A Phase 2b Study of Daclatasvir in Combination With Peg-Interferon Alfa-2a and Ribavirin in Treatment Naive Subjects With Chronic Hepatitis C Genotype 1 and 4 Infection
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 558
- 试验地点
- 36
- 主要终点
- Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), and Who Died
研究概览
简要总结
To establish that at least 1 dose of daclatasvir combined with standard of care (pegylated interferon and ribavirin) is safe and well tolerated and demonstrates extended rapid virologic response rates at least 35% greater than those with placebo.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients chronically infected with hepatitis C virus (HCV) genotype 1 or 4
- •HCV RNA viral load of ≥100,000 IU/mL
- •No previous exposure to interferon, pegIFNα, or RBV
- •Results of a liver biopsy demonstrating absence of cirrhosis obtained ≤24 months prior to randomization. Compensated cirrhotics with Hepatitis C virus genotype 1 infection are eligible, but will be capped at 10% of the randomized study population (biopsy can be from any time period prior to randomization)
- •Findings on ultrasound, computed tomography scan, or magnetic resonance imaging 12 months prior to randomization that do not demonstrate evidence of hepatocellular carcinoma
- •Body mass index of 18 to 35 kg/m^2
排除标准
- •Positive for hepatitis B or HIV-1/HIV-2 antibody at screening
- •Evidence of a medical condition associated with chronic liver disease other than HCV
- •Evidence of decompensated cirrhosis based on radiologic criteria or biopsy
研究组 & 干预措施
Placebo plus peg-interferon alfa-2a and ribavirin
干预措施: peg-interferon alfa-2a (Drug)
Daclatasvir plus peg-interferon alfa-2a and ribavirin (20 mg)
干预措施: Daclatasvir (Drug)
Daclatasvir plus peg-interferon alfa-2a and ribavirin (20 mg)
干预措施: peg-interferon alfa-2a (Drug)
Daclatasvir plus peg-interferon alfa-2a and ribavirin (20 mg)
干预措施: ribavirin (Drug)
Daclatasvir plus peg-interferon alfa-2a and ribavirin (60 mg)
干预措施: Daclatasvir (Drug)
Daclatasvir plus peg-interferon alfa-2a and ribavirin (60 mg)
干预措施: peg-interferon alfa-2a (Drug)
Daclatasvir plus peg-interferon alfa-2a and ribavirin (60 mg)
干预措施: ribavirin (Drug)
Placebo plus peg-interferon alfa-2a and ribavirin
干预措施: Placebo (Drug)
Placebo plus peg-interferon alfa-2a and ribavirin
干预措施: ribavirin (Drug)
结局指标
主要结局
Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), and Who Died
时间窗: From start of study treatment (day 1) up to follow-up Week 48
SAE was defined as a medical event that at any dose resulted in death, persistent or significant disability/incapacity, or drug dependency/abuse; was life threatening, an important medical event, or a congenital anomaly/birth defect; or required or prolonged hospitalization.
Percentage of Hepatitis C Virus (HCV) Genotype 1 Participants With Extended Rapid Virologic Response (eRVR)
时间窗: Weeks 4 and 12
eRVR was defined as HCV RNA \<lower limit of quantitation and target not detected at both Weeks 4 and 12 on treatment.
Percentage of Hepatitis C Virus (HCV) Genotype 1 Participants With Sustained Virologic Response (SVR24)
时间窗: Follow-up Week 24
SVR24 was defined as HCV \<lower limit of quantitation (LLOQ) and target not detected (TND) at follow-up Week 24. The LLOQ was 25 IU/mL, and \<LLOQ, TND was 10 IU/mL. 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 Hepatitis C Virus (HCV) Genotype 1 Participants With Rapid Virologic Response (RVR)(Week 4)
- Percentage of Hepatitis C Virus (HCV) Genotype 1 Participants With Complete Early Virologic Response (cEVR)(Week 12)
- Percentage of Hepatitis C Virus (HCV) Genotype 1 Participants With 12-week Sustained Virologic Response (SVR12)(Follow-up Week 12)
- Percentage of Resistant Variants Associated With Virologic Failure(Follow-up Week 48)