<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/NCT04405011</url>
  </required_header>
  <id_info>
    <org_study_id>201807069MINB</org_study_id>
    <nct_id>NCT04405011</nct_id>
  </id_info>
  <brief_title>NUC in Preventing HBV Reactivation in HCV/HBV Co-infected Patients Receiving DAA for CHC</brief_title>
  <official_title>Role of Nucleoside Analogue in Preventing Clinical Reactivation of HBV in HCV/HBV Co-infected Patients Receiving DAA Therapy for Chronic Hepatitis C</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Taiwan University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Taiwan University Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      HBV reactivation is common in HCV/HBV coinfected patients receiving DAA therapy for chronic&#xD;
      hepatitis C. How to prevent HBV reactivation remains unclear. In this trial, we aim to&#xD;
      investigate whether prophylactic nucleos(t)ide analogue (NUC) at the start of DAA could&#xD;
      prevent HBV reactivation or not. And whether prolonged NUC prophylaxis (24 weeks) would be&#xD;
      better than 12-week prophylaxis. This will be a three-arm, open-label, randomized, active&#xD;
      controlled, study. Totally, 60 HBV/HCV co-infected treatment-naïve or treatment-experienced&#xD;
      patients without decompensated liver cirrhosis will be included in this study. Group 1&#xD;
      patients (n=20) will receive 12-week ETV from the start of DAA therapy. Group 2 patients&#xD;
      (n=20) will receive 24-week ETV from the start of DAA till 12 weeks after end of DAA. Group 3&#xD;
      patients (n=20) will not receive ETV during the period of DAA and will serve as controls. The&#xD;
      rate of HBV reactivation and clinical reactivation will be compared among 3 groups of&#xD;
      patients. Expected outcomes: The rate of HBV reactivation and clinical reactivation will be&#xD;
      lower in the ETV prophylaxis group, and will be the lowest in the group receiving 24-week ETV&#xD;
      prophylaxis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      We will determine the incidence of virologic and clinical reactivation of HBV during DAA&#xD;
      treatment for CHC, in two prophylactic groups versus control group. We will also examine&#xD;
      whether extending the duration of prophylactic NUC would be more beneficial than the 3-month&#xD;
      prophylaxis regimen.&#xD;
&#xD;
      Patients with the following criteria will be enrolled: age ≥20 years; anti-HCV positive and&#xD;
      HCV RNA &gt;1000 IU/ml; any HCV genotype; all received 12 weeks of DAA treatment; treatment&#xD;
      naïve or experienced of pegylated interferon/ribavirin; concurrent HBV infection which is&#xD;
      defined by positive HBsAg for at least 6 months. Patients with the following criteria will be&#xD;
      excluded: history of treatment regimen that included any kind of direct antiviral agents;&#xD;
      presence of other etiology of chronic hepatitis including HIV, autoimmune hepatitis, NASH,&#xD;
      etc; uncontrolled diabetes mellitus (Hba1c &gt;8.5); current evidence or suspicion of&#xD;
      malignancy; severe cardiovascular or other severe comorbid diseases; autoimmune disorders;&#xD;
      presence of liver cirrhosis clinically or pathologically; any one of following hematology or&#xD;
      biochemical or clinical abnormalities: AST/ALT &gt;10x ULN, Albumin &lt;3.5g/dL, Bilirubin&#xD;
      &gt;2.5mg/dL, eGFR &lt;30 ml/min/1.73m2, prothrombin time prolongation &gt;4 sec or INR &gt;1.7, platelet&#xD;
      count &lt;100 x 103 uL, and history or presence of ascites or hepatic encephalopathy;&#xD;
      child-bearing age women without the willing to contraceptive control; and pregnant women or&#xD;
      lactating women.&#xD;
&#xD;
      Briefly, 60 HCV/HBV coinfected patients will be enrolled and randomized to receive 12-week&#xD;
      DAA regimen for reimbursed for the the treatment of patients with CHC in Taiwan.&#xD;
&#xD;
      Entecavir (0.5mg; ETV) 1 # daily will be used in the prophylactic group. Group 1 patients&#xD;
      (n=20) will receive 12-week ETV from the start of DAA therapy. Group 2 patients (n=20) will&#xD;
      receive 24-week ETV from the start of DAA till 12 weeks after end of DAA. Group 3 patients&#xD;
      (n=20) will not receive ETV during the period of DAA and serve as controls. The rate of HBV&#xD;
      reactivation and clinical reactivation will be compared among 3 groups of patients.&#xD;
&#xD;
      The primary endpoint will be the incidence of virologic and clinical reactivation of HBV&#xD;
      during DAA treatment for CHC. Secondary objectives include the rate of HBV virologic and&#xD;
