X) 
n 
Subj. 
n 
Dev. 
n Subj. 
n 
Dev. 
n 
Subj. 
n 
Dev. 
n 
Subj. 
n 
Dev. 
 
Pharmacy error 
 
 
 
 
 
 
 
 
 
PharmaJet malfunction 
 
 
 
 
 
 
 
 
 
Laboratory error 
 
 
 
 
 
 
 
 
 
Investigator/study decision 
 
 
 
 
 
 
 
 
 
Other 
 
 
 
 
 
 
 
 
Adverse event 
Any type 
 
 
 
 
 
 
 
 
 
Subject illness 
 
 
 
 
 
 
 
 
 
Subject unable to comply 
 
 
 
 
 
 
 
 
 
Subject refusal 
 
 
 
 
 
 
 
 
 
Clinic error 
 
 
 
 
 
 
 
 
 
Pharmacy error 
 
 
 
 
 
 
 
 
 
PharmaJet malfunction 
 
 
 
 
 
 
 
 
 
Laboratory error 
 
 
 
 
 
 
 
 
 
Investigator/study decision 
 
 
 
 
 
 
 
 
 
Other 
 
 
 
 
 
 
 
 
Serious adverse event 
Any type 
 
 
 
 
 
 
 
 
 
Subject illness 
 
 
 
 
 
 
 
 
 
Subject unable to comply 
 
 
 
 
 
 
 
 
 
Subject refusal 
 
 
 
 
 
 
 
 
 
Clinic error 
 
 
 
 
 
 
 
 
 
Pharmacy error 
 
 
 
 
 
 
 
 
 
PharmaJet malfunction 
 
 
 
 
 
 
 
 

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Category 
Reason for Deviation 
Group 1: 4 mg 
ZIKVwt DNA, 2 
injections  
(N=X) 
Group 2: 4 mg 
ZIKVwt DNA, 4 
injections 
(N=X) 
Group 3: 8 mg 
ZIKVwt DNA, 4 
injections 
(N=X) 
All Subjects 
(N=X) 
n 
Subj. 
n 
Dev. 
n Subj. 
n 
Dev. 
n 
Subj. 
n 
Dev. 
n 
Subj. 
n 
Dev. 
 
Laboratory error 
 
 
 
 
 
 
 
 
 
Investigator/study decision 
 
 
 
 
 
 
 
 
 
Other 
 
 
 
 
 
 
 
 
[Implementation note: any rows with zero deviations for the category/reason being reporting should not be displayed] 
 
Tables with similar format: 
Table 10: 
Summary of Subject-Specific Protocol Deviations by Category, Reason, and Study Group, ITT Population – 
Part B 
Table 11: 
Summary of Subject-Specific Protocol Deviations by Category and Reason – Screening Segment 
Table 12: 
Summary of Non-Subject Specific Protocol Deviations by Category, Reason, and Site – Parts A and B 
Category 
Reason for Deviation 
Number of Deviations 
[Site 1]  
[Site 2] 
[Site 3] 
All Sites 
Eligibility 
Any type 
x 
x 
x 
x 
 
Subject illness 
 
 
 
 
 
Subject unable to comply 
 
 
 
 
 
Subject refusal 
 
 
 
 
 
Clinic error 
 
 
 
 
 
Pharmacy error 
 
 
 
 
 
PharmaJet malfunction 
 
 
 
 
 
Laboratory error 
 
 
 
 
 
Investigator/study decision 
 
 
 
 

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Category 
Reason for Deviation 
Number of Deviations 
[Site 1]  
[Site 2] 
[Site 3] 
All Sites 
 
Other 
 
 
 
 
Product administration schedule 
Any type 
 
 
 
 
 
Subject illness 
 
 
 
 
 
Subject unable to comply 
 
 
 
 
 
Subject refusal 
 
 
 
 
 
Clinic error 
 
 
 
 
 
Pharmacy error 
 
 
 
 
 
PharmaJet malfunction 
 
 
 
 
 
Laboratory error 
 
 
 
 
 
Investigator/study decision 
 
 
 
 
 
Other 
 
 
 
 
Follow-up visit schedule 
Any type 
 
 
 
 
 
Subject illness 
 
 
 
 
 
Subject unable to comply 
 
 
 
 
 
Subject refusal 
 
 
 
 
 
Clinic error 
 
 
 
 
 
Pharmacy error 
 
 
 
 
 
PharmaJet malfunction 
 
 
 
 
 
Laboratory error 
 
 
 
 
 
Investigator/study decision 
 
 
 
 
 
Other 
 
 
 
 
Protocol procedure/assessment 
Any type 
 
 
 
 
 
Subject illness 
 
 
 
 
 
Subject unable to comply 
 
 
 
 

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Category 
Reason for Deviation 
Number of Deviations 
[Site 1]  
[Site 2] 
[Site 3] 
All Sites 
 
Subject refusal 
 
 
 
 
 
Clinic error 
 
 
 
 
 
Pharmacy error 
 
 
 
 
 
PharmaJet malfunction 
 
 
 
 
 
Laboratory error 
 
 
 
 
 
Investigator/study decision 
 
 
 
 
 
Other 
 
 
 
 
Product administration 
Any type 
 
 
 
 
 
Subject illness 
 
 
 
 
 
Subject unable to comply 
 
 
 
 
 
Subject refusal 
 
 
 
 
 
Clinic error 
 
 
 
 
 
Pharmacy error 
 
 
 
 
 
PharmaJet malfunction 
 
 
 
 
 
Laboratory error 
 
 
 
 
 
Investigator/study decision 
 
 
 
 
 
Other 
 
 
 
 
Blinding policy/procedure 
Any type 
 
 
 
 
 
Subject illness 
 
 
 
 
 
Subject unable to comply 
 
 
 
 
 
Subject refusal 
 
 
 
 
 
Clinic error 
 
 
 
 
 
Pharmacy error 
 
 
 
 
 
PharmaJet malfunction 
 
 
 
 

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Category 
Reason for Deviation 
Number of Deviations 
[Site 1]  
[Site 2] 
[Site 3] 
All Sites 
 
Laboratory error 
 
 
 
 
 
Investigator/study decision 
 
 
 
 
 
Other 
 
 
 
 
Informed consent/assent 
Any type 
 
 
 
 
 
Subject illness 
 
 
 
 
 
Subject unable to comply 
 
 
 
 
 
Subject refusal 
 
 
 
 
 
Clinic error 
 
 
 
 
 
Pharmacy error 
 
 
 
 
 
PharmaJet malfunction 
 
 
 
 
 
Laboratory error 
 
 
 
 
 
Investigator/study decision 
 
 
 
 
 
Other 
 
 
 
 
Study product dispensation 
Any type 
 
 
 
 
 
Subject illness 
 
 
 
 
 
Subject unable to comply 
 
 
 
 
 
Subject refusal 
 
 
 
 
 
Clinic error 
 
 
 
 
 
Pharmacy error 
 
 
 
 
 
PharmaJet malfunction 
 
 
 
 
 
Laboratory error 
 
 
 
 
 
Investigator/study decision 
 
 
 
 
 
Other 
 
 
 
 
Clinical endpoint 
Any type 
 
 
 
 

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Category 
Reason for Deviation 
Number of Deviations 
[Site 1]  
[Site 2] 
[Site 3] 
All Sites 
 
Subject illness 
 
 
 
 
 
Subject unable to comply 
 
 
 
 
 
Subject refusal 
 
 
 
 
 
Clinic error 
 
 
 
 
 
Pharmacy error 
 
 
 
 
 
PharmaJet malfunction 
 
 
 
 
 
Laboratory error 
 
 
 
 
 
Investigator/study decision 
 
 
 
 
 
Other 
 
 
 
 
Adverse event 
Any type 
 
 
 
 
 
Subject illness 
 
 
 
 
 
Subject unable to comply 
 
 
 
 
 
Subject refusal 
 
 
 
 
 
Clinic error 
 
 
 
 
 
Pharmacy error 
 
 
 
 
 
PharmaJet malfunction 
 
 
 
 
 
Laboratory error 
 
 
 
 
 
Investigator/study decision 
 
 
 
 
 
Other 
 
 
 
 
Serious adverse event 
Any type 
 
 
 
 
 
Subject illness 
 
 
 
 
 
Subject unable to comply 
 
 
 
 
 
Subject refusal 
 
 
 
 
 
Clinic error 
 
 
 
 

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Category 
Reason for Deviation 
Number of Deviations 
[Site 1]  
[Site 2] 
[Site 3] 
All Sites 
 
Pharmacy error 
 
 
 
 
 
PharmaJet malfunction 
 
 
 
 
 
Laboratory error 
 
 
 
 
 
Investigator/study decision 
 
 
 
 
 
Other 
 
 
 
 
 
Table 13: 
Summary of Demographic Characteristics, by Study Group, ITT population– Part A 
Category 
Characteristic 
Group 1: 4 mg 
ZIKVwt DNA, 2 
injections  
(N=X) 
Group 2: 4 mg 
ZIKVwt DNA, 4 
injections 
(N=X) 
Group 3: 8 mg 
ZIKVwt DNA, 4 
injections 
(N=X) 
All Subjects 
(N=X) 
n 
% 
n 
% 
n 
% 
n 
% 
GENDER 
Male 
 
 
 
 
 
 
 
 
 
Female 
 
 
 
 
 
 
 
 
 
Unknown or Not Reported 
 
 
 
 
 
 
 
 
AGE 
18-20 
 
 
 
 
 
 
 
 
 
21-30 
 
 
 
 
 
 
 
 
 
31-35 
 
 
 
 
 
 
 
 
 
Mean (S.D.) 
 
 
 
 
 
 
 
 
 
Range 
 
 
 
 
 
 
 
 
ETHNICITY 
Hispanic/Latino 
 
 
 
 
 
 
 
 
 
Non-Hispanic/Latino 
 
 
 
 
 
 
 
 
 
Unknown or Not Reported 
 
 
 
 
 
 
 
 
RACE 
White 
 
 
 
 
 
 
 
 

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Category 
Characteristic 
Group 1: 4 mg 
ZIKVwt DNA, 2 
injections  
(N=X) 
Group 2: 4 mg 
ZIKVwt DNA, 4 
injections 
(N=X) 
Group 3: 8 mg 
ZIKVwt DNA, 4 
injections 
(N=X) 
All Subjects 
(N=X) 
n 
% 
n 
% 
n 
% 
n 
% 
 
Black or African American 
 
 
 
 
 
 
 
 
 
American Indian or Alaska Native 
 
 
 
 
 
 
 
 
 
Asian  
 
 
 
 
 
 
 
 
 
Native Hawaiian or Other Pacific Islander 
 
 
 
 
 
 
 
 
 
Multiracial 
 
 
 
 
 
 
 
 
 
Unknown or Not Reported 
 
 
 
 
 
 
 
 
LANGUAGE 
English 
 
 
 
 
 
 
 
 
 
French 
 
 
 
 
 
 
 
 
 
Spanish 
 
 
 
 
 
 
 
 
 
Portuguese 
 
 
 
 
 
 
 
 
 
Creole 
 
 
 
 
 
 
 
 
 
German 
 
 
 
 
 
 
 
 
 
Polish 
 
 
 
 
 
 
 
 
 
Other 
 
 
 
 
 
 
 
 
WEIGHT (kg) 
Mean (S.D.) 
 
 
 
 
 
 
 
 
 
Range 
 
 
 
 
 
 
 
 
 
 
Tables with similar format: Part B tables should include an additional Age category of 15-18 

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Table 14: 
Summary of Demographic Characteristics, by Study Group, mITT Population – Part A 
Table 15: 
Summary of Demographic Characteristics, by Study Group, ITT Population – Part B 
Table 16: 
Summary of Demographic Characteristics, by Study Group, mITT Population – Part B 
Table 17: 
Summary of Demographic Characteristics, by Site, All Enrolled Subjects – Part A 
Table 18: 
Summary of Demographic Characteristics, by Site, All Enrolled Subjects – Part B 
 
 
 

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Table 19: 
Summary of Pre-Existing Medical Conditions by MedDRA® System Organ Class and Study Group, ITT 
Population – Part A  
MedDRA® System Organ Class 
Group 1: 4 mg 
ZIKVwt DNA, 
2 injections 
(N=X) 
Group 2: 4 mg 
ZIKVwt DNA, 
4 injections 
(N=X) 
Group 3: 8 mg 
ZIKVwt DNA, 
4 injections 
(N=X) 
All Subjects 
(N=X) 
n 
% 
n 
% 
n 
% 
n 
% 
Any SOC 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
[SOC 1] 
 
 
 
 
 
 
 
 
[SOC 2] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: A subject is only counted once per SOC. 
 
Table with similar format 
Table 20: 
Summary of Pre-Existing Medical Conditions by MedDRA® System Organ Class and Study Group, ITT 
Population – Part B 
 
 
 

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Table 21: 
Summary of Subjects with Positive Response to ZIKV Neutralizing Antibody (EC50) by Study Visit, Study 
Group and Baseline Zika Serostatus, ITT Population – Part A 
 
Study Visit 
Group 1: 4 mg ZIKVwt DNA, 2 
injections 
(N=X) 
Group 2: 4 mg ZIKVwt DNA, 4 
injections 
(N=X) 
Group 3: 8 mg ZIKVwt DNA, 4 injections 
(N=X) 
Chi-Square test  
p-value 
N  
meas. 
N  
resp 
% 
95% 
CI 
N  
meas. 
N  
resp 
% 
95% 
CI 
N  
meas. 
N  
resp 
% 
95% CI 
Group 1 vs 
Group 2 
Group 2 vs 
Group 3 
Group 1 vs 
Group 3 
All Subjects 
 
Baseline, Pre-administration 
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.xxx 
x.xxx 
x.xxx 
Visit 05, 4 weeks post 3rd 
administration  
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.xxx 
x.xxx 
x.xxx 
Baseline Zika Negative 
 
Baseline, Pre-administration 
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.xxx 
x.xxx 
x.xxx 
Visit 05, 4 weeks post 3rd 
administration  
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.xxx 
x.xxx 
x.xxx 
Baseline Zika Positive 
 
Baseline, Pre-administration 
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.xxx 
x.xxx 
x.xxx 
Visit 05, 4 weeks post 3rd 
administration  
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.xxx 
x.xxx 
x.xxx 
N meas = number of subjects with Neutralizing Antibody data reported. N resp = number of responders.  Positive response is defined as a titer >30.  
95% CIs calculated using Clopper-Pearson exact methodology. 
[Implementation note: Additional visits may be added to this table if NAb data are available for exploratory time points. For Part B 
tables include a Chi-square test comparing Group 4 and Group 5] 
 
Tables with similar format: 

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Table 22: 
Summary of Subjects with Positive Response to ZIKV Neutralizing Antibody (EC50) by Study Visit, Study 
Group and Baseline Zika Serostatus, mITT Population – Part A 
Table 23: 
Summary of Subjects with Positive Response to ZIKV Neutralizing Antibody (EC50) by Study Visit and Study 
Group, Per Protocol Population – Part A 
Table 24: 
Summary of Subjects with Positive Response to ZIKV Neutralizing Antibody (EC80) by Study Visit, Study 
Group and Baseline Zika Serostatus, ITT Population – Part A 
Table 25: 
Summary of Subjects with Positive Response to ZIKV Neutralizing Antibody (EC80) by Study Visit, Study 
Group and Baseline Zika Serostatus, mITT Population – Part A 
Table 26: 
Summary of Subjects with Positive Response to ZIKV Neutralizing Antibody (EC80) by Study Visit and Study 
Group, Per Protocol Population – Part A 
Table 27: 
Summary of Subjects with Positive Response to ZIKV Neutralizing Antibody (EC50) by Study Visit, Study 
Group and Baseline Zika Serostatus, ITT Population – Part B 
Table 28: 
Summary of Subjects with Positive Response to ZIKV Neutralizing Antibody (EC50) by Study Visit, Study 
Group and Baseline Zika Serostatus, mITT Population – Part B 
Table 29: 
Summary of Subjects with Positive Response to ZIKV Neutralizing Antibody (EC50) by Study Visit and Study 
Group, Per Protocol Population – Part B 
Table 30: 
Summary of Subjects with Positive Response to ZIKV Neutralizing Antibody (EC80) by Study Visit, Study 
Group and Baseline Zika Serostatus, ITT Population – Part B 
Table 31: 
Summary of Subjects with Positive Response to ZIKV Neutralizing Antibody (EC80) by Study Visit, Study 
Group and Baseline Zika Serostatus, mITT Population – Part B 
Table 32: 
Summary of Subjects with Positive Response to ZIKV Neutralizing Antibody (EC80) by Study Visit and Study 
Group, Per Protocol Population – Part B 
 
