A Phase 2/3 Study to Evaluate the Safety and Efficacy of Long-Acting Capsid Inhibitor GS-6207 in Combination With an Optimized Background Regimen in Heavily Treatment Experienced People Living With HIV-1 Infection With Multidrug Resistance
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 72
- 试验地点
- 140
- 主要终点
- Percentage of Participants in Cohort 1 Achieving a Reduction of ≥ 0.5 log10 Copies/mL in Human Immunodeficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) From Baseline to the End of Functional Monotherapy Period
研究概览
简要总结
The primary objective of this study is to evaluate the antiviral activity of lenacapavir (formerly GS-6207) administered as an add-on to a failing regimen for 14 days (functional monotherapy) in people with human immunodeficiency virus type 1 (HIV-1) (PWH) with multi-drug resistance (MDR).
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult aged ≥ 18 years (at all sites) or adolescent aged ≥ 12 and weighing ≥ 35 kg (at sites in North America and Dominican Republic)
- •Currently receiving a stable failing ARV regimen for > 8 weeks
- •Have HIV-1 RNA ≥ 400 copies/mL at screening
- •Have multidrug resistance (resistance to ≥2 agents from ≥3 of the 4 main classes of ARV)
- •Have no more than 2 fully active ARV remaining from the 4 main classes that can be effectively combined to form a viable regimen
- •Able and willing to receive an OBR together with lenacapavir
- •No Hepatitis C virus (HCV) ongoing infection
- •Note: Other protocol defined Inclusion/
排除标准
- 未提供
研究组 & 干预措施
Cohort 1A: Lenacapavir
Participants with HIV-1 ribonucleic acid (RNA) ≥ 400 copies/mL and with a <0.5 log10 HIV-1 RNA decline at Cohort Selection visit compared with screening visit will receive oral lenacapavir (LEN) 600 mg tablet on Days 1 and 2 and 300 mg tablet on Day 8, while continuing their failing regimen in the blinded Functional Monotherapy Period (Baseline to Day 14); followed by unblinded Maintenance Period where participants will receive subcutaneous (SC) LEN 927 mg and will initiate an optimized background regimen (OBR) at Day 1 SC Visit (14 days after the first dose of oral LEN).
At Week 52 (relative to Day 1 SC), participants will be given an option to receive SC lenacapavir injections every 6 months (26 weeks), while continuing their OBR, until the product becomes accessible to participants through an access program or until Gilead elects to discontinue the study in the country.
干预措施: Oral Lenacapavir (Drug)
Cohort 1A: Lenacapavir
Participants with HIV-1 ribonucleic acid (RNA) ≥ 400 copies/mL and with a <0.5 log10 HIV-1 RNA decline at Cohort Selection visit compared with screening visit will receive oral lenacapavir (LEN) 600 mg tablet on Days 1 and 2 and 300 mg tablet on Day 8, while continuing their failing regimen in the blinded Functional Monotherapy Period (Baseline to Day 14); followed by unblinded Maintenance Period where participants will receive subcutaneous (SC) LEN 927 mg and will initiate an optimized background regimen (OBR) at Day 1 SC Visit (14 days after the first dose of oral LEN).
At Week 52 (relative to Day 1 SC), participants will be given an option to receive SC lenacapavir injections every 6 months (26 weeks), while continuing their OBR, until the product becomes accessible to participants through an access program or until Gilead elects to discontinue the study in the country.
干预措施: Subcutaneous Lenacapavir (Drug)
Cohort 1A: Lenacapavir
Participants with HIV-1 ribonucleic acid (RNA) ≥ 400 copies/mL and with a <0.5 log10 HIV-1 RNA decline at Cohort Selection visit compared with screening visit will receive oral lenacapavir (LEN) 600 mg tablet on Days 1 and 2 and 300 mg tablet on Day 8, while continuing their failing regimen in the blinded Functional Monotherapy Period (Baseline to Day 14); followed by unblinded Maintenance Period where participants will receive subcutaneous (SC) LEN 927 mg and will initiate an optimized background regimen (OBR) at Day 1 SC Visit (14 days after the first dose of oral LEN).
At Week 52 (relative to Day 1 SC), participants will be given an option to receive SC lenacapavir injections every 6 months (26 weeks), while continuing their OBR, until the product becomes accessible to participants through an access program or until Gilead elects to discontinue the study in the country.
干预措施: Failing ARV Regimen (Drug)
Cohort 1A: Lenacapavir
Participants with HIV-1 ribonucleic acid (RNA) ≥ 400 copies/mL and with a <0.5 log10 HIV-1 RNA decline at Cohort Selection visit compared with screening visit will receive oral lenacapavir (LEN) 600 mg tablet on Days 1 and 2 and 300 mg tablet on Day 8, while continuing their failing regimen in the blinded Functional Monotherapy Period (Baseline to Day 14); followed by unblinded Maintenance Period where participants will receive subcutaneous (SC) LEN 927 mg and will initiate an optimized background regimen (OBR) at Day 1 SC Visit (14 days after the first dose of oral LEN).
At Week 52 (relative to Day 1 SC), participants will be given an option to receive SC lenacapavir injections every 6 months (26 weeks), while continuing their OBR, until the product becomes accessible to participants through an access program or until Gilead elects to discontinue the study in the country.
干预措施: Optimized Background Regimen (OBR) (Drug)
Cohort 1B: Placebo to Lenacapavir
Participants with HIV-1 RNA ≥ 400 copies/mL and with a <0.5 log10 HIV-1 RNA decline at the Cohort Selection visit compared with screening visit will receive oral LEN placebo on Days 1, 2, and 8 while continuing their failing regimen in the blinded Functional Monotherapy Period (Baseline to Day 14); followed by unblinded Maintenance Period where participants will receive oral LEN 600 mg on Days 15 and 16 and 300 mg on Day 22, and will initiate an OBR on Day 15. At Day 1 SC (14 days after the first dose of oral LEN), participants will receive SC LEN 927 mg while continuing OBR.
At Week 52 (relative to Day 1 SC), participants will be given an option to receive SC lenacapavir injections every 6 months (26 weeks), while continuing their OBR, until the product becomes accessible to participants through an access program or until Gilead elects to discontinue the study in the country.
干预措施: Oral Lenacapavir (Drug)
Cohort 1B: Placebo to Lenacapavir
Participants with HIV-1 RNA ≥ 400 copies/mL and with a <0.5 log10 HIV-1 RNA decline at the Cohort Selection visit compared with screening visit will receive oral LEN placebo on Days 1, 2, and 8 while continuing their failing regimen in the blinded Functional Monotherapy Period (Baseline to Day 14); followed by unblinded Maintenance Period where participants will receive oral LEN 600 mg on Days 15 and 16 and 300 mg on Day 22, and will initiate an OBR on Day 15. At Day 1 SC (14 days after the first dose of oral LEN), participants will receive SC LEN 927 mg while continuing OBR.
At Week 52 (relative to Day 1 SC), participants will be given an option to receive SC lenacapavir injections every 6 months (26 weeks), while continuing their OBR, until the product becomes accessible to participants through an access program or until Gilead elects to discontinue the study in the country.
干预措施: Oral Lenacapavir Placebo (Drug)
Cohort 1B: Placebo to Lenacapavir
Participants with HIV-1 RNA ≥ 400 copies/mL and with a <0.5 log10 HIV-1 RNA decline at the Cohort Selection visit compared with screening visit will receive oral LEN placebo on Days 1, 2, and 8 while continuing their failing regimen in the blinded Functional Monotherapy Period (Baseline to Day 14); followed by unblinded Maintenance Period where participants will receive oral LEN 600 mg on Days 15 and 16 and 300 mg on Day 22, and will initiate an OBR on Day 15. At Day 1 SC (14 days after the first dose of oral LEN), participants will receive SC LEN 927 mg while continuing OBR.
At Week 52 (relative to Day 1 SC), participants will be given an option to receive SC lenacapavir injections every 6 months (26 weeks), while continuing their OBR, until the product becomes accessible to participants through an access program or until Gilead elects to discontinue the study in the country.
干预措施: Subcutaneous Lenacapavir (Drug)
Cohort 1B: Placebo to Lenacapavir
Participants with HIV-1 RNA ≥ 400 copies/mL and with a <0.5 log10 HIV-1 RNA decline at the Cohort Selection visit compared with screening visit will receive oral LEN placebo on Days 1, 2, and 8 while continuing their failing regimen in the blinded Functional Monotherapy Period (Baseline to Day 14); followed by unblinded Maintenance Period where participants will receive oral LEN 600 mg on Days 15 and 16 and 300 mg on Day 22, and will initiate an OBR on Day 15. At Day 1 SC (14 days after the first dose of oral LEN), participants will receive SC LEN 927 mg while continuing OBR.
At Week 52 (relative to Day 1 SC), participants will be given an option to receive SC lenacapavir injections every 6 months (26 weeks), while continuing their OBR, until the product becomes accessible to participants through an access program or until Gilead elects to discontinue the study in the country.
干预措施: Failing ARV Regimen (Drug)
Cohort 1B: Placebo to Lenacapavir
Participants with HIV-1 RNA ≥ 400 copies/mL and with a <0.5 log10 HIV-1 RNA decline at the Cohort Selection visit compared with screening visit will receive oral LEN placebo on Days 1, 2, and 8 while continuing their failing regimen in the blinded Functional Monotherapy Period (Baseline to Day 14); followed by unblinded Maintenance Period where participants will receive oral LEN 600 mg on Days 15 and 16 and 300 mg on Day 22, and will initiate an OBR on Day 15. At Day 1 SC (14 days after the first dose of oral LEN), participants will receive SC LEN 927 mg while continuing OBR.
At Week 52 (relative to Day 1 SC), participants will be given an option to receive SC lenacapavir injections every 6 months (26 weeks), while continuing their OBR, until the product becomes accessible to participants through an access program or until Gilead elects to discontinue the study in the country.
干预措施: Optimized Background Regimen (OBR) (Drug)
Cohort 2: Lenacapavir
Participants with a ≥ 0.5 log10 copies/mL HIV-1 RNA decline at the Cohort Selection Visit compared with the screening visit or with HIV-1 RNA < 400 copies/mL or if Cohort 1 is fully enrolled will receive oral LEN 600 mg tablet on Days 1 and 2 and 300 mg tablet on Day 8, and will initiate an OBR on Day 1 in Oral Lead-in Period (Baseline to Day 14); followed by Maintenance Period where participants will receive SC LEN 927 mg at Day 1 SC Visit (14 days after the first dose of oral LEN) while continuing their OBR.
At Week 52 (relative to Day 1 SC), participants will be given an option to receive SC lenacapavir injections every 6 months (26 weeks), while continuing their OBR, until the product becomes accessible to participants through an access program or until Gilead elects to discontinue the study in the country.
干预措施: Oral Lenacapavir (Drug)
Cohort 2: Lenacapavir
Participants with a ≥ 0.5 log10 copies/mL HIV-1 RNA decline at the Cohort Selection Visit compared with the screening visit or with HIV-1 RNA < 400 copies/mL or if Cohort 1 is fully enrolled will receive oral LEN 600 mg tablet on Days 1 and 2 and 300 mg tablet on Day 8, and will initiate an OBR on Day 1 in Oral Lead-in Period (Baseline to Day 14); followed by Maintenance Period where participants will receive SC LEN 927 mg at Day 1 SC Visit (14 days after the first dose of oral LEN) while continuing their OBR.
At Week 52 (relative to Day 1 SC), participants will be given an option to receive SC lenacapavir injections every 6 months (26 weeks), while continuing their OBR, until the product becomes accessible to participants through an access program or until Gilead elects to discontinue the study in the country.
干预措施: Subcutaneous Lenacapavir (Drug)
Cohort 2: Lenacapavir
Participants with a ≥ 0.5 log10 copies/mL HIV-1 RNA decline at the Cohort Selection Visit compared with the screening visit or with HIV-1 RNA < 400 copies/mL or if Cohort 1 is fully enrolled will receive oral LEN 600 mg tablet on Days 1 and 2 and 300 mg tablet on Day 8, and will initiate an OBR on Day 1 in Oral Lead-in Period (Baseline to Day 14); followed by Maintenance Period where participants will receive SC LEN 927 mg at Day 1 SC Visit (14 days after the first dose of oral LEN) while continuing their OBR.
At Week 52 (relative to Day 1 SC), participants will be given an option to receive SC lenacapavir injections every 6 months (26 weeks), while continuing their OBR, until the product becomes accessible to participants through an access program or until Gilead elects to discontinue the study in the country.
干预措施: Optimized Background Regimen (OBR) (Drug)
结局指标
主要结局
Percentage of Participants in Cohort 1 Achieving a Reduction of ≥ 0.5 log10 Copies/mL in Human Immunodeficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) From Baseline to the End of Functional Monotherapy Period
时间窗: Baseline up to Day 1 SC Visit (14 days after the first dose of oral lencapavir) or Day 15
次要结局
- Percentage of Participants in Cohort 1 With Plasma HIV-1 RNA < 50 Copies/mL at Week 26 Based on the US FDA-defined Snapshot Algorithm(Week 26 (26 weeks after first dose of subcutaneous lenacapavir))
- Percentage of Participants in Cohort 1 With Plasma HIV-1 RNA < 200 Copies/mL at Week 26 Based on the US FDA-defined Snapshot Algorithm(Week 26 (26 weeks after first dose of subcutaneous lenacapavir))
- Percentage of Participants in Cohort 1 With Plasma HIV-1 RNA < 50 Copies/mL at Week 52 Based on the US FDA-defined Snapshot Algorithm(Week 52 (52 weeks after first dose of subcutaneous lenacapavir))
- Percentage of Participants in Cohort 1 With Plasma HIV-1 RNA < 200 Copies/mL at Week 52 Based on the US FDA-defined Snapshot Algorithm(Week 52 (52 weeks after first dose of subcutaneous lenacapavir))
- Percentage of Participants in Combined Cohorts 1 and 2 With Plasma HIV-1 RNA < 50 Copies/mL at Week 104 Based on the US FDA-defined Snapshot Algorithm(Week 104 (104 weeks after first dose of subcutaneous lenacapavir))
- Percentage of Participants in Combined Cohorts 1 and 2 With Plasma HIV-1 RNA < 200 Copies/mL at Week 104 Based on the US FDA-defined Snapshot Algorithm(Week 104 (104 weeks after first dose of subcutaneous lenacapavir))
- Percentage of Participants in Combined Cohorts 1 and 2 With Plasma HIV-1 RNA < 50 Copies/mL at Week 156 Based on the US FDA-defined Snapshot Algorithm(Week 156 (156 weeks after first dose of subcutaneous lenacapavir))
- Percentage of Participants in Combined Cohorts 1 and 2 With Plasma HIV-1 RNA < 200 Copies/mL at Week 156 Based on the US FDA-defined Snapshot Algorithm(Week 156 (156 weeks after first dose of subcutaneous lenacapavir))