Belatacept for Renal Transplant Recipients With Delayed Graft Function

Study Overview
=================
Brief Summary
-----------------
Currently looking for individuals that have received a kidney transplant, are experiencing delayed graft function (DGF), and meet the criteria for study participation.

Detailed Description
-----------------
Patients who undergo kidney transplantation require long term immunosuppressive therapy (therapy that reduces your body's ability to respond to anything foreign) to prevent damage to the graft, and some experience delayed graft function (DGF, a condition in which the transplanted kidney does not function properly) after transplantation. This study is being conducted to determine if kidney transplant recipients with delayed graft function (DGF) who are switched to the immunosuppressive regimen of belatacept with mycophenolate and steroid will recover from delayed graft function (DGF) in less time (which could potentially lower the risk of rejection associated with delayed graft function) than kidney transplant recipients with delayed graft function (DGF) who remain on the current standard immunosuppressive regimen (standard of care).

Official Title
-----------------
Prospective, Randomized Trial of Belatacept Switch in Renal Transplant Recipients With Delayed Graft Function

Conditions
-----------------
Delayed Graft Function

Intervention / Treatment
-----------------
* Drug: Belatacept
* Drug: Everolimus


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Signed Written Informed Consent Deceased donor renal transplant recipient Men and women, aged 18-60 years of age Exclusion Criteria: Seronegative or unknown EBV serostatus Patients unwilling or incapable of providing informed consent. Patients with active tuberculosis or positive TB test without evidence of infection treatment. Patients with demonstrated acute rejection on first biopsy evaluation for delayed graft function; Second transplant or multiple organ transplant; patients more than 12 days post renal transplant prior to enrollment Evidence of Sepsis or other clinical indicators deemed clinically contraindicated for study enrollment by the primary physician Inadequate vein access to receive monthly IV infusions Prior proven allergy or severe adverse drug reaction to mycophenolate, steroid or Belatacept preventing therapy. Pregnant women or women of child bearing age not willing to commit to dual contraception prophylaxis Use of alemtuzumab (Campath 1-H©), basilixumab (Simulect©) and daclizumab (Zenapax©) are not permitted in this protocol; Use of other immunosuppressive agents must be limited to those specified in this protocol. Prisoners or subjects who are involuntarily incarcerated. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness. Pre-sensitized patients with alloscreen antibody levels of 80% or more class I or class II

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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: Belatacept<br>Belatacept 10mg/kg administered intravenously on days 1, 4, 15, and 28, weeks 8 and 12. Then continue at 5mg/kg every 4 weeks throughout the completion of the study. | Drug: Belatacept<br> <br> * Other names: NULOJIX;|
| Active Comparator: Everolimus<br>Everolimus 1.5 mg/kg twice a day by mouth, the dose will be adjusted after Day 3. | Drug: Everolimus<br> <br> * Other names: zortress;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to recover from Delayed Graft Function | For renal transplant recipients with DGF, time (days) to recover from DGF as defined as: date of enrollment (day 1) until calculated MDRD IV eGFR at least 21 ml/min: at least 2 days after last dialysis if meeting dialysis criteria for enrollment (end date) and no requirement for dialysis at least 2 weeks, with a stable or improving MDRD calculated eGFR (assessed weekly for at least three weeks). | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent patients reaching recovery (defined above) by 14 days and 3 months. | Percent patients reaching recovery (defined above) by 14 days and 3 months. | Assessed at 3, 6, 12 months | 
| Hospital length of stay (days) from date of transplant to discharge | by monitoring patient while inpatient | up to 7 days | 
| Number of dialysis treatments | by monitoring patients health at each visit, and notification of hospitalizations/AE's | Assessed at 3, 6, 12 months | 
| Number of biopsies | medical record review of clinically indicated renal allograft biopsies performed within the followup 12 month period | Assessed at 3, 6, 12 months | 
| Biopsy proven acute rejection events | by blood draws, and by monitoring patients health at each visit, and notification of hospitalizations/AE's | Assessed at 3, 6, 12 months | 
| Patient and graft survival | by monitoring patients health at each visit, and notification of hospitalizations/AE's | Assessed at 3, 6, 12 months | 
| Number of hospital readmissions | by monitoring patients health at each visit, and notification of hospitalizations/AE's | Assessed at 3, 6, 12 months | 
| Detection of DSA (Luminex) | by blood draw | Assessed at 3, 6, 12 months | 
| Incidence and type of infection | by monitoring patients health at each visit, and notification of hospitalizations/AE's | Assessed at 3, 6, 12 months | 
| Measured or estimated creatinine clearance. | by blood draw | Assessed at 3, 6, 12 months | 
| Banff score of rejection episodes and immune suppression treatment/management of rejection | by monitoring patients health at each visit, and notification of hospitalizations/AE's | Assessed at 3, 6, 12 months | 
| Immune suppression drug levels (everolimus or sirolimus, cyclosporine, or mycophenolate as clinically monitored). | by blood draw, and by monitoring patients health at each visit, and notification of hospitalizations/AE's | Assessed at 3, 6, 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Dialysis, Kidney Transplant, immunosuppressive therapy, Delayed Graft Function, Belatacept