A Study of PEGASYS (Peginterferon Alfa-2a (40KD)) Plus Entecavir in Treatment-Naive Patients With HBeAg-Positive Chronic Hepatitis B.

Study Overview
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Brief Summary
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This 3 arm study will assess the efficacy and safety of PEGASYS + entecavir combination therapy in treatment-naive patients with HBeAg positive chronic hepatitis B. Patients will be randomized to receive 1)PEGASYS 180 micrograms s.c./week for 48 weeks, 2)PEGASYS 180 micrograms s.c./week for 48 weeks + entecavir 0.5mg p.o. once daily from week 13 to week 36 or 3) entecavir 0.5mg p.o. once daily for 24 weeks + PEGASYS 180 micrograms s.c./week from week 21 to 68. Treatment will be followed by 24 weeks treatment-free follow up. The anticipated time on study treatment is 3-12 months for groups 1 and 2, and 1-2 years for group 3, and the target sample size is 100-500 individuals.

Official Title
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A Randomized, Open Label Study of the Effect of Peginterferon Alfa-2a (40KD) (PEGASYS®) Plus Entecavir (Baraclude®) Combination Therapy on Quantitative Changes in HBeAg in Treatment-naive Patients With HBeAg Positive Chronic Hepatitis B

Conditions
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Hepatitis B, Chronic

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients, 18-65 years of age; HBsAg positive, HBeAg positive and anti-HBe negative for at least 6 months, anti-HBs negative; absence of cirrhosis confirmed by liver biopsy in previous 12 months. Exclusion Criteria: previous treatment for chronic hepatitis B within previous 6 months; antiviral, anti-neoplastic or immunomodulatory treatment in previous 6 months; co-infection with active hepatitis A, hepatitis C, hepatitis D or HIV; history or other evidence of a medical condition associated with chronic liver disease other than viral hepatitis.

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: 1<br> | Drug: peginterferon alfa-2a [Pegasys]<br>* 180 micrograms sc/week for 48 weeks<br>|
| Experimental: 2<br> | Drug: Entecavir<br>* 0.5mg po daily from week 13 to week 36<br>Drug: peginterferon alfa-2a [Pegasys]<br>* 180 micrograms sc/week for 48 weeks<br>|
| Experimental: 3<br> | Drug: Entecavir<br>* 0.5mg po daily for 24 weeks<br>Drug: peginterferon alfa-2a [Pegasys]<br>* 180 micrograms sc/week from week 21 to week 68<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Log change in quantitative HBeAg from baseline to 24 weeks after end of treatment. |  | Week 72 for Arms 1 and 2. Week 92 for Arm 3. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HBeAg seroconversion, HBV-DNA <1000 copies/mL, loss of HBeAg, HBV DNA reduction, ALT normalization, loss of HBsAg seroconversion, reduction of HBsAg 24 weeks after end of treatment. |  | Week 72 for Arms 1 and 2. Week 92 for Arm 3. | 
| AEs, laboratory parameters. |  | Throughout study |