Therapeutic HIV vaccines are designed to control HIV infection by boosting the body's natural immune response. There are currently no FDA-approved therapeutic HIV vaccines. This study will test whether giving an HIV-1 vaccine together with or without interleukin 12 (IL-12) is safe and effective. This study will also test a new way of giving the vaccine called electroporation (EP).
Although highly active antiretroviral therapy (HAART) has greatly reduced HIV infection-related morbidity and mortality, individual response to therapy can be variable. Therapeutic vaccination works by augmenting virus-specific immunity and can be given with or without immunomodulatory agents or adjuvants. In conjunction with HAART, therapeutic vaccination may be a more effective treatment for the suppression of HIV-1 replication. This study will examine the safety and efficacy of giving an investigational vaccine with or without IL-12 in HIV-1 infected adults receiving HAART. This study will also test whether delivering the vaccine using EP is safe and increases the efficacy of the vaccine. Participation in this study will last approximately 36 weeks. Participants will be randomly assigned to one of five cohorts. Cohort 1 will receive the HIV multi-antigen plasmid DNA (HIV MAG pDNA) vaccine or placebo intramuscularly (IM) in the upper arm followed by EP. Cohorts 2 through 4 will receive the HIV MAG pDNA vaccine and sequentially increasing doses of GENEVAX IL-12 pDNA or placebo by IM/EP. Cohort 5 will receive the HIV MAG pDNA vaccine with the highest dose of IL-12 pDNA or placebo by needle and syringe in the upper arm. Participants receive two injections at Weeks 0, 4, and 12. Participants will complete a questionnaire that assesses the acceptability of the vaccine and remain at the clinic 30 minutes for observation after each vaccination. Participants will be contacted by telephone 2 to 3 days post-vaccination to assess vaccination-related signs and/or symptoms. All participants will be asked to record their temperatures and any symptoms they experience daily for 4 days following each vaccination on a Vaccination Report Card (VRC). All nonstudy vaccines or medications should also be recorded on the VRC. Study visits will occur at Weeks 0, 1, 2, 4, 5, 6, 8, 12, 13, 14, 16, 24, and 36. At most visits, participants will undergo a physical examination. Women of reproductive potential will also undergo pregnancy testing before receiving injections on Weeks 0, 4, and 12. Blood will be drawn at various time points to evaluate participants' health and measure immunologic markers, CD4 and CD8 T-cell counts, and cytokine levels. Blood and plasma will also be stored for future exploratory studies.
Study Type
3,000 mcg admixture of two vaccine plasmids: ProfectusVax DNA Plasmid (HIV-1 gag/pol) and ProfectusVax DNA Plasmid (HIV-1 nef/tat/vif, env) at Weeks 0, 4, and 12
Administered at Weeks 0, 4, and 12
Saline injections at Weeks 0, 4, and 12
UCLA CARE Center CRS
Los Angeles, California, United States
Stanford AIDS Clinical Trials Unit CRS
Palo Alto, California, United States
Ucsf Hiv/Aids Crs
San Francisco, California, United States
Occurrence of at least one greater than Grade 3 adverse event (AE) including signs/symptoms, lab toxicities, and/or clinical events that is possibly, probably, or definitely related to study treatment, as judged by the core team
Time frame: From the first day of study treatment until 28 days after the last study vaccine administration
Change in the number of interferon (IFN)-gamma generating (in response to gag) CD4 T cells/million peripheral blood mononuclear cells (PBMCs) as measured by intracellular cytokine staining (ICS)
Time frame: From Baseline to Week 14
Answering "no" to the question, "In your opinion, would this study's vaccination procedure be acceptable as part of a treatment for HIV, if it proved to be effective?"
Time frame: From Week 0 to Week 36
Answering "no" to the question, "In your opinion, would this study's vaccination procedure be acceptable if it could contribute to increased scientific knowledge about how best to administer vaccines to prevent or treat infections?"
Time frame: From Week 0 to Week 36
Premature treatment discontinuation for reasons related to study treatment or related to any real or perceived effect of study vaccination or its administration
Time frame: From Week 0 to Week 36
Rated pain (for participants administered vaccine/placebo by the EP device)
Time frame: When the device was placed on the skin and the vaccine/placebo was injected; at the time of the electrical stimulation and muscle contraction; and at 10 and 30 minutes after the procedure was completed at Weeks 0, 4, and 12
Changes from baseline and absolute values of multiple functions of CD4 and CD8 T cells in response to gag and other vaccine-coded antigens individually and in sum
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INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
62
University of Colorado Hospital CRS
Aurora, Colorado, United States
Massachusetts General Hospital Clinical Research Site (MGH CRS) CRS
Boston, Massachusetts, United States
Brigham and Women's Hospital Therapeutics Clinical Research Site (BWH TCRS) CRS
Boston, Massachusetts, United States
Washington University Therapeutics (WT) CRS
St Louis, Missouri, United States
Trillium Health ACTG CRS
Rochester, New York, United States
Univ. of Rochester ACTG CRS
Rochester, New York, United States
Cincinnati CRS
Cincinnati, Ohio, United States
...and 3 more locations
Time frame: At Week 8, Week 14, and possibly other time points depending on the first set of data in an ICS assay