12-month open label, randomized, multicenter study evaluating efficacy, safety and tolerability of oral AEB071 plus tacrolimus (converted to myfortic after 3 months), vs. myfortic plus tacrolimus in de novo renal transplant recipients

• Conditions: 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.

• Registration Number: EUCTR2005-003494-25-GB
• Lead Sponsor: ovartis Pharma Services AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2006-05-24
• Last Update Posted: 18 April 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 195

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) < 30 hours
•Recipients of a kidney from a donor 10-65 years old
•Recipients of a functional graft i.e producing a urinary output of = 250 mL/12h (applicable only in patients with no residual urinary output from native kidneys) or a decrease in serum creatinine. Functionality must be achieved no later than 36h aftr transplantation.
•Patients able to swallow the first dose of oral study drug within 36 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

Pregnancy has to be excluded in any female study participant below age 60 by a negative hCG laboratory test in serum (=10 IU/L) at study start, with results available within 2 days past randomisation.
All women physiologically capable of becoming pregnant and receiving tacrolimus,
should receive reproductive counseling as per local standards for patients on tacrolimus. Counseling needs to address the potential drug-drug interaction between tacrolimus and hormonal contraceptives which may decrease the effectiveness of hormonal contraception. For women on an AEB071 study arm, non-hormonal contraception is mandatory until finishing the conversion from tacrolimus to myfortic. Reliable nonhormonal contraception consists of any form of intra-uterine devices (without hormones) or of other double-barrier methods. Barrier method includes essure, condom, diaphragm, shield, cap, sponge and spermicides. Acceptable methods of contraception may also include methods with a Pearl index of <1 at the discretion of the investigator. In women receiving AEB071 but not tacrolimus, hormonal contraception can be used. Counseling should include the potential drug-drug interaction between AEB071 and hormonal contraceptives which may moderately increase the exposure to hormonalcontraceptives and thereby decrease their tolerability.

Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
Postmenopausal women (defined as 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels >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

•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 <40%)
•Patients with a history, in the preceding 3 months, of significant and persistent
arrhythmias such as ventricular fibrillation or tachycardia, or atrial fibrillation or flutter.
•Patients requiring antiarrhythmic drugs with QT-prolonging properties (such as amiodarone, stalol, dofetilide, quinidine, procainamide, disopyramide)
•Patients with Symptomatic coronary artery disease.
•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
•Patients with an absolute neutrophil count of < 1,500/mm3, or absolute leukocytes count < 2,500/mm3.
•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]).
•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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified