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A Study of the Safety and Efficacy of Pegylated Inferferon Alfa-2b (PEG-Intron™) Versus Pegylated Interferon Alfa-2a (PEGASYS™) in Participants With Chronic Hepatitis B (P08450)

Primary Purpose

Hepatitis B, Chronic

Status
Terminated
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
PEG-Intron™
PEGASYS™
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

Eligibility Criteria

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

Inclusion Criteria:

  • Must be able to adhere to dose and visit schedules
  • ≥ 40 kg
  • Hepatitis B surface antigen (HBsAg) positive for at least 6 months
  • Anti-HBs negative
  • Female participants of childbearing potential must agree to use an acceptable

method of contraception from at least 2 weeks prior to Day 1 and continue until at least 1 month after last dose of study drug

Inclusion Criteria for HBeAg(+) participants:

  • HBeAg(+)
  • Anti-HBe(-)

Inclusion Criteria for HBeAg(-) participants:

  • HBeAg(-)
  • Anti-HBe(+)

Exclusion Criteria:

  • Co-infection with the human immunodeficiency virus (HIV) or hepatitis C or hepatitis D virus
  • Prior treatment with interferon for hepatitis B
  • Use of nucleoside/nucleotide analogues within 6 months of the screening visit or at any time during the study
  • Use of any investigational drug within 30 days of the screening visit
  • Prior treatment with herbal remedies with known hepatotoxicity. All herbal remedies used for hepatitis B treatment must be discontinued before Day 1
  • Evidence of decompensated liver disease including, but not limited to, a history or presence of clinical ascites, bleeding varices, or hepatic encephalopathy
  • Diabetic and/or hypertensive with clinically significant ocular examination findings
  • History of stroke or transient ischemic attack
  • Immunologically mediated disease (e.g., inflammatory bowel disease [Crohn's disease, ulcerative colitis], celiac disease, rheumatoid arthritis, idiopathic thrombocytopenic purpura, systemic lupus erythematosus, autoimmune hemolytic anemia, scleroderma, sarcoidosis, severe psoriasis requiring oral or injected treatment, or symptomatic thyroid disorder)
  • Chronic pulmonary disease (e.g., chronic obstructive pulmonary disease, interstitial lung disease, pulmonary fibrosis, sarcoidosis)
  • Current or history of any clinically significant cardiac abnormalities/dysfunction
  • Any medical condition requiring, or likely to require, chronic systemic administration of corticosteroids during the course of the trial
  • Myelodysplastic syndromes
  • Organ transplants (including hematopoietic stem cell transplants) other than cornea and hair
  • Pregnant or nursing, or intending to become pregnant during the trial period

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm Type

    Experimental

    Active Comparator

    Experimental

    Active Comparator

    Arm Label

    HBeAg(+) PEG-Intron

    HBeAg(+) PEGASYS

    HBeAg(-) PEG-Intron

    HBeAG(-) PEGASYS

    Arm Description

    HBeAg-positive participants receive 1.5 mcg/kg/wk PEG-Intron subcutaneously (SC) once weekly for 48 weeks.

    HBeAg-positive participants receive 180 mcg/kg/wk PEGASYS SC once weekly for 48 weeks.

    HBeAg-negative participants receive 1.5 mcg/kg/wk PEG-Intron SC once weekly for 48 weeks.

    HBeAg-negative participants receive 180 mcg/kg/wk PEGASYS SC once weekly for 48 weeks.

    Outcomes

    Primary Outcome Measures

    Percentage of HBeAg(+) Participants Achieving HBeAg Seroconversion at 24 Weeks Post-treatment
    Blood samples were drawn to assess the participant's seroconversion status at Follow-up (FU) Week 24. HBeAg seroconversion was defined as loss of HBeAg in HBeAg(+) participants and development of antibody to HBeAg.
    Percentage of HBeAg(-) Participants Achieving Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels <2000 IU/mL at 24 Weeks Post-treatment
    The Roche COBAS TaqMan HBV-(High Pure System Assay) was used to measure HBV DNA in blood samples of HBeAg(-) participants. The percentage of HBeAg(-) participants with HBV DNA <2000 IU/mL at 24 weeks post-treatment was reported.

