Prospera Test for Heart Transplant Rejection

(ACES-EMB Trial)

Recruiting at 10 trial locations

Overseen By Kiara Stoddard

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Natera, Inc.

Disqualifiers: Multiple transplants, Prior transplants, Pregnant, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

250 Participants Needed

Trial Summary

What is the purpose of this trial?

This is an open label Comparative Effectiveness Research (CER) study in which patients will be randomized at the site level to Prospera surveillance or EMB surveillance in a 2:1 ratio (Prospera to EMB) at each site. Subjects will be enrolled into the study while under evaluation for heart transplantation or on the transplant waiting list prior to heart transplantation. All subjects will follow the center's standard of care surveillance schedule from transplant through 4 weeks post-transplantation. EMB during this phase is expected to occur roughly weekly or bi-weekly. Study group assignment will take place at randomization. Subjects will be randomized 30 days (± 10 days) post-transplant to Prospera surveillance versus EMB surveillance in a 2:1 ratio. Rejection surveillance (Prospera Group and EMB Group) will be performed at times corresponding to the institutional standard of care schedule for rejection surveillance.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the Prospera Heart Test for heart transplant rejection?

The Prospera Heart Test, which uses donor-derived cell-free DNA (dd-cfDNA), is effective in detecting heart transplant rejection noninvasively. Studies show that dd-cfDNA is a reliable marker for identifying rejection in heart, kidney, and lung transplants, helping doctors monitor and manage transplant health without invasive procedures. ^{1 2 3 4 5}

Is the Prospera Test for Heart Transplant Rejection safe for humans?

The Prospera Test, which uses donor-derived cell-free DNA (dd-cfDNA) to monitor transplant rejection, is a non-invasive blood test and is generally considered safe for humans. It has been used in both kidney and heart transplant patients without reports of safety concerns in the available studies. ^{1 2 3 4 6}

How does the Prospera Test for heart transplant rejection differ from other treatments?

The Prospera Test is unique because it uses donor-derived cell-free DNA (dd-cfDNA) to non-invasively detect heart transplant rejection, offering a high negative predictive value and allowing for local laboratory testing, unlike traditional invasive biopsy methods. ^{1 2 4 5 6}

Research Team

Michael Olymbios, MD

Principal Investigator

Natera, Inc.

Josef Stehlik, MD

Principal Investigator

University of Utah

Palak Shah, MD

Principal Investigator

Inova Schar Heart and Vascular

Eligibility Criteria

This trial is for adults over 18 who can consent, are being evaluated for or on the waiting list for a heart transplant, and willing to follow the study's visit schedule and procedures. It excludes those unable to meet these requirements.

Inclusion Criteria

Able and willing to comply with the study visit schedule, study procedures and study requirements

I am 18 years old or older.

I am being evaluated for or am on the waiting list for a heart transplant.

Exclusion Criteria

Planned use of other commercially available or investigational cfDNA or gene expression profile assays for rejection surveillance

I have had multiple organ or tissue transplants.

Pregnant

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Post-Transplant Surveillance

All subjects follow the center's standard of care surveillance schedule from transplant through 4 weeks post-transplantation, with EMB occurring roughly weekly or bi-weekly.

4 weeks

Weekly or bi-weekly visits

Randomized Surveillance

Subjects are randomized 30 days post-transplant to either Prospera surveillance or EMB surveillance, following the institutional standard of care schedule.

11 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including quality of life assessments at week 4, month 6, and month 12 post-transplant.

12 months

Treatment Details

Interventions

• The Prospera™ Test

Trial Overview The study compares two methods of monitoring heart transplant rejection: Prospera™ Test (blood test) versus Endomyocardial Biopsy (tissue sample). Patients will be assigned randomly in a 2:1 ratio favoring Prospera after their transplant.

Participant Groups

Group I: Prospera Surveillance Cohort Experimental Treatment 1 Intervention

Subjects are required to undergo Prospera testing at times corresponding to the institution's graft surveillance schedule. Prospera test results will be provided to the clinical team. Prospera cfDNA level \< 0.15% will be interpreted as low risk for acute rejection (AR). Prospera cfDNA ≥ 0.15% will be interpreted as increased risk for AR and may be followed by EMB to rule out AR at the discretion of the treating clinicians. All other standard of care modalities for assessing AR can be used at the discretion of the treating clinicians at any time throughout the study. As per standard of care, in subjects with clinical signs or symptoms of rejection, a for cause EMB can be done per the clinical team's discretion at any time during the study.

Group II: Endomyocardial Biopsy Surveillance Cohort Active Control 1 Intervention

Subjects will undergo surveillance EMB per the institution's standard clinical care. Biopsy interpretation will be per the institutional pathologist using international guidelines for grading of acute cellular or antibody-mediated rejection. Subjects will also have Prospera testing performed at the time of surveillance EMB for the purpose of measuring concordance between dd-cfDNA surveillance testing and surveillance EMB; Prospera results will not be returned to investigators for subjects in the EMB surveillance group.

