Phase 3 Double-blind Multicenter Randomized Active-Controlled Study to Evaluate the Safety and Efficacy of Bictegravir/Lenacapavir Versus Biktarvy® (Bictegravir/Emtricitabine/Tenofovir Alafenamide) in Virologically Suppressed People With HIV-1
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 577
- 试验地点
- 102
- 主要终点
- Proportion of Participants with HIV-1 RNA ≥ 50 copies/mL at Week 48 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)/lenacapavir (LEN), fixed-dose combination (FDC) versus current therapy bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) FDC in people living with HIV-1 (PWH).
The primary objective of this study is to learn how effective it is to switch to BIC/LEN FDC tablets versus continuing on B/F/TAF FDC tablets in virologically suppressed 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
- 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
- •Currently receiving B/F/TAF for at least 6 months prior to screening.
- •If plasma human immunodeficiency virus type 1 (HIV-1) ribonucleic acid (RNA) measurements in the last 6 months prior to screening are available, all levels must be < 50 copies/mL.
- •At least one documented 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.
- •No documented or suspected resistance to BIC (including integrase strand-transfer inhibitor resistant (INSTI-R) mutations T66A/I/K, E92G/Q, G118R, F121Y, Y143C/H/R, S147G, Q148H/K/R, N155H/S, or R263K in the integrase gene).
- •No documented or suspected resistance to tenofovir alafenamide (TAF) (TAF; mutations K65R, K65N, K70E, Q151M or T69 insertion, or ≥ 3 of the following thymidine analog mutations [M41L, D67N, K70R, L210W, T215Y/F, K219Q/E/N/R] in the reverse transcriptase gene).
- •Estimated glomerular filtration rate ≥ 30 mL/min according to the Cockcroft-Gault formula for creatinine clearance.
排除标准
- •Positive serum pregnancy test or pregnant at screening or a positive pregnancy test prior to Day 1 randomization.
- •Breastfeeding (nursing).
- •Prior use of, or exposure to, LEN.
- •Active, serious infections (other than HIV-1) requiring parenteral therapy < 30 days prior to randomization.
- •Active tuberculosis infection.
- •Acute hepatitis < 30 days before randomization.
- •Chronic hepatitis B virus (HBV) infection, as determined by either:
- •Positive HBV surface antigen and negative HBV surface antibody, regardless of HBV core antibody status, at the screening visit.
- •Positive HBV core antibody and negative HBV surface antibody, regardless of HBV surface antigen status, at the screening visit.
- •Known hypersensitivity to the study drug, its metabolites, or any formulation excipient.
- •History of or current clinical decompensated liver cirrhosis (eg, ascites, encephalopathy, or variceal bleeding).
- •Abnormal electrocardiogram (ECG) at the screening visit that is clinically significant as determined by the investigator.
- •Active malignancy requiring acute systemic therapy.
- •Any of the following laboratory values at screening:
- •Alanine aminotransferase > 5 × upper limit of normal (ULN).
- •Direct bilirubin > 1.5 × ULN.
- •Platelets < 50,000/mm^
- •Hemoglobin < 8.0 g/dL.
- •Requirement for ongoing therapy with or prior use of any prohibited medications listed in the protocol.
- •Participation or planned participation in any other clinical study (including observational studies) without prior approval from the sponsor.
- •Any other clinical condition or prior therapy that, in the opinion of the investigator, would make the participant unsuitable for the study or unable to comply with dosing requirements.
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Treatment Group 1: Bictegravir (BIC)/ Lenacapavir (LEN) (75/50 mg) + PTM B/F/TAF
Blinded Phase: Participants will switch from bictegravir/emtricitabine/tenofovir (B/F/TAF) FDC tablets to BIC/LEN (75/50 mg) FDC tablets and placebo-to-match (PTM) B/F/TAF. Participants will receive a 2-day oral loading dose of LEN 600 mg on Day 1 and on Day 2, in addition to the daily doses of BIC/LEN FDC tablet starting on Day 1 up to end of blinded treatment (EBT) visit.
Open-label (OL) Phase: Following treatment in the Blinded Phase, participants from Treatment Group 1 will receive BIC/LEN FDC tablets through Week 48 in the Open-label Phase. At the OL Week 48 visit, participants from Treatment Group 1 will be given the option to continue to receive BIC/LEN FDC tablets until the conclusion of the OL Phase.
干预措施: Bictegravir (Drug)
Treatment Group 1: Bictegravir (BIC)/ Lenacapavir (LEN) (75/50 mg) + PTM B/F/TAF
Blinded Phase: Participants will switch from bictegravir/emtricitabine/tenofovir (B/F/TAF) FDC tablets to BIC/LEN (75/50 mg) FDC tablets and placebo-to-match (PTM) B/F/TAF. Participants will receive a 2-day oral loading dose of LEN 600 mg on Day 1 and on Day 2, in addition to the daily doses of BIC/LEN FDC tablet starting on Day 1 up to end of blinded treatment (EBT) visit.
