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VRC 705: A Zika Virus DNA Vaccine in Healthy Adults and Adolescents (DNA)

Primary Purpose

Zika Virus, Zika Virus Infection, Virus Diseases

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
VRC-ZKADNA090-00-VP
VRC-PBSPLA043-00-VP
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Zika Virus focused on measuring Flavivirus, Zika, Vaccine, Physiological Effects of Drugs, Immunologic Factors, Virus-like Particles, Zika vaccine

Eligibility Criteria

15 Years - 35 Years (Child, Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

A participant must meet all of the following criteria:

Part A:

  • 18 to 35 years of age
  • Available for clinical follow-up through Study Week 32
  • Accessible injection sites on each limb as follows: 1 injection site in the deltoid muscle of each arm and 1 injection site in the vastus lateralis muscle of each anterolateral thigh

Part B:

  • 15 to 35 years of age
  • Available for clinical follow-up through Study Week 96
  • Accessible injection sites on the deltoid muscle of each arm. Injection in the vastus lateralis muscle of the anterolateral thighs may have been allowed with IND Sponsor approval if an injection site on each deltoid muscle was not available.

Part A and B:

  • Able to provide proof of identity to the satisfaction of the clinician completing the enrollment process
  • Able and willing to complete the informed consent/assent process
  • Able and willing to complete the Assessment of Understanding and to verbalize understanding of all questions answered incorrectly prior to signing consent/assent
  • Willing to donate blood and urine to be stored and used for future research
  • In good general health without clinically significant medical history
  • Physical examination and laboratory results without clinically significant findings within the 56 days prior to randomization
  • Weight >30 kilograms (kg)
  • Agree not to receive any licensed or investigational flavivirus vaccines through 4 weeks after last product administration

Laboratory Criteria within 56 days prior to randomization:

  • Hemoglobin within site institutional normal limits
  • Absolute neutrophil count (ANC) within site institutional normal limits
  • Total lymphocyte count ≥800 cells/mm^3
  • Platelets = 125,000-510,000 cells/mm^3
  • Alanine aminotransferase (ALT) ≤1.5 x upper limit of normal (ULN) based on site institutional normal range for respective age group
  • Serum creatinine ≤1.2 x ULN based on site institutional normal range for respective age group
  • Negative result on a human immunodeficiency virus (HIV) test that meets local standards for identification of HIV infection

Criteria applicable to women and adolescents of childbearing potential:

  • Negative result on a human chorionic gonadotropin pregnancy test (urine or serum) on day of randomization before receiving study product
  • Agree to use effective means of birth control from at least 21 days before randomization through 12 weeks after the last product administration

Criteria applicable to adolescents:

  • Capability of the parent/guardian of the minor to understand and comply with planned study procedures
  • Capability of the minor and their parent/guardian to provide informed consent/assent

Exclusion Criteria:

Criteria applicable to women and adolescents of childbearing potential:

• Breast-feeding or planning to become pregnant while participating through 12 weeks after the last product administration

Participant has received any of the following:

  • More than 10 days of systemic immunosuppressive medications or cytotoxic medications within the 4 weeks prior to randomization
  • Any systemic immunosuppressive medications or cytotoxic medications within the 14 days prior to randomization
  • Blood products within 16 weeks prior to randomization
  • Immunoglobulin within 8 weeks prior to randomization
  • Investigational research agents within 4 weeks prior to randomization or planning to receive investigational products while on the study
  • Any vaccination within 2 weeks prior to randomization
  • Any live attenuated vaccination within 4 weeks prior to randomization
  • Current anti-tuberculosis (TB) prophylaxis or therapy

Participant has any of the following:

  • Confirmed history of ZIKV infection (as reported by participant)
  • Serious reactions to vaccines
  • Chronic angioedema or chronic urticaria
  • Asthma that is not well-controlled
  • Diabetes mellitus (type I or II)
  • Clinically significant autoimmune disease or immunodeficiency
  • Hypertension that is not well-controlled
  • Bleeding disorder diagnosed by a doctor (e.g., factor deficiency, coagulopathy, or platelet disorder requiring special precautions)
  • Significant bruising or bleeding difficulties with IM injections or blood draws
  • Malignancy that is active or history of a malignancy that is likely to recur during the period of the study
  • Seizure or treatment for a seizure disorder within the last 3 years
  • Asplenia, functional asplenia or any condition resulting in the absence or removal of the spleen
  • History of Guillain-Barré Syndrome
  • Psychiatric condition that may preclude compliance with the protocol; past or present psychoses; or a history of suicide plan or attempt within 5 years prior to randomization
  • Any medical psychiatric, or social condition that, in the judgment of the investigator, is a contraindication to protocol participation or impairs a participant's ability to give informed consent

