A Phase 2, Open-Label Study of Daclatasvir (BMS-790052) and TMC435 in Combination With or Without Ribavirin (RBV) For Treatment-Naive Subjects or Null Responders to Prior Peginterferon Alfa (PegIFN)/RBV Therapy With Genotype 1 Chronic Hepatitis C
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 230
- 试验地点
- 8
- 主要终点
- Percentage of Participants With Sustained Virologic Response Rate at Post-treatment Week 12 (SVR12)
研究概览
简要总结
The purpose of this study is to assess the safety and efficacy of daclatasvir and simeprevir with and without ribavirin for genotype 1 chronic hepatitis C virus infection in patients who are treatment-naive or null responders to previous pegylated interferon/ribavirin therapy.
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
- •Hepatitis C virus (HCV) genotype 1a or 1b
- •Males and females, ≥18 years of age
- •HCV RNA ≥10,000 IU/mL
- •Participants with compensated cirrhosis are permitted
- •Advanced fibrosis (F3/F4) is capped at approximately 35% of the total treated population with a minimum of 20% F4 patients
- •If no cirrhosis, a liver biopsy within 3 years prior to enrollment
- •If cirrhosis is present, any prior liver biopsy
排除标准
- •Liver or any other transplant (other than cornea and hair)
- •Evidence of a medical condition contributing to chronic liver disease other than HCV infection
- •Current or known history of cancer, (except in situ carcinoma of the cervix or adequately treated basal or squamous cell carcinoma of the skin) within 5 years prior to enrollment
- •Evidence of decompensated liver disease including, but not limited to, radiologic criteria, a history or presence of ascites, bleeding varices, or hepatic encephalopathy
- •Patients infected with HIV or hepatitis B virus
- •Gastrointestinal disease impacting absorption of study drug
- •Uncontrolled diabetes or hypertension
- •Prior exposure to an HCV direct-acting agent
- •Any criteria that would exclude the patient from receiving ribavirin
- •Absolute neutrophil count <1.5*1,000,000,000 cells/L (<1.2*1,000,000,000 cells/L for Black/African Americans)
- •Platelets <90*1,000,000,000 cells/L
- •Hemoglobin <12 g/dL for females, <13 g/dL for males
- •Alanine aminotransferase ≥5*upper limit of normal
- •In patients without cirrhosis, total bilirubin ≥2 mg/dL unless patient has a documented history of Gilbert's disease
- •In patients with cirrhosis, total bilirubin o ≥1.5 mg/dL
- •International normalized ratio ≥1.7
- •QTcF or QTcB >500 mSec
- •Creatinine clearance ≤50 mL/min
- •Alpha fetoprotein (AFP) >100 ng/mL OR
- •AFP ≥50 ng/mL and ≤100 ng/mL requiring liver ultrasound
- •Albumin <3.5 g/dL
研究组 & 干预措施
Cohort 1: (Genotype 1b) Daclatasvir + Simeprevir
Participants with hepatitis C virus genotype 1b received daclatasvir, 30 mg, once daily with or without food + simeprevir, 150 mg, once daily with a meal for 12 weeks
干预措施: Daclatasvir (Drug)
Cohort 1: (Genotype 1b) Daclatasvir + Simeprevir
Participants with hepatitis C virus genotype 1b received daclatasvir, 30 mg, once daily with or without food + simeprevir, 150 mg, once daily with a meal for 12 weeks
干预措施: Simeprevir (Drug)
Cohort 2: (Genotype 1b) Daclatasvir + Simeprevir + Ribavirin
Participants with hepatitis C virus genotype 1b received daclatasvir, 30 mg, once daily with or without food + simeprivir, 150 mg, once daily with a meal + ribavirin, twice daily with food (patients weighing <75 kg received a total ribavirin dose of 1000 mg per day; those weighing >=75 kg received 1200 mg per day) for 12 weeks.
干预措施: Daclatasvir (Drug)
Cohort 2: (Genotype 1b) Daclatasvir + Simeprevir + Ribavirin
Participants with hepatitis C virus genotype 1b received daclatasvir, 30 mg, once daily with or without food + simeprivir, 150 mg, once daily with a meal + ribavirin, twice daily with food (patients weighing <75 kg received a total ribavirin dose of 1000 mg per day; those weighing >=75 kg received 1200 mg per day) for 12 weeks.
