Summary

Eligibility
for people ages 18-75 (full criteria)
Location
at San Francisco, California and other locations
Dates
study started
estimated completion

Description

Summary

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.

Official Title

A Pivotal Phase 3 Trial to Evaluate the Safety and Efficacy of Clazakizumab for the Treatment of Chronic Active Antibody-mediated Rejection in Kidney Transplant Recipients

Keywords

Antibody-mediated Rejection, Chronic Active, Antibody-mediated Rejection (AMR), Clazakizumab, Physiologic saline solution

Eligibility

You can join if…

Open to people ages 18-75

  1. Age 18-75 years.
  2. Living donor/deceased donor kidney transplant recipients ≥6 months from time of transplant.
  3. 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.

  1. 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.

You CAN'T join if...

  1. Multi-organ transplant recipient (except for simultaneous kidney-pancreas or previous multiple kidney transplants) or cell transplant (islet, bone marrow, stem cell) recipient.
  2. Treatment for ABMR (including CABMR) or TCMR within 3 months prior to the start of screening with the exception of steroids.
  3. Received T cell depleting agents (e.g., alemtuzumab, anti-thymocyte globulin) within 3 months prior to the start of screening.
  4. Pregnant, breastfeeding, or unwillingness to practice adequate contraception.
  5. Active tuberculosis (TB) or history of active TB.
  6. History of human immunodeficiency virus (HIV) infection or positive for HIV.
  7. Seropositive for hepatitis B surface antigen (HBsAg)
  8. Hepatitis C virus (HCV) RNA positive.

Locations

  • University of California, San Francisco Medical Center accepting new patients
    San Francisco California 94143 United States
  • Kaiser Permanente accepting new patients
    San Francisco California 94118 United States
  • California Pacific Medical Center accepting new patients
    San Francisco California 94109 United States
  • Mayo Clinic accepting new patients
    Rochester Minnesota 55095 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
CSL Behring
ID
NCT03744910
Phase
Phase 3 research study
Study Type
Interventional
Participants
Expecting 350 study participants
Last Updated