A Phase 2b Randomized, Active-Controlled, Staged, Open-Label Trial to Investigate Safety and Efficacy of BMS-955176/GSK3532795 in Combination With Dolutegravir and Atazanavir (With or Without Ritonavir) in Treatment-Experienced HIV-1 Infected Adults
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 86
- 试验地点
- 1
- 主要终点
- Percentage of Participants With Plasma HIV-1 RNA <40 c/mL at Week 24-Stage 2
研究概览
简要总结
The purpose of this study is to evaluate whether the combination of BMS-955176 with atazanavir (ATV) [with or without ritonavir (RTV)] and dolutegravir (DTG) is efficacious, safe, and well-tolerated in HIV-1 infected treatment experienced adults.
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
- •Men and non-pregnant women, at least 18 years of age
- •Antiretroviral treatment-experienced, defined as having documented evidence of having failed 1 or 2 regimens that include 2 or 3 classes of antiretroviral (ARV) (with or without documented resistance)
- •CD4+ T-cell count > 50 cells/mm3
- •Screening genotype/phenotype indicating susceptibility to study drugs (unboosted ATV, FC < 2.2; DTG; TDF)
排除标准
- •Antiretroviral treatment-experienced adults who have failed > 2 ARV regimens
- •Resistance or partial resistance to any study drug determined by tests at Screening
- •Historical or documented genotypic and/or phenotypic drug resistance testing showing certain resistance mutations to ATV, TDF, RAL, Protease Inhibitors, and certain TAMs
- •Chronic hepatitis B virus (HBV)/ hepatitis C virus (HCV)
- •Blood tests that indicate normal liver function
- •Hemoglobin < 8.0 g/dL, Platelets < 50,000 cells/mm3
研究组 & 干预措施
Arm 1: BMS-955176 + ATV + RTV + DTG
BMS-955176 at 120 mg tablet per day + Atazanavir boosted with ritonavir (ATV/r) 300/100 mg tablets per day + DTG 50 mg tablet per day, orally
干预措施: BMS-955176 (Drug)
Arm 1: BMS-955176 + ATV + RTV + DTG
BMS-955176 at 120 mg tablet per day + Atazanavir boosted with ritonavir (ATV/r) 300/100 mg tablets per day + DTG 50 mg tablet per day, orally
干预措施: Atazanavir (ATV) (Drug)
Arm 1: BMS-955176 + ATV + RTV + DTG
BMS-955176 at 120 mg tablet per day + Atazanavir boosted with ritonavir (ATV/r) 300/100 mg tablets per day + DTG 50 mg tablet per day, orally
干预措施: Ritonavir (RTV) (Drug)
Arm 1: BMS-955176 + ATV + RTV + DTG
BMS-955176 at 120 mg tablet per day + Atazanavir boosted with ritonavir (ATV/r) 300/100 mg tablets per day + DTG 50 mg tablet per day, orally
干预措施: Dolutegravir (DTG) (Drug)
Arm 2: TDF + ATV + RTV + DTG
TDF 300 mg tablet per day + ATV/r at 300/100 mg tablets per day + DTG 50 mg per day, orally
干预措施: Atazanavir (ATV) (Drug)
Arm 2: TDF + ATV + RTV + DTG
TDF 300 mg tablet per day + ATV/r at 300/100 mg tablets per day + DTG 50 mg per day, orally
干预措施: Ritonavir (RTV) (Drug)
Arm 2: TDF + ATV + RTV + DTG
