An Operationally Seamless Phase 2/3, Randomized, Active-Controlled Study Evaluating the Safety and Efficacy of an Oral Weekly Regimen of GS-1720 in Combination With GS-4182 Versus Biktarvy in Treatment-Naive People With HIV-1
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 73
- 试验地点
- 111
- 主要终点
- Phase 2: Proportion of Participants With HIV-1 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
The goal of this clinical study is to learn more about the experimental drugs lepetegravir (formerly GS-1720) (an oral, long-acting integrase strand transfer inhibitor (INSTI)) and lenacapavir pacfosacil (formerly GS-4182) (a prodrug of Lenacapavir (LEN)); to compare the combination of lepetegravir and lenacapavir pacfosacil with the current standard-of-care treatment bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (Biktarvy), to see if the combination of lepetegravir and lenacapavir pacfosacil is safe and if it works for treating human immunodeficiency virus type 1 (HIV-1) infection in treatment-naive people with HIV-1 (PWH).
This study has two phases: Phase 2 and Phase 3.
The primary objectives of this study are:
Phase 2: To evaluate the efficacy of oral weekly lepetegravir coadministered with lenacapavir pacfosacil versus continuing Biktarvy (BVY) in treatment-naive PWH at Week 24.
Phase 3: To evaluate the efficacy of oral weekly lepetegravir/lenacapavir pacfosacil fixed-dose combination (FDC) tablet regimen versus continuing BVY in treatment-naive PWH at Week 48.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
Phase 2 of the study has 2 periods: Randomized and Extension, which are both open label.
Phase 3 of the study has 2 periods: Randomized Period which would be double-blind (at least Week 96), followed by an Extension Period which will be Open-label.
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 ≥ 500 copies/mL at screening.
- •Antiretroviral (ARV) treatment-naive, except the use of oral pre-exposure prophylaxis (PrEP) or postexposure prophylaxis (PEP) with emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) or F/TAF, up to 1 month prior to screening.
排除标准
- •Prior use of any long acting parenteral antiretrovirals (ARVs) such as monoclonal antibodies, broadly neutralizing antibodies targeting HIV-1, LEN, injectable cabotegravir (including oral cabotegravir lead-in), and/or injectable rilpivirine.
- •Documented resistance to the integrase strand-transfer inhibitor class, specifically, resistance-associated mutations E92G/Q, G118R, F121Y, Y143C/H/R, S147G, Q148H/K/R, N155H/S, or R263K in the integrase gene.
- •Any of the following laboratory values at screening:
- •CD4 cell count < 200 cells/mm3 at screening.
- •Estimated glomerular filtrations arate < 60 mL/min according to the Modification of Diet in Renal Disease formula.
- •Hepatic transaminases (aspartate aminotransferase and alanine aminotransferase) > 1.5 × upper limit of normal (ULN).
- •Direct bilirubin > 1.5 × ULN.
- •Platelets count < 50,000 cells/mm
- •Hemoglobin < 8.0 g/dL.
- •Active or occult hepatitis B virus infection.
- •Active hepatitis C virus infection.
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Phase 2: Lepetegravir + Lenacapavir Pacfosacil (Treatment Group 1)
Participants will receive a 1-day loading dose of lepetegravir (1300 mg) and lenacapavir pacfosacil (600 mg) on Day 1.Thereafter, participants will take weekly doses of single agent lepetegravir (650 mg) and lenacapavir pacfosacil (300 mg) coadministered for at least 48 weeks.
干预措施: lepetegravir (Drug)
Phase 2: Lepetegravir + Lenacapavir Pacfosacil (Treatment Group 1)
Participants will receive a 1-day loading dose of lepetegravir (1300 mg) and lenacapavir pacfosacil (600 mg) on Day 1.Thereafter, participants will take weekly doses of single agent lepetegravir (650 mg) and lenacapavir pacfosacil (300 mg) coadministered for at least 48 weeks.
干预措施: lenacapavir pacfosacil (Drug)
Phase 2 Extension Phase: Lepetegravir/Lenacapavir Pacfosacil Fixed-dose Combination (FDC)
At the end of the randomized treatment, Phase 2 participants will be given the option to participate in the Extension Phase. Phase 2 Treatment Group 1 will switch to lepetegravir/lenacapavir pacfosacil FDC (650/300 mg) weekly. Phase 2 Treatment Group 2 will receive a loading dose of lepetegravir/lenacapavir pacfosacil FDC (1300 mg/600 mg) on Extension Phase Day 1, then lepetegravir/lenacapavir pacfosacil FDC (650/300 mg) weekly. Participants who choose to enter the Extension Phase will receive lepetegravir/lenacapavir pacfosacil FDC tablets until the product becomes available or until Gilead Sciences elects to discontinue the study, whichever occurs first.
干预措施: lepetegravir/lenacapavir pacfosacil FDC (Drug)
Phase 3: Lepetegravir/Lenacapavir Pacfosacil FDC + Placebo to Match B/F/TAF (Treatment Group 1)
Participants will receive a 1-day loading dose of lepetegravir/lenacapavir pacfosacil FDC on Day 1. Thereafter, participants will receive lepetegravir/lenacapavir pacfosacil FDC tablets weekly + placebo to match (PTM) B/F/TAF once daily. Participants will receive treatment for at least 96 weeks.
干预措施: lepetegravir/lenacapavir pacfosacil FDC (Drug)
Phase 3: Lepetegravir/Lenacapavir Pacfosacil FDC + Placebo to Match B/F/TAF (Treatment Group 1)
Participants will receive a 1-day loading dose of lepetegravir/lenacapavir pacfosacil FDC on Day 1. Thereafter, participants will receive lepetegravir/lenacapavir pacfosacil FDC tablets weekly + placebo to match (PTM) B/F/TAF once daily. Participants will receive treatment for at least 96 weeks.