 

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Table 33: 
Geometric Mean Titers of ZIKV Neutralizing Antibody (EC50) by Study Visit, Study Group and Baseline Zika 
Serostatus, ITT Population – Part A 
 
Study Visit 
Group 1: 4 mg ZIKVwt DNA, 2 
injections 
(N=X) 
Group 2: 4 mg ZIKVwt DNA, 4 
injections 
(N=X) 
Group 3: 8 mg ZIKVwt DNA, 4 
injections 
(N=X) 
t- test  
p-value 
N  
meas. 
GMT 
95% CI 
N  
meas. 
GMT 
95% CI 
N  
meas. 
GMT 
95% CI 
Group 1 vs 
Group 2 
Group 2 vs 
Group 3 
Group 1 vs 
Group 3 
All Subjects 
 
Baseline, Pre-administration 
x 
x 
x.x-x.x 
x 
x 
x.x-x.x 
x 
x 
x.x-x.x 
x.xxx 
x.xxx 
x.xxx 
Visit 05, 4 weeks post 3rd 
administration  
x 
x 
x.x-x.x 
x 
x 
x.x-x.x 
x 
x 
x.x-x.x 
x.xxx 
x.xxx 
x.xxx 
Geometric Mean Fold Rise (Visit 
05) 
x 
x 
x.x-x.x 
x 
x 
x.x-x.x 
x 
x 
x.x-x.x 
- 
- 
- 
Baseline Zika Negative 
 
Baseline, Pre-administration 
x 
x 
x.x-x.x 
x 
x 
x.x-x.x 
x 
x 
x.x-x.x 
x.xxx 
x.xxx 
x.xxx 
4 weeks post 3rd administration  
x 
x 
x.x-x.x 
x 
x 
x.x-x.x 
x 
x 
x.x-x.x 
x.xxx 
x.xxx 
x.xxx 
Geometric Mean Fold Rise (Visit 
05) 
x 
x 
x.x-x.x 
x 
x 
x.x-x.x 
x 
x 
x.x-x.x 
- 
- 
- 
Baseline Zika Positive 
 
Baseline, Pre-administration 
x 
x 
x.x-x.x 
x 
x 
x.x-x.x 
x 
x 
x.x-x.x 
x.xxx 
x.xxx 
x.xxx 
4 weeks post 3rd administration  
x 
x 
x.x-x.x 
x 
x 
x.x-x.x 
x 
x 
x.x-x.x 
x.xxx 
x.xxx 
x.xxx 
Geometric Mean Fold Rise (Visit 
05) 
x 
x 
x.x-x.x 
x 
x 
x.x-x.x 
x 
x 
x.x-x.x 
- 
- 
- 
N meas = number of subjects with Neutralizing Antibody data reported. For geometric mean fold-rise only subjects with baseline and post-administration are included.  
 

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Table 34: 
Geometric Mean Titers of ZIKV Neutralizing Antibody (EC50) by Study Visit, Study Group and Baseline Zika 
Serostatus, mITT Population – Part A 
Table 35: 
Geometric Mean Titers of ZIKV Neutralizing Antibody (EC50) by Study Visit, Study Group and Baseline Zika 
Serostatus, Per Protocol Population – Part A 
Table 36: 
Geometric Mean Titers of ZIKV Neutralizing Antibody (EC80) by Study Visit, Study Group and Baseline Zika 
Serostatus, mITT Population – Part A 
Table 37: 
Geometric Mean Titers of ZIKV Neutralizing Antibody (EC80) by Study Visit, Study Group and Baseline Zika 
Serostatus, mITT Population – Part A 
Table 38: 
Geometric Mean Titers of ZIKV Neutralizing Antibody (EC80) by Study Visit, Study Group and Baseline Zika 
Serostatus, Per Protocol Population – Part A 
Table 39: 
Geometric Mean Titers of ZIKV Neutralizing Antibody (EC50) by Study Visit, Study Group and Baseline Zika 
Serostatus, ITT Population – Part B 
Table 40: 
Geometric Mean Titers of ZIKV Neutralizing Antibody (EC50) by Study Visit, Study Group and Baseline Zika 
Serostatus, mITT Population – Part B 
Table 41: 
Geometric Mean Titers of ZIKV Neutralizing Antibody (EC50) by Study Visit, Study Group and Baseline Zika 
Serostatus, Per Protocol Population – Part B 
Table 42: 
Geometric Mean Titers of ZIKV Neutralizing Antibody (EC80) by Study Visit, Study Group and Baseline Zika 
Serostatus, mITT Population – Part B 
Table 43: 
Geometric Mean Titers of ZIKV Neutralizing Antibody (EC80) by Study Visit, Study Group and Baseline Zika 
Serostatus, mITT Population – Part B 
Table 44: 
Geometric Mean Titers of ZIKV Neutralizing Antibody (EC80) by Study Visit, Study Group and Baseline Zika 
Serostatus, Per Protocol Population – Part B 
 
 

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Table 45: 
Incidence of ZIKV Cases by Serostatus and Study Group, ITT Population - Part B 
ZIKV Case Definition 
Baseline Serostatus 
[Group 4]  
(N=X) 
[Group 5]  
(N=X) 
Overall 
(N=X) 
n 
% 
95% CI 
n 
% 
95% CI 
n 
% 
95% CI 
Virologic ZIKV Case 
Overall 
x 
x.x 
x.x, x.x 
x 
x.x 
x.x, x.x 
x 
x.x 
x.x, x.x 
 
ZIKV Positive 
x 
x.x 
x.x, x.x 
x 
x.x 
x.x, x.x 
x 
x.x 
x.x, x.x 
 
ZIKV Negative 
x 
x.x 
x.x, x.x 
x 
x.x 
x.x, x.x 
x 
x.x 
x.x, x.x 
Subclinical ZIKV Case 
Overall 
 
 
 
 
 
 
 
 
 
 
ZIKV Positive 
 
 
 
 
 
 
 
 
 
 
ZIKV Negative 
 
 
 
 
 
 
 
 
 
Symptomatic ZIKV Case 
Overall 
 
 
 
 
 
 
 
 
 
 
ZIKV Positive 
 
 
 
 
 
 
 
 
 
 
ZIKV Negative 
 
 
 
 
 
 
 
 
 
 
Tables with similar formats: 
Table 46: 
Incidence of ZIKV Cases by Serostatus and Study Group, mITT Population - Part B 
Table 47: 
Incidence of ZIKV Cases by Serostatus and Study Group, PP Population - Part B 
 
 

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Table 48: 
Incidence of ZIKV Cases by Site and Study Group, ITT Population – Part B 
ZIKV Case Definition 
Site 
[Group 4]  
(N=X) 
[Group 5]  
(N=X) 
Overall 
(N=X) 
n 
% 
95% CI 
n 
% 
95% CI 
n 
% 
95% CI 
Virologic ZIKV Case 
[Site 1] 
x 
x.x 
x.x, x.x 
x 
x.x 
x.x, x.x 
x 
x.x 
x.x, x.x 
 
[Site 2] 
x 
x.x 
x.x, x.x 
x 
x.x 
x.x, x.x 
x 
x.x 
x.x, x.x 
 
[Repeat for all sites] 
x 
x.x 
x.x, x.x 
x 
x.x 
x.x, x.x 
x 
x.x 
x.x, x.x 
Subclinical ZIKV Case 
[Site 1] 
 
 
 
 
 
 
 
 
 
 
[Site 2] 
 
 
 
 
 
 
 
 
 
 
[Repeat for all sites] 
 
 
 
 
 
 
 
 
 
Symptomatic ZIKV Case 
[Site 1] 
 
 
 
 
 
 
 
 
 
 
[Site 2] 
 
 
 
 
 
 
 
 
 
 
[Repeat for all sites] 
 
 
 
 
 
 
 
 
 
 
Tables with similar formats: 
Table 49: 
Incidence of ZIKV Cases by Site and Study Group, mITT Population – Part B 
Table 50: 
Incidence of ZIKV Cases by Site and Study Group, PP Population – Part B 
 
 

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Table 51: 
Number and Percentage of Subjects Reporting ZIKV Signs/Symptoms by Study Group, ITT Population – Part 
B 
Zika Signs/Symptoms 
[Group 4] 
(N=X) 
[Group 5] 
(N=X) 
Overall 
(N=X) 
 
n 
% 
n 
% 
n 
% 
Fever 
 
 
 
 
 
 
Rash 
 
 
 
 
 
 
Conjunctivitis 
 
 
 
 
 
 
Arthralgia 
 
 
 
 
 
 
Headache 
 
 
 
 
 
 
Myalgia 
 
 
 
 
 
 
Peripheral edema 
 
 
 
 
 
 
Retro-orbital pain 
 
 
 
 
 
 
Sore throat 
 
 
 
 
 
 
Vomiting/Nausea 
 
 
 
 
 
 
Malaise/Fatigue 
 
 
 
 
 
 
Guillain-Barre Syndrome 
 
 
 
 
 
 
Meningitis 
 
 
 
 
 
 
Encephalitis 
 
 
 
 
 
 
Meningoencephalitis 
 
 
 
 
 
 
Other 
 
 
 
 
 
 
Tables with similar format: 

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Table 52: 
Number and Percentage of Subjects Reporting ZIKV Signs/Symptoms by Study Group, mITT Population – 
Part B 
Table 53: 
Number and Percentage of Subjects Reporting ZIKV Signs/Symptoms by Study Group, PP Population – Part B 
 
 

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Table 54: 
Vaccine Efficacy for Time to Occurrence of ZIKV Cases by Serostatus and Study Group, ITT Population - Part 
B 
 
ZIKV Case Definition 
Baseline Serostatus 
[Group 4]  [Group 5]  
Vaccine Efficacy 
N 
N 
% 
95% CI 
p-value 
Virologic ZIKV Case 
Overall 
x 
x 
x 
x.x, x.x 
x.xxx 
 
ZIKV Positive 
x 
x 
x 
x.x, x.x 
x.xxx 
 
ZIKV Negative 
x 
x 
x 
x.x, x.x 
x.xxx 
Subclinical ZIKV Case 
Overall 
 
 
 
 
 
 
ZIKV Positive 
 
 
 
 
 
 
ZIKV Negative 
 
 
 
 
 
Symptomatic ZIKV Case 
Overall 
 
 
 
 
 
 
ZIKV Positive 
 
 
 
 
 
 
ZIKV Negative 
 
 
 
 
 
 
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 
Tables with similar format: 
Table 55: 
Vaccine Efficacy for Time to Occurrence of ZIKV Cases by Serostatus and Study Group, mITT Population - 
Part B 
Table 56: 
Vaccine Efficacy for Time to Occurrence of ZIKV Cases by Serostatus and Study Group, PP Population - Part 
B 
 
 

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Table 57: 
Duration of ZIKV Illness, ITT Population - Part B 
 
Statistic 
[Group 4]  
(N=X) 
[Group 5] 
(N=X) 
Overall 
(N=X) 
Duration of ZIKV Illness 
N 
x 
 
 
 
Mean 
xx.x 
 
 
 
Standard Deviation 
xx.x 
 
 
 
Median 
xx.x 
 
 
 
Min, Max 
xx.x, xx.x 
 
 
 
Tables with similar format: 
Table 58: 
Duration of ZIKV Illness, mITT Population - Part B 
Table 59: 
Duration of ZIKV Illness, PP Population - Part B 
 
 

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Table 60: 
Number and Percentage of Subjects Experiencing Solicited Events, Safety Analysis Population – Part A 
 
Symptom 
Group 1: 4 mg ZIKVwt DNA, 2 
injections 
(N=X) 
Group 2: 4 mg ZIKVwt DNA, 4 
injections 
(N=X) 
Group 3: 8 mg ZIKVwt DNA, 4 
injections 
(N=X) 
Chi-Square test  
p-value 
N  
meas. 
N  
resp 
% 
95% 
CI 
N  
meas. 
N  
resp 
% 
95% 
CI 
N  
meas. 
N  
resp 
% 
95% CI 
Group 1 vs 
Group 2 
Group 2 vs 
Group 3 
Group 1 vs 
Group 3 
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.xxx 
x.xxx 
x.xxx 
Any Systemic 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.xxx 
x.xxx 
x.xxx 
Malaise 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Myalgia 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Headache 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Chills 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Nausea 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Joint Pain 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Temperature 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Any Local Symptom 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pain/Tenderness 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Swelling 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Redness 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Subjects are counted at most once for each symptom considering solicited symptoms reported after any an administration 
N. meas = the number of subjects with non-missing data for at least one post-administration assessment for the symptom being summarized. 
 
Table with similar format: 
Table 61: 
Number and Percentage of Subjects Experiencing Solicited Events, Safety Analysis Population – Part B 
 
 
 

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Table 62: 
Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Maximum Severity, 
Administration, and Study Group, Safety Analysis Population – Part A 
 
 
Group 1: 4 mg ZIKVwt DNA, 2 injections 
(N=X) 
Group 2: 4 mg ZIKVwt DNA, 4 injections 
(N=X) 
Group 3: 8 mg ZIKVwt DNA, 4 injections 
(N=X) 
 
Symptoms 
Intensity 
Admin 1 
(N=X) 
Admin 2 
(N=X) 
Admin 3 
(N=X) 
Overall 
(N=X) 
Admin 1 
(N=X) 
Admin 2 
(N=X) 
Admin 3 
(N=X) 
Overall 
(N=X) 
Admin 1 
(N=X) 
Admin 2 
(N=X) 
Admin 3 
(N=X) 
Overall 
(N=X) 
Overall 
Incidence 
(N=X) 
PAIN/TENDERNESS 
 
 
 
 
 
 
 
 
 
 
 
 
 
None 
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%) 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
Missing 
 
 
 
 
 
 
 
 
 
 
 
 
 
SWELLING 
 
 
 
 
 
 
 
 
 
 
 
 
 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
Missing 
 
 
 
 
 
 
 
 
 
 
 
 
 
REDNESS 
 
 
 
 
 
 
 
 
 
 
 
 
 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
Missing 
 
 
 
 
 
 
 
 
 
 
 
 
 
ANY LOCAL SYMPTOM  
 
 
 
 
 
 
 
 
 
 
 
 

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Group 1: 4 mg ZIKVwt DNA, 2 injections 
(N=X) 
Group 2: 4 mg ZIKVwt DNA, 4 injections 
(N=X) 
Group 3: 8 mg ZIKVwt DNA, 4 injections 
(N=X) 
 
Symptoms 
Intensity 
Admin 1 
(N=X) 
Admin 2 
(N=X) 
Admin 3 
(N=X) 
Overall 
(N=X) 
Admin 1 
(N=X) 
Admin 2 
(N=X) 
Admin 3 
(N=X) 
Overall 
(N=X) 
Admin 1 
(N=X) 
Admin 2 
(N=X) 
Admin 3 
(N=X) 
Overall 
(N=X) 
Overall 
Incidence 
(N=X) 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
Missing 
 
 
 
 
 
 
 
 
 
 
 
 
 
MALAISE 
 
 
 
 
 
 
 
 
 
 
 
 
 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
Missing 
 
 
 
 
 
 
 
 
 
 
 
 
 
MYALGIA 
 
 
 
 
 
