<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/NCT03759782</url>
  </required_header>
  <id_info>
    <org_study_id>20180733</org_study_id>
    <nct_id>NCT03759782</nct_id>
  </id_info>
  <brief_title>Ribavirin to Enhance Hepatitis B Virus Nucleotide Analog Antiviral Activity</brief_title>
  <official_title>Use of Immune Modulatory Properties of Ribavirin to Enhance Hepatitis B Virus Nucleotide Analog Antiviral Activity: Proposal for Pilot Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ottawa Hospital Research Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ottawa Hospital Research Institute</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Hepatitis B virus (HBV) leads to life-threatening disease like liver failure and liver&#xD;
      cancer. For most, a cure is unattainable as current HBV antiviral therapy (using nucleoside&#xD;
      analogues) are not able to clear the virus from their liver. While HBV treatments are&#xD;
      typically administered alone (monotherapy), this study will explore the use of Ribavirin in&#xD;
      combination with standard therapy to enhance current treatment regimens. Ribavirin is&#xD;
      commonly used to treat Hepatitis C Virus (HCV) but there is evidence that Ribavirin also&#xD;
      induces immune effects that are beneficial in HBV treatment. The aim of this study is to&#xD;
      determine whether combination of Ribavirin and a nucleoside analog is more effective compared&#xD;
      to nucleoside analog treatment alone. Enrolled patients will be followed for treatment&#xD;
      response according to standard clinical and virological tests, as well as immune response to&#xD;
      HBV. Our ultimate goal is to find a more effective treatment and improve health outcomes for&#xD;
      persons living with HBV.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">January 10, 2019</start_date>
  <completion_date type="Anticipated">September 30, 2022</completion_date>
  <primary_completion_date type="Anticipated">January 31, 2022</primary_completion_date>
  <phase>Phase 3</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>
    <intervention_model_description>Open-label</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The Decline of Participants Serum HBV DNA values for both study arms at each study.</measure>
    <time_frame>24 weeks</time_frame>
    <description>The absolute decline in HBV DNA and quantitative HBsAg titre will be compared with baseline level at each study visit overall and between study arms (with or without RBV).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Fibroscan score</measure>
    <time_frame>24 weeks</time_frame>
    <description>Individual fibroscan scores pre and post treatment for each group, using fibrosis scores calculated in kilopascal F0 representing no fibrosis and F4 value indicating cirrhosis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Liver enzyme values</measure>
    <time_frame>24 weeks</time_frame>
    <description>Participants individual reduction in liver enzymes at each visit.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with treatment related adverse events as assessed by CTCAE v4.0.</measure>
    <time_frame>28 weeks</time_frame>
    <description>Safety profile of TDF plus Ribavirin regime</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">24</enrollment>
  <condition>Hepatitis B, Chronic</condition>
  <arm_group>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tenofovir (TDF) 300 mg po once a day (OD)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Tenofovir 300 mg po OD + Ribavirin 400 mg twice a day (BID) if &lt;70kg / 600 mg every (q) in the morning (AM) and 400 mg q in the evening (PM) if ≥70kg</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ribavirin</intervention_name>
    <description>Ribavirin will be added to the standard of care treatment (tenofovir) regime for 24 weeks.</description>
    <arm_group_label>Group 2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tenofovir</intervention_name>
    <description>Tenofovir as per standard of care</description>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_label>Group 2</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. HBV Hepatitis B surface antigen (HBsAg) positive for a minimum of 24 weeks&#xD;
&#xD;
          2. HBV DNA level &gt;20,000 IU/mL&#xD;
&#xD;
          3. ≥ 18 years of age&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Willingness and ability to sign an informed consent&#xD;
&#xD;
          2. HBV nucleos(t)ides and/or interferon exposure within 24 weeks of study medication&#xD;
             dosing&#xD;
&#xD;
          3. HIV and other immune compromising condition (e.g. cancer with the exception of&#xD;
             non-invasive cutaneous malignancy, autoimmune condition) or therapy (i.e. systemic&#xD;
             steroids, chemotherapy)&#xD;
&#xD;
          4. HCV co-infected&#xD;
&#xD;
          5. Cirrhosis (defined by biopsy criteria or as &gt;18.4 kilopascal (kPa) by transient&#xD;
             elastography)&#xD;
&#xD;
          6. Creatinine Clearance &lt;60 ml/min&#xD;
&#xD;
          7. Baseline hemoglobin &lt;130 g/L in males and &lt;120 g/L in females&#xD;
&#xD;
          8. Unwilling or unable to use contraception (unless confirmed surgical sterilization)&#xD;
&#xD;
          9. Pregnancy confirmed by blood test&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Curtis L Cooper, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ottawa Hospital Research Institute</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Curtis L Cooper, MD</last_name>
