Allogenic Hepatocyte Transplantation Into Periduodenal Lymph Nodes
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|ClinicalTrials.gov Identifier: NCT04496479|
Recruitment Status : Enrolling by invitation
First Posted : August 3, 2020
Last Update Posted : February 1, 2023
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|Condition or disease||Intervention/treatment||Phase|
|End Stage Liver Disease||Biological: LYG-LIV0001||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||12 participants|
|Intervention Model:||Sequential Assignment|
|Intervention Model Description:||Open-Label Dose Escalation of Three Increasing Dosages|
|Masking:||None (Open Label)|
|Masking Description:||This is no masking in the open-label dose escalation phase.|
|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 Who Are Ineligible for Liver Transplantation|
|Actual Study Start Date :||March 11, 2022|
|Estimated Primary Completion Date :||December 31, 2023|
|Estimated Study Completion Date :||December 31, 2023|
Open label group of subjects with end stage liver disease receiving increasing doses of the experimental therapy.
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.
- Dosage Selection [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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
- Effectiveness of Selected Treatment to Modify the Liver Function Panel [ Time Frame: 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
- Change from Baseline in Ascities/Sarcopenia [ Time Frame: Week 52 ]Changes from baseline in ascities/sarcopenia as measured by Computerized Tomography (CT) Scan
- Change from Baseline in Lean Body Mass [ Time Frame: 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 [ Time Frame: Week 52 ]Changes from baseline in liver reserve as measured through the Disease Severity Index
- Change from Baseline in Hepatic Function [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Week 52 ]Changes from baseline in fatigue as measured through the Neuro-QOL Short Form (Fatigue Scale)
- Change from Baseline in Neuropsychological Status [ Time Frame: Week 52 ]Changes from baseline in neuropsychological status as measured by the Repeatable Battery of Neuropsychological Status (RBNS) test
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|Ages Eligible for Study:||18 Years to 70 Years (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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.
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04496479
|United States, Massachusetts|
|Tufts Medical Center|
|Boston, Massachusetts, United States, 02111|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|
|Study Chair:||Paulo Fontes, MD||LyGenesis, Inc.|
|Responsible Party:||LyGenesis, Inc.|
|Other Study ID Numbers:||
|First Posted:||August 3, 2020 Key Record Dates|
|Last Update Posted:||February 1, 2023|
|Last Verified:||May 2022|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
End Stage Liver Disease
Digestive System Diseases