Study of Lenacapavir for HIV Pre-Exposure Prophylaxis in People Who Are at Risk for HIV Infection
NCT ID: NCT04925752
Last Updated: 2025-12-23
Study Results
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View full resultsBasic Information
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ACTIVE_NOT_RECRUITING
PHASE3
3292 participants
INTERVENTIONAL
2021-06-28
2028-08-31
Brief Summary
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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.
Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
PREVENTION
DOUBLE
Study Groups
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Randomized Blinded Phase: LEN + Placebo-to-match (PTM) F/TDF
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.
Oral Lenacapavir (LEN)
Tablets administered orally without regard to food
Sub-cutaneous (SC) Lenacapavir (LEN)
Administered via SC injections
PTM F/TDF
Tablets administered orally
Randomized Blinded Phase: Placebo LEN + F/TDF
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.
F/TDF
Tablets administered orally
Placebo SC LEN
Administered via SC injections
PTM Oral LEN
Tablets administered orally
LEN Open-Label Extension (OLE) Phase
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.
Oral Lenacapavir (LEN)
Tablets administered orally without regard to food
Sub-cutaneous (SC) Lenacapavir (LEN)
Administered via SC injections
Pharmacokinetic (PK) Tail Phase
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.
F/TDF
Tablets administered orally
F/TAF (for US participants only)
F/TAF tablets administered orally once daily
Interventions
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Oral Lenacapavir (LEN)
Tablets administered orally without regard to food
F/TDF
Tablets administered orally
Sub-cutaneous (SC) Lenacapavir (LEN)
Administered via SC injections
Placebo SC LEN
Administered via SC injections
PTM F/TDF
Tablets administered orally
PTM Oral LEN
Tablets administered orally
F/TAF (for US participants only)
F/TAF tablets administered orally once daily
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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).
Exclusion Criteria
* 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.
16 Years
ALL
Yes
Sponsors
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Gilead Sciences
INDUSTRY
Responsible Party
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Principal Investigators
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Gilead Study Director
Role: STUDY_DIRECTOR
Gilead Sciences
Locations
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UAB Sexual Health Research Clinic
Birmingham, Alabama, United States
Loma Linda University Clinical Trial Center Clinic
Loma Linda, California, United States
Ruane Clinical Research Group Inc.
Los Angeles, California, United States
UCLA CBAM Vine Street Clinic
Los Angeles, California, United States
Charles R. Drew University of Medicine and Science (CDU) - Clinical Translational Research Center (CTRC)
Los Angeles, California, United States
Mills Clinical Research
Los Angeles, California, United States
The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Los Angeles, California, United States
BIOS Clinical Research
Palm Springs, California, United States
UCSD Anti Viral Research Center
San Diego, California, United States
Bridge HIV at the San Francisco Department of Public Health
San Francisco, California, United States
Optimus Medical Group
San Francisco, California, United States
University of Colorado Clinical and Translational Research Centers (CTRC)
Aurora, Colorado, United States
Yale University, School of Medicine
New Haven, Connecticut, United States
Whitman-Walker Institute Inc.
Washington D.C., District of Columbia, United States
Washington Health Institute
Washington D.C., District of Columbia, United States
Therafirst Medical Center
Fort Lauderdale, Florida, United States
Gary Richmond, MD, PA
Fort Lauderdale, Florida, United States
Midway Immunology & Research Center, LLC
Ft. Pierce, Florida, United States
CAN Community Health Clinic
Jacksonville, Florida, United States
University of Miami Miller School of Medicine Division of Infectious Disease Research - Converge Miami
Miami, Florida, United States
CAN Community Health
Miami Gardens, Florida, United States
Orlando Immunology Center
Orlando, Florida, United States
CAN Community Health
Sarasota, Florida, United States
The Hope Clinic at Emory University
Atlanta, Georgia, United States
Emory University
Atlanta, Georgia, United States
Emory University Hospital Midtown Infectious Disease Clinic
Atlanta, Georgia, United States
RMR Core Center
Chicago, Illinois, United States
University of Illinois at Chicago, Department of Medicine, Division of Infectious Diseases, Project WISH
Chicago, Illinois, United States
Howard Brown Health Center
Chicago, Illinois, United States
Indiana University Infectious Diseases Research
Indianapolis, Indiana, United States
Baptist Health Lexington
Lexington, Kentucky, United States
Norton Infectious Disease Specialists
Louisville, Kentucky, United States
LSU-CrescentCare Sexual Health Center- New Orleans Community Health Center
New Orleans, Louisiana, United States
