A Phase 1b Randomized, Double-Blinded, Placebo Controlled, Multi-Cohort Study of the Safety, Pharmacokinetics, and Antiviral Activity of GS-6207 Administered Subcutaneously in HIV-1 Infected Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 53
- 试验地点
- 12
- 主要终点
- Part A and Part B: Maximum Reduction From Day 1 (Baseline) Through Day 10 in Plasma HIV-1 RNA
研究概览
简要总结
The primary objectives of this study are:
Part A: To evaluate the short-term antiviral activity of lenacapavir (formerly GS-6207) with respect to the maximum reduction of plasma HIV-1 RNA (log10 copies/mL) from Day 1 through Day 10 compared to placebo in HIV-1 infected adults who are antiretroviral treatment naive or are experienced but capsid inhibitor (CAI) naive.
Part B: To evaluate the short-term antiviral activity of tenofovir alafenamide (TAF) with respect to the maximum reduction of plasma HIV-1 RNA (log10 copies/mL) from Day 1 through Day 10 in HIV-1 infected adult subjects who are antiretroviral treatment naïve or are experienced but without resistance to TAF.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Plasma HIV-1 RNA ≥ 5,000 copies/mL but ≤ 400,000 copies/mL and CD4+ cell count > 200 cells/mm^3
- •Treatment naive or experienced but CAI (for Part A only) and integrase strand transfer inhibitor (INSTI) naïve, and have not received any antiretroviral therapy (ART) within 12 weeks of screening
- •Screening genotype report must show sensitivity to B/F/TAF to allow its initiation on Day 10
- •Screening genotype report must show sensitivity to at least one agent in either non-nucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI) class to allow its use as part of standard of care oral antiretroviral treatment in the future
- •Have adequate renal function (estimated glomerular filtration rate ≥ 70 mL/min)
- •No clinically significant abnormalities in electrocardiography (ECG) at Screening
- •Willing to initiate B/F/TAF on Day 10 after completion of all assessments
排除标准
- •Pregnant or lactating females
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Part A: Lenacapavir 20 mg
Participants will receive single dose of lenacapavir 20 mg on Day 1 followed by bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) as per standard-care therapy starting on Day 10 through Day 225.
干预措施: Lenacapavir (Drug)
Part A: Lenacapavir 20 mg
Participants will receive single dose of lenacapavir 20 mg on Day 1 followed by bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) as per standard-care therapy starting on Day 10 through Day 225.
干预措施: B/F/TAF (Drug)
Part A: Lenacapavir 50 mg
Participants will receive single dose of lenacapavir 50 mg on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225.
干预措施: Lenacapavir (Drug)
Part A: Lenacapavir 50 mg
Participants will receive single dose of lenacapavir 50 mg on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225.
干预措施: B/F/TAF (Drug)
Part A: Lenacapavir 150 mg
Participants will receive single dose of lenacapavir 150 mg on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225.
干预措施: Lenacapavir (Drug)
Part A: Lenacapavir 150 mg
Participants will receive single dose of lenacapavir 150 mg on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225.
干预措施: B/F/TAF (Drug)
Part A: Lenacapavir 450 mg
Participants will receive single dose of lenacapavir 450 mg on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225.
干预措施: Lenacapavir (Drug)
Part A: Lenacapavir 450 mg
Participants will receive single dose of lenacapavir 450 mg on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225.
干预措施: B/F/TAF (Drug)
Part A: Lenacapavir 750 mg
Participants will receive single dose of lenacapavir 750 mg on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225.
干预措施: Lenacapavir (Drug)
Part A: Lenacapavir 750 mg
Participants will receive single dose of lenacapavir 750 mg on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225.
干预措施: B/F/TAF (Drug)
Part A: Placebo
Participants will receive single dose of placebo matched to lenacapavir on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225.
干预措施: Placebo (Drug)
Part A: Placebo
Participants will receive single dose of placebo matched to lenacapavir on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225.
干预措施: B/F/TAF (Drug)
Part B: TAF 200 mg
Participants will receive a single dose of TAF 200 mg on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225.
干预措施: B/F/TAF (Drug)
Part B: TAF 200 mg
Participants will receive a single dose of TAF 200 mg on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225.
干预措施: TAF (Drug)
Part B: TAF 600 mg
Participants will receive a single dose of TAF 600 mg on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225.
干预措施: B/F/TAF (Drug)
Part B: TAF 600 mg
Participants will receive a single dose of TAF 600 mg on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225.
干预措施: TAF (Drug)
结局指标
主要结局
Part A and Part B: Maximum Reduction From Day 1 (Baseline) Through Day 10 in Plasma HIV-1 RNA
时间窗: Day 1 through Day 10
Maximum reduction is defined as the minimum of change from baseline in plasma HIV-1 RNA (i.e. smallest change in HIV-RNA from baseline).
次要结局
- Part A and Part B: Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs)(Day 1 through 225 days)
- Part A and Part B: Percentage of Participants Experiencing Treatment Emergent Laboratory Abnormalities(Day 1 through 225 days)
- Part A and Part B Pharmacokinetic (PK) Parameter: AUCinf of Lenacapavir, TAF and Its Metabolite TFV(Part A: 0 (predose),1,2,4,8,12,24 h postdose on Day 1, anytime on Days 3,4,7,8,9,10,14,29,43,57,85,113,141,169,197,225; Part B: 0 (predose),0.5,1,2,3,4,6,8,10,12,24 and 48 h postdose on Day 1, approximately Day 1 predose time on Days 4,5,6,7,8,9,10)
- Part A and Part B PK Parameter: AUClast of Lenacapavir, TAF and Its Metabolite TFV(Part A: 0 (predose),1,2,4,8,12,24 h postdose on Day 1, anytime on Days 3,4,7,8,9,10,14,29,43,57,85,113,141,169,197,225; Part B: 0 (predose),0.5,1,2,3,4,6,8,10,12,24 and 48 h postdose on Day 1, approximately Day 1 predose time on Days 4,5,6,7,8,9,10)
- Part A and Part B PK Parameter: Cmax of Lenacapavir, TAF and Its Metabolite TFV(Part A: 0 (predose),1,2,4,8,12,24 h postdose on Day 1, anytime on Days 3,4,7,8,9,10,14,29,43,57,85,113,141,169,197,225; Part B: 0 (predose),0.5,1,2,3,4,6,8,10,12,24 and 48 h postdose on Day 1, approximately Day 1 predose time on Days 4,5,6,7,8,9,10)
- Part B PK Parameter: AUCinf of TFV-DP Metabolite of TAF(Part B: 0 (predose), 1, 2, 4, 6, 8, 12, 24 and 48 hours post dose on Day 1, approximately Day 1 predose time on Days 4, 5 (if possible), 6 (if possible), 7, 8, 9, 10)
- Part B PK Parameter: AUClast of TFV-DP Metabolite of TAF(Part B: 0 (predose), 1, 2, 4, 6, 8, 12, 24 and 48 hours post dose on Day 1, approximately Day 1 predose time on Days 4, 5 (if possible), 6 (if possible), 7, 8, 9, 10)
- Part B PK Parameter: Cmax of TFV-DP Metabolite of TAF(Part B: 0 (predose), 1, 2, 4, 6, 8, 12, 24 and 48 hours post dose on Day 1, approximately Day 1 predose time on Days 4, 5 (if possible), 6 (if possible), 7, 8, 9, 10)
- Part A: Percentage of Participants Ever Achieving HIV-1 RNA < 50 Copies/mL by Day 10(Day 10)
- Part A: Number of Participants Experiencing Any Emergence of Capsid Inhibitor Resistance(Day 10 through Day 225)
- Part B: Number of Participants Experiencing Any Emergence of TAF Resistance(Day 10 through Day 225)