Who Is Running the Clinical Trial?

Natera, Inc.

Lead Sponsor

Trials

56

Recruited

50,700+

Findings from Research

In a study involving 428 samples from 112 heart transplant patients, donor-derived cell-free DNA (dd-cfDNA) testing demonstrated high specificity (82% for standard and 84% for expanded SNP assays) for detecting acute rejection (AR), but low sensitivity (39%).

The study found that dd-cfDNA testing was more specific than gene-expression profiling (GEP) for AR detection, suggesting that dd-cfDNA could be a better alternative to GEP in clinical practice, although both methods showed low sensitivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of two donor-derived cell-free DNA tests and a blood gene-expression profile test in heart transplantation. Rodgers, N., Gerding, B., Cusi, V., et al.[2023]

In a study involving 26 heart transplant patients, the use of a local laboratory-run dd-cfDNA assay allowed for effective monitoring of graft health, enabling 88% of invasive endomyocardial biopsies to be avoided without missing any cases of rejection.

The results demonstrate that dd-cfDNA is a feasible and reliable non-invasive method for rejection surveillance in heart transplant patients, significantly reducing the need for more invasive procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Local laboratory-run donor-derived cell-free DNA assay for rejection surveillance in heart transplantation-first six months of clinical experience. Teszak, T., Bödör, C., Hegyi, L., et al.[2023]

In a study of 87 heart transplant recipients, circulating graft-derived cell-free DNA (dd-cfDNA) levels were found to be significantly higher in patients experiencing biopsy-proven cardiac rejection compared to clinically stable patients, indicating its potential as a noninvasive marker for rejection diagnostics.

The study also revealed that dd-cfDNA levels could increase up to 30 days before a biopsy confirmed rejection, suggesting it may serve as an early warning signal; however, factors like pericardial effusions and timing of sample collection post-biopsy can affect the accuracy of dd-cfDNA measurements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Graft-derived Cell-free DNA as a Noninvasive Biomarker of Cardiac Allograft Rejection: A Cohort Study on Clinical Validity and Confounding Factors. Knüttgen, F., Beck, J., Dittrich, M., et al.[2023]

Donor-derived cell-free DNA (dd-cfDNA) is a promising biomarker for early diagnosis of kidney transplant rejection, with assays like Allosure and Prospera receiving Medicare approval for their diagnostic value.

The review highlights the importance of considering factors such as the type of rejection (antibody-mediated or T-cell mediated), timing of the test, and background levels of cell-free DNA to optimize the use of dd-cfDNA assays in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The clinical value of donor-derived cell-free DNA measurements in kidney transplantation. Garg, N., Mandelbrot, DA., Parajuli, S., et al.[2021]

In a study of 170 lung transplant recipients, donor-derived cell-free DNA (dd-cfDNA) levels were found to be significantly higher in patients experiencing acute rejection (AR) compared to those with stable conditions, indicating its potential as a biomarker for monitoring transplant rejection.

The study established specific thresholds for dd-cfDNA: 1.17% for diagnosing AR with high sensitivity (89.19%) and specificity (86.47%), and 0.89% for chronic lung allograft dysfunction (CLAD) with even higher sensitivity (95.00%), suggesting dd-cfDNA is a promising noninvasive tool for assessing lung allograft injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Application of plasma donor-derived cell free DNA for lung allograft rejection diagnosis in lung transplant recipients. Ju, C., Xu, X., Zhang, J., et al.[2023]

In a study of 82 kidney transplant recipients, the use of donor-derived cell-free DNA (dd-cfDNA) testing identified acute rejection in 3 out of 5 patients who underwent biopsy, suggesting it can help detect rejection events.

However, the overall benefit of routine dd-cfDNA monitoring was marginal, as most patients with negative tests did not show significant issues, indicating that the cost-effectiveness of this testing in low-risk patients may need further evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protocol-based donor-derived cell-free DNA surveillance in kidney transplant recipients: A single-center experience. Nissaisorakarn, P., Patel, H., Amtul, A., et al.[2022]

References

1. Denmark pubmed.ncbi.nlm.nih.gov

Comparison of two donor-derived cell-free DNA tests and a blood gene-expression profile test in heart transplantation. [2023]

2. Denmark pubmed.ncbi.nlm.nih.gov

Local laboratory-run donor-derived cell-free DNA assay for rejection surveillance in heart transplantation-first six months of clinical experience. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Graft-derived Cell-free DNA as a Noninvasive Biomarker of Cardiac Allograft Rejection: A Cohort Study on Clinical Validity and Confounding Factors. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

The clinical value of donor-derived cell-free DNA measurements in kidney transplantation. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Application of plasma donor-derived cell free DNA for lung allograft rejection diagnosis in lung transplant recipients. [2023]

6. Germany pubmed.ncbi.nlm.nih.gov

Protocol-based donor-derived cell-free DNA surveillance in kidney transplant recipients: A single-center experience. [2022]