 
 
 
 
 
 
 
 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
Missing 
 
 
 
 
 
 
 
 
 
 
 
 
 
HEADACHE 
 
 
 
 
 
 
 
 
 
 
 
 
 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Group 1: 4 mg ZIKVwt DNA, 2 injections 
(N=X) 
Group 2: 4 mg ZIKVwt DNA, 4 injections 
(N=X) 
Group 3: 8 mg ZIKVwt DNA, 4 injections 
(N=X) 
 
Symptoms 
Intensity 
Admin 1 
(N=X) 
Admin 2 
(N=X) 
Admin 3 
(N=X) 
Overall 
(N=X) 
Admin 1 
(N=X) 
Admin 2 
(N=X) 
Admin 3 
(N=X) 
Overall 
(N=X) 
Admin 1 
(N=X) 
Admin 2 
(N=X) 
Admin 3 
(N=X) 
Overall 
(N=X) 
Overall 
Incidence 
(N=X) 
Missing 
 
 
 
 
 
 
 
 
 
 
 
 
 
CHILLS 
 
 
 
 
 
 
 
 
 
 
 
 
 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
Missing 
 
 
 
 
 
 
 
 
 
 
 
 
 
NAUSEA 
 
 
 
 
 
 
 
 
 
 
 
 
 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
Missing 
 
 
 
 
 
 
 
 
 
 
 
 
 
JOINT PAIN 
 
 
 
 
 
 
 
 
 
 
 
 
 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
Missing 
 
 
 
 
 
 
 
 
 
 
 
 
 
TEMPERATURE 
 
 
 
 
 
 
 
 
 
 
 
 
 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Group 1: 4 mg ZIKVwt DNA, 2 injections 
(N=X) 
Group 2: 4 mg ZIKVwt DNA, 4 injections 
(N=X) 
Group 3: 8 mg ZIKVwt DNA, 4 injections 
(N=X) 
 
Symptoms 
Intensity 
Admin 1 
(N=X) 
Admin 2 
(N=X) 
Admin 3 
(N=X) 
Overall 
(N=X) 
Admin 1 
(N=X) 
Admin 2 
(N=X) 
Admin 3 
(N=X) 
Overall 
(N=X) 
Admin 1 
(N=X) 
Admin 2 
(N=X) 
Admin 3 
(N=X) 
Overall 
(N=X) 
Overall 
Incidence 
(N=X) 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
Missing 
 
 
 
 
 
 
 
 
 
 
 
 
 
ANY SYSTEMIC 
SYMPTOM 
 
 
 
 
 
 
 
 
 
 
 
 
 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
Missing 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severity is the maximum severity reported post dosing for each subject. 
 
Table with similar format: 

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Table 63: 
Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Maximum Severity, 
Administration, and Study Group, Safety Analysis Population – Part B 
Table 64: 
Number and Percentage of Subjects Experiencing Unsolicited Adverse Events with 95% Confidence Intervals 
by MedDRA® System Organ Class and Preferred Term, and Study Group, Safety Analysis Population Post Any 
Administration– Part A 
 
SYSTEM ORGAN CLASS/ 
Preferred Term 
Group 1: 4 mg ZIKVwt DNA, 2 
injections 
(N=X) 
Group 2: 4 mg ZIKVwt DNA, 4 
injections 
(N=X) 
Group 3: 8 mg ZIKVwt DNA, 4 
injections 
(N=X) 
Fisher’s Exact 
p-value 
n 
% 
95% CI 
n 
% 
95% CI 
n 
% 
95% CI 
Group 1 vs 
Group 2 
Group 2 vs 
Group 3 
Group 1 vs 
Group 3 
SYSTEM ORGAN CLASS #1 
x 
x 
x.x-x.x 
x 
x 
x.x-x.x 
x 
x 
x.x-x.x 
x.xxx 
x.xxx 
x.xxx 
Preferred Term #1 
x 
x 
x.x-x.x 
x 
x 
x.x-x.x 
x 
x 
x.x-x.x 
x.xxx 
x.xxx 
x.xxx 
Preferred Term #2 
x 
x 
x.x-x.x 
x 
x 
x.x-x.x 
x 
x 
x.x-x.x 
x.xxx 
x.xxx 
x.xxx 
SYSTEM ORGAN CLASS #2 
x 
x 
x.x-x.x 
x 
x 
x.x-x.x 
x 
x 
x.x-x.x 
x.xxx 
x.xxx 
x.xxx 
Preferred Term #1 
x 
x 
x.x-x.x 
x 
x 
x.x-x.x 
x 
x 
x.x-x.x 
x.xxx 
x.xxx 
x.xxx 
Preferred Term #2 
x 
x 
x.x-x.x 
x 
x 
x.x-x.x 
x 
x 
x.x-x.x 
x.xxx 
x.xxx 
x.xxx 
SYSTEM ORGAN CLASS #3 
x 
x 
x.x-x.x 
x 
x 
x.x-x.x 
x 
x 
x.x-x.x 
x.xxx 
x.xxx 
x.xxx 
Preferred Term #1 
x 
x 
x.x-x.x 
x 
x 
x.x-x.x 
x 
x 
x.x-x.x 
x.xxx 
x.xxx 
x.xxx 
Preferred Term #2 
x 
x 
x.x-x.x 
x 
x 
x.x-x.x 
x 
x 
x.x-x.x 
x.xxx 
x.xxx 
x.xxx 
Note: A subject is counted at most once per SOC and PT  
N = the number of subjects in the Safety analysis population who received the applicable dose. 
 
[Implementation note: Table for Part A should use Fisher’s exact test for calculating p-values. Tables for Part B should use Chi-square 
test for calculating p-values.] 

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Table 65: 
 Number and Percentage of Subjects Experiencing Unsolicited Adverse Events with 95% Confidence Intervals 
by MedDRA® System Organ Class and Preferred Term, and Study Group, Safety Analysis Population Post 
First Administration– Part A 
[Implementation note: Table will only include unsolicited adverse events occurring after the first administration but before the second 
administration.] 
MedDRA® System Organ Class 
MedDRA® Preferred 
Term 
Post Dose 1 
Group 1: 4 mg 
ZIKVwt DNA, 2 
injections 
(N=X) 
Post Dose 1 
Group 2: 4 mg 
ZIKVwt DNA, 4 
injections 
(N=X) 
Post Dose 1 
Group 3: 8 mg ZIKVwt 
DNA, 4 injections 
(N=X) 
All Subjects 
(N=X) 
n 
% 
95% CI 
n 
% 
95% CI 
n 
% 
95% CI 
n 
% 
95% CI 
Any SOC 
Any PT 
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 
[SOC 1] 
Any PT 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 1] 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
 
 
 
 
 
 
[SOC 2] 
Any PT 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 1] 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: This table presents number and percentage of subjects.  A subject is only counted once per PT/time point. 
 

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Table 66: 
Number and Percentage of Subjects Experiencing Unsolicited Adverse Events with 95% Confidence Intervals 
by MedDRA® System Organ Class and Preferred Term, and Study Group, Safety Analysis Population Post 
Second Administration– Part A 
Table 67: 
Number and Percentage of Subjects Experiencing Unsolicited Adverse Events with 95% Confidence Intervals 
by MedDRA® System Organ Class and Preferred Term, and Study Group, Safety Analysis Population Post 
Third Administration– Part A 
Table 68: 
Number and Percentage of Subjects Experiencing Unsolicited Adverse Events with 95% Confidence Intervals 
by MedDRA® System Organ Class and Preferred Term, and Study Group, Safety Analysis Population Post Any 
Administration– Part B 
Table 69: 
Number and Percentage of Subjects Experiencing Unsolicited Adverse Events with 95% Confidence Intervals 
by MedDRA® System Organ Class and Preferred Term, and Study Group, Safety Analysis Population Post 
First Administration– Part B 
Table 70: 
Number and Percentage of Subjects Experiencing Unsolicited Adverse Events with 95% Confidence Intervals 
by MedDRA® System Organ Class and Preferred Term, and Study Group, Safety Analysis Population Post 
Second Administration– Part B 
Table 71: 
Number and Percentage of Subjects Experiencing Unsolicited Adverse Events with 95% Confidence Intervals 
by MedDRA® System Organ Class and Preferred Term, and Study Group, Safety Analysis Population Post 
Third Administration– Part B 
Table 72: 
Number and Percentage of Subjects Experiencing Unsolicited Adverse Events with 95% Confidence Intervals 
by MedDRA® System Organ Class and Preferred Term, All Enrolled Subjects, Pre-First Administration 
Table 73: 
Number and Percentage of Subjects Experiencing Unsolicited Adverse Events by MedDRA® System 
Organ Class and Preferred Term, Severity, Relationship, and Study Group – Part A, Group 1 (N=X) 

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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 
% 
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] 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
 
 
 
 
 
 
 
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. 
 
Tables with similar format: 
Table 74: 
Number and Percentage of Subjects Experiencing Unsolicited Adverse Events by MedDRA® System 
Organ Class and Preferred Term, Severity, Relationship, and Study Group – Part A, Group 2 (N=X) 
Table 75: 
Number and Percentage of Subjects Experiencing Unsolicited Adverse Events by MedDRA® System 
Organ Class and Preferred Term, Severity, Relationship, and Study Group – Part A, Group 3 (N=X) 

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Table 76: 
Number and Percentage of Subjects Experiencing Unsolicited Adverse Events by MedDRA® System 
Organ Class and Preferred Term, Severity, Relationship, and Study Group – Part B, Group 4 (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 
% 
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] 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
 
 
 
 
 
 
 
Tables with similar format: 
Table 77: 
Number and Percentage of Subjects Experiencing Unsolicited Adverse Events by MedDRA® System 
Organ Class and Preferred Term, Severity, Relationship, and Study Group – Part B, Group 5 (N=X) 
Table 78: 
Number and Percentage of Subjects Experiencing Unsolicited Adverse Events by MedDRA® System 
Organ Class and Preferred Term, Severity, Relationship, and Study Group – Screening Segment (N=X) 
 
 

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Table 79: 
Number and Percentage of Subjects Experiencing Related Unsolicited Adverse Events by MedDRA® 
System Organ Class and Preferred Term, Severity, and Study Group – Part A, Group 1 (N=X) 
MedDRA® System Organ Class 
MedDRA® Preferred Term 
Any Incidence 
Severity 
Mild 
Moderate 
Severe 
n 
% 
n 
% 
n 
% 
n 
% 
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] 
 
 
 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
 
 
 
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. 
 
Tables with a similar format: 
Table 80: 
Number and Percentage of Subjects Experiencing Related Unsolicited Adverse Events by MedDRA® 
System Organ Class and Preferred Term, Severity, and Study Group – Part A, Group 2 (N=X) 
Table 81: 
Number and Percentage of Subjects Experiencing Related Unsolicited Adverse Events by MedDRA® 
System Organ Class and Preferred Term, Severity, and Study Group – Part A, Group 3 (N=X) 
 
 
 

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Table 82: 
Number and Percentage of Subjects Experiencing Related Unsolicited Adverse Events by MedDRA® 
System Organ Class and Preferred Term, Severity, and Study Group – Part B, Group 4 (N=X) 
MedDRA® System Organ Class 
MedDRA® Preferred Term 
Any Incidence 
Severity 
Mild 
Moderate 
Severe 
n 
% 
n 
% 
n 
% 
n 
% 
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] 
 
 
 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
 
 
 
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 
Tables with similar format: 
Table 83: 
Number and Percentage of Subjects Experiencing Related Unsolicited Adverse Events by MedDRA® 
System Organ Class and Preferred Term, Severity, and Study Group – Part B, Group 5 (N=X) 
Table 84: 
Number and Percentage of Subjects Experiencing Related Unsolicited Adverse Events by MedDRA® 
System Organ Class and Preferred Term, Severity, and Study Group – Screening Segment (N=X) 
 
 

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Table 85: 
Number and Percentage of Subjects Experiencing Related Unsolicited Adverse Events Post Dosing by 
MedDRA® System Organ Class and Preferred Term, Dose, and Study Group – Part A, Group 1  
 
 
Post Dose 1 
(N=X) 
 
Post Dose 2 
(N=X) 
 
Post Dose 3 
(N=X) 
Post Any Dose 
(N=X) 
MedDRA® System Organ Class 
MedDRA® Preferred Term 
n 
% 
n 
% 
n 
% 
n 
% 
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] 
 
 
 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
 
 
 
Note: This table presents number and percentage of subjects.  A subject is only counted once per PT/Time point. 
 
Tables with similar format: 
Table 86: 
Number and Percentage of Subjects Experiencing Related Unsolicited Adverse Events Post Dosing by 
MedDRA® System Organ Class and Preferred Term, Dose, and Study Group – Part A, Group 2  
Table 87: 
Number and Percentage of Subjects Experiencing Related Unsolicited Adverse Events Post Dosing by 
MedDRA® System Organ Class and Preferred Term, Dose, and Study Group – Part A, Group 3  
 

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Table 88: 
Number and Percentage of Subjects Experiencing Related Unsolicited Adverse Events Post Dosing by 
MedDRA® System Organ Class and Preferred Term, Dose, and Study Group – Part B, Group 4 
Table 89: 
Number and Percentage of Subjects Experiencing Related Unsolicited Adverse Events Post Dosing by 
MedDRA® System Organ Class and Preferred Term, Dose, and Study Group – Part B, Group 5 
Table 90: 
Number of Unsolicited Adverse Events by MedDRA® System Organ Class and Preferred Term, Dose, and Study 
Group – Part A, Group 1  
[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.] 
 
 
Post Dose 1 
(N=X) 
Post Dose 2 
(N=X) 
Post Dose 3 
(N=X) 
Post Any Dose 
(N=X) 
MedDRA® System Organ Class 
MedDRA® Preferred Term 
# of Events 
# of Events 
# of Events 
# of Events 
Any SOC 
Any PT 
x 
x 
x 
x 
[SOC 1] 
Any PT 
 
 
 
 
 
[PT 1] 
 
 
 
 
 
[PT 2] 
 
 
 
 
[SOC 2] 
Any PT 
 
 
 
 
 
[PT 1] 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
Note: This table presents number of events. 
 