Sites / Locations

  • QPS-Miami Research Associates
  • Doctors Hospital at Renaissance
  • Baylor College of Medicine
  • Hospital Das Clinicas Da Universidade Federal de Minas Gerais
  • Centro de Pesquisas Clínicas Do Instituto Central Do Hospital Das Clínicas Da FMUSP
  • Clinica de la Costa Ltda
  • Centro de Atencion y Diagnostico de Enfermedades Infecciosas
  • CCIM Costa Rican Center Center of Medical Research, Sociedad Anonima
  • AGA Clinical Centro de Investigaciones
  • Hospital Civil Fray Antonio Alcalde
  • Instituto Conmemorativo Gorgas
  • Asociacion Civil Selva Amazonica
  • Unidad de Ensayos (UNIDEC) del Policlinico Universidad Nacional Mayor de San Marcos
  • Ponce Medical School Foundation Inc./CAIMED Center
  • Fundación de Investigación de Diego
  • San Juan Hospital Research Unit
  • Puerto Rico Clinical and Translational Research Consortium

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Placebo Comparator

Arm Label

Part A, Group 1: VRC-ZKADNA090-00-VP (4 mg), 2 injections

Part A, Group 2: VRC-ZKADNA090-00-VP (4 mg), 4 injections

Part A, Group 3: VRC-ZKADNA090-00-VP (8 mg), 4 injections

Part B, Group 4: VRC-ZKADNA090-00-VP (4 mg), 2 injections

Part B, Group 5: Placebo (VRC-PBSPLA043-00-VP), 2 injections

Arm Description

Zika virus wildtype (ZIKVwt) DNA vaccine (VRC-ZKADNA090-00-VP), in 2 limbs (both arms) on Day 0, Day 28 (+/-7 days), and Day 56 (-7/+14 days); 4 mg of vaccine administered intramuscularly (IM) by a needle-free injection device

ZIKVwt DNA vaccine (VRC-ZKADNA090-00-VP), in 4 limbs (both arms and legs) on Day 0, Day 28 (+/-7 days), and Day 56 (-7/+14 days); 4 mg of vaccine administered IM by a needle-free injection device

ZIKVwt DNA vaccine (VRC-ZKADNA090-00-VP), in 4 limbs (both arms and legs) on Day 0, Day 28 (+/-7 days), and Day 56 (-7/+14 days); 8 mg of vaccine administered IM by a needle-free injection device

ZIKVwt DNA vaccine (VRC-ZKADNA090-00-VP), in 2 limbs (both arms) on Day 0, Day 28 (+/-7 days), and Day 56 (-7/+14 days); 4 mg of vaccine administered IM by a needle-free injection device

Sterile phosphate-buffered saline (PBS) (VRC-PBSPLA043-00-VP), the placebo, in 2 limbs (both arms) on Day 0, Day 28 (+/-7 days), and Day 56 (-7/+14 days); 1 mL of placebo administered IM by a needle-free injection device

