<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/NCT03020004</url>
  </required_header>
  <id_info>
    <org_study_id>ASC08201502</org_study_id>
    <nct_id>NCT03020004</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of Danoprevir/r + PR 12-week Triple Therapy in Treatment-Naive, Non-Cirrhotic, G1 CHC China II</brief_title>
  <official_title>A Phase 2,Multicenter,Open-Label Study to Investigate the Efficacy, Safety and Pharmacokinetics of Ritonavir-boosted Danoprevir in Combination With Peg-IFN and RBV in Treatment-Naive Non-Cirrhotic Patients Who Have Chronic Hepatitis GT1</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 Pharmacokinetics of&#xD;
      Ritonavir-boosted Danoprevir (ASC08) in Combination with Peg-IFN and RBV in Treatment-Naive&#xD;
      Non-Cirrhotic Patients Who Have Chronic Hepatitis Genotype 1.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>January 2016</start_date>
  <completion_date type="Actual">February 2017</completion_date>
  <primary_completion_date type="Actual">November 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>24 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">70</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 a combination of Ritonavir-boosted Danoprevir 100mg/100mg BID, subcutaneous injection of weekly peginterferon alfa-2a at 180 mcg and oral Ribavirin (RBV)1000/1200 mg/day (bodyweight&lt;75/≥75 kg) for 12 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Danoprevir</intervention_name>
    <description>Danoprevir (DNV) 100mg tablet administered orally twice daily</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 100mg tablet administered orally twice daily</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>PegIFN subcutaneous injection at 180 mcg weekly</description>
    <arm_group_label>Danoprevir,Ritonavir, Peg-IFN,RBV</arm_group_label>
    <other_name>PegIFN</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ribavirin (RBV)</intervention_name>
    <description>Ribavirin (RBV)1000/1200 mg/day (bodyweight&lt;75/≥75 kg)</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;
          -  Positive HCV antibody&#xD;
&#xD;
          -  Serum HCV RNA of ≥ 1 × 104 IU/mL&#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;
          -  The liver biopsy methods in the protocol (non-cirrhosis is defined as: Metavir score ˂&#xD;
             4), or as determined by Fibroscan defined as: ˂ 14.6 kPa. Patients who have not&#xD;
             obtained a liver biopsy or Fibroscan in the last 1 years will have a study related&#xD;
             Fibroscan performed in order to confirm the diagnosis&#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, 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;
          -  Patients with a history of liver cell cancer, screening before or screening suspected&#xD;
             hepatocellular carcinoma (HCC) patients, or imaging studies found suspicious nodules,&#xD;
             or AFP &gt; 50 ng/mL&#xD;
&#xD;
          -  Positive hepatitis A antibody，positive hepatitis B surface antigen，syphilis antibody&#xD;
             or HIV antibody at screening&#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 9, 2018</results_first_submitted>
  <results_first_submitted_qc>January 9, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">February 7, 2018</results_first_posted>
  <last_update_submitted>June 27, 2018</last_update_submitted>
  <last_update_submitted_qc>June 27, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">July 26, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Danoprevir</keyword>
  <keyword>SVR12</keyword>
  <keyword>Chinese HCV G1</keyword>
  <keyword>non-cirrhotic</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>
    <mesh_term>Peginterferon alfa-2a</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Danoprevir,Ritonavir, Peg-IFN,RBV</title>
          <description>Participants will receive a combination of Ritonavir-boosted Danoprevir 100mg/100mg BID, subcutaneous injection of weekly peginterferon alfa-2a at 180 mcg and oral Ribavirin (RBV)1000/1200 mg/day (bodyweight&lt;75/≥75 kg) for 12 weeks.&#xD;
Danoprevir: Danoprevir (DNV) 100mg tablet administered orally twice daily&#xD;
Ritonavir: Ritonavir 100mg tablet administered orally twice daily&#xD;
peginterferon alfa-2a: PegIFN subcutaneous injection at 180 mcg weekly&#xD;
Ribavirin (RBV): Ribavirin (RBV)1000/1200 mg/day (bodyweight&lt;75/≥75 kg)</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="70"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="69"/>
              </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>Danoprevir,Ritonavir, Peg-IFN,RBV</title>
