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
141 Sites
350 Participants
Recruiting
18 Years to 75 Years

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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
Royal Adelaide Hospital
Adelaide,Australia,V5Z 1M9
Royal Prince Alfred Hospital
Camperdown,Australia,V6Z 1Y6
Monash Medical Centre
Clayton,Australia,R3A 1R9
Linear Clinical Research
Nedlands,Australia,B3H 1V7
Westmead Hospital
Westmead,Australia,N6A 5A5
Princess Alexandra Hospital
Woolloongabba,Australia,M5C 2T2
LKHUniversitt Hospital Graz
Graz,Austria,H4A 3J1
Universittsklinik fr Innere Medizin III Innsbruck
Innsbruck,Austria,S7M 0Z9
Medizinische Universitt Wien, Allgemeines Krankenhaus der S
Vienna,Austria,14000
UZ Antwerpen
Edegem,Belgium,38043
UZ Leuven
Leuven,Belgium,76230
Centre Hospitalier Universitaire Sart Tilman
Liège,Belgium,33076
Vancouver General Hospital Gordon & Leslie Diamond Centre
Vancouver,Canada,94010
St. Paul's Hospital, Providence Health Care, Univ. Of British Columbia
Vancouver,Canada,94270
Shared Health Inc. operating as the Health Sciences Centre
Winnipeg,Canada,87042
Queen Elizabeth II Health Sciences Centre
Halifax,Canada,69003
London Health Sciences Centre
London,Canada,13005
St. Michael's Health Centre
Toronto,Canada,34295
McGill University Health Center
Montréal,Canada,44093
St Paul's Hospital Foundation
Saskatoon,Canada,06001
Centre de Recherche du Centre Hospitalier de l'Universite de Montreal (CRCHUM)
Montréal,Canada,75010
University Health Network
Toronto,Canada,75015
Centrum kardiovaskulrn a transplantacn chirurgie Brno
Brno Střed,Czechia,86021
Fakultn Nemocnice Olomouc
Olomouc,Czechia,67098
IKEM
Prague,Czechia,31059
CHU GRENOBLE ALPES Consultation Nphrologie Bureau des ARC (Ct Chartreuse, RezdeChausse Haut)
Grenoble,France,37044
Nphrologie Pavillon Sainte Venise CHU de Rouen Hpital de Bois Guillaume
Bois-Guillaume,France,10117
Centre Hospitalier Universitaire (CHU) de Bordeaux Groupe Hospitalier Pellegrin
Bordeaux,France,4032
Centre Hospitalier Universitaire (CHU) Hopital Henri Mondor
Créteil,France,1105 AZ
Hopital Kremlin Bicetre
Le Kremlin-Bicêtre,France,1105AZ
Centre Hospitalier Universitaire (CHU) De Limoges Hopital Dupuytren
Limoges Cedex,France,9713 GZ
Hopital Edouard Herriot
Lyon,France,2333 ZA
Centre Hospitalier Regional Universitaire (CHRU) Montpellier Arnaud de Villeneuve
Montpellier,France,8003
CHU de Nantes Houtel Dieu
Nantes Cedex 1,France,8035
Centre Hospitalier Universitaire de Nice, Hopital Pasteur
Nice Cedex 1,France,8036
Hospital SaintLouis APHP
Paris,France,8907
Hopital Necker Enfants Malades
Paris,France,28034
Centre Hospitalier Universitaire de Poitiers
Poitiers,France,28040
Hopitaux Universitaire de StrasbourgCentre de References des Maladies Autoimmunes
Strasbourg,France,28041
CHU Rangueil
Toulouse,France,39008
Centre Hospitalier Regional Universitaire de Tours (CHRU de Tours) Hopital Bretonneau
Tours Cedex 9,France,46017
Charite Universitaetsmedizin Berlin Campus Charite Mitte (CCM)
Berlin,Germany,50009
Debreceni Egyetem, Klinikai Kzpont, Auguszta
Debrecen,Hungary,SE-141 86
Debreceni Egyetem Klinikai Kozpont
Debrecen,Hungary,75185
Pusan National University Hospital
Busan,Korea, Republic of
Keimyung Dongsan Medical Center
Daegu,Korea, Republic of
Asan Medical Center
Seoul,Korea, Republic of
Kangdong Sacred Heart Hospital
Seoul,Korea, Republic of
Korea University Anam Hospital
Seoul,Korea, Republic of
Kosin University Gospel Hospital
Seoul,Korea, Republic of
Kyung Hee University Hospital at Gangdong
Seoul,Korea, Republic of
Samsung Medical Center
Seoul,Korea, Republic of
Seoul National University Bundang Hospital
Seoul,Korea, Republic of
Seoul National University Hospital
Seoul,Korea, Republic of
Severance Hospital Yonsei University
Seoul,Korea, Republic of
The Catholic University of Korea, Seoul St. Mary's Hospital
Seoul,Korea, Republic of
Pusan National University Yangsan Hospital
Yangsan,Korea, Republic of
Amsterdam University Medical Center (Amsterdam UMC), Academic Medical Center (AMC)
Amsterdam,Netherlands
Amsterdam UMC location AMC
Amsterdam,Netherlands
University Medical Center Groningen
Groningen,Netherlands
Leiden University Medical Center (LUMC)
Leiden,Netherlands
Maastricht University Medical Centre
Maastricht,Netherlands
Radboud UMC
Nijmegen,Netherlands
Erasmus University Medical Center
Rotterdam,Netherlands
Universitair Medisch Centrum Utrecht
Utrecht,Netherlands
Auckland City Hospital
Auckland,New Zealand
Hospital Del Mar
Barcelona,Spain
Hospital Vall d'Hebron
Barcelona,Spain
Hospital Clinic Barcelona
Barcelona,Spain
Hospital Universitari de Bellvitge
Barcelona,Spain
Hospital Universitario Ramon y Cajal
Madrid,Spain
Hospital Clinico San Carlos
Madrid,Spain
Hospital Universitario de OctubreCentro de Actividades Ambulatorias
Madrid,Spain
Hospital Universitario Marques De Valdecilla
Santander,Spain
Centro Hospital Universitario Dr. Preset
Valencia,Spain
Hospital Universitario Miguel Servet
Zaragoza,Spain
Karolinska University Hospital
Huddinge,Sweden
Karolinska University Hospital
Solna,Sweden
Uppsala Universitet Akademiska Sjukhuset
Uppsala,Sweden
Uppsala Universitet Akademiska Sjukhuset
Uppsala,Sweden
Hualien Tzu Chi Hospital
Hualien City,Taiwan
Far Eastern Memorial Hospital
New Taipei City,Taiwan
Taichung Veterans General Hospital
Taichang,Taiwan
National Taiwan University Hospital
Taipei,Taiwan
Linkou Chang Gung Memorial Hospital
Taoyuan,Taiwan

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. 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:
  • Morphologic evidence of chronic tissue injury, as demonstrated by transplant glomerulopathy (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:
  • 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.
  • 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