<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/NCT03020095</url>
  </required_header>
  <id_info>
    <org_study_id>ASC162001</org_study_id>
    <nct_id>NCT03020095</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of Ravidasvir + Danoprevir/r 12-week Oral Therapy in Treatment-Naive Non Cirrhotic G1 CHC Taiwan</brief_title>
  <official_title>Phase 2 Study To Investigate the Efficacy, Safety And Pharmacokinetics Of Ravidasvir In Combination With Ritonavir-boosted Danoprevir And Ribavirin In Treatment-naive Non-cirrhotic Taiwanese Patients Who Have Chronic Hepatitis C Genotype 1</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ascletis Pharmaceuticals Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ascletis Pharmaceuticals Co., Ltd.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the efficacy, safety and tolerability of Ravidasvir&#xD;
      (ASC16) in combination with Ritonavir-boosted Danoprevir(ASC08) and Ribavirin in&#xD;
      treatment-naive no-cirrhotic Taiwanese patients who have chronic hepatitis C genotype1.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>August 2015</start_date>
  <completion_date type="Actual">February 2017</completion_date>
  <primary_completion_date type="Actual">August 2016</primary_completion_date>
  <phase>Phase 2</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>Percentage of Subjects With Sustained Virologic Response (SVR12) 12 Weeks Post-treatment</measure>
    <time_frame>12 weeks</time_frame>
    <description>SVR12, defined as undetectable HCV RNA 12 weeks after the last day of study drug administration.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">38</enrollment>
  <condition>Chronic Hepatitis C</condition>
  <arm_group>
    <arm_group_label>Ravidasvir,Danoprevir/r,RBV</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive Ravidasvir 200mg plus Ritonavir boosted Danoprevir 200/200mg,and Ribavirin 1000/1200mg daily for 12 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ravidasvir</intervention_name>
    <description>Ravidasvir 200mg tablet administered orally once daily</description>
    <arm_group_label>Ravidasvir,Danoprevir/r,RBV</arm_group_label>
    <other_name>Asclevir</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Danoprevir</intervention_name>
    <description>Danoprevir 100mg tablet administered orally twice daily</description>
    <arm_group_label>Ravidasvir,Danoprevir/r,RBV</arm_group_label>
    <other_name>Ganovo</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ritonavir</intervention_name>
    <description>Ritonavir 100mg tablet administered orally twice daily</description>
    <arm_group_label>Ravidasvir,Danoprevir/r,RBV</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ribavirin</intervention_name>
    <description>Ribavirin(RBV)1000/1200 mg/day (bodyweight&lt;75/≥75 kg)administered orally</description>
    <arm_group_label>Ravidasvir,Danoprevir/r,RBV</arm_group_label>
    <other_name>Ribasphere®</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Willing and able to provide written informed consent&#xD;
&#xD;
          -  Chronic HCV infection (≥6 months) , HCV RNA ≥ 1 × 104 IU/mL&#xD;
&#xD;
          -  Never received prior-treatment for HCV with interferon, RBV, or other direct-acting or&#xD;
             host-targeting antivirals for HCV&#xD;
&#xD;
          -  Chronic liver disease consistent with CHC infection without cirrhosis as determined by&#xD;
             biopsy obtained within the past calendar 36 months using one of the liver biopsy&#xD;
             methods in the protocol (non-cirrhosis is defined as: Metavir score ˂ 4), or as&#xD;
             determined by Fibroscan defined as: ˂ 14.6 kPa. Patients who have not obtained a liver&#xD;
             biopsy or Fibroscan in the last 3 years will have a study related Fibroscan performed&#xD;
             in order to confirm the diagnosis. Liver biopsy will be performed by investigator's&#xD;
             judgement&#xD;
&#xD;
          -  All male patients with female partners of childbearing potential must use two reliable&#xD;
             forms of effective contraception (combined) during treatment and for 6 months&#xD;
             following the last dose of ribavirin&#xD;
&#xD;
          -  Others as specified in detailed protocol.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant or lactating women.&#xD;
&#xD;
          -  History or presence of decompensated liver disease (history of ascites, hepatic&#xD;
