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

NCT ID: NCT06071767

Last Updated: 2025-07-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

45 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-04-01

Study Completion Date

2029-08-01

Brief Summary

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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

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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

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HIV-1-infection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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

Group Type EXPERIMENTAL

ChAdOx1.tHIVconsv1

Intervention Type BIOLOGICAL

Administered as 0.4 mL intramuscularly (IM) at Week 0

ChAdOx1.HIVconsv62

Intervention Type BIOLOGICAL

Administered as 0.3 mL IM at Week 0

MVA.tHIVconsv3

Intervention Type BIOLOGICAL

Administered as 0.3 mL IM at Week 4

MVA.tHIVconsv4

Intervention Type BIOLOGICAL

Administered as 0.5 mL IM at week 4

Vesatolimod (VES)

Intervention Type 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.

GS-5423

Intervention Type DRUG

Administered via intravenous (IV) infusion at week 7

GS-2872

Intervention Type DRUG

Administered via IV infusion at week 7

MVA.tHIVconsv4

Intervention Type BIOLOGICAL

Administered 0.5 mL IM at week 60

Arm B: Placebos for vaccines, vesatolimod and bnAbs

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type BIOLOGICAL

Placebos for vaccines, VES, and bnAbs

Interventions

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ChAdOx1.tHIVconsv1

Administered as 0.4 mL intramuscularly (IM) at Week 0

Intervention Type BIOLOGICAL

ChAdOx1.HIVconsv62

Administered as 0.3 mL IM at Week 0

Intervention Type BIOLOGICAL

MVA.tHIVconsv3

Administered as 0.3 mL IM at Week 4

Intervention Type BIOLOGICAL

MVA.tHIVconsv4

Administered as 0.5 mL IM at week 4

Intervention Type BIOLOGICAL

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.

Intervention Type DRUG

GS-5423

Administered via intravenous (IV) infusion at week 7

Intervention Type DRUG

GS-2872

Administered via IV infusion at week 7

Intervention Type DRUG

MVA.tHIVconsv4

Administered 0.5 mL IM at week 60

Intervention Type BIOLOGICAL

Placebo

Placebos for vaccines, VES, and bnAbs

Intervention Type BIOLOGICAL

Other Intervention Names

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3BNC117-LS Teropavimab 10-1074-LS Zinlirvimab

Eligibility Criteria

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Inclusion Criteria

* Provision of written informed consent.
* History of Initiation of combination ART within 90 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 ≤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) 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 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 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Oxford

OTHER

Sponsor Role collaborator

Gilead Sciences

INDUSTRY

Sponsor Role collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Sharon Riddler, MD, MPH

Role: STUDY_CHAIR

University of Pittsburgh

Locations

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University of California, San Diego AntiViral Research Center CRS

San Diego, California, United States

Site Status RECRUITING

Ponce de Leon Center CRS

Atlanta, Georgia, United States

Site Status RECRUITING

Northwestern University CRS

Chicago, Illinois, United States

Site Status RECRUITING

Massachusetts General Hospital CRS (MGH CRS)

Boston, Massachusetts, United States

Site Status NOT_YET_RECRUITING

Washington University Therapeutics CRS

St Louis, Missouri, United States

Site Status RECRUITING

Columbia Physicians & Surgeons CRS

New York, New York, United States

Site Status RECRUITING

Chapel Hill CRS

Chapel Hill, North Carolina, United States

Site Status RECRUITING

Greensboro CRS

Greensboro, North Carolina, United States

Site Status NOT_YET_RECRUITING

Cincinnati CRS

Cincinnati, Ohio, United States

Site Status NOT_YET_RECRUITING

Ohio State University CRS

Columbus, Ohio, United States

Site Status RECRUITING

Penn Therapeutics CRS

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

Houston AIDS Research Team CRS

Houston, Texas, United States

Site Status RECRUITING

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

Porto Alegre, Rio Grande do Sul, Brazil

Site Status RECRUITING

Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS

Rio de Janeiro, , Brazil

Site Status NOT_YET_RECRUITING

Countries

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United States Brazil

Facility Contacts

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Steven Hendrickx, BSN

Role: primary

619-543-6968

Ericka Patrick, RN, MSN

Role: primary

404-616-6313

Baiba Berzins, MPH

Role: primary

312-695-5012

Amy Sbrolla, ACRN, BSN

Role: primary

617-726-5598

Michael Klebert, RN, NP-C, PhD

Role: primary

314-747-1098

Mascha Elskamp

Role: primary

212-305-2201

Erin Hoffman, BS

Role: primary

919-843-0720

Kim Epperson, RN, BSN, CCRC

Role: primary

336-832-3262

Kelly Phillips, PAC, MPAS

Role: backup

336-832-7297

Michelle Saemann, RN

Role: primary

513-584-2245

Lindsay Summers, MPH

Role: primary

614-293-8529

Jamie Doyle

Role: primary

215-615-2316

Maria Martinez, BS

Role: primary

713-500-6718

Rita de Cassia Alves Lira, M.D.

Role: primary

55-51-33572603

Brenda Hoagland, MD

Role: primary

55-21-38659122

Other Identifiers

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12025

Identifier Type: OTHER

Identifier Source: secondary_id

HIV-CORE 009

Identifier Type: OTHER

Identifier Source: secondary_id

A5374

Identifier Type: -

Identifier Source: org_study_id

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