A Phase 3 Study With Asunaprevir and Daclatasvir (DUAL) for Null or Partial Responders to Peginterferon Alfa and Ribavirin (P/R), Intolerant or Ineligible to P/R Subjects and Treatment-Naive Subjects With Chronic Hepatitis C Genotype 1b Infection
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 748
- 试验地点
- 27
- 主要终点
- Proportion of treated subjects with SVR12, defined as HCV RNA < LOQ at post treatment Week 12, for subjects who are prior null or partial responders to P/R or are treatment-naive
研究概览
简要总结
The purpose of this study is to estimate efficacy, as determined by the proportion of subjects with Sustained virologic response at post-treatment Week 12 (SVR12), defined as Hepatitis C virus (HCV) Ribonucleic acid (RNA) < Limit of quantitation (LOQ) at post-treatment Week 12, for subjects who are prior null or partial responders to P/R or who are treatment-naive.
详细描述
Allocation: Treatment naive cohort: Randomized Controlled Trial, Null/partial responder and intolerant/ineligible cohorts: N/A (Single arm study)
Masking: Treatment naive cohort: Double Blind, Null/partial responder and intolerant/ineligible cohorts: Open
Intervention Model: Treatment naive cohort: Parallel, Null/partial responder and intolerant/ineligible cohorts: Single group
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
- •Males and females, ≥ 18 years of age
- •HCV Genotype 1b who previously failed treatment with peginterferon alfa and ribavirin, classified as previous null or partial responders based on previous therapy, OR intolerant or ineligible to P/R due to neutropenia, anemia, depression or thrombocytopenia with fibrosis/cirrhosis, OR treatment naive
- •HCV RNA ≥ 10,000 IU/mL
- •Seronegative for Human immunodeficiency virus (HIV) and Hepatitis B surface antigen (HBsAg)
- •Subjects with compensated cirrhosis are permitted (compensated cirrhotics are capped at approximately 25% of treated population)
排除标准
- •Prior treatment of HCV with HCV direct acting antiviral (DAA)
- •Evidence of a medical condition contributing to chronic liver disease other than HCV
- •Evidence of decompensated liver disease including, but not limited to, a history or presence of ascites, bleeding varices, or hepatic encephalopathy
- •Diagnosed or suspected hepatocellular carcinoma or other malignancies
- •Uncontrolled diabetes or hypertension
研究组 & 干预措施
Arm 1: Null or Partial Responder to P/R (ASV + DCV)
Asunaprevir 100 mg Capsules by mouth, Twice daily for 24 Weeks
Daclatasvir 60 mg Tablet by mouth, Once daily for 24 Weeks
干预措施: Asunaprevir (ASV) (Drug)
Arm 1: Null or Partial Responder to P/R (ASV + DCV)
Asunaprevir 100 mg Capsules by mouth, Twice daily for 24 Weeks
Daclatasvir 60 mg Tablet by mouth, Once daily for 24 Weeks
干预措施: Daclatasvir (DCV) (Drug)
Arm 2: Intolerant to or Ineligible for P/R (ASV + DCV)
Asunaprevir 100 mg Capsules by mouth, Twice daily for 24 Weeks
Daclatasvir 60 mg Tablet by mouth, Once daily for 24 Weeks
干预措施: Asunaprevir (ASV) (Drug)
Arm 2: Intolerant to or Ineligible for P/R (ASV + DCV)
Asunaprevir 100 mg Capsules by mouth, Twice daily for 24 Weeks
Daclatasvir 60 mg Tablet by mouth, Once daily for 24 Weeks
干预措施: Daclatasvir (DCV) (Drug)
Arm 3: Treatment naive (ASV + DCV)
[Subjects will receive ASV + DCV for 24 weeks] followed by ASV + DCV for 24 weeks in protocol AI444026]
