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

Phase 3

Completed

• Conditions: Hepatitis B, Chronic
• Interventions: Drug: pegylated interferon alpha-2b

• Registration Number: NCT00536263
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design

Study Timeline

• Study Start: 2007-09
• Study First Submitted: 2007-09-26
• Study First Submitted QC: 2007-09-26
• Study First Posted: 2007-09-27
• Primary Completion: 2009-11
• Study Completion: 2009-11
• Results First Submitted: 2010-11-23
• Results First Submitted QC: 2010-11-23
• Results First Posted: 2010-12-21
• Status Verified: 2017-03
• Last Update Submitted: 2017-03-09
• Last Update Posted: 2017-04-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 671

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PEG 1.0 mcg/kg weekly (QW) * 24 weeks	pegylated interferon alpha-2b	PegIntron 1.0 mcg/kg weekly (QW) \* 24 weeks + 24 weeks follow-up
PEG 1.5 mcg/kg QW * 24 wks	pegylated interferon alpha-2b	PegIntron 1.5 mcg/kg QW \* 24 wks + 24 wks follow-up
PEG 1.5 mcg/kg QW * 48 wks	pegylated interferon alpha-2b	PegIntron 1.5 mcg/kg QW \* 48 wks + 24 wks follow-up

Primary Outcome Measures

Name	Time	Method
Number of Participants With Hepatitis B Envelope Antigen (HBe or HBeAg) Loss	24 weeks after end of treatment (EOT)	HBeAg Loss was tested by Abbott Microparticle Enzyme Immunoassay (MEIA)

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Combined Response	End of treatment (EOT) and 24 weeks after EOT	Combined response was defined as HBV DNA \<20,000 IU/mL and HBe seroconversion and alanine aminotransferase (ALT) normalization
Number of Participants With HBeAg Loss	Up to Treatment Week 48	HBeAg Loss was tested by assay of Abbott MEIA
Number of Participants With HBV-DNA Undetectable	End of treatment (EOT) and 24 weeks after EOT	Undetectable HBV-DNA was defined as having a level \<6 IU/mL by polymerase chain reaction (PCR).
Hepatitis B Surface Antigen (HBs) Seroconversion	End of treatment (EOT) and 24 weeks after EOT	HBs seroconversion was defined as having HBsAg Loss and Anti-HBs Positive
HBe Seroconversion	End of treatment (EOT) and 24 weeks after EOT	HBe seroconversion was defined as HBeAg Loss and Anti-HBeAg Positive. These were tested by assay of Abbott MEIA.
Change From Baseline in Liver Biopsy Score	Baseline to 24 weeks after end of treatment	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).
Number of Participants With Hepatitis B Virus - Deoxyriboncleic Acid (HBV-DNA) <20,000 IU/mL	End of treatment (EOT) and 24 weeks after EOT	HBV-DNA was tested by assay of Roche Cobas Taqman (the test; lowest limit is 6 IU/mL)
Number of Participants With HBV-DNA < 200 IU/mL	End of treatment (EOT) and 24 weeks after EOT	HBV-DNA was tested by assay of Roche Cobas Taqman (the test lowest limit is 6 IU/mL)
Hepatitis B Surface Antigen (HBsAg) Loss	End of treatment (EOT) and 24 weeks after EOT	HBsAg Loss was tested by assay of Abbott MEIA
Number of Participants With Biochemical Response	End of treatment (EOT) and 24 weeks after EOT	Biochemical response was defined as alanine aminotransferase (ALT) normalization.