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

NCT05729568 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 1 other identifier: GS-US-536-5939
• Study Type: interventional
• Target: 83
• Locations: 4 countries
• Sites: 34

Brief Summary

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.

Conditions

HIV-1 Infection

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) ≥ 50 Copies/mL at Week 26 as Determined by the United States Food and Drug Administration (US FDA)-Defined Snapshot Algorithm

  Percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 26 was analyzed using US FDA-defined snapshot algorithm, which defines a participant's virologic outcome and included participants a) who had last available on-treatment HIV-1 RNA ≥ 50 copies/mL in the Week 26 analysis window; or b) who did not have on-treatment HIV-1 RNA data in the Week 26 analysis window and i) discontinued study drug prior to or in the Week 26 analysis window due to lack of efficacy, or ii) discontinued study drug prior to or in the Week 26 analysis window due to adverse event (AE) or death and had last available on-treatment HIV-1 RNA ≥ 50 copies/mL, or iii) discontinued study drug prior to or in the Week 26 analysis window due to reasons other than AE, death, or lack of efficacy and had the last available on-treatment HIV-1 RNA ≥ 50 copies/mL. Clopper-Pearson exact method was used to calculate the 95% confidence interval (CI) for the outcome measure of each treatment. Percentages were rounded off.

  Week 26

Secondary Outcomes (16)

• Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 52 as Determined by the US FDA-defined Snapshot Algorithm

  Week 52

• Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 26 as Determined by the US FDA-defined Snapshot Algorithm

  Week 26

• Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 52 as Determined by the US FDA-defined Snapshot Algorithm

  Week 52

• Change From Baseline in Clusters of Differentiation 4 (CD4) + T-cell Counts at Week 26

  Baseline, Week 26

• Change From Baseline in CD4+ T-cell Counts at Week 52

  Baseline, Week 52

Study Arms (4)

Randomized Phase Treatment Group 1: LEN + TAB + ZAB

EXPERIMENTAL

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 26 weeks up to Week 52 in the Randomized Phase. 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.

Drug: Teropavimab; Drug: Zinlirvimab; Drug: Lenacapavir Tablet; Drug: Lenacapavir Injection

Randomized Phase Treatment Group 3: SBR

EXPERIMENTAL

Participants in Stay on Baseline Regimen (SBR) group will continue their baseline oral antiretroviral therapy (ART) up to Week 52. Antiretroviral therapy will include 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. 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 switch from oral ART to LEN, TAB and ZAB, every 26 weeks. The participants will switch to receive LEN, TAB, and ZAB every 26 weeks beginning at Week 52.

Drug: Antiretroviral Therapy

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

EXPERIMENTAL

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 receive LEN 927 mg SC, TAB 2550 mg IV infusion and ZAB 2550 mg IV infusion.

Drug: Teropavimab; Drug: Zinlirvimab; Drug: Lenacapavir Injection

Extension Phase Treatment Group 3: SBR

EXPERIMENTAL

At Week 52, participants in this group will be given the option to participate in the Extension Phase to switch from oral ART to LEN 927 mg SC, TAB 2550 mg IV infusion and ZAB 2550 mg IV infusion, every 26 weeks at the dose specified for Treatment Group 1.

Drug: Teropavimab; Drug: Zinlirvimab; Drug: Lenacapavir Tablet; Drug: Lenacapavir Injection

Interventions

Teropavimab DRUG

Administered intravenously

Also known as: GS-5423, 3BNC117-LS

Extension Phase Treatment Group 3: SBR; Extension Phase: Treatment Group 1: LEN + TAB + ZAB; Randomized Phase Treatment Group 1: LEN + TAB + ZAB

Zinlirvimab DRUG

Administered intravenously

Also known as: GS-2872, 10-1074-LS

Extension Phase Treatment Group 3: SBR; Extension Phase: Treatment Group 1: LEN + TAB + ZAB; Randomized Phase Treatment Group 1: LEN + TAB + ZAB

Lenacapavir Tablet DRUG

Administered orally

Also known as: GS-6207

Extension Phase Treatment Group 3: SBR; Randomized Phase Treatment Group 1: LEN + TAB + ZAB

Lenacapavir Injection DRUG

Administered subcutaneously

Also known as: GS-6207, Sunlenca®

Extension Phase Treatment Group 3: SBR; Extension Phase: Treatment Group 1: LEN + TAB + ZAB; Randomized Phase Treatment Group 1: LEN + TAB + ZAB

Antiretroviral Therapy 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.

