A Platform, Active-Controlled Study Evaluating the Safety and Efficacy of Long-Acting Oral Regimens in People With HIV-1; Substudy-01: Phase 2, Open-Label, Weekly, Long-Acting, Oral Regimens in Virologically Suppressed People With HIV-1
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 125
- 主要终点
- Proportion of Participants With HIV-1 Ribonucleic Acid (RNA) ≥ 50 copies/mL at Week 24 as Determined by the United States (US) Food and Drug Administration (FDA)-Defined Snapshot Algorithm
研究概览
简要总结
Master Protocol: The main goal of this master clinical study is to evaluate the safety, tolerability, efficacy, and pharmacokinetic (PK) of long-acting oral (LAO) regimens in people with HIV-1 (PWH).
The main goal of this Substudy-01 is to assess the safety, tolerability, effectiveness, and PK of switching to weekly LAO regimens, including GS-3242 + LEN, versus continuing on once daily oral bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF; coformulated; Biktarvy®) in PWH with controlled HIV infection, B/F/TAF for at least 6 months prior to study start.
The primary objective is to evaluate the efficacy of switching to each LAO regimen versus continuing B/F/TAF in virologically suppressed PWH at Week 24.
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
- •Individuals assigned male or female at birth, 18 years of age or older, able to understand and give written informed consent and comply with treatment and follow-up.
- •Individuals assigned male or female at birth who are of childbearing potential and engage in heterosexual intercourse must agree to use approved method(s) of contraception.
- •Negative serum pregnancy test at screening and negative urine test at enrollment.
- •Receiving B/F/TAF for ≥ 6 months prior to screening.
- •Documented plasma HIV-1 RNA < 50 copies/mL for ≥ 6 months before and at screening.
- •No resistance to GS-3242 (integrase mutation Q148H/K/R plus at least 2 of the following integrase mutations: L74I/M, T97A, E138A/K/T, or G140A/C/S) on available historical resistance reports.
- •CD4 ≥ 200 cells/mm^3 at screening
排除标准
- •Plans to breastfeed during the study period and 60 days following the last dose of study intervention.
- •History of virologic failure while on an integrase strand-transfer inhibitor-based regimen.
- •Creatinine clearance according to the Cockcroft-Gault formula < 60 mL/min.
研究组 & 干预措施
Treatment Arm A: B/F/TAF
Participants will receive B/F/TAF 50/200/25 mg once daily for at least 48 weeks.
After Week 48, participants in the Randomized Phase may be offered to continue to receive study drug in the Extension Phase.
干预措施: B/F/TAF (Drug)
Treatment Arm B: GS-3242 + LEN
Participants will be randomized to oral loading dose of GS-3242 in combination with LEN, followed by a once-weekly oral combination regimen of GS-3242 and LEN (at a different dose than Treatment C), administered concomitantly for at least 48 weeks.
After Week 48, participants in the Randomized Phase may be offered to continue to receive study drug in the Extension Phase.
干预措施: Lenacapavir (Drug)
Treatment Arm B: GS-3242 + LEN
Participants will be randomized to oral loading dose of GS-3242 in combination with LEN, followed by a once-weekly oral combination regimen of GS-3242 and LEN (at a different dose than Treatment C), administered concomitantly for at least 48 weeks.
After Week 48, participants in the Randomized Phase may be offered to continue to receive study drug in the Extension Phase.
干预措施: GS-3242 (Drug)
Treatment Arm C: GS-3242 + LEN
Participants will be randomized to oral loading dose of GS-3242 in combination with LEN, followed by a once-weekly oral combination regimen of GS-3242 and LEN (at a different dose than Treatment Arm B), administered concomitantly for at least 48 weeks.
After Week 48, participants in the Randomized Phase may be offered to continue to receive study drug in the Extension Phase.
干预措施: Lenacapavir (Drug)
Treatment Arm C: GS-3242 + LEN
Participants will be randomized to oral loading dose of GS-3242 in combination with LEN, followed by a once-weekly oral combination regimen of GS-3242 and LEN (at a different dose than Treatment Arm B), administered concomitantly for at least 48 weeks.
After Week 48, participants in the Randomized Phase may be offered to continue to receive study drug in the Extension Phase.
干预措施: GS-3242 (Drug)
结局指标
主要结局
Proportion of Participants With HIV-1 Ribonucleic Acid (RNA) ≥ 50 copies/mL at Week 24 as Determined by the United States (US) Food and Drug Administration (FDA)-Defined Snapshot Algorithm
时间窗: Week 24
次要结局
- Change From Baseline in CD4 Cell Count at Week 24(Week 24)
- Change From Baseline in CD4 Cell Count at Week 48(Week 48)
- Proportion of Participants With HIV-1 RNA ≥ 50 copies/mL at Weeks 12 as Determined by the US FDA-defined Snapshot Algorithm(Week 12)
- 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 Week 12 as Determined by the US FDA-defined Snapshot Algorithm(Week 12)
- Proportion of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Determined by the US FDA-defined Snapshot Algorithm(Week 24)
- Proportion of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm(Week 48)
- Change From Baseline in Clusters of Differentiation 4 (CD4) Cell Count at Week 12(Week 12)
- The Percentage of Participants Experiencing Treatment-Emergent Aadverse Events (TEAEs) Through Week 12(Week 12)
- The Percentage of Participants Experiencing Treatment-Emergent Aadverse Events (TEAEs) Through Week 24(Week 24)
- The Percentage of Participants Experiencing Treatment-Emergent Aadverse Events (TEAEs) Through Week 48(Week 48)
- Pharmacokinetic (PK) Parameter: Cmax of GS-3242(Up to 48 weeks)
- PK Parameter: Tmax of GS-3242(Up to 48 weeks)
- PK Parameter: Ctau of GS-3242(Up to 48 weeks)
- PK Parameter: AUCtau of GS-3242(Up to 48 weeks)