<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/NCT03794258</url>
  </required_header>
  <id_info>
    <org_study_id>H&amp;H_YANGTZE_1</org_study_id>
    <nct_id>NCT03794258</nct_id>
  </id_info>
  <brief_title>Triple or Quadruple Combination DAAs Treatment for Subjects With HCV GT 1b Infection</brief_title>
  <official_title>A Phase 2a, Open-label, Randomized Study of the Safety and Preliminary Efficacy of Triple or Quadruple Combination DAAs With Ultra-short Duration Therapy in Subjects With HCV Genotype 1b Infection (YANGTZE Study)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Humanity &amp; Health Medical Group Limited</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Humanity &amp; Health Medical Group Limited</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a phase 2a, open-label, randomized study. The study is designed to test the&#xD;
      hypothesis that the nucleoside inhibitor sofosbuvir combined with NS5A inhibitor daclatasvir&#xD;
      and NS5B non-nucleoside inhibitor CDI-31244 with/without the protease inhibitor asunaprevir&#xD;
      will result in high SVR rate with a shortened treatment duration (2 weeks) in non-cirrhotic&#xD;
      HCV genotype 1b-infected subjects.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Can not recruit the patients due to the pandemic of COVID-19&#xD;
  </why_stopped>
  <start_date type="Actual">May 1, 2019</start_date>
  <completion_date type="Actual">April 30, 2020</completion_date>
  <primary_completion_date type="Actual">April 15, 2020</primary_completion_date>
  <phase>Phase 2</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>
    <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>Post treatment Week 12</time_frame>
    <description>SVR12 is defined as HCV RNA &lt; lower limit of quantification (LLOQ) 12 weeks after last dose of study drug.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Frequency and severity of adverse events</measure>
    <time_frame>Baseline up to Week 24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of participants with unquantifiable HCV viral load at specified time points during and after treatment</measure>
    <time_frame>Baseline up to Week 24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>HCV RNA levels and change during and after treatment</measure>
    <time_frame>Baseline up to Week 24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of participants with on-treatment virologic breakthrough and relapse</measure>
    <time_frame>Baseline up to Week 24</time_frame>
    <description>Viral breakthrough is defined as having achieved undetectable HCV RNA levels (HCV RNA &lt; LLOQ) during treatment, but did not achieve a sustained virologic response (SVR). Viral relapse is defined as having achieved undetectable HCV RNA levels (HCV RNA &lt; LLOQ) within 4 weeks of end of treatment, but did not achieve an SVR.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>HCV Infection</condition>
  <arm_group>
    <arm_group_label>SOF+DCV+CDI-31244</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will receive two weeks of sofosbuvir, daclatasvir, and CDI-31244 if they achieve HCV RNA &lt; 500 IU/mL on Day 2 and HCV RNA &lt; LLOQ (&lt; 25 IU/mL) on Week 1.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SOF+DCV+CDI-31244+ASV</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will receive two weeks of sofosbuvir, daclatasvir, CDI-31244 and asunaprevir if they achieve HCV RNA &lt; 500 IU/mL on Day 2 and HCV RNA &lt; LLOQ (&lt; 25 IU/mL) on Week 1.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SOF+DCV+CDI-31244</intervention_name>
    <description>Sofosbuvir (SOF) 400 mg administered orally once daily; Daclatasvir (DCV) 60 mg administered orally once daily; CDI-31244 400 mg administered orally once daily.</description>
    <arm_group_label>SOF+DCV+CDI-31244</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SOF+DCV+CDI-31244+ASV</intervention_name>
    <description>Sofosbuvir (SOF) 400 mg administered orally once daily; Daclatasvir (DCV) 60 mg administered orally once daily; CDI-31244 400 mg orally once daily; Asunaprevir (ASV) 200mg administered orally twice daily.</description>
    <arm_group_label>SOF+DCV+CDI-31244+ASV</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Willing and able to provide written informed consent.&#xD;
&#xD;
          2. Male or female, age 18-70 years.&#xD;
&#xD;
          3. HCV genotype 1b infection as determined by the Laboratory. Any non-definitive results&#xD;
             will exclude the subject from study participation.&#xD;
&#xD;
          4. HCV RNA level ≥ 10,000 IU/mL and &lt; 10,000,000 IU/mL.&#xD;
&#xD;