             encephalopathy, HCC, or bleeding esophageal varices)&#xD;
&#xD;
          -  Presence or history of non-hepatitis C chronic liver disease, including but not&#xD;
             limited to, autoimmune hepatitis, α-1-antitrypsin deficiency, C282Y homozygous&#xD;
             hemochromatosis, Wilson's disease, drug- or toxin-induced liver disease,&#xD;
             alcohol-related liver disease, primary biliary cirrhosis, sclerosing cholangitis, and&#xD;
             porphyria cutanea tarda causing liver pathology or requiring phlebotomy&#xD;
&#xD;
          -  Positive hepatitis B surface antigen or HIV antibody at screening&#xD;
&#xD;
          -  History or presence of liver cirrhosis&#xD;
&#xD;
          -  History of severe psychiatric disease, including psychosis and/or depression, who is&#xD;
             not able to participate or able to give written informed consent and to comply with&#xD;
             the study restrictions&#xD;
&#xD;
          -  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;
          -  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). Patients with stable coronary&#xD;
             artery disease (e.g., 6 months after by-pass surgery, angioplasty with or without&#xD;
             stent placement, etc.) as confirmed by a cardiologist will be permitted. In addition,&#xD;
             patients with documented or presumed unstable coronary artery disease, cardiovascular&#xD;
             disease, or cerebrovascular disease should not be enrolled.&#xD;
&#xD;
          -  Any patient with an increased risk for anemia (e.g., thalassemia, sickle cell anemia,&#xD;
             or spherocytosis) or for whom anemia would be medically problematic&#xD;
&#xD;
          -  History of pre-existing renal disease, patients with a history of nephrolithiasis will&#xD;
             be allowed&#xD;
&#xD;
          -  Others as specified in detailed protocol.&#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>Huoling Tang, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Ascletis Pharmaceuticals Co., Ltd.</affiliation>
  </overall_official>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>January 5, 2017</study_first_submitted>
  <study_first_submitted_qc>January 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 13, 2017</study_first_posted>
  <results_first_submitted>August 18, 2020</results_first_submitted>
  <results_first_submitted_qc>October 20, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">October 22, 2020</results_first_posted>
  <last_update_submitted>October 20, 2020</last_update_submitted>
  <last_update_submitted_qc>October 20, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 22, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Ravidasvir</keyword>
  <keyword>HCV GT1</keyword>
  <keyword>SVR12</keyword>
  <keyword>Danoprevir/r</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hepatitis C</mesh_term>
    <mesh_term>Hepatitis C, Chronic</mesh_term>
    <mesh_term>Hepatitis</mesh_term>
    <mesh_term>Hepatitis, Chronic</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ritonavir</mesh_term>
    <mesh_term>Ribavirin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Ravidasvir,Danoprevir/r,RBV</title>
          <description>Participants will receive Ravidasvir 200mg plus Ritonavir boosted Danoprevir 200/200mg,and Ribavirin 1000/1200mg daily for 12 weeks.&#xD;
Ravidasvir: Ravidasvir 200mg tablet administered orally once daily&#xD;
Danoprevir: Danoprevir 100mg tablet administered orally twice daily&#xD;
Ritonavir: Ritonavir 100mg tablet administered orally twice daily&#xD;
Ribavirin: Ribavirin(RBV)1000/1200 mg/day (bodyweight&lt;75/≥75 kg)administered orally</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="38"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="37"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Ravidasvir,Danoprevir/r,RBV</title>
          <description>Participants will receive Ravidasvir 200mg plus Ritonavir boosted Danoprevir 200/200mg,and Ribavirin 1000/1200mg daily for 12 weeks.&#xD;
Ravidasvir: Ravidasvir 200mg tablet administered orally once daily&#xD;
Danoprevir: Danoprevir 100mg tablet administered orally twice daily&#xD;
Ritonavir: Ritonavir 100mg tablet administered orally twice daily&#xD;
