<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/NCT03004625</url>
  </required_header>
  <id_info>
    <org_study_id>AI444-406</org_study_id>
    <nct_id>NCT03004625</nct_id>
  </id_info>
  <brief_title>Daclatasvir, Asunaprevir Plus Ribavirin for HCV Genotype 1b Without NS5A RAV</brief_title>
  <official_title>Treatment Efficacy and Safety of 12 Weeks of Daclatasvir, Asunaprevir Plus Ribavirin for HCV Genotype 1b Without Baseline NS5A Resistance-associated Variants (DARING)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Kaohsiung Medical University Chung-Ho Memorial Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Chang Gung Memorial Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Taiwan University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Taipei Veterans General Hospital, Taiwan</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>China Medical University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Cheng-Kung University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Kaohsiung Medical University Chung-Ho Memorial Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      A single-arm, multi-center study of HCV-1b patients without baseline non-structure protein&#xD;
      (NS5A) resistance-associated variants. Daclatasvir (60mg/day) and asunaprevir (100 mg twice&#xD;
      daily) plus weight-based ribavirin (1000-1200 mg/d) for 12 weeks will be prescribed.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Twenty-four weeks of Daclatasvir plus Asunaprevir provided a high treatment efficacy in&#xD;
      hepatitis C virus genotype 1b (HCV-1b) patients. Patients with non-structural protein 5A&#xD;
      (NS5A) resistance associated variants (RAVs) would have an inferior response. The&#xD;
      investigators anticipate that12 weeks of daclatasvir and asunaprevir plus ribavirin is highly&#xD;
      effective for HCV Genotype 1b patients without baseline NS5A RAVs.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2016</start_date>
  <completion_date type="Actual">April 2018</completion_date>
  <primary_completion_date type="Actual">April 2018</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>To determine the treatment efficacy (SVR12) of 12 weeks of daclatasvir and asunaprevir plus ribavirin for HCV-1b patients without baseline RAVs</measure>
    <time_frame>6 months (including 3 months of treatment and 3 months of post-treatment follow-up peroid</time_frame>
    <description>SVR12 is defined as undetectable HCV RNA 12 weeks throughout 12 weeks of post-treatment follow-up peroid</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>To evaluate the number of participants with treatment-related adverse events of 12 weeks of daclatasvir and asunaprevir plus ribavirin for HCV-1b patients without baseline RAVs.</measure>
    <time_frame>3 months</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">70</enrollment>
  <condition>Hepatitis C</condition>
  <arm_group>
    <arm_group_label>Study Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>HCV-1b patients without baseline NS5A resistance-associated variants receiving Daclatasvir (60mg/day) and asunaprevir (100 mg twice daily) plus weight-based ribavirin (1000-1200 mg/d) for 12 weeks. (daclatasvir, asunaprevir plus ribavirin)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>daclatasvir</intervention_name>
    <description>to evaluate the treatment efficacy and safety of the drug in HCV patients</description>
    <arm_group_label>Study Arm</arm_group_label>
    <other_name>Daklinza</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>asunaprevir</intervention_name>
    <description>to evaluate the treatment efficacy and safety of the drug in HCV patients</description>
    <arm_group_label>Study Arm</arm_group_label>
    <other_name>Sunvepra</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ribavirin</intervention_name>
    <description>to evaluate the treatment efficacy and safety of the drug in HCV patients</description>
    <arm_group_label>Study Arm</arm_group_label>
    <other_name>Robatrol</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Treatment naïve, interferon-experienced, interferon-intolerant or&#xD;
             interferon-ineligible, HCV genotype 1b patients with compensated liver disease.&#xD;
&#xD;
          2. Patients with compensated liver cirrhosis will be capped at 40%.&#xD;
&#xD;
             Cirrhosis is defined as any one of the following:&#xD;
&#xD;
               -  Liver biopsy showing cirrhosis&#xD;
&#xD;
               -  Fibroscan indicative of cirrhosis as evidenced by a result &gt; 12.5 kilopascal&#xD;
&#xD;
             Absence of cirrhosis is defined as any one of the following:&#xD;
&#xD;
               -  Liver biopsy within 2 years of Screening showing absence of cirrhosis&#xD;
&#xD;
               -  Fibroscan within 6 months of Baseline with a result of ≤ 12.5 kilopascal&#xD;
&#xD;
          3. History of chronic HCV infection &gt; 6 months&#xD;
&#xD;
          4. Aged at least 20 years&#xD;
&#xD;
          5. HCV RNA of 10,000 IU/mL or greater&#xD;
&#xD;
          6. Negative serum or urine pregnancy test result (sensitivity of 25 international units&#xD;
             or better) for women with childbearing potential within the 24-hour period before the&#xD;
             first dose of study drugs&#xD;
&#xD;
          7. Female patients with childbearing potential must agree to use two reliable forms of&#xD;
             effective non-hormonal contraception (i.e., condoms, cervical barriers, intrauterine&#xD;
             device, spermicides, or sponge), at least 1 of which must be a physical barrier&#xD;
             method, during treatment and for at least 6 months following the last dose of&#xD;
             ribavirin.&#xD;
&#xD;
          8. A hormonal contraception (in lieu of non-hormonal) plus a physical barrier method can&#xD;