          5. No evidence of cirrhosis. Cirrhosis defined as any 1 of the following, within 6 months&#xD;
             of study entry:&#xD;
&#xD;
               1. Liver biopsy showing cirrhosis;&#xD;
&#xD;
               2. Fibroscan showing cirrhosis or results &gt;12.5 kPa;&#xD;
&#xD;
               3. FibroTest® score &gt;0.75 and an aspartate aminotransferase (AST): platelet ratio&#xD;
                  index (APRI) &gt;2 during screening.&#xD;
&#xD;
          6. Subjects must have the following laboratory parameters at screening:&#xD;
&#xD;
               1. ALT ≤ 10 x the upper limit of normal (ULN);&#xD;
&#xD;
               2. AST ≤ 10 x ULN;&#xD;
&#xD;
               3. Direct bilirubin ≤1.5 x ULN;&#xD;
&#xD;
               4. Platelets ≥ 50,000;&#xD;
&#xD;
               5. HbA1c ≤ 8.5%;&#xD;
&#xD;
               6. Creatinine clearance (CLcr) ≥ 60 mL /min, as calculated by the Cockcroft-Gault&#xD;
                  equation;&#xD;
&#xD;
               7. Hemoglobin ≥ 11 g/dL for female subjects; ≥ 12 g/dL for male subjects;&#xD;
&#xD;
               8. Albumin ≥ 3g/dL;&#xD;
&#xD;
               9. INR ≤ 1.5 x ULN unless subject has known hemophilia or is stable on an&#xD;
                  anticoagulant regimen affecting INR.&#xD;
&#xD;
          7. Subject has not been treated with any investigational drug or device within 30 days of&#xD;
             the Screening visit.&#xD;
&#xD;
          8. A female subject is eligible to enter the study if it is confirmed that she is:&#xD;
&#xD;
               1. Not pregnant or nursing;&#xD;
&#xD;
               2. Of non-childbearing potential (i.e., women who have had a hysterectomy, have both&#xD;
                  ovaries removed or medically documented ovarian failure, or are postmenopausal -&#xD;
                  women &gt; 50 years of age with cessation (for ≥12 months) of previously occurring&#xD;
                  menses), or&#xD;
&#xD;
               3. Of childbearing potential (i.e., women who have not had a hysterectomy, both&#xD;
                  ovaries removed, or no medically documented ovarian failure) based on the&#xD;
                  following conditions.&#xD;
&#xD;
             Women ≤ 50 years of age with amenorrhea will be considered to be of childbearing&#xD;
             potential. These women must have a negative serum pregnancy test at Screening and a&#xD;
             negative urine pregnancy test on the Baseline/Day 0 visit prior to randomization. They&#xD;
             must also agree to one of the following from 3 weeks prior to Baseline/Day 0 until 4&#xD;
             months after last dose of the triple/quadruple therapies:&#xD;
&#xD;
             - Complete abstinence from intercourse. Periodic abstinence from intercourse (e.g.,&#xD;
             calendar, ovulation, symptothermal, post-ovulation methods) is not permitted.&#xD;
&#xD;
             Or&#xD;
&#xD;
               -  Consistent and correct use of 1 of the following methods of birth control listed&#xD;
                  below in addition to a male partner who correctly uses a condom from 3 weeks&#xD;
                  prior to Baseline/Day 0 until 4 months after last dose of the triple/quadruple&#xD;
                  therapies. Women of childbearing potential must not rely only on&#xD;
                  hormone-containing contraceptives as a form of birth control during the study.&#xD;
                  Female subjects using a hormone-containing contraceptive prior to Screening may&#xD;
                  continue their contraceptive regimen in addition to the study specified methods&#xD;
                  of birth control.&#xD;
&#xD;
               -  intrauterine device (IUD) with a failure rate of &lt;1% per year&#xD;
&#xD;
               -  female barrier method: cervical cap or diaphragm with spermicidal agent&#xD;
&#xD;
               -  tubal sterilization&#xD;
&#xD;
               -  vasectomy in male partner&#xD;
&#xD;
          9. All male study participants must agree to consistently and correctly use a condom,&#xD;
             while their female partner agrees to use either 1 of the non-hormonal methods of birth&#xD;
             control listed above or a hormone-containing contraceptive listed below, from the date&#xD;
             of Screening until 4 months after their last dose of the triple/quadruple therapies:&#xD;
&#xD;
               -  implants of levonorgestrel&#xD;
&#xD;
               -  injectable progesterone&#xD;
&#xD;
               -  oral contraceptives (either combined or progesterone only)&#xD;
&#xD;
               -  contraceptive vaginal ring&#xD;
&#xD;
               -  transdermal contraceptive patch&#xD;
