RECRUITING

Assessment of Biomarker-Guided CNI Substitution In Kidney Transplantation

Talk to us

Conditions

Kidney TransplantAbataceptHLA-DR/DQ mMM

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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).

Official Title

Assessment of Biomarker-Guided Calcineurin Inhibitor (CNI) Substitution In Kidney Transplantation (RTB-015)

Quick Facts

Study Start:2023-12-07
Study Completion:2029-07
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT05917522

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 70 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. 1. Subject must be able to understand and provide informed consent
  2. 2. Received (within 14 days) or candidate for an ABO-compatible kidney transplant, including A2 to B
  3. 3. Panel Reactive Antibody \<=60% as determined by local site
  4. 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. 5. Female subjects of childbearing potential must have a negative pregnancy test upon study entry
  6. 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. 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. 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. 9. Triple Immunosuppression - Calcineurin Inhibitor/Mycophenolic Acid/Steroid (CNI/MPA/steroid)
  10. 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\])
  11. 2. MPA \[target dose: mycophenolate mofetil \>=500 mg bid or mycophenolate sodium \>=360 mg bid\]); and
  12. 3. Glucocorticoid, with a minimum dose equivalent to 5mg of prednisone per day
  13. 1. Subject must be able to understand and provide informed consent
  14. 2. A 6-month protocol biopsy free of Biopsy Proven Acute Rejection (BPAR)(by Central Pathology Core)
  15. 3. Negative 6-month serum test for DSA (by Central HLA Core)
  16. 4. eGFRCKD-EPI 30-90 ml/min/1.73m\^2 at 6 months
  17. 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
  18. 6. Minimum Mycophenolate mofetil (MPA) dose (MPA 500 mg po bid, or Mycophenolate sodium 360 mg po bid)
  19. 7. Minimum Prednisone dose of 5mg per day
  20. 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
  21. 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
  22. 10. Female subjects of childbearing potential must have a negative pregnancy test upon study entry
  23. 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
  1. 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. 2. Non-Kidney Transplant (KTx) (pre-existing or concurrent)
  3. 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. 4. Transplant in which the kidney donor is the recipient's Identical twin
  5. 5. Epstein-Barr virus (EBV) sero-negative KTx recipient
  6. 6. Chronic obstructive pulmonary disease (COPD)
  7. 7. Untreated Latent Tuberculosis (TB)
  8. 8. Human immunodeficiency virus (HIV) infection
  9. 9. Active Hepatitis B infection (HBsAg+ or anti-HBcore +)
  10. 10. Enrollment in another investigational trial
  11. 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. 12. Recent recipient of any licensed or investigational live attenuated vaccine(s) within 4 weeks of enrollment
  13. 13. Use of investigational drugs within 8 weeks of participation
  14. 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. 15. Use of Campath(R)
  16. 1. Inability or unwillingness of a participant to give written informed consent or comply with study protocol
  17. 2. Biopsy Proven Acute Rejection (BPAR) or treated clinically-diagnosed rejection in the 6 months following enrollment in the Observational Study
  18. 3. Positive for a Donor Specific Antibody (DSA) 0-6 months post-kidney transplant
  19. 4. Acute Banff interstitial (i) score \>0 on a 6-month protocol biopsy as determined by core pathology read
  20. 5. Presence of recurrent on de novo glomerulonephropathy 0-6 months post-kidney transplant
  21. 6. Presence of active infection including BK virus (BKV), Cytomegalovirus (CMV) or EBV viremia by Polymerase chain reaction (PCR) analysis
  22. 7. Unable or unwilling to undergo protocol biopsies
  23. 8. Not on Tacrolimus/Mycophenolic Acid (MPA)/Pred
  24. 9. Unable to administer therapy s.c.
  25. 10. Thrombocytopenia (\<50,000/mm\^3)
  26. 11. Pregnant, or unwilling to practice highly effective birth control
  27. 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
  28. 13. Use of investigational drugs since transplant
  29. 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 and Locations

Principal Investigator

Peter S Heeger, M.D.
STUDY_CHAIR
Cedars Sinai Medical Center: Transplantation
Peter Nickerson, M.D.
STUDY_CHAIR
University of Manitoba Max Rady College of Medicine - Transplantation

Study Locations (Sites)

University of Alabama School of Medicine: Transplantation
Birmingham, Alabama, 35233
United States
Cedars Sinai Medical Center: Transplantation
Los Angeles, California, 90048
United States
Ronald Reagan UCLA Medical Center: Transplantation
Los Angeles, California, 90095
United States
Yale University, School of Medicine: Transplantation
New Haven, Connecticut, 06519
United States
Johns Hopkins Hospital:Transplantation
Baltimore, Maryland, 21287
United States
Massachusetts General Hospital: Transplantation
Boston, Massachusetts, 02114
United States
Mayo Clinic Rochester: Transplantation
Rochester, Minnesota, 55905
United States
Washington University School of Medicine in St. Louis
Saint Louis, Missouri, 63110
United States
University of Nebraska Medical Center: Transplantation
Omaha, Nebraska, 68198
United States
Duke University Medical Center: Transplantation
Durham, North Carolina, 27710
United States
Cleveland Clinic Foundation: Transplantation
Cleveland, Ohio, 44195
United States
University of Pennsylvania Medical Center: Transplantation
Philadelphia, Pennsylvania, 19104
United States
University of Pittsburgh Medical Center: Transplantation
Pittsburgh, Pennsylvania, 15213
United States
University of Virginia Health System: Transplantation
Charlottesville, Virginia, 22908
United States
University of Wisconsin School of Medicine and Public Health: Transplantation
Madison, Wisconsin, 53726
United States

Collaborators and Investigators

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

  • Peter S Heeger, M.D., STUDY_CHAIR, Cedars Sinai Medical Center: Transplantation
  • Peter Nickerson, M.D., STUDY_CHAIR, University of Manitoba Max Rady College of Medicine - Transplantation

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-12-07
Study Completion Date2029-07

Study Record Updates

Study Start Date2023-12-07
Study Completion Date2029-07

Terms related to this study

Keywords Provided by Researchers

  • Kidney Transplant
  • Abatacept
  • HLA-DR/DQ mMM

Additional Relevant MeSH Terms

  • Kidney Transplant