Clinical Trial: Safety of and Immune Response to a DNA HIV Vaccine Boosted With a Modified Vaccinia HIV Vaccine and Protein HIV Vaccine in Healthy Adults
Study Status: Completed
Recruit Status: Unknown status
Study Type: Interventional
Official Title: A Phase 1 Placebo-controlled Clinical Trial to Evaluate the Safety and Immunogenicity of SAAVI DNA-C2, SAAVI MVA-C and Novartis Subtype C gp140 With MF59 Adjuvant in Various Vaccination Schedules in H
Brief Summary: Sub-Saharan Africa is the region most affected by the global Human Immunodeficiency Virus (HIV) epidemic. A vaccine is the most promising preventive approach against new HIV infections. The purpose of this study is to evaluate the safety and immunogenicity of 4 experimental preventive HIV vaccine regimens in HIV-uninfected adults in South Africa.
Detailed Summary:
The worldwide Human Immunodeficiency Virus / Acquired Immunodeficiency Syndrome (HIV/AIDS) epidemic may only be controlled through development and utilization of a safe and effective vaccine that will prevent HIV infection. Due to the high prevalence of HIV-1 subtype C in southern Africa, the South African AIDS Vaccine Initiative (SAAVI), the HIV Vaccine Trials Network (HVTN), Novartis, and the National Institute of Allergy and Infectious Diseases (NIAID) are evaluating three subtype C HIV vaccines, SAAVI DNA-C2, SAAVI MVA-C, and Novartis Subtype C gp140 through this study. These vaccines will be used together in four prime-boost regimens. The SAAVI DNA-C2 vaccine is a multigene deoxyribonucleic acid (DNA) vaccine consisting of two DNA plasmids in equal amounts that express an HIV-1 subtype C polyprotein comprising of Gag-Reverse Transcriptase-Tat-Nef and an HIV-1 subtype C truncated Env. SAAVI MVA-C is a recombinant modified vaccinia Ankara (MVA) vaccine expressing the same immunogens as the SAAVI DNA-C2 vaccine. MVA is a highly attenuated vaccinia virus. The Novartis protein subunit vaccine is a Subtype C oligomeric V2 loop deleted glycoprotein 140 (gp140) vaccine (gp140[delta]V2.TV1), given with MF59 adjuvant.
This trial is designed to build upon the Thai RV144 HIV vaccine trial, which demonstrated an efficacy of 31.2% among participants who received a different vaccine regimen of a pox prime followed by a concurrently-administered protein boost. This primary purpose of HVTN 086 is to evaluate the safety and immunogenicity of SAAVI DNA-C2, SAAVI MVA-C and Novartis Clade C gp140TV1ΔV2 with MF59 adjuvant in various vaccination regimens. The primary analysis will focus on a ranking strategy of the vaccine regimens that is guided by measurements of the immune responses elicited by these vaccines and their respective modes of delivery in various combinations, both sequ
Sponsor: HIV Vaccine Trials Network
Current Primary Outcome:
- Signs and symptoms of local and systemic reactogenicity, laboratory measures of safety, and adverse events [ Time Frame: Measured through approximately Month 12 ]
- Neutralizing antibody titers to tier 1 and tier 2 virus isolates as assessed by magnitude-breadth curves [ Time Frame: Measured through approximately Month 12 ]
Original Primary Outcome: Same as current
Current Secondary Outcome:
- T-cell response rate and magnitude as detected by HIV-1 specific interferon-gamma/interleukin-2 intracellular cytokine staining [ Time Frame: Measured 2 weeks after the 3rd and 4th vaccinations in Arms 1, 3, 4; measured 14 weeks after 2nd vaccination in Arm 2 ]
- Total HIV-1 Env-specific immunoglobulin G (IgG)-binding antibodies as determined by HIV-1 multiplex Ab assay ConS gp140, Du151 Env, and/or TV1gp140 specific IgG subclass (IgG1- IgG4) and IgA characterization determined by HIV-1 multiplex antibody assay [ Time Frame: Measured 2 weeks after the 3rd and 4th vaccinations in Arms 1, 3, 4; measured 14 weeks after 2nd vaccination in Arm 2 ]
Original Secondary Outcome: Same as current
Information By: HIV Vaccine Trials Network
Dates:
Date Received: June 17, 2011
Date Started: June 2011
Date Completion: June 2015
Last Updated: October 14, 2014
Last Verified: October 2014
