<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/NCT03254758</url>
  </required_header>
  <id_info>
    <org_study_id>ADR-001-01</org_study_id>
    <nct_id>NCT03254758</nct_id>
  </id_info>
  <brief_title>A Study of ADR-001 in Patients With Liver Cirrhosis</brief_title>
  <official_title>A Phase 1/2 Study of ADR-001 in Patients With Liver Cirrhosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Rohto Pharmaceutical Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Rohto Pharmaceutical Co., Ltd.</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a first-in-human Phase1/2 study of ADR-001, adipose-derived mesenchymal stem cells&#xD;
      (AD-MSCs). The safety and preliminary efficacy are evaluated in Phase 1 in patients with&#xD;
      liver cirrhosis caused by Hepatitis C or Nonalcoholic Steatohepatitis and a recommended Phase&#xD;
      2 dose is determined by the evaluation. The exploratory efficacy and safety are investigated&#xD;
      against the same target population in Phase 2.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients with decompensated liver cirrhosis (Child-Pugh score; Grade B) caused by Hepatitis C&#xD;
      or Nonalcoholic Steatohepatitis are enrolled to the study. In Phase 1, one of 3 doses of&#xD;
      AD-MSCs is administered by 1 hour single intravenous infusion. Patients are hospitalized for&#xD;
      1 week and a recommended dose for Phase 2 is determined by the evaluation of the safety and&#xD;
      efficacy. In Phase 2, patients with the same disease criteria are enrolled and dosed to&#xD;
      investigate the exploratory efficacy and safety.&#xD;
&#xD;
      The safety and efficacy are evaluated until 24 weeks after dosing both in Phase 1 and Phase&#xD;
      2.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 20, 2017</start_date>
  <completion_date type="Actual">April 13, 2023</completion_date>
  <primary_completion_date type="Actual">April 13, 2023</primary_completion_date>
  <phase>Phase 1/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>Safety profile of ADR-001 including the incidence of adverse events (Phase 1)</measure>
    <time_frame>24 weeks</time_frame>
    <description>Safety will be evaluated based on the medical review of adverse event reports and the results of clinical laboratory tests, vital sign, and physical examinations.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Improvement rate of Child-Pugh score (Phase 2)</measure>
    <time_frame>24 weeks</time_frame>
    <description>Improvement rate of Child-Pugh score from the baseline will be evaluated.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change of liver function evaluated by Child-Pugh score (Phase 1)</measure>
    <time_frame>24 weeks</time_frame>
    <description>Change of liver function from the baseline will be evaluated by Child-Pugh score.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Improvement rate of Child-Pugh score (Phase 1)</measure>
    <time_frame>24 weeks</time_frame>
    <description>Improvement rate of Child-Pugh score from the baseline will be evaluated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Improvement rate of Child-Pugh grade (Phase 1)</measure>
    <time_frame>24 weeks</time_frame>
    <description>Improvement rate of Child-Pugh grade from the baseline will be evaluated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of liver function evaluated by Child-Pugh score (Phase 2)</measure>
    <time_frame>24 weeks</time_frame>
    <description>Change of liver function from the baseline will be evaluated by Child-Pugh score.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Improvement rate of Child-Pugh grade (Phase 2)</measure>
    <time_frame>24 weeks</time_frame>
    <description>Improvement rate of Child-Pugh grade from the baseline will be evaluated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety profile of ADR-001 including the incidence of adverse events (Phase 2)</measure>
    <time_frame>24 weeks</time_frame>
    <description>Safety will be evaluated based on the medical review of adverse event reports and the results of clinical laboratory tests, vital sign, and physical examinations.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">21</enrollment>
  <condition>Decompensated Liver Cirrhosis</condition>
  <arm_group>
    <arm_group_label>Mesenchymal stem cell</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Phase 1 Dose escalation : low Mid High Single administalation of ADR-001&#xD;
Phase 2 The recommended dose of ADR-001</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Mesenchymal stem cell</intervention_name>
    <description>Phase1 The dose of AD-MSCs are escalated from low to mid and high step by step. Each administration is one time via intravenous infusion for one hour.&#xD;
Phase2 The recommended dose of ADR-001 is administrated once a week 4 times. The administration route and time is same method with Phase 1.</description>
    <arm_group_label>Mesenchymal stem cell</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Men and women ≥ 20 years of age&#xD;
&#xD;
          -  Chronic hepatitis C or nonalcoholic steatohepatitis(NASH)&#xD;
&#xD;
          -  Child-Pugh grade B liver cirrhosis&#xD;
&#xD;
          -  ECOG Performance Status ≤ 2&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Liver cirrhosis patients other than hepatitis C or NASH&#xD;
&#xD;
