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

Primary Purpose

Hepatitis C, Chronic

Status
Withdrawn
Phase
Phase 2
Locations
Egypt
Study Type
Interventional
Intervention
Legalon® SIL (Silibinin)
Pegylated interferon alfa2b
Ribavirin
Sponsored by
Rottapharm
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatitis C, Chronic focused on measuring HCV, Hepatitis C

Eligibility Criteria

21 Years - 45 Years (Adult)All SexesDoes not accept 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

Sites / Locations

  • Al-Manial University Hospital, Kasr El-Aini Faculty Medicine, Cairo University

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Experimental

Experimental

Arm Label

Group C: RIB + Peg-IFN

Group B:Legalon® SIL + RIB + Peg-IFN

Group A: Legalon® SIL + RIB

Arm 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

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)

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)

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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
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)
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;
Number of Participants with adverse events (AEs)

Full Information

First Posted
May 30, 2013
Last Updated
March 4, 2015
Sponsor
Rottapharm
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1. Study Identification

Unique Protocol Identification Number
NCT01871662
Brief Title
Randomized Study for the Assessment of Silibinin (Legalon® SIL) in the Treatment of naïve Genotype 4 Patients With Chronic Hepatitis C
Acronym
HEPASIL
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 Type
Interventional

2. Study Status

Record Verification Date
March 2015
Overall Recruitment Status
Withdrawn
Study Start Date
August 2013 (undefined)
Primary Completion Date
February 2016 (Anticipated)
Study Completion Date
February 2016 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Rottapharm

4. Oversight

Data Monitoring Committee
Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis C, Chronic
Keywords
HCV, Hepatitis C

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group C: RIB + Peg-IFN
Arm Type
Active Comparator
Arm 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
Arm Title
Group B:Legalon® SIL + RIB + Peg-IFN
Arm Type
Experimental
Arm 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)
Arm Title
Group A: Legalon® SIL + RIB
Arm Type
Experimental
Arm 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)
Intervention Type
Drug
Intervention Name(s)
Legalon® SIL (Silibinin)
Intervention Description
Silibinin 20 mg/Kg/day
Intervention Type
Drug
Intervention Name(s)
Pegylated interferon alfa2b
Other Intervention Name(s)
PEG-INTRON®
Intervention Description
1.5 µg/kg once-weekly
Intervention Type
Drug
Intervention Name(s)
Ribavirin
Other Intervention Name(s)
REBETOL®
Intervention Description
At weight-based dose 800-1400 mg/day (BID, OS)
Primary Outcome Measure Information:
Title
Undetectable HCV-RNA at 24 Weeks After the end of the Study Treatment
Description
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.
Time Frame
24 weeks after the end of treatment (e.g. at week 49 or 73)
Secondary Outcome Measure Information:
Title
Undetectable HCV-RNA
Description
Proportion of patients with Rapid Viral Response (RVR), i.e. undetectable HCV-RNA levels 4 weeks after the beginning of the study treatment course.
Time Frame
4 weeks after the beginning of the study treatment
Title
HCV-RNA decrease ≥ 2 log10 IU/mL
Description
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
Time Frame
12 weeks after the beginning of the study treatment
Title
Undetectable HCV-RNA
Description
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)
Time Frame
At the end of study treatment (e.g. at week 25 or 49)
Title
Normalization of Serum Alanine Aminotransferase
Description
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;
Time Frame
4 weeks after the beginning of study treatment, at EOT and at 24 weeks after the completion of the study treatment
Title
Number of Participants with adverse events (AEs)
Time Frame
Up to 24 weeks after the end of treatment (e.g. up to week 49 or 73)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gamal Esmat, MD
Organizational Affiliation
Al-Manial University Hospital, Kasr El-Aini Faculty Medicine, Cairo University, Egypt
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Samer El-Kamary, MD
Organizational Affiliation
University of Maryland School of Medicine,Baltimore, USA
Official's Role
Study Chair
Facility Information:
Facility Name
Al-Manial University Hospital, Kasr El-Aini Faculty Medicine, Cairo University
City
Cairo
Country
Egypt

12. IPD Sharing Statement

Learn more about this trial

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

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