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

NCT ID: NCT03744910

Last Updated: 2025-07-23

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

194 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-10-14

Study Completion Date

2024-04-08

Brief Summary

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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.

Detailed Description

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Conditions

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Antibody-mediated Rejection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Clazakizumab

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

Group Type ACTIVE_COMPARATOR

Clazakizumab

Intervention Type BIOLOGICAL

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

Placebo

Physiologic saline solution that is administered subcutaneously.

Group Type PLACEBO_COMPARATOR

Physiologic saline solution

Intervention Type DRUG

Normal saline

Interventions

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Clazakizumab

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

Intervention Type BIOLOGICAL

Physiologic saline solution

Normal saline

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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ICON Clinical Research

INDUSTRY

Sponsor Role collaborator

CSL Behring

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Study Director

Role: STUDY_DIRECTOR

CSL Behring

Locations

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

Birmingham, Alabama, United States

Site Status

Mayo Clinic Hospital

Phoenix, Arizona, United States

Site Status

Keck Medical Center Of USC

Los Angeles, California, United States

Site Status

Cedars-Sinai Medical Center

Los Angeles, California, United States

Site Status

UCLA Kidney Transplant Research Program

Los Angeles, California, United States

Site Status

University of California Davis Medical Center

Sacramento, California, United States

Site Status

California Institute of Renal Research

San Diego, California, United States

Site Status

North America Research Institute

San Dimas, California, United States

Site Status

California Pacific Medical Center

San Francisco, California, United States

Site Status

Kaiser Permanente

San Francisco, California, United States

Site Status

University of California, San Francisco Medical Center

San Francisco, California, United States

Site Status

University Of Colorado Hospital - Anschutz Medical Campus

Aurora, Colorado, United States

Site Status

Tampa General Medical Group

Tampa, Florida, United States

Site Status

Northwestern Memorial Hospital

Chicago, Illinois, United States

Site Status

Rush University Medical Center - University Cardiovascular Surgeons

Chicago, Illinois, United States

Site Status

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

Indianapolis, Indiana, United States

Site Status

Unity Point Health

Des Moines, Iowa, United States

Site Status

Holden Comprehensive Cancer Center, University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Site Status

University of Louisville Research Foundation

Louisville, Kentucky, United States

Site Status

Tulane University Health Sciences Center

New Orleans, Louisiana, United States

Site Status

Massachusetts General Cancer Center

Boston, Massachusetts, United States

Site Status

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

Henry Ford Health System

Detroit, Michigan, United States

Site Status

University of Minnesota

Minneapolis, Minnesota, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

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

St Louis, Missouri, United States

Site Status

University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

Saint Barnabas Medical Center

Livingston, New Jersey, United States

Site Status

Erie County Medical Center Corp.

Buffalo, New York, United States

Site Status

NYU Langone Medical Center

New York, New York, United States

Site Status

New York Presbyterian Hospital / Weill Cornell Medical Center

New York, New York, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

Duke Cancer Institute

Durham, North Carolina, United States

Site Status

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Site Status

The Ohio State University, Comprehensive Transplant Center

Columbus, Ohio, United States

Site Status

University of Cincinnati

Toledo, Ohio, United States

Site Status

Integris Baptist Medical Center

Oklahoma City, Oklahoma, United States

Site Status

Lehigh Valley Health Network

Allentown, Pennsylvania, United States

Site Status

Central Pennsylvania Transplant Foundation

Harrisburg, Pennsylvania, United States

Site Status

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Jefferson University Hospital

Philadelphia, Pennsylvania, United States

Site Status

Rhode Island Hospital

Providence, Rhode Island, United States

Site Status

Renal Disease Research Institute

Dallas, Texas, United States

Site Status

UT Southwestern Medical Center

Dallas, Texas, United States

Site Status

Methodist Healthcare System of San Antonio

San Antonio, Texas, United States

Site Status

VCU Health

Richmond, Virginia, United States

Site Status

University of Washington

Seattle, Washington, United States

Site Status

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

Madison, Wisconsin, United States

Site Status

Medical College of WI Froedtert Hospital

Milwaukee, Wisconsin, United States

Site Status

Royal Prince Alfred Hospital

Camperdown, New South Wales, Australia

Site Status

WSLHD, Westmead Hospital

Westmead, New South Wales, Australia

Site Status

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Site Status

The University of Queensland - Princess Alexandra Hospital (PAH)

Woolloongabba, Queensland, Australia

Site Status

Monash Health Monash Medical Centre

Clayton, Victoria, Australia

Site Status

The Royal Melbourne Hospital

Parkville, Victoria, Australia

Site Status

Sir Charles Gairdner Hospital (SCGH)

Nedlands, Western Australia, Australia

Site Status

Royal Adelaide Hospital

Adelaide, , Australia

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Royal Prince Alfred Hospital

Camperdown, , Australia

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Monash Medical Centre

Clayton, , Australia

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Linear Clinical Research

Nedlands, , Australia

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Westmead Hospital

Westmead, , Australia

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Princess Alexandra Hospital

Woolloongabba, , Australia

Site Status

LKH-Universität Hospital Graz

Graz, , Austria

Site Status

Universitätsklinik für Innere Medizin III Innsbruck

Innsbruck, , Austria

Site Status

Medizinische Universität Wien, Allgemeines Krankenhaus der S

Vienna, , Austria

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UZ Antwerpen

Edegem, , Belgium

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UZ Leuven

Leuven, , Belgium

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Centre Hospitalier Universitaire Sart Tilman

Liège, , Belgium

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Vancouver General Hospital - Gordon & Leslie Diamond Centre