    Secondary Outcome Measures

    Percentage of HBeAg(+) Participants Achieving HBV DNA <2000 IU/mL at 24 Weeks Post-treatment
    The Roche COBAS TaqMan HBV-(High Pure System Assay) was used to measure HBV DNA in blood samples of HBeAg(+)participants. The percentage of HBeAg(+) participants with HBV DNA <2000 IU/mL at 24 weeks post-treatment was reported.
    Percentage of HBeAg(+) and HBeAg(-) Participants Achieving Alanine Aminotransferase (ALT) Normalization at 24 Weeks Post-treatment
    ALT normalization is a desired goal of HBV treatment, which is defined as having abnormal ALT levels at baseline and subsequently normal ALT levels after receiving treatment, where normal is defined as ≤ 1x the upper limit of normal (ULN). The percentage of HBeAg(+) and HBeAg(-) participants achieving ALT normalization at 24 weeks post-treatment was reported.
    Percentage of HBeAg(+) Participants Achieving the Combined Response of HBeAg Seroconversion and HBV DNA <2000 IU/mL at 24 Weeks Post-treatment
    HBeAg seroconversion was defined as loss of HBeAg in HBeAg(+) participants and development of antibody to HBeAg. HBV DNA levels in blood were measured by the Roche COBAS TaqMan HBV-(High Pure System Assay). The percentage of HBeAg(+) participants with the combined response of achieving both HBeAg conversion and HBV DNA levels <2000 IU/mL at 24 weeks post-treatment was reported.

    Full Information

    First Posted
    July 11, 2012
    Last Updated
    July 27, 2018
    Sponsor
    Merck Sharp & Dohme LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01641926
    Brief Title
    A Study of the Safety and Efficacy of Pegylated Inferferon Alfa-2b (PEG-Intron™) Versus Pegylated Interferon Alfa-2a (PEGASYS™) in Participants With Chronic Hepatitis B (P08450)
    Official Title
    A Multicenter Open-label Study to Evaluate the Safety and Efficacy of PEG-Intron™ Versus PEGASYS™ in Subjects With HBeAg Positive Chronic Hepatitis B and HBeAg Negative Chronic Hepatitis B Protocol No. MK-4031-376-00 (Also Known as SCH 054031, P08450)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    July 2018
    Overall Recruitment Status
    Terminated
    Why Stopped
    This study was terminated early due to poor recruitment
    Study Start Date
    November 26, 2012 (Actual)
    Primary Completion Date
    January 21, 2016 (Actual)
    Study Completion Date
    January 21, 2016 (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 study is being done to compare the safety and efficacy of PEG-Intron™ to that of PEGASYS™ in participants with chronic hepatitis B (hepatitis B envelope antigen [HBeAg] positive or negative) who have not previously been treated with interferon.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Hepatitis B, Chronic

