Phase I, Open-label, Dose-Ranging Study to Evaluate the Safety, Tolerability, and Immunogenicity of GLS-5700 Administered ID Followed by EP in Dengue Virus-Naïve Adults
Phase: PHASE1
Conditions: Healthy
Sponsor: GeneOne Life Science, Inc.

 
 
 
ZIKA-001 
 
 
PHASE I, OPEN-LABEL, DOSE RANGING STUDY TO EVALUATE THE 
SAFETY, 
TOLERABILITY, 
AND 
IMMUNOGENICITY 
OF 
GLS-5700 
ADMINISTERED ID FOLLOWED BY ELECTROPORATION IN DENGUE  
VIRUS-NAÏVE ADULTS 
 
 
Sponsored by: 
GeneOne Life Science Inc. 
 
 
U.S. BB-IND 17012 
 
 
 
 
Version 1.2 
 

GLS-5700 
 
ZIKA-001 
GeneOne Life Science, Inc. 
 
Clinical Protocol 
Date: 1 July 2016 
 
v1.2 
-2- 
 
PHASE I, OPEN-LABEL, DOSE-RANGING STUDY TO EVALUATE THE 
SAFETY, 
TOLERABILITY, 
AND 
IMMUNOGENICITY 
OF 
GLS-5700 
ADMINISTERED ID FOLLOWED BY EP IN DENGUE VIRUS-NAÏVE ADULTS  
 
Drug:  
GLS-5700  
Protocol Number:  
ZIKA-001 
Sponsor:  
GeneOne Life Science, Inc. 
 
1040 DeKalb Pike, Suite 200 
 
Blue Bell, PA 19422 
 
 
Medical Monitor:  
Joel Maslow, MD PhD MBA FACP 
Version and Date:  
Version Draft 1.2; 1 July 2016 
 
CONFIDENTIAL 
The information in this document is considered privileged and confidential by 
GeneOne Life Science, Inc. and may not be disclosed to others except to the extent 
necessary to obtain Institutional Review Board/Ethics committee approval and 
informed consent, or as required by local regulatory authorities. Persons to whom 
this information is disclosed must be informed that this information is privileged 
and confidential and that it must not be further disclosed without the written 
permission of GeneOne Life Science, Inc. Any supplemental information added to 
this document is also confidential and proprietary information of GeneOne Life 
Science, Inc. and must be kept in confidence in the same manner as the contents of 
this document. 

GLS-5700 
 
ZIKA-001 
GeneOne Life Science, Inc. 
 
Clinical Protocol 
Date: 1 July 2016 
 
v 1.2 
-3- 
 
 
PROTOCOL ACKNOWLEDGEMENT 
 
 
I have read this Protocol and agree that it contains all necessary details for carrying out 
the study described. I understand that it must be reviewed by the Institutional Review 
Board or Independent Ethics Committee overseeing the conduct of the study and receive 
approval or a favorable opinion before implementation. 
 
The signature of the Principal Investigator and Sponsor below constitute their approval of 
this protocol and provide the necessary assurances that this study will be conducted 
according to the Declaration of Helsinki, GCP, ICH guidelines, local legal and regulatory 
regulations as well as to all stipulations of the protocol in both the clinical and 
administrative sections, including statements regarding confidentiality. 
 
 
 
 
_________________________________ 
 
 
_________________ 
Investigator’s printed name and signature 
 
 
Date 
 
 
 
1 July 2016 
_________________________________ 
 
 
_________________ 
Medical Monitor 
 
 
 
 
 
Date 
 
 
 
 
Protocol Number: ZIKA-001 
Site Number: xxx 
Version Number: Final 1.2/Version Date: 1 July 2016 
 

GLS-5700 
 
ZIKA-001 
GeneOne Life Science, Inc. 
 
Clinical Protocol 
 
Date: 1 July 2016 
 
v 1.2 
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TABLE OF CONTENTS 
PROTOCOL ACKNOWLEDGEMENT .............................................................................3 
TABLE OF CONTENTS .....................................................................................................4 
CLINICAL PROTOCOL SYNOPSIS .................................................................................8 
1. 
INTRODUCTION .................................................................................13 
1.1 
Background and Rationale ....................................................................13 
1.1.1 
Zika Virus Epidemiology and Clinical Illness ..................................... 13 
1.1.2 
Current Treatment ................................................................................ 13 
1.1.3 
Pre-clinical experience with GLS-5700 ............................................... 14 
1.1.4 
Target population for Zika virus vaccines and therapies ..................... 15 
1.1.5 
Human experience with GLS-5700 ...................................................... 16 
1.1.6 
Administration of similar DNA plasmids by Electroporation (EP) ..... 16 
1.2 
GLS-5700 ..............................................................................................19 
1.3 
Dose and Regimen Rationale ................................................................19 
1.4  
Risks/Benefit Assessment .....................................................................19 
2. 
HYPOTHESIS AND STUDY OBJECTIVES ......................................21 
2.1 
Hypothesis .............................................................................................21 
2.2 
Primary Objectives ................................................................................21 
2.3 
Secondary Objectives ............................................................................21 
2.4 
Exploratory Objectives ..........................................................................21 
3. 
STUDY DESIGN ..................................................................................22 
3.1 
Treatment Progression Scheme / Interim Safety Monitoring ................22 
4. 
SELECTION AND ENROLLMENT OF PARTICIPANTS ................23 
4.1 
Recruitment of Participants ...................................................................23 
4.2 
Inclusion Criteria ...................................................................................23 
4.3 
Exclusion Criteria ..................................................................................24 
4.4 
Discontinuation/Withdrawal of Study Participants ...............................25 
5. 
STUDY PRODUCT ..............................................................................26 
5.1 
Investigational Product ..........................................................................26 

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5.2 
Packaging and Labeling of GLS-5700 ..................................................26 
5.3 
Handling of GLS-5700 ..........................................................................26 
5.4 
Dispensing of GLS-5700 .......................................................................27 
5.5 
Precautions with Investigational Medicinal Product .............................27 
5.6 
Preparation of Investigational Product ..................................................27 
5.6.1 
Preparation of 1 mg ID Dose ................................................................ 27 
5.6.2 
Preparation of 2 mg ID Dose ................................................................ 28 
5.7 
Records of Investigational Product Disposition at Site .........................28 
5.8 
Return and Destruction of Investigational Product ...............................28 
5.9 
Use of CELLECTRA® Electroporation Device ...................................29 
5.10 
Investigational Device Accountability ..................................................29 
6. 
STUDY PROCEDURES AND TREATMENTS..................................29 
6.1 
Procedure by Visit .................................................................................30 
6.1.1 
Screening Evaluations .......................................................................... 30 
6.1.2 
Study Evaluations ................................................................................. 30 
6.1.2.1 
Vaccine Administration Visits ............................................................. 30 
6.1.2.2 
Telephone assessment (Day 1 post 1st vaccination) ............................. 31 
6.1.2.3 
Non-vaccination study visits ................................................................ 31 
6.1.2.4 
End of Study Visit (Week 60) / Early Termination .............................. 31 
6.1.2.5 
Premature Withdrawal .......................................................................... 31 
6.2 
Timing and Evaluations .........................................................................32 
6.2.1 
Informed Consent ................................................................................. 32 
6.2.2 
Patient Identification Number and Group Assignments ....................... 32 
6.2.3 
Safety Assessments .............................................................................. 33 
6.2.3.1 
Patient self-evaluations ......................................................................... 33 
6.2.3.2 
Physical Assessments and Targeted Physical Assessment ................... 33 
6.2.3.3 
Vital Signs ............................................................................................ 33 
6.2.3.4 
Weight and Height ................................................................................ 33 
6.2.3.5 
12-Lead ECGs ...................................................................................... 34 
6.2.3.6 
Laboratory Evaluations ........................................................................ 34 

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6.3 
Injection of Investigational Product followed by Electroporation ........34 
6.3.1 
Management of anxiety and pain due to EP procedure ........................ 35 
6.4 
Assessment of Laboratory Abnormalities .............................................35 
6.5 
Assessment of Clinical Adverse Events ................................................35 
6.6 
Assessment of Injection Site Reactions .................................................35 
6.7 
Handling and shipment of biological specimens ...................................36 
6.8 
Immunogenicity Assessments ...............................................................36 
6.8.1 
ELISA ................................................................................................... 36 
6.8.2 
Neutralizing antibodies ......................................................................... 36 
6.8.3 
ELISPOT .............................................................................................. 36 
6.8.4 
Flow Cytometry .................................................................................... 37 
6.9 
Downloading of EP Data from CELLECTRA® Device ......................37 
6.10 
Concomitant medications and medical procedures ...............................37 
6.11 
Restrictions ............................................................................................37 
7. 
EVALUATION OF SAFETY AND MANAGEMENT OF TOXICITY37 
7.1 
Safety Parameters ..................................................................................37 
7.1.1 
Adverse Events (AEs) .......................................................................... 38 
7.1.2 
Serious Adverse Events (SAEs) ........................................................... 39 
7.1.3 
Medically Attended Adverse Events (MAAE) .................................... 40 
7.1.4 
Unexpected Adverse Drug Reactions ................................................... 40 
7.1.5 
Assessing Severity (Intensity) .............................................................. 40 
7.1.6 
Causal Relationship of Clinical Material to Adverse Events ............... 40 
7.1.7 
Abnormal Laboratory Value ................................................................ 41 
7.1.8 
Procedures for Documenting Pregnancy During Study ....................... 42 
7.1.9 
Post-Study Reporting Requirements .................................................... 43 
7.2 
Methods and Timing for Collection and Recording of Safety Data ......43 
7.3 
Safety and Toxicity Management ..........................................................44 
7.3.1 
Events Requiring Expedited Reporting .................................................44 
7.3.2 
Stopping Rules (Criteria for Pausing of Study) .....................................44 
8. 
STATISTICAL CONSIDERATIONS ..................................................45 
8.1 
General Considerations .........................................................................45 

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8.2 
Demographic and Other Baseline Characteristics .................................45 
8.3 
Safety Analysis ......................................................................................45 
8.3.1 
Adverse events ......................................................................................45 
8.3.2 
Laboratory Data .....................................................................................47 
8.4 
Immunogenicity analysis .......................................................................47 
8.5 
Sample Size ...........................................................................................48 
8.6 
Missing Values ......................................................................................48 
8.7 
Interim analyses .....................................................................................48 
9. 
DATA COLLECTION, MONITORING, AND AE REPORTING ......48 
9.1 
Confidentiality .......................................................................................48 
9.2 
Source Documents .................................................................................49 
9.3 
Records to be kept .................................................................................49 
9.4 
Records Retention .................................................................................49 
9.5 
Safety and Quality Monitoring and Record Availability ......................49 
9.6 
Adverse Experience (AE) Reporting .....................................................50 
9.6.1 
Study Reporting Period of Adverse Events .......................................... 50 
9.6.2 
Study Reporting Period of Serious Adverse Events ............................. 50 
9.6.3 
Notifications of Serious Adverse Events .............................................. 51 
9.7 
Reporting of Medically Attended Adverse Events ................................52 
9.8 
Reporting of Device Related Complaints ..............................................52 
9.9 
Study Discontinuation ...........................................................................52 
10. 
PUBLICATION OF RESEARCH FINDINGS .....................................53 
11. 
LIST OF ABBREVIATIONS ...............................................................54 
12. 
REFERENCES ......................................................................................56 
13. 
APPENDIX ...........................................................................................60 
Appendix A: Participant Memory Aid ...........................................................................60 
Appendix B:  Toxicity Grading Scale ..........................................................................61 
Appendix C:   CELLECTRA® Error Reporting Form ................................................62 

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CLINICAL PROTOCOL SYNOPSIS 
Title of Study: Phase I, open-label, dose-ranging study to evaluate the safety, tolerability, 
and immunogenicity of GLS-5700, administered ID followed by EP in dengue virus-
naïve adults.  
Estimated Number of Study Centers and Countries/Regions: 3 sites US and Canada 
Study Phase: I 
Research Hypothesis: GLS-5700 administered by intradermal (ID) injection followed by 
electroporation (EP) will be well tolerated and immunogenic in dengue virus naïve adults.  
Primary Objective:  
• 
Evaluate the safety and tolerability of GLS-5700 when administered by ID injection 
followed by EP in healthy dengue-virus naïve adult subjects to 14 days from final vaccine 
administration 
Primary Safety Endpoints:  
• Incidence of adverse events classified by system organ class (SOC), preferred term (PT) 
severity, and relationship to study treatment and schedule to 14 days post-vaccination 
• Administration (injection) site reactions (described by frequency and severity grade) and 
administration site pain to 14 days post-final vaccination 
• Changes in safety laboratory parameters described by frequency and severity grade (e.g., 
liver panel tests, vital signs) 
Secondary Objectives:  
• 
Evaluate the safety to 1 year post vaccination of GLS-5700 in dengue-virus naïve adults.  
• 
Evaluate cellular and humoral responses of GLS-5700 when delivered ID and followed by 
EP in dengue-virus naïve adults  
Secondary Immunologic Endpoints: 
• 
Binding antibody titers to the Zika envelope (E) protein as measured by ELISA 
• 
Neutralizing antibody titers against Zika virus as measured in viral neutralization assay 
• 
Antigen specific cellular immune responses to Zika virus as determined by Interferon-
gamma (IFN-γ) ELISpot and/or Intracellular Staining (ICS) assays 
Exploratory Objectives: 
• 
Explore whether end point antibody titers are dose related.  
• 
Explore the immunogenicity and longevity of  GLS-5700 vaccination 
• 
Explore the time to onset and longevity of immune  responses, both humoral and cellular 
• 
Explore if increasing dose levels of GLS-5700 more rapidly induce cellular and humoral 
immunity  
• 
Explore the epitope specificity for T cell reactions of GLS-5700 to Zika virus 
Exploratory Endpoints: 
• 
Comparison of ELISA, neutralization titers, IFN-γ ELISpot and/or ICS across different 
vaccine regimens 
• 
Other analyses as indicated to assess protective mechanisms against Zika virus. 
• 
Epitope mapping of CD4+ and CD8+ T lymphocyte responses 

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Study Design: 
This Phase I clinical trial will evaluate whether GLS-5700 administered via ID injection and 
followed by electroporation (EP) is safe, tolerated and able to generate an immune response 
against Zika virus in dengue virus-naïve participants and whether immune reactivity is dose-
dependent. Injections will be given in the deltoid muscle followed immediately by EP with the 
CELLECTRA®-3P device.  
GLS-5700 contains plasmid pGX7201 that encodes for a consensus sequence of the pre-
membrane (prM) and envelope (E) proteins of Zika virus.  
Currently there are no approved treatments or prophylactic vaccines for Zika virus. Nor have 
any vaccine candidates for Zika virus been advanced into human trials.   
Evaluation of ID administration of GLS-5700:  
There are two arms for ZIKA-001. Participants (n=20 per group) will be administered GLS-
5700 at one of two dose levels: 1 mg or 2 mg DNA/dose. Vaccine will be administered as 0.1 ml 
ID injections followed by EP with the CELLECTRA®-3P device. Participants will receive one 
or two injections into the deltoid region at vaccination at 0, 4, and 12 weeks (3 vaccination 
series).  
Safety assessment: Participants will be monitored for adverse events utilizing the “Toxicity 
Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine 
Clinical Trials (Appendix B)” with labs assessed as per site normal values. Pain will be assessed 
immediately after EP and at 30 minutes post-EP. Laboratory safety assessments will be obtained 
at screening, 1 week following the 1st vaccination, and 2 weeks following the 2nd and 3rd 
vaccinations. Adverse events, including assessment of injection site reactions, will be monitored 
through 12 months after the final vaccination.   
In the event that a stopping criterion is reached (Section 7.3.2), the study will not continue until 
a full discussion has been conducted with the Medical Monitor, Principal Investigator, and 
IRB/CER (if applicable). 
Immunogenicity assessment: Blood will be obtained for Zika immune responses at baseline; at 
weeks 1, and 4; at 2 and 8 weeks following the 2nd and 3rd vaccinations; and at study weeks 36 
and 60. Serum will be separated and sent for analysis for humoral responses (neutralizing and 
binding antibody titers). Whole blood will be processed to obtain peripheral blood mononuclear 
cells (PBMC) for ELISpot and/or ICS analysis.  
Table S1: Dosing Arms and Regimens 
Group 
Vaccine 
Schedule 
n 
Route  No. injections 
per dose 
Dose 
(mg) 
1 
GLS-5700 
0-4-12 weeks 20 
ID 
1 
1 
2 
GLS-5700 
0-4-12 weeks 20 
ID 
2 
2 
 
TOTAL 
 
40 
 
 
 
 

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Clinical Protocol 
 
Date: 1 July 2016 
 
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Study Population:  
Inclusion Criteria: 
a. 
Age 18-65 years;  
b. Able to provide consent to participate and having signed an Informed Consent Form (ICF); 
c. 
Able and willing to comply with all study procedures; 
d. Women of child-bearing potential agree to use medically effective contraception (oral 
contraception, barrier methods, spermicide, etc.) or have a partner who is sterile from enrollment 
to 3 months following the last injection, or have a partner who is medically unable to induce 
pregnancy. 
e. 
Sexually active men who are considered sexually fertile must agree to use either a barrier method 
of contraception during the study, and agree to continue the use for at least 3 months following 
the last injection, or have a partner who is permanently sterile or is medically unable to become 
pregnant;  
f. 
Normal screening ECG or screening ECG with no clinically significant findings; 
g. Screening laboratory must be within normal limits or have only Grade 0-1 findings; 
h. No history of clinically significant immunosuppressive or autoimmune disease. 
i. 
No history of dengue virus vaccination or illness; no history of yellow fever vaccination. 
j. 
Dengue seronegative at baseline by screening laboratory evaluation 
k. Not currently or within the previous 4 weeks taking immunosuppressive agents (excluding 
inhaled, topical skin and/or eye drop-containing corticosteroids, low-dose methotrexate, or 
prednisone at a dose less than 10 mg/day or steroid dose-equivalent). 
 