      clinical reactivation between 12-week versus 24-week entecavir (ETV) prophylaxis during and&#xD;
      after DAA treatment; the profiles of serum HBV DNA/qHBsAg during and after DAA treatment; and&#xD;
      sustained virological response at post-DAA treatment 12 weeks (SVR12).&#xD;
&#xD;
      The data will be expressed as percentages for category variables and as mean +- standard&#xD;
      deviation for continuous variables. Category variables will be evaluated by Chi-square test&#xD;
      or Fisher exact test. Student's t test or Mann-Whitney U test will be applied for comparison&#xD;
      of the continuous variables. Multivariate analysis will be used to identify factors that are&#xD;
      associated with HBV reactivation. A p value less than 0.05 is considered to be significant.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">August 1, 2018</start_date>
  <completion_date type="Anticipated">December 28, 2020</completion_date>
  <primary_completion_date type="Anticipated">December 28, 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Factorial Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>HBV virologic and clinical reactivation rates</measure>
    <time_frame>72 weeks</time_frame>
    <description>The primary endpoint will be the incidence of virologic and clinical reactivation of HBV during DAA treatment for CHC.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>HBV reactivation rate: 12-week prophylaxis versus 24-week prophylaxis</measure>
    <time_frame>72 weeks</time_frame>
    <description>12 weeks or 24 weeks of ETV prophylaxis in the control of HBV activity during and after DAA treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Profiles of serum HBV DNA/qHBsAg during and after DAA treatment.</measure>
    <time_frame>72 weeks</time_frame>
    <description>The profiles of HBV DNA and qHBsAg will be compared among 3 study groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sustained virological response at post-DAA treatment 12 weeks (SVR12)</measure>
    <time_frame>72 weeks</time_frame>
    <description>The SVR12 will be compared among 3 study groups</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>HBV/HCV Co-infection</condition>
  <arm_group>
    <arm_group_label>Entecavir 0.5mg daily for 24 weeks</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Entecavir will be delivered for 24-week and will be the experimental arm</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Entecavir 0.5mg daily for 12 weeks</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>12-week entecavir will be served as active comparator</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Control group does not receive prophylactic ETV</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>24-week Entecavir</intervention_name>
    <description>Entecavir 0.5mg for 24 weeks will be delivered</description>
    <arm_group_label>Entecavir 0.5mg daily for 24 weeks</arm_group_label>
    <other_name>Prophylaxis arm 1</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>12-week Entecavir</intervention_name>
    <description>Entecavir for 12 weeks will be delivered and serve as the active comparator arm</description>
    <arm_group_label>Entecavir 0.5mg daily for 12 weeks</arm_group_label>
    <other_name>Prophylaxis arm 2</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria&#xD;
&#xD;
          1. Age ≥20 years;&#xD;
&#xD;
          2. Anti-HCV positive and HCV RNA &gt;1000 IU/ml;&#xD;
&#xD;
          3. Any HCV genotype; all received 12 weeks of DAA treatment.&#xD;
&#xD;
          4. Treatment naïve or experienced of pegylated interferon/ribavirin;&#xD;
&#xD;
          5. Concurrent HBV infection which is defined by positive HBsAg for at least 6 months.&#xD;
&#xD;
        Exclusion criteria&#xD;
&#xD;
          1. History of treatment regimen that included any kind of direct antiviral agents;&#xD;
&#xD;
          2. Presence of other etiology of chronic hepatitis including HIV, autoimmune hepatitis,&#xD;
             NASH, etc;&#xD;
&#xD;
          3. Uncontrolled diabetes mellitus (Hba1c &gt;8.5);&#xD;
&#xD;
          4. Current evidence or suspicion of malignancy;&#xD;
&#xD;
          5. Severe cardiovascular or other severe comorbid diseases;&#xD;
&#xD;
          6. Autoimmune disorders;&#xD;
&#xD;
          7. Presence of liver cirrhosis clinically or pathologically;&#xD;
&#xD;
          8. Any one of following hematology or biochemical or clinical abnormalities:&#xD;
&#xD;
             AST/ALT &gt;10x ULN, Albumin &lt;3.5g/dL, Bilirubin &gt;2.5mg/dL, eGFR &lt;30 ml/min/1.73m2,&#xD;
             prothrombin time prolongation &gt;4 sec or INR &gt;1.7, platelet count &lt;100 x 103 uL, and&#xD;
