Safety and Immunogenicity of a Zika Virus DNA Vaccine, VRC-ZKADNA085-00-VP, in Healthy Adults
Condition: Prevention of Zika Infection; Zika-Specific Immune Response
MeSH terms: Zika Virus Infection
Study type: Interventional
Phase: Phase 1

Summary: 
      Background:

      The Zika virus is passed to humans by infected mosquitos. It usually causes fever, rash,
      joint pain, and red eyes. Recently, some cases of microcephaly (abnormally small head) were
      reported in babies born to mothers infected with the Zika virus. Rare cases of a severe nerve
      weakness called Guillain-Barr(SqrRoot)(Copyright) syndrome were reported in some people with
      Zika virus infection. There is currently no cure for or vaccine against the infection.
      VRC-ZKADNA085-00-VP is a new vaccine that instructs the body to make a small amount of Zika
      virus protein. The body may use this to build an immune response.

      Objective:

      To see if VRC-ZKADNA085-00-VP is safe and causes any side effects.

      Eligibility:

      Healthy people ages 18 35

      Design:

      Participants will be screened through a separate protocol with:

        -  Medical history

        -  Physical exam

        -  Lab and urine tests

      Participants will be randomly assigned to 1 of 4 study groups. They will have about 18 clinic
      visits over 2 years. Most will occur in the first year, with long-term follow-up visits at
      months 18 and 24. Visits include a physical exam and blood and urine tests.

      Participants will have vaccine injections. A high-pressure device pushes the vaccine through
      the skin and into the muscle of the upper arm. They will have 2-3 injections depending on
      their group.

      Vaccine visits last 4-6 hours. Others last 1-2 hours.

      Participants will keep a diary for 7 days after each injection. They will record their
      temperature and measure any skin changes at the injection site each day.

      Participants might have extra visits and blood tests if they have health changes.
    

Detailed description: 
      Study Design:

      This is a Phase I/Ib, randomized, multicenter clinical study to evaluate the safety,
      tolerability, and immunogenicity of four vaccination regimens against Zika virus (ZIKV)
      disease. Vaccination regimens with the VRC-ZKADNA085-00-VP (ZIKV DNA) vaccine administered on
      Day 0 and Week 8 (Group 1); on Day 0 and Week 12 (Group 2); on Day 0, Weeks 4 and 8 (Group
      3); and on Day 0, Weeks 4 and 20 (Group 4) will be tested. The primary hypothesis is that the
      ZIKV DNA vaccine will be safe and well tolerated in healthy adults. A secondary hypothesis is
      that all vaccine regimens will elicit a ZIKV-specific immune response. The primary objectives
      are to evaluate the safety and tolerability of the investigational vaccine regimens in
      healthy adults. Secondary objectives are related to the immunogenicity of the vaccination
      regimens.

      Product Description:

      The investigational VRC-ZKADNA085-00-VP vaccine was developed by the Vaccine Research Center
      (VRC), NIAID, and is composed of a single closed-circular DNA plasmid that encodes the wild
      type precursor transmembrane M (prM) and envelope (E) proteins from the H/PF/2013 strain of
      ZIKV. Vaccine is supplied in single dose vials at a concentration of 4 mg/mL. ZIKV DNA
      vaccine dose will be 4 mg administered as an intramuscular (IM) injection in the deltoid
      muscle.

      Subjects:

      Healthy adults 18 to 35 years of age.

      Study Plan:

      Subjects will be enrolled at up to 3 study sites, randomized equally into the 4 study groups,
      and will receive 2-3 vaccinations. The protocol requires up to 18 scheduled clinic visits and
      a telephone follow-up contact after each study injection. 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
      through the 44 weeks on the study.

      -VRC 319 Study Schema

        -  Group:1; Subjects*: 20; Day 0; Week 8;

        -  Group:2; Subjects*: 20; Day 0; Week 12;

        -  Group:3; Subjects*: 20; Day 0; Week 4; Week 8;

        -  Group:4; Subjects*: 20; Day 0; Week 4; Week 20;

        -  TOTAL; Subjects*: 80

             -  Up to 120 total enrollments are permitted if additional subjects are needed for
                assessment of safety and immune responses.

      Study Duration:

      Subjects will be evaluated for safety and immune responses throughout the study for 44 weeks
      following the first vaccine administration and for durability of immune responses at two
      additional long term follow-up visits at 18 and 24 months.
    

Intervention name(s): VRC-ZKADNA085-00-VP
Intervention type(s): Biological
Intervention description(s): VRC-ZKADNA085-00-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; Flavivirus; Vaccine-Mediated Protection; Immune Response; Arthropod-Borne Virus