Hepatocyte Transplantation Into Periduodenal Lymph Nodes in End-Stage Liver Disease

What is the Purpose of this Study?

The purpose of this study is to evaluate an experimental treatment called allogeneic hepatocyte transplantation (injection of donor liver cells) as a possible treatment for end-stage liver disease (ESLD). The study aims to identify the ideal dose of transplanted cells needed, as well as assess the safety of this treatment for people with ESLD. Study procedures include injection of donor liver cells during an endoscopic procedure under sedation. Participants will be hospitalized for an overnight stay for additional monitoring and will undergo physical exams, imaging tests, and blood tests to evaluate liver functioning. They will also receive immunosuppressive medication to ensure that the transplanted liver cells are not rejected. This study focuses on patients who are not candidates for liver transplantation.

Eligibility

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).

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.

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Where can I participate?

Beverly

More about this Clinical Trial

What is the full name of this clinical trial?

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

Study Details

Disease Type/Condition

Other

Principal Investigator

Kuo, Alexander

Age Group

Adult

Phase

IRB Number

STUDY00002646

ClinicalTrials.gov ID

NCT04496479

Key Eligibility

ClinicalTrials.gov

How do I learn more about this study?

clinicaltrials@cshs.org