ADVANCE Study: A Study of PEGASYS (Peginterferon Alfa-2a (40KD)) + Adefovir Dipivoxil in Patients With Hbe(-) Chronic Hepatitis B

Study Overview
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Brief Summary
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This 3 arm study will compare the efficacy and safety of combination therapy with PEGASYS + adefovir dipivoxil (ADV) versus PEGASYS monotherapy, in HBeAg-negative chronic hepatitis B patients.Patients will be randomized to receive 1)PEGASYS 180 micrograms sc weekly + ADV 10mg po daily for 48 weeks, followed by ADV 10mg po monotherapy for an additional 48 weeks, and a further 48 week treatment-free follow-up, 2)PEGASYS 180 micrograms sc weekly + ADV 10mg po daily for 48 weeks, followed by a 96 week treatment-free follow-up, or 3)PEGASYS 180 micrograms sc monotherapy weekly for 48 weeks, followed by a 96 week treatment-free follow-up. The anticipated time on study treatment is 1-2 years, and the target sample size is <100 individuals.

Official Title
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A Randomized, Open Label Study to Compare the Effect of Combination Treatment With PEGASYS + Adefovir Dipivoxil Versus PEGASYS Monotherapy on HBV-DNA and ALT Levels in Patients With HBeAg-negative, Chronic Hepatitis B.'

Conditions
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Hepatitis B, Chronic

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients, 18-70 years of age; chronic hepatitis B; positive HBsAg, positive anti-HBe, negative anti HBsAg, negative HBeAg for at least the prior 6 months; either nucleoside analogue naive, or has not received IFN-a in the past 6 months. Exclusion Criteria: positive for hepatitis A, C, D or HIV; history or other evidence of a medical condition associated with chronic liver disease other than hepatitis B; antiviral, antineoplastic or immunomodulatory treatment <=6 months prior to first dose of randomized treatment.

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

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: adefovir dipivoxil<br>* 10mg po daily for 96 weeks (arm 1) or 48 weeks (arm 2)<br>Drug: peginterferon alfa-2a [Pegasys]<br>* 180 micrograms weekly for 48 weeks<br>|
| Experimental: 2<br> | Drug: adefovir dipivoxil<br>* 10mg po daily for 96 weeks (arm 1) or 48 weeks (arm 2)<br>Drug: peginterferon alfa-2a [Pegasys]<br>* 180 micrograms weekly for 48 weeks<br>|
| Active Comparator: 3<br> | Drug: peginterferon alfa-2a [Pegasys]<br>* 180 micrograms weekly for 48 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Normalization of ALT, and HBV-DNA <400 copies/mL |  | Week 96 for arm 1; week 48 for arms 2 and 3 | 
| HBsAg quantitative loss and anti-HBs seroconversion |  | Weeks 48, 96 and 144 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AEs, lab parameters, vital signs |  | Throughtout study |