Assessment of Biomarker-Guided CNI Substitution In Kidney Transplantation
Assessment of Biomarker-Guided Calcineurin Inhibitor (CNI) Substitution In Kidney Transplantation (RTB-015)
National Institute of Allergy and Infectious Diseases (NIAID)
800 participants
Dec 7, 2023
INTERVENTIONAL
Conditions
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).
Eligibility
Inclusion Criteria25
- Observational Study:
- 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
- Female subjects of childbearing potential must have a negative pregnancy test upon study entry
- All subjects with reproductive potential must agree to use highly effective contraception for the duration of the study (http://www.fda.gov/birthcontrol)
- Hepatitis C Virus Ab positive subjects with negative Hepatitis C Virus polymerase chain reaction (HCV PCR) are eligible if they have spontaneously cleared infection or are in sustained virologic remission
- Vaccines up to date as per Division of Allergy, Immunology, and Transplantation (DAIT) guidance for patients in transplant trials (Refer to Manual of Procedures).
- Triple Immunosuppression - Calcineurin Inhibitor/Mycophenolic Acid/Steroid (CNI/MPA/steroid)
- CNI (Tacrolimus (TAC), target trough \[C0\] level: 0-3 mo, 8-12 ng/mL; 4-6 mo, 6-10 ng/mL; \>6 mo, 5-8 ng/mL\])
- MPA \[target dose: mycophenolate mofetil \>=500 mg bid or mycophenolate sodium \>=360 mg bid\]); and
- Glucocorticoid, with a minimum dose equivalent to 5mg of prednisone per day
- Nested Randomized Control Trial (RCT):
- Subject must be able to understand and provide informed consent
- A 6-month protocol biopsy free of Biopsy Proven Acute Rejection (BPAR)(by Central Pathology Core)
- Negative 6-month serum test for DSA (by Central HLA Core)
- eGFRCKD-EPI 30-90 ml/min/1.73m\^2 at 6 months
- Has a verified negative purified protein derivative (PPD) or negative testing for tuberculosis using an approved IGRA blood test, such as QuantiFERON Gold TB or T-SPOT-TB assay OR has completed treatment for latent tuberculosis and has a negative chest x-ray. PPD or IGRA testing must occur within 52 weeks prior to randomization. These requirements apply as well to prior recipients of Bacille Calmette-Gurin (BCG) vaccination
- Minimum Mycophenolate mofetil (MPA) dose (MPA 500 mg po bid, or Mycophenolate sodium 360 mg po bid)
- Minimum Prednisone dose of 5mg per day
- Hepatitis C Virus Ab positive subjects with negative HCV PCR are eligible if they have spontaneously cleared infection or are in sustained virologic remission
- Hepatitis C Virus negative recipients of a Hepatitis C Virus positive organ are eligible if they have undergone treatment and are in sustained virologic remission
- Female subjects of childbearing potential must have a negative pregnancy test upon study entry
- All subjects with reproductive potential, must agree to use highly effective contraception the duration of the study-specific methods may be listed, if applicable
Exclusion Criteria31
- Observational Study:
- 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
- Epstein-Barr virus (EBV) sero-negative KTx recipient
- Chronic obstructive pulmonary disease (COPD)
- Untreated Latent Tuberculosis (TB)
- Human immunodeficiency virus (HIV) infection
- Active Hepatitis B infection (HBsAg+ or anti-HBcore +)
- Enrollment in another investigational trial
- Current, diagnosed, mental illness or current, diagnosed or self-reported drug or alcohol abuse that, in the opinion of the investigator, would interfere with the participant's ability to comply with study requirements
- Recent recipient of any licensed or investigational live attenuated vaccine(s) within 4 weeks of enrollment
- Use of investigational drugs within 8 weeks of participation
- Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study
- Use of Campath(R)
- Nested Randomized Control Trial (RCT):
- Inability or unwillingness of a participant to give written informed consent or comply with study protocol
- Biopsy Proven Acute Rejection (BPAR) or treated clinically-diagnosed rejection in the 6 months following enrollment in the Observational Study
- Positive for a Donor Specific Antibody (DSA) 0-6 months post-kidney transplant
- Acute Banff interstitial (i) score \>0 on a 6-month protocol biopsy as determined by core pathology read
- Presence of recurrent on de novo glomerulonephropathy 0-6 months post-kidney transplant
- Presence of active infection including BK virus (BKV), Cytomegalovirus (CMV) or EBV viremia by Polymerase chain reaction (PCR) analysis
- Unable or unwilling to undergo protocol biopsies
- Not on Tacrolimus/Mycophenolic Acid (MPA)/Pred
- Unable to administer therapy s.c.
- Thrombocytopenia (\<50,000/mm\^3)
- Pregnant, or unwilling to practice highly effective birth control
- Use of immunomodulatory agents (including but not limited to Rituximab, anti-TNF mAb, or Belatacept, abatacept, Janus kinase inhibitors) \* since enrollment, other than cytolytic agents (i.e., Thymoglobulin(R)or Campath(R) or Basiliximab(R) used for induction therapy at the time of transplant
- Use of investigational drugs since transplant
- Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study
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Interventions
Injection: 125 mg/mL of a clear to slightly opalescent, colorless to pale-yellow solution in a single-dose prefilled ClickJect autoinjector
Control group, remaining on SOC (Tacrolimus/ Mycophenolic Acid (MPA)/ Prednisone (Pred))
Locations(15)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT05917522