Allogenic Hepatocyte Transplantation Into Periduodenal Lymph Nodes

Sponsor

LyGenesis, Inc. (Industry)

Overall Status

Enrolling by invitation

CT.gov ID

NCT04496479

Collaborator

(none)

Enrollment

Location

Arm

21.7

Anticipated Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
End Stage Liver Disease	Biological: LYG-LIV0001	Phase 2

Detailed Description

This safety, tolerability, and efficacy study includes an open-label dose-escalation phase for up to 12 subjects with end-stage liver disease (ESLD).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

12 participants

Allocation:

N/A

Intervention Model:

Sequential Assignment

Intervention Model Description:

Open-Label Dose Escalation of Three Increasing DosagesOpen-Label Dose Escalation of Three Increasing Dosages

Masking:

None (Open Label)

Masking Description:

This is no masking in the open-label dose escalation phase.

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Mar 11, 2022

Anticipated Primary Completion Date :

Dec 31, 2023

Anticipated Study Completion Date :

Dec 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LYG-LIV0001 Open label group of subjects with end stage liver disease receiving increasing doses of the experimental therapy.	Biological: LYG-LIV0001 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.

Arm

Intervention/Treatment

Experimental: LYG-LIV0001

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

Biological: LYG-LIV0001

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.

Outcome Measures

Primary Outcome Measures

Dosage Selection [Week 12]
The primary objective of the dose escalation is to confirm the optimal dose of transplanted hepatocytes to safely achieve adequate allogeneic hepatocyte (AH) engraftment
Safety of Engraftment of Hepatocytes in to Lymph Nodes [Week 12]
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
Efficacy of Engraftment of Hepatocytes in to Lymph Nodes [Week 12]
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

Secondary Outcome Measures

Effectiveness of Selected Treatment to Modify the Liver Function Panel [Week 52]
Evaluate the effectiveness of hepatocyte transplants in modifying the liver function panel (total serum bilirubin, ammonia, prothrombin time, international normalized ratio, sodium, blood urea nitrogen, and creatinine) as measured through changes in laboratory biomarkers caused by end-stage liver disease

Other Outcome Measures

Change from Baseline in Ascities/Sarcopenia [Week 52]
Changes from baseline in ascities/sarcopenia as measured by Computerized Tomography (CT) Scan
Change from Baseline in Lean Body Mass [Week 52]
Changes from baseline in lean body mass as measured by Skinfold Testing, Bioelectrical Impedance Analysis, or DexaScan
Change from Baseline in Liver Reserve [Week 52]
Changes from baseline in liver reserve as measured through the Disease Severity Index
Change from Baseline in Hepatic Function [Week 52]
Changes from baseline in hepatic function as measured through the HepQuant SHUNT Testing (assessing liver function in chronic liver disease)
Change from Baseline in Quality of Life [Week 52]
Changes from baseline in quality of life as measured through the SF-36 (total score and sub-scale scores) Questionnaire
Change from Baseline in Fatigue [Week 52]
Changes from baseline in fatigue as measured through the Neuro-QOL Short Form (Fatigue Scale)
Change from Baseline in Neuropsychological Status [Week 52]
Changes from baseline in neuropsychological status as measured by the Repeatable Battery of Neuropsychological Status (RBNS) test

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.