An Operationally Seamless Phase 2/3 Randomized, Open-label, Multicenter, Active-Controlled Study to Evaluate the Safety and Efficacy of Bictegravir/Lenacapavir Versus Stable Baseline Regimen in Virologically Suppressed People With HIV-1 on Stable Complex Treatment Regimens
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 689
- 试验地点
- 164
- 主要终点
- Phase 2: Proportion of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 24 as Determined by the US FDA-defined Snapshot Algorithm
研究概览
简要总结
The goal of this clinical study is to learn more about the effects of switching to the study drugs, bictegravir (BIC) plus lenacapavir (LEN), versus current therapy (Phase 2) and BIC/LEN fixed-dose combination (FDC) versus current therapy (Phase 3) in people living with HIV (PWH).
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
- None
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
- •If plasma HIV-1 RNA measurements in the 6 months prior to screening are available, all levels must be < 50 copies/mL.
- •At least one documented plasma HIV-1 RNA level measured between 6 and 12 months (± 2 months) prior to screening. This and any other HIV-1 RNA measurements documented in this period must be < 50 copies/mL
- •Plasma HIV-1 RNA levels < 50 copies/mL at screening.
- •Currently receiving a complex antiretroviral (ARV) regimen due to previous viral resistance, or intolerance, or contraindication to existing single-tablet regimens (STR), and on this regimen for at least 6 months prior to the screening visit. The criteria to define a complex regimen in this study are as follows:
- •A regimen containing a boosted protease inhibitor or a nonnucleos(t)ide reverse transcriptase inhibitor (NRTI) plus at least 1 other third agent (ie, an agent from a class other than NRTIs) (eg, bictegravir/emtricitabine/tenofovir alafenamide (coformulated; Biktarvy®)(BVY) + darunavir/cobicistat, BVY + etravirine), or
- •A regimen of ≥ 2 pills/day, or a regimen requiring dosing more than once daily, or
- •A regimen containing parenteral agent(s) (excluding a complete long-acting injectable regimen, such as intramuscular cabotegravir plus rilpivirine) as well as oral agents.
- •No documented or suspected resistance to bictegravir (BIC).
- •Estimated glomerular filtration rate ≥ 15 mL/min according to the Cockcroft-Gault formula for creatinine clearance (CLcr) who are not on renal replacement therapy.
排除标准
- •Prior use of, or exposure to, lenacapavir (LEN)
- •Active tuberculosis infection
- •Chronic hepatitis B virus (HBV) infection
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Phase 3: BIC/LEN 75 mg/50 mg Fixed-dose Combination (FDC)
Participants will switch from their SBR to a regimen of BIC/LEN 75 mg/50 mg FDC. Participants will receive a 2-day loading dose regimen of LEN 600 mg, in addition to the daily doses of BIC/LEN 75 mg/50 mg FDC starting on Day 1 up to the ERT visit, participants will be treated for at least 48 weeks during the Randomized Period.
Following Randomized Period, the participants will have an option to participate in an Extension Period to receive BIC/LEN 75 mg/50 mg FDC.
干预措施: BIC/LEN FDC (Drug)
Phase 2: BIC 75 mg + LEN 50 mg
Participants will switch from their SBR to a regimen of BIC 75 mg + LEN 50 mg. Participants will receive a 2-day loading dose regimen of LEN 600 mg, in addition to the daily doses of BIC 75 mg + LEN 50 mg starting on Day 1 up to the ERT visit, participants will be treated for at least 24 weeks during the Randomized Period.
Following Randomized Period, the participants will have an option to participate in an Extension Period to receive BIC/LEN 75 mg/50 mg FDC.
干预措施: Lenacapavir (Drug)
Phase 2: BIC 75 mg + LEN 50 mg
Participants will switch from their SBR to a regimen of BIC 75 mg + LEN 50 mg. Participants will receive a 2-day loading dose regimen of LEN 600 mg, in addition to the daily doses of BIC 75 mg + LEN 50 mg starting on Day 1 up to the ERT visit, participants will be treated for at least 24 weeks during the Randomized Period.
Following Randomized Period, the participants will have an option to participate in an Extension Period to receive BIC/LEN 75 mg/50 mg FDC.
干预措施: Bictegravir (Drug)
Phase 2: Bictegravir (BIC) 75 mg + Lenacapavir (LEN) 25 mg
Participants will switch from their stable baseline regimen (SBR) to a regimen of BIC 75 mg + LEN 25 mg. Participants will receive a 2-day loading dose regimen of LEN 600 mg, in addition to the daily doses of BIC 75 mg + LEN 25 mg starting on Day 1 up to the end of randomized treatment (ERT) visit, participants will be treated for at least 24 weeks during the Randomized Period.
