Clazakizumab for the Treatment of Chronic Active Antibody Mediated Rejection in Kidney Transplant Recipients (IMAGINE)

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.

Study Overview

• Status: Terminated
• Conditions: Antibody-mediated Rejection
• Intervention / Treatment: Biological: Clazakizumab; Drug: Physiologic saline solution

• Study Type: Interventional
• Enrollment (Actual): 194
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Adelaide, Australia
    • Royal Adelaide Hospital
  • Camperdown, Australia
    • Royal Prince Alfred Hospital
  • Clayton, Australia
    • Monash Medical Centre
  • Nedlands, Australia
    • Linear Clinical Research
  • Westmead, Australia
    • Westmead Hospital
  • Woolloongabba, Australia
    • Princess Alexandra Hospital
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
    • Westmead, New South Wales, Australia, 2145
      • WSLHD, Westmead Hospital
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital
    • Woolloongabba, Queensland, Australia, 4102
      • The University of Queensland - Princess Alexandra Hospital (PAH)
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Health Monash Medical Centre
    • Parkville, Victoria, Australia, 3064
      • The Royal Melbourne Hospital
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Sir Charles Gairdner Hospital (SCGH)
• Austria
  • Graz, Austria
    • LKH-Universität Hospital Graz
  • Innsbruck, Austria
    • Universitätsklinik für Innere Medizin III Innsbruck
  • Vienna, Austria
    • Medizinische Universität Wien, Allgemeines Krankenhaus der S
• Belgium
  • Edegem, Belgium
    • UZ Antwerpen
  • Leuven, Belgium
    • UZ Leuven
  • Liège, Belgium
    • Centre Hospitalier Universitaire Sart Tilman
• Canada
  • Montréal, Canada
    • Centre de Recherche du Centre Hospitalier de l'Université de Montreal (CRCHUM)
  • Toronto, Canada
    • University Health Network
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Vancouver General Hospital - Gordon & Leslie Diamond Centre
    • Vancouver, British Columbia, Canada, V6Z 1Y6
      • St. Paul's Hospital, Providence Health Care, Univ. Of British Columbia
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3A 1R9
      • Shared Health Inc. operating as the Health Sciences Centre
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • Queen Elizabeth II Health Sciences Centre
  • Ontario
    • London, Ontario, Canada, N6A 5A5
      • London Health Sciences Centre
    • Toronto, Ontario, Canada, M5C 2T2
      • St. Michael's Health Centre
  • Quebec
    • Montréal, Quebec, Canada, H4A 3J1
      • McGill University Health Center
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7M 0Z9
      • St Paul's Hospital Foundation
• Czechia
  • Brno Střed, Czechia
    • Centrum kardiovaskulární a transplantacní chirurgie Brno
  • Olomouc, Czechia
    • Fakultni nemocnice Olomouc
  • Prague, Czechia, 14000
    • IKEM
• France
  • Bois-Guillaume, France, 76230
    • Néphrologie - Pavillon Sainte Venise - CHU de Rouen - Hôpital de Bois Guillaume
  • Bordeaux, France, 33076
    • Centre Hospitalier Universitaire (CHU) de Bordeaux - Groupe Hospitalier Pellegrin
  • Créteil, France, 94010
    • Centre Hospitalier Universitaire (CHU) - Hopital Henri Mondor
  • Le Kremlin-Bicêtre, France, 94270
    • Hôpital Kremlin Bicêtre
  • Limoges Cedex, France, 87042
    • Centre Hospitalier Universitaire (CHU) De Limoges Hopital Dupuytren
  • Lyon, France, 69003
    • Hôpital Edouard Herriot
  • Marseille, France, 13005
    • Hopital de la Conception - APHM
  • Montpellier, France, 34295
    • Centre Hospitalier Regional Universitaire (CHRU) Montpellier Arnaud de Villeneuve
  • Nantes Cedex 1, France, 44093
    • CHU de Nantes - Houtel Dieu
  • Nice Cedex 1, France, 06001
    • Centre Hospitalier Universitaire de Nice, Hopital Pasteur 2
  • Paris, France, 75015
    • Hopital Necker Enfants Malades
  • Paris, France, 75010
    • Hospital Saint-Louis - APHP
  • Poitiers, France, 86021
    • Centre Hospitalier Universitaire de Poitiers
  • Strasbourg, France, 67098
    • Hopitaux Universitaire de Strasbourg-Centre de References des Maladies Autoimmunes
  • Toulouse, France, 31059
    • CHU Rangueil
  • Tours Cedex 9, France, 37044
    • Centre Hospitalier Regional Universitaire de Tours (CHRU de Tours) - Hopital Bretonneau
  • Grenoble Cédex 09
    • Grenoble, Grenoble Cédex 09, France, 38043
      • CHU GRENOBLE ALPES - Consultation Néphrologie Bureau des ARC (Côté Chartreuse, Rez-de-Chaussée Haut)
• Germany
  • Berlin, Germany, 10117
    • Charite - Universitaetsmedizin Berlin - Campus Charite Mitte (CCM)
• Hungary
  • Debrecen, Hungary
    • Debreceni Egyetem Klinikai Kozpont
  • Debrecen, Hungary, 4032
    • Debreceni Egyetem, Klinikai Központ, Auguszta
• Korea, Republic of
  • Busan, Korea, Republic of
    • Pusan National University Hospital
  • Daegu, Korea, Republic of
    • Keimyung Dongsan Medical Center
  • Seoul, Korea, Republic of
    • Seoul National University Hospital
  • Seoul, Korea, Republic of
    • Asan Medical Center
  • Seoul, Korea, Republic of
    • Samsung Medical Center
  • Seoul, Korea, Republic of
    • Kyung Hee University Hospital at Gangdong
  • Seoul, Korea, Republic of
    • Kangdong Sacred Heart Hospital
  • Seoul, Korea, Republic of
    • Korea University Anam Hospital
  • Seoul, Korea, Republic of
    • The Catholic University of Korea, Seoul St. Mary's Hospital
  • Seoul, Korea, Republic of
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of
    • Severance Hospital Yonsei University
  • Seoul, Korea, Republic of
    • Kosin University Gospel Hospital
  • Yangsan, Korea, Republic of
