PegIntron Treatment of Chronic Hepatitis B e Antigen-Positive Patients (P05170/MK-4031-327)

Study Overview
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Brief Summary
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The purpose of this study is to determine the efficacy and safety of two dosages of PegIntron for treating hepatitis B e antigen (HBeAg) positive chronic hepatitis B compared with the approved dosage, which is PegIntron 1.0 microgram (mcg)/kg given once a week for 24 weeks. This study compares dosages of (1) 1.5 mcg/kg once a week for 24 weeks and (2) 1.5 mcg/kg once a week for 48 weeks with the approved dosage. All subjects are followed for 24 weeks after their treatment ends.

Official Title
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An Open-label, Randomized Study of PegIntron in the Treatment of HBeAg Positive Chronic Hepatitis B Patients

Conditions
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Hepatitis B, Chronic

Intervention / Treatment
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* Drug: pegylated interferon alpha-2b
* Drug: pegylated interferon alpha-2b
* Drug: pegylated interferon alpha-2b


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults with chronic hepatitis B: Serum hepatitis B surface antigen positive for at least 6 months Serum hepatitis B e antigen positive Serum negative for hepatitis B surface and e antibodies Plasma hepatitis B virus deoxyribonucleic acid (DNA) level greater than 20,000 IU/mL Alanine aminotransferase (ALT) 2- to 10-times the upper limit of normal Compensated liver disease with certain minimum hematological and serum biochemical criteria Exclusion Criteria: Significant hepatic disease from an etiology other than hepatitis B virus Antiviral treatment for hepatitis within previous 6 months History of severe psychiatric disease, especially depression Unstable or significant cardiovascular disease Prolonged exposure to known hepatotoxins such as alcohol or drugs Any condition that could interfere with the subject participating in and completing the study

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: PEG 1.0 mcg/kg weekly (QW) * 24 weeks<br>PegIntron 1.0 mcg/kg weekly (QW) * 24 weeks + 24 weeks follow-up | Drug: pegylated interferon alpha-2b<br>* 1.0 mcg/kg subcutaneously (S.C.) QW for 24 weeks<br>|
| Experimental: PEG 1.5 mcg/kg QW * 24 wks<br>PegIntron 1.5 mcg/kg QW * 24 wks + 24 wks follow-up | Drug: pegylated interferon alpha-2b<br>* 1.5 mcg/kg S.C. QW for 24 weeks<br>|
| Experimental: PEG 1.5 mcg/kg QW * 48 wks<br>PegIntron 1.5 mcg/kg QW * 48 wks + 24 wks follow-up | Drug: pegylated interferon alpha-2b<br>* 1.5 mcg/kg S.C. QW for 48 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Hepatitis B Envelope Antigen (HBe or HBeAg) Loss | HBeAg Loss was tested by Abbott Microparticle Enzyme Immunoassay (MEIA) | 24 weeks after end of treatment (EOT) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With HBeAg Loss | HBeAg Loss was tested by assay of Abbott MEIA | Up to Treatment Week 48 | 
| HBe Seroconversion | HBe seroconversion was defined as HBeAg Loss and Anti-HBeAg Positive. These were tested by assay of Abbott MEIA. | End of treatment (EOT) and 24 weeks after EOT | 
| Number of Participants With Hepatitis B Virus - Deoxyriboncleic Acid (HBV-DNA) <20,000 IU/mL | HBV-DNA was tested by assay of Roche Cobas Taqman (the test lowest limit is 6 IU/mL) | End of treatment (EOT) and 24 weeks after EOT | 
| Number of Participants With HBV-DNA < 200 IU/mL | HBV-DNA was tested by assay of Roche Cobas Taqman (the test lowest limit is 6 IU/mL) | End of treatment (EOT) and 24 weeks after EOT | 
| Number of Participants With HBV-DNA Undetectable | Undetectable HBV-DNA was defined as having a level <6 IU/mL by polymerase chain reaction (PCR). | End of treatment (EOT) and 24 weeks after EOT | 
| Number of Participants With Biochemical Response | Biochemical response was defined as alanine aminotransferase (ALT) normalization. | End of treatment (EOT) and 24 weeks after EOT | 
| Number of Participants With Combined Response | Combined response was defined as HBV DNA <20,000 IU/mL and HBe seroconversion and alanine aminotransferase (ALT) normalization | End of treatment (EOT) and 24 weeks after EOT | 
| Hepatitis B Surface Antigen (HBsAg) Loss | HBsAg Loss was tested by assay of Abbott MEIA | End of treatment (EOT) and 24 weeks after EOT | 
| Hepatitis B Surface Antigen (HBs) Seroconversion | HBs seroconversion was defined as having HBsAg Loss and Anti-HBs Positive | End of treatment (EOT) and 24 weeks after EOT | 
| Change From Baseline in Liver Biopsy Score | Method for biopsy scoring was Knodell Scoring System (Histology Activity Index-HAI Score System): Score I (periportal +/- bridging necrosis): 0 (none) to 10 (multilobular necrosis). Score II (Intralobular degeneration and focal necrosis): 0 (none) to 4 (Marked [involvement of >2/3 of lobules or nodules]). Score III (portal inflammation): 0 (none) to 4 (Marked [dense packing of inflammatory cells in >2/3 of portal tracts]). Score IV (fibrosis): 0 (none) to 4 (cirrhosis). | Baseline to 24 weeks after end of treatment |