Subjects meeting prespecified rescue criteria in the treatment naive cohort may have therapeutic rescue instituted with QUAD regimen (QUAD= ASV + DCV + P/R)
Asunaprevir 100 mg Capsules by mouth, Twice daily for 24 or 48 Weeks
Daclatasvir 60 mg Tablet by mouth, Once daily for 24 or 48 Weeks
Pegylated-interferon alfa 2a (PegIFN) 180 mcg/0.5 mL injection subcutaneously (SC), once weekly for 24 or 48 weeks
Ribavirin 1000 mg/1200 mg (total daily dose) tablet by mouth for 24 or 48 weeks
干预措施: Asunaprevir (ASV) (Drug)
Arm 3: Treatment naive (ASV + DCV)
[Subjects will receive ASV + DCV for 24 weeks] followed by ASV + DCV for 24 weeks in protocol AI444026]
Subjects meeting prespecified rescue criteria in the treatment naive cohort may have therapeutic rescue instituted with QUAD regimen (QUAD= ASV + DCV + P/R)
Asunaprevir 100 mg Capsules by mouth, Twice daily for 24 or 48 Weeks
Daclatasvir 60 mg Tablet by mouth, Once daily for 24 or 48 Weeks
Pegylated-interferon alfa 2a (PegIFN) 180 mcg/0.5 mL injection subcutaneously (SC), once weekly for 24 or 48 weeks
Ribavirin 1000 mg/1200 mg (total daily dose) tablet by mouth for 24 or 48 weeks
干预措施: Daclatasvir (DCV) (Drug)
Arm 3: Treatment naive (ASV + DCV)
[Subjects will receive ASV + DCV for 24 weeks] followed by ASV + DCV for 24 weeks in protocol AI444026]
Subjects meeting prespecified rescue criteria in the treatment naive cohort may have therapeutic rescue instituted with QUAD regimen (QUAD= ASV + DCV + P/R)
Asunaprevir 100 mg Capsules by mouth, Twice daily for 24 or 48 Weeks
Daclatasvir 60 mg Tablet by mouth, Once daily for 24 or 48 Weeks
Pegylated-interferon alfa 2a (PegIFN) 180 mcg/0.5 mL injection subcutaneously (SC), once weekly for 24 or 48 weeks
Ribavirin 1000 mg/1200 mg (total daily dose) tablet by mouth for 24 or 48 weeks
干预措施: Pegylated-interferon alfa 2a (PegIFN) (Drug)
Arm 3: Treatment naive (ASV + DCV)
[Subjects will receive ASV + DCV for 24 weeks] followed by ASV + DCV for 24 weeks in protocol AI444026]
Subjects meeting prespecified rescue criteria in the treatment naive cohort may have therapeutic rescue instituted with QUAD regimen (QUAD= ASV + DCV + P/R)
Asunaprevir 100 mg Capsules by mouth, Twice daily for 24 or 48 Weeks
Daclatasvir 60 mg Tablet by mouth, Once daily for 24 or 48 Weeks
Pegylated-interferon alfa 2a (PegIFN) 180 mcg/0.5 mL injection subcutaneously (SC), once weekly for 24 or 48 weeks
Ribavirin 1000 mg/1200 mg (total daily dose) tablet by mouth for 24 or 48 weeks
干预措施: Ribavirin (RBV) (Drug)
Arm 4: Null or Partial Responder to P/R (ASV + DCV) 24/48 week
Subjects meeting prespecified rescue criteria in the null or partial responder cohort or active arm of the treatment naive cohort may have therapeutic rescue instituted with QUAD regimen (QUAD= ASV + DCV + P/R)
Asunaprevir 100 mg Capsules by mouth, Twice daily for 24 or 48 Weeks
Daclatasvir 60 mg Tablet by mouth, Once daily for 24 or 48 Weeks
Pegylated-interferon alfa 2a (PegIFN) 180 mcg/0.5 mL injection subcutaneously (SC), once weekly for 24 or 48 weeks
Ribavirin 1000 mg / 1200 mg (total daily dose) Tablet by mouth, for 24 or 48 weeks
干预措施: Asunaprevir (ASV) (Drug)
Arm 4: Null or Partial Responder to P/R (ASV + DCV) 24/48 week
