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Antibody-mediated Rejection

Clazakizumab for the Treatment of Chronic Active Antibody Mediated Rejection in Kidney Transplant Recipients
NCT03744910 | Phase 3 | Interventional

This trial investigates the efficacy and safety of clazakizumab [an anti-interleukin (IL)-6 monoclonal antibody (mAb)] for the treatment of CABMR in recipients of a kidney transplant.

Trial Information
21 Sites
350 Participants
18 Years to 75 Years

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Mayo Clinic Hospital
Phoenix, Arizona, 85054, United States
California Institute of Renal Research
San Diego, California, 92123, United States
NU Comprehensive Transplant Center
Chicago, Illinois, 60611, United States
Maine Medical Center Maine Medical Center Research Institute
Scarborough, Maine, 04074, United States
University of Maryland Medical Center
Baltimore, Maryland, 21201, United States
Henry Ford Health System
Detroit, Michigan, 48202, United States
Mayo Clinic
Rochester, Minnesota, 55095, United States
University of Nebraska Medical Center
Omaha, Nebraska, 68105, United States
Montefiore Medical Center
Bronx, New York, 10467, United States
NYU Langone Medical Center
New York, New York, 10016, United States
Columbia University Medical Center
New York, New York, 10032, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157, United States
University of Cincinnati
Cincinnati, Ohio, 45267, United States
Central Pennsylvania Transplant Foundation
Harrisburg, Pennsylvania, 17104, United States
Medical University of South Carolina
Charleston, South Carolina, 29425, United States
Vanderbilt Nephrology Clinical Trials
Nashville, Tennessee, 37232, United States
Renal Disease Research Institute
Dallas, Texas, 75204, United States
VCU Health
Richmond, Virginia, 23298, United States
University of Washington
Seattle, Washington, 98195, United States
Providence Medical Research Center
Spokane, Washington, 99204, United States
University of Wisconsin School of Medicine and Public Health (UWSMPH)
Madison, Wisconsin, 53705, United States

Study Eligibility Criteria

  • Age 18-75 years.
  • Living donor/deceased donor kidney transplant recipients ≥6 months from time of transplant.
  • Diagnosis of CABMR determined by kidney biopsy and the presence of HLA DSA using single-antigen bead-based assays.
  • NOTE: If conducted within 12 months (+3 weeks) prior to the start of the screening period, and no intervening treatments have been administered, the biopsy does not need to be repeated at Screening. If conducted within 6 months (+ 3 weeks) prior to the start of Screening, the DSA analysis does not need to be repeated at screening. To be considered for determination of study eligibility, the biopsy and DSA analysis must be performed at least 2 months ± 2 weeks after the end of any prior treatment for ABMR (including CABMR) or TCMR, in order to show continuing CABMR and presence of HLA DSA. In addition, with the exception of steroids, treatments for ABMR or TCMR are not allowed within 3 months prior to the start of screening.
  • The following histopathologic and serologic diagnostic criteria (based on Banff 2015 criteria [Loupy et al, 2017]) must be met for inclusion:
  • Morphologic evidence of chronic tissue injury, as demonstrated by TG (cg>0). Biopsies without evidence of chronic tissue injury on light microscopy, but with glomerular basement membrane double contours on electron microscopy (cg1a) are eligible.
  • Evidence of current/recent antibody interaction with vascular endothelium, including 1 or more of the following.
  • Linear C4d staining in peritubular capillaries or medullary vasa recta (C4d2 or C4d3 by immunofluorescence on frozen sections, or C4d > 0 by immunohistochemistry on paraffin sections).
  • At least moderate microvascular inflammation ([g + ptc] ≥ 2) in the absence of recurrent or de novo glomerulonephritis, although in the presence of acute TCMR, borderline infiltrate, or infection, ptc ≥ 2 alone is not sufficient and g must be ≥ 1.
  • NOTE: The local pathologist's diagnosis must be reviewed by a central pathologist to confirm eligibility for entry into the study. Biopsies with other histopathologic changes (eg, BKV nephropathy or recurrent glomerulonephritis) may be eligible if concurrent CABMR changes (as detailed above) are present and determined to be the predominant cause of renal dysfunction.
  • Serologic evidence of circulating DSA to HLA. NOTE: The local laboratory DSA results must be reviewed and confirmed by the central HLA reviewer during the screening period.
  • Multi-organ transplant recipient (except for simultaneous kidney-pancreas or previous multiple kidney transplants) or cell transplant (islet, bone marrow, stem cell) recipient.
  • Treatment for ABMR (including CABMR) or TCMR within 3 months prior to the start of screening with the exception of steroids.
  • Received T cell depleting agents (e.g., alemtuzumab, anti-thymocyte globulin) within 3 months prior to the start of screening.
  • Pregnant, breastfeeding, or unwillingness to practice adequate contraception.
  • Active tuberculosis (TB) or history of active TB.
  • History of human immunodeficiency virus (HIV) infection or positive for HIV.
  • Seropositive for hepatitis B surface antigen (HBsAg)
  • Hepatitis C virus (HCV) RNA positive.

Additional Studies

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