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Study Population Continued:  
Exclusion: 
a. 
Administration of an investigational compound either currently or within 30 days of first dose; 
b. Previous receipt of an investigational product for the treatment or prevention of Zika virus except 
if participant is verified to have received placebo; 
c. 
Administration of any vaccine within 4 weeks of first dose; 
d. Administration of any monoclonal or polyclonal antibody product within 4 weeks of the first 
dose 
e. 
Administration of any blood product within 3 months of first dose; 
f. 
Pregnancy or breast feeding or plans to become pregnant during the course of the study;  
g. Positive serologic result for dengue virus (any serotype) or history of receipt of either dengue 
virus or yellow fever virus vaccination at any time in the past; 
h. Positive serologic test for HIV, hepatitis B surface antigen (HBsAg); or any potentially 
communicable infectious disease as determined by the Principal Investigator or Medical 
Monitor; 
i. 
Positive serologic test for hepatitis C (exception: successful treatment with confirmation of 
sustained virologic response); 
j. 
Baseline evidence of kidney disease as measured by creatinine greater than 1.5 (CKD Stage II or 
greater); 
k. Baseline screening lab(s) with Grade 2 or higher abnormality, except for Grade 2 creatinine; 
l. 
Chronic liver disease or cirrhosis; 
m. Immunosuppressive illness including hematologic malignancy, history of solid organ or bone 
marrow transplantation; 
n. Current or anticipated concomitant immunosuppressive therapy (excluding inhaled, topical skin 
and/or eye drop-containing corticosteroids, low-dose methotrexate, or prednisone at a dose 
greater than 10 mg/day or steroid dose-equivalent); 
o. Current or anticipated treatment with TNF-α inhibitors such as infliximab, adalimumab, 
etanercept; 
p. Prior major surgery or any radiation therapy within 4 weeks of group assignment; 
q. Any pre-excitation syndromes, e.g., Wolff-Parkinson-White syndrome; 
r. 
Presence of a cardiac pacemaker or automatic implantable cardioverter defibrillator (AICD) 
s. 
Metal implants within 20 cm of the planned site(s) of injection; 
t. 
Presence of keloid scar formation or hypertrophic scar as a clinically significant medical 
condition at the planned site(s) of injection. 
u. Prisoner or participants who are compulsorily detained (involuntary incarceration) for treatment 
of either a physical or psychiatric illness;  
v. Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere 
with adherence to study requirements or assessment of immunologic endpoints; or 
w. Not willing to allow storage and future use of samples for Zika virus related research 
x. Any illness or condition that in the opinion of the investigator may affect the safety of the 
participant or the evaluation of any study endpoint. 

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 Table S2.  Schedule of Events: 3 vaccinations 
 
Tests and 
Observations 
Screen 
(Day -7 
to -30) 
Day0  
Day1  
Wk1 
(±2d) 
Wk4 
(±5d) 
Wk6 
(±5d) 
Wk12 
(±5d) 
Wk14 
(±5d) 
Wk20 
(±10d) 
Wk36 
(±10d) 
Wk60 
(±10d) / 
Early 
termination 
Clinical 
Assessments 
 
 
 
 
 
 
 
 
 
 
 
Consent 
X 
 
 
 
 
 
 
 
 
 
 
Med history 
X 
X 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
Travel hx a 
X 
 
 
 
 
 
 
 
 
 
 
Medications b 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Phys Exam c 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Vital signs c 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Laboratory 
Assessments 
 
 
 
 
 
 
 
 
 
 
 
12-lead ECG 
X 
 
 
 
 
 
 
 
 
 
 
CBC w/diff 
X 
 
 
X 
 
X 
 
X 
 
 
 
Chemistries d 
X 
 
 
X 
 
X 
 
X 
 
 
 
Serologies e 
X 
 
 
 
 
 
 
 
 
 
 
Pregnancy f 
X 
X 
 
 
X 
 
X 
 
 
 
 
Serum g 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
PBMCs g 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Blood Vol. 
per visit (mL) 
15 
70 
 
80 
70 
80 
70 
80 
70 
70 
70 
Study Related 
Procedures 
 
 
 
 
 
 
 
 
 
 
 
Vaccine + EP 
 
X 
 
 
X 
 
X 
 
 
 
 
EP Data h 
 
X 
 
 
X 
 
X 
 
 
 
 
Memory aid i  
 
X 
 
 
X 
 
X 
 
 
 
 
AEs  
 
X 
X j 
X 
X 
X 
X 
X 
X 
X 
X 
 
a Travel history to Central America, South America, Caribbean Islands, and South Pacific Islands at any time in past 
b   Prior and concomitant, new medications will be recorded at all study visits (Day 0 through study discharge) 
c  Full physical examination performed at screening and last visit or early termination only; perform targeted examinations 
at other visits as determined by Investigator or per participant complaints; record history of weight lifting or other 
significant physical activity; Vital signs will be performed pre and post vaccination at week 0, 4, and 12 week visits; 
height and weight will be recorded at screening. 
d  Sodium (Na), potassium (K), chloride (Cl), bicarbonate (HCO3), glucose, BUN, Cr, ALT, AST, CPK 
e HIV antibody or rapid test, HBsAg, HCV antibody, dengue, West Nile, and chikungunya virus antibodies 
f Serum pregnancy test at screening and urine pregnancy test thereafter  
g  Collect 4 tubes whole blood in ACD (yellow top) tubes for PBMCs; and 3 tubes of whole blood (red top) to obtain ~10 
mL serum at the indicated time points 
h  Download EP data within 48 hours of dose and transfer to GeneOne or its designee 
i  Provide memory aid to study participants and review on next visit 
j  Detail AEs assessed via telephone.   

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1. 
INTRODUCTION 
1.1 
Background and Rationale 
1.1.1 Zika Virus Epidemiology and Clinical Illness 
Zika virus was discovered in 1947 during a survey to map the extent of yellow fever in 
the Entebbe region of Uganda. The virus was cultured from the serum of a sentinel 
macaque placed in the Zika forest that developed fever but was otherwise well. Initially 
restricted to equatorial regions of Africa and Asia, Zika started to spread eastward across 
the Pacific Ocean with an outbreak on Yap Island, Micronesia in 2007 [1], in French 
Polynesia in 2014 [2], and reaching Brazil in late 2014 or early 2015 [3, 4]. Although 
cases of Guillain Barré syndrome (GBS) were documented in the French Polynesian Zika 
outbreak [5], it was not until cases of microcephaly were documented in October 2015 
during the outbreak in Brazil that global awareness of Zika disease was raised. 
Epidemiologic studies since then have documented a rate of GBS of approximately 1 in 
5000 following Zika virus infection [6] and microcephaly affecting 1-2% of fetuses 
infected during pregnancy. 
Zika virus infection presents similarly to dengue or chikungunya with fever in most, rash, 
malaise, myalgias, conjunctivitis and retroorbital pain but may present with few, if any, 
discernable symptoms [7]. The propensity for neurologic sequelae coupled with the rapid 
spread across South America, Central America, and the Caribbean has raised 
international alarm [8]. Moreover, alternative non-mosquito-borne routes of Zika virus 
spread include through blood transfusion, breast milk [9], sexual transmission [10-12], 
and may include urine and saliva [13, 14].  
Zika virus is spread primarily through Aedes species mosquitoes, mainly Aedes aegypti, 
but can be carried and transmitted by many other mosquito species [15]. Aedes species 
mosquitoes also transmit other arboviruses such as dengue and chikungunya. In fact, 
these infections are co-endemic in most regions and may cause concurrent infections [16-
18]. Most commercial flavivirus diagnostic assays are based on the NS1 protein, 
however, there is significant cross-reactivity between the NS1 proteins of yellow fever, 
dengue, and Zika.  Whether prior exposure to any other arbovirus may affect the clinical 
response to Zika virus, or vice versa, is unknown.  
1.1.2 Current Treatment 
There are no approved therapies or vaccines for Zika virus infection, nor have any 
products advanced into clinical testing. Moreover, while many companies and academic 
groups have announced development plans for Zika virus vaccines, none have been 
published to date.   
There have been a number of vaccines developed for other flavivirus infections. Live 
virus vaccines utilizing chimeric viral constructs have been approved for use for yellow 
fever and dengue. DNA vaccines have been developed and published for dengue [19, 20], 
West Nile virus [21-24], and Japanese encephalitis virus [23]. Notably, DNA vaccines 

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targeting West Nile virus [21, 22] and Dengue virus [20] have been tested as part of 
Phase I clinical trials without vaccine associated toxicity.  
1.1.3 Pre-clinical experience with GLS-5700 
The immunogenicity of pGX7201, the DNA plasmid that is the component comprising 
GLS-5700, has been studied in mice, guinea pigs, rabbits, and rhesus macaques. As of 
this writing, challenge trials are in progress. Details are presented in the Investigators 
Brochure and are summarized below.  
pGX7201 encodes for the pre-membrane and envelope (prME) structural proteins of the 
Zika virus. The coding sequence is a synthetic compilation based on a statistical average 
of the amino acid sequence of African and Asian lineage strains published prior to 
December 2015, weighted towards the Asian lineage. The prME sequence is expressed 
from a modified pVAX1 expression vector, pGX0001. Expression, identity, and 
specificity were first determined in E. coli following transfection into tissue culture. The 
genetic structure of pGX7201 is such that prior work with West Nile virus and other 
flaviviruses has shown that proper folding of the envelope region occurs by inclusion of 
the premembrane region.  
Mice were immunized intramuscularly (IM) into the quadriceps muscle with either 12.5 
µg/dose or 25 µg/dose of pGX7201 at 0, 2, and 4 weeks. Injection of vaccine was 
immediately followed by EP using the CELLECTRA-3P device. Seroconversion was 
seen following a single vaccination with endpoint titers reaching ~1:10,000 following the 
third immunization. Immunization also induced neutralizing antibodies titers of ≥1:80, 
(neutralizing titers ≥1:10 are considered as protective for other viruses).  pGX7201 also 
induced broad based, high-level T cell responses; ≥ 400 SFU/106 peripheral blood 
mononuclear cells (PBMCs). Based on the predicted crystal structure of the Zika virus 
mature pre-membrane and envelope proteins, mapping of the T cell response 
demonstrated responses to multiple envelope domains (DI, DII, and DIII, and the carboxy 
terminal region) with minimal to no reactivity to the pre-membrane and membrane 
region.  
Specificity of the response was assessed by determining cross-reactivity of serum from 
pGX7201 (Zika virus vaccine) immunized mice against the envelope proteins of the four 
dengue serotypes; the Zika virus prME protein complex served as a positive control. 
There was no reactivity detected against any of the flavivirus dengue serotypes. 
Additional experiments to determine whether there was any cross-reactivity against the 
chikungunya envelope (chikungunya is an α arbovirus) similarly showed no reactivity 
over baseline at any titer. Thus, pGX7201 reactivity was specific to Zika virus with no 
cross-reactivity to the dengue flavivirus or other arboviruses such as chikungunya. 
These data demonstrate that the vaccine was able to generate levels of antibody and T-
cell responses that would be predictive of protection from infection. Since the pre-
membrane and membrane regions would be predicted to be conserved across flaviviruses, 
the lack of reactivity to this region would further support a Zika-specific response for 
GLS-5700 based on pGX7201.  
pGX7201 was also administered to guinea pigs and rabbits with similar B and T cell 
responses, demonstrating its utility across multiple mammalian species. 

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Non-human primates were immunized with pGX7201 at either low dose (0.5 
mg/vaccination) or high dose (2 mg/vaccination) for three vaccinations spaced 3 weeks 
apart by either intradermal (ID) or IM injection and followed by electroporation (EP). 
These experiments are still in progress. Notably, after a single vaccination, 7 of 10 NHPs 
administered pGX7201 via ID injection and followed by EP developed robust B cell 
responses versus only 1 of 10 animals dosed IM (5 animals in each dose group (0.5 and 2 
mg)). All animals, whether injected ID or IM seroconverted after 2 injections. 
Neutralizing activity has been detected with a single ID injection; quantification of the 
magnitude of the response has not yet been completed. pGX7201 also generated T cell 
responses in NHPs; quantification of response is in progress.  
Importantly, as Zika virus circulates with dengue and chikungunya, and uses the same 
mosquito vectors to spread the disease, co-immunization experiments are underway to 
assess the immunogenicity of  a single vaccine composed of DNA plasmid components 
against the Zika virus prME (pGX7201), the four dengue serotypes, and chikungunya 
virus in both guinea pigs and non-human primates. 
Challenge studies to assess whether pGX7201 is protective in mouse and primate models 
of disease are underway. IFNAR mice (IFNα and IFNβ receptor knockouts) were first 
shown to be susceptible to Zika virus infection with mortality observed in approximately 
7 days. IFNAR mice have been used successfully to assess a DNA vaccine against the 
Usutu flavivirus [27]. Histopathology of IFNAR mice infected with Zika virus following 
SQ administration demonstrates abnormalities restricted to the central nervous system, 
mimicking human disease. AG129 mice (IFN α, β, γ receptor knockouts) have also been 
shown to represent a lethal model for dengue virus [28], as well as for Zika virus 
infection (unpublished). While this mouse strain has been utilized to assess the response 
against a live-virus chimeric dengue virus vaccine [29], its response to a DNA vaccine 
has been questioned because of the complete loss of IFN responsiveness.  
1.1.4 Target population for Zika virus vaccines and therapies 
As reviewed above, Zika virus infection typically causes a self-limited illness that is 
minimally symptomatic for many. However, the occurrence of severe neurologic 
complications has focused development efforts. The most publicized and dramatic 
complications of infection are those occurring during fetal development and include 
microcephaly, 
intra-uterine 
growth 
retardation, 
cerebral 
calcifications, 
ocular 
calcifications, and other ocular abnormalities – with an attack rate estimated at 1 – 2% of 
women who become infected during pregnancy. The rate of Zika virus-induced fetal loss 
resulting in spontaneous miscarriage is, however, unknown. In adults, the most common 
complication of Zika virus infection is Guillain Barré syndrome occurring at an estimated 
rate of 1 in 5,000 cases. Additional complications include encephalomyelitis and acute 
demyelinating encephalomyelitis (ADEM). Zika has also resulted in deaths among adults 
with and without other complicating factors.  
Key target groups for a vaccine are therefore women of child-bearing potential, men who 
have sexual relations with women of child-bearing potential, non-immune women who 
become pregnant, and adults in general – especially those with underlying severe disease. 
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prevent primary and secondary (via sexual transmission) cases, especially those returning 
to regions with permissive mosquito populations, to limit the spread of the virus globally.  
This clinical study will assess the safety and immunogenicity of GLS-5700 in a dengue 
virus naïve population. Other studies will assess the safety and immunogenicity in a 
dengue-virus seropositive population.  
1.1.5 Human experience with GLS-5700  
There is no clinical experience with GLS-5700. 
The safety of GLS-5700 can be informed from past experience with similar DNA vaccine 
candidates that are in, or have completed, human clinical trials.  Specific examples of 
DNA vaccine human experience include: Phase I and 2 trials of INO-3100, targeting the 
human papilloma virus (HPV) that incorporates the HPV E6 and E7 proteins of HPV 16 
and 18 [25, 26]; and current studies of VGX-6150 Hepatitis C vaccine in patients with 
chronic infection (NCT02027116), INO-4212 Zaire Ebola virus vaccine (NCT02464670), 
and GLS-5300 against the Middle East Respiratory syndrome coronavirus (MERS-CoV, 
NCT02670187).  Each of these vaccine products use the same plasmid backbone but with 
different pathogen-specific antigen inserts. All of these products have been well tolerated 
and without vaccine associated serious adverse events (SAEs).  
1.1.6 Administration of similar DNA plasmids by Electroporation (EP) 
Experience with DNA vaccines using the modified pVAX1 plasmid backbone by Inovio 
Pharmaceuticals and GeneOne Life Science is extensive. Ongoing collaborative clinical 
trials between Inovio Pharmaceuticals and GeneOne Life Science include a prophylactic 
vaccines against MERS-CoV (NCT02670187) and the Zaire strain of Ebola virus 
(NCT02464670); and a therapeutic vaccine against genotype 1 hepatitis C virus 
(NCT02027116). Prior studies have also examined a DNA plasmid based vaccine against 
H5N1 Avian influenza (NCT01184976). Each vaccine construct has a similar structure: 
utilizing a pVAX1 expression vector with an insert comprising a portion of the viral 
DNA representing a consensus sequence not found in nature. All of these vaccine 
constructs have been administered either ID or IM and followed by electroporation with 
vaccine formulated in sterile water or sterile saline salt citrate (SSC) buffer. In each case, 
there have been no vaccine-associated safety concerns; the primary adverse events 
reported are transient injection site reactions.  
Many groups have also published on DNA plasmid-based vaccine trials. Use of DNA 
vaccines for treatment of advanced HIV infection was first published in 1998 [30] with a 
recent review summarizing HIV related studies of greater than 1200 participants with no 
serious DNA-vaccine associated adverse events [31, 32]. Other notable studies include 
Phase I trials of DNA plasmid vaccines against Ebola virus [33-35], HPV [25, 26], HIV 
[36], and influenza [37]. In fact, a DNA vaccine for HPV has completed Phase II and 
demonstrated the ability to reverse pre-cancerous changes of the cervix causing 
regression of cervical intraepithelial neoplasia (CIN) grades 2 and 3, and clearance of 
chronic HPV infection in affected women [26]. Thus the DNA-based vaccine in this 
study, INO-3100, is the first vaccine to achieve clearance of a chronic viral infection.  

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Electroporation (EP) enhances gene expression of plasmid DNA delivered by the 
intramuscular (IM) and intradermal (ID) routes of administration. Following IM or ID 
delivery of a DNA vaccine or therapeutic product, EP facilitates entry of the plasmid 
DNA into the target site for antigen production: muscle or dermal cells. Following 
cellular uptake, there is efficient production of the defined pathogen-specific antigen 
proteins encoded by the DNA plasmid expression system. The different EP devices, each 
with varying electrical parameters and protocols, have been reviewed [38]. EP has been 
extensively used in large animal species, such as dogs, pigs, cattle, and NHPs to deliver 
therapeutic genes that encode for a variety of hormones, cytokines, enzymes or antigens 
[38], resulting in the activation of both cellular and humoral responses in these animal 
models [39, 40]. Importantly, antigen-specific immune responses for DNA vaccines 
delivered with EP are far superior to administration without EP [40]. The IM delivery of 
DNA with EP is well studied and optimum conditions for plasmid uptake and expression 
are described for therapeutic indications, vaccines, and tumor animal model systems [41, 
42]. ID delivery with EP has also been shown to yield similar, if not superior results, and 
may be better tolerated. [43]. 
As of this writing, more than 800 human participants have undergone electroporation 
with the CELLECTRA® IM or ID devices in approximately 20 studies (Table 1.1). More 
than 2000 doses of DNA have been administered. The most significant finding has been 
moderate but self-resolving administration site pain. Evaluation of CPK for muscle 
damage with IM delivery and ECG for cardiac conduction abnormalities has been 
unremarkable and no significant EP-related safety issues have been identified.  
 

