Randomized, Open-Label, Multicenter Study of Safety, Efficacy, and Tolerability of the Combination of RO5466731, RO5190591, Ritonavir, and Copegus With or Without RO5024048 in HCV Genotype 1 Infected Patients Who Are Either Treatment Naïve or Null Responders to Previous Interferon-Based Treatment
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 110
- 主要终点
- Sustained virological response (defined as undetectable serum HCV RNA) 12 weeks after end of treatment
研究概览
简要总结
This randomized, open-label, multicenter study will evaluate the safety , efficacy and tolerability of the combination treatment RO5466731, RO5190591, ritonavir and Copegus (ribavirin) with or without RO5024048 in patients with chronic hepatitis C genotype 1. In Part 1, treatment-naïve patients will be randomized to receive treatment with RO5466731, RO5190591 plus ritonavir, and Copegus, with or without RO5024048. In Part 2, further treatment-naïve patients will receive a successful regimen from Part 1, or a reduced intensity regimen, and patients who have previously experienced null response to interferon-based treatment will be added to the study.
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
- •Adult patients, >/= 18 years of age
- •Chronic hepatitis C genotype 1 of >/= 6 months duration at screening
- •Part 1 and Part 2: Naïve to treatment with interferon (pegylated or non-pegylated). Patients who have participated in studies investigating a direct-acting antiviral agent with or without interferon are excluded
- •Part 2: Treatment experienced patients having a previous null response to treatment with interferon containing regimen
- •Liver biopsy or non-invasive (e.g. Fibroscan) evaluation in the past 24 calendar months showing absence of cirrhosis or incomplete/transition to cirrhosis
- •Body mass index (BMI) 18 to 35 kg/m2 inclusive and body weight >/= 45 kg
排除标准
- •Pregnant or lactating women or males with female partners who are pregnant or lactating
- •Decompensated liver disease or impaired liver function (as defined by protocol)
- •Cirrhosis or incomplete/transition to cirrhosis
- •Non- hepatitis C chronic liver disease
- •Positive for hepatitis B or HIV infection
- •History of pre-existing renal disease
- •History of severe cardiac disease
- •History of neoplastic disease within the last 5 years, except for localized or in situ carcinoma of the skin
- •History of drug abuse within the last year; history of cannabinoid use is not excluded
- •Evidence of alcohol abuse within 1 year of screening and consumption of more than 2 units of alcohol per day
- •Medical condition that requires use of systemic corticosteroids
- •Received warfarin or other anticoagulants during the 21 days immediately prior to screening or is expected to require warfarin or other anticoagulants during the study
- •Anticipated use or need for significant medical treatment during the study or use of concomitant medications or nutrients that are excluded by protocol (e.g. drugs that are contraindicated with ritonavir, hormonal methods of contraception)
研究组 & 干预措施
D: GT1b 3DAA
including RO5466731, RO5190591, ritonavir, ribavirin [Copegus] and RO5024048
干预措施: RO5466731 (Drug)
Part II
干预措施: ribavirin [Copegus] (Drug)
A: GT1a 3DAA
including RO5466731, RO5190591, ritonavir, ribavirin [Copegus] and RO5024048
干预措施: ritonavir (Drug)
A: GT1a 3DAA
including RO5466731, RO5190591, ritonavir, ribavirin [Copegus] and RO5024048
干预措施: RO5024048 (Drug)
A: GT1a 3DAA
including RO5466731, RO5190591, ritonavir, ribavirin [Copegus] and RO5024048
干预措施: RO5190591 (Drug)
A: GT1a 3DAA
including RO5466731, RO5190591, ritonavir, ribavirin [Copegus] and RO5024048
干预措施: RO5466731 (Drug)
A: GT1a 3DAA
including RO5466731, RO5190591, ritonavir, ribavirin [Copegus] and RO5024048
干预措施: ribavirin [Copegus] (Drug)
B: GT1a 3DAA
including RO5466731, RO5190591, ritonavir, ribavirin [Copegus] and RO5024048
干预措施: RO5024048 (Drug)
B: GT1a 3DAA
including RO5466731, RO5190591, ritonavir, ribavirin [Copegus] and RO5024048
干预措施: RO5190591 (Drug)
B: GT1a 3DAA
including RO5466731, RO5190591, ritonavir, ribavirin [Copegus] and RO5024048
干预措施: RO5466731 (Drug)
B: GT1a 3DAA
including RO5466731, RO5190591, ritonavir, ribavirin [Copegus] and RO5024048
干预措施: ribavirin [Copegus] (Drug)
B: GT1a 3DAA
including RO5466731, RO5190591, ritonavir, ribavirin [Copegus] and RO5024048
干预措施: ritonavir (Drug)
C: GT1a 2DAA
including RO5466731, RO5190591, ritonavir and ribavirin [Copegus]
干预措施: RO5190591 (Drug)
C: GT1a 2DAA
including RO5466731, RO5190591, ritonavir and ribavirin [Copegus]
干预措施: RO5466731 (Drug)
C: GT1a 2DAA
including RO5466731, RO5190591, ritonavir and ribavirin [Copegus]
干预措施: ribavirin [Copegus] (Drug)
C: GT1a 2DAA
including RO5466731, RO5190591, ritonavir and ribavirin [Copegus]
干预措施: ritonavir (Drug)
D: GT1b 3DAA
including RO5466731, RO5190591, ritonavir, ribavirin [Copegus] and RO5024048
干预措施: RO5024048 (Drug)
D: GT1b 3DAA
including RO5466731, RO5190591, ritonavir, ribavirin [Copegus] and RO5024048
干预措施: RO5190591 (Drug)
D: GT1b 3DAA
including RO5466731, RO5190591, ritonavir, ribavirin [Copegus] and RO5024048
干预措施: ribavirin [Copegus] (Drug)
D: GT1b 3DAA
including RO5466731, RO5190591, ritonavir, ribavirin [Copegus] and RO5024048
干预措施: ritonavir (Drug)
E: GT1b 2DAA
including RO54664731, RO5190591, ritonavir and ribavirin [Copegus]
干预措施: RO5190591 (Drug)
E: GT1b 2DAA
including RO54664731, RO5190591, ritonavir and ribavirin [Copegus]
干预措施: RO5466731 (Drug)
E: GT1b 2DAA
including RO54664731, RO5190591, ritonavir and ribavirin [Copegus]
干预措施: ribavirin [Copegus] (Drug)
E: GT1b 2DAA
including RO54664731, RO5190591, ritonavir and ribavirin [Copegus]
干预措施: ritonavir (Drug)
Part II
干预措施: RO5024048 (Drug)
Part II
干预措施: RO5190591 (Drug)
Part II
干预措施: RO5466731 (Drug)
Part II
干预措施: ritonavir (Drug)
结局指标
主要结局
Sustained virological response (defined as undetectable serum HCV RNA) 12 weeks after end of treatment
时间窗: approximately 20 months
Safety: Incidence of adverse events
时间窗: approximately 20 months
次要结局
- Antiviral activity: Change in serum HCV RNA levels(from baseline to 24 weeks after end of treatment)
- Pharmacokinetics in coadministration: Area under the concentration-time curve (AUC)(Pre-dose Weeks 1, 2, 3, 4, 6, 10, and 12 and up to 12 hours post-dose Weeks 1, and 4 or 3 and 6)
- Quality of life: Short-Form 36v2/Brief Fatigue Inventory questionnaires(approximately 20 months)
- HCV drug resistance(approximately 20 months)