Trifecta-Kidney cfDNA-MMDx Study

• Sponsor: University of Alberta (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT04239703
• Collaborator: Natera, Inc. (Industry), One Lambda (Other)
• Enrollment: 300
• Locations: 31
• Anticipated Duration (Months): 60
• Patients Per Site: 9.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

Demonstrate the relationship between DD-cfDNA levels and HLA antibodies in blood, and the Molecular Microscope® (MMDx) Diagnostic System results in indication biopsies.

Condition or Disease	Intervention/Treatment	Phase
Kidney Transplant Rejection	Diagnostic Test: MMDx; Diagnostic Test: Prospera; Diagnostic Test: HLA antibody

Detailed Description

There is a need for better screening of kidney transplant patients for rejection. Patients with kidney transplants are routinely tested (creatinine, urine protein, histology and donor specific antibody (DSA) as standard of care to detect rejection, but these tests are not adequate. Rejection is often missed by these tests (false negatives) and other processes such as acute kidney injury can produce false-positive results. Moreover, histology has a high interobserver disagreement diagnosing rejection, and cannot accurately assess acute injury. A definitive molecular assessment of rejection and injury in kidney biopsies has emerged - the Molecular Microscope® Diagnostic System (MMDx) - developed by the Alberta Transplant Applied Genomics Centre, University of Alberta. Now a new screening test is being introduced: the monitoring of donor-derived cell-free DNA (DD-cfDNA) released in the blood by the kidney during rejection. The Natera Inc DD-cfDNA Prospera® test is based on the massively multiplex PCR that targets 13,392 single nucleotide polymorphisms and targeted sequences are quantified by Next Generation Sequencing. The Prospera® test done on kidney transplant recipients detected "active rejection" and differentiated it from borderline rejection and no rejection. It is likely, however, that DD-cfDNA test may miss some T cell-mediated rejection (TCMR) cases and the distinction between early and fully developed antibody-mediated rejection (ABMR) was not tested. No study has actually examined the DD-cfDNA results in kidney transplants with acute or chronic kidney disease (AKI and CKD). DD-cfDNA measurements have only been correlated with histology, a flawed standard. DD-cf-DNA test must now be calibrated against MMDx that is based on global gene expression, the new standard for biopsy interpretation. The present study will calibrate centrally measured (Natera Inc) DD-cfDNA levels obtained at the time of an indication biopsy against the MMDx measurements of TCMR, and ABMR (early-stage, fully-developed, and late-stage), AK, and atrophy-fibrosis. We will compare blood DD-cfDNA measurements in 600 samples at the time of 300 indication biopsies to the MMDx results, as well as central assessment of HLA antibody (One Lambda) in 300 blood samples, interpreted centrally as DSA based on the tissue typing results. This study is an extension of the INTERCOMEX ClinicalTrials.gov Identifier: NCT01299168. We have collected 675 kidney biopsies and corresponding blood samples. Due to considerable interest from participating centers, we extend this study to the total of 1100 biopsies and 3300 blood samples.

Study Design

• Study Type: Observational
• Anticipated Enrollment: 300 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Trifecta-Kidney cfDNA-MMDx Study: Comparing the DD-cfDNA Test to MMDx Microarray Test, Central HLA Antibody Test, and Histology.
• Actual Study Start Date: Dec 1, 2019
• Anticipated Primary Completion Date: Dec 1, 2023
• Anticipated Study Completion Date: Dec 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Kidney transplant biopsies for cause The study population includes patients with a functioning kidney transplant undergoing a biopsy for clinical indications as standard of care.	Diagnostic Test: MMDx; Portion of kidney transplant indication biopsy; Diagnostic Test: Prospera; Transplant patient blood sample; Other Names: transplant patient blood sample ; Diagnostic Test: HLA antibody; Transplant patient blood sample; Other Names: transplant patient blood sample

Outcome Measures

Primary Outcome Measures

1. Calibration of Prospera test for T cell-mediated rejection [18 months]

   Calibration of DD-cfDNA test cut-off values against the probability of T cell-mediated rejection in the biopsy as reported by MMDx.

2. Calibration of Prospera test for antibody-mediated rejection [18 months]

   Calibration of DD-cfDNA test cut-off values against the probability of antibody-mediated rejection in the biopsy as reported by MMDx.

3. Calibration of Prospera test for kidney injury [18 months]

   Calibration of DD-cfDNA test cut-off values against the probability of acute and chronic kidney injury in the biopsy as reported by MMDx.

