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-DE
• Date of registration: 28/03/2007
• Prospective Registration: No
• 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: 08/03/2007
• Target sample size: 258
• 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: no

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 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 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 < 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 (see Appendix 3)
• Patients with long QT-syndrome, or QTc at baseline exceeding 500 msec, or who are treated with drugs inducing QT prolongation at screening (see appendix 3), and can not discontinue this treatment
• Patients a family history of long QT syndrome or of sudden unexplained death
• Patients with left branch bundle block (LBBB) or who experienced, during the previous 6 months, hospitalization for heart failure not due to volume overload, or post-MI left ventricular dysfunction (LVEF <30%)
Use of other investigational drugs or a non-protocol immunosuppressant, including induction agents other than Simulect, at randomization, or within 30 days or 5 half-lives prior to randomization, 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, exceot 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 positive 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 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

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 type: equal
Concentration number: 100-

Trade Name: Myfortic
Product Name: Myfortic 180 mg magensaftresistente Filmtabletten
Pharmaceutical Form: Gastro-resistant tablet
INN or Proposed INN: Mycophenolat-Natrium
CAS Number: 37415-62-6
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 180-

Trade Name: Myfortic
Product Name: Myfortic 360 mg magensaftresistente Filmtabletten
Pharmaceutical Form: Gastro-resistant tablet
INN or Proposed INN: Mycophenolat-Natrium
CAS Number: 37415-62-6
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 360-

Trade Name: Prograf 0.5 mg Kapseln
Product Name: Prograf 0.5 mg Kapseln
Pharmaceutical Form: Capsule*
INN or Proposed INN: Tacrolimus
CAS Number: 104987-11-3
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.5-

Trade Name: Prograf 1 mg Kapseln
Product Name: Prograf 1 mg Kapseln
Pharmaceutical Form: Capsule*
INN or Proposed INN: Tacrolismus
CAS Number: 104987-11-3
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-

Trade Name: Prograf 5 mg Kapseln
Product Name: Prograf 5 mg Kapseln
Pharmaceutical Form: Capsule*
INN or Proposed INN: Tacrolismus
CAS Number: 104987-11-3
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-

Trade Name: Simulect
Product Name: Simulect 20 mg
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: Basiliximab
CAS Number: 179045-86-4
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-

Pharmaceutical Form:
INN or Proposed INN: Corticosteroids
CAS Number: 50-22-6

Primary Outcome(s)

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.

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 ID(s)

CAEB071A2207

2006-004128-35-SE