Allogenic Hepatocyte Transplantation Into Periduodenal Lymph Nodes

• ClinicalTrials.gov Identifier: NCT04496479
• Recruitment Status: Recruiting
• First Posted: August 3, 2020
• Last Update Posted: September 21, 2023
• Sponsor: LyGenesis, Inc.
• Information provided by (Responsible Party): LyGenesis, Inc.

Tracking Information

• First Submitted Date: July 22, 2020
• First Posted Date: August 3, 2020
• Last Update Posted Date: September 21, 2023
• Actual Study Start Date: March 11, 2022
• Estimated Primary Completion Date: February 22, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 19, 2021)

• Dosage Selection [ Time Frame: Week 12 ]
  The primary objective of the dose escalation is to confirm the optimal dose of transplanted hepatocytes to safely achieve adequate allogeneic hepatocyte (AH) engraftment
• Safety of Engraftment of Hepatocytes in to Lymph Nodes [ Time Frame: Week 12 ]
  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
• Efficacy of Engraftment of Hepatocytes in to Lymph Nodes [ Time Frame: Week 12 ]
  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

Original Primary Outcome Measures (submitted: July 29, 2020)

• Dosage Selection [ Time Frame: Week 12 ]
  The primary objective of the dose exploration phase is to confirm the minimal dose of transplanted hepatocytes to safely achieve adequate allogeneic hepatocyte (AH) engraftment
• Safety of Engraftment of Hepatocytes in to Lymph Nodes [ Time Frame: Week 24 ]
  The primary safety objective of the feasibility assessment phase is to determine whether AH engraftments into the peri-duodenal lymph nodes in subjects with end-stage liver disease is safe as determined by the number/severity of adverse events
• Efficacy of Engraftment of Hepatocytes in to Lymph Nodes [ Time Frame: Week 24 ]
  The primary efficacy objective of the feasibility assessment phase is to determine whether AH engraftments into the peri-duodenal lymph nodes in subjects with end-stage liver disease is efficacious as determined by the percentage of engraftments into the PDLN

Current Secondary Outcome Measures (submitted: January 19, 2021)

Effectiveness of Selected Treatment to Modify the Liver Function Panel [ Time Frame: Week 52 ]

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

Original Secondary Outcome Measures (submitted: July 29, 2020)

Effectiveness of Selected Treatment to Modify the Liver Function Panel Compared to Placebo [ Time Frame: Week 24 ]

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 progressive and irreversible end-stage liver disease as compared to placebo

Current Other Pre-specified Outcome Measures (submitted: September 19, 2023)

• Change from Baseline in Ascities/Sarcopenia [ Time Frame: Week 52 ]
  Changes from baseline in ascities/sarcopenia as measured by Computerized Tomography (CT) Scan
• Change from Baseline in Lean Body Mass [ Time Frame: Week 52 ]
  Changes from baseline in lean body mass as measured by Skinfold Testing, Bioelectrical Impedance Analysis, or DexaScan
• Change from Baseline in Liver Reserve [ Time Frame: Week 52 ]
  Changes from baseline in liver reserve as measured through the Disease Severity Index
• Change from Baseline in Hepatic Function [ Time Frame: Week 52 ]
  Changes from baseline in hepatic function as measured through the HepQuant SHUNT Testing (assessing liver function in chronic liver disease)
• Change from Baseline in Quality of Life [ Time Frame: Week 52 ]
  Changes from baseline in quality of life as measured through the SF-36 (total score and sub-scale scores) Questionnaire
• Change from Baseline in Fatigue [ Time Frame: Week 52 ]
  Changes from baseline in fatigue as measured through the Neuro-QOL Short Form (Fatigue Scale)
• Change from Baseline in Neuropsychological Status [ Time Frame: Week 52 ]
  Changes from baseline in neuropsychological status as measured by the Repeatable Battery of Neuropsychological Status (RBANS) test

Original Other Pre-specified Outcome Measures (submitted: July 29, 2020)

• Change from Baseline in Ascites Formation [ Time Frame: Week 52 ]
  Changes from baseline in ascites volume measured by Computerized Tomography (CT) Scan as compared between treatment and placebo subjects
• Change from Baseline in Sarcopenia [ Time Frame: Week 52 ]
  Changes from baseline in sarcopenia as measured by Computerized Tomography (CT) Scan as compared between treatment and placebo subjects
• Change from Baseline in Lean Body Mass [ Time Frame: Week 52 ]
  Changes from baseline in lean body mass as measured by Skinfold Testing, Bioelectrical Impedance Analysis, or DexaScan as compared between treatment and placebo subjects
• Change from Baseline in Liver Reserve [ Time Frame: Week 52 ]
  Changes from baseline in liver reserve as measured through the Disease Severity Index as compared between treatment and placebo subjects
• Change from Baseline in Hepatic Function [ Time Frame: Week 52 ]
  Changes from baseline in hepatic function as measured through the HepQuant SHUNT Testing (assessing liver function in chronic liver disease) as compared between treatment and placebo subjects
• Change from Baseline in Quality of Life [ Time Frame: Week 52 ]
  Changes from baseline in quality of life as measured through the SF-36 (total score and sub-scale scores) Questionnaire as compared between treatment and placebo subjects
• Change from Baseline in Fatigue [ Time Frame: Week 52 ]
  Changes from baseline in fatigue as measured through the Neuro-QOL Short Form (Fatigue Scale) as compared between treatment and placebo subjects
• Change from Baseline in Neuropsychological Status [ Time Frame: Week 52 ]
  Changes from baseline in neuropsychological status as measured by the Repeatable Battery of Neuropsychological Status (RBNS) test as compared between treatment and placebo subjects
• Change in Survival Duration [ Time Frame: Week 52 ]
  Changes in subject survival duration as compared between treatment and placebo subjects

