<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/NCT03020082</url>
  </required_header>
  <id_info>
    <org_study_id>ASC08201503</org_study_id>
    <nct_id>NCT03020082</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of Danoprevir/r + PR 12week Triple Therapy in Treatment Naive Non-Cirrhotic G1 CHC China III</brief_title>
  <official_title>A Multi-centered, Open Label, Phase III Study on Efficacy, Safety of Ritonavir-boosted ASC08 (Danoprevir) in Combination With Peg-IFN and RBV in Treatment-Naive Non-Cirrhotic Patients Who Have Chronic Hepatitis 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 and safety of Ritonavir-boosted ASC08&#xD;
      (Danoprevir) in Combination with Peg-IFN and RBV in Treatment-Naive Non-Cirrhotic Patients&#xD;
      Who Have Chronic Hepatitis Genotype 1.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>June 2016</start_date>
  <completion_date type="Actual">May 2017</completion_date>
  <primary_completion_date type="Actual">May 2017</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>Proportion of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12)</measure>
    <time_frame>12 weeks</time_frame>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">141</enrollment>
  <condition>Chronic Hepatitis C</condition>
  <arm_group>
    <arm_group_label>Danoprevir, Ritonavir, Peg-IFN,RBV</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive Ritonavir- boosted Danoprevir 100mg/100mg BID in combination with subcutaneous injection of weekly peginterferon alfa-2a at 180 mcg and RBV administered orally 500mg (5 tablets)( body weight &lt;75Kg) BID, 600mg (6 tablets) BID body weight ≥75Kg for 12 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Danoprevir</intervention_name>
    <description>Danoprevir (DNV)administered orally 100mg BID for 12 weeks;</description>
    <arm_group_label>Danoprevir, Ritonavir, Peg-IFN,RBV</arm_group_label>
    <other_name>ASC08</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ritonavir</intervention_name>
    <description>Ritonavir administered orally 100mg BID for 12 weeks;</description>
    <arm_group_label>Danoprevir, Ritonavir, Peg-IFN,RBV</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>peginterferon alfa-2a</intervention_name>
    <description>PEG-IFN abdominal or thigh subcutaneous injection, 180μg, once a week for 12 weeks;</description>
    <arm_group_label>Danoprevir, Ritonavir, Peg-IFN,RBV</arm_group_label>
    <other_name>Peg-IFN</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>RBV</intervention_name>
    <description>RBV administered orally 500mg (5 tablets)( body weight &lt;75Kg) BID, 600mg (6 tablets) BID body weight ≥75Kg, for 12 weeks.</description>
    <arm_group_label>Danoprevir, Ritonavir, Peg-IFN,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)&#xD;
&#xD;
          -  Serum HCV RNA of ≥ 1 × 104 IU/mL are documented&#xD;
&#xD;
          -  Hepatitis C virus GT1&#xD;
&#xD;
          -  Never received prior-treatment for HCV with interferon, RBV, or other direct-acting or&#xD;
             host-targeting antivirals for HCV&#xD;
&#xD;
          -  Non-cirrhosis patients: Non-cirrhosis is defined (1)Fibroscan defined as: ˂ 14.6 kPa&#xD;
             during screening period, or liver biopsy determined 1 year before recruiting (Metavir&#xD;
             score ˂ 3);(2) during screening period 9.6&lt;Fibroscan indicator ≤12.9, liver biopsy&#xD;
             need to confirm non-cirrhosis.&#xD;
&#xD;
          -  Others as specified in the detailed protocol&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with Fibroscan detection value &gt; 12.9 kPa, or histologic examination for&#xD;
             liver cirrhosis patients&#xD;
&#xD;
          -  Presence or history of non-hepatitis C chronic liver disease (e.g. HH, AIH, Wilson's&#xD;
             disease, α1 antitrypsin deficiency, drug- or toxin-induced liver disease)&#xD;
&#xD;
          -  History of liver cell cancer, or suspected hepatocellular carcinoma (HCC) patients&#xD;
             before or during screening , or imaging studies found suspicious nodules, or AFP &gt; 50&#xD;
             ng/mL&#xD;
&#xD;
          -  Positive hepatitis A antibody，positive hepatitis B surface antigen，HIV antibody&#xD;
&#xD;
