800 adult first time kidney transplant recipients will be enrolled in the Observational Study and followed to evaluate their Human Leukocyte Antigen (HLA)-DR/DQ molecular mismatch (mMM) score as a risk-stratifying prognostic biomarker. Six months after transplant the study will identify those who meet the eligibility criteria for the Nested Randomized Control Trial (RCT). 300 eligible subjects will be randomized 2:1 to abatacept or Standard of care (SOC) in the randomization and followed for 18 months monitoring for safety and improvement in renal function, neurocognitive function, and a life participation patient reported outcome measure (PROM).
The primary objective of the Observational Study is to test the validity of the HLA-DR/DQ mMM score as a prognostic biomarker for stratification of post-transplant alloimmune risk. Whereas the objective of the Nested RCT is to test whether a superior outcome in kidney function (primary endpoint), as well as secondary endpoints (neurocognitive function, and life participation PROM), will be achieved in patients who are transitioned from Tacrolimus (TAC) to abatacept, while maintaining efficacy (freedom from biopsy proven acute rejection).
Subject must be able to understand and provide informed consent
Received (within 14 days) or candidate for an ABO-compatible kidney transplant, including A2 to B
Panel Reactive Antibody <=60% as determined by local site
Virtual cross-match negative as determined by local site or Donor Specific Antibody (DSA) negative by central lab within 14 days post-transplant
Inability or unwillingness of a participant to give written informed consent or comply with study protocol including a mandated 6-mo kidney transplant biopsy
Non-Kidney Transplant (KTx) (pre-existing or concurrent)
Current use of immunomodulatory agents (including but not limited to: Rituximab, anti-Tumor necrosis factor(TNF) Monoclonal antibodies (mAb), or Belatacept, abatacept, Janus kinase inhibitors)
Transplant in which the kidney donor is the recipient's Identical twin
Parallel
Abatacept
Biological/VaccineInjection: 125 mg/mL of a clear to slightly opalescent, colorless to pale-yellow solution in a single-dose prefilled ClickJect autoinjector
Standard of Care at US Transplant Centers
Procedure/SurgeryControl group, remaining on SOC (Tacrolimus/ Mycophenolic Acid (MPA)/ Prednisone (Pred))
In the Observational Study - The occurrence of any alloimmune event
including de novo Donor Specific Antibody (DSA), any Biopsy Proven Acute Rejection (BPAR) (Banff borderline or greater, on a for-cause or the 6-month post-transplant protocol biopsy) and censored by non-alloimmune graft failure or death with function or lost-to-follow up.
In the Nested Randomized Control Trial (RCT) - Renal function, measured as the difference in eGFRCKD-EPI at 24-months between groups (adjusted for renal function at randomization).
In the Observational Study - The occurrence of any alloimmune event
Each component of the primary outcome, de novo Class II Donor Specific Antibody (DSA), and renal function (eGFRCKD-EPI)
In the Nested Randomized Control Trial (RCT) - Composite neurocognitive function (NIH-Toolbox Cognitive Battery) score
Adjusted for score (Uncorrected Standard Score (59-140) Higher score indicates better cognitive performance) at randomization )
In the Nested Randomized Control Trial (RCT) - Biopsy Proven Acute Rejection (BPAR) efficacy failure
Defined as time to first of: BPAR (including borderline), Death, Graft loss, Lost to follow up
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