VRC 308: An Open-Label Phase I Study of the Safety and Immunogenicity of an Investigational H1 DNA Influenza Vaccine, VRC-FLUDNA057-00-VP, in Healthy Adults 18-70 Years Old
Condition: Influenza A Virus, H1N1 Subtype; Novel Swine-Origin
MeSH terms: Influenza, Human
Study type: Interventional
Phase: Phase 1

Summary: 
      Background:

        -  Vaccines are substances used to try to create resistance (or immunity) to a disease and
           to prevent an infection. Researchers are testing a new DNA vaccine designed for a new
           type of influenza, often referred to as swine flu. The DNA vaccine will instruct the
           body to make a particular kind of influenza protein that the immune system will be able
           to recognize.

        -  Researchers are interested in determining if the vaccine is safe and effective in
           humans, and would like to study the immune system's response to the vaccine. The vaccine
           will not give participants influenza; however, it may not be effective in preventing
           them from getting influenza at a later date.

      Objectives:

        -  To evaluate the safety and tolerability of the VRC-FLUDNA057-00-VP influenza vaccine as
           administered to healthy adults.

        -  To evaluate antibody responses to the new influenza vaccine.

      Eligibility:

      - Healthy adults between the ages of 18 and 70.

      Design:

        -  Participants will have seven planned clinic visits during this study (enrollment day and
           study weeks 1, 4, 8, 9, 12, and 32).

        -  All participants will receive three injections of the test vaccine, given as individual
           doses on day 0, day 28, and day 56 of the study. The vaccine will be given in the upper
           arm muscle.

        -  Injections will be given using a needleless system that delivers the vaccine through the
           skin by using the pressure of carbon dioxide to inject the vaccine through the skin and
           into the muscle. Participants will remain at the National Institutes of Health (NIH)
           Clinical Center for at least 30 minutes after the injection to be monitored for any
           reaction.

        -  Participants will be asked to keep a 7-day diary card after each injection to record
           their physical reactions to the vaccine.

        -  Participants will be asked to return to the NIH Clinical Center as requested by
           researchers for additional blood tests and other procedures, as required by the study.
    

Detailed description: 
      STUDY DESIGN- This is an open-label Phase I study to evaluate the safety, tolerability, and
      immunogenicity of 3- injection vaccination regimen with an investigational plasmid DNA
      vaccine that encodes for H1 hemagglutinin (HA) of an H1N1 influenza virus. All study
      participants will be offered to receive an additional optional booster immunization with
      licensed inactivated monovalent H1N1 influenza vaccine.

      The hypothesis is that the DNA vaccine will be safe for human administration and will elicit
      an antibody response. The primary objectives are to evaluate the safety and tolerability of
      the VRC-FLUDNA057-00-VP DNA vaccine at a dosage of 4 mg administered in a 3-injection
      schedule. The secondary objectives are to evaluate antibody responses including induced
      antibody titer as measured by a hemagglutination inhibition (HAI) assay and to document the
      reactogenicity of the inactivated H1N1 influenza vaccine when administered to subjects
      previously vaccinated with the VRC-FLUDNA057-00-VP DNA vaccine.

      Exploratory objectives are related to further evaluation of the humoral and cellular immune
      responses, including the responses after each injection and after the boost with licensed
      H1N1 inactivated influenza vaccine.

      PRODUCT DESCRIPTIONS- The VRC-FLUDNA057-00-VP vaccine was developed and manufactured by VRC,
      NIAID and is composed of 1 closed-circular DNA plasmid with a CMV/R promoter that encodes for
      the H1 hemagglutinin from the Influenza A/California/04/2009 H1N1 virus, identified late in
      the 2008-2009 northern hemisphere (NH) influenza season that has been referred to as swine
      flu in news reports. Vaccine vials will be supplied at 4 mg/mL and each 4 mg dosage will
      require a 1 mL injection. Vaccinations with the H1 DNA vaccine will be administered
      intramuscularly (IM) in the deltoid muscle using the Biojector[R] 2000 Needle-Free Injection
      Management System (Biojector). Licensed inactivated monovalent H1N1 influenza vaccine will be
      obtained through the NIH Clinical Center (CC) pharmacy, for use as a booster injection, and
      administered with needle and syringe. The brand administered will depend upon what is
      available through the NIH CC.

      SUBJECTS- A total of 20 healthy adults in the 18-70 years age range will be enrolled;
      however, no more than 10 subjects will be in the 51-70 year old age range.

      STUDY PLAN- All subjects will receive 3 injections of the H1 DNA vaccine as shown in the
      schedule below. No more than 5 subjects may be enrolled in the first week of the study.
      Following the 5th enrollment, the remainder of subjects may be enrolled without restrictions
      on enrollment rate. All subjects that have no contraindications to the licensed - inactivated
      H1N1 influenza vaccine or to additional blood drawing will be offered the option to receive
      the licensed inactivated H1N1 influenza vaccine. The study includes 7 clinic visits and 3
      telephone contacts as well as 3 additional visits for subjects that opt to receive an
      inactivated influenza vaccine. Subjects who have received the inactivated H1N1 vaccine
      outside of the VRC Clinic after Study Week 12 may consent to contribute the additional
      research samples through completing the extra visits on the schedule for post boost
      evaluations. A target window for the inactivated H1N1 vaccine is shown in the schema below.
      However, given that all subjects will be at or beyond Study Week 12, the earliest mutually
      convenient date after the H1N1 vaccine supply and amended protocol become available is
      acceptable for administration of the optional injection. The added post-boost research sample
      collections will then be scheduled to occur relative to the date the H1N1 booster injection.

      Number of Subjects = 20

      VRC-FLUDNA057-00-VP 4 mg on Day 0; 4mg on Day 28 plus or minus 7; 4mg on Day 56 plus or minus
      7, at least 21 days between injections. Inactivated licensed H1N1 influenza vaccine
      (optional) Day 168 plus or minus 28 - 1 dose

      STUDY DURATION- Each participant will complete 32 weeks of clinical follow up.
    

Intervention name(s): VRC-FLUDNA057-00-VP
Intervention type(s): Biological
Intervention description(s): DNA Vaccine Expressing H1 HA from Influenza A/California/04/2009 H1N1 Virus
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Influenza; Healthy; Immunity; Preventive; Pandemic