             history or presence of ascites or hepatic encephalopathy.&#xD;
&#xD;
          9. Child-bearing age women without the willing to contraceptive control; pregnant women&#xD;
             or lactating women.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Chun-Jen Liu, MDPHD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Internal Medicine, NTUH</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Chun-Jen Liu</last_name>
    <phone>0972651071</phone>
    <email>cjliu@ntu.edu.tw</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Ting-Chih Chen</last_name>
    <phone>0920228525</phone>
    <email>tingchih@g.ntu.edu.tw</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>National Taiwan University Hospital</name>
      <address>
        <city>Taipei City</city>
        <zip>100</zip>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Chun-Jen Liu, MDPHD</last_name>
      <phone>0972651071</phone>
      <email>cjliu@ntu.edu.tw</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>TC Chen</name>
      <address>
        <city>Taipei</city>
        <zip>100</zip>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>April 17, 2020</study_first_submitted>
  <study_first_submitted_qc>May 26, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 28, 2020</study_first_posted>
  <last_update_submitted>July 1, 2020</last_update_submitted>
  <last_update_submitted_qc>July 1, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 2, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>HCV,HBV</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Coinfection</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Entecavir</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/NCT04405011
org study id: 201807069MINB
nct id: NCT04405011
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
HBV reactivation is common in HCV/HBV coinfected patients receiving DAA therapy for chronic
      hepatitis C. How to prevent HBV reactivation remains unclear. In this trial, we aim to
      investigate whether prophylactic nucleos(t)ide analogue (NUC) at the start of DAA could
      prevent HBV reactivation or not. And whether prolonged NUC prophylaxis (24 weeks) would be
      better than 12-week prophylaxis. This will be a three-arm, open-label, randomized, active
      controlled, study. Totally, 60 HBV/HCV co-infected treatment-naïve or treatment-experienced
      patients without decompensated liver cirrhosis will be included in this study. Group 1
      patients (n=20) will receive 12-week ETV from the start of DAA therapy. Group 2 patients
      (n=20) will receive 24-week ETV from the start of DAA till 12 weeks after end of DAA. Group 3
      patients (n=20) will not receive ETV during the period of DAA and will serve as controls. The
      rate of HBV reactivation and clinical reactivation will be compared among 3 groups of
      patients. Expected outcomes: The rate of HBV reactivation and clinical reactivation will be
      lower in the ETV prophylaxis group, and will be the lowest in the group receiving 24-week ETV
      prophylaxis.
We will determine the incidence of virologic and clinical reactivation of HBV during DAA
      treatment for CHC, in two prophylactic groups versus control group. We will also examine
      whether extending the duration of prophylactic NUC would be more beneficial than the 3-month
      prophylaxis regimen.

      Patients with the following criteria will be enrolled: age ≥20 years; anti-HCV positive and
      HCV RNA >1000 IU/ml; any HCV genotype; all received 12 weeks of DAA treatment; treatment
      naïve or experienced of pegylated interferon/ribavirin; concurrent HBV infection which is
      defined by positive HBsAg for at least 6 months. Patients with the following criteria will be
      excluded: history of treatment regimen that included any kind of direct antiviral agents;
      presence of other etiology of chronic hepatitis including HIV, autoimmune hepatitis, NASH,
      etc; uncontrolled diabetes mellitus (Hba1c >8.5); current evidence or suspicion of
      malignancy; severe cardiovascular or other severe comorbid diseases; autoimmune disorders;
      presence of liver cirrhosis clinically or pathologically; any one of following hematology or
      biochemical or clinical abnormalities: AST/ALT >10x ULN, Albumin <3.5g/dL, Bilirubin
      >2.5mg/dL, eGFR <30 ml/min/1.73m2, prothrombin time prolongation >4 sec or INR >1.7, platelet
      count <100 x 103 uL, and history or presence of ascites or hepatic encephalopathy;
      child-bearing age women without the willing to contraceptive control; and pregnant women or
      lactating women.

