AzTrials
AzTrials

Antibody-mediated RejectionPhase 3IMAGINENCT03744910

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

A Phase 3 study testing Clazakizumab and Physiologic saline solution in people with Antibody-mediated Rejection, run by CSL Behring at 142 sites in 15 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Antibody-mediated Rejection
What is being tested?
Clazakizumab and Physiologic saline solution
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
194 participants
Where
142 sitesin 15 countries
Study dates
14 Oct 2019to 8 Apr 2024
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 14Show fewer
  • 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:
  • 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).
  • 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.
  • 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.

Who cannot join

  • 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.

Trial locations and contacts

142 sites in 15 countries.

142 sites in 15 countries

United States49 sites

  • Lehigh Valley Health Network

    Allentown, Pennsylvania, 18103

  • University Of Colorado Hospital - Anschutz Medical Campus

    Aurora, Colorado, 80045

  • University of Alabama at Birmingham (UAB) - University of Alabama Hospital (UAB Hospital)

    Birmingham, Alabama, 35294

  • Massachusetts General Cancer Center

    Boston, Massachusetts, 02114

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • Erie County Medical Center Corp.

    Buffalo, New York, 14215

  • Northwestern Memorial Hospital

    Chicago, Illinois, 60611

  • Rush University Medical Center - University Cardiovascular Surgeons

    Chicago, Illinois, 60612

  • The Ohio State University, Comprehensive Transplant Center

    Columbus, Ohio, 43210

  • Renal Disease Research Institute

    Dallas, Texas, 75204

  • UT Southwestern Medical Center

    Dallas, Texas, 75235

  • Unity Point Health

    Des Moines, Iowa, 50309

  • Henry Ford Health System

    Detroit, Michigan, 48202

  • Duke Cancer Institute

    Durham, North Carolina, 27710

  • Central Pennsylvania Transplant Foundation

    Harrisburg, Pennsylvania, 17104

  • Indiana University (IU) Health Physicians - Kidney Diseases Clinic - Medical Diagnostic Center Location

    Indianapolis, Indiana, 46202

  • Holden Comprehensive Cancer Center, University of Iowa Hospitals and Clinics

    Iowa City, Iowa, 52242

  • Saint Barnabas Medical Center

    Livingston, New Jersey, 07039

  • Keck Medical Center Of USC

    Los Angeles, California, 90033

  • Cedars-Sinai Medical Center

    Los Angeles, California, 90048

  • UCLA Kidney Transplant Research Program

    Los Angeles, California, 90095

  • University of Louisville Research Foundation

    Louisville, Kentucky, 40202

  • University of Wisconsin School of Medicine and Public Health (UWSMPH)

    Madison, Wisconsin, 53705

  • Medical College of WI Froedtert Hospital

    Milwaukee, Wisconsin, 53226

  • University of Minnesota

    Minneapolis, Minnesota, 55455

  • Tulane University Health Sciences Center

    New Orleans, Louisiana, 70112

  • NYU Langone Medical Center

    New York, New York, 10016

  • New York Presbyterian Hospital / Weill Cornell Medical Center

    New York, New York, 10021

  • Columbia University Medical Center

    New York, New York, 10032

  • Integris Baptist Medical Center

    Oklahoma City, Oklahoma, 73112

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68105

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Jefferson University Hospital

    Philadelphia, Pennsylvania, 19107

  • Mayo Clinic Hospital

    Phoenix, Arizona, 85054

  • Rhode Island Hospital

    Providence, Rhode Island, 02906

  • VCU Health

    Richmond, Virginia, 23298

  • Mayo Clinic

    Rochester, Minnesota, 55095

  • University of California Davis Medical Center

    Sacramento, California, 95817

  • Methodist Healthcare System of San Antonio

    San Antonio, Texas, 78229

  • California Institute of Renal Research

    San Diego, California, 92123

  • North America Research Institute

    San Dimas, California, 91773

  • California Pacific Medical Center

    San Francisco, California, 94109

  • Kaiser Permanente

    San Francisco, California, 94118

  • University of California, San Francisco Medical Center

    San Francisco, California, 94143

  • University of Washington

    Seattle, Washington, 98195

  • Washington University School of Medicine - Infectious Diseases (WU ID) Clinic

    St Louis, Missouri, 63110

  • Tampa General Medical Group

    Tampa, Florida, 33606

  • University of Cincinnati

    Toledo, Ohio, 43614

  • Wake Forest University Health Sciences

    Winston-Salem, North Carolina, 27157

Other trials in United States

France17 sites

  • Néphrologie - Pavillon Sainte Venise - CHU de Rouen - Hôpital de Bois Guillaume

