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A Study to Compare Efficacy and Safety of Tenofovir Used Alone or in Combination With Pegylated Interferon Alpha-2b in Participants With Chronic Hepatitis B and Elevated Alanine Aminotransferase (MK-4031-384)

Primary Purpose

Hepatitis B

Status
Withdrawn
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Tenofovir
Pegylated interferon alpha-2b
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

Eligibility Criteria

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

Inclusion Criteria:

  • Chronic hepatitis B (hepatitis B surface antigen [HBsAg]-positive for >6 months or evidence of chronic hepatitis B in liver biopsy)
  • Elevated serum ALT level
  • Liver biopsy or a non-invasive investigation within 12 months prior to randomization with Chronic Hepatitis B
  • Treatment naïve or history of interferon for not more than 1 month, taken at least 6 months before enrollment
  • Compensated liver disease

Exclusion Criteria:

  • Known hypersensitivity to tenofovir, interferon alpha-2b, and/or any other component of the study products
  • Co-infection with hepatitis C virus (HCV), hepatitis D virus (HDV) or human immunodeficiency virus (HIV)
  • Need for prolonged or frequent use of systemic acyclovir or famciclovir
  • Previously received lamivudine or an investigational anti-hepatitis B virus (HBV) nucleoside or nucleotide analog and were resistant to these drugs
  • History of variceal bleeding or other GI bleeding due to portal hypertension, hepatic encephalopathy, spontaneous bacterial peritonitis, Grade III and IV esophageal varices unless banded or other clinical signs of hepatic decompensation
  • History of hepatocellular carcinoma (HCC) or findings suggestive of possible HCC
  • Need for potentially hepatotoxic drugs (e.g. dapsone, erythromycin, fluconazole, ketoconazole, rifampin, and anti-tuberculosis regimens) or nephrotoxic drugs (e.g. frequent nonsteroidal anti-inflammatories, aminoglycosides, amphotericin B, and foscarnet)
  • One or more additional known primary or secondary causes of liver disease, other than hepatitis B
  • History of clinical pancreatitis
  • Pregnant or breastfeeding
  • Female participants of childbearing potential and male participants must be willing to use acceptable method of birth control.
  • Medical condition that requires frequent or prolonged use of systemic corticosteroids
  • Use of warfarin or other anticoagulants during 30 days prior to screening or if expected to be needed during the study period

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm Type

    Active Comparator

    Experimental

    Experimental

    Arm Label

    Tenofovir Monotherapy

    PegIFN-2b/Tenofovir Sequential Therapy

    Peg-IFN-2b + Tenofovir Combination Therapy

    Arm Description

    Tenofovir 300 mg tablet, orally (PO) once daily for 8 weeks, then Tenofovir 300 mg tablet, PO, once daily for an additional 96 weeks (total treatment duration 104 weeks)

    Tenofovir 300 mg tablet, PO, once daily for 8 weeks, then PegIFN-2b, 1.5 mcg/kg subcutaneously (SC), once weekly, for 24 weeks, then Tenofovir 300 mg tablet, PO, once daily for 72 weeks (total treatment duration 104 weeks)

    Tenofovir 300 mg tablet, PO once daily for 8 weeks, then pegIFN-2b, 1.5 mcg/kg SC once weekly and tenofovir 300 mg tablet, PO, once daily for 24 weeks, and then tenofovir 300 mg tablet, PO, once daily for 72 weeks (total treatment duration 104 weeks)

    Outcomes

    Primary Outcome Measures

    Number of participants who responded to treatment
    Number of participants experiencing adverse events (AEs)
    Number of participants discontinuing study therapy due to AEs

    Secondary Outcome Measures

    Full Information

    First Posted
    November 12, 2012
    Last Updated
    September 18, 2013
    Sponsor
    Merck Sharp & Dohme LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01727271
    Brief Title
    A Study to Compare Efficacy and Safety of Tenofovir Used Alone or in Combination With Pegylated Interferon Alpha-2b in Participants With Chronic Hepatitis B and Elevated Alanine Aminotransferase (MK-4031-384)
    Official Title
    An Open-Label, Pilot, Randomized, Multi-Center Study to Compare Efficacy and Safety of Tenofovir Monotherapy Alone With Tenofovir Monotherapy Followed by Concurrent Combination of Pegylated Interferon-Alpha-2b and Tenofovir or Tenofovir Monotherapy Followed by Sequential Therapy of Pegylated Interferon-Alpha-2b and Tenofovir in HBeAG-Positive Chronic Hepatitis B Patients With Raised ALT.
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2013
    Overall Recruitment Status
    Withdrawn
    Study Start Date
    August 2013 (undefined)
    Primary Completion Date
    August 2017 (Anticipated)
    Study Completion Date
    August 2017 (Anticipated)

    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 will compare monotherapy with tenofovir to sequential therapy with pegylated interferon alpha-2b (pegIFN-2b) followed by tenofovir, and to combination therapy with pegIFN-2b + tenofovir, in participants with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B and elevated alanine aminotransferase (ALT). All enrolled participants will be be administered tenofovir alone for 8 weeks and then will be randomly assigned to 1 of the 3 treatment arms.

