Study of Lenacapavir for HIV Pre-Exposure Prophylaxis in People Who Are at Risk for HIV Infection
- 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 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 3292
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
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 Randomized Blinded Phase: LEN + Placebo-to-match (PTM) F/TDF Oral Lenacapavir (LEN) 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. Randomized Blinded Phase: LEN + Placebo-to-match (PTM) F/TDF Sub-cutaneous (SC) Lenacapavir (LEN) 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. Randomized Blinded Phase: LEN + Placebo-to-match (PTM) F/TDF 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. Randomized Blinded Phase: Placebo LEN + F/TDF 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. Randomized Blinded Phase: Placebo LEN + F/TDF Placebo SC LEN 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. Randomized Blinded Phase: Placebo LEN + F/TDF PTM Oral LEN 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. LEN Open-Label Extension (OLE) Phase Oral Lenacapavir (LEN) 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. LEN Open-Label Extension (OLE) Phase Sub-cutaneous (SC) Lenacapavir (LEN) 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. Pharmacokinetic (PK) Tail Phase F/TDF 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. Pharmacokinetic (PK) Tail Phase F/TAF (for US participants only) 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.
- Primary Outcome Measures
Name Time Method Incidence Phase: Recent Infection Testing Algorithm (RITA) Estimate of the Background Human Immunodeficiency-1 Virus Infection Incidence Rate (bHIV) Per 100 Person Years (PY) Incidence Phase Screening Visit (Day 1) 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.Randomized Blinded Phase: HIV-1 Incidence Reported Per 100 PY for LEN Compared to Background HIV (bHIV, Participants in All Screened Set) Up to 149 weeks 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.
- Secondary Outcome Measures
Name Time Method Randomized Blinded Phase: HIV-1 Incidence Reported Per 100 PY for LEN Compared to F/TDF Up to 149 weeks HIV-1 incidence per 100 PY 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.
Randomized Blinded Phase: HIV-1 Incidence Among Participants Adherent to LEN Up to 149 weeks A participant was defined as adherent to LEN if they have received all per-protocol administrations of LEN within 28 weeks since the previous administration. The incidence of HIV-1 infection per 100 PY calculation is defined in outcome measure #2.
Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) Up to 4 years TEAEs were defined as 1 or both of the following:
Any adverse events (AEs) leading to premature discontinuation of study drug, or Any AEs with an onset date on or after the study drug start date and no later than the last exposure date after permanent discontinuation of the study drug.
An AE was any untoward medical occurrence in a clinical study participant administered a study drug that did not necessarily have a causal relationship with the treatment.Percentage of Participants Experiencing Clinically Significant Laboratory Abnormalities Up to 4 years Treatment-emergent laboratory abnormalities were defined as values that increased at least 1 toxicity grade from baseline at any post-baseline visit, up to and including the last exposure date for participants who permanently discontinued study drug, or the last available date in the database snapshot for participants who were still on treatment at the time of an analysis.
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