Outcomes

Primary Outcome Measures

Number of Participants Reporting Local Reactogenicity Signs and Symptoms for 7 Days After Each Product Administration (Part A and Part B)
Participants recorded the occurrence of solicited symptoms on a diary card for 7 days after each study product administration and reviewed the diary card with clinic staff at a follow up visit. Participants were counted once for each symptom at the worst severity if they indicated experiencing the symptom more than one time at any severity during the reporting period. The number reported for "Any Local Symptom" is the number of participants reporting any local symptom at the worst severity. Reactogenicity grading (Mild, Moderate, Severe) was done using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (FDA Guidance - September 2007).
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms for 7 Days After Each Product Administration (Part A and Part B)
Participants recorded the occurrence of solicited symptoms on a diary card for 7 days after each study product administration and reviewed the diary card with clinic staff at a follow up visit. Participants were counted once for each symptom at the worst severity if they indicated experiencing the symptom more than once at any severity during the reporting period. The number reported for "Any Systemic Symptom" is the number of participants reporting any systemic symptom at the worst severity. Reactogenicity grading (Mild, Moderate, Severe) was done using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (FDA Guidance - September 2007).
Number of Participants With Abnormal Laboratory Measures of Safety (Part A)
Any abnormal laboratory results recorded as unsolicited AEs are summarized. Safety laboratory parameters included: alanine aminotransferase (ALT), white blood cells (WBC), red blood cells (RBC), hemoglobin, hematocrit, mean corpuscular volume (MCV), platelets, neutrophils, lymphocytes, monocytes, eosinophils, and basophils. Laboratory safety evaluations were scheduled at baseline and weeks 4, 6, 8, 10, 12, and 16. Institutional laboratory normals as well as the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventative Vaccine Clinical Trials FDA Guidance, September 2007 were used.
Number of Participants With Abnormal Laboratory Measures of Safety (Part B)
Any abnormal laboratory results recorded as unsolicited AEs are summarized. Safety laboratory parameters included: alanine aminotransferase (ALT), white blood cells (WBC), red blood cells (RBC), hemoglobin, hematocrit, mean corpuscular volume (MCV), platelets, neutrophils, lymphocytes, monocytes, eosinophils, and basophils. Laboratory safety evaluations were scheduled at baseline and weeks 4, 8, 16, and 44. Institutional laboratory normals as well as the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventative Vaccine Clinical Trials FDA Guidance, September 2007 were used.
Number of Participants With Serious Adverse Events (SAEs) Following Product Administration (Part A)
Any SAEs recorded from receipt of first study product administration through the last expected study visit at Day 224 are summarized. The relationship between a SAE and the study product was assessed by the investigator on the basis of his or her clinical judgment and the definitions outlined in the protocol.
Number of Participants With Serious Adverse Events (SAEs) Following Product Administration (Part B)
Any SAEs recorded from receipt of first study product administration through the last expected study visit at Day 672 are summarized. The relationship between a SAE and the study product was assessed by the investigator on the basis of his or her clinical judgment and the definitions outlined in the protocol.
Number of Participants With New Chronic Medical Conditions Following Product Administration (Part A)
New onset chronic medical conditions were reported from receipt of first study product administration through the last expected study visit at Day 224.The relationship between a chronic medical condition and the study product was assessed by the investigator on the basis of his or her clinical judgment and the definitions outlined in the protocol.
Number of Participants With New Chronic Medical Conditions Following Product Administration (Part B)
New onset chronic medical conditions were reported from receipt of first study product administration through the last expected study visit at Day 672.The relationship between a chronic medical condition and the study product was assessed by the investigator on the basis of his or her clinical judgment and the definitions outlined in the protocol.
Number of Participants With One or More Unsolicited Non-Serious Adverse Events (AEs) Following Product Administration (Part A and Part B)
Unsolicited AEs and attribution assessments were recorded in the study database from receipt of the first study product administration through the one month visit that followed the last study product administration (Visit 05), 84 days for both Parts A and B for participants who received all three study product administrations. If a participant received the first and second product administrations but not the third, then the time frame was through 56 days (Visit 04). If a participant only received the first product administration but not the second or third, then the time frame was through 28 days (Visit 03). The relationship between an AE and the study product was assessed by the investigator on the basis of his or her clinical judgment and the definitions outlined in the protocol. A participant with multiple experiences of the same event is counted once using the event of worst severity.
Number of Participants With Virologically Confirmed Cases of ZIKV (Part B Only)
Virologically confirmed Zika infection, irrespective of symptoms, by polymerase chain reaction (PCR) in blood or in urine were recorded from receipt of first study product administration through the last expected study visit.

Secondary Outcome Measures

Zika Antigen-specific Neutralizing Antibody Geometric Mean Titer (GMT) - (Part A)
Antibody response as measured by ZIKV neutralization antibody (NAb) assay. Neutralizing activity is reported as the dilution of sera required to neutralize eighty percent of infection events (EC80).
Number of Participants With Positive Response to Zika Antigen-specific Neutralizing Antibody (Part A)
A participant was a responder or met the threshold of a positive response if the post vaccination anti-ZIKV antibody titer was 30 or greater.
Number of Participants With Subclinical Cases of ZIKV (Part B Only)
Virologically confirmed cases of Zika infection without clinical signs or symptoms were recorded from receipt of first study product administration through the last expected study visit by PCR virus detection in blood of participants at regularly defined intervals. Subclinical cases of ZIKV infection were identified by retrospective PCR.
Zika Antigen-specific Neutralizing Antibody Geometric Mean Titer (GMT) - (Part B)
Antibody response as measured by ZIKV neutralization antibody (NAb) assay. Neutralizing activity is reported as the dilution of sera required to neutralize eighty percent of infection events (EC80). Data is not yet available for this outcome measure as this particular outcome is based on the results from retrospective ZIKV neutralizing antibody assays which are still being performed on the samples. Outcome measure data will be provided once testing is complete. Testing is anticipated to be completed in 2022 and data will be reported as soon as it is available.
Number of Participants With Positive Response to Zika Antigen-specific Neutralizing Antibody (Part B)
A participant is a responder or met the threshold of a positive response if the post vaccination anti-ZIKV antibody titer was 30 or greater. Data is not yet available for this outcome measure as it is based on the results from retrospective ZIKV PCR assays which are still being performed on the samples. There are tens of thousands of samples that are still being tested for this outcome measure and outcome measure data will be provided once testing is complete. Testing is anticipated to be completed in 2022 and data will be reported as soon as it is available.

Full Information

First Posted
March 28, 2017
Last Updated
January 10, 2023
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
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1. Study Identification

Unique Protocol Identification Number
NCT03110770
Brief Title
VRC 705: A Zika Virus DNA Vaccine in Healthy Adults and Adolescents
Acronym
DNA
Official Title
VRC 705: A Phase 2/2B, Randomized Trial to Evaluate the Safety, Immunogenicity and Efficacy of a Zika Virus DNA Vaccine in Healthy Adults and Adolescents
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Completed
Study Start Date
March 29, 2017 (Actual)
Primary Completion Date
October 4, 2019 (Actual)
Study Completion Date
October 4, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This was a multicenter, randomized study to evaluate the safety, immunogenicity, and efficacy of VRC-ZKADNA090-00-VP (Zika virus wildtype DNA vaccine) or placebo. In Part A, the primary objective was to evaluate the safety and tolerability of the vaccine in different vaccination regimens. In Part B, the primary objectives were to evaluate the safety and efficacy of the vaccine compared to placebo.
Detailed Description
This was a multicenter, randomized study to evaluate safety, immunogenicity, and efficacy of a 3-dose vaccination regimen with the Zika virus wildtype (ZIKVwt) DNA vaccine (VRC-ZKADNA090-00-VP) or placebo (VRC-PBSPLA043-00-VP). The placebo was a sterile phosphate-buffered saline (PBS). The hypotheses were that the ZIKVwt DNA vaccine would be safe and would elicit a ZIKV-specific immune response. Participants received study product intramuscularly (IM) in the limbs as specified by the group assignment by PharmaJet needle-free device. In Part A, 90 participants were randomized to vaccine at a 1:1:1 ratio to receive a 4 mg dose split between 2 injections, 4 mg dose split between 4 injections or 8 mg dose split between 4 injections. In Part B, 2338 participants were randomized to vaccine or placebo in a 1:1 ratio to receive a 4 mg (1 mL) dose of vaccine or 1 mL of placebo split between 2 injections. The vaccine dose and administration plan for Part B was selected based on Part A and Phase 1 data. Vaccine safety and tolerability were assessed by monitoring of clinical and laboratory parameters throughout the study. Solicited reactogenicity symptoms were collected for 7 days after each product administration. The study schedule included clinic visits with safety and immunogenicity blood samples collected at particular time points. Vaccine efficacy was evaluated in Part B by comparing incidence of virologic ZIKV cases between vaccine and placebo groups. During the study, when participants exhibited any possible symptom of ZIKV infection, they were evaluated by blood and urine ZIKV polymerase chain reaction (PCR). Stored blood samples were also assessed retrospectively by ZIKV PCR to identify possible asymptomatic cases. A Data and Safety Monitoring Board (DSMB) oversaw the study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Zika Virus, Zika Virus Infection, Virus Diseases, Flavivirus Infections, Flaviviral Diseases, Flaviviridae Infections, RNA Virus Infections
Keywords
Flavivirus, Zika, Vaccine, Physiological Effects of Drugs, Immunologic Factors, Virus-like Particles, Zika vaccine

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Model Description
Part A participants (n=90) were randomized to study groups at a 1:1:1 ratio to receive a 4 mg or 8 mg dose of vaccine split between 2 or 4 injections. In Part B, participants (n=2338) were randomized to vaccine or placebo in a 1:1 ratio to receive a 4 mg (1 mL) dose of vaccine or 1 mL of placebo split between 2 injections. The vaccine dose and number of injections in Part B was determined by preliminary data from the Phase 1 trial and from Part A.
Masking
ParticipantInvestigatorOutcomes Assessor
Masking Description
Part A was open-label. For Part A, the participant, investigator and outcome assessor knew what the participant received. Part B injections were prepared by an unblinded site pharmacist or designee who was not involved in any participant assessments and did not discuss randomizations with study clinicians. Participants, study personnel, site data entry personnel, and laboratory personnel performing immunologic assays were blinded to the treatment assignment of all product administrations. The investigational new drug (IND) Sponsor unblinded treatment assignments for Part B at the end of the study.
Allocation
Randomized
Enrollment
2428 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Part A, Group 1: VRC-ZKADNA090-00-VP (4 mg), 2 injections
Arm Type
Experimental
Arm Description
Zika virus wildtype (ZIKVwt) DNA vaccine (VRC-ZKADNA090-00-VP), in 2 limbs (both arms) on Day 0, Day 28 (+/-7 days), and Day 56 (-7/+14 days); 4 mg of vaccine administered intramuscularly (IM) by a needle-free injection device
Arm Title
Part A, Group 2: VRC-ZKADNA090-00-VP (4 mg), 4 injections
Arm Type
Experimental
Arm Description
ZIKVwt DNA vaccine (VRC-ZKADNA090-00-VP), in 4 limbs (both arms and legs) on Day 0, Day 28 (+/-7 days), and Day 56 (-7/+14 days); 4 mg of vaccine administered IM by a needle-free injection device
Arm Title
Part A, Group 3: VRC-ZKADNA090-00-VP (8 mg), 4 injections
Arm Type
Experimental
Arm Description
ZIKVwt DNA vaccine (VRC-ZKADNA090-00-VP), in 4 limbs (both arms and legs) on Day 0, Day 28 (+/-7 days), and Day 56 (-7/+14 days); 8 mg of vaccine administered IM by a needle-free injection device
Arm Title
Part B, Group 4: VRC-ZKADNA090-00-VP (4 mg), 2 injections
Arm Type
Experimental
Arm Description
ZIKVwt DNA vaccine (VRC-ZKADNA090-00-VP), in 2 limbs (both arms) on Day 0, Day 28 (+/-7 days), and Day 56 (-7/+14 days); 4 mg of vaccine administered IM by a needle-free injection device
Arm Title
Part B, Group 5: Placebo (VRC-PBSPLA043-00-VP), 2 injections
Arm Type
Placebo Comparator
Arm Description
Sterile phosphate-buffered saline (PBS) (VRC-PBSPLA043-00-VP), the placebo, in 2 limbs (both arms) on Day 0, Day 28 (+/-7 days), and Day 56 (-7/+14 days); 1 mL of placebo administered IM by a needle-free injection device
Intervention Type
Biological
Intervention Name(s)
VRC-ZKADNA090-00-VP
Intervention Description
VRC-ZKADNA090-00-VP is composed of a single closed-circular DNA plasmid (VRC 5283) that encodes with wild type (wt) precursor transmembrane M (prM) and envelope (E) proteins from the H/PF/2013 strain of ZIKV
Intervention Type
Other
Intervention Name(s)
VRC-PBSPLA043-00-VP
Other Intervention Name(s)
Placebo
Intervention Description
A sterile phosphate-buffered saline (PBS) prepared for human administration as a placebo
Primary Outcome Measure Information:
Title
Number of Participants Reporting Local Reactogenicity Signs and Symptoms for 7 Days After Each Product Administration (Part A and Part B)
Description
Participants recorded the occurrence of solicited symptoms on a diary card for 7 days after each study product administration and reviewed the diary card with clinic staff at a follow up visit. Participants were counted once for each symptom at the worst severity if they indicated experiencing the symptom more than one time at any severity during the reporting period. The number reported for "Any Local Symptom" is the number of participants reporting any local symptom at the worst severity. Reactogenicity grading (Mild, Moderate, Severe) was done using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (FDA Guidance - September 2007).
Time Frame
7 days after each product administration
Title
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms for 7 Days After Each Product Administration (Part A and Part B)
Description
Participants recorded the occurrence of solicited symptoms on a diary card for 7 days after each study product administration and reviewed the diary card with clinic staff at a follow up visit. Participants were counted once for each symptom at the worst severity if they indicated experiencing the symptom more than once at any severity during the reporting period. The number reported for "Any Systemic Symptom" is the number of participants reporting any systemic symptom at the worst severity. Reactogenicity grading (Mild, Moderate, Severe) was done using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (FDA Guidance - September 2007).
Time Frame
7 days after each product administration
Title
Number of Participants With Abnormal Laboratory Measures of Safety (Part A)
Description
Any abnormal laboratory results recorded as unsolicited AEs are summarized. Safety laboratory parameters included: alanine aminotransferase (ALT), white blood cells (WBC), red blood cells (RBC), hemoglobin, hematocrit, mean corpuscular volume (MCV), platelets, neutrophils, lymphocytes, monocytes, eosinophils, and basophils. Laboratory safety evaluations were scheduled at baseline and weeks 4, 6, 8, 10, 12, and 16. Institutional laboratory normals as well as the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventative Vaccine Clinical Trials FDA Guidance, September 2007 were used.
Time Frame
Day 0 after first product administration through Day 112
Title
Number of Participants With Abnormal Laboratory Measures of Safety (Part B)
Description
Any abnormal laboratory results recorded as unsolicited AEs are summarized. Safety laboratory parameters included: alanine aminotransferase (ALT), white blood cells (WBC), red blood cells (RBC), hemoglobin, hematocrit, mean corpuscular volume (MCV), platelets, neutrophils, lymphocytes, monocytes, eosinophils, and basophils. Laboratory safety evaluations were scheduled at baseline and weeks 4, 8, 16, and 44. Institutional laboratory normals as well as the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventative Vaccine Clinical Trials FDA Guidance, September 2007 were used.
Time Frame
Day 0 after first product administration through Day 308
Title
Number of Participants With Serious Adverse Events (SAEs) Following Product Administration (Part A)
Description
Any SAEs recorded from receipt of first study product administration through the last expected study visit at Day 224 are summarized. The relationship between a SAE and the study product was assessed by the investigator on the basis of his or her clinical judgment and the definitions outlined in the protocol.
Time Frame
Day 0 through Day 224
Title
Number of Participants With Serious Adverse Events (SAEs) Following Product Administration (Part B)
Description
Any SAEs recorded from receipt of first study product administration through the last expected study visit at Day 672 are summarized. The relationship between a SAE and the study product was assessed by the investigator on the basis of his or her clinical judgment and the definitions outlined in the protocol.
Time Frame
Day 0 through Day 672
Title
Number of Participants With New Chronic Medical Conditions Following Product Administration (Part A)
Description
New onset chronic medical conditions were reported from receipt of first study product administration through the last expected study visit at Day 224.The relationship between a chronic medical condition and the study product was assessed by the investigator on the basis of his or her clinical judgment and the definitions outlined in the protocol.
Time Frame
Day 0 through Day 224
Title
Number of Participants With New Chronic Medical Conditions Following Product Administration (Part B)
Description
New onset chronic medical conditions were reported from receipt of first study product administration through the last expected study visit at Day 672.The relationship between a chronic medical condition and the study product was assessed by the investigator on the basis of his or her clinical judgment and the definitions outlined in the protocol.
Time Frame
Day 0 through Day 672
Title
Number of Participants With One or More Unsolicited Non-Serious Adverse Events (AEs) Following Product Administration (Part A and Part B)
Description
Unsolicited AEs and attribution assessments were recorded in the study database from receipt of the first study product administration through the one month visit that followed the last study product administration (Visit 05), 84 days for both Parts A and B for participants who received all three study product administrations. If a participant received the first and second product administrations but not the third, then the time frame was through 56 days (Visit 04). If a participant only received the first product administration but not the second or third, then the time frame was through 28 days (Visit 03). The relationship between an AE and the study product was assessed by the investigator on the basis of his or her clinical judgment and the definitions outlined in the protocol. A participant with multiple experiences of the same event is counted once using the event of worst severity.
Time Frame
Day 0 through the one month visit that follows the last product administration (Visit 05), 84 days for both Parts A and B
Title
Number of Participants With Virologically Confirmed Cases of ZIKV (Part B Only)
Description
Virologically confirmed Zika infection, irrespective of symptoms, by polymerase chain reaction (PCR) in blood or in urine were recorded from receipt of first study product administration through the last expected study visit.
Time Frame
Day 0 through Day 672
Secondary Outcome Measure Information:
Title
Zika Antigen-specific Neutralizing Antibody Geometric Mean Titer (GMT) - (Part A)
Description
Antibody response as measured by ZIKV neutralization antibody (NAb) assay. Neutralizing activity is reported as the dilution of sera required to neutralize eighty percent of infection events (EC80).
Time Frame
Day 0 to 28 days after the final product administration
Title
Number of Participants With Positive Response to Zika Antigen-specific Neutralizing Antibody (Part A)
Description
A participant was a responder or met the threshold of a positive response if the post vaccination anti-ZIKV antibody titer was 30 or greater.
Time Frame
Day 0 to 28 days after the final product administration
Title
Number of Participants With Subclinical Cases of ZIKV (Part B Only)
Description
Virologically confirmed cases of Zika infection without clinical signs or symptoms were recorded from receipt of first study product administration through the last expected study visit by PCR virus detection in blood of participants at regularly defined intervals. Subclinical cases of ZIKV infection were identified by retrospective PCR.
Time Frame
Day 0 through Day 672
Title
Zika Antigen-specific Neutralizing Antibody Geometric Mean Titer (GMT) - (Part B)
Description
Antibody response as measured by ZIKV neutralization antibody (NAb) assay. Neutralizing activity is reported as the dilution of sera required to neutralize eighty percent of infection events (EC80). Data is not yet available for this outcome measure as this particular outcome is based on the results from retrospective ZIKV neutralizing antibody assays which are still being performed on the samples. Outcome measure data will be provided once testing is complete. Testing is anticipated to be completed in 2022 and data will be reported as soon as it is available.
Time Frame
Day 0 to 28 days after the final product administration
Title
Number of Participants With Positive Response to Zika Antigen-specific Neutralizing Antibody (Part B)
Description
A participant is a responder or met the threshold of a positive response if the post vaccination anti-ZIKV antibody titer was 30 or greater. Data is not yet available for this outcome measure as it is based on the results from retrospective ZIKV PCR assays which are still being performed on the samples. There are tens of thousands of samples that are still being tested for this outcome measure and outcome measure data will be provided once testing is complete. Testing is anticipated to be completed in 2022 and data will be reported as soon as it is available.
Time Frame
Day 0 to 28 days after the final product administration

10. Eligibility

Sex
All
Minimum Age & Unit of Time
15 Years
Maximum Age & Unit of Time
35 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: A participant must meet all of the following criteria: Part A: 18 to 35 years of age Available for clinical follow-up through Study Week 32 Accessible injection sites on each limb as follows: 1 injection site in the deltoid muscle of each arm and 1 injection site in the vastus lateralis muscle of each anterolateral thigh Part B: 15 to 35 years of age Available for clinical follow-up through Study Week 96 Accessible injection sites on the deltoid muscle of each arm. Injection in the vastus lateralis muscle of the anterolateral thighs may have been allowed with IND Sponsor approval if an injection site on each deltoid muscle was not available. Part A and B: Able to provide proof of identity to the satisfaction of the clinician completing the enrollment process Able and willing to complete the informed consent/assent process Able and willing to complete the Assessment of Understanding and to verbalize understanding of all questions answered incorrectly prior to signing consent/assent Willing to donate blood and urine to be stored and used for future research In good general health without clinically significant medical history Physical examination and laboratory results without clinically significant findings within the 56 days prior to randomization Weight >30 kilograms (kg) Agree not to receive any licensed or investigational flavivirus vaccines through 4 weeks after last product administration Laboratory Criteria within 56 days prior to randomization: Hemoglobin within site institutional normal limits Absolute neutrophil count (ANC) within site institutional normal limits Total lymphocyte count ≥800 cells/mm^3 Platelets = 125,000-510,000 cells/mm^3 Alanine aminotransferase (ALT) ≤1.5 x upper limit of normal (ULN) based on site institutional normal range for respective age group Serum creatinine ≤1.2 x ULN based on site institutional normal range for respective age group Negative result on a human immunodeficiency virus (HIV) test that meets local standards for identification of HIV infection Criteria applicable to women and adolescents of childbearing potential: Negative result on a human chorionic gonadotropin pregnancy test (urine or serum) on day of randomization before receiving study product Agree to use effective means of birth control from at least 21 days before randomization through 12 weeks after the last product administration Criteria applicable to adolescents: Capability of the parent/guardian of the minor to understand and comply with planned study procedures Capability of the minor and their parent/guardian to provide informed consent/assent Exclusion Criteria: Criteria applicable to women and adolescents of childbearing potential: • Breast-feeding or planning to become pregnant while participating through 12 weeks after the last product administration Participant has received any of the following: More than 10 days of systemic immunosuppressive medications or cytotoxic medications within the 4 weeks prior to randomization Any systemic immunosuppressive medications or cytotoxic medications within the 14 days prior to randomization Blood products within 16 weeks prior to randomization Immunoglobulin within 8 weeks prior to randomization Investigational research agents within 4 weeks prior to randomization or planning to receive investigational products while on the study Any vaccination within 2 weeks prior to randomization Any live attenuated vaccination within 4 weeks prior to randomization Current anti-tuberculosis (TB) prophylaxis or therapy Participant has any of the following: Confirmed history of ZIKV infection (as reported by participant) Serious reactions to vaccines Chronic angioedema or chronic urticaria Asthma that is not well-controlled Diabetes mellitus (type I or II) Clinically significant autoimmune disease or immunodeficiency Hypertension that is not well-controlled Bleeding disorder diagnosed by a doctor (e.g., factor deficiency, coagulopathy, or platelet disorder requiring special precautions) Significant bruising or bleeding difficulties with IM injections or blood draws Malignancy that is active or history of a malignancy that is likely to recur during the period of the study Seizure or treatment for a seizure disorder within the last 3 years Asplenia, functional asplenia or any condition resulting in the absence or removal of the spleen History of Guillain-Barré Syndrome Psychiatric condition that may preclude compliance with the protocol; past or present psychoses; or a history of suicide plan or attempt within 5 years prior to randomization Any medical psychiatric, or social condition that, in the judgment of the investigator, is a contraindication to protocol participation or impairs a participant's ability to give informed consent
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Julie Ledgerwood, DO
Organizational Affiliation
VRC, NIAID, NIH
Official's Role
Study Chair
Facility Information:
Facility Name
QPS-Miami Research Associates
City
Miami
State/Province
Florida
ZIP/Postal Code
33143
Country
United States
Facility Name
Doctors Hospital at Renaissance
City
Edinburg
State/Province
Texas
ZIP/Postal Code
78539
Country
United States
Facility Name
Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Hospital Das Clinicas Da Universidade Federal de Minas Gerais
City
Belo Horizonte
State/Province
MG
ZIP/Postal Code
30130-100
Country
Brazil
Facility Name
Centro de Pesquisas Clínicas Do Instituto Central Do Hospital Das Clínicas Da FMUSP
City
São Paulo
State/Province
SP
ZIP/Postal Code
05403-010
Country
Brazil
Facility Name
Clinica de la Costa Ltda
City
Barranquilla
State/Province
Atlantico
ZIP/Postal Code
080020
Country
Colombia
Facility Name
Centro de Atencion y Diagnostico de Enfermedades Infecciosas
City
Bucaramanga
State/Province
Santander
ZIP/Postal Code
680003
Country
Colombia
Facility Name
CCIM Costa Rican Center Center of Medical Research, Sociedad Anonima
City
San José
State/Province
Los Yoses
Country
Costa Rica
Facility Name
AGA Clinical Centro de Investigaciones
City
Guayaquil
State/Province
Guayas
ZIP/Postal Code
090506
Country
Ecuador
Facility Name
Hospital Civil Fray Antonio Alcalde
City
Guadalajara
State/Province
Jalisco
ZIP/Postal Code
44280
Country
Mexico
Facility Name
Instituto Conmemorativo Gorgas
City
Panamá
State/Province
San Miguelito Province
Country
Panama
Facility Name
Asociacion Civil Selva Amazonica
City
Iquitos
State/Province
Maynas/Loreto
ZIP/Postal Code
16001
Country
Peru
Facility Name
Unidad de Ensayos (UNIDEC) del Policlinico Universidad Nacional Mayor de San Marcos
City
Lima
ZIP/Postal Code
15081
Country
Peru
Facility Name
Ponce Medical School Foundation Inc./CAIMED Center
City
Ponce
ZIP/Postal Code
00716
Country
Puerto Rico
Facility Name
Fundación de Investigación de Diego
City
San Juan
ZIP/Postal Code
00927
Country
Puerto Rico
Facility Name
San Juan Hospital Research Unit
City
San Juan
ZIP/Postal Code
00935
Country
Puerto Rico
Facility Name
Puerto Rico Clinical and Translational Research Consortium
City
San Juan
ZIP/Postal Code
00936-5067
Country
Puerto Rico

