The objectives of this dose escalation study are to confirm the optimal dose of transplanted hepatocytes to safely achieve adequate allogeneic hepatocyte (AH) engraftment into the periduodenal lymph nodes (PDLNs) via endoscopic ultrasound (EUS) in subjects with end-stage liver disease.
- Subjects must have a diagnosis of end-stage liver disease (ESLD) due to alcohol, chronic hepatitis B virus (HBV) and 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 to <25 at screening.
- Subjects have a Body Mass Index (BMI) <35.
- Subject must have stable control of portal hypertension and upper gastrointestinal bleeding with medical therapy and/or endoscopic therapy.
- Subject has primary hepatic neoplasms (hepatocellular carcinoma and cholangiocarcinoma).
- Subject has active and/or uncontrolled severe infections requiring hospitalization and prolonged antimicrobial therapy.
- Subject has an extrahepatic neoplastic disease requiring active chemotherapy, immunotherapy, and/or surgical resection.
The total duration of the study is expected to be approximately 24 months, including 3 months (12 weeks) for subject recruitment, 9 months for analyses from the dose escalation, and 12 months for safety follow-up visits.
Screening: Up to 3 months (12 weeks).
Treatment: Subjects will receive the hepatocyte transplantation (HT) through the endoscopic ultrasound (EUS) approach. Immediately following the EUS procedure, subjects will be hospitalized overnight for a 23-hour observation period to allow for continuous acute clinical and laboratorial monitoring as needed. The initial follow-up should be weekly for the first month.
Primary Evaluation: 12 weeks after dosing.
Safety/Tolerability/Efficacy Follow-up: conducted throughout the study as Weeks 1, 2, 3, 4, 6, 8, 1