Validation of Donor-Derived Cell-Free DNA (Dd-cfDNA) for Kidney Transplant Monitoring

GraftAssureDx Study: Validation of Donor-Derived Cell-Free DNA (Dd-cfDNA) for Kidney Transplant Monitoring

The goal of this observational study is to learn if the donor-derived cell-free DNA (dd-cfDNA) test can assess rejection in kidney transplant recipients. Participants will have blood and urine collected at their study visit.

Researchers will compare results of the GraftAssureDx to rejection detected by standard-of-care graft biopsies.

Study Overview

• Status: Recruiting
• Conditions: Kidney Transplant Rejection; Cell-free DNA
• Intervention / Treatment: Diagnostic test: donor-derived cell-free DNA test

• Study Type: Observational
• Enrollment (Estimated): 125

Contacts and Locations

• Study Contact: Name: Robert Rogers, M.S.; Phone Number: 14436258427; Email: rrogers@imdxinc.com
• Study Contact Backup: Name: Ekkehard Schuetz, MD, PhD; Phone Number: 615-927-1528; Email: eschuetz@imdxinc.com

Study Locations

• Germany
  • Berlin, Germany, 10117
    • Active, not recruiting
    • Charité Universitätsmedizin
  • Baden-Wurttemberg
    • Heidelberg, Baden-Wurttemberg, Germany, 69120
      • Active, not recruiting
      • Institute of Immunology - Transplantation Immunology
• United States
  • California
    • Los Angeles, California, United States, 90033
      • Active, not recruiting
      • University of Southern California Keck School of Medicine
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Recruiting
      • Mayo Clinic in Florida
      • Contact: Carla Palmucci; Phone Number: 904-953-3182; Email: Palmucci.Carla@mayo.edu
      • Principal Investigator: Mohamed Elrefaei, MD, PhD
    • Tampa, Florida, United States, 33606
      • Recruiting
      • Tampa General Hospital
      • Contact: Sandra Sanchez; Email: slsanchez@tgh.org
      • Principal Investigator: Suzane Gilbert, MD
      • Contact: Anelys Marin, B.S.; Phone Number: 813-844-2673; Email: research@tgh.org
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic
      • Principal Investigator: Ziad Zaky, MD
      • Contact: Jennifer Seaman-Czerr; Phone Number: 216-990-0436; Email: Czerrj@ccf.org
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Active, not recruiting
      • University of Pittsburgh Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Recruiting
      • Vanderbilt University Medical Center
      • Principal Investigator: Anthony Langone, MD
      • Contact: Keyann Reaves; Phone Number: 615-936-0695; Email: Keyann.d.reaves@vumc.org
  • Texas
    • Dallas, Texas, United States, 75246
      • Recruiting
      • Baylor, Scott & White Research Institute
      • Contact: Eric Javier Martinez, MD; Phone Number: 214-820-2050; Email: Eric.Martinez1@BSWHealth.org
      • Contact: Ashley McAllister; Phone Number: 214-820-1710; Email: ashley.mcallister@bswhealth.org
  • Utah
    • Murray, Utah, United States, 84107
      • Recruiting
      • Intermountain Health
      • Principal Investigator: Sanjiv Anand, MD
      • Contact: Shannon Sell; Phone Number: 801-507-8390; Email: Shannon.sell@imail.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Individuals who have received a kidney transplant at centers in the United States and Germany will be invited to participate.

Description

Inclusion Criteria:

1. Subject is 18 years of age or older
2. At least 12 calendar days have elapsed since the subject received a kidney transplant.
3. Subject has provided legally effective informed consent
4. Subject agrees to comply with all study procedures

Exclusion Criteria:

1. Kidney donor is an identical twin of the subject.
2. The subject has another previously transplanted organ in situ.
3. Subject has received a hematopoietic stem cell transplant.
4. Subject has received a bone marrow graft.
5. Subject has self-reported as pregnant.
6. In the opinion of the investigator, the subject's participation in the study would pose a risk to data integrity or to the subject's safety and welfare.

Sample Inclusion Criteria:

1. A graft biopsy is obtained within ±1 week of blood draw.

• If blood draw is obtained after biopsy, blood draw should be taken at least 2 days after an uncomplicated biopsy procedure.

