VRC 320: A Phase I, Randomized Clinical Trial to Evaluate the Safety and Immunogenicity of a Zika Virus DNA Vaccine, VRC-ZKADNA090-00-VP, Administered Via Needle and Syringe or Needle-free Injector, PharmaJet, inHealthy Adults
Condition: Prevention of Zika Infection; Zika-Specific Immune Response
MeSH terms: Zika Virus Infection
Study type: Interventional
Phase: Phase 1

Summary: 
      Background:

      People get Zika virus from infected mosquitos. They usually don t get very sick. But birth
      defects were reported in babies born to mothers who had Zika infection. In rare cases, people
      with Zika infection had a nervous system disease that causes severe muscle weakness and can
      be life threatening. A new vaccine made from DNA in the code for a Zika virus protein could
      help the body build an immune response against the virus.

      Objectives:

      To see if a new vaccine against Zika virus disease is safe and causes any side effects. To
      study specific immune responses to the vaccine.

      Eligibility:

      Healthy people ages 18-50

      Design:

      Participants will be screened with:

      Medical history

      Physical exam

      Urine tests

      Participants will have 18 visits over 2 years.

      Participants will be randomly assigned to 1 of 3 groups. All will get 3 vaccines at 3
      separate monthly visits. They will receive the vaccine in the upper arm muscle. Some will get
      it by needle and syringe, others by a device that uses high pressure to push the vaccine
      through the skin.

      Vaccine visits last 4-6 hours. Participants will get a thermometer to measure their
      temperature and a ruler to measure any skin changes at the injection site. They will record
      this data for 7 days after each injection.

      Other visits last 1-2 hours. These include:

      Evaluation of any health changes or problems

      Blood tests: Some samples may be used for future research.

      Participants with side effects may have extra visits.

      ...
    

Detailed description: 
      STUDY DESIGN:

      This is a Phase I, randomized clinical study to evaluate the safety, tolerability, and
      immunogenicity of a 3 dose vaccination regimen with the Zika virus (ZIKVwt) DNA vaccine,
      VRC-ZKADNA090-00-VP. Subjects will be randomized to one of three groups to receive a full 4
      mg dose: 1) full dose by one intramuscular (IM) injection with needle and syringe; 2) split
      dose given as two 0.5 mL IM injections with needle and syringe; 3) split dose given as two
      0.5 mL IM injections with PharmaJet, a needle-free injection device. The primary hypothesis
      is that the investigational ZIKVwt DNA vaccine will be safe and well tolerated in healthy
      adults. A secondary hypothesis is that the vaccine will elicit a ZIKV-specific immune
      response. The primary objectives are to evaluate the safety and tolerability of the vaccine
      in healthy adults. Secondary objectives are related to the immunogenicity of the vaccine and
      vaccination regimens.

      PRODUCT DESCRIPTION:

      The investigational vaccine, VRC-ZKADNA090-00-VP, was developed by the Vaccine Research
      Center (VRC), National Institute of Allergy and Infectious Diseases (NIAID), National
      Institutes of Health (NIH) and is composed of a single closed-circular DNA plasmid (VRC 5283)
      that encodes the wild type (wt) precursor membrane M (prM) and envelope (E) proteins from the
      H/PF/2013 strain of ZIKV. ZIKVwt

      SUBJECTS:

      Healthy adults 18 to 50 years of age.

      STUDY PLAN:

      Forty-five subjects will be enrolled at the NIH Clinical Center and randomized to 3 groups to
      receive study product on Day 0, Week 4 and Week 8. The protocol requires about 18 scheduled
      clinic visits and a telephone follow-up contact after each study product administration.
      Solicited reactogenicity will be evaluated using a 7-day diary card. Assessment of vaccine
      safety will include clinical observation and monitoring of hematological and chemical
      parameters at clinical visits throughout the study.

      VRC 320 STUDY SCHEMA:

        -  Group 1:

             -  Administration Method = Single Dose Needle and Syringe;

             -  Subjects = 15;

             -  Administration Schedule = Day 0 (ZIKVwt DNA(1 (1 mL) injection)), Week 4 (ZIKVwt
                DNA (1 (1 mL) injection)), Week 8 (ZIKVwt DNA (1 (1 mL) injection))

        -  Group 2:

             -  Administration Method = Split Dose Needle and Syringe;

             -  Subjects = 15;

             -  Administration Schedule = Day 0 (ZIKVwt DNA(2 (0.5 mL) injections)), Week 4 (ZIKVwt
                DNA (2 (0.5 mL) injections)), Week 8 (ZIKVwt DNA (2 (0.5 mL) injections))

        -  Group 3:

             -  Administration Method = Split Dose PharmaJet;

             -  Subjects = 15;

             -  Administration Schedule = Day 0 (ZIKVwt DNA(2 (0.5 mL) injections)), Week 4 (ZIKVwt
                DNA (2 (0.5 mL) injections)), Week 8 (ZIKVwt DNA (2 (0.5 mL) injections))

             -  Subjects Total = 45 (All injections total a dose of 4 mg. ** Up to 50 total
                enrollments are permitted if additional subjects are needed to assess safety or
                immunogenicity.)

      STUDY DURATION:

      Subjects will be evaluated for safety and immune responses throughout the study for 44 weeks
      following the first vaccine administration. Durability of immune responses will be evaluated
      at two long term follow-up visits, occurring at 18 and 24 months
    

Intervention name(s): VRC-ZKADNA090-00-VP
Intervention type(s): Biological
Intervention description(s): VRC-ZKADNA090-00-VP is an investigational ZIKV DNA vaccine that is intended to prevent Zika virus infection.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Zika Infection; Immune Response; Flavivirus; Arthropod-Borne Virus