             be used after end of treatment. All men with female partners of childbearing potential&#xD;
             must use two reliable forms of effective contraception (combined) during treatment and&#xD;
             for 6 months following the last dose of ribavirin&#xD;
&#xD;
          9. Ability to participate and willingness to give written informed consent and to comply&#xD;
             with the study restrictions.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. The existence of baseline NS5A RAV &quot;Lycine 31 (L31F/I/M)&quot; or &quot;Tyrosine93 (Y93H)&quot;, by&#xD;
             using direct-sequencing with RAV of &gt; 20%.&#xD;
&#xD;
          2. Hepatitis B virus or HIV co-infection.&#xD;
&#xD;
          3. Patients with experience of ascites, oesophageal varices, or other evidence of hepatic&#xD;
             decompensation, and/or hepatocellular carcinoma.&#xD;
&#xD;
          4. History of organ transplantation, except cornea transplantation.&#xD;
&#xD;
          5. Hemoglobin concentration &lt; 12 g/dl for male, 11 g/dl for female&#xD;
&#xD;
          6. Platelet count &lt; 50,000/mm3&#xD;
&#xD;
          7. Prior direct antiviral agents (DAAs) experienced.&#xD;
&#xD;
          8. History of active malignancy within the last 5 years, with the exception of localized&#xD;
             or in situ carcinoma (e.g., basal or squamous cell carcinoma of the skin)&#xD;
&#xD;
          9. History of severe cardiac disease (e.g., New York Heart Association Functional Class&#xD;
             III or IV, myocardial infarction within 6 months, ventricular tachyarrhythmia's&#xD;
             requiring ongoing treatment, unstable angina or other unstable, uncontrolled or&#xD;
             significant cardiovascular disease within 6 months).&#xD;
&#xD;
         10. Poorly controlled diabetes (Hemoglobin A1c value ≥ 8.5%) and endocrine condition.&#xD;
&#xD;
         11. Total bilirubin &gt;2 mg/dL, unless subject has a documented history of Gilbert's&#xD;
             disease.&#xD;
&#xD;
         12. Creatinine Clearance (CrCl) &lt;30 mL/min (as estimated by Cockcroft and Gault)&#xD;
&#xD;
         13. Pregnant or lactating women.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ming-Lung Yu, MD., PhD.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Kaohsiung Medical University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Kaohsiung Medical Universsity</name>
      <address>
        <city>Kaohsiung</city>
        <zip>807</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>December 21, 2016</study_first_submitted>
  <study_first_submitted_qc>December 28, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 29, 2016</study_first_posted>
  <last_update_submitted>January 7, 2019</last_update_submitted>
  <last_update_submitted_qc>January 7, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 9, 2019</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 C</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ribavirin</mesh_term>
    <mesh_term>Asunaprevir</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>June 9, 2019</submitted>
    <returned>July 26, 2019</returned>
  </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/NCT03004625
org study id: AI444-406
nct id: NCT03004625
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
A single-arm, multi-center study of HCV-1b patients without baseline non-structure protein
      (NS5A) resistance-associated variants. Daclatasvir (60mg/day) and asunaprevir (100 mg twice
      daily) plus weight-based ribavirin (1000-1200 mg/d) for 12 weeks will be prescribed.
Twenty-four weeks of Daclatasvir plus Asunaprevir provided a high treatment efficacy in
      hepatitis C virus genotype 1b (HCV-1b) patients. Patients with non-structural protein 5A
      (NS5A) resistance associated variants (RAVs) would have an inferior response. The
      investigators anticipate that12 weeks of daclatasvir and asunaprevir plus ribavirin is highly
      effective for HCV Genotype 1b patients without baseline NS5A RAVs.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: To determine the treatment efficacy (SVR12) of 12 weeks of daclatasvir and asunaprevir plus ribavirin for HCV-1b patients without baseline RAVs
time frame: 6 months (including 3 months of treatment and 3 months of post-treatment follow-up peroid
description: SVR12 is defined as undetectable HCV RNA 12 weeks throughout 12 weeks of post-treatment follow-up peroid
measure: To evaluate the number of participants with treatment-related adverse events of 12 weeks of daclatasvir and asunaprevir plus ribavirin for HCV-1b patients without baseline RAVs.
time frame: 3 months
arm group label: Study Arm
arm group type: Experimental
description: HCV-1b patients without baseline NS5A resistance-associated variants receiving Daclatasvir (60mg/day) and asunaprevir (100 mg twice daily) plus weight-based ribavirin (1000-1200 mg/d) for 12 weeks. (daclatasvir, asunaprevir plus ribavirin)
intervention type: Drug
intervention name: daclatasvir
description: to evaluate the treatment efficacy and safety of the drug in HCV patients
arm group label: Study Arm
other name: Daklinza
intervention type: Drug
intervention name: asunaprevir
description: to evaluate the treatment efficacy and safety of the drug in HCV patients
arm group label: Study Arm
other name: Sunvepra
intervention type: Drug
intervention name: Ribavirin
description: to evaluate the treatment efficacy and safety of the drug in HCV patients
arm group label: Study Arm
other name: Robatrol
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: No
last name: Ming-Lung Yu, MD., PhD.
role: Principal Investigator
affiliation: Kaohsiung Medical University
facility: 
country: Taiwan
responsible party type: Sponsor
mesh term: Hepatitis C
mesh term: Ribavirin
mesh term: Asunaprevir
sharing ipd: No
submitted: June 9, 2019
returned: July 26, 2019