The PROspera Kidney Transplant ACTIVE Rejection Assessment Registry (ProActive) (ProActive)

• ClinicalTrials.gov Identifier: NCT04091984
• Recruitment Status: Recruiting
• First Posted: September 17, 2019
• Last Update Posted: August 29, 2022
• Sponsor: Natera, Inc.
• Collaborator: University of Maryland
• Information provided by (Responsible Party): Natera, Inc.

Tracking Information

• First Submitted Date: September 6, 2019
• First Posted Date: September 17, 2019
• Last Update Posted Date: August 29, 2022
• Actual Study Start Date: November 6, 2019
• Estimated Primary Completion Date: October 1, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 17, 2019)

• Efficiency of biopsies [ Time Frame: 3 years ]
  The proportion of clinically indicated biopsies that show Active Rejection (AR) will be measured in the Prospera arm and the control arm. Specifically, the proportion of clinically indicated biopsies showing AR in individuals with a positive donor derived-cell free DNA dd-cfDNA test at the time of Bx in the test arm, where Prospera has been integrated into the care paradigm, will be compared against the proportion of clinically indicated biopsies showing AR in the control arm.
• Graft function [ Time Frame: 3 years ]
  Graft function in the Prospera arm and control arm will be measured. This will be assessed by examining the average eGFR score (as calculated using serum creatinine Chronic Kidney Disease-EPIdemiology collaboration CKD_EPI equation) at year three in the Prospera arm compared to the average eGFR score determined at year three in the historical control arm.

Original Primary Outcome Measures (submitted: September 13, 2019)

• Efficiency of biopsies [ Time Frame: 3 years ]
  Will the use of Prospera significantly increase the proportion of clinically indicated biopsies that show Active Rejection (AR) in the test arm as compared to SCr / eGFR? Specifically, the proportion of clinically indicated biopsies showing AR in individuals with a positive donor derived-cell free DNA dd-cfDNA test at the time of Bx in the test arm, where Prospera has been integrated into the care paradigm, will be compared against the proportion of clinically indicated biopsies showing AR in the control arm.
• Graft function [ Time Frame: 3 years ]
  Will the use of Natera's assay result in a significant change in graft function than the standard of care. This will be assessed by examining the average eGFR score (as calculated using serum creatinine Chronic Kidney Disease-EPIdemiology collaboration CKD_EPI equation) at year three in the Prospera arm compared to the average eGFR score determined at year three in the historical control arm.

Current Secondary Outcome Measures (submitted: September 17, 2019)

• Evaluate the performance of Prospera [ Time Frame: 5 years ]
  The performance of Prospera to detect AR will be evaluated. The sensitivity, specificity, Positive & Negative Predictive Value of the assay in sub-cohorts of patients will be calculated and compared to the performance of serum creatinine to detect AR in those cohorts.
• Evaluate whether Prospera can detect acute rejection earlier than serum creatinine [ Time Frame: 3 years ]
  The grade of rejection observed in biopsies in the Prospera arm will be compared to the historical control arm which used serum creatinine.
• Determine if and how Prospera testing impacts patient care [ Time Frame: 5 years ]
  The proportion of Prospera assay results that doctors felt influenced their decisions around management of patients and biopsies will be calculated. This will be analyzed separately for the for-cause and protocol biopsies.

Original Secondary Outcome Measures (submitted: September 13, 2019)

• Evaluate the performance of Prospera [ Time Frame: 5 years ]
  A secondary outcome is to further observe the performance of Prospera to detect AR, namely, measure the sensitivity, specificity and Positive & Negative Predictive Value of the assay in sub-cohorts of patients, and compare the performance of Prospera to serum creatinine in those cohorts.
• Evaluate whether Prospera can detect acute rejection earlier than serum creatinine [ Time Frame: 3 years ]
  An additional secondary endpoint is to determine if Prospera can detect AR earlier than serum creatinine. Specifically, to evaluate the grade of rejection observed in biopsies in the Prospera arm compared to the historical control arm.
• Determine if and how Prospera testing impacts patient care [ Time Frame: 5 years ]
  Another secondary endpoint is to assess whether Prospera has an impact on decision making in the management of patients around biopsy. The proportion of Prospera assay results that doctors felt influenced their decision will be calculated. This will also be calculated separately for the for-cause and protocol biopsies.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: The PROspera Kidney Transplant ACTIVE Rejection Assessment Registry (ProActive)
• Official Title: The PROspera Kidney Transplant ACTIVE Rejection Assessment Registry (ProActive)
• Brief Summary: The ProActive registry is a longitudinal, multi-center study with a prospective arm observing clinical care for patients receiving physician ordered Prospera, an allograft rejection test, and a historical control arm collecting data on cases at the same sites whose kidney allograft rejection status was managed with Serum Creatinine SCr/estimated Glomerular Filtration Rate eGFR. This registry will compare patient management and outcomes in patients who receive Prospera (Prospera arm) to the outcomes of the historical control group (control arm) to determine Prospera's clinical utility. High-risk subjects defined as having a biopsy-demonstrated rejection event or at least one pre-existing Donor Specific Antibody DSA with total Mean Fluorescent Intensity MFI>3000 or a calculated Panel Reactive Antibodies cPRA>70% will be followed for an additional period up to 24 months in both the Prospera arm and historical control arm.

