Study to Compare an Oral Weekly Islatravir/Lenacapavir Regimen With Standard of Care in Virologically Suppressed People With HIV-1

NCT06630299 | Active Not Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: GS-US-563-59262024-514047-28
• Study Type: interventional
• Target: 600
• Locations: 14 countries
• Sites: 100

Brief Summary

The goal of this clinical study is to learn more about the safety and efficacy of switching to a once weekly tablet of islatravir/lenacapavir (ISL/LEN) regimen versus continuing standard of care treatment in people with human immunodeficiency virus (PWH) who are virologically suppressed (HIV-1 RNA levels \< 50 copies/mL) on a stable standard of care regimen for ≥ 6 months prior to screening. The standard of care includes 2 or 3 medicines, antiretroviral agents (ARVs). The primary objective of the study is to evaluate the efficacy of switching to oral weekly ISL/LEN tablet regimen versus continuing standard of care in virologically suppressed PWH at Week 48.

Conditions

HIV-1-Infection

Outcome Measures

Primary Outcomes (1)

• Proportion of participants with HIV-1 RNA ≥ 50 copies/mL at Week 48 as Determined by the United States (US) Food and Drug Administration (FDA)-defined Snapshot Algorithm

  Week 48

Secondary Outcomes (6)

• Proportion of Participants with HIV-1 RNA ≥ 50 copies/mL at Week 96 as Determined by the US FDA-defined Snapshot Algorithm

  Week 96

• Proportion of Participants with HIV-1 RNA < 50 copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm

  Week 48

• Proportion of Participants with HIV-1 RNA < 50 copies/mL at Week 96 as Determined by the US FDA-defined Snapshot Algorithm

  Week 96

• Change from Baseline in clusters of differentiation 4 (CD4) T-Cell Count at Week 48

  Baseline, Week 48

• Change from Baseline in CD4 T-Cell Count at Week 96

  Baseline, Week 96

Study Arms (3)

ISL/LEN

EXPERIMENTAL

Participants will receive an initial dose of ISL/LEN (Dose A), followed by once weekly ISL/LEN (Dose B) from Day 8 onwards up to Week 96.

Drug: ISL/LEN

Standard of Care Treatment

ACTIVE COMPARATOR

Participants will continue standard of care treatment with 2-3 ARVs up to Week 96: * Integrase Strand Transfer Inhibitor (INSTI) class: INSTI combined with 1 or 2 nucleoside reverse transcriptase inhibitors (NRTIs; bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF; coformulated; Biktarvy®), dolutegravir (DTG)/abacavir (ABC)/lamivudine (3TC), DTG+ TAF or TDF (TXF)/emtricitabine (FTC; Emtriva®), DTG/tenofovir disoproxil fumarate (TDF; Viread®)/3TC, DTG/3TC, raltegravir (RAL) + TXF/FTC, RAL+TDF/3TC, elvitegravir (EVG; Vitekta®)/cobicistat (c; Tybost®)/TXF/FTC), or * PI class: Boosted protease inhibitor (PI) combined with 2 NRTIs (darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF; coformulated), boosted darunavir (DRV)+TXF/FTC, boosted DRV+TDF/3TC), or * NNRTI class: Nonnucleoside reverse transcriptase inhibitor (NNRTI) combined with 2 NRTIs (doravirine (DOR)/TDF/3TC, DOR+TXF/FTC, DOR+TDF/3TC, rilpivirine (RPV)/TXF/FTC, RPV+TXF/FTC, RPV+TDF/3TC)

Drug: ISL/LEN; Drug: Antiretroviral Combinations

Extension Phase

EXPERIMENTAL

At the end of randomized treatment visit, if safety and efficacy of ISL/LEN are demonstrated following review of randomized data, participants will be given the option to receive ISL/LEN tablets in an extension phase until ISL/LEN becomes available or until the sponsor elects to discontinue the study, whichever occurs first. Participants receiving ISL/LEN during the randomized phase will continue to take ISL/LEN weekly. Participants receiving standard of care during the randomized phase will take an initial dose of ISL/LEN (Dose A), followed by once weekly ISL/LEN (Dose B) from Day 8 onwards.