Table with similar format: 

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Table 91: 
Number of Unsolicited Adverse Events by MedDRA® System Organ Class and Preferred Term, Dose, and Study 
Group – Part A, Group 2  
Table 92: 
Number of Unsolicited Adverse Events by MedDRA® System Organ Class and Preferred Term, Dose, and Study 
Group – Part A, Group 3 
Table 93: 
Number of Unsolicited Adverse Events by MedDRA® System Organ Class and Preferred Term, Dose, and Study 
Group – Part B, Group 4  
Table 94: 
Number of Unsolicited Adverse Events by MedDRA® System Organ Class and Preferred Term, Dose, and Study 
Group – Part B, Group 5  
 
 

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Table 95: 
Number and Percentage of Subjects Experiencing Adverse Events Above 5% Frequency Threshold by MedDRA 
System Organ Class, Preferred Term, and Study Group – Part A  

 
 
 
 
 
 
 
 
 
 
 
 
 
Table with similar format: 
Table 96: 
Number and Percentage of Subjects Experiencing Adverse Events Above 5% Frequency Threshold by MedDRA 
System Organ Class, Preferred Term, and Study Group – Part B  
 
 
 
Group 1: 
4 mg 
ZIKVwt 
DNA, 2 
injections  
(N=X) 
Group 2: 4 
mg 
ZIKVwt 
DNA, 4 
injections  
(N=X) 
Group 3: 8 
mg 
ZIKVwt 
DNA, 4 
injections  
(N=X) 
 
n 
% 
n 
% 
n 
% 
At least one solicited or unsolicited 
adverse event above 5% 
 
 
 
 
 
 
[SOC 1] 
 
 
 
 
 
 
[PT 1] 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
[SOC 1] 
 
 
 
 
 
 

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Table 97: 
Overall Summary of Adverse Events 
 
Group 1: 4 
mg ZIKVwt 
DNA, 2 
injections 
(N=X) 
Group 2: 4 
mg ZIKVwt 
DNA, 4 
injections 
(N=X) 
Group 3: 
8 mg 
ZIKVwt 
DNA, 4 
injections 
(N=X) 
[Group 
4] 
(N=X) 
[Group 
5] 
(N=X) 
All Part A 
Subjects 
(N=X) 
All Part B 
Subjects 
(N=X) 
All 
Randomized 
Subjects 
(N=X) 
Subjects in 
Screening 
Subjectsa with 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
At least one local solicited reactogenicity 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
- 
At least one systemic solicited reactogenicity 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
- 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
At least one unsolicited adverse event 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
At least one related unsolicited adverse event 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
     Mild (Grade 1) 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
     Moderate (Grade 2)  
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
     Severe (Grade 3)  
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
     Not yet assessed 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
At least one severe (Grade 3) unsolicited 
adverse event 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
     Related  
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
     Unrelated 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
At least one serious adverse eventb 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
At least one related, serious adverse event 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
At least one adverse event leading to early 
terminationc  
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
At least one new onset chronic medical 
condition 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
- 

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Group 1: 4 
mg ZIKVwt 
DNA, 2 
injections 
(N=X) 
Group 2: 4 
mg ZIKVwt 
DNA, 4 
injections 
(N=X) 
Group 3: 
8 mg 
ZIKVwt 
DNA, 4 
injections 
(N=X) 
[Group 
4] 
(N=X) 
[Group 
5] 
(N=X) 
All Part A 
Subjects 
(N=X) 
All Part B 
Subjects 
(N=X) 
All 
Randomized 
Subjects 
(N=X) 
Subjects in 
Screening 
Subjectsa with 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
N = Number of subjects in the Safety Population 
a Subjects are counted once for each category regardless of the number of events. 
b A listing of Serious Adverse Events is included in Table 99 through Table 101. 
c As reported on the Adverse Event eCRF. 
 
Table 98: 
Number and Percentage of Subjects Experiencing Serious Adverse Events by MedDRA System Organ Class, 
Preferred Term, and Study Group 
 
SYSTEM ORGAN CLASS/ 
Preferred Term 
Group 1: 4 mg 
ZIKVwt DNA, 2 
injections 
(N=X) 
Group 2: 4 mg 
ZIKVwt DNA, 
4 injections 
(N=X) 
Group 3: 8 mg 
ZIKVwt DNA, 4 
injections 
(N=X) 
[Group 4] 
(N=X)  
[Group 5] 
(N=X) 
All Randomized 
Subjects 
(N=X) 
Subjects in 
Screening 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
SYSTEM ORGAN CLASS #1 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Preferred Term #1 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Preferred Term #2 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
SYSTEM ORGAN CLASS #2 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Preferred Term #1 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Preferred Term #2 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
SYSTEM ORGAN CLASS #3 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Preferred Term #1 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Preferred Term #2 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Note: A subject is counted at most once per SOC and PT  
N = the number of subjects in the Safety analysis population 
 

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Table 99: 
Listing of Serious Adverse Events – Part A 
# 1  
Subject ID 
Study 
Group 
AE Number 
Adverse Event 
Associated with 
Dose # 
# of Days Post 
Associated Dose 
Duration (Days) 
Reason Reported 
as an SAE 
Severity 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
#2 
Subject ID 
Adverse 
Event 
Relationship 
to Study 
Treatment 
Action Taken 
with Study 
Treatment 
Subject 
Discontinued 
Due to AE 
Outcome 
Comments 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Table 100: 
Listing of Serious Adverse Events – Part B 
# 1  
Subject ID 
Study 
Group 
AE 
Number 
Adverse Event 
Associated 
with Dose # 
# of Days Post 
Associated 
Dose 
Duration 
(Days) 
Reason 
Reported as 
an SAE 
Severity 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
# 2  
Subject ID 
Adverse 
Event 
Relationship 
to Study 
Treatment 
Action Taken 
with Study 
Treatment 
Subject 
Discontinued 
Due to AE 
Outcome 
Comments 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Table 101: 
Listing of Serious Adverse Events – Screening Segment 
Subject ID 
Study 
Group 
AE 
Number 
Adverse Event 
Duration 
(Days) 
Reason 
Reported as 
an SAE 
Severity 
Action Taken 
with Study 
Treatment 
Outcome 
Comments 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Table 102: 
Listing of Non-Serious, Unsolicited, Moderate or Severe Adverse Events – Part A 
# 1  
Subject ID 
Study 
Group 
AE Number 
Adverse Event 
Associated with 
Dose # 
# of Days Post 
Associated Dose 
Duration (Days) 
Severity 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
#2 
Subject ID 
Adverse 
Event 
Relationship 
to Study 
Treatment 
Action Taken 
with Study 
Treatment 
Subject 
Discontinued 
Due to AE 
Outcome 
Comments 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Table 103: 
Listing of Non-Serious, Unsolicited, Moderate or Severe Adverse Events – Part B 
# 1  
Subject ID 
Study 
Group 
AE Number 
Adverse Event 
Associated with 
Dose # 
# of Days Post 
Associated Dose 
Duration (Days) 
Reason Reported 
as an SAE 
Severity 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
#2 
Subject ID 
Adverse 
Event 
Relationship 
to Study 
Treatment 
Action Taken 
with Study 
Treatment 
Subject 
Discontinued 
Due to AE 
Outcome 
Comments 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Table 104: 
Listing of New Onset Chronic Medical Conditions – Part A 
 
Subject 
ID 
Age 
(Years) 
Study 
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 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
Table with similar format: 
Table 105: 
Listing of New Onset Chronic Medical Conditions – Part B 
 
 

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Table 106: 
Narratives of Deaths, Other Serious and Significant Adverse Events- All Enrolled Subjects  
 
Table 107: 
Confirmed Cases of DENV, Safety Population – Part B 
 
[Group 4] 
(N=X) 
[Group 5]  
(N=X) 
Overall 
(N=X) 
Group 4 vs Group 5 
p-value 
n 
% 
95% CI 
n 
% 
95% CI 
n 
% 
95% CI 
Confirmed DENV Case 
x 
x.x 
x.x, x.x 
x 
x.x 
x.x, x.x 
x 
x.x 
x.x, x.x 
x.xxx 
Baseline Zika Negative 
Confirmed DENV Case 
x 
x.x 
x.x, x.x 
x 
x.x 
x.x, x.x 
x 
x.x 
x.x, x.x 
x.xxx 
Baseline Zika Positive 
Confirmed DENV Case 
x 
x.x 
x.x, x.x 
x 
x.x 
x.x, x.x 
x 
x.x 
x.x, x.x 
x.xxx 
 
Table 108: 
Number of Pregnancies by Outcome and Study Group – Part A  
 
Group 1: 4 mg 
ZIKVwt DNA, 2 
injections 
(N=X) 
Group 2: 4 mg 
ZIKVwt DNA, 4 
injections 
(N=X) 
Group 3: 8 mg 
ZIKVwt DNA, 4 
injections 
(N=X) 
All Subjects 
(N=X) 
Total pregnancies 
x 
x 
x 
x 
Live birth 
x 
x 
x 
x 
Congenital anomalies 
x 
x 
x 
x 
Neonatal deaths 
x 
x 
x 
x 
Miscarriage 
x 
x 
x 
x 
Elective abortion 
x 
x 
x 
x 
Ectopic pregnancy 
x 
x 
x 
x 
Still birth 
x 
x 
x 
x 
Congenital anomalies 
x 
x 
x 
x 

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Table with similar format: 
Table 109: 
Number of Pregnancies by Outcome and Study Group – Part B 
Table 110: 
Distribution of Laboratory Results (Binary-Graded) by Parameter, Severity, Study Day, and Study Group – 
Part A 
[For binary parameters, not contained in tox table] 
Laboratory Parameter 
Study Day 
Group 1: 4 mg ZIKVwt DNA, 2 
injections 
Group 2: 4 mg ZIKVwt DNA, 4 
injections 
Group 3: 8 mg ZIKVwt DNA, 
4 injections 
N 
Normal 
Abnormal 
N 
Normal 
Abnormal 
N 
Normal 
Abnormal 
 
n 
% 
n 
% 
 
n 
% 
n 
% 
 
n 
% 
n 
% 
Any Parameter 
Baseline 
 
x 
x.x 
x 
x.x 
 
x 
x.x 
x 
x.x 
 
x 
x.x 
x 
x.x 
 
Day 28 (Visit 03) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 42 (Visit 03B) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 56 (Visit 04) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 70 (Visit 04B) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 84 (Visit 05) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 112 (Visit 06) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Max Post Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[Parameter 1] 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 28 (Visit 03) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 42 (Visit 03B) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 56 (Visit 04) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 70 (Visit 04B) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 84 (Visit 05) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 112 (Visit 06) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Laboratory Parameter 
Study Day 
Group 1: 4 mg ZIKVwt DNA, 2 
injections 
Group 2: 4 mg ZIKVwt DNA, 4 
injections 
Group 3: 8 mg ZIKVwt DNA, 
4 injections 
N 
Normal 
Abnormal 
N 
Normal 
Abnormal 
N 
Normal 
Abnormal 
 
n 
% 
n 
% 
 
n 
% 
n 
% 
 
n 
% 
n 
% 
 
Max Post Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[Parameter 2] 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 28 (Visit 03) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 42 (Visit 03B) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 56 (Visit 04) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 70 (Visit 04B) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 84 (Visit 05) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 112 (Visit 06) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Max Post Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: The “Max Post Baseline” column includes the maximum severity experienced by each subject at any time point post baseline, including unscheduled assessments.   
Table 111: 
Distribution of Laboratory Results (Ordinal-Graded) by Parameter, Severity, Study Day, and Study Group – 
Part A, Group 1 
[For graded parameters, in tox table] 
Laboratory Parameter 
Study Day 
 
Normal 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
N 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Any Parameter 
Baseline 
 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
 
Day 28 (Visit 03) 
 
 
 
 
 
 
 
 
 
 
 

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Laboratory Parameter 
Study Day 
 
Normal 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
N 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
 
Day 42 (Visit 03B) 
 
 
 
 
 
 
 
 
 
 
 
 
Day 56 (Visit 04) 
 
 
 
 
 
 
 
 
 
 
 
 
Day 70 (Visit 04B) 
 
 
 
 
 
 
 
 
 
 
 
 
Day 84 (Visit 05) 
 
 
 
 
 
 
 
 
 
 
 
 
Day 112 (Visit 06) 
 
 
 
 
 
 
 
 
 
 
 
 
Max Post Baseline 
 
 
 
 
 
 
 
 
 
 
 
[Parameter 1] 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
Day 28 (Visit 03) 
 
 
 
 
 
 
 
 
 
 
 
 
Day 42 (Visit 03B) 
 
 
 
 
 
 
 
 
 
 
 
 
Day 56 (Visit 04) 
 
 
 
 
 
 
 
 
 
 
 
 
Day 70 (Visit 04B) 
 
 
 
 
 
 
 
 
 
 
 
 
Day 84 (Visit 05) 
 
 
 
 
 
 
 
 
 
 
 
 
Day 112 (Visit 06) 
 
 
 
 
 
 
 
 
 
 
 
 
Max Post Baseline 
 
 
 
 
 
 
 
 
 
 
 
[Parameter 2] 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
Day 28 (Visit 03) 
 
 
 
 
 
 
 
 
 
 
 
 
Day 42 (Visit 03B) 
 
 
 
 
 
 
 
 
 
 
 
 
Day 56 (Visit 04) 
 
 
 
 
 
 
 
 
 
 
 
 
Day 70 (Visit 04B) 
 
 
 
 
 
 
 
 
 
 
 
 
Day 84 (Visit 05) 
 
 
 
 
 
 
 
 
 
 
 
 
Day 112 (Visit 06) 
 
 
 
 
 
 
 
 
 
 
 

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Laboratory Parameter 
Study Day 
 
Normal 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
N 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
 
Max Post Baseline 
 
 
 
 
 
 
 
 
 
 
 
Note: The “Max Post Baseline” row includes the maximum severity experienced by each subject at any time point post baseline, including unscheduled assessments.   
 
Tables with similar format: 
Table 112: 
Distribution of Laboratory Results (Ordinal-Graded) by Parameter, Severity, Study Day, and Study Group – 
Part A, Group 2  
Table 113: 
Distribution of Laboratory Results (Ordinal-Graded) by Parameter, Severity, Study Day, and Study Group – 
Part A, Group 3  
Table 114: 
Distribution of Laboratory Results (Binary-Graded) by Parameter, Severity, Study Day, and Study Group – 
Part B 
Table 115: 
Distribution of Laboratory Results (Ordinal-Graded) by Parameter, Severity, Study Day, and Study Group – 
Part B, Group 4  
Table 116: 
Distribution of Laboratory Results (Ordinal-Graded) by Parameter, Severity, Study Day, and Study Group – 
Part B, Group 5  
Table 117: 
Laboratory Summary Statistics by Parameter, Study Day, and Study Group – Part A, Group 1 
 
Laboratory Parameter 
Statistic 
Baseline 
Day 28 (Visit 
03) 
Day 42 (Visit 
03B) 
Day 56 (Visit 
04) 
Day 70 (Visit 
04B) 
Day 84 (Visit 
05) 
Day 112 (Visit 
06) 
[Parameter 1] 
N 
x 
 
 
 
 
 
 
 
Mean 
xx.x 
 
 
 
 
 
 
 
Standard Deviation 
xx.x 
 
 
 
 
 
 
 
Median 
xx.x 
 
 
 
 
 
 

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Laboratory Parameter 
Statistic 
Baseline 
Day 28 (Visit 
03) 
Day 42 (Visit 
03B) 
Day 56 (Visit 
04) 
Day 70 (Visit 
04B) 
Day 84 (Visit 
05) 
Day 112 (Visit 
06) 
 
Min, Max 
xx.x, xx.x 
 
 
 
 
 
 
[Parameter 1 Change from Baseline] N 
N/A 
 
 
 
 
 
 
 
Mean 
N/A 
 
 
 
 
 
 
 
Standard Deviation 
N/A 
 
 
 
 
 
 
 
Median 
N/A 
 
 
 
 
 
 
 
Min, Max 
N/A 
 
 
 
 
 
 
[Parameter 2] 
N 
x 
 
 
 
 
 
 
 
Mean 
xx.x 
 
 
 
 
 
 
 
Standard Deviation 
xx.x 
 
 
 
 
 
 
 
Median 
xx.x 
 
 
 
 
 
 
 
Min, Max 
xx.x, xx.x 
 
 
 
 
 
 
[Parameter 2 Change from Baseline] N 
N/A 
 
 
 
 
 
 
 
Mean 
N/A 
 
 
 
 
 
 
 
Standard Deviation 
N/A 
 
 
 
 
 
 
 
Median 
N/A 
 
 
 
 
 
 
 
Min, Max 
N/A 
 
 
 
 
 
 
 
[Implementation Note: If the number of Study Groups or assessment time points causes this table to be too wide (wider than the page), 
then split this table by Study Group (i.e., one table per Study Group). 
If there are a lot of hematology and biochemistry values, or if the time points differ for the two sets of parameters, then split this table 
into separate hematology and biochemistry tables.  A separate table will also likely be needed for urinalysis. 
Include change from baseline for each test as a Laboratory Parameter.  See example below. 
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.] 
 