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Table 1.1:  Total Participants and Total DNA Doses Administered with IM and ID 
followed by EP with the CELLECTRA® Device 
IM + EP Studies 
# Subject 
# Dose 
ID + EP Studies 
# Subject 
# Dose 
CEL-001 
10 
10 
CEL-002 
10 
10 
HPV-001 
18 
54 
FLU-002 
22 
39 
HPV-002 
13 
13 
FLU-101 
105 
307 
HPV-003 active 
125 
360 
FLUPRIME 
40 
94 
HPV-003 placebo 
42 
124 
FLUPRIME placebo 
10 
20 
FLU-001 
32 
56 
FLUPRIME extension 
32 
32 
FLU-001K 
30 
59 
EBOV-001 
15 
42 
HIV-001 
12 
48 
HVTN098 
39 
232 
HVTN 080 
40 
117 
 
 
 
HVTN 080 
8 
22 
 
 
 
RV262 A 
7 
14 
 
 
 
RV262 B 
42 
75 
 
 
 
VGX-6150-01 
18 
71 
 
 
 
HPV-004 
1 
4 
 
 
 
HPV-005 
12 
41 
 
 
 
HPV-006 
1 
4 
 
 
 
EBOV-001 (Ebola) 
60 
180 
 
 
 
WRAIR-2274 (MERS) 
75 
225 
 
 
 
 

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1.2 
GLS-5700  
GLS-5700 contains a single plasmid, pGX7201, in sterile saline salt citrate buffer (SSC).  
Common name: pGX7201  
Chemical name: pGX7201 is a circular, double stranded, deoxyribonucleic acid plasmid 
consisting of 5066 base pairs. 
Distinguishing name: This is a eukaryotic expression plasmid containing DNA encoding 
for pre-membrane and envelope (prME) proteins of the Zika virus. pGX7201 
incorporates a consensus prME sequence of published Zika virus clinical isolate strains. 
The prME sequence has been codon optimized for mammalian expression. The 
transcription unit is controlled by a synthetic CMV promoter and elements required for 
replication and selection in E coli, namely a pUC origin of replication (pUC-Ori) and 
kanamycin resistance gene (KanR), respectively.  
1.3 
Dose and Regimen Rationale 
The optimal dose and dosing regimen for GLS-5700 are as yet uncharacterized. In 
addition to safety, this study will assess two different doses of vaccine to evaluate 
optimal humoral and cellular immune responses to Zika prME. Based on prior experience 
with other DNA vaccines, there may be a plateau effect above 2 mg for DNA vaccines 
administered by EP. Preclinical studies of pGX7201 (the plasmid that comprises GLS-
5700) in rhesus macaques assessed high (2 mg/vaccination) and low (0.5 mg/vaccination) 
doses with similar immunogenicity. No significant difference was seen in mice between 
doses of 12.5 µg and 25 µg/dose. Additionally, robust antibody and T-cell immune 
responses in humans were elicited with a dose of 2 mg/vaccination with a similar DNA 
construct in a Phase I dose-ranging study for the treatment of cervical dysplasia related to 
HPV cervical infection [25, 26]. Assessment of antibody and T-cell responses following 
each vaccination will determine  the immune response to vaccination. Follow-up after the 
primary vaccination series will determine the longevity of immunogenicity of the 
vaccine.  
1.4  
Risks/Benefit Assessment 
In accordance with the International Conference on Harmonisation (ICH), this study has 
been designed to minimize risk to study participants. Potential risks of study products and 
administration from studies using similar plasmids with the identical DNA backbone are 
listed in Table 1.4.  
The potential side effects of treatment with the investigational products may include but 
not limited to discomfort related to the vaccine administration and electroporation 
technique such as local edema, swelling, or pain. Systemic side effects observed with 
vaccines based on the identical backbone have been demonstrated to be generally 
minimal in more than 725 participants. Since the volunteers in this clinical trial have 
unknown risk for exposure to Zika virus, no direct benefit is expected. The potential 
benefit is to determine whether this vaccine could generate immune responses with 
potential to be sufficient as prophylactic treatment for those at risk for Zika virus 
infection.  

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Table 1.4: 
Summary of Reported Adverse Events of DNA Vaccines Delivered 
IM+EP or ID+EP with CELLECTRA®  
Common 
• 
Mild to moderate administration site pain, erythema, tenderness, 
swelling, induration   
• 
Malaise/fatigue, myalgia, or headache in the first few days following 
injection 
• 
Visible lesion(s) at the injection site, such as erythematous papules with 
eschar, hypopigmentation, hyperpigmentation, or scar (ID 
administration only) 
Less common 
• 
Administration site bruising/ecchymosis, hematoma or pruritus 
• 
Arthralgia or nausea 
• 
Injection site hematoma, bruising/ecchymosis, laceration, other 
transient lesions, or bleeding related to the injection procedure 
Uncommon or 
rare 
• 
Administration site, laceration, other transient lesions, or bleeding 
related to the injection procedure 
• 
Severe administration site pain or tenderness 
• 
Rash following injection/EP  
• 
Scar formation (ID administration) 
• 
Vasovagal reaction/lightheadedness/dizziness related to the 
injection/EP procedure 
• 
Transient changes in clinical laboratory values 
Unknown 
frequency or 
theoretical 
potential risks 
• 
Severe localized administration site reaction, such as sterile abscess or 
secondary bacterial infection  
• 
Allergic reaction, including urticaria, angioedema, bronchospasm, or 
anaphylaxis  
• 
Chills, flu-like syndrome 
• 
Muscle damage at the administration site 
• 
Autoimmune disease 
• 
Electrical injury  
• 
Disruption of function of implanted electronic medical devices 
• 
Exacerbation of cardiac arrhythmia 
• 
Effects on the fetus and on pregnancy 
 
The full safety monitoring plan is described in detail in the Evaluation of Safety and 
Management of Toxicity section below (Section 7).  

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2. 
HYPOTHESIS AND STUDY OBJECTIVES  
2.1 
Hypothesis 
GLS-5700 administered intradermally (ID) followed by EP will be safe, well tolerated 
and immunogenic in dengue virus-naïve adults.  
2.2 
Primary Objectives 
• Evaluate the safety and tolerability of GLS-5700 when administered by ID injection 
followed by EP in healthy dengue virus-naïve adult participants within 14 days post 
final vaccination.  
Primary Safety Endpoints 
• Incidence of adverse events classified by system organ class (SOC), preferred term 
(PT) severity, and relationship to study treatment and schedule to 14 days post final 
vaccination in dengue virus-naïve adults 
• Administration (injection) site reactions (described by frequency and severity grade) 
and administration site pain to 14 days post final vaccination 
• Changes in safety laboratory parameters described by frequency and severity grade 
(e.g., liver panel tests, vital signs) 
2.3 
Secondary Objectives 
• Evaluate the safety to 1 year post vaccination of GLS-5700 in dengue virus-naïve 
adults 
• Evaluate the cellular and humoral response of GLS-5700 when delivered ID 
followed by EP in dengue virus-naïve adults 
Secondary Immunologic Endpoints 
• Binding antibody titers to the Zika envelope (E) protein as measured by ELISA 
• Neutralizing antibody titers against Zika virus as measured in viral neutralization 
assay 
• Antigen specific cellular immune responses to Zika virus as determined by 
Interferon-gamma (IFN-γ) ELISpot and/or Intracellular Staining (ICS) assays 
2.4 
Exploratory Objectives 
• Explore whether end point antibody titers are dose related.  
• Explore the time to onset and longevity of immune  responses, both humoral and 
cellular 
• Explore if increasing dose levels of GLS-5700 more rapidly induce cellular and 
humoral immunity  
• Explore the epitope specificity for T cell reactions of GLS-5700 to Zika virus 
        
Exploratory Endpoints 
• Comparison of ELISA, neutralization titers, IFN-γ ELISpot, and ICS responses 
across different vaccine regimens 
• Other analyses as indicated to assess protective mechanisms against Zika virus. 
• Epitope mapping of CD4+ and CD8+ T lymphocyte responses 

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3. 
STUDY DESIGN  
This is a Phase I open-label, dose-ranging study to assess the safety, tolerability, and 
immunogenicity of GLS-5700 in dengue virus-naïve adults. Eligible participants who 
consent to participate will be administered GLS-5700 via ID injection followed 
immediately by EP using the CELLECTRA® 3P Adaptive Constant Current 
Electroporation device.  
Prospective participants who read and sign the ICF will be screened for eligibility for up 
to 30 days prior to their first dose. Screening evaluation will consist of a medical history, 
vital signs including height and weight, ECG, and laboratory evaluations. Participants 
without a history of exclusionary conditions, not clinically significant or normal ECG, 
and Grade 0-1 laboratory values (per the Toxicity Grading Scale for Healthy Adults 
Appendix B) for CBC, serum chemistry, and CPK, will be eligible for participation in the 
trial.   
Evaluation of ID administration of GLS-5700:  
Group 1 Participants (n=20) will be administered 1 mg GLS-5700 DNA/dose given as an 
ID injection followed by EP with the CELLECTRA®-3P device. Participants will receive 
a 3-dose series with immunizations at 0, 4, and 12 weeks.  
Group 2 Participants (n=20) will be administered 2 mg GLS-5700 DNA/dose given as 
two ID injections per immunization followed by EP with the CELLECTRA®-3P device. 
Participants will receive a 3-dose series with immunizations at 0, 4, and 12 weeks.  
See Tables S1 and S2 for a summary of study treatments and dosing schedule.  
Safety assessments: All participants will be monitored for  
 Local and systemic adverse events (AE’s) at each study visit.   
 Laboratory related AE’s following each vaccination.   
Immunogenicity assessments:  
 
The study will explore humoral and cell mediated immune responses in blood samples 
collected at the following times:  
 Day 0 (prior to 1st dose of vaccine) 
 Week 1 and week 4 post 1st vaccination 
 Week 6 and 12 (2 and 8 weeks post 2nd vaccination)  
 Week 14 and 20 (2 weeks and 8 weeks post 3rd vaccination) 
 Weeks 36 and 60  
3.1 
Treatment Progression Scheme / Interim Safety Monitoring 
This study will utilize a treatment progression scheme similar to WRAIR-2274 
(assessment of GLS-5300 against MERS CoV) to assess and ensure the safety of each 
dose level of vaccine as follows.  

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Participants will be contacted by telephone to report reactions the day following the 1st 
vaccination to determine whether there are any AE’s or other reactions. If no vaccine 
associated AEs requiring expedited reporting have occurred for the first 5 participants 
enrolled at 1 mg, then enrollment of the remainder of Group 1 at 1 mg/dose can proceed. 
Progression to the 2nd dose of vaccine at 1 mg/dose or enrollment of Group 2 at 2 
mg/dose will require safety assessment as detailed below. 
Safety laboratory assessments will be performed 1 week after the 1st dose of vaccine and 
2 weeks after the 2nd and 3rd doses for all study participants, as appropriate. If no vaccine 
associated Grade 3 or Grade 4 AEs or any Serious Adverse Events (SAE) are 
encountered for the first 5 participants enrolled at 1 mg dose after review of their safety 
data, then enrollment into the 2 mg group can proceed. If there are no vaccine associated 
Grade 3 or 4 or serious safety events noted for the first 5 participants 24 hr post 
administration of 2 mg, then dosing will continue. Safety labs will be reviewed for the 1st 
5 participants at the 2 mg dose by the monitoring committee. Safety labs will be reviewed 
monthly thereafter.  
Review of safety labs will be conducted by a safety monitoring committee consisting of 
the study medical monitor with input from the site PI. The IRB/CER will be provided a 
summary statement of each safety review. The Safety Monitoring Committee (SMC) will 
meet to review safety laboratory assessments after 5 persons have received vaccine at 
each dose level. The committee will meet between 2-5 business days following the 
collection of safety labs for all 5 persons at the respective dose level. SMC meetings 
thereafter will occur on an ad hoc basis in response to any potential safety concerns.  
4. 
SELECTION AND ENROLLMENT OF PARTICIPANTS  
4.1 
Recruitment of Participants 
Adult volunteers will be recruited for the study.  
4.2 
Inclusion Criteria 
a. Age 18-65 years;  
b. Able to provide consent to participate and having signed an Informed Consent Form 
(ICF); 
c. Able and willing to comply with all study procedures; 
d. Women of child-bearing potential agree to use medically effective contraception (oral 
contraception, barrier methods, spermicide, etc.), or have a partner who is sterile from 
enrollment to 3 months following the last injection, or have a partner who is 
medically unable to induce pregnancy. 
e. Sexually active men who are considered fertile must agree to use either a barrier 
method of contraception during the study, and agree to continue the use for at least 3 
months following the last injection, or have a partner who is permanently sterile or 
medically unable to become pregnant;  
f. Normal screening ECG or screening ECG with no clinically significant findings; 

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g. Screening labs must be within normal limits or have only Grade 0-1 findings, except 
that creatinine may be grade 2 at baseline; 
h. No history of clinically significant immunosuppressive or autoimmune disease. 
i. No history of dengue virus vaccination or illness; no history of yellow fever 
vaccination 
j. Dengue seronegative at baseline by screening laboratory evaluation 
k. Not currently or within the previous 4 weeks taking immunosuppressive agents 
(excluding inhaled, topical skin and/or eye drop-containing corticosteroids, low-dose 
methotrexate, or prednisone at a dose less than 10 mg/day or steroid dose-equivalent). 
4.3 
Exclusion Criteria 
a. Administration of an investigational compound either currently or within 30 days of 
first dose; 
b. Previous receipt of an investigational product for the treatment or prevention of Zika 
virus infection except if participant is verified to have received placebo; 
c. Administration of any vaccine within 4 weeks of first dose; 
d. Administration of any monoclonal or polyclonal antibody product within 4 weeks of 
the first dose 
e. Administration of any blood product within 3 months of first dose; 
f. Pregnancy or breast feeding or have plans to become pregnant during the course of 
the study;  
g. Positive serologic result for dengue virus (any serotype) or history of receipt of either 
dengue virus or yellow fever virus vaccination at any time in the past; 
h. Positive serologic test for HIV, hepatitis B surface antigen (HBsAg); or any 
potentially communicable infectious disease as determined by the Principal 
Investigator or Medical Monitor; 
i. Positive serologic test for hepatitis C (exception: successful treatment with 
confirmation of sustained virologic response); 
j. Baseline evidence of kidney disease as measured by creatinine greater than 1.5 (CKD 
Stage II or greater); 
k. Baseline screening lab(s) with Grade 2 or higher abnormality; 
l. Chronic liver disease or cirrhosis; 
m. Immunosuppressive illness including hematologic malignancy, history of solid organ 
or bone marrow transplantation; 
n. Current or anticipated concomitant immunosuppressive therapy (excluding inhaled, 
topical skin and/or eye drop-containing corticosteroids, low-dose methotrexate, or 
corticosteroids at a dose greater than 10 mg/day or steroid dose-equivalent); 
o. Current or anticipated treatment with TNF-α inhibitors such as infliximab, 
adalimumab, etanercept; 
p. Prior major surgery or any radiation therapy within 4 weeks of group assignment; 
q. Any pre-excitation syndromes, e.g., Wolff-Parkinson-White syndrome; 

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r. Presence of a cardiac pacemaker or automatic implantable cardioverter defibrillator 
(AICD) 
s. Metal implants within 20 cm of the planned site(s) of injection; 
t. Presence of keloid scar formation or hypertrophic scar as a clinically significant 
medical condition at the planned site(s) of injection. 
u. Prisoner or participants who are compulsorily detained (involuntary incarceration) for 
treatment of either a physical or psychiatric illness;  
v. Active drug or alcohol use or dependence that, in the opinion of the investigator, 
would interfere with adherence to study requirements or assessment of immunologic 
endpoints; or 
w. Not willing to allow storage and future use of samples for Zika virus related research 
x. Any illness or condition that in the opinion of the investigator may affect the safety of 
the participant or the evaluation of any study endpoint. 
4.4 
Discontinuation/Withdrawal of Study Participants 
A participant will be considered to have completed the study when he/she completes all 
scheduled study treatments and follow-up visits. If a participant discontinues the study at 
any time after dosing, the investigator will make every effort to have the participant 
complete all assessments as indicated in Section 7.1 – Safety Parameters. The 
investigator will make every effort to have all scheduled immune assessment blood 
samples collected as indicated in the Schedule of Events, Table S2. 
Unless a participant refuses to continue participation, all follow-up visits and procedures 
should be completed as indicated in the Schedule of Events, Table S2, following the last 
dose whether or not the participant has completed all doses.  
The reason for any discontinuation of investigational product will be discussed with the 
Sponsor’s Medical Monitor and indicated on the study forms. The primary reason for a 
participant discontinuing further dosing or withdrawal from the study itself is to be 
selected from the following standard categories: 
• 
Adverse Event (Adverse Reaction): Clinical or laboratory events occurred that, in the 
medical judgment of the investigator, are grounds for discontinuation for the best 
interest of the participant. This includes serious and non-serious adverse events 
regardless of relation to study drug. 
• 
Death: The participant died. 
• 
Withdrawal of Consent: The participant desired to withdraw from further 
participation in the study in the absence of an investigator-determined medical need 
to withdraw. If the participant gave a reason for withdrawal, it must be recorded on 
the case report form (CRF). This reason does not allow for further data collection or 
later study related procedures. 
• 
Protocol Violation: The participant failed to meet the protocol entry criteria or failed 
to adhere to the protocol requirements (e.g., treatment noncompliance, failure to 
return for defined number of visits). The violation should be discussed with the 
Sponsor’s Medical Monitor prior to discontinuation of either study treatments or 
study withdrawal. 

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• 
Lost to Follow-up: The participant fails to attend study visits and study personnel are 
unable to contact the participant after repeated attempts including letter sent by 
certified mail or its equivalent. 
• 
Physician Decision: The participant was terminated for a reason other than those 
listed above by the physician caring for the participant. 
• 
Other: The participant was terminated for a reason other than those listed above, such 
as termination of study by the Sponsor. 
5. 
STUDY PRODUCT 
5.1 
Investigational Product 
GLS-5700, the investigational product to be used in this study, contains a DNA plasmid 
encoding for the pre membrane and envelope (prME) proteins of Zika virus and is 
formulated in sterile salt citrate buffer (SSC). GLS-5700 will be provided (Table 5.1) at a 
concentration of 10 mg/ml.  
Table 5.1: Investigational Product 
GLS-5700   
 
Recoverable volume per container 
0.4 mL minimum 
Concentration 
10 mg/mL  
Container Size and Type 
2 mL glass vial 
5.2 
Packaging and Labeling of GLS-5700 
Study product will be supplied in a non-blinded fashion. Study product will be shipped 
directly from the manufacturer or its designee to the study site. Each vial will be labeled 
with a single panel label (Table 5.2).  
Table 5.2: Sample labels for the final drug product components 
Biologic Product/ Diluent 
Sample Label 
GLS-5700 / SSC 
 
GLS-5700 [10 mg/ml] 
0.4 mL/Vial Single Use Vial 
Lot: GLS-5700.xxxxx 
Date of Manufacture: DD MMM YYYY 
Final Retest Date DD MMM YYYY 
Store at  2 - 8ºC 
CAUTION New Drug – Limited by 
Federal Law to Investigational Use 
GeneOne Life Science, Inc.   Rev 000 
 
5.3 
Handling of GLS-5700 
Study product accounting will be performed continuously during the study. Details on 
study product volume, administration, and accountability are documented in the CRF and 
on respective pharmacy forms. At completion/termination of the study, all unused and 
partially used supplies must be returned to GeneOne Life Science, Inc. The investigator, 
pharmacist/drug administrator and monitor must verify that no drug supplies remain at 
the site at the time of study close-out. Appropriate records will be maintained in the 
investigator’s site file. 

