E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
De Novo renal transplantation |
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MedDRA Classification |
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 |
To demonstrate superior renal allograft function in de novo renal transplant recipients after early conversion from CNI to everolimus, assessed by Glomerular Filtration Rate (eGFR) estimated by the Modification of Diet in Renal Disease formula 4 (MDRD4) at Month 12 versus the active control |
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E.2.2 | Secondary objectives of the trial |
- To demonstrate non-inferior efficacy (defined by a composite efficacy endpoint of treated Biopsy Proven Acute Rejection (BPAR) ≥ IB, graft loss or death) at Month 12. - To demonstrate improvement of Left Ventricular Hypertrophy (LVH) in comparable patients (assessed by LV mass index, LVMi) by echocardiogram at Month 12.
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
at various centres of excellence, the following will be recorded: 1. arterial stiffness (measured from month 12 to m 24, by Pulse Wave Velocity) 2. 24 hour blood pressure monitoring 3. Pharmacokinetics of Myfortic in co-exposure with either cyclosporine or tacrolimus or everolimus (measured from month 6 to month 12) |
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E.3 | Principal inclusion criteria |
- Male or female renal allograft recipients at least 18 years old. - Patients who have given written informed consent to participate in the study. If consent cannot be expressed in writing, it must be formally documented and witnessed, ideally via an independent trusted witness. - Patient who has received a primary or secondary kidney transplant from a cadaveric or living unrelated-/related donor. - Recipient of a kidney allograft with a cold ischemia time (CIT) < 24 hours. - Female patients must have a negative pregnancy test prior to study enrollment.
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E.4 | Principal exclusion criteria |
- Recipient of multiple organ transplants. - Recipient of ABO incompatible allograft or a positive cross-match. - Patient with most recent Panel Reactive Antibodies (PRA) level ≥ 30 % or a positive luminex test for any permitted antigen of the recipient - Patient who is human immunodeficiency virus (HIV) positive. - Patient who received an allograft from a Hepatitis B surface Antigen (HBsAg) or a Hepatitis C Virus (HCV) positive donor. - HBsAg and/or a HCV positive patient with evidence of elevated LFTs (ALT/AST levels ≥ 2.5 times ULN). Viral serology results obtained within 6 months prior to randomization are acceptable. - Patient with severe restrictive or obstructive pulmonary disorders. - Patient with severe allergy requiring acute (within 4 weeks of baseline) or chronic treatment that would prevent patient from potential exposure to everolimus, or with hypersensitivity to drugs similar to everolimus (e.g. macrolides). - Patient with severe hypercholesterolemia or hypertriglyceridemia that cannot be controlled. - Patient with white blood cell (WBC) count < 2,000 /mm3 or with platelet count < 50,000 /mm3. - History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
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E.5 End points |
E.5.1 | Primary end point(s) |
To demonstrate superior renal allograft function in de novo renal transplant recipients after early CNI to everolimus conversion assessed by Glomerular Filtration Rate (eGFR) estimated by the Modification of Diet in Renal Disease formula 4 (MDRD4) at Month 12 versus the active control |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 60 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
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
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is provided in the protocol, section 5.4.11
End of study will be after: - all patients have completed the Month 24 visit and - all data have been cleaned and the data base has been locked and - Statistical outputs have been received |
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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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |