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: July 15, 2014
Last verified: July 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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: July 15, 2014
Health Authority: China: Food and Drug Administration

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

ClinicalTrials.gov processed this record on October 29, 2014