Dapansutrile, an oral selective NLRP3 inflammasome inhibitor, for treatment of gout flares: an open-label, dose-adaptive, proof-of-concept, phase 2a trial
| Autor: | Damaris B. Skouras, Kiki Schraa, Curtis L. Scribner, T.L.Th.A. Jansen, Viola Klück, Matthijs Janssen, Charles A. Dinarello, Antoaneta Comarniceanu, Isak W. Tengesdal, Maartje C. P. Cleophas, Leo A. B. Joosten, M. Efde, Carlo Marchetti |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
medicine.medical_specialty
education.field_of_study business.industry Immunology Population lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] Interleukin Inflammasome medicine.disease Article Gout Clinical trial All institutes and research themes of the Radboud University Medical Center Rheumatology Joint pain Internal medicine medicine Immunology and Allergy Outpatient clinic medicine.symptom Open label business education medicine.drug |
| Zdroj: | Lancet Rheumatol The Lancet. Rheumatology, 2, E270-E280 The Lancet. Rheumatology, 2, 5, pp. E270-E280 |
| ISSN: | 2665-9913 |
| Popis: | SUMMARY: BACKGROUND: Gout flares are driven by interleukin (IL)-1β. Dapansutrile inhibits the NLRP3 inflammasome and subsequent activation of IL-1β. In this study we aimed to investigate the safety and efficacy of orally administered dapansutrile in patients with a gout flare. METHODS: In this open-label, proof-of-concept, phase 2a trial, adult patients (aged 18–80 years) with a monoarticular monosodium urate crystal-proven gout flare were enrolled at an outpatient clinic in the Netherlands and sequentially assigned using a dose-adaptive design to receive 100 mg/day, 300 mg/day, 1000 mg/day, or 2000 mg/day oral dapansutrile for 8 days. The coprimary outcomes were change in patient-reported target joint pain from baseline to day 3 and from baseline to day 7, assessed in the per-protocol population (all patients who received at least 80% of the study drug and had no major protocol deviations). Safety was assessed in the intention-to-treat population. This trial is registered with the EU Clinical Trials Register, EudraCT 2016-000943-14, and is completed. FINDINGS: Between May 18, 2017, and Jan 21, 2019, 144 patients were assessed for eligibility, of whom 34 were enrolled and 29 were included in the per-protocol population (three patients were excluded due to receiving |
| Databáze: | OpenAIRE |
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