Drug: ISL/LEN

Interventions

ISL/LEN DRUG

Tablet administered orally

Extension Phase; ISL/LEN; Standard of Care Treatment

Antiretroviral Combinations DRUG

2 or 3 antiretrovirals (ARVs) administered as defined by the investigator, according to the prescribing information.

Standard of Care Treatment

Eligibility Criteria

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

You may qualify if:

• HIV-1 RNA \< 50 copies/mL for ≥ 6 months before screening, as documented by:
• One HIV-1 RNA \< 50 copies/mL immediately preceding the 24 weeks period prior to screening.
• Within 24 weeks prior to screening, if HIV-1 RNA results are available, all levels must be \< 50 copies/mL.
• During the 6 to 12 months period prior to screening, transient detectable viremia ≥ 50 copies/mL is acceptable ("blip") as long as it is not confirmed on 2 consecutive visits.
• Plasma HIV-1 RNA levels \< 50 copies/mL at screening.
• Are receiving guideline-recommended standard of care treatment such as International Antiviral Society (IAS), Department of Health and Human Services (DHHS), European AIDS Clinical Society (EACS) consisting of 2 or 3 ARVs for ≥ 6 months prior to screening and willing to continue until Day 1. Individuals in Treatment Group 2 must also be willing to continue their standard of care through at least Week 96.
• Individuals assigned female at birth and of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified methods of contraception.

You may not qualify if:

• Prior virologic failure.
• Prior use of, or exposure to, ISL or LEN.
• Active, serious infections requiring parenteral therapy within 30 days before randomization.
• Active tuberculosis infection.
• Acute hepatitis within 30 days before randomization.
• Hepatitis B virus (HBV) infection, as determined below at the screening visit:
• positive HBV surface antigen OR
• positive HBV core antibody and negative HBV surface antibody. Note: individuals found to be susceptible to HBV infection (eg negative hepatitis B surface antibody at the screening visit, regardless of prior HBV vaccination history) should be recommended to receive HBV vaccination.
• Active hepatitis C virus (HCV) coinfection, defined as detectable HCV RNA. Note: individuals with prior/inactive HCV infection (defined as undetectable HCV RNA) may be enrolled.
• Any of the following laboratory values at screening:
• Creatinine clearance (CLcr) ≤ 30 mL/min according to the Cockcroft-Gault formula
• Alanine aminotransferase (ALT) \> 5 x upper limit of normal (ULN)
• Direct bilirubin \> 1.5 x ULN
• Platelets \< 50,000/μL
• Hemoglobin \< 8.0 g/dL

Sponsors & Collaborators

• Gilead Sciences: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (100)

University of Alabama at Birmingham(UAB) 1917 Research Clinic

Birmingham, Alabama, 35294, United States

Location

Pueblo Family Physicians

Phoenix, Arizona, 85015, United States

Location

Vv-Tmf-5366229

Los Angeles, California, 90027, United States

Location

Ruane Clinical Research Group

Los Angeles, California, 90036, United States

Location

BIOS Clinical Research

Palm Springs, California, 92262, United States

Location

Vivent Health

Denver, Colorado, 80246, United States

Location

University of Colorado Clinical and Translational Research Center

Denver, Colorado, 80262, 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

Aids Healthcare Foundation - Northpoint

Fort Lauderdale, Florida, 33308, United States

Location

Midway Immunology and Research Center

Ft. Pierce, Florida, 34982, United States

Location

CAN Community Health

Miami Gardens, Florida, 33055, United States

Location

Orlando Immunology Center

Orlando, Florida, 32803, United States

Location

AHF Pensacola

Pensacola, Florida, 32503, United States

Location

CAN Community Health

Sarasota, Florida, 34237, United States

Location

BayCare Health System, Inc./St. Joseph's Hospital

Tampa, Florida, 33607, United States

Location

Triple O Research Institute, P.A.

