The Everolimus-Transplant Exit Strategy Trial (E-TEST)

Study Overview
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Brief Summary
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The purpose of this study is to test the safety and effectiveness of everolimus (Zortress®) in preventing antibody formation in patients with chronic failing kidney transplants. Everolimus (Zortress®) is approved by the U.S. Food and Drug Administration for the prevention of rejection in kidney transplant. The primary objective for the study is to determine whether conversion of patients with chronic renal graft failure approaching dialysis to an everolimus-based regimen will prevent allosensitization. The secondary objective will be to determine whether conversion of patients with chronic renal graft failure to everolimus (elimination of calcineurin inhibitor) will delay the onset of dialysis.

Official Title
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Zortress (Everolimus) to Prevent Alloantibody Formation in Patients With Late Stage Renal Allograft Failure: The Everolimus-Transplant Exit Strategy Trial (E-TEST)

Conditions
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Kidney Failure, Chronic

Intervention / Treatment
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* Drug: Everolimus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: recipient of deceased or living donor kidney transplant Age 18-75 years (inclusive) Male or female renal allograft dysfunction/deterioration evidenced by glomerular filtration rate (GFR) less than or equal to 35 Grade 2 or 3 Interstitial fibrosis/tubular atrophy (IF/TA) on renal allograft biopsy within 5 years of enrollment Willing and able to provide informed consent for study participation Exclusion Criteria: Prior solid organ transplant (other than kidney) History of donor-specific antibody History of biopsy-proven acute rejection within 1 year prior to enrollment Proteinuria greater than or equal to 1.5 gm on spot urine protein/creatinine ratio Evidence of Hepatitis C virus infection (antibody positive or polymerase chain reaction(PCR) positive) Epstein Barr Virus (EBV) or cytomegalovirus (CMV) viremia at the time of enrollment Subjects receiving belatacept (Nulojix) Pregnant or nursing (lactating) women Women of child-bearing potential (WOCBP) who are unwilling or unable to use two birth-control methods throughout participation in the study

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 |
| --- | --- |
| Experimental: Everolimus conversion<br>Subjects who have previously undergone a kidney transplant and are in late stage renal allograft failure will be randomized to take everolimus 0.75 mg twice daily after discontinuing current calcineurin inhibitor. Subjects will be weaned off of all other immunosuppression medicines when dialysis starts. | Drug: Everolimus<br>* Everolimus will initially be dosed at 0.75 mg tablet taken orally twice a day. The dose will be adjusted to maintain serum trough concentrations of 5-8 ng/ml.<br>* Other names: Zortress;|
| No Intervention: Control<br>Subjects who have previously undergone a kidney transplant and are in late stage renal allograft failure will be randomized to continue on current immunosuppressive regimen. Subjects will be weaned off of all immunosuppression medicines when dialysis starts. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Fluorescence Index (MFI) of Donor Specific Alloantibodies (DSA) | Development of new donor-specific alloantibody as determined by solid phase bead array (Luminex) technology defining MFIs for fine specificity at Class I and Class II antigens (human leukocyte antigens (HLA) - A, B, C, DR, DP, and DQ) with an MFI >5000 defined as positive | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Return to Dialysis Dependence |  | 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic allograft failure, Kidney Transplantation