&#xD;
         10. Male subjects must agree to refrain from sperm donation from the date of screening&#xD;
             until at least 4 months after the last dose of the triple therapies.&#xD;
&#xD;
         11. Subject must be of generally good health, with the exception of chronic HCV infection,&#xD;
             as determined by the Investigator.&#xD;
&#xD;
         12. Subject must be able to comply with the dosing instructions for study drug&#xD;
             administration and able to complete the study schedule of assessments.&#xD;
&#xD;
         13. Screening ECG without clinically significant abnormalities.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Child-Pugh scoring of B and C.&#xD;
&#xD;
          2. Creatinine Clearance &lt; 30ml/min.&#xD;
&#xD;
          3. Mixed HCV genotypes.&#xD;
&#xD;
          4. Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV).&#xD;
&#xD;
          5. Hepatocellular carcinoma or other malignancy (with exception of certain resolved skin&#xD;
             cancers).&#xD;
&#xD;
          6. Current or prior history of any of the following:&#xD;
&#xD;
               1. Clinically-significant illness (other than HCV) or any other major medical&#xD;
                  disorder that may interfere with subject treatment, assessment or compliance with&#xD;
                  the protocol; subjects currently under evaluation for a potentially&#xD;
                  clinically-significant illness (other than HCV) are also excluded.&#xD;
&#xD;
               2. Gastrointestinal disorder or post operative condition that could interfere with&#xD;
                  the absorption of the study drug.&#xD;
&#xD;
               3. Difficulty with blood collection and/or poor venous access for the purposes of&#xD;
                  phlebotomy.&#xD;
&#xD;
               4. Clinical hepatic decompensation (i.e., ascites, encephalopathy or variceal&#xD;
                  hemorrhage).&#xD;
&#xD;
               5. Solid organ transplantation.&#xD;
&#xD;
               6. Significant pulmonary disease, significant cardiac disease or porphyria.&#xD;
&#xD;
               7. Psychiatric hospitalization, suicide attempt, and/or a period of disability as a&#xD;
                  result of their psychiatric illness within the last 5 years. Subjects with&#xD;
                  psychiatric illness that is well-controlled on a stable treatment regimen for at&#xD;
                  least 12 months prior to randomization or has not required medication in the last&#xD;
                  12 months may be included.&#xD;
&#xD;
               8. Malignancy diagnosed or treated within 5 years (recent localized treatment of&#xD;
                  squamous or non-invasive basal cell skin cancers is permitted; cervical carcinoma&#xD;
                  in situ is allowed if appropriately treated prior to screening); subjects under&#xD;
                  evaluation for malignancy are not eligible.&#xD;
&#xD;
               9. Significant drug allergy (such as anaphylaxis or hepatotoxicity).&#xD;
&#xD;
              10. History or current evidence of any condition, therapy, laboratory abnormality or&#xD;
                  other circumstance that might confound the results of the study, or interfere&#xD;
                  with the subject's participation for the full duration of the study, such that it&#xD;
                  is not in the best interest of the subject to participate&#xD;
&#xD;
          7. Pregnant or nursing female or male with pregnant female partner.&#xD;
&#xD;
          8. Chronic liver disease of a non-HCV etiology (e.g., hemochromatosis, Wilson's disease,&#xD;
             alpha-1 antitrypsin deficiency, cholangitis).&#xD;
&#xD;
          9. Donation or loss of more than 400 mL blood within 2 months prior to Baseline/Day 1.&#xD;
&#xD;
         10. Clinically-relevant drug abuse within 12 months of screening. A positive drug screen&#xD;
             will exclude subjects unless it can be explained by a prescribed medication; the&#xD;
             diagnosis and prescription must be approved by the investigator.&#xD;
&#xD;
         11. Active or recent history (≤ 1 year) of drug or alcohol abuse.&#xD;
&#xD;
         12. Use of any following drugs that might interact with the study drugs.&#xD;
&#xD;
               1. Treatment with amiodarone within 180 days before study entry;&#xD;
&#xD;
               2. Treatment with digoxin within 30 days before study entry;&#xD;
&#xD;
               3. Treatment with rifabutin, rifampin, rifapentine, phenytoin, phenobarbital, St.&#xD;
                  John's wort, carbamazepine, oxcarbazepine, rosuvastatin, or atorvastatin within&#xD;