Detailed Description

The primary objective is to differentiate the clinical utility of Prospera testing from the use of creatinine testing as measured by the proportion of positive biopsies in post renal allograft patients.

Secondary objectives include:

• To observe the performance of the Prospera assay in detecting AR (repeated validation)
• To evaluate whether Prospera can detect AR earlier and more often than SCr
• To determine whether use of Prospera will significant decrease the rate of overall number of biopsies when compared to the rate of biopsies in the control arm

• Study Type: Observational [Patient Registry]
• Study Design: Observational Model: Case-Control; Time Perspective: Other
• Target Follow-Up Duration: 5 Years

Biospecimen

Retention:   Samples With DNA

Description:

There are two arms to this study: A prospective arm and a historical control (retrospective arm).

Each participant in the Prospective arm will have received the commercially available Prospera test.

Subjects prospectively enrolled and whom consent to "Optional future Research" may have bio-specimens stored for future research.

The historical arm (retrospective cohort) will not have any bio-specimens collected or stored.

• Sampling Method: Non-Probability Sample
• Study Population: Approximately 5,000 adult renal allograft participants will be enrolled in this study, and data will be collected from a de-identified cohort of approximately 500 historical control patients who had a renal allograft.
• Condition: Kidney Transplant Rejection

Intervention

Diagnostic Test: Prospera

No Interventions, this is an observational study.

Study Groups/Cohorts

• Prospera Arm
  There is no intervention in this study. Adult patients who have received a kidney allograft from a genetically different donor in the past 2 years including within 60 days and who have been selected by their healthcare provider to receive Prospera dd-cfDNA testing according to their regular interval testing schedule as part of their clinical care will have medical records pertaining to their kidney rejection status collected at each study visit.
  Intervention: Diagnostic Test: Prospera
• Control Arm
  The control arm will consist of retrospective data review of cases where a renal allograft from a genetically different donor was performed. Data pertaining to to their kidney rejection status from a minimum of 3 time points per year post allograft (up to 5 years) or until renal allograft failure will be collected.

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 18, 2022): 5000
• Original Estimated Enrollment (submitted: September 13, 2019): 4000
• Estimated Study Completion Date: October 1, 2027
• Estimated Primary Completion Date: October 1, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria Prospera Arm:

1. 18 years of age or older
2. Renal allograft (kidney transplant) up to 2 years prior to signing informed consent. Newly transplanted patients to receive Prospera testing within 60 days of transplant
3. A genetically different donor (not an identical twin)
4. Selected by a healthcare provider to receive Prospera dd-cfDNA test according to the regular interval testing schedule as part of their practical care
5. Able to read, understand and provide written informed consent
6. Willing and able to comply with the study visit schedule and study requirements

Exclusion Criteria Prospera Arm:

1. Pregnant
2. Routine ongoing testing with another dd-cfDNA or RNA biomarker test after enrollment into the ProActive study. Receipt of another dd-cfDNA test within 30 days of a patient being enrolled in the study.
3. History of another organ transplant (i.e. aside from renal allograph)
4. A serious medical condition that may adversely affect ability to participate in the study (e.g, dementia, current diagnosis of cancer)
5. Previously enrolled in the ProActive Registry, with the exception of a graft failure and a new renal allograft

Inclusion Criteria Control Arm:

1. 18 years of age or older at the time of transplant
2. Had a renal allograft
3. Had a genetically different donor
4. Had a minimum of three evaluations per year during the three years since the renal allograft or until allograft failure

Exclusion Criteria Control Arm:

1. Female patients who were pregnant at any time during the 3-year historical control data collection period
2. Had a transplanted organ other than kidney
3. Received results from a dd-cfDNA test designed to assess renal allograft rejection during the historical control data collection period

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Amy Yang, BSN, RN; 215.375.4817; proactiveprosperastudy@natera.com

Contact: Kiara Stoddard; proactiveprosperastudy@natera.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04091984
• Other Study ID Numbers: 18-039-TRP; Pro00037470 ( Other Identifier: Advarra IRB )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Natera, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Natera, Inc.
• Original Study Sponsor: Same as current
• Collaborators: University of Maryland

Investigators

• Principal Investigator: Jonathan Bromberg, MD; University of Maryland

• PRS Account: Natera, Inc.
• Verification Date: August 2022