A Study to Evaluate Safety, Tolerability, Pharmacokinetics and Antiviral Activity of Ritonavir-Boosted DANOPREVIR and RO5024048 in Different Combinations in Null Responder or Treatment Naïve Patients With Chronic Hepatitis C and Compensated Cirrhosis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 43
- 主要终点
- Pharmacokinetics (PK): Area under the concentration-time curve (AUC)
研究概览
简要总结
This open-label, parallel cohort study will evaluate the safety, pharmacokinetics and antiviral activity of ritonavir-boosted danoprevir in combination with Pegasys (peginterferon alfa-2a) and ribavirin in treatment-naïve patients, and with RO5024048 added to the combination treatment in prior null responder patients with chronic hepatitis C genotype 1 or 4 and compensated cirrhosis. All patients will receive danoprevir 100 mg orally twice daily (bid) , ritonavir 100 mg orally bid, Pegasys 180 mcg subcutaneously weekly and ribavirin 1000-1200 mg/kg/day orally. Prior non-responders will receive RO5024048 1000 mg orally bid additionally. Anticipated time on study treatment is 24 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patients, 18 to 65 years of age inclusive
- •Chronic hepatitis C, genotype 1 or 4
- •Cohort 1: Treatment-naïve for hepatitis C
- •Cohort 2: Prior null responder to treatment with approved doses of pegylated interferon plus ribavirin
- •Liver biopsy confirming cirrhosis
- •Compensated cirrhosis (Child-Pugh A)
排除标准
- •Pregnant or lactating women or male partners of women who are pregnant
- •History or presence of decompensated liver disease (ascites, hepatic encephalopathy, hepatocellular carcinoma, or bleeding esophageal varices)
- •Cohort 2: Patients who discontinued previous pegylated interferon plus ribavirin treatment due to reasons other than null response
- •History of clinically significant cardiovascular or cerebrovascular disease
研究组 & 干预措施
Combination without RO5024048
Ritonavir-boosted danoprevir in combination with Pegasys (peginterferon alfa-2a) and ribavirin in treatment-naïve patients
干预措施: danoprevir (Drug)
Combination without RO5024048
Ritonavir-boosted danoprevir in combination with Pegasys (peginterferon alfa-2a) and ribavirin in treatment-naïve patients
干预措施: peginterferon alfa-2a [Pegasys] (Drug)
Combination without RO5024048
Ritonavir-boosted danoprevir in combination with Pegasys (peginterferon alfa-2a) and ribavirin in treatment-naïve patients
干预措施: ribavirin (Drug)
Combination without RO5024048
Ritonavir-boosted danoprevir in combination with Pegasys (peginterferon alfa-2a) and ribavirin in treatment-naïve patients
干预措施: ritonavir (Drug)
Combination with RO5024048
RO5024048 added to the combination treatment (ritonavir-boosted danoprevir in combination with Pegasys [peginterferon alfa-2a] and ribavirin) in prior null responder patients
干预措施: RO5024048 (Drug)
Combination with RO5024048
RO5024048 added to the combination treatment (ritonavir-boosted danoprevir in combination with Pegasys [peginterferon alfa-2a] and ribavirin) in prior null responder patients
干预措施: danoprevir (Drug)
Combination with RO5024048
RO5024048 added to the combination treatment (ritonavir-boosted danoprevir in combination with Pegasys [peginterferon alfa-2a] and ribavirin) in prior null responder patients
干预措施: peginterferon alfa-2a [Pegasys] (Drug)
Combination with RO5024048
RO5024048 added to the combination treatment (ritonavir-boosted danoprevir in combination with Pegasys [peginterferon alfa-2a] and ribavirin) in prior null responder patients
干预措施: ribavirin (Drug)
Combination with RO5024048
RO5024048 added to the combination treatment (ritonavir-boosted danoprevir in combination with Pegasys [peginterferon alfa-2a] and ribavirin) in prior null responder patients
干预措施: ritonavir (Drug)
结局指标
主要结局
Pharmacokinetics (PK): Area under the concentration-time curve (AUC)
时间窗: Intensive PK sample collection during initial 2 week dosing period, followed by routine sampling during treatment up to Week 24
Antiviral activity: Hepatitis C virus (HCV) RNA levels assessed by Roche COBAS Taqman HCV Test
时间窗: 48 weeks
Safety: Incidence of adverse events
时间窗: 48 weeks
次要结局
- Emergence of viral resistance: HCV RNA gene sequence variations(From baseline to Week 48)
- Virologic response: HCV RNA levels(approximately 1 year)