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Purpose

The purpose of this study is to evaluate the safety, tolerability, and efficacy of therapeutic vaccination with chimpanzee adenovirus (ChAdV)- 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).

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Provision of written informed consent. - History of Initiation of combination ART within 28 days of acute HIV diagnosis - No known ART interruption >14 consecutive days since initiation of ART. - ART with an integrase inhibitor-based regimen with two NRTIs or dolutegravir/lamivudine regimen for at least 6 weeks prior to study entry. - Willingness to participate in the ATI and willingness to restart ART according to study guidelines. - Willingness to adhere to protocol therapy and complete all study visits. - Weight ≥50 kg and ≤115 kg at Screening. - CD4 cell count ≥500 cells/mm3 obtained within 60 days prior to study Entry. - HIV-1 RNA <50 copies/mL since initial viral suppression on ART and for at least 1 year and within 60 days prior to study Entry. - Select laboratory results within 60 days of study entry - For cisgender women and transgender men of reproductive potential, negative urine or serum pregnancy test within 48 hours prior to or at study Entry. - Participants who are able to become pregnant and who are engaging in sexual activity that could lead to pregnancy must agree to use two methods of contraception, one of which must be a highly effective methods for contraception. Barrier methods of contraception are required for the second method of contraception. - Availability of results of HLA typing (required for randomization). - Completion of pre-entry leukapheresis or LVBD.

Exclusion Criteria

  • Currently pregnant or breastfeeding or planning to become pregnant during study participation. - Prior receipt of monoclonal antibody therapy (except for COVID treatment). - Prior receipt of a latency-reversing agent (LRA). - Receipt of HIV-1 or other investigational vaccines within 6 months prior to study Entry. - Receipt of a live-virus vaccine within 60 days or any vaccination within 14 days prior to entry. - Prior receipt of any simian adenovirus-vectored vaccine (e.g., anti-COVID-19 AZD1222). - Known allergy/sensitivity or any hypersensitivity to components of study treatments or their formulations. - Known severe chicken egg allergy. - Known history of a severe reaction or anaphylaxis to prior vaccinations or antibody preparations (e.g., intravenous immunoglobulin). - Significant drug sensitivity or drug allergy (such as anaphylaxis or hepatoxicity). - Any history of anaphylaxis and related symptoms such as hives, respiratory difficulty, or angioedema. - Previous or current history of bleeding factor deficiency, coagulopathy or platelet disorder or on chronic anticoagulation. - History of inflammatory neurologic diseases. - History of pregnancy, head trauma or major surgery within 90 days prior to study Entry. - History of use of any immunomodulatory medications within the 6 months prior to study entry. - Significant serious skin disease, such as but not limited to active rash, eczema, psoriasis, or urticaria. - Autoimmune disease (e.g., lupus, multiple sclerosis, and others) requiring ongoing immunosuppression. - Known history of CDC Stage 3 opportunistic infection (OI). - Any history of an HIV-associated malignancy. - Known or suspected active or untreated latent Mycobacterium tuberculosis infection. - Active or recent non-HIV-associated malignancy. - Serious illness requiring systemic treatment and/or hospitalization within 90 days prior to study entry. - Known resistance to one or more drugs in two or more ARV drug classes. - History of or current clinical atherosclerotic cardiovascular disease - Current advanced liver disease. - Use of complementary or alternative medicines within 14 days prior study entry.

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Double (Participant, Investigator)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Arm A: Active ChAdV and MVA vaccines, vesatolimod and bnAbs
  • 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
    Other names:
    • 3BNC117-LS
  • Drug: GS-2872
    Administered via IV infusion at week 7
    Other names:
    • 10-1074-LS
  • Biological: MVA.tHIVconsv4
    Administered 0.5 mL IM at week 60
Placebo Comparator
Arm B: Placebos for vaccines, vesatolimod and bnAbs
  • Biological: Placebo
    Placebos for vaccines, VES, and bnAbs

Recruiting Locations

Houston AIDS Research Team CRS
Houston, Texas 77004
Contact:
Maria Martinez, BS
713-500-6718
maria.l.martinez@uth.tmc.edu

More Details

Status
Recruiting
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

Study Contact

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 (ChAdV)- 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 with continued virologic control for 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).

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.