    Bois-Guillaume, 76230

  • Centre Hospitalier Universitaire (CHU) de Bordeaux - Groupe Hospitalier Pellegrin

    Bordeaux, 33076

  • Centre Hospitalier Universitaire (CHU) - Hopital Henri Mondor

    Créteil, 94010

  • CHU GRENOBLE ALPES - Consultation Néphrologie Bureau des ARC (Côté Chartreuse, Rez-de-Chaussée Haut)

    Grenoble, Grenoble Cédex 09, 38043

  • Hopital Kremlin Bicetre

    Le Kremlin-Bicêtre, 94270

  • Centre Hospitalier Universitaire (CHU) De Limoges Hopital Dupuytren

    Limoges, 87042

  • Hopital Edouard Herriot

    Lyon, 69003

  • Hopital de la Conception - APHM

    Marseille, 13005

  • Centre Hospitalier Regional Universitaire (CHRU) Montpellier Arnaud de Villeneuve

    Montpellier, 34295

  • CHU de Nantes - Houtel Dieu

    Nantes, 44093

  • Centre Hospitalier Universitaire de Nice, Hopital Pasteur 2

    Nice, 06001

  • Hospital Saint-Louis - APHP

    Paris, 75010

  • Hopital Necker Enfants Malades

    Paris, 75015

  • Centre Hospitalier Universitaire de Poitiers

    Poitiers, 86021

  • Hopitaux Universitaire de Strasbourg-Centre de References des Maladies Autoimmunes

    Strasbourg, 67098

  • CHU Rangueil

    Toulouse, 31059

  • Centre Hospitalier Regional Universitaire de Tours (CHRU de Tours) - Hopital Bretonneau

    Tours, 37044

Other trials in France

Australia13 sites

  • Royal Adelaide Hospital

    Adelaide

  • Royal Prince Alfred Hospital

    Camperdown, New South Wales, 2050

  • Royal Prince Alfred Hospital

    Camperdown

  • Monash Health Monash Medical Centre

    Clayton, Victoria, 3168

  • Monash Medical Centre

    Clayton

  • Sir Charles Gairdner Hospital (SCGH)

    Nedlands, Western Australia, 6009

  • Linear Clinical Research

    Nedlands

  • The Royal Melbourne Hospital

    Parkville, Victoria, 3064

  • WSLHD, Westmead Hospital

    Westmead, New South Wales, 2145

  • Westmead Hospital

    Westmead

  • Princess Alexandra Hospital

    Woolloongabba, Queensland, 4102

  • The University of Queensland - Princess Alexandra Hospital (PAH)

    Woolloongabba, Queensland, 4102

  • Princess Alexandra Hospital

    Woolloongabba

Other trials in Australia

South Korea13 sites

  • Pusan National University Hospital

    Busan

  • Keimyung Dongsan Medical Center

    Daegu

  • Asan Medical Center

    Seoul

  • Kangdong Sacred Heart Hospital

    Seoul

  • Korea University Anam Hospital

    Seoul

  • Kosin University Gospel Hospital

    Seoul

  • Kyung Hee University Hospital at Gangdong

    Seoul

  • Samsung Medical Center

    Seoul

  • Seoul National University Bundang Hospital

    Seoul

  • Seoul National University Hospital

    Seoul

  • Severance Hospital Yonsei University

    Seoul

  • The Catholic University of Korea, Seoul St. Mary's Hospital

    Seoul

  • Pusan National University Yangsan Hospital

    Yangsan

Other trials in South Korea

Canada10 sites

  • Queen Elizabeth II Health Sciences Centre

    Halifax, Nova Scotia, B3H 1V7

  • London Health Sciences Centre

    London, Ontario, N6A 5A5

  • McGill University Health Center

    Montreal, Quebec, H4A 3J1

  • Centre de Recherche du Centre Hospitalier de l'Universite de Montreal (CRCHUM)

    Montreal

  • St Paul's Hospital Foundation

    Saskatoon, Saskatchewan, S7M 0Z9

  • St. Michael's Health Centre

    Toronto, Ontario, M5C 2T2

  • University Health Network

    Toronto

  • Vancouver General Hospital - Gordon & Leslie Diamond Centre

    Vancouver, British Columbia, V5Z 1M9

  • St. Paul's Hospital, Providence Health Care, Univ. Of British Columbia

    Vancouver, British Columbia, V6Z 1Y6

  • Shared Health Inc. operating as the Health Sciences Centre

    Winnipeg, Manitoba, R3A 1R9

Other trials in Canada

Spain10 sites

  • Hospital Del Mar

    Barcelona, 8003

  • Hospital Vall d'Hebron

    Barcelona, 8035

  • Hospital Clinic Barcelona

    Barcelona, 8036

  • Hospital Universitari de Bellvitge

    Barcelona, 8907

  • Hospital Universitario Ramon y Cajal

    Madrid, 28034

  • Hospital Clinico San Carlos

    Madrid, 28040

  • Hospital Universitario 12 de Octubre-Centro de Actividades Ambulatorias

    Madrid, 28041

  • Hospital Universitario Marques De Valdecilla

    Santander, 39008

  • Centro Hospital Universitario Dr. Preset

    Valencia, 46017

  • Hospital Universitario Miguel Servet

    Zaragoza, 50009

Other trials in Spain

Netherlands8 sites

  • Amsterdam University Medical Center (Amsterdam UMC), Academic Medical Center (AMC)

    Amsterdam, 1105 AZ

  • Amsterdam UMC location AMC

    Amsterdam, 1105AZ

  • University Medical Center Groningen

    Groningen, 9713 GZ

  • Leiden University Medical Center (LUMC)

    Leiden, 2333 ZA

  • Maastricht University Medical Centre

    Maastricht, 6248 HX

  • Radboud UMC

    Nijmegen

  • Erasmus University Medical Center

    Rotterdam

  • Universitair Medisch Centrum Utrecht

    Utrecht

Other trials in Netherlands

Taiwan5 sites

  • Hualien Tzu Chi Hospital

    Hualien City

  • Far Eastern Memorial Hospital

    New Taipei City

  • Taichung Veterans General Hospital

    Taichang

  • National Taiwan University Hospital

    Taipei

  • Linkou Chang Gung Memorial Hospital

    Taoyuan

Other trials in Taiwan

Sweden4 sites

  • Karolinska University Hospital

    Huddinge, SE-141 86

  • Karolinska University Hospital

    Solna

  • Uppsala Universitet - Akademiska Sjukhuset

    Uppsala, 75185

  • Uppsala Universitet - Akademiska Sjukhuset

    Uppsala

Other trials in Sweden

Austria3 sites

  • LKH-Universität Hospital Graz

    Graz

  • Universitätsklinik für Innere Medizin III Innsbruck

    Innsbruck

  • Medizinische Universität Wien, Allgemeines Krankenhaus der S

    Vienna

Other trials in Austria

Belgium3 sites

  • UZ Antwerpen

    Edegem

  • UZ Leuven

    Leuven

  • Centre Hospitalier Universitaire Sart Tilman

    Liège

Other trials in Belgium

Czechia3 sites

  • Centrum kardiovaskulární a transplantacní chirurgie Brno

    Brno-střed

  • Fakultní Nemocnice Olomouc

    Olomouc

  • IKEM

    Prague, 14000

Other trials in Czechia

Hungary2 sites

  • Debreceni Egyetem, Klinikai Központ, Auguszta

    Debrecen, 4032

  • Debreceni Egyetem Klinikai Kozpont

    Debrecen

Other trials in Hungary

Germany1 site

  • Charite - Universitaetsmedizin Berlin - Campus Charite Mitte (CCM)

    Berlin, 10117

Other trials in Germany

New Zealand1 site

  • Auckland City Hospital

    Auckland

Other trials in New Zealand

About this study

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

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.

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

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ClazakizumabBiological

    Clazakizumab is a genetically engineered humanized immunoglobulin G1 (IgG1) mAb that binds to human IL-6

  • Physiologic saline solutionDrug

    Normal saline

Study groups in NCT03744910
Study groupRoleWhat they receive
ClazakizumabActive comparatorClazakizumab is a genetically engineered humanized immunoglobulin G1 (IgG1) mAb that binds to human IL-6 that is administered subcutaneously.
Receives: Biological: Clazakizumab
PlaceboPlacebo comparatorPhysiologic saline solution that is administered subcutaneously.
Receives: Drug: Physiologic saline solution

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change From Baseline to Week 52 in Estimated Glomerular Filtration Rate (eGFR)

    This primary outcome measure was the one from the first interim analysis.

    Measured: From Baseline to Week 52

  2. 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.

    Measured: From Baseline to 4 years

  3. 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.

    Measured: From Baseline to 4 years

  4. Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, and Adverse Events of Special Interest (AESIs)

    Measured: Up to 4 years

  5. Percentage of Participants With TEAEs, Serious TEAEs, and AESIs

    Measured: Up to 4 years

  6. 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.

    Measured: From baseline up to 4 years

  7. 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.

    Measured: Up to 4 years

  8. 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.

    Measured: Up to 4 years

  9. Number of Participants With Clinically Significant Change in Vital Signs, Electrocardiograms (ECGs), and Physical Examination

    Measured: Up to 4 years

  10. Number of Participants With Positive Anti-drug Antibodies

    Measured: Baseline, Weeks 12, 24, and 48

  11. Percentage of Participants With Positive Anti-drug Antibodies

    Measured: Baseline, Weeks 12, 24, and 48

Secondary outcomes (15)

  1. 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.

    Measured: From Baseline to 4 years

  2. 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.

    Measured: From Baseline to 4 years

  3. 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.

    Measured: From Baseline to 4 years

  4. 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.

    Measured: From Baseline to 4 years

  5. 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.

    Measured: From Baseline to 4 years

  6. 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.

    Measured: From Baseline to 4 years

  7. Change From Baseline in Urine Albumin Creatinine Ratio (UACR)

    Measured: From Baseline to Week 52

  8. Percent Change From Baseline in Mean Fluorescent Intensity for Donor-Specific Antibodies (DSA)

    Measured: From Baseline to Week 52

  9. 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.

    Measured: From Baseline to Week 52

  10. 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.

    Measured: Baseline up to End of treatment (up to approximately 4 years)

  11. Overall Participant Survival

    Number of participants who were alive up to Week 52 are reported for this outcome measure.

    Measured: Up to Week 52

  12. 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.

    Measured: Up to Week 24

  13. 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.

    Measured: Up to Week 24

  14. 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.

    Measured: Up to Week 24

  15. 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.

    Measured: Up to Week 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Nov 2018
  2. Study start14 Oct 2019
  3. Primary completion8 Apr 2024
  4. Study completion8 Apr 2024

Why it stopped: Early stop for lack of efficacy/futility (at Interim analysis)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
194 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03744910
Sponsor's protocol ID
CSL300_3001
Other IDs
2018-003682-34, VKTX01, 2018
Acronym
IMAGINE
Status last verified
Jul 2025
First submitted
6 Nov 2018
Last updated
23 Jul 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.

Publications

  • Mayer KA, Budde K, Diebold M, Halloran PF, Bohmig GA. Targeting CD38 in Antibody-Mediated Rejection. Transpl Int. 2025 May 15;38:14343. doi: 10.3389/ti.2025.14343. eCollection 2025.

    PubMed 40444214

  • Mannon RB, Vincenti FG. Poised for Innovation: Considerations for End Points for New Drug Development in Kidney Transplantation. J Am Soc Nephrol. 2024 Nov 1;35(11):1603-1606. doi: 10.1681/ASN.0000000000000475. Epub 2024 Aug 5. No abstract available.

    PubMed 39102302

  • Nickerson PW, Bohmig GA, Chadban S, Kumar D, Mannon RB, van Gelder T, Lee JC, Adler S, Chong E, Djamali A. Clazakizumab for the treatment of chronic active antibody-mediated rejection (AMR) in kidney transplant recipients: Phase 3 IMAGINE study rationale and design. Trials. 2022 Dec 22;23(1):1042. doi: 10.1186/s13063-022-06897-3.

    PubMed 36550562

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Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Clazakizumab and Physiologic saline solution in people with Antibody-mediated Rejection, run by CSL Behring at 142 sites in 15 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 23 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 142 sites in United States, France, Australia, South Korea, Canada and 10 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Jul 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline to Week 52 in Estimated Glomerular Filtration Rate (eGFR) (time frame: From Baseline to Week 52). The study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03744910, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jul 2025.

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