Kidney Transplant Immunosuppression
Conditions
Brief summary
The purpose of the study is to identify kidney transplant patients that can be transitioned from multi-drug immunosuppression therapy to Belatacept monotherapy, using cell free DNA and gene expression as markers of immune quiescence. The primary objective will be to determine if donor derived-cell free DNA (AlloSure) can be utilized to facilitate Belatacept monotherapy, and to determine if Belatacept is safe and effective as immunosuppression in kidney transplant recipients. The secondary objective is to determine the utility of AlloMap as a predictor of immune quiescence and tolerance of immunosuppressive de-escalation to Belatacept monotherapy, and to evaluate the performance of iBox in predicting adverse outcomes in patients transitioned to Belatacept monotherapy
Interventions
DRUGBelatacept
Patients will have tapering of their multi-drug immunosuppression, until Belatacept is the sole medication in their immunosuppression regimen. Belatacept will be administered as an infusion, as is routinely done clinically.
Sponsors
University of Texas Southwestern Medical Center
CareDx
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult (\>18 years) recipients of a kidney-only transplant, including re-transplants * Non-HLA identical Living or Deceased Donor Grafts * Able to provide informed consent * Absence of donor specific antigens * Stable renal function (eGFR\>40mL/min for 3 months prior to enrollment) * Patients treated with Belatacept as part of de novo immunosuppression or converted to Belatacept with stable kidney function for 3 months (as stated above) * Patients who underwent kidney transplantation at least 9 months prior to study entry
Exclusion criteria
* Prior or concurrent non-kidney organ transplants * Presence of BK nephropathy in current graft * Recipient on any other investigational drug in the 12 weeks prior to inclusion * Patient with history of recent (\<3mo), recurrent, or severe (Banff Grade 2 or greater or unable to be treated with steroids) acute rejection episodes * Female participant who is pregnant, lactating or planning pregnancy during the course of the trial * Significant hepatic impairment * Bilateral kidney transplantation * Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Acute Kidney Graft Rejection | 12 months after the date of the first immunosuppression taper | Number of patients with Acute kidney graft rejection confirmed by biopsy by 2017 Banff Criteria. Incidence of biopsy proven acute kidney graft rejection at 12 months after the start of immunosuppression taper |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Who Died | 12 months after the start of immunosuppression wean | Incidence of death will be measured from 12 months after the start of immunosuppresion wean. |
| Number of Patients With Kidney Graft Failure | 12 months after the start of immunosuppression wean | Incidence of kidney graft failure will be measured from the start of immunosuppresion wean until 12 months after. Graft failure is defined as date of patient death or date of retransplant |
| Mean Change in Estimated Glomerular Filtration Rate (eGFR) | Baseline, 12 months after the start of immunosuppression wean | Estimated glomerular filtration rate (eGFR) in blood will be measured at the beginning of enrollment and the difference will be measured to the end of the study as a measure of change in kidney function. |
| Number of Participants With Proteinuria | 12 months after the start of immunosuppression weaning | Proteinuria will be detected by a semiquantitative method of the protein concentration in urine. |
| Number of Participants With Appearance of De-novo Donor Specific Antibodies (dnDSA) | 12 months after the start of immunosuppression wean | HLA type I and type II in blood will be used to detect the presence of de-novo donor specific antibodies (dnDSA) |
| AlloMap® Level | 12 months after the start of immunosuppression wean | Negative predictable value measured by AlloMap®, expressed as a percent, that the patient is not experiencing rejection at the time of testing. AlloMap® is a panel of 20 gene assays, 11 informative and 9 used for normalization and/or quality control, which produces gene expression data used in the calculation of an AlloMap Test score is an integer ranging from 0 to 40. Compared with patients in the same post- transplant period, the lower the score, the lower the probability of acute cellular rejection at the time of testing. |
| Mean Prediction Score of Allograft Loss as Measured by iBox | 12 months after the start of immunosuppression wean | iBox is the validated tool for predicting the risk of kidney transplant loss based on artificial intelligence. Range of score is 0%-100%, higher score indicates better kidney survival. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORDavid Wojciechowski, DO
University of Texas Southwestern Medical Center
PRINCIPAL_INVESTIGATORCyrus Feizpour, MD
University of Texas Southwestern Medical Center
Participant flow
Recruitment details
25 kidney transplant recipients whose maintenance immunosuppression regimen included Belatacept were recruited from an outpatient clinic. Patients were identified through medical record review to determine eligibility based upon inclusion and exclusion criteria. An investigator called eligible patients to discuss interest in participation and written, informed consent was obtained at a routine outpatient visit for those agreeable.
Pre-assignment details
Eligible patients were enrolled in the study for a 3-month lead-in period to demonstrate stability and establish baseline molecular diagnostic markers. During this initial observation period, immune quiescence was assessed using the following criteria: stable renal function (eGFR no more than 20% below the value at inclusion), AlloSure ≤1%, AlloMap \< 11.5, absence of proteinuria (UPCR \<0.5 g/g), and no evidence of de novo DSA or biopsy-proven acute rejection.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 8 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants |
| Etiology Diabetes | 10 Participants |
| Etiology Glomerulonephritis | 1 Participants |
| Etiology Hypertension | 5 Participants |
| Etiology Other | 7 Participants |
| Human Leukocyte Antigen (HLA) Mismatch 0 HLA Mismatch | 1 Participants |
| Human Leukocyte Antigen (HLA) Mismatch 1 HLA Mismatch | 0 Participants |
| Human Leukocyte Antigen (HLA) Mismatch 2 HLA Mismatch | 0 Participants |
| Human Leukocyte Antigen (HLA) Mismatch 3 HLA Mismatch | 2 Participants |
| Human Leukocyte Antigen (HLA) Mismatch 4 HLA Mismatch | 4 Participants |
| Human Leukocyte Antigen (HLA) Mismatch 5 HLA Mismatch | 12 Participants |
| Human Leukocyte Antigen (HLA) Mismatch 6 HLA Mismatch | 4 Participants |
| Immunosuppression Therapy Belatacept + Everolimus + Prednisone | 3 Participants |
| Immunosuppression Therapy Belatacept + Mycophenolate | 2 Participants |
| Immunosuppression Therapy Belatacept + Mycophenolate + Prednisone | 15 Participants |
| Immunosuppression Therapy Belatacept + Prednisone | 2 Participants |
| Immunosuppression Therapy Belatacept + Sirolimus | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 12 Participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 15 Participants |
| Type of Transplant Donation after Brain Death (DBD) Donor | 14 Participants |
| Type of Transplant Donation after Circulatory Death (DCD) Donor | 6 Participants |
| Type of Transplant Living Donor | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 | 0 / 25 |
| other Total, other adverse events | 5 / 12 | 6 / 12 | 0 / 25 |
| serious Total, serious adverse events | 2 / 12 | 4 / 12 | 1 / 25 |
Outcome results
None listed