          -  Malignant neoplasm (except hepatocellular carcinoma patients without recurrence more&#xD;
             than 2 years)&#xD;
&#xD;
          -  History of venous thrombosis or pulmonary embolism&#xD;
&#xD;
          -  Serum creatinine ≥ 2 mg/dL or T-Bil ≥ 5.0 mg/dL&#xD;
&#xD;
          -  Infection with hepatitis B, HIV, ATLV-1 or parvovirus B19&#xD;
&#xD;
          -  Patients experienced transplantation or cell therapy&#xD;
&#xD;
          -  Pregnancy or positive on pregnancy test&#xD;
&#xD;
          -  Complications of significant heart disease, kidney disorder, or respiratory disease&#xD;
&#xD;
          -  Drug or alcohol abuse&#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>Shuji Terai, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Niigata University Medical &amp; Dental Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Niigata University Medical &amp; Dental Hospital</name>
      <address>
        <city>Niigata</city>
        <zip>951-8510</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nihon University Itabashi Hospital</name>
      <address>
        <city>Tokyo</city>
        <zip>173-8610</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Japan</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>August 3, 2017</study_first_submitted>
  <study_first_submitted_qc>August 16, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 18, 2017</study_first_posted>
  <last_update_submitted>July 4, 2023</last_update_submitted>
  <last_update_submitted_qc>July 4, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 6, 2023</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>Liver Cirrhosis</mesh_term>
    <mesh_term>Fibrosis</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/NCT03254758
org study id: ADR-001-01
nct id: NCT03254758
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
This is a first-in-human Phase1/2 study of ADR-001, adipose-derived mesenchymal stem cells
      (AD-MSCs). The safety and preliminary efficacy are evaluated in Phase 1 in patients with
      liver cirrhosis caused by Hepatitis C or Nonalcoholic Steatohepatitis and a recommended Phase
      2 dose is determined by the evaluation. The exploratory efficacy and safety are investigated
      against the same target population in Phase 2.
Patients with decompensated liver cirrhosis (Child-Pugh score; Grade B) caused by Hepatitis C
      or Nonalcoholic Steatohepatitis are enrolled to the study. In Phase 1, one of 3 doses of
      AD-MSCs is administered by 1 hour single intravenous infusion. Patients are hospitalized for
      1 week and a recommended dose for Phase 2 is determined by the evaluation of the safety and
      efficacy. In Phase 2, patients with the same disease criteria are enrolled and dosed to
      investigate the exploratory efficacy and safety.

      The safety and efficacy are evaluated until 24 weeks after dosing both in Phase 1 and Phase
      2.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety profile of ADR-001 including the incidence of adverse events (Phase 1)
time frame: 24 weeks
description: Safety will be evaluated based on the medical review of adverse event reports and the results of clinical laboratory tests, vital sign, and physical examinations.
measure: Improvement rate of Child-Pugh score (Phase 2)
time frame: 24 weeks
description: Improvement rate of Child-Pugh score from the baseline will be evaluated.
measure: Change of liver function evaluated by Child-Pugh score (Phase 1)
time frame: 24 weeks
description: Change of liver function from the baseline will be evaluated by Child-Pugh score.
measure: Improvement rate of Child-Pugh score (Phase 1)
time frame: 24 weeks
description: Improvement rate of Child-Pugh score from the baseline will be evaluated.
measure: Improvement rate of Child-Pugh grade (Phase 1)
time frame: 24 weeks
description: Improvement rate of Child-Pugh grade from the baseline will be evaluated.
measure: Change of liver function evaluated by Child-Pugh score (Phase 2)
time frame: 24 weeks
description: Change of liver function from the baseline will be evaluated by Child-Pugh score.
measure: Improvement rate of Child-Pugh grade (Phase 2)
time frame: 24 weeks
description: Improvement rate of Child-Pugh grade from the baseline will be evaluated.
measure: Safety profile of ADR-001 including the incidence of adverse events (Phase 2)
time frame: 24 weeks
description: Safety will be evaluated based on the medical review of adverse event reports and the results of clinical laboratory tests, vital sign, and physical examinations.
arm group label: Mesenchymal stem cell
arm group type: Experimental
description: Phase 1 Dose escalation : low Mid High Single administalation of ADR-001
Phase 2 The recommended dose of ADR-001
intervention type: Biological
intervention name: Mesenchymal stem cell
description: Phase1 The dose of AD-MSCs are escalated from low to mid and high step by step. Each administration is one time via intravenous infusion for one hour.
Phase2 The recommended dose of ADR-001 is administrated once a week 4 times. The administration route and time is same method with Phase 1.
arm group label: Mesenchymal stem cell
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: No
last name: Shuji Terai, MD
role: Principal Investigator
affiliation: Niigata University Medical & Dental Hospital
facility: 
facility: 
country: Japan
responsible party type: Sponsor
mesh term: Liver Cirrhosis
mesh term: Fibrosis