First evaluation of the efficacy and safety of AEB071 in its target indication: prevention of rejection in solid organ tranplantation. The study population will consist of a representative group of male and female de novo renal transplant patients.
Conditions
Interventions
Product Name: AEB071
Product Code: AEB071A
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: not established
CAS Number: n/a
Current Sponsor code: AEB071 drug substance, mono acetate
Other descr
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
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) 100 IU/L) can participate without contraception. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: •Multi-organ transplant recipients •Recipients of an organ from a non-heart beating donor •Patients who are recipients of A-B-O incompatible transplants, all crossmatch positive transplants •Use of other investigational drugs or a non-protocol immunosuppressant, including induction agents other than Simulect®, at the time of enrollment, or within 30 days or 5 half-lives prior to enrollment, whichever is longer •History of hypersensitivity to any of the study drugs or to drugs with similar chemical structures •Patients who are anti-HIV-positive, or HBsAg-positive. Anti-HCV-positive patients are excluded, except patients with spontaneously negative PCR-result (patients who cleared the virus under treatment remain excluded). Laboratory results obtained more than 6 months prior to study entry should be repeated within the first week after randomization. Patients who test positve for any of the viral indicators after randomization will be discontinued from study treatment •Recipients of a kidney from a donor who tests positive for HIV, HBsAg or anti-HCV •Sensitized patients (most recent anti-HLA Class I Panel Reactive Antibodies >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 QTc >500msec, long QT-syndrome (own or with a family history) or with a family history of sudden unexplained death •Patients with left branch bundle block (LBBB) or who experienced, during the previous 6 months, hospitalisation for heart failure of cardiac etiology, or significant and persistent left ventricular dysfunction (LVEF 3 times upper limit of normal [ULN]). •Patients with a severe digestive system disorder (including functional disorders). •Patients with any condition which is expected to prohibit full-dose myfortic therapy, or tacrolimus withdrawal in the maintenance period. •Patients with any surgical or medical condition, which in the opinion of the investigator, precludes enrollment in this trial •Patients who are unlikely to comply with the study requirements or unable to cooperate or communicate with the investigator •Pregnant or nursing (lactating) women, and women who might become pregnant during the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to demonstrate that in de novo renal transplant patients, at least one of the AEB071 treatment regimens is not inferior to the control treatment (myfortic® + tacrolimus) within 6 months of the initial dose of study drug with respect to primary efficacy failure, defined as a composite efficacy endpoint of treated BPAR, graft loss, death or loss to follow-up.;Secondary Objective: •Evaluate the AEB071 regimens in comparison to the control arm with respect to primary efficacy failure at Month 3 post-transplant •Compare renal function in the AEB071 treatment arms with the control arm at Month 6 post-transplant (MDRD formula for GFR). •Compare the AEB071 treatment arms to the control arm with respect to various efficacy endpoints at Month 3, 6 and 12, using treated BPAR, treated AR, death, graft loss, loss to follow-up and combinations thereof. •Compare the changes in renal function (GFR) in the AEB071 treatment arms from Month 3 (before conversion to myfortic®) to Month 6 with the change in the control arm. •Compare renal function in the AEB071 treatment arms to the control arm at various time points using the Cockroft-Gault formula (creatinine clearance) and the Filler formula (GFR). •Compare the safety and tolerability, including GI-tolerability, in the AEB071 treatment arms and the control arm ;Primary end point(s): The primary objective of the study is to demonstrate that in de novo renal transplant patients, non inferior rates of efficacy failure, defined as the first occurrence of treated biopsy-proven acute rejection of grade =1A, graft loss, death, or loss to follow-up, are achieved with at least one AEB071 regimen compared to the control regimen within 6 months of the initial dose of study medication (Simulect® and steroids will be administered in all treatment arms). Based on the available data [Stefoni et al (2005)] [Vincenti et al (2005)], the rate of efficacy failure was assumed to be 10% in each t | — |
Countries
Germany, Italy, Spain, United Kingdom
Outcome results
None listed