          -  Presence or history of nervous system diseases and/or mental illness, inability to&#xD;
             control oneself or express oneself.&#xD;
&#xD;
          -  Patients with obvious cardiovascular dysfunction&#xD;
&#xD;
          -  Pregnant or nursing female, nor unwilling to take reliable contraception&#xD;
&#xD;
          -  Others as specified in the detailed protocol&#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>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>January 27, 2021</results_first_submitted>
  <results_first_submitted_qc>February 28, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">March 23, 2021</results_first_posted>
  <last_update_submitted>February 28, 2021</last_update_submitted>
  <last_update_submitted_qc>February 28, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 23, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Danoprevir</keyword>
  <keyword>non-cirrhotic</keyword>
  <keyword>Chinese HCV G1</keyword>
  <keyword>SVR12</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>Peginterferon alfa-2a</mesh_term>
    <mesh_term>Ribavirin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>March 21, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/82/NCT03020082/SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>January 16, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/82/NCT03020082/Prot_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Danoprevir, Ritonavir, Peg-IFN,RBV</title>
          <description>Participants will receive Ritonavir- boosted Danoprevir 100mg/100mg BID in combination with subcutaneous injection of weekly peginterferon alfa-2a at 180 mcg and RBV administered orally 500mg (5 tablets)( body weight &lt;75Kg) BID, 600mg (6 tablets) BID body weight ≥75Kg for 12 weeks.&#xD;
Danoprevir: Danoprevir (DNV)administered orally 100mg BID for 12 weeks;&#xD;
Ritonavir: Ritonavir administered orally 100mg BID for 12 weeks;&#xD;
peginterferon alfa-2a: PEG-IFN abdominal or thigh subcutaneous injection, 180μg, once a week for 12 weeks;&#xD;
RBV: RBV administered orally 500mg (5 tablets)( body weight &lt;75Kg) BID, 600mg (6 tablets) BID body weight ≥75Kg, for 12 weeks.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="141"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="138"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Danoprevir, Ritonavir, Peg-IFN,RBV</title>
          <description>Participants will receive Ritonavir- boosted Danoprevir 100mg/100mg BID in combination with subcutaneous injection of weekly peginterferon alfa-2a at 180 mcg and RBV administered orally 500mg (5 tablets)( body weight &lt;75Kg) BID, 600mg (6 tablets) BID body weight ≥75Kg for 12 weeks.&#xD;
Danoprevir: Danoprevir (DNV)administered orally 100mg BID for 12 weeks;&#xD;
Ritonavir: Ritonavir administered orally 100mg BID for 12 weeks;&#xD;
peginterferon alfa-2a: PEG-IFN abdominal or thigh subcutaneous injection, 180μg, once a week for 12 weeks;&#xD;
RBV: RBV administered orally 500mg (5 tablets)( body weight &lt;75Kg) BID, 600mg (6 tablets) BID body weight ≥75Kg, for 12 weeks.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="141"/>
          </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="42" spread="12.1"/>
                  </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="70"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <description>Asia</description>
          <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="141"/>
                  </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_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Proportion of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12)</title>
        <time_frame>12 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Danoprevir, Ritonavir, Peg-IFN,RBV</title>
            <description>Participants will receive Ritonavir- boosted Danoprevir 100mg/100mg BID in combination with subcutaneous injection of weekly peginterferon alfa-2a at 180 mcg and RBV administered orally 500mg (5 tablets)( body weight &lt;75Kg) BID, 600mg (6 tablets) BID body weight ≥75Kg for 12 weeks.&#xD;
Danoprevir: Danoprevir (DNV)administered orally 100mg BID for 12 weeks;&#xD;
Ritonavir: Ritonavir administered orally 100mg BID for 12 weeks;&#xD;
peginterferon alfa-2a: PEG-IFN abdominal or thigh subcutaneous injection, 180μg, once a week for 12 weeks;&#xD;
