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Introduction of everolimus with reduced cyclosporine or tacrolimus dose, the earliest 1 month and the latest 6 months after liver transplantation · 1 trial · 2 indications
Evolution of renal function assessed by estimated Glomerular Filtration Rate (eGFR) calculated by the Chronic Kidney Disease in Children (CKiD) Schwartz formula (Schwartz 2009), expressed in mean change in eGFR of CKiD between start of study (baseline assessment) and Month 12.
| Arm | Type | Description |
|---|---|---|
| Everolimus based regimen | EXPERIMENTAL | 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. |
| Name | Type | Description |
|---|---|---|
| Introduction of everolimus with reduced cyclosporine or tacrolimus dose, the earliest 1 month and the latest 6 months after liver transplantation. | DRUG | Immunosuppression after liver transplantation. Pediatric transplant recipients received a starting dose of 0.8 mg/m\^2/dose in combination wit Cyclosporine A or 2.0 mg/m\^2/dose in combination with tacrolimus, twice-daily. Thereafter, doses were adjusted to achieve everolimus C-0h blood trough level between 3 to 8 ng/ml. |
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 late...
Everolimus is used in pediatric liver transplant recipients to support renal function when introduced with reduced doses of cyclosporine or tacrolimus. The regimen is started no earlier than one month and no later than six months after transplantation, aiming to preserve kidney function while maintaining immunosuppression.
Novartis AG, which trades under the ticker NVS, is the developer of everolimus. The company sponsored the Phase 3 study evaluating the drug in combination with reduced exposure cyclosporine or tacrolimus in pediatric liver transplant recipients.
Everolimus reached Phase 3 development for this use. The single Phase 3 trial, NCT01598987, has been completed. The study enrolled 56 pediatric liver transplant recipients and was conducted across the United States, Australia, Belgium, Canada, Denmark, France, Germany, Hungary, Italy, Spain, Sweden, and the United Kingdom.
The trial is NCT01598987, titled Efficacy, Safety and Tolerability of Everolimus in Combination With Reduced Exposure Cyclosporine or Tacrolimus in Paediatric Liver Transplant Recipients. It was a completed Phase 3 study with 56 enrolled participants, including patients as young as one month old, and it evaluated renal function and liver transplant outcomes.
Everolimus is the immunosuppressant being studied, while cyclosporine and tacrolimus are separate calcineurin inhibitors given at reduced doses alongside it. The regimen combines everolimus with lower exposure to one of those two agents, and it is introduced between one and six months after liver transplantation.
NCT01598987 was an uncontrolled Phase 3 study, not randomized and not double blinded, enrolling 56 pediatric liver transplant recipients. Participants received everolimus with reduced exposure cyclosporine or tacrolimus, and the trial assessed efficacy, safety, and tolerability in that population.