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

Gabay C, Fautrel B, Rech J, Spertini F, Feist E, Koetter I, Hachulla E, Morel J, Schaeverbeke T, Hamidou MA, Martin T, Hellmich B, Lamprecht P, Schulze-Koops H, Courvoisier DS, Sleight A, Schiffrin EJ (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Annals of the Rheumatic Diseases BMJ Publishing Group

Book Volume: 77

Pages Range: 840-847

Journal Issue: 6

DOI: 10.1136/annrheumdis-2017-212608

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.

Authors with CRIS profile

Hans Jürgen Rech Department of Medicine 3 – Rheumatology and Immunology

Involved external institutions

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

How to cite

APA:

Gabay, C., Fautrel, B., Rech, J., Spertini, F., Feist, E., Koetter, I.,... 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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