E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Recipients of a de novo kidney transplant. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10023438 |
E.1.2 | Term | Kidney transplant |
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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 of the study is to demonstrate, in renal transplant patients receiving everolimus and cyclosporin, the non-inferiority of one of the two following regimens: once-a-day regimen (Group A) OR steroid withdrawal regimen (Group B) in comparison with the standard twice-a-day regimen (Group C), using the treatment failure rate (composite endpoint of biopsy-proven acute rejection, graft loss, death or lost to follow-up) between randomization and Month 12 as primary endpoint. |
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E.2.2 | Secondary objectives of the trial |
.to compare the changes in the estimated GFR (Nankivell) between randomization and Month 12 in the once-a-day group (Group A) and in the steroid withdrawal group (Group B) to the change observed in the standard twice-a-day group (Group C), for non inferiority. To compare between groups the biopsy-proven acute rejection (BPAR) rate after randomization; To compare between groups the death censored graft survival, raft survival and patient survival after randomization; To compare the 6 and 12-month renal function between groups, using the estimated creatinine clearance (Cockcroft and Gault and MDRD 4-variable equation), the GFR (Nankivell) and serum creatinine; To estimate the percentage of patients who are compliant to the randomized treatment in the three groups, by month 12; |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Males or females, >18 years of age at transplant; Recipients of 1st or 2nd single kidney transplant; Donor age >14 years; Females capable of becoming pregnant must have a negative serum pregnancy test within 7 days prior to or at Baseline (Visit 2), and are required to practice an approved method of birth control for the duration of the study and for a period of 2 months following discontinuation of study medication; Patients who are willing and able to participate in the study and from whom written informed consent has been obtained. |
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E.4 | Principal exclusion criteria |
recipients of kidney-pancreas transplant, double kidney or any other transplant; recipients of a 2nd kidney transplant who lost the 1st for immunological reasons; Focal segmental glomerulosclerosis (FSGS), primary oxaluria or other diseases (as cause of end stage renal failure - ESRF) at high risk of rapid recurrence or requiring continuous corticosteroid treatment; Recipients of A-B-O incompatible transplants; Historical or current peak PRA of > 25% (current = 3 months); Patients with already existing antibodies against the donor; Thrombocytopenia (platelets < 75,000/mm³), absolute neutrophil count of <1,500/mm³, leucopenia (leucocytes < 2,500/mm³), or hemoglobin < 6 g/dL; Symptoms of significant somatic or mental illness. Inability to cooperate or communicate with the investigator, or to comply with the study requirements, or to give informed consent; 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; Patients who are HIV positive or Hepatitis B surface antigen positive (HbsAg); HCV positive patients receiving interferon and/or ribavirin; Evidence of severe liver disease (incl. abnormal liver enzyme profile, i.e. AST, ALT or total bilirubin > 3 times UNL); Evidence of drug or alcohol abuse; Body mass index (BMI) > 35; |
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E.5 End points |
E.5.1 | Primary end point(s) |
The purpose of this study is to compare the following immunosuppressive regimens in recipients of kidney transplantation: A) everolimus, cyclosporine and steroids given once-a-day; B) everolimus and cyclosporine given twice a day with steroid withdrawal; C) everolimus, cyclosporine given twice a day and continuous steroids. Regimens A and B will be compared for non-inferiority with the control group (group C) using as main endpoint the treatment failure rate, a composite endpoint including death, graft loss, BPAR and lost to follow-up between randomization and Month 12. |
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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 | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
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 | 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) | 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 |
- same IMP used at different dosage |
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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.8.4.1 | Number of sites anticipated in Member State concerned | 25 |
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 | 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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |