Assessment of Biomarker-Guided CNI Substitution In Kidney Transplantation
Recruiting
Phase 2Interventional Study
Kidney Transplant
No Placebo Group
Every participant receives an active treatment — no one gets a placebo.
Prior Safety Data
This treatment has already been tested in at least one earlier human trial.
Ready to participate?
Review the details below, then apply to join this clinical trial.
At a Glance
Age
18 – 70
Sex
Any
Trial phase
Phase 2
Study type
Interventional
Purpose
Treatment
Participants needed
800 (estimated)
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID) · NIH
Who this trial is looking for
This trial is looking for adults who are first-time kidney transplant recipients. Participants will be monitored to see how well their body accepts the new kidney and how well they can function over time.
Are You a Good Fit for This Trial?
Must be takingTacrolimusMycophenolateSteroid
Rules you outChronic Obstructive Pulmonary DiseaseHIV infectionActive Hepatitis B infection
You may be able to join if
I can understand and give consent to participate
I am a first-time kidney transplant recipient
My blood test shows I have less than or equal to 60% Panel Reactive Antibody
I have a negative test for specific antibodies within 14 days post-transplant
I agree to use effective birth control if I can get pregnant
Vaccines are up to date as per guidelines
I am on triple immunosuppression treatment
You may not be able to join if
I am unable to provide consent or follow the study rules
I have had a kidney transplant from an identical twin
I have current lung disease or untreated latent tuberculosis
I am HIV positive or have an active hepatitis B infection
I am enrolled in another trial
I have a serious mental illness or substance abuse problem
I have had a live vaccine in the past 4 weeks
I have had recent treatment with investigational drugs
Summarized in plain language from this trial's official eligibility criteria.
The full criteria are further down this page — only the research team can
confirm whether you qualify.
Think this trial could be right for you?
Answer a few quick questions to see if you may meet the eligibility requirements.
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 wil…
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).
Trial Locations
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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 nega…
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
Contacts
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