<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/NCT04496479</url>
  </required_header>
  <id_info>
    <org_study_id>LYG-LIV-02-01</org_study_id>
    <nct_id>NCT04496479</nct_id>
  </id_info>
  <brief_title>Allogenic Hepatocyte Transplantation Into Periduodenal Lymph Nodes</brief_title>
  <official_title>A Phase 2a, Open Label, Dose Escalation Study for Safety, Tolerability, and Efficacy of Hepatocyte Transplantation Into Periduodenal Lymph Nodes Among Subjects With End-Stage Liver Disease Who Are Ineligible for Liver Transplantation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>LyGenesis, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>LyGenesis, Inc.</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      This Phase 2a clinical trial is a dose escalation study of the safety, tolerability, and&#xD;
      efficacy of hepatocyte transplantation into lymph nodes via endoscopic ultrasound among&#xD;
      subjects with end-stage liver disease.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This safety, tolerability, and efficacy study includes an open-label dose-escalation phase&#xD;
      for up to 12 subjects with end-stage liver disease (ESLD).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Enrolling by invitation</overall_status>
  <start_date type="Actual">March 11, 2022</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2023</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>Sequential Assignment</intervention_model>
    <intervention_model_description>Open-Label Dose Escalation of Three Increasing Dosages</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>This is no masking in the open-label dose escalation phase.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Dosage Selection</measure>
    <time_frame>Week 12</time_frame>
    <description>The primary objective of the dose escalation is to confirm the optimal dose of transplanted hepatocytes to safely achieve adequate allogeneic hepatocyte (AH) engraftment</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety of Engraftment of Hepatocytes in to Lymph Nodes</measure>
    <time_frame>Week 12</time_frame>
    <description>The primary safety objective of the dose escalation is to determine whether AH engraftments into the periduodenal lymph nodes in subjects with end-stage liver disease is safe as determined by the number/severity of adverse events</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Efficacy of Engraftment of Hepatocytes in to Lymph Nodes</measure>
    <time_frame>Week 12</time_frame>
    <description>The primary efficacy objective of the dose escalation is to determine whether AH engraftments into the periduodenal lymph nodes in subjects with end-stage liver disease is efficacious in addressing some of the signs and symptoms of end-stage liver disease</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Effectiveness of Selected Treatment to Modify the Liver Function Panel</measure>
    <time_frame>Week 52</time_frame>
    <description>Evaluate the effectiveness of hepatocyte transplants in modifying the liver function panel (total serum bilirubin, ammonia, prothrombin time, international normalized ratio, sodium, blood urea nitrogen, and creatinine) as measured through changes in laboratory biomarkers caused by end-stage liver disease</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Change from Baseline in Ascities/Sarcopenia</measure>
    <time_frame>Week 52</time_frame>
    <description>Changes from baseline in ascities/sarcopenia as measured by Computerized Tomography (CT) Scan</description>
  </other_outcome>
  <other_outcome>
    <measure>Change from Baseline in Lean Body Mass</measure>
    <time_frame>Week 52</time_frame>
    <description>Changes from baseline in lean body mass as measured by Skinfold Testing, Bioelectrical Impedance Analysis, or DexaScan</description>
  </other_outcome>
  <other_outcome>
    <measure>Change from Baseline in Liver Reserve</measure>
    <time_frame>Week 52</time_frame>
    <description>Changes from baseline in liver reserve as measured through the Disease Severity Index</description>
  </other_outcome>
  <other_outcome>
    <measure>Change from Baseline in Hepatic Function</measure>
    <time_frame>Week 52</time_frame>
    <description>Changes from baseline in hepatic function as measured through the HepQuant SHUNT Testing (assessing liver function in chronic liver disease)</description>
  </other_outcome>
  <other_outcome>
    <measure>Change from Baseline in Quality of Life</measure>
    <time_frame>Week 52</time_frame>
    <description>Changes from baseline in quality of life as measured through the SF-36 (total score and sub-scale scores) Questionnaire</description>
  </other_outcome>
  <other_outcome>
    <measure>Change from Baseline in Fatigue</measure>
    <time_frame>Week 52</time_frame>
    <description>Changes from baseline in fatigue as measured through the Neuro-QOL Short Form (Fatigue Scale)</description>
  </other_outcome>
  <other_outcome>
    <measure>Change from Baseline in Neuropsychological Status</measure>
    <time_frame>Week 52</time_frame>
    <description>Changes from baseline in neuropsychological status as measured by the Repeatable Battery of Neuropsychological Status (RBNS) test</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">12</enrollment>
  <condition>End Stage Liver Disease</condition>
  <arm_group>
    <arm_group_label>LYG-LIV0001</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Open label group of subjects with end stage liver disease receiving increasing doses of the experimental therapy.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>LYG-LIV0001</intervention_name>
    <description>Allogenic hepatocytes suspended in a buffered cell preservation solution with increasing number of lymph nodes being transplanted for the dose escalation. Subjects will also receive immune suppression, including tacrolimus capsules to follow the dose prescribed by the investigator as well as a short course of prednisone.</description>
    <arm_group_label>LYG-LIV0001</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adults of either gender and ages 18 to 70 years old&#xD;
&#xD;
          -  Subjects must have a diagnosis of end-stage liver disease (ESLD) due to alcohol,&#xD;
             chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, autoimmune&#xD;
             hepatitis, primary sclerosis cholangitis, primary biliary cirrhosis (cholangitis),&#xD;
             cirrhosis as the result of Wilson disease, hemochromatosis, sarcoidosis and alpha 1&#xD;
             antitrypsin deficiency, cryptogenic cirrhosis and nonalcoholic steatohepatitis&#xD;
             cirrhosis with a MELD-Na score &gt;10 to &lt;25 at screening.&#xD;
&#xD;
          -  Subjects have a Body Mass Index (BMI) &lt;35.&#xD;
&#xD;
          -  Subjects with HCV associated ESLD must have been treated and demonstrate 24 weeks of&#xD;
             negative HCV RNA.&#xD;
&#xD;
          -  Subjects with HBV must be on stable therapy for 6 months and have HBV DNA &lt;500 c/mL.&#xD;
&#xD;
          -  Women of childbearing potential (WOCBP) or sexual partners of male subjects who are&#xD;
             WOCBP must be able and willing to use at least 1 highly effective method of&#xD;
             contraception during the study and for 1 month after the last study visit. A female&#xD;
             subject is considered to be a WOCBP after menarche and until she is in a&#xD;
             postmenopausal state for 12 months or otherwise permanently sterile (for which&#xD;
             acceptable methods include hysterectomy, bilateral salpingectomy, and bilateral&#xD;
             oophorectomy).&#xD;
&#xD;
          -  Subject must have stable control of portal hypertension and upper gastrointestinal&#xD;
             bleeding with medical therapy and/or endoscopic therapy.&#xD;
&#xD;
          -  If the subject has undergone a transjugular intrahepatic portosystemic shunt (TIPS)&#xD;
             procedure for the clinical management of portal hypertension, they must be stable for&#xD;
             at least 1 month after the successful TIPS procedure, and not experiencing serious&#xD;
             complications from the TIPS procedure itself (e.g., infection and intractable hepatic&#xD;
             encephalopathy).&#xD;
&#xD;
          -  Subject must have serum BUN &lt;80 mg/dL.&#xD;
&#xD;
          -  Subject must have a eGFR &lt;45 mL/min/1.73m2.&#xD;
&#xD;
          -  Subject may have had current and/or previous cardiopulmonary diseases precluding&#xD;
             standard liver transplantation (e.g., coronary artery disease, portopulmonary&#xD;
             hypertension, moderate chronic obstructive pulmonary disease).&#xD;
&#xD;
          -  Subject must agrees to avoid alcohol consumption during the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subject has primary hepatic neoplasms (hepatocellular carcinoma and&#xD;
             cholangiocarcinoma).&#xD;
&#xD;
          -  Subject has active and/or uncontrolled severe infections requiring hospitalization and&#xD;
             prolonged antimicrobial therapy.&#xD;
&#xD;
          -  Subject has renal failure with BUN &gt;= 80 mg/dL.&#xD;
&#xD;
          -  Subject has a eGFR &gt;= 45 mL/min/1.73m2.&#xD;
&#xD;
          -  Subject has severe coagulopathy (INR &gt;2, and/or platelet count &lt;50,000/μL).&#xD;
&#xD;
          -  Subject has psychiatric and/or social issues that could lead to noncompliance.&#xD;
&#xD;
          -  Subject has an extrahepatic neoplastic disease requiring active chemotherapy,&#xD;
             immunotherapy, and/or surgical resection.&#xD;
&#xD;
          -  Subject has previously treated neoplastic disease with less than a 2-year cancer free&#xD;
             period.&#xD;
&#xD;
          -  Subject is pregnant or lactating.&#xD;
&#xD;
          -  Subject has known hypersensitivity to human serum albumin.&#xD;
&#xD;
          -  Subjects with uncontrolled hypertension (defined as a diastolic blood pressure of 110&#xD;
             mm Hg or higher).&#xD;
&#xD;
          -  Subject has recurrent/intractable ascites refractory to diuretics and requiring&#xD;
             periodic large volume paracentesis.&#xD;
&#xD;
          -  Subject has primary alcoholic liver disease and has not demonstrated abstinence for at&#xD;
             least 6 months while attending mandatory rehab programs (e.g., AA) and psychotherapy.&#xD;
&#xD;
          -  Subject has grade 3 esophageal varcies requiring the continuous use of Propanolol and&#xD;
             cannot afford to have this medication withheld and/or discontinued.&#xD;
&#xD;
          -  Subject has a Child-Turcotte-Pugh (CTP) Score of C.&#xD;
&#xD;
          -  Subject is receiving or plans to receive treatment with another investigational&#xD;
             product or device.&#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>Paulo Fontes, MD</last_name>
    <role>Study Chair</role>
    <affiliation>LyGenesis, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Tufts Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>July 22, 2020</study_first_submitted>
  <study_first_submitted_qc>July 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 3, 2020</study_first_posted>
  <last_update_submitted>January 30, 2023</last_update_submitted>
  <last_update_submitted_qc>January 30, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 1, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Allogeneic</keyword>
  <keyword>Organogenesis</keyword>
  <keyword>Hepatocyte</keyword>
  <keyword>Transplantation</keyword>
  <keyword>Liver Disease</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Liver Diseases</mesh_term>
    <mesh_term>End Stage Liver Disease</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT04496479
org study id: LYG-LIV-02-01
nct id: NCT04496479
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This Phase 2a clinical trial is a dose escalation study of the safety, tolerability, and
      efficacy of hepatocyte transplantation into lymph nodes via endoscopic ultrasound among
      subjects with end-stage liver disease.
This safety, tolerability, and efficacy study includes an open-label dose-escalation phase
      for up to 12 subjects with end-stage liver disease (ESLD).
allocation: N/A
intervention model: Sequential Assignment
intervention model description: Open-Label Dose Escalation of Three Increasing Dosages
primary purpose: Treatment
masking: None (Open Label)
masking description: This is no masking in the open-label dose escalation phase.
measure: Dosage Selection
time frame: Week 12
description: The primary objective of the dose escalation is to confirm the optimal dose of transplanted hepatocytes to safely achieve adequate allogeneic hepatocyte (AH) engraftment
measure: Safety of Engraftment of Hepatocytes in to Lymph Nodes
time frame: Week 12
description: The primary safety objective of the dose escalation is to determine whether AH engraftments into the periduodenal lymph nodes in subjects with end-stage liver disease is safe as determined by the number/severity of adverse events
measure: Efficacy of Engraftment of Hepatocytes in to Lymph Nodes
time frame: Week 12
description: The primary efficacy objective of the dose escalation is to determine whether AH engraftments into the periduodenal lymph nodes in subjects with end-stage liver disease is efficacious in addressing some of the signs and symptoms of end-stage liver disease
measure: Effectiveness of Selected Treatment to Modify the Liver Function Panel
time frame: Week 52
description: Evaluate the effectiveness of hepatocyte transplants in modifying the liver function panel (total serum bilirubin, ammonia, prothrombin time, international normalized ratio, sodium, blood urea nitrogen, and creatinine) as measured through changes in laboratory biomarkers caused by end-stage liver disease
measure: Change from Baseline in Ascities/Sarcopenia
time frame: Week 52
description: Changes from baseline in ascities/sarcopenia as measured by Computerized Tomography (CT) Scan
measure: Change from Baseline in Lean Body Mass
time frame: Week 52
description: Changes from baseline in lean body mass as measured by Skinfold Testing, Bioelectrical Impedance Analysis, or DexaScan
measure: Change from Baseline in Liver Reserve
time frame: Week 52
description: Changes from baseline in liver reserve as measured through the Disease Severity Index
measure: Change from Baseline in Hepatic Function
time frame: Week 52
description: Changes from baseline in hepatic function as measured through the HepQuant SHUNT Testing (assessing liver function in chronic liver disease)
measure: Change from Baseline in Quality of Life
time frame: Week 52
description: Changes from baseline in quality of life as measured through the SF-36 (total score and sub-scale scores) Questionnaire
measure: Change from Baseline in Fatigue
time frame: Week 52
description: Changes from baseline in fatigue as measured through the Neuro-QOL Short Form (Fatigue Scale)
measure: Change from Baseline in Neuropsychological Status
time frame: Week 52
description: Changes from baseline in neuropsychological status as measured by the Repeatable Battery of Neuropsychological Status (RBNS) test
arm group label: LYG-LIV0001
arm group type: Experimental
description: Open label group of subjects with end stage liver disease receiving increasing doses of the experimental therapy.
intervention type: Biological
intervention name: LYG-LIV0001
description: Allogenic hepatocytes suspended in a buffered cell preservation solution with increasing number of lymph nodes being transplanted for the dose escalation. Subjects will also receive immune suppression, including tacrolimus capsules to follow the dose prescribed by the investigator as well as a short course of prednisone.
arm group label: LYG-LIV0001
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Paulo Fontes, MD
role: Study Chair
affiliation: LyGenesis, Inc.
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Liver Diseases
mesh term: End Stage Liver Disease
sharing ipd: No