Immunosuppression, Kidney Transplant Rejection
Conditions
Brief summary
* To determine the utility of novel blood-based immune monitoring tools (Allosure and Trugraf) to facilitate belatacept monotherapy. * To determine the percent of belatacept-treated renal transplant patients that can be safely converted to belatacept monotherapy.
Detailed description
This study will examine whether renal transplant recipients treated with a belatacept-based immunosuppressive regimen can safely be weaned off all non-belatacept immunosuppression (mycophenolate, mTORi, prednisone) in a stepwise fashion. To this end, participants will undergo monthly immune monitoring using the Allosure (dd-cfDNA) and Trugraf (RNA profiling) blood tests to determine if they are in a state of immune quiescence. Only patients who are deemed to be immune quiescent, will continue to be weaned of non-belatacept immunosuppression.
Interventions
DIAGNOSTIC_TESTAllosure
Monthly monitoring of dd-cfDNA levels in blood
Stepwise reduction in the dose, and ultimate discontinuation of, all non-belatacept immunosuppression (mycophenolate, sirolimus, everolimus, prednisone) guided by monitoring of Allosure and Trugraf results
DIAGNOSTIC_TESTTrugraf
Monthly monitoring of Trugraf result
Sponsors
Transplant Genomics, Inc.
CareDx
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention model description
Prospective single-center, single-arm pilot study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age minimum 18 years * Written informed consent * Single kidney transplant recipient (i.e. no combined organ transplants) * Treated with de novo belatacept since transplantation (i.e. no previous use of calcineurin inhibitor or mTOR inhibitor for the current transplant) * At least 1 year after transplantation or after initiation of belatacept * Stable renal function (eGFR \> 40 ml/min continuously during previous 6 months) * Blood biomarkers indicate immune quiescence (for Allosure this corresponds to dd-cfDNA \< 1%; for Trugraf this corresponds to TX signature) * No history of BK viremia in current allograft
Exclusion criteria
* History of biopsy-proven acute rejection * Presence of donor-specific antibodies (at any MFI) * Spot urine protein/creatinine ratio \> 0.5 g/g
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Acute Rejection | Enrollment through 12 months | Biopsy-proven according to Banff 2017 criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Increase in eGFR | From baseline to 12 months | Calculated using CKD-EPI formula |
| Rate of New-onset Proteinuria | At 12 months | Defined as g/g creatinine, measured on random urine sample |
| Incidence of de Novo Donor Specific Antibodies | At 12 months | Screened for using Luminex platform |
| Survival | At 12 months | Overall and death-censored graft survival |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Belatacept Treated Patients Renal transplant recipients treated with a combination of belatacept and any of the following: mycophenolate, sirolimus, everolimus and prednisone
Allosure: Monthly monitoring of dd-cfDNA levels in blood
Immunosuppression reduction: Stepwise reduction in the dose, and ultimate discontinuation of, all non-belatacept immunosuppression (mycophenolate, sirolimus, everolimus, prednisone) guided by monitoring of Allosure and Trugraf results
Trugraf: Monthly monitoring of Trugraf result | 17 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Problems with the Trugraf assay | 1 |
| Overall Study | Screen Failure | 3 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Belatacept Treated Patients |
|---|---|
| Age, Customized 18 years or older | 17 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 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 | 1 Participants |
| Race (NIH/OMB) White | 12 Participants |
| Region of Enrollment United States | 17 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 12 |
| other Total, other adverse events | 5 / 12 |
| serious Total, serious adverse events | 0 / 12 |
Outcome results
Primary
Incidence of Acute Rejection
Biopsy-proven according to Banff 2017 criteria
Time frame: Enrollment through 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Belatacept Treated Patients | Incidence of Acute Rejection | 0 Participants |
Primary
Incidence of Acute Rejection
Biopsy-proven according to Banff 2017 criteria
Time frame: Through study completion, 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Belatacept Treated Patients | Incidence of Acute Rejection | 0 Participants |
Secondary
Incidence of de Novo Donor Specific Antibodies
Screened for using Luminex platform
Time frame: At 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Belatacept Treated Patients | Incidence of de Novo Donor Specific Antibodies | 0 Participants |
Secondary
Increase in eGFR
Calculated using CKD-EPI formula
Time frame: From baseline to 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Belatacept Treated Patients | Increase in eGFR | 6 Participants |
Secondary
Rate of New-onset Proteinuria
Defined as g/g creatinine, measured on random urine sample
Time frame: At 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Belatacept Treated Patients | Rate of New-onset Proteinuria | 1 Participants |
Secondary
Survival
Overall and death-censored graft survival
Time frame: At 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Belatacept Treated Patients | Survival | 12 Participants |