Liver Cell Transplant for End-Stage Liver Disease
Recruiting in Palo Alto (17 mi)
+2 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: LyGenesis, Inc.
Must be taking: HBV therapy
Must not be taking: Propranolol
Disqualifiers: Cancer, Severe infections, Hypertension, others
No Placebo Group
Prior Safety Data
Approved in 1 Jurisdiction
Trial Summary
What is the purpose of this trial?
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.
Will I have to stop taking my current medications?
The trial protocol does not specify if you need to stop taking your current medications. However, if you have grade 3 esophageal varices and are continuously using propranolol, you cannot participate if you cannot stop this medication.
What data supports the effectiveness of the treatment LYG-LIV0001 for end-stage liver disease?
Is liver cell transplantation generally safe for humans?
Liver cell transplantation has been tested in animals, showing some reversible side effects like changes in liver enzymes and signs of apathy, but no unexpected reactions. In a small human study with a similar liver support system, no serious adverse events were noted, suggesting it may be generally safe with proper monitoring.678910
How is the treatment LYG-LIV0001 different from other treatments for end-stage liver disease?
LYG-LIV0001 is a cell therapy that offers a potential alternative to liver transplantation, which is currently the only curative treatment for end-stage liver disease but is limited by the shortage of available donor organs. This treatment may provide liver function support or serve as a bridging therapy until a transplant can be performed.56111213
Eligibility Criteria
Adults aged 18-70 with end-stage liver disease (ESLD) from various causes and a MELD-Na score of >10 to <25. Must have stable control of portal hypertension, BMI <35, no severe infections or recent cancers, not pregnant or breastfeeding, and willing to avoid alcohol. Those with HBV/HCV must meet specific treatment criteria.Inclusion Criteria
Subject must agrees to avoid alcohol consumption during the study
I am between 18 and 70 years old.
I have heart or lung conditions that prevent me from having standard liver transplant.
See 9 more
Exclusion Criteria
I have alcoholic liver disease and haven't abstained from alcohol for 6 months despite rehab.
Subject has severe coagulopathy (INR >2, and/or platelet count <50,000/μL)
I had cancer before and have been cancer-free for less than 2 years.
See 13 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Dose Escalation
Open-label dose escalation phase to determine the optimal dose of hepatocyte transplantation into periduodenal lymph nodes
12 weeks
Regular visits for dose escalation and monitoring
Follow-up
Participants are monitored for safety and effectiveness after treatment, including changes in liver reserve, fatigue, neuropsychological status, and quality of life
52 weeks
Periodic visits for assessment and monitoring
Treatment Details
Interventions
- LYG-LIV0001 (Hepatocyte Transplantation)
Trial OverviewThe trial is testing the safety and effectiveness of transplanting hepatocytes (liver cells) into lymph nodes near the duodenum using an endoscopic ultrasound in patients with ESLD. It's a Phase 2a dose escalation study.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: LYG-LIV0001Experimental Treatment1 Intervention
Open label group of subjects with end stage liver disease receiving increasing doses of the experimental therapy.
LYG-LIV0001 is already approved in United States for the following indications:
🇺🇸 Approved in United States as LYG-LIV0001 for:
- End-stage liver disease
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Massachusetts General HospitalBoston, MA
Tufts Medical CenterBoston, MA
Houston Methodist HospitalHouston, TX
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Who Is Running the Clinical Trial?
LyGenesis, Inc.Lead Sponsor
References
Living Donor Liver Transplantation: Technical Innovations. [2018]Living donor liver transplantation (LDLT) has found a place to serve the end-stage liver disease community as the donor safety and recipient suitability has been elucidated. Donor safety is of paramount importance and transplant programs must continue endeavors to maintain the highest possible standards. At the same time, adequacy of grafts based on recipient clinical status via their model for end-stage liver disease (MELD) score and volumetric studies to achieve a GRBWR >0.8, along with special attention to anatomic tailoring and portal venous flow optimization are necessary for successful transplantation. Technical innovations have improved sequentially the utility and availability of LDLT.
[Autologous peripheral blood CD34+ stem cells transplanted into 100 patients with advanced cirrhosis]. [2022]To investigate whether transplantation of autologous peripheral blood CD34+ stem cells is a viable approach for treating patients with advanced cirrhosis,which is currently hindered by a shortage in liver donors.
A high model for end-stage liver disease score should not be considered a contraindication to living donor liver transplantation. [2017]To analyze the outcomes of patients with high Model for End-Stage Liver Disease (MELD) scores who underwent adult-to-adult live donor liver transplantation (A-A LDLT).
Autologous CD34+ and CD133+ stem cells transplantation in patients with end stage liver disease. [2022]To assess the utility of an autologous CD34(+) and CD133(+) stem cells infusion as a possible therapeutic modality in patients with end-stage liver diseases.
Comparable Short- and Long-term Outcomes in Living Donor and Deceased Donor Liver Transplantations for Patients With Model for End-stage Liver Disease Scores ≥35 in a Hepatitis-B Endemic Area. [2019]To evaluate if living donor liver transplantation (LDLT) should be offered to patients with Model for End-stage Liver Disease (MELD) scores ≥35.