TDF 300 mg tablet per day + ATV/r at 300/100 mg tablets per day + DTG 50 mg per day, orally
干预措施: Dolutegravir (DTG) (Drug)
Arm 2: TDF + ATV + RTV + DTG
TDF 300 mg tablet per day + ATV/r at 300/100 mg tablets per day + DTG 50 mg per day, orally
干预措施: Tenofovir (TDF) (Drug)
Arm 3: BMS-955176 + ATV + DTG
BMS-955176 at 120 mg tablet per day + ATV at 400 mg tablet per day + DTG at 50 mg tablet per day, orally
干预措施: BMS-955176 (Drug)
Arm 3: BMS-955176 + ATV + DTG
BMS-955176 at 120 mg tablet per day + ATV at 400 mg tablet per day + DTG at 50 mg tablet per day, orally
干预措施: Atazanavir (ATV) (Drug)
Arm 3: BMS-955176 + ATV + DTG
BMS-955176 at 120 mg tablet per day + ATV at 400 mg tablet per day + DTG at 50 mg tablet per day, orally
干预措施: Dolutegravir (DTG) (Drug)
Arm 4: BMS-955176 + ATV + DTG
BMS-955176 at 180 mg tablet per day + ATV at 400 mg tablet per day + DTG at 50 mg tablet per day, orally
干预措施: BMS-955176 (Drug)
Arm 4: BMS-955176 + ATV + DTG
BMS-955176 at 180 mg tablet per day + ATV at 400 mg tablet per day + DTG at 50 mg tablet per day, orally
干预措施: Atazanavir (ATV) (Drug)
Arm 4: BMS-955176 + ATV + DTG
BMS-955176 at 180 mg tablet per day + ATV at 400 mg tablet per day + DTG at 50 mg tablet per day, orally
干预措施: Dolutegravir (DTG) (Drug)
Arm 5: TDF + ATV + RTV + DTG
TDF 300 mg tablet per day + ATV/r at 300/100 mg tablets per day + DTG 50 mg per day, orally
干预措施: Atazanavir (ATV) (Drug)
Arm 5: TDF + ATV + RTV + DTG
TDF 300 mg tablet per day + ATV/r at 300/100 mg tablets per day + DTG 50 mg per day, orally
干预措施: Ritonavir (RTV) (Drug)
Arm 5: TDF + ATV + RTV + DTG
TDF 300 mg tablet per day + ATV/r at 300/100 mg tablets per day + DTG 50 mg per day, orally
干预措施: Dolutegravir (DTG) (Drug)
Arm 5: TDF + ATV + RTV + DTG
TDF 300 mg tablet per day + ATV/r at 300/100 mg tablets per day + DTG 50 mg per day, orally
干预措施: Tenofovir (TDF) (Drug)
结局指标
主要结局
Percentage of Participants With Plasma HIV-1 RNA <40 c/mL at Week 24-Stage 2
时间窗: Week 24
Blood samples were planned to be collected for quantitative analysis of plasma HIV-1 RNA. The analysis was not performed in Stage 2 due to early termination of the study during Stage 1.
Percentage of Participants With Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) <40 Copies Per Milliliter (c/mL) at Week 24-Stage 1
时间窗: Week 24
Blood samples were collected for quantitative analysis of plasma HIV-1 RNA. Percentage of participants with plasma HIV-1 RNA \<40 c/mL at Week 24 was assessed using the Food and Drug Administration (FDA) snapshot algorithm which used the last on-treatment plasma HIV-1 RNA measurement, within an FDA-specified visit window (18 to 30 weeks), to determine response. Analysis was performed on the modified intent to treat (mITT) Population which comprised of all randomized participants who received atleast one dose of BMS-955176 or TDF.
