Assessment of Biomarker-Guided Calcineurin Inhibitor (CNI) Substitution In Kidney Transplantation (RTB-015)
National Institute of Allergy and Infectious Diseases (NIAID)
Summary
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).
Description
Observational Study: Enrolling 800 adult first time kidney transplant recipients. Consent and enrollment will be targeted to occur pre- or post-kidney transplant during the initial hospitalization. All subjects enrolled in the study will be followed observationally to evaluate HLA-DR/DQ molecular mismatched (mMM) as a risk-stratifying prognostic biomarker. This prospective, multi-center, observational study of 800 kidney transplant recipients at clinically low risk for alloimmune memory (DSA negative pre-kidney transplant) who are initiated on standard of care (SOC) therapy will be used to s…
Eligibility
- Age range
- 18–70 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: Observational Study: 1. Subject must be able to understand and provide informed consent 2. Received (within 14 days) or candidate for an ABO-compatible kidney transplant, including A2 to B 3. Panel Reactive Antibody \<=60% as determined by local site 4. Virtual cross-match negative as determined by local site or Donor Specific Antibody (DSA) negative by central lab within 14 days post-transplant 5. Female subjects of childbearing potential must have a negative pregnancy test upon study entry 6. All subjects with reproductive potential must agree to use highly effective co…
Interventions
- BiologicalAbatacept
Injection: 125 mg/mL of a clear to slightly opalescent, colorless to pale-yellow solution in a single-dose prefilled ClickJect autoinjector
- ProcedureStandard of Care at US Transplant Centers
Control group, remaining on SOC (Tacrolimus/ Mycophenolic Acid (MPA)/ Prednisone (Pred))
Locations (15)
- University of Alabama School of Medicine: TransplantationBirmingham, Alabama
- Cedars Sinai Medical Center: TransplantationLos Angeles, California
- Ronald Reagan UCLA Medical Center: TransplantationLos Angeles, California
- Yale University, School of Medicine: TransplantationNew Haven, Connecticut
- Johns Hopkins Hospital:TransplantationBaltimore, Maryland
- Massachusetts General Hospital: TransplantationBoston, Massachusetts