E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
pediatric de novo renal trasplant |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 7.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10050432 |
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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 |
1. To evaluate the safety and tolerability of RAD001 administered b.i.d. in combination with Neoral® and corticosteroids in pediatric de novo renal transplant recipients, and to provide additional safety data (quantitative protein/creatinine ratio in urine). |
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E.2.2 | Secondary objectives of the trial |
1.To evaluate the efficacy of RAD001 administered b.i.d. in combination with Neoral® and corticosteroids as measured by the incidence of biopsy proven acute allograft rejection episodes, graft loss or death at 6 and 12 months after initial dose of study medication. 2.To characterize the multiple dose pharmacokinetics of RAD001 administered b.i.d. 3.To evaluate the efficacy of RAD001 administered b.i.d. in combination with Neoral® and corticosteroids in the prevention of chronic allograft rejection (chronic graft dysfunction) at 12 months post-transplantation.
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
a.Male and female patients 16 years of age. b.Patients receiving a primary cadaveric or non-HLA identical living donor (related or unrelated) renal transplant. c.The graft must be functional within 48 hours post transplantation. A functional graft is defined at the investigator’s determination by a 50 % fall of serum creatinine from the pre-transplant value. In the event of dialysis immediately preceding transplantation, the pre-dialysis serum creatinine value may be used. d.Females capable of becoming pregnant must have a negative pregnancy test (qualitative dip stick test on urine) immediately prior to study entry. Females of child bearing potential must practice an approved method of birth control for the one year duration of the study and for a period of three months following discontinuation of study medication. e.Patients who are willing and able to participate in the whole course of the study and for whom written informed consent has been obtained from the parent(s) or legal guardian.
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E.4 | Principal exclusion criteria |
a.Cold ischemia time > 40 hours. b.Patients who are recipients of multiple solid organ transplants, including dual and en bloc kidneys, or who have previously received transplanted organs. c.Patients with non-diarrhea associated hemolytic-uremic syndrome. d.Recipients of donor specific transfusions. e.Patients with panel reactive T cell antibodies of 50 % or higher at the last assessment before transplantation. f.Patients unable to undergo renal biopsies post-transplant. g.Induction therapy with ALG, ATG and OKT3. h.Use of anti-fungal azoles such as ketoconazole, itraconazole and fluconazole. i.Patients requiring treatments with rifampin, carbamazepine, phenobarbital, phenytoin at the time of entry in the study. j.The use of any investigational drug within 4 weeks prior to administration of the initial dose of study medication. k.Patients who have received an investigational immunosuppressive agent within 4 months prior to administration of the initial dose of study medication. l.Presence of any severe allergy (within 4 weeks prior to administration of the initial dose of study medication) requiring acute or chronic treatment; or hypersensitivity to drugs similar to RAD001 (e.g., erythromycin or other macrolide antibiotics) or to any component of the formulation. m.Patients with any known contraindication to CsA. n.Patients with severe or unstable medical conditions likely to affect patient safety or the objectives of this study. Other social circumstances that prevent full compliance with the protocol. o.Patients with a history of alcohol or drug abuse, or signs of alcohol-induced organ damage, mental dysfunction or other factors limiting their ability to cooperate fully with the study. p.Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of any drug. The investigator should be guided by evidence of any of the following: presence of inflammatory bowel syndrome, or gastrointestinal bleeding; history of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection (bladder augmentations and feeding tubes are acceptable). q.Patients who are Hepatitis C positive, HIV positive, or Hepatitis B surface antigen positive. Laboratory results obtained within 6 months prior to administration of the initial dose of study medication are acceptable. Recipients of organs from donors who test positive for Hepatitis B surface antigen, Hepatitis C or HIV. r.Evidence of liver injury as indicated by abnormal liver tests (AST or ALT > 3 times ULN, total bilirubin > 2 mg/dL). s.Presence of uncontrolled hypercholesterolemia ( ≥350 mg/dL, ≥ 9.1 mmol/L) or hypertriglyceridemia (≥ 500 mg/dL, ≥ 5.6 mmol/L). t.White blood cell count ≤ 4500/mm3 or platelet count ≤ 100,000/mm3. u.Patients with severe systemic infections. v.Patients with any past or present malignancy (other than excised basal cell carcinoma). w.History of splenectomy. x.Patients with any history of significant coagulopathy or medical condition requiring long term systemic anticoagulation after transplantation which would interfere with obtaining biopsies. Low dose aspirin is allowed. y.Abnormal physical or laboratory findings of clinical significance which would interfere with the objectives of the study. z.Females who are breast feeding.
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E.5 End points |
E.5.1 | Primary end point(s) |
To evaluate the safety and tolerability of RAD001 administered b.i.d. in combination with Neoral® and corticosteroids in pediatric de novo renal transplant recipients |
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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 | 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) | 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 | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
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 | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |