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PegIntron Versus Adefovir in the Treatment of Chronic Hepatitis B (CHB) e Antigen Positive Patients in Taiwan (P04498/MK-4031-278)

Primary Purpose

Hepatitis B, Chronic (CHB)

Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Pegylated interferon alfa-2b (PegIntron)
Adefovir dipivoxil (adefovir)
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatitis B, Chronic (CHB) focused on measuring Hepatitis B virus, Pegylated interferon alfa-2b (PegIntron)

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Adult male or female, 18 to 70 years of age.
  • Documented positive serum hepatitis B surface antigen (HBsAg) for a minimum of 6 months prior to randomization.

  • Hepatitis B virus (HBV) replication and hepatitis documented by:

    • Serum HBV DNA (Hepatitis B Virus Deoxyribonucleic acid) >= 10^5 copies/mL within 3 months prior to entry
    • Positive serum hepatitis B e antigen (HBeAg) within 3 months prior to entry
    • Documented presence of ALT (Alanine Aminotransferase) twice (1 month apart) within 3 months prior to entry (2 to 10 folds above the upper normal level)
    • Liver biopsy finding shows evidence of chronic hepatitis without liver cirrhosis, document acceptable if no anti-HBV treatment within 1 year prior to randomization
    • Naïve or exposed to lamivudine (3 months treatment-free interval prior to randomization)
    • Adequate renal function (creatinine within normal upper limit).
  • Compensated liver disease with certain minimum hematological and serum biochemical criteria.
  • Thyroid stimulating hormone (TSH) and free T4 within normal ranges.
  • Negative antibody to hepatitis C and hepatitis D.
  • Negative antibody to human immunodeficiency virus.
  • Negative evidence for hepatocellular carcinoma by alfa-fetoprotein and ultrasound within 1 month prior to randomization.

Exclusion Criteria:

  • Women who are pregnant or nursing.
  • Prior treatment for hepatitis with any interferon or adefovir, or other investigational anti-virus agents.
  • Prior treatment for hepatitis with immunomodulatory drug within 2 years prior to randomization.
  • Suspected hypersensitivity to interferon or adefovir.
  • Liver cirrhosis.
  • History of severe psychiatric disease, especially depression.
  • Concurrent malignancies (including hepatocellular carcinoma).
  • Unstable or significant cardiovascular diseases.
  • Prolonged exposure to known hepatotoxins.
  • History of thyroid disease poorly controlled on prescribed medication.
  • Poorly controlled diabetes mellitus.
  • Have suspected or confirmed significant hepatic disease from an etiology other than HBV.
  • Severe renal disease or myeloid dysfunction.
  • History of organ transplantation other than cornea and hair transplant.
  • Any medical condition requiring chronic systemic administration of steroids.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    PegIntron

    Adefovir

    Arm Description

    PegIntron, 1.5 micrograms/kg weekly, for up to 24 weeks followed by a 48-week observation phase

    Adefovir, 10 mg daily, for up to 48 weeks followed by a 24-week observation phase

    Outcomes

    Primary Outcome Measures

    Number of Participants With a Combined Response Consisting of All Three Responses - (a) Serological Response, (b) Virological Response, and (c) Biochemical Response
    Serological response is defined as Loss of HBeAg (Hepatitis B e antigen) and Appearance of anti-HBe (Hepatitis B e antibodies); participant is HBeAg negative and anti-HBe positive. Virological response was defined as having < 10^5 copies/mL of serum HBV DNA (Hepatitis B Virus Deoxyribonucleic Acid) by real-time PCR (Polymerase Chain Reaction). Biochemical response was defined as acheiving normal levels of ALT (Alanine Aminotransferase) level in Units/L.

    Secondary Outcome Measures

    Full Information

    First Posted
    August 31, 2006
    Last Updated
    March 8, 2017
    Sponsor
    Merck Sharp & Dohme LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00371761
    Brief Title
    PegIntron Versus Adefovir in the Treatment of Chronic Hepatitis B (CHB) e Antigen Positive Patients in Taiwan (P04498/MK-4031-278)
    Official Title
    An Open-Label, Randomized, Comparative Study With PegIntron vs. Adefovir in the Treatment of Chronic Hepatitis B (CHB) e Antigen Positive Patients in Taiwan
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    March 2017
    Overall Recruitment Status
    Completed
    Study Start Date
    September 2006 (undefined)
    Primary Completion Date
    February 2009 (Actual)
    Study Completion Date
    February 2009 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Merck Sharp & Dohme LLC

