TRU-IMMUNO: Optimizing Liver Immunosuppression

NCT05335551 | Unknown

• 1 other identifier: TGRP09
• Study Type: observational
• Target: 130
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a prospective, multi-center, randomized study. The primary objective is to evaluate the feasibility and utility of TruGraf/TRAC Liver testing used in addition to standard of care measures of liver dysfunction to guide immunosuppression management.

Conditions

Liver Transplant Rejection

Keywords

Biomarkers; Subclinical Rejection; Immunosuppression

Outcome Measures

Primary Outcomes (1)

• Immunosuppression reduction

  Percent of subjects in each arm achieving at least 50% reduction from baseline total immunosuppressant (non-corticosteroid) dose at 6 months

  6-months

Secondary Outcomes (14)

• Immunosuppressant trough

  6-months

• Median and mean IS trough

  6-months

• monotherapy immunosuppression

  1 year

• clinical utility

  1 year

• Liver testing workflow

  1 year

Study Arms (2)

Patients monitored with TruGraf/TRAC Liver testing

Subjects in the biomarker arm will have TruGraf Liver and TRAC Liver testing at study enrollment (1-2 months post-liver transplant) and thereafter every month for 6 months. Subjects will also have Trugraf Liver and TRAC Liver testing at months 9 and 12 following transplantation (7-8 and 10-11 months postbaseline) The TruGraf and TRAC Liver results will be used in the biomarker arm in conjunction with all other clinical parameters available to guide decisions of the Principal Investigator and Sub-Investigators related to immunosuppression management. changes.

Diagnostic Test: Patients monitored with TruGraf and TRAC Liver testing

Patients not monitored with TruGraf/TRAC Liver testing

Patients in control/ stamdard of care arm will have immusuppresion reduction based on the clinical judgement and management of the Principal Investigator and Sub-Investigators.

Interventions

Patients monitored with TruGraf and TRAC Liver testing DIAGNOSTIC_TEST

This is an observational study there are no protocol mandated interventions. TruGraf and TRAC Liver results will be utilized in conjunction with standard of care assessments to determine patient management in the study arm.

Patients monitored with TruGraf/TRAC Liver testing

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

-This study is an observational study in adult (age ≥ 18 years), liver transplant patients who are 1-2 months post-transplantation. Approximately 130 subjects will be enrolled.

You may qualify if:

• At least 18 years of age.
• Recipient of a primary or subsequent deceased-donor or living donor liver transplantation.
• Normal liver function tests at the time of or within 2 weeks of the baseline visit, defined by Total Bilirubin (TB) ≤1.5 mg/dL and Direct Bilirubin (DB) \<0.5 mg/dL, Alkaline Phosphatase (AP) ≤200 U/L, and Alanine Transaminase (ALT) ≤60 U/L (males) ≤36 U/L (females).
• Between 1-2 months post-liver transplantation

You may not qualify if:

• Inability or unwillingness to provide informed consent.
• Recipients of previous hepatic or non-hepatic solid organ transplantation
• History of ≥2 mild or moderate rejections or 1 severe rejection prior to enrollment defined by BANFF 2016 criteria
• History of autoimmune liver disease
• Listed for repeat liver transplantation
• Infection with HIV
• Active HBV or HCV viremia (patients with undetectable virus can be included)

Sponsors & Collaborators

• Transplant Genomics, Inc.: lead

Related Publications (10)

• Shaked A, DesMarais MR, Kopetskie H, Feng S, Punch JD, Levitsky J, Reyes J, Klintmalm GB, Demetris AJ, Burrell BE, Priore A, Bridges ND, Sayre PH. Outcomes of immunosuppression minimization and withdrawal early after liver transplantation. Am J Transplant. 2019 May;19(5):1397-1409. doi: 10.1111/ajt.15205. Epub 2018 Dec 31.