Tables with similar format: 

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Table 118: 
Laboratory Summary Statistics by Parameter, Study Day, and Study Group – Part A, Group 2  
Table 119: 
Laboratory Summary Statistics by Parameter, Study Day, and Study Group – Part A, Group 3  
 
 

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Table 120: 
Laboratory Summary Statistics by Parameter, Study Day, and Study Group – Part B, Group 4 
 
[Implementation Note: If the number of Study Groups or assessment time points causes this table to be too wide (wider than the page), 
then split this table by Study Group (i.e., one table per Study Group). 
If there are a lot of hematology and biochemistry values, or if the time points differ for the two sets of parameters, then split this table 
into separate hematology and biochemistry tables.  A separate table will also likely be needed for urinalysis. 
Include change from baseline for each test as a Laboratory Parameter.  See example below. 
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.] 
Laboratory Parameter 
Statistic 
Baseline 
 
Day 28 (Visit 
03) 
Day 56 (Visit 
04) 
Day 112 (Visit 
06) 
Day 308 (Visit 
13) 
[Parameter 1] 
N 
x 
 
 
 
 
 
Mean 
xx.x 
 
 
 
 
 
Standard Deviation 
xx.x 
 
 
 
 
 
Median 
xx.x 
 
 
 
 
 
Min, Max 
xx.x, xx.x 
 
 
 
 
[Parameter 1 Change from Baseline] 
N 
N/A 
 
 
 
 
 
Mean 
N/A 
 
 
 
 
 
Standard Deviation 
N/A 
 
 
 
 
 
Median 
N/A 
 
 
 
 
 
Min, Max 
N/A 
 
 
 
 
[Parameter 2] 
N 
x 
 
 
 
 
 
Mean 
xx.x 
 
 
 
 
 
Standard Deviation 
xx.x 
 
 
 
 
 
Median 
xx.x 
 
 
 
 
 
Min, Max 
xx.x, xx.x 
 
 
 
 
[Parameter 2 Change from Baseline] 
N 
N/A 
 
 
 
 
 
Mean 
N/A 
 
 
 
 

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Standard Deviation 
N/A 
 
 
 
 
 
Median 
N/A 
 
 
 
 
 
Min, Max 
N/A 
 
 
 
 
 
Table with a similar format: 
Table 121: 
Laboratory Summary Statistics by Parameter, Study Day, and Study Group – Part B, Group 5 
 
 
 

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Table 122: 
Shift Table for RBC by Study Group Comparing Baseline to Post-Baseline Measures – Part A 
 
Group 1: 4 mg ZIKVwt 
DNA, 2 injections 
Baseline 
Group 2: 4 mg ZIKVwt 
DNA, 4 injections 
Baseline 
Group 3: 8 mg ZIKVwt DNA, 
4 injections 
Baseline 
 
Normal Abnormal Total Normal Abnormal Total Normal Abnormal Total 
Post Baseline Week 4 (Visit 03) 
Normal 
 
 
 
 
 
 
 
 
 
Abnormal 
 
 
 
 
 
 
 
 
 
Total 
 
 
 
 
 
 
 
 
 
Post Baseline Week 6 (Visit 03B) 
Normal 
 
 
 
 
 
 
 
 
 
Abnormal 
 
 
 
 
 
 
 
 
 
Total 
 
 
 
 
 
 
 
 
 
Post Baseline Week 8 (Visit 04) 
Normal 
 
 
 
 
 
 
 
 
 
Abnormal 
 
 
 
 
 
 
 
 
 
Total 
 
 
 
 
 
 
 
 
 
Post Baseline Week 10 (Visit 04B) 
Normal 
 
 
 
 
 
 
 
 
 
Abnormal 
 
 
 
 
 
 
 
 
 
Total 
 
 
 
 
 
 
 
 
 
Post Baseline Week 12 (Visit 05) 
Normal 
 
 
 
 
 
 
 
 
 
Abnormal 
 
 
 
 
 
 
 
 
 
Total 
 
 
 
 
 
 
 
 
 
Post Baseline Week 16 (Visit 06) 

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Group 1: 4 mg ZIKVwt 
DNA, 2 injections 
Baseline 
Group 2: 4 mg ZIKVwt 
DNA, 4 injections 
Baseline 
Group 3: 8 mg ZIKVwt DNA, 
4 injections 
Baseline 
 
Normal Abnormal Total Normal Abnormal Total Normal Abnormal Total 
Normal 
 
 
 
 
 
 
 
 
 
Abnormal 
 
 
 
 
 
 
 
 
 
Total 
 
 
 
 
 
 
 
 
 
Tables with a similar format: 
Table 123: 
Shift Table for Hematocrit by Study Group Comparing Baseline to Post-Baseline Measures – Part A 
Table 124: 
Shift Table for MCV by Study Group Comparing Baseline to Post-Baseline Measures – Part A 
Table 125: 
Shift Table for Monocytes by Study Group Comparing Baseline to Post-Baseline Measures – Part A 
Table 126: 
Shift Table for Basophils by Study Group Comparing Baseline to Post-Baseline Measures – Part A 
 
 
 

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Table 127: 
Shift Table for ALT by Study Group Comparing Baseline to Post-Baseline Measures – Part A, Group 1 
 
 
 
Baseline 
 
Normal Grade 1 Grade 2 Grade 3 Grade 4 
Total 
Post Baseline Week 4 (Visit 03) 
Normal 
x 
x 
x 
x 
x 
x 
Grade 1 
x 
x 
x 
x 
x 
x 
Grade 2 
x 
x 
x 
x 
x 
x 
Grade 3 
x 
x 
x 
x 
x 
x 
Grade 4 
x 
x 
x 
x 
x 
x 
Total 
x 
x 
x 
x 
x 
x 
Post Baseline Week 6 (Visit 03B) 
Normal 
x 
x 
x 
x 
x 
x 
Grade 1 
x 
x 
x 
x 
x 
x 
Grade 2 
x 
x 
x 
x 
x 
x 
Grade 3 
x 
x 
x 
x 
x 
x 
Grade 4 
x 
x 
x 
x 
x 
x 
Total 
x 
x 
x 
x 
x 
x 
Post Baseline Week 8 (Visit 04) 
Normal 
x 
x 
x 
x 
x 
x 
Grade 1 
x 
x 
x 
x 
x 
x 
Grade 2 
x 
x 
x 
x 
x 
x 
Grade 3 
x 
x 
x 
x 
x 
x 
Grade 4 
x 
x 
x 
x 
x 
x 

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Baseline 
 
Normal Grade 1 Grade 2 Grade 3 Grade 4 
Total 
Total 
x 
x 
x 
x 
x 
x 
Post Baseline Week 10 (Visit 04B) 
Normal 
x 
x 
x 
x 
x 
x 
Grade 1 
x 
x 
x 
x 
x 
x 
Grade 2 
x 
x 
x 
x 
x 
x 
Grade 3 
x 
x 
x 
x 
x 
x 
Grade 4 
x 
x 
x 
x 
x 
x 
Total 
x 
x 
x 
x 
x 
x 
Post Baseline Week 12 (Visit 05) 
Normal 
x 
x 
x 
x 
x 
x 
Grade 1 
x 
x 
x 
x 
x 
x 
Grade 2 
x 
x 
x 
x 
x 
x 
Grade 3 
x 
x 
x 
x 
x 
x 
Grade 4 
x 
x 
x 
x 
x 
x 
Total 
x 
x 
x 
x 
x 
x 
Post Baseline Week 16 (Visit 06) 
Normal 
x 
x 
x 
x 
x 
x 
Grade 1 
x 
x 
x 
x 
x 
x 
Grade 2 
x 
x 
x 
x 
x 
x 
Grade 3 
x 
x 
x 
x 
x 
x 
Grade 4 
x 
x 
x 
x 
x 
x 
Total 
x 
x 
x 
x 
x 
x 

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Tables with similar format: 
Table 128: 
Shift Table for ALT by Study Group Comparing Baseline to Post-Baseline Measures – Part A, Group 2  
Table 129: 
Shift Table for ALT by Study Group Comparing Baseline to Post-Baseline Measures – Part A, Group 3 
Table 130: 
Shift Table for WBC by Study Group Comparing Baseline to Post-Baseline Measures – Part A, Group 1  
Table 131: 
Shift Table for WBC by Study Group Comparing Baseline to Post-Baseline Measures – Part A, Group 2 
Table 132: 
Shift Table for WBC by Study Group Comparing Baseline to Post-Baseline Measures – Part A, Group 3 
Table 133: 
Shift Table for Hemoglobin by Study Group Comparing Baseline to Post-Baseline Measures – Part A, Group 1  
Table 134: 
Shift Table for Hemoglobin by Study Group Comparing Baseline to Post-Baseline Measures – Part A, Group 2 
Table 135: 
Shift Table for Hemoglobin by Study Group Comparing Baseline to Post-Baseline Measures – Part A, Group 3 
Table 136: 
Shift Table for Platelets by Study Group Comparing Baseline to Post-Baseline Measures – Part A, Group 1  
Table 137: 
Shift Table for Platelets by Study Group Comparing Baseline to Post-Baseline Measures – Part A, Group 2 
Table 138: 
Shift Table for Platelets by Study Group Comparing Baseline to Post-Baseline Measures – Part A, Group 3 
Table 139: 
Shift Table for Neutrophils by Study Group Comparing Baseline to Post-Baseline Measures – Part A, Group 1  
Table 140: 
Shift Table for Neutrophils by Study Group Comparing Baseline to Post-Baseline Measures – Part A, Group 2 
Table 141: 
Shift Table for Neutrophils by Study Group Comparing Baseline to Post-Baseline Measures – Part A, Group 3 
Table 142: 
Shift Table for Lymphocytes by Study Group Comparing Baseline to Post-Baseline Measures – Part A, Group 1  
Table 143: 
Shift Table for Lymphocytes by Study Group Comparing Baseline to Post-Baseline Measures – Part A, Group 2 
Table 144: 
Shift Table for Lymphocytes by Study Group Comparing Baseline to Post-Baseline Measures – Part A, Group 3 
Table 145: 
Shift Table for Eosinophils by Study Group Comparing Baseline to Post-Baseline Measures – Part A, Group 1  
Table 146: 
Shift Table for Eosinophils by Study Group Comparing Baseline to Post-Baseline Measures – Part A, Group 2 
Table 147: 
Shift Table for Eosinophils by Study Group Comparing Baseline to Post-Baseline Measures – Part A, Group 3 


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Table 148: 
Shift Table for RBC by Study Group Comparing Baseline to Post-Baseline Measures – Part B 
Table 149: 
Shift Table for Hematocrit by Study Group Comparing Baseline to Post-Baseline Measures – Part B 
Table 150: 
Shift Table for MCV by Study Group Comparing Baseline to Post-Baseline Measures – Part B 
Table 151: 
Shift Table for Monocytes by Study Group Comparing Baseline to Post-Baseline Measures – Part B 
Table 152: 
Shift Table for Basophils by Study Group Comparing Baseline to Post-Baseline Measures – Part B 
Table 153: 
Shift Table for ALT by Study Group Comparing Baseline to Post-Baseline Measures – Part B, Group 4  
Table 154: 
Shift Table for ALT by Study Group Comparing Baseline to Post-Baseline Measures – Part B, Group 5 
Table 155: 
Shift Table for WBC by Study Group Comparing Baseline to Post-Baseline Measures – Part B, Group 4  
Table 156: 
Shift Table for WBC by Study Group Comparing Baseline to Post-Baseline Measures – Part B, Group 5 
Table 157: 
Shift Table for Hemoglobin by Study Group Comparing Baseline to Post-Baseline Measures – Part B, Group 4  
Table 158: 
Shift Table for Hemoglobin by Study Group Comparing Baseline to Post-Baseline Measures – Part B, Group 5 
Table 159: 
Shift Table for Platelets by Study Group Comparing Baseline to Post-Baseline Measures – Part B, Group 4  
Table 160: 
Shift Table for Platelets by Study Group Comparing Baseline to Post-Baseline Measures – Part B, Group 5 
Table 161: 
Shift Table for Neutrophils by Study Group Comparing Baseline to Post-Baseline Measures – Part B, Group 4 
Table 162: 
Shift Table for Neutrophils by Study Group Comparing Baseline to Post-Baseline Measures – Part B, Group 5 
Table 163: 
Shift Table for Lymphocytes by Study Group Comparing Baseline to Post-Baseline Measures – Part B, Group 4  
Table 164: 
Shift Table for Lymphocytes by Study Group Comparing Baseline to Post-Baseline Measures – Part B, Group 5 
Table 165: 
Shift Table for Eosinophils by Study Group Comparing Baseline to Post-Baseline Measures – Part B, Group 4  
Table 166: 
Shift Table for Eosinophils by Study Group Comparing Baseline to Post-Baseline Measures – Part B, Group 5 

Table 167: 
Listing of Abnormal Laboratory Results- Part A 
[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. 

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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). 
In the “If Not Related, Alternate Etiology” column, merge the 2 data fields for collecting alternate etiology, separate by a colon.] 
Subject 
ID 
Study 
Group 
Sex 
Age 
(years) 
Visit 
Number 
Date 
Specimen 
Collected 
Laboratory 
Parameter 
(Units) 
Result 
(Severity) 
Relationship to 
Treatment 
Action 
Taken with 
Study 
Treatment 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Table 168: 
Listing of Abnormal Laboratory Results- Part B 
Subject 
ID 
Study 
Group 
Sex 
Age 
(years) 
Visit 
Number 
Date 
Specimen 
Collected 
Laboratory 
Parameter 
(Units) 
Result 
(Severity) 
Relationship to 
Treatment 
Action 
Taken with 
Study 
Treatment 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Table 169: 
Distribution of Abnormal Laboratory Results (Ordinal-Graded) Related to Study Treatment by Parameter, 
Severity, Study Day, and Study Group – Part A, Group 1  
 
Laboratory 
Parameter 
Study Day 
 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
N 
n 
% 
n 
% 
n 
% 
n 
% 
Any Parameter 
Baseline 
 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
 
Day 28 (Visit 03) 
 
 
 
 
 
 
 
 
 
 
Day 42 (Visit 03B) 
 
 
 
 
 
 
 
 
 
 
Day 56 (Visit 04) 
 
 
 
 
 
 
 
 
 
 
Day 70 (Visit 04B) 
 
 
 
 
 
 
 
 
 
 
Day 84 (Visit 05) 
 
 
 
 
 
 
 
 
 
 
Day 112 (Visit 06) 
 
 
 
 
 
 
 
 
 
[Parameter 1] 
Baseline 
 
 
 
 
 
 
 
 
 
 
Day 28 (Visit 03) 
 
 
 
 
 
 
 
 
 
 
Day 42 (Visit 03B) 
 
 
 
 
 
 
 
 
 

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Laboratory 
Parameter 
Study Day 
 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
N 
n 
% 
n 
% 
n 
% 
n 
% 
 
Day 56 (Visit 04) 
 
 
 
 
 
 
 
 
 
 
Day 70 (Visit 04B) 
 
 
 
 
 
 
 
 
 
 
Day 84 (Visit 05) 
 
 
 
 
 
 
 
 
 
 
Day 112 (Visit 06) 
 
 
 
 
 
 
 
 
 
[Parameter 2] 
Baseline 
 
 
 
 
 
 
 
 
 
 
Day 28 (Visit 03) 
 
 
 
 
 
 
 
 
 
 
Day 42 (Visit 03B) 
 
 
 
 
 
 
 
 
 
 
Day 56 (Visit 04) 
 
 
 
 
 
 
 
 
 
 
Day 70 (Visit 04B) 
 
 
 
 
 
 
 
 
 
 
Day 84 (Visit 05) 
 
 
 
 
 
 
 
 
 
 
Day 112 (Visit 06) 
 
 
 
 
 
 
 
 
 
 
Tables with similar formats: 

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Table 170: 
Distribution of Abnormal Laboratory Results (Ordinal-Graded) Related to Study Treatment by Parameter, 
Severity, Study Day, and Study Group – Part A, Group 2  
Table 171: 
Distribution of Abnormal Laboratory Results (Ordinal-Graded) Related to Study Treatment by Parameter, 
Severity, Study Day, and Study Group – Part A, Group 3  
Table 172: 
Distribution of Abnormal Laboratory Results (Ordinal-Graded) Related to Study Treatment by Parameter, 
Severity, Study Day, and Study Group – Part B, Group 4  
Table 173: 
Distribution of Abnormal Laboratory Results (Ordinal-Graded) Related to Study Treatment by Parameter, 
Severity, Study Day, and Study Group – Part B, Group 5  
 

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Table 174: 
Distribution of Vital Signs by Day Post Dosing, Grade, and Study Group – Part A, Group 1 
[Implementation Note: If the number of Study Groups or assessment time points causes this table to be too wide (wider than the page), 
then split this table by Study Group (i.e., one table per Study Group). 
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, as shown below for Assessment 1.  If not, then just include one row per severity, as shown below for Assessment 2.  “Any 
Assessment” will just summarize one row per severity. 
If there are subjects with a max severity that is both high AND low for the same parameter, then break out the “Max Severity Post 
Baseline” columns into a separate table.] 
Vital Sign Assessment 
Study Day 
 
Normal 
Mild 
Moderate 
Severe 
N 
n 
% 
n 
% 
n 
% 
n 
% 
Any Assessment 
Baseline 
 
x 
x.x 
x 
x.x 
x 
x.x 
x 
x.x 
 
Day 28 (Visit 03) 
 
 
 
 
 
 
 
 
 
 
Day 42 (Visit 03B) 
 
 
 
 
 
 
 
 
 
 
Day 56 (Visit 04) 
 
 
 
 
 
 
 
 
 
 
Day 70 (Visit 04B) 
 
 
 
 
 
 
 
 
 
 
Day 84 (Visit 05) 
 
 
 
 
 
 
 
 
 
 
Day 112 (Visit 06) 
 
 
 
 
 
 
 
 
 
 
[continue for all visits 
with VS] 
 
 
 
 
 
 
 
 
 
 
Max Post Baseline 
 
 
 
 
 
 
 
 
 
[Assessment 1] 
Baseline 
 
 
 
 
 
 
 
 
 
 
Day 28 (Visit 03) 
 
 
 
 
 
 
 
 
 
 
Day 42 (Visit 03B) 
 
 
 
 
 
 
 
 
 
 
Day 56 (Visit 04) 
 
 
 
 
 
 
 
 
 

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Vital Sign Assessment 
Study Day 
 
Normal 
Mild 
Moderate 
Severe 
N 
n 
% 
n 
% 
n 
% 
n 
% 
 
Day 70 (Visit 04B) 
 
 
 
 
 
 
 
 
 
 
Day 84 (Visit 05) 
 
 
 
 
 
 
 
 
 
 
Day 112 (Visit 06) 
 
 
 
 
 
 
 
 
 
 
[continue for all visit 
with VS] 
 
 
 
 
 
 
 
 
 
 
Max Post Baseline 
 
 
 
 
 
 
 
 
 
[Assessment 2] 
Baseline 
 
 
 
 
 
 
 
 
 
 
Day 28 (Visit 03) 
 
 
 
 
 
 
 
 
 
 
Day 42 (Visit 03B) 
 
 
 
 
 
 
 
 
 
 
Day 56 (Visit 04) 
 
 
 
 
 
 
 
 
 
 
Day 70 (Visit 04B) 
 
 
 
 
 
 
 
 
 
 
Day 84 (Visit 05) 
 
 
 
 
 
 
 
 
 
 
Day 112 (Visit 06) 
 
 
 
 
 
 
 
 
 
 
[continue for all visits 
with VS] 
 
 
 
 
 
 
 
 
 
 
Max Post Baseline 
 
 
 
 
 
 
 
 
 
 
Table with similar format: 
Table 175: 
Distribution of Vital Signs by Day Post Dosing, Grade, and Study Group – Part A, Group 2  
Table 176: 
Distribution of Vital Signs by Day Post Dosing, Grade, and Study Group – Part A, Group 3  
 

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Table 177: 
Distribution of Vital Signs by Day Post Dosing, Grade, and Study Group – Part B, Group 4  
Table 178: 
Distribution of Vital Signs by Day Post Dosing, Grade, and Study Group – Part B, Group 5  
 

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APPENDIX 2: 
FIGURES 
Figure 1:
CONSORT Flow Diagram – Part A .........................................................................117
Figure 2:
CONSORT Flow Diagram – Part B .........................................................................118
Figure 3:
Reverse Cumulative Distribution of ZIKV Neutralizing Antibody (ID50) by 
Time Point and Study Group, ITT Population – Part A ...........................................118
Figure 4:
Reverse Cumulative Distribution of ZIKV Neutralizing Antibody (ID50) by 
Time Point and Study Group, mITT Population – Part A ........................................119
Figure 5:
Reverse Cumulative Distribution of ZIKV Neutralizing Antibody (ID50) by 
Time Point and Study Group, Per Protocol Population – Part A..............................119
Figure 6:
Reverse Cumulative Distribution of ZIKV Neutralizing Antibody (ID80) by 
Time Point and Study Group, ITT Population – Part A ...........................................119
Figure 7:
Reverse Cumulative Distribution of ZIKV Neutralizing Antibody (ID80) by 
Time Point and Study Group, mITT Population – Part A ........................................119
Figure 8:
Reverse Cumulative Distribution of ZIKV Neutralizing Antibody (ID80) by 
Time Point and Study Group, Per Protocol Population – Part A..............................119
Figure 9:
Reverse Cumulative Distribution of Neutralizing Antibody (ID50) by Time 
Point and Study Group, ITT Population – Part B .....................................................119
Figure 10: Reverse Cumulative Distribution of ZIKV Neutralizing Antibody (ID50) by 
Time Point and Study Group, mITT Population – Part B ........................................119
Figure 11: Reverse Cumulative Distribution of ZIKV Neutralizing Antibody (ID50) by 
Time Point and Study Group, Per Protocol Population – Part B ..............................119
Figure 12: Reverse Cumulative Distribution of ZIKV Neutralizing Antibody (ID80) by 
Time Point and Study Group, ITT Population – Part B ...........................................119
Figure 13: Reverse Cumulative Distribution of ZIKV Neutralizing Antibody (ID80) by 
Time Point and Study Group, mITT Population – Part B ........................................119
Figure 14: Reverse Cumulative Distribution of ZIKV Neutralizing Antibody (ID80) by 
Time Point and Study Group, Per Protocol Population – Part B ..............................119
Figure 15: Boxplots with Overlaid Scatter Plots Summarizing ZIKV Neutralizing 
Antibody (ID50) by Time Point and Study Group, ITT Population – Part A............120
Figure 16: Boxplots with Overlaid Scatter Plots Summarizing ZIKV Neutralizing 
Antibody (ID50) by Time Point and Study Group, mITT Population – Part A ........121
Figure 17: Boxplots with Overlaid Scatter Plots Summarizing ZIKV Neutralizing 
Antibody (ID50) by Time Point and Study Group, Per Protocol Population – 
Part A ........................................................................................................................121
Figure 18: Boxplots with Overlaid Scatter Plots Summarizing ZIKV Neutralizing 
Antibody (ID80) by Time Point and Study Group, ITT Population – Part A............121

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Figure 19: Boxplots with Overlaid Scatter Plots Summarizing ZIKV Neutralizing 
Antibody (ID80) by Time Point and Study Group, mITT Population – Part A ........121
Figure 20: Boxplots with Overlaid Scatter Plots Summarizing ZIKV Neutralizing 
Antibody (ID80) by Time Point and Study Group, Per Protocol Population – 
Part A ........................................................................................................................121
Figure 21: Boxplots with Overlaid Scatter Plots Summarizing ZIKV Neutralizing 
Antibody (ID50) by Time Point and Study Group, ITT Population – Part B ..........121
Figure 22: Boxplots with Overlaid Scatter Plots Summarizing ZIKV Neutralizing 
Antibody (ID50) by Time Point and Study Group, mITT Population – Part B .........121
Figure 23: Boxplots with Overlaid Scatter Plots Summarizing ZIKV Neutralizing 
Antibody (ID50) by Time Point and Study Group, Per Protocol Population – 
Part B ........................................................................................................................121
Figure 24: Boxplots with Overlaid Scatter Plots Summarizing ZIKV Neutralizing 
Antibody (ID80) by Time Point and Study Group, ITT Population – Part B ............121
Figure 25: Boxplots with Overlaid Scatter Plots Summarizing ZIKV Neutralizing 
Antibody (ID80) by Time Point and Study Group, mITT Population – Part B .........121
Figure 26: Boxplots with Overlaid Scatter Plots Summarizing ZIKV Neutralizing 
Antibody (ID80) by Time Point and Study Group, Per Protocol Population – 
Part B ........................................................................................................................121
Figure 27: Kaplan-Meier Plots of Time to Infection (Virologic ZIKV cases) by Study 
Group, ITT population ..............................................................................................121
Figure 28: Kaplan-Meier Plots of Time to Infection (Virologic ZIKV cases) by 
Serostatus and Study Group, ITT population ...........................................................123
Figure 29: Kaplan-Meier Plots of Time to Infection (Virologic ZIKV cases) by Study 
Group, mITT population ...........................................................................................123
Figure 30: Kaplan-Meier Plots of Time to Infection (Virologic ZIKV cases) by 
Serostatus and Study Group, mITT population ........................................................123
Figure 31: Kaplan-Meier Plots of Time to Infection (Virologic ZIKV cases) by Study 
Group, PP population................................................................................................123
Figure 32: Kaplan-Meier Plots of Time to Infection (Virologic ZIKV cases) by 
Serostatus and Study Group, PP population .............................................................123
Figure 33: Kaplan-Meier Plots of Time to Infection (Subclinical ZIKV cases) by Study 
Group, ITT population ..............................................................................................123
Figure 34: Kaplan-Meier Plots of Time to Infection (Subclinical ZIKV cases) by 
Serostatus and Study Group, ITT population ...........................................................123
Figure 35: Kaplan-Meier Plots of Time to Infection (Subclinical ZIKV cases) by Study 
Group, mITT population ...........................................................................................123
Figure 36: Kaplan-Meier Plots of Time to Infection (Subclinical ZIKV cases) by 
Serostatus and Study Group, mITT population ........................................................123

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Figure 37: Kaplan-Meier Plots of Time to Infection (Subclinical ZIKV cases) by Study 
Group, PP population................................................................................................123
Figure 38: Kaplan-Meier Plots of Time to Infection (Subclinical ZIKV cases) by 
Serostatus and Study Group, PP population .............................................................123
Figure 39: Kaplan-Meier Plots of Time to Infection (Symptomatic ZIKV cases) by 
Study Group, ITT population ...................................................................................123
Figure 40: Kaplan-Meier Plots of Time to Infection (Symptomatic ZIKV cases) by 
Serostatus and Study Group, ITT population ...........................................................123
Figure 41: Kaplan-Meier Plots of Time to Infection (Symptomatic ZIKV cases) by 
Study Group, mITT population ................................................................................123
Figure 42: Kaplan-Meier Plots of Time to Infection (Symptomatic ZIKV cases) by 
Serostatus and Study Group, mITT population ........................................................123
Figure 43: Kaplan-Meier Plots of Time to Infection (Symptomatic ZIKV cases) by 
Study Group, PP population .....................................................................................123
Figure 44: Kaplan-Meier Plots of Time to Infection (Symptomatic ZIKV cases) by 
Serostatus and Study Group, PP population .............................................................123
Figure 45: Maximum Severity of Solicited Systemic Symptoms per Subject by Day 
Post Treatment, Part A ..............................................................................................123
Figure 46: Maximum Severity of Solicited Systemic Symptoms per Subject by Day 
Post Treatment, Part B ..............................................................................................125
Figure 47: Maximum Severity of Solicited Local Symptoms per Subject by Day Post 
Treatment, Part A ......................................................................................................126
Figure 48: Maximum Severity of Solicited Local Symptoms per Subject by Day Post 
Treatment, Part B ......................................................................................................127
Figure 49: Frequency of Related Adverse Events by MedDRA System Organ Class and 
Severity, Part A .........................................................................................................128
Figure 50: Frequency of Related Adverse Events by MedDRA System Organ Class and 
Severity, Part B .........................................................................................................128
Figure 51: Incidence of Related Adverse Events by MedDRA® System Organ Class 
and Maximum Severity, Part A ................................................................................129
Figure 52: Incidence of Related Adverse Events by MedDRA® System Organ Class 
and Maximum Severity, Part B ................................................................................129
Figure 53: Incidence of Solicited and Unsolicited Adverse Events by MedDRA® 
Preferred Term for Adverse Events Reported by 5% or More of Subjects, 
Part A ........................................................................................................................129
Figure 54: Incidence of Solicited and Unsolicited Adverse Events by MedDRA® 
Preferred Term for Adverse Events Reported by 5% or More of Subjects, 
Part B ........................................................................................................................129

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Figure 55: Boxplot of Laboratory Results by Scheduled Visits, Part A – ALT ........................130
Figure 56: Boxplot of Laboratory Results by Scheduled Visits, Part A – RBC ........................131
Figure 57: Boxplot of Laboratory Results by Scheduled Visits, Part A – WBC .......................131
Figure 58: Boxplot of Laboratory Results by Scheduled Visits, Part A – Hemoglobin ............131
Figure 59: Boxplot of Laboratory Results by Scheduled Visits, Part A – Hematocrit ..............131
Figure 60: Boxplot of Laboratory Results by Scheduled Visits, Part A – Platelets ...................131
Figure 61: Boxplot of Laboratory Results by Scheduled Visits, Part A – MCV .......................131
Figure 62: Boxplot of Laboratory Results by Scheduled Visits, Part A – Monocytes ..............131
Figure 63: Boxplot of Laboratory Results by Scheduled Visits, Part A – Neutrophils .............131
Figure 64: Boxplot of Laboratory Results by Scheduled Visits, Part A – Lymphocytes ..........131
Figure 65: Boxplot of Laboratory Results by Scheduled Visits, Part A – Eosinophils .............131
Figure 66: Boxplot of Laboratory Results by Scheduled Visits, Part A – Basophils ................131
Figure 67: Boxplot of Laboratory Results by Scheduled Visits, Part B – ALT .........................131
Figure 68: Boxplot of Laboratory Results by Scheduled Visits, Part B – RBC ........................131
Figure 69: Boxplot of Laboratory Results by Scheduled Visits, Part B – WBC .......................131
Figure 70: Boxplot of Laboratory Results by Scheduled Visits, Part B – Hemoglobin ............131
Figure 71: Boxplot of Laboratory Results by Scheduled Visits, Part B – Hematocrit ..............131
Figure 72: Boxplot of Laboratory Results by Scheduled Visits, Part B – Platelets ...................131
Figure 73: Boxplot of Laboratory Results by Scheduled Visits, Part B – MCV .......................131
Figure 74: Boxplot of Laboratory Results by Scheduled Visits, Part B – Monocytes ...............131
Figure 75: Boxplot of Laboratory Results by Scheduled Visits, Part B – Neutrophils..............131
Figure 76: Boxplot of Laboratory Results by Scheduled Visits, Part B – Lymphocytes ...........131
Figure 77: Boxplot of Laboratory Results by Scheduled Visits, Part B – Eosinophils..............131
Figure 78: Boxplot of Laboratory Results by Scheduled Visits, Part B – Basophils .................131
Figure 79: Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Sex and Study Group, Part A – ALT ........................................................................132
Figure 80: Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Sex and Study Group, Part A – RBC ........................................................................133
Figure 81: Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Sex and Study Group, Part A – WBC .......................................................................133
Figure 82: Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Sex and Study Group, Part A – Hemoglobin ............................................................133
Figure 83: Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Sex and Study Group, Part A – Hematocrit ..............................................................133

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Figure 84: Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Sex and Study Group, Part A – Platelets ..................................................................133
Figure 85: Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Sex and Study Group, Part A – MCV .......................................................................133
Figure 86: Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Sex and Study Group, Part A – Monocytes ..............................................................133
Figure 87: Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Sex and Study Group, Part A – Neutrophils .............................................................133
Figure 88: Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Sex and Study Group, Part A – Lymphocytes ..........................................................133
Figure 89: Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Sex and Study Group, Part A – Eosinophils .............................................................133
Figure 90: Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Sex and Study Group, Part A – Basophils ................................................................133
Figure 91: Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Sex and Study Group, Part B – ALT ........................................................................133
Figure 92: Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Sex and Study Group, Part B – RBC ........................................................................133
Figure 93: Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Sex and Study Group, Part B – WBC .......................................................................134
Figure 94: Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Sex and Study Group, Part B – Hemoglobin ............................................................134
Figure 95: Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Sex and Study Group, Part B – Hematocrit ..............................................................134
Figure 96: Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Sex and Study Group, Part B – Platelets ..................................................................134
Figure 97: Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Sex and Study Group, Part B – MCV .......................................................................134
Figure 98: Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Sex and Study Group, Part B – Monocytes ..............................................................134
Figure 99: Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Sex and Study Group, Part B – Neutrophils .............................................................134
Figure 100:Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Sex and Study Group, Part B – Lymphocytes ..........................................................134
Figure 101:Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Sex and Study Group, Part B – Eosinophils .............................................................134
Figure 102:Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Sex and Study Group, Part B – Basophils ................................................................134

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Figure 103:Boxplot of Vital Sign Assessments by Scheduled Visits and Study Group, 
Part A – Systolic Blood Pressure ..............................................................................135
Figure 104:Boxplot of Vital Sign Assessments by Scheduled Visits and Study Group, 
Part A – Diastolic Blood Pressure ............................................................................137
Figure 105:Boxplot of Vital Sign Assessments by Scheduled Visits and Study Group, 
Part A – Pulse ...........................................................................................................137
Figure 106:Boxplot of Vital Sign Assessments by Scheduled Visits and Study Group, 
Part A – Temperature ................................................................................................137
Figure 107:Boxplot of Vital Sign Assessments by Scheduled Visits and Study Group, 
Part B – Systolic Blood Pressure ..............................................................................137
Figure 108:Boxplot of Vital Sign Assessments by Scheduled Visits and Study Group, 
Part B – Diastolic Blood Pressure ............................................................................137
Figure 109:Boxplot of Vital Sign Assessments by Scheduled Visits and Study Group, 
Part B – Pulse............................................................................................................137
Figure 110:Boxplot of Vital Sign Assessments by Scheduled Visits and Study Group, 
Part B – Temperature ................................................................................................137
 

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Figure 1: 
CONSORT Flow Diagram – Part A 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Allocated to Group 1 (n=x) 
♦Received allocated intervention (n=x) 
♦Did not receive allocated intervention (n=x) 
Discontinued Intervention (n=x) 
♦[Reason 1] (x), [Reason 2] (x) 
 
Early Termination (n=32) 
Analysed for immunogenicity (n=x) 
♦Excluded from immuno analyses (n=x) 
[Reason 1] (x), [Reason 2] (x) 
Analyzed for safety (n=x) 
♦Excluded from safety analyses (n=x) 
Assessed for Eligibility (n=x) 
Excluded* (n=x) 
♦   [Reason 1] (n=x) 
♦   Concern of potential risk (n=x) 
Randomized (n=x) 
Allocation 
Analysis 
Follow-Up 
Enrollment 
Allocated to Group 1 (n=x) 
♦Received allocated intervention (n=x) 
♦Did not receive allocated intervention (n=x) 
Allocated to Group 1 (n=x) 
♦Received allocated intervention (n=x) 
♦Did not receive allocated intervention (n=x) 
Discontinued Intervention (n=x) 
♦[Reason 1] (x), [Reason 2] (x) 
Early Termination (n=32) 
Discontinued Intervention (n=x) 
♦[Reason 1] (x), [Reason 2] (x) 
Early Termination (n=32) 
Analysed for immunogenicity (n=x) 
♦Excluded from immuno analyses (n=x) 
[Reason 1] (x), [Reason 2] (x) 
Analyzed for safety (n=x) 
♦Excluded from safety analyses (n=x) 
[R
1] ( ) [R
2] ( )
Analysed for immunogenicity (n=x) 
♦Excluded from immuno analyses (n=x) 
[Reason 1] (x), [Reason 2] (x) 
Analyzed for safety (n=x) 
♦Excluded from safety analyses (n=x) 

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Figure with similar format: 
 
Figure 2: 
CONSORT Flow Diagram – Part B  
Figure 3: 
Reverse Cumulative Distribution of ZIKV Neutralizing Antibody (ID50) by Time Point 
and Study Group, ITT Population – Part A 
 
Reverse Cumulative Distribution Curves
Hemagglutination Titer
A/New Caledonia/20/99
Pre-Vaccination
IVV without IFN
 IVV with 1M IFN
 IVV with 10M IFN
Cumulative Percent
0
10
20
30
40
50
60
70
80
90
100
TITER
1.4
4
8
16
32
64
128
256
512
1280
2048
4096
Reverse Cumulative Distribution Curves
Hemagglutination Titer
A/New Caledonia/20/99
14 Days Post Vaccination
IVV without IFN
 IVV with 1M IFN
 IVV with 10M IFN
Cumulative Percent
0
10
20
30
40
50
60
70
80
90
100
TITER
1.4
4
8
16
32
64
128
256
512
1280
2048
4096
Reverse Cumulative Distribution Curves
Hemagglutination Titer
A/New Caledonia/20/99
28 Days Post Vaccination
IVV without IFN
 IVV with 1M IFN
 IVV with 10M IFN
Cumulative Percent
0
10
20
30
40
50
60
70
80
90
100
TITER
1.4
4
8
16
32
64
128
256
512
1280
2048
4096

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Figures with similar format: 
Figure 4: 
Reverse Cumulative Distribution of ZIKV Neutralizing Antibody (ID50) by Time Point 
and Study Group, mITT Population – Part A 
Figure 5: 
Reverse Cumulative Distribution of ZIKV Neutralizing Antibody (ID50) by Time Point 
and Study Group, Per Protocol Population – Part A 
Figure 6: 
Reverse Cumulative Distribution of ZIKV Neutralizing Antibody (ID80) by Time Point 
and Study Group, ITT Population – Part A 
Figure 7: 
Reverse Cumulative Distribution of ZIKV Neutralizing Antibody (ID80) by Time Point 
and Study Group, mITT Population – Part A 
Figure 8: 
Reverse Cumulative Distribution of ZIKV Neutralizing Antibody (ID80) by Time Point 
and Study Group, Per Protocol Population – Part A 
Figure 9: 
Reverse Cumulative Distribution of Neutralizing Antibody (ID50) by Time Point and 
Study Group, ITT Population – Part B 
Figure 10: 
Reverse Cumulative Distribution of ZIKV Neutralizing Antibody (ID50) by Time Point 
and Study Group, mITT Population – Part B 
Figure 11: 
Reverse Cumulative Distribution of ZIKV Neutralizing Antibody (ID50) by Time Point 
and Study Group, Per Protocol Population – Part B 
Figure 12: 
Reverse Cumulative Distribution of ZIKV Neutralizing Antibody (ID80) by Time Point 
and Study Group, ITT Population – Part B 
Figure 13: 
Reverse Cumulative Distribution of ZIKV Neutralizing Antibody (ID80) by Time Point 
and Study Group, mITT Population – Part B 
Figure 14: 
Reverse Cumulative Distribution of ZIKV Neutralizing Antibody (ID80) by Time Point 
and Study Group, Per Protocol Population – Part B  
 
 

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Figure 15: 
Boxplots with Overlaid Scatter Plots Summarizing ZIKV Neutralizing Antibody (ID50) 
by Time Point and Study Group, ITT Population – Part A 
 
 
 

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Figures with similar format: 
Figure 16: 
Boxplots with Overlaid Scatter Plots Summarizing ZIKV Neutralizing Antibody (ID50) 
by Time Point and Study Group, mITT Population – Part A 
Figure 17: 
Boxplots with Overlaid Scatter Plots Summarizing ZIKV Neutralizing Antibody (ID50) 
by Time Point and Study Group, Per Protocol Population – Part A 
Figure 18: 
Boxplots with Overlaid Scatter Plots Summarizing ZIKV Neutralizing Antibody (ID80) 
by Time Point and Study Group, ITT Population – Part A 
Figure 19: 
Boxplots with Overlaid Scatter Plots Summarizing ZIKV Neutralizing Antibody (ID80) 
by Time Point and Study Group, mITT Population – Part A 
Figure 20: 
Boxplots with Overlaid Scatter Plots Summarizing ZIKV Neutralizing Antibody (ID80) 
by Time Point and Study Group, Per Protocol Population – Part A 
Figure 21: 
Boxplots with Overlaid Scatter Plots Summarizing ZIKV Neutralizing Antibody (ID50) 
by Time Point and Study Group, ITT Population – Part B 
Figure 22: 
Boxplots with Overlaid Scatter Plots Summarizing ZIKV Neutralizing Antibody (ID50) 
by Time Point and Study Group, mITT Population – Part B 
Figure 23: 
Boxplots with Overlaid Scatter Plots Summarizing ZIKV Neutralizing Antibody (ID50) 
by Time Point and Study Group, Per Protocol Population – Part B 
Figure 24: 
Boxplots with Overlaid Scatter Plots Summarizing ZIKV Neutralizing Antibody (ID80) 
by Time Point and Study Group, ITT Population – Part B 
Figure 25: 
Boxplots with Overlaid Scatter Plots Summarizing ZIKV Neutralizing Antibody (ID80) 
by Time Point and Study Group, mITT Population – Part B 
Figure 26: 
Boxplots with Overlaid Scatter Plots Summarizing ZIKV Neutralizing Antibody (ID80) 
by Time Point and Study Group, Per Protocol Population – Part B 
Figure 27: 
Kaplan-Meier Plots of Time to Infection (Virologic ZIKV cases) by Study Group, ITT 
population 

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The x-axis for the Time to Infection Kaplan-Meier Plots will be measured in days. Separate curves on the same 
plot will be defined as the study groups. Censored observations will be represented using a + sign. The y-axis 
will be labeled as Infection-free Survival. 

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Figures of similar format 
Figure 28: 
Kaplan-Meier Plots of Time to Infection (Virologic ZIKV cases) by Serostatus and Study 
Group, ITT population 
Figure 29: 
Kaplan-Meier Plots of Time to Infection (Virologic ZIKV cases) by Study Group, mITT 
population 
Figure 30: 
Kaplan-Meier Plots of Time to Infection (Virologic ZIKV cases) by Serostatus and Study 
Group, mITT population 
Figure 31: 
Kaplan-Meier Plots of Time to Infection (Virologic ZIKV cases) by Study Group, PP 
population 
Figure 32: 
Kaplan-Meier Plots of Time to Infection (Virologic ZIKV cases) by Serostatus and Study 
Group, PP population 
Figure 33: 
Kaplan-Meier Plots of Time to Infection (Subclinical ZIKV cases) by Study Group, ITT 
population 
Figure 34: 
Kaplan-Meier Plots of Time to Infection (Subclinical ZIKV cases) by Serostatus and 
Study Group, ITT population 
Figure 35: 
Kaplan-Meier Plots of Time to Infection (Subclinical ZIKV cases) by Study Group, mITT 
population 
Figure 36: 
Kaplan-Meier Plots of Time to Infection (Subclinical ZIKV cases) by Serostatus and 
Study Group, mITT population 
Figure 37: 
Kaplan-Meier Plots of Time to Infection (Subclinical ZIKV cases) by Study Group, PP 
population 
Figure 38: 
Kaplan-Meier Plots of Time to Infection (Subclinical ZIKV cases) by Serostatus and 
Study Group, PP population 
Figure 39: 
Kaplan-Meier Plots of Time to Infection (Symptomatic ZIKV cases) by Study Group, 
ITT population 
Figure 40: 
Kaplan-Meier Plots of Time to Infection (Symptomatic ZIKV cases) by Serostatus and 
Study Group, ITT population 
Figure 41: 
Kaplan-Meier Plots of Time to Infection (Symptomatic ZIKV cases) by Study Group, 
mITT population 
Figure 42: 
Kaplan-Meier Plots of Time to Infection (Symptomatic ZIKV cases) by Serostatus and 
Study Group, mITT population 
Figure 43: 
Kaplan-Meier Plots of Time to Infection (Symptomatic ZIKV cases) by Study Group, PP 
population 
Figure 44: 
Kaplan-Meier Plots of Time to Infection (Symptomatic ZIKV cases) by Serostatus and 
Study Group, PP population 
Figure 45: 
Maximum Severity of Solicited Systemic Symptoms per Subject by Day Post Treatment, 
Part A 

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Or… 

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Figure with similar format: 
Figure 46: 
Maximum Severity of Solicited Systemic Symptoms per Subject by Day Post Treatment, 
Part B 

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Figure 47: 
Maximum Severity of Solicited Local Symptoms per Subject by Day Post Treatment, 
Part A 
 
 
Or… 

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Figure with similar format: 
Figure 48: 
Maximum Severity of Solicited Local Symptoms per Subject by Day Post Treatment, 
Part B 

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Figure 49: 
Frequency of Related Adverse Events by MedDRA System Organ Class and Severity, 
Part A 
 
 
 
 
Figure with similar format: 
Figure 50: 
Frequency of Related Adverse Events by MedDRA System Organ Class and Severity, 
Part B 

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Figure 51: 
Incidence of Related Adverse Events by MedDRA® System Organ Class and Maximum 
Severity, Part A  
 
 
Figure with similar format: 
Figure 52: 
Incidence of Related Adverse Events by MedDRA® System Organ Class and Maximum 
Severity, Part B  
Figure 53: 
Incidence of Solicited and Unsolicited Adverse Events by MedDRA® Preferred Term for 
Adverse Events Reported by 5% or More of Subjects, Part A 
Figure 54: 
Incidence of Solicited and Unsolicited Adverse Events by MedDRA® Preferred Term for 
Adverse Events Reported by 5% or More of Subjects, Part B 

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Figure 55: 
Boxplot of Laboratory Results by Scheduled Visits, Part A – ALT 
 

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Figures with similar format: 
Figure 56: 
Boxplot of Laboratory Results by Scheduled Visits, Part A – RBC 
Figure 57: 
Boxplot of Laboratory Results by Scheduled Visits, Part A – WBC 
Figure 58: 
Boxplot of Laboratory Results by Scheduled Visits, Part A – Hemoglobin 
Figure 59: 
Boxplot of Laboratory Results by Scheduled Visits, Part A – Hematocrit 
Figure 60: 
Boxplot of Laboratory Results by Scheduled Visits, Part A – Platelets 
Figure 61: 
Boxplot of Laboratory Results by Scheduled Visits, Part A – MCV 
Figure 62: 
Boxplot of Laboratory Results by Scheduled Visits, Part A – Monocytes 
Figure 63: 
Boxplot of Laboratory Results by Scheduled Visits, Part A – Neutrophils 
Figure 64: 
Boxplot of Laboratory Results by Scheduled Visits, Part A – 
Lymphocytes 
Figure 65: 
Boxplot of Laboratory Results by Scheduled Visits, Part A – Eosinophils 
Figure 66: 
Boxplot of Laboratory Results by Scheduled Visits, Part A – Basophils 
Figure 67: 
Boxplot of Laboratory Results by Scheduled Visits, Part B – ALT 
Figure 68: 
Boxplot of Laboratory Results by Scheduled Visits, Part B – RBC 
Figure 69: 
Boxplot of Laboratory Results by Scheduled Visits, Part B – WBC 
Figure 70: 
Boxplot of Laboratory Results by Scheduled Visits, Part B – Hemoglobin 
Figure 71: 
Boxplot of Laboratory Results by Scheduled Visits, Part B – Hematocrit 
Figure 72: 
Boxplot of Laboratory Results by Scheduled Visits, Part B – Platelets 
Figure 73: 
Boxplot of Laboratory Results by Scheduled Visits, Part B – MCV 
Figure 74: 
Boxplot of Laboratory Results by Scheduled Visits, Part B – Monocytes 
Figure 75: 
Boxplot of Laboratory Results by Scheduled Visits, Part B – Neutrophils 
Figure 76: 
Boxplot of Laboratory Results by Scheduled Visits, Part B – 
Lymphocytes 
Figure 77: 
Boxplot of Laboratory Results by Scheduled Visits, Part B – Eosinophils 
Figure 78: 
Boxplot of Laboratory Results by Scheduled Visits, Part B – Basophils 

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Figure 79: 
Laboratory Results by Scheduled Visits: Mean Changes from Baseline by Sex and Study Group, Part A – ALT 
 
Figures with similar format: 

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Figure 80: 
Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Sex and Study Group, Part A – RBC 
Figure 81: 
Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Sex and Study Group, Part A – WBC 
Figure 82: 
Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Sex and Study Group, Part A – Hemoglobin 
Figure 83: 
Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Sex and Study Group, Part A – Hematocrit 
Figure 84: 
Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Sex and Study Group, Part A – Platelets 
Figure 85: 
Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Sex and Study Group, Part A – MCV 
Figure 86: 
Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Sex and Study Group, Part A – Monocytes 
Figure 87: 
Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Sex and Study Group, Part A – Neutrophils 
Figure 88: 
Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Sex and Study Group, Part A – Lymphocytes 
Figure 89: 
Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Sex and Study Group, Part A – Eosinophils 
Figure 90: 
Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Sex and Study Group, Part A – Basophils 
Figure 91: 
Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Sex and Study Group, Part B – ALT 
Figure 92: 
Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Sex and Study Group, Part B – RBC 

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Figure 93: 
Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Sex and Study Group, Part B – WBC 
Figure 94: 
Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Sex and Study Group, Part B – Hemoglobin 
Figure 95: 
Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Sex and Study Group, Part B – Hematocrit 
Figure 96: 
Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Sex and Study Group, Part B – Platelets 
Figure 97: 
Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Sex and Study Group, Part B – MCV 
Figure 98: 
Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Sex and Study Group, Part B – Monocytes 
Figure 99: 
Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Sex and Study Group, Part B – Neutrophils 
Figure 100: 
Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Sex and Study Group, Part B – Lymphocytes 
Figure 101: 
Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Sex and Study Group, Part B – Eosinophils 
Figure 102: 
Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Sex and Study Group, Part B – Basophils 
 
 
 

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Figure 103: 
Boxplot of Vital Sign Assessments by Scheduled Visits and Study Group, Part A – Systolic Blood Pressure 

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Figures with similar format: 
Figure 104: 
Boxplot of Vital Sign Assessments by Scheduled Visits and Study Group, Part A – Diastolic Blood Pressure 
Figure 105: 
Boxplot of Vital Sign Assessments by Scheduled Visits and Study Group, Part A – Pulse 
Figure 106: 
Boxplot of Vital Sign Assessments by Scheduled Visits and Study Group, Part A – Temperature 
Figure 107: 
Boxplot of Vital Sign Assessments by Scheduled Visits and Study Group, Part B – Systolic Blood Pressure 
Figure 108: 
Boxplot of Vital Sign Assessments by Scheduled Visits and Study Group, Part B – Diastolic Blood Pressure 
Figure 109: 
Boxplot of Vital Sign Assessments by Scheduled Visits and Study Group, Part B – Pulse 
Figure 110: 
Boxplot of Vital Sign Assessments by Scheduled Visits and Study Group, Part B – Temperature 
 
 
 
 

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APPENDIX 3: 
LISTINGS  
Listing 1: Early Terminations or Discontinued Subjects ..........................................................140
Listing 2: Early Terminations or Discontinued Subjects, Part B ..............................................140
Listing 3: Subject-Specific Protocol Deviations, Part A ...........................................................141
Listing 4: Subject-Specific Protocol Deviations, Part B ...........................................................141
Listing 5: Non-Subject-Specific Protocol Deviations ...............................................................142
Listing 6: Unanticipated Problems, Part A ...............................................................................142
Listing 7: Unanticipated Problems, Part B ................................................................................142
Listing 8: Subjects Excluded from Analysis Populations, Part A .............................................143
Listing 9: Subjects Excluded from Analysis Populations, Part B .............................................143
Listing 10: Demographic Data, Part A ........................................................................................144
Listing 11: Demographic Data, Part B ........................................................................................144
Listing 12: Pre-Existing and Concurrent Medical Conditions, Part A ........................................145
Listing 13: Pre-Existing and Concurrent Medical Conditions, Part B ........................................145
Listing 14: Compliance and/or Drug Concentration Data, Part A ..............................................146
Listing 15: Compliance and/or Drug Concentration Data, Part B ..............................................146
Listing 16: Individual Immunogenicity Response Data, Part A .................................................147
Listing 17: Individual Immunogenicity Response Data, Part B .................................................147
Listing 18: Individual Efficacy Response Data - ZIKV Endpoints, Part A ................................148
Listing 19: Individual Efficacy Response Data - ZIKV Signs/Symptoms, Part A .....................148
Listing 20: Individual Efficacy Response Data - ZIKV Endpoints, Part B ................................148
Listing 21: Individual Efficacy Response Data - ZIKV Signs/Symptoms, Part B .....................148
Listing 22: Solicited Events – Systemic Symptoms, Part A .......................................................149
Listing 23: Solicited Events – Systemic Symptoms, Part B .......................................................149
Listing 24: Solicited Events – Local Symptoms, Part A .............................................................150
Listing 25: Solicited Events – Local Symptoms, Part B .............................................................150
Listing 26: Unsolicited Adverse Events – Part A .......................................................................151
Listing 27: Unsolicited Adverse Events – Part B........................................................................151
Listing 28: Unsolicited Adverse Events – Screening Segment ...................................................151
Listing 29: Clinical Laboratory Results – Chemistry, Part A .....................................................152
Listing 30: Clinical Laboratory Results – Chemistry, Part B .....................................................152

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Listing 31: Clinical Laboratory Results – Chemistry, Screening Segment ................................152
Listing 32: Clinical Laboratory Results – Hematology, Part A ..................................................153
Listing 33: Clinical Laboratory Results – Hematology, Part B ..................................................153
Listing 34: Clinical Laboratory Results – Hematology, Screening Segment .............................153
Listing 35: Vital Signs, Part A ....................................................................................................154
Listing 36: Vital Signs, Part B ....................................................................................................154
Listing 37: Vital Signs, Screening Segment ...............................................................................154
Listing 38: Concomitant Medications, Part A .............................................................................155
Listing 39: Concomitant Medications, Part B .............................................................................155
Listing 40: Pregnancy Reports, Part A ........................................................................................156
Listing 41: Pregnancy Reports, Part B ........................................................................................156

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Listing 1: 
Early Terminations or Discontinued Subjects 
Treatment Group 
 Subject ID 
Category 
Reason for Early Termination or Product Administration Discontinuation 
Study Day 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Listing with a similar format: 
Listing 2: 
Early Terminations or Discontinued Subjects, Part B 
 
 

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Listing 3: 
Subject-Specific Protocol Deviations, Part A 
Treatment 
Group 
Subject ID 
DV Number 
Deviation 
Deviation 
Category 
Study 
Day 
Reason for 
Deviation 
Deviation 
Resulted 
in AE? 
Deviation 
Resulted in 
Subject 
Termination? 
Deviation 
Affected 
Product 
Stability? 
Deviation 
Resolution 
Comments 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Listing with a similar format: 
Listing 4: 
Subject-Specific Protocol Deviations, Part B 
 
 

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Listing 5: 
Non-Subject-Specific Protocol Deviations 
Site 
Start Date  
Deviation 
End Date 
Reason for 
Deviation 
Deviation 
Resulted in 
Subject 
Termination? 
Deviation 
Affected 
Product 
Stability? 
Deviation 
Category 
Deviation 
Resolution 
Comments 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Listing 6: 
Unanticipated Problems, Part A 
Site 
Problem 
Date  
Unanticipated 
Problem 
Description 
Unexpected in 
Nature, 
Severity, or 
Frequency? 
Event Related 
to 
Participation
? 
Subjects or Others 
at Greater Risk 
that Previously 
Known? 
Require Report 
to IRB/EC? If 
Yes, Date 
Reported 
Event Summary 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Listing with a similar format: 
Listing 7: 
Unanticipated Problems, Part B 
 
 

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Listing 8: 
Subjects Excluded from Analysis Populations, Part A 
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, PP] 
[e.g., Safety, ITT, PP, Day x] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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. 
 
Listing with a similar format: 
Listing 9: 
Subjects Excluded from Analysis Populations, Part B 
 
 

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Listing 10: 
Demographic Data, Part A 
Treatment Group 
 Subject ID 
Sex 
Age at Enrollment (years) 
Ethnicity 
Race 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Listing with a similar format: 
Listing 11: 
Demographic Data, Part B 
 
 

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Listing 12: 
Pre-Existing and Concurrent Medical Conditions, Part A 
Treatment 
Group 
 Subject 
ID 
MH Number 
Medical History 
Term 
Condition Start 
Day  
Condition End 
Day 
MedDRA System Organ Class 
MedDRA Preferred Term 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Listing with a similar format: 
Listing 13: 
Pre-Existing and Concurrent Medical Conditions, Part B 
 
 

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Listing 14: 
Compliance and/or Drug Concentration Data, Part A 
 
Treatment 
Group  
Subject ID  
Dose Number  
Dose Missed? 
Actual [Dosage/Concentration] 
Administered 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Listing with similar format: 
Listing 15: 
Compliance and/or Drug Concentration Data, Part B 
 
 

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Listing 16: 
Individual Immunogenicity Response Data, Part A 
Treatment 
Group  
Subject ID  
Vendor Name 
Test Category 
Date 
Study Day 
Result 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Listing with similar format: 
Listing 17: 
Individual Immunogenicity Response Data, Part B 
 
 

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Listing 18: 
Individual Efficacy Response Data - ZIKV Endpoints, Part A 
Subject 
ID 
Illness 
Onset 
Date 
PDL 
None-PDL 
Determined 
to be ZKIV 
Neurological 
Symptoms 
Severity 
SAE Outcome 
of ZKIV 
Infection 
Illness 
Resolution 
Date 
Illness 
Duration 
(Days) 
Co-enroll 
ZIKV 
Treatment 
Blood 
PCR 
Test 1 
Blood 
PCR 
Test 2 
Blood 
PCR 
Test 3 
Urine 
PCR 
Test 1 
Urine 
PCR 
Test 2 
Urine 
PCR 
Test 3 
Blood 
PCR 
Test  
Urine 
PCR 
Test  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Listing 19: 
Individual Efficacy Response Data - ZIKV Signs/Symptoms, Part A 
Subject 
ID 
Illness Onset 
Date 
Signs/Symptoms 
Summary 
Samples 
Collected 
for PDL 
Determined 
to be ZKIV 
Reported 
as AE 
Medical Term 
 
 
 
 
 
 
 
 
 
Listings with similar formats: 
Listing 20: 
Individual Efficacy Response Data - ZIKV Endpoints, Part B 
Listing 21: 
Individual Efficacy Response Data - ZIKV Signs/Symptoms, Part B 
 
 

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Listing 22: 
Solicited Events – Systemic Symptoms, Part A 
Treatment 
Group  
Subject ID  
Dose Number 
Post Dose Day 
Assessmenta 
Symptom 
Severity 
 
 
 
 
DC 
 
 
 
 
 
 
Clinic 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
a DC = Data reported by subject on the Diary Card and reviewed by clinic staff and reported in Diary Card Assessment 
eCRF. 
Note: Clinic = Data collected by clinic staff during physical exam or symptom assessment (treatment administration record, 
in-clinic assessment, etc.) 
 
Listing with similar format: 
Listing 23: 
Solicited Events – Systemic Symptoms, Part B 
 
 

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Listing 24: 
Solicited Events – Local Symptoms, Part A 
Treatment 
Group  
Subject ID  
Dose Number 
Post Dose Day 
Assessmenta 
Symptom 
Severity 
 
 
 
 
DC 
 
 
 
 
 
 
Clinic 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
a DC = Data reported by subject on the Diary Card and reviewed by clinic staff and reported in Diary Card Assessment eCRF. 
Note: Clinic = Data collected by clinic staff during physical exam or symptom assessment (treatment administration record, in-clinic assessment, etc.) 
 
Listing with similar format: 
Listing 25: 
Solicited Events – Local Symptoms, Part B 
 
 

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Listing 26: 
Unsolicited Adverse Events – Part A 
Adverse 
Event 
Associated 
with Dose 
No. 
No. of 
Days Post 
Associated 
Dose 
(Duration) 
Date of 
Onset 
Severity 
SAE? 
Relationship 
to Study 
Product 
Effect on 
Product 
Administration 
Schedule 
Outcome 
Date of 
Resolution 
or Death 
MedDRA 
System 
Organ 
Class 
MedDRA 
Preferred 
Term 
Treatment Group: , Subject ID: , AE Number:  
 
 
 
 
 
 
 
 
 
 
 
 
Comments: 
 
 
 
 
 
 
 
 
 
 
 
 
Treatment Group: , Subject ID: , AE Number:  
 
 
 
 
 
 
 
 
 
 
 
 
Comments: 
Note: For additional details about SAEs, see Table: xx. 
Listings with similar format: 
Listing 27: 
Unsolicited Adverse Events – Part B 
Listing 28: 
Unsolicited Adverse Events – Screening Segment 
 
 

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Listing 29: 
Clinical Laboratory Results – Chemistry, Part A 
Treatment 
Group 
Subject ID 
Visit 
Number  
Date Lab 
Performed  
Sex  
Age (years) 
Laboratory 
Parameter (Units) 
Result 
(Severity 
Grade) 
Reference 
Range Low 
Reference Range 
High 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Listings with similar format: 
Listing 30: 
Clinical Laboratory Results – Chemistry, Part B 
Listing 31: 
Clinical Laboratory Results – Chemistry, Screening Segment 
 
 

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Listing 32: 
Clinical Laboratory Results – Hematology, Part A 
Treatment 
Group 
Subject ID 
Visit 
Number  
Date Lab 
Performed  
Sex  
Age 
(years) 
Laboratory 
Parameter (Units) 
Result (Severity 
Grade) 
Reference 
Range Low 
Reference Range 
High 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Listings with a similar format: 
Listing 33: 
Clinical Laboratory Results – Hematology, Part B 
Listing 34: 
Clinical Laboratory Results – Hematology, Screening Segment 
 
 

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Listing 35: 
Vital Signs, Part A 
Treatment 
Group 
Subject ID 
Planned 
Time Point 
Actual 
Study Day 
Temperature 
(°C) 
Systolic Blood 
Pressure 
(mmHg) 
Diastolic Blood 
Pressure 
(mmHg) 
Heart Rate 
(beats/min) 
Weight 
(kg) 
Height 
(cm) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Listings with a similar format: 
Listing 36: 
Vital Signs, Part B 
Listing 37: 
Vital Signs, Screening Segment 
 
 

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Listing 38: 
Concomitant Medications, Part A 
Treatment 
Group 
Subject 
ID 
CM 
Number 
Medication 
Medication Start 
Date 
Medication End 
Date (if not 
ongoing) 
Indication 
ATC Level 1  
(ATC Level 2) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Listing with a similar format: 
Listing 39: 
Concomitant Medications, Part B 
 

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Listing 40: 
Pregnancy Reports, Part A  
Treatment 
Group  
Subject 
ID  
Pregnancy 
Number 
Date Site 
Notified 
Start Date 
of Last 
Menstrual 
Period 
Gravidity Parity 
Stated Method 
of 
Contraception 
Date of 
Delivery or 
Pregnancy 
Termination 
Estimated 
Gestational 
Age 
Pregnancy 
Outcome 
If live or still 
birth, Any 
Congenital 
Anomalies or 
Birth 
Defects? 
If live birth, 
Neonatal 
Death? 
 
 
 
 
 
 
 
 
 
 
 
 
 
Comments: 
 
 
 
 
 
 
 
 
 
 
 
 
 
Comments: 
 
Listing with similar format: 
Listing 41: 
Pregnancy Reports, Part B