A 12-month open-label, randomized, multicenter, sequential cohort, dose finding study to evaluate the efficacy, safety and tolerability of oral AEB071 versus tacrolimus® in combination with myfortic®, Simulect® and corticosteroids in de novo adult renal transplant recipient

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2006-004128-35-BE
• Date of registration: 16/05/2007
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: A 12-month open-label, randomized, multicenter, sequential cohort, dose finding study to evaluate the efficacy, safety and tolerability of oral AEB071 versus tacrolimus® in combination with myfortic®, Simulect® and corticosteroids in de novo adult renal transplant recipient
• Scientific title: A 12-month open-label, randomized, multicenter, sequential cohort, dose finding study to evaluate the efficacy, safety and tolerability of oral AEB071 versus tacrolimus® in combination with myfortic®, Simulect® and corticosteroids in de novo adult renal transplant recipient
• Date of first enrolment: 09/07/2007
• Target sample size: 279
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-004128-35
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: yes Other trial design description: sequential cohort If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: yes Other specify the comparator: myfortic + tacrolimus

Countries of recruitment

Belgium, Germany, Spain, Sweden, United Kingdom

Key inclusion & exclusion 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) < 24 hours
• Recipients of a kidney from a donor 10-65 years old
• • Patients with functional graft within 24 hours after graft reperfusion; functional graft being defined as one of the following:
• For patients without residual urinary output from the native kidneys, urine output of more than 250mL/12 hours
Or
• For patients with residual urinary output from the native kidneys either of the following conditions must be met:
• a decrease from pretransplant in serum creatinine by at least 20%
Or
• must be a recipient of an uncomplicated live-donor transplant that in the opinion of the investigator is not likely to result in Delayed Graft Function (e.g. Prolonged warm ischemic time, or excessively long period of increased intraperitoneal pressure during laparoscopic nephrectomy)
• Patients expected to be able to take oral medication within 24 hours after graft reperfusion
• Patients willing and capable of giving written informed consent for study participation and able to participate in the study for 12 months

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:
• 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 with an absolute neutrophil count of < 1,500/mm3, or absolute leukocytes count < 2,500/mm3 or platelet count < 100,000/mm3 at screening.
• Patients who are treated with drugs that are strong inducers or inhibitors of cytochrome P450 3A4 at screening and can not discontinue this treatment
• Patients with long QT-syndrome, or QTcF at baseline exceeding 500 msec, or who are treated with drugs inducing QT prolongation at screening, and can not discontinue this treatment



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

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.

Intervention(s)

Product Name: AEB071
Product Code: AEB071A
Pharmaceutical Form: Capsule, hard
Current Sponsor code: AEB071A
Concentration unit: mg milligram(s)
Concentration number: 100-

Trade Name: Prograft
Product Name: Tacrolimus
Pharmaceutical Form: Capsule*
Other descriptive name: Prograft
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0,5-

Trade Name: Prograft
Product Name: Tacrolimus
Pharmaceutical Form: Capsule*
Other descriptive name: Prograft
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1,0-

Primary Outcome(s)

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).

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.

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 Month 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.

Other secondary objectives are to:
.........

Secondary ID(s)

2006-004128-35-SE

CAEB071A2207