| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | M15 | | E.1.2 | Classification code | 10023438 | |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial | The primary objective is to compare renal function in the two treatment groups at month 12 post-transplant, as measured by calculated GFR (Nankivell), serum creatinine and calculated creatinine clearance (Cockroft- Gault).
Intra-group change in GFR , as determined by Nankivell’s formula, and the GFR’s slope in the period between visits 6 and 12 months will also be determined.
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| E.2.2 | Secondary objectives of the trial | The secondary objectives of this study are:
•To evaluate the incidence of biopsy-proven acute rejection (BPAR) episodes, graft loss, death or loss to follow-up after 12 months in both groups.
•To evaluate the incidence of graft loss, death, BPAR episodes, antibody treated acute rejection episodes, clinically confirmed acute rejection episodes, clinically confirmed chronic rejection episodes and biopsy-proven chronic allograft nephropathy after 12 months in both groups.
•To evaluate the safety of Certican® in combination with Simulect® and steroids, with either Neoral® discontinuation at 3 months post-transplant, or Neoral® minimization.
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| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria | Each patient must meet all of the following inclusion criteria:
1. Male or female patients between 18 and 65 years of age
2. Male or female patients who are recipients of a first renal transplant from a primary cadaveric or non-HLA identical living related donor .
3. The renal cold ischemic time (CIT) must be < 36 hours
4. The age of the donor must be < 65 years
5. Females of childbearing potential must have a negative pregnancy test at baseline and are required to practice an approved method of birth control for the duration of the study and for a period of three months following discontinuation of study medication.
6. Patients who have given written informed consent to participate in the study
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| E.4 | Principal exclusion criteria | Patients meeting any of the following criteria at baseline will be excluded from study participation.
1. Patients who are recipients of multiple organ transplants including any organ other than kidney
2. Patients who have been previously transplanted with any organ other than a kidney
3. Recipients of non heart-beating donor organs
4. Patients with current or past panel reactive T-cell antibodies (PRA) titers of >50%
5. Patients that had been treated with any investigational drug 4 weeks before the baseline period
6. Presence of any severe allergy requiring acute (within 4 weeks of baseline) or chronic treatment, or hypersensitivity to drugs similar to RAD001 (e.g. macrolides)
7. Existence of any surgical or medical condition, other than the current transplant, which in the opinion of the investigator, precludes enrollment in this trial
8. Evidence of liver dysfunction as indicated by an abnormal liver profile (AST, ALT, alkaline phosphatase or total bilirubin ≥ 3 times ULN) before transplantation
9. Patients who are known to have a positive hepatitis C serology, who are human immunodeficiency virus (HIV) or hepatitis B surface antigen positive. Laboratory results obtained within 6 months prior to randomization are acceptable. Recipients of organs from donors who test positive for Hepatitis B surface antigen or Hepatitis C are excluded.
10. Patients with symptoms of significant somatic or mental illness. Unresolved history of drug or alcohol abuse
11. Presence of revascularized ischemic heart disease or AMI, (or any cardiac disease considered to be unsafe for the study by the investigator)
12. Presence of severe hypercholesterolemia (≥ 350 mg/dL, 9.1 mmoL/dL) or hypertriglyceridemia (≥ 500mg/dL, 5.6 mmoL/L). Patients with controlled hyperlipidemia are acceptable
13. White blood cell (WBC) count≤ 3,500/mm3, or platelet count ≤ 100,000/mm3
14. Patients with severe systemic infections
15. Patients with current or past malignancies (except for successfully treated localized basal cell carcinoma of the skin)
16. Patients who are recipients of A-B-O incompatible transplants or T-cell cross-match positive transplants
17. Patients with coagulopathy or any medical condition requiring long-term anticoagulation after transplantation (low dose aspirin is allowed)
18. Abnormal physical or laboratory findings of clinical significance within 2 weeks prior to baseline visit, which at investigators discretion would interfere with the objectives of the study
19. Breast feeding women
20. Inability to cooperate or communicate with the investigator
21. Patients who have been treated with non-protocol immunosuppressive drug or treatment within 4 weeks prior to baseline visit
Exclusion criteria for randomization at the end of month 3 (week 12):
1. Any episode of acute rejection grade IIb/III (Banff classification) or a vascular acute rejection in the previous 4 weeks or any episode of acute rejection episode during the month prior to randomization.
2. Patients depending on dialysis
3. Serum creatinine >3 mg/dL and/or more than 30% elevated during the previous month.
4. Patients who do not tolerate any increase in Certican ® dose.
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| E.5 End points |
| E.5.1 | Primary end point(s) | | The GFR value is calculated using the Nankivell formula. This is the end point in witch sample size is based. | |
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description | | The control arm is the no drug discont of one of the drugs,and the changes of the trial drug dosages | |
| E.8.3 | The trial involves single site in the Member State concerned | No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| E.8.8 | Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial | |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 4 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
