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

NCT01871662 | Withdrawn Phase 2 DMC

• 1 other identifier: LEG-SIL-2-02
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Hepatitis C, Chronic

Keywords

HCV; Hepatitis C

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Undetectable HCV-RNA

  4 weeks after the beginning of the study treatment

• HCV-RNA decrease ≥ 2 log10 IU/mL

  12 weeks after the beginning of the study treatment

• Undetectable HCV-RNA

  At the end of study treatment (e.g. 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

• Number of Participants with adverse events (AEs)

  Up to 24 weeks after the end of treatment (e.g. up to week 49 or 73)

Study Arms (3)

Group C: RIB + Peg-IFN

ACTIVE COMPARATOR

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; Drug: Ribavirin

Group B:Legalon® SIL + RIB + Peg-IFN

EXPERIMENTAL

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); Drug: Pegylated interferon alfa2b; Drug: Ribavirin

Group A: Legalon® SIL + RIB

EXPERIMENTAL

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); Drug: Ribavirin

Interventions

Legalon® SIL (Silibinin) DRUG

Silibinin 20 mg/Kg/day

Group A: Legalon® SIL + RIB; Group B:Legalon® SIL + RIB + Peg-IFN

Pegylated interferon alfa2b DRUG

1.5 µg/kg once-weekly

Also known as: PEG-INTRON®

Group B:Legalon® SIL + RIB + Peg-IFN; Group C: RIB + Peg-IFN

Ribavirin DRUG

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

Also known as: REBETOL®

Group A: Legalon® SIL + RIB; Group B:Legalon® SIL + RIB + Peg-IFN; Group C: RIB + Peg-IFN

Eligibility Criteria

• Age: 21 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Rottapharm: lead

Study Sites (1)

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

Cairo, Egypt

Location

MeSH Terms

Conditions

Hepatitis C, Chronic; Hepatitis C

Interventions

Silybin; peginterferon alfa-2b; Ribavirin

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Silymarin; Flavonolignans; Flavonoids; Chromones; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Gamal Esmat, MD

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

  PRINCIPAL INVESTIGATOR

• Samer El-Kamary, MD

  University of Maryland School of Medicine,Baltimore, USA

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 30, 2013
• First Posted: June 7, 2013
• Study Start: August 1, 2013
• Primary Completion: February 1, 2016
• Study Completion: February 1, 2016
• Last Updated: March 5, 2015

Record last verified: 2015-03

Locations

EG (1)