Randomized Study for the Assessment of Silibinin (Legalon® SIL) in the Treatment of naïve Genotype 4 Patients With Chronic Hepatitis C
- Conditions
- Hepatitis C, Chronic
- Interventions
- Registration Number
- NCT01871662
- Lead Sponsor
- Rottapharm
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
- 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
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Liver transplant patients
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Co-Infection with HIV and/or HBV
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ALT >10-fold the upper limit of normal i.e. > 400 U/L
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Evidence of hepatocellular carcinoma (HCC)
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Fibroscan® at screening with a score ≥ 14.5 kPa
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Evidence of liver disease due to causes other than chronic HCV infection
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Evidence of poorly controlled diabetes (defined as HbA1c > 8%)
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History of alcohol or drug abuse within the last 12 months
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History or clinical evidence of liver decompensation, e.g. presence of ascites or encephalopathy, or bleeding from esophageal varices
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Serum albumin levels < 3.2 g/dL
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INR > 1.3 N
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Total Bilirubin levels > 2.0 mg/dL unless explained by Gilbert's disease
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Platelet Count < 100,000 µL
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Absolute Neutrophil counts < 1500 µL (mm3)
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Active or suspected non-hepatic malignancy or history of malignancy within the last 5 years
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Body Mass Index < 16 or > 35 kg/m2
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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)
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Male patients not vasectomized, who do not agree to abstain from intercourse or who do not use a condom
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group B:Legalon® SIL + RIB + Peg-IFN Legalon® SIL (Silibinin) 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) Group B:Legalon® SIL + RIB + Peg-IFN Pegylated interferon alfa2b 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) Group A: Legalon® SIL + RIB Legalon® SIL (Silibinin) 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) Group C: RIB + Peg-IFN Pegylated interferon alfa2b 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 Group C: RIB + Peg-IFN Ribavirin 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 Group B:Legalon® SIL + RIB + Peg-IFN Ribavirin 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) Group A: Legalon® SIL + RIB Ribavirin 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)
- Primary Outcome Measures
Name Time Method Undetectable HCV-RNA at 24 Weeks After the end of the Study Treatment 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.
- Secondary Outcome Measures
Name Time Method HCV-RNA decrease ≥ 2 log10 IU/mL 12 weeks after the beginning of the study treatment Number and percentage of patients with Early Viral Response (EVR), i.e. HCV-RNA decrease ≥ 2 log10 IU/mL 12 weeks after the beginning of the study treatment course
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 Proportion of patients with a normalization of Serum Alanine Aminotransferase (ALT \<40 U/L) values 4 weeks after the beginning of study treatment, at EOT and at 24 weeks after the completion of the study treatment course;
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) Proportion of patients with End Of Treatment (EOT) Response, i.e. undetectable HCV-RNA levels at the end of the study treatment (e.g. at the end of treatment at week 25 or 49)
Trial Locations
- Locations (1)
Al-Manial University Hospital, Kasr El-Aini Faculty Medicine, Cairo University
🇪🇬Cairo, Egypt