A Phase 2 Study to Evaluate the Efficacy of GS-9131 Functional Monotherapy in HIV-1-Infected Adults Failing a Nucleos(t)Ide Reverse Transcriptase Inhibitor-Containing Regimen With Nucleos(t)Ide Reverse Transcriptase Inhibitor Resistant Virus
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 21
- 试验地点
- 2
- 主要终点
- Part 1 Randomized Cohort: Percentage of Participants With Plasma HIV-1 RNA Decreases From Baseline Exceeding 0.5 log10 at Day 15
研究概览
简要总结
The primary objective of this study is to evaluate the short-term antiviral potency of GS-9131 functional monotherapy compared to placebo-to-match (PTM) GS-9131, each administered once daily with the existing failing antiretroviral (ARV) regimen as demonstrated by the proportion of participants achieving human immunodeficiency virus ribonucleic acid (HIV-1 RNA) > 0.5 log10 decreases from baseline after up to 14 days of therapy in HIV-1 positive, ARV treatment experienced adult participants with nucleos(t)ide resistant virus.
This is a two-part study. Part 1 consists of three cohorts: 2 Sentinel Cohorts and 1 Randomized Cohort. Eligible participants from Part 1 will proceed to Part 2 followed by an optional open-label extension.
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 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Plasma HIV-1 RNA ≥ 500 copies/mL at screening Visit
- •Currently taking a failing ARV regimen that contains 2 NRTIs and a NNRTI
- •No prior or current ARV regimens containing integrase inhibitor (INSTI) or protease inhibitor (PI)
- •Screening genotype must show at least the protocol defined resistance mutation profile
排除标准
- •Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Day 1
- •Participation in any other clinical trial, including observational studies, without prior approval from the sponsor is prohibited while participating in this trial
- •Use of an investigational drug other than the study drug
- •Individuals with chronic hepatitis B virus (HBV) infection are not permitted to participate
- •Active tuberculosis infection
- •NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.
研究组 & 干预措施
Part 1 Sentinel Cohort 1: GS-9131 60 mg
Treatment experienced participants will receive GS-9131 60 mg in addition to their current failing ARV regimen for a period of 10 days.
干预措施: GS-9131 (Drug)
Part 1 Sentinel Cohort 1: GS-9131 60 mg
Treatment experienced participants will receive GS-9131 60 mg in addition to their current failing ARV regimen for a period of 10 days.
干预措施: ARV regimen (Drug)
Part 1 Sentinel Cohort 2: GS-9131 180 mg
Treatment experienced participants will receive GS-9131 180 mg in addition to their current failing ARV regimen for a period of 14 days.
干预措施: GS-9131 (Drug)
Part 1 Sentinel Cohort 2: GS-9131 180 mg
Treatment experienced participants will receive GS-9131 180 mg in addition to their current failing ARV regimen for a period of 14 days.
干预措施: ARV regimen (Drug)
Part 1: Randomized Cohort
Participants will be randomized in 1:1:1:1 so as to receive GS-9131 in 3 active dose levels up to a maximum of 180 mg or Placebo to match GS-9131 in addition to their current failing ARV regimen for a period of 14 days in Part 1.
干预措施: GS-9131 (Drug)
Part 1: Randomized Cohort
Participants will be randomized in 1:1:1:1 so as to receive GS-9131 in 3 active dose levels up to a maximum of 180 mg or Placebo to match GS-9131 in addition to their current failing ARV regimen for a period of 14 days in Part 1.
干预措施: ARV regimen (Drug)
Part 2 Sentinel Cohort 1: GS-9131 + BIC + DRV + RTV
Participants who complete dosing in Sentinel Cohort 1 of Part 1 and show a reduction in plasma HIV RNA > 0.5 log10 from their pre-GS-9131 baseline value at Day 11 and discontinue their current failing regimen will receive an optimized regimen consisting of GS-9131 60 mg + bictegravir (BIC) 30 mg + darunavir (DRV) 800 mg + ritonavir (RTV) 100 mg for a period of 24 weeks. After Week 24, participants will be given the option to participate in an open label extension and receive GS-9131 60 mg + BIC 75 mg + tenofovir alafenamide (TAF) 25 mg, for an additional 24 weeks or until Gilead Sciences elects to discontinue the study drug in that country, whichever occurs first.
干预措施: GS-9131 (Drug)
Part 2 Sentinel Cohort 1: GS-9131 + BIC + DRV + RTV
Participants who complete dosing in Sentinel Cohort 1 of Part 1 and show a reduction in plasma HIV RNA > 0.5 log10 from their pre-GS-9131 baseline value at Day 11 and discontinue their current failing regimen will receive an optimized regimen consisting of GS-9131 60 mg + bictegravir (BIC) 30 mg + darunavir (DRV) 800 mg + ritonavir (RTV) 100 mg for a period of 24 weeks. After Week 24, participants will be given the option to participate in an open label extension and receive GS-9131 60 mg + BIC 75 mg + tenofovir alafenamide (TAF) 25 mg, for an additional 24 weeks or until Gilead Sciences elects to discontinue the study drug in that country, whichever occurs first.
