Safety, Tolerability and Immune Response to LC002, an Experimental Therapeutic Vaccine, in Adults Receiving HAART
Condition: HIV Infections
MeSH terms: HIV Infections
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      LC002 is an experimental therapeutic vaccine designed to boost the immune response of people
      infected with HIV. The purpose of this study was to determine the safety and tolerability of
      and immune response to LC002 in HIV-1-infected adults who are currently receiving anti-HIV
      treatment.
    

Detailed description: 
      The use of highly active antiretroviral therapy (HAART) has dramatically improved the rates
      of survival, morbidity, and mortality among HIV-infected people throughout the world.
      However, the costs, long-term toxicity, and problems with adherence associated with HAART
      regimens make such treatment plans less than optimal for individuals seeking treatment for
      HIV infection. Also, because viral reservoirs cannot be eradicated, HIV-infected people must
      usually be on HAART indefinitely in order to keep their infection under control. While the
      mechanism is still unclear, the immune system weakens as HIV disease progresses. A
      therapeutic HIV vaccine given to HIV infected people may help to promote better immune
      responses. LC002 is a novel HIV therapeutic vaccine containing a DNA plasmid that codes for
      most of HIV-1's proteins. LC002 is a unique vaccine in that it is given through topical
      administration; this allows for Langerhans cells (immune cells located under the surface of
      the skin) to pick up the vaccine and deliver it to the lymph nodes, causing an immune
      reaction. This study evaluated the safety, tolerability, and immunogenicity of LC002 in
      HIV-infected adults currently receiving HAART.

      There were three cohorts in this study which were enrolled sequentially. Participants in a
      given cohort were randomly assigned to receive either LC002 (6 participants) or placebo (2
      participants).

        -  In Cohort 1, participants received three separate low-dose vaccinations of LC002 (Arm A:
           0.1 mg DNA/participant, 0.8 ml total, administered over two skin sites of 80 cm^2 each,
           0.4 ml/site) or 3 separate vaccinations of placebo (Arm B: 0.8 ml total, administered
           over two skin sites of 80 cm^2 each, 0.4 ml/site). Vaccinations were given over two skin
           sites on the left and right upper back. Participants received vaccinations at weeks 1,
           7, and 13.

        -  In Cohort 2, participants received three separate high-dose vaccinations of LC002 (Arm
           C: 0.4 mg DNA/participant, 3.2 ml total, administered over four skin sites of 80 cm^2
           each, 0.8 ml/site) or three separate vaccinations of placebo (Arm D: 3.2 ml total,
           administered over four skin sites of 80 cm^2 each, 0.8 ml/site). Vaccinations were given
           over four skin sites on the left and right upper back and left and right upper ventral
           thigh. Participants received vaccinations at weeks 1, 7, and 13.

        -  In Cohort 3, participants received six separate high-dose vaccinations of LC002 (Arm E:
           0.4 mg DNA/participant, 3.2 ml total, administered over four skin sites of 80 cm^2 each,
           0.8 ml/site) or six vaccinations of placebo (Arm F: 3.2 ml total, administered over four
           skin sites of 80 cm^2 each, 0.8 ml/site). Vaccinations were given over four skin sites
           on the left and right upper back and left and right upper ventral thigh. Participants
           received vaccinations at study entry and weeks 1, 6, 7, 12, and 13.

      The decision to open the next cohort was made when all participants in the current cohort
      have remained on study for >=14 days after the second vaccination or prematurely discontinued
      from study or had a primary safety endpoint (see primary outcome measure definition). Dose
      escalation required no primary safety endpoint and on-study follow-up for >=6 participants in
      the previous cohort(s).

      Prior to receiving the vaccine, the chosen vaccine administration site on the back or thigh
      was disinfected and exfoliated. A skin patch was applied to the site, and the vaccine
      solution was placed on the skin underneath the patch with a needleless syringe. Participants
      were allowed to remove the skin patch 3 hours post vaccination. For the first and second
      vaccinations, participants were required to remain at the clinic for 3 hours post-vaccination
      so study staff can assess for side effects. If no side effects occurred after the first two
      vaccinations, participants were required to stay at the clinic for only 30 minutes after
      receiving later vaccinations.

      At the start of the study, participants were asked to keep a diary and record daily any side
      effects or skin irritation they may have experienced following vaccination. Participants were
      required to bring their diaries with them to their next clinic visit. Two days after
      vaccination, participants were followed-up by phone and were asked about any side effects
      they may have experienced. Participants who experienced side effects were asked to return to
      the clinic for examination. There were 13 study visits; they occurred at study entry and
      Weeks 1, 3, 6, 7, 9, 12, 13, 15, 17, 24, 37, and 61. Study visits included medication
      history, a physical exam, and collection of diaries. Blood and urine collection occurred at
      selected visits. HAART was not be provided by the study.
    

Intervention name(s): LC002 standard vaccination; LC002 high-dose vaccination; LC002 placebo vaccination
Intervention type(s): Biological; Biological; Biological
Intervention description(s): 0.1 mg DNA/participant, 0.8 ml total administered subcutaneously; 0.4 mg DNA/participant, 3.2 ml total administered subcutaneously; Placebo vaccination administered subcutaneously
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Treatment Experienced; HIV Therapeutic Vaccine