Liver Cell Transplant for End-Stage Liver Disease

Recruiting at 2 trial locations

Overseen By Paulo Fontes, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: LyGenesis, Inc.

Must be taking: HBV therapy

Must not be taking: Propranolol

Disqualifiers: Cancer, Severe infections, Hypertension, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

12 Participants Needed

Trial Summary

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?

Research on similar treatments, like the use of CD34+ stem cells, shows promise in treating end-stage liver disease by potentially improving liver function. This suggests that LYG-LIV0001, if it involves similar components, might also be effective. ^{1 2 3 4 5}

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. ^{6 7 8 9 10}

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. ^{5 6 11 12 13}

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.

Research Team

Paulo Fontes, MD

Principal Investigator

LyGenesis, Inc.

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 have heart or lung conditions that prevent me from having standard liver transplant.

I have hepatitis B, am on stable treatment for 6 months, and my HBV DNA is below 500 c/mL.

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.

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

Trial Overview The 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

Group I: LYG-LIV0001 Experimental Treatment 1 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

Who Is Running the Clinical Trial?

LyGenesis, Inc.

Lead Sponsor

Trials

1

Recruited

10+

Findings from Research

Living donor liver transplantation (LDLT) is a safe and effective option for patients with end-stage liver disease, emphasizing the importance of donor safety and recipient suitability.

Successful LDLT requires careful assessment of the donor's health and the recipient's clinical status, including MELD scores and graft volume, along with technical innovations to optimize outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Living Donor Liver Transplantation: Technical Innovations. Tulla, KA., Jeon, H.[2018]

Transplantation of autologous peripheral blood CD34+ stem cells in 100 patients with advanced cirrhosis resulted in a 100% one-year survival rate, demonstrating its safety and potential as a treatment option.

Patients showed significant improvements in liver function and histology, with many experiencing a reduction in ascites and enhanced quality of life, indicating the efficacy of this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Autologous peripheral blood CD34+ stem cells transplanted into 100 patients with advanced cirrhosis]. Yao, Y., Luo, L., Xue, H., et al.[2022]

In a study of 143 adult patients who underwent adult-to-adult live donor liver transplantation (A-A LDLT), those with high Model for End-Stage Liver Disease (MELD) scores (above 30) had similar short-term and long-term survival rates compared to those with low MELD scores (30 or below).

The findings suggest that high MELD scores should not be considered a contraindication for A-A LDLT, as there were no significant differences in hospital stay or survival rates between the two groups over a median follow-up of 21.5 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A high model for end-stage liver disease score should not be considered a contraindication to living donor liver transplantation. Poon, KS., Chen, TH., Jeng, LB., et al.[2017]

In a study of 140 patients with end-stage liver diseases, those receiving autologous CD34(+) and CD133(+) stem cell infusions showed significant improvements, with 54.5% experiencing near normalization of liver enzymes and enhanced liver function.

The treatment was well-tolerated with no adverse effects reported, suggesting that stem cell infusion could be a safe and supportive option for patients with severe liver conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous CD34+ and CD133+ stem cells transplantation in patients with end stage liver disease. Salama, H., Zekri, AR., Bahnassy, AA., et al.[2022]

Living donor liver transplantation (LDLT) can be safely offered to patients with high Model for End-stage Liver Disease (MELD) scores (≥35), showing comparable outcomes to deceased donor liver transplantation (DDLT) in terms of survival rates and complications.

In a study of 672 liver transplant recipients, LDLT demonstrated similar one, three, and five-year survival rates compared to DDLT, suggesting that MELD scores ≥35 should not automatically exclude patients from receiving LDLT, especially in experienced centers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Chok, KS., Fung, JY., Chan, AC., et al.[2019]

The study involved 120 patients with chronic severe hepatitis and compared three hybrid bioartificial liver support systems (HBLSS) to standard treatments, showing that HBLSS significantly improved clinical symptoms and liver function more effectively than control treatments.

The H1 (BAL+MARS) and H2 (BAL+SPE+CHDF) groups demonstrated the highest improvement rates (65% and 60% respectively) and were more effective in reducing harmful substances like creatinine and ammonia, with no serious side effects reported during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Observation on hybrid bioartificial liver support systems in treating chronic severe hepatitis: a study of 60 cases]. Luo, HT., Liu, QM., Tan, JJ., et al.[2006]

The Excorp Medical BLSS device, used in a Phase I safety evaluation with four patients suffering from various liver conditions, showed no serious adverse events, indicating a promising safety profile for this bioartificial liver assist device.

All patients experienced moderate biochemical improvements during treatment, suggesting that the BLSS device may effectively support liver function in critical care settings, although further evaluation is needed to fully assess its safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioartificial liver assist devices in support of patients with liver failure. Patzer II, JF., Lopez, RC., Zhu, Y., et al.[2006]

Human liver stem cells (HLSCs), specifically the HYX1 line, have shown protective effects against acute liver injury induced by concanavalin A (ConA) in mice, significantly reducing liver damage markers like ALT and AST.