Randomized Phase Treatment Group 3: SBR

Eligibility Criteria

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

You may qualify if:

• 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 by the PhenoSense Assay (Monogram Biosciences).
• Screening clusters of differentiation 4 (CD4)+ T-cell count ≥ 200 cells/μL at screening visit 2.

You may not qualify if:

• Comorbid condition requiring ongoing immunosuppression.
• Hepatitis C virus (HCV) antibody positive and HCV RNA detectable.
• 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.

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (34)

Ruane Clinical Research Group, Inc.

Los Angeles, California, 90036, United States

Location

Mills Clinical Research

Los Angeles, California, 90069, United States

Location

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

San Diego, California, 92103, United States

Location

Optimus Medical Group

San Francisco, California, 94102, United States

Location

University of Colorado Clinical and Translational Research Center

Aurora, Colorado, 80045, United States

Location

Yale University; School of Medicine; AIDS Program

New Haven, Connecticut, 06510, United States

Location

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

Midland Florida Clinical Research Center, LLC

DeLand, Florida, 32720, United States

Location

Can Community Health Care

Fort Lauderdale, Florida, 33316, United States

Location

Midway Immunology and Research Center

Ft. Pierce, Florida, 34982, United States

Location

Orlando Immunology Center

Orlando, Florida, 32803, United States

Location

Triple O Research Institute, P.A.

West Palm Beach, Florida, 33407, United States

Location

Emory University Hospital Midtown Infectious Disease Clinic

Atlanta, Georgia, 30308, United States

Location

Infectious Disease Specialists of Atlanta

Decatur, Georgia, 30033, United States

Location

Southhampton Healthcare, Inc

St Louis, Missouri, 63139, United States

Location

AXCES Research Group, LLC

Albuquerque, New Mexico, 87109, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

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

Chapel Hill, North Carolina, 27514, United States

Location

Duke University Health Center

Durham, North Carolina, 27710, United States

Location

Regional Center for Infectious Disease Research

Greensboro, North Carolina, 27401, United States

Location

The Brody School of Medicine at East Carolina University

Greenville, North Carolina, 27858, United States

Location

Rosedale Health and Wellness

Huntersville, North Carolina, 28078, United States

Location

Prisma Health - Clinical Research Unit

Columbia, South Carolina, 29203, United States

Location

St Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Central Texas Clinical Research

Austin, Texas, 78705, United States

Location

AIDS Arms, Inc. DBA Prism Health North Texas

Dallas, Texas, 75208, United States

Location

AXCES Research Group, LLC

El Paso, Texas, 79902, United States

Location

The Crofoot Research Center, INC

Houston, Texas, 77098, United States

Location

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

Annandale, Virginia, 22003, United States

Location

East Sydney Doctors

Darlinghurst, New South Wales, 2010, Australia

Location

Holdsworth House Medical Practice

Sydney, New South Wales, 2010 NSW, Australia

Location

Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

Maple Leaf Research/Maple Leaf Medical Clinic

Toronto, M5G 1K2, Canada

Location

Clinical Research Puerto Rico

San Juan, 909, Puerto Rico

Location

Related Publications (2)

• 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.

  BACKGROUND

• Ogbuagu O, Gaur A, McMahon JH, Gorgos L, Morales-Ramirez JO, Workowski K, Brunetta J, Mponponsuo K, Collins SE, VanderVeen LA, Zhang N, Huang H, Baeten JM, Eron J. Efficacy and safety of lenacapavir, teropavimab, and zinlirvimab: week-26 primary outcome results from a multicentre, open-label, randomised, active-controlled, phase 2 study. Lancet Microbe. 2026 Mar;7(3):101283. doi: 10.1016/j.lanmic.2025.101283. Epub 2026 Feb 17.

  PMID: 41720146 DERIVED

Related Links

• Gilead Clinical Trials Website

MeSH Terms

Interventions

lenacapavir; Antiretroviral Therapy, Highly Active

Intervention Hierarchy (Ancestors)

Drug Therapy, Combination; Drug Therapy; Therapeutics

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 6, 2023
• First Posted: February 15, 2023
• Study Start: May 15, 2023
• Primary Completion: July 2, 2024
• Study Completion (Estimated): December 1, 2030
• Last Updated: April 27, 2026
• Results First Posted: July 15, 2025

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

PR (1); AU (3); CA (1); US (29)