    • Pusan National University Yangsan Hospital
• Netherlands
  • Amsterdam, Netherlands, 1105AZ
    • Amsterdam UMC location AMC
  • Amsterdam, Netherlands, 1105 AZ
    • Amsterdam University Medical Center (Amsterdam UMC), Academic Medical Center (AMC)
  • Groningen, Netherlands, 9713 GZ
    • University Medical Center Groningen
  • Leiden, Netherlands, 2333 ZA
    • Leiden University Medical Center (LUMC)
  • Maastricht, Netherlands, 6248 HX
    • Maastricht University Medical Centre
  • Nijmegen, Netherlands
    • Radboud UMC
  • Rotterdam, Netherlands
    • Erasmus University Medical Center
  • Utrecht, Netherlands
    • Universitair Medisch Centrum Utrecht
• New Zealand
  • Auckland, New Zealand
    • Auckland City Hospital
• Spain
  • Barcelona, Spain, 8003
    • Hospital Del Mar
  • Barcelona, Spain, 8035
    • Hospital Vall d'Hebron
  • Barcelona, Spain, 8036
    • Hospital Clinic Barcelona
  • Barcelona, Spain, 8907
    • Hospital Universitari de Bellvitge
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre-Centro de Actividades Ambulatorias
  • Santander, Spain, 39008
    • Hospital Universitario Marqués de Valdecilla
  • Valencia, Spain, 46017
    • Centro Hospital Universitario Dr. Preset
  • Zaragoza, Spain, 50009
    • Hospital Universitario Miguel Servet
• Sweden
  • Huddinge, Sweden, SE-141 86
    • Karolinska University Hospital
  • Solna, Sweden
    • Karolinska University Hospital
  • Uppsala, Sweden, 75185
    • Uppsala Universitet - Akademiska Sjukhuset
  • Uppsala, Sweden
    • Uppsala Universitet - Akademiska Sjukhuset
• Taiwan
  • Hualien City, Taiwan
    • Hualien Tzu Chi Hospital
  • New Taipei City, Taiwan
    • Far Eastern Memorial Hospital
  • Taichang, Taiwan
    • Taichung Veterans General Hospital
  • Taipei, Taiwan
    • National Taiwan University Hospital
  • Taoyuan, Taiwan
    • Linkou Chang Gung Memorial Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham (UAB) - University of Alabama Hospital (UAB Hospital)
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Hospital
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Los Angeles, California, United States, 90033
      • Keck Medical Center of USC
    • Los Angeles, California, United States, 90095
      • UCLA Kidney Transplant Research Program
    • Sacramento, California, United States, 95817
      • University of California Davis Medical Center
    • San Diego, California, United States, 92123
      • California Institute of Renal Research
    • San Dimas, California, United States, 91773
      • North America Research Institute
    • San Francisco, California, United States, 94143
      • University of California, San Francisco Medical Center
    • San Francisco, California, United States, 94118
      • Kaiser Permanente
    • San Francisco, California, United States, 94109
      • California Pacific Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital - Anschutz Medical Campus
  • Florida
    • Tampa, Florida, United States, 33606
      • Tampa General Medical Group
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center - University Cardiovascular Surgeons
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University (IU) Health Physicians - Kidney Diseases Clinic - Medical Diagnostic Center Location
  • Iowa
    • Des Moines, Iowa, United States, 50309
      • Unity Point Health
    • Iowa City, Iowa, United States, 52242
      • Holden Comprehensive Cancer Center, University of Iowa Hospitals and Clinics
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville Research Foundation
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University Health Sciences Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Cancer Center
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
    • Rochester, Minnesota, United States, 55095
      • Mayo Clinic
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine - Infectious Diseases (WU ID) Clinic
  • Nebraska
    • Omaha, Nebraska, United States, 68105
      • University of Nebraska Medical Center
  • New Jersey
    • Livingston, New Jersey, United States, 07039
      • Saint Barnabas Medical Center
  • New York
    • Buffalo, New York, United States, 14215
      • Erie County Medical Center Corp.
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10016
      • NYU Langone Medical Center
    • New York, New York, United States, 10021
      • New York Presbyterian Hospital / Weill Cornell Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Cancer Institute
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University, Comprehensive Transplant Center
    • Toledo, Ohio, United States, 43614
      • University of Cincinnati
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • INTEGRIS Baptist Medical Center
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
      • Lehigh Valley Health Network
    • Harrisburg, Pennsylvania, United States, 17104
      • Central Pennsylvania Transplant Foundation
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Jefferson University Hospital
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • Rhode Island Hospital
  • Texas
    • Dallas, Texas, United States, 75235
      • UT Southwestern Medical Center
    • Dallas, Texas, United States, 75204
      • Renal Disease Research Institute
    • San Antonio, Texas, United States, 78229
      • Methodist Healthcare System of San Antonio
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Vcu Health
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • University of Wisconsin School of Medicine and Public Health (UWSMPH)
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of WI Froedtert Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

• Inclusion criteria:

  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. 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:

     1. 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.
     2. 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.

  4. Written informed consent obtained from subject (or legally acceptable representative) before any trial-related procedures.

• Exclusion criteria:

  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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Clazakizumab; Clazakizumab is a genetically engineered humanized immunoglobulin G1 (IgG1) mAb that binds to human IL-6 that is administered subcutaneously.	Biological: Clazakizumab; Clazakizumab is a genetically engineered humanized immunoglobulin G1 (IgG1) mAb that binds to human IL-6
Placebo Comparator: Placebo; Physiologic saline solution that is administered subcutaneously.	Drug: Physiologic saline solution; Normal saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 52 in Estimated Glomerular Filtration Rate (eGFR)	This primary outcome measure was the one from the first interim analysis.	From Baseline to Week 52
Number of Participants With Composite All-cause Allograft Loss or Irreversible Loss of Allograft Function	Composite all-cause allograft loss or irreversible loss of allograft function, defined as time to first occurrence of any of the following components: eGFR < 15 milliliters per minute per 1.73 square meters (mL/min/1.73 m^2)*; return to dialysis*; allograft nephrectomy; retransplantation; death from any cause, or; a sustained (greater than or equal to [>=] 60 days) 40% decline in eGFR from Baseline. (*Total cumulative duration of sustained eGFR < 15 mL/min/1.73 m^2 AND / OR dialysis >= 60 days.) If the eGFR < 15 mL/min/1.73 m^2 was the only component reached, the value must be sustained over at least 60 days and must be confirmed by a repeat measurement after >= 60 days from the first measurement. The number of participants with composite all-cause allograft loss or irreversible loss of allograft function are reported here. Time-to-event data were not calculated due to the study's termination.	From Baseline to 4 years
Percentage of Participants With Composite All-cause Allograft Loss or Irreversible Loss of Allograft Function	Composite all-cause allograft loss or irreversible loss of allograft function, defined as time to first occurrence of any of the following components: eGFR < 15 mL/min/1.73 m^2*; return to dialysis*; allograft nephrectomy; retransplantation; death from any cause, or; a sustained (greater than or equal to [>=] 60 days) 40% decline in eGFR from Baseline. (*Total cumulative duration of sustained eGFR < 15 mL/min/1.73 m^2 AND / OR dialysis >= 60 days.) If the eGFR < 15 mL/min/1.73 m^2 was the only component reached, the value must be sustained over at least 60 days and must be confirmed by a repeat measurement after >= 60 days from the first measurement. The percentage of participants with composite all-cause allograft loss or irreversible loss of allograft function are reported here.	From Baseline to 4 years
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, and Adverse Events of Special Interest (AESIs)		Up to 4 years
Percentage of Participants With TEAEs, Serious TEAEs, and AESIs		Up to 4 years
Number of Participants Who Tested Positive for Polyoma BK Virus (BKV), Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV)	Number of participants who tested positive for BKV, CMV or EBV according to the maximum measured viral amount (International Units/mL [IU/mL]) after baseline are reported here.	From baseline up to 4 years
Number of Participants With Abnormal Laboratory Test Results	Laboratory tests included liver function test (LFTs), complete blood count (CBC), plasma lipids, high-sensitivity C-reactive protein (hsCRP). Only participants with abnormal laboratory test results are reported here. Here, ULN = upper limit of normal, LLN = lower limit of normal, ALT = Alanine aminotransferase and AST = Aspartate aminotransferase.	Up to 4 years
Percentage of Participants With Abnormal Laboratory Test Results	Laboratory tests included LFTs, CBC, plasma lipids, hsCRP. Only percentage of participants with abnormal laboratory test results are reported here. Here, ULN = upper limit of normal, LLN = lower limit of normal, ALT = Alanine aminotransferase and AST = Aspartate aminotransferase.	Up to 4 years
Number of Participants With Clinically Significant Change in Vital Signs, Electrocardiograms (ECGs), and Physical Examination		Up to 4 years
Number of Participants With Positive Anti-drug Antibodies		Baseline, Weeks 12, 24, and 48
Percentage of Participants With Positive Anti-drug Antibodies		Baseline, Weeks 12, 24, and 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Composite All-cause Allograft Loss	Composite all-cause allograft loss, defined as, time to first occurrence of any of the following components: eGFR < 15 mL/min/1.73 m^2*; return to dialysis*; allograft nephrectomy; retransplantation, or; death from any cause. (*Total cumulative duration of sustained eGFR < 15 mL/min/1.73 m^2 AND / OR dialysis >= 60 days.) If the eGFR < 15 mL/min/1.73 m^2 was the only component reached, the value must be sustained over at least 60 days and must be confirmed by a repeat measurement after >= 60 days from the first measurement. The number of participants with composite all-cause allograft loss are reported here.	From Baseline to 4 years
Percentage of Participants With Composite All-cause Allograft Loss	Composite all-cause allograft loss, defined as, time to first occurrence of any of the following components: eGFR < 15 mL/min/1.73 m^2*; return to dialysis*; allograft nephrectomy; retransplantation, or; death from any cause. (*Total cumulative duration of sustained eGFR < 15 mL/min/1.73 m^2 AND / OR dialysis >= 60 days.) If the eGFR < 15 mL/min/1.73 m^2 was the only component reached, the value must be sustained over at least 60 days and must be confirmed by a repeat measurement after >= 60 days from the first measurement. The percentage of participants with composite all-cause allograft loss are reported here.	From Baseline to 4 years
Number of Participants With Irreversible Loss of Allograft Function	Irreversible loss of allograft function as defined by a 40% decline in eGFR from Baseline sustained for at least 60 days.	From Baseline to 4 years
Percentage of Participants With Irreversible Loss of Allograft Function	Irreversible loss of allograft function as defined by a 40% decline in eGFR from Baseline sustained for at least 60 days.	From Baseline to 4 years
Number of Participants With Death-censored Allograft Loss	Time to death-censored allograft loss, was defined as occurrence of any of the following components: eGFR < 15 mL/min/1.73 m^2*; return to dialysis*; allograft nephrectomy, or; retransplantation. (*Total cumulative duration of sustained eGFR < 15 mL/min/1.73 m^2 AND / OR dialysis >= 60 days.) If the eGFR < 15 mL/min/1.73 m^2 was the only component reached, the value must be sustained over at least 60 days and must be confirmed by a repeat measurement after >= 60 days from the first measurement. The number of participants with death-censored allograft loss are reported here.	From Baseline to 4 years
Percentage of Participants With Death-censored Allograft Loss	Death-censored allograft loss was defined as the occurrence of any of the following components: eGFR < 15 mL/min/1.73 m^2*; return to dialysis*; allograft nephrectomy, or; retransplantation. (*Total cumulative duration of sustained eGFR < 15 mL/min/1.73 m^2 AND / OR dialysis >= 60 days.) If the eGFR < 15 mL/min/1.73 m^2 was the only component reached, the value must be sustained over at least 60 days and must be confirmed by a repeat measurement after >= 60 days from the first measurement. The percentage of participants who experienced death-censored allograft loss are reported here.	From Baseline to 4 years
Change From Baseline in Urine Albumin Creatinine Ratio (UACR)		From Baseline to Week 52
Percent Change From Baseline in Mean Fluorescent Intensity for Donor-Specific Antibodies (DSA)		From Baseline to Week 52
Change From Baseline in Banff Lesion Grading Score (2015 Criteria) of Pre-treatment to Post-treatment (Week 52) Kidney Biopsies	Banff lesion grading scores assess the presence and the degree of histopathological changes in the different compartments of kidney biopsies. Here, the improved category is defined as a decline in the Banff lesion grading score. Participants with improved scores, not improved scores, and missing biopsies for C4d staining, interstitial fibrosis, tubular atrophy, glomerular basement membrane double contours, glomerulitis and peritubular capillaritis are reported for this outcome measure.	From Baseline to Week 52
Incidence of Acute Rejection Episodes of T Cell-mediated Rejection (TCMR) and Antibody-mediated Rejection (ABMR)	Number of participants who had at least one acute rejection episode (TCMR or ABMR) are reported for this outcome measure.	Baseline up to End of treatment (up to approximately 4 years)
Overall Participant Survival	Number of participants who were alive up to Week 52 are reported for this outcome measure.	Up to Week 52
Maximum Concentration at Steady State (Cmax ss) of CSL300	A subset of participants (out of the enrolled participants in the main study) had the option to participate in a pharmacokinetic (PK)/ Pharmacodynamic (PD) sub-study.	Up to Week 24
Trough Concentrations at Steady State (Ctrough ss) of CSL300	A subset of participants (out of the enrolled participants in the main study) had the option to participate in a PK/PD sub-study.	Up to Week 24
Area Under the Concentration-time Curve (AUC0-tau) at Steady State of CSL300	A subset of participants (out of the enrolled participants in the main study) had the option to participate in a PK/PD sub-study.	Up to Week 24
Time of Maximum Concentration at Steady State (Tmax ss) of CSL300	A subset of participants (out of the enrolled participants in the main study) had the option to participate in a PK/PD sub-study.	Up to Week 24

