Evaluation of Safety, Immunogenicity and Efficacy of a Triple Immune Regimen in Adults Initiated on ART During Acute HIV-1
Start Date
4/1/2024
Completion Date
8/1/2029
Summary
The purpose of this study is to evaluate the safety, tolerability, and efficacy of therapeutic vaccination with chimpanzee adenovirus ChAdOx1- and poxvirus modified vaccinia Ankara (MVA)-vectored conserved mosaic T-cell vaccines in a sequential regimen with the toll-like receptor 7 (TLR7) agonist vesatolimod (VES) and two broadly neutralizing antibodies (bNAbs) compared to placebo, to induce HIV-1 control during analytic treatment interruption (ATI).
Detailed Description
A5374 is a phase I/IIa randomized, two-arm, double-blind placebo-controlled, multi-step strategy trial to evaluate safety and efficacy of therapeutic vaccination with chimpanzee adenovirus ChAdOx1- and poxvirus modified vaccinia Ankara (MVA)-vectored conserved mosaic T-cell vaccines in a sequential regimen with the toll-like receptor 7 (TLR7) agonist vesatolimod (VES) and two broadly neutralizing antibodies (bNAbs) of the CD4 binding site and V3-loop base classes in individuals with HIV-1 who started suppressive antiretroviral therapy (ART) during acute HIV-1. Participants will be screened for eligibility and have a pre-entry visit. After determination of eligibility, participants will be randomized prior to entry to either the active intervention arm (Arm A) or the placebo arm (Arm B) in a 2:1 ratio. The study consists of four steps including an analytic treatment interruption (ATI) for all participants, and two subsequent optional steps including a second ATI for placebo participants. * Step 1: Study Intervention and ART (67 weeks) * Step 2: Analytic Treatment Interruption (up to 24 weeks) * Step 3: ART Restart (24 weeks) * Step 4: Continuation of ATI (up to 24 weeks) * Step 5 (optional): Study Intervention and ART (Placebo roll-over) * Step 6 (optional): Analytic Treatment Interruption 2 (ATI 2) Each participant will complete Step 1 and Step 2. At any time on Step 2\[mw1.1\]\[KM1.2\], participants on Arm A who meet criteria to restart ART will enter Step 3 and resume ART. Arm B (placebo) participants who have experienced virologic restart criteria may choose to enter Step 3 to resume ART or elect to enter Step 5 to resume ART and receive active study products. Participants who elect to enter Step 5 will undergo second ATI in Step 6. Participants who do not meet ART restart criteria after 24 weeks in Step 2 will enter Step 4 for an extended ATI. Each participant will be enrolled for up to approximately 110 weeks. The total time on study for each participant is dependent on the time spent in the treatment interruption steps (Step 2 and 4). Eligible participants participating in for Steps 5 and 6 will have up to 110 additional weeks on study.
Eligibility Criteria
Age Range: 18 years to No maximum
Interventions
ChAdOx1.tHIVconsv1
ChAdOx1.HIVconsv62
MVA.tHIVconsv3
MVA.tHIVconsv4
Vesatolimod (VES)
GS-5423
GS-2872
MVA.tHIVconsv4
Placebo
Conditions
Locations
University of California, San Diego AntiViral Research Center CRS
San Diego, California 92103
United States
Ponce de Leon Center CRS
Atlanta, Georgia 30308
United States
Northwestern University CRS
Chicago, Illinois 60611
United States
Massachusetts General Hospital CRS (MGH CRS)
Boston, Massachusetts 02114
United States
Washington University Therapeutics CRS
St Louis, Missouri 63110
United States
Columbia Physicians & Surgeons CRS
New York, New York 10032
United States
Chapel Hill CRS
Chapel Hill, North Carolina 27599
United States
Ohio State University CRS
Columbus, Ohio 43210
United States
Penn Therapeutics CRS
Philadelphia, Pennsylvania 19104
United States
Houston AIDS Research Team CRS
Houston, Texas 77004
United States
Instituto de Pesquisas em AIDS do Rio Grande do Sul - IPARGS CRS
Porto Alegre, Rio Grande do Sul 91350-180
Brazil
Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS
Rio de Janeiro,
Brazil