                  10 days before study entry. However, switching to another statin is acceptable.&#xD;
&#xD;
         13. Screening or baseline electrocardiogram (ECG) with clinically significant findings.&#xD;
&#xD;
         14. QTcF (QT interval corrected using Fridericia's formula) &gt; 450 msec at screening.&#xD;
&#xD;
         15. Chronic use of systemically administered immunosuppressive agents (e.g., prednisone&#xD;
             equivalent &gt; 10 mg/day).&#xD;
&#xD;
         16. Known hypersensitivity to sofosbuvir, daclatasvir, CDI-31244 and asunaprevir or&#xD;
             formulation recipients.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Georg Lau, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Humanity &amp; Health Research Centre</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Humanity &amp; Health Research Centre</name>
      <address>
        <city>Hong Kong</city>
        <state>Hong Kong SAR</state>
        <country>Hong Kong</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Hong Kong</country>
  </location_countries>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>January 3, 2019</study_first_submitted>
  <study_first_submitted_qc>January 3, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 7, 2019</study_first_posted>
  <last_update_submitted>May 5, 2020</last_update_submitted>
  <last_update_submitted_qc>May 5, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">May 7, 2020</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>Infections</mesh_term>
    <mesh_term>Communicable Diseases</mesh_term>
    <mesh_term>Hepatitis C</mesh_term>
  </condition_browse>
  <!-- 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/NCT03794258
org study id: H&H_YANGTZE_1
nct id: NCT03794258
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This is a phase 2a, open-label, randomized study. The study is designed to test the
      hypothesis that the nucleoside inhibitor sofosbuvir combined with NS5A inhibitor daclatasvir
      and NS5B non-nucleoside inhibitor CDI-31244 with/without the protease inhibitor asunaprevir
      will result in high SVR rate with a shortened treatment duration (2 weeks) in non-cirrhotic
      HCV genotype 1b-infected subjects.
allocation: Randomized
intervention model: Parallel 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: Post treatment Week 12
description: SVR12 is defined as HCV RNA < lower limit of quantification (LLOQ) 12 weeks after last dose of study drug.
measure: Frequency and severity of adverse events
time frame: Baseline up to Week 24
measure: Proportion of participants with unquantifiable HCV viral load at specified time points during and after treatment
time frame: Baseline up to Week 24
measure: HCV RNA levels and change during and after treatment
time frame: Baseline up to Week 24
measure: Proportion of participants with on-treatment virologic breakthrough and relapse
time frame: Baseline up to Week 24
description: Viral breakthrough is defined as having achieved undetectable HCV RNA levels (HCV RNA < LLOQ) during treatment, but did not achieve a sustained virologic response (SVR). Viral relapse is defined as having achieved undetectable HCV RNA levels (HCV RNA < LLOQ) within 4 weeks of end of treatment, but did not achieve an SVR.
arm group label: SOF+DCV+CDI-31244
arm group type: Experimental
description: Subjects will receive two weeks of sofosbuvir, daclatasvir, and CDI-31244 if they achieve HCV RNA < 500 IU/mL on Day 2 and HCV RNA < LLOQ (< 25 IU/mL) on Week 1.
arm group label: SOF+DCV+CDI-31244+ASV
arm group type: Experimental
description: Subjects will receive two weeks of sofosbuvir, daclatasvir, CDI-31244 and asunaprevir if they achieve HCV RNA < 500 IU/mL on Day 2 and HCV RNA < LLOQ (< 25 IU/mL) on Week 1.
intervention type: Drug
intervention name: SOF+DCV+CDI-31244
description: Sofosbuvir (SOF) 400 mg administered orally once daily; Daclatasvir (DCV) 60 mg administered orally once daily; CDI-31244 400 mg administered orally once daily.
arm group label: SOF+DCV+CDI-31244
intervention type: Drug
intervention name: SOF+DCV+CDI-31244+ASV
description: Sofosbuvir (SOF) 400 mg administered orally once daily; Daclatasvir (DCV) 60 mg administered orally once daily; CDI-31244 400 mg orally once daily; Asunaprevir (ASV) 200mg administered orally twice daily.
arm group label: SOF+DCV+CDI-31244+ASV
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Georg Lau, MD
role: Principal Investigator
affiliation: Humanity & Health Research Centre
facility: 
country: Hong Kong
responsible party type: Sponsor
mesh term: Infections
mesh term: Communicable Diseases
mesh term: Hepatitis C