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
100 Sites
350 Participants
Recruiting
18 Years to 75 Years

If interested, contact clinicaltrials@cslbehring.com for more information

SUBMIT
University of Alabama at Birmingham (UAB) University of Alabama Hospital (UAB Hospital)
Birmingham,Alabama,United States,35294
Mayo Clinic Hospital
Phoenix,Arizona,United States,85054
Keck Medical Center Of USC
Los Angeles,California,United States,90033
CedarsSinai Medical Center
Los Angeles,California,United States,90048
UCLA Kidney Transplant Research Program
Los Angeles,California,United States,90095
University of California Davis Medical Center
Sacramento,California,United States,95817
California Institute of Renal Research
San Diego,California,United States,92123
North America Research Institute
San Dimas,California,United States,91773
California Pacific Medical Center
San Francisco,California,United States,94109
Kaiser Permanente
San Francisco,California,United States,94118
University of California, San Francisco Medical Center
San Francisco,California,United States,94143
University Of Colorado Hospital Anschutz Medical Campus
Aurora,Colorado,United States,80045
Tampa General Medical Group
Tampa,Florida,United States,33606
Northwestern Memorial Hospital
Chicago,Illinois,United States,60611
Rush University Medical Center University Cardiovascular Surgeons
Chicago,Illinois,United States,60612
Indiana University (IU) Health Physicians Kidney Diseases Clinic Medical Diagnostic Center Location
Indianapolis,Indiana,United States,46202
Unity Point Health
Des Moines,Iowa,United States,50309
Holden Comprehensive Cancer Center, University of Iowa Hospitals and Clinics
Iowa City,Iowa,United States,52242
University of Louisville Research Foundation
Louisville,Kentucky,United States,40202
Tulane University Health Sciences Center
New Orleans,Louisiana,United States,70112
Massachusetts General Cancer Center
Boston,Massachusetts,United States,02114
Beth Israel Deaconess Medical Center
Boston,Massachusetts,United States,02215
Henry Ford Health System
Detroit,Michigan,United States,48202
University of Minnesota
Minneapolis,Minnesota,United States,55455
Mayo Clinic
Rochester,Minnesota,United States,55095
Washington University School of Medicine Infectious Diseases (WU ID) Clinic
Saint Louis,Missouri,United States,63110
University of Nebraska Medical Center
Omaha,Nebraska,United States,68105
Saint Barnabas Medical Center
Livingston,New Jersey,United States,07039
Erie County Medical Center Corp.
Buffalo,New York,United States,14215
NYU Langone Medical Center
New York,New York,United States,10016
New York Presbyterian Hospital Weill Cornell Medical Center
New York,New York,United States,10021
Columbia University Medical Center
New York,New York,United States,10032
Duke Cancer Institute
Durham,North Carolina,United States,27710
Wake Forest University Health Sciences
Winston-Salem,North Carolina,United States,27157
The Ohio State University, Comprehensive Transplant Center
Columbus,Ohio,United States,43210
University of Cincinnati
Toledo,Ohio,United States,43614
Integris Baptist Medical Center
Oklahoma City,Oklahoma,United States,73112
Lehigh Valley Health Network
Allentown,Pennsylvania,United States,18103
Central Pennsylvania Transplant Foundation
Harrisburg,Pennsylvania,United States,17104
University of Pennsylvania
Philadelphia,Pennsylvania,United States,19104
Jefferson University Hospital
Philadelphia,Pennsylvania,United States,19107
Rhode Island Hospital
Providence,Rhode Island,United States,02906
Renal Disease Research Institute
Dallas,Texas,United States,75204
UT Southwestern Medical Center
Dallas,Texas,United States,75235
Methodist Healthcare System of San Antonio
San Antonio,Texas,United States,78229
VCU Health
Richmond,Virginia,United States,23298
