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

Sponsor

Rottapharm (Industry)

Overall Status

Withdrawn

CT.gov ID

NCT01871662

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C, Chronic	Drug: Legalon® SIL (Silibinin) Drug: Pegylated interferon alfa2b Drug: Ribavirin	Phase 2/Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Aug 1, 2013

Anticipated Primary Completion Date :

Feb 1, 2016

Anticipated Study Completion Date :

Feb 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 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	Drug: Pegylated interferon alfa2b 1.5 µg/kg once-weekly Other Names: PEG-INTRON® Drug: Ribavirin At weight-based dose 800-1400 mg/day (BID, OS) Other Names: REBETOL®
Experimental: 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)	Drug: Legalon® SIL (Silibinin) Silibinin 20 mg/Kg/day Drug: Pegylated interferon alfa2b 1.5 µg/kg once-weekly Other Names: PEG-INTRON® Drug: Ribavirin At weight-based dose 800-1400 mg/day (BID, OS) Other Names: REBETOL®
Experimental: 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)	Drug: Legalon® SIL (Silibinin) Silibinin 20 mg/Kg/day Drug: Ribavirin At weight-based dose 800-1400 mg/day (BID, OS) Other Names: REBETOL®

Arm

Intervention/Treatment

Active Comparator: 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

Drug: Pegylated interferon alfa2b

1.5 µg/kg once-weekly

Other Names:

PEG-INTRON®

Drug: Ribavirin

At weight-based dose 800-1400 mg/day (BID, OS)

Other Names:

REBETOL®

Experimental: 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)

Drug: Legalon® SIL (Silibinin)

Silibinin 20 mg/Kg/day

Drug: Pegylated interferon alfa2b

1.5 µg/kg once-weekly

Other Names:

PEG-INTRON®

Drug: Ribavirin

At weight-based dose 800-1400 mg/day (BID, OS)

Other Names:

REBETOL®

Experimental: 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)

Drug: Legalon® SIL (Silibinin)

Silibinin 20 mg/Kg/day

Drug: Ribavirin

At weight-based dose 800-1400 mg/day (BID, OS)

Other Names:

REBETOL®

Outcome Measures

Primary Outcome Measures

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

Undetectable HCV-RNA [4 weeks after the beginning of the study treatment]
Proportion of patients with Rapid Viral Response (RVR), i.e. undetectable HCV-RNA levels 4 weeks after the beginning of the study treatment course.
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
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)
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)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years to 45 Years

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Al-Manial University Hospital, Kasr El-Aini Faculty Medicine, Cairo University	Cairo		Egypt

Sponsors and Collaborators

Rottapharm

Investigators

Principal Investigator: Gamal Esmat, MD, Al-Manial University Hospital, Kasr El-Aini Faculty Medicine, Cairo University, Egypt
Study Chair: Samer El-Kamary, MD, University of Maryland School of Medicine,Baltimore, USA