Study of Lenacapavir for HIV Pre-Exposure Prophylaxis in People Who Are at Risk for HIV Infection
Phase 3
Active, not recruiting
- Conditions
- Pre-Exposure Prophylaxis of HIV Infection
- Interventions
- Drug: Placebo SC LENDrug: F/TAF (for US participants only)Drug: PTM F/TDFDrug: PTM Oral LEN
- Registration Number
- NCT04925752
- Lead Sponsor
- Gilead Sciences
- Brief Summary
The goal of this clinical study is to test how well the study drug, lenacapavir (LEN), works in preventing the risk of HIV.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 3295
Inclusion Criteria
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).
Key
Exclusion Criteria
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.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Blinded Phase: LEN + Placebo-to-match (PTM) F/TDF Oral Lenacapavir (LEN) Participants will receive the following for 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 LEN Open-Label Extension (OLE) Phase Oral Lenacapavir (LEN) Participants will be offered entry into the LEN OLE Phase, following the 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 the LEN OLE Phase will complete the phase, once LEN becomes available or the sponsor decides to discontinue the study, whichever happens first. After completing the 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 ESDD visit, be referred to local PrEP services if needed, and have a 30-day follow-up visit. Blinded Phase: LEN + Placebo-to-match (PTM) F/TDF Sub-cutaneous (SC) Lenacapavir (LEN) Participants will receive the following for 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 Blinded Phase: LEN + Placebo-to-match (PTM) F/TDF PTM F/TDF Participants will receive the following for 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 Blinded Phase: Placebo LEN + F/TDF F/TDF Participants will receive the following for 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 Blinded Phase: Placebo LEN + F/TDF Placebo SC LEN Participants will receive the following for 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 Blinded Phase: Placebo LEN + F/TDF PTM Oral LEN Participants will receive the following for 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 LEN Open-Label Extension (OLE) Phase Sub-cutaneous (SC) Lenacapavir (LEN) Participants will be offered entry into the LEN OLE Phase, following the 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 the LEN OLE Phase will complete the phase, once LEN becomes available or the sponsor decides to discontinue the study, whichever happens first. After completing the 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 ESDD visit, be referred to local PrEP services if needed, and have a 30-day follow-up visit. PK Tail Phase F/TDF Participants who prematurely discontinue study drug during 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. PK Tail Phase F/TAF (for US participants only) Participants who prematurely discontinue study drug during 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.
- Primary Outcome Measures
Name Time Method Randomized Phase: Number of Participants with Diagnosis of HIV-1 Infection When all participants have completed a minimum of 52 weeks of follow-up in the study, or permanent discontinuation, whichever occurs first (maximum approximately 130 weeks) Incidence Phase: Background HIV Incidence per 100-Person-Years (PY) At Screening
- Secondary Outcome Measures
Name Time Method Percentage of Participants Experiencing Treatment-Emergent Adverse Events When all participants have completed a minimum of 52 weeks of follow-up in the study, or permanent discontinuation, whichever occurs first (maximum approximately 130 weeks) Number of Participants with Diagnosis of HIV Among Participants While Adherent to Study Drug When all participants have completed a minimum of 52 weeks of follow-up in the study, or permanent discontinuation, whichever occurs first (maximum approximately 130 weeks) Percentage of Participants Experiencing Clinically Significant Laboratory Abnormalities When all participants have completed a minimum of 52 weeks of follow-up in the study, or permanent discontinuation, whichever occurs first (maximum approximately 130 weeks)
Trial Locations
- Locations (90)
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
Scroll for more (80 remaining)UAB Sexual Health Research Clinic🇺🇸Birmingham, Alabama, United States