xml: <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/NCT05984303</url>
    </required_header>
    <id_info>
      <org_study_id>MSC-DLC-1b</org_study_id>
      <nct_id>NCT05984303</nct_id>
    </id_info>
    <brief_title>Human Umbilical Cord-derived Mesenchymal Stem Cells for Decompensated Cirrhosis (MSC-DLC-1b)</brief_title>
    <official_title>Treatment of Decompensated Cirrhosis Using Human Umbilical Cord-derived Mesenchymal Stem Cells: A Phase 1, Multiple Administration, Dose-escalasion Trial (MSC-DLC-1b)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Beijing 302 Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Wuhan Optics Valley Zhongyuan Pharmaceutical Co., Ltd., Hubei, China</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Beijing 302 Hospital</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        This clinical trial is a Phase 1, multiple administration, dose-escalasion clinical trial of&#xD;
        human umbilical cord-derived mesenchymal stem cells for the treatment of decompensated&#xD;
        cirrhosis. The primary objective of this study is to assess the safety of intravenous&#xD;
        infusion of human umbilical cord-derived mesenchymal stem cells in patients with&#xD;
        decompensated cirrhosis.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Decompensated cirrhosis has a high overall mortality rate. There is unmet need for safe and&#xD;
        alternative therapeutic potions. This clinical trial is a Phase 1, multiple administration,&#xD;
        dose-escalasion clinical trial of human umbilical cord-derived mesenchymal stem cells for the&#xD;
        treatment of decompensated cirrhosis. The primary objective of this study is to assess the&#xD;
        safety of intravenous infusion of human umbilical cord-derived mesenchymal stem cells in&#xD;
        patients with decompensated cirrhosis.In order to illustrate the safety and effectiveness of&#xD;
        human umbilical cord-derived mesenchymal stem cells and the patient's dose tolerance to human&#xD;
        umbilical cord-derived mesenchymal stem cells.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 30, 2023</start_date>
    <completion_date type="Anticipated">August 30, 2025</completion_date>
    <primary_completion_date type="Anticipated">August 30, 2024</primary_completion_date>
    <phase>Phase 1</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>Incidence of Adverse Events</measure>
      <time_frame>from baseline to 28th day</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>incidence of dose-limiting toxicity-related adverse events</measure>
      <time_frame>from baseline to 28th day</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>maximum tolerated dose</measure>
      <time_frame>from baseline to 28th day</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in Model for End-Stage Liver Disease (MELD) score from baseline to 28th day</measure>
      <time_frame>at 28th day</time_frame>
      <description>The Model for End-stage Liver Disease (MELD) is a scoring system that evaluates the liver function reserve and prognosis of patients with chronic liver disease by creatinine, international normalized ratio (INR), and bilirubin-conjugated cirrhosis etiology.&#xD;
  The MELD score is calculated by the formula: R = 9.6 × ln (creatinine mg/dl) + 3.8 × ln (bilirubin mg/dl) + 11.2 × ln (INR) + 6.4 × etiology, and the results are taken as integers. ( 0 for cholestatic and alcoholic cirrhosis and 1 for other causes of cirrhosis such as viruses).</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Change in Model for End-Stage Liver Disease (MELD) score from baseline to 3 days, 7days, 14 days, 21 days, 1 month, 2 months, 3 months, 6 months, 12 months, 18 months, and 24 months</measure>
      <time_frame>3 days, 7days, 14 days, 21 days, 1 month, 2 months, 3 months, 6 months, 12 months, 18 months, and 24 months</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence of each complication associated with decompensated cirrhosis</measure>
      <time_frame>up to 24 months</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>liver transplant-free survival</measure>
      <time_frame>up to 24 months</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence of liver failure</measure>
      <time_frame>up to 24 months</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>plasma albumin (ALB)</measure>
      <time_frame>up to 24 months</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>plasma prealbumin (PALB)</measure>
      <time_frame>up to 24 months</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>total bilirubin (TBIL)</measure>
      <time_frame>up to 24 months</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>serum cholinesterase (CHE)</measure>
      <time_frame>up to 24 months</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>prothrombin time (PT)</measure>
      <time_frame>up to 24 months</time_frame>
      <description>Prothrombin time (PT) is a blood test that measures the time it takes for plasma to clot, to check for bleeding problems, or to check whether medicine to prevent blood clots is working.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Child-Turcotte-Pugh (CTP) score</measure>
      <time_frame>up to 24 months</time_frame>
      <description>Child-Turcotte-Pugh (CTP) score is a scoring system that evaluates the liver function.&#xD;
  Maximum is 15, minimum is 5. Higher scores mean a worse outcome.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>EuroQol Group 5-Dimension Self-Report Questionnaire (EQ-5D)</measure>
      <time_frame>up to 24 months</time_frame>
      <description>Quality of life assessment. Maximum is 5, minimum is 1. Lower scores mean a better outcome.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence of liver cancer</measure>
      <time_frame>up to 24 months</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>ChronicLiver Disease Questionnaire (CLDQ)</measure>
      <time_frame>up to 24 months</time_frame>
      <description>Quality of life assessment. The Chronic Liver Disease Questionnaire (CLDQ) was developed as an evaluative instrument to measure longitudinal change in health status within individuals with chronic liver disease. In addition to measuring both physical and mental health, the instrument was designed to be a disease-specific tool for assessing areas of function important to patients with chronic liver disease. Maximum is 7, minimum is 1. Higher scores mean a better outcome.</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">6</enrollment>
    <condition>Decompensated Cirrhosis</condition>
    <arm_group>
      <arm_group_label>Human Umbilical Cord-derived Mesenchymal Stem Cells</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Standard of care (SOC) plus a multiple administration and dose-escalasion with 2 cohorts with 3 subjects/cohort who receive doses of 1 and 2 ×10E8 cells. Each person received 3 infusions, 1 week apart, Proceed from lower dose to higher dose if no safety concerns for each cohort.</description>
    </arm_group>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>Human Umbilical Cord-derived Mesenchymal Stem Cells</intervention_name>
      <description>Human Umbilical Cord-derived Mesenchymal Stem Cells will be administered intravenously.</description>
      <arm_group_label>Human Umbilical Cord-derived Mesenchymal Stem Cells</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Willing to provide written informed consent;&#xD;
  &#xD;
            2. Aged 18 to 75 years (including 18 and 75 years), male or female;&#xD;
  &#xD;
            3. Patients diagnosed with decompensated liver cirrhosis based on clinical findings,&#xD;
               laboratory tests, imaging findings and/or representative pathological findings&#xD;
               (decompensated liver cirrhosis is defined as the occurrence of at least one serious&#xD;
               complication, including esophageal and gastric varices bleeding, hepatic&#xD;
               encephalopathy, ascites, spontaneous bacterial peritonitis and other serious&#xD;
               complications);&#xD;
  &#xD;
            4. Child-Turcotte-Pugh (CTP) score 7 to 12 points.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Hepatitis B virus (HBV) DNA ≥ detection limit at the time of screening, or patients&#xD;
               with hepatitis B virus-related decompensated liver cirrhosis may discontinue antiviral&#xD;
               therapy during the study, or those who with antiviral therapy for HBV for less than 12&#xD;
               months.&#xD;
  &#xD;
            2. Hepatitis C virus (HCV) RNA ≥ detection limit at the time of screening, or patients&#xD;
               with hepatitis C virus-related decompensated liver cirrhosis not more than 12 months&#xD;
               on antiviral therapy.&#xD;
  &#xD;
            3. Patients under treatment with corticosteroids for autoimmune hepatitis for less than 6&#xD;
               months.&#xD;
  &#xD;
            4. Trans-jugular intrahepatic portosystemic shunts (TIPS) insertion within 6 months prior&#xD;
               to study inclusion.&#xD;
  &#xD;
            5. Active drinkers with alcohol-related decompensated cirrhosis are unwilling to stop&#xD;
               alcohol abuse after inclusion.&#xD;
  &#xD;
            6. Patients with biliary obstruction, or portal patients with vein spongiosis.&#xD;
  &#xD;
            7. Patients are known with other malignancies within 5 years prior to the signing of ICF,&#xD;
               except have had curative therapy of Basal Cell Cancer, Squamous Cell Carcinoma and/or&#xD;
               radical resection of Carcinoma in Situ.&#xD;
  &#xD;
               Known to have had other malignancies within 5 years prior to signing the informed&#xD;
               consent, except for basal cell carcinoma of the skin, squamous cell carcinoma of the&#xD;
               skin, and/or carcinoma in situ with curable resection.&#xD;
  &#xD;
            8. Patients with history of organ transplantation.&#xD;
  &#xD;
            9. Patients with severe heart, lung, kidney and blood system diseases.&#xD;
  &#xD;
           10. Patients with drug abuse, drug dependence and patients who receive methadone treatment&#xD;
               or with psychosis.&#xD;
  &#xD;
           11. Patients with history of immunodeficiency disease, including a positive test result&#xD;
               for human immunodeficiency virus (HIV) antibodies, or other acquired or congenital&#xD;
               immunodeficiency diseases;&#xD;
  &#xD;
           12. Pregnant or lactating female. Fertile patients who were unable or unwilling to use&#xD;
               effective non-pharmaceutical contraception during the trial and within 6 months after&#xD;
               the end of the trial.&#xD;
  &#xD;
           13. Patients who had cardiovascular and cerebrovascular events (such as Unstable Angina,&#xD;
               Brain Hemorrhage, severe Ischemic Infarction) within 3 months before the first&#xD;
               dose；Patients who had Myocardial Infarct or a clinically significant&#xD;
               Arrhythmia/Conduction Abnormalities within 12 months before the first dose.&#xD;
  &#xD;
           14. Patients with hypersensitivity (allergic to more than two foods or drugs) or with a&#xD;
               history of severe allergy, or patients with Severe allergy to a known experimental&#xD;
               drug or to any excipient.&#xD;
  &#xD;
           15. Patients previously received stem cell therapy or are intolerance to cell therapy;&#xD;
  &#xD;
           16. Participants in other clinical trials within the last 3 months.&#xD;
  &#xD;
           17. Any other clinical condition which the investigator considers would make the patient&#xD;
               unsuitable for the trial.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>75 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Fu-Sheng Wang, MD, PhD</last_name>
      <role>Study Chair</role>
      <affiliation>Beijing 302 Hospital</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Lei Shi, MD,PhD</last_name>
      <phone>86-10-66949623</phone>
      <email>shilei302@126.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Fu-Sheng Wang, MD,PhD</last_name>
      <phone>86-10-66933332</phone>
      <email>fswang302@163.com</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Beijing 302 Hospital</name>
        <address>
          <city>Beijing</city>
          <country>China</country>
        </address>
      </facility>
      <contact>
        <last_name>Lei Shi, MD,PhD</last_name>
        <phone>86-10-66949623</phone>
        <email>shilei302@126.com</email>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 28, 2023</study_first_submitted>
    <study_first_submitted_qc>August 2, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 9, 2023</study_first_posted>
    <last_update_submitted>August 2, 2023</last_update_submitted>
    <last_update_submitted_qc>August 2, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 9, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Beijing 302 Hospital</investigator_affiliation>
      <investigator_full_name>Fu-Sheng Wang</investigator_full_name>
      <investigator_title>Head of Treatment and Research Center for Infectious Diseases, Principle Investigator, Clinical Professor</investigator_title>
    </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>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>After approval from the steering committee and the Human Genetic Resources Administration of China, this trial data can be shared with qualifying researchers who submit a proposal with a valuable research question. A contract should be signed.</ipd_description>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05984303
  org study id: MSC-DLC-1b
  nct id: NCT05984303
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  This clinical trial is a Phase 1, multiple administration, dose-escalasion clinical trial of
        human umbilical cord-derived mesenchymal stem cells for the treatment of decompensated
        cirrhosis. The primary objective of this study is to assess the safety of intravenous
        infusion of human umbilical cord-derived mesenchymal stem cells in patients with
        decompensated cirrhosis.
  Decompensated cirrhosis has a high overall mortality rate. There is unmet need for safe and
        alternative therapeutic potions. This clinical trial is a Phase 1, multiple administration,
        dose-escalasion clinical trial of human umbilical cord-derived mesenchymal stem cells for the
        treatment of decompensated cirrhosis. The primary objective of this study is to assess the
        safety of intravenous infusion of human umbilical cord-derived mesenchymal stem cells in
        patients with decompensated cirrhosis.In order to illustrate the safety and effectiveness of
        human umbilical cord-derived mesenchymal stem cells and the patient's dose tolerance to human
        umbilical cord-derived mesenchymal stem cells.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Incidence of Adverse Events
  time frame: from baseline to 28th day
  measure: incidence of dose-limiting toxicity-related adverse events
  time frame: from baseline to 28th day
  measure: maximum tolerated dose
  time frame: from baseline to 28th day
  measure: Change in Model for End-Stage Liver Disease (MELD) score from baseline to 28th day
  time frame: at 28th day
  description: The Model for End-stage Liver Disease (MELD) is a scoring system that evaluates the liver function reserve and prognosis of patients with chronic liver disease by creatinine, international normalized ratio (INR), and bilirubin-conjugated cirrhosis etiology.
