Biomarker-Guided CNI Substitution in Kidney Transplantation

What is the Purpose of this Study?

The purpose of this study is to evaluate whether a blood test can predict how a person’s immune system will respond to a transplanted kidney. Researchers also aim to determine whether a non-standard (experimental) drug treatment will result in a better outcome after a kidney transplant. The study focuses on adults who will be receiving their first kidney transplant. The first part of the study is observational, which means that patients will receive standard transplant care. During this time, researchers will collect medical information, including blood and urine samples. The second part of the study will only include patients who are free of rejection and infection and have a well-functioning transplanted kidney. These participants will be randomly assigned to either continue on current (standard transplant) treatment or receive experimental drug treatment that includes giving themselves a weekly injection under the skin.

Eligibility

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

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

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Where can I participate?

Beverly

More about this Clinical Trial

What is the full name of this clinical trial?

Assessment of Biomarker-Guided CNI Substitution in Kidney Transplantation

Study Details

Disease Type/Condition

Other

Principal Investigator

Shoji, Jun

Co-Investigators

Noriko Ammerman

Age Group

Adult

Phase

IRB Number

STUDY00002438

ClinicalTrials.gov ID

NCT05917522

Key Eligibility

ClinicalTrials.gov

How do I learn more about this study?

clinicaltrials@cshs.org