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
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
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.
Inclusion 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. For eligibility, kidney biopsy must not be older than 12 months and DSA analysis must be performed no longer than 6 months prior to the start of Screening.
NOTE: • Within 3 months prior to the start of Screening, treatments for ABMR or TCMR, with the exception of steroids*, are not allowed (see Exclusion Criterion 3).
• If treatment for ABMR (including CABMR) or TCMR (other than steroids*) was given between 3 to 12 months of Screening, a repeat kidney biopsy and DSA analysis are required at least 6 weeks after the end of treatment to confirm continuing CABMR and presence of HLA DSA and to determine eligibility.
* A maximum dose of 2g of methylprednisolone intravenously (or dose equivalent of other steroids), followed by a taper to the original maintenance steroid dose is allowed.
The following histopathologic and serologic diagnostic criteria (based on Banff 2015 criteria [Loupy et al, 2017]) must be met for inclusion:
i. Linear C4d staining in peritubular capillaries or medullary vasa recta (Banff scores C4d2 or C4d3 by immunofluorescence on frozen sections, or C4d > 0 by immunohistochemistry on paraffin sections).
ii. At least moderate microvascular inflammation ([glomerulitis score, g + peritubular capillaritis score, 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.
c. Serologic evidence of circulating HLA DSA. NOTE: The local laboratory DSA results must be reviewed and confirmed by the central HLA reviewer during the screening period.
Written informed consent obtained from subject (or legally acceptable representative) before any trial-related procedures.
Exclusion criteria:
Birmingham, Alabama 35294, United States
San Francisco, California 94143, United States
Chicago, Illinois 60612, United States
Indianapolis, Indiana 46202, United States
Iowa City, Iowa 52242, United States
St Louis, Missouri 63110, United States
New York, New York 10021, United States
Madison, Wisconsin 53705, United States
Woolloongabba, Queensland 4102, Australia
Vancouver, British Columbia V5Z 1M9, Canada
Vancouver, British Columbia V6Z 1Y6, Canada
Grenoble, Grenoble Cédex 09 38043, France
Bois-Guillaume, 76230, France
Bordeaux, 33076, France
Montpellier, 34295, France
Strasbourg, 67098, France
Tours, 37044, France
Amsterdam, 1105 AZ, Netherlands