Efficacy, Safety and Tolerability of Everolimus in Combination With Reduced Exposure Cyclosporine or Tacrolimus in Paediatric Liver Transplant Recipients.

Novartis

Status and phase: Completed; Phase 3

Conditions: Renal Function; Liver Transplant

Treatments: Drug: Introduction of everolimus with reduced cyclosporine or tacrolimus dose, the earliest 1 month and the latest 6 months after liver transplantation.

Study type: Interventional

Funder types: Industry

Identifiers

NCT01598987

CRAD001H2305

2011-003069-14

Details and patient eligibility

About

This study was designed to assess the evolution of renal function and to collect efficacy, safety, and tolerability data of everolimus in co-exposure with reduced CNI in paediatric liver transplant recipients.

Full description

Study is completed (was active and ongoing but no longer recruiting since December 2014). The study Data Monitoring Committee meeting communicated to Novartis the following safety findings in the study population: high rate of premature discontinuation of study medication, high rate of post-transplant lymphoproliferative disease and high rate of related serious infections leading to hospitalization. In light of the safety findings, Novartis followed the DMC recommendation to discontinue the study medication in this age group and to stop enrolling new patients in this study (regardless of age).

Enrollment: 56 patients

Sex: All

Ages: 1 month to 17 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

Signed informed consent from both parents or legal guardian(s) prior to patient participation in the study.

Paediatric liver transplant recipients aged greater than or equal to 1 month and younger than 18 years of age.

Paediatric recipients at the earliest 1 month and latest 6 month after liver transplantation.

Key Exclusion Criteria:

Patients with hepato-biliary malignancies and/or patients transplanted due to fulminant hepatitis /acute liver failure.

Presence of thrombosis of any major hepatic arteries, major/reconstructed hepatic veins, portal vein or inferior vena cava at any time prior to the start of study drug.

Patients with serum creatinine value >2 times age-related ULN at Baseline or who received renal replacement therapy within one week prior to the start of study drug and patients with a confirmed spot urine protein/creatinine ratio indicating a urinary protein excretion >500 mg/m2/24 hrs, at Baseline.

Patients with clinically significant systemic infection and/or in a critical care setting requiring life support measures such as mechanical ventilation, dialysis, or vasopressor agents.

Patients with a known hypersensitivity to the drugs used on study or their class, or to any of the excipients.

Pregnant or nursing (lactating) female patients, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive βHCG laboratory test (>9 mIU/mL) at Baseline.

Female patients of child-bearing potential, defined as all women physiologically capable of becoming pregnant, UNLESS they agree for abstinence from sexual activity.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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56 participants in 1 patient group

Everolimus based regimen

Experimental group

Description:

Conversion at Baseline from an immunosuppressive regimen which contains either cyclosporine (CsA) or tacrolimus (TAC) with or without mycophenolic acid (MPA), with or without corticosteroids in a regimen which contains everolimus combined reduced dose of either cyclosporine (CsA) or tacrolimus (TAC). The dosing schedule was twice daily, 12 hours apart.

Treatment:

Drug: Introduction of everolimus with reduced cyclosporine or tacrolimus dose, the earliest 1 month and the latest 6 months after liver transplantation.