[Observation on hybrid bioartificial liver support systems in treating chronic severe hepatitis: a study of 60 cases]. [2006]To study the clinical efficacy of three kinds of hybrid bioartificial liver support systems (HBLSS) in treating chronic severe hepatitis.
Bioartificial liver assist devices in support of patients with liver failure. [2006]Bioartificial liver assist devices (BALs) offer an opportunity for critical care physicians and transplant surgeons to stabilize patients prior to orthotopic liver transplantation. Such devices may also act as a bridge to transplant, providing liver support to patients awaiting transplant, or as support for patients post living-related donor transplant. Four BAL devices that rely on hepatocytes cultured in hollow fiber membrane cartridges (Circe Biomedical HepatAssist(r), Vitagen ELADTM, Gerlach BELS, and Excorp Medical BLSS) are currently in various stages of clinical evaluation. Comparison of the four devices shows that several unique approaches based upon the same overall system architecture are possible. Preliminary results of the Excorp Medical BLSS Phase I safety evaluation at the University of Pittsburgh, after treating four patients (F, 41, acetominophen-induced, two support periods; M, 50, Wilson's disease, one support period; F, 53, acute alcoholic hepatitis, two support periods; F, 24, chemotherapy-induced, one support period, are presented. All patients presented with hypoglycemia and transient hypotension at the start of extracorporeal perfusion. Hypoglycemia was treated by IV dextrose and the transient hypotension responded positively to IV fluid bolus. Heparin anticoagulation was used only in the second patient. No serious or adverse events were noted in the four patients. Moderate Biochemical response to support was noted in all patients. More complete characterization of the safety of the BLSS requires completion of the Phase I safety evaluation.
Human liver stem cells attenuate concanavalin A-induced acute liver injury by modulating myeloid-derived suppressor cells and CD4+ T cells in mice. [2020]Acute liver failure (ALF) is a serious threat to the life of people all over the world. Finding an effective way to manage ALF is important. Human liver stem cells (HLSCs) are early undifferentiated cells that have been implicated in the regeneration and functional reconstruction of the liver. In this study, we aimed to evaluate the protective effects of the HLSC line HYX1 against concanavalin A (ConA)-induced acute liver injury.
[Clinical study on hybrid bioartificial liver supporting system for acute on chronic liver failure patients]. [2018]To construct an hybrid bioartificial liver supporting system, and observe its effectiveness and safety on patients with acute on chronic liver failure.
Safety assessment of intraportal liver cell application in New Zealand white rabbits under GLP conditions. [2013]Liver cell transplantation (LCT) is considered a new therapeutic strategy for the treatment of acute liver failure and inborn metabolic defects of the liver. Although minimally invasive, known safety risks of the method include portal vein thrombosis and pulmonary embolism. Since no systematic data on these potential side effects exist, we investigated the toxicological profile of repeated intraportal infusion of allogeneic liver cells in 30 rabbits under GLP conditions. Rabbit liver cells were administered once daily for 6 consecutive days at 3 different dose levels, followed by a 2-week recovery period. No test item-related mortality was observed. During cell infusion, clinical findings such as signs of apathy and hyperventilation, moderate elevations of liver enzymes ALT and AST and a slight decrease in AP were observed, all fully reversible. Cell therapy-related macroscopic and histological findings, especially in liver and lungs, were observed in animals of all dose groups. In conclusion, the liver and lungs were identified as potential toxicological target organs of intraportal allogeneic liver cell infusion. A NOAEL (no observed adverse effect level) was not defined because of findings observed also in the low-dose group. No unexpected reactions became apparent in this GLP study. Overall, LCT at total doses up to 12 % (2 % daily over 6 days) of the total liver cell count were tolerated in rabbits. Observed adverse effects are not considered critical for treatment in the intended patient populations provided that a thorough monitoring of safety relevant parameters is in place during the application procedure.
A high MELD score, combined with the presence of hepatitis C, is associated with a poor prognosis in living donor liver transplantation. [2021]The feasibility of performing living donor liver transplantation (LDLT) for patients with high end-stage liver disease (MELD) scores needs to be assessed.
Cell therapy in chronic liver disease. [2018]To date, the only curative treatment for end-stage liver disease is liver transplantation, which is limited by the shortage of available organs. Cell therapy, in the form of cell transplantation or cell-based extracorporeal support devices, may in the future offer an alternative to transplantation, or at least provide liver function support as a bridging therapy until surgery may be performed. The purpose of this review is to highlight the most recent advances made in the field of cell therapy and regenerative medicine for the treatment of chronic liver disease.
New Tools in Experimental Cellular Therapy for the Treatment of Liver Diseases. [2020]The current standard of care for end stage liver disease is orthotopic liver transplantation (OLT). Through improvement in surgical techniques, immunosuppression, and general medical care, liver transplantation has become an effective treatment over the course of the last half-century. Unfortunately, due to the limited availability of donor organs, there is a finite limit to the number of patients who will benefit from this therapy. This review will discuss current research in experimental cellular therapies for acute, chronic, and metabolic liver failure that may be appropriate when liver transplantation is not an immediate option.