An Open-Label, Randomized Phase I Study in Healthy Adults of the Safety and Immunogenicity of Prime-Boost Intervals With Monovalent Influenza Subunit Virion (H5N1) Vaccine, A/Indonesia/05/2005 (Sanofi Pasteur, Inc.) Administered Alone or Following Re...
Condition: Influenza A Virus, H5N1 Subtype
MeSH terms: Influenza, Human; Influenza in Birds
Study type: Interventional
Phase: Phase 1

Summary: 
      Background:

      - New vaccines against avian influenza, also known as "bird flu," are being developed and
      require testing to determine if they are safe and effective and whether they have any side
      effects. Researchers are interested in testing two experimental avian influenza vaccines to
      see whether they are safe, if there are any side effects from the vaccines, and how the
      body's immune response differs in response to different vaccination schedules. One vaccine is
      an inactivated vaccine (made with killed or weakened influenza) and one is a DNA vaccine that
      allows the body to use vaccine to make an immune system response to a specific part of an
      avian influenza protein.

      Objectives:

        -  To determine the safety and potential side effects of two experimental vaccines against
           avian influenza.

        -  To evaluate whether the time between the two experimental vaccine injections affects the
           immune response to the vaccine.

      Eligibility:

      - Healthy individuals between 18 and 60 years of age.

      Design:

        -  Participants will be randomly divided (by chance) into six groups to receive two
           injections of vaccine at different intervals. One group will receive only the
           inactivated vaccine, while the other groups will receive the DNA vaccine followed by the
           inactivated vaccine at different intervals (e.g., 4 weeks, 8 weeks, 12 weeks, 16 weeks
           or 24 weeks later).

        -  Participants will remain at the clinical center for at least 30 minutes after each
           vaccination. A few days after each injection, participants will contact staff by
           telephone or have a clinic visit. Participants will also be asked to complete a diary
           card at home for 5 days to keep track of temperature changes, injection site skin
           changes, and other effects.

        -  Four weeks after the first injection, participants will return for a clinic visit and to
           provide blood samples for testing.

        -  Two weeks after the second injection, participants will return for a clinic visit and
           provide blood samples (collected through apheresis) to provide information on immune
           response to the vaccine.
    

Detailed description: 
      An Open-Label, Randomized Phase I Study in Healthy Adults of the Safety and Immunogenicity of
      Prime-Boost Intervals with Monovalent Influenza Subunit Virion (H5N1) Vaccine,
      A/Indonesia/05/2005 (Sanofi Pasteur, Inc), Administered Alone or Following Recombinant DNA
      Plasmid (H5) Vaccine, VRC-AVIDNA036-00-VP (VRC, NIAID)

      Study Design:

      This is a Phase I, randomized, open-label study to evaluate the safety, tolerability, and
      immunogenicity of prime-boost vaccination regimens against the influenza virus hemagglutinin
      H5. One group will receive A/Indonesia/05/2005 (inactivated H5N1) vaccine as both prime and
      boost, and the other groups will receive the VRC-AVIDNA036-00-VP (DNA) vaccine as prime with
      inactivated H5N1 boost but with various boost intervals. The VRC 310 study will provide data
      from different prime-boost schedules to identify whether homologous or heterologous schedules
      result in a better antibody response as well as which interval of time between vaccinations
      is associated with the best immune response. The hypothesis is that all of the study regimens
      will be safe for human administration and will elicit antibody and T cell responses against
      the H5 protein. The primary objectives are to evaluate the safety and tolerability of the
      investigational vaccine regimens, at a dose of 4 mg for the DNA vaccine and 90 microg for the
      inactivated H5N1, in healthy adults. Secondary and exploratory objectives are related to the
      immunogenicity of the study vaccine regimens and identification of an interval between prime
      and boost that has the highest frequency of strong immune responses.

      Product Description:

      The inactivated H5N1 vaccine is monovalent subunit virion vaccine, A/Indonesia/05/2005 clade
      2, manufactured by Sanofi Pasteur, Inc (Swiftwater, PA). Vaccine vials will be supplied at 90
      microg/0.5mL. The VRC-AVIDNA036-00-VP vaccine was developed and manufactured by VRC, NIAID
      and is composed of a single closed-circular DNA plasmid that encodes the H5 protein with a
      CMV/R promoter. Vaccine vials will be supplied at 4 mg/mL. Each vaccination will be
      administered intramuscularly (IM) in the deltoid muscle using needle and syringe for the H5N1
      vaccine and the Biojector 2000 Needle-Free Injection Management System (Biojector) for the
      DNA vaccine.

      Subjects:

      A total of 60 healthy adults, ages 18-60 years will be enrolled.

      Study Plan:

      Subjects will be simultaneously randomized equally into one of 6 groups. Subjects and
      clinicians will be blinded to group assignment until Day 0 following completion of the
      enrollment. At the point of enrollment the randomly assigned regimen will become known to
      subjects and clinicians. Subjects will receive two injections on the schedule shown in the
      schema. The protocol requires 5 or 6 clinic visits, depending upon the group, and telephone
      follow-up contact after the first study injection and 24 weeks after the second study
      injection. Additional optional visits may be conducted at study weeks 48 and 72 to collect
      blood for evaluation of immune response durability.

      Study Duration:

      Each participant will complete clinical follow up through 24 weeks after the second
      vaccination. Duration of the expected time on study will vary from 28 to 48 weeks depending
      upon the Group, but may be extended to 72 weeks after enrollment for subjects who agree to
      complete the optional research blood drawas.
    

Intervention name(s): VRC-AVIDNA036-00-VP; Monovalent Influenza Subunit Virion (Inactive H5N1) Vaccine
Intervention type(s): Biological; Biological
Intervention description(s): H5 DNA Vaccine; Inactive H5N1 Vaccine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Bird Flu; Avian Influenza; Healthy; Immunity; Prevention; Healthy Volunteer; HV