    6. Conditions and Keywords

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

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 4
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Tenofovir Monotherapy
    Arm Type
    Active Comparator
    Arm Description
    Tenofovir 300 mg tablet, orally (PO) once daily for 8 weeks, then Tenofovir 300 mg tablet, PO, once daily for an additional 96 weeks (total treatment duration 104 weeks)
    Arm Title
    PegIFN-2b/Tenofovir Sequential Therapy
    Arm Type
    Experimental
    Arm Description
    Tenofovir 300 mg tablet, PO, once daily for 8 weeks, then PegIFN-2b, 1.5 mcg/kg subcutaneously (SC), once weekly, for 24 weeks, then Tenofovir 300 mg tablet, PO, once daily for 72 weeks (total treatment duration 104 weeks)
    Arm Title
    Peg-IFN-2b + Tenofovir Combination Therapy
    Arm Type
    Experimental
    Arm Description
    Tenofovir 300 mg tablet, PO once daily for 8 weeks, then pegIFN-2b, 1.5 mcg/kg SC once weekly and tenofovir 300 mg tablet, PO, once daily for 24 weeks, and then tenofovir 300 mg tablet, PO, once daily for 72 weeks (total treatment duration 104 weeks)
    Intervention Type
    Drug
    Intervention Name(s)
    Tenofovir
    Other Intervention Name(s)
    Truvada
    Intervention Type
    Biological
    Intervention Name(s)
    Pegylated interferon alpha-2b
    Other Intervention Name(s)
    SCH 054031, MK-4031
    Primary Outcome Measure Information:
    Title
    Number of participants who responded to treatment
    Time Frame
    Week 128
    Title
    Number of participants experiencing adverse events (AEs)
    Time Frame
    Up to 128 weeks
    Title
    Number of participants discontinuing study therapy due to AEs
    Time Frame
    Up to 104 weeks

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Chronic hepatitis B (hepatitis B surface antigen [HBsAg]-positive for >6 months or evidence of chronic hepatitis B in liver biopsy) Elevated serum ALT level Liver biopsy or a non-invasive investigation within 12 months prior to randomization with Chronic Hepatitis B Treatment naïve or history of interferon for not more than 1 month, taken at least 6 months before enrollment Compensated liver disease Exclusion Criteria: Known hypersensitivity to tenofovir, interferon alpha-2b, and/or any other component of the study products Co-infection with hepatitis C virus (HCV), hepatitis D virus (HDV) or human immunodeficiency virus (HIV) Need for prolonged or frequent use of systemic acyclovir or famciclovir Previously received lamivudine or an investigational anti-hepatitis B virus (HBV) nucleoside or nucleotide analog and were resistant to these drugs History of variceal bleeding or other GI bleeding due to portal hypertension, hepatic encephalopathy, spontaneous bacterial peritonitis, Grade III and IV esophageal varices unless banded or other clinical signs of hepatic decompensation History of hepatocellular carcinoma (HCC) or findings suggestive of possible HCC Need for potentially hepatotoxic drugs (e.g. dapsone, erythromycin, fluconazole, ketoconazole, rifampin, and anti-tuberculosis regimens) or nephrotoxic drugs (e.g. frequent nonsteroidal anti-inflammatories, aminoglycosides, amphotericin B, and foscarnet) One or more additional known primary or secondary causes of liver disease, other than hepatitis B History of clinical pancreatitis Pregnant or breastfeeding Female participants of childbearing potential and male participants must be willing to use acceptable method of birth control. Medical condition that requires frequent or prolonged use of systemic corticosteroids Use of warfarin or other anticoagulants during 30 days prior to screening or if expected to be needed during the study period

    12. IPD Sharing Statement

    Learn more about this trial

    A Study to Compare Efficacy and Safety of Tenofovir Used Alone or in Combination With Pegylated Interferon Alpha-2b in Participants With Chronic Hepatitis B and Elevated Alanine Aminotransferase (MK-4031-384)

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