A Phase IIb Randomized, Controlled, Partially-Blinded Trial to Investigate Safety, Efficacy and Dose-Response of BMS-663068 in Treatment-experienced HIV-1 Subjects, Followed by an Open-Label Period on the Recommended Dose
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 254
- 试验地点
- 1
- 主要终点
- Number of Participants With Serious Adverse Events (SAE) and Discontinuation Due to AEs up to Week 24
研究概览
简要总结
The purpose of this study is to assess the safety, efficacy, tolerability and pharmacokinetics of four doses of BMS-663068 with Raltegravir (RAL) + Tenofovir Disoproxil Fumarate (TDF). At least 1 dose of BMS-663068 can be identified which is safe, well tolerated, and efficacious when combined with RAL + TDF for treatment-experienced HIV-1 infected subjects. PHENOSENSE® is a registered trademark of Monogram Biosciences.
详细描述
Masking: Double-blind for BMS-6630368 treatment groups until the Week 24 Primary Endpoint analysis, then open label. The reference groups is all open-label.
Arms: 5 (4 BMS-663068 treatment groups and 1 reference group)
Intervention Model: Parallel (with unblinding after the Week 24 primary endpoint analysis)
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Plasma HIV-1 RNA ≥ 1000 copies/ml at Screening
- •Treatment experience with antiretroviral therapies (excluding integrase inhibitors)
- •Screening PHENOSENSE Entry indicating BMS-626529 inhibitory concentration (IC)50 < 0.1 μM
- •Cluster of differentiation (CD)4+ T-cell count > 50 cells/mm3
排除标准
- •History (or evidence at Screening) of genotypic resistance to any component of the study regimen [ Tenofovir Disoproxil Fumarate (TDF), Atazanavir (ATV), Raltegravir (RAL)]
- •Certain laboratory and electrocardiogram (ECG) values
研究组 & 干预措施
Arm A: BMS-663068 (400mg) + Raltegravir + Tenofovir
Treatment Group 1
干预措施: BMS-663068 400 mg (Drug)
Arm A: BMS-663068 (400mg) + Raltegravir + Tenofovir
Treatment Group 1
干预措施: Raltegravir 400 mg (Drug)
Arm A: BMS-663068 (400mg) + Raltegravir + Tenofovir
Treatment Group 1
干预措施: Tenofovir 300 mg (Drug)
Arm B: BMS-663068 (800 mg) + Raltegravir + Tenofovir
Treatment Group 2
干预措施: BMS-663068 800 mg (Drug)
Arm B: BMS-663068 (800 mg) + Raltegravir + Tenofovir
Treatment Group 2
干预措施: Raltegravir 400 mg (Drug)
Arm B: BMS-663068 (800 mg) + Raltegravir + Tenofovir
Treatment Group 2
干预措施: Tenofovir 300 mg (Drug)
Arm C: BMS-663068 (600 mg) + Raltegravir + Tenofovir
Treatment Group 3
干预措施: BMS-663068 600 mg (Drug)
Arm C: BMS-663068 (600 mg) + Raltegravir + Tenofovir
Treatment Group 3
干预措施: Raltegravir 400 mg (Drug)
Arm C: BMS-663068 (600 mg) + Raltegravir + Tenofovir
Treatment Group 3
干预措施: Tenofovir 300 mg (Drug)
Arm D: BMS-663068 (1200 mg) + Raltegravir + Tenofovir
Treatment Group 4
干预措施: BMS-663068 1200 mg (Drug)
Arm D: BMS-663068 (1200 mg) + Raltegravir + Tenofovir
Treatment Group 4
干预措施: Raltegravir 400 mg (Drug)
Arm D: BMS-663068 (1200 mg) + Raltegravir + Tenofovir
Treatment Group 4
干预措施: Tenofovir 300 mg (Drug)
Arm E: Atazanavir + Ritonavir + Raltegravir + Tenofovir
Treatment Group 1 (reference arm)
干预措施: Raltegravir 400 mg (Drug)
Arm E: Atazanavir + Ritonavir + Raltegravir + Tenofovir
Treatment Group 1 (reference arm)
干预措施: Tenofovir 300 mg (Drug)
Arm E: Atazanavir + Ritonavir + Raltegravir + Tenofovir
Treatment Group 1 (reference arm)
干预措施: Ritonavir 100 mg (Drug)
