A Study of Early Immunologic Response in Asian Patients With Chronic Hepatitis B, Treated With Pegasys (Peginterferon Alfa-2a (40KD)), Nucleoside Analogues, or Both

Study Overview
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Brief Summary
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This open-label, randomized, parallel-arm study will assess the early immunologic response in treatment-naïve Asian male patients with chronic hepatitis B after initiation of treatment with Pegasys or tenofovir or Pegasys plus tenofovir. Patients will be randomized to one of 4 cohorts to receive either Pegasys (360mcg subcutaneously weekly) or tenofovir (300mg orally daily) or both or no treatment for 2 weeks. After 2 weeks on study treatment, patients may opt to receive standard of care treatment with Pegasys. Target sample size is <50.

Official Title
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An Open-label, Randomized Study to Evaluate the Acute Immunologic Responses in Asian Subjects With E Antigen Positive Chronic Hepatitis B Following Initiation of Therapy for Hepatitis B With Pegasys, Nucleoside Analogues, or Both.

Conditions
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Hepatitis B, Chronic

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: male adults of Southeast and/or East Asian origin, 18-55 years of age HBeAg-positive chronic hepatitis B detectable HBV DNA Exclusion Criteria: prior antiviral therapy for chronic hepatitis B evidence of bridging fibrosis, cirrhosis or decompensated liver disease positive test at screening for HAV (IgM), HCV, HDV or HIV history or evidence of medical condition associated with chronic liver disease antineoplastic or immunomodulatory treatment </=6 months prior to first dose of study drug

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

Sexes Eligible for Study
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Male

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 |
| --- | --- |
| Active Comparator: 1<br> | Drug: tenofovir<br>* 300mg po daily for 2 weeks<br>|
| Experimental: 2<br> | Drug: peginterferon alfa-2a [Pegasys]<br>* 360 micrograms sc/week for 2 weeks<br>Drug: tenofovir<br>* 300mg po daily for 2 weeks<br>|
| Experimental: 3<br> | Drug: peginterferon alfa-2a [Pegasys]<br>* 360 micrograms sc/week for 2 weeks<br>|
| No Intervention: 4<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Viral Quantitative e Antibody | An acute virologic response was determined by change from baseline in viral antigen/antibody laboratory data. | Day 1, 3, 5, 8, 10, 14, Week 3, 4, 5, 6 (weeks are computed from the first dose of Pegasys) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in HBV-DNA log10 | An acute virologic response was determined by change from baseline in HBV-DNA log10. | Day 1, 3, 5, 8, 10, 14, Week 3, 4, 5, 6 (weeks are computed from the first dose of Pegasys) | 
| Early Changes in Viral Sequence Associated With Viral Suppression | Viral sequence data was obtained from the first 10 participants enrolled in Study but on analysis of the data, numerous low frequency deviations from the HBV consensus sequences were observed in the 454 SLX sequence data which were not replicated in data obtained from routine Sanger sequencing. These sequence deviations did not correspond to a temporal pattern consistent with selection of mutations following HBV treatment. Moreover, they could not be reliably distinguished from sequencing artifacts. It was also revealed that complete genome coverage was not obtained due to errors in the design of the primer sequences. For these reasons, further sequence analyses were not performed for the remaining treatment population. | Day 1, 5, 14, Week 4 and 6 |