Safety and Immunogenicity of an HIV Vaccine in Normal Adult Volunteers
Condition: Healthy; HIV Infections
MeSH terms: HIV Infections
Study type: Interventional
Phase: Phase 1

Summary: 
      This study will test the safety of an experimental vaccine against HIV infection and see if
      it causes an immune response to HIV. The vaccine is given by injection (shot) in the upper
      arm. It is made from DNA that codes for three HIV proteins. The DNA is inserted into an
      adenovirus that carries it into the muscle cells. The adenovirus normally can cause eye or
      upper respiratory infections, such as a cold; however, for the vaccine, it has been modified
      so that it cannot cause illness. Nor can the vaccine cause HIV infection, because it codes
      for only three of the nine HIV proteins.

      Healthy, normal volunteers between 18 and 44 years of age who are not HIV-infected may be
      eligible for this study. Candidates are screened with a medical history and physical
      examination and blood and urine tests.

      Participants are randomly assigned to receive either the experimental vaccine or a placebo
      (an inactive substance that looks like the vaccine). The vaccine or placebo is administered
      to participants in groups, according to their entry into the study. The first group receives
      the lowest study dose of vaccine. If this dose is safe, then the second group receives a
      higher dose. If this dose is also safe, then the third and final group receives the highest
      study dose. Clinic staff observe the subjects for side effects for 30 minutes after the
      injection, and subjects keep a diary card for the next 5 days, recording their temperature
      and any symptoms that may appear. Subjects are contacted by a nurse 2 days after the
      injection for follow-up.

      Participants are seen at the clinic for follow-up visits 1, 2, 4, 12, and 24 weeks after the
      injection, and then are contacted by telephone for follow-up once a year until 5 years after
      the injection. The clinic visits include a physical examination, medical history, blood and
      urine tests, and HIV counseling, as needed. Women have pregnancy tests at the screening
      evaluation and again at study week 24. All subjects are tested for HIV at screening and at
      study weeks 12 and 24, and all subjects complete a "social impact questionnaire" at week 24.
      All subjects are asked questions about their sexual behavior and drug use.

      ...
    

Detailed description: 
      Study Design:

      This is a Phase I, randomized, placebo-controlled, double-blinded study to examine safety,
      tolerability and immune response of a multiclade HIV adenoviral vector vaccine in uninfected
      adults. The hypothesis is that this vaccine will be safe and elicit immune responses to HIV.
      The primary objective is to evaluate the safety and tolerability of VRC-HIVADV014-00-VP in
      uninfected subjects and the secondary objectives include immunogenicity evaluations and
      adenovirus serotype 5 (Ad5) antibody titers through Week 4 and social impacts at Week 24.
      Exploratory evaluations include immunogenicity evaluations at Weeks 12 and 24 and Ad5
      antibody titers at Week 24.

      Product Description:

      VRC-HIVADV014-00-VP is a recombinant product composed of 4 adenoviral vectors (Ad) (in a
      3:1:1:1 ratio) that encode the HIV-1 Gag/Pol polyprotein from clade B and HIV-1 Env
      glycoproteins from clades A, B, and C, respectively. The final formulation buffer,
      VRC-DILUENT013-DIL-VP will be used as the diluent and as the placebo control. Injections will
      be administered intramuscularly (IM).

      Subjects:

      Healthy adult volunteers (18 to 44 years old).

      Study Plan:

      Thirty-six volunteers will receive one 1.0 mL injection of the study agent or placebo in a
      deltoid muscle as shown in the schema. Dose escalation will occur about three weeks after the
      last injection in a dose group following an interim safety data review by a DSMB, provided
      that there are no significant toxicities.

      Study Duration:

      Subjects will be evaluated at 5 or more clinical visits for 24 weeks after the study
      injection, followed by annual telephone or mail contact for the subsequent 4 years.

      Study Endpoints:

      The primary endpoint is safety of the vaccine administered at doses of 1 x 10(9), 1 x 10(10)
      and 1 x 10(11) particle units (PU) by intramuscular injection. Secondary endpoints are
      immunogenicity as indicated by HIV-specific antibody and cellular immune responses through
      Week 4, Ad5 antibody titer at Week 0 and Week 4 and social impact at Week 24. Exploratory
      analyses of immunogenicity at Weeks 12 and 24 and Ad5 antibody titer at Week 24 will also be
      performed.
    

Intervention name(s): VRC-HIVADV014-00-VP
Intervention type(s): Drug
Primary purpose: Treatment
Keywords: Healthy; T Cells; Immunity; Healthy Volunteer; HV