Arm E: Atazanavir + Ritonavir + Raltegravir + Tenofovir
Treatment Group 1 (reference arm)
干预措施: Atazanavir 300 mg (Drug)
结局指标
主要结局
Number of Participants With Serious Adverse Events (SAE) and Discontinuation Due to AEs up to Week 24
时间窗: Up to Week 24
Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or suspected transmission of an infectious agent via the study drug were categorized as SAE. AEs leading to discontinuation of study therapy were also reported as safety assessment. Safety population included all participants who received at least one dose of study treatment. Summaries of SAEs and AEs leading to discontinuation or withdrawal through Week 24 included AEs with onset on or after the start of study treatment (i.e. study date of first study treatment intake) up to and including the end of the Week 24 visit snapshot window.
Percentage of Participants With Plasma HIV-1 Ribonucleic Acid (RNA) < 50 Copies Per Milliliter (c/mL) at Week 24
时间窗: Week 24
Percentage of participants with plasma HIV 1 RNA \< 50 c/mL at Week 24 using the Food and Drug Administration (FDA) snapshot algorithm was assessed to evaluate the antiviral activity. Treatment comparisons were not performed as this was an estimation study. Response rates were tabulated by treatment arm with exact Clopper-Pearson binomial 95 percentage confidence intervals (CI). Virologic success or failure was determined by the last available HIV-1 RNA assessment while the participant was on-treatment within the snapshot window of the visit of interest. Intent-To-Treat-Exposed (ITT-E) Population includes all randomized participants who received at least one dose of study treatment.
次要结局
- Percentage of Participants With Plasma HIV-1 RNA < 50 c/mL at Day 8 of the Monotherapy Period(Up to Day 8 of the monotherapy period)
- Percentage of Participants With Plasma HIV-1 RNA < 50 c/mL at Primary Study(Weeks 48 and 96)
- Number of Participants With SAE and Discontinuation Due to AEs During Primary Study(Weeks 48 and 96)
- Change From Baseline in IC50 Fold Change Among Participants With VF at Week 96(Baseline and up to Week 96)
- Maximum Decrease From Monotherapy Baseline in log10 Plasma HIV-1 RNA(Baseline and up to Day 8 of the monotherapy period)
- Number of Participants With SAE and Discontinuation Due to AEs During Monotherapy Period(Up to Day 8 of the monotherapy period)
- Number of Participants With Newly-emergent Genotypic Substitutions at Week 24(Up to Week 24)
- Change From Monotherapy Baseline in Cluster of Differentiation (CD)4+ and CD8+ T-cell Counts During Monotherapy(Baseline and Day 8)
- Number of Participants With Newly-emergent Genotypic Substitutions at Week 48(Up to Week 48)
- Number of Participants With Newly-emergent Genotypic Substitutions at Week 96(Up to Week 96)
- Maximum Change From Baseline in Inhibitory Concentration at 50% (IC50) Fold Change Among Participants With VF at Week 24(Baseline and up to Week 24)
- Change From Monotherapy Baseline in log10 HIV RNA of the Monotherapy Period(Baseline and up to Day 8 of the monotherapy period)
- Change From Monotherapy Baseline in CD4+ and CD8+ T-cell Proportion During Monotherapy(Baseline and Day 8)
- Change From Baseline in CD4+ T-cell Count(Baseline and Weeks 24, 48 and 96)
- Change From Baseline in IC50 Fold Change Among Participants With VF at Week 48(Baseline and up to Week 48)