Open-label, multicentre, dose-escalating phase II clinical trial on the safety and efficacy of tadekinig alfa (IL-18BP) in adult-onset Still's disease

Journal article


Publication Details

Author(s): Gabay C, Fautrel B, Fautrel B, Rech J, Spertini F, Feist E, Feist E, Koetter I, Hachulla E, Morel J, Schaeverbeke T, Hamidou MA, Hamidou MA, Martin T, Hellmich B, Lamprecht P, Schulze-Koops H, Courvoisier DS, Sleight A, Schiffrin EJ
Journal: Annals of the Rheumatic Diseases
Publication year: 2018
Volume: 77
Journal issue: 6
Pages range: 840-847
ISSN: 0003-4967


Abstract

OBJECTIVES: Adult-onset Still's disease (AOSD) is a rare systemic autoinflammatory disease; its management is largely empirical. This is the first clinical study to determine if interleukin (IL)-18 inhibition, using the recombinant human IL-18 binding protein, tadekinig alfa, is a therapeutic option in AOSD.
METHODS: In this phase II, open-label study, patients were ≥18 years with active AOSD plus fever or C reactive protein (CRP) levels ≥10 mg/L despite treatment with prednisone and/or conventional synthetic disease-modifying antirheumatic drugs (DMARDs). Previous biological DMARD treatment was permitted. Patients received tadekinig alfa 80 mg or 160 mg subcutaneously three times per week for 12 weeks; those receiving 80 mg not achieving early predicted response criteria (reduction of ≥50% CRP values from baseline and fever resolution) were up-titrated to 160 mg for a further 12 weeks. The primary endpoint was the occurrence of adverse events (AEs) throughout the study.
RESULTS: Ten patients were assigned to receive 80 mg tadekinig alfa and 13 patients to the 160 mg dose. One hundred and fifty-five treatment-emerging AEs were recorded, and 47 were considered related to the study drug. Most AEs were mild and resolved after drug discontinuation. Three serious AEs occurred, one possibly related to treatment (toxic optic neuropathy). At week 3, 5 of 10 patients receiving 80 mg and 6 of 12 patients receiving 160 mg achieved the predefined response criteria.
CONCLUSIONS: Our results indicate that tadekinig alfa appears to have a favourable safety profile and is associated with early signs of efficacy in patients with AOSD.
TRIAL REGISTRATION NUMBER: NCT02398435.


External institutions
AB2 Bio Ltd.
Asklepios Kliniken
Centre Hospitalier Universitaire de Bordeaux / CHU Bordeaux
Geneva University Hospitals / Hôpitaux universitaires de Genève (HUG)
Hôpitaux universitaires de Strasbourg (HUS) / University Hospital Strasbourg
Humboldt-Universität zu Berlin
Lausanne University Hospital / Centre hospitalier universitaire vaudois (CHUV)
LILLE 1 University - Science and Technology
Ludwig-Maximilians-Universität (LMU)
medius KLINIKEN gemeinnützige GmbH
Nantes University Hospital / Centre hospitalier universitaire de Nantes (CHU)
Universität zu Lübeck
University of Montpellier / Université Montpellier
University of Pittsburgh Medical Center (UPMC)


How to cite

APA:
Gabay, C., Fautrel, B., Fautrel, B., Rech, J., Spertini, F., Feist, E.,... Schiffrin, E.J. (2018). Open-label, multicentre, dose-escalating phase II clinical trial on the safety and efficacy of tadekinig alfa (IL-18BP) in adult-onset Still's disease. Annals of the Rheumatic Diseases, 77(6), 840-847. https://dx.doi.org/10.1136/annrheumdis-2017-212608

MLA:
Gabay, Cem, et al. "Open-label, multicentre, dose-escalating phase II clinical trial on the safety and efficacy of tadekinig alfa (IL-18BP) in adult-onset Still's disease." Annals of the Rheumatic Diseases 77.6 (2018): 840-847.

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Last updated on 2019-24-01 at 22:08