Study Comparing the Tolerability and Viral Reduction of the Combination of IFN a-2b XL + Ribavirin Versus Peg IFN a-2b + Ribavirin in Patients With Chronic Hepatitis C, Genotype 1 or 4

Study Overview
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Brief Summary
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Three-parallel-arm, open-label, international (France and Romania) study, comparing three treatments The purpose of this study is to confirm if IFN alfa-2b XL has a better antiviral activity and tolerability as compared with current marketed reference, while combined with ribavirin, in a 3-month therapy setting.

Detailed Description
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Interferon alfa-2b XL (IFN alfa-2b XL) is a novel sustained release interferon α-2b drug product that is being developed by FLAMEL TECHNOLOGIES using its Medusa® technology, aiming at reducing the toxicity and enhancing the biological response. In the present study, patients will be randomly assigned to either IFN alfa-2b XL 27 MUI, IFN alfa-2b XL 36 MUI, or IFN peg alfa-2b 1.5 µg/kg, all administered once a week for 12 weeks by subcutaneous injections, in combination with weight dosed ribavirin daily administered orally in two divided doses. Doses will be adapted according to the dose modification guidelines for combination therapy labelled in the ribavirin prescribing information.

Official Title
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Multicentre, Randomised, Open-label Study Comparing the Tolerability and Viral Reduction of the Combination of IFN Alpha-2b XL + Ribavirin Versus Peg IFN Alpha-2b + Ribavirin in Patients With Chronic Hepatitis C, Genotype 1 or 4.

Conditions
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Chronic Hepatitis C

Intervention / Treatment
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* Drug: IFN alfa-2b XL 27 MUI + Ribavirin
* Drug: IFN alfa-2b XL 36 MUI + Ribavirin
* Drug: IFN peg alfa-2b 1.5 µg/kg + Ribavirin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient having voluntarily signed the Informed Consent Form prior to any study specific procedure being performed Male or female HCV genotype 1 or 4 infected patients (positive serum HCV RNA), aged between 18 and 65 years inclusive, with a body mass within the range over or equal of 45Kg and below or equal to 100 Kg Patient being either naïve to therapy, either non-responder to previous standard Peg-interferon α + ribavirin therapy, With no absolute contra-indication to interferon α or ribavirin Female patients must be non-lactating and of non-childbearing potential, or have a negative pregnancy test results to enter the study No evidence of acute or advanced liver disease, uncontrolled diabetes, cardiovascular, immunological, or thyroid disease, and no recently diagnosed malignancy Vital signs within normal ranges, or if outside the normal ranges, not deemed clinically significant in the opinion of the Investigator. An ECG with no clinically significant abnormalities Exclusion Criteria: History of solid organ transplantation Severe systemic infection, uncontrolled diabetes, cancers, associated liver disease General anesthesia or recent blood transfusion

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GP1N IFN alfa-2bXL 27 MUI + Ribavirin<br>IFN alfa-2bXL 27 MUI, powder and solvent for solution injection | Drug: IFN alfa-2b XL 27 MUI + Ribavirin<br>* IFN alfa-2b XL 27 MUI administered once a week for 12 weeks by subcutaneous injections, in combination with weight dosed ribavirin daily administered orally in two divided doses<br>|
| Experimental: GP2N IFN alfa-2b XL 36 MUI + Ribavirin<br>IFN alfa-2b XL 36 MUI, powder and solvent for solution injection | Drug: IFN alfa-2b XL 36 MUI + Ribavirin<br>* IFN alfa-2b XL 36 MUI administered once a week for 12 weeks by subcutaneous injections in combination with weight dosed ribavirin daily administered orally in two divided doses<br>|
| Active Comparator: GP3N IFN peg alfa-2b 1.5 µg/kg + Ribavirin<br>IFN peg alfa-2b 1.5 µg/kg,administered once a week for 12 weeks by subcutaneous injections | Drug: IFN peg alfa-2b 1.5 µg/kg + Ribavirin<br>* IFN peg alfa-2b 1.5 µg/kg administered once a week for 12 weeks by subcutaneous injections in combination with weight dosed ribavirin daily administered orally in two divided doses<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Viral load decrease at Week 4 and Week 12 of treatment with IFN alfa-2b XL 27 MIU, IFN alfa-2b XL 36 MIU and the marketed reference product (PEG IFN alfa-2b 1.5μg/kg) in combination with ribavirin |  | Week 4 and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with early virologic response (EVR) (reduction of at least 2 log viral load) at the end of week 12 |  | Week 4 and Week 12 | 
| Percentage of patients with complete early virologic response (EVR) (viral load <15 IU) at the end of the week 12 |  | Week 4 and Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hepatitis C, viral kinetics, antiviral response, Genotype 1 or 4