A Study of Teropavimab and Zinlirvimab in Combination With Capsid Inhibitor Lenacapavir in Virologically Suppressed Adults With HIV-1 Infection

NCT ID: NCT05729568

Last Updated: 2025-07-15

Study Results

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Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

83 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-05-15

Study Completion Date

2029-12-31

Brief Summary

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The goal of this study is to test the effectiveness, safety, and tolerability of the combination of broadly neutralizing antibodies (bNAbs) (teropavimab (TAB; GS-5423) and zinlirvimab (ZAB; GS-2872)) with lenacapavir (LEN) in virologically suppressed adults with HIV-1 infection.

The purpose of this study is to evaluate the efficacy of switching to a regimen of LEN, TAB and ZAB, versus continuing on baseline oral antiretroviral therapy (ART) as determined by the proportion of participants with human immunodeficiency virus-1 (HIV-1) ribonucleic acid (RNA) ≥ 50 copies/mL at Week 26.

Detailed Description

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Participants will be randomized in Treatment Groups 1 and 2 to receive LEN, TAB, and ZAB, with differing doses of TAB and ZAB between the 2 groups and in Treatment Group 3 to continue their baseline oral ART for 52 weeks. Eligible participants in Treatment Groups 1 through 3 will have the option of participating in the study extension phase to receive LEN, TAB and ZAB after completing study follow-up through Week 52.

Treatment Group 2 was removed prior to dosing of all groups during Protocol Amendment 2.

Conditions

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HIV Infection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Randomized Phase Treatment Group 1: LEN + TAB + ZAB

Participants will receive loading dose of lenacapavir (LEN) 600 mg tablets, orally, on Day 1 and Day 2. They will receive LEN 927 mg subcutaneous (SC) injection along with teropavimab (TAB) 2550 mg intravenous (IV) infusion and zinlirvimab (ZAB) 2550 mg IV infusion on Day 1 and every 6 months (Q6M) up to Week 52 in the Randomized Phase.

Group Type EXPERIMENTAL

Teropavimab

Intervention Type DRUG

Administered intravenously

Zinlirvimab

Intervention Type DRUG

Administered intravenously

Lenacapavir Tablet

Intervention Type DRUG

Administered orally

Lenacapavir Injection

Intervention Type DRUG

Administered subcutaneously

Randomized Phase Treatment Group 3: SBR

Participants in Stay on Baseline Regimen (SBR) group will continue their baseline oral antiretroviral therapy (ART) up to Week 52. ART included drugs like bictegravir/emtricitabine/tenofovir alafenamide, darunavir/cobicistat/emtricitabine/tenofovir alafenamide, dolutegravir/abacavir lamivudine, and rilpivirine/emtricitabine/tenofovir alafenamide, administered as per standard of care.

Group Type EXPERIMENTAL

Antiretroviral Therapy

Intervention Type DRUG

Antiretroviral therapy, administered orally may include regimens such as: bictegravir/emtricitabine/tenofovir alafenamide, darunavir/cobicistat/emtricitabine/tenofovir alafenamide, dolutegravir/abacavir lamivudine, and rilpivirine/emtricitabine/tenofovir alafenamide.

Extension Phase: Treatment Group 1: LEN + TAB + ZAB

At Week 52, participants in this group with HIV-1 RNA \< 50 copies/mL will be given the option to participate in the study extension phase. In the study extension phase, participants will continue to receive their randomized study drugs every 26 weeks.

Group Type EXPERIMENTAL

Teropavimab

Intervention Type DRUG

Administered intravenously

Zinlirvimab

Intervention Type DRUG

Administered intravenously

Lenacapavir Injection

Intervention Type DRUG

Administered subcutaneously

Extension Phase Treatment Group 3: SBR

At Week 52, participants in this group with HIV-1 RNA \< 50 copies/mL and in the absence of confirmed virologic rebound throughout the Randomized Phase of the study will be given the option to participate in the Extension Phase to switch from oral ART to LEN, TAB and ZAB, every 26 weeks at the dose specified for Treatment Group 1.

Group Type EXPERIMENTAL

Teropavimab

Intervention Type DRUG

Administered intravenously

Zinlirvimab

Intervention Type DRUG

Administered intravenously

Lenacapavir Tablet

Intervention Type DRUG

Administered orally

Lenacapavir Injection

Intervention Type DRUG

Administered subcutaneously

Interventions

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Teropavimab

Administered intravenously

Intervention Type DRUG

Zinlirvimab

Administered intravenously

Intervention Type DRUG

Lenacapavir Tablet

Administered orally

Intervention Type DRUG

Lenacapavir Injection

Administered subcutaneously

Intervention Type DRUG

Antiretroviral Therapy

Antiretroviral therapy, administered orally may include regimens such as: bictegravir/emtricitabine/tenofovir alafenamide, darunavir/cobicistat/emtricitabine/tenofovir alafenamide, dolutegravir/abacavir lamivudine, and rilpivirine/emtricitabine/tenofovir alafenamide.

