NCT06071767

Evaluation of Safety, Immunogenicity and Efficacy of a Triple Immune Regimen in Adults Initiated on ART During Acute HIV-1

A Phase I/IIa Randomized, Placebo-Controlled Trial of Conserved-Mosaic T-cell Vaccine in a Regimen With Vesatolimod and Broadly Neutralizing Antibodies in Adults Initiated on Suppressive Antiretroviral Therapy During Acute HIV-1

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 36 (estimated)
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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 analytical treatment interruption (ATI). * 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) Each participant will complete Step 1 and Step 2. At the end of Step 2, participants who have experienced virologic rebound will enter Step 3 and resume ART. Participants who did 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).

Conditions

• HIV-1-infection

Interventions

Type	Name	Description
BIOLOGICAL	ChAdOx1.tHIVconsv1	Administered as 0.4 mL intramuscularly (IM) at Week 0
BIOLOGICAL	ChAdOx1.HIVconsv62	Administered as 0.3 mL IM at Week 0
BIOLOGICAL	MVA.tHIVconsv3	Administered as 0.3 mL IM at Week 4
BIOLOGICAL	MVA.tHIVconsv4	Administered as 0.5 mL IM at week 4
DRUG	Vesatolimod (VES)	VES 6 mg administered orally once every 2 weeks for two doses, then VES 8 mg once every 2 weeks for 8 doses. Dose escalation may be held or the 8 mg dose may be reduced for intolerability for weeks 6 through 24.
DRUG	GS-5423	Administered via intravenous (IV) infusion at week 7
DRUG	GS-2872	Administered via IV infusion at week 7
BIOLOGICAL	MVA.tHIVconsv4	Administered 0.5 mL IM at week 60
BIOLOGICAL	Placebo	Placebos for vaccines, VES, and bnAbs

Timeline

• Start date: 2024-04-01
• Primary completion: 2028-04-29
• Completion: 2029-08-01
• First posted: 2023-10-06
• Last updated: 2026-02-09

Locations

12 sites across 2 countries: United States, Brazil

Regulatory

• FDA-regulated drug study