Analysis of HBV-Specific Immune Response in Patients With HBeAg Negative Chronic Hepatitis B Treated With Pegasys (Peginterferon Alfa-2a (40KD)) - Immunology Sub-Study of ML18253

Study Overview
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Brief Summary
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This study will evaluate immune responses in patients with HBeAg-negative chronic Hepatitis B treated with Pegasys (peginterferon alfa-2a). Eligible patients will have been randomized in study ML18253 to receive Pegasys 180 mcg subcutaneously for 48 or 96 weeks. Sample collection period for each patients will occur in the first 24 weeks.

Official Title
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Longitudinal Analysis of HBV-specific T Cell Responses in Patients With HBeAg-negative Chronic Hepatitis B (CHB) Treated With Pegylated Interferon Alfa-2a (40 KD) (Pegasys - RO258310). Immunology Sub-study of ML18253

Conditions
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Hepatitis B, Chronic

Intervention / Treatment
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* Drug: peginterferon alfa-2a [Pegasys]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients 18-55 years of age Chronic HBeAg negative hepatitis B Liver disease consistent with chronic hepatitis documented by liver biopsy within 18 months prior to enrollment Participation in study ML18253. Exclusion Criteria: Interferon-based or any systemic anti-HBV therapy </= 12 months prior to first dose of study drug Antiviral, anti-neoplastic, or immunomodulatory treatment </= 12 months prior to first dose of study drug Nonresponders to previous interferon therapy and resistant to lamivudine Co-infection with hepatitis A, C or D, or with human immunodeficiency virus (HIV) Hepatocellular cancer Compensated (Child A, score 6) or decompensated liver disease (Child B or C) History or evidence of medical condition associated with chronic liver disease other than HBV

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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: peginterferon alfa-2a [Pegasys]<br>* 180 mcg sc weekly<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CD4 and CD8 mediated immune response: Interferon-y (ELISPOT analysis, flow cytometry) |  | 24 weeks | 
| CD4 and CD8 mediated immune response: Interleukin-2 production (Flow cytometry) |  | 24 weeks | 
| CD4 and CD8 mediated immune response: Cytokine profile analysis by supernatant culture |  | 24 weeks | 
| CD4 and CD8 mediated immune response: Proliferative response upon T-cell stimulation |  | 24 weeks | 
| CD8 response in HLA-A2 positive patients |  | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Profile of proinflammatory cytokines: analysis of cytokines in serum |  | 24 weeks | 
| HBV viremia (HBV RNA assessed by COBAS PaqMan HCV test) |  | 24 weeks |