    <phone>613.737.8924</phone>
    <email>ccooper@toh.ca</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Miriam I Muir, RN BA</last_name>
    <phone>613737.8899</phone>
    <phone_ext>72723</phone_ext>
    <email>mimmuir@toh.ca</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Cumming School of Medicine, University of Calgary</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <zip>T2N4Z6</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Carla Coffin, MD</last_name>
      <phone>403-592-5049</phone>
      <email>cacoffin@ucalgary.ca</email>
    </contact>
    <contact_backup>
      <last_name>Leah Kilvert, BSCN</last_name>
      <phone>403.220.8966</phone>
      <email>lvkilver@ucalgary.ca</email>
    </contact_backup>
    <investigator>
      <last_name>Carla Coffin, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Ottawa Hospital Research Institute</name>
      <address>
        <city>Ottawa</city>
        <state>Ontario</state>
        <zip>K1H8L6</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Curtis Cooper, MD</last_name>
      <phone>6137378924</phone>
      <email>ccooper@toh.ca</email>
    </contact>
    <contact_backup>
      <last_name>Miriam Muir, RN</last_name>
      <phone>6137378899</phone>
      <phone_ext>72723</phone_ext>
      <email>mmuir@toh.ca</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>October 2, 2018</study_first_submitted>
  <study_first_submitted_qc>November 28, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 30, 2018</study_first_posted>
  <last_update_submitted>September 10, 2021</last_update_submitted>
  <last_update_submitted_qc>September 10, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 14, 2021</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>Tenofovir</mesh_term>
    <mesh_term>Ribavirin</mesh_term>
  </intervention_browse>
  <pending_results>
    <submitted>April 26, 2022</submitted>
    <returned>January 26, 2023</returned>
    <submitted>February 10, 2023</submitted>
  </pending_results>
  <!-- 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/NCT03759782
org study id: 20180733
nct id: NCT03759782
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Hepatitis B virus (HBV) leads to life-threatening disease like liver failure and liver
      cancer. For most, a cure is unattainable as current HBV antiviral therapy (using nucleoside
      analogues) are not able to clear the virus from their liver. While HBV treatments are
      typically administered alone (monotherapy), this study will explore the use of Ribavirin in
      combination with standard therapy to enhance current treatment regimens. Ribavirin is
      commonly used to treat Hepatitis C Virus (HCV) but there is evidence that Ribavirin also
      induces immune effects that are beneficial in HBV treatment. The aim of this study is to
      determine whether combination of Ribavirin and a nucleoside analog is more effective compared
      to nucleoside analog treatment alone. Enrolled patients will be followed for treatment
      response according to standard clinical and virological tests, as well as immune response to
      HBV. Our ultimate goal is to find a more effective treatment and improve health outcomes for
      persons living with HBV.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Open-label
primary purpose: Treatment
masking: None (Open Label)
measure: The Decline of Participants Serum HBV DNA values for both study arms at each study.
time frame: 24 weeks
description: The absolute decline in HBV DNA and quantitative HBsAg titre will be compared with baseline level at each study visit overall and between study arms (with or without RBV).
measure: Fibroscan score
time frame: 24 weeks
description: Individual fibroscan scores pre and post treatment for each group, using fibrosis scores calculated in kilopascal F0 representing no fibrosis and F4 value indicating cirrhosis.
measure: Liver enzyme values
time frame: 24 weeks
description: Participants individual reduction in liver enzymes at each visit.
measure: Number of participants with treatment related adverse events as assessed by CTCAE v4.0.
time frame: 28 weeks
description: Safety profile of TDF plus Ribavirin regime
arm group label: Group 1
arm group type: Experimental
description: Tenofovir (TDF) 300 mg po once a day (OD)
arm group label: Group 2
arm group type: Active Comparator
description: Tenofovir 300 mg po OD + Ribavirin 400 mg twice a day (BID) if <70kg / 600 mg every (q) in the morning (AM) and 400 mg q in the evening (PM) if ≥70kg
intervention type: Drug
intervention name: Ribavirin
description: Ribavirin will be added to the standard of care treatment (tenofovir) regime for 24 weeks.
arm group label: Group 2
intervention type: Drug
intervention name: Tenofovir
description: Tenofovir as per standard of care
arm group label: Group 1
arm group label: Group 2
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Curtis L Cooper, MD
role: Principal Investigator
affiliation: Ottawa Hospital Research Institute
last name: Curtis L Cooper, MD
phone: 613.737.8924
email: ccooper@toh.ca
last name: Miriam I Muir, RN BA
phone: 613737.8899
phone ext: 72723
email: mimmuir@toh.ca
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
country: Canada
responsible party type: Sponsor
mesh term: Hepatitis A
mesh term: Hepatitis B
mesh term: Hepatitis B, Chronic
mesh term: Hepatitis
mesh term: Tenofovir
mesh term: Ribavirin
submitted: April 26, 2022
returned: January 26, 2023
submitted: February 10, 2023