A Randomized, Single Center, Comparative Study to Evaluate the Efficacy and Safety of Silibinin (Legalon® SIL) in Combination With Ribavirin or With Peginterferon and Ribavirin, Versus Peginterferon and Ribavirin Based Standard of Care (SoC) in Treatment of naïve Genotype 4 Patients With Chronic Hepatitis C
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 发起方
- Rottapharm
- 试验地点
- 1
- 主要终点
- Undetectable HCV-RNA at 24 Weeks After the end of the Study Treatment
研究概览
简要总结
The purpose of this study is to explore whether silibinin plus ribavirin with/without peg-interferon can be more effective than the peg-interferon plus ribavirin based standard of care (SoC) in the treatment of patients infected with hepatitis C virus genotype 4.
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
- 21 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient must be willing to give written informed consent
- •Male and female patients; age between 21 and 45 years inclusive
- •Chronic hepatitis C infection with genotype 4 confirmed by genotypic testing at screening or within 6 months of screening period
- •Patients eligible to be treated with RBV and Peg-IFN as per the instructions present in their prescribing information documents
- •No history of prior interferon therapy (treatment naïve)
- •Detectable HCV-RNA levels
- •Normal BUN and creatinine
- •Ability to communicate, participate, and comply with the requirements of the entire study
排除标准
- •Liver transplant patients
- •Co-Infection with HIV and/or HBV
- •ALT >10-fold the upper limit of normal i.e. > 400 U/L
- •Evidence of hepatocellular carcinoma (HCC)
- •Fibroscan® at screening with a score ≥ 14.5 kPa
- •Evidence of liver disease due to causes other than chronic HCV infection
- •Evidence of poorly controlled diabetes (defined as HbA1c > 8%)
- •History of alcohol or drug abuse within the last 12 months
- •History or clinical evidence of liver decompensation, e.g. presence of ascites or encephalopathy, or bleeding from esophageal varices
- •Serum albumin levels < 3.2 g/dL
- •INR > 1.3 N
- •Total Bilirubin levels > 2.0 mg/dL unless explained by Gilbert's disease
- •Platelet Count < 100,000 µL
- •Absolute Neutrophil counts < 1500 µL (mm3)
- •Active or suspected non-hepatic malignancy or history of malignancy within the last 5 years
- •Body Mass Index < 16 or > 35 kg/m2
- •Females of childbearing potential:
- •Pregnancy (i.e. positive urine pregnancy test at screening) or lactation
- •Failure to agree to practice adequate contraception methods (e.g. oral contraceptives, intra-uterine device (IUD), transdermal contraceptive patch)
- •Male patients not vasectomized, who do not agree to abstain from intercourse or who do not use a condom
研究组 & 干预措施
Group C: RIB + Peg-IFN
Ribavirin(800-1400 mg/day,divided BID PO) + Peg-IFN alfa2b (1.5 μg/kg/week SC)for 25 weeks if RVR has been achieved or 49 weeks if EVR has been achieved
干预措施: Pegylated interferon alfa2b (Drug)
Group C: RIB + Peg-IFN
Ribavirin(800-1400 mg/day,divided BID PO) + Peg-IFN alfa2b (1.5 μg/kg/week SC)for 25 weeks if RVR has been achieved or 49 weeks if EVR has been achieved
干预措施: Ribavirin (Drug)
Group B:Legalon® SIL + RIB + Peg-IFN