  PMID: 30506630 BACKGROUND

• Fischer L, Klempnauer J, Beckebaum S, Metselaar HJ, Neuhaus P, Schemmer P, Settmacher U, Heyne N, Clavien PA, Muehlbacher F, Morard I, Wolters H, Vogel W, Becker T, Sterneck M, Lehner F, Klein C, Kazemier G, Pascher A, Schmidt J, Rauchfuss F, Schnitzbauer A, Nadalin S, Hack M, Ladenburger S, Schlitt HJ. A randomized, controlled study to assess the conversion from calcineurin-inhibitors to everolimus after liver transplantation--PROTECT. Am J Transplant. 2012 Jul;12(7):1855-65. doi: 10.1111/j.1600-6143.2012.04049.x. Epub 2012 Apr 11.

  PMID: 22494671 BACKGROUND

• Sterneck M, Kaiser GM, Heyne N, Richter N, Rauchfuss F, Pascher A, Schemmer P, Fischer L, Klein CG, Nadalin S, Lehner F, Settmacher U, Neuhaus P, Gotthardt D, Loss M, Ladenburger S, Paulus EM, Mertens M, Schlitt HJ. Everolimus and early calcineurin inhibitor withdrawal: 3-year results from a randomized trial in liver transplantation. Am J Transplant. 2014 Mar;14(3):701-10. doi: 10.1111/ajt.12615. Epub 2014 Feb 6.

  PMID: 24502384 BACKGROUND

• Levitsky J, Asrani SK, Schiano T, Moss A, Chavin K, Miller C, Guo K, Zhao L, Kandpal M, Bridges N, Brown M, Armstrong B, Kurian S, Demetris AJ, Abecassis M; Clinical Trials in Organ Transplantation - 14 Consortium. Discovery and validation of a novel blood-based molecular biomarker of rejection following liver transplantation. Am J Transplant. 2020 Aug;20(8):2173-2183. doi: 10.1111/ajt.15953. Epub 2020 May 25.

  PMID: 32356368 BACKGROUND

• Levitsky J, Kandpal M, Guo K, Zhao L, Kurian S, Whisenant T, Abecassis M. Prediction of Liver Transplant Rejection With a Biologically Relevant Gene Expression Signature. Transplantation. 2022 May 1;106(5):1004-1011. doi: 10.1097/TP.0000000000003895. Epub 2021 Jul 22.

  PMID: 34342962 BACKGROUND

• 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.

  PMID: 26184824 BACKGROUND

• 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.

  PMID: 28771616 BACKGROUND

• Levitsky J, Kandpal M, Guo K, Kleiboeker S, Sinha R, Abecassis M. Donor-derived cell-free DNA levels predict graft injury in liver transplant recipients. Am J Transplant. 2022 Feb;22(2):532-540. doi: 10.1111/ajt.16835. Epub 2021 Sep 24.

  PMID: 34510731 BACKGROUND

• Charlton M, Levitsky J, Aqel B, O'Grady J, Hemibach J, Rinella M, Fung J, Ghabril M, Thomason R, Burra P, Little EC, Berenguer M, Shaked A, Trotter J, Roberts J, Rodriguez-Davalos M, Rela M, Pomfret E, Heyrend C, Gallegos-Orozco J, Saliba F. International Liver Transplantation Society Consensus Statement on Immunosuppression in Liver Transplant Recipients. Transplantation. 2018 May;102(5):727-743. doi: 10.1097/TP.0000000000002147.

  PMID: 29485508 RESULT

• Levitsky J, O'Leary JG, Asrani S, Sharma P, Fung J, Wiseman A, Niemann CU. Protecting the Kidney in Liver Transplant Recipients: Practice-Based Recommendations From the American Society of Transplantation Liver and Intestine Community of Practice. Am J Transplant. 2016 Sep;16(9):2532-44. doi: 10.1111/ajt.13765. Epub 2016 Apr 22.

  PMID: 26932352 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Whole Blood

Study Officials

• Patty West-Thielke, PharmD

  Transplant Genomics

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Isioma Agboli, MD

CONTACT

15107678609; isiomaagboli@eurofins-tgi.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 12, 2022
• First Posted: April 19, 2022
• Study Start: May 1, 2022
• Primary Completion: May 1, 2023
• Study Completion: May 1, 2023
• Last Updated: May 2, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share