Collaborators and Investigators

• Sponsor: CSL Behring
• Collaborators: ICON Clinical Research
• Investigators: Study Director: Study Director, CSL Behring

Publications and helpful links

General Publications

• Jordan SC, Ammerman N, Choi J, Huang E, Najjar R, Peng A, Sethi S, Sandhu R, Atienza J, Toyoda M, Ge S, Lim K, Gillespie M, Zhang X, Haas M, Vo A. Evaluation of Clazakizumab (Anti-Interleukin-6) in Patients With Treatment-Resistant Chronic Active Antibody-Mediated Rejection of Kidney Allografts. Kidney Int Rep. 2022 Feb 9;7(4):720-731. doi: 10.1016/j.ekir.2022.01.1074. eCollection 2022 Apr.

Study record dates

Study Major Dates

• Study Start (Actual): October 14, 2019
• Primary Completion (Actual): April 8, 2024
• Study Completion (Actual): April 8, 2024

Study Registration Dates

• First Submitted: November 6, 2018
• First Submitted That Met QC Criteria: November 13, 2018
• First Posted (Actual): November 19, 2018

Study Record Updates

• Last Update Posted (Actual): July 23, 2025
• Last Update Submitted That Met QC Criteria: July 22, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Chronic Active; Antibody-mediated Rejection (AMR)
• Other Study ID Numbers: CSL300_3001; 2018-003682-34 (EudraCT Number); VKTX01 (Other Identifier: Vitaeris)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: CSL will consider on a case-by-case basis requests to share Individual Patient Data (IPD) with external bona-fide, qualified scientific and medical researchers. For information on the process and requirements for submitting a voluntary data sharing request for IPD, please contact CSL at clinicaltrials@cslbehring.com.
• IPD Sharing Time Frame: Requests for IPD will generally be considered once review by major regulatory authorities (ie FDA, EMA) is complete and the primary publication is available.

IPD Sharing Access Criteria

Proposed research should seek to answer a previously unanswered important medical or scientific question.

Applicable country specific privacy and other laws and regulations will be considered and may prevent sharing of IPD.

If the request is approved and the researcher has executed an appropriate data sharing agreement, IPD that has been appropriately anonymized will be available.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No