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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

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

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

NCT ID

NCT03110770

First Posted

March 28, 2017

Last Updated

January 10, 2023

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

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

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

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

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

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

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

Time Frame

Day 0 through Day 224

Title

Number of Participants With Serious Adverse Events (SAEs) Following Product Administration (Part B)

Description

Time Frame

Day 0 through Day 672

Title

Number of Participants With New Chronic Medical Conditions Following Product Administration (Part A)

Description

Time Frame

Day 0 through Day 224

Title

Number of Participants With New Chronic Medical Conditions Following Product Administration (Part B)

Description

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

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

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

Time Frame

Day 0 through Day 672

Title

Zika Antigen-specific Neutralizing Antibody Geometric Mean Titer (GMT) - (Part B)

Description

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

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

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

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

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

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

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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

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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

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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

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Learn more about this trial

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

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