干预措施: Placebo to Match BVY (Drug)
Phase 3: B/F/TAF + PTM lepetegravir/Lenacapavir Pacfosacil FDC (Treatment Group 2)
Participants will receive oral B/F/TAF daily along with PTM lepetegravir/lenacapavir pacfosacil FDC weekly for at least 96 weeks. Additionally, participants will receive a 1-day loading dose of PTM lepetegravir/lenacapavir pacfosacil on Day 1.
干预措施: Bictegravir/emtricitabine/tenofovir alafenamide (Drug)
Phase 3: B/F/TAF + PTM lepetegravir/Lenacapavir Pacfosacil FDC (Treatment Group 2)
Participants will receive oral B/F/TAF daily along with PTM lepetegravir/lenacapavir pacfosacil FDC weekly for at least 96 weeks. Additionally, participants will receive a 1-day loading dose of PTM lepetegravir/lenacapavir pacfosacil on Day 1.
干预措施: Placebo to Match GS1720/GS-4182 FDC (Drug)
Phase 3 Extension Phase: Lepetegravir/Lenacapavir Pacfosacil Fixed-dose Combination (FDC)
After the end of blinded treatment, Phase 3 participants will be given the option to participate in the Extension Phase. Phase 3 Treatment Group 1 will continue to receive lepetegravir/lenacapavir pacfosacil FDC weekly while PTM B/F/TAF will be discontinued. Phase 3 Treatment Group 2 will switch to receive lepetegravir/lenacapavir pacfosacil FDC tablets weekly. Participants in Treatment Group 2 will also receive a 1-day loading dose of lepetegravir/lenacapavir pacfosacil FDC on Extension Phase Day 1.
Participants who choose to enter the Phase 3 Extension Phase will receive lepetegravir/lenacapavir pacfosacil FDC tablets until the product becomes available or until Gilead Sciences elects to discontinue the study, whichever occurs first.
干预措施: lepetegravir/lenacapavir pacfosacil FDC (Drug)
Phase 2: B/F/TAF (Treatment Group 2)
Participants will receive B/F/TAF (50/200/25 mg) daily for at least 48 weeks.
干预措施: Bictegravir/emtricitabine/tenofovir alafenamide (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 United States (US) Food and Drug Administration (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 2: Proportion of Participants With HIV-1 RNA < 50 copies/mL at Week 12 as Determined by the US FDA-defined Snapshot Algorithm(Week 12)
- Phase 2: 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 2: Change From Baseline in log10 HIV-1 RNA at Week 12(Baseline, Week 12)
- Phase 2: Change From Baseline in log10 HIV-1 RNA at Week 24(Baseline, Week 24)
- Phase 2: Change From Baseline in log10 HIV-1 RNA at Week 48(Baseline, Week 48)
- Phase 2: Change From Baseline in Clusters of Differentiation 4 (CD4) Cell Count at Week 12(Baseline, Week 12)
- Phase 2: Change From Baseline in CD4 Cell Count at Week 24(Baseline, Week 24)
- Phase 2: Change From Baseline in CD4 Cell Count at Week 48(Baseline, Week 48)
- Phase 2: Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) Through Week 12(First dose date up to Week 12)
- Phase 2: Percentage of Participants Experiencing TEAEs Through Week 24(First dose date up to Week 24)
- Phase 2: Percentage of Participants Experiencing TEAEs Through Week 48(First dose date up to Week 48)
- Phase 2: Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities Through Week 12(First dose date up to Week 12)
- Phase 2: Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities Through Week 24(First dose date up to Week 24)
- Phase 2: Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities Through Week 48(First dose date up to Week 48)
- Phase 2: Pharmacokinetic (PK) Parameter: Cmax of GS-1720 and Lenacapavir (LEN), as Applicable(Day 1 up to Week 24)
- Phase 2: PK Parameter: Tmax of GS-1720 and LEN, as Applicable(Day 1 up to Week 24)
- Phase 2: PK Parameter: Ctau of GS-1720 and LEN, as Applicable(Day 1 up to Week 24)
- Phase 2: PK Parameter: AUCtau of GS-1720 and LEN, as Applicable(Day 1 up to Week 24)
- Phase 3: Proportion of Participants With HIV-1 RNA < 50 copies/mL at Week 96 as Determined by the US FDA-defined Snapshot Algorithm(Week 96)
- Phase 3: Change From Baseline in log10 HIV-1 RNA at Week 48(Baseline, Week 48)
- Phase 3: Change From Baseline in log10 HIV-1 RNA at Week 96(Baseline, Week 96)
- Phase 3: Change From Baseline in CD4 Cell Count at Week 48(Baseline, Week 48)
- Phase 3: Change From Baseline in CD4 Cell Count at Week 96(Baseline, Week 96)
- Phase 3: Percentage of Participants Experiencing TEAEs Through Week 48(First dose date up to Week 48)
- Phase 3: Percentage of Participants Experiencing TEAEs Through Week 96(First dose date up to Week 96)
- Phase 3: Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities Through Week 48(First dose date up to Week 48)
- Phase 3: Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities Through Week 96(First dose date up to Week 96)
- Phase 2: Pharmacokinetic (PK) Parameter: Cmax of Lepetegravir and Lenacapavir (LEN), as Applicable(Day 1 up to Week 24)
- Phase 2: PK Parameter: Tmax of Lepetegravir and LEN, as Applicable(Day 1 up to Week 24)
- Phase 2: PK Parameter: Ctau of Lepetegravir and LEN, as Applicable(Day 1 up to Week 24)
- Phase 2: PK Parameter: AUCtau of Lepetegravir and LEN, as Applicable(Day 1 up to Week 24)