干预措施: Simeprevir (Drug)
Cohort 3: (Genotype 1a) Daclatasvir + Simeprevir + Ribavirin
Participants with hepatitis C virus genotype 1a received daclatasvir, 30 mg, once daily with or without food + simeprevir, 150 mg, once daily with a meal + ribavirin, twice daily with food (patients weighing <75 kg received a total ribavirin dose of 1000 mg per day; those weighing >=75 kg received 1200 mg per day) for 12 weeks.
干预措施: Daclatasvir (Drug)
Cohort 3: (Genotype 1a) Daclatasvir + Simeprevir + Ribavirin
Participants with hepatitis C virus genotype 1a received daclatasvir, 30 mg, once daily with or without food + simeprevir, 150 mg, once daily with a meal + ribavirin, twice daily with food (patients weighing <75 kg received a total ribavirin dose of 1000 mg per day; those weighing >=75 kg received 1200 mg per day) for 12 weeks.
干预措施: Simeprevir (Drug)
Cohort 3: (Genotype 1a) Daclatasvir + Simeprevir + Ribavirin
Participants with hepatitis C virus genotype 1a received daclatasvir, 30 mg, once daily with or without food + simeprevir, 150 mg, once daily with a meal + ribavirin, twice daily with food (patients weighing <75 kg received a total ribavirin dose of 1000 mg per day; those weighing >=75 kg received 1200 mg per day) for 12 weeks.
干预措施: Ribavirin (Drug)
Cohort 4: (Genotype 1a) Daclatasvir + Simeprevir + Ribavirin
Participants with hepatitis C virus genotype 1a received daclatasvir, 30 mg, once daily with or without food + simeprivir, 150 mg, once daily with a meal + ribavirin, twice daily with food (patients weighing <75 kg received a total ribavirin dose of 1000 mg per day; those weighing >=75 kg received 1200 mg per day.
干预措施: Daclatasvir (Drug)
Cohort 4: (Genotype 1a) Daclatasvir + Simeprevir + Ribavirin
Participants with hepatitis C virus genotype 1a received daclatasvir, 30 mg, once daily with or without food + simeprivir, 150 mg, once daily with a meal + ribavirin, twice daily with food (patients weighing <75 kg received a total ribavirin dose of 1000 mg per day; those weighing >=75 kg received 1200 mg per day.
干预措施: Simeprevir (Drug)
Cohort 4: (Genotype 1a) Daclatasvir + Simeprevir + Ribavirin
Participants with hepatitis C virus genotype 1a received daclatasvir, 30 mg, once daily with or without food + simeprivir, 150 mg, once daily with a meal + ribavirin, twice daily with food (patients weighing <75 kg received a total ribavirin dose of 1000 mg per day; those weighing >=75 kg received 1200 mg per day.
干预措施: Ribavirin (Drug)
结局指标
主要结局
Percentage of Participants With Sustained Virologic Response Rate at Post-treatment Week 12 (SVR12)
时间窗: Post Treatment Week 12 (Follow-up period)
SVR12 rate was defined as hepatitis C virus (HCV) RNA levels to be \<lower limit of quantitation, target detected or target not detected, at post-treatment Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.
次要结局
- Percentage of Participants With Rapid Virologic Response (RVR) at Week 4(Week 4)
- Percentage of Participants With Extended Rapid Virologic Response (eRVR)(Week 4 and Week 12)
- Percentage of Participants With End of Treatment Response (EOTR)(End of treatment (Week 24))
- Number of Participants With Serious Adverse Events (SAEs) and Discontinuations Due to Adverse Events (AEs) and Who Died(From start of treatment (Day 1) up to 7 days post last dose of study treatment (Week 24))
- Percentage of Participants With Complete Early Virologic Response (cEVR)(Week 12)
- Percentage of Participants With Sustained Virologic Response at Week 12 (SVR12) by rs12979860 Single Nucleotide Polymorphisms in the IL-28B Gene Categories(Baseline, post-treatment Week 12 (Follow-up period))