The mechanism of action involves HYX1 cells promoting the migration of myeloid-derived suppressor cells (MDSCs) and altering cytokine secretion, leading to reduced inflammation and improved liver function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human liver stem cells attenuate concanavalin A-induced acute liver injury by modulating myeloid-derived suppressor cells and CD4+ T cells in mice. Bi, Y., Li, J., Yang, Y., et al.[2020]

The hybrid bioartificial liver supporting system (HBALSS) using HepG2 cells showed potential effectiveness in treating acute on chronic liver failure, with four out of six patients in the treatment group recovering compared to two out of six in the control group.

The HBALSS demonstrated a certain level of safety, as it was successfully established and used in patients, although some patients still experienced severe complications, highlighting the need for further research and monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical study on hybrid bioartificial liver supporting system for acute on chronic liver failure patients]. You, SL., Liu, HL., Rong, YH., et al.[2018]

In a study involving 30 rabbits, repeated intraportal infusion of allogeneic liver cells was found to be generally safe, with no test item-related mortality and reversible mild clinical signs, indicating potential for liver cell transplantation as a treatment for liver failure.

However, the liver and lungs were identified as potential target organs for toxicity, with some adverse effects observed even at low doses, suggesting that careful monitoring of safety parameters is essential during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety assessment of intraportal liver cell application in New Zealand white rabbits under GLP conditions. Kafert-Kasting, S., Schneider, A., Attaran, M., et al.[2013]

In a study of 357 patients who underwent living donor liver transplantation (LDLT), those with high MELD scores (≥ 25) had similar graft survival rates compared to those with low MELD scores (< 25), indicating that LDLT can be feasible for high MELD patients.

However, patients with high MELD scores and hepatitis C had significantly lower 5-year graft survival rates (33.7%) compared to those with low MELD scores, highlighting the need for careful consideration of these factors in prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A high MELD score, combined with the presence of hepatitis C, is associated with a poor prognosis in living donor liver transplantation. Ikegami, T., Shirabe, K., Yoshiya, S., et al.[2021]

Cell therapy, including hepatocyte transplantation and the use of mesenchymal stem cells, shows promise in treating chronic liver disease by potentially reducing liver fibrosis and supporting liver regeneration.

Bioartificial liver devices are being developed to preserve hepatocytes effectively, with one device demonstrating a survival benefit in a porcine model of liver failure, suggesting a potential bridging therapy until liver transplantation can occur.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cell therapy in chronic liver disease. Nicolas, CT., Wang, Y., Nyberg, SL.[2018]

Orthotopic liver transplantation (OLT) is the current standard treatment for end-stage liver disease, significantly improved by advancements in surgical techniques and immunosuppression over the last 50 years.

Due to a shortage of donor organs, research is focusing on experimental cellular therapies as alternative treatments for liver failure when transplantation is not immediately available.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Tools in Experimental Cellular Therapy for the Treatment of Liver Diseases. Ferrer, JR., Chokechanachaisakul, A., Wertheim, JA.[2020]

References

1. United States pubmed.ncbi.nlm.nih.gov

Living Donor Liver Transplantation: Technical Innovations. [2018]

2. China pubmed.ncbi.nlm.nih.gov

[Autologous peripheral blood CD34+ stem cells transplanted into 100 patients with advanced cirrhosis]. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

A high model for end-stage liver disease score should not be considered a contraindication to living donor liver transplantation. [2017]

4. United States pubmed.ncbi.nlm.nih.gov

Autologous CD34+ and CD133+ stem cells transplantation in patients with end stage liver disease. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

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]

6. China pubmed.ncbi.nlm.nih.gov

[Observation on hybrid bioartificial liver support systems in treating chronic severe hepatitis: a study of 60 cases]. [2006]

7. Singapore pubmed.ncbi.nlm.nih.gov

Bioartificial liver assist devices in support of patients with liver failure. [2006]

8. England pubmed.ncbi.nlm.nih.gov

Human liver stem cells attenuate concanavalin A-induced acute liver injury by modulating myeloid-derived suppressor cells and CD4+ T cells in mice. [2020]

9. China pubmed.ncbi.nlm.nih.gov

[Clinical study on hybrid bioartificial liver supporting system for acute on chronic liver failure patients]. [2018]

10. Germany pubmed.ncbi.nlm.nih.gov

Safety assessment of intraportal liver cell application in New Zealand white rabbits under GLP conditions. [2013]

11. Japan pubmed.ncbi.nlm.nih.gov

A high MELD score, combined with the presence of hepatitis C, is associated with a poor prognosis in living donor liver transplantation. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

Cell therapy in chronic liver disease. [2018]

13. Switzerland pubmed.ncbi.nlm.nih.gov

New Tools in Experimental Cellular Therapy for the Treatment of Liver Diseases. [2020]