A Phase 2 Randomized, Open Label, Active Controlled Study Evaluating the Safety and Efficacy of Long-acting Capsid Inhibitor GS-6207 in Combination With Other Antiretroviral Agents in People Living With HIV
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 183
- 试验地点
- 53
- 主要终点
- Percentage of Participants With Human Immunodeficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) < 50 Copies/mL at Week 54 as Determined by the United States Food and Drug Administration (US FDA)-Defined Snapshot Algorithm
研究概览
简要总结
The primary objective of this study is to evaluate the efficacy of lenacapavir (formerly GS-6207) containing regimens in people living with human immunodeficiency virus (HIV) (PLWH).
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
- •Antiretroviral (ARV) naive with no use of any ARV within one month of screening. Use of pre-exposure prophylaxis (PrEP) (any duration), post-exposure prophylaxis (PEP) (any duration), or HIV-1 treatment (< 10 days therapy total) > 1 month prior to screening is permitted
- •HIV-1 ribonucleic acid (RNA) ≥ 200 copies/mL at screening
- •Cluster Determinant 4+ (CD4+) cell count ≥ 200 cells/microliter at screening
排除标准
- •Current Hepatitis B Virus (HBV) or Hepatitis C virus (HCV) infection
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Lenacapavir, F/TAF, and TAF
Induction phase: Participants will receive lenacapavir (LEN) 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus emtricitabine/ tenofovir alafenamide (F/TAF) (200/25 mg) fixed-dose combination (FDC) tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via subcutaneous (SC) injection on Day 15.
Maintenance phase: Participants will receive LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and will continue up to Week 80.
Participants willing to continue the study beyond Week 80 will continue to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards.
干预措施: Oral Lenacapavir (Drug)
Lenacapavir, F/TAF, and TAF
Induction phase: Participants will receive lenacapavir (LEN) 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus emtricitabine/ tenofovir alafenamide (F/TAF) (200/25 mg) fixed-dose combination (FDC) tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via subcutaneous (SC) injection on Day 15.
Maintenance phase: Participants will receive LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and will continue up to Week 80.
Participants willing to continue the study beyond Week 80 will continue to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards.
干预措施: F/TAF (Drug)
Lenacapavir, F/TAF, and TAF
Induction phase: Participants will receive lenacapavir (LEN) 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus emtricitabine/ tenofovir alafenamide (F/TAF) (200/25 mg) fixed-dose combination (FDC) tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via subcutaneous (SC) injection on Day 15.
Maintenance phase: Participants will receive LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and will continue up to Week 80.
Participants willing to continue the study beyond Week 80 will continue to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards.
干预措施: Subcutaneous Lenacapavir (Drug)
Lenacapavir, F/TAF, and TAF
Induction phase: Participants will receive lenacapavir (LEN) 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus emtricitabine/ tenofovir alafenamide (F/TAF) (200/25 mg) fixed-dose combination (FDC) tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via subcutaneous (SC) injection on Day 15.
Maintenance phase: Participants will receive LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and will continue up to Week 80.
Participants willing to continue the study beyond Week 80 will continue to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards.
干预措施: TAF (Drug)
Lenacapavir, F/TAF, and BIC
Induction phase: Participants will receive LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Day 15.
Maintenance phase: Participants will receive LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus bictegravir (BIC) 75 mg tablets once daily orally at Week 28 and will continue up to Week 80.
Participants willing to continue the study beyond Week 80 will continue to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily BIC 75 mg tablets from Week 80 onwards.
干预措施: Oral Lenacapavir (Drug)
Lenacapavir, F/TAF, and BIC
Induction phase: Participants will receive LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Day 15.
Maintenance phase: Participants will receive LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus bictegravir (BIC) 75 mg tablets once daily orally at Week 28 and will continue up to Week 80.
Participants willing to continue the study beyond Week 80 will continue to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily BIC 75 mg tablets from Week 80 onwards.
干预措施: F/TAF (Drug)
Lenacapavir, F/TAF, and BIC
Induction phase: Participants will receive LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Day 15.
Maintenance phase: Participants will receive LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus bictegravir (BIC) 75 mg tablets once daily orally at Week 28 and will continue up to Week 80.
Participants willing to continue the study beyond Week 80 will continue to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily BIC 75 mg tablets from Week 80 onwards.
干预措施: Subcutaneous Lenacapavir (Drug)
Lenacapavir, F/TAF, and BIC
Induction phase: Participants will receive LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Day 15.
Maintenance phase: Participants will receive LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus bictegravir (BIC) 75 mg tablets once daily orally at Week 28 and will continue up to Week 80.
Participants willing to continue the study beyond Week 80 will continue to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily BIC 75 mg tablets from Week 80 onwards.
干预措施: BIC (Drug)
Lenacapavir and F/TAF
Induction phase: Participants will receive LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Day 15.
Maintenance phase: Participants will receive LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus bictegravir (BIC) 75 mg tablets once daily orally at Week 28 and will continue up to Week 80.
Participants willing to continue the study beyond Week 80 will continue to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily BIC 75 mg tablets from Week 80 onwards.
干预措施: Oral Lenacapavir (Drug)
Lenacapavir and F/TAF
Induction phase: Participants will receive LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Day 15.
Maintenance phase: Participants will receive LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus bictegravir (BIC) 75 mg tablets once daily orally at Week 28 and will continue up to Week 80.
Participants willing to continue the study beyond Week 80 will continue to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily BIC 75 mg tablets from Week 80 onwards.
干预措施: F/TAF (Drug)
B/F/TAF
Participants will receive bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (50/200/25 mg) FDC tablets once daily orally from Day 1 and throughout their participation in the study up to Week 80
干预措施: B/F/TAF (Drug)
结局指标
主要结局
Percentage of Participants With Human Immunodeficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) < 50 Copies/mL at Week 54 as Determined by the United States Food and Drug Administration (US FDA)-Defined Snapshot Algorithm
时间窗: Week 54
The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 54 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. Week 54 window was between Day 323 and 413 (inclusive). Percentages were rounded off.
次要结局
- Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 28 as Determined by the US FDA-defined Snapshot Algorithm(Week 28)
- Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 38 as Determined by the US FDA-defined Snapshot Algorithm(Week 38)
- Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 80 as Determined by the US FDA-defined Snapshot Algorithm(Week 80)
- Change From Baseline in Log10 HIV-1 RNA at Week 28(Baseline, Week 28)
- Change From Baseline in Log10 HIV-1 RNA at Week 38(Baseline, Week 38)
- Change From Baseline in Log10 HIV-1 RNA at Week 54(Baseline, Week 54)
- Change From Baseline in Log10 HIV-1 RNA at Week 80(Baseline, Week 80)
- Change From Baseline in Clusters of Differentiation 4+ (CD4+) Cell Count at Week 28(Baseline, Week 28)
- Change From Baseline in CD4+ Cell Count at Week 38(Baseline, Week 38)
- Change From Baseline in CD4+ Cell Count at Week 54(Baseline, Week 54)
- Change From Baseline in CD4+ Cell Count at Week 80(Baseline, Week 80)
- Percentage of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)(Up to 174.9 weeks)
- Percentage of Participants Who Experienced Maximum Postbaseline Laboratory Abnormalities(Up to 174.9 weeks)
- Pharmacokinetics (PK) of LEN: Plasma LEN Pre-dose Concentrations for SC LEN(Day 2, 8, Day 1 SC (Day 15), Week 28 and Week 54)
- PK of LEN : Plasma LEN Single Anytime Concentrations for the Oral LEN + DVY(Day 2, 8, 15 , Week 28 and Week 54)
- PK of TAF (Tenofovir Alafenamide) and TFV (Tenofovir): Area Under the Concentration Versus Time Curve (AUClast) on Day 1(0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose on Day 1)
- PK of TAF and TFV: AUClast at Weeks 16, 22, or 28(0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose)
- PK of TAF and TFV (Tenofovir): Maximum Observed Concentration of Drug (Cmax) on Day 1(0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose on Day 1)
- PK of TAF and TFV: Time (Observed Time Point) of Cmax (Tmax) on Day 1(0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose on Day 1)
- PK of TFV: Last Observed Quantifiable Concentration of the Drug (Clast) on Day 1(0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose on Day 1)
- PK of TAF and TFV: Cmax at Weeks 16, 22, or 28(0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose)
- PK of TAF and TFV: Tmax at Weeks 16, 22, or 28(0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose)
- PK of TFV: Clast at Weeks 16, 22, or 28(0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose)
- PK of TAF: AUClast at Week 38(0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose)
- PK of TAF: Cmax at Week 38(0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose)
- PK of TAF: Tmax at Week 38(0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose)
- PK of Tenofovir Diphosphate (TFV-DP): AUClast at Weeks 4, 10, 16, or 22(0 hours (Predose) and at 1, 2, and 6 hours postdose)
- PK of TFV-DP: Cmax at Weeks 4, 10, 16, or 22(0 hours (Predose) and at 1, 2, and 6 hours postdose)
- PK of TFV-DP: Tmax at Weeks 4, 10, 16, or 22(0 hours (Predose) and at 1, 2, and 6 hours postdose)
- PK of Bictegravir (BIC): AUClast at Week 38(0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose)
- PK of BIC: Cmax at Week 38(0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose)
- PK of BIC: Tmax at Week 38(0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose)
- PK of BIC: Clast at Week 38(0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose)