Clinical trial NCT04491552: TruGraf® Long-term Clinical Outcomes Study
Official title: TruGraf® Long-term Clinical Outcomes Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Kidney Transplant Rejection
Keywords: Biomarkers
Subclinical Rejection
Lead sponsor: Transplant Genomics, Inc.
Sponsor class: INDUSTRY
First posted: 2020-07-29
Enrollment: 2000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This study is an observational study in adult (age ≥ 18 years), kidney transplant patients who are at least one year from the time of transplant. Approximately 2000 subjects will be enrolled.

Brief summary: This is a prospective, multi-center, observational study. Subjects will have OmniGraf™ (TruGraf® and TRAC™) testing at study enrollment and thereafter every 3 months. In addition subjects will have OmniGraf™ (TruGraf® and TRAC™) testing at any time there is a clinical suspicion of acute rejection. Data collection for the primary objective extends over a 2-year period.

Detailed description: Several studies have validated TruGraf® in stable renal transplant patients to rule out subclinical acute rejection. These studies generally evaluated the diagnostic value of TruGraf® at single timepoints. Thus the value of serial monitoring and changes over time has not been previously investigated. In addition, no study has assessed TruGraf® and TRAC™in a serial and longitudinal fashion.

Therefore the aim of this study is to evaluate the impact of serial monitoring renal transplant patients with both TruGraf® and TRAC™ on long term outcomes.

Eligibility criteria: Inclusion Criteria:

* Written informed consent and HIPAA authorization;
* At least 18 years of age;
* Recipient of a primary or subsequent deceased-donor or living-donor kidney transplant;
* At least 3-months post-transplant;
* Stable serum creatinine (per Principal Investigator);
* Treated with any immunosuppressive regimen, and;
* Selected by provider to undergo OmniGraf™ (TruGraf® and TRAC™) testing as part of post-transplant care; and

Exclusion Criteria:

* Recipient of a combined organ transplant with an extra-renal organ and/or islet cell transplant;
* Recipient of a previous non-renal solid organ and/or islet cell transplant;
* Known to be pregnant;
* Known to be infected with HIV;
* Known to have Active BK nephropathy;
* Known to have nephrotic proteinuria (Per Principal Investigator);
* Participation in other biomarker studies testing clinical utility.

Primary outcomes:
measure: occurrence of either biopsy proven acute rejection (BPAR) on a for cause biopsy or graft loss, or a decrease from baseline in eGFR > 10 mL/min.
timeFrame: Baseline to month 24
Secondary outcomes:
measure: First occurrence of biopsy proven acute rejection (on a for cause biopsy)
timeFrame: Baseline to month 24
measure: First occurrence of clinically treated acute rejection
timeFrame: Baseline to month 24
measure: Proteinuria
timeFrame: Baseline to month 24
measure: TruGraf results
timeFrame: Baseline to month 24
measure: TRAC results
timeFrame: Baseline to month 24
measure: Clinical Utility of TruGraf and TRAC in clinical decision making
timeFrame: Baseline to month 24
measure: Proportion of subjects who develop de novo donor-specific HLA antibodies class I and class II (dnDSA)
timeFrame: Baseline to month 24
measure: Proportion of subjects with graft loss
timeFrame: Baseline to month 24
measure: Graft survival
timeFrame: Baseline to month 24
measure: Proportion of subjects with death-censored graft loss
timeFrame: Baseline to month 24
measure: Percent subject death period
timeFrame: Baseline to month 24
measure: Subject survival
timeFrame: Baseline to month 24
measure: Estimated GFR
timeFrame: Baseline to month 24
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Banner University Medical Center Tucson
state: Arizona
city: Fresno
country: United States
facility: Fresno Nephrology Medical Group
state: California
city: La Jolla
country: United States
facility: Scripps Memorial Hospital La Jolla
state: California
city: Los Angeles
country: United States
facility: Keck Hospital of USC
state: California
city: Riverside
country: United States
facility: House of Transplant and Cancer- Riverside Community Hospital
state: California
city: Sacramento
country: United States
facility: University of California Davis
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: Washington
country: United States
facility: MedStar Georgetown University Hospital
state: District of Columbia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Illinois-Chicago Medical Center
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: New Orleans
country: United States
facility: Tulane University Hospital and Clinic
state: Louisiana
city: Shreveport
country: United States
facility: Willis-Knighton Medical Center
state: Louisiana
city: Baltimore
country: United States
facility: Universtiy of Maryland Medical Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Springfield
country: United States
facility: Renal and Transplant Associates of New England
state: Massachusetts
city: Saint Louis
country: United States
facility: Primary Coordinator Coordinator
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Albuquerque
country: United States
facility: University of New Mexico Health Sciences Center
state: New Mexico
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Buffalo
country: United States
facility: Erie County Medical Center
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Rochester
country: United States
facility: UR Medicine Strong Memorial Hospital
state: New York
city: Greenville
country: United States
facility: Vidant Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Clinical Research Strategies
state: Texas
city: Salt Lake City
country: United States
facility: Utah Kidney Research Institute
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah Hospital
state: Utah
city: Falls Church
country: United States
facility: Inova Fairfax Hospital
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: Primary Coordinator
state: Washington
Study officials:
affiliation: Transplant Genomics, Inc.
name: Patty W. Thielke, PharmD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tonelli M, Wiebe N, Knoll G, Bello A, Browne S, Jadhav D, Klarenbach S, Gill J. Systematic review: kidney transplantation compared with dialysis in clinically relevant outcomes. Am J Transplant. 2011 Oct;11(10):2093-109. doi: 10.1111/j.1600-6143.2011.03686.x. Epub 2011 Aug 30.
citation: Hart A, Smith JM, Skeans MA, Gustafson SK, Stewart DE, Cherikh WS, Wainright JL, Boyle G, Snyder JJ, Kasiske BL, Israni AK. Kidney. Am J Transplant. 2016 Jan;16 Suppl 2(Suppl 2):11-46. doi: 10.1111/ajt.13666.
citation: Meier-Kriesche HU, Schold JD, Srinivas TR, Kaplan B. Lack of improvement in renal allograft survival despite a marked decrease in acute rejection rates over the most recent era. Am J Transplant. 2004 Mar;4(3):378-83. doi: 10.1111/j.1600-6143.2004.00332.x.
citation: Rush D, Nickerson P, Gough J, McKenna R, Grimm P, Cheang M, Trpkov K, Solez K, Jeffery J. Beneficial effects of treatment of early subclinical rejection: a randomized study. J Am Soc Nephrol. 1998 Nov;9(11):2129-34. doi: 10.1681/ASN.V9112129.
citation: El Ters M, Grande JP, Keddis MT, Rodrigo E, Chopra B, Dean PG, Stegall MD, Cosio FG. Kidney allograft survival after acute rejection, the value of follow-up biopsies. Am J Transplant. 2013 Sep;13(9):2334-41. doi: 10.1111/ajt.12370. Epub 2013 Jul 19.
citation: Loupy A, Vernerey D, Tinel C, Aubert O, Duong van Huyen JP, Rabant M, Verine J, Nochy D, Empana JP, Martinez F, Glotz D, Jouven X, Legendre C, Lefaucheur C. Subclinical Rejection Phenotypes at 1 Year Post-Transplant and Outcome of Kidney Allografts. J Am Soc Nephrol. 2015 Jul;26(7):1721-31. doi: 10.1681/ASN.2014040399. Epub 2015 Jan 2.
citation: First MR, Pierry, D, McNultuy, M et al. Analytical and clinical validation of a molecular diagnostic signature in kidney transplant recipients. J Transplant. Technol. Res. 2017; 7(3).
citation: US Renal Data System. 2016 USRDS annual data report: Epidemiology of kidney disease in the United States. Bethesda, MD: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; 2016.
citation: Marsh CL, Kurian SM, Rice JC, Whisenant TC, David J, Rose S, Schieve C, Lee D, Case J, Barrick B, Peddi VR, Mannon RB, Knight R, Maluf D, Mandelbrot D, Patel A, Friedewald JJ, Abecassis MM, First MR. Application of TruGraf v1: A Novel Molecular Biomarker for Managing Kidney Transplant Recipients With Stable Renal Function. Transplant Proc. 2019 Apr;51(3):722-728. doi: 10.1016/j.transproceed.2019.01.054. Epub 2019 Jan 26.
citation: Snyder TM, Khush KK, Valantine HA, Quake SR. Universal noninvasive detection of solid organ transplant rejection. Proc Natl Acad Sci U S A. 2011 Apr 12;108(15):6229-34. doi: 10.1073/pnas.1013924108. Epub 2011 Mar 28.
citation: De Vlaminck I, Martin L, Kertesz M, Patel K, Kowarsky M, Strehl C, Cohen G, Luikart H, Neff NF, Okamoto J, Nicolls MR, Cornfield D, Weill D, Valantine H, Khush KK, Quake SR. Noninvasive monitoring of infection and rejection after lung transplantation. Proc Natl Acad Sci U S A. 2015 Oct 27;112(43):13336-41. doi: 10.1073/pnas.1517494112. Epub 2015 Oct 12.
citation: Gielis EM, Ledeganck KJ, De Winter BY, Del Favero J, Bosmans JL, Claas FH, Abramowicz D, Eikmans M. Cell-Free DNA: An Upcoming Biomarker in Transplantation. Am J Transplant. 2015 Oct;15(10):2541-51. doi: 10.1111/ajt.13387. Epub 2015 Jul 16.
citation: Sharon E, Shi H, Kharbanda S, Koh W, Martin LR, Khush KK, Valantine H, Pritchard JK, De Vlaminck I. Quantification of transplant-derived circulating cell-free DNA in absence of a donor genotype. PLoS Comput Biol. 2017 Aug 3;13(8):e1005629. doi: 10.1371/journal.pcbi.1005629. eCollection 2017 Aug.