4. Report calibrated Prospera test results for rejection [6 months]

   Report new DD-cfDNA test cut-off values for rejection

5. Report calibrated Prospera test results for kidney injury [6 month]

   Report new DD-cfDNA test cut-off values for acute and chronic kidney injury

Secondary Outcome Measures

1. Determine if Prospera blood test can replace kidney biopsy test [6 months]

   Determine if Prospera test, as calibrated by this DD-cfDNA-HLA-MMDx study, will avoid need for indication biopsy when kidney transplant function deteriorates. This will be based on the consensus between participating clinicians.

2. Assessment of donor-specific antibody status [6 months]

   Report and compare the DSA status based on centralized and local HLA antibody measurement.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• All kidney transplant recipients undergoing a kidney biopsy for clinical indications, as determined by their physician or surgeon, will be eligible to enroll in the study.

Exclusion Criteria:

• Patients will be excluded from the study if they decline participation or are unable to give informed consent or multiple organ recipients.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Tampa General Hospital	Tampa	Florida	United States	33606
2	University of Maryland School of Medicine	Baltimore	Maryland	United States	21201
3	The Johns Hopkins University, School of Medicine	Baltimore	Maryland	United States	21205
4	Detroit Medical Center, Harper University Hospital of Wayne State University	Detroit	Michigan	United States	48201
5	Henry Ford Hospital	Detroit	Michigan	United States	48202
6	Barnes-Jewish Hospital, Washington University at St. Louis	Saint Louis	Missouri	United States	63110
7	University Hospitals Cleveland Medical Ctr.	Cleveland	Ohio	United States	44106-5048
8	Cleveland Clinic	Cleveland	Ohio	United States	44195
9	Intermountain Transplant Services	Murray	Utah	United States	84107
10	Virginia Commonwealth University Medical Center	Richmond	Virginia	United States	23298
11	Division of Nephrology & UW Organ Transplant Center University of Washington	Seattle	Washington	United States	98195
12	Department of Nephrology, The Royal Melbourne Hospital 1 South East	Melbourne		Australia	VIC 3050
13	University of Alberta, Department of Medicine	Edmonton	Alberta	Canada	T6G 2G3
14	ST. Paul's Hospital, 6A Providence Building, 1081 Burrard Street	Vancouver	British Columbia	Canada	V6Z 1Y6
15	University Hospital Merkur Renal Division	Zagreb		Croatia	1910000
16	Institute for Clinical and Experimental Medicine (IKEM)	Prague		Czechia	140 21 Praha 4
17	Charite-Medical University of Berlin Department of Nephrology	Berlin		Germany	10117
18	Centre of Nephrology, Vilnius University Hospital Santaros Klinikos	Vilnius		Lithuania	LT-08661
19	Department of Nephrology and Transplantation Medical University in Bialystok	Białystok		Poland	15-540
20	University Hospital nr1 Bydgoszcz, Klinika Transplantologii	Bydgoszcz		Poland	85-094
21	Medical University of Gdańsk Klinika Nefrologii Transplantologii i Chorób Wewnętrznych	Gdańsk		Poland	80-259
22	Medical University of Silesia	Katowice		Poland	40-027
23	Department of Transplantation and General Surgery, Wojewodzki Hospital	Poznań		Poland	60-479
24	Department of Nephrology, Transplantation and Internal Medicine, University Hospital n.2	Szczecin		Poland	70-111
25	Pomeranian Medical University, Samodzielny Publiczny Woj. Szpital Zespolony, Oddzial Nefrologii i Transplantacji Nerek	Szczecin		Poland	71-455
26	Medical University of Warsaw, Department of Transplantation Medicine, Nephrology and Internal Diseases	Warsaw		Poland	02-006
27	Transplant Medicine & Nephrology Clinic, Medical University of Warsaw	Warsaw		Poland	02-006
28	The Children's Memorial Health Institute, Department of Nephrology, Kidney Transplantation and Hypertension	Warsaw		Poland	04-730
29	Wroclaw Medical University, Department of Nephrology and Transplantation Medicine	Wrocław		Poland	50-556
30	Department of Nephrology, University Medical Centre	Ljubljana		Slovenia	21000
31	University Hospital Zurich	Zürich		Switzerland	8091

Sponsors and Collaborators

• University of Alberta
• Natera, Inc.
• One Lambda

Investigators

• Principal Investigator: Philip F Halloran, MD, PhD, University of Alberta

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Philip Halloran, Distinguished Professor, University of Alberta
• ClinicalTrials.gov Identifier: NCT04239703
• Other Study ID Numbers: ATAGC05
• First Posted: Jan 27, 2020
• Last Update Posted: Jul 6, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Philip Halloran, Distinguished Professor, University of Alberta: donor derived cell-free DNA; blood; kidney biopsy
• Additional relevant MeSH terms: Antibodies

Study Results

No Results Posted as of Jul 6, 2022