Evaluation of the efficacy and safety of AEB071 in de novo CNI free regimen for prevention of rejection in solid organ transplantation. Combination of AEB071 with a well established, effective adjunct regimen to provide a safe entry into the transplant indication. Determination of the appropriate AEB071 dose(s) or target range for therapeutic drug monitoring on fixed or concentration controlled approach in de novo renal transplant patients.
Conditions
Interventions
Product Name: AEB071
Product Code: AEB071A
Pharmaceutical Form: Capsule, hard
Current Sponsor code: AEB071A
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Tr
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion criteria • Male and female patients of any race = 18 years old • Recipients of a primary kidney transplant from a deceased, living unrelated or non-HLA identical living related donor • Recipients of a kidney with a cold ischemic time (CIT) =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Multi-organ transplant recipients or if the patient previously received an organ transplant • Recipients of an organ from a non-heart beating donor • Patients who are recipients of A-B-O incompatible transplants, all CDC crossmatch positive transplants • Patients without functional graft 36 hours after graft reperfusion at randomization defined as the absence of urine output of more than 250 mL/12 hours for patients without residual urinary output from native kidneys or decreasing serum creatinine of > 20% from pre-transplant • Patients with an absolute neutrophil count of 20% by a CDC-based assay or > 50% by a Flow cytometry or ELISA-based assay) or patients identified otherwise to be at high immunological risk • History of malignancy of any organ system, treated or untreated, within the past 5 years regardless of evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin (excised = 2 years prior to randomization) • Patients with severe systemic infections, current or within the 2 weeks prior to randomization. • Patients with any history of significant coagulopathy or medical condition requiring long-term systemic anticoagulation after transplantation, which would interfere with obtaining biopsies. Aspirin treatment is allowed. • Evidence of severe liver disease, including abnormal liver profile (aspartate aminotransferase [AST], alanine aminotransferase [ALT] or total bilirubin > 3 times upper limit of normal [ULN]) at screening. • Patients with a severe digestive system disorder (including functional disorders) at screening. • Patients with any condition which is expected to prohibit full-dose myfortic® therapy or tacrolimus therapy • Patients with any surgical or medical con
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to compare, in stage 1, the efficacy of the first dose of AEB071 to tacrolimus, both in combination with myfortic®, Simulect®, and steroids, at 3 months after transplantation. Efficacy will be defined using a composite efficacy failure end point (treated biopsy-proven acute rejection (BPAR), graft loss, death or loss to follow-up). ;Secondary Objective: To compare the composite efficacy failure end point (treated BPAR, graft loss, death or loss to follow-up) of the additional AEB071 treatment regimens in stage 2 with the control regimen (myfortic® + tacrolimus) at Month 3 post transplant and for all AEB071 regimens at 12 months post transplant. To compare renal function in the AEB071 treatment arms with the control arm at Month 3 and Month 12 post-transplant with calculated GFR using the MDRD formula. ;Primary end point(s): The primary end point of the study is the occurrence of composite efficacy failure end point defined as treated biopsy-proven acute rejection (BPAR), graft loss, death or loss to follow-up within 3 months of the initial dose of study drug in de novo adult renal transplant patients. | — |
Countries
Belgium, Germany, Spain, Sweden, United Kingdom
Outcome results
None listed