KidneyCare Immuno-optimization in Renal Allografts (KIRA)

NCT05423496 | Withdrawn DMC

• 1 other identifier: SN-C-00013
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is an unblinded, randomized, four-arm interventional research study enrolling patients who are undergoing kidney transplantation. The aim of the study is to determine whether patients at low risk of rejection can safely reduce the doses of their post-transplant immunosuppression medications using a combination of tests that include donor-specific antibodies (DSA), histology (looking at tissue from the donor graft), and donor-derived cell-free DNA (AlloSure). Eligible participants will be randomized in a 2:1 ratio into one of two immune-optimization (intervention) arms or the corresponding observational (control) arms. Two thirds of the participants in the study will have their decision to reduce immunosuppression made based on these test results and the other third will have the decision made based on standard of care clinical assessment and laboratory testing. The study will include two additional parameters under investigation - the AlloMap Kidney gene expression profiling test and the iBox prediction algorithm, but these will not be actively used to make any decisions as part of the trial. AlloSure, AlloMap Kidney, and iBox are the three components of the KidneyCare panel developed by CareDx.

Conditions

Kidney Transplant; Immunosuppression; Allograft

Keywords

Calcineurin inhibitors; allograft loss and survival; Chronic immunosuppression; Steroid avoidance; Low-risk kidney transplant recipients; Acute rejection; KidneyCare; Immunological risk assessment; Cross-match testing; Donor-specific antibodies; Donor-derived cell-free DNA; AlloSue; AlloMap; iBox; Gene expression profiling; HistoMap assay; Immune optimization

Outcome Measures

Primary Outcomes (9)

• Estimated glomerular filtration rate (eGFR) at 12 months, non-inferiority

  Demonstrate the safety and efficacy of KidneyCare as tool to successfully adjust immunosuppressant agents using regular surveillance for safe drug minimization. (safety endpoint)

  12 months

• Estimated glomerular filtration rate (eGFR) at 24 months, non-inferiority

  Demonstrate the safety and efficacy of KidneyCare as tool to successfully adjust immunosuppressant agents using regular surveillance for safe drug minimization. (safety endpoint)

  24 months

• Interstitial fibrosis/tubular atrophy (IF/TA) quantified by Banff Working Group biopsy grade(s) at 12-months post-transplant

  Demonstrate the safety and efficacy of KidneyCare as tool to successfully adjust immunosuppressant agents using regular surveillance for safe drug minimization. (safety)

  12 months

• Interstitial fibrosis/tubular atrophy (IF/TA) quantified by Banff Working Group biopsy grade(s) at 24-months post-transplant

  Demonstrate the safety and efficacy of KidneyCare as tool to successfully adjust immunosuppressant agents using regular surveillance for safe drug minimization. (safety)

  24 months

• Transplant glomerulopathy (TG) at 12-months post-transplant, quantified by biopsy-based histopathology grade(s)

  Demonstrate the safety and efficacy of KidneyCare as tool to successfully adjust immunosuppressant agents using regular surveillance for safe drug minimization. (safety)

  12 months

• Transplant glomerulopathy (TG) at 24-months post-transplant, quantified by biopsy-based histopathology grade(s)

  Demonstrate the safety and efficacy of KidneyCare as tool to successfully adjust immunosuppressant agents using regular surveillance for safe drug minimization. (safety)

  24 months

• Total number of biopsies performed post-transplant, including both surveillance and clinically indicated biopsies

  Demonstrate the safety and efficacy of KidneyCare as tool to successfully adjust immunosuppressant agents using regular surveillance for safe drug minimization. (efficacy)

  24 months

• Number of clinically indicated biopsies planned and performed in the first 12- months post- transplant

  Demonstrate the safety and efficacy of KidneyCare as tool to successfully adjust immunosuppressant agents using regular surveillance for safe drug minimization. (efficacy)

  12 months

• Number of clinically indicated biopsies planned and performed in the 24-months post- transplant

  Demonstrate the safety and efficacy of KidneyCare as tool to successfully adjust immunosuppressant agents using regular surveillance for safe drug minimization. (efficacy)

  24 months

Secondary Outcomes (2)

• Histological assessment of tissue biopsy with paired AlloSure dd-cfDNA result - performed both 'For Cause' and 'Surveillance', using standard biopsy and HistoMap molecular assessment using nCounter.

