A Study of the Safety and Efficacy of Pegylated Inferferon Alfa-2b (PEG-Intron™) Versus Pegylated Interferon Alfa-2a (PEGASYS™) in Participants With Chronic Hepatitis B (P08450)

Study Overview
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Brief Summary
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This study is being done to compare the safety and efficacy of PEG-Intron™ to that of PEGASYS™ in participants with chronic hepatitis B (hepatitis B envelope antigen [HBeAg] positive or negative) who have not previously been treated with interferon.

Official Title
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A Multicenter Open-label Study to Evaluate the Safety and Efficacy of PEG-Intron™ Versus PEGASYS™ in Subjects With HBeAg Positive Chronic Hepatitis B and HBeAg Negative Chronic Hepatitis B Protocol No. MK-4031-376-00 (Also Known as SCH 054031, P08450)

Conditions
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Hepatitis B, Chronic

Intervention / Treatment
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* Biological: PEG-Intron™
* Biological: PEGASYS™


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must be able to adhere to dose and visit schedules ≥ 40 kg Hepatitis B surface antigen (HBsAg) positive for at least 6 months Anti-HBs negative Female participants of childbearing potential must agree to use an acceptable method of contraception from at least 2 weeks prior to Day 1 and continue until at least 1 month after last dose of study drug Inclusion Criteria for HBeAg(+) participants: HBeAg(+) Anti-HBe(-) Inclusion Criteria for HBeAg(-) participants: HBeAg(-) Anti-HBe(+) Exclusion Criteria: Co-infection with the human immunodeficiency virus (HIV) or hepatitis C or hepatitis D virus Prior treatment with interferon for hepatitis B Use of nucleoside/nucleotide analogues within 6 months of the screening visit or at any time during the study Use of any investigational drug within 30 days of the screening visit Prior treatment with herbal remedies with known hepatotoxicity. All herbal remedies used for hepatitis B treatment must be discontinued before Day 1 Evidence of decompensated liver disease including, but not limited to, a history or presence of clinical ascites, bleeding varices, or hepatic encephalopathy Diabetic and/or hypertensive with clinically significant ocular examination findings History of stroke or transient ischemic attack Immunologically mediated disease (e.g., inflammatory bowel disease [Crohn's disease, ulcerative colitis], celiac disease, rheumatoid arthritis, idiopathic thrombocytopenic purpura, systemic lupus erythematosus, autoimmune hemolytic anemia, scleroderma, sarcoidosis, severe psoriasis requiring oral or injected treatment, or symptomatic thyroid disorder) Chronic pulmonary disease (e.g., chronic obstructive pulmonary disease, interstitial lung disease, pulmonary fibrosis, sarcoidosis) Current or history of any clinically significant cardiac abnormalities/dysfunction Any medical condition requiring, or likely to require, chronic systemic administration of corticosteroids during the course of the trial Myelodysplastic syndromes Organ transplants (including hematopoietic stem cell transplants) other than cornea and hair Pregnant or nursing, or intending to become pregnant during the trial period

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HBeAg(+) PEG-Intron<br>HBeAg-positive participants receive 1.5 mcg/kg/wk PEG-Intron subcutaneously (SC) once weekly for 48 weeks. | Biological: PEG-Intron™<br>* PEG-Intron subcutaneously (SC) once weekly for a total of 48 weeks<br>* Other names: Pegylated interferon alfa-2b;|
| Active Comparator: HBeAg(+) PEGASYS<br>HBeAg-positive participants receive 180 mcg/kg/wk PEGASYS SC once weekly for 48 weeks. | Biological: PEGASYS™<br>* PEGASYS subcutaneously (SC) once weekly for a total of 48 weeks<br>* Other names: Pegylated interferon alfa-2a;|
| Experimental: HBeAg(-) PEG-Intron<br>HBeAg-negative participants receive 1.5 mcg/kg/wk PEG-Intron SC once weekly for 48 weeks. | Biological: PEG-Intron™<br>* PEG-Intron subcutaneously (SC) once weekly for a total of 48 weeks<br>* Other names: Pegylated interferon alfa-2b;|
| Active Comparator: HBeAG(-) PEGASYS<br>HBeAg-negative participants receive 180 mcg/kg/wk PEGASYS SC once weekly for 48 weeks. | Biological: PEGASYS™<br>* PEGASYS subcutaneously (SC) once weekly for a total of 48 weeks<br>* Other names: Pegylated interferon alfa-2a;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of HBeAg(+) Participants Achieving HBeAg Seroconversion at 24 Weeks Post-treatment | Blood samples were drawn to assess the participant's seroconversion status at Follow-up (FU) Week 24. HBeAg seroconversion was defined as loss of HBeAg in HBeAg(+) participants and development of antibody to HBeAg. | FU Week 24 (Study Week 72) | 
| Percentage of HBeAg(-) Participants Achieving Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels <2000 IU/mL at 24 Weeks Post-treatment | The Roche COBAS TaqMan HBV-(High Pure System Assay) was used to measure HBV DNA in blood samples of HBeAg(-) participants. The percentage of HBeAg(-) participants with HBV DNA <2000 IU/mL at 24 weeks post-treatment was reported. | FU Week 24 (Study Week 72) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of HBeAg(+) Participants Achieving HBV DNA <2000 IU/mL at 24 Weeks Post-treatment | The Roche COBAS TaqMan HBV-(High Pure System Assay) was used to measure HBV DNA in blood samples of HBeAg(+)participants. The percentage of HBeAg(+) participants with HBV DNA <2000 IU/mL at 24 weeks post-treatment was reported. | FU Week 24 (Study Week 72) | 
| Percentage of HBeAg(+) and HBeAg(-) Participants Achieving Alanine Aminotransferase (ALT) Normalization at 24 Weeks Post-treatment | ALT normalization is a desired goal of HBV treatment, which is defined as having abnormal ALT levels at baseline and subsequently normal ALT levels after receiving treatment, where normal is defined as ≤ 1x the upper limit of normal (ULN). The percentage of HBeAg(+) and HBeAg(-) participants achieving ALT normalization at 24 weeks post-treatment was reported. | FU Week 24 (Study Week 72) | 
| Percentage of HBeAg(+) Participants Achieving the Combined Response of HBeAg Seroconversion and HBV DNA <2000 IU/mL at 24 Weeks Post-treatment | HBeAg seroconversion was defined as loss of HBeAg in HBeAg(+) participants and development of antibody to HBeAg. HBV DNA levels in blood were measured by the Roche COBAS TaqMan HBV-(High Pure System Assay). The percentage of HBeAg(+) participants with the combined response of achieving both HBeAg conversion and HBV DNA levels <2000 IU/mL at 24 weeks post-treatment was reported. | FU Week 24 (Study Week 72) |