A Study of PEGASYS (Peginterferon Alfa-2a (40KD)) in Patients With Hepatitis Be Antigen (HBeAg) Positive Chronic Hepatitis B (CHB).

Study Overview
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Brief Summary
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This 4 arm study will compare the efficacy and safety of PEGASYS given for 24 or 48 weeks, and at doses of 90 or 180 micrograms weekly, in the treatment of HBeAg positive patients with chronic hepatitis B. Patients will be randomized to one of 4 treatment groups: a)PEGASYS 90 micrograms subcutaneous (sc) weekly for 24 weeks, b)PEGASYS 180 micrograms sc weekly for 24 weeks, c)PEGASYS 90 micrograms sc weekly for 48 weeks or d)PEGASYS 180 micrograms sc weekly for 48 weeks. Following treatment there will be a 24 week period of treatment-free follow-up in all treatment groups for the primary endpoint. The anticipated time on study treatment is 3-12 months, and the target sample size is 500+ individuals.

Official Title
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A Randomized, Double-blind Study of the Effect of Treatment Duration and Dose of PEGASYS on HBeAg Seroconversion and Safety in Patients With HBeAg Positive Chronic Hepatitis B.

Conditions
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Hepatitis B, Chronic

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients, >=18 years of age; positive Hepatitis B surface antigen (HBsAg) for >6 months, positive HBeAg, HBV DNA >500,000 copies/mL, and anti-HBs negative; liver disease consistent with Chronic Hepatitis B. Exclusion Criteria: antiviral therapy for CHB within previous 6 months; co-infection with Hepatitis A virus (HAV), Hepatitis C virus (HCV), Hepatitis D virus (HDV) or Human immuno deficiency virus (HIV); evidence of decompensated liver disease; 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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: peginterferon alfa-2a 90 μg_24 Weeks<br>Participants received 90 micrograms (μg) peginterferon alfa-2a subcutaneous once a week for 24 weeks. | Drug: peginterferon alfa-2a [Pegasys]<br>* 90 or 180 micrograms subcutaneous weekly for 24 weeks or 48 weeks.<br>|
| Experimental: peginterferon alfa-2a 180 μg_24 Weeks<br>Participants received 180 μg peginterferon alfa-2a subcutaneous once a week for 24 weeks. | Drug: peginterferon alfa-2a [Pegasys]<br>* 90 or 180 micrograms subcutaneous weekly for 24 weeks or 48 weeks.<br>|
| Experimental: peginterferon alfa-2a 90 μg_48 Weeks<br>Participants received 90 μg peginterferon alfa-2a subcutaneous once a week for 48 weeks. | Drug: peginterferon alfa-2a [Pegasys]<br>* 90 or 180 micrograms subcutaneous weekly for 24 weeks or 48 weeks.<br>|
| Experimental: peginterferon alfa-2a 180 μg_48 Weeks<br>Participants received 180 μg peginterferon alfa-2a subcutaneous once a week for 48 weeks. | Drug: peginterferon alfa-2a [Pegasys]<br>* 90 or 180 micrograms subcutaneous weekly for 24 weeks or 48 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Hepatitis Be Antigen (HBeAg) Seroconversion 24 Weeks Following End of Treatment | Blood was collected for HBeAg. HBeAg seroconversion was defined as the absence of HBeAg (a negative result for HBeAg) and the presence of anti-HBe (a positive result for anti-HBe) determined at 24 weeks after the end of treatment. | 24 Weeks following end of treatment (Week 48 for 24 Week Treatment or Week 72 for 48 Week Treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Hepatitis Be Antigen (HBeAg) Seroconversion at Week 72 | Blood was collected for HBeAg. HBeAg seroconversion was defined as the absence of HBeAg (a negative result for HBeAg) and the presence of anti-HBe (a positive result for anti-HBs) determined at Week 72. | Week 72 | 