West Palm Beach, Florida, 33401, United States

Location

Metro Infectious Disease Consultants, P.L.L.C.

Decatur, Georgia, 30033, United States

Location

Mercer University, Department of Internal Medicine

Macon, Georgia, 31201, United States

Location

Chatham County Health Department

Savannah, Georgia, 31401, United States

Location

Howard Brown Health Center

Chicago, Illinois, 60613, United States

Location

Indiana CTSI Clinical Research Center

Indianapolis, Indiana, 46202, United States

Location

Brigham and Womens's Hospital

Boston, Massachusetts, 02115, United States

Location

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

Community Research Initiative of New England d/b/a Community Resource Initiative (CRI)

Boston, Massachusetts, 02129, United States

Location

Be Well Medical Center

Berkley, Michigan, 48072, United States

Location

Henry Ford Health

Detroit, Michigan, 48202, United States

Location

Trinity Health Michigan d/b/a Trinity Health Grand Rapids Hospital

Grand Rapids, Michigan, 49503, United States

Location

ID Care

Hillsborough, New Jersey, 08844, United States

Location

Saint Michael's Medical Center

Newark, New Jersey, 07102, United States

Location

AXCES Research Group, LLC

Santa Fe, New Mexico, 87505, United States

Location

NewYork-Presbyterian Queens

Flushing, New York, 11355, United States

Location

Northwell Health/Division of Infectious Diseases

Manhasset, New York, 11030, United States

Location

Jacobi Medical Center

The Bronx, New York, 10461, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Duke University Health System(DUHS)

Durham, North Carolina, 27710, United States

Location

ECU Health Leo Jenkins Cancer Building

Greenville, North Carolina, 27834, United States

Location

Rosedale Health and Wellness

Huntersville, North Carolina, 28078, United States

Location

University of Cincinnati College of Medicine

Cincinnati, Ohio, 45267, United States

Location

Prisma Health Midlands - Clinical Research Unit

Columbia, South Carolina, 29203, United States

Location

Central Texas Clinical Research

Austin, Texas, 78705, United States

Location

North Texas Infectious Diseases Consultants, PA

Dallas, Texas, 75246, United States

Location

AXCES Research Group, LLC

El Paso, Texas, 79902, United States

Location

Texas Centers for Infectious Disease Associates

Fort Worth, Texas, 76104, United States

Location

The Crofoot Research Center, INC.

Houston, Texas, 77098, United States

Location

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

Longview, Texas, 75605, United States

Location

AXCES Research Group, LLC

Salt Lake City, Utah, 84102, United States

Location

Clinical Alliance for Research& Education - Infectious Diseases, LLC

Annandale, Virginia, 22003, United States

Location

MultiCare Rockwood Main Clinic

Spokane, Washington, 99202, United States

Location

Hospital General de Agudos Dr. J.M. Ramos Mejia

Buenos Aires, 1072, Argentina

Location

Fundacion Huesped

Buenos Aires, 1202, Argentina

Location

Helios Salud S.A.

Buenos Aires, 1425, Argentina

Location

East Sydney Doctors

Darlinghurst, New South Wales, 2010, Australia

Location

St Vincent's Hospital

Darlinghurst, New South Wales, 2010, Australia

Location

Taylor Square Private Clinic

Surry Hills, New South Wales, 2010, Australia

Location

Monash Health

Clayton, Victoria, 3168, Australia

Location

Prahran Market Clinic

South Yarra, Victoria, 3141, Australia

Location

Dr. Scholten & Schneeweiß GbR

Cologne, 50674, Germany

Location

University Hospital Hannover, Department for Rheumatology and Immunology

Hanover, 30625, Germany

Location

Mannheimer Onkologie Praxis

Mannheim, 68167, Germany

Location

MVZ München am Goetheplatz, MUC Research GmbH

München, 80337, Germany

Location

Chiba University Hospital

Chiba, Japan

Location

National Hospital Organization Nagoya Medical Center

Nagoya, 460-0001, Japan

Location

University of the Ryukyus Hospital

Okinawa, Japan

Location

Osaka City General Hospital

Osaka, 534-0021, Japan

Location

National Hospital Organization Osaka National Hospital

Osaka Fu, 540-0006, Japan

Location

Tokyo Medical University Hospital

Tokyo, 160-0023, Japan

Location

Japan Institute for Health Security National Center for Global Health and Medicine

