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

Rottapharm

Status and phase: Withdrawn; Phase 3; Phase 2

Conditions: Hepatitis C, Chronic

Treatments: Drug: Pegylated interferon alfa2b; Drug: Legalon® SIL (Silibinin); Drug: Ribavirin

Study type: Interventional

Funder types: Industry

Identifiers

NCT01871662

LEG-SIL-2-02

Details and patient eligibility

About

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.

Sex: All

Ages: 21 to 45 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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0 participants in 3 patient groups

Group C: RIB + Peg-IFN

Active Comparator group

Description:

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

Treatment:

Drug: Ribavirin

Drug: Pegylated interferon alfa2b

Group B:Legalon® SIL + RIB + Peg-IFN

Experimental group

Description:

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)

Treatment:

Drug: Ribavirin

Drug: Legalon® SIL (Silibinin)

Drug: Pegylated interferon alfa2b

Group A: Legalon® SIL + RIB

Experimental group

Description:

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)

Treatment:

Drug: Ribavirin

Drug: Legalon® SIL (Silibinin)