TRU-IMMUNO: Optimizing Liver Immunosuppression

• Conditions: Liver Transplant Rejection
• Interventions: Diagnostic Test: Patients monitored with TruGraf and TRAC Liver testing

• Registration Number: NCT05335551
• Lead Sponsor: Transplant Genomics, Inc.

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.

Study Timeline

• Status Verified: 2022-04
• Study First Submitted: 2022-04-12
• Study First Submitted QC: 2022-04-12
• Study First Posted: 2022-04-19
• Last Update Submitted: 2022-04-26
• Study Start: 2022-05
• Last Update Posted: 2022-05-02
• Primary Completion: 2023-05
• Study Completion: 2023-05

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 130

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)

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Patients monitored with TruGraf/TRAC Liver testing	Patients monitored with TruGraf and 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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Immunosuppressant trough	6-months	Immunosuppressant trough levels at 6 months post transplant
Median and mean IS trough	6-months	Median and mean change in IS trough levels from baseline to 6 months
Liver testing workflow	1 year	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).
Infections	1 year	Incidence of grade 3 or greater infections at months 6 and 12
monotherapy immunosuppression	1 year	Percent of patients achieving monotherapy immunosuppression
clinical utility	1 year	Percent and total number of TruGraf Liver and TRAC Liver results that the PI identified as having clinical utility (Utility).
CKD score	1 year	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)
BPAR for-cause biopsy	1 year	Incidence of biopsy proven acute rejection on a for cause biopsy at months 6 and 12
Acute rejection	1 year	Incidence of clinically treated acute rejection at months 6 and 12
eGFR timepoints	1 year	eGFR at months 6 and 12
eGFR timepoint range	1 year	eGFR change from baseline to months 6 and 12
Slope of eGFR	1 year	Slope of eGFR from baseline to months 6 and 12
SF-36 scores	1 year	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.
eGFR decline or progression of CKD	1 year	Risk factors for eGFR decline or progression of CKD score