A Study of PEGASYS (Peginterferon Alfa-2a (40KD)) in Combination With Adefovir or Entecavir in 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 alone, or in combination with Adefovir or Entecavir in patients with HBeAg positive chronic hepatitis B. Patients will be randomized to receive 1)PEGASYS 180 micrograms sc weekly for 48 weeks + placebo from weeks -4 to 2;2)PEGASYS 180 micrograms sc weekly for 48 weeks + Adefovir from weeks -4 to 2; or 3)PEGASYS 180 micrograms sc weekly for 48 weeks + Entecavir from weeks -4 to 2. Treatment will be followed by 24 weeks of treatment-free follow-up.The anticipated time on study treatment is 1 year, 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) in Combination With Adefovir or Entecavir on HBeAg Seroconversion in Patients With HBeAg Positive Chronic Hepatitis B

Conditions
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Hepatitis B, Chronic

Intervention / Treatment
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* Drug: Adefovir
* Drug: Entecavir
* Drug: Placebo
* 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; HBeAg+ve for >=3 months; positive serum HBV DNA within 3 months prior to entry; patients with chronic hepatitis B, either naive to HBV treatment, or not responded/relapsed to nucleoside analogues; >=3 months treatment-free interval from nucleotide analogues. Exclusion Criteria: evidence of decompensated liver disease; history or other evidence of a medical condition associated with chronic liver disease othr than viral hepatitis; co-infection with active hepatitis A,C or D, or HIV.

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: Adefovir<br>* From week -4 to week 2<br>Drug: peginterferon alfa-2a [Pegasys]<br>* 180 micrograms sc weekly, from week 1-48<br>|
| Experimental: 2<br> | Drug: Entecavir<br>* From week -4 to week 2<br>Drug: peginterferon alfa-2a [Pegasys]<br>* 180 micrograms sc weekly, from week 1-48<br>|
| Placebo Comparator: 3<br> | Drug: Placebo<br>* From week -4 to week 2<br>Drug: peginterferon alfa-2a [Pegasys]<br>* 180 micrograms sc weekly, from week 1-48<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Hepatitis B e-Antigen (HBeAg) Seroconversion at 100 Weeks After Start of Treatment | HBeAg seroconversion was defined as the absence of HBeAg (a negative result for HBeAg) and the presence of hepatitis B e-antibody (anti-HBe/HBeAb) (a positive result for anti-HBe). | Week 100 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) Levels at Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, and 100 | HBV DNA (copies per milliliter [copies/mL]) represented the viral load for Hepatitis B Virus (HBV), and was considered an indicator of viral replication. | Baseline, Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, and 100 | 
| Percentage of Participants Who Were HBeAg Negative |  | Baseline, Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, and 100 | 
| Percentage of Participant Who Were Both Hepatitis B Surface Antigen (HBsAg) Negative and Hepatitis B Surface Antibody (Anti-HBs/HBsAb) Positive |  | Baseline, Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, and 100 | 
| Percentage of Participant With Normal Alanine Aminotransferase (ALT) Levels | The normal range for ALT is 10 to 40 international units per liter (IU/L). | Baseline, Weeks 6, 12, 16, 22, 28, 34, 40, 46, 52, 64, 76, 88, and 100 | 
| Change From Baseline in HBsAg Levels at Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, and 100 |  | Baseline, Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, and 100 | 
| Percentage of Participants With Combined Response | Combined response was defined as having negative HBeAg, HBV DNA less than (<) 100,000 copies/mL, and normal ALT level (10-40 IU/L). | Baseline, Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, and 100 |