Vancouver, British Columbia, Canada

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

Vancouver, British Columbia, Canada

Site Status

Shared Health Inc. operating as the Health Sciences Centre

Winnipeg, Manitoba, Canada

Site Status

Queen Elizabeth II Health Sciences Centre

Halifax, Nova Scotia, Canada

Site Status

London Health Sciences Centre

London, Ontario, Canada

Site Status

St. Michael's Health Centre

Toronto, Ontario, Canada

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McGill University Health Center

Montreal, Quebec, Canada

Site Status

St Paul's Hospital Foundation

Saskatoon, Saskatchewan, Canada

Site Status

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

Montreal, , Canada

Site Status

University Health Network

Toronto, , Canada

Site Status

Centrum kardiovaskulární a transplantacní chirurgie Brno

Brno střed, , Czechia

Site Status

Fakultní Nemocnice Olomouc

Olomouc, , Czechia

Site Status

IKEM

Prague, , Czechia

Site Status

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

Grenoble, Grenoble Cédex 09, France

Site Status

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

Bois-Guillaume, , France

Site Status

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

Bordeaux, , France

Site Status

Centre Hospitalier Universitaire (CHU) - Hopital Henri Mondor

Créteil, , France

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Hopital Kremlin Bicetre

Le Kremlin-Bicêtre, , France

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Centre Hospitalier Universitaire (CHU) De Limoges Hopital Dupuytren

Limoges, , France

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Hopital Edouard Herriot

Lyon, , France

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Hopital de la Conception - APHM

Marseille, , France

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Centre Hospitalier Regional Universitaire (CHRU) Montpellier Arnaud de Villeneuve

Montpellier, , France

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CHU de Nantes - Houtel Dieu

Nantes, , France

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Centre Hospitalier Universitaire de Nice, Hopital Pasteur 2

Nice, , France

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Hospital Saint-Louis - APHP

Paris, , France

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Hopital Necker Enfants Malades

Paris, , France

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Centre Hospitalier Universitaire de Poitiers

Poitiers, , France

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Hopitaux Universitaire de Strasbourg-Centre de References des Maladies Autoimmunes

Strasbourg, , France

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CHU Rangueil

Toulouse, , France

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

Tours, , France

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Charite - Universitaetsmedizin Berlin - Campus Charite Mitte (CCM)

Berlin, , Germany

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Debreceni Egyetem, Klinikai Központ, Auguszta

Debrecen, , Hungary

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Debreceni Egyetem Klinikai Kozpont

Debrecen, , Hungary

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

Amsterdam, , Netherlands

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Amsterdam UMC location AMC

Amsterdam, , Netherlands

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University Medical Center Groningen

Groningen, , Netherlands

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Leiden University Medical Center (LUMC)

Leiden, , Netherlands

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Maastricht University Medical Centre

Maastricht, , Netherlands

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Radboud UMC

Nijmegen, , Netherlands

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Erasmus University Medical Center

Rotterdam, , Netherlands

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Universitair Medisch Centrum Utrecht

Utrecht, , Netherlands

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Auckland City Hospital

Auckland, , New Zealand

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Pusan National University Hospital

Busan, , South Korea

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Keimyung Dongsan Medical Center

Daegu, , South Korea

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Asan Medical Center

Seoul, , South Korea

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Kangdong Sacred Heart Hospital

Seoul, , South Korea

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Korea University Anam Hospital

Seoul, , South Korea

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Kosin University Gospel Hospital

Seoul, , South Korea

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Kyung Hee University Hospital at Gangdong

Seoul, , South Korea

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Samsung Medical Center

Seoul, , South Korea

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Seoul National University Bundang Hospital

Seoul, , South Korea

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Seoul National University Hospital

Seoul, , South Korea

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Severance Hospital Yonsei University

Seoul, , South Korea

Site Status

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

Seoul, , South Korea

Site Status

Pusan National University Yangsan Hospital

Yangsan, , South Korea

Site Status

Hospital Del Mar

Barcelona, , Spain

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Hospital Vall d'Hebron

Barcelona, , Spain

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Hospital Clinic Barcelona

Barcelona, , Spain

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Hospital Universitari de Bellvitge

Barcelona, , Spain

Site Status

Hospital Universitario Ramon y Cajal

Madrid, , Spain

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Hospital Clinico San Carlos

Madrid, , Spain

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Hospital Universitario 12 de Octubre-Centro de Actividades Ambulatorias

Madrid, , Spain

Site Status

Hospital Universitario Marques De Valdecilla

Santander, , Spain

Site Status

Centro Hospital Universitario Dr. Preset

Valencia, , Spain

Site Status

Hospital Universitario Miguel Servet

Zaragoza, , Spain

Site Status

Karolinska University Hospital

Huddinge, , Sweden

Site Status

Karolinska University Hospital

Solna, , Sweden

Site Status

Uppsala Universitet - Akademiska Sjukhuset

Uppsala, , Sweden

Site Status

Uppsala Universitet - Akademiska Sjukhuset

Uppsala, , Sweden

Site Status

Hualien Tzu Chi Hospital

Hualien City, , Taiwan

Site Status

Far Eastern Memorial Hospital

New Taipei City, , Taiwan

Site Status

Taichung Veterans General Hospital

Taichang, , Taiwan

Site Status

National Taiwan University Hospital

Taipei, , Taiwan

Site Status

Linkou Chang Gung Memorial Hospital

Taoyuan District, , Taiwan

Site Status

Countries

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United States Australia Austria Belgium Canada Czechia France Germany Hungary Netherlands New Zealand South Korea Spain Sweden Taiwan

References

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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.

Reference Type DERIVED
PMID: 39102302 (View on PubMed)

Borski 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.

Reference Type DERIVED
PMID: 35969004 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35497778 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2018-003682-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

VKTX01

Identifier Type: OTHER

Identifier Source: secondary_id

CSL300_3001

Identifier Type: -

Identifier Source: org_study_id

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