Allogenic Hepatocyte Transplantation Into Periduodenal Lymph Nodes
Allogenic Hepatocyte Transplantation Into Periduodenal Lymph Nodes
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 who are ineligible for standard liver transplantation.
This safety, tolerability, and efficacy study includes an open-label dose-escalation phase
 for up to 12 subjects with end-stage liver disease (ESLD).
Inclusion Criteria:

 -  Adults of either gender and ages 18 to 70 years old

 -  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.

 -  Subjects with HCV associated ESLD must have been treated and demonstrate 24 weeks of
 negative HCV RNA.

 -  Subjects with HBV must be on stable therapy for 6 months and have HBV DNA <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).

 -  Subject must have stable control of portal hypertension and upper gastrointestinal
 bleeding with medical therapy and/or endoscopic therapy.

 -  If the subject has undergone a transjugular intrahepatic portosystemic shunt (TIPS)
 procedure for the clinical management of portal hypertension, they must be stable for
 at least 1 month after the successful TIPS procedure, and not experiencing serious
 complications from the TIPS procedure itself (e.g., infection and intractable hepatic
 encephalopathy).

 -  Subject must have serum BUN <80 mg/dL.

 -  Subject must have a eGFR <45 mL/min/1.73m2.

 -  Subject may have had current and/or previous cardiopulmonary diseases precluding
 standard liver transplantation (e.g., coronary artery disease, portopulmonary
 hypertension, moderate chronic obstructive pulmonary disease).

 -  Subject must agrees to avoid alcohol consumption during the study.

 Exclusion Criteria:

 -  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 renal failure with BUN >= 80 mg/dL.

 -  Subject has a eGFR >= 45 mL/min/1.73m2.

 -  Subject has severe coagulopathy (INR >2, and/or platelet count <50,000/μL).

 -  Subject has psychiatric and/or social issues that could lead to noncompliance.

 -  Subject has an extrahepatic neoplastic disease requiring active chemotherapy,
 immunotherapy, and/or surgical resection.

 -  Subject has previously treated neoplastic disease with less than a 2-year cancer free
 period.

 -  Subject is pregnant or lactating.

 -  Subject has known hypersensitivity to human serum albumin.

 -  Subjects with uncontrolled hypertension (defined as a diastolic blood pressure of 110
 mm Hg or higher).

 -  Subject has recurrent/intractable ascites refractory to diuretics and requiring
 periodic large volume paracentesis.

 -  Subject has primary alcoholic liver disease and has not demonstrated abstinence for at
 least 6 months while attending mandatory rehab programs (e.g., AA) and psychotherapy.

 -  Subject has grade 3 esophageal varcies requiring the continuous use of Propanolol and
 cannot afford to have this medication withheld and/or discontinued.

 -  Subject has a Child-Turcotte-Pugh (CTP) Score of C.

 -  Subject is receiving or plans to receive treatment with another investigational
 product or device.