次要结局
- Percentage of Participants With Plasma HIV-1 RNA <40 c/mL at Weeks 48 and 96-Stage 1(Weeks 48 and 96)
- Percentage of Participants With Plasma HIV-1 RNA <40 c/mL at Weeks 48 and 96-Stage 2(Weeks 48 and 96)
- Percentage of Participants With HIV-1 RNA <200 c/mL at Weeks 24, 48 and 96-Stage 1(Weeks 24, 48 and 96)
- Percentage of Participants With HIV-1 RNA <200 c/mL at Weeks 24, 48 and 96-Stage 2(Weeks 24, 48 and 96)
- Change From Baseline in log10 HIV-1 RNA Over Time-Stage 2(Baseline and up to Week 96)
- Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Count Over Time-Stage 1(Baseline and up to Week 72)
- Change From Baseline in CD4+ Cell Count Over Time-Stage 2(Baseline and up to Week 96)
- Change From Baseline in Percentage of CD4+ Cells Over Time-Stage 1(Baseline and up to Week 72)
- Number of Participants With Serious Adverse Events (SAEs) and Adverse Events (AEs) Leading to Discontinuation (AELD)-Stage 1(Up to Week 96)
- Number of Participants With SAEs and AELDs-Stage 2(Up to Week 96)
- Cmax for BMS-955176-Stage 2(Week 2 (pre-dose, 1, 2, 2.5, 3, 4, 4.5, 5, 6, 8, 12 hours post-dose and 24 hours [morning pre-dose]))
- Tmax for BMS-955176-Stage 2(Week 2 (pre-dose, 1, 2, 2.5, 3, 4, 4.5, 5, 6, 8, 12 hours post-dose and 24 hours [morning pre-dose]))
- Observed Plasma Concentration at the End of a Dosing Interval (Ctau) for BMS-955176-Stage 1(Week 2 (pre-dose, 1, 2, 2.5, 3, 4, 4.5, 5, 6, 8, 12 hours post-dose and 24 hours [morning pre-dose]))
- Change From Baseline in Logarithm to the Base 10 (log10) HIV-1 RNA Over Time-Stage 1(Baseline and up to Week 72)
- Number of Participants With Occurrence of New Acquired Immunodeficiency Syndrome (AIDS) Defining Events-Stage 1(Up to Week 96)
- Number of Participants With Occurrence of New AIDS Defining Events-Stage 2(Up to Week 96)
- Change From Baseline in Percentage of CD4+ Cells Over Time-Stage 2(Baseline and up to Week 96)
- Maximum Observed Concentration (Cmax) for BMS-955176-Stage 1(Week 2 (pre-dose, 1, 2, 2.5, 3, 4, 4.5, 5, 6, 8, 12 hours post-dose and 24 hours [morning pre-dose]))
- Time of Maximum Observed Plasma Concentration (Tmax) for BMS-955176-Stage 1(Week 2 (pre-dose, 1, 2, 2.5, 3, 4, 4.5, 5, 6, 8, 12 hours post-dose and 24 hours [morning pre-dose]))
- Area Under the Concentration-time Curve in One Dosing Interval (AUC[Tau]) for BMS-955176-Stage 1(Week 2 (pre-dose, 1, 2, 2.5, 3, 4, 4.5, 5, 6, 8, 12 hours post-dose and 24 hours [morning pre-dose]))
- Ctau for BMS-955176-Stage 2(Week 2 (pre-dose, 1, 2, 2.5, 3, 4, 4.5, 5, 6, 8, 12 hours post-dose and 24 hours [morning pre-dose]))
- C0 for BMS-955176-Stage 2(Week 2 (pre-dose, 1, 2, 2.5, 3, 4, 4.5, 5, 6, 8, 12 hours post-dose and 24 hours [morning pre-dose]))
- Observed Pre-dose Plasma Concentration (C0) for BMS-955176-Stage 1(Week 2 (pre-dose, 1, 2, 2.5, 3, 4, 4.5, 5, 6, 8, 12 hours post-dose and 24 hours [morning pre-dose]))
- AUC(Tau) for BMS-955176-Stage 2(Week 2 (pre-dose, 1, 2, 2.5, 3, 4, 4.5, 5, 6, 8, 12 hours post-dose and 24 hours [morning pre-dose]))
- Number of Participants With Emergence of HIV Drug Resistance-Stage 1(Up to Week 96)
- Number of Participants With Emergence of HIV Drug Resistance-Stage 2(Up to Week 96)