Descriptive Information

• Brief Title: Allogenic Hepatocyte Transplantation Into Periduodenal Lymph Nodes
• 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
• Brief Summary: 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.
• Detailed Description: This safety, tolerability, and efficacy study includes an open-label dose-escalation phase for up to 12 subjects with end-stage liver disease (ESLD).
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: N/A
Intervention Model: Sequential Assignment
Intervention Model Description:

Open-Label Dose Escalation of Three Increasing Dosages

Masking: None (Open Label)
Masking Description:

This is no masking in the open-label dose escalation phase.

Primary Purpose: Treatment

• Condition: End Stage Liver Disease

Intervention

Biological: LYG-LIV0001

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.

Study Arms

Experimental: LYG-LIV0001

Open label group of subjects with end stage liver disease receiving increasing doses of the experimental therapy.

Intervention: Biological: LYG-LIV0001

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: December 14, 2020): 12
• Original Estimated Enrollment (submitted: July 29, 2020): 45
• Estimated Study Completion Date: August 7, 2026
• Estimated Primary Completion Date: February 22, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Have read, understood, and signed the informed consent form (ICF).
2. Adults of either gender and ages 18 to 70 years old with a diagnosis of ESLD due to alcohol, chronic hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infections, autoimmune hepatitis, primary sclerosis cholangitis, primary biliary cirrhosis (cholangitis), cirrhosis as the result of Wilson disease, hemochromatosis, sarcoidosis and alpha 1 antitrypsin deficiency, cryptogenic cirrhosis, and nonalcoholic steatohepatitis cirrhosis with a MELD-Na score >10 and <25 at screening.
3. Subjects must have a body mass index (BMI) <35.
4. Subjects with HCV associated ESLD must have been treated and demonstrate 24 weeks of negative HCV ribonucleic acid (RNA).
5. Subjects with HBV must be on stable therapy for 6 months and have HBV deoxyribonucleic acid <500 c/mL.
6. Women of childbearing potential (WOCBP) or sexual partners of male subjects who are WOCBP must be able and willing to use at least 1 highly effective method of contraception during the study and for 1 month after the last study visit. A female subject is considered to be a WOCBP after menarche and until she is in a postmenopausal state for 12 months or otherwise permanently sterile (for which acceptable methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy; HMA, 2014). For the definition and list of highly effective methods of contraception, see Appendix 1.
7. Has stable control of portal hypertension and upper gastrointestinal bleeding with medical therapy and/or endoscopic therapy.
8. If the subject has undergone a TIPS procedure for the clinical management of portal hypertension, they must be stable after the successful TIPS procedure, and not experiencing serious complications from the TIPS procedure itself (e.g., infection and intractable hepatic encephalopathy).
9. Has blood urea nitrogen (BUN) <80 mg/dL.
10. Has an estimated glomerular filtration rate (eGFR) ≥45 mL/min/1.73 m2.
11. Agrees to avoid alcohol consumption during the study.
12. Is willing and able to comply with all requirements of the study protocol.

Exclusion Criteria:

1. Has primary hepatic neoplasms (hepatocellular carcinoma and cholangiocarcinoma).
2. Has active and/or uncontrolled severe infections requiring hospitalization and prolonged antimicrobial therapy.
3. Has severe coagulopathy (international normalized ratio [INR] >2, and/or platelet count <50,000/μL).
4. Has psychiatric and/or social issues that could lead to noncompliance.
5. Has an extrahepatic neoplastic disease requiring active chemotherapy, immunotherapy, and/or surgical resection.
6. Has previously treated neoplastic disease with less than a 2-year cancer free period.
7. Pregnant and lactating women should not be in the study.
8. Known hypersensitivity to human serum albumin.
9. Subjects with uncontrolled hypertension (defined as a diastolic blood pressure of 110 mmHg or higher).
10. Has recurrent/intractable ascites refractory to diuretics and requiring periodic large volume paracentesis.
11. Has primary alcoholic liver disease and has not demonstrated abstinence for at least 24 weeks (6 months) prior to enrollment while attending mandatory rehab programs (e.g., Alcoholics Anonymous) and psychotherapy.
12. Has grade 3 esophageal varices requiring the continuous use of propranolol and cannot afford to have this medication withheld and/or discontinued.
13. Has a Child-Turcotte-Pugh (CTP) Class of C.
14. Is receiving or plans to receive treatment with another investigational product or device.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Paulo Fontes, MD; 412-860-3599; fontesp@lygenesis.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04496479
• Other Study ID Numbers: LYG-LIV-02-01
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: LyGenesis, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: LyGenesis, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: Paulo Fontes, MD; LyGenesis, Inc.

• PRS Account: LyGenesis, Inc.
• Verification Date: September 2023