Subjects meeting prespecified rescue criteria in the null or partial responder cohort or active arm of the treatment naive cohort may have therapeutic rescue instituted with QUAD regimen (QUAD= ASV + DCV + P/R)
Asunaprevir 100 mg Capsules by mouth, Twice daily for 24 or 48 Weeks
Daclatasvir 60 mg Tablet by mouth, Once daily for 24 or 48 Weeks
Pegylated-interferon alfa 2a (PegIFN) 180 mcg/0.5 mL injection subcutaneously (SC), once weekly for 24 or 48 weeks
Ribavirin 1000 mg / 1200 mg (total daily dose) Tablet by mouth, for 24 or 48 weeks
干预措施: Daclatasvir (DCV) (Drug)
Arm 4: Null or Partial Responder to P/R (ASV + DCV) 24/48 week
Subjects meeting prespecified rescue criteria in the null or partial responder cohort or active arm of the treatment naive cohort may have therapeutic rescue instituted with QUAD regimen (QUAD= ASV + DCV + P/R)
Asunaprevir 100 mg Capsules by mouth, Twice daily for 24 or 48 Weeks
Daclatasvir 60 mg Tablet by mouth, Once daily for 24 or 48 Weeks
Pegylated-interferon alfa 2a (PegIFN) 180 mcg/0.5 mL injection subcutaneously (SC), once weekly for 24 or 48 weeks
Ribavirin 1000 mg / 1200 mg (total daily dose) Tablet by mouth, for 24 or 48 weeks
干预措施: Pegylated-interferon alfa 2a (PegIFN) (Drug)
Arm 4: Null or Partial Responder to P/R (ASV + DCV) 24/48 week
Subjects meeting prespecified rescue criteria in the null or partial responder cohort or active arm of the treatment naive cohort may have therapeutic rescue instituted with QUAD regimen (QUAD= ASV + DCV + P/R)
Asunaprevir 100 mg Capsules by mouth, Twice daily for 24 or 48 Weeks
Daclatasvir 60 mg Tablet by mouth, Once daily for 24 or 48 Weeks
Pegylated-interferon alfa 2a (PegIFN) 180 mcg/0.5 mL injection subcutaneously (SC), once weekly for 24 or 48 weeks
Ribavirin 1000 mg / 1200 mg (total daily dose) Tablet by mouth, for 24 or 48 weeks
干预措施: Ribavirin (RBV) (Drug)
结局指标
主要结局
Proportion of treated subjects with SVR12, defined as HCV RNA < LOQ at post treatment Week 12, for subjects who are prior null or partial responders to P/R or are treatment-naive
时间窗: At 12 weeks post-treatment
次要结局
- On treatment safety, as measured by frequency of Serious Adverse Events (SAEs) and discontinuations due to Adverse Events (AEs)(End of Treatment (up to 48 weeks) plus 7 days)
- Differences in rates of selected grade 3-4 laboratory abnormalities during the first 12 weeks between treatments (ASV + DCV vs PBO) for naive subjects(Up to first 12 weeks)
- Proportion of subjects with anemia(At 12 weeks post-treatment)
- Proportion of genotype 1b subjects with HCV RNA undetectable(At weeks 1, 2, 4, 6, 8 and 12; at both Weeks 4 and 12 [eRVR]; EOT (up to 24 weeks), post-treatment Week 12, or post-treatment Week 24 for each cohort)
- Proportion of treated subjects with SVR12, defined as HCV RNA < LOQ at post-treatment Week 12, for subjects who are intolerant or ineligible to P/R(Post-treatment Week 12)
- Proportion of genotype 1b subjects with SVR12 (HCV RNA < LOQ at post treatment Week 12) by the rs12979860 single nucleotide polymorphisms (SNP) in the IL28B gene for each cohort(Post-treatment Week 12)
- Proportion of subjects with rash(At 12 weeks post-treatment)
- Proportion of genotypes 1b subjects with HCV RNA < LOQ(At weeks 1, 2, 4, 6, 8 and 12; at both Weeks 4 and 12 [VR(4&12)]; EOT (up to 24 weeks), post-treatment Week 24 (SVR24) for each cohort)