Evaluation of Patient Outcomes From the Kidney Allograft Outcomes AlloSure Registry

Study Overview
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Brief Summary
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This is an observational study to evaluate safety and efficacy outcomes in renal transplant recipients in whom post-transplant care is managed using AlloSure®. AlloSure® is a non-invasive test to measure donor-derived cell-free DNA (dd-cfDNA). The AlloSure test is intended to assess the probability of allograft rejection in kidney transplant recipients with clinical suspicion of rejection and to inform clinical decision-making regarding the necessity of renal biopsy in such patients at least 2 weeks post-transplant in conjunction with standard clinical assessment. Amendment 1 (A1): Is an observational study to develop and validate the clinical use of KidneyCare®.

Detailed Description
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The AlloSure test has been approved for Medicare coverage for clinical use when a physician determines there is a need to assess the probability of allograft rejection in kidney transplant recipients. The DART study suggests that use of the non-invasive AlloSure test to measure donor-derived cell-free DNA (dd-cfDNA) can be used to discriminate active rejection in a renal transplant recipient. Use of the test may reduce invasive percutaneous renal biopsy procedures among patients with a suspicion of rejection. Amendment 1 (A1) is intended to enable the development of KidneyCare® which is a panel test which includes the clinically validated commercial AlloSure dd-cfDNA test, combined with AlloMap Kidney which is a peripheral blood gene expression profiling test currently under development, and iBox, which is an analytic platform that predicts allograft survival at 3, 5, 7 and 10 years using a proprietary software algorithm based on a number of clinical inputs. The AlloMap Kidney and the iBox components are not yet clinically validated and so will not be used for patient management and are being developed through this study.

Official Title
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Evaluation of Patient Outcomes From the Kidney Allograft Outcomes AlloSure Registry

Conditions
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Kidney Transplant Rejection

Intervention / Treatment
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* Diagnostic Test: Donor-derived cell-free DNA (AlloSure®)
* Other: Standard care
* Diagnostic Test: Peripheral blood gene expression profiling (AlloMap Kidney)
* Diagnostic Test: Analytic platform (IBox)


Participation Criteria
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Eligibility Criteria
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KOAR Inclusion Criteria: Patient's health care provider adopts and intends to apply the center's AlloSure Routine Testing Schedule as part of the information used to manage the patient. Subjects willing to provide written informed consent to participate. KOAR Exclusion Criteria: ___________________________________________________________ Exclusions for AlloSure® Intended Use Specimens from patients for whom any of the following are true will not be tested: Recipients of transplanted organs other than kidney Recipients of a transplant from a monozygotic (identical) Recipients of a bone marrow transplant Recipients who are pregnant Recipients who are under the age of 18 Recipient who are less than 14 days post-transplant

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Primary donor-derived cell-free DNA<br>300 patients with planned renal surveillance biopsies at 12 months post-transplantation | Diagnostic Test: Donor-derived cell-free DNA (AlloSure®)<br>* Patients will receive donor-derived cell-free DNA testing for surveillance and for-cause. The planned surveillance will occur at months 1, 2, 3, 4, 6, 9, and 12 post-transplant and quarterly in year 2 and year 3.<br>|
| Control<br>A matched control cohort of 1000 patients with planned renal surveillance biopsies at 12 months post-transplantation but were not managed with donor-derived cell-free DNA (AlloSure®) or KidneyCare will be retrospectively selected | Other: Standard care<br>* Current standard methods for monitoring of renal allograft recipients for rejection (e.g. donor-specific antibodies, serum creatinine, proteinuria, renal allograft biopsy)<br>|
| Secondary donor-derived cell-free DNA<br>1200 patients without planned renal surveillance biopsies at 12 months post-transplantation | Diagnostic Test: Donor-derived cell-free DNA (AlloSure®)<br>* Patients will receive donor-derived cell-free DNA testing for surveillance and for-cause. The planned surveillance will occur at months 1, 2, 3, 4, 6, 9, and 12 post-transplant and quarterly in year 2 and year 3.<br>|
| Primary KidneyCare®<br>300 patients with planned renal surveillance biopsies at 12 months post-transplantation | Diagnostic Test: Donor-derived cell-free DNA (AlloSure®)<br>* Patients will receive donor-derived cell-free DNA testing for surveillance and for-cause. The planned surveillance will occur at months 1, 2, 3, 4, 6, 9, and 12 post-transplant and quarterly in year 2 and year 3.<br>Diagnostic Test: Peripheral blood gene expression profiling (AlloMap Kidney)<br>* Patients will receive peripheral blood gene expression profiling testing for surveillance and for-cause. The planned surveillance will occur at months 1, 2, 3, 4, 6, 9, and 12 post-transplant and quarterly in year 2 and year 3.<br>Diagnostic Test: Analytic platform (IBox)<br>* Patients will receive IBox testing for surveillance and for-cause. The planned surveillance will occur at months 1, 2, 3, 4, 6, 9, and 12 post-transplant and quarterly in year 2 and year 3.<br>|
| Secondary KidneyCare®<br>1200 patients without planned renal surveillance biopsies at 12 months post-transplantation | Diagnostic Test: Donor-derived cell-free DNA (AlloSure®)<br>* Patients will receive donor-derived cell-free DNA testing for surveillance and for-cause. The planned surveillance will occur at months 1, 2, 3, 4, 6, 9, and 12 post-transplant and quarterly in year 2 and year 3.<br>Diagnostic Test: Peripheral blood gene expression profiling (AlloMap Kidney)<br>* Patients will receive peripheral blood gene expression profiling testing for surveillance and for-cause. The planned surveillance will occur at months 1, 2, 3, 4, 6, 9, and 12 post-transplant and quarterly in year 2 and year 3.<br>Diagnostic Test: Analytic platform (IBox)<br>* Patients will receive IBox testing for surveillance and for-cause. The planned surveillance will occur at months 1, 2, 3, 4, 6, 9, and 12 post-transplant and quarterly in year 2 and year 3.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Interstitial fibrosis/tubular atrophy (IF/TA) quantified by Banff Working Group biopsy grade(s) at 12 months post-transplant in AlloSure® and renal allograft biopsy managed patients |  | Feb-2020 | 
| Total number of biopsies planned and performed post-transplant, including both surveillance and clinically indicated biopsies |  | Feb-2020 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Transplant glomerulopathy (TG) | Evaluated at one-year post-transplant, quantified by biopsy-based histopathology grade(s) | Dec-2022 | 
| Patient and graft survival | Evaluated at years 1, 2, and 3 post-transplant | Dec-2022 | 
| Serum creatinine | Evaluated at years 1, 2, and 3 post-transplant | Dec-2022 | 
| Estimated glomerular filtration rate | Evaluated at years 1, 2, and 3 post-transplant | Dec-2022 | 
| Sensitivity of AlloSure for active rejection |  | Dec-2022 | 
| Specificity of AlloSure for active rejection |  | Dec-2022 | 
| Negative Predictive Value (NPV) of AlloSure for active rejection |  | Dec-2022 | 
| Positive Predictive Value (PPV) of AlloSure for active rejection |  | Dec-2022 | 
| Develop and validate the clinical use of KidneyCare® |  | Dec-2022 |