Study Stopped
Early stop for lack of efficacy/futility (at Interim analysis)
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
3 other identifiers
interventional
194
14 countries
129
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3
Started Oct 2019
Typical duration for phase_3
129 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 6, 2018
CompletedFirst Posted
Study publicly available on registry
November 19, 2018
CompletedStudy Start
First participant enrolled
October 14, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 8, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
April 8, 2024
CompletedResults Posted
Study results publicly available
July 23, 2025
CompletedJuly 23, 2025
July 1, 2025
4.5 years
November 6, 2018
April 3, 2025
July 22, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (11)
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 Outcomes (15)
Number of Participants With Composite All-cause Allograft Loss
From Baseline to 4 years
Percentage of Participants With Composite All-cause Allograft Loss
From Baseline to 4 years
Number of Participants With Irreversible Loss of Allograft Function
From Baseline to 4 years
Percentage of Participants With Irreversible Loss of Allograft Function
From Baseline to 4 years
Number of Participants With Death-censored Allograft Loss
From Baseline to 4 years
- +10 more secondary outcomes
Study Arms (2)
Clazakizumab
ACTIVE COMPARATORClazakizumab is a genetically engineered humanized immunoglobulin G1 (IgG1) mAb that binds to human IL-6 that is administered subcutaneously.
Placebo
PLACEBO COMPARATORPhysiologic saline solution that is administered subcutaneously.
Interventions
Clazakizumab is a genetically engineered humanized immunoglobulin G1 (IgG1) mAb that binds to human IL-6
Eligibility Criteria
You may qualify if:
- 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.
- 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.
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- CSL Behringlead
- ICON Clinical Researchcollaborator
Study Sites (142)
University of Alabama at Birmingham (UAB) - University of Alabama Hospital (UAB Hospital)
Birmingham, Alabama, 35294, United States
Mayo Clinic Hospital
Phoenix, Arizona, 85054, United States
Keck Medical Center Of USC
Los Angeles, California, 90033, United States
Cedars-Sinai Medical Center
Los Angeles, California, 90048, United States
UCLA Kidney Transplant Research Program
Los Angeles, California, 90095, United States
University of California Davis Medical Center
Sacramento, California, 95817, United States
California Institute of Renal Research
San Diego, California, 92123, United States
North America Research Institute
San Dimas, California, 91773, United States
California Pacific Medical Center
San Francisco, California, 94109, United States
Kaiser Permanente
San Francisco, California, 94118, United States
University of California, San Francisco Medical Center
San Francisco, California, 94143, United States
University Of Colorado Hospital - Anschutz Medical Campus
Aurora, Colorado, 80045, United States
Tampa General Medical Group
Tampa, Florida, 33606, United States
Northwestern Memorial Hospital
Chicago, Illinois, 60611, United States
Rush University Medical Center - University Cardiovascular Surgeons
Chicago, Illinois, 60612, United States
Indiana University (IU) Health Physicians - Kidney Diseases Clinic - Medical Diagnostic Center Location
Indianapolis, Indiana, 46202, United States
Unity Point Health
Des Moines, Iowa, 50309, United States
Holden Comprehensive Cancer Center, University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242, United States
University of Louisville Research Foundation
Louisville, Kentucky, 40202, United States
Tulane University Health Sciences Center
New Orleans, Louisiana, 70112, United States
Massachusetts General Cancer Center
Boston, Massachusetts, 02114, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215, United States
Henry Ford Health System
Detroit, Michigan, 48202, United States
University of Minnesota
Minneapolis, Minnesota, 55455, United States
Mayo Clinic
Rochester, Minnesota, 55095, United States
Washington University School of Medicine - Infectious Diseases (WU ID) Clinic
St Louis, Missouri, 63110, United States
University of Nebraska Medical Center
Omaha, Nebraska, 68105, United States
Saint Barnabas Medical Center
Livingston, New Jersey, 07039, United States
Erie County Medical Center Corp.
Buffalo, New York, 14215, United States
NYU Langone Medical Center
New York, New York, 10016, United States
New York Presbyterian Hospital / Weill Cornell Medical Center
New York, New York, 10021, United States
Columbia University Medical Center
New York, New York, 10032, United States
Duke Cancer Institute
Durham, North Carolina, 27710, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157, United States
The Ohio State University, Comprehensive Transplant Center
Columbus, Ohio, 43210, United States
University of Cincinnati
Toledo, Ohio, 43614, United States
Integris Baptist Medical Center
Oklahoma City, Oklahoma, 73112, United States
Lehigh Valley Health Network
Allentown, Pennsylvania, 18103, United States
Central Pennsylvania Transplant Foundation
Harrisburg, Pennsylvania, 17104, United States
University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
Jefferson University Hospital
Philadelphia, Pennsylvania, 19107, United States
Rhode Island Hospital
Providence, Rhode Island, 02906, United States
Renal Disease Research Institute
Dallas, Texas, 75204, United States
UT Southwestern Medical Center
Dallas, Texas, 75235, United States
Methodist Healthcare System of San Antonio
San Antonio, Texas, 78229, United States
VCU Health
Richmond, Virginia, 23298, United States
University of Washington
Seattle, Washington, 98195, United States
University of Wisconsin School of Medicine and Public Health (UWSMPH)
Madison, Wisconsin, 53705, United States
Medical College of WI Froedtert Hospital
Milwaukee, Wisconsin, 53226, United States
Royal Prince Alfred Hospital
Camperdown, New South Wales, 2050, Australia
WSLHD, Westmead Hospital
Westmead, New South Wales, 2145, Australia
Princess Alexandra Hospital
Woolloongabba, Queensland, 4102, Australia
The University of Queensland - Princess Alexandra Hospital (PAH)
Woolloongabba, Queensland, 4102, Australia
Monash Health Monash Medical Centre
Clayton, Victoria, 3168, Australia
The Royal Melbourne Hospital
Parkville, Victoria, 3064, Australia
Sir Charles Gairdner Hospital (SCGH)
Nedlands, Western Australia, 6009, Australia
Royal Adelaide Hospital
Adelaide, Australia
Royal Prince Alfred Hospital
Camperdown, Australia
Monash Medical Centre
Clayton, Australia
Linear Clinical Research
Nedlands, Australia
Westmead Hospital
Westmead, Australia
Princess Alexandra Hospital
Woolloongabba, Australia
LKH-Universität Hospital Graz
Graz, Austria
Universitätsklinik fĂ¼r Innere Medizin III Innsbruck
Innsbruck, Austria
Medizinische Universität Wien, Allgemeines Krankenhaus der S
Vienna, Austria
UZ Antwerpen
Edegem, Belgium
UZ Leuven
Leuven, Belgium
Centre Hospitalier Universitaire Sart Tilman
Liège, Belgium
Vancouver General Hospital - Gordon & Leslie Diamond Centre
Vancouver, British Columbia, V5Z 1M9, Canada
St. Paul's Hospital, Providence Health Care, Univ. Of British Columbia
Vancouver, British Columbia, V6Z 1Y6, Canada
Shared Health Inc. operating as the Health Sciences Centre
Winnipeg, Manitoba, R3A 1R9, Canada
Queen Elizabeth II Health Sciences Centre
Halifax, Nova Scotia, B3H 1V7, Canada
London Health Sciences Centre
London, Ontario, N6A 5A5, Canada
St. Michael's Health Centre
Toronto, Ontario, M5C 2T2, Canada
McGill University Health Center
Montreal, Quebec, H4A 3J1, Canada
St Paul's Hospital Foundation
Saskatoon, Saskatchewan, S7M 0Z9, Canada
Centre de Recherche du Centre Hospitalier de l'Universite de Montreal (CRCHUM)
Montreal, Canada
University Health Network
Toronto, Canada
Centrum kardiovaskulĂ¡rnĂ a transplantacnĂ chirurgie Brno
Brno-střed, Czechia
FakultnĂ Nemocnice Olomouc
Olomouc, Czechia
IKEM
Prague, 14000, Czechia
CHU GRENOBLE ALPES - Consultation Néphrologie Bureau des ARC (Côté Chartreuse, Rez-de-Chaussée Haut)
Grenoble, Grenoble CĂ©dex 09, 38043, France
NĂ©phrologie - Pavillon Sainte Venise - CHU de Rouen - HĂ´pital de Bois Guillaume
Bois-Guillaume, 76230, France
Centre Hospitalier Universitaire (CHU) de Bordeaux - Groupe Hospitalier Pellegrin
Bordeaux, 33076, France
Centre Hospitalier Universitaire (CHU) - Hopital Henri Mondor
Créteil, 94010, France
Hopital Kremlin Bicetre
Le Kremlin-BicĂªtre, 94270, France
Centre Hospitalier Universitaire (CHU) De Limoges Hopital Dupuytren
Limoges, 87042, France
Hopital Edouard Herriot
Lyon, 69003, France
Hopital de la Conception - APHM
Marseille, 13005, France
Centre Hospitalier Regional Universitaire (CHRU) Montpellier Arnaud de Villeneuve
Montpellier, 34295, France
CHU de Nantes - Houtel Dieu
Nantes, 44093, France
Centre Hospitalier Universitaire de Nice, Hopital Pasteur 2
