KidneyCare Immuno-optimization in Renal Allografts (KIRA)

March 24, 2023 updated by: CareDx

KidneyCare Immuno-optimization in Renal Allografts

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a prospective, multicenter, open-label randomized controlled four-arm interventional trial of kidney transplant recipients receiving KidneyCare (AlloSure-Kidney, AlloMap Kidney, and iBox) surveillance testing. Eligible patients who meet inclusion/exclusion criteria and provide consent will undergo standard immune induction per their center protocol and begin a post-transplant maintenance regimen of tacrolimus and mycophenolate mofetil (MMF), with or without steroids after transplantation. If all prerequisite criteria are satisfied at 3 months, participants will be randomized and participants in the intervention arms will begin protocolized immuno-optimization, with the objective of the study being the gradual elimination of one immunosuppressive agent (either MMF or steroids) and optimization of calcineurin inhibitors (CNI) dosing. Any immune optimization changes in the control/observational arms will occur based on clinician discretion.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

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

Exclusion Criteria:

The participant may not enter the trial if ANY of the following apply:

  1. Female participant who is pregnant, lactating, or planning pregnancy during the trial
  2. Preformed DSA or ABO incompatible transplant
  3. Chronic oral steroid use (for any reason)
  4. Planned post-transplant immunosuppression regimen utilizing cyclosporine, azathioprine, mTOR inhibitors, and/or co-stimulatory blockers
  5. Donor organ from identical twin or history of prior kidney transplant
  6. Multivisceral transplant (heart/kidney, kidney/pancreas, liver/kidney, etc.) or history of hematopoietic stem cell transplant
  7. 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)
  8. 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
  9. Participants who are currently or have previously participated in another research trial involving an investigational drug/product in the past 12 weeks
  10. 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:

  1. Maintenance immunosuppression that includes cyclosporine, azathioprine, mTOR inhibitors, and/or co-stimulatory blockers
  2. Baseline proteinuria ≥0.5g/day (confirmed by repeat measurement)
  3. Baseline eGFR <45mL/min (average of 3 most recent prior readings)
  4. Any episodes of biopsy-proven acute rejection (TCMR ≥1A or ABMR) since the time of transplant
  5. Any interval detection of de novo DSA since the time of transplant (per center-specific threshold)
  6. AlloSure result >0.5% at Month 3

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Steroid Control Arm
133 patient undergoing KidneyCare Surveillance with Immune optimization at clinician discretion
Diagnostic test: KidneyCare
Using KidneyCare platform as a tool to successfully augment immunosuppressant agents through regular surveillance allowing minimization of doses and number of agents.
Experimental: Steroid Immuno-optimization Arm
267 patient undergoing KidneyCare Surveillance with protocolized AlloSure-guided immuno-optimization of steroids/CNI
Diagnostic test: KidneyCare
Using KidneyCare platform as a tool to successfully augment immunosuppressant agents through regular surveillance allowing minimization of doses and number of agents.
Drug: steroid
optimization of steroids
Active Comparator: Tacrolimus and mycophenolate mofetil (MMF) Control Arm
133 patient undergoing KidneyCare Surveillance with Immune optimization at clinician discretion
Diagnostic test: KidneyCare
Using KidneyCare platform as a tool to successfully augment immunosuppressant agents through regular surveillance allowing minimization of doses and number of agents.
Experimental: MMF Immuno-optimization Arm
267 patient undergoing KidneyCare Surveillance with protocolized AlloSure-guided immuno-optimization of MMF/CNI
Diagnostic test: KidneyCare
Using KidneyCare platform as a tool to successfully augment immunosuppressant agents through regular surveillance allowing minimization of doses and number of agents.
Drug: MMF
optimization of MMF

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Estimated glomerular filtration rate (eGFR) at 12 months, non-inferiority
Time Frame: 12 months
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
Time Frame: 24 months
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
Time Frame: 12 months
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
Time Frame: 24 months
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)
Time Frame: 12 months
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)
Time Frame: 24 months
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
Time Frame: 24 months
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
Time Frame: 12 months
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
Time Frame: 24 months
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
Time Frame: 24 months
Identify correlation between dd-cfDNA and histopathological allograft rejection based on all clinical biopsies.
24 months
Results of DSA testing, performed as outlined in the testing schedule
Time Frame: 24 months
Compare rates of de-novo DSA antibody formation in immuno-optimization and control groups.
24 months

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Incidence of clinically-relevant infections among study participants (defined as infection requiring inpatient admission for evaluation/treatment)
Time Frame: 24 months
Assessment of all medical events throughout the duration of the study.
24 months
Correlation between longitudinal AlloMap Kidney Scores / iBox Results and dosing of immunosuppressive agents
Time Frame: 24 months
Assess utility of AlloMap Kidney and iBox results for purposes of immuno-optimization and post-transplant surveillance
24 months
Correlation between longitudinal AlloMap Kidney Scores / iBox Results and eFGR.
Time Frame: 24 months
Assess utility of AlloMap Kidney and iBox results for purposes of immuno-optimization and post-transplant surveillance
24 months
Correlation between longitudinal AlloMap Kidney Scores / iBox Results and dnDSA rate.
Time Frame: 24 months
Assess utility of AlloMap Kidney and iBox results for purposes of immuno-optimization and post-transplant surveillance
24 months
Correlation between cross-sectional AlloMap Kidney Scores / iBox Results and rejection (TCMR, ABMR) on histology from for-cause & surveillance biopsies.
Time Frame: 24 months
Assess utility of AlloMap Kidney and iBox results for purposes of immuno-optimization and post-transplant surveillance
24 months
Correlation between cross-sectional AlloMap Kidney Scores / iBox Results and severity/grading of transplant glomerulopathy and IFTA on for-cause & surveillance biopsies
Time Frame: 24 months
Assess utility of AlloMap Kidney and iBox results for purposes of immuno-optimization and post-transplant surveillance
24 months
Immunosuppression Dosing
Time Frame: 24 months
Comparison of cumulative immunosuppression exposure in each arm (average daily dose over time)
24 months
Immunosuppression Exposure
Time Frame: 24 months
Comparison of final dosage of each immunosuppressive agent at the conclusion of the study in each arm (tacrolimus, mycophenolate/Myfortic, prednisone)
24 months
Incidence of viremia ( including BK & CMV), defined as copies/mL in excess of the limit of detection
Time Frame: 24 months
Assessment of all medical events throughout the duration of the study
24 months
PCR viral load over time (defined as time to resolution after initial identification of infection)
Time Frame: 24 months
Assessment of all medical events throughout the duration of the study
24 months
Incidence of any associated end-organ manifestations of viral infection
Time Frame: 24 months
Assessment of all medical events throughout the duration of the study
24 months
Changes in immunosuppression, defined as the change in the median daily dose (mg/day) of immunosuppressive agents
Time Frame: 24 months
Assessment of all medical events throughout the duration of the study
24 months
Incidence of proteinuria, defined by urine protein to creatinine ratio >0.5g/g, confirmed on serial samples
Time Frame: 24 months
Assessment of all medical events throughout the duration of the study
24 months
Number of clinically defined and/or biopsy-confirmed allograft rejection events, including the specific histologic diagnosis made, and if treated, description and duration of therapeutic regimen
Time Frame: 24 months
Assessment of all medical events throughout the duration of the study
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
CareDx

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 1, 2022

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 23, 2023

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 23, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 31, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 14, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 21, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 27, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 24, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2023

More Information

Terms related to this study

Keywords

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • SN-C-00013

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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