      Briefly, 60 HCV/HBV coinfected patients will be enrolled and randomized to receive 12-week
      DAA regimen for reimbursed for the the treatment of patients with CHC in Taiwan.

      Entecavir (0.5mg; ETV) 1 # daily will be used in the prophylactic group. Group 1 patients
      (n=20) will receive 12-week ETV from the start of DAA therapy. Group 2 patients (n=20) will
      receive 24-week ETV from the start of DAA till 12 weeks after end of DAA. Group 3 patients
      (n=20) will not receive ETV during the period of DAA and serve as controls. The rate of HBV
      reactivation and clinical reactivation will be compared among 3 groups of patients.

      The primary endpoint will be the incidence of virologic and clinical reactivation of HBV
      during DAA treatment for CHC. Secondary objectives include the rate of HBV virologic and
      clinical reactivation between 12-week versus 24-week entecavir (ETV) prophylaxis during and
      after DAA treatment; the profiles of serum HBV DNA/qHBsAg during and after DAA treatment; and
      sustained virological response at post-DAA treatment 12 weeks (SVR12).

      The data will be expressed as percentages for category variables and as mean +- standard
      deviation for continuous variables. Category variables will be evaluated by Chi-square test
      or Fisher exact test. Student's t test or Mann-Whitney U test will be applied for comparison
      of the continuous variables. Multivariate analysis will be used to identify factors that are
      associated with HBV reactivation. A p value less than 0.05 is considered to be significant.
allocation: Randomized
intervention model: Factorial Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: HBV virologic and clinical reactivation rates
time frame: 72 weeks
description: The primary endpoint will be the incidence of virologic and clinical reactivation of HBV during DAA treatment for CHC.
measure: HBV reactivation rate: 12-week prophylaxis versus 24-week prophylaxis
time frame: 72 weeks
description: 12 weeks or 24 weeks of ETV prophylaxis in the control of HBV activity during and after DAA treatment
measure: Profiles of serum HBV DNA/qHBsAg during and after DAA treatment.
time frame: 72 weeks
description: The profiles of HBV DNA and qHBsAg will be compared among 3 study groups
measure: Sustained virological response at post-DAA treatment 12 weeks (SVR12)
time frame: 72 weeks
description: The SVR12 will be compared among 3 study groups
arm group label: Entecavir 0.5mg daily for 24 weeks
arm group type: Experimental
description: Entecavir will be delivered for 24-week and will be the experimental arm
arm group label: Entecavir 0.5mg daily for 12 weeks
arm group type: Active Comparator
description: 12-week entecavir will be served as active comparator
arm group label: Control
arm group type: No Intervention
description: Control group does not receive prophylactic ETV
intervention type: Drug
intervention name: 24-week Entecavir
description: Entecavir 0.5mg for 24 weeks will be delivered
arm group label: Entecavir 0.5mg daily for 24 weeks
other name: Prophylaxis arm 1
intervention type: Drug
intervention name: 12-week Entecavir
description: Entecavir for 12 weeks will be delivered and serve as the active comparator arm
arm group label: Entecavir 0.5mg daily for 12 weeks
other name: Prophylaxis arm 2
criteria: 
gender: All
minimum age: 20 Years
maximum age: 70 Years
healthy volunteers: No
last name: Chun-Jen Liu, MDPHD
role: Principal Investigator
affiliation: Department of Internal Medicine, NTUH
last name: Chun-Jen Liu
phone: 0972651071
email: cjliu@ntu.edu.tw
last name: Ting-Chih Chen
phone: 0920228525
email: tingchih@g.ntu.edu.tw
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
country: Taiwan
responsible party type: Sponsor
mesh term: Coinfection
mesh term: Entecavir