Following Randomized Period, the participants will have an option to participate in an Extension Period to receive BIC/LEN 75 mg/50 mg fixed dose combination (FDC).
干预措施: Bictegravir (Drug)
Phase 2: Bictegravir (BIC) 75 mg + Lenacapavir (LEN) 25 mg
Participants will switch from their stable baseline regimen (SBR) to a regimen of BIC 75 mg + LEN 25 mg. Participants will receive a 2-day loading dose regimen of LEN 600 mg, in addition to the daily doses of BIC 75 mg + LEN 25 mg starting on Day 1 up to the end of randomized treatment (ERT) visit, participants will be treated for at least 24 weeks during the Randomized Period.
Following Randomized Period, the participants will have an option to participate in an Extension Period to receive BIC/LEN 75 mg/50 mg fixed dose combination (FDC).
干预措施: Lenacapavir (Drug)
Phase 2: Stable Baseline Regimen (SBR)
Participants will continue with their SBR per prescription for up to the ERT visit, participants will be treated for at least 24 weeks during the Randomized Period.
Following Randomized Period, the participants will have an option to participate in an Extension Period to receive BIC/LEN 75 mg/50 mg FDC.
干预措施: Stable Baseline Regimen (Drug)
Phase 3: Stable Baseline Regimen
Participants will continue with their SBR per prescription for up to the ERT visit, participants will be treated for at least 48 weeks during the Randomized Period.
Following Randomized Period, the participants will have an option to participate in an Extension Period to receive BIC/LEN 75 mg/50 mg FDC.
干预措施: Stable Baseline Regimen (Drug)
结局指标
主要结局
Phase 2: Proportion of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 24 as Determined by the US FDA-defined Snapshot Algorithm
时间窗: Week 24
Phase 3: Proportion of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm
时间窗: Week 48
次要结局
- Phase 3 (BIC/LEN 75 mg/50 mg FDC): Proportion of Participants from With HIV-1 RNA ≥ 50 Copies/mL at Week 144 as Determined by the US FDA-defined Snapshot Algorithm(Week 144)
- Phase 3 (BIC/LEN 75 mg/50 mg FDC): Proportion of Participants from With HIV-1 RNA < 50 Copies/mL at Week 96 as Determined by the US FDA-defined Snapshot Algorithm(Week 96)
- Phase 3 (BIC/LEN 75 mg/50 mg FDC): Proportion of Participants from With HIV-1 RNA < 50 Copies/mL at Week 144 as Determined by the US FDA-defined Snapshot Algorithm(Week 144)
- Phase 3 (BIC/LEN 75 mg/50 mg FDC): Change From Baseline in CD4 Cell Count at Week 144(Baseline, Week 144)
- Phase 3 (BIC/LEN 75 mg/50 mg FDC): Proportion of Participants from Experiencing Treatment-emergent AEs Through Week 144(Week 144)
- Phase 2: Proportion of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Determined by the US FDA-defined Snapshot Algorithm(Week 24)
- Phase 2: Change From Baseline in CD4 Cell Count at Week 24(Baseline, Week 24)
- Phase 2: Percentage of Participants Experiencing Treatment-emergent Adverse Events (AEs) Through Week 24(First dose date up to Week 24)
- Phase 2: Pharmacokinetic (PK) Parameter: Cmax of Bictegravir (BIC) and Lenacapavir (LEN) at Steady State(Day 1 up to Week 24)
- Phase 3 (BIC/LEN 75 mg/50 mg FDC): Proportion of Participants from Experiencing Treatment-emergent AEs Through Week 96(Week 96)
- Phase 2: PK Parameter: AUCtau of BIC and LEN at Steady State(Day 1 up to Week 24)
- Phase 2: PK Parameter: Ctau of BIC and LEN at Steady State(Day 1 up to Week 24)
- Phase 3: Proportion of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm(Week 48)
- Phase 3: Change From Baseline in CD4 Cell Count at Week 48(Baseline, Week 48)
- Phase 3 (BIC/LEN 75 mg/50 mg FDC): Proportion of Participants from With HIV-1 RNA ≥ 50 Copies/mL at Week 96 as Determined by the US FDA-defined Snapshot Algorithm(Week 96)
- Phase 3 (BIC/LEN 75 mg/50 mg FDC): Change From Baseline in CD4 Cell Count at Week 96(Baseline, Week 96)
- Phase 3: Percentage of Participants Experiencing Treatment-emergent AEs Through Week 48(First dose date up to Week 48)