Discontinuation of immunosuppression in liver transplantation MedDRA version: 20.0 Level: PT Classification code 10024714 Term: Liver transplant System Organ Class: 10042613 - Surgical and medical procedures
Conditions
Interventions
Trade Name: Proleukin
Product Name: Proleukin
Pharmaceutical Form: Powder for solution for injection/infusion
INN or Proposed INN: Interleukin-2
CAS Number: 110942-02-4
Other descriptive name: Aldesle
Sponsors
King's College London
King's College Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Adult liver transplant recipients 2-6 years post-transplant and age =50 years; 2. Recipient of single organ transplant only; 3. Liver function tests: direct bilirubin and ALT =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Serum positivity for HCV-RNA at screening; 2. Serum positivity for HIV-1 infection, HBV surface antigen or HBV-DNA at screening; 3. Active liver or systemic immune-mediated disease in which IS discontinuation is inadvisable (autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cirrhosis); 4. Acute or chronic rejection within the 52 weeks prior to screening; 5. GFR 1). 12. Participation in another IMP study within 3 months from consent; 13. Any known allergy or intolerance to the IMP components; 14. Any contraindication to Proleukin administration as per SmPC; 15. Pregnancy or lactation; 16. Lack of effective methods of contraception for women and men of childbearing potential (as per section 7.6 of the Protocol); 17. Hypersensitivity to Proleukin or to any of the excipients.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to determine the capacity of a short course of low-dose IL-2 to facilitate the complete discontinuation of immunosuppressive drugs in liver recipients 2-6 years after transplantation.;Secondary Objective: 1) To determine the capacity of low-dose IL-2 to expand endogenous regulatory T cells (Tregs) in patients under calcineurin inhibitor immunosuppression; 2) to assess the safety of low-dose IL-2 administration in liver transplantation; 3) to investigate the sequential changes in Treg function, immunophenotype, and molecular profile following low-dose IL-2 treatment and calcineurin inhibitor discontinuation; 4) to determine if the baseline Treg function, immunophenotype, and molecular profile predict the response to low-dose IL-2; 5) to assess the changes in the blood and liver tissue inflammatory microenvironment; 6) to evaluate the development of anti-HLA antibodies.;Primary end point(s): The primary endpoint is defined as the proportion of subjects who achieve successful immunosuppression withdrawal as defined by the absence of rejection and a rejection free biopsy at 1 year following discontinuation of immunosuppression.;Timepoint(s) of evaluation of this end point: 1 year following discontinuation of immunosuppression | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Clinical: • Rejection (incidence, severity, timing, steroid resistant rejection, chronic rejection); • Patient survival; • Graft loss; Mechanistic: • IL-2-related adverse events; • Effect of IL-2 on blood and liver Treg numbers; • Sequential immunophenotypic changes in blood and liver tissue; • Sequential changes in Treg function, immunophenotype, and molecular profile following low-dose IL-2 treatment and calcineurin inhibitor discontinuation; • Sequential changes in the inflammatory microenvironment in blood and liver tissue; • Development of serum anti-HLA antibodies.;Timepoint(s) of evaluation of this end point: Clinical: 1 year following the discontinuation of immunosuppression Mechanistic: at the time points of sample collection specified in Table 3 of the LITE protocol. | — |
Countries
United Kingdom
Contacts
Public ContactProf Alberto Sanchez-Fueyo
King's College London
Outcome results
None listed