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GeneOne Life Science, Inc. will be responsible for assuring the quality of the 
investigational product is adequate for the duration of the trial. GLS-5700 will be shipped 
refrigerated. If there the cold packs are at room temperature when the shipment is 
received, the Sponsor must be contacted immediately. 
Investigational product(s) must be stored in a secure area according to local regulations. 
All study products must be transferred from the shipping container to the appropriate 
storage conditions upon arrival.  GLS-5700 must be stored refrigerated at 2 to 8°C.  
Refrigerator/freezer temperature logs must be maintained at the clinical site and 
temperatures must be recorded and monitored regularly.  
5.4 
Dispensing of GLS-5700 
It is the responsibility of the Investigator to ensure that GLS-5700 is only dispensed to 
study participants. Authorized personnel at the official study site must be the only ones to 
dispense the product according to local regulations. 
The dosing syringe must be labeled with a four-hour expiration date from the time the 
vial(s) are removed from storage.  
Detailed instructions on handling and dispensing of Investigational Product are provided 
below. 
5.5 
Precautions with Investigational Medicinal Product 
A dose of the study product known or suspected to have been taken (accidentally or 
intentionally) in excess of the dose mandated by the protocol, and any misuse or abuse of 
study products or any other product taken as a concomitant medication, whether or not 
associated with an adverse experience, must be reported to GeneOne Life Science within 
24 hours. Any clinical sequelae in association with the overdose will be reported as an 
AE or SAE. Details of signs or symptoms, clinical management, and outcome should be 
reported, if available. 
5.6 
Preparation of Investigational Product 
GLS-5700 is supplied in single dose 2 mL vials at a concentration of 10 mg/mL at a 
minimum recoverable volume of 0.4 mL. GLS-5700 is formulated in SSC. 
Study drug is to be prepared by site staff who are trained and knowledgeable in mixing 
and dispensing investigational agents. Documentation of certification will be kept with 
the pharmacy documents. Study drug should be diluted and prepared in a BioSafety level 
2 cabinet. Personnel will wear safety glasses, gloves and lab coat.  
Remove investigational product from the refrigerator. Briefly centrifuge the vials 
between 500-2500 rpm for 3-5 seconds to remove any vaccine from the cap to the bottom 
of the vials. After centrifugation, maintain the vials in an upright position until use.  
5.6.1 Preparation of 1 mg ID Dose 
To prepare study drug for 1 mg ID dose, the pharmacy staff should have a 1 mL 
tuberculin syringe with 25 or 27 gauge needle. Label syringe as “1 mg GLS-5700 

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Dosing”. Withdraw 0.20 mL of study drug (at 10mg/mL) into the syringe and 
prime to 0.1 mL.  
5.6.2 Preparation of 2 mg ID Dose 
To prepare study drug for 2 mg ID dose, the pharmacy staff should have two 1 
mL tuberculin syringes with 25 or 27 gauge needles. Label both syringes as “2 mg 
GLS-5700 Dosing”. Withdraw 0.20 mL of study drug (at 10mg/mL) into each of 
the two syringes and prime to 0.1 mL.  
Additional instructions for Investigational Product preparation are provided in the 
Pharmacy Manual. 
5.7 
Records of Investigational Product Disposition at Site 
It is the responsibility of the Investigator to ensure that a current record of investigational 
product disposition is maintained at each study site where investigational product is 
inventoried and disposed. Records or logs must comply with applicable regulations and 
guidelines, and should include: 
• 
Amount received and placed in storage area; 
• 
Amount currently in storage area; 
• 
Label ID number or batch number and use date or expiry date; 
• 
Dates and initials of person responsible for each investigational product inventory 
entry/movement; 
• 
Amount dispensed to each participant, including unique participant identifiers; 
• 
Amount transferred to another area/site for dispensing or storage; 
• 
Amount returned to Sponsor; 
• 
Amount destroyed at study site, if applicable. 
5.8 
Return and Destruction of Investigational Product 
Upon completion or termination of the study, all unused and/or partially used 
investigational product must be returned to GeneOne Life Science, Inc., or its designee, if 
not authorized by GeneOne Life Science, Inc. to be destroyed at the site. 
All investigational products returned to GeneOne Life Science, Inc., or its designee, must 
be accompanied by the appropriate documentation. Returned supplies should be in the 
original containers. It is the Investigator’s responsibility to arrange for disposal for all 
empty containers, provided that procedures for proper disposal have been established 
according to applicable federal, state, local and institutional guidelines and procedures, 
and provided that appropriate records of disposal are kept. The return of unused 
investigational product(s) should be arranged by the responsible Study Monitor. 
If investigational products are to be destroyed on site, it is the Investigator’s 
responsibility to ensure that arrangements have been made for the disposal, written 
authorization has been granted by GeneOne Life Science, Inc., or its designee, procedures 
for proper disposal have been established according to applicable regulation and 
guidelines and institutional procedures, and appropriate records of the disposal have been 
documented. The unused investigational products can only be destroyed after being 
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designated Study Monitor.Used investigational product must NOT be destroyed until 
accountability has been completed by the responsible GeneOne Life Science employee or 
designated Study Monitor.  
5.9 
Use of CELLECTRA® Electroporation Device 
Instructions for use of the CELLECTRA device are located in the Operations Manual. 
Each clinical site will receive training for the use of the CELLECTRA device. The 
following specifications will be used during the study: 
CELLECTRA® 3P-ID 
Number of pulses per treatment = 4 
Maximum Current Strength = 0.2 Amperes 
Voltage Strength = 1 - 200 Volts 
Electroporation pulse duration = 52 milliseconds/pulse 
Interval separating pulses = 1 second 
EP needle array length (injection depth) = 3 mm (with array guide in place) 
 
The treatment/electroporation procedure must be performed by qualified personnel. 
Any individual designated to perform the procedure should be permitted by the relevant 
local authorities to administer vaccinations or parenteral drugs to patients (e.g. MD, DO, 
RN). Non-licensed individuals (i.e., other than an MD, DO, or RN) may perform the 
treatment/electroporation procedure under both of the conditions below: 
1. The non-licensed individual has been trained by the PI, approved Sub-
Investigator, or sponsor in EP. The non-licensed individual will perform the 
procedure under the direct supervision of the Principal Investigator or an 
approved Sub-Investigator who has already been trained by sponsor personnel. 
2. The CV and any relevant qualifications of the individual have been reviewed and 
approved by the sponsor or its designee to perform the procedure. 
All individuals designated to perform the EP procedure must satisfactorily complete 
device training from the sponsor or its designee regardless of their qualifications. Any 
deviation from the above procedures must be approved by the sponsor or its designee. 
5.10 Investigational Device Accountability  
Each clinical site is responsible for maintaining investigational device accountability.  
This includes recording the CELLECTRA® serial number, applicator serial number, and 
array lot number used for treatment/ EP of each participant. 
6. 
STUDY PROCEDURES AND TREATMENTS 
See Table S2 in the Clinical Protocol Synopsis for Schedule of Events showing study 
procedures and the times at which they are to be carried out. 

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6.1 
Procedure by Visit 
6.1.1 Screening Evaluations 
The assessments during the screening phase will determine the participants’ 
eligibility for the study and also their ability to comply with protocol requirements 
by completing all screening assessments. The following additional screening 
evaluations will be performed within 30 days prior to dosing on Day 0. All 
screening assessment values must be reviewed prior to study treatment. 
o Signed informed consent (Section 6.2.1); 
o Review and confirm all inclusion/exclusion criteria (section 4.2, 4.3); 
o Collect demographics, including gender, ethnic origin, and travel history; 
o Obtain complete medical history (including procedures history), present 
conditions and concomitant illnesses, and travel history (Section 6.2.2); 
o Record concomitant medications/treatments at present and in past 8 weeks; 
o Record vital signs (heart rate, blood pressure, oral temperature), body weight, 
height, heart rate (HR), blood pressure (BP), and oral temperature (Section 
6.2.3.3); 
o Collect blood for CBC with differential, blood chemistry [Sodium (Na), 
potassium (K), chloride (Cl), bicarbonate (HCO3), glucose, BUN, creatinine, 
AST, ALT, CPK (Section 6.2.3.6); 
o Collect blood for serologic assessment of HIV, Hepatitis B surface antigen 
(HBsAg), Hepatitis C antibody (HCV), and dengue, West Nile, and 
chikungunya virus antibodies 
o Serum pregnancy (Section 6.2.3.6); 
o 12 lead ECG (Section 6.2.3.5); 
o Physical Exam (Section 6.2.3.2); and 
o Determine proposed site of injection(s) 
6.1.2 Study Evaluations 
6.1.2.1 Vaccine Administration Visits  
The following procedures will be performed at vaccination visits: 
The following study evaluations will be performed prior to dosing: 
o Review of medical history from screening 
o Concomitant medications/treatments; 
o Vital signs; 
o Urine pregnancy test, if applicable 
o Collect blood for serum or PBMCs for immune assessment as 
indicated; 
o Targeted physical assessment 
o Adverse event assessment 

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Administer study treatment followed by EP 
The following study evaluations will be performed post dose: 
o Pain assessment immediately and 30 minutes after EP; 
o Injection site reaction assessment 30 minutes after EP; 
o Distribute Participant Reminder Diary; 
o Download EP data from device as directed and forward to GeneOne 
Life Science or its designee  
 
6.1.2.2 Telephone assessment (Day 1 post 1st vaccination)  
The following procedures will be performed the day following the 1st 
vaccination: 
o Contact the study participant (either by phone or in person); 
o Local and systemic injection site review;  
o Adverse and Serious adverse event assessment; 
6.1.2.3 Non-vaccination study visits  
The following procedures will be performed during non-vaccination visits: 
o Concomitant medications/treatments; 
o Vital signs; 
o Targeted physical assessment; 
o Local and systemic injection site review;  
o Adverse and Serious adverse event assessment; 
o Collect blood for serum or PBMCs for immune assessment as 
indicated; 
o Collect blood for safety laboratory assessment (CBC, serum 
chemistries, CPK) [as indicated] 
o Review Participant memory aids [as indicated] 
6.1.2.4 End of Study Visit (Week 60) / Early Termination 
The following procedures will be performed 12 months after the end of 
treatment (week 60 visit): 
o Concomitant medications/treatments; 
o Vital signs; 
o Full physical exam; 
o Local and systemic injection site review; 
o Adverse event assessment; 
o Collect blood for serum or PBMCs for immune assessment as 
indicated; 
 
6.1.2.5 Premature Withdrawal 
Participants may refuse further vaccinations and/or terminate participation 
in the study at any time. In the event a participant decides to terminate 
participation prematurely, efforts should be made to perform all study 

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assessments. Participants may also discontinue participation in the study 
or have their participation discontinued by the principal investigator if 
safety and/or tolerability issues are considered intolerable and/or not 
manageable with symptomatic treatment. 
At a minimum, all assessments from Week 14 visit should be performed 
prior to withdrawal if not already completed.  
In the case of a fatal outcome, all relevant information (including cause of 
death, concomitant medication, and relationship to study treatment or 
underlying disease) will be collected. 
6.2 
Timing and Evaluations 
6.2.1 Informed Consent 
Study personnel will meet with prospective study participants, explain the study, 
and provide them with an informed consent form (ICF) that describes the 
screening tests, eligibility criteria for entering the study, and study treatments and 
follow-up procedures. An informed consent must be signed prior to any study 
related procedures being performed. A copy of the signed and dated consent form 
will be given to the participant. 
6.2.2 Patient Identification Number and Group Assignments 
Each participant who consents will be assigned a unique participant identification 
designation number (PID#), which identifies the participant for all study-related 
procedures that occur prior to receiving an allocation number. Once assigned, PID 
numbers cannot be reused for any reason. Information regarding participant’s 
PID# and screen date will be documented on a screening log. 
Study participants will be allocated to each of the two dosing groups such that the 
initial 5 eligible participants at each of the three study sties will be assigned to 
Group 1 at 1 mg/dose, the next 5 eligible participants at each study site will be 
assigned to Group 2 at 2 mg/dose. The final study participants will be allocated to 
the three study sites with 5 participants assigned to the 1 mg/dose group and 
allocated in a proportional manner between sites and the final 5 participants 
assigned to the 2 mg/dose group and similarly allocated in a proportional manner 
between study sites. Sponsor reserves the right to revise allocations between study 
sites should unexpected delays occur or any site cannot meet recruitment goals. 
Medical History 
Investigators should document all significant illnesses that the participant has 
experienced as Medical History. Illnesses’ first occurring or detected during the 
study and/or worsening of an existing illness(es) that occur after the first 
vaccination are to be documented as AEs on the CRF. Prior treatments, defined as 
administered up to 8 weeks prior to the time of informed consent, will be recorded 
in the CRF as prior medications. Concomitant treatments, defined as continuing 

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or new treatments taken at or after the signing of the informed consent, will be 
recorded in the CRF as concomitant medications. 
Travel History 
Investigators should inquire as to travel to any country or region to include the 
South Pacific Islands, South America, Central America, or the Caribbean.  
6.2.3 Safety Assessments 
The following patient evaluations for safety will be performed. 
6.2.3.1 Patient self-evaluations 
Participants record any post treatment reactions (local and systemic) and 
enter this information in the Post Vaccination Memory Aid (shown in 
Appendix A) on the evening of each dose and for 7 days post each dose. 
Local administration site reactions will be recorded using the supplied 
measuring tool. The study staff will review the memory aid; the reported 
events will be assessed for clinical significance and recorded on the CRFs 
as appropriate. Memory aids are considered the property of the 
participants and are not collected nor considered as source documents. 
Study staff should evaluate each unique memory aid entry according to 
“Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers 
Enrolled in Preventive Vaccine Clinical Trials”, issued in September 2007 
(Appendix B). Any memory aid entry determined to meet the criteria for a 
Grade 1 or higher adverse event must be documented as an adverse event. 
If the reminder diary entry does not meet the criteria of a Grade 1 or 
higher AE as per the toxicity grading scale, clinical judgment can be used 
to determine whether the entry should be recorded as an AE. For cases 
where the reminder diary entry and final AE reporting (i.e., grading) do 
not agree, the reasoning must be recorded in the source documents. 
6.2.3.2 Physical Assessments and Targeted Physical Assessment 
A full physical examination will be conducted at screening. A targeted 
physical assessment will be performed at other visits as determined by the 
Investigator or directed per participant complaints. The injection site is to 
be assessed by the study personnel within 30 to 45 minutes after EP, as 
well as at the follow up visits.  
6.2.3.3 Vital Signs 
Vital signs including oral temperature, respiration rate, blood pressure and 
heart rate will be measured at specified visits.  
6.2.3.4 Weight and Height 
Weight (kg) and height (cm) will be collected at screening.  

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6.2.3.5 12-Lead ECGs 
An ECG will be performed at screening for all participants to determine 
eligibility. The ECG should include measurements of ventricular rate, PR, 
QRS, QT, QTc with assessment as to whether the ECG is normal or 
abnormal. Abnormal ECGs will be interpreted as clinically significant or 
not clinically significant. Dosing will be delayed in the event of a 
clinically significant abnormal pre-dose ECG until it has been reviewed by 
the PI, qualified PI designee, Medical Monitor or Sponsor consultant 
cardiologist and deemed safe to proceed.    
6.2.3.6 Laboratory Evaluations 
At screening, Week 1, Week 6, and Week 14 (as indicated) blood samples 
will be taken to be tested for serum chemistry and hematology. 
Approximately 425 mL of blood will be drawn from each participant 
during the entire duration of the study. 
Hematology 
CBC: White blood cell (WBC) count and differential count, Red 
blood cell (RBC) count, Hemoglobin, Hematocrit, Platelet count;  
Serum Chemistry  
Serum electrolytes, blood urea nitrogen (BUN), creatinine (Cr), 
glucose, ALT, AST, CPK;  
Serology (screening only): 
Antibody to HIV (human immunodeficiency virus), Hepatitis B 
surface antigen (HBsAg), Hepatitis C antibody (HCV Ab), and 
West Nile virus, chikungunya virus, and dengue virus antibodies; 
Pregnancy Test 
For female participants of reproductive potential, a serum 
pregnancy test will be obtained at screening with a negative result. 
Participants who have a screening pregnancy test that is positive 
will be considered as ineligible for the study. If a pregnancy test is 
positive prior to completing the prescribed regimen, additional 
doses of vaccine must not be given. Every attempt should be made 
to follow pregnant participants for the remainder of the study and to 
determine the outcome of the pregnancy and to follow the outcome 
post-delivery for a year.  
6.3 
Injection of Investigational Product followed by Electroporation 
Participants will receive a 3 -vaccination series.  
• Group 1 (n=20) will receive 3 vaccinations of 1 mg GLS-5700 given by ID injection 
followed by EP with CELLECTRA®-3P at 0, 4, and 12 weeks 
• Group 2 (n=20) will receive 3 vaccinations of 2 mg GLS-5700 given by ID injection 
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Vaccinations will be delivered ID into the deltoid region, followed immediately by EP 
(see Section 5.9 - Use of CELLECTRA® Electroporation Device). Vaccinations must not 
be given within 2 cm of a tattoo, scar, or active lesion/rash. The timing of the initial dose 
will be designated Day 0 with the subsequent doses scheduled for administration as per 
the Schedule of Events (Table S2). Within 48 hours following each Study Treatment, 
data should be downloaded from the EP device and sent to the Sponsor (GeneOne Life 
Science, Inc.) or designee by courier or email. 
For individuals assigned to Group 1, injections should be alternated side to side between 
vaccinations.  
For individuals assigned to Group 2 (2 mg per injection), injections should preferentially 
be given into both deltoid regions, i.e. at each vaccination both arms will have vaccine 
injections. If, however, one arm cannot be injected due to the reasons cited above, then 
injections should be given no closer than 3 cm apart.  
6.3.1 Management of anxiety and pain due to EP procedure 
Participants will be offered an analgesic (e.g. ibuprofen, acetaminophen) after 
injection/EP or EMLA cream before the procedure; the latter applied at least 15 
min prior to vaccination.  
Participants who are allergic to or have contraindications for use of ibuprofen or 
acetaminophen may be offered a suitable alternative. 
6.4 
Assessment of Laboratory Abnormalities 
Blood will be drawn for serum chemistries and hematology assessments at the visits 
listed in the Schedule of Events, (Table S2) and as listed in section 6.2.3.6.  
Laboratory AEs will be assessed and graded. See Section 7.1.7 for details. 
6.5 
Assessment of Clinical Adverse Events 
The injection site will be assessed by study personnel prior to and within 30 to 45 
minutes after injection/EP. Participants will be given an oral thermometer and instructed 
to take and record their oral temperature daily (at the same time each day). Participants 
will also be advised to record local and systemic events for 6 days after vaccination in a 
Post Vaccination Memory Aid (Appendix A). 
Participants will also be queried regarding the occurrence of any adverse events, 
concomitant medications and new onset chronic disease during their clinic visits. 
Participants will be reminded to contact study personnel and immediately report any 
event that may happen for the duration of the study up to and including the final study 
visit. These events will be recorded on the participant’s case report form (CRF).  
6.6 
Assessment of Injection Site Reactions  
The Study Treatment procedure consists of insertion of the CELLECTRA 
electroporation array needles (electrodes) into the dermis, followed by delivery of the 
electroporation pulses. This procedure is broadly described as administration because it 
involves more than the injection of a drug. Attributing any reaction (e.g. pain, erythema, 

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or swelling) that is observed at or near the site of the Study Treatment procedure to 
injection of the study drug(s) versus administration of the electroporation pulses will be 
difficult and is not necessary. Consequently, reactions arising from the Study Treatment 
procedure may be reported as administration site or injection site reactions. When 
evaluating administration (injection) site reactions throughout the study, it is most 
important to be as specific as possible by selecting the most appropriate term (see 
components below) and use the grading scale as outlined in Appendix B. Each injection 
site is considered as separate injection sites. The following observations, including grade 
of severity, will be recorded on the CRF: 
• Time of occurrence relative to dose (e.g., immediately after, 1 day after dose, etc.) 
• Site of injection 
• 
Components of administration (injection) site reactions: 
o Tenderness (present or absent and severity) 
o Pruritus (present or absent and severity) 
o Erythema (diameter in cm) 
o Induration/Swelling (diameter in cm) 
o Bruising (diameter in cm) 
• Resolution date 
• 
Pain (see Section 6.3.1) 
6.7 
Handling and shipment of biological specimens 
Information regarding collection, handling and shipping of biological specimens for this 
protocol will be provided by GeneOne Life Science. 
6.8 
Immunogenicity Assessments 
6.8.1 ELISA 
A standardized ELISA will be performed to measure the Zika virus binding antibody responses 
to the envelope protein. Briefly, 96-well enzyme immunoassay plates will be coated with 
purified recombinant Zika virus envelope protein. Samples will be scored as positive if the 
average OD is greater than 0.15 absorbance units and greater than the average OD before 
immunization plus 2.5 times the standard deviation (SD) of the OD before immunization at the 
same dilution. Results will be presented as end-point titer, i.e. the last dilution where the OD 
value is above threshold. 
6.8.2 Neutralizing antibodies 
Neutralizing antibodies against Zika virus will be performed by standard methodology as 
50% plaque reduction tittered against immune serum.  
6.8.3 ELISPOT 
The number of antigen-specific IFN-γ secreting cells will be determined by IFN-γ 
ELISpot assays in response to stimulation with Zika virus peptides using 15-mer peptides 
overlapping by 11 amino acids spanning the entire pre-membrane and envelope regions. 

