NCT05917522 Assessment of Biomarker-Guided CNI Substitution In Kidney Transplantation
| NCT ID | NCT05917522 |
| Status | Recruiting |
| Phase | Phase 2 |
| Sponsor | National Institute of Allergy and Infectious Diseases (NIAID) |
| Condition | Kidney Transplant |
| Study Type | INTERVENTIONAL |
| Enrollment | 800 participants |
| Start Date | 2023-12-07 |
| Primary Completion | 2027-07 |
Eligibility & Interventions
Eligibility Fast-Check
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What to Expect as a Participant
You will actively receive the study intervention — which may be a drug, biologic, device, or procedure.
In Phase 2, researchers evaluate early signs of effectiveness. You may be randomized to receive the active treatment or a comparator. Monitoring continues closely.
This trial targets 800 participants in total. It began in 2023-12-07 with a primary completion date of 2027-07.
⚠ This information is for research awareness only. Always consult your physician before joining any clinical trial. Participation is voluntary and you may withdraw at any time.
Brief 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 Criteria
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 contraception for the duration of the study (http://www.fda.gov/birthcontrol) 7. 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 8. Vaccines up to date as per Division of Allergy, Immunology, and Transplantation (DAIT) guidance for patients in transplant trials (Refer to Manual of Procedures). 9. Triple Immunosuppression - Calcineurin Inhibitor/Mycophenolic Acid/Steroid (CNI/MPA/steroid) 1. 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\]) 2. MPA \[target dose: mycophenolate mofetil \>=500 mg bid or mycophenolate sodium \>=360 mg bid\]); and 3. Glucocorticoid, with a minimum dose equivalent to 5mg of prednisone per day Nested Randomized Control Trial (RCT): 1. Subject must be able to understand and provide informed consent 2. A 6-month protocol biopsy free of Biopsy Proven Acute Rejection (BPAR)(by Central Pathology Core) 3. Negative 6-month serum test for DSA (by Central HLA Core) 4. eGFRCKD-EPI 30-90 ml/min/1.73m\^2 at 6 months 5. 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 6. Minimum Mycophenolate mofetil (MPA) dose (MPA 500 mg po bid, or Mycophenolate sodium 360 mg po bid) 7. Minimum Prednisone dose of 5mg per day 8. Hepatitis C Virus Ab positive subjects with negative HCV PCR are eligible if they have spontaneously cleared infection or are in sustained virologic remission 9. 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 10. Female subjects of childbearing potential must have a negative pregnancy test upon study entry 11. 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 Criteria: Observational Study: 1. Inability or unwillingness of a participant to give written informed consent or comply with study protocol including a mandated 6-mo kidney transplant biopsy 2. Non-Kidney Transplant (KTx) (pre-existing or concurrent) 3. 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) 4. Transplant in which the kidney donor is the recipient's Identical twin 5. Epstein-Barr virus (EBV) sero-negative KTx recipient 6. Chronic obstructive pulmonary disease (COPD) 7. Untreated Latent Tuberculosis (TB) 8. Human immunodeficiency virus (HIV) infection 9. Active Hepatitis B infection (HBsAg+ or anti-HBcore +) 10. Enrollment in another investigational trial 11. 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 12. Recent recipient of any licensed or investigational live attenuated vaccine(s) within 4 weeks of enrollment 13. Use of investigational drugs within 8 weeks of participation 14. 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 15. Use of Campath(R) Nested Randomized Control Trial (RCT): 1. Inability or unwillingness of a participant to give written informed consent or comply with study protocol 2. Biopsy Proven Acute Rejection (BPAR) or treated clinically-diagnosed rejection in the 6 months following enrollment in the Observational Study 3. Positive for a Donor Specific Antibody (DSA) 0-6 months post-kidney transplant 4. Acute Banff interstitial (i) score \>0 on a 6-month protocol biopsy as determined by core pathology read 5. Presence of recurrent on de novo glomerulonephropathy 0-6 months post-kidney transplant 6. Presence of active infection including BK virus (BKV), Cytomegalovirus (CMV) or EBV viremia by Polymerase chain reaction (PCR) analysis 7. Unable or unwilling to undergo protocol biopsies 8. Not on Tacrolimus/Mycophenolic Acid (MPA)/Pred 9. Unable to administer therapy s.c. 10. Thrombocytopenia (\<50,000/mm\^3) 11. Pregnant, or unwilling to practice highly effective birth control 12. 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 13. Use of investigational drugs since transplant 14. 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
Contact & Investigator
Peter S Heeger, M.D.
STUDY CHAIR
Cedars Sinai Medical Center: Transplantation
Frequently Asked Questions
Who can join the NCT05917522 clinical trial?
This trial is open to participants of all sexes, aged 18 Years or older, up to 70 Years, studying Kidney Transplant. Full inclusion and exclusion criteria are listed in the Eligibility Criteria section. Always confirm your eligibility with the research team before applying.
What phase is the NCT05917522 trial and what does that mean for participants?
Phase 2 trials evaluate whether the treatment shows signs of effectiveness while continuing to monitor safety. More participants are enrolled than in Phase 1 to help refine the treatment protocol.
Is NCT05917522 currently recruiting?
Yes, NCT05917522 is actively recruiting participants. Visit ClinicalTrials.gov or contact National Institute of Allergy and Infectious Diseases (NIAID) to inquire about joining.
Where is the NCT05917522 trial being conducted?
This trial is being conducted at Birmingham, United States, Los Angeles, United States, Los Angeles, United States, New Haven, United States and 11 additional locations.
Who is sponsoring the NCT05917522 clinical trial?
NCT05917522 is sponsored by National Institute of Allergy and Infectious Diseases (NIAID). The principal investigator is Peter S Heeger, M.D. at Cedars Sinai Medical Center: Transplantation. The trial plans to enroll 800 participants.
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