48 Weeks Combination Therapy for Patients With HBeAg-negative Chronic Hepatitis B Virus (HBV) Infection

Study Overview
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Brief Summary
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The purpose of this study is to investigate whether in patients with chronic HBeAg-negative hepatitis B, PEG-IFN-ribavirin combination therapy for 1 year leads to enhanced response (HBV DNA <10E4 copies/ml and normal ALT 24 weeks after treatment discontinuation) in comparison with pegylated interferon (PEG-IFN) monotherapy.

Detailed Description
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Despite the introduction of newer drugs for the treatment of chronic hepatitis B, there is still no optimal treatment. Pegylated interferon alfa has proven sustained efficacy in approximately 30-40% of patients with HBeAg-positive or HBeAg-negative chronic hepatitis B. It is likely that combination therapy of pegylated interferon alfa with ribavirin in chronic hepatitis B is more effective than pegylated interferon alfa monotherapy. In chronic hepatitis C, adding ribavirin to pegylated interferon therapy doubled the sustained response rate (29% vs. 56%) and has become the standard option of treatment. To investigate the effect of the treatment with pegylated interferon and ribavirin on the amount of inflammation and fibrosis in the liver, a liver biopsy will be performed within one year prior to screening and at the end of follow-up. When patients with chronic hepatitis B are treated outside any study with pegylated interferon, they visit the outpatient clinic approximately every month for blood samples. So in this study the amount of blood samples taken from every patient is not increased as compared with treatment outside a study.

Official Title
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Peginterferon Alfa-2a and Ribavirin Combination Therapy in Patients With HBeAg-negative Chronic HBV Infection (PARC Study)

Conditions
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Hepatitis B

Intervention / Treatment
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* Drug: Ribavirin
* Drug: Peginterferon alpha 2a


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic hepatitis B Biopsy performed within one year prior to screening or during screening ALT > 1.5 x ULN HBeAg negative, anti-HBeAg positive HBV DNA > 10E5 copies/ml Age 18-70 years Written informed consent Hepatic imaging without evidence of HCC All fertile males and females must be using two forms of effective contraception Exclusion Criteria: Antiviral therapy against HBV within the previous 6 months; treatment with any investigational drug within 30 days of entry to this protocol Severe hepatitis activity as documented by ALT > 10 x ULN Advanced liver disease Pre-existent leucopenia or thrombopenia Co-infection with HCV,HDV or HIV Other acquired or inherited causes of liver disease Alpha fetoprotein > 50 ng/ml. Evidence of severe renal disease Hyper- or hypothyroidism Significant cardiovascular or pulmonary dysfunction, malignancy,immunodeficiency syndromes Immune suppressive treatment within the previous 6 months Contra-indications for alpha-interferon therapy Pregnancy, breast-feeding Any medical condition requiring chronic systemic administration of steroids Substance alcohol or drug abuse Subjects with clinically significant retinal abnormalities Subjects with clinically significant hearing abnormalities Hemoglobinopathies Subjects with known hypersensitivity to ribavirin

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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

Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Ribavirin + Peg IFN | Drug: Ribavirin<br>* 1200 mg a day, 48 weeks<br>|
| Active Comparator: 2<br>Peg IFN + Placebo | Drug: Peginterferon alpha 2a<br>* 180 µg per week, 48 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The combined presence of HBV DNA level < 10E4 copies/ml and ALT normalization at the end of follow-up |  | may 2008 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ALT normalization |  | May 2008 | 
| HBV DNA negativity(undetectable by Taqman PCR) |  | May 2008 | 
| HBsAg loss from serum |  | May 2008 | 
| Improvement liver histology |  | May 2008 | 
| Combined virological, biochemical and histological response |  | May 2008 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HBeAg-negative, chronic, hepatitis B, viral