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The average number of spot forming units (SFU) counted in media control wells will be 
subtracted from the average in individual Zika virus peptide wells and then adjusted to 
1x106 PBMCs for each Zika virus peptide pool.  
6.8.4 Flow Cytometry 
Additional assessment of cellular immune activity may be performed via flow cytometry if 
sample volumes allow. Flow cytometric assays will include an examination of the influence of 
vaccination on the ability of patient T cells to exhibit phenotypic markers associated with 
cytolytic potential after short-term stimulation by Zika virus (hereafter referred to as “CTL 
Phenotyping”), the ability of patient T cells to remain active in the presence of long-term antigen 
exposure and efficiently synthesize proteins used in lytic activity (hereafter referred to as “Lytic 
Granule Loading”), and the ability of patient T cells to effectively employ Granzyme B for the 
purposes of lytic degranulation and killing of target cells expressing the S antigen (hereafter 
referred to as “Killing”). These panels may vary as new information becomes available. CTL 
Phenotyping will be prioritized while Lytic Granule Loading and Killing will only be run if 
sufficient patient samples are present.  
6.9 
Downloading of EP Data from CELLECTRA® Device 
As directed by study staff, data will be downloaded from the EP device and forwarded by 
email or courier on a storage device to the sponsor (GeneOne Life Science, Inc.) or 
designee. Instructions on how to download the data and contact information will be 
provided under a separate cover. Training will also be provided. 
6.10 Concomitant medications and medical procedures 
All medications taken or medical procedures performed within 8 weeks prior to 
enrollment and during the study that do not affect a participant’s eligibility for 
participation (see Section 4.3 - Exclusion Criteria) must be recorded on the CRFs. 
Dosage and frequency of immunosuppressive medications will also be recorded.  
6.11 Restrictions 
Participants must not be vaccinated (e.g. influenza vaccine) or have received polyclonal 
or monoclonal antibodies within 4 weeks of the first dose or 2 weeks before a subsequent 
dose of investigational product. 
7. 
EVALUATION OF SAFETY AND MANAGEMENT OF 
TOXICITY 
7.1 
Safety Parameters 
The safety of GLS-5700 will be measured and graded as outlined in Appendix B. 
Throughout the course of the study, all AEs will be monitored and reported on an AE 
CRF, including the event’s seriousness, severity, action taken, and relationship to study 
drug. If AEs occur, the first concern will be the safety of the study participants. AEs must 
be followed until resolution or stable and the outcome will be documented on the 

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appropriate CRF. All AEs must be recorded in standard medical terminology rather than 
the participant’s own words. 
7.1.1 Adverse Events (AEs) 
An adverse event (AE) is defined as any unfavorable and unintended change in 
the structure, function, or chemistry of the body, or worsening of a pre-existing 
condition, temporally associated with the use of a product whether or not 
considered related to the use of the product. In this study, such changes will be 
monitored, classified, and summarized, as Clinical or Laboratory AEs. Medical 
condition/diseases present before starting the investigational drug will be 
considered adverse events only if they worsen after starting study treatment. An 
unexpected AE is one not identified in the Investigator’s Brochure (IB) or 
otherwise not expected from the characteristics of the clinical material. 
Study related AEs include the following: 
• 
Pre- or post-treatment complications that occur as a result of protocol 
mandated procedure during or after Screening (before the administration of 
study drug) 
• 
Any pre-existing condition that increases in severity, or changes in nature 
during or as a consequence of the study drug phase of a human clinical trial, 
will also be considered an AE 
• 
Complications and termination of pregnancy; see Section 7.1.8 for additional 
information 
• 
All AEs that occur from the study Day 0 visit onwards and throughout the 
duration of the study, including the follow-up of study drug period will be 
recorded as an AE 
Study related AEs do not include the following: 
• 
Medical or surgical procedures (e.g., surgery, endoscopy, tooth extraction, 
transfusion) performed; the condition that leads to the procedure is an AE 
• 
Pre-existing diseases or conditions or laboratory abnormalities present or 
detected before the first vaccination that do not worsen 
• 
Situations where an untoward medical occurrence has not occurred (e.g., 
hospitalization for elective surgery, social and/or convenience admissions). 
• 
Overdose without clinical sequelae  
• 
Any medical condition or clinically significant laboratory abnormality with an 
onset date before the first vaccination and not related to a protocol associated 
procedure is not an AE. It is considered to be pre-existing and will be 
documented on the medical history CRF 
• 
Any laboratory abnormality that is considered as non-significant or considered 
as related to another non-study related condition  
• 
Uncomplicated pregnancy 
• 
An induced elective abortion to terminate a pregnancy without medical reason 

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7.1.2 Serious Adverse Events (SAEs) 
A serious adverse event (SAE) is any AE that meets one of the following 
conditions: 
• Death during the period of surveillance defined by the protocol; 
• Is immediately life-threatening (e.g., participant was, in the view of the 
Investigator, at immediate risk of death from the event as it occurred). This 
does not include an AE that, had it occurred in a more serious form, might 
have caused death; 
• An event requiring inpatient hospitalization or prolongation of existing 
hospitalization during the period of protocol defined surveillance (including 
any overnight stay in the hospital, regardless of the length of stay, even if the 
hospitalization is only a precautionary measure to allow continued 
observation. However, hospitalization (including hospitalization for an 
elective procedure) for continued treatment or assessment of a pre-existing 
condition that has not worsened, does not constitute an SAE. NOTE: 
Evaluation in a physician’s office, or at a hospital or other urgent care setting 
in an observational, non-admitted status regardless of the time period of 
observation, does not constitute an SAE; 
• Results in congenital anomaly or birth defect; 
• Results in persistent or significant disability/incapacity or substantial 
disruption of the ability to conduct normal life functions; 
• Is an important medical event that may not result in death, be life threatening, 
or require hospitalization, but based upon appropriate medical judgment, may 
jeopardize the participant and may require medical or surgical intervention to 
prevent one of the outcomes listed above. 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; 
• Is medically significant or requires intervention to prevent one or other of the 
outcomes listed above. 
Clarification of Serious Adverse Events 
• Death is an outcome of an AE, and not an adverse event in itself 
• The participant may not have been on investigational medicinal product at the 
occurrence of the event. Dosing may have been given as treatment cycles or 
interrupted temporarily before the onset of the SAE, but may have contributed 
to the event.  
• “Life-threatening” means that the participant was at immediate risk of death 
from the event as it occurred. This does not include an event that might have 
led to death if it had occurred with greater severity 
• Complications that occur during hospitalizations are AEs. If a complication 
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• Inpatient hospitalization means that the participant has been formally admitted 
to a hospital for medical reasons, for any length of time. This may or may not 
be overnight. Observation status or evaluation in an emergency department, 
urgent care setting, or outpatient office does not constitute an SAE.  
• The investigator will attempt to establish a diagnosis of the event on the basis 
of signs, symptoms, and/or other clinical information. In such cases, the 
diagnosis will be documented as the AE and/or SAE and not the individual 
signs/symptoms. 
Serious adverse events that are ongoing should be followed until resolution. The 
reporting period for SAEs is described in Section 9.6.2. 
7.1.3 Medically Attended Adverse Events (MAAE) 
A medically attended adverse event (MAAE) is defined as an adverse event that 
leads to an unplanned contact with a health care provider.  
7.1.4 Unexpected Adverse Drug Reactions 
An unexpected adverse drug reaction (ADR) is a reaction for which the nature or 
severity is not consistent with the applicable product information (Investigator’s 
Brochure). Until product information is amended, expedited reporting is required 
for additional occurrences of the reaction. Reports that add significant information 
on specificity or severity of a known, already documented SAE constitute 
unexpected events. For example, an event more specific or more severe than 
described in the Investigator's Brochure would be considered "unexpected.” 
Specific examples would be (a) acute renal failure as a labeled ADR with a 
subsequent new report of interstitial nephritis and (b) hepatitis with a first report 
of fulminant hepatitis. 
7.1.5 Assessing Severity (Intensity) 
The investigator will grade laboratory AEs and clinical AEs (based on discussions 
with study participants) as outlined in Appendix B.: 
• Mild (Grade 1) 
• Moderate (Grade 2) 
• Severe (Grade 3) 
• Potentially Life Threatening (Grade 4) 
Adverse events will be captured on the CRF at the maximum severity reported. 
7.1.6 Causal Relationship of Clinical Material to Adverse Events 
A causally related AE is one judged to have a suspected relationship to the 
administration of the clinical material (GLS-5700), and/or the investigational 
CELLECTRA® device. An AE may also be assessed as not related to the 
investigational product or device. The Investigator is responsible for reporting 

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adverse events and judging the relationship between the administration of the 
clinical material and a subsequent AE because the investigator is knowledgeable 
about the participant (e.g., medical history, concomitant medications), administers 
the investigational product, and monitors the participant’s response to the 
investigational product. The Investigator is aware of the participant’s clinical state 
and thus may be sensitive to distinctions between events due to the underlying 
disease process versus events that may be product related and may have observed 
the event. The Sponsor will assess the overall safety of the investigational product 
and determine whether to report expeditiously to the regulatory agencies. 
Investigators should use their knowledge of the Study Participant, the 
circumstances surrounding the event, and an evaluation of any potential 
alternative causes to determine whether or not an adverse event is considered to 
be related to the study drug, indicating “yes” or “no” accordingly. Causality 
should be assessed by the Investigator as “yes, related” or “no, unrelated” by the 
following criteria: 
• 
Yes – there is reasonable possibility that administration of the Study 
Treatment contributed to the event; 
• 
No – there is no reasonable possibility that administration of the Study 
Treatment contributed to the event and there are more likely causes. 
 
The following guidance should also be taken into consideration: 
• 
Temporal relationship of event to initiation of study drug; 
• 
Course of the event, considering especially the effects of dose reduction, 
discontinuation of study drug, or reintroduction of study drug (where 
applicable); 
• 
Known association of the event with the study drug or with similar treatments; 
• 
Known association of the event with the disease under study; 
• 
Presence of risk factors in the Study Participant or use of concomitant 
medications known to increase the occurrence of the event. 
7.1.7 Abnormal Laboratory Value 
Laboratory abnormalities are usually not recorded as AEs or SAEs. However, 
laboratory abnormalities (e.g., serum chemistry, CBC, CPK) independent of the 
underlying medical condition that require medical or surgical intervention or lead 
to investigational medicinal product interruption or discontinuation must be 
recorded as an AE, as well as an SAE, if applicable. In addition, laboratory or 
other abnormal assessments (e.g., electrocardiogram, x-rays, vital signs) that are 
associated with signs and/or symptoms must be recorded as an AE or SAE if they 
meet the definition of an AE (or SAE) as described in Sections 7.1.1 and 7.1.2. If 
the laboratory abnormality is part of a syndrome, record the syndrome or 
diagnosis (e.g., anemia) not the laboratory result (e.g., decreased hemoglobin). 
Any laboratory abnormality that is new in onset or worsened in severity or 
frequency from the baseline condition and meets one of the following criteria will 
be recorded as an AE: 

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• 
Requires therapeutic intervention or diagnostic tests 
• 
Leads to discontinuation of study treatment 
• 
Has accompanying or inducing symptoms or signs 
• 
Is judged by the investigator as clinically significant 
Severity will be assessed as detailed in Section 7.1.5. 
7.1.8 Procedures for Documenting Pregnancy During Study 
Participants who are pregnant or expect to become pregnant during the course of 
the study will be excluded from participation in the study. Should a participant 
become pregnant after enrolling in the study, she will not be given any further 
treatments with GLS-5700. The Investigator will report the event to the study 
team and medical monitor, or its designee, and to the IRB. Sites must request the 
participant’s permission to query pregnancy outcome and follow each participant 
to determine the outcome of the pregnancy. Results will be summarized in the 
clinical study report (CSR).  
Participants who become pregnant at any point during the study will continue to 
be followed for safety assessments without receiving further investigational 
product. Procedures that are contraindicated during pregnancy, including 
additional treatments, must not be performed. Investigators should use clinical 
judgment regarding subsequent study-related blood collection based on the 
presence or absence of anemia in each participant. Participants who are not 
withdrawn will continue to be followed for safety assessments to study discharge 
per protocol.  
All pregnancies that occur from the time of first screening procedure through the 
follow up visits must be reported. Monitoring of the participant and the outcome 
of the pregnancy will be followed by the investigator. If the end of the pregnancy 
occurs after the study has been completed, the outcome will be reported directly 
to the study team and the medical monitor. 
Male participants will be instructed through the Informed Consent Form to 
immediately inform the investigator if their partner becomes pregnant through till 
the end of follow-up period. A Pregnancy Form will be completed by the 
investigator and submitted to the sponsor within 24 hours after learning of the 
pregnancy. Attempts will be made to collect and report details of the course and 
outcome of any pregnancy in the partner of a male participant exposed to Study 
Treatment. The pregnant partner will need to sign an Authorization for Use and 
Disclosure of Pregnancy Health Information to allow for follow-up on her 
pregnancy. Once the authorization has been signed, the investigator will update 
the Pregnancy Form with additional information on the course and outcome of the 
pregnancy. An investigator who is contacted by the male participant or his 
pregnant partner may provide information on the risks of the pregnancy and the 
possible effects on the fetus, to support an informed decision in cooperation with 
the treating physician and/or obstetrician.  
Participants who are detected as pregnant as part of the screening laboratory 
assessment, but who have not received study product, will not be enrolled into the 

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study and will be deemed as screen failures since the criteria for enrollment have 
not been met.   
7.1.9 Post-Study Reporting Requirements 
All AEs and SAEs including deaths, regardless of cause or relationship, must be 
reported for participants on study (including any protocol-required post-treatment 
follow-up). 
Investigators are not obligated to actively seek AEs or SAEs beyond the follow up 
period for participants. However, if the investigator learns of an AE or SAE that 
occurs after the completion or termination visit and the event is deemed by the 
investigator to be probably or possibly related to the study treatment, he/she 
should promptly document and report the event to the study team and medical 
monitor. 
7.2 
Methods and Timing for Collection and Recording of Safety Data  
0-6 days after each dose: Study participants will be directly observed by study personnel 
for 30 minutes after injection of GLS-5700 and contacted by study personnel on Day 1 
post vaccination for immediate reactions. The occurrence and severity of any AE during 
this period or the lack of same will be recorded on the appropriate CRF. After that, 
participants will be given an oral thermometer and a Participant Memory Aid. They will 
be asked to take and record their oral temperature daily at the same time and to note and 
characterize in their own words any local or systemic AEs they experience which are to 
be reviewed at the next study visit. 
Throughout the Study: In addition to the daily record of oral temperature, injection site 
reactions, and systemic complaints recorded for 7 days after injection of clinical material, 
study participants will be queried at each clinic visit regarding the occurrence of any SAE 
or other unexpected AE that may have occurred since the last visit. They will be 
reminded to contact study personnel and immediately report any such event that happens 
during the course of the study. These events will be recorded on the CRFs. 
All AEs, regardless of severity, seriousness, or presumed relationship to study treatment, 
must be recorded using medical terminology in source documents and on the CRF. 
Whenever possible, a diagnosis will be documented, in lieu of symptoms. The source 
document and the CRF must contain the investigator’s opinion concerning the 
relationship of the AE to study treatment. 
AEs should be described with the following attributes: 
• 
Duration (start and end dates) 
• 
Seriousness 
• 
Severity 
• 
Causality 
• 
Action(s) taken 
• 
Outcome 

