A Study to Evaluate Efficacy and Safety of Peginterferon Alfa-2a (Pegasys) and Adeforvir Dipivoxil (ADV) in Participants With Lamivudine-Resistant Hepatitis B e Antigen (HBeAg)-Positive Chronic Hepatitis B

Study Overview
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Brief Summary
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This study will evaluate the efficacy and safety of peginterferon alfa-2a or ADV, in participants with lamivudine-resistant HBeAg-positive chronic hepatitis B. Participants will be randomized to receive either peginterferon alfa-2a for 48 weeks in combination with oral lamivudine for the first 12 weeks, or ADV for 72 weeks in combination with oral lamivudine for the first 12 weeks. The anticipated time on study treatment is 72 weeks, and the target sample size is 255 individuals.

Official Title
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A Randomized, Open-label Study Evaluating the Efficacy and Safety of Peginterferon Alfa-2a (40KD) (PEGASYS®) or Adefovir Dipivoxil (ADV) in Patients With Lamivudine-resistant HBeAg Positive Chronic Hepatitis B

Conditions
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Hepatitis B, Chronic

Intervention / Treatment
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* Drug: Adefovir dipivoxil
* Drug: Lamivudine
* Drug: Peginterferon alfa-2a


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult participants 18-65 years of age Hepatitis B surface antigen (HBsAg)-positive, HBeAg-positive, and anti-HBs-negative for greater than or equal to (>=) 6 months Receiving lamivudine currently, and for >=6 months hepatitis B virus (HBV)-deoxyribonucleic acid (DNA) decreased >=2 log during lamivudine treatment on >=1 occasion Absence of cirrhosis confirmed by liver biopsy in previous 6 months Exclusion Criteria: Other drugs with activity against HBV within the prior 6 months, except lamivudine Antiviral, anti-neoplastic, or immunomodulatory therapy less than or equal to (<=) 6 months before study - Active infection with hepatitis A, C, or D virus, or human immunodeficiency virus Decompensated liver disease Medical condition associated with another chronic liver disease

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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 |
| --- | --- |
| Active Comparator: ADV + Lamivudine<br>Participants will receive ADV and lamivudine tablets at a dose of 10 mg orally QD for first 12 weeks followed by ADV for 60 weeks. | Drug: Adefovir dipivoxil<br>* ADV will be administered orally at a dose of 10 mg QD for 72 weeks.<br>Drug: Lamivudine<br>* Lamivudine tablets will be administered orally at a dose of 10 mg QD for 12 weeks.<br>|
| Experimental: Peginterferon alfa-2a + Lamivudine<br>Participants will receive peginterferon alfa-2a injection at a dose of 180 micrograms (mcg) once weekly (QW) and 100 milligrams (mg) lamivudine tablets orally once daily (QD) for first 12 weeks followed by peginterferon alfa-2a for 36 weeks. | Drug: Lamivudine<br>* Lamivudine tablets will be administered orally at a dose of 10 mg QD for 12 weeks.<br>Drug: Peginterferon alfa-2a<br>* Peginterferon alfa-2a injection will be administered at a dose of 180 mcg QW for 48 weeks.<br>* Other names: Pegasys;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HBeAg seroconversion (defined as loss of HBeAg and presence of anti-HBe) at Week 72 |  | Week 72 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Loss of HBeAg |  | Week 48, and 72 | 
| Reduction in hepatitis B virus deoxyribonucleic acid (HBV DNA) |  | Week 48, and 72 | 
| Alanine transaminase (ALT) normalization |  | Week 48, and 72 | 
| Hepatitis B surface antigen (HBsAg) seroconversion |  | Week 48, and 72 |