End-stage Liver Disease
Conditions
Brief summary
'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
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.
Interventions
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.
Sponsors
King's College London
Guy's and St Thomas' NHS Foundation Trust
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Graft Loss | 24 months | Rate of cellular rejection |
| Rate of dose limiting toxicities (DLTs) | 1 month after IMP administration | rate of adverse events qualifying as dose limiting toxicities |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Prevention of acute and chronic rejection | 24 months | incidence of rejection episodes |
| Acute and Chronic Toxicity | 24 months | incidence of immunological reactions, biochemical disturbances |
| Rate of successful immunosuppressive drug withdrawal | 24 months | total dose of immunosuppressive medication administered |
| Liver histology | 12 months | liver biopsy analysis |
| Immunosuppressive doses | 24 months | total dose of immunosuppressive medication administered |
Other
| Measure | Time frame | Description |
|---|---|---|
| Immunological biomarkers | 12 months | immune monitoring analysis of blood samples investigating the effect of TR002 on blood cell immunophenotype |
Countries
United Kingdom
Outcome results
None listed