Safety and Efficacy of Basiliximab in Calcineurin Inhibitor Intolerant Long-term Kidney Transplant Recipients Treated With Mycophenolic Acid and Steroids

Study Overview
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Brief Summary
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The long-term use of calcineurin inhibitors (CNI) in patients who have received a kidney transplantation is associated with renal dysfunction and hypertension. The study will evaluate the safety and efficacy of replacing the calcineurin inhibitors by using basiliximab at monthly doses.

Official Title
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REPLACE: Safety and Efficacy of Basiliximab in Calcineurin Inhibitor Intolerant Long-term Kidney Transplant Recipients Treated With Mycophenolic Acid and Steroids

Conditions
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Kidney Transplantation, Adverse Effects

Intervention / Treatment
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* Drug: basiliximab
* Drug: MMF/EC-MPS
* Drug: Corticosteroids


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with a first kidney transplant from a living or deceased donor at least 12 months after transplantation. Patients receiving CNI, mycophenolic acid (MPA) and oral corticosteroids. Patients who are able to tolerate full dose MPA. Patients with glomerular filtration rate (GFR) > 30 mL/min. Patients without an acute rejection episode during the preceding 6 months. Patients with signs or symptoms of CNI intolerance (renal dysfunction, poor blood pressure control, diabetes, poor lipid control, hyperuricemia and gout, significant hypophosphatemia or hypomagnesemia, gingival hyperplasia, hypertrichosis, etc.) in whom CNI interruption is justified. Exclusion Criteria: Patients with preformed positive skin test against basiliximab Patients with preformed panel reactive antibody (PRA) > 10%. Signs of active immune process on graft biopsy. Patients with multi-organ or second kidney transplant Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Maintenance immunosuppression<br>40mg Simulect i.v, once every 28 days for 24 weeks (treatment periods) 1g MMF or 720mg EC-MPS p.o twice daily Oral corticosteroids | Drug: basiliximab<br>* 40 mg once every 28 days intravenously for 24 weeks<br>* Other names: Simulect;Drug: MMF/EC-MPS<br>* 1g MMF or 720mg EC-MPS p.o twice daily<br>* Other names: Cellcept;Drug: Corticosteroids<br>* Oral corticosteroids, equivalent to prednisone p.o, ≥ 5mg daily or ≥ 10mg on alternate days<br>* Other names: Methyl-prednisolone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| to describe the pharmacokinetics of basiliximab over the 6-month study course and to determine whether serum concentrations remain above CD25 receptor saturation levels |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| to evaluate the risk of sensitization against the chimeric antibody over 6 months |  | 6 months | 
| to assess the changes in renal parameters after CNI discontinuation |  | Month 1-6 post trasnplant | 
| to assess the quantifiable changes in vital signs and lab abnormalities possibly related to CNIs |  | 6 months | 
| to assess semi-quantitatively changes of clinical symptoms possibly related to CNIs |  | 6 month | 
| to determine the percentage of CD25 positive T cells (CD3) during therapy with Simulect |  | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Side effects, calcineurin inhibitors, maintenance, basiliximab, Kidney maintenance transplant