Tokyo, 162-8655,, Japan

Location

Amsterdam UMC, Iocation AMC

Amsterdam, 1105 az, Netherlands

Location

Leiden University Medical Center (LUMC)

Leiden, 2333 ZA, Netherlands

Location

Samodzielny Publiczny Wojewodzig Szpital Zespolony Poradnia Nabytych Niedoborow Immunologicznych

Szczecin, 71-455, Poland

Location

Wroclawskie Centrum Zorowia Samodzielny Publiczn Zaklad Opieki Zdrowotnej Sp Zoo Osrodek Profilaktyczno-Leczniczy Chorob Zakaznych I Terapi Uzaleznien

Wroclaw, 50-136, Poland

Location

HOPE Clinical Research

San Juan, PR, 00909, Puerto Rico

Location

Maternal Infant Studies Center(CEMI)

San Juan, 00936-5067, Puerto Rico

Location

Desmond Tutu Health Foundation, Clinical Trials Unit

Cape Town, 7925, South Africa

Location

Perinatal HIV Research Unit

Soweto, 2013, South Africa

Location

Hospital Germans Trias I Pujol

Barcelona, 08916, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Inselspital, Freiburgstrasse 20. Bern

Bern, 3010, Switzerland

Location

Hopitaux Universitaires de Geneve

Geneva, 1205, Switzerland

Location

Centre Hospitalier Universitaire Vaudois

Lausanne, 1011, Switzerland

Location

Kaohsiung Medical University Hospital

Kaohsiung City, 80756, Taiwan

Location

Kaohsiung Veterans General Hospital

Kaohsiung City, 81362, Taiwan

Location

Far Eastern Memorial Hospital

New Taipei City, 22060, Taiwan

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Taoyuan General Hospital

Taoyuan, 33004, Taiwan

Location

The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), Thai Red Cross AIDS Research

Bangkok, 10330, Thailand

Location

Siriraj Hospital

Bangkok, 10700, Thailand

Location

Chiang Mai University

Chiang Mai, 50200, Thailand

Location

Khon Kaen University

Khon Kaen, 40002, Thailand

Location

Bamrasnaradura Infectious Disease Institute

Nonthaburi, 11000, Thailand

Location

Institute of HIV Research and Innovation (IHRI)

Pathumwan, 10330, Thailand

Location

Clinical Research Facility -University Hospitals Sussex NHS Foundation Trust

Brighton, BN2 3EW, United Kingdom

Location

Harrison Wing Research Unit, Southwark Wing, Guy's Hospital (Guy's & St. Thomas' NHS Foundation Trust)

Great Maze Pond, SE1 3RR, United Kingdom

Location

Grahame Hayton Unit, Ambrose King Centre, Royal London Hospital (Barts Health NHS Trust)

London, E1 1BB., United Kingdom

Location

Royal Free Hospital (Royal Free London NHS Foundation Trust)

London, NW3 2QG, United Kingdom

Location

Caldecot Centre, King's College Hospital (King's College Hospital NHS Foundation Trust)

London, SE5 9RJ, United Kingdom

Location

Mortimer Market Centre (Central and North West London NHS Foundation Trust)

London, WC1E 6JB, United Kingdom

Location

Related Links

• Gilead Clinical Trials Website

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 4, 2024
• First Posted: October 8, 2024
• Study Start: October 8, 2024
• Primary Completion: April 1, 2026
• Study Completion (Estimated): August 1, 2030
• Last Updated: November 14, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (49); NL (2); PR (2); ZA (2); DE (4); CH (3); TW (5); PL (2); AU (5); AR (3); JP (7); ES (4); TH (6); GB (6)