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    This is an open label, randomized, comparative, multi-center study. Subjects will be screened within 2 weeks prior to study entry to establish eligibility. Subjects who meet all the selection criteria will be randomly assigned 1:1 to (1) once-a-week, subcutaneous Pegylated interferon alfa-2b (PegIntron) (1.5 mcg/kg body weight) or (2) oral adefovir 10 mg daily. The treatment phase will be 24 weeks for PegIntron and 48 weeks for adefovir. All subjects completing the assigned treatment phase will be followed up for an additional 48 weeks for PegIntron and 24 weeks for adefovir as observation phase. The primary objective is to establish the efficacy profile of PegIntron. Secondary objectives are to compare the efficacy profile of PegIntron with that of adefovir, compare efficacy of PegIntron in lamivudine-naïve and lamivudine-experienced subjects, and to establish the safety profile of PegIntron in treating patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Hepatitis B, Chronic (CHB)
    Keywords
    Hepatitis B virus, Pegylated interferon alfa-2b (PegIntron)

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    25 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    PegIntron
    Arm Type
    Experimental
    Arm Description
    PegIntron, 1.5 micrograms/kg weekly, for up to 24 weeks followed by a 48-week observation phase
    Arm Title
    Adefovir
    Arm Type
    Active Comparator
    Arm Description
    Adefovir, 10 mg daily, for up to 48 weeks followed by a 24-week observation phase
    Intervention Type
    Biological
    Intervention Name(s)
    Pegylated interferon alfa-2b (PegIntron)
    Other Intervention Name(s)
    SCH 54031, Peg-Intron
    Intervention Description
    Powder for injection in vials ( 100, and 120 microgram strengths), subcutaneous, dose of 1.5 micrograms/kg, weekly for up to 24 weeks
    Intervention Type
    Drug
    Intervention Name(s)
    Adefovir dipivoxil (adefovir)
    Other Intervention Name(s)
    Hepsera
    Intervention Description
    10 mg adefovir dipivoxil (equivalent to 5.4.5 mg adefovir) tablets, oral, dose of 1 tablet per day for up to 48 weeks
    Primary Outcome Measure Information:
    Title
    Number of Participants With a Combined Response Consisting of All Three Responses - (a) Serological Response, (b) Virological Response, and (c) Biochemical Response
    Description
    Serological response is defined as Loss of HBeAg (Hepatitis B e antigen) and Appearance of anti-HBe (Hepatitis B e antibodies); participant is HBeAg negative and anti-HBe positive. Virological response was defined as having < 10^5 copies/mL of serum HBV DNA (Hepatitis B Virus Deoxyribonucleic Acid) by real-time PCR (Polymerase Chain Reaction). Biochemical response was defined as acheiving normal levels of ALT (Alanine Aminotransferase) level in Units/L.
    Time Frame
    At Week 72 [for Pegylated interferon alfa-2b (PegIntron), at 48 weeks post PegIntron treatment for up to 24 weeks; for Adefovir, at 24 weeks post adefovir treatment for up to 48 weeks]

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    70 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Adult male or female, 18 to 70 years of age. Documented positive serum hepatitis B surface antigen (HBsAg) for a minimum of 6 months prior to randomization. Hepatitis B virus (HBV) replication and hepatitis documented by: Serum HBV DNA (Hepatitis B Virus Deoxyribonucleic acid) >= 10^5 copies/mL within 3 months prior to entry Positive serum hepatitis B e antigen (HBeAg) within 3 months prior to entry Documented presence of ALT (Alanine Aminotransferase) twice (1 month apart) within 3 months prior to entry (2 to 10 folds above the upper normal level) Liver biopsy finding shows evidence of chronic hepatitis without liver cirrhosis, document acceptable if no anti-HBV treatment within 1 year prior to randomization Naïve or exposed to lamivudine (3 months treatment-free interval prior to randomization) Adequate renal function (creatinine within normal upper limit). Compensated liver disease with certain minimum hematological and serum biochemical criteria. Thyroid stimulating hormone (TSH) and free T4 within normal ranges. Negative antibody to hepatitis C and hepatitis D. Negative antibody to human immunodeficiency virus. Negative evidence for hepatocellular carcinoma by alfa-fetoprotein and ultrasound within 1 month prior to randomization. Exclusion Criteria: Women who are pregnant or nursing. Prior treatment for hepatitis with any interferon or adefovir, or other investigational anti-virus agents. Prior treatment for hepatitis with immunomodulatory drug within 2 years prior to randomization. Suspected hypersensitivity to interferon or adefovir. Liver cirrhosis. History of severe psychiatric disease, especially depression. Concurrent malignancies (including hepatocellular carcinoma). Unstable or significant cardiovascular diseases. Prolonged exposure to known hepatotoxins. History of thyroid disease poorly controlled on prescribed medication. Poorly controlled diabetes mellitus. Have suspected or confirmed significant hepatic disease from an etiology other than HBV. Severe renal disease or myeloid dysfunction. History of organ transplantation other than cornea and hair transplant. Any medical condition requiring chronic systemic administration of steroids.

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf http://engagezone.msd.com/ds_documentation.php

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    PegIntron Versus Adefovir in the Treatment of Chronic Hepatitis B (CHB) e Antigen Positive Patients in Taiwan (P04498/MK-4031-278)

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