TRU-IMMUNO: Optimizing Liver Immunosuppression

Liver Transplant Rejection Clinical Trial

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)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05335551
• Other study ID #: TGRP09
• Status: Not yet recruiting
• Start date: May 2022
• Est. completion date: May 2023

Study information

• Verified date: April 2022
• Source: Transplant Genomics, Inc.
• Contact: Isioma Agboli, MD
• Phone: 15107678609
• Email: isiomaagboli[@]eurofins-tgi.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 130
• Est. completion date: May 2023
• Est. primary completion date: May 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Liver Transplant Rejection

Intervention

Diagnostic Test:
• Patients monitored with TruGraf and TRAC Liver testing
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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Transplant Genomics, Inc.

References & Publications (10)

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 — View 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. — View 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. Review. — View 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. — View 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. — View 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. — View 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 Tr — View 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. Erratum in: Am J Transplant. 2019 Aug;19(8):2393. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Immunosuppressant trough	Immunosuppressant trough levels at 6 months post transplant	6-months
Secondary	Median and mean IS trough	Median and mean change in IS trough levels from baseline to 6 months	6-months
Secondary	monotherapy immunosuppression	Percent of patients achieving monotherapy immunosuppression	1 year
Secondary	clinical utility	Percent and total number of TruGraf Liver and TRAC Liver results that the PI identified as having clinical utility (Utility).	1 year
Secondary	Liver testing workflow	Percent and total number of eligible patients for whom the PI was able to complete the entire TruGraf Liver and TRAC Liver testing workflow (Feasibility).	1 year
Secondary	CKD score	Progression of CKD score managed by the KDIGO (Kidney Disease: Improving Global Outcomes) criteria from a scale of GI (normal kidney) to G5 (kidney failure)	1 year
Secondary	BPAR for-cause biopsy	Incidence of biopsy proven acute rejection on a for cause biopsy at months 6 and 12	1 year
Secondary	Acute rejection	Incidence of clinically treated acute rejection at months 6 and 12	1 year
Secondary	eGFR timepoints	eGFR at months 6 and 12	1 year
Secondary	eGFR timepoint range	eGFR change from baseline to months 6 and 12	1 year
Secondary	Slope of eGFR	Slope of eGFR from baseline to months 6 and 12	1 year
Secondary	eGFR decline or progression of CKD	Risk factors for eGFR decline or progression of CKD score	1 year
Secondary	Infections	Incidence of grade 3 or greater infections at months 6 and 12	1 year
Secondary	SF-36 scores	Change in SF-36 scores from baseline to 6 months and end of study (SF 36 is a 36-item patient-reported questionnaire that covers eight health domains: physical functioning (10 items), bodily pain (2 items), role limitations due to physical health problems (4 items), role limitations due to personal or emotional problems (4 items), emotional well-being (5 items), social functioning (2 items), energy/fatigue (4 items), and general health perceptions (5 items). Scores for each domain range from 0 to 100, with a higher score defining a more favorable health state.	1 year