Silibinin (20 mg/Kg/day) for 6 days, followed by Silibinin + ribavirin (800-1400 mg/day, divided BID PO) + Peg-IFN alfa2b (1.5 μg/kg/week SC) for 15 days, followed by ribavirin (800-1400 mg/day, divided BID PO) + Peg-IFN alfa2b (1.5 μg/kg/week SC) + 2 days of Silibinin per week for 9 weeks, followed by ribavirin (800-1400 mg/day, divided BID PO) + Peg-IFN alfa2b (1.5 μg/kg/week SC) for 13 weeks if RVR has been achieved (for a total of 25 weeks of treatment) or 37 weeks if EVR has been achieved (for a total of 49 weeks of treatment)
干预措施: Legalon® SIL (Silibinin) (Drug)
Group B:Legalon® SIL + RIB + Peg-IFN
Silibinin (20 mg/Kg/day) for 6 days, followed by Silibinin + ribavirin (800-1400 mg/day, divided BID PO) + Peg-IFN alfa2b (1.5 μg/kg/week SC) for 15 days, followed by ribavirin (800-1400 mg/day, divided BID PO) + Peg-IFN alfa2b (1.5 μg/kg/week SC) + 2 days of Silibinin per week for 9 weeks, followed by ribavirin (800-1400 mg/day, divided BID PO) + Peg-IFN alfa2b (1.5 μg/kg/week SC) for 13 weeks if RVR has been achieved (for a total of 25 weeks of treatment) or 37 weeks if EVR has been achieved (for a total of 49 weeks of treatment)
干预措施: Pegylated interferon alfa2b (Drug)
Group B:Legalon® SIL + RIB + Peg-IFN
Silibinin (20 mg/Kg/day) for 6 days, followed by Silibinin + ribavirin (800-1400 mg/day, divided BID PO) + Peg-IFN alfa2b (1.5 μg/kg/week SC) for 15 days, followed by ribavirin (800-1400 mg/day, divided BID PO) + Peg-IFN alfa2b (1.5 μg/kg/week SC) + 2 days of Silibinin per week for 9 weeks, followed by ribavirin (800-1400 mg/day, divided BID PO) + Peg-IFN alfa2b (1.5 μg/kg/week SC) for 13 weeks if RVR has been achieved (for a total of 25 weeks of treatment) or 37 weeks if EVR has been achieved (for a total of 49 weeks of treatment)
干预措施: Ribavirin (Drug)
Group A: Legalon® SIL + RIB
Silibinin (20 mg/Kg/day) for 6 days, followed by Silibinin + ribavirin (800-1400 mg/day, divided BID PO) for 15 days, followed by ribavirin (800-1400 mg/day, divided BID PO) + 2 days of Silibinin per week for 9 weeks, followed by ribavirin (800-1400 mg/day, divided BID PO) for 13 weeks if RVR has been achieved (for a total of 25 weeks of treatment) or 37 weeks if EVR has been achieved (for a total of 49 weeks of treatment)
干预措施: Legalon® SIL (Silibinin) (Drug)
Group A: Legalon® SIL + RIB
Silibinin (20 mg/Kg/day) for 6 days, followed by Silibinin + ribavirin (800-1400 mg/day, divided BID PO) for 15 days, followed by ribavirin (800-1400 mg/day, divided BID PO) + 2 days of Silibinin per week for 9 weeks, followed by ribavirin (800-1400 mg/day, divided BID PO) for 13 weeks if RVR has been achieved (for a total of 25 weeks of treatment) or 37 weeks if EVR has been achieved (for a total of 49 weeks of treatment)
干预措施: Ribavirin (Drug)
结局指标
主要结局
Undetectable HCV-RNA at 24 Weeks After the end of the Study Treatment
时间窗: 24 weeks after the end of treatment (e.g. at week 49 or 73)
The primary efficacy endpoint is the proportion of patients with Sustained Virological Response (SVR), i.e. undetectable HCV-RNA level lasting for 24 weeks after the completion of the study treatment course.
次要结局
- HCV-RNA decrease ≥ 2 log10 IU/mL(12 weeks after the beginning of the study treatment)
- Normalization of Serum Alanine Aminotransferase(4 weeks after the beginning of study treatment, at EOT and at 24 weeks after the completion of the study treatment)
- Number of Participants with adverse events (AEs)(Up to 24 weeks after the end of treatment (e.g. up to week 49 or 73))
- Undetectable HCV-RNA(At the end of study treatment (e.g. at week 25 or 49))