          <description>Participants will receive a combination of Ritonavir-boosted Danoprevir 100mg/100mg BID, subcutaneous injection of weekly peginterferon alfa-2a at 180 mcg and oral Ribavirin (RBV)1000/1200 mg/day (bodyweight&lt;75/≥75 kg) for 12 weeks.&#xD;
Danoprevir: Danoprevir (DNV) 100mg tablet administered orally twice daily&#xD;
Ritonavir: Ritonavir 100mg tablet administered orally twice daily&#xD;
peginterferon alfa-2a: PegIFN subcutaneous injection at 180 mcg weekly&#xD;
Ribavirin (RBV): Ribavirin (RBV)1000/1200 mg/day (bodyweight&lt;75/≥75 kg)</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="70"/>
          </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="41.2" spread="12.4"/>
                  </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="30"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="40"/>
                  </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="70"/>
                  </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>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>24 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Danoprevir,Ritonavir, Peg-IFN,RBV</title>
            <description>Participants will receive a combination of Ritonavir-boosted Danoprevir 100mg/100mg BID, subcutaneous injection of weekly peginterferon alfa-2a at 180 mcg and oral Ribavirin (RBV)1000/1200 mg/day (bodyweight&lt;75/≥75 kg) for 12 weeks.&#xD;
Danoprevir: Danoprevir (DNV) 100mg tablet administered orally twice daily&#xD;
Ritonavir: Ritonavir 100mg tablet administered orally twice daily&#xD;
peginterferon alfa-2a: PegIFN subcutaneous injection at 180 mcg weekly&#xD;
Ribavirin (RBV): Ribavirin (RBV)1000/1200 mg/day (bodyweight&lt;75/≥75 kg)</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="70"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="66"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Danoprevir,Ritonavir, Peg-IFN,RBV</title>
          <description>Participants will receive a combination of Ritonavir-boosted Danoprevir 100mg/100mg BID, subcutaneous injection of weekly peginterferon alfa-2a at 180 mcg and oral Ribavirin (RBV)1000/1200 mg/day (bodyweight&lt;75/≥75 kg) for 12 weeks.&#xD;
Danoprevir: Danoprevir (DNV) 100mg tablet administered orally twice daily&#xD;
Ritonavir: Ritonavir 100mg tablet administered orally twice daily&#xD;
peginterferon alfa-2a: PegIFN subcutaneous injection at 180 mcg weekly&#xD;
Ribavirin (RBV): Ribavirin (RBV)1000/1200 mg/day (bodyweight&lt;75/≥75 kg)</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>acute pancreatitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="70"/>
              </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="70" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="85" subjects_affected="63" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" events="69" subjects_affected="58" subjects_at_risk="70"/>
              </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 Pharmaceuticals Co., Ltd</organization>
      <phone>+86057185389732</phone>
      <email>yicheng.zhao@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/NCT03020004
org study id: ASC08201502
nct id: NCT03020004
lead sponsor: 
has dmc: Yes
The purpose of this study is to evaluate the Efficacy, Safety and Pharmacokinetics of
      Ritonavir-boosted Danoprevir (ASC08) 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: Percentage of Subjects With Sustained Virologic Response (SVR12) 12 Weeks Post-treatment
time frame: 24 weeks
description: SVR12, defined as undetectable HCV RNA 12 weeks after the last day of study drug administration
arm group label: Danoprevir,Ritonavir, Peg-IFN,RBV
arm group type: Experimental
description: Participants will receive a combination of Ritonavir-boosted Danoprevir 100mg/100mg BID, subcutaneous injection of weekly peginterferon alfa-2a at 180 mcg and oral Ribavirin (RBV)1000/1200 mg/day (bodyweight<75/≥75 kg) for 12 weeks.
intervention type: Drug
intervention name: Danoprevir
description: Danoprevir (DNV) 100mg tablet administered orally twice daily
arm group label: Danoprevir,Ritonavir, Peg-IFN,RBV
other name: ASC08
intervention type: Drug
intervention name: Ritonavir
description: Ritonavir 100mg tablet administered orally twice daily
arm group label: Danoprevir,Ritonavir, Peg-IFN,RBV
intervention type: Drug
intervention name: peginterferon alfa-2a
description: PegIFN subcutaneous injection at 180 mcg weekly
arm group label: Danoprevir,Ritonavir, Peg-IFN,RBV
other name: PegIFN
intervention type: Drug
intervention name: Ribavirin (RBV)
description: Ribavirin (RBV)1000/1200 mg/day (bodyweight<75/≥75 kg)
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: Ribavirin
mesh term: Peginterferon alfa-2a
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 