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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00536263
First received: September 26, 2007
Last updated: January 14, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Hepatitis B, Chronic
Drug: pegylated interferon alpha-2b
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label, Randomized Study of PegIntron in the Treatment of HBeAg Positive Chronic Hepatitis B Patients

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Number of Participants With Hepatitis B Envelope Antigen (HBe or HBeAg) Loss [ Time Frame: 24 weeks after end of treatment (EOT) ] [ Designated as safety issue: No ]
    HBeAg Loss was tested by Abbott Microparticle Enzyme Immunoassay (MEIA)


Secondary Outcome Measures:
  • Number of Participants With HBeAg Loss [ Time Frame: Up to Treatment Week 48 ] [ Designated as safety issue: No ]
    HBeAg Loss was tested by assay of Abbott MEIA

  • HBe Seroconversion [ Time Frame: End of treatment (EOT) and 24 weeks after EOT ] [ Designated as safety issue: No ]
    HBe seroconversion was defined as HBeAg Loss and Anti-HBeAg Positive. These were tested by assay of Abbott MEIA.

  • Number of Participants With Hepatitis B Virus - Deoxyriboncleic Acid (HBV-DNA) <20,000 IU/mL [ Time Frame: End of treatment (EOT) and 24 weeks after EOT ] [ Designated as safety issue: No ]

    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 [ Time Frame: End of treatment (EOT) and 24 weeks after EOT ] [ Designated as safety issue: No ]
    HBV-DNA was tested by assay of Roche Cobas Taqman (the test lowest limit is 6 IU/mL)

  • Number of Participants With HBV-DNA Undetectable [ Time Frame: End of treatment (EOT) and 24 weeks after EOT ] [ Designated as safety issue: No ]
    Undetectable HBV-DNA was defined as having a level <6 IU/mL by polymerase chain reaction (PCR).

  • Number of Participants With Biochemical Response [ Time Frame: End of treatment (EOT) and 24 weeks after EOT ] [ Designated as safety issue: No ]
    Biochemical response was defined as alanine aminotransferase (ALT) normalization.

  • Number of Participants With Combined Response [ Time Frame: End of treatment (EOT) and 24 weeks after EOT ] [ Designated as safety issue: No ]
    Combined response was defined as HBV DNA <20,000 IU/mL and HBe seroconversion and alanine aminotransferase (ALT) normalization

  • Hepatitis B Surface Antigen (HBsAg) Loss [ Time Frame: End of treatment (EOT) and 24 weeks after EOT ] [ Designated as safety issue: No ]
    HBsAg Loss was tested by assay of Abbott MEIA

  • Hepatitis B Surface Antigen (HBs) Seroconversion [ Time Frame: End of treatment (EOT) and 24 weeks after EOT ] [ Designated as safety issue: No ]
    HBs seroconversion was defined as having HBsAg Loss and Anti-HBs Positive

  • Change From Baseline in Liver Biopsy Score [ Time Frame: Baseline to 24 weeks after end of treatment ] [ Designated as safety issue: No ]

    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).



Enrollment: 671
Study Start Date: September 2007
Study Completion Date: November 2009
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: PEG 1.0 mcg/kg weekly (QW) * 24 weeks
PegIntron 1.0 mcg/kg weekly (QW) * 24 weeks + 24 weeks follow-up
Drug: pegylated interferon alpha-2b
1.0 mcg/kg subcutaneously (S.C.) QW for 24 weeks
Experimental: PEG 1.5 mcg/kg QW * 24 wks
PegIntron 1.5 mcg/kg QW * 24 wks + 24 wks follow-up
Drug: pegylated interferon alpha-2b
1.5 mcg/kg S.C. QW for 24 weeks
Experimental: PEG 1.5 mcg/kg QW * 48 wks
PegIntron 1.5 mcg/kg QW * 48 wks + 24 wks follow-up
Drug: pegylated interferon alpha-2b
1.5 mcg/kg S.C. QW for 48 weeks

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00536263     History of Changes
Other Study ID Numbers: P05170
Study First Received: September 26, 2007
Results First Received: November 23, 2010
Last Updated: January 14, 2014
Health Authority: China: Food and Drug Administration

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Hepatitis, Chronic
Hepatitis B, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Interferon-alpha
Interferon Alfa-2a
Interferon Alfa-2b
Interferons
Peginterferon alfa-2b
Reaferon
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors

ClinicalTrials.gov processed this record on April 16, 2014