Study to Evaluate the Safety and Efficacy of Lenacapavir (GS-6207) in Combination With an Optimized Background Regimen (OBR) in Heavily Treatment Experienced Participants Living With HIV-1 Infection With Multidrug Resistance

NCT ID: NCT04150068

Last Updated: 2025-09-26

Study Results

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Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2/PHASE3

Total Enrollment

72 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-11-21

Study Completion Date

2027-01-31

Brief Summary

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The primary objective of this study is to evaluate the antiviral activity of lenacapavir (formerly GS-6207) administered as an add-on to a failing regimen (functional monotherapy) in people with human immunodeficiency virus (HIV) (PWH) with multi-drug resistance (MDR).

Detailed Description

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Conditions

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HIV-1-infection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Cohort 1A: Lenacapavir

Participants with HIV-1 ribonucleic acid (RNA) ≥ 400 copies/mL and with a \<0.5 log10 HIV-1 RNA decline at Cohort Selection visit compared with screening visit will receive oral lenacapavir (LEN) 600 mg tablet on Days 1 and 2 and 300 mg tablet on Day 8, while continuing their failing regimen in blinded Functional Monotherapy Period (Baseline to Day 14); followed by unblinded Maintenance Period where participants will receive subcutaneous (SC) LEN 927 mg and will initiate an optimized background regimen (OBR) at Day 1 SC Visit (14 days after the first dose of oral LEN).

Participants will receive their subsequent SC LEN injection at Week 26 Visit (relative to Day 1 SC). Participants will be given an option to receive SC LEN injection at Weeks 52 and 156, while continuing their OBR, until product becomes accessible to participants through an access program or until Gilead elects to discontinue the study in the country.

Group Type EXPERIMENTAL

Oral Lenacapavir

Intervention Type DRUG

Tablets administered without regard to food

Subcutaneous Lenacapavir

Intervention Type DRUG

Administered in the abdomen via subcutaneous injections

Failing ARV Regimen

Intervention Type DRUG

Failing antiretroviral (ARV) regimen defined by the lack of efficacy. Any combination of approved and unapproved agents that could potentially be part of the failing regimen.

Optimized Background Regimen (OBR)

Intervention Type DRUG

Optimized background regimen as prescribed by the Investigator

Cohort 1B: Placebo to Lenacapavir

Participants with HIV-1 RNA ≥ 400 copies/mL and with a \<0.5 log10 HIV-1 RNA decline at the Cohort Selection visit compared with screening visit will receive oral LEN placebo on Days 1, 2, and 8 while continuing their failing regimen in blinded Functional Monotherapy Period (Baseline to Day 14); followed by unblinded Maintenance Period where participants will receive oral LEN 600 mg on Days 15 and 16 and 300 mg on Day 22, and will initiate an OBR on Day 15. At Day 1 SC (14 days after the first dose of oral LEN), participants will receive SC LEN 927 mg while continuing OBR.

Participants will receive their subsequent SC LEN injection at Week 26 Visit (relative to Day 1 SC). Participants will be given an option to receive SC LEN injection at Weeks 52 and 156, while continuing their OBR, until the product becomes accessible to participants through an access program or until Gilead elects to discontinue study in the country.

Group Type PLACEBO_COMPARATOR

Oral Lenacapavir

Intervention Type DRUG

Tablets administered without regard to food

Oral Lenacapavir Placebo

Intervention Type DRUG

Tablets administered without regard to food

Subcutaneous Lenacapavir

Intervention Type DRUG

Administered in the abdomen via subcutaneous injections

Failing ARV Regimen

Intervention Type DRUG

Failing antiretroviral (ARV) regimen defined by the lack of efficacy. Any combination of approved and unapproved agents that could potentially be part of the failing regimen.

