A Comparative Effectiveness Study in Heart Transplant Patients of Rejection Surveillance With Cell-free DNA Versus Endomyocardial Biopsy

Condition(s) studied

Investigational drug(s) / intervention(s)

The Prospera™ Test: The Prospera™ test is a non-invasive test intended to detect and quantify the fraction of donor-derived cell-free DNA (dd-cfDNA) to supplement management and surveillance of allograft rejection in patients who have undergone organ transplantation. It employs Next Generation Sequencing (NGS), which is performed on cell-free DNA (cfDNA) that is extracted from the patient's plasma to discriminate between the patient's DNA and the solid organ-allograft DNA. In study 23-069-TRP, the Prospera test is indicated for heart allograft rejection surveillance in lieu of surveillance endomyocardial biopsy. Prospera results should be considered together with clinical evaluations and other diagnostic testing or imaging results. Prospera will be run as a centralized laboratory developed test that is developed and validated under Design Controls. The test will be run within Natera's CLIA-certified and CAP-accredited laboratory.

Study summary

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.

Eligibility

Primary outcome measure(s)

• Primary Clinical Endpoint — 12 months
  Incidence of the composite endpoint defined as the first occurrence of treated rejection with graft dysfunction\*, treated rejection without graft dysfunction, graft dysfunction, retransplantation, and/or death. Clinical endpoints are defined as follows: 1. Rejection: ISHLT ACR Grade ≥ 2R or AMR Grade ≥ pAMR1 2. Graft dysfunction: LVEF decline ≥ 10% from baseline and \< 50% absolute LVEF by echocardiography 3. Retransplantation: being listed for re-transplant or being re-transplanted * Treated rejection with graft dysfunction and/or graft dysfunction requiring treatment with pulse dose steroids, monoclonal antibodies, plasmapheresis, and/or intravenous immunoglobulin (IVIg).

Trial sites (16)

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