Clinical trial NCT05335551: TRU-IMMUNO: Optimizing Liver Immunosuppression
Official title: A Clinical Pilot Study to Test the Acceptability and Feasibility of TruGraf Liver and TRAC Liver Testing as Part of Standard of Care: Optimizing Liver ImmunoSuppression (TRU-IMMUNO)
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Liver Transplant Rejection
Keywords: Biomarkers
Subclinical Rejection
Immunosuppression
Lead sponsor: Transplant Genomics, Inc.
Sponsor class: INDUSTRY
First posted: 2022-04-19
Enrollment: 130
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), liver transplant patients who are 1-2 months post-transplantation. Approximately 130 subjects will be enrolled.

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.

Detailed description: This study will provide TruGraf Liver and TRAC liver tests to one group of transplant providers early after liver transplantation to clarify if the Trugraf Liver and TRAC Liver results can complement their immunosuppression minimization strategies to avoid complications and reduce the occurrence of acute rejection. The ability to decrease IS will be compared to the group that does not receive the test results.

Subjects will be randomized into 2 groups: one will receive Trugraf/TRAC Liver testing and the other will not. 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 post baseline). The TruGraf and TRAC Liver results will be used in the biomarker arm in conjunction with all other clinical parameters available to guide decisions related to immunosuppression changes. There are no protocol mandated immunosuppression changes. Subjects in the standard of care arm will not have biomarkers available for decisions related to immunosuppression changes.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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)

Primary outcomes:
measure: Immunosuppression reduction
timeFrame: 6-months
Secondary outcomes:
measure: Immunosuppressant trough
timeFrame: 6-months
measure: Median and mean IS trough
timeFrame: 6-months
measure: monotherapy immunosuppression
timeFrame: 1 year
measure: clinical utility
timeFrame: 1 year
measure: Liver testing workflow
timeFrame: 1 year
measure: CKD score
timeFrame: 1 year
measure: BPAR for-cause biopsy
timeFrame: 1 year
measure: Acute rejection
timeFrame: 1 year
measure: eGFR timepoints
timeFrame: 1 year
measure: eGFR timepoint range
timeFrame: 1 year
measure: Slope of eGFR
timeFrame: 1 year
measure: eGFR decline or progression of CKD
timeFrame: 1 year
measure: Infections
timeFrame: 1 year
measure: SF-36 scores
timeFrame: 1 year
Other outcomes:
Locations:
Study officials:
affiliation: Transplant Genomics
name: Patty West-Thielke, PharmD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
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.
citation: 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.
citation: 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.
citation: 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.