Belatacept in Renal Transplantation With Intermediate Risk Maryland Aggregate Pathology Index (MAPI) Scores

Study Overview
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Brief Summary
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This will be a pilot study to investigate the use of belatacept (BMS) therapy in kidney transplant patients who have a MAPI score of greater than or equal to 8. The MAPI (Maryland Aggregate Pathology Index) score is a preimplantation donor scoring system which has five histopathological parameters that impact long-term kidney outcomes. Many kidney transplant recipients use calcineurin inhibitors (CNIs) as one of their anti-rejection medi cations. Kidney function may be affected by anti-rejection medications known as calcineurin inhibitors (CNIs). Sometimes CNIs can lead to toxicities and eventually loss of the kidney or episodes of chronic allograft nephropathy (CAN). Avoiding CNI immunosuppression and using belatacept therapy (BMS) instead, may be associated with improved kidney transplant outcomes.

Official Title
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A 12 Month, Single-center, Non-randomized, Open-label Study of Outcomes of Intermediate Risk Maryland Aggregate Pathology Index (MAPI) Scores in de Novo Renal Transplant Recipients

Conditions
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End-Stage Renal Disease

Intervention / Treatment
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* Drug: Belatacept


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female renal recipients 18-70 years of age undergoing primary kidney transplantation. Recipients of deceased donor (including expanded criteria donor organs and deceased donor organs after cardiac death) with MAPI score ≥ 8. Cold ischemic time less than 40 hours at time of reperfusion. Negative serum pregnancy test for female patients. Patients who can understand the purposes and risks of the study, provide informed consent, and can comply with the treatment and follow-up requirements. Exclusion Criteria: Cold ischemic time (CIT) > 40 hours Patients who are sensitized with current PRA>40%, ABO incompatible transplants, or T, or B cell crossmatch positive transplant. Patients without antibody to EBV Patients receiving multiple organ transplants. Patients unable to take oral medication at time of randomization Patient with a history of malignancy of any organ system, treated or untreated, within the past 2 years whether or not there is evidence of local recurrence or metastases, with the exception of carcinoma in situ Patients who tested positive for HIV, Hepatitis C or Hepatitis B surface antigen. Recipients of organs from donors who test positive for HIV, Hepatitis C or Hepatitis B surface antigen Patients with a clinically significant systemic infection within 30 days prior to transplant Patients who have cardiac failure at time of screening or any other severe cardiac disease as determined by the investigator Patients with abnormal laboratory findings of clinical significance within 2 weeks of randomization which would interfere with the objectives of the study. Females, pregnant or lactating, or are of childbearing potential unwilling to use an effective means of contraception or are planning to become pregnant. Patient with active tuberculosis infection

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Belatacept therapy<br>20 Patients receiving belatacept based immunosuppressive protocol for 12 months post-transplantation. | Drug: Belatacept<br>* Belatacept infusion intravenous at 10 mg/kg on post-operative days 1, 5, and weeks 2, 4, 8, 12; 5mg/kg intravenous dose at weeks 16, 20, 24, 28, 32, 36, 40, 44, and 48.<br>* Other names: Nulojix;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Renal Function | To evaluate renal function in Belatacept treated recipients of intermediate risk MAPI score allografts in terms of estimated glomerular filtration rate (eGFR, calculated using the MDRD formula) assessed at 12 months. The 12 month eGFR will be compared to existing cohorts of calcineurin inhibitor treated patients with MAPI scores above 8. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rejection rate | Secondary objectives include the biopsy proven rejection rates at 12 months and comparison to existing cohorts of calcineurin inhibitor treated patients. | 12 months | 
| Graft survival | Secondary objectives include renal allograft survival at 12 months. | 12 months | 
| MAPI biopsy score | Secondary objectives include the MAPI score at 3 and 12 months. The MAPI score change compared to baseline in the study group will be important in comparison to existing cohorts of calcineurin inhibitor treated patients, to determine whether calcineurin free-regimens are associated with both functional and histologic differences as compared to calcineurin based therapies. | 12 months | 
| Patient survival | Secondary objectives include patient survival at 12 months. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Kidney Transplantation, Biopsy, Belatacept