A Phase 3, Randomized, Double-blind, Active-controlled Study to Evaluate a Switch to an Oral Weekly Islatravir/Lenacapavir Regimen in People With HIV-1 Who Are Virologically Suppressed on Bictegravir/Emtricitabine/Tenofovir Alafenamide (B/F/TAF)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 609
- 试验地点
- 103
- 主要终点
- Proportion of Participants with HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Determined by the United States (US) Food and Drug Administration (FDA)-Defined Snapshot Algorithm
研究概览
简要总结
The goal of this clinical study is to learn about the safety and efficacy of switching to once weekly tablet of islatravir/lenacapavir (ISL/LEN) regimen versus continuing standard treatment of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in people with human immunodeficiency virus (PWH) who are virologically suppressed (HIV-1 RNA levels < 50 copies/mL) on B/F/TAF for ≥ 6 months prior to screening.
The primary objective is to evaluate the efficacy of switching to oral weekly ISL/LEN tablet regimen versus continuing B/F/TAF in virologically suppressed PWH at Week 48.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •HIV-1 RNA < 50 copies/mL for ≥ 6 months before screening, as documented by:
- •One HIV-1 RNA < 50 copies/mL immediately preceding the 24 week period prior to screening.
- •Within 24 weeks prior to screening, if HIV-1 RNA results are available, all levels must be < 50 copies/mL.
- •During the 6 to 12 months period prior to screening, transient detectable viremia ≥ 50 copies/mL is acceptable ("blip"), as long as it is not confirmed on 2 consecutive visits.
- •Plasma HIV-1 RNA levels < 50 copies/mL at screening.
- •Individuals are receiving B/F/TAF for ≥ 6 months prior to screening and willing to continue until Day
- •Individuals assigned female at birth and of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified methods of contraception.
排除标准
- •Prior virologic failure.
- •Prior use of, or exposure to ISL or LEN.
- •Active, serious infections requiring parenteral therapy within 30 days before randomization.
- •Active tuberculosis infection.
- •Acute hepatitis within 30 days before randomization.
- •Hepatitis B virus (HBV) infection as determined below at the screening visit:
- •Positive HBV surface antigen OR
- •Positive HBV core antibody and negative HBV surface antibody. Note: individuals found to be susceptible to HBV infection (eg negative hepatitis B surface antibody at the screening visit, regardless of prior HBV vaccination history) should be recommended to receive HBV vaccination.
- •Active hepatitis C virus (HCV) coinfection, defined as detectable HCV RNA. Note: individuals with prior/inactive HCV infection (defined as undetectable HCV RNA) may be enrolled.
- •Any of the following laboratory values at screening:
- •Creatinine clearance (CLcr) ≤ 30 mL/min according to the Cockcroft-Gault formula
- •Alanine aminotransferase > 5 x upper limit of normal (ULN)
- •Direct bilirubin > 1.5 x ULN
- •Platelets < 50,000/μL
- •Hemoglobin < 8.0 g/dL
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Blinded Phase: ISL/LEN + Placebo-to-Match (PTM) B/F/TAF
Participants will receive an initial dose of ISL/LEN (Dose A), followed by once weekly ISL/LEN (Dose B) from Day 8 onwards up to Week 96. Participants will also receive PTM B/F/TAF once daily from Day 1 up to Week 96.
干预措施: ISL/LEN (Drug)
Blinded Phase: ISL/LEN + Placebo-to-Match (PTM) B/F/TAF
Participants will receive an initial dose of ISL/LEN (Dose A), followed by once weekly ISL/LEN (Dose B) from Day 8 onwards up to Week 96. Participants will also receive PTM B/F/TAF once daily from Day 1 up to Week 96.
干预措施: PTM B/F/TAF (Drug)
Blinded Phase: PTM ISL/LEN + B/F/TAF
Participants will receive an initial dose of PTM ISL/LEN (Dose A), followed by once weekly PTM ISL/LEN (Dose B) from Day 8 onwards up to Week 96. Participants will also receive B/F/TAF (50/200/25 mg) once daily up from Day 1 up to Week 96.
干预措施: B/F/TAF (Drug)
Blinded Phase: PTM ISL/LEN + B/F/TAF
Participants will receive an initial dose of PTM ISL/LEN (Dose A), followed by once weekly PTM ISL/LEN (Dose B) from Day 8 onwards up to Week 96. Participants will also receive B/F/TAF (50/200/25 mg) once daily up from Day 1 up to Week 96.
干预措施: PTM ISL/LEN (Drug)
Open- Label Extension (OLE) Phase
After the end of Blinded Phase at Week 96, if safety and efficacy of ISL/LEN are demonstrated following review of unblinded data, all participants will be given an option to enter the open-label extension phase to receive ISL/LEN in an extension phase until ISL/LEN becomes available or until the sponsor elects to discontinue the study, whichever occurs first.
Participants receiving ISL/LEN and PTM B/F/TAF during the blinded phase will continue to take ISL/LEN weekly.
Participants receiving B/F/TAF and PTM ISL/LEN during the blinded phase will take an initial dose of ISL/LEN (Dose A), followed by once weekly ISL/LEN (Dose B) from Day 8 onwards.
干预措施: ISL/LEN (Drug)
结局指标
主要结局
Proportion of Participants with HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Determined by the United States (US) Food and Drug Administration (FDA)-Defined Snapshot Algorithm
时间窗: Week 48
次要结局
- Proportion of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 96 as Determined by the US FDA-Defined Snapshot Algorithm(Week 96)
- Proportion of Participants with HIV-1 RNA < 50 Copies/mL at Weeks 48 as Determined by the US FDA-Defined Snapshot Algorithm(Week 48)
- Proportion of Participants with HIV-1 RNA < 50 Copies/mL at Weeks 96 as Determined by the US FDA-Defined Snapshot Algorithm(Week 96)
- Change From Baseline in Cluster of Differentiation 4 (CD4) T-Cell Count at Weeks 48(Week 48)
- Change From Baseline in CD4 T-Cell Count at Weeks 96(Week 96)
- Proportion of Participants Discontinuing ISL/LEN due to Treatment-Emergent Adverse Events (TEAEs)(Day 1 up to Week 48)