Immune Monitoring to Facilitate Belatacept Monotherapy

Study Overview
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Brief Summary
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To determine the utility of novel blood-based immune monitoring tools (Allosure and Trugraf) to facilitate belatacept monotherapy. To determine the percent of belatacept-treated renal transplant patients that can be safely converted to belatacept monotherapy.

Detailed Description
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This study will examine whether renal transplant recipients treated with a belatacept-based immunosuppressive regimen can safely be weaned off all non-belatacept immunosuppression (mycophenolate, mTORi, prednisone) in a stepwise fashion. To this end, participants will undergo monthly immune monitoring using the Allosure (dd-cfDNA) and Trugraf (RNA profiling) blood tests to determine if they are in a state of immune quiescence. Only patients who are deemed to be immune quiescent, will continue to be weaned of non-belatacept immunosuppression.

Official Title
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Immune Monitoring to Facilitate Belatacept Monotherapy

Conditions
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Kidney Transplant Rejection, Immunosuppression

Intervention / Treatment
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* Diagnostic Test: Allosure
* Drug: Immunosuppression reduction
* Diagnostic Test: Trugraf


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age minimum 18 years Written informed consent Single kidney transplant recipient (i.e. no combined organ transplants) Treated with de novo belatacept since transplantation (i.e. no previous use of calcineurin inhibitor or mTOR inhibitor for the current transplant) At least 1 year after transplantation or after initiation of belatacept Stable renal function (eGFR > 40 ml/min continuously during previous 6 months) Blood biomarkers indicate immune quiescence (for Allosure this corresponds to dd-cfDNA < 1%; for Trugraf this corresponds to TX signature) No history of BK viremia in current allograft Exclusion Criteria: History of biopsy-proven acute rejection Presence of donor-specific antibodies (at any MFI) Spot urine protein/creatinine ratio > 0.5 g/g

Ages Eligible for Study
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Minimum Age: 18 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: Diagnostic
Intervention Model: Single Group Assignment
Interventional Model Description: Prospective single-center, single-arm pilot study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Belatacept treated patients<br>Renal transplant recipients treated with a combination of belatacept and any of the following: mycophenolate, sirolimus, everolimus and prednisone | Diagnostic Test: Allosure<br>* Monthly monitoring of dd-cfDNA levels in blood<br>* Other names: donor-derived cell-free DNA (dd-cfDNA);Drug: Immunosuppression reduction<br>* Stepwise reduction in the dose, and ultimate discontinuation of, all non-belatacept immunosuppression (mycophenolate, sirolimus, everolimus, prednisone) guided by monitoring of Allosure and Trugraf results<br>* Other names: prednisone;Diagnostic Test: Trugraf<br>* Monthly monitoring of Trugraf result<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Acute Rejection | Biopsy-proven according to Banff 2017 criteria | Enrollment through 12 months | 
| Incidence of Acute Rejection | Biopsy-proven according to Banff 2017 criteria | Through study completion, 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Increase in eGFR | Calculated using CKD-EPI formula | From baseline to 12 months | 
| Rate of New-onset Proteinuria | Defined as g/g creatinine, measured on random urine sample | At 12 months | 
| Incidence of de Novo Donor Specific Antibodies | Screened for using Luminex platform | At 12 months | 
| Survival | Overall and death-censored graft survival | At 12 months |