Johns Hopkins University School of Medicine
Baltimore, Maryland, United States
The Fenway Institute
Boston, Massachusetts, United States
Be Well Medical Center
Berkley, Michigan, United States
Henry Ford Hospital
Detroit, Michigan, United States
Open Arms Healthcare Center
Jackson, Mississippi, United States
KC CARE Health Center
Kansas City, Missouri, United States
St. Michael's Medical Center
Newark, New Jersey, United States
South Jersey Infectious Disease
Somers Point, New Jersey, United States
Icahn School of Medicine at Mount Sinai- Mount Sinai Downtown
New York, New York, United States
NC TraCS Institute - CTRC; University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States
Cone Health/Regional Center for Infectious Disease Research Center
Greensboro, North Carolina, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States
University of Cincinnati
Cincinnati, Ohio, United States
The Ohio State University Wexner Medical Center
Columbus, Ohio, United States
Penn Prevention Unit
Philadelphia, Pennsylvania, United States
Philadelphia FIGHT Community Health Centers, Jonathan Lax Treatment Center
Philadelphia, Pennsylvania, United States
Medical University of South Carolina, Infectious Disease Clinic
Charleston, South Carolina, United States
Prisma Health-Midlands Clinical Research Unit
Columbia, South Carolina, United States
Prisma Health Internal Medicine Clinic
Greenville, South Carolina, United States
Methodist University Hospital/University of Tennessee Health Science Center, Clinical Research Center
Memphis, Tennessee, United States
St Jude Children's Research Hospital
Memphis, Tennessee, United States
Meharry Medical College Clinical and Transitional Research Center
Nashville, Tennessee, United States
Central Texas Clinical Research
Austin, Texas, United States
Centro San Vincente
El Paso, Texas, United States
UT Health Science Center at Houston
Houston, Texas, United States
The Crofoot Research Center, INC
Houston, Texas, United States
Ofiice of Dr. Peter Shalit, MD
Seattle, Washington, United States
Hospital General de Agudos JM Ramos Mejia
Buenos Aires, , Argentina
Fundacion Huesped
Buenos Aires, , Argentina
Instituto de Investigaciones Clinicas Mar del Plata
Buenos Aires, , Argentina
Unidade de Pesquisa Clinica em Vacinas (UPqVac) da Faculdade de Medicina da Universidade
Belo Horizonte - MG, , Brazil
Fundação Bahiana de Infectologia
Canela-Salvador, , Brazil
Fundação de Medicina Tropical Doutor Heitor Vieira Dourado / Fundação Medicina Tropical do Amazonas - FMT/IMT/AM
Manauas, , Brazil
Hospital General de Nova Iguaçu - HGNI
Nova Iguaçu, , Brazil
Grupo Hospitalar Conceição/ Hospital Nossa Senhora da Conceição S.A.
Porto Alegre, , Brazil
Instituto Nacional de Infectologia Evandro Chagas / Fundação Oswaldo Cruz - INI FIOCRUZ
Rio de Janeiro, , Brazil
Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
São Paulo, , Brazil
Centro de Referência e Treinamento DST/AIDS
São Paulo, , Brazil
Center for Management and Research. SPDM-Paulista Association for the Development of Medicine-Hospital São Paulo/Federal
São Paulo, , Brazil
Centro de Investigacion Farmaceutica Especializada de Occidente S.C.
Guadalajara C.P., , Mexico
Asociacion Civil Impacta Salud y Educacion - Sede Barranco
Barranco, , Peru
Instituto de Medicina Tropical "Daniel Alcides Carrion", Facultad de Medicina Humana, UNMSM
Callao, , Peru
Asociacion Civil Selva Amazonica
Iquitos, , Peru
Via Libre
Lima, , Peru
Asociacion Civil Impacta Salud y Educacion - Sede San Miguel
Lima, , Peru
Ararat Research Center
San Juan, PR, Puerto Rico
Centro Ararat- San Juan
San Juan, PR, Puerto Rico
Desmond Tutu Health Foundation
Cape Town, , South Africa
Wits Reproductive Health and HIV Institute (Wits RHI)
Johannesburg, , South Africa
The Aurum Institute: Pretoria Clinical Research Centre
Pretoria, , South Africa
Setshaba Research Centre
Soshanguvhe, , South Africa
The Aurum Institute Tembisa CRC, Clinic 4
Tembisa, , South Africa
FPD-DTHF Ndevana Commuity Research Site
Vincent, , South Africa
Institute of HIV Research and Innovation
Bangkok, , Thailand
King Chulalongkorn Memorial Hospital
Bangkok, , Thailand
The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), Thai Red Cross AIDS research Centre
Bangkok, , Thailand
Ramathibodi Hospital, Mahidol University
Bangkok, , Thailand
Research Institute for Health Sciences, Chiang Mai University
Chiang Mai, , Thailand
Srinagarind Hospital, Khon Kaen University
Khon Kaen, , Thailand
Bamrasnaradura Infectious Disease Institute
Nonthaburi, , Thailand
Countries
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References
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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.
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.
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.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Related Links
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Gilead Clinical Trials Website
Other Identifiers
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DOH-27-102021-6681
Identifier Type: OTHER
Identifier Source: secondary_id
GS-US-528-9023
Identifier Type: -
Identifier Source: org_study_id