  The MELD score is calculated by the formula: R = 9.6 × ln (creatinine mg/dl) + 3.8 × ln (bilirubin mg/dl) + 11.2 × ln (INR) + 6.4 × etiology, and the results are taken as integers. ( 0 for cholestatic and alcoholic cirrhosis and 1 for other causes of cirrhosis such as viruses).
  measure: Change in Model for End-Stage Liver Disease (MELD) score from baseline to 3 days, 7days, 14 days, 21 days, 1 month, 2 months, 3 months, 6 months, 12 months, 18 months, and 24 months
  time frame: 3 days, 7days, 14 days, 21 days, 1 month, 2 months, 3 months, 6 months, 12 months, 18 months, and 24 months
  measure: Incidence of each complication associated with decompensated cirrhosis
  time frame: up to 24 months
  measure: liver transplant-free survival
  time frame: up to 24 months
  measure: Incidence of liver failure
  time frame: up to 24 months
  measure: plasma albumin (ALB)
  time frame: up to 24 months
  measure: plasma prealbumin (PALB)
  time frame: up to 24 months
  measure: total bilirubin (TBIL)
  time frame: up to 24 months
  measure: serum cholinesterase (CHE)
  time frame: up to 24 months
  measure: prothrombin time (PT)
  time frame: up to 24 months
  description: Prothrombin time (PT) is a blood test that measures the time it takes for plasma to clot, to check for bleeding problems, or to check whether medicine to prevent blood clots is working.
  measure: Child-Turcotte-Pugh (CTP) score
  time frame: up to 24 months
  description: Child-Turcotte-Pugh (CTP) score is a scoring system that evaluates the liver function.
  Maximum is 15, minimum is 5. Higher scores mean a worse outcome.
  measure: EuroQol Group 5-Dimension Self-Report Questionnaire (EQ-5D)
  time frame: up to 24 months
  description: Quality of life assessment. Maximum is 5, minimum is 1. Lower scores mean a better outcome.
  measure: Incidence of liver cancer
  time frame: up to 24 months
  measure: ChronicLiver Disease Questionnaire (CLDQ)
  time frame: up to 24 months
  description: Quality of life assessment. The Chronic Liver Disease Questionnaire (CLDQ) was developed as an evaluative instrument to measure longitudinal change in health status within individuals with chronic liver disease. In addition to measuring both physical and mental health, the instrument was designed to be a disease-specific tool for assessing areas of function important to patients with chronic liver disease. Maximum is 7, minimum is 1. Higher scores mean a better outcome.
  arm group label: Human Umbilical Cord-derived Mesenchymal Stem Cells
  arm group type: Experimental
  description: Standard of care (SOC) plus a multiple administration and dose-escalasion with 2 cohorts with 3 subjects/cohort who receive doses of 1 and 2 ×10E8 cells. Each person received 3 infusions, 1 week apart, Proceed from lower dose to higher dose if no safety concerns for each cohort.
  intervention type: Biological
  intervention name: Human Umbilical Cord-derived Mesenchymal Stem Cells
  description: Human Umbilical Cord-derived Mesenchymal Stem Cells will be administered intravenously.
  arm group label: Human Umbilical Cord-derived Mesenchymal Stem Cells
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: Fu-Sheng Wang, MD, PhD
  role: Study Chair
  affiliation: Beijing 302 Hospital
  last name: Lei Shi, MD,PhD
  phone: 86-10-66949623
  email: shilei302@126.com
  last name: Fu-Sheng Wang, MD,PhD
  phone: 86-10-66933332
  email: fswang302@163.com
  facility: 
  contact: 
  country: China
  responsible party type: Principal Investigator
  investigator affiliation: Beijing 302 Hospital
  investigator full name: Fu-Sheng Wang
  investigator title: Head of Treatment and Research Center for Infectious Diseases, Principle Investigator, Clinical Professor
  mesh term: Liver Cirrhosis
  mesh term: Fibrosis
  sharing ipd: Yes
  ipd description: After approval from the steering committee and the Human Genetic Resources Administration of China, this trial data can be shared with qualifying researchers who submit a proposal with a valuable research question. A contract should be signed.