A Phase 2b Randomized, Active-Controlled, Double-Blind Trial to Investigate Safety, Efficacy, and Dose-response of BMS-955176, Given on a Backbone of Tenofovir/Emtricitabine, in Treatment-Naive HIV-1 Infected Adults
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 210
- 试验地点
- 1
- 主要终点
- Number of Participants With Plasma HIV-1 Ribonucleic Acid (RNA) <40 Copies Per Milliliter (c/mL) at Week 24 Using Food and Drug Administration (FDA) Snapshot Algorithm
研究概览
简要总结
The purpose of this study is to find at least one dose of BMS-955176 that will be safe, effective and tolerable for HIV-1 infected treatment naive 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
- Triple (Participant, Care Provider, Investigator)
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-naïve; defined as no current or previous exposure to > 1 week of an antiretroviral drug
- •Plasma HIV-1 RNA ≥ 1000 copies/mL
- •CD4 T-cell count > 200 cells/mm3
排除标准
- •Resistance or partial resistance to any study drug determined by tests at Screening
- •Current or historical genotypic and/or phenotypic drug resistance testing showing certain resistance mutations to EFV, TDF, FTC, Protease Inhibitors
- •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 60 mg + TDF/FTC
BMS-955176 at 60 mg active dose per day + BMS-955176 placebo matching 120 mg + efavirenz (EFV) placebo matching 600 mg + tenofovir/emtricitabine (TDF/FTC) 300/200 mg per day, orally
干预措施: BMS-955176 (Drug)
Arm 1: BMS-955176 60 mg + TDF/FTC
BMS-955176 at 60 mg active dose per day + BMS-955176 placebo matching 120 mg + efavirenz (EFV) placebo matching 600 mg + tenofovir/emtricitabine (TDF/FTC) 300/200 mg per day, orally
干预措施: TDF/FTC (Drug)
Arm 2: BMS-955176 120 mg + TDF/FTC
BMS-955176 placebo matching 60 mg + BMS-955176 at 120mg active dose per day + EFV placebo matching 600mg + TDF/FTC 300/200mg per day, orally
干预措施: BMS-955176 (Drug)
Arm 2: BMS-955176 120 mg + TDF/FTC
BMS-955176 placebo matching 60 mg + BMS-955176 at 120mg active dose per day + EFV placebo matching 600mg + TDF/FTC 300/200mg per day, orally
干预措施: TDF/FTC (Drug)
Arm 3: BMS-955176 180 mg + TDF/FTC
BMS-955176 at 60mg active dose per day + BMS-955176 at 120mg active dose per day + EFV placebo matching 600mg + TDF/FTC at 300/200mg per day, orally
干预措施: BMS-955176 (Drug)
Arm 3: BMS-955176 180 mg + TDF/FTC
BMS-955176 at 60mg active dose per day + BMS-955176 at 120mg active dose per day + EFV placebo matching 600mg + TDF/FTC at 300/200mg per day, orally
干预措施: TDF/FTC (Drug)
Arm 4: EFV + TDF/FTC
BMS-955176 placebo matching 60mg + BMS-955176 placebo matching 120mg + EFV at 600mg per day + TDF/FTC 300/200mg per day
干预措施: EFV (Drug)
Arm 4: EFV + TDF/FTC
BMS-955176 placebo matching 60mg + BMS-955176 placebo matching 120mg + EFV at 600mg per day + TDF/FTC 300/200mg per day
干预措施: TDF/FTC (Drug)
结局指标
主要结局
Number of Participants With Plasma HIV-1 Ribonucleic Acid (RNA) <40 Copies Per Milliliter (c/mL) at Week 24 Using Food and Drug Administration (FDA) Snapshot Algorithm
时间窗: Week 24
Blood samples were collected for quantitative analysis of plasma HIV-1 RNA. The antiviral efficacy was determined by the number of participants with plasma HIV 1 RNA \<40 c/mL at Week 24 using the FDA snapshot algorithm. This 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 mITT Population, which comprised of randomized participants who received at least 1 dose of BMS-955176/GSK3532795 or EFV.
次要结局
- Number of Participants With Plasma HIV-1 RNA < 200 c/mL at Weeks 48 and 96(Weeks 48 and 96)
- Number of Participants With Serious Adverse Events (SAEs) and Adverse Events Leading to Discontinuation (AELD)(Up to Week 96)
- Area Under the Concentration-time Curve in One Dosing Interval (AUC [Tau]) of BMS-955176/GSK3532795(Pre-dose (morning) and at 0.5, 1, 1.5, 2, 4, 4.5, 5, 6, 8, 12 (evening pre-dose) and 24 hours (morning pre-dose) at Week 2 (Days 12 to 16))
- Maximum Observed Plasma Concentration (Cmax), Observed Pre-dose Plasma Concentration (C0) and Observed Plasma Concentration at the End of a Dosing Interval (Ctau) of BMS-955176/GSK3532795(Pre-dose (morning) and at 0.5, 1, 1.5, 2, 4, 4.5, 5, 6, 8, 12 (evening pre-dose) and 24 hours (morning pre-dose) at Week 2 (Days 12 to 16))
- Number of Participants With Newly Emergent Genotypic Resistance Using All On-treatment Isolates(Week 24)
- Change From Baseline in Logarithm to the Base 10 (log10) HIV-1 RNA Over Time(Baseline (Day 1) and Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48, 60, 72 and 84)
- Change From Baseline in Cluster of Differentiation (CD)4+ Thymus (T)-Cell Counts Over Time(Baseline (Day 1) and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72 and 84)
- Number of Participants With Plasma HIV-1 RNA < 40 c/mL at Weeks 48 and 96 Using FDA Snapshot Algorithm(Weeks 48 and 96)
- Number of Participants With Newly Emergent Phenotypic Resistance Using All On-treatment Isolates(Week 24)
- Number of Participants With at Least One Centers for Disease Control (CDC) Class C Events(Up to Week 96)
- Time of Maximum Observed Plasma Concentration (Tmax) of BMS-955176/GSK3532795(Pre-dose (morning) and 0.5, 1, 1.5, 2, 4, 4.5, 5, 6, 8, 12 (evening pre-dose) and 24 hours (morning pre-dose) at Week 2 (Days 12 to 16))
- Number of Participants With Plasma HIV-1 RNA < 200 c/mL at Week 24 Using FDA Snapshot Algorithm(Week 24)
- Change From Baseline in the Percentage of CD4+ T-cells Over Time(Baseline (Day 1) and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72 and 84)