A Pilot Trial of Clazakizumab in Late ABMR
Safety, Tolerability and Efficacy of Anti-IL-6 Antibody Clazakizumab in Late Antibody-Mediated Rejection After Kidney Transplantation - a Pilot Trial
2 other identifiers
interventional
20
2 countries
2
Brief Summary
This bi-center study (Medical University of Vienna \& Charité Berlin) is an investigator-driven pilot trial designed to assess the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy (preliminary assessment) of humanized anti-IL-6 monoclonal antibody clazakizumab in kidney transplant recipients with late antibody-mediated rejection (ABMR). The study is designed as a phase 2 trial and has two subsequent sub-parts, a randomized placebo-controlled trial (part A) of 12 weeks, where recipients are allocated to receive either anti-IL-6 antibody clazakizumab (n=10) or placebo (n=10), followed by an open-label prospective study, where all 20 study patients will receive clazakizumab for a period of 40 weeks. Study protocol biopsies will be performed at the end of part A and part B.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started Jan 2018
2 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
January 16, 2018
CompletedStudy Start
First participant enrolled
January 16, 2018
CompletedFirst Posted
Study publicly available on registry
February 23, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 30, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
June 30, 2020
CompletedSeptember 9, 2020
September 1, 2020
2.5 years
January 16, 2018
September 6, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Number of adverse events and severe adverse events (AE's, SAE's)
Serious and Non-Serious adverse events probably or possibly attributable to clazakizumab
12 months
Secondary Outcomes (26)
Anti-clazakizumab antibodies in serum
At 0, 12 and 52 weeks
Clazakizumab serum concentration
At 0, 12 and 52 weeks
Pantoprazole serum concentration
At 0, 12 and 52 weeks
Protocol biopsy results - microcirculation inflammation
At week 11 and at week 52
Protocol biopsy results - chronic damage
At week 11 and at week 52
- +21 more secondary outcomes
Study Arms (2)
Clazakizumab / Clazakizumab
ACTIVE COMPARATORMonthly subcutaneous injections of 25mg clazakizumab for three months (after completion of part A, monthly injection of 25mg clazakizumab for nine months).
Placebo / Clazakizumab
PLACEBO COMPARATORMonthly subcutaneous injections of placebo (saline) for three months (after completion of part A, monthly injection of 25mg clazakizumab for nine months).
Interventions
Humanized monoclonal anti-IL-6 antibody
Eligibility Criteria
You may qualify if:
- Voluntary written informed consent
- Age \>18 years
- Functioning living or deceased donor allograft after ≥365 days post-transplantation
- eGFR \>30 ml/min/1.73 m2
- Detection of HLA class I and/or II antigen-specific antibodies (preformed and/or de novo DSA).
- Acute/active or chronic/active ABMR (±C4d in PTC) according to Banff 2013/2015
- Molecular ABMR score (ABMRpm) ≥0.2
You may not qualify if:
- Patients actively participating in another clinical trial
- Age ≤18 years
- Female subject is pregnant or lactating
- Index biopsy results:
- T-cell-mediated rejection classified Banff grade ≥I
- De novo or recurrent severe thrombotic microangiopathy
- Polyoma virus nephropathy
- De novo or recurrent glomerulonephritis
- Acute rejection treatment \<3 month before screening
- Acute deterioration of graft function (eGFR decline within 1-3 months \>25%)
- Nephrotic range proteinuria \>3500 mg/g protein/creatinine ratio
- Active viral, bacterial or fungal infection precluding intensified immunosuppression
- Active malignant disease precluding intensified immunosuppressive therapy
- Abnormal liver function tests (ALT, AST, bilirubin \> 1.5 x upper limit of normal)
- Other significant liver disease
- +7 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Medical University of Viennalead
- CSL Behringcollaborator
- University of Albertacollaborator
- Charite University, Berlin, Germanycollaborator
Study Sites (2)
Medical University of Vienna
Vienna, 1090, Austria
Charité University
Berlin, 10117, Germany
Related Publications (6)
Mease PJ, Gottlieb AB, Berman A, Drescher E, Xing J, Wong R, Banerjee S. The Efficacy and Safety of Clazakizumab, an Anti-Interleukin-6 Monoclonal Antibody, in a Phase IIb Study of Adults With Active Psoriatic Arthritis. Arthritis Rheumatol. 2016 Sep;68(9):2163-73. doi: 10.1002/art.39700.
PMID: 27059799BACKGROUNDChoi J, Aubert O, Vo A, Loupy A, Haas M, Puliyanda D, Kim I, Louie S, Kang A, Peng A, Kahwaji J, Reinsmoen N, Toyoda M, Jordan SC. Assessment of Tocilizumab (Anti-Interleukin-6 Receptor Monoclonal) as a Potential Treatment for Chronic Antibody-Mediated Rejection and Transplant Glomerulopathy in HLA-Sensitized Renal Allograft Recipients. Am J Transplant. 2017 Sep;17(9):2381-2389. doi: 10.1111/ajt.14228. Epub 2017 Mar 10.
PMID: 28199785BACKGROUNDEskandary F, Regele H, Baumann L, Bond G, Kozakowski N, Wahrmann M, Hidalgo LG, Haslacher H, Kaltenecker CC, Aretin MB, Oberbauer R, Posch M, Staudenherz A, Handisurya A, Reeve J, Halloran PF, Bohmig GA. A Randomized Trial of Bortezomib in Late Antibody-Mediated Kidney Transplant Rejection. J Am Soc Nephrol. 2018 Feb;29(2):591-605. doi: 10.1681/ASN.2017070818. Epub 2017 Dec 14.
PMID: 29242250BACKGROUNDMayer KA, Doberer K, Halloran PF, Budde K, Haindl S, Muhlbacher J, Eskandary F, Viard T, Casas S, Jilma B, Bohmig GA. Anti-interleukin-6 Antibody Clazakizumab in Antibody-mediated Kidney Transplant Rejection: Effect on Donor-derived Cell-free DNA and C-X-C Motif Chemokine Ligand 10. Transplant Direct. 2022 Nov 10;8(12):e1406. doi: 10.1097/TXD.0000000000001406. eCollection 2022 Dec.
PMID: 36382130DERIVEDMuhlbacher J, Schorgenhofer C, Doberer K, Durr M, Budde K, Eskandary F, Mayer KA, Schranz S, Ely S, Reiter B, Chong E, Adler SH, Jilma B, Bohmig GA. Anti-interleukin-6 antibody clazakizumab in late antibody-mediated kidney transplant rejection: effect on cytochrome P450 drug metabolism. Transpl Int. 2021 Aug;34(8):1542-1552. doi: 10.1111/tri.13954. Epub 2021 Jul 8.
PMID: 34153143DERIVEDEskandary F, Durr M, Budde K, Doberer K, Reindl-Schwaighofer R, Waiser J, Wahrmann M, Regele H, Spittler A, Lachmann N, Firbas C, Muhlbacher J, Bond G, Halloran PF, Chong E, Jilma B, Bohmig GA. Clazakizumab in late antibody-mediated rejection: study protocol of a randomized controlled pilot trial. Trials. 2019 Jan 11;20(1):37. doi: 10.1186/s13063-018-3158-6.
PMID: 30635033DERIVED
Related Links
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Bernd Jilma, MD
Department of Clinical Pharmacology, Medical University Vienna
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
January 16, 2018
First Posted
February 23, 2018
Study Start
January 16, 2018
Primary Completion
June 30, 2020
Study Completion
June 30, 2020
Last Updated
September 9, 2020
Record last verified: 2020-09
Data Sharing
- IPD Sharing
- Will not share