Ribavirin: Ribavirin(RBV)1000/1200 mg/day (bodyweight&lt;75/≥75 kg)administered orally</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="38"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="56.6" spread="12.76"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="38"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Taiwan</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Subjects With Sustained Virologic Response (SVR12) 12 Weeks Post-treatment</title>
        <description>SVR12, defined as undetectable HCV RNA 12 weeks after the last day of study drug administration.</description>
        <time_frame>12 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Ravidasvir,Danoprevir/r,RBV</title>
            <description>Participants will receive Ravidasvir 200mg plus Ritonavir boosted Danoprevir 200/200mg,and Ribavirin 1000/1200mg daily for 12 weeks.&#xD;
Ravidasvir: Ravidasvir 200mg tablet administered orally once daily&#xD;
Danoprevir: Danoprevir 100mg tablet administered orally twice daily&#xD;
Ritonavir: Ritonavir 100mg tablet administered orally twice daily&#xD;
Ribavirin: Ribavirin(RBV)1000/1200 mg/day (bodyweight&lt;75/≥75 kg)administered orally</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Subjects With Sustained Virologic Response (SVR12) 12 Weeks Post-treatment</title>
          <description>SVR12, defined as undetectable HCV RNA 12 weeks after the last day of study drug administration.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Ravidasvir,Danoprevir/r,RBV</title>
          <description>Participants will receive Ravidasvir 200mg plus Ritonavir boosted Danoprevir 200/200mg,and Ribavirin 1000/1200mg daily for 12 weeks.&#xD;
Ravidasvir: Ravidasvir 200mg tablet administered orally once daily&#xD;
Danoprevir: Danoprevir 100mg tablet administered orally twice daily&#xD;
Ritonavir: Ritonavir 100mg tablet administered orally twice daily&#xD;
Ribavirin: Ribavirin(RBV)1000/1200 mg/day (bodyweight&lt;75/≥75 kg)administered orally</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>anemia</sub_title>
                <counts group_id="E1" events="10" subjects_affected="10" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>After conclusion of the study and without prior written approval from Ascletis, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met:&#xD;
The study has been completed at all study sites for at least 3 years.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Clinical Trial Disclosures</name_or_title>
      <organization>Ascletis Pharmaceticals Co., Ltd</organization>
      <phone>86057187707910</phone>
      <email>xin.li@ascletis.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03020095
org study id: ASC162001
nct id: NCT03020095
lead sponsor: 
has dmc: Yes
The purpose of this study is to evaluate the efficacy, safety and tolerability of Ravidasvir
      (ASC16) in combination with Ritonavir-boosted Danoprevir(ASC08) and Ribavirin in
      treatment-naive no-cirrhotic Taiwanese patients who have chronic hepatitis C genotype1.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of Subjects With Sustained Virologic Response (SVR12) 12 Weeks Post-treatment
time frame: 12 weeks
description: SVR12, defined as undetectable HCV RNA 12 weeks after the last day of study drug administration.
arm group label: Ravidasvir,Danoprevir/r,RBV
arm group type: Experimental
description: Participants will receive Ravidasvir 200mg plus Ritonavir boosted Danoprevir 200/200mg,and Ribavirin 1000/1200mg daily for 12 weeks.
intervention type: Drug
intervention name: Ravidasvir
description: Ravidasvir 200mg tablet administered orally once daily
arm group label: Ravidasvir,Danoprevir/r,RBV
other name: Asclevir
intervention type: Drug
intervention name: Danoprevir
description: Danoprevir 100mg tablet administered orally twice daily
arm group label: Ravidasvir,Danoprevir/r,RBV
other name: Ganovo
intervention type: Drug
intervention name: Ritonavir
description: Ritonavir 100mg tablet administered orally twice daily
arm group label: Ravidasvir,Danoprevir/r,RBV
intervention type: Drug
intervention name: Ribavirin
description: Ribavirin(RBV)1000/1200 mg/day (bodyweight<75/≥75 kg)administered orally
arm group label: Ravidasvir,Danoprevir/r,RBV
other name: Ribasphere®
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: No
last name: Huoling Tang, PhD
role: Study Director
affiliation: Ascletis Pharmaceuticals Co., Ltd.
responsible party type: Sponsor
mesh term: Hepatitis C
mesh term: Hepatitis C, Chronic
mesh term: Hepatitis
mesh term: Hepatitis, Chronic
mesh term: Ritonavir
mesh term: Ribavirin
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 