Three-Month Results of a Phase 2 Trial Evaluating Clazakizumab in Late Antibody-Mediated Rejection – Early Impact of Interleukin-6 Blockade on Donor-Specific Antibody Levels, Rejection Morphology and Gene Expression
1Department of Medicine III, Medical University of Vienna, Vienna, Austria, 2Nephrology Department, Charité Berlin, Berlin, Germany, 3Dept. of Clin. Pharmacology, Medical University of Vienna, Vienna, Austria, 4Vitaeris Inc., Vancouver, BC, Canada, 5Dept. of Clin. Pathology, Medical University of Vienna, Vienna, Austria, 6Alberta Transplant Applied Genomics Centre, ATAGC, University of Alberta, Edmonton, AB, Canada
Meeting: 2020 American Transplant Congress
Abstract number: 245
Keywords: Biopsy, Monoclonal antibodies, Multicenter studies, Rejection
Session Information
Session Name: Kidney Chronic Antibody Mediated Rejection
Session Type: Oral Abstract Session
Date: Saturday, May 30, 2020
Session Time: 3:15pm-4:45pm
Presentation Time: 3:39pm-3:51pm
Location: Virtual
*Purpose: Targeting Interleukin-6 (IL-6) is a promising strategy to counteract antibody-mediated rejection (ABMR). This phase 2 trial (NCT03444103) was designed to evaluate the safety and efficacy of anti-IL-6 antibody clazakizumab in late ABMR.
*Methods: The study included 20 kidney transplant recipients with late ABMR (median time to index biopsy: 10.6 yrs). For the first 3 months patients were randomized to receive clazakizumab (25 mg s.c. injection in 4-weekly intervals; n=10) or placebo (n=10), followed by an open-label study with all subjects receiving clazakizumab for a period of 40 weeks (3 patients still active). Here we report on the results of the first randomized part of the trial.
*Results: Index biopsies showed chronic active ABMR in 18 and active ABMR in 2 patients: median g+ptc and cg scores: 3 (interquartile range: 2-5) and 3 (2-3), respectively. Molecular analysis (MMDx) revealed a median ABMR score of 0.65 (all rejection score: 0.71; TCMR score: 0.01; reference ranges: 0.0-1.0), with full active ABMR being the most prevalent phenotype. As assessed in dilution experiments, 3 months treatment with clazakizumab led to a 44% (median; vs. 0% in the placebo group, p=0.001) reduction in DSA levels. Protocol biopsies after this short period, however, showed no significant differences with respect to g+ptc scores [2 (2-3) vs. 3 (2-4); p=0.27], molecular rejection scores [ABMR: 0.78 (0.46-0.85) vs. 0.54 (0.28-0.90), p=0.74; all rejection: 0.72 (0.44-0.88) vs. 0.56 (0.41-0.87), p=0.53] and a variety of different pathogenesis based transcript sets. There were no inter-group differences regarding renal function and proteinuria.
*Conclusions: The initial results of our trial suggest early modulation of DSA levels. There was, however, no immediate effect of IL-6 blockade on the morphologic and molecular activity of ABMR. The second part of our trial and a recently initiated large phase 3 multicenter trial (IMAGINE; NCT03744910) will clarify the therapeutic impact of prolonged clazakizumab treatment.
To cite this abstract in AMA style:
Böhmig GA, Dürr M, Jilma B, Eskandary F, Chong E, Schranz S, Doberer K, Wahrmann M, Borski A, Regele H, Kläger J, Reindl-Schwaighofer R, Reeve J, Budde K, Halloran PF. Three-Month Results of a Phase 2 Trial Evaluating Clazakizumab in Late Antibody-Mediated Rejection – Early Impact of Interleukin-6 Blockade on Donor-Specific Antibody Levels, Rejection Morphology and Gene Expression [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/three-month-results-of-a-phase-2-trial-evaluating-clazakizumab-in-late-antibody-mediated-rejection-early-impact-of-interleukin-6-blockade-on-donor-specific-antibody-levels-rejection-morphology-and/. Accessed May 16, 2025.« Back to 2020 American Transplant Congress