A Phase 3, Double-Blind, Multicenter, Randomized Study to Evaluate the Efficacy and Safety of Subcutaneous Twice Yearly Long-Acting Lenacapavir for HIV Pre-Exposure Prophylaxis in Cisgender Men, Transgender Women, Transgender Men, and Gender Nonbinary People ≥ 16 Years of Age Who Have Sex With Male Partners and Are at Risk for HIV Infection
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 3,292
- 试验地点
- 92
- 主要终点
- Incidence Phase: Recent Infection Testing Algorithm (RITA) Estimate of the Background Human Immunodeficiency-1 Virus Infection Incidence Rate (bHIV) Per 100 Person Years (PY)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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).
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Oral Lenacapavir (LEN) (Drug)
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.
干预措施: Sub-cutaneous (SC) Lenacapavir (LEN) (Drug)
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.
干预措施: PTM F/TDF (Drug)
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.
干预措施: F/TDF (Drug)
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.
干预措施: Placebo SC LEN (Drug)
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.
干预措施: PTM Oral LEN (Drug)
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.
干预措施: Oral Lenacapavir (LEN) (Drug)
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.
干预措施: Sub-cutaneous (SC) Lenacapavir (LEN) (Drug)
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.
干预措施: F/TDF (Drug)
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.
干预措施: F/TAF (for US participants only) (Drug)
结局指标
主要结局
Incidence Phase: Recent Infection Testing Algorithm (RITA) Estimate of the Background Human Immunodeficiency-1 Virus Infection Incidence Rate (bHIV) Per 100 Person Years (PY)
时间窗: 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)
时间窗: 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.
次要结局
- 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)
研究者
研究点 (92)
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