Liver Cell Transplant for End-Stage Liver Disease

Recruiting at 1 trial location

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for individuals with end-stage liver disease, a condition where the liver is severely damaged and cannot function properly. The study tests the safety and effectiveness of transplanting liver cells into lymph nodes using a special technique. This treatment, known as LYG-LIV0001, aims to improve liver function. Suitable candidates may have liver disease from causes such as alcohol, hepatitis, or other conditions and experience liver-related health issues in daily life. Participants must manage their liver condition with current treatments and be prepared to avoid alcohol during the trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that LYG-LIV0001 is likely to be safe for humans?

Research shows that LYG-LIV0001, a treatment using liver cell transplants, is being tested for safety and tolerability in people with severe liver disease. Earlier patients have generally tolerated this treatment well. The study examines the safety of placing these cells into lymph nodes using a technique called endoscopic ultrasound.

Since this study is in an early stage, some evidence suggests it is safe, but more research is needed for confirmation. So far, no serious side effects have been reported, indicating the treatment might be safe for many people. However, as with any new treatment, more information is needed about possible side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for end-stage liver disease, which often involves liver transplantation or management with medications, LYG-LIV0001 is unique because it involves liver cell transplantation. This experimental therapy is exciting because it introduces healthy liver cells directly into the patient, potentially restoring liver function without the need for a full organ transplant. Researchers are particularly interested in this treatment because it could offer a less invasive alternative and might be available to more patients, especially given the shortage of donor organs.

What evidence suggests that LYG-LIV0001 might be an effective treatment for end-stage liver disease?

Research has shown that LYG-LIV0001 might help people with severe liver disease. In earlier studies, patients who received this liver cell transplant experienced improved liver function and healthier liver tissue. Many also had reduced fluid buildup in their abdomen (ascites) and reported an improved quality of life. Additionally, these patients lived 10% longer on average than those who did not receive the treatment. These results suggest that LYG-LIV0001 could be a promising option for people with serious liver disease. ^{2 4 6 7 8}

Who Is on the Research Team?

Paulo Fontes, MD

Principal Investigator

LyGenesis, Inc.

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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 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]

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]

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]

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 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]

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]

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]

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]

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]

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]

Citations

1. withpower.com withpower.com/trial/phase-3-liver-diseases-10-2021-46fa4

Liver Cell Transplant for End-Stage Liver Disease Patients showed significant improvements in liver function and histology, with many experiencing a reduction in ascites and enhanced quality of life, indicating ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10210428/

Cell therapy in end-stage liver disease: replace and remodel The results revealed that HT patients had a 10% higher overall survival rate than controls [55]. Birir et al. described five patients with ALF ...

3. resolution-tx.com resolution-tx.com/resolution-therapeutics-founders-present-clinical-proof-of-concept-for-macrophage-cell-therapy-in-end-stage-liver-disease-at-aasld/

Clinical proof-of-concept achieved for macrophage cell ... The primary analysis will focus on safety, major clinical events including death, and Model for End-Stage Liver Disease (MELD) score which is used to assess ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2980678/

Autologous CD34+ and CD133+ stem cells transplantation ... CONCLUSION: Our data showed that a CD34+ and CD133+ stem cells infusion can be used as supportive treatment for end-stage liver disease with satisfactory ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2213671123002345

Cell transplantation-based regenerative medicine in liver ... Overall, the major outcomes for HT in ALF showed that full recovery of liver function has been occasionally obtained after treatment, but ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04496479

NCT04496479 | Allogenic Hepatocyte Transplantation Into ... This safety, tolerability, and efficacy study includes an open-label dose-escalation phase for up to 12 subjects with end-stage liver disease (ESLD). Official ...

7. lygenesis.com lygenesis.com/media/press-releases/lygenesis-announces-first-patient-dosed-in-its-phase-2a-clinical-trial-of-a-first-in-class-regenerative-cell-therapy-for-patients-with-end-stage-liver-disease/

LyGenesis Announces First Patient Dosed in its Phase 2a ... LyGenesis Announces First Patient Dosed in its Phase 2a Clinical Trial of a First-in-Class Regenerative Cell Therapy for Patients with End-Stage ...

8. synapse-patsnap-com.libproxy1.nus.edu.sg synapse-patsnap-com.libproxy1.nus.edu.sg/drug/a86d763bbb034d7d86f8d179f40b6ba9

LYG-LIV0001 - Drug Targets, Indications, Patents A Phase 2a, Open Label, Dose Escalation Study for Safety, Tolerability, and Efficacy of Hepatocyte Transplantation Into Periduodenal Lymph ...