A Phase 3 Evaluation of a Daclatasvir/Asunaprevir/BMS-791325 Fixed Dose Combination in Subjects With Genotype 1 Chronic Hepatitis C and Compensated Cirrhosis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 202
- 试验地点
- 27
- 主要终点
- Proportion of treated subjects in each of the naive arms with sustained virologic response (SVR12)
研究概览
简要总结
To demonstrate the effectiveness of DCV 3DAA fixed dose combination with or without Ribavirin in treatment naive cirrhotic subjects.
详细描述
Masking is Double blind for RBV: two or more parties are unaware of the intervention assignment.
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
- •Subjects chronically infected with HCV genotype 1
- •Subjects with compensated cirrhosis
- •HCV RNA ≥ 10,000 IU/mL at screening
- •Treatment-naïve subjects with no previous exposure to an interferon formulation (ie, IFNα, pegIFNα), Ribavirin (RBV), or HCV Direct Acting Antivirals (DAA) (protease, polymerase inhibitor, etc.)
- •Treatment-experienced subjects are eligible including exposure to anti-HCV agents of a mechanistic class other than those contained in the Daclatasvir (DCV) / Asunaprevir (ASV) /BMS-791325 triple regimen is permitted. Examples of permitted agents include, but are not limited to nucleoside/nucleotide inhibitors of nonstructural protein 5B (NS5B) polymerase, inhibitors of cyclophilin, or inhibitors of microRNA.
排除标准
- •Subjects without cirrhosis
- •Liver or any other organ transplant
- •Current or known history of cancer within 5 years prior to screening
- •Documented or suspected hepatocellular carcinoma(HCC)
- •Evidence of decompensated liver disease including, but not limited to, radiologic criteria, a history or presence of ascites, bleeding varices, or hepatic encephalopathy
研究组 & 干预措施
A1: DCV/ASV/BMS-791325+Placebo matching RBV (naive)
Triple fixed dose combination (Daclatasvir 30 mg, Asunaprevir 200 mg, BMS-791325 75 mg) tablet orally twice a day for 12 weeks
Placebo matching Ribavirin 0mg tablet orally twice a day for 12 weeks
干预措施: Daclatasvir (Drug)
A1: DCV/ASV/BMS-791325+Placebo matching RBV (naive)
Triple fixed dose combination (Daclatasvir 30 mg, Asunaprevir 200 mg, BMS-791325 75 mg) tablet orally twice a day for 12 weeks
Placebo matching Ribavirin 0mg tablet orally twice a day for 12 weeks
干预措施: Asunaprevir (Drug)
A1: DCV/ASV/BMS-791325+Placebo matching RBV (naive)
Triple fixed dose combination (Daclatasvir 30 mg, Asunaprevir 200 mg, BMS-791325 75 mg) tablet orally twice a day for 12 weeks
Placebo matching Ribavirin 0mg tablet orally twice a day for 12 weeks
干预措施: BMS-791325 (Drug)
A1: DCV/ASV/BMS-791325+Placebo matching RBV (naive)
Triple fixed dose combination (Daclatasvir 30 mg, Asunaprevir 200 mg, BMS-791325 75 mg) tablet orally twice a day for 12 weeks
Placebo matching Ribavirin 0mg tablet orally twice a day for 12 weeks
干预措施: Placebo matching Ribavirin (Drug)
A2: DCV/ASV/BMS-791325 + RBV (naive)
Triple fixed dose combination (Daclatasvir 30 mg, Asunaprevir 200 mg, BMS-791325 75 mg) tablet orally twice a day for 12 weeks
Ribavirin 200mg tablet orally twice a day for 12 weeks
干预措施: Daclatasvir (Drug)
A2: DCV/ASV/BMS-791325 + RBV (naive)
Triple fixed dose combination (Daclatasvir 30 mg, Asunaprevir 200 mg, BMS-791325 75 mg) tablet orally twice a day for 12 weeks
Ribavirin 200mg tablet orally twice a day for 12 weeks
干预措施: Asunaprevir (Drug)
A2: DCV/ASV/BMS-791325 + RBV (naive)
Triple fixed dose combination (Daclatasvir 30 mg, Asunaprevir 200 mg, BMS-791325 75 mg) tablet orally twice a day for 12 weeks
Ribavirin 200mg tablet orally twice a day for 12 weeks
干预措施: BMS-791325 (Drug)
A2: DCV/ASV/BMS-791325 + RBV (naive)
Triple fixed dose combination (Daclatasvir 30 mg, Asunaprevir 200 mg, BMS-791325 75 mg) tablet orally twice a day for 12 weeks
Ribavirin 200mg tablet orally twice a day for 12 weeks
干预措施: Ribavirin (Drug)
A3: DCV/ASV/BMS-791325+Placebo matching RBV (experienced)
Triple fixed dose combination (Daclatasvir 30 mg, Asunaprevir 200 mg, BMS-791325 75 mg) tablet orally twice a day for 12 weeks
Placebo matching Ribavirin 0 mg tablet orally twice a day for 12 weeks
干预措施: Daclatasvir (Drug)
A3: DCV/ASV/BMS-791325+Placebo matching RBV (experienced)