RBV: RBV administered orally 500mg (5 tablets)( body weight &lt;75Kg) BID, 600mg (6 tablets) BID body weight ≥75Kg, for 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Proportion of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="141"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="136"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>24 weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Danoprevir, Ritonavir, Peg-IFN,RBV</title>
          <description>Participants will receive Ritonavir- boosted Danoprevir 100mg/100mg BID in combination with subcutaneous injection of weekly peginterferon alfa-2a at 180 mcg and RBV administered orally 500mg (5 tablets)( body weight &lt;75Kg) BID, 600mg (6 tablets) BID body weight ≥75Kg for 12 weeks.&#xD;
Danoprevir: Danoprevir (DNV)administered orally 100mg BID for 12 weeks;&#xD;
Ritonavir: Ritonavir administered orally 100mg BID for 12 weeks;&#xD;
peginterferon alfa-2a: PEG-IFN abdominal or thigh subcutaneous injection, 180μg, once a week for 12 weeks;&#xD;
RBV: RBV administered orally 500mg (5 tablets)( body weight &lt;75Kg) BID, 600mg (6 tablets) BID body weight ≥75Kg, for 12 weeks.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <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="141"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="141"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="141"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Ventricular tachyarrhythmia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="141"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Acquired digital fibrokeratoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="141"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Tuberculosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="141"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Transient ischemic attack</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="141"/>
              </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="76" subjects_at_risk="141"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" subjects_affected="76" subjects_at_risk="141"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" subjects_affected="53" subjects_at_risk="141"/>
              </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: 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/NCT03020082
org study id: ASC08201503
nct id: NCT03020082
lead sponsor: 
has dmc: Yes
The purpose of this study is to evaluate the efficacy and safety of Ritonavir-boosted ASC08
      (Danoprevir) in Combination with Peg-IFN and RBV in Treatment-Naive Non-Cirrhotic Patients
      Who Have Chronic Hepatitis Genotype 1.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Proportion of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12)
time frame: 12 weeks
arm group label: Danoprevir, Ritonavir, Peg-IFN,RBV
arm group type: Experimental
description: Participants will receive Ritonavir- boosted Danoprevir 100mg/100mg BID in combination with subcutaneous injection of weekly peginterferon alfa-2a at 180 mcg and RBV administered orally 500mg (5 tablets)( body weight <75Kg) BID, 600mg (6 tablets) BID body weight ≥75Kg for 12 weeks.
intervention type: Drug
intervention name: Danoprevir
description: Danoprevir (DNV)administered orally 100mg BID for 12 weeks;
arm group label: Danoprevir, Ritonavir, Peg-IFN,RBV
other name: ASC08
intervention type: Drug
intervention name: Ritonavir
description: Ritonavir administered orally 100mg BID for 12 weeks;
arm group label: Danoprevir, Ritonavir, Peg-IFN,RBV
intervention type: Drug
intervention name: peginterferon alfa-2a
description: PEG-IFN abdominal or thigh subcutaneous injection, 180μg, once a week for 12 weeks;
arm group label: Danoprevir, Ritonavir, Peg-IFN,RBV
other name: Peg-IFN
intervention type: Drug
intervention name: RBV
description: RBV administered orally 500mg (5 tablets)( body weight <75Kg) BID, 600mg (6 tablets) BID body weight ≥75Kg, for 12 weeks.
arm group label: Danoprevir, Ritonavir, Peg-IFN,RBV
other name: Ribasphere®
criteria: 
gender: All
minimum age: 18 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: Peginterferon alfa-2a
mesh term: Ribavirin
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 