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
21398392
Citation
Ledgerwood JE, Pierson TC, Hubka SA, Desai N, Rucker S, Gordon IJ, Enama ME, Nelson S, Nason M, Gu W, Bundrant N, Koup RA, Bailer RT, Mascola JR, Nabel GJ, Graham BS; VRC 303 Study Team. 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 May 15;203(10):1396-404. doi: 10.1093/infdis/jir054. Epub 2011 Mar 11.
Results Reference
background
PubMed Identifier
18190252
Citation
Martin JE, Pierson TC, Hubka S, Rucker S, Gordon IJ, Enama ME, Andrews CA, Xu Q, Davis BS, Nason M, Fay M, Koup RA, Roederer M, Bailer RT, Gomez PL, Mascola JR, Chang GJ, Nabel GJ, Graham BS. A West Nile virus DNA vaccine induces neutralizing antibody in healthy adults during a phase 1 clinical trial. J Infect Dis. 2007 Dec 15;196(12):1732-40. doi: 10.1086/523650.
Results Reference
background
PubMed Identifier
27708058
Citation
Dowd KA, Ko SY, Morabito KM, Yang ES, Pelc RS, DeMaso CR, Castilho LR, Abbink P, Boyd M, Nityanandam R, Gordon DN, Gallagher JR, Chen X, Todd JP, Tsybovsky Y, Harris A, Huang YS, Higgs S, Vanlandingham DL, Andersen H, Lewis MG, De La Barrera R, Eckels KH, Jarman RG, Nason MC, Barouch DH, Roederer M, Kong WP, Mascola JR, Pierson TC, Graham BS. Rapid development of a DNA vaccine for Zika virus. Science. 2016 Oct 14;354(6309):237-240. doi: 10.1126/science.aai9137. Epub 2016 Sep 22.
Results Reference
background
PubMed Identifier
29217376
Citation
Gaudinski MR, Houser KV, Morabito KM, Hu Z, Yamshchikov G, Rothwell RS, Berkowitz N, Mendoza F, Saunders JG, Novik L, Hendel CS, Holman LA, Gordon IJ, Cox JH, Edupuganti S, McArthur MA, Rouphael NG, Lyke KE, Cummings GE, Sitar S, Bailer RT, Foreman BM, Burgomaster K, Pelc RS, Gordon DN, DeMaso CR, Dowd KA, Laurencot C, Schwartz RM, Mascola JR, Graham BS, Pierson TC, Ledgerwood JE, Chen GL; VRC 319; VRC 320 study teams. Safety, tolerability, and immunogenicity of two Zika virus DNA vaccine candidates in healthy adults: randomised, open-label, phase 1 clinical trials. Lancet. 2018 Feb 10;391(10120):552-562. doi: 10.1016/S0140-6736(17)33105-7. Epub 2017 Dec 5.
Results Reference
background

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VRC 705: A Zika Virus DNA Vaccine in Healthy Adults and Adolescents

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