Pegylated Interferon and Ribavirin Therapy in Chronic Hepatitis Genotype 4

Study Overview
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Brief Summary
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Genotype 4 is the least-studied hepatitis C virus genotype and was considered a difficult to treat genotype due to the disappointing response of chronic hepatitis C genotype 4 to conventional interferon monotherapy. Recent reports showed that pegylated interferon and ribavirin combination therapy markedly increased the SVR rate to 55-70%. The duration of treatment has not been accurately defined. The main objective of this is to assess the duration of pegylated interferon ribavirin therapy in chronic hepatitis genotype 4 and assess the clinical utility of rapid and early virologic response in determining the optimal duration of peg interferon ribavirin therapy in chronic hepatitis C.

Detailed Description
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Hepatitis C virus (HCV) genotype 4 is the most frequent cause of chronic hepatitis C in Middle East, North Africa and sub-Saharan Africa. In countries like Egypt, 73 to 90% of cases of chronic hepatitis C are caused by genotype 4. Recently, epidemiological reports showed spread of HCV-4 infection in Western countries such as France, Italy, Greece, Spain and the United States particularly among intravenous drug users. Genotype 4 is the least-studied hepatitis C virus genotype and was considered a difficult to treat genotype due to the disappointing response of chronic hepatitis C genotype 4 to conventional interferon monotherapy. Recent reports showed that pegylated interferon and ribavirin combination therapy markedly increased the SVR rate to 55-70%. We have previously shown that, treatment patients with chronic HVCG4with PEG-IFN α-2b plus ribavirin for 36 or 48 weeks was more effective (SVR 66% and 69%, respectively) than for 24 weeks. It has been shown in previous studies on chronic hepatitis C genotype 1 that individuals who achieve an early virologic have a higher chance to achieve a sustained virologic response. Peg interferon and ribavirin therapy is associated with adverse events and is expensive; therefore, careful determination of the optimal treatment duration is crucial as it spares the patient unnecessary or prolonged therapy and enhances the cost-effectiveness of therapy. Therefore the main objective of this randomized, multicenter trial is to assess the clinical utility of rapid and early virologic response in determining the optimal duration of peg interferon ribavirin therapy in chronic hepatitis C.

Official Title
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Role of Rapid Virologic Response in Determining Treatment Duration of Peginterferon Alfa-2b/Ribavirin in Chronic Hepatitis C Genotype 4

Conditions
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Hepatitis C

Intervention / Treatment
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* Drug: Pegylated IFN- alpha 2b
* Drug: Ribavirin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria:Adult males and females, 18 to 50 years of age; with documented chronic hepatitis C according to the following criteria: elevated serum alanine aminotransferase (ALT) above the upper limit of normal (40 U/l) on two occasions during the preceding six months; anti-HCV positive anti-body status assessed by second generation enzyme linked immunosorbent assay (Roche Diagnostics, Branchburg, New Jersey, USA); positive polymerase chain reaction for HCV RNA (Cobas Amplicor HCV Monitor v2.0; lower limit of quantitation 50 IU/mL); genotype 4; and criteria for chronic hepatitis C in liver biopsy performed within the preceding year with no signs of cirrhosis or bridging fibrosis on pretreatment liver biopsy. - Exclusion Criteria: Previous IFN-alpha therapy; other liver diseases such as hepatitis A, hepatitis B, schistosomiasis, autoimmune hepatitis, alcoholic liver disease, drug induced hepatitis, or decompensated liver disease; coinfection with schistosomiasis or human immunodeficiency virus; neutro¬penia (,1 500/mm3); thrombocytopenia (,90 000/mm3); creatinine concentration .1.5 times the upper limit of normal; serum a fetoprotein concentration .25 ng/ml; organ transplant; neoplastic disease; severe cardiac or pulmonary disease; unstable thyroid dysfunction; psychiatric disorder; current pregnancy or breast feeding; or therapy with immunomodulatory agents within the last six months.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Pegylated IFN- alpha 2b Ribavirin for 24 weeks (patients with RVR) | Drug: Pegylated IFN- alpha 2b<br> <br> * Other names: PEG-Intron™;Drug: Ribavirin<br> <br> * Other names: Ribavrin;|
| Active Comparator: 2<br>Pegylated IFN- alpha 2b Ribavirin for 36 weeks (patients with complete EVR) | Drug: Pegylated IFN- alpha 2b<br> <br> * Other names: PEG-Intron™;Drug: Ribavirin<br> <br> * Other names: Ribavrin;|
| Active Comparator: 3<br>Pegylated IFN- alpha 2b Ribavirin for 48 weeks (patients with partial EVR) | Drug: Pegylated IFN- alpha 2b<br> <br> * Other names: PEG-Intron™;Drug: Ribavirin<br> <br> * Other names: Ribavrin;|
| Active Comparator: 4<br>Pegylated IFN- alpha 2b Ribavirin for 48 weeks (control) | Drug: Pegylated IFN- alpha 2b<br> <br> * Other names: PEG-Intron™;Drug: Ribavirin<br> <br> * Other names: Ribavrin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| sustained virologic response defined as undetectable serum HCV RNA levels (Amplicor HCV, Roche Molecular Systems; lower limit of detection (LLD) of 50 IU/mL) |  | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Virologic response at the end of treatment (EOT) defined as undetectable HCV RNA serum levels (50 IU/ml) at the end of the scheduled treatment period |  | 6-12 months and 6 months follow-up | 
| sustained virologic response (primary) histological response (secondary) biochemical response (secondary) |  | 6-12 months treatment), 6 months follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chronic hepatitis C;, peg-interferon alfa-2b;, ribavirin,, rapid virologic response,, sustained virological response