Allogenic Hepatocyte Transplantation Into Periduodenal Lymph Nodes

NCT04496479 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: LYG-LIV-02-01
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

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.

Conditions

End Stage Liver Disease

Keywords

Allogeneic; Organogenesis; Hepatocyte; Transplantation; Liver Disease

Outcome Measures

Primary Outcomes (3)

• Dosage Selection

  The primary objective of the dose escalation is to confirm the optimal dose of transplanted hepatocytes to safely achieve adequate allogeneic hepatocyte (AH) engraftment

  Week 12

• Safety of Engraftment of Hepatocytes in to Lymph Nodes

  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

  Week 12

• Efficacy of Engraftment of Hepatocytes in to Lymph Nodes

  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

  Week 12

Secondary Outcomes (1)

• Effectiveness of Selected Treatment to Modify the Liver Function Panel

  Week 52

Other Outcomes (7)

• Change from Baseline in Ascities/Sarcopenia

  Week 52

• Change from Baseline in Lean Body Mass

  Week 52

• Change from Baseline in Liver Reserve

  Week 52

Study Arms (1)

LYG-LIV0001

EXPERIMENTAL

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

Biological: LYG-LIV0001

Interventions

LYG-LIV0001 BIOLOGICAL

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.

LYG-LIV0001

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have read, understood, and signed the informed consent form (ICF).
• 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.
• Subjects must have a body mass index (BMI) \<35.
• Subjects with HCV associated ESLD must have been treated and demonstrate 24 weeks of negative HCV ribonucleic acid (RNA).
• Subjects with HBV must be on stable therapy for 6 months and have HBV deoxyribonucleic acid \<500 c/mL.
• 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.
• Has stable control of portal hypertension and upper gastrointestinal bleeding with medical therapy and/or endoscopic therapy.
• 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).
• Has blood urea nitrogen (BUN) \<80 mg/dL.
• Has an estimated glomerular filtration rate (eGFR) ≥45 mL/min/1.73 m2.
• Agrees to avoid alcohol consumption during the study.
• Is willing and able to comply with all requirements of the study protocol.

You may not qualify if:

• Has primary hepatic neoplasms (hepatocellular carcinoma and cholangiocarcinoma).
• Has active and/or uncontrolled severe infections requiring hospitalization and prolonged antimicrobial therapy.
• Has severe coagulopathy (international normalized ratio \[INR\] \>2, and/or platelet count \<50,000/μL).
• Has psychiatric and/or social issues that could lead to noncompliance.
• Has an extrahepatic neoplastic disease requiring active chemotherapy, immunotherapy, and/or surgical resection.
• Has previously treated neoplastic disease with less than a 2-year cancer free period.
• Pregnant and lactating women should not be in the study.
• Known hypersensitivity to human serum albumin.
• Subjects with uncontrolled hypertension (defined as a diastolic blood pressure of 110 mmHg or higher).
• Has recurrent/intractable ascites refractory to diuretics and requiring periodic large volume paracentesis.
• 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.
• Has grade 3 esophageal varices requiring the continuous use of propranolol and cannot afford to have this medication withheld and/or discontinued.
• Has a Child-Turcotte-Pugh (CTP) Class of C.
• Is receiving or plans to receive treatment with another investigational product or device.

Sponsors & Collaborators

• LyGenesis, Inc.: lead

Study Sites (2)

Tufts Medical Center

Boston, Massachusetts, 02111, United States

WITHDRAWN

Houston Methodist Hospital

Houston, Texas, 77030, United States

RECRUITING

MeSH Terms

Conditions

End Stage Liver Disease; Liver Diseases

Condition Hierarchy (Ancestors)

Liver Failure; Hepatic Insufficiency; Digestive System Diseases

Study Officials

• Paulo Fontes, MD

  LyGenesis, Inc.

  STUDY CHAIR

Central Study Contacts

Paulo Fontes, MD

CONTACT

412-860-3599; fontesp@lygenesis.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: This is no masking in the open-label dose escalation phase.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open-Label Dose Escalation of Three Increasing Dosages

Study Record Dates

• First Submitted: July 22, 2020
• First Posted: August 3, 2020
• Study Start: March 11, 2022
• Primary Completion (Estimated): August 20, 2027
• Study Completion (Estimated): December 30, 2027
• Last Updated: August 8, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)