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

NCT06071767 | Recruiting Phase 1 FDA Drug

• 3 other identifiers: A537412025HIV-CORE 009
• Study Type: interventional
• Target: 36
• Locations: 2 countries
• Sites: 12

Brief 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).

Conditions

HIV-1-infection

Keywords

Suppressive Antiretroviral Therapy; HIV; Acute HIV-1; HIV vaccine; T-cell vaccine; Therapeutic T-cell vaccine; ChAdOx1; MVA; Conserved region vaccine; HIVconsvX; Toll-like receptor 7 agonist; TLR7; Broadly neutralizing antibody; Antibodies; HIV antibody; HIV Broadly neutralizing antibody

Outcome Measures

Primary Outcomes (2)

• Occurrence of any serious adverse event (AE), Grade 3 or higher AE, or AE that leads to permanent discontinuation of study treatment regardless of grade, that is related to ChAdOx1-MVA/HIVconsvX vaccines, vesatolimod, GS-5423 or GS-2872

  Week 0 to Week 64

• Proportion of participants with viral control during an ATI defined as remaining off ART with HIV-1 RNA <1,000 copies/mL at Week 16 following ATI.

  Week 0 to Week 16 on Step 2

Secondary Outcomes (13)

• Change in cell-associated HIV-1 RNA and DNA levels

  Weeks 0 to Week 24 on Step 2

• Change in plasma HIV-1 RNA viral load as measured by single copy assay (SCA)

  Weeks 0 to Week 24 on Step 2

• Change in intact proviral DNA levels (IPDA)

  Weeks 0 to Week 24 on Step 2

• HIV-1-specific T-cell responses to the conserved regions present in the vaccines as measured by IFN-γ ELISPOT - total frequency and breadth (number of recognized peptide pools out of 10).

  Week 0 to Week 24 on Step 2

• Change in soluble markers of systemic inflammation and immune activation: sCD163 (pg/mL)

  Weeks 0 to Week 24 on Step 2

Study Arms (2)

Arm A: Active ChAdOx1 and MVA/HIVconsvX vaccines, vesatolimod and bnAbs

EXPERIMENTAL

Biological: ChAdOx1.tHIVconsv1; Biological: ChAdOx1.HIVconsv62; Biological: MVA.tHIVconsv3; Biological: MVA.tHIVconsv4; Drug: Vesatolimod (VES); Drug: GS-5423; Drug: GS-2872

Arm B: Placebos for vaccines, vesatolimod and bnAbs

PLACEBO COMPARATOR

Biological: Placebo

Interventions

ChAdOx1.HIVconsv62 BIOLOGICAL

Administered as 0.3 mL IM at Week 0

Arm A: Active ChAdOx1 and MVA/HIVconsvX vaccines, vesatolimod and bnAbs

MVA.tHIVconsv3 BIOLOGICAL

Administered as 0.3 mL IM at Week 4

Arm A: Active ChAdOx1 and MVA/HIVconsvX vaccines, vesatolimod and bnAbs

MVA.tHIVconsv4 BIOLOGICAL

Administered as 0.5 mL IM at week 4

Arm A: Active ChAdOx1 and MVA/HIVconsvX vaccines, vesatolimod and bnAbs

Vesatolimod (VES) DRUG

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.

Arm A: Active ChAdOx1 and MVA/HIVconsvX vaccines, vesatolimod and bnAbs

GS-5423 DRUG

Administered via intravenous (IV) infusion at week 7

Also known as: 3BNC117-LS, Teropavimab

Arm A: Active ChAdOx1 and MVA/HIVconsvX vaccines, vesatolimod and bnAbs

GS-2872 DRUG

Administered via IV infusion at week 7

Also known as: 10-1074-LS, Zinlirvimab

Arm A: Active ChAdOx1 and MVA/HIVconsvX vaccines, vesatolimod and bnAbs

Placebo BIOLOGICAL

Placebos for vaccines, VES, and bnAbs

Arm B: Placebos for vaccines, vesatolimod and bnAbs

ChAdOx1.tHIVconsv1 BIOLOGICAL

Administered as 0.4 mL intramuscularly (IM) at Week 0

Arm A: Active ChAdOx1 and MVA/HIVconsvX vaccines, vesatolimod and bnAbs

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of written informed consent.
• History of Initiation of combination ART within 90 days of acute HIV diagnosis
• On ART for at least 12 months with no known ART interruption \>28 consecutive days within 12 months prior to Step 1 Study Entry
• 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 ≤150 kg at Screening.
• CD4 cell count ≥500 cells/mm3 obtained within 60 days prior to Study Entry.
• HIV-1 RNA \<50 copies/mL (or below the assay limit of quantification if local assay lower limit of quantification is \>50 copies/mL) 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.

You may not qualify if:

• Currently pregnant or breastfeeding or planning to become pregnant during study participation.
• Prior receipt of anti-HIV broadly neutralizing antibody therapy.
• Receipt of any non-HIV monoclonal antibody therapy within 1 year prior to study entry.
• 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 Study Entry.
• Receipt of any simian adenovirus-vectored vaccine (e.g., anti-COVID-19 AZD1222) within 12 months prior to Step 1 Study Entry.
• 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 Step 1 Study Entry.

Sponsors & Collaborators

• University of Oxford: collaborator
• Gilead Sciences: collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (12)

University of California, San Diego AntiViral Research Center CRS

San Diego, California, 92103, United States

RECRUITING

Ponce de Leon Center CRS

Atlanta, Georgia, 30308, United States

RECRUITING

Northwestern University CRS

Chicago, Illinois, 60611, United States

RECRUITING

Massachusetts General Hospital CRS (MGH CRS)

Boston, Massachusetts, 02114, United States

NOT YET RECRUITING

Washington University Therapeutics CRS

St Louis, Missouri, 63110, United States

RECRUITING

Columbia Physicians & Surgeons CRS

New York, New York, 10032, United States

RECRUITING

Chapel Hill CRS

Chapel Hill, North Carolina, 27599, United States

RECRUITING

Ohio State University CRS

Columbus, Ohio, 43210, United States

RECRUITING

Penn Therapeutics CRS

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Houston AIDS Research Team CRS

Houston, Texas, 77004, United States

RECRUITING

Instituto de Pesquisas em AIDS do Rio Grande do Sul - IPARGS CRS

Porto Alegre, Rio Grande do Sul, 91350-180, Brazil

RECRUITING

Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS

Rio de Janeiro, Brazil

NOT YET RECRUITING

MeSH Terms

Interventions

vesatolimod

Study Officials

• Sharon Riddler, MD, MPH

  University of Pittsburgh

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 5, 2023
• First Posted: October 6, 2023
• Study Start: April 1, 2024
• Primary Completion (Estimated): April 29, 2028
• Study Completion (Estimated): August 1, 2029
• Last Updated: February 9, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 3 months following publication and available throughout period of funding of the AIDS Clinical Trials Group by NIH.
• Access Criteria: * With whom? Researchers who provide a methodologically sound proposal for use of the data that is approved by the AIDS Clinical Trials Group. * For what types of analyses? To achieve aims in the proposal approved by the AIDS Clinical Trials Group. * By what mechanism will data be made available? Researchers may submit a request for access to data using the AIDS Clinical Trials Group "Data Request" form at: https://actgnetwork.org/submit-a-proposal/. Researchers of approved proposals will need to sign an AIDS Clinical Trials Group Data Use Agreement before receiving the data.

Locations

BR (2); US (10)