A Study of 48 Versus 96 Weeks of Peginterferon Alfa-2a [Pegasys] Treatment, With or Without Entecavir, in Patients With Chronic Hepatitis B.

Study Overview
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Brief Summary
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This randomized, 2 x 2 factorial, parrallel group study will compare the efficacy and safety of 48 versus 96 weeks of peginterferon alfa-2a [Pegasys], with or without entecavir, in patients with HbeAg negative chronic hepatitis B. Patients will be randomly allocated to receive Pegasys (180mcg subcutaneously weekly) for 48 weeks plus placebo (group A) or entecavir (0,5mg orally daily, group B) during weeks 12-36, or Pegasys (180mcg subcutaneously weekly) for 96 weeks plus placebo (group C) or entecavir (group D) during weeks 12-36. Anticipated time on study treatment is 48 or 96 weeks, with a follow-up of 48 weeks. Target sample size is <500 patients.

Official Title
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A Phase IV, 2x2 Factorial, Double Blind Study of 48 Versus 96 Weeks of PEGASYS 180µg, With or Without 24 Weeks of Entecavir in Adult Patients With HBeAg Negative Chronic Hepatitis B.

Conditions
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Hepatitis B, Chronic

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients, >/= 18 years of age chronic hepatitis B for >/= 6 months HBeAg negative at screening adequate renal function Exclusion Criteria: antiviral therapy for chronic hepatitis B within the previous 6 months hepatitis A, C, D or HIV infection treatment with systemic acyclovir or famciclovir within the previous 6 months decompensated liver disease (Childs B-C) history or evidence of a medical condition associated with chronic liver disease

Ages Eligible for Study
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Minimum Age: 18 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: Factorial Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: A<br> | Drug: peginterferon alfa-2a [Pegasys]<br>* 180 mcg sc weekly, 48 weeks<br>Drug: placebo<br>* orally daily, 24 weeks (weeks 12-36)<br>|
| Experimental: B<br> | Drug: entecavir<br>* 0.5 mg orally daily, 24 weeks (weeks 12-36)<br>Drug: peginterferon alfa-2a [Pegasys]<br>* 180 mcg sc weekly, 48 weeks<br>|
| Placebo Comparator: C<br> | Drug: peginterferon alfa-2a [Pegasys]<br>* 180 mcg sc weekly, 96 weeks<br>Drug: placebo<br>* orally daily, 24 weeks (weeks 12-36)<br>|
| Experimental: D<br> | Drug: entecavir<br>* 0.5 mg orally daily, 24 weeks (weeks 12-36)<br>Drug: peginterferon alfa-2a [Pegasys]<br>* 180 mcg sc weekly, 96 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy: HBV-DNA reduction to <10,000 copies/ml (<2,000 IU/ml) |  | 48 weeks after the end of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation early HBsAg response - response end of treatment/follow-up |  | every 6 weeks up to week 48, every 12 weeks therafter |