Once-a-day Regimen With Everolimus, Low Dose Cyclosporine and Steroids in Comparison With Steroid Withdrawal or Twice a Day Regimen With Everolimus, Low Dose Cyclosporine and Steroids. (EVIDENCE)

• Changes in the estimated GFR (Nankivell) between randomization (Month 3) and Month 12 [ Time Frame: Month 3 to Month 12 ] [ Designated as safety issue: No ]
• BPAR rate between randomization and month 12 [ Time Frame: Month 3 to Month 12 ] [ Designated as safety issue: No ]
• patient survival, graft survival and death censored graft survival and between randomization (month 3) and month 12 [ Time Frame: Month 3 to Month 12 ] [ Designated as safety issue: No ]
• The estimated creatinine clearance (Cockcroft and Gault and MDRD 4-variable equation), the GFR (Nankiwell) and serum creatinine [ Time Frame: 6 and 12 months ] [ Designated as safety issue: No ]
• The incidence of new onset diabetes after transplantation. [ Time Frame: Month 6 and month 12 ] [ Designated as safety issue: Yes ]

This study will 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. The purpose of this study is to evaluate regimens A and B in comparison with the control group (group C) for efficacy, 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.

• Renal Transplantation
• Steroids
• Treatment

• Drug: everolimus, cyclosporine and steroids
  once-a-day regimen
• Drug: everolimus, cyclosporine b.i.d. and steroid withdrawal
  steroid bid
• Drug: everolimus, cyclosporine b.i.d. and continuous steroids
  continuous steroids

• Experimental: A
  once-a-day regimen
  Intervention: Drug: everolimus, cyclosporine and steroids
• Experimental: B
  everolimus, cyclosporine b.i.d. and steroid withdrawal
  Intervention: Drug: everolimus, cyclosporine b.i.d. and steroid withdrawal
• Active Comparator: C
  continuous steroids
  Intervention: Drug: everolimus, cyclosporine b.i.d. and continuous steroids

Inclusion criteria:

• Males or females,

  • 18 years of age at transplant;
• Recipients of 1st or 2nd single kidney transplant,
• with donor age >14 years;
• Females capable of becoming pregnant must have a negative serum pregnancy test prior to or at baseline, 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;

Exclusion criteria:

• recipients of any other transplant;
• patients who lost a 1st transplant for immunological reasons;
• Any diseases, as cause of end stage renal failure, at high risk of rapid recurrence or requiring continuous corticosteroid treatment;
• Recipients of A-B-O incompatible transplants;
• Patients with already existing antibodies against the donor;
• Thrombocytopenia, neutropenia or leucopenia;
• History of malignancy of any organ system
• 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);
• Obesity (body mass index > 35);
• Women of child-bearing potential, UNLESS they are using two birth control methods (i.e. a double barrier method or a barrier method plus a hormonal method);
• Pregnant or lactating women,
• Patients with severe active infections or any other medical condition(s) that in the view of the investigator prohibits participation in the study (specify as required).
• Other protocol-defined inclusion/exclusion criteria may apply