| Percentage of Participants With Loss of Hepatitis Be Antigen (HBeAg) 24 Weeks Following End of Treatment | Blood was collected HBeAg 24 Weeks following the end of treatment. Loss of HBeAg is defined as the absence of HBeAg. | 24 Weeks following end of treatment (Week 48 for 24 Week Treatment or Week 72 for 48 Week Treatment) | 
| Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Seroconversion 24 Weeks Following the End of Treatment | HBsAg seroconversion was defined as the absence of HBsAg (a negative result for HBsAg) and the presence of anti-HBs (a positive result for anti-HBs) determined at 24 weeks after the end of treatment. | 24 Weeks following end of treatment (Week 48 for 24 Week Treatment or Week 72 for 48 Week Treatment) | 
| Percentage of Participants With Loss of Hepatitis B Surface Antigen (HBsAg) 24 Weeks Following End of Treatment | Blood was collected for HBsAg 24 weeks following the end of treatment. Loss of HBsAg is defined as the absence of HBsAg. | 24 Weeks following end of treatment (Week 48 for 24 Week Treatment or Week 72 for 48 Week Treatment) | 
| Percentage of Participants With Normal Alanine Aminotransferase (ALT) | Blood was collected 24 weeks following the end of treatment for ALT and was analyzed at a local laboratory. A normal ALT is a value within the normal range of the assay. | 24 Weeks following end of treatment (Week 48 for 24 Week Treatment or Week 72 for 48 Week Treatment) | 
| Percentage of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV-DNA) Suppression < 20,000 IU/mL 24 Weeks Following End of Treatment | Blood was collected for HBV-DNA 24 weeks following the end of treatment and was analyzed at the central laboratory using the Roche approved polymerase chain reaction (PCR) methodology. Percentage of participants with a HBV-DNA suppression of < 20,000 IU/mL (Less than 100,000 copies/mL) is reported. | 24 Weeks following end of treatment (Week 48 for 24 Week Treatment or Week 72 for 48 Week Treatment) | 
| Percentage of Participants With Hepatitis Deoxyribonucleic Acid (HBV-DNA) Suppression < 2,000 IU/mL 24 Weeks Following End of Treatment | Blood was collected for HBV-DNA and was analyzed at the central laboratories using the Roche approved PCR methodology 24 weeks following the end of treatment. Percentage of participants with A HBV-DNA Suppression of < 2,000 IU/mL (Less than 10,000 copies/mL) is reported. | 24 Weeks following end of treatment (Week 48 for 24 Week Treatment of Week 72 for 48 Week Treatment) | 
| Percentage of Participants With Combined Endpoint Response 24 Weeks Following End of Treatment | Combined endpoint was defined as HBeAg seroconversion, a normal serum ALT and HBV-DNA suppression below 20,000 IU/mL. | 24 Weeks following end of treatment (Week 48 for 24 Week Treatment or Week 72 for 48 Week Treatment) | 
| Percentage of Participants With Dual Endpoint Response 24 Weeks Following End of Treatment | Dual endpoint was defined as the achievement of both HBeAg seroconversion and a HBV-DNA <2,000 IU/ml (Less than 10,000 copies/mL). | 24 Weeks following end of treatment (Week 48 for 24 Week Treatment or Week 72 for 48 Week Treatment) | 
| Quantitative Serum Alanine Aminotransferase (ALT) 24 Weeks Following End of Treatment | Blood was collected 24 weeks following the end of treatment for ALT and was analyzed at a local laboratory. A normal ALT is a value within the normal range of the assay: 0- 55 units/liter (U/L). | 24 Weeks following end of treatment (Week 48 for 24 Week Treatment or Week 72 for 48 Week Treatment) | 
| Quantitative HBV-DNA 24 Weeks Following End of Treatment | Blood was collected for HBV-DNA and was analyzed at the central laboratories using the Roche approved PCR methodology 24 weeks following the end of treatment. | 24 Weeks following end of treatment (Week 48 for 24 Week Treatment or Week 72 for 48 Week Treatment) |