A Study of PEGASYS (Peginterferon Alfa-2a (40KD)) in Patients With 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 PEGASYS (peginterferon alfa-2a) in patients with HBeAg positive chronic hepatitis B. Patients will be stratified into group A (treatment naïve patients) or B (YMDD mutant patients). All patients will receive PEGASYS 180 micrograms subcutaneously once weekly for 48 weeks, followed by 24 weeks of treatment-free follow up.

Official Title
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An Open Label Phase IV Multicenter Study for Efficacy and Safety of Peginterferon Alfa-2a (40KD) (PEGASYS®) 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, 18-65 years of age HBsAg +ve for more than 6 months, HBeAg +ve, AntiHBs -ve Detectable hepatitis B virus (HBV) DNA (>100,000 copies/mL) Exclusion Criteria: Coinfection with hepatitis A, hepatitis C or human immunodeficiency virus (HIV) Evidence of decompensated liver disease 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PEG-IFN alfa-2a (Treatment naïve)<br>Eligible treatment naïve participants received peginterferon alfa-2a (PEGASYS) 180 micrograms (mcg) subcutaneously (SC) once weekly for 48 weeks, followed by 24 weeks of treatment-free follow-up. | Drug: peginterferon alfa-2a [Pegasys]<br>* Peginterferon alfa-2a (Pegasys) 180 mcg subcutaneously once a week for 48 weeks<br>|
| Experimental: PEG-IFN alfa-2a (YMDD mutant)<br>Eligible tyrosine-methionine-aspartate-aspartate (YMDD) mutant participants received PEGASYS 180 mcg SC once weekly for 48 weeks, followed by 24 weeks of treatment-free follow- up. Participants received lamivudine concomitantly for the initial 12 weeks. | Drug: peginterferon alfa-2a [Pegasys]<br>* Peginterferon alfa-2a (Pegasys) 180 mcg subcutaneously once a week for 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 B Virus DNA <100,000 Copies/mL At Week 72 | Participants who had Hepatitis B Virus Deoxyribonucleic Acid (HBV-DNA) levels below 100,000 copies per milliliter (mL) at the end of follow-up (EOF) period (24 weeks after the end of treatment) were classified as responders. | Week 72 | 
| Percentage of Participants With Hepatitis B Virus e Antigen Loss At Week 72 | Participants with loss of hepatitis B virus e antigen (HBeAg) at the EOF period (24 weeks after the end of treatment) were classified as responders. | Week 72 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With ALT Normalization At Week 48 and Week 72 | Participants with ALT less than the upper limit of normal (ULN) at end of treatment (EOT) and EOF period were responders. | Week 48 and Week 72 | 
| Percentage of Participants With Hepatitis B Virus DNA Below the Limit of Detection At Week 48 and Week 72 | Participants with HBV-DNA below the limit of detection i.e. <174 copies/mL at EOT and EOF period were responders. | Week 48 and Week 72 | 
| Percentage of Participants With a Combined Response At Week 48 and Week 72 | A responder with Combined Response was a participant with HBV-DNA<100,000 copies/mL, HBeAg seroconversion (i.e. loss of HBeAg and presence of anti-HBe) and ALT normalization at EOT and EOF period. | Week 48 and Week 72 | 
| Percentage of Participants With Hepatitis B Virus e Antigen Seroconversion | A responder was a participant with loss of HBeAg and presence of anti-HBe at EOT and EOF period. | Week 48 and Week 72 | 
| Percentage of Participants With Loss of Hepatitis B Surface Antigen At Week 48 and Week 72 | A responder was a participant who were analysed with loss of Hepatitis B Surface Antigen (HBsAg) at EOT and EOF period. | Week 48 and Week 72 | 
| Percentage of Participants With Hepatitis B Surface Antigen Seroconversion At Week 48 and Week 72 | A responder was a participant with loss of HBsAg and presence of anti-HBs at EOT and EOF period. | Week 48 and Week 72 | 
| Number of Participants With Any Adverse Events and Any Serious Adverse Events | An adverse event (AE) was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started. An adverse event was therefore any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A Serious Adverse Events (SAE) is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect. Participants with any AEs and any SAEs have been presented. | Up to Week 72 |