Randomized, Multi-Center, Partially Placebo-Controlled Phase IV-Study to Compare Efficacy and Tolerability of 48-Week Combined Therapy With Peginterferon Alfa-2a, Ribavirin and Amantadine Sulphate Versus Placebo in Untreated Patients With Chronic Hepatitis C Virus-Genotype-1-Infection
Overview
- Phase
- Phase 4
- Intervention
- Not specified
- Conditions
- Hepatitis C, Chronic
- Sponsor
- University Hospital, Saarland
- Enrollment
- 700
- Primary Endpoint
- Proof that peginterferon alfa-2a, ribavirin and amantadine sulphate over a period of 50 weeks improves the permanent virological efficacy by more than 10% compared to peginterferon alfa-2a and ribavirin
- Last Updated
- 20 years ago
Overview
Brief Summary
This was a randomized, multi-center, partially placebo-controlled Phase IV study to compare the efficacy and tolerability of a 48-week combined therapy with pegylated interferon alpha-2a, ribavirin and amantadine sulphate versus placebo in untreated patients with chronic hepatitis C virus-genotype-1-infection. The hypothesis was that there will be an increase in sustained response rate for triple therapy compared to current standard treatment.
Detailed Description
Primary Objective: * Proof that a triple-therapy (peginterferon alfa-2a, ribavirin and amantadine sulphate) dispensed over a period of 50 weeks, improves the permanent virological efficacy by more than 10% as compared to a combination therapy with peginterferon alpha-2a and ribavirin, defined as negative HCV-RNA result obtained by a molecular verification method (e.g. Roche AmplicorTM HCV, v.2.0, sensitivity \<50 IE/ml) 24 weeks after the end of the therapy. Secondary Objectives: * Verification of the initial virological efficacy up to week 12, defined as negative HCV-RNA test results by means of quantitative proof methods, e.g. Roche AmplicorTM HCV Monitor v.2.0 (sensitivity \<600 IE/ml). * Biochemical efficacy, defined by the serum GPT values 24 weeks after the end of the therapy. * Virological efficacy, measured on the basis of the HCV-RNA values at the end of the therapy. * Biochemical efficacy defined by the serum GPT values at the end of the therapy.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Female and male subjects over 18 years of age and below 70 years of age
- •Serological indication of chronic hepatitis C infection with positive anti-HCV test and serum HCV-RNA quantification \>600 IE/ml by means of quantitative proof methods, e.g. Roche AmplicorTM HCV Monitor test, v.2.
- •Untreated patients with HCV-induced chronic infection.
- •Indication of a genotype HCV-1 on the basis of the reverse hybridizing assay Inno LiPA from Bayer Versant (Innogenetics).
- •Increased GPT serum level on at least one determination date within the 56-day screening phase prior to start of administration of study medication.
- •Histological identification of inflammatory activity in the liver, with or without an indication of compensated cirrhosis, during the 24 months prior to start of the study.
- •Compensated liver disease (Child-Pugh Grade A).
- •Negative urine or serum pregnancy test in fertile female subjects within 24 hours before taking the first dose of study medication.
- •During the administration of study medication and for 24 weeks after the treatment has stopped, patients must apply two approved contraception methods, one of which must have a barrier effect on the male, e.g. condom.
- •If one or more of the above inclusion criteria are not fulfilled, the patient is excluded from the study!
Exclusion Criteria
- •Any known sensitive reaction to interferon, ribavirin or amantadine sulphate.
- •Pregnant or breast-feeding women and fertile women who do not practice contraception.
- •Male partners of pregnant women.
- •Previous treatment with interferon and/or ribavirin.
- •Treatment with systemic anti-neoplastic or immunomodulatory medication (supraphysiologic doses of steroids or radiation included) within the last 6 months prior to the study and throughout the whole study.
- •Immunosuppressed/immunocompromised patients.
- •Participation in a clinical study within the last three months.
- •Infection with HCV genotype-2, -3, -4, -5 or -
- •Positive indication of HBsAg, HIV antibodies in the screening phase.
- •Non-hepatitis C virus-induced chronic hepatitis (e.g. hematochromatosis, autoimmune hepatitis, metabolic or alcoholic liver disease).
Outcomes
Primary Outcomes
Proof that peginterferon alfa-2a, ribavirin and amantadine sulphate over a period of 50 weeks improves the permanent virological efficacy by more than 10% compared to peginterferon alfa-2a and ribavirin
Secondary Outcomes
- Verification of the initial virological efficacy up to week 12, defined as negative HCV-RNA test results by means of quantitative proof methods, e.g. Roche AmplicorTM HCV Monitor v.2.0 (sensitivity <600 IE/ml)
- Biochemical efficacy, defined by the serum GPT values 24 weeks after the end of the therapy
- Virological efficacy, measured on the basis of the HCV-RNA values at the end of the therapy
- Biochemical efficacy defined by the serum GPT values at the end of the therapy