Study of Lenacapavir for HIV Pre-Exposure Prophylaxis in People Who Are at Risk for HIV Infection

NCT04925752 | Active Not Recruiting Phase 3 Results DMC FDA Drug

• 2 other identifiers: GS-US-528-9023DOH-27-102021-6681
• Study Type: interventional
• Target: 3,292
• Locations: 8 countries
• Sites: 93

Brief Summary

The goal of this study is to evaluate the efficacy of the study drugs, lenacapavir (LEN) in preventing HIV infection, in participants ≥ 16 years of age who have condomless receptive anal sex with partners assigned male at birth and are at risk for HIV-1 infection. The primary objective of this study is to evaluate the efficacy of LEN for HIV-1 PrEP in participants ≥ 16 years of age who have condomless receptive anal sex with partners assigned male at birth at risk of HIV-1 infection.

Conditions

Pre-Exposure Prophylaxis of HIV Infection

Outcome Measures

Primary Outcomes (2)

• Incidence Phase: Recent Infection Testing Algorithm (RITA) Estimate of the Background Human Immunodeficiency-1 Virus Infection Incidence Rate (bHIV) Per 100 Person Years (PY)

  bHIV per 100 PY in the Incidence Phase was calculated using RITA. The RITA incorporated HIV-1 testing results and recency assay testing results to estimate the bHIV. Recency assay testing was performed for participants in the All Screened Set found to have HIV-1 infection at the Incidence Phase Screening Visit as defined below. Participants were considered to have recent HIV-1 infection if the normalized optical density (ODn) was below 1.5 threshold using the Sedia limiting antigen avidity enzyme immunoassay (LAg-EIA) and the HIV-1 RNA (viral load) was \> 75 copies/mL of blood. HIV-1 infection was defined as participants having at least one of the following central lab results at the Incidence Phase screening visit: * Positive HIV-1/2 differentiation Ab, OR * Positive HIV-1 ribonucleic acid (RNA) qualitative test, OR * HIV-1 RNA quantitative test ≥200 copies/mL.

  Incidence Phase Screening Visit (Day 1)

• Randomized Blinded Phase: HIV-1 Incidence Reported Per 100 PY for LEN Compared to Background HIV (bHIV, Participants in All Screened Set)

  HIV-1 incidence per 100 PY for LEN was calculated as the number of participants who acquired HIV-1 divided by the total of a) for participants not diagnosed with HIV-1, sum of all duration of follow-up time in years, while at risk of HIV-1 infection (where a year is 365.25 days) and b) for participants diagnosed with HIV-1, sum of all duration of follow-up time up to confirmed HIV-1 diagnoses. HIV-1 diagnosis was determined by an HIV adjudication committee who reviewed potential HIV-1 infection events in the randomized participants. The committee, in a blinded, consistent, and unbiased manner, determined whether HIV test results confirmed HIV-1 infection and determined the date of diagnosis for each case, defined as the date of the earliest study visit with evidence of HIV infection considering both prospective HIV testing and back-testing of archived samples. bHIV incidence per 100 PY in All Screened Set was estimated as described in outcome measure#1.

  Up to 149 weeks

Secondary Outcomes (4)

• Randomized Blinded Phase: HIV-1 Incidence Reported Per 100 PY for LEN Compared to F/TDF

  Up to 149 weeks

• Randomized Blinded Phase: HIV-1 Incidence Among Participants Adherent to LEN

  Up to 149 weeks

• Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)

  Up to 4 years

• Percentage of Participants Experiencing Clinically Significant Laboratory Abnormalities

  Up to 4 years

Study Arms (4)

Randomized Blinded Phase: LEN + Placebo-to-match (PTM) F/TDF

EXPERIMENTAL

Participants will receive the following for up to approximately 52 weeks: * Subcutaneous (SC) lenacapavir (LEN) 927 mg every 26 weeks * Oral PTM Emtricitabine/Tenofovir Disoproxil Fumarate (F/TDF) once daily * Oral LEN 600 mg on Days 1 and 2 Participants will receive oral LEN if SC injections are not available.

Drug: Oral Lenacapavir (LEN); Drug: Sub-cutaneous (SC) Lenacapavir (LEN); Drug: PTM F/TDF

Randomized Blinded Phase: Placebo LEN + F/TDF

EXPERIMENTAL

Participants will receive the following for up to approximately 52 weeks: * SC LEN placebo every 26 weeks * Oral F/TDF 200/300 mg once daily * PTM Oral LEN on Days 1 and 2 Participants will receive oral LEN placebo if SC injections are not available.

Drug: F/TDF; Drug: Placebo SC LEN; Drug: PTM Oral LEN

LEN Open-Label Extension (OLE) Phase

EXPERIMENTAL

Participants will be offered entry into LEN OLE Phase, following completion of primary analysis, if LEN demonstrates acceptable safety and efficacy in the Randomized Blinded Phase. Participants randomized to LEN will continue to receive SC LEN 927 mg, every 26 weeks (± 7 days), and have study visits every 13 weeks (± 7 days). Participants randomized to F/TDF will switch to SC LEN 927 mg on OLE Day 1, Week 26 and every 26 weeks thereafter. Participants will also receive oral LEN 600 mg on OLE Days 1 and 2. All participants in LEN OLE Phase will complete the phase, once LEN becomes available or the sponsor decides to discontinue the study, whichever happens first. After completing LEN OLE Phase or study discontinuation, participants will transition to local PrEP, including LEN or other options. If a participant exits early, they will complete an early study drug discontinuation (ESDD), be referred to local PrEP services if needed, and have a 30-day follow-up visit.

Drug: Oral Lenacapavir (LEN); Drug: Sub-cutaneous (SC) Lenacapavir (LEN)

Pharmacokinetic (PK) Tail Phase

EXPERIMENTAL

Participants who prematurely discontinue study drug during the Randomized Blinded Phase and participants that were randomized to LEN who choose not to continue in the LEN OLE Phase will transition to the PK Tail Phase. Participants will receive oral F/TDF (or Emtricitabine/Tenofovir Alafenamide (F/TAF) for US participants only) once daily for 78 weeks to cover the PK tail and complete visits every 13 weeks (+/- 7 days). Upon unblinding, participants who were randomized to F/TDF in the Randomized Blinded Phase who decline to participate in the LEN OLE Phase will complete the ESDD visit, transition to local HIV prevention services, and return for a 30-day follow-up visit.

Drug: F/TDF; Drug: F/TAF (for US participants only)

Interventions

Oral Lenacapavir (LEN) DRUG

Tablets administered orally without regard to food

Also known as: GS-6207

LEN Open-Label Extension (OLE) Phase; Randomized Blinded Phase: LEN + Placebo-to-match (PTM) F/TDF

F/TDF DRUG

Tablets administered orally

Also known as: Truvada®

Pharmacokinetic (PK) Tail Phase; Randomized Blinded Phase: Placebo LEN + F/TDF

PTM F/TDF DRUG

Tablets administered orally

Randomized Blinded Phase: LEN + Placebo-to-match (PTM) F/TDF

Sub-cutaneous (SC) Lenacapavir (LEN) DRUG

Administered via SC injections

Also known as: GS-6207; Yeztugo

LEN Open-Label Extension (OLE) Phase; Randomized Blinded Phase: LEN + Placebo-to-match (PTM) F/TDF

Placebo SC LEN DRUG

Administered via SC injections

Randomized Blinded Phase: Placebo LEN + F/TDF

PTM Oral LEN DRUG

Tablets administered orally

Randomized Blinded Phase: Placebo LEN + F/TDF

F/TAF (for US participants only) DRUG

F/TAF tablets administered orally once daily

Also known as: Descovy

Pharmacokinetic (PK) Tail Phase

Eligibility Criteria

• Age: 16 Years+
• Gender Eligibility Details: Cisgender male (CGM), Transgender male (TGM), Transgender women (TGW), and Gender non-binary (GNB)
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Incidence Phase
• CGM, TGW, TGM, and GNB who have condomless receptive anal sex with partners assigned male at birth and are at risk for HIV infection.
• HIV-1 status unknown at screening and no prior HIV-1 testing within the last 3 months.
• Sexually active with ≥ 1 partner assigned male at birth (condomless receptive anal sex) in the last 12 months and 1 of the following:
• Condomless receptive anal sex with ≥ 2 partners in the last 12 weeks.
• History of syphilis, rectal gonorrhea, or rectal chlamydia in the last 24 weeks.
• Self-reported use of stimulants with sex in the last 12 weeks.
• Randomized Phase
• Negative local rapid fourth generation HIV-1/2 Ab/Ag, central fourth generation HIV-1/2 Ab/Ag, and HIV-1 RNA quantitative nucleic acid amplification testing (NAAT).
• Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min at screening according to the Cockcroft-Gault formula for creatinine clearance (CLcr).

