VRC 705: A Zika Virus DNA Vaccine in Healthy Adults and Adolescents
Condition: Zika Virus; Zika Virus Infection; Virus Diseases; Flavivirus Infections; Flaviviral Diseases; Flaviviridae Infections; RNA Virus Infections
MeSH terms: Infections; Communicable Diseases; Virus Diseases; Zika Virus Infection; RNA Virus Infections; Flaviviridae Infections; Flavivirus Infections
Intervention: VRC-ZKADNA090-00-VP; VRC-PBSPLA043-00-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; A sterile phosphate-buffered saline (PBS) prepared for human administration as a placebo
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Sequential Assignment
Intervention 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: Triple (Participant, Investigator, Outcomes 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.
Enrollment: 2428.0
Sex: All
Minimum age: 15 Years
Maximum age: 35 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Flavivirus; Zika; Vaccine; Physiological Effects of Drugs; Immunologic Factors; Virus-like Particles; Zika vaccine

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.
    

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