AlloSure for the Monitoring of Antibody Mediated Processes After Kidney Transplantation

NCT ID: NCT04057742

Last Updated: 2024-09-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

52 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-10-07

Study Completion Date

2024-04-07

Brief Summary

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This is a prospective cohort observational study to assess the role of AlloSure Donor Derived Cell Free DNA (ddcfDNA) assay in the monitoring of three high-risk groups of kidney transplant patients for antibody mediated processes.

* Group A. Thirty participants with a positive Virtual Cross-Match (VXM) at the time of transplant will be monitored for 12 months
* Group B. Similarly, 24 participants with dnDSA will undergo a SOC biopsy within approximately three months to determine the incidence of Active Antibody Mediated Rejection (AMR)
* Group C. 15 additional participants with the diagnosis of Chronic Active Antibody Mediated Rejection (cAMR) will undergo standard of care therapy and be monitored for treatment response with a follow-up biopsy at three months

Detailed Description

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This is a prospective cohort observational study to assess the role of AlloSure Donor Derived Cell Free DNA (ddcfDNA) assay in the monitoring of three high-risk groups of patients for antibody mediated processes.

The AlloSure assay will be combined with the AlloMAP assay (PAXgene blood sample); which is the first in history FDA-cleared genomic solid organ transplantation rejection blood test (AlloMap). Immune cell phenotypes and inflammatory cytokines will be examined. The combination of the three assays will provide a comprehensive molecular diagnostic and prognostic approach to antibody-mediated processes after renal transplantation. Additionally, formalin fixed paraffin embedded (FFPE) samples from kidney biopsies for subjects in all groups will be used to validate the nCounter platform. 3 slides from each biopsy will be sent to CareDx to be examined on the nCounter system. Other routine clinical data will be examined and assessed for correlation with the nCounter results. This will include AlloSure, Molecular Microscope, eGFR, creatinine, DSA as well as other key data fields taken from the Electronic Medical Record (EMR).

AlloMap Kidney is a lab-developed test and will be provided by CareDx, Inc. located at Brisbane, CA, and is designed, manufactured and used within a single CareDx laboratory. AlloMap Kidney is currently provided as "For Research use only" test and results are not intended for clinical diagnosis or patient management for "KidneyCare", which is the AlloSure-Kidney and AlloMap-Kidney tests combined.

* Group A. Thirty participants with a positive VXM at the time of transplant will be monitored for 12 months and undergo protocol biopsies on months 3 and 12 to detect subclinical rejection. Participants may also undergo clinically indicated biopsies for suspicion of rejection. AlloSure, AlloMap, immune cell phenotypes, and inflammatory cytokines will be measured at baseline (within 48 hours of transplant), 3 weeks, 6 weeks, 3M (SOC biopsy), 6M, 12M (SOC biopsy) and additionally at the time of any indication biopsy (5-7 time points/patient). Subjects in this group will be monitored for 12 months.
* Group B. Similarly, 24 participants with dnDSA will undergo a SOC biopsy within approximately three months to determine the incidence of AMR. Immune cell phenotyping, AlloSure and AlloMap will be measured at the time of the SOC biopsy (1 timepoint/patient). This is a single-time point study, unless participants are diagnosed with AMR and require treatment. In this case, they would be enrolled in group C (see below).
* Group C. 15 additional participants with the diagnosis of cAMR will undergo standard of care therapy and be monitored for treatment response with a follow-up biopsy at three months. Immune cell phenotyping, AlloSure and AlloMap will be used at baseline (prior to index biopsy) and 3M (follow-up surveillance biopsy) (2 timepoints/patient). Participants in this group will be monitored per SOC for three months (time between the two biopsies).

For all three groups, history and physical, blood draws and urine sample collections are performed per SOC. The only addition is blood sample collection and additional urine collection at the indicated SOC timepoints for AlloSure, AlloMap, immune cell flow cytometry, RNA-signatures, and inflammatory cytokines. In addition, leftover pathology slides that are stored in the pathology department will be sent out to CareDx for the purposes of performing the NanoString analysis. The slides will be returned to the pathology department after the NanoString analysis is complete.

Conditions

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Kidney Transplant Failure and Rejection

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Group A

30 participants with a positive virtual crossmatch (VXM) at the time of transplant will be monitored for 12 months and undergo protocol biopsies on months 3 and 12 to detect subclinical rejection. Participants may also undergo clinically indicated biopsies for suspicion of rejection. AlloSure, AlloMap, immune cell phenotypes, and inflammatory cytokines will be measured at baseline (within 48 hours of transplant), 3 weeks, 6 weeks, 3 months (Standard of Care (SOC) biopsy), 6 months, 12 months (SOC biopsy), and additionally at the time of any indication biopsy (5-7 time points/participant). Participants in this group will be monitored for 12 months. Participants will be offered the option of donating either 22.5 mL of blood (Allosure+AlloMap+cytokines) or 52.5 mL of blood (Allosure+AlloMap+cytokines+immune cell phenotyping) at each visit. Participants may change their donation volume from 22.5 mL to 52.5 mL at any point during the study.

