Study to Evaluate the Safety of Chronic Administration of Simulect to Subjects Receiving a First Kidney Transplant

Study Overview
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Brief Summary
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The study is undertaken to explore the safety of using Simulect at monthly dose intervals to reduce the need of high dose/level CNI's such as Prograf.

Detailed Description
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The use of CNI's after kidney transplantation is associated with typical adverse effects such as potential contribution to progressive impairment of renal function, hypertension, and metabolic abnormalities. The study consists of a run-in phase (1 month),and treatment phase (11 months) and safety assessment phase (1 month).

Official Title
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One-year Exploratory Study to Evaluate the Safety of Partial Replacement of CNI With Chronic Administration of Simulect in de Novo Normal-risk Kidney Transplant Recipients Treated With MPA

Conditions
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End Stage Renal Disease

Intervention / Treatment
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* Drug: basiliximab
* Drug: basiliximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female 18-75 First kidney transplant from a living or deceased donor Receiving CNI and MPA Able to tolerate full dose MPA Calculated glomerular filtration rate >=30ml/min by Cockcroft-Gault equation Able to tolerate renal graft biopsies Provided written, informed consent Females of childbearing potential must have a negative pregnancy test within 48 hours prior to the first Simulect administration Exclusion Criteria: Known hypersensitivity to Simulect Current preformed PRA>10% Multi organ or second kidney transplant Use of any investigational immunosuppressive drug within 1 month of inclusion Female patients who are pregnant, lactating or of child bearing potential and not practicing two approved methods of birth control Known malignancy or history of malignancy other than excised basal or squamous cell carcinoma of the skin HBV, HCV, or HIV positive patients Current severe infection Receiving an organ from an extended criteria donor per United Network for Organ Sharing (UNOS) guidelines Dialysis dependent one month post transplant Live too far away from the transplant center for adequate follow up

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Control<br>Standard of care administration with Simulect (basiliximab)being administered as per induction therapy on day of transplant and day 4. | Drug: basiliximab<br>* Simulect 20 mg intravenously day of transplant and day 4<br>* Other names: Simulect;|
| Experimental: Simulect<br>Simulect (basiliximab) intravenously day of transplant and day 4. Chronic Simulect (basiliximab) administration monthly for one year duration. Concomitant decrease in Prograf administration. | Drug: basiliximab<br>* Simulect (basiliximab) 20mg intravenously day of transplant and day 4 post operatively. Then Monthly administration of Simulect (basiliximab) 40 mg intravenously for one year duration.<br>* Other names: Simulect (basiliximab);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the risk of sensitization against the chimeric antibody, Simulect. |  | one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To describe the pharmacokinetics of Simulect over the study course. |  | one year | 
| To determine the absolute and relative number of CD25 receptors on T cells at the end of each dosing interval. |  | one year | 
| To assess the difference in calculated and measured GFR. |  | one year | 
| To assess the difference in biopsy proven acute rejection rates and the acute and chronic parameters (chronic allograft injury) on surveillance biopsies. |  | one year | 
| To assess the difference in vital signs and lab abnormalities |  | one year | 
| To determine the difference in incidence and severity of albuminuria/proteinuria |  | one year | 
| To collect safety data on infections and malignancies |  | one year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Simulect, de novo kidney transplant subjects, calcineurin inhibitors, Prograf