University of Washington
Seattle,Washington,United States,98195
University of Wisconsin School of Medicine and Public Health (UWSMPH)
Madison,Wisconsin,United States,53705
Medical College of WI Froedtert Hospital
Milwaukee,Wisconsin,United States,53226
Royal Prince Alfred Hospital
Camperdown,Australia,2050
WSLHD, Westmead Hospital
Westmead,Australia,2145
Princess Alexandra Hospital
Woolloongabba,Australia,4102
The University of Queensland Princess Alexandra Hospital (PAH)
Woolloongabba,Australia,4102
Monash Health Monash Medical Centre
Clayton,Australia,3168
The Royal Melbourne Hospital
Parkville,Australia,3064
Sir Charles Gairdner Hospital (SCGH)
Nedlands,Australia,6009
Vancouver General Hospital Gordon & Leslie Diamond Centre
Vancouver,Canada,V5Z 1M9
St. Paul's Hospital, Providence Health Care, Univ. Of British Columbia
Vancouver,Canada,V6Z 1Y6
Shared Health Inc. operating as the Health Sciences Centre
Winnipeg,Canada,R3A 1R9
Queen Elizabeth II Health Sciences Centre
Halifax,Canada,B3H 1V7
London Health Sciences Centre
London,Canada,N6A 5A5
St. Michael's Health Centre
Toronto,Canada,M5C 2T2
McGill University Health Center
Montréal,Canada,H4A 3J1
St Paul's Hospital Foundation
Saskatoon,Canada,S7M 0Z9
IKEM
Prague,Czechia,14000
CHU GRENOBLE ALPES Consultation Nphrologie Bureau des ARC (Ct Chartreuse, RezdeChausse Haut)
Grenoble,France,38043
Nphrologie Pavillon Sainte Venise CHU de Rouen Hpital de Bois Guillaume
Bois-Guillaume,France,76230
Centre Hospitalier Universitaire (CHU) de Bordeaux Groupe Hospitalier Pellegrin
Bordeaux,France,33076
Centre Hospitalier Universitaire (CHU) Hopital Henri Mondor
Créteil,France,94010
Hopital Kremlin Bicetre
Le Kremlin-Bicêtre,France,94270
Centre Hospitalier Universitaire (CHU) De Limoges Hopital Dupuytren
Limoges Cedex,France,87042
Hopital Edouard Herriot
Lyon,France,69003
Centre Hospitalier Regional Universitaire (CHRU) Montpellier Arnaud de Villeneuve
Montpellier,France,34295
CHU de Nantes Houtel Dieu
Nantes Cedex 1,France,44093
Centre Hospitalier Universitaire de Nice, Hopital Pasteur
Nice Cedex 1,France,06001
Hospital SaintLouis APHP
Paris,France,75010
Hopital Necker Enfants Malades
Paris,France,75015
Centre Hospitalier Universitaire de Poitiers
Poitiers,France,86021
Hopitaux Universitaire de StrasbourgCentre de References des Maladies Autoimmunes
Strasbourg,France,67098
CHU Rangueil
Toulouse,France,31059
Centre Hospitalier Regional Universitaire de Tours (CHRU de Tours) Hopital Bretonneau
Tours Cedex 9,France,37044
Charite Universitaetsmedizin Berlin Campus Charite Mitte (CCM)
Berlin,Germany,10117
Debreceni Egyetem, Klinikai Kzpont, Auguszta
Debrecen,Hungary,4032
Amsterdam University Medical Center (Amsterdam UMC), Academic Medical Center (AMC)
Amsterdam,Netherlands,1105 AZ
Amsterdam UMC location AMC
Amsterdam,Netherlands,1105AZ
University Medical Center Groningen
Groningen,Netherlands,9713 GZ
Leiden University Medical Center (LUMC)
Leiden,Netherlands,2333 ZA
Maastricht University Medical Centre
Maastricht,Netherlands,6248 HX
Hospital Del Mar
Barcelona,Spain,8003
Hospital Vall d'Hebron
Barcelona,Spain,8035
Hospital Clinic Barcelona
Barcelona,Spain,8036
Hospital Universitari de Bellvitge
Barcelona,Spain,8907
Hospital Universitario Ramon y Cajal
Madrid,Spain,28034
Hospital Clinico San Carlos
Madrid,Spain,28040
Hospital Universitario de OctubreCentro de Actividades Ambulatorias
Madrid,Spain,28041
Hospital Universitario Marques De Valdecilla
Santander,Spain,39008
Centro Hospital Universitario Dr. Preset
Valencia,Spain,46017
Hospital Universitario Miguel Servet
Zaragoza,Spain,50009
Karolinska University Hospital
Huddinge,Sweden,SE-141 86
Uppsala Universitet Akademiska Sjukhuset
Uppsala,Sweden,75185

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

Additional studies can be found at ClinicalTrials.gov