Nice, 06001, France
Hospital Saint-Louis - APHP
Paris, 75010, France
Hopital Necker Enfants Malades
Paris, 75015, France
Centre Hospitalier Universitaire de Poitiers
Poitiers, 86021, France
Hopitaux Universitaire de Strasbourg-Centre de References des Maladies Autoimmunes
Strasbourg, 67098, France
CHU Rangueil
Toulouse, 31059, France
Centre Hospitalier Regional Universitaire de Tours (CHRU de Tours) - Hopital Bretonneau
Tours, 37044, France
Charite - Universitaetsmedizin Berlin - Campus Charite Mitte (CCM)
Berlin, 10117, Germany
Debreceni Egyetem, Klinikai Központ, Auguszta
Debrecen, 4032, Hungary
Debreceni Egyetem Klinikai Kozpont
Debrecen, Hungary
Amsterdam University Medical Center (Amsterdam UMC), Academic Medical Center (AMC)
Amsterdam, 1105 AZ, Netherlands
Amsterdam UMC location AMC
Amsterdam, 1105AZ, Netherlands
University Medical Center Groningen
Groningen, 9713 GZ, Netherlands
Leiden University Medical Center (LUMC)
Leiden, 2333 ZA, Netherlands
Maastricht University Medical Centre
Maastricht, 6248 HX, Netherlands
Radboud UMC
Nijmegen, Netherlands
Erasmus University Medical Center
Rotterdam, Netherlands
Universitair Medisch Centrum Utrecht
Utrecht, Netherlands
Auckland City Hospital
Auckland, New Zealand
Pusan National University Hospital
Busan, South Korea
Keimyung Dongsan Medical Center
Daegu, South Korea
Asan Medical Center
Seoul, South Korea
Kangdong Sacred Heart Hospital
Seoul, South Korea
Korea University Anam Hospital
Seoul, South Korea
Kosin University Gospel Hospital
Seoul, South Korea
Kyung Hee University Hospital at Gangdong
Seoul, South Korea
Samsung Medical Center
Seoul, South Korea
Seoul National University Bundang Hospital
Seoul, South Korea
Seoul National University Hospital
Seoul, South Korea
Severance Hospital Yonsei University
Seoul, South Korea
The Catholic University of Korea, Seoul St. Mary's Hospital
Seoul, South Korea
Pusan National University Yangsan Hospital
Yangsan, South Korea
Hospital Del Mar
Barcelona, 8003, Spain
Hospital Vall d'Hebron
Barcelona, 8035, Spain
Hospital Clinic Barcelona
Barcelona, 8036, Spain
Hospital Universitari de Bellvitge
Barcelona, 8907, Spain
Hospital Universitario Ramon y Cajal
Madrid, 28034, Spain
Hospital Clinico San Carlos
Madrid, 28040, Spain
Hospital Universitario 12 de Octubre-Centro de Actividades Ambulatorias
Madrid, 28041, Spain
Hospital Universitario Marques De Valdecilla
Santander, 39008, Spain
Centro Hospital Universitario Dr. Preset
Valencia, 46017, Spain
Hospital Universitario Miguel Servet
Zaragoza, 50009, Spain
Karolinska University Hospital
Huddinge, SE-141 86, Sweden
Karolinska University Hospital
Solna, Sweden
Uppsala Universitet - Akademiska Sjukhuset
Uppsala, 75185, 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 District, Taiwan
Related Publications (4)
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.
PMID: 39102302DERIVEDNickerson 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.
PMID: 36550562DERIVEDBorski A, Eskandary F, Haindl S, Doberer K, Muhlbacher J, Mayer KA, Budde K, Halloran PF, Chong E, Jilma B, Bohmig GA, Wahrmann M. Anti-interleukin-6 Antibody Clazakizumab in Antibody-mediated Renal Allograft Rejection: Accumulation of Antibody-neutralized Interleukin-6 Without Signs of Proinflammatory Rebound Phenomena. Transplantation. 2023 Feb 1;107(2):495-503. doi: 10.1097/TP.0000000000004285. Epub 2023 Jan 26.
PMID: 35969004DERIVEDJordan 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.
PMID: 35497778DERIVED
MeSH Terms
Interventions
Limitations and Caveats
This study was not able to complete secondary endpoint assessments as planned. The study was terminated due to futility after the planned interim analysis based on the change in eGFR from baseline to Week 52 and analysis was conducted where feasible using the data collected at Week 52 or by the time of study termination.
Results Point of Contact
- Title
- Study Director
- Organization
- CSL Behring
Study Officials
- STUDY DIRECTOR
Study Director
CSL Behring
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 6, 2018
First Posted
November 19, 2018
Study Start
October 14, 2019
Primary Completion
April 8, 2024
Study Completion
April 8, 2024
Last Updated
July 23, 2025
Results First Posted
July 23, 2025
Record last verified: 2025-07
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- 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.
- 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.
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.