- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04496479
Allogenic Hepatocyte Transplantation Into Periduodenal Lymph Nodes
September 19, 2023 updated by: LyGenesis, Inc.
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
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.
Study Overview
Status
Recruiting
Conditions
Intervention / Treatment
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 Type
Interventional
Enrollment (Estimated)
12
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Paulo Fontes, MD
- Phone Number: 412-860-3599
- Email: fontesp@lygenesis.com
Study Locations
-
-
Massachusetts
-
Boston, Massachusetts, United States, 02111
- Recruiting
- Tufts Medical Center
-
Contact:
- Raffi Karagozian, MD
-
-
Texas
-
Houston, Texas, United States, 77030
- Recruiting
- Houston Methodist Hospital
-
Contact:
- Constance Mobley, MD
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 70 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Have read, understood, and signed the informed consent form (ICF).
- 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.
- Subjects must have a body mass index (BMI) <35.
- Subjects with HCV associated ESLD must have been treated and demonstrate 24 weeks of negative HCV ribonucleic acid (RNA).
- Subjects with HBV must be on stable therapy for 6 months and have HBV deoxyribonucleic acid <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; HMA, 2014). For the definition and list of highly effective methods of contraception, see Appendix 1.
- Has stable control of portal hypertension and upper gastrointestinal bleeding with medical therapy and/or endoscopic therapy.
- 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).
- Has blood urea nitrogen (BUN) <80 mg/dL.
- Has an estimated glomerular filtration rate (eGFR) ≥45 mL/min/1.73 m2.
- Agrees to avoid alcohol consumption during the study.
- Is willing and able to comply with all requirements of the study protocol.
Exclusion Criteria:
- Has primary hepatic neoplasms (hepatocellular carcinoma and cholangiocarcinoma).
- Has active and/or uncontrolled severe infections requiring hospitalization and prolonged antimicrobial therapy.
- Has severe coagulopathy (international normalized ratio [INR] >2, and/or platelet count <50,000/μL).
- Has psychiatric and/or social issues that could lead to noncompliance.
- Has an extrahepatic neoplastic disease requiring active chemotherapy, immunotherapy, and/or surgical resection.
- Has previously treated neoplastic disease with less than a 2-year cancer free period.
- Pregnant and lactating women should not be in the study.
- Known hypersensitivity to human serum albumin.
- Subjects with uncontrolled hypertension (defined as a diastolic blood pressure of 110 mmHg or higher).
- Has recurrent/intractable ascites refractory to diuretics and requiring periodic large volume paracentesis.
- 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.
- Has grade 3 esophageal varices requiring the continuous use of propranolol and cannot afford to have this medication withheld and/or discontinued.
- Has a Child-Turcotte-Pugh (CTP) Class of C.
- Is receiving or plans to receive treatment with another investigational product or device.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: LYG-LIV0001
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
Week 12
|
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
|
Week 12
|
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
|
Week 12
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
Week 52
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change from Baseline in Ascities/Sarcopenia
Time Frame: Week 52
|
Changes from baseline in ascities/sarcopenia as measured by Computerized Tomography (CT) Scan
|
Week 52
|
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
|
Week 52
|
Change from Baseline in Liver Reserve
Time Frame: Week 52
|
Changes from baseline in liver reserve as measured through the Disease Severity Index
|
Week 52
|
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)
|
Week 52
|
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
|
Week 52
|
Change from Baseline in Fatigue
Time Frame: Week 52
|
Changes from baseline in fatigue as measured through the Neuro-QOL Short Form (Fatigue Scale)
|
Week 52
|
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 (RBANS) test
|
Week 52
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Chair: Paulo Fontes, MD, LyGenesis, Inc.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
March 11, 2022
Primary Completion (Estimated)
February 22, 2026
Study Completion (Estimated)
August 7, 2026
Study Registration Dates
First Submitted
July 22, 2020
First Submitted That Met QC Criteria
July 29, 2020
First Posted (Actual)
August 3, 2020
Study Record Updates
Last Update Posted (Actual)
September 21, 2023
Last Update Submitted That Met QC Criteria
September 19, 2023
Last Verified
September 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- LYG-LIV-02-01
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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