Optimized Background Regimen (OBR)

Intervention Type DRUG

Optimized background regimen as prescribed by the Investigator

Cohort 2: Lenacapavir

Participants with a ≥ 0.5 log10 copies/mL HIV-1 RNA decline at the Cohort Selection Visit compared with the screening visit or with HIV-1 RNA \< 400 copies/mL or if Cohort 1 is fully enrolled will receive oral LEN 600 mg tablet on Days 1 and 2 and 300 mg tablet on Day 8, and will initiate an OBR on Day 1 in Oral Lead-in Period (Baseline to Day 14); followed by Maintenance Period where participants will receive SC LEN 927 mg at Day 1 SC Visit (14 days after the first dose of oral LEN) while continuing their OBR.

Participants will receive their subsequent SC LEN injection at Week 26 Visit (relative to Day 1 SC). Participants will be given an option to receive SC LEN injection at Weeks 52 and 156, while continuing their OBR, until the product becomes accessible to participants through an access program or until Gilead elects to discontinue the study in the country.

Group Type EXPERIMENTAL

Oral Lenacapavir

Intervention Type DRUG

Tablets administered without regard to food

Subcutaneous Lenacapavir

Intervention Type DRUG

Administered in the abdomen via subcutaneous injections

Optimized Background Regimen (OBR)

Intervention Type DRUG

Optimized background regimen as prescribed by the Investigator

Interventions

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Oral Lenacapavir

Tablets administered without regard to food

Intervention Type DRUG

Oral Lenacapavir Placebo

Tablets administered without regard to food

Intervention Type DRUG

Subcutaneous Lenacapavir

Administered in the abdomen via subcutaneous injections

Intervention Type DRUG

Failing ARV Regimen

Failing antiretroviral (ARV) regimen defined by the lack of efficacy. Any combination of approved and unapproved agents that could potentially be part of the failing regimen.

Intervention Type DRUG

Optimized Background Regimen (OBR)

Optimized background regimen as prescribed by the Investigator

Intervention Type DRUG

Other Intervention Names

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Sunlenca® GS-6207 Sunlenca® GS-6207

Eligibility Criteria

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Inclusion Criteria

* Adult aged ≥ 18 years (at all sites) or adolescent aged ≥ 12 and weighing ≥ 35 kg (at sites in North America and Dominican Republic)
* Currently receiving a stable failing ARV regimen for \> 8 weeks
* Have HIV-1 RNA ≥ 400 copies/mL at screening
* Have multidrug resistance (resistance to ≥2 agents from ≥3 of the 4 main classes of ARV)
* Have no more than 2 fully active ARV remaining from the 4 main classes that can be effectively combined to form a viable regimen
* Able and willing to receive an OBR together with lenacapavir
* No Hepatitis C virus (HCV) ongoing infection
Minimum Eligible Age

12 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

Eisenhower Health Center at Rimrock

Palm Springs, California, United States

Site Status

One Community Health

Sacramento, California, United States

Site Status

Yale University; School of Medicine

New Haven, Connecticut, United States

Site Status

Washington Health Institute

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

Site Status

Midland Florida Clinical Research Center, LLC

DeLand, Florida, United States

Site Status

Gary J. Richmond, M.D., P.A.

Fort Lauderdale, Florida, United States

Site Status

Midway Immunology and Research Center

Ft. Pierce, Florida, United States

Site Status

Floridian Clinical Research

Hialeah, Florida, United States

Site Status

AIDS Healthcare Foundation - South Beach

Miami Beach, Florida, United States

Site Status

Orlando Immunology Center

Orlando, Florida, United States

Site Status

St. Joseph's Hospital Comprehensive Research Institute

Tampa, Florida, United States

Site Status

Triple O Research Institute, P.A.

West Palm Beach, Florida, United States

Site Status

Emory Hospital Midtown Infectious Disease Clinic

Atlanta, Georgia, United States

Site Status

Atlanta ID Group, PC

Atlanta, Georgia, United States

Site Status

Chatham County Health Department

Savannah, Georgia, United States

Site Status

Howard Brown Health Center

Chicago, Illinois, United States

Site Status

Northstar Healthcare

Chicago, Illinois, United States

Site Status

Be Well Medical Center

Berkley, Michigan, United States

Site Status

Southampton Healthcare, Inc.

St Louis, Missouri, United States

Site Status

New York-Presbyterian/Queens

Flushing, New York, United States

Site Status

North Shore University Hospital/Division of Infectious Diseases

Manhasset, New York, United States

Site Status

Jacobi Medical Center

The Bronx, New York, United States

Site Status

Atrium Health- Infectious Disease Consultants

Charlotte, North Carolina, United States

Site Status

Perelman Center for Advanced Medicine at the Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

The Miriam Hospital

Providence, Rhode Island, United States

Site Status

1265 Union Avenue, 8 East

Memphis, Tennessee, United States

Site Status

Central Texas Clinical Research

Austin, Texas, United States

Site Status

St Hope Foundation

Bellaire, Texas, United States

Site Status

AIDS Arms, Inc. DBA Prism Health North Texas

Dallas, Texas, United States

Site Status

North Texas Infectious Diseases Consultants, P.A.

Dallas, Texas, United States

Site Status

The Crofoot Research Center, INC.

Houston, Texas, United States

Site Status

DCOL Center for Clinical Research

Longview, Texas, United States

Site Status

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

Annandale, Virginia, United States

Site Status

Vancouver ID Research and Care Centre Society

Vancouver, British Columbia, Canada

Site Status

Maple Leaf Research/Maple Leaf Medical Clinic

Toronto, Ontario, Canada

Site Status

Clinique de médecine urbaine du Quartier Latin

Montreal, Quebec, Canada

Site Status

The Ottawa Hospital

Ottawa, , Canada

Site Status

Instituto Dominicano de Estudios Virologicos (IDEV)

Santo Domingo, , Dominican Republic

Site Status

Hospital Dr. Salvador Bienvenido Gautier

Santo Domingo, , Dominican Republic

Site Status

Hôpital Sainte-Marguerite

Marseille, , France

Site Status

Hôpital Saint-Louis

Paris, , France

Site Status

Hôpital Saint-Antoine

Paris, , France

Site Status

Hôpital Bichat-Claude Bernard

Paris, , France

Site Status

Universitätsklinikum Frankfurt, Medizinische Klinik II

Frankfurt am Main, Hesse, Germany

Site Status

Universitätsklinikum Essen, Klinik für Dermatologie und Venerologie

Essen, , Germany

Site Status

ICH Study Center GmbH & Co. KG

Hamburg, , Germany

Site Status

University of Naples Federico II

Bergamo, , Italy

Site Status

UOC Malattie Infettive - ASST Spedali Civili Di Brescia - Piazzale Spedali Civili 1

Brescia, , Italy

Site Status

Divisione di Malattie Infettive, IRCCS Ospedale San Raffaele

Milan, , Italy

Site Status

U.O.C. IMMUNODEFICIENZE VIRALI - Istituto Nazionale Malattie Infettive Lazzaro Spallanzani IRCCS

Roma, , Italy

Site Status

U.O.C. Malattie Infettive - Fondazione Policlinico Universitario A. Gemelli IRCCS

Rome, , Italy

Site Status

National Hospital Organization Nagoya Medical Center

Nagoya, , Japan

Site Status

National Hospital Organization Osaka National Hospital

Osaka, , Japan

Site Status

Tokyo Medical University Hospital

Tokyo, , Japan

Site Status

Center Hospital of the National Center for Global Health and Medicine

Tokyo, , Japan

Site Status

Durban International Clinical Research Site, Enhancing Care Foundation

Durban, , South Africa

Site Status

Helen Joseph Hospital

Johannesburg, , South Africa

Site Status

Vx Pharma

Pretoria, , South Africa

Site Status

Perinatal HIV Research Unit (PHRU)