Sample Exclusion Criteria:

1. Sample collected from someone that had an invasive graft biopsy ≤ 48 hours prior to blood draw.
2. Sample collected from subject that received immunosuppressive treatment for biopsy-proven acute rejection ≤ 30 days prior to blood draw
3. Sample collected from subject that received a blood transfusion ≤ 30 days prior to blood draw.
4. Sample collected from a subject that provided another sample for the study within the past 7 days.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical validation of the dd-cfDNA test when compared to biopsy-confirmed rejection	Relative percentage of dd-cfDNA levels of 0.5% and absolute values of 50cp/mL are considered to be the diagnostic cutoff for rejection, which will be refined during the first study phase.	Samples tested after final assay cutoffs have been established will be analyzed to demonstrate clinical performance of the investigational assay. This testing will occur from enrollment to 18 weeks after acquisition of the samples.
Clinical validation of the dd-cfDNA test when compared to biopsy-confirmed rejection	Clinical sensitivity of the dd-cfDNA test shall be better or equal to published values (≥56%). Current literature shows an average sensitivity of 69% with a SD of 13%. Therefore, 56% represents the lower boundary (average - 1SD) of the distribution of published values.	Samples tested after the final assay cutoffs have been established will be analyzed to demonstrate clinical performance of the investigational assay. This testing will occur from enrollment to 24 weeks after acquisition of the samples.
Clinical validation of the dd-cfDNA test when compared to biopsy-confirmed rejection	Clinical Specificity of the dd-cfDNA test shall be better or equal to published values (≥75%). Current literature shows an average specificity of 81% with a SD of 6%. Therefore, 75% represents the lower boundary (average - 1SD) of the distribution of published values.	Samples tested after the assay final cutoffs have been established will be analyzed to demonstrate clinical performance of the investigational assay. This testing will occur from enrollment to 24 weeks after acquisition of the samples.
Clinical validation of the dd-cfDNA test when compared to biopsy-confirmed rejection	Predictive values are mathematically derived from sensitivity and specificity using the Bayes' theorem. Therefore, success criteria are defined as the lower boundary of the current literature at any given a priori probability. E.g., for an a priori probability of 20%, the lower boundary for NPV is 85%.	Samples tested after the final assay cutoffs have been established will be analyzed to demonstrate clinical performance of the investigational assay. This testing will occur from enrollment to 24 weeks after acquisition of the samples.
Clinical validation of the dd-cfDNA test when compared to biopsy-confirmed rejection	Predictive values are mathematically derived from sensitivity and specificity using the Bayes' theorem. Therefore, success criteria are defined as the lower boundary of the current literature at any given a priori probability. E.g., for an a priori probability of 20%, the lower boundary for Positive Predictive Value (PPV) is 49%.	Samples tested after the final assay cutoffs have been established will be analyzed to demonstrate clinical performance of the investigational assay. This testing will occur from enrollment to 24 weeks after acquisition of the samples.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ROC-AUC of dd-cfDNA vs. biopsy-confirmed rejection.	The second endpoint is for investigational use only and therefore has no predefined success criteria.	This testing will occur from assay cutoff up to 24 weeks after acquisition of the samples.
Correlation between GraftAssureDx results and traditional biomarkers of kidney rejection (creatinine, estimated glomerular filtration rate, blood urea nitrogen).	The second endpoint is for investigational use only and therefore has no predefined success criteria.	This testing will occur from assay cutoff up to 24 weeks after acquisition of the samples.

Collaborators and Investigators

• Sponsor: Insight Molecular Diagnostics
• Investigators: Study Chair: Ekkehard Schuetz, MD, PhD, Insight Molecular Diagnostics

Study record dates

Study Major Dates

• Study Start (Actual): September 8, 2025
• Primary Completion (Estimated): November 30, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: June 2, 2025
• First Submitted That Met QC Criteria: July 1, 2025
• First Posted (Actual): July 11, 2025

Study Record Updates

• Last Update Posted (Actual): November 19, 2025
• Last Update Submitted That Met QC Criteria: November 18, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: CLN-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: only IPD used in the results publication

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No