Open-label (OL) Phase: Following treatment in the Blinded Phase, participants from Treatment Group 1 will receive BIC/LEN FDC tablets through Week 48 in the Open-label Phase. At the OL Week 48 visit, participants from Treatment Group 1 will be given the option to continue to receive BIC/LEN FDC tablets until the conclusion of the OL Phase.
干预措施: Lenacapavir (Drug)
Treatment Group 1: Bictegravir (BIC)/ Lenacapavir (LEN) (75/50 mg) + PTM B/F/TAF
Blinded Phase: Participants will switch from bictegravir/emtricitabine/tenofovir (B/F/TAF) FDC tablets to BIC/LEN (75/50 mg) FDC tablets and placebo-to-match (PTM) B/F/TAF. Participants will receive a 2-day oral loading dose of LEN 600 mg on Day 1 and on Day 2, in addition to the daily doses of BIC/LEN FDC tablet starting on Day 1 up to end of blinded treatment (EBT) visit.
Open-label (OL) Phase: Following treatment in the Blinded Phase, participants from Treatment Group 1 will receive BIC/LEN FDC tablets through Week 48 in the Open-label Phase. At the OL Week 48 visit, participants from Treatment Group 1 will be given the option to continue to receive BIC/LEN FDC tablets until the conclusion of the OL Phase.
干预措施: Placebo to match B/F/TAF (Drug)
Treatment Group 2: B/F/TAF (50/200/25 mg) + PTM BIC/LEN
Blinded Phase: Participants will continue with their B/F/TAF (50/200/25 mg) FDC tablets and start PTM BIC/LEN tablets on Day 1. Participants will receive PTM LEN tablets for 2 days (2 PTM LEN tablets on Day 1 and on Day 2. The blinded phase will continue until the EBT visit.
Open Label Phase: Participants in Treatment Group 2 who complete the EBT visit will be given the option to enter the OL phase to receive BIC/LEN FDC tablets until the conclusion of the OL Phase.
干预措施: Bictegravir (Drug)
Treatment Group 2: B/F/TAF (50/200/25 mg) + PTM BIC/LEN
Blinded Phase: Participants will continue with their B/F/TAF (50/200/25 mg) FDC tablets and start PTM BIC/LEN tablets on Day 1. Participants will receive PTM LEN tablets for 2 days (2 PTM LEN tablets on Day 1 and on Day 2. The blinded phase will continue until the EBT visit.
Open Label Phase: Participants in Treatment Group 2 who complete the EBT visit will be given the option to enter the OL phase to receive BIC/LEN FDC tablets until the conclusion of the OL Phase.
干预措施: Lenacapavir (Drug)
Treatment Group 2: B/F/TAF (50/200/25 mg) + PTM BIC/LEN
Blinded Phase: Participants will continue with their B/F/TAF (50/200/25 mg) FDC tablets and start PTM BIC/LEN tablets on Day 1. Participants will receive PTM LEN tablets for 2 days (2 PTM LEN tablets on Day 1 and on Day 2. The blinded phase will continue until the EBT visit.
Open Label Phase: Participants in Treatment Group 2 who complete the EBT visit will be given the option to enter the OL phase to receive BIC/LEN FDC tablets until the conclusion of the OL Phase.
干预措施: B/F/TAF (Drug)
Treatment Group 2: B/F/TAF (50/200/25 mg) + PTM BIC/LEN
Blinded Phase: Participants will continue with their B/F/TAF (50/200/25 mg) FDC tablets and start PTM BIC/LEN tablets on Day 1. Participants will receive PTM LEN tablets for 2 days (2 PTM LEN tablets on Day 1 and on Day 2. The blinded phase will continue until the EBT visit.
Open Label Phase: Participants in Treatment Group 2 who complete the EBT visit will be given the option to enter the OL phase to receive BIC/LEN FDC tablets until the conclusion of the OL Phase.
干预措施: Placebo to match BIC/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 US 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 48 as Determined by the US FDA-defined Snapshot Algorithm(Week 48)
- Treatment Group 1: Change from Baseline in CD4 Cell Count at Week 96(Baseline; Week 96)
- Treatment Group 1: Percentage of Participants Experiencing Treatment-Emergent AEs through Week 96(From first dose date up to Week 96)
- Change From Baseline in Clusters of Differentiation 4 (CD4) Cell Count at Week 48(Baseline; Week 48)
- Treatment Group 1: Proportion of Participants with HIV-1 RNA ≥ 50 copies/mL at Week 96 as Determined by the US FDA-defined Snapshot Algorithm(Week 96)
- Treatment Group 1: Proportion of Participants with HIV-1 RNA < 50 copies/mL at Week 96 as Determined by US FDA-defined Snapshot Algorithm(Week 96)
- Percentage of Participants Experiencing Treatment-Emergent Adverse Events (AEs) through Week 48(From first dose date up to Week 48)