Phase 1 Safety Study of Two Experimental HIV Vaccines
Condition: AIDS Vaccines; HIV Infections; HIV-1
MeSH terms: HIV Infections
Study type: Interventional
Phase: Phase 1

Summary: 
      This study will test whether two experimental HIV vaccines are safe and whether they cause
      any side effects in healthy adults. It will examine the body s immune response to the
      vaccines and monitor the social impact, if any, of being in an HIV vaccine study. The
      experimental vaccines in this study are the VRC-HIVADV027-00-VP (also called the rAd35-EnvA
      vaccine) and VRC-HIVADV038-00-VP (also called the rAd5-EnvA vaccine). The vaccines are made
      using an adenovirus (virus that normally causes respiratory infections and colds) that has
      been modified to contain DNA that codes for HIV proteins. The vaccines cannot cause HIV or
      adenoviral infections.

      Healthy normal volunteers between 18 and 50 years of age may be eligible for this 2-part
      study. Part 1 includes 15 people. Part 2 includes 20 people.

      Part 1 participants receive only the rAd35-EnvA vaccine. The first five people enrolled
      receive the lowest study dose of the vaccine. If this dose is safe, then the next five people
      enrolled receive a higher dose. If this dose is safe, then the last 5 people enrolled receive
      the highest study dose. Subjects in Part I have about five clinic visits over 24 weeks.

      Part II of the study starts after all injections in Part 1 are given. Subjects in Part 2 are
      randomly assigned to one of two vaccination schedules. One group receives the rAd35-EnvA
      vaccine first, followed 12 weeks later with the rAd5-EnvA vaccine. The other group receives
      the vaccines in reverse order; that is, first the rAd5-EnvA vaccine, followed 12 weeks later
      with the rAd35-EnvA vaccine. In this schedule, the first vaccination primes the immune system
      and then the immune response is boosted 12 weeks later with a different vaccine. Everyone in
      study Part 2 receives the rAd35-EnvA vaccine at the middle dose tested in Part 1. Subjects in
      Part 2 have about eight clinic visits over 36 weeks.

      All vaccinations are given as injections in the upper arm. At each clinic visit, participants
      are checked for health changes or problems. They are asked how they are feeling and if they
      have taken any medications. Urine samples are collected and blood is drawn at some visits.
      They are tested for HIV several times and asked questions about their sexual behavior and
      drug use. Throughout the study, participants are counseled on HIV risk reduction. Subjects
      are asked about any social effects they may have experienced from their participation in this
      study.
    

Detailed description: 
      Study Design:

      The VRC recombinant adenoviral vector serotype 5 (rAd5) multiclade vaccine has been
      previously shown to elicit immune responses to HIV-1-specific peptides when administered
      intramuscularly (IM) alone and in prime-boost schedules with the greatest magnitude and
      frequency of response to the Envelope A immunogen (EnvA).

      Part I of this study is an open label, dose escalation evaluation of an HIV-1 adenoviral
      vector serotype 35 vaccine (rAd35-EnvA).

      Subjects in Group 1 will receive one vaccination of rAd35-EnvA 10(9) PU.

      Subjects in Group 2 will receive one vaccination of rAd35-EnvA 10(10) PU.

      Subjects in Group 3 will receive one vaccination of rAd35-EnvA 10(11) PU.

      Part II (Group 4) of this study is a randomized, double blind evaluation of the rAd35-EnvA
      vaccine in comparison to and in combination with a rAd5-EnvA vaccine in prime-boost
      schedules.

      The hypotheses are: 1) rAd35-EnvA vaccine will be safe for human administration at dosages up
      to 10(11) PU as a single agent and both the rAd35-EnvA and rAd5-EnvA vaccines will be safe in
      prime-boost regimens; 2) both the rAd35-EnvA and rAd5-EnvA vaccines will elicit immune
      responses to the EnvA immunogen and 3) the heterologous prime-boost regimens will elicit a
      greater frequency and magnitude of response than after the priming vaccinations alone. The
      primary objectives relate to evaluation of the safety and tolerability of the rAd35-EnvA and
      rAd5-EnvA vaccines. Secondary objectives are related to evaluation of the immunogenicity of
      the vaccines when comparing rAd35-EnvA to rAd5-EnvA when administered as a prime or as a
      boost vaccination.

      Product Description: Both the VRC-HIVADV038-00-VP (rAd5-EnvA) and the VRC-HIVADV027-00-VP
      (rAd35-EnvA) vaccines are composed of recombinant, replication deficient adenoviral vectors
      that encode for HIV-1 clade A Env glycoprotein.

      Subjects: Thirty-five healthy adult volunteers, 18 to 50 years old; beginning with the
      Version 2.0 protocol, subjects in Part I must be Ad35 antibody (Ab) seronegative and subjects
      in Part II must be both Ad5- and Ad35-seronegative.

      Study Plan: Part I: Fifteen subjects will receive an open-label 1 mL IM deltoid injection via
      needle and syringe of the study agent. No more than one subject per day will be enrolled into
      each dose group. Five days following vaccination of the fifth volunteer in each dose group,
      there will be an internal safety review including the principal investigator, clinical team
      and medical officer to determine whether to proceed to next dose level.

      Part II: Initiation of enrollment into Part II will be contingent upon completion of
      enrollment into Group 3 and a safety review of 10(9) and 10(10) PU dosage by the Data and
      Safety Monitoring Board (DSMB). The safety review will take place when at least 2 weeks of
      follow-up on the last 10(10) PU injection in Group 2 is available in the safety reports; the
      DSMB safety review may occur during enrollment of Group 3.

      Enrollment into Group 4 will be randomized and double-blinded. The first 10 subjects in Group
      4 will be randomized in a 1:1 ratio into heterologous prime-boost vaccination schedules in
      which both rAd5-EnvA and rAd35-EnvA are administered at the 10(10) PU dosage. The last 10
      subjects in Group 4 will be randomized in a 1:1 ratio into heterologous prime-boost
      vaccination schedules in which the rAd5-EnvA is administered at 10(10) PU and rAd35-EnvA is
      administered at 10(11) PU. All subjects will receive each study agent administered as 1 mL IM
      deltoid injections (12 weeks apart) according to the schedule.

      Study Duration

      The vaccination regimen and clinical follow-up schedule for Part I requires 24 weeks and for
      Part II requires 52 weeks to complete. Part II subjects will be contacted annually for 4
      years after study completion for collection of long-term follow-up information.
    

Intervention name(s): VRC-HIVADV027-00-VP; VRC-HIVADV038-00-VP
Intervention type(s): Drug; Drug
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: HIV-Negative; Healthy; Immunity; Preventive; Virus; Healthy Volunteer; HV; HIV Preventive Vaccine