Randomized Study for the Assessment of Silibinin (Legalon® SIL) in the Treatment of naïve Genotype 4 Patients With Chronic Hepatitis C

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Hepatitis C, Chronic

Intervention / Treatment
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* Drug: Legalon® SIL (Silibinin)
* Drug: Pegylated interferon alfa2b
* Drug: Ribavirin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group C: RIB + Peg-IFN<br>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 | Drug: Pegylated interferon alfa2b<br>* 1.5 µg/kg once-weekly<br>* Other names: PEG-INTRON®;Drug: Ribavirin<br>* At weight-based dose 800-1400 mg/day (BID, OS)<br>* Other names: REBETOL®;|
| Experimental: Group B:Legalon® SIL + RIB + Peg-IFN<br>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) | Drug: Legalon® SIL (Silibinin)<br>* Silibinin 20 mg/Kg/day<br>Drug: Pegylated interferon alfa2b<br>* 1.5 µg/kg once-weekly<br>* Other names: PEG-INTRON®;Drug: Ribavirin<br>* At weight-based dose 800-1400 mg/day (BID, OS)<br>* Other names: REBETOL®;|
| Experimental: Group A: Legalon® SIL + RIB<br>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) | Drug: Legalon® SIL (Silibinin)<br>* Silibinin 20 mg/Kg/day<br>Drug: Ribavirin<br>* At weight-based dose 800-1400 mg/day (BID, OS)<br>* Other names: REBETOL®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Undetectable HCV-RNA at 24 Weeks After the end of the Study Treatment | 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. | 24 weeks after the end of treatment (e.g. at week 49 or 73) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Undetectable HCV-RNA | Proportion of patients with Rapid Viral Response (RVR), i.e. undetectable HCV-RNA levels 4 weeks after the beginning of the study treatment course. | 4 weeks after the beginning of the study treatment | 
| HCV-RNA decrease ≥ 2 log10 IU/mL | 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 | 12 weeks after the beginning of the study treatment | 
| Undetectable HCV-RNA | 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) | At the end of study treatment (e.g. at week 25 or 49) | 
| Normalization of Serum Alanine Aminotransferase | 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; | 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HCV, Hepatitis C