Soweto, , South Africa

Site Status

Hospital Universitari Germans Trías i Pujol

Badalona, , Spain

Site Status

Hospital Clinic de Barcelona

Barcelona, , Spain

Site Status

Hospital Universitario La Paz

Madrid, , Spain

Site Status

Hospital Universitario Virgen del Rocío

Seville, , Spain

Site Status

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, , Taiwan

Site Status

Kaohsiung Veterans General Hospital

Kaohsiung City, , Taiwan

Site Status

Far Eastern Memorial Hospital

New Taipei City, , Taiwan

Site Status

National Taiwan University Hospital

Taipei, , Taiwan

Site Status

Taoyuan General Hospital, Ministry of Health and Welfare

Taoyuan, , Taiwan

Site Status

Thai Red Cross AIDS Research Center

Bangkok, , Thailand

Site Status

Faculty of Medicine Ramathibodi Hospital, Mahidol University

Bangkok, , Thailand

Site Status

Faculty of Medicine Siriraj Hospital, Mahidol University

Bangkok, , Thailand

Site Status

Faculty of Medicine, Khon Kaen University

Khon Kaen, , Thailand

Site Status

Bamrasnaradura Infectious Diseases Institute

Nonthaburi, , Thailand

Site Status

Countries

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United States Canada Dominican Republic France Germany Italy Japan South Africa Spain Taiwan Thailand

References

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Segal-Maurer S, Castagna A, Berhe M, et al. Potent Antiviral Activity of Lenacapavir in Phase 2/3 in Heavily ART-Experienced PWH [Abstract 127]. Presented at: Conference on Retroviruses and Opportunistic Infections; 2021 March 6-10.

Reference Type BACKGROUND

Ogbuagu O, Molina JM, Chetchotisakd P, Ramgopal MN, Sanchez W, Brunetta J, Castelli F, Crofoot GE, Hung CC, Ronot-Bregigeon S, Margot NA, Wang H, Dvory-Sobol H, Rhee MS, Segal-Maurer S. Efficacy and Safety of Long-Acting Subcutaneous Lenacapavir in Heavily Treatment-Experienced People with Multidrug-Resistant HIV-1: Week 104 Results of a Phase 2/3 Trial. Clin Infect Dis. 2025 Mar 17;80(3):566-574. doi: 10.1093/cid/ciae423.

Reference Type DERIVED
PMID: 39206943 (View on PubMed)

Ogbuagu O, Segal-Maurer S, Ratanasuwan W, Avihingsanon A, Brinson C, Workowski K, Antinori A, Yazdanpanah Y, Trottier B, Wang H, Margot N, Dvory-Sobol H, Rhee MS, Baeten JM, Molina JM; GS-US-200-4625 investigators. Efficacy and safety of the novel capsid inhibitor lenacapavir to treat multidrug-resistant HIV: week 52 results of a phase 2/3 trial. Lancet HIV. 2023 Aug;10(8):e497-e505. doi: 10.1016/S2352-3018(23)00113-3. Epub 2023 Jul 11.

Reference Type DERIVED
PMID: 37451297 (View on PubMed)

Segal-Maurer S, DeJesus E, Stellbrink HJ, Castagna A, Richmond GJ, Sinclair GI, Siripassorn K, Ruane PJ, Berhe M, Wang H, Margot NA, Dvory-Sobol H, Hyland RH, Brainard DM, Rhee MS, Baeten JM, Molina JM; CAPELLA Study Investigators. Capsid Inhibition with Lenacapavir in Multidrug-Resistant HIV-1 Infection. N Engl J Med. 2022 May 12;386(19):1793-1803. doi: 10.1056/NEJMoa2115542.

Reference Type DERIVED
PMID: 35544387 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan: Primary Efficacy Endpoint Analysis

View Document

Document Type: Statistical Analysis Plan: Week 26 Interim Analysis

View Document

Related Links

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Other Identifiers

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2019-003814-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GS-US-200-4625

Identifier Type: -

Identifier Source: org_study_id

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