  24 months

• Results of DSA testing, performed as outlined in the testing schedule

  24 months

Other Outcomes (14)

• Incidence of clinically-relevant infections among study participants (defined as infection requiring inpatient admission for evaluation/treatment)

  24 months

• Correlation between longitudinal AlloMap Kidney Scores / iBox Results and dosing of immunosuppressive agents

  24 months

• Correlation between longitudinal AlloMap Kidney Scores / iBox Results and eFGR.

  24 months

Study Arms (4)

Steroid Control Arm

ACTIVE COMPARATOR

133 patient undergoing KidneyCare Surveillance with Immune optimization at clinician discretion

Diagnostic Test: KidneyCare

Steroid Immuno-optimization Arm

EXPERIMENTAL

267 patient undergoing KidneyCare Surveillance with protocolized AlloSure-guided immuno-optimization of steroids/CNI

Diagnostic Test: KidneyCare; Drug: steroid

Tacrolimus and mycophenolate mofetil (MMF) Control Arm

ACTIVE COMPARATOR

133 patient undergoing KidneyCare Surveillance with Immune optimization at clinician discretion

Diagnostic Test: KidneyCare

MMF Immuno-optimization Arm

EXPERIMENTAL

267 patient undergoing KidneyCare Surveillance with protocolized AlloSure-guided immuno-optimization of MMF/CNI

Diagnostic Test: KidneyCare; Drug: MMF

Interventions

KidneyCare DIAGNOSTIC_TEST

Using KidneyCare platform as a tool to successfully augment immunosuppressant agents through regular surveillance allowing minimization of doses and number of agents.

MMF Immuno-optimization Arm; Steroid Control Arm; Steroid Immuno-optimization Arm; Tacrolimus and mycophenolate mofetil (MMF) Control Arm

steroid DRUG

optimization of steroids

Steroid Immuno-optimization Arm

MMF DRUG

optimization of MMF

MMF Immuno-optimization Arm

Eligibility Criteria

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

You may qualify if:

• Participant is willing and able to give informed consent for participation in the trial
• Patients aged 18 years or older
• cPRA \<20% \& no preformed DSA at time of transplant (using center-specific threshold)
• Recipient (or planned recipient, if pre-transplant) of single, first-time, deceased (DBD/DCD) or living donor Kidney Transplant
• Planned post-transplant maintenance immunosuppression regimen consisting of tacrolimus and MMF, with or without prednisone
• Negative virtual crossmatch (performed by transplant center)
• Female participants of childbearing potential must be willing to ensure that they or their partner use effective contraception during the trial
• In the Investigator's opinion, is able and willing to comply with all trial requirements

You may not qualify if:

• The participant may not enter the trial if ANY of the following apply:
• Female participant who is pregnant, lactating, or planning pregnancy during the trial
• Preformed DSA or ABO incompatible transplant
• Chronic oral steroid use (for any reason)
• Planned post-transplant immunosuppression regimen utilizing cyclosporine, azathioprine, mTOR inhibitors, and/or co-stimulatory blockers
• Donor organ from identical twin or history of prior kidney transplant
• Multivisceral transplant (heart/kidney, kidney/pancreas, liver/kidney, etc.) or history of hematopoietic stem cell transplant
• Participant with life expectancy of less than 6 months or is inappropriate for immuno-optimization (including those patients at increased risk of primary disease recurrence w/ reduction in post-transplant immunosuppression)
• Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial
• Participants who are currently or have previously participated in another research trial involving an investigational drug/product in the past 12 weeks
• Any condition that would preclude protocol biopsies (e.g. patients on lifelong anticoagulation for whom anticoagulation cannot be safely held)
• Randomization Criteria (assessed at 3 months)
• The participant may not proceed with randomization if ANY of the following apply:
• Maintenance immunosuppression that includes cyclosporine, azathioprine, mTOR inhibitors, and/or co-stimulatory blockers
• Baseline proteinuria ≥0.5g/day (confirmed by repeat measurement)

Sponsors & Collaborators

• CareDx: lead

MeSH Terms

Interventions

Steroids

Intervention Hierarchy (Ancestors)

Fused-Ring Compounds; Polycyclic Compounds

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 31, 2022
• First Posted: June 21, 2022
• Study Start: August 1, 2022
• Primary Completion: February 23, 2023
• Study Completion: February 23, 2023
• Last Updated: March 27, 2023

Record last verified: 2023-03