Triple fixed dose combination (Daclatasvir 30 mg, Asunaprevir 200 mg, BMS-791325 75 mg) tablet orally twice a day for 12 weeks
Placebo matching Ribavirin 0 mg tablet orally twice a day for 12 weeks
干预措施: Asunaprevir (Drug)
A3: DCV/ASV/BMS-791325+Placebo matching RBV (experienced)
Triple fixed dose combination (Daclatasvir 30 mg, Asunaprevir 200 mg, BMS-791325 75 mg) tablet orally twice a day for 12 weeks
Placebo matching Ribavirin 0 mg tablet orally twice a day for 12 weeks
干预措施: BMS-791325 (Drug)
A3: DCV/ASV/BMS-791325+Placebo matching RBV (experienced)
Triple fixed dose combination (Daclatasvir 30 mg, Asunaprevir 200 mg, BMS-791325 75 mg) tablet orally twice a day for 12 weeks
Placebo matching Ribavirin 0 mg tablet orally twice a day for 12 weeks
干预措施: Placebo matching Ribavirin (Drug)
A4: DCV/ASV/BMS-791325 + RBV (experienced)
Triple fixed dose combination (Daclatasvir 30 mg, Asunaprevir 200 mg, BMS-791325 75 mg) tablet orally twice a day for 12 weeks
Ribavirin 200 mg tablet orally twice a day for 12 weeks, Weight based dosing: If < 75 kg, 1000 mg per day (two 200 mg tablets in AM and three 200 mg tablets in PM); if ≥ 75 kg, 1200 mg per day (three 200 mg tablets in AM and three 200 mg tablets in PM), AM=in the morning, PM=in the evening
干预措施: Daclatasvir (Drug)
A4: DCV/ASV/BMS-791325 + RBV (experienced)
Triple fixed dose combination (Daclatasvir 30 mg, Asunaprevir 200 mg, BMS-791325 75 mg) tablet orally twice a day for 12 weeks
Ribavirin 200 mg tablet orally twice a day for 12 weeks, Weight based dosing: If < 75 kg, 1000 mg per day (two 200 mg tablets in AM and three 200 mg tablets in PM); if ≥ 75 kg, 1200 mg per day (three 200 mg tablets in AM and three 200 mg tablets in PM), AM=in the morning, PM=in the evening
干预措施: Asunaprevir (Drug)
A4: DCV/ASV/BMS-791325 + RBV (experienced)
Triple fixed dose combination (Daclatasvir 30 mg, Asunaprevir 200 mg, BMS-791325 75 mg) tablet orally twice a day for 12 weeks
Ribavirin 200 mg tablet orally twice a day for 12 weeks, Weight based dosing: If < 75 kg, 1000 mg per day (two 200 mg tablets in AM and three 200 mg tablets in PM); if ≥ 75 kg, 1200 mg per day (three 200 mg tablets in AM and three 200 mg tablets in PM), AM=in the morning, PM=in the evening
干预措施: BMS-791325 (Drug)
A4: DCV/ASV/BMS-791325 + RBV (experienced)
Triple fixed dose combination (Daclatasvir 30 mg, Asunaprevir 200 mg, BMS-791325 75 mg) tablet orally twice a day for 12 weeks
Ribavirin 200 mg tablet orally twice a day for 12 weeks, Weight based dosing: If < 75 kg, 1000 mg per day (two 200 mg tablets in AM and three 200 mg tablets in PM); if ≥ 75 kg, 1200 mg per day (three 200 mg tablets in AM and three 200 mg tablets in PM), AM=in the morning, PM=in the evening
干预措施: Ribavirin (Drug)
结局指标
主要结局
Proportion of treated subjects in each of the naive arms with sustained virologic response (SVR12)
时间窗: Post treatment 12 week
SVR12 is defined as Hepatitis C virus ribonucleic acid (HCV RNA) \< Limit of Quantification (LOQ) target detected or target not detected (LOQ TD/TND)
次要结局
- Safety as measured by frequency of Serious Adverse Events(SAEs)and discontinuations due to Adverse Events(AEs)(Up to end of treatment (week 12) + 7 days)
- Proportion of subjects in each arm who achieve HCV RNA < LOQ TD/TND(Weeks: 1, 2, 4, 6, 8, and 12; Post treatment Weeks 4 (SVR4), 8 (SVR8) and 24 (SVR24))
- Proportion of subjects in each arm who achieve HCV RNA < LOQ TND(Weeks: 1, 2, 4, 6, 8, and 12; Post treatment Weeks 4 (SVR4), 8 (SVR8), 12 (SVR12) and 24 (SVR24))
- Proportion of subjects achieving SVR12 associated with HCV geno subtype 1a vs 1b(Post treatment 12 Week)
- Differences in rates of selected Grade 3 - 4 laboratory test result abnormalities(Up to end of treatment (week 12) + 7 days)
- Proportion of treated subjects in each of the experienced arms with SVR12(Post treatment 12 Week)
- Proportion of subjects with anemia defined as Hg < 10 g/dL on-treatment and Hg ≥ 10 g/dL at baseline in each arm within each cohort(Up to end of treatment (week 12) + 7 days)
- Proportion of subjects in each arm achieving SVR12 associated with IL28B rs12979860 single nucleotide polymorphism(SNP) status (CC genotype or non-CC genotype)(Post treatment 12 Week)