AlloSure ddcfDNA assay

Intervention Type DIAGNOSTIC_TEST

2.5 mL collection for Donor Derived Cell Free DNA at transplant, 3 weeks, 6 weeks, 6 months, 12 months post-transplant for Group A, at transplant for Group B, and transplant and 3 months for Group C

AlloMap assay

Intervention Type DIAGNOSTIC_TEST

10 mL collection PAXgene blood sample at transplant, 3 weeks, 6 weeks, 6 months, 12 months post-transplant for Group A, at transplant for Group B, and transplant and 3 months for Group C

Inflammatory Cytokines

Intervention Type DIAGNOSTIC_TEST

10 mL collection at transplant, 3 weeks, 6 weeks, 6 months, 12 months post-transplant for Group A

Immune Cell Phenotypes

Intervention Type DIAGNOSTIC_TEST

Collection of up to 1 cup of urine for per participant each study visit

Group B

24 participants with De novo donor specific antibodies (dnDSA) will undergo a SOC biopsy within approximately three months to determine the incidence of Active Antibody Mediated Rejection (AMR). Immune cell phenotyping, AlloSure, and AlloMap will be measured at the time of the SOC biopsy (1 timepoint/patient). This is a single-time point study, unless participants are diagnosed with AMR and require treatment. In this case, they would be enrolled in group C (see below).

AlloSure ddcfDNA assay

Intervention Type DIAGNOSTIC_TEST

2.5 mL collection for Donor Derived Cell Free DNA at transplant, 3 weeks, 6 weeks, 6 months, 12 months post-transplant for Group A, at transplant for Group B, and transplant and 3 months for Group C

AlloMap assay

Intervention Type DIAGNOSTIC_TEST

10 mL collection PAXgene blood sample at transplant, 3 weeks, 6 weeks, 6 months, 12 months post-transplant for Group A, at transplant for Group B, and transplant and 3 months for Group C

Immune Cell Phenotypes

Intervention Type DIAGNOSTIC_TEST

Collection of up to 1 cup of urine for per participant each study visit

Group C

15 additional participants with the diagnosis of Chronic Active Antibody Mediated Rejection (cAMR) will undergo standard of care therapy and be monitored for treatment response with a follow-up biopsy at three months. Immune cell phenotyping, AlloSure, and AlloMap will be used at baseline (prior to index biopsy) and 3 month (follow-up surveillance biopsy) (2 timepoints/participant). Participants in this group will be monitored per SOC for three months (time between the two biopsies).

AlloSure ddcfDNA assay

Intervention Type DIAGNOSTIC_TEST

2.5 mL collection for Donor Derived Cell Free DNA at transplant, 3 weeks, 6 weeks, 6 months, 12 months post-transplant for Group A, at transplant for Group B, and transplant and 3 months for Group C

AlloMap assay

Intervention Type DIAGNOSTIC_TEST

10 mL collection PAXgene blood sample at transplant, 3 weeks, 6 weeks, 6 months, 12 months post-transplant for Group A, at transplant for Group B, and transplant and 3 months for Group C

Immune Cell Phenotypes

Intervention Type DIAGNOSTIC_TEST

Collection of up to 1 cup of urine for per participant each study visit

Interventions

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AlloSure ddcfDNA assay

2.5 mL collection for Donor Derived Cell Free DNA at transplant, 3 weeks, 6 weeks, 6 months, 12 months post-transplant for Group A, at transplant for Group B, and transplant and 3 months for Group C

Intervention Type DIAGNOSTIC_TEST

AlloMap assay

10 mL collection PAXgene blood sample at transplant, 3 weeks, 6 weeks, 6 months, 12 months post-transplant for Group A, at transplant for Group B, and transplant and 3 months for Group C

Intervention Type DIAGNOSTIC_TEST

Inflammatory Cytokines

10 mL collection at transplant, 3 weeks, 6 weeks, 6 months, 12 months post-transplant for Group A

Intervention Type DIAGNOSTIC_TEST

Immune Cell Phenotypes

Collection of up to 1 cup of urine for per participant each study visit

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

* Kidney transplant recipients (de novo or retransplant)
* Positive Virtual Crossmatch at transplant (Group A)
* Undergoing SOC biopsy for dnDSA (Group B)
* Proven cAMR (Group C)

Exclusion Criteria

* Multi-Visceral transplant
* Contraindication to renal biopsy
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role collaborator

CareDx

INDUSTRY

Sponsor Role collaborator

University of Wisconsin, Madison

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Sarah Panzer, MD

Role: PRINCIPAL_INVESTIGATOR

University of Wisconsin, Madison

Locations

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University of Wisconsin - Madison

Madison, Wisconsin, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Informed Consent Form

View Document

Related Links

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https://banfffoundation.org/

Banff Foundation for Allograft Pathology

Other Identifiers

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1K23DK122136-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

A534280

Identifier Type: OTHER

Identifier Source: secondary_id

SMPH/MEDICINE/MEDICINE*N

Identifier Type: OTHER

Identifier Source: secondary_id

Protocol Version 3/13/2023

Identifier Type: OTHER

Identifier Source: secondary_id

2019-0750

Identifier Type: -

Identifier Source: org_study_id

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