Intervention Type DRUG

Other Intervention Names

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GS-5423 GS-2872 GS-6207 GS-6207 Sunlenca®

Eligibility Criteria

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Inclusion Criteria

* On stable oral antiretroviral therapy (ART) consisting of no more than 2 drug classes (with the exception of pharmacologic boosters cobicistat or ritonavir) for ≥ 1 year prior to screening visit 2. A change in ART regimen ≥ 28 days prior to screening visit 2 for reasons other than virologic failure (VF) (eg, tolerability, simplification, drug-drug interaction profile) is allowed.
* No clinically significant documented historical resistance to the current ART regimen with the exception of isolated nucleoside reverse transcriptase inhibitor mutations including M184V or ≤ 2 thymidine analog mutations (TAMs: M41L, D67N, K70R, L210W, T215Y, and/or K219Q).
* Plasma human immunodeficiency virus-1 (HIV-1) ribonucleic acid (RNA) \< 50 copies/mL at screening visit 2.
* Documented plasma HIV-1 RNA \< 50 copies/mL for ≥ 12 months preceding screening visit 2 (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL). Virologic elevations of ≥ 50 copies/mL (transient detectable viremia or "blips") prior to screening are acceptable.
* Proviral phenotypic sensitivity to both teropavimab and zinlirvimab at screening or from protocol GS-US-536-5816 within 24 months prior to screening.
* Screening clusters of differentiation 4 (CD4)+ T-cell count ≥ 200 cells/μL at screening visit 2.

Exclusion Criteria

* Comorbid condition requiring ongoing immunosuppression.
* Evidence of hepatitis C virus (HCV) infection (prior infection cleared spontaneously or with treatment is acceptable)
* Evidence of current hepatitis B virus (HBV) infection regardless of HBV surface antigen status, at the screening visit 2.
* History of opportunistic infection or illness indicative of Stage 3 HIV disease.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

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Ruane Clinical Research Group, Inc.

Los Angeles, California, United States

Site Status

Mills Clinical Research

Los Angeles, California, United States

Site Status

UC San Diego (UCSD) AntiViral Research Center (AVRC)

San Diego, California, United States

Site Status

Optimus Medical Group

San Francisco, California, United States

Site Status

University of Colorado Clinical and Translational Research Center

Aurora, Colorado, United States

Site Status

Yale University; School of Medicine; AIDS Program

New Haven, Connecticut, United States

Site Status

Georgetown University Medical Center

Washington D.C., District of Columbia, United States

Site Status

Midland Florida Clinical Research Center, LLC

DeLand, Florida, United States

Site Status

Can Community Health Care

Fort Lauderdale, Florida, United States

Site Status

Midway Immunology and Research Center

Ft. Pierce, Florida, United States

Site Status

Orlando Immunology Center

Orlando, Florida, United States

Site Status

Triple O Research Institute, P.A.

West Palm Beach, Florida, United States

Site Status

Emory University Hospital Midtown Infectious Disease Clinic

Atlanta, Georgia, United States

Site Status

Infectious Disease Specialists of Atlanta

Decatur, Georgia, United States

Site Status

Southhampton Healthcare, Inc

St Louis, Missouri, United States

Site Status

AXCES Research Group, LLC

Albuquerque, New Mexico, United States

Site Status

Montefiore Medical Center

The Bronx, New York, United States

Site Status

NC TraCS Institute - CTRC; University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Site Status

Duke University Health Center

Durham, North Carolina, United States

Site Status

Regional Center for Infectious Disease Research

Greensboro, North Carolina, United States

Site Status

The Brody School of Medicine at East Carolina University

Greenville, North Carolina, United States

Site Status

Rosedale Health and Wellness

Huntersville, North Carolina, United States

Site Status

Prisma Health - Clinical Research Unit

Columbia, South Carolina, United States

Site Status

St Jude Children's Research Hospital

Memphis, Tennessee, United States

Site Status

Central Texas Clinical Research

Austin, Texas, United States

Site Status

AIDS Arms, Inc. DBA Prism Health North Texas

Dallas, Texas, United States

Site Status

AXCES Research Group, LLC

El Paso, Texas, United States

Site Status

The Crofoot Research Center, INC

Houston, Texas, United States

Site Status

Clinical Alliance for Research & Education, Infectious Diseases LLC (CARE-ID)

Annandale, Virginia, United States

Site Status

East Sydney Doctors

Darlinghurst, New South Wales, Australia

Site Status

Holdsworth House Medical Practice

Sydney, New South Wales, Australia

Site Status

Alfred Hospital

Melbourne, Victoria, Australia

Site Status

Maple Leaf Research/Maple Leaf Medical Clinic

Toronto, , Canada

Site Status

Clinical Research Puerto Rico

San Juan, , Puerto Rico

Site Status

Countries

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United States Australia Canada Puerto Rico

References

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Mponponsuo K, McMahon JH, Gorgos L, Morales-Ramirez J, Workowski K, Brunetta J, Ogbuagu O, Collins SE, VanderVeen LA, Huang H, Baeten JM, Eron JJ. Efficacy and Safety of Lenacapavir, Teropavimab, and Zinlirvimab: Phase II Week 26 Primary Outcome [Oral 07]. Conference on Retroviruses and Opportunistic Infections (CROI); 2025 9-12 March, San Francisco, CA.

Reference Type BACKGROUND

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

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GS-US-536-5939

Identifier Type: -

Identifier Source: org_study_id

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