Safety and Efficacy Study of Regulatory T Cell Therapy in Liver Transplant Patients

Study Overview
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Brief Summary
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'ThRIL' aims to explore the feasibility, safety and efficacy of TR002, a regulatory cell therapy, as adjunct immunosuppressive treatment in the context of liver transplantation

Detailed Description
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Stage I: To evaluate the safety of administering TR002 to liver transplant recipients. Stage II: To evaluate the efficacy of TR002 administration in allowing for the discontinuation of immunosuppressive therapy in liver transplant recipients.

Official Title
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Pilot Study Evaluating the Safety and Efficacy Profile of Regulatory T Cell Therapy in Liver Transplant Recipients

Conditions
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End-stage Liver Disease

Intervention / Treatment
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* Drug: Autologous regulatory T cell product


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to give informed consent adult patients with end-stage liver disease listed for primary liver transplant; calculated MELD score ≤ 25 at time of transplantation Exclusion Criteria: HIV or RNA-positive Hepatitis C Virus infection; autoimmune liver disease previous organ transplant Ebstein Virus and/or Cytomegalovirus sero-negativity chronic use of systemic immunosuppressants hepatocellular carcinoma outside Milano criteria leukocytes <1.5x10^9/L and/or platelets <50x10^9/L.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Autologous Regulatory T cell therapy<br>Autologous regulatory T cell therapy infused intravenously (2 dose groups: low dose and high dose) | Drug: Autologous regulatory T cell product<br>* Autologous regulatory T cell therapy infused intravenously (2 dose groups: low dose and high dose). The patients also receive rabbit Antithymocyte Globulin (rATG), tacrolimus, and sirolimus.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of dose limiting toxicities (DLTs) | rate of adverse events qualifying as dose limiting toxicities | 1 month after IMP administration | 
| Graft Loss | Rate of cellular rejection | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunosuppressive doses | total dose of immunosuppressive medication administered | 24 months | 
| Prevention of acute and chronic rejection | incidence of rejection episodes | 24 months | 
| Acute and Chronic Toxicity | incidence of immunological reactions, biochemical disturbances | 24 months | 
| Liver histology | liver biopsy analysis | 12 months | 
| Rate of successful immunosuppressive drug withdrawal | total dose of immunosuppressive medication administered | 24 months |