You may not qualify if:

• Incidence Phase
• Prior use of HIV PrEP (including F/TDF or F/TAF) or HIV postexposure prophylaxis (PEP) in the past 12 weeks or any prior use of long-acting systemic PrEP (including cabotegravir or islatravir).
• Prior recipient of an HIV vaccine or HIV broadly neutralizing antibody formulation.
• Randomized Phase
• Acute viral hepatitis A, B or C or evidence of chronic hepatitis B or C infection.
• Severe hepatic impairment or a history of or current clinical decompensated liver cirrhosis.

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (93)

UAB Sexual Health Research Clinic

Birmingham, Alabama, 35233, United States

Location

Loma Linda University Clinical Trial Center Clinic

Loma Linda, California, 92354, United States

Location

Ruane Clinical Research Group Inc.

Los Angeles, California, 90036, United States

Location

UCLA CBAM Vine Street Clinic

Los Angeles, California, 90038, United States

Location

Charles R. Drew University of Medicine and Science (CDU) - Clinical Translational Research Center (CTRC)

Los Angeles, California, 90059, United States

Location

Mills Clinical Research

Los Angeles, California, 90069, United States

Location

The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Los Angeles, California, 90502, United States

Location

BIOS Clinical Research

Palm Springs, California, 92262, United States

Location

UCSD Anti Viral Research Center

San Diego, California, 92103, United States

Location

Bridge HIV at the San Francisco Department of Public Health

San Francisco, California, 94102, United States

Location

Optimus Medical Group

San Francisco, California, 94102, United States

Location

University of Colorado Clinical and Translational Research Centers (CTRC)

Aurora, Colorado, 80045, United States

Location

Yale University, School of Medicine

New Haven, Connecticut, 06510, United States

Location

Whitman-Walker Institute Inc.

Washington D.C., District of Columbia, 20009, United States

Location

Washington Health Institute

Washington D.C., District of Columbia, 20017, United States

Location

Therafirst Medical Center

Fort Lauderdale, Florida, 33308, United States

Location

Gary Richmond, MD, PA

Fort Lauderdale, Florida, 33316, United States

Location

Midway Immunology & Research Center, LLC

Ft. Pierce, Florida, 34982, United States

Location

CAN Community Health Clinic

Jacksonville, Florida, 32207, United States

Location

University of Miami Miller School of Medicine Division of Infectious Disease Research - Converge Miami

Miami, Florida, 33136, United States

Location

CAN Community Health

Miami Gardens, Florida, 33055, United States

Location

Orlando Immunology Center

Orlando, Florida, 32803, United States

Location

CAN Community Health

Sarasota, Florida, 34237, United States

Location

The Hope Clinic at Emory University

Atlanta, Georgia, 30030, United States

Location

Emory University

Atlanta, Georgia, 30303, United States

Location

Emory University Hospital Midtown Infectious Disease Clinic

Atlanta, Georgia, 30308, United States

Location

RMR Core Center

Chicago, Illinois, 60612, United States

Location

University of Illinois at Chicago, Department of Medicine, Division of Infectious Diseases, Project WISH

Chicago, Illinois, 60612, United States

Location

Howard Brown Health Center

Chicago, Illinois, 60613, United States

Location

Indiana University Infectious Diseases Research

Indianapolis, Indiana, 46202, United States

Location

Baptist Health Lexington

Lexington, Kentucky, 40503, United States

Location

Norton Infectious Disease Specialists

Louisville, Kentucky, 40241, United States

Location

LSU-CrescentCare Sexual Health Center- New Orleans Community Health Center

New Orleans, Louisiana, 70119, United States

Location

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21287, United States

Location

The Fenway Institute

Boston, Massachusetts, 02215, United States

Location

Be Well Medical Center

Berkley, Michigan, 48072, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Open Arms Healthcare Center

Jackson, Mississippi, 39202, United States

Location

KC CARE Health Center

Kansas City, Missouri, 64111, United States

Location

St. Michael's Medical Center

Newark, New Jersey, 07102, United States

Location

South Jersey Infectious Disease

Somers Point, New Jersey, 08244, United States

Location

Icahn School of Medicine at Mount Sinai- Mount Sinai Downtown

New York, New York, 10029, United States

Location

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

Chapel Hill, North Carolina, 27514, United States

Location

Cone Health/Regional Center for Infectious Disease Research Center

Greensboro, North Carolina, 27401, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27103, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

Penn Prevention Unit

Philadelphia, Pennsylvania, 19104, United States

Location

Philadelphia FIGHT Community Health Centers, Jonathan Lax Treatment Center

Philadelphia, Pennsylvania, 19107, United States

Location

Medical University of South Carolina, Infectious Disease Clinic

Charleston, South Carolina, 29425, United States

Location

Prisma Health-Midlands Clinical Research Unit

Columbia, South Carolina, 29203, United States

Location

Prisma Health Internal Medicine Clinic

Greenville, South Carolina, 29605, United States

Location

Methodist University Hospital/University of Tennessee Health Science Center, Clinical Research Center

Memphis, Tennessee, 38103, United States

Location

St Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Meharry Medical College Clinical and Transitional Research Center

Nashville, Tennessee, 37208, United States

Location

Central Texas Clinical Research

Austin, Texas, 78705, United States

Location

Centro San Vincente

El Paso, Texas, 79915, United States

Location

UT Health Science Center at Houston

Houston, Texas, 77009, United States

Location

The Crofoot Research Center, INC

Houston, Texas, 77098, United States

Location

Ofiice of Dr. Peter Shalit, MD

Seattle, Washington, 98104, United States

Location

Hospital General de Agudos JM Ramos Mejia

Buenos Aires, 1072, Argentina

Location

Fundacion Huesped

Buenos Aires, 1202, Argentina

Location

Instituto de Investigaciones Clinicas Mar del Plata

Buenos Aires, B7600, Argentina

Location

Unidade de Pesquisa Clinica em Vacinas (UPqVac) da Faculdade de Medicina da Universidade

Belo Horizonte - MG, 30130-100, Brazil

Location

Fundação Bahiana de Infectologia

Canela-Salvador, 40110-060, Brazil

Location

Fundação de Medicina Tropical Doutor Heitor Vieira Dourado / Fundação Medicina Tropical do Amazonas - FMT/IMT/AM

Manauas, 69040-000, Brazil

Location

Hospital General de Nova Iguaçu - HGNI

Nova Iguaçu, 26030-380, Brazil

Location

Grupo Hospitalar Conceição/ Hospital Nossa Senhora da Conceição S.A.

Porto Alegre, RS 91350 200, Brazil

Location

Instituto Nacional de Infectologia Evandro Chagas / Fundação Oswaldo Cruz - INI FIOCRUZ

Rio de Janeiro, 21040-360, Brazil

Location

Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo

São Paulo, 01246-903, Brazil

Location

Centro de Referência e Treinamento DST/AIDS

São Paulo, 04121-000, Brazil

Location

Center for Management and Research. SPDM-Paulista Association for the Development of Medicine-Hospital São Paulo/Federal

São Paulo, 06519-332, Brazil

Location

Centro de Investigacion Farmaceutica Especializada de Occidente S.C.

Guadalajara C.P., 44160, Mexico

Location

Asociacion Civil Impacta Salud y Educacion - Sede Barranco

Barranco, 15063, Peru

Location

Instituto de Medicina Tropical "Daniel Alcides Carrion", Facultad de Medicina Humana, UNMSM

Callao, 7006, Peru

Location

Asociacion Civil Selva Amazonica

Iquitos, Peru

Location

Via Libre

Lima, 15001, Peru

Location

Asociacion Civil Impacta Salud y Educacion - Sede San Miguel

Lima, 15088, Peru

Location

Ararat Research Center

San Juan, PR, 00717, Puerto Rico

Location

Centro Ararat- San Juan

San Juan, PR, 00909, Puerto Rico

Location

Desmond Tutu Health Foundation

Cape Town, 7925, South Africa

Location

Wits Reproductive Health and HIV Institute (Wits RHI)

Johannesburg, 2038, South Africa

Location

The Aurum Institute: Pretoria Clinical Research Centre

Pretoria, 87, South Africa

Location

Setshaba Research Centre

Soshanguvhe, 0152, South Africa

Location

The Aurum Institute Tembisa CRC, Clinic 4

Tembisa, 1632, South Africa

Location

FPD-DTHF Ndevana Commuity Research Site

Vincent, 5217, South Africa

Location

Institute of HIV Research and Innovation

Bangkok, 10330, Thailand

Location

King Chulalongkorn Memorial Hospital

Bangkok, 10330, Thailand

Location

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

Bangkok, 10330, Thailand

Location

Ramathibodi Hospital, Mahidol University

Bangkok, 10400, Thailand

Location

Research Institute for Health Sciences, Chiang Mai University

Chiang Mai, 50200, Thailand

Location

Srinagarind Hospital, Khon Kaen University

Khon Kaen, 40002, Thailand

Location

Bamrasnaradura Infectious Disease Institute

Nonthaburi, 11000, Thailand

Location

Related Publications (3)

• Kelley CF, Acevedo-Quiñones M, Agwu AL, et al. Twice-yearly lenacapavir PrEP in cisgender gay men, transgender women and men, and gender-diverse people (PURPOSE 2). Presented at: HIV Drug Therapy Glasgow; November 10-13, 2024; Glasgow, United Kingdom.

  BACKGROUND

• Kelley CF, Acevedo-Quinones M, Agwu AL, Avihingsanon A, Benson P, Blumenthal J, Brinson C, Brites C, Cahn P, Cantos VD, Clark J, Clement M, Creticos C, Crofoot G, Diaz RS, Doblecki-Lewis S, Gallardo-Cartagena JA, Gaur A, Grinsztejn B, Hassler S, Hinojosa JC, Hodge T, Kaplan R, Lacerda M, LaMarca A, Losso MH, Valdez Madruga J, Mayer KH, Mills A, Mounzer K, Ndlovu N, Novak RM, Perez Rios A, Phanuphak N, Ramgopal M, Ruane PJ, Sanchez J, Santos B, Schine P, Schreibman T, Spencer LY, Van Gerwen OT, Vasconcelos R, Vasquez JG, Zwane Z, Cox S, Deaton C, Ebrahimi R, Wong P, Singh R, Brown LB, Carter CC, Das M, Baeten JM, Ogbuagu O; PURPOSE 2 Study Team. Twice-Yearly Lenacapavir for HIV Prevention in Men and Gender-Diverse Persons. N Engl J Med. 2025 Apr 3;392(13):1261-1276. doi: 10.1056/NEJMoa2411858. Epub 2024 Nov 27.

  PMID: 39602624 BACKGROUND

• Cespedes M, Das M, Hojilla JC, Blumenthal J, Mounzer K, Ramgopal M, Hodge T, Torres TS, Peterson C, Shibase S, Elliott A, Demidont AC, Callaghan L, Watson CC, Carter C, Kintu A, Baeten JM, Ogbuagu O. Proactive strategies to optimize engagement of Black, Hispanic/Latinx, transgender, and nonbinary individuals in a trial of a novel agent for HIV pre-exposure prophylaxis (PrEP). PLoS One. 2022 Jun 3;17(6):e0267780. doi: 10.1371/journal.pone.0267780. eCollection 2022.

  PMID: 35657826 BACKGROUND

Related Links

• Gilead Clinical Trials Website

MeSH Terms

Interventions

lenacapavir; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; emtricitabine tenofovir alafenamide

Intervention Hierarchy (Ancestors)

Tenofovir; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations

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 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2021
• First Posted: June 14, 2021
• Study Start: June 28, 2021
• Primary Completion: August 21, 2024
• Study Completion (Estimated): August 1, 2028
• Last Updated: December 23, 2025
• Results First Posted: September 17, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

PR (2); BR (9); TH (7); ME (1); PE (5); US (60); AR (3); ZA (6)