A Phase 3, Open-Label Study With Asunaprevir and Daclatasvir Plus Peginterferon Alfa-2a (Pegasys) and Ribavirin (Copegus) (P/R) (QUAD) for Subjects Who Are Null or Partial Responders to Peginterferon Alfa 2a or 2b Plus Ribavirin With Chronic Hepatitis C Genotypes 1 or 4 Infection
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 398
- 试验地点
- 21
- 主要终点
- Proportion of genotype 1 subjects with SVR12, defined as HCV RNA < LOQ at post-treatment Week 12, for all subjects infected with HCV genotype 1
研究概览
简要总结
The purpose of this study is to assess 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.
详细描述
- ASV = Asunaprevir (BMS-650032)
- DCV = Daclatasvir (BMS-790052)
- Peg = Peg-interferon Alfa-2a (PegIFN)
- Rib = Ribavirin (RBV)
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Males and females, ≥ 18 years of age
- •HCV Genotype 1 or 4 who previously failed treatment with Peginterferon alfa-2a or peginterferon alfa-2b and Ribavirin (P/R), classified as previous null and partial responders based on previous therapy
- •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
- •Total bilirubin ≥ 34 μmol/L (or ≥ 2 mg/dL) unless subject has a documented history of Gilbert's disease
- •Alanine aminotransferase (ALT) ≥ 5x Upper limit of normal (ULN)
- •Albumin < 3.5 g/dL (35 g/L)
- •Alpha Fetoprotein (AFP) > 100 ng/mL (>82.6 IU/mL) or ≥ 50 and ≤ 100 ng/mL requires a liver ultrasound and subjects with findings suspicious of Hepatocellular carcinoma (HCC) are excluded
- •Absolute neutrophil count (ANC) < 1.5 x 1000,000,000 cells/L (< 1.2 x 1000,000,000 cells/L for Black/African-Americans)
- •Platelets < 90 x 1000,000,000 cells/L
- •Hemoglobin < 12 g/dL for females or < 13 g/dL for males
- •Any criteria that would exclude the subject from receiving P/R
研究组 & 干预措施
QUAD: Asunaprevir+Daclatasvir+Peg-interferon Alfa-2a+Ribavirin
Asunaprevir: Capsule, Oral, 100 mg, Twice daily, 24 weeks
Daclatasvir: Tablet, Oral, 60 mg, Once daily, 24 weeks
Peg-interferon Alfa-2a: Injection, subcutaneous (SC), 180 mcg/0.5 mL, Once weekly, 24 weeks
Ribavirin: Tablet, Oral, 1000 mg/1200 mg (total daily dose), 24 weeks
干预措施: Asunaprevir (Drug)
QUAD: Asunaprevir+Daclatasvir+Peg-interferon Alfa-2a+Ribavirin
Asunaprevir: Capsule, Oral, 100 mg, Twice daily, 24 weeks
Daclatasvir: Tablet, Oral, 60 mg, Once daily, 24 weeks
Peg-interferon Alfa-2a: Injection, subcutaneous (SC), 180 mcg/0.5 mL, Once weekly, 24 weeks
Ribavirin: Tablet, Oral, 1000 mg/1200 mg (total daily dose), 24 weeks
干预措施: Daclatasvir (Drug)
QUAD: Asunaprevir+Daclatasvir+Peg-interferon Alfa-2a+Ribavirin
Asunaprevir: Capsule, Oral, 100 mg, Twice daily, 24 weeks
Daclatasvir: Tablet, Oral, 60 mg, Once daily, 24 weeks
Peg-interferon Alfa-2a: Injection, subcutaneous (SC), 180 mcg/0.5 mL, Once weekly, 24 weeks
Ribavirin: Tablet, Oral, 1000 mg/1200 mg (total daily dose), 24 weeks
干预措施: Peg-interferon Alfa-2a (Drug)
QUAD: Asunaprevir+Daclatasvir+Peg-interferon Alfa-2a+Ribavirin
Asunaprevir: Capsule, Oral, 100 mg, Twice daily, 24 weeks
Daclatasvir: Tablet, Oral, 60 mg, Once daily, 24 weeks
Peg-interferon Alfa-2a: Injection, subcutaneous (SC), 180 mcg/0.5 mL, Once weekly, 24 weeks
Ribavirin: Tablet, Oral, 1000 mg/1200 mg (total daily dose), 24 weeks
干预措施: Ribavirin (Drug)
结局指标
主要结局
Proportion of genotype 1 subjects with SVR12, defined as HCV RNA < LOQ at post-treatment Week 12, for all subjects infected with HCV genotype 1
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) through the end of treatment(Through the end of treatment (maximum up to 24 weeks) plus 7 days)
- Proportion of subjects with HCV RNA undetectable(Weeks 1, 2, 4, 6, 8 and 12; at both Weeks 4 and 12 [Extended rapid virologic response (eRVR)], end of treatment (up to 24 weeks), post-treatment Week 12 or post-treatment Week 24)
- Proportion of subjects with SVR12 (HCV RNA < LOQ at post-treatment Week 12) by the rs12979860 single nucleotide polymorphisms (SNP) in the IL28 gene(At post-treatment Week 12)
- Proportion of subjects with HCV RNA < LOQ(Weeks 1, 2, 4, 6, 8 and 12; at both Weeks 4 and 12, end of treatment (up to 24 weeks), post-treatment Week 24 (SVR24))
- Proportion of patients with SVR12 (HCV RNA < LOQ at post-treatment Week 12) for HCV genotype 4 subjects(Post-treatment Week 12)