Transplanting liver cells into lymph nodes for treating severe liver disease

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

This study is testing if putting liver cells into lymph nodes can help people with severe liver disease feel better and improve their liver function.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 12 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: LyGenesis, Inc. (Industry-sponsored)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 2 sites (Boston, Massachusetts and 1 other locations)
• Trial ID: NCT04496479 on ClinicalTrials.gov

What this trial studies

This Phase 2a clinical trial investigates the safety, tolerability, and efficacy of transplanting hepatocytes into lymph nodes using endoscopic ultrasound in patients with end-stage liver disease (ESLD). The study features an open-label dose-escalation design involving up to 12 subjects. Participants will be monitored for their response to the treatment and any potential side effects. The goal is to assess whether this innovative approach can improve liver function in individuals suffering from severe liver conditions.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 70 with a diagnosis of end-stage liver disease and a MELD-Na score between 10 and 25.

Not a fit: Patients with a MELD-Na score outside the specified range or those with a BMI over 35 may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with end-stage liver disease, potentially improving liver function and quality of life.

How similar studies have performed: While hepatocyte transplantation is a novel approach, similar studies have shown promise in the field of organogenesis and regenerative medicine.

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.

Where this trial is running

Boston, Massachusetts and 1 other locations

• Tufts Medical Center — Boston, Massachusetts, United States (Withdrawn)
• Houston Methodist Hospital — Houston, Texas, United States (Recruiting)

Study contacts

• Study coordinator: Paulo Fontes, MD

Conditions End Stage Liver Disease; Allogeneic; Organogenesis; Hepatocyte; Transplantation; Liver Disease