    7. Study Design

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

    8. Arms, Groups, and Interventions

    Arm Title
    HBeAg(+) PEG-Intron
    Arm Type
    Experimental
    Arm Description
    HBeAg-positive participants receive 1.5 mcg/kg/wk PEG-Intron subcutaneously (SC) once weekly for 48 weeks.
    Arm Title
    HBeAg(+) PEGASYS
    Arm Type
    Active Comparator
    Arm Description
    HBeAg-positive participants receive 180 mcg/kg/wk PEGASYS SC once weekly for 48 weeks.
    Arm Title
    HBeAg(-) PEG-Intron
    Arm Type
    Experimental
    Arm Description
    HBeAg-negative participants receive 1.5 mcg/kg/wk PEG-Intron SC once weekly for 48 weeks.
    Arm Title
    HBeAG(-) PEGASYS
    Arm Type
    Active Comparator
    Arm Description
    HBeAg-negative participants receive 180 mcg/kg/wk PEGASYS SC once weekly for 48 weeks.
    Intervention Type
    Biological
    Intervention Name(s)
    PEG-Intron™
    Other Intervention Name(s)
    SCH 054031, Pegylated interferon alfa-2b
    Intervention Description
    PEG-Intron subcutaneously (SC) once weekly for a total of 48 weeks
    Intervention Type
    Biological
    Intervention Name(s)
    PEGASYS™
    Other Intervention Name(s)
    Pegylated interferon alfa-2a
    Intervention Description
    PEGASYS subcutaneously (SC) once weekly for a total of 48 weeks
    Primary Outcome Measure Information:
    Title
    Percentage of HBeAg(+) Participants Achieving HBeAg Seroconversion at 24 Weeks Post-treatment
    Description
    Blood samples were drawn to assess the participant's seroconversion status at Follow-up (FU) Week 24. HBeAg seroconversion was defined as loss of HBeAg in HBeAg(+) participants and development of antibody to HBeAg.
    Time Frame
    FU Week 24 (Study Week 72)
    Title
    Percentage of HBeAg(-) Participants Achieving Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels <2000 IU/mL at 24 Weeks Post-treatment
    Description
    The Roche COBAS TaqMan HBV-(High Pure System Assay) was used to measure HBV DNA in blood samples of HBeAg(-) participants. The percentage of HBeAg(-) participants with HBV DNA <2000 IU/mL at 24 weeks post-treatment was reported.
    Time Frame
    FU Week 24 (Study Week 72)
    Secondary Outcome Measure Information:
    Title
    Percentage of HBeAg(+) Participants Achieving HBV DNA <2000 IU/mL at 24 Weeks Post-treatment
    Description
    The Roche COBAS TaqMan HBV-(High Pure System Assay) was used to measure HBV DNA in blood samples of HBeAg(+)participants. The percentage of HBeAg(+) participants with HBV DNA <2000 IU/mL at 24 weeks post-treatment was reported.
    Time Frame
    FU Week 24 (Study Week 72)
    Title
    Percentage of HBeAg(+) and HBeAg(-) Participants Achieving Alanine Aminotransferase (ALT) Normalization at 24 Weeks Post-treatment
    Description
    ALT normalization is a desired goal of HBV treatment, which is defined as having abnormal ALT levels at baseline and subsequently normal ALT levels after receiving treatment, where normal is defined as ≤ 1x the upper limit of normal (ULN). The percentage of HBeAg(+) and HBeAg(-) participants achieving ALT normalization at 24 weeks post-treatment was reported.
    Time Frame
    FU Week 24 (Study Week 72)
    Title
    Percentage of HBeAg(+) Participants Achieving the Combined Response of HBeAg Seroconversion and HBV DNA <2000 IU/mL at 24 Weeks Post-treatment
    Description
    HBeAg seroconversion was defined as loss of HBeAg in HBeAg(+) participants and development of antibody to HBeAg. HBV DNA levels in blood were measured by the Roche COBAS TaqMan HBV-(High Pure System Assay). The percentage of HBeAg(+) participants with the combined response of achieving both HBeAg conversion and HBV DNA levels <2000 IU/mL at 24 weeks post-treatment was reported.
    Time Frame
    FU Week 24 (Study Week 72)

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Must be able to adhere to dose and visit schedules ≥ 40 kg Hepatitis B surface antigen (HBsAg) positive for at least 6 months Anti-HBs negative Female participants of childbearing potential must agree to use an acceptable method of contraception from at least 2 weeks prior to Day 1 and continue until at least 1 month after last dose of study drug Inclusion Criteria for HBeAg(+) participants: HBeAg(+) Anti-HBe(-) Inclusion Criteria for HBeAg(-) participants: HBeAg(-) Anti-HBe(+) Exclusion Criteria: Co-infection with the human immunodeficiency virus (HIV) or hepatitis C or hepatitis D virus Prior treatment with interferon for hepatitis B Use of nucleoside/nucleotide analogues within 6 months of the screening visit or at any time during the study Use of any investigational drug within 30 days of the screening visit Prior treatment with herbal remedies with known hepatotoxicity. All herbal remedies used for hepatitis B treatment must be discontinued before Day 1 Evidence of decompensated liver disease including, but not limited to, a history or presence of clinical ascites, bleeding varices, or hepatic encephalopathy Diabetic and/or hypertensive with clinically significant ocular examination findings History of stroke or transient ischemic attack Immunologically mediated disease (e.g., inflammatory bowel disease [Crohn's disease, ulcerative colitis], celiac disease, rheumatoid arthritis, idiopathic thrombocytopenic purpura, systemic lupus erythematosus, autoimmune hemolytic anemia, scleroderma, sarcoidosis, severe psoriasis requiring oral or injected treatment, or symptomatic thyroid disorder) Chronic pulmonary disease (e.g., chronic obstructive pulmonary disease, interstitial lung disease, pulmonary fibrosis, sarcoidosis) Current or history of any clinically significant cardiac abnormalities/dysfunction Any medical condition requiring, or likely to require, chronic systemic administration of corticosteroids during the course of the trial Myelodysplastic syndromes Organ transplants (including hematopoietic stem cell transplants) other than cornea and hair Pregnant or nursing, or intending to become pregnant during the trial period
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Study Director
    Organizational Affiliation
    Merck Sharp & Dohme LLC
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
    IPD Sharing URL
    http://engagezone.msd.com/ds_documentation.php

    Learn more about this trial

    A Study of the Safety and Efficacy of Pegylated Inferferon Alfa-2b (PEG-Intron™) Versus Pegylated Interferon Alfa-2a (PEGASYS™) in Participants With Chronic Hepatitis B (P08450)

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