干预措施: BIC (Drug)
Part 2 Sentinel Cohort 1: GS-9131 + BIC + DRV + RTV
Participants who complete dosing in Sentinel Cohort 1 of Part 1 and show a reduction in plasma HIV RNA > 0.5 log10 from their pre-GS-9131 baseline value at Day 11 and discontinue their current failing regimen will receive an optimized regimen consisting of GS-9131 60 mg + bictegravir (BIC) 30 mg + darunavir (DRV) 800 mg + ritonavir (RTV) 100 mg for a period of 24 weeks. After Week 24, participants will be given the option to participate in an open label extension and receive GS-9131 60 mg + BIC 75 mg + tenofovir alafenamide (TAF) 25 mg, for an additional 24 weeks or until Gilead Sciences elects to discontinue the study drug in that country, whichever occurs first.
干预措施: DRV (Drug)
Part 2 Sentinel Cohort 1: GS-9131 + BIC + DRV + RTV
Participants who complete dosing in Sentinel Cohort 1 of Part 1 and show a reduction in plasma HIV RNA > 0.5 log10 from their pre-GS-9131 baseline value at Day 11 and discontinue their current failing regimen will receive an optimized regimen consisting of GS-9131 60 mg + bictegravir (BIC) 30 mg + darunavir (DRV) 800 mg + ritonavir (RTV) 100 mg for a period of 24 weeks. After Week 24, participants will be given the option to participate in an open label extension and receive GS-9131 60 mg + BIC 75 mg + tenofovir alafenamide (TAF) 25 mg, for an additional 24 weeks or until Gilead Sciences elects to discontinue the study drug in that country, whichever occurs first.
干预措施: RTV (Drug)
Part 2 Sentinel Cohort 2: GS-9131 + BIC + TAF
Participants who complete dosing in Sentinel Cohort 2 of Part 1 and show a reduction in plasma HIV RNA > 0.5 log10 from their pre-GS-9131 baseline value at Day 15 and discontinue their current failing regimen will receive an optimized regimen consisting of GS-9131 180 mg + BIC 75 mg + TAF 25 mg, for a period of 24 weeks. After Week 24, participants will be given the option to participate in an open label extension and receive GS-9131 180 mg + BIC 75 mg + TAF 25 mg, for an additional 24 weeks or until Gilead Sciences elects to discontinue the study drug in that country, whichever occurs first.
干预措施: GS-9131 (Drug)
Part 2 Sentinel Cohort 2: GS-9131 + BIC + TAF
Participants who complete dosing in Sentinel Cohort 2 of Part 1 and show a reduction in plasma HIV RNA > 0.5 log10 from their pre-GS-9131 baseline value at Day 15 and discontinue their current failing regimen will receive an optimized regimen consisting of GS-9131 180 mg + BIC 75 mg + TAF 25 mg, for a period of 24 weeks. After Week 24, participants will be given the option to participate in an open label extension and receive GS-9131 180 mg + BIC 75 mg + TAF 25 mg, for an additional 24 weeks or until Gilead Sciences elects to discontinue the study drug in that country, whichever occurs first.
干预措施: BIC (Drug)
Part 2 Sentinel Cohort 2: GS-9131 + BIC + TAF
Participants who complete dosing in Sentinel Cohort 2 of Part 1 and show a reduction in plasma HIV RNA > 0.5 log10 from their pre-GS-9131 baseline value at Day 15 and discontinue their current failing regimen will receive an optimized regimen consisting of GS-9131 180 mg + BIC 75 mg + TAF 25 mg, for a period of 24 weeks. After Week 24, participants will be given the option to participate in an open label extension and receive GS-9131 180 mg + BIC 75 mg + TAF 25 mg, for an additional 24 weeks or until Gilead Sciences elects to discontinue the study drug in that country, whichever occurs first.
干预措施: TAF (Drug)
结局指标
主要结局
Part 1 Randomized Cohort: Percentage of Participants With Plasma HIV-1 RNA Decreases From Baseline Exceeding 0.5 log10 at Day 15
时间窗: Day 15
The criteria for analyzing percentage of participants with plasma HIV-1 RNA \> 0.5 log10 decrease from baseline in randomized cohort was at least 50% of the participants should achieve HIV-1 RNA \> 0.5 log10 decrease from baseline in the Part 1 sentinel cohort 2.
次要结局
- Part 2: Change From Baseline in Plasma log10 HIV-1 RNA at Week 24(Baseline, Week 24)
- Part 1 Sentinel Cohort 1: Change From Baseline in Plasma log10 HIV-1 RNA at Day 11(Baseline, Day 11)
- Part 1 Randomized Cohort: Change From Baseline in Plasma log10 HIV-1 RNA at Day 15(Baseline, Day 15)
- Part 1 Sentinel Cohort 2: Change From Baseline in Plasma log10 HIV-1 RNA at Day 15(Baseline, Day 15)
- Part 2: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Analysis at Week 24(Week 24)
- Part 2: Change From Baseline in CD4+ Cell Count at Week 24(Baseline, Week 24)
- Part 2: Number of Participants With Treatment Emergent Nucleos(t)Ide Reverse Transcriptase Inhibitor (NRTI) Mutations at the Time of Virologic Failure(From first dose up to Week 24)
- Part 2: Number of Participants With Treatment Emergent Protease Inhibitor (PI) Mutations at the Time of Virologic Failure(From first dose up to Week 24)
- Part 2: Number of Participants With Treatment Emergent Integrase Strand Transfer Inhibitor (INSTI) Mutations at the Time of Virologic Failure(From first dose up to Week 24)