Study to Evaluate the Efficacy, Safety and Tolerability of Everolimus in de Novo Renal Transplant Recipients Participating in the Eurotransplant Senior Program

Study Overview
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Brief Summary
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This study wants to address whether a calcineurin-inhibitor (CNI)-free regimen six weeks after transplantation for Eurotransplant Senior Program (ESP) patients is as safe and well tolerated as standard treatment but optimizing immunosuppressive therapy with benefits in renal function, new-onset diabetes mellitus, cardiovascular risk, cancer and allograft nephropathy.

Official Title
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6-month, Open-label, Randomized, Multicenter, Prospective, Controlled Study to Evaluate the Efficacy, Safety and Tolerability of Everolimus in de Novo Renal Transplant Recipients Participating in the Eurotransplant Senior Program

Conditions
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Renal Transplantation

Intervention / Treatment
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* Drug: Basiliximab
* Drug: Enteric Coated Mycophenolic Acid (MPA)
* Drug: RAD001
* Drug: Cyclosporin A (CsA)
* Drug: Corticosteroids


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Patients receiving a primary kidney from a donor aged > 65 years In the Eurotransplant Senior Program Recipients of de novo cadaveric kidney transplants Exclusion criteria: Multi-organ recipients (e.g., kidney and pancreas) Patients receiving a kidney from a non-heart beating donor Patients who are recipients of A-B-O incompatible transplants Patients with already existing antibodies against the HLA-type of the receiving transplant Patients who have received an investigational immunosuppressive drug within four weeks prior to study entry (Baseline visit 1) Patients with thrombocytopenia, with an absolute neutrophil count of < 1,500/mm³ or leucopenia or hemoglobin < 6 g/dL Patients who are HIV, HCV RNA, or Hepatitis B surface antigen positive Evidence of severe liver disease Females at randomization who will be not considered post-menopausal Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control group<br>During the pre-randomized treatment phase, all participants received a CNI-based regimen consisting of basiliximab, mycophenolic acid (MPA), cyclosporin A (CsA) and corticosteroids (optional). Upon randomization, participants in this group continued with a CNI-based regimen of MPA and CsA. | Drug: Basiliximab<br>* On day 0, 2 hours prior to transplant and day 4 post-transplant, 20 mg x2 were given to all participants. Post randomization, 20mg at weeks 7 and 12 were given to the Everolimus group.<br>* Other names: Simulect;Drug: Enteric Coated Mycophenolic Acid (MPA)<br>* A loading dose regimen of 2880 mg/day during weeks 1 and 2 (pre-randomization) were given. During weeks 3 - 6 (pre-randomization), 2160 mg/day were given and during weeks 7 - 24, 1440 mg/day were given if tolerated. Dose reductions due to side effects were possible.<br>* Other names: Myfortic;Drug: Cyclosporin A (CsA)<br>* Dosage was based according to blood level<br>* Other names: Sandimmun Optoral;Drug: Corticosteroids<br>* Dosage was administered according to local standards and administration was optional as per clinical need and the Investigators' discretion. Steroid withdrawal occurred after week 2 (pre-randomization).<br>|
| Experimental: Everolimus group<br>During the pre-randomized treatment phase, all participants received a CNI-based regimen consisting of basiliximab, mycophenolic acid (MPA), cyclosporin A (CsA) and corticosteroids (optional). Upon randomization, participants in this group made a stepwise switch to a CNI-free regimen of everolimus and MPA. | Drug: Basiliximab<br>* On day 0, 2 hours prior to transplant and day 4 post-transplant, 20 mg x2 were given to all participants. Post randomization, 20mg at weeks 7 and 12 were given to the Everolimus group.<br>* Other names: Simulect;Drug: Enteric Coated Mycophenolic Acid (MPA)<br>* A loading dose regimen of 2880 mg/day during weeks 1 and 2 (pre-randomization) were given. During weeks 3 - 6 (pre-randomization), 2160 mg/day were given and during weeks 7 - 24, 1440 mg/day were given if tolerated. Dose reductions due to side effects were possible.<br>* Other names: Myfortic;Drug: RAD001<br>* Upon randomization, 3 mg (od) on Day 1, and 3 mg (1.5 mg every 12 hours) on Day 2 was given. Afterwards, the dosage was based on blood trough level (5 - 10 ng/mL).<br>* Other names: RAD001, Certcian;Drug: Cyclosporin A (CsA)<br>* Dosage was based according to blood level<br>* Other names: Sandimmun Optoral;Drug: Corticosteroids<br>* Dosage was administered according to local standards and administration was optional as per clinical need and the Investigators' discretion. Steroid withdrawal occurred after week 2 (pre-randomization).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Renal Function by Glomerular Filtration Rate (GFR) Via Cockcroft-Gault Method | The study was terminated prematurely and not powered for efficacy. | Month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Renal Function by GFR Via Modification of Diet in Renal Diseases (MDRD) and Nankivell Method | The study was terminated prematurely and not powered for efficacy. | Month 6 | 
| Renal Function by Serum Creatinine | The study was terminated prematurely and not powered for efficacy. | Months 6, 12, 24, 36, 48 and 60 | 
| Biopsy Proven Acute Rejection (BPAR), Graft Loss and Death | The study was terminated prematurely and not powered for efficacy. | Months 6, 12, 24, 36, 48 and 60 | 
| Occurrence of Treatment Failures | The study was terminated prematurely and not powered for efficacy. | Month 6 | 
| Evolution of Renal Function (Creatinine Slope) | The study was terminated prematurely and not powered for efficacy. | Week 7, Month 6 | 
| CD25 Saturation on Lymphocytes |  | Month 6 | 
| Number of Participants Who Experienced Adverse Events, Serious Adverse Events and Death | Participants with adverse events (serious plus non-serious), serious adverse events and death were reported. | Months 6, 12, 24, 36, 48 and 60 | 
| Renal Function by GFR Over Time |  | Months 12, 24, 36, 48 and 60 | 
| Renal Function by Proteinuria |  | Months12, 24, 36, 48 and 60 |