The PROspera Kidney Transplant ACTIVE Rejection Assessment Registry (ProActive)

Study Overview
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Brief Summary
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The ProActive registry is a longitudinal, multi-center study with a prospective arm observing clinical care for patients receiving physician ordered Prospera, an allograft rejection test, and a historical control arm collecting data on cases at the same sites whose kidney allograft rejection status was managed with Serum Creatinine SCr/estimated Glomerular Filtration Rate eGFR. This registry will compare patient management and outcomes in patients who receive Prospera (Prospera arm) to the outcomes of the historical control group (control arm) to determine Prospera's clinical utility. High-risk subjects defined as having a biopsy-demonstrated rejection event or at least one pre-existing Donor Specific Antibody DSA with total Mean Fluorescent Intensity MFI>3000 or a calculated Panel Reactive Antibodies cPRA>70% will be followed for an additional period up to 24 months in both the Prospera arm and historical control arm.

Detailed Description
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The primary objective is to differentiate the clinical utility of Prospera testing from the use of creatinine testing as measured by the proportion of positive biopsies in post renal allograft patients. Secondary objectives include: To observe the performance of the Prospera assay in detecting AR (repeated validation) To evaluate whether Prospera can detect AR earlier and more often than SCr To determine whether use of Prospera will significant decrease the rate of overall number of biopsies when compared to the rate of biopsies in the control arm

Official Title
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The PROspera Kidney Transplant ACTIVE Rejection Assessment Registry (ProActive)

Conditions
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Kidney Transplant Rejection

Intervention / Treatment
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* Diagnostic Test: Prospera


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Prospera Arm: 18 years of age or older Renal allograft (kidney transplant) up to 2 years prior to signing informed consent. Newly transplanted patients to receive Prospera testing within 60 days of transplant A genetically different donor (not an identical twin) Selected by a healthcare provider to receive Prospera dd-cfDNA test according to the regular interval testing schedule as part of their practical care Able to read, understand and provide written informed consent Willing and able to comply with the study visit schedule and study requirements Exclusion Criteria Prospera Arm: Pregnant Routine ongoing testing with another dd-cfDNA or RNA biomarker test after enrollment into the ProActive study. Receipt of another dd-cfDNA test within 30 days of a patient being enrolled in the study. History of another organ transplant (i.e. aside from renal allograph) A serious medical condition that may adversely affect ability to participate in the study (e.g, dementia, current diagnosis of cancer) Previously enrolled in the ProActive Registry, with the exception of a graft failure and a new renal allograft Inclusion Criteria Control Arm: 18 years of age or older at the time of transplant Had a renal allograft Had a genetically different donor Had a minimum of three evaluations per year during the three years since the renal allograft or until allograft failure Exclusion Criteria Control Arm: Female patients who were pregnant at any time during the 3-year historical control data collection period Had a transplanted organ other than kidney Received results from a dd-cfDNA test designed to assess renal allograft rejection during the historical control data collection period

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Prospera Arm<br>There is no intervention in this study. Adult patients who have received a kidney allograft from a genetically different donor in the past 2 years including within 60 days and who have been selected by their healthcare provider to receive Prospera dd-cfDNA testing according to their regular interval testing schedule as part of their clinical care will have medical records pertaining to their kidney rejection status collected at each study visit. | Diagnostic Test: Prospera<br>* No Interventions, this is an observational study.<br>|
| Control Arm<br>The control arm will consist of retrospective data review of cases where a renal allograft from a genetically different donor was performed. Data pertaining to to their kidney rejection status from a minimum of 3 time points per year post allograft (up to 5 years) or until renal allograft failure will be collected. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficiency of biopsies | The proportion of clinically indicated biopsies that show Active Rejection (AR) will be measured in the Prospera arm and the control arm. Specifically, the proportion of clinically indicated biopsies showing AR in individuals with a positive donor derived-cell free DNA dd-cfDNA test at the time of Bx in the test arm, where Prospera has been integrated into the care paradigm, will be compared against the proportion of clinically indicated biopsies showing AR in the control arm. | 3 years | 
| Graft function | Graft function in the Prospera arm and control arm will be measured. This will be assessed by examining the average eGFR score (as calculated using serum creatinine Chronic Kidney Disease-EPIdemiology collaboration CKD_EPI equation) at year three in the Prospera arm compared to the average eGFR score determined at year three in the historical control arm. | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the performance of Prospera | The performance of Prospera to detect AR will be evaluated. The sensitivity, specificity, Positive & Negative Predictive Value of the assay in sub-cohorts of patients will be calculated and compared to the performance of serum creatinine to detect AR in those cohorts. | 5 years | 
| Evaluate whether Prospera can detect acute rejection earlier than serum creatinine | The grade of rejection observed in biopsies in the Prospera arm will be compared to the historical control arm which used serum creatinine. | 3 years | 
| Determine if and how Prospera testing impacts patient care | The proportion of Prospera assay results that doctors felt influenced their decisions around management of patients and biopsies will be calculated. This will be analyzed separately for the for-cause and protocol biopsies. | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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donor-derived cfDNA