A Phase 2b Randomized, Double-Blind, Double-Dummy Trial of 100 or 200 mg Once-Daily Doses of Cenicriviroc (CVC, TBR 652) or Once-Daily EFV, Each With Open-Label FTC/TDF, in HIV 1-Infected, Antiretroviral Treatment-Naïve, Adult Patients With Only CCR5-Tropic Virus
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 143
- 试验地点
- 48
- 主要终点
- To determine the percentage of patients who achieve HIV-1 RNA levels below 50 copies/mL at Week 24
研究概览
简要总结
This is a randomized, double-blind, double-dummy, 48-week, comparative study. Approximately 150 HIV-infected, treatment-naïve patients with CCR5-tropic virus will be stratified by HIV-1 RNA: ≥100,000 copies/mL versus <100,000 copies/mL and will be randomized 2:2:1 to receive:
- Arm A: CVC 100 mg (2 tablets, 50 mg each) QD + CVC matching placebo (2 tablets) QD + EFV matching placebo (1 tablet) QHS + FTC/TDF (1 tablet) QD.
- Arm B: CVC 200 mg (4 tablets, 50 mg each) QD + EFV matching placebo (1 tablet) QHS + FTC/TDF (1 tablet) QD.
- Arm C: CVC matching placebo (4 tablets) QD + EFV 600 mg (1 tablet) QHS + FTC/TDF (1 tablet) QD.
Doses of both CVC/placebo and EFV/ placebo will be administered as double-blinded study drug. FTC/TDF will be administered as open-label study drug in a fixed-dose combination formulation (Truvada). CVC/placebo should be taken following breakfast; EFV should be taken on an empty stomach at bedtime.
HIV-1 RNA levels and CD4+ and CD8+ cell counts, percentages, and ratios will be measured at every visit. Samples for viral tropism and resistance testing in case of virologic failure will be collected at Screening and each on-treatment visit.
Biomarkers associated with inflammation and immune activation will be measured at Baseline (predose) and each study visit thereafter, with flow cytometry obtained at weeks 4, 12, 24, 48, and 52.
Fasting metabolic indicators of glucose control (glucose and insulin for HOMA-IR, HbA1c) and fasting lipid profiles (HDL, LDL, total cholesterol, and triglycerides) will be measured at Baseline (predose) and Weeks 4, 12, 24, 48, and 52. Waist-to-hip ratios will be measured at Baseline and Weeks 24 and 48.
Plasma samples will be collected and stored for possible future studies at Baseline (predose) and every visit thereafter.
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
- •Adult male and female, HIV-1-infected patients 18 years old and older.
- •Body mass index (BMI) 18 to < 35 kg/m
- •Antiretroviral treatment-naïve. Treatment-naïve is defined as:
- •No prior nonnucleoside reverse transcriptase inhibitor, other than in women who received a single dose of perinatal nevirapine who have no K103 viral mutation.
- •No prior CCR5 antagonist therapy.
- •No more than 10 days of any other prior antiretroviral therapy.
- •HIV-1 CCR5-tropic-only virus.
- •Plasma HIV-1 RNA level >/=1,000 copies/mL at first Screening.
- •CD4 cell count >/=250 cells/mm3 at first Screening.
排除标准
- •Presence of CXCR4- or dual/mixed-tropic HIV-1 virus.
- •Presence of primary resistance mutations or phenotypic resistance to TDF, FTC, or EFV and/or mutations associated with multidrug nucleoside/nucleotide resistance.
- •An active CDC category C disease (except cutaneous Kaposi's sarcoma not requiring systemic therapy during the trial).
- •Any historical CD4 count < 200 cells/mm
- •Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value Grade > 2 or total bilirubin greater than the upper limit of normal (ULN).
- •History of HIV-2, hepatitis B and/or C, cirrhosis of the liver, or any known active or chronic liver disease. Hepatitis B vaccinated patients are eligible.
研究组 & 干预措施
CVC 100 mg + Truvada
干预措施: Cenicriviroc 100 mg (Drug)
CVC 200 mg + Truvada
干预措施: Cenicriviroc 200 mg + Truvada (Drug)
Sustiva + Truvada
干预措施: Sustiva + Truvada (Drug)
结局指标
主要结局
To determine the percentage of patients who achieve HIV-1 RNA levels below 50 copies/mL at Week 24
时间窗: 24 weeks
次要结局
未报告次要终点