E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | M15 |
E.1.2 | Classification code | 10023438 |
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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 investigate whether initiation of everolimus together with reduction or discontinuation of CNI in maintenance renal transplant patients with renal impairment will improve renal function. This will be assessed by comparing renal function evaluated by measured glomerular filtration rate among 3 groups of patients at month 24. |
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E.2.2 | Secondary objectives of the trial |
To compare patient and graft survival at 24 months. To compare the progression of chronic allograft nephropathy . To compare the progression of atherosclerosis assessed by carotid artery ultrasonography Doppler examinations (intima-media thickness (IMT)) at 24 months. To compare mGFR between Group B and Group C at 24 months. To compare other renal function data: slopes of serum creatinine (Cr) and slopes of its reciprocal (1/Cr) and calculated creatinine clearance (Cockcroft-Gault and Nankivell formula) over 24 months study duration. To compare the number and severity of biopsy proven acute rejections at 24 months. To compare safety parameters including incidence of hypertension, hyperlipidemia, diabetes mellitus, anemia, leucopenia, thrombocytopenia, malignancies and infections at 24 months. To summarize everolimus C-0h, Neoral® C-2h and Prograf® C-0h over the 24 months. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
NEW TEXT ARISING FROM AMENDMENT III SHOWN IN CAPITAL LETTERS
Male or female patient at least 18 years of age. Patient who have undergone a primary or secondary renal transplant AT LEAST 6 MONTHS PREVIOUSLY from a living related or unrelated donor or a cadaveric donor. Patient receiving Neoral® with a C2-h level ≥ 400 ng/mL or Prograf® with a C0-h level ≥ 5 ng/mL in combination with MPA or AZA plus or minus steroids. Patient with renal impairment defined as measured GFR between 30 and 70 mL/min/1.73m2. Patient in whom an allograft biopsy is not contraindicated. |
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E.4 | Principal exclusion criteria |
Patient recipient of multiple organ transplants. Patient with protein/creatinine ratio ≥ 150 (mg/mmol). Patient with an acute rejection episode within the last 3 months. Patient with any past or present BK-polyomavirus nephropathy. Patient with de novo or recurrent glomerular nephritis. Patient with a platelet count of < 50,000/mm3 or with a white blood cell count of ≤ 2,500/mm3 or with a hemoglobin value < 8 g/dL. Presence of severe hypercholesterolemia (≥ 350 mg/dL or ≥9.1 mmol/L) or hypertriglyceridemia (≥ 750 mg/dL or ≥8.55 mmol/L). Patient being currently treated or who has been treated with a mTOR inhibitor. Patient who had received an investigational drug within 4 weeks. Patient who is human immunodeficiency virus (HIV) positive or who has a current severe systemic infection according to the investigator judgment requiring continued therapy. Present use of any other immunosuppressive drugs than Neoral®/Prograf® , MPA/AZA and steroids. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective will be assessed by comparing the renal function as assessed by measured GFR at 24 months among the 3 groups of patients: • Group A: current immunosuppressive regimen continuation (Control arm) • Group B: initiation of everolimus (8-12 ng/mL) with discontinuation of CNI (Test arm) • Group C: initiation of everolimus (3 - 8 ng/mL) with reduction by 70-90% in CNI blood levels (Test arm). That is, the primary objective is to show either Group B or Group C will be superior to control Group A with respect to mean mGFR at 24 months. |
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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 | 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 | Yes |
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 |
Current Immunosuppressive regimen continuation |
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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.8.6 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 | 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
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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 | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |