Study Evaluating of Calcineurin Inhibitors Versus Sirolimus in Renal Allograft Recipient

This open-label, randomized, parallel-group, comparative, outpatient study will be conducted in multiple centers in Taiwan.

The study will randomize approximately 120 patients. 80 patients will be randomized to the SRL therapy group (conversion from CI- to SRL-based immunosuppression: group A) and 40 patients to the CI therapy group (continued CI therapy: group B).

Dosage and Administration

SRL Therapy: At the time of randomization on day 1, each patient will have been receiving:

• triple therapy with a CI (tacrolimus or CsA) that began at the time of transplantation or within 2 weeks thereafter AND
• corticosteroids corresponding to a dosage range of 2.5 to 15 mg/day for prednisone or prednisolone (2 to 12 mg/day for methylprednisolone) or the alternate day equivalent for at least 12 weeks before randomization, PLUS
• either MMF (minimum dose 500 mg/day)/MPS (minimum dose 360 mg/day) or AZA (minimum dose 50 mg/day) for at least 12 weeks before randomization.

SRL will be added to the immunosuppressive regimen for Group A. Group B will continue on this CI immunosuppressive regimen.

• Drug: Sirolimus+MMF or MPS or AZA+Steroid
  
  Corticosteroids will be administered according to local practice, within a daily maintenance dosage range of 2.5 to15 mg for prednisone or prednisolone (2 to 12 mg/day for methylprednisolone) or the alternate day equivalent.
• Drug: Calcineurin Inhibitors (either cyclosporine or tacrolimus)+MMF or MPS or AZA+Steroid
  

  The maintenance dose of:

  1. MMF will not exceed 1500 mg/day or PMS will not exceed 1080 mg/day
  2. AZA will not exceed 75 mg/day

  Thereafter, at the discretion of the investigator, MMF/MPS or AZA may be:

  1. continued for the entire 104-week period of randomized therapy
  2. subsequently discontinued
  3. restarted after discontinuation

• Experimental: 1
  
  Sirolimus therapy
  Intervention: Drug: Sirolimus+MMF or MPS or AZA+Steroid
• Active Comparator: 2
  
  Calcineurin Inhibitor therapy (either cyclosporine or tacrolimus)
  Intervention: Drug: Calcineurin Inhibitors (either cyclosporine or tacrolimus)+MMF or MPS or AZA+Steroid

Inclusion Criteria:

• Subjects must be at least 18 years of age.
• Subjects who are 6 to 60 months after renal transplantation.
• Subjects who have a stable graft function.

Exclusion Criteria:

• Subjects with active major infection, including HIV, decreased platelets, elevated lipids, or multiple organ transplants.