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7.3 
Safety and Toxicity Management 
The Medical Monitor will be responsible for the overall safety monitoring of the study. 
The site PI will be responsible locally for safety. The Safety Monitoring Committee will 
review safety laboratory studies as delineated in Section 3.1.  
Safety assessments include the following: 
• 
Incidence of all adverse events classified by system organ class (SOC), preferred 
term, severity, and relationship to study treatment 
• 
Changes in safety laboratory parameters (e.g., hematology, serum chemistry, and 
urinalysis) 
• 
Local and systemic injection site review; special attention will be paid to the 
examination of the injection site. Administration site reactions and the participant's 
complaints will be documented. 
7.3.1 Events Requiring Expedited Reporting 
Events requiring expedited reporting (ERER) will be defined as any Adverse 
Event of Special Interest (see section 7.1.3) regardless of intensity or relationship 
to Study Treatment or any Study Treatment-related adverse events that follow: 
• Grade 3 or greater administration site erythema, and/or induration recorded ≥ 
2 hours after Study Treatment;  
• Grade 4 or greater administration site pain, tenderness recorded ≥ 2 hours 
after Study Treatment; 
• Grade 3 or greater fever; 
• Grade 3 or greater systemic symptoms, including generalized pruritus;  
• Grade 3 or greater laboratory abnormalities 
As per the Toxicity Grade for Healthy Adults (Appendix B).  The most severe 
grade for that particular event is to be documented in the CRFs. 
Sites will inform the Sponsor of any ERER within 24 hours to discuss whether 
dosing to the participant should continue. 
7.3.2 Stopping Rules (Criteria for Pausing of Study) 
If any of the following situations occur then further enrollment and Study 
Treatments will be halted immediately until a thorough investigation has been 
conducted by the Medical Monitor and Principal Investigator and the IRB/REC (if 
applicable): 
• One third (1/3) or more participants experience an ERER assessed as related to 
Study Treatment;  
• Three or more participants in the same treatment arm discontinue due to an AE 
related to the Study Treatment; 
• Any participant experiences a potentially life threatening AE,  Grade 4 AE or 
death assessed as related to Study Treatment; 
• Two or more participants within a treatment arm experience the same or 
similar grade 3 or 4 adverse event, assessed as related to Study Treatment;  
• Seven or more participants across all treatment arms experience the same or 
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• Any report of anaphylaxis of Grade 3 or greater assessed as related to Study 
Treatment. 
Upon conclusion, the sponsor or designee will notify all investigators and IRBs/EC 
(if required) regarding the outcome of any investigation stemming from a Study 
Pause.  
Any SAE or death assessed as related to Study Treatment will lead to an 
immediate halt of study enrollment and Study Treatments. 
Guidelines for assessing relatedness are detailed in Section 7.1.6. 
8. STATISTICAL CONSIDERATIONS 
8.1 
General Considerations 
The statistical analysis of the data will be performed by GeneOne Life Science or its 
representative. Descriptive statistics will be presented from the data collected in this 
Phase I study. 
For the baseline characteristics, we will present continuous variables as means, medians, 
standard deviations, and interquartile ranges, and categorical variables as frequencies and 
percentages.  
Analysis populations will include: 
Per-protocol (PP) analysis to comprise participants who receive all Study Treatments 
and have no protocol violations. Participants in this sample will be grouped to 
treatment arms as randomized.  
The modified intention to treat (mITT) analysis includes all participants who receive at 
least one Study Treatment. Participants in this sample will be grouped to treatment 
arms as randomized. Analyses on the mITT sample will be considered supportive of 
the corresponding PP analyses.  
The safety analysis set includes all participants who receive at least one Study 
Treatment. Participants will be analyzed as to the treatment they received.  
Participants who do not complete the study will not be replaced.  
8.2 
Demographic and Other Baseline Characteristics  
Demographic and baseline data, vital signs, medical history, concomitant illnesses, and 
current medications/treatments will be summarized by means of descriptive statistics: 
continuous variables as mean, median, standard deviation, and interquartile ranges and 
categorical variables as frequencies and percentages, stratified by treatment arm based on 
the mITT population.  
8.3 
Safety Analysis 
8.3.1 Adverse events 
Treatment emergent AEs will be summarized by estimates of proportions, exact 
95% binomial CIs, and 95% CIs. The differences between the groups (proportions 

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and GMT ratio) will be calculated. We will use the chi-square test to evaluate the 
significance of the differences in frequency between groups. These frequencies 
will be presented separately by dose and overall, i.e. based on pooled doses, and 
will depict overall, by system organ class and by preferred term, the number and 
percentage of participants affected. Additional frequencies will be presented with 
respect to maximum severity and to strongest relationship to Study Treatment. 
Multiple occurrences of the same AE will be counted only once following a 
worst-case approach with respect to severity and relationship to Study Treatment. 
All serious AEs and administration site events will also be summarized as above.  
For the purpose of summarizing the safety all active vaccine groups will be 
grouped together. The proportion of participants experiencing grade 3 or grade 4 
adverse events following the vaccine will be presented. The precision with which 
this sample result estimates the rate of similar adverse events in the population 
represented by the study sample will be reported in terms of 95% confidence 
intervals (CI) around the sample proportions. This will provide 95% confidence 
that the rate of severe adverse effects is not greater than the upper limit of the CI 
around the proportion of participants with grade 3+ events in the study sample.  
 
Table 8.3.1 illustrates the confidence intervals for a range of hypothetical 
proportions of adverse events. This table shows (e.g.) that a sample finding of no 
grade 3 or grade 4 adverse events in a total evaluable sample of 40 participants 
would provide 95% confidence that the rate in the population from which the 
sample was drawn is no greater than 8.8%.  
 
Table 8.3.2 shows the probability of detecting at least 1 adverse event of a given 
type and/or level of severity in the study sample, given a range of hypothesized 
rates in the population from which the sample was drawn. The table demonstrates 
that the probability of observing one or more events in a sample of 40 participants 
is >70% with events whose population probabilities are at least 2%, while the 
probability of observing two or more events is >34% for events whose population 
probabilities are at least 3%. 
Table 8.3.1: Exact 95% confidence intervals around potential proportions of 
participants exhibiting Grade 3+ adverse events (total sample and selected 
subsample sizes)  
 
N 
Samples Rate (%) 
Lower Limit (%) 
Upper Limit (% 
40 
0 
0 
8.8 
 
1 
0 
10.7 
 
2 
0 
12.4 
 
3 
0.1 
13.9 
 
4 
0.3 
15.5 
 
5 
0.6 
16.9 
 
6 
1.0 
18.3 
 
7 
1.4 
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8 
1.8 
21.1 
 
9 
2.3 
22.4 
 
10 
2.8 
23.7 
 
 
Table 8.3.2. Probability of detecting Adverse Events 
 
True Event Rate in the 
Population 
Represented by the 
Study Sample 
Probability of Observing Event(s)  in the 
Study Sample (N = 40) 
1 or more 
Event 
2 or more 
Events 
0.5% 
18% 
2% 
1% 
33% 
6% 
2% 
55% 
19% 
3% 
70% 
33% 
4% 
80% 
48% 
5% 
87% 
60% 
 
The main summary of safety data will be based on events occurring within 14 
days of administration of Study Treatment (as specified in Section 9.6.1).  
8.3.2 Laboratory Data  
Continuous response variables per time point and changes from baseline will be 
summarized with mean, median, minimum, and maximum values. Categorical 
response variables will be summarized per time point with percentages. These 
will be calculated according to treatment arm.  
8.4 
Immunogenicity analysis 
Data classified as positive/negative or responder/non-responder will be analyzed as the 
frequency of response for each assay within treatment arm at each time point at which an 
assessment is performed. For secondary immunogenicity outcomes, estimates of 
proportions and exact 95% binomial CIs and 95% CIs for the differences between the 
groups (proportions and geometric mean test (GMT) ratio) will be calculated. We will 
use the chi-square test to evaluate the significance of the differences between groups. For 
GMT and mean fold increase in GMT, we will calculate the mean and 95% CI for the 
log10-transformed titers and then transformed back to the original units by 
exponentiation. We will use the t test to compare the GMTs between groups. The 
proportion of participants meeting the criteria for immunologic response following 
vaccination will be presented for each study arm. The precision with which this sample 
result estimates the rate of immunologic response rates in the population represented by 
the study sample will be reported in terms of 90% CIs around the sample proportions. 
This will provide 95% confidence that the rate of immune response is not less that the 
lower limit of the proportion of study participants meeting immune response criteria. The 
primary immunogenicity analysis will include all subjects having evaluable data.  

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Table 8.4.1 illustrates the confidence intervals for a range of hypothetical proportions of 
immunologic response. This table shows (e.g.) that a sample finding of 30 (75%) 
responders in the total sample of 40 participants would provide 95% confidence that the 
rate in the population from which the sample was drawn was no lower than 62%.  
The rate of response in arms will be compared using the chi-square test. Comparison 
between treatment arms will be carried out using a Mann Whitney U test for continuous 
variables, and a Fisher's Exact Test or Pearson's Chi-square Test for categorical factors. 
Because the study is small the study is underpowered for comparisons between arms. 
Table 8.4.1:   Exact 90% confidence intervals around potential proportions of 
participants achieving immunologic response criteria for each study arm (total 
sample and selected subsample sizes) 
N 
Sample rate 
Lower Limit 
Upper Limit 
40 
25% 
14% 
39% 
 
50% 
36% 
64% 
 
75% 
61% 
86% 
 
90% 
79% 
97% 
 
95% 
85% 
99% 
 
The primary immunogenicity analysis will include all participants having evaluable data 
A secondary qualitative analysis will assess immune responses relative to presence of 
pre-existing antibodies to other flaviviruses (West Nile or dengue) or chikungunya virus.  
8.5 
Sample Size 
See section 8.3 for a power calculation of the probabilities of observing adverse events 
and immunological responses in the present trial. 
With 40 participants receiving vaccine at any level, the study provides 80% probability of 
detecting an event if the incidence is greater than 4% in the vaccinated population (Table 
8.4.1).   
8.6 
Missing Values 
Missing data will not be replaced, and calculations will be done on reported values.  
8.7 
Interim analyses 
No formal interim analyses will be performed for this study.  
9. DATA COLLECTION, MONITORING, AND AE REPORTING 
9.1 
Confidentiality 
Information about study participants will be kept confidential to the best of the study 
site’s ability. 
In the event that a participant revokes authorization to collect or use personal health 
information (PHI), the sponsor retains the ability to use all information collected prior to 
the revocation of participant authorization. For participants that have revoked 

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authorization to collect or use PHI, attempts should be made to obtain permission to 
collect at least vital status (i.e., that the participant is alive) at the end of their scheduled 
study period. 
9.2 
Source Documents 
Source data is all information, original records or clinical findings, observations, or other 
activities in a clinical trial necessary for the reconstruction and evaluation of the trial. 
Source data are contained in original source documents. Examples of these original 
documents, and data records include: hospital records, clinical and office charts, 
laboratory notes, memoranda, participant’s diaries or evaluation checklists, pharmacy 
dispensing records, recorded data from automated instruments, copies or transcriptions 
certified after verification as being accurate and complete, microfiches, photographic 
negatives, microfilm or magnetic media, x-rays, participant files, and records kept at the 
pharmacy, at the laboratories, and at medical records and within information technology 
systems that are involved in the clinical trial.  
Monitoring of the clinical trial will be performed by experienced monitors, who will 
report to the Sponsor or the Sponsor designee. Records for all clinical participants in this 
trial will be monitored. Monitoring functions and activities are outlined in the separate 
Monitoring Plan.  
9.3 
Records to be kept 
CRFs will be provided for each study participant. Participants must not be identified by 
name on any CRF. Participants will be identified by their participant identification 
number (PID).  
9.4 
Records Retention 
It is the investigator’s responsibility to retain study essential documents as per country 
regulations: in the US for at least 2 years after the last approval of a marketing 
application in their country and until there are no pending or contemplated marketing 
applications in their country or at least 2 years have elapsed since the formal 
discontinuation of clinical development of the investigational product. The sponsor will 
inform the investigator/institution as to when these documents are no longer needed to be 
retained; and 25 years for Canada.  
9.5 
Safety and Quality Monitoring and Record Availability 
Monitoring 
Monitoring of the clinical trial will be performed by experienced monitors, who will 
report to the Sponsor or the Sponsor designee as outlined in the Monitoring Plan.: 
Record availability and auditing 
The investigator will make study documents (e.g., ICFs, drug accountability forms, 
CRFs) and pertinent hospital or clinic records readily available for inspection by the local 
IRB/EC, the site monitors, regulatory agencies, GeneOne Life Science, Inc. or its 
designee for confirmation of the study data. 

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Participation as an investigator in this study implies acceptance of potential inspection by 
regulatory authorities and applicable compliance and quality assurance offices. 
9.6 
Adverse Experience (AE) Reporting 
To assure the safety of the participants, information about all AEs (see Section 7.1 Safety 
Parameters for definitions), whether volunteered by the participant, discovered by 
investigator or study staff questioning, or detected through physical examination, 
laboratory test or other means, will be collected and recorded in the participant’s source 
documents and followed as appropriate. 
In addition to AE reporting, a summary of the study’s overall progress will be forwarded 
to regulatory agencies according to the local requirements (e.g., every 6 months, annual). 
9.6.1 Study Reporting Period of Adverse Events 
All solicited and unsolicited adverse events will be collected throughout the study 
and recorded on the CRFs. The Study Report will analyze and summarize all  
adverse events throughout the study.  Unsolicited AEs will be summarized for the 
14 day period following each administration of Study Treatment. See next section 
for SAEs. 
9.6.2 Study Reporting Period of Serious Adverse Events 
The reporting period for SAEs (without regard to causality) is the entire period 
following the signing of the informed consent form until the end of the study.  
Each AE will be assessed to determine whether it meets seriousness criteria. If the 
AE is considered serious, the investigator should record this event to GeneOne 
Life Science within 24 hours of becoming aware of the event. The investigator 
may also directly report this event to the clinical site IRB/EC per standard 
operating procedures within 24 hrs.  
Expectedness of SAEs will be determined by GeneOne Life Science using 
reference safety information specified in the Investigator’s Brochure. An event 
may qualify for expedited reporting to regulatory authorities if it is an SAE, 
unexpected per reference safety information and considered related following the 
guidelines in Section 7.1.4  (Suspected Unexpected Serious Adverse Reaction, 
SUSAR) in line with relevant legislation. All investigators will receive a safety 
letter notifying them of relevant SUSAR reports. The investigator should notify 
the Ethics Committee as soon as is practical, of serious events in writing where 
this is required by local regulatory authorities, and in accordance with the local 
institutional policy.  
At any time after completion of the SAE reporting period, if an investigator 
becomes aware of an SAE that is suspected by the investigator to be related to the 
study drug, the event will be reported to the Sponsor or its designee. 
If the investigator becomes aware of an SAE, an AESI, or an MAAE in a study 
participant after the last scheduled follow-up visit, and considers the event related 
to prior Study Treatment, the investigator will report it to GeneOne Life Science. 

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SAE TELEPHONE AND CONTACT INFORMATION: 
MEDICAL 
MONITOR: 
Joel Maslow, MD PhD MBA 
 
MAILING ADDRESS: 
PHONE: 
(484) 965-9147p; (610) 331-7844 c 
 GeneOne Life Science, Inc. 
SAFETY PHONE: (215) 703-5843 
 
1040 DeKalb Pike 
FACSIMILE: 
(877) 464-7787 
 
Suite 200 
EMAIL: 
INCDrugSafety@INCResearch.com 
 
Blue Bell, PA 19422 
 
The report should contain as much clinical safety information as possible, but at 
minimum, the initial report must include the following information: 
• 
Event 
• 
Study code 
• 
Participant number, initials and date of birth 
• 
Investigational study product 
• 
Reporter name and contact information 
In the case of a “minimum report” (one that is solely comprised of the information 
bulleted above), a more detailed follow-up report will be sent as soon as more 
information becomes available but no later than 7 calendar days after the date of 
the initial report. Each SAE must be followed up until resolution or stabilization 
and for a reported death, the investigator will supply GeneOne Life Science and 
the Ethics Committee with any additional requested information (e.g., autopsy 
reports and terminal medical reports). 
The original SAE form must be kept at the study site. GeneOne Life Science or its 
representative will be responsible for determining and in turn, reporting SAEs to 
regulatory authorities according to the applicable regulatory requirements.  
SAEs must be followed by the investigator until resolution, even if this extends 
beyond the study-reporting period. Resolution of an SAE is defined as the return 
to baseline status or stabilization of the condition with the expectation that it will 
remain chronic.  
9.6.3 Notifications of Serious Adverse Events 
In accordance with local regulations, the Sponsor shall notify the appropriate 
regulatory authorities, and all participating investigators in a written safety report 
of any adverse experience associated with the use of the product that is both 
serious and unexpected (e.g., FDA Form 3500A in the US). Reports of serious 
adverse events shall be made as soon as possible and in no event later than 15 
calendar days after the Sponsor’s initial receipt of the information. Written 
notification may be submitted on the form described above or equivalent or in a 
narrative format and shall bear prominent identification of its contents. Each 
written notification to regulatory agencies shall be transmitted to the division that 
has responsibility for review. In each written safety report, the Sponsor shall 
identify all safety reports previously filed concerning a similar adverse 
experience, and shall analyze the significance of the adverse experience in light of 

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the previous, similar reports. The Sponsor shall also notify the relevant regulatory 
authorities by telephone or by facsimile transmission of all deaths regardless of 
causality and any unexpected fatal or life-threatening experience associated with 
the use of the drug as soon as possible but in no event later than 7 calendar days 
after the sponsor’s initial receipt of the information. Each telephone call or 
facsimile transmission to regulatory agencies shall be transmitted to the division 
that has responsibility for review.  
Follow up information to a safety report shall be submitted as soon as the relevant 
information is available. If the results of a Sponsor’s event investigation show that 
an adverse drug experience not initially determined to be reportable is, in fact, 
reportable, the Sponsor shall report such experience in a written safety report as 
soon as possible, but in no event later than 15 calendar days after the 
determination is made. Results of investigations of other safety information shall 
be submitted, as appropriate, in an information amendment or annual report. 
In addition to the reporting period for SAEs specified in Section 9.6.2, should the 
Investigator become aware of an SAE (assessed as related to the investigational 
product following the guidelines in Section 7.1.6) that occurs within 14 days after 
stopping the investigational product, the SAE must be reported in accordance with 
procedures specified in this protocol. 
In the event of death, if an autopsy is performed, a copy of the report will be sent 
to GeneOne Life Science, Inc. 
9.7 
Reporting of Medically Attended Adverse Events 
MAAE will be collected during the entire study through one year following the last Study 
Treatment. As such, the reporting period for MAAE is the entire period following the 
signing of the informed consent form until study discharge.  
A tabulation of all MAAE and their assessed relationship to Study Treatment will be 
included in all required periodic reports to regulatory agencies.  
9.8 
Reporting of Device Related Complaints 
Any problems experienced during the treatment procedure including potential 
malfunctions of the CELLECTRA® device, error messages displayed on the device 
screen following treatment or errors that occur during the treatment procedure must be 
reported to the Sponsor or designee immediately for evaluation. The error reporting form 
provided in Appendix C must be completed and emailed to the Sponsor, at 
error@geneonels-us.com and to the Program Manager and study staff as outlined. 
9.9 
Study Discontinuation 
GeneOne Life Science reserves the right to discontinue the study at this site or at multiple 
sites for safety or administrative reasons at any time. In particular, a site that does not 
recruit at a reasonable rate may be discontinued. Should the study be terminated and/or 
the site closed for whatever reason, all documentation and study product pertaining to the 
study must be returned to GeneOne Life Science or its representative.  

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10.     PUBLICATION OF RESEARCH FINDINGS 
Publication of the results of this trial will be allowed. The proposed presentation, abstract 
and/or manuscript must be made available to GeneOne Life Science, Inc. 60 days prior to 
submission for publication. GeneOne Life Science, Inc. shall have thirty (30) days after 
receipt of the copies to object to the proposed presentation or publication because there is 
patentable participant matter that needs protection. In the event that GeneOne Life 
Science, Inc. makes such objection, the researcher(s) shall refrain from making such 
publication or presentation for a maximum of three (3) months from the date of receipt of 
such objection in order for patent application(s) directed to the patentable participant 
matter contained in the proposed publication or presentation to be filed with the United 
States Patent and Trademark Office and/or foreign patent office(s). 

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11. 
LIST OF ABBREVIATIONS 
AdV 
Adenovirus 
AE 
Adverse Reaction 
AESI 
Adverse Event of Special Interest 
ALT 
Alanine Aminotransferase 
Alk Phos 
Alkaline Phosphatase 
AST 
Aspartate Aminotransferase 
bGH 
Bovine Growth Hormone 
BMI 
Body Mass Index 
BUN 
Blood Urea Nitrogen 
CFR 
Code of Federal Regulations 
CIB 
Clinical Investigator’s Brochure 
CMV 
Cytomegalovirus 
CPK 
Creatine Phosphokinase 
CoV 
Coronavirus 
Cr 
Creatinine 
CRF 
Case Report Forms 
CRO 
CSR 
Clinical Research Organization  
Clinical Study Report 
DNA 
Deoxyribonucleic Acid 
EC 
Ethics Committee 
ECG 
Electrocardiogram 
eDC 
Electronic Data Capture 
ELISA 
Enzyme Linked Immunosorbent Assay 
ELISpot 
Enzyme Linked Immunosorbent Spot-forming Assay 
EP 
Electroporation 
ERER 
Events Requiring Expedited Reporting 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GMP 
Good Manufacturing Practice 
GMT 
Geometric Mean Titer 
GP 
Glycoprotein 
HBsAg 
Hepatitis B surface antigen 

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HCG 
Human Chorionic Gonadotrophin 
HCV 
Hepatitis C virus antibody 
HIV 
Human Immunodeficiency Virus 
HPV 
Human Papilloma Virus 
HLA 
Human Leukocyte Antigen 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
ID 
Intradermal 
IFN 
Interferon 
IL-12 
Interleukin 12 
IM 
Intramuscular 
IND 
Investigational New Drug Application 
INF-γ 
Interferon Gamma 
IRB 
Institutional Review Board 
L 
Ebola virus RNA polymerase 
MAAE 
Medically Attended Adverse Event 
MedDRA 
Medical Dictionary for Drug Regulatory Affairs 
MERS 
Middle East Respiratory Syndrome 
MERS CoV 
Middle East Respiratory Syndrome Coronavirus 
NP 
Ebola virus nucleoprotein 
PBMC 
Peripheral Blood Mononuclear Cells 
PCR 
Polymerase Chain Reaction  
PHI 
Personal Health Information 
PID 
Participant Identification Number 
prME 
Pre-membrane and envelope proteins of Zika virus 
S protein 
MERS Spike protein 
SAE 
Serious Adverse Event 
SSC 
Sterile saline salt citrate buffer 
SynCon® 
Synthetic consensus 
ULN 
Upper Limit of Normal 
VAS 
Visual Analog Scale 
WFI 
Water for Injection 
WOCBP 
Women of Childbearing Potential 
ZEBOV 
Zaire Ebola virus 

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12. 
REFERENCES 
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2. 
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8. 
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Detection of Zika virus in urine. Emerg Infect Dis 2015,21:84-86. 
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Musso D, Roche C, Nhan TX, Robin E, Teissier A, Cao-Lormeau VM. Detection 
of Zika virus in saliva. J Clin Virol 2015,68:53-55. 
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P, et al. Co-infection with Zika and dengue viruses in 2 patients, New Caledonia, 
2014. Emerg Infect Dis 2015,21:381-382. 

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Ioos S, Mallet HP, Leparc Goffart I, Gauthier V, Cardoso T, Herida M. Current 
Zika virus epidemiology and recent epidemics. Med Mal Infect 2014,44:302-307. 
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and chikungunya? The Lancet 2015,386:243-244. 
19. 
Tang CT, Li PC, Liu IJ, Liao MY, Chiu CY, Chao DY, et al. An epitope-
substituted DNA vaccine improves safety and immunogenicity against dengue 
virus type 2. PLoS Negl Trop Dis 
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Evaluation of a prototype dengue-1 DNA vaccine in a Phase 1 clinical trial. 
Vaccine 2011,29:960-968. 
21. 
Ledgerwood JE, Pierson TC, Hubka SA, Desai N, Rucker S, Gordon IJ, et al. A 
West Nile virus DNA vaccine utilizing a modified promoter induces neutralizing 
antibody in younger and older healthy adults in a phase I clinical trial. J Infect Dis 
2011,203:1396-1404. 
22. 
Martin JE, Pierson TC, Hubka S, Rucker S, Gordon IJ, Enama ME, et al. A West 
Nile virus DNA vaccine induces neutralizing antibody in healthy adults during a 
phase 1 clinical trial. J Infect Dis 2007,196:1732-1740. 
23. 
Ramanathan MP, Kutzler MA, Kuo YC, Yan J, Liu H, Shah V, et al. 
Coimmunization with an optimized IL-15 plasmid adjuvant enhances humoral 
immunity via stimulating B cells induced by genetically engineered DNA 
vaccines expressing consensus JEV and WNV E DIII Vaccine 2009,27:4370-
4380. 
24. 
Yang J-S, Kim JJ, Hwang D, Choo AY, Dang K, Maguire H, et al. Induction of 
Potent Th1-Type Immune Responses from a Novel DNA Vaccine for West Nile 
Virus New York Isolate (WNV-NY1999). J Infect Dis 2001,184:809-816. 
25. 
Bagarazzi ML, Yan J, Morrow MP, Shen X, Parker L, Lee JC, et al. 
Immunotherapy against HPV16/18 generates potent TH1 and cytotoxic cellular 
immune responses. Sci Transl Med 2012,4:15Sra138. 
26. 
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efficacy, and immunogenicity of VGX-3100, a therapeutic synthetic DNA 
vaccine targeting human papillomavirus 16 and 18 E6 and E7 proteins for cervical 
intraepithelial neoplasia 2/3: a randomised, double-blind, placebo-controlled 
phase 2b trial. The Lancet 2015,386:2078-2088. 
27. 
Martín-Acebesa MA, Blázqueza A-B, Canas-Arranzb R, Vázquez-Calvoa Á, 
Merino-Ramosa T, Escribano-Romeroa E, et al. A recombinant DNA vaccine 
protects mice deficient in the alpha/beta interferon receptor against lethal 
challenge with Usutu virus. In: Vaccine; 2016. 
28. 
Tan GK, Ng JKW, Trasti SL, Schul W, Yip G, Alonso S. A non mouse-adapted 
dengue virus strain as a new model of severe dengue infection in AG129 mice. 
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29. 
Brewoo JN, Kinney RM, Powell TD, Arguello JJ, Silengo SJ, Partidos CD, et al. 
Immunogenicity and efficacy of chimeric dengue vaccine (DENVax) 
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30. 
MacGregor R, Boyer JD, Ugen KE, Lacy K, Gluckman S, Bagarazzi ML, et al. 
Firsts human trial of a DNA-based vaccine for treatment of human 

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immunodeficiency virus type 1 infection: safety and host response. J Infect Dis 
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factors affect immunogenicity of DNA plasmid HIV vaccines in human clinical 
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32. 
Quirk EK, Brown EL, Leavitt RY, Mogg R, Mehrotra DV, Evans RK, et al. 
Safety Profile of the Merck Human Immunodeficiency Virus-1 Clade B gag DNA 
Plasmid Vaccine With and Without Adjuvants. Open Forum Infect Dis 
2014,1:ofu016. 
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Kibuuka H, Berkowitz NM, Millard M, Enama ME, Tindikahwa A, Sekiziyivu 
AB, et al. Safety and immunogenicity of Ebola virus and Marburg virus 
glycoprotein DNA vaccines assessed separately and concomitantly in healthy 
Ugandan adults: a phase 1b, randomised, double-blind, placebo-controlled clinical 
trial. The Lancet 2014,385:1545-1554. 
34. 
Martin JE, Sullivan NJ, Enama ME, Gordon IJ, Roederer M, Koup RA, et al. A 
DNA vaccine for Ebola virus is safe and immunogenic in a phase I clinical trial. 
Clin Vaccine Immunol 2006,13:1267-1277. 
35. 
Sarwar UN, Costner P, Enama ME, Berkowitz N, Hu Z, Hendel CS, et al. Safety 
and immunogenicity of DNA vaccines encoding Ebolavirus and Marburgvirus 
wild-type glycoproteins in a phase I clinical trial. J Infect Dis 2015,211:549-557. 
36. 
Kalams SA, Parker S, Jin X, Elizaga M, Metch B, Wang M, et al. Safety and 
immunogenicity of an HIV-1 gag DNA vaccine with or without IL-12 and/or IL-
15 plasmid cytokine adjuvant in healthy, HIV-1 uninfected adults. PLoS One 
2012,7:e29231. 
37. 
Ledgerwood JE, Bellamy AR, Belshe R, Bernstein DI, Edupuganti S, Patel SM, et 
al. DNA priming for seasonal influenza vaccine: a phase 1b double-blind 
randomized clinical trial. PLoS One 2015,10:e0125914. 
38. 
Prud’homme GJ, Glinka Y, Khan AS, Draghia-Akli R. Electroporation-enhanced 
nonviral gene transfer for the prevention or treatment of immunological, 
endocrine and neoplastic diseases. 2006. 
39. 
Hirao LA, Wu L, Khan AS, Hokey DA, Yan J, Dai A, et al. Combined effects of 
IL-12 and electroporation enhances the potency of DNA vaccination in macaques. 
Vaccine 2008,26:3112-3120. 
40. 
Rosati M, Valentin A, Jalah R, Patel V, von Gegerfelt A, Bergamaschi C, et al. 
Increased immune responses in rhesus macaques by DNA vaccination combined 
with electroporation. Vaccine 2008,26:5223-5229. 
41. 
Curcio C, Khan AS, Amici A, Spadaro M, Quaglino E, Cavallo F, et al. DNA 
immunization using constant-current electroporation affords long-term protection 
from autochthonous mammary carcinomas in cancer-prone transgenic mice. 
Cancer Gene Ther 2008,15:108-114. 
42. 
Ugen KE, Kutzler MA, Marrero B, Westover J, Coppola D, Weiner DB, et al. 
Regression of subcutaneous B16 melanoma tumors after intratumoral delivery of 
an IL-15-expressing plasmid followed by in vivo electroporation. Cancer Gene 
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43. 
Hirao LA, Wu L, Khan AS, Satishchandran A, Draghia-Akli R, Weiner DB. 
Intradermal/subcutaneous immunization by electroporation improves plasmid 

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vaccine delivery and potency in pigs and rhesus macaques. Vaccine 2008,26:440-
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13. APPENDIX 
Appendix A: Participant Memory Aid 

 
 
 
  
 
Protocol 
MEMORY AID 
 
Subject number 
Zika-001 
VACCINATION 
Day 0 - Day 6 
 
|__|__|__|__|__|__| 
 
 
 
 
LOCAL SYMPTOMS (at injection site) 
 
 
Please fill in below and assess the occurrence of any of the following signs or symptoms according to the criteria listed hereafter: 
INTENSITY: 
Pain (at injection site) 
0: 
Absent. 
1: 
Painful on touch. Any pain that does not interfere with or 
prevent normal everyday activities. 
2: 
Painful when limb is moved that interferes with normal activities 
or requires repeated use of pain relievers 
3: Significant pain at rest; prevents normal activities as assessed 
by inability to attend/do work or school  Please contact your 
study site when the intensity of your pain is 3 during the 7 
day follow-up period for solicited AE’s. 
Other local symptoms 
1: Mild: 
An adverse event which is easily tolerated, causing 
minimal discomfort and not interfering with everyday 
activities. 
2: Moderate: 
An adverse event which is sufficiently discomforting to 
interfere with normal everyday activities. 
3: Severe: 
An adverse event which prevents normal, everyday 
activities. (Such an adverse would, for example, prevent 
attendance at work and would necessitate the 
administration of corrective therapy). 
Redness, Swelling, Bruising at injection site:  Please measure the greatest diameter (in cm).  
 
Day 0 = date of vaccination : |__|__||__|__|__||__|__|__|__| 
 
LOCAL 
SYMPTOMS 
Day 0 
Day 1  
Day 2 
Day 3  
Day 4  
Day 5 
Day 6  
Ongoing 
After Day 6? 
Date of last Day of Symptoms 
day 
  month 
year 
Sought 
medical 
attention? 
Redness 
 size (cm): 
_____ 
_____ 
_____ 
_____ 
_____ 
_____ 
_____ 
  No 
  Yes  
|__|__| |__|__|__| |__|__|__|__| 
  No 
  Yes  
Swelling 
 size (cm): 
_____ 
_____ 
_____ 
_____ 
_____ 
_____ 
_____ 
  No 
  Yes  
|__|__| |__|__|__| |__|__|__|__| 
  No 
  Yes  
Bruising 
 size (cm): 
_____ 
_____ 
_____ 
_____ 
_____ 
_____ 
_____ 
  No 
  Yes  
|__|__| |__|__|__| |__|__|__|__| 
  No 
  Yes 
Pain 
 Intensity: 
|___| 
|___| 
|___| 
|___| 
|___| 
|___| 
|___| 
  No 
  Yes  
|__|__| |__|__|__| |__|__|__|__| 
  No 
  Yes  
Tenderness 
 Intensity: 
|___| 
|___| 
|___| 
|___| 
|___| 
|___| 
|___| 
  No 
  Yes  
|__|__| |__|__|__| |__|__|__|__| 
  No 
  Yes 
Itching/Pruritus 
 Intensity: 
|___| 
|___| 
|___| 
|___| 
|___| 
|___| 
|___| 
  No 
  Yes  
|__|__| |__|__|__| |__|__|__|__| 
  No 
  Yes 
 
 
OTHER LOCAL SYMPTOMS (from Day 0 to Day 6) 
Sought 
medical 
attention? 
Description - please specify side(s) and site(s) 
Intensity 
Start date 
End date or check box if continuing 
day 
month 
year 
day 
month 
year 
 
 
|___| 
|__|__| |__|__|__| |__|__|__|__| |__|__| |__|__|__| |__|__|__|__| 
 
  No 
  Yes  
 
|___| 
|__|__| |__|__|__| |__|__|__|__| |__|__| |__|__|__| |__|__|__|__| 
 
  No 
  Yes  
 
|___| 
|__|__| |__|__|__| |__|__|__|__| |__|__| |__|__|__| |__|__|__|__| 
 
  No 
  Yes  
 
|___| 
|__|__| |__|__|__| |__|__|__|__| |__|__| |__|__|__| |__|__|__|__| 
 
  No 
  Yes  
 
 
MEDICATION 
Please fill in below if any medication (including vaccination) has been taken since the vaccination 
Trade/Generic  name 
Reason 
Total Daily 
Dose  
Start date 
End date or check box if continuing 
day 
month 
year 
day 
month 
year 
 
 
 
|__|__| |__|__|__| |__|__|__|__| 
|__|__| |__|__|__| |__|__|__|__| 
 
 
 
 
|__|__| |__|__|__| |__|__|__|__| 
|__|__| |__|__|__| |__|__|__|__| 
 
 
 
 
|__|__| |__|__|__| |__|__|__|__| 
|__|__| |__|__|__| |__|__|__|__| 
 
 
 
 
|__|__| |__|__|__| |__|__|__|__| 
|__|__| |__|__|__| |__|__|__|__| 
 
 
 
 
|__|__| |__|__|__| |__|__|__|__| 
|__|__| |__|__|__| |__|__|__|__| 
 
 
 
 
|__|__| |__|__|__| |__|__|__|__| 
|__|__| |__|__|__| |__|__|__|__| 
 
 

 
 
 
  
Protocol 
MEMORY AID 
 
Subject number 
ZIKA-001 
VACCINATION 
Day 0 - Day 6 
 
|__|__|__|__|__|__| 
 
 
GENERAL SYMPTOMS 
 
Please fill in below and assess the occurrence of any of the following signs or symptoms according to the criteria listed hereafter: 
Temperature: 
Please record temperature every day in the evening. If temperature has been taken more than once a day, please report the highest value for the 
day. Please contact your study site when you experience temperature greater or equal to 100.4 °F during the 7 day follow-up period for 
solicited AE’s. 
INTENSITY:  
Feeling Unwell/Malaise (*) 
Headache, Muscle aches (widespread, not limited to the injection site) (*) 
0: 
Normal 
1: 
Symptoms that are easily tolerated 
2: 
Symptoms that interfere with normal activity  
3: 
Symptoms that prevent normal activity or 
requires repeated use of pain relievers 
0: 
Normal 
1: 
Symptoms that are easily tolerated 
2: 
Symptoms that interfere with normal activity or requires repeated use of pain relievers 
3: 
Symptoms that prevent normal activity  
Arthralgia, Joint Aches, Shivering  (*) 
(*) Please contact your study site when the intensity of your Fatigue, 
Headache, Arthralgia, Muscle aches or Shivering is 3 during the 7 
day follow-up period for solicited AE’s. 
0: 
Normal 
1: 
Symptoms that are easily tolerated 
2: 
Symptoms that interfere with normal activity 
3: 
Symptoms that prevent normal activity  
Other general symptoms: 
1: Mild: 
An adverse event which is easily tolerated, causing minimal discomfort and not interfering with everyday activities. 
2: Moderate: 
An adverse event which is sufficiently discomforting to interfere with normal everyday activities. 
3: Severe: 
An adverse event which prevents normal, everyday activities. (Such an adverse would, for example, prevent attendance at work 
and would necessitate the administration of corrective therapy).  
 
Day 0 = date of vaccination : |__|__||__|__|__||__|__|__|__| 
 
GENERAL 
SYMPTOMS 
Day 
0 
Day 1  
Day 2 
Day 3  
Day 4  
Day 5 
Day 6  
Ongoing 
After Day 
6? 
Date of last Day of 
Symptoms 
day 
  month 
year 
Medically 
attended 
Visit 
Temperature  [TE] 
→ 
  °F 
[O]  
Oral  
 
 
__ . _ 
 
 
__ . _ 
 
 
__ . _ 
 
 
__ . _ 
 
 
__ . _ 
 
 
__ . _ 
 
 
__ . _ 
 
  No 
  Yes  |__|__| |__|__|__| |__|__|__|__| 
  No 
  Yes  
Feeling 
Unwell/Malaise 
  intensity: 
|___| 
|___| 
|___| 
|___| 
|___| 
|___| 
|___| 
  No 
  Yes  |__|__| |__|__|__| |__|__|__|__| 
  No 
  Yes  
Headache 
  intensity: 
|___| 
|___| 
|___| 
|___| 
|___| 
|___| 
|___| 
  No 
  Yes  |__|__| |__|__|__| |__|__|__|__| 
  No 
  Yes  
Joint 
aches/Arthralgia 
  intensity: 
|___| 
|___| 
|___| 
|___| 
|___| 
|___| 
|___| 
  No 
  Yes  |__|__| |__|__|__| |__|__|__|__| 
  No 
  Yes  
Muscle 
aches/Myalgia 
  intensity: 
|___| 
|___| 
|___| 
|___| 
|___| 
|___| 
|___| 
  No 
  Yes  |__|__| |__|__|__| |__|__|__|__| 
  No 
  Yes  
Nausea 
  intensity: 
|___| 
|___| 
|___| 
|___| 
|___| 
|___| 
|___| 
  No 
  Yes  |__|__| |__|__|__| |__|__|__|__| 
  No 
  Yes  
 
OTHER GENERAL SYMPTOMS (from Day 0 to Day 6) 
Medically 
attended 
Visit? 
Description - please specify side(s) and site(s) 
Intensity 
Start date 
End date or check box if continuing 
day 
month 
year 
day 
month 
year 
 
 
|___| 
|__|__| |__|__|__| |__|__|__|__| |__|__| |__|__|__| |__|__|__|__| 
 
  No 
  Yes  
 
|___| 
|__|__| |__|__|__| |__|__|__|__| |__|__| |__|__|__| |__|__|__|__| 
 
  No 
  Yes  
 
|___| 
|__|__| |__|__|__| |__|__|__|__| |__|__| |__|__|__| |__|__|__|__| 
 
  No 
  Yes  
 
|___| 
|__|__| |__|__|__| |__|__|__|__| |__|__| |__|__|__| |__|__|__|__| 
 
  No 
  Yes  
 
PLEASE DO NOT FORGET TO BRING BACK THE DIARY CARD ON   |__|__| |__|__|__| |__|__|__|__| 
IN CASE OF HOSPITALIZATION, PLEASE INFORM _ _ _ _ __ _ _ __ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ __ _    _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ __ _ _ _ _  
 
 

GLS-5700 
    
 ZIKA-001 
GeneOne Life Science, Inc. 
Clinical Protocol 
Date: 1 July 2016 
 
v 1.2 
-61- 
 
Appendix B:  Toxicity Grading Scale  
 
 
Toxicity Grading Scale for Healthy Adult and Adolescent 
Volunteers Enrolled in Preventive Vaccine Clinical Trials, 
September 2007 
 

Guidance for Industry 
 
Toxicity Grading Scale for Healthy 
Adult and Adolescent Volunteers 
Enrolled in Preventive Vaccine 
Clinical Trials 
 
 
 
 
 
 
 
 
 
 
 
 
 
Additional copies of this guidance are available from the Office of Communication, Training and 
Manufacturers Assistance (HFM-40), 1401 Rockville Pike, Suite 200N, Rockville, MD 20852-
1448, or by calling 1-800-835-4709 or 301-827-1800, or from the Internet at 
http://www.fda.gov/cber/guidelines.htm. 
 
For questions on the content of this guidance, contact the Division of Vaccines and Related 
Products Applications, Office of Vaccines Research and Review at 301-827-3070. 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Biologics Evaluation and Research 
September 2007 

Contains Nonbinding Recommendations 
 
 
Table of Contents 
 
 
I. 
INTRODUCTION............................................................................................................. 1 
II. 
BACKGROUND ............................................................................................................... 2 
III. 
TOXICITY GRADING SCALE TABLES..................................................................... 2 
A. 
Tables for Clinical Abnormalities ....................................................................... 3 
B. 
Tables for Laboratory Abnormalities................................................................. 6 
IV. 
REFERENCES.................................................................................................................. 8 
i 

Contains Nonbinding Recommendations 
 
Guidance for Industry 
 
Toxicity Grading Scale for Healthy Adult and Adolescent 
Volunteers Enrolled in Preventive Vaccine Clinical Trials 
 
 
This guidance represents the Food and Drug Administration’s (FDA’s) current thinking on this 
topic.  It does not create or confer any rights for or on any person and does not operate to bind 
FDA or the public.  You can use an alternative approach if the approach satisfies the 
requirements of the applicable statutes and regulations.  If you want to discuss an alternative 
approach, contact the appropriate FDA staff.  If you cannot identify the appropriate FDA staff, 
call the appropriate number listed on the title page of this guidance. 
 
 
I. 
INTRODUCTION 
 
Preventive vaccines are usually developed to prevent disease in a healthy population.  The Office 
of Vaccines Research and Review, Center for Biologics Evaluation and Research, regulates 
preventive vaccines under authority of section 351 of the Public Health Service Act (42 U.S.C. 
262), as well as specific sections of the Federal Food, Drug, and Cosmetic Act, and reviews 
investigational new drug applications (INDs) and biologics license applications (BLAs).  (See, 
for example, Title 21 Code of Federal Regulations (CFR) Parts 312, 600, and 601).  Most of the 
clinical trials of preventive vaccines conducted to support INDs and BLAs enroll healthy 
volunteers in all phases of vaccine testing.  The enrollment of healthy volunteers warrants a very 
low tolerance for risk in those clinical trials. 
 
This guidance provides you, sponsors, monitors, and investigators of vaccine trials, with 
recommendations on assessing the severity of clinical and laboratory abnormalities in healthy 
adult and adolescent volunteers enrolled in clinical trials.  The grading system described in the 
table can also be useful in defining a particular study’s stopping rules (e.g., a certain number of 
adverse events, as defined in the table, may call for stopping the study).  Less extreme 
observations (e.g., mild) may not require discontinuing the study vaccine but can still contribute 
to evaluating safety by identifying parameters to focus upon in subsequent product development.  
Uniform criteria for categorizing toxicities in healthy volunteers can improve comparisons of 
safety data among groups within the same study and also between different studies.  We, FDA, 
recommend using toxicity grading scale tables, provided below, as a guideline for selecting the 
assessment criteria to be used in a clinical trial of a preventive vaccine.  We recommend 
incorporation of such appropriate, uniform, criteria into the investigational plan, case report 
forms, and study reports and correspondence with FDA, sponsors, monitors, investigators, and 
IRBs. 
 
This guidance finalizes the draft guidance of the same title dated April 2005 (70 FR 22664, May 
2, 2005). 
 
1 

Contains Nonbinding Recommendations 
 
FDA’s guidance documents, including this guidance, do not establish legally enforceable 
responsibilities.  Instead, guidances describe FDA’s current thinking on a topic and should be 
viewed only as recommendations, unless specific regulatory or statutory requirements are cited.  
The use of the word should in FDA’s guidances means that something is suggested or 
recommended, but not required. 
 
 
II. 
BACKGROUND 
 
Standardized toxicity assessment scales have been widely used to evaluate products treating 
specific diseases.  For example, the National Cancer Institute’s Common Toxicity Criteria Scale 
and the Division of AIDS’ Toxicity Grading Scale standardize the evaluation of adverse events 
among patients with cancer and HIV/AIDS, respectively (Refs. 1, 2).  The defined toxicity 
parameters in those scales are designed for patients who may already experience mild, moderate, 
or severe adverse clinical or laboratory events due to the disease process, and may not be 
appropriate for healthy volunteers. 
 
In the development of the toxicity grading scales for healthy volunteers, we chose parameter 
limit values based on published information, when such values were available (Refs. 1-6).  For 
example, the Brighton Collaboration has developed case definitions and guidelines to evaluate 
some adverse events associated with administering vaccines (Ref. 3).  In some cases, parameter 
limit values were based on clinical experience and experience reviewing vaccine clinical trials 
that enroll normal healthy subjects. 
 
Toxicity grading scales for laboratory abnormalities should consider the local laboratory 
reference values when the parameter limit values are defined.  The characterization of laboratory 
parameters among some populations of healthy adults and adolescents may require the exercise 
of clinical judgment, for example, consideration of the potential for ethnic differences in white 
blood cell (WBC) counts or gender differences in creatine phosphokinase (CPK) values. 
 
 
III. 
TOXICITY GRADING SCALE TABLES 
 
Adverse events in a clinical trial of an investigational vaccine must be recorded and monitored 
and, when appropriate, reported to FDA and others involved in an investigation (sponsors, IRBs, 
and investigators).  (See, for example, 21 CFR 312.32, 312.33, 312.50, 312.55, 312.56, 312.60, 
312.62, 312.64, 312.66).  Although the use of a toxicity grading scale for adverse events would 
not replace these regulatory requirements, using a scale to categorize adverse events observed 
during a clinical trial may assist you in monitoring safety and making required reports.  
Nonetheless, we believe that categorization or grading of data as outlined in this document is 
supplementary to and should not replace full and complete data analysis. 
 
These guidelines for toxicity grading scales are primarily intended for healthy adult and 
adolescent volunteers.  The parameters in the tables below are not necessarily applicable to every 
clinical trial of healthy volunteers.  The parameters monitored should be appropriate for the 
specific study vaccine.  For some preventive vaccines under development, it may be appropriate 
2 

Contains Nonbinding Recommendations 
 
to include additional parameters to be monitored during a clinical trial or to alter the choice of 
values in the toxicity table.  For example, additional parameters might be added based on one or 
more of the following:  safety signals observed in pre-clinical toxicology studies, the biological 
plausibility of the occurrence of certain adverse events, or previous experience with a similar 
licensed product. 
 
As discussed above, the tables do not represent a recommendation to monitor all the listed 
parameters in all clinical trials of healthy volunteers, nor do the tables represent all possible 
parameters to be monitored.  In addition, these tables do not represent study inclusion or 
exclusion criteria.  We recommend that the parameters monitored be appropriate for the study 
vaccine administered to healthy volunteers participating in the clinical trial. 
 
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  
Emergency room 
(ER) visit or 
hospitalization 
Tenderness 
Mild discomfort to 
touch 
Discomfort with 
movement 
Significant 
discomfort at rest 
ER visit or 
hospitalization 
Erythema/Redness * 
2.5 – 5 cm 
5.1 – 10 cm 
> 10 cm 
Necrosis or 
exfoliative 
dermatitis 
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 
* 
In addition to grading the measured local reaction at the greatest single diameter, the measurement should be 
 
recorded as a continuous variable. 
** Induration/Swelling should be evaluated and graded using the functional scale as well as the actual measurement. 
3 

Contains Nonbinding Recommendations 
 
 
Vital Signs * 
Mild (Grade 1) 
Moderate(Grade 2) 
Severe (Grade 3) 
Potentially Life 
Threatening 
(Grade 4) 
Fever (°C) ** 
          (°F) ** 
38.0 – 38.4 
100.4 – 101.1 
38.5 – 38.9 
101.2 – 102.0 
39.0 – 40 
102.1 – 104 
> 40 
> 104 
Tachycardia - beats per 
minute 
101 – 115 
116 – 130 
> 130 
ER visit or 
hospitalization for 
arrhythmia 
Bradycardia - beats per 
minute***  
50 – 54 
45 – 49 
< 45 
ER visit or 
hospitalization for 
arrhythmia 
Hypertension (systolic) - 
mm Hg 
141 – 150 
151 – 155 
> 155 
ER visit or 
hospitalization for 
malignant 
hypertension 
Hypertension (diastolic) -  
mm Hg 
91 – 95 
96 – 100 
> 100 
ER visit or 
hospitalization for 
malignant 
hypertension 
Hypotension (systolic) – 
mm Hg 
85 – 89 
80 – 84 
< 80 
ER visit or 
hospitalization for 
hypotensive shock 
Respiratory Rate – breaths 
per minute 
17 – 20 
21 – 25 
> 25 
Intubation 
* 
Subject should be at rest for all vital sign measurements. 
** Oral temperature; no recent hot or cold beverages or smoking. 
*** When resting heart rate is between 60 – 100 beats per minute.  Use clinical judgement when characterizing 
 
bradycardia among some healthy subject populations, for example, conditioned athletes. 
 
 
Systemic (General) 
Mild (Grade 1) 
Moderate(Grade 2) 
Severe (Grade 3) 
Potentially Life 
Threatening 
(Grade 4) 
Nausea/vomiting 
No interference 
with activity or 1 – 2
episodes/24 hours 
Some interference 
with activity or > 2 
episodes/24 hours  
Prevents daily 
activity, requires 
outpatient IV 
hydration 
ER visit or 
hospitalization for 
hypotensive shock 
Diarrhea 
2 – 3 loose stools or
< 400 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 
ER visit or 
hospitalization 
Headache 
No interference with
activity 
Repeated use of non- 
narcotic pain 
reliever > 24 hours or
some interference 
with activity  
Significant; any 
use of narcotic 
pain reliever or 
prevents daily 
activity  
ER visit or 
hospitalization 
Fatigue 
No interference with
activity 
Some interference 
with activity 
Significant; 
prevents daily 
activity 
ER visit or 
hospitalization 
Myalgia 
No interference with
activity 
Some interference 
with activity 
Significant; 
prevents daily 
activity 
ER visit or 
hospitalization 
4 

Contains Nonbinding Recommendations 
 
 
Systemic Illnes 
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 
ER visit or 
hospitalization 
 
5 

Contains Nonbinding Recommendations 
 
B. 
Tables for Laboratory Abnormalities 
 
The laboratory values provided in the tables below serve as guidelines and are dependent 
upon institutional normal parameters.  Institutional normal reference ranges should be 
provided to demonstrate that they are appropriate. 
 
Serum * 
Mild (Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially Life 
Threatening 
(Grade 4)** 
Sodium – Hyponatremia mEq/L 
132 – 134 
130 – 131 
125 – 129 
< 125  
Sodium – Hypernatremia mEq/L 
144 – 145  
146 – 147  
148 – 150  
> 150  
Potassium – Hyperkalemia mEq/L 
5.1 – 5.2  
5.3 – 5.4 
5.5 – 5.6 
> 5.6  
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. 
6 

Contains Nonbinding Recommendations 
 
 
Hematology * 
Mild (Grade 1) 
Moderate 
(Grade 2) 
Severe (Grade 3) 
Potentially Life 
Threatening 
(Grade 4) 
Hemoglobin (Female) - gm/dL 
11.0 – 12.0 
9.5 – 10.9 
8.0 – 9.4 
< 8.0 
Hemoglobin (Female) 
change from baseline value -  gm/dL 
Any decrease – 1.5 
1.6 – 2.0 
2.1 – 5.0 
> 5.0 
Hemoglobin (Male) - gm/dL 
12.5 – 13.5 
10.5 – 12.4 
8.5 – 10.4 
< 8.5 
Hemoglobin (Male) 
change from baseline value – gm/dL 
Any decrease – 1.5  
1.6 – 2.0 
2.1 – 5.0 
> 5.0 
WBC Increase - cell/mm3
10,800 – 15,000 
15,001 – 20,000  
20,001 – 25, 000 
> 25,000 
WBC Decrease - cell/mm3
2,500 – 3,500 
1,500 – 2,499 
1,000 – 1,499 
< 1,000 
Lymphocytes Decrease - cell/mm3
750 – 1,000 
500 – 749 
250 – 499 
< 250 
Neutrophils Decrease - cell/mm3
1,500 – 2,000 
1,000 – 1,499 
500 – 999 
< 500 
Eosinophils - cell/mm3
650 – 1500 
1501 - 5000 
> 5000 
Hypereosinophilic 
Platelets Decreased - cell/mm3
125,000 – 140,000 
100,000 – 124,000 
25,000 – 99,000 
< 25,000 
PT – increase by factor 
(prothrombin time) 
1.0 – 1.10 x 
ULN** 
1.11 – 1.20 x ULN 
1.21 – 1.25 x ULN 
> 1.25 ULN 
PTT – increase by factor 
(partial thromboplastin time) 
1.0 – 1.2 x ULN 
1.21 – 1.4 x ULN 
1.41 – 1.5 x ULN 
> 1.5 x ULN 
Fibrinogen increase - mg/dL 
400 – 500  
501 – 600  
> 600  
-- 
Fibrinogen decrease - mg/dL 
150 – 200 
125 – 149 
100 – 124 
< 100 or associated 
with gross bleeding 
or disseminated 
intravascular 
coagulation (DIC) 
* 
The laboratory values provided in the tables serve as guidelines and are dependent upon institutional normal 
parameters.  Institutional normal reference ranges should be provided to demonstrate that they are appropriate. 
** “ULN” is the upper limit of the normal range. 
 
 
Urine * 
Mild (Grade 1) 
Moderate 
(Grade 2) 
Severe (Grade 3) 
Potentially Life 
Threatening 
(Grade 4) 
Protein 
Trace 
1+ 
2+ 
Hospitalization or 
dialysis 
Glucose 
Trace 
1+ 
2+ 
Hospitalization for 
hyperglycemia 
Blood (microscopic) – 
red blood cells per 
high power field (rbc/hpf) 
1 - 10 
11 – 50 
> 50 and/or gross 
blood 
Hospitalization or 
packed red blood 
cells (PRBC) 
transfusion 
* 
The laboratory values provided in the tables serve as guidelines and are dependent upon institutional normal 
parameters.  Institutional normal reference ranges should be provided to demonstrate that they are appropriate. 
7 

Contains Nonbinding Recommendations 
 
IV. 
REFERENCES  
 
1. National Cancer Institute Common Toxicity Criteria, April 30, 1999.  
(http://ctep.cancer.gov/reporting/CTC-3.html) 
 
2. Division of AIDS Table for Grading Severity of Adult Adverse Experiences; August 1992.  
(http://rcc.tech-res-intl.com/tox_tables.htm) 
 
3. The Brighton Collaboration.  Finalized Case Definitions and Guidelines.  
(http://brightoncollaboration.org/internet/en/index/definition___guidelines.html) 
 
4. HIV Vaccine Trials Network Table for Grading Severity of Adverse Experiences; September 
18, 2002.  (http://rcc.tech-res-intl.com/tox_tables.htm) 
 
5. Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, 
December 2004.  
(http://www3.niaid.nih.gov/research/resources/DAIDSClinRsrch/PDF/Safety/DAIDSAEGra
dingTable.pdf) 
 
6. Kratz A, Ferraro M, Sluss PM, Lewandrowski KB.  Laboratory Reference Values.  New 
England Journal of Medicine.  2004;351:1548-1563. 
8 

GLS-5700 
    
 ZIKA-001 
GeneOne Life Science, Inc. 
Clinical Protocol 
Date: 1 July 2016 
 
v 1.2 
-62- 
 
Appendix C:   CELLECTRA® Error Reporting Form 
 
 
Please complete the form and fax to (267) 440-4242 or scan the form to EPerror@inovio.com 
Protocol#  
Site#  
Participant 
 ID Week#  
Visit Date 
DEVICEINFORMATION 
CELLECTRA® Serial No: 
Located on label on the front cover 
CELLECTRA® Applicator Serial No: 
Located on label on the handle 
CELLECTRA® Array Lot No: 
Located on label on the package 
Time of Electroporation: 
Location of Treatment/EP: ☐ Deltoid Right/Left 
ϒ Other Location, specify: 
Was IM-5PEP guide used? ☐ YES ☐ NO 
If EP Guide was used, please provide reason and include participant’s BMI. 
Was injection successful? ☐ YES ☐ NO 
If NO, please provide reason and include needle gauge and syringe volume used. 
Did the display on the device read EP successful?  
☐ YES ☐ NO 
If NO, please check all complications that led to failure and describe complication below 
☐ Impedance Test Error message displayed, fill out Impedance Test Error section below 
☐ Electroporation Error message displayed, fill out Electroporation Error section below 
☐ EP aborted by trigger or keypad error message displayed 
☐ Battery level too low for electroporation message displayed 
☐ Difficulty inserting array into muscle or skin 
☐ Other, please specify below 
Describe device complication below (continue on back if necessary): 
Total # of arrays used: 
Impedance Test Error 
Was the array inserted in participant’s arm?  
☐ YES ☐ NO # of attempts: 
Were all attempts performed on the same day?  
☐ YES ☐ NO 
 
(provide other date(s): 
Was a different location used for each attempt? 
☐ YES ☐ NO 
Was a new array used for each attempt?  
☐ YES ☐ NO 
Please provide any additional information below (continue on back if necessary): 
Electroporation Error 
Were there 3 (IM) or 4 (ID) involuntary muscle contractions?  ☐ YES ☐ NO (how many 
Was the array fully inserted in the participant’s arm?  
☐ YES ☐ NO 
Was the array inserted perpendicular to the participant’s skin?  
☐ YES ☐ NO 
Did the needles of the array appear damaged in any way?  
☐ YES ☐ NO 
If you were provided a sharps shuttle, please eject the array into a shuttle and ship to Inovio.