<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01727271</url>
  </required_header>
  <id_info>
    <org_study_id>4031-384</org_study_id>
    <nct_id>NCT01727271</nct_id>
  </id_info>
  <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)</brief_title>
  <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.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Merck Sharp &amp; Dohme LLC</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will compare monotherapy with tenofovir to sequential therapy with pegylated&#xD;
      interferon alpha-2b (pegIFN-2b) followed by tenofovir, and to combination therapy with&#xD;
      pegIFN-2b + tenofovir, in participants with hepatitis B e antigen (HBeAg)-positive chronic&#xD;
      hepatitis B and elevated alanine aminotransferase (ALT). All enrolled participants will be be&#xD;
      administered tenofovir alone for 8 weeks and then will be randomly assigned to 1 of the 3&#xD;
      treatment arms.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <start_date>August 2013</start_date>
  <completion_date type="Anticipated">August 2017</completion_date>
  <primary_completion_date type="Anticipated">August 2017</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants who responded to treatment</measure>
    <time_frame>Week 128</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants experiencing adverse events (AEs)</measure>
    <time_frame>Up to 128 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants discontinuing study therapy due to AEs</measure>
    <time_frame>Up to 104 weeks</time_frame>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Hepatitis B</condition>
  <arm_group>
    <arm_group_label>Tenofovir Monotherapy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <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)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>PegIFN-2b/Tenofovir Sequential Therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <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)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Peg-IFN-2b + Tenofovir Combination Therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <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)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tenofovir</intervention_name>
    <arm_group_label>Peg-IFN-2b + Tenofovir Combination Therapy</arm_group_label>
    <arm_group_label>PegIFN-2b/Tenofovir Sequential Therapy</arm_group_label>
    <arm_group_label>Tenofovir Monotherapy</arm_group_label>
    <other_name>Truvada</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Pegylated interferon alpha-2b</intervention_name>
    <arm_group_label>Peg-IFN-2b + Tenofovir Combination Therapy</arm_group_label>
    <arm_group_label>PegIFN-2b/Tenofovir Sequential Therapy</arm_group_label>
    <other_name>SCH 054031</other_name>
    <other_name>MK-4031</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Chronic hepatitis B (hepatitis B surface antigen [HBsAg]-positive for &gt;6 months or&#xD;
             evidence of chronic hepatitis B in liver biopsy)&#xD;
&#xD;
          -  Elevated serum ALT level&#xD;
&#xD;
          -  Liver biopsy or a non-invasive investigation within 12 months prior to randomization&#xD;
             with Chronic Hepatitis B&#xD;
&#xD;
          -  Treatment naïve or history of interferon for not more than 1 month, taken at least 6&#xD;
             months before enrollment&#xD;
&#xD;
          -  Compensated liver disease&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known hypersensitivity to tenofovir, interferon alpha-2b, and/or any other component&#xD;
             of the study products&#xD;
&#xD;
          -  Co-infection with hepatitis C virus (HCV), hepatitis D virus (HDV) or human&#xD;
             immunodeficiency virus (HIV)&#xD;
&#xD;
          -  Need for prolonged or frequent use of systemic acyclovir or famciclovir&#xD;
&#xD;
          -  Previously received lamivudine or an investigational anti-hepatitis B virus (HBV)&#xD;
             nucleoside or nucleotide analog and were resistant to these drugs&#xD;
&#xD;
          -  History of variceal bleeding or other GI bleeding due to portal hypertension, hepatic&#xD;
             encephalopathy, spontaneous bacterial peritonitis, Grade III and IV esophageal varices&#xD;
             unless banded or other clinical signs of hepatic decompensation&#xD;
&#xD;
          -  History of hepatocellular carcinoma (HCC) or findings suggestive of possible HCC&#xD;
&#xD;
          -  Need for potentially hepatotoxic drugs (e.g. dapsone, erythromycin, fluconazole,&#xD;
             ketoconazole, rifampin, and anti-tuberculosis regimens) or nephrotoxic drugs (e.g.&#xD;
             frequent nonsteroidal anti-inflammatories, aminoglycosides, amphotericin B, and&#xD;
             foscarnet)&#xD;
&#xD;
          -  One or more additional known primary or secondary causes of liver disease, other than&#xD;
             hepatitis B&#xD;
&#xD;
          -  History of clinical pancreatitis&#xD;
&#xD;
          -  Pregnant or breastfeeding&#xD;
&#xD;
          -  Female participants of childbearing potential and male participants must be willing to&#xD;
             use acceptable method of birth control.&#xD;
&#xD;
          -  Medical condition that requires frequent or prolonged use of systemic corticosteroids&#xD;
&#xD;
          -  Use of warfarin or other anticoagulants during 30 days prior to screening or if&#xD;
             expected to be needed during the study period&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <verification_date>September 2013</verification_date>
  <study_first_submitted>November 12, 2012</study_first_submitted>
  <study_first_submitted_qc>November 12, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 15, 2012</study_first_posted>
  <last_update_submitted>September 18, 2013</last_update_submitted>
  <last_update_submitted_qc>September 18, 2013</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 19, 2013</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hepatitis A</mesh_term>
    <mesh_term>Hepatitis B</mesh_term>
    <mesh_term>Hepatitis B, Chronic</mesh_term>
    <mesh_term>Hepatitis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Interferons</mesh_term>
    <mesh_term>Tenofovir</mesh_term>
    <mesh_term>Interferon-alpha</mesh_term>
    <mesh_term>Interferon alpha-2</mesh_term>
    <mesh_term>Peginterferon alfa-2b</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01727271
org study id: 4031-384
nct id: NCT01727271
lead sponsor: 
has dmc: No
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of participants who responded to treatment
time frame: Week 128
measure: Number of participants experiencing adverse events (AEs)
time frame: Up to 128 weeks
measure: Number of participants discontinuing study therapy due to AEs
time frame: Up to 104 weeks
arm group label: Tenofovir Monotherapy
arm group type: Active Comparator
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 group label: PegIFN-2b/Tenofovir Sequential Therapy
arm group type: Experimental
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 group label: Peg-IFN-2b + Tenofovir Combination Therapy
arm group type: Experimental
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: Tenofovir
arm group label: Peg-IFN-2b + Tenofovir Combination Therapy
arm group label: PegIFN-2b/Tenofovir Sequential Therapy
arm group label: Tenofovir Monotherapy
other name: Truvada
intervention type: Biological
intervention name: Pegylated interferon alpha-2b
arm group label: Peg-IFN-2b + Tenofovir Combination Therapy
arm group label: PegIFN-2b/Tenofovir Sequential Therapy
other name: SCH 054031
other name: MK-4031
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
responsible party type: Sponsor
mesh term: Hepatitis A
mesh term: Hepatitis B
mesh term: Hepatitis B, Chronic
mesh term: Hepatitis
mesh term: Interferons
mesh term: Tenofovir
mesh term: Interferon-alpha
mesh term: Interferon alpha-2
mesh term: Peginterferon alfa-2b