Safety, pharmacokinetic, and pharmacodynamic study of sibofimloc, a novel FimH blocker in patients with active Crohn's disease - Archive ouverte HAL Access content directly
Journal Articles Journal of Gastroenterology and Hepatology Year : 2022

Safety, pharmacokinetic, and pharmacodynamic study of sibofimloc, a novel FimH blocker in patients with active Crohn's disease

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Abstract

Background and aim: Expression of FimH adhesin by invasive Escherichia coli in the gastrointestinal tract of patients with Crohn's disease (CD) facilitates binding to epithelial glycoproteins and release of pro-inflammatory cytokines. Sibofimloc is a first-in-class FimH blocker that showed little systemic absorption in healthy volunteers. The current study evaluated systemic absorption, safety, and effect on inflammatory biomarkers of sibofimloc in patients with CD. Methods: This was an open-label, multicenter phase 1b study in adults with active CD. In part 1, two patients received a single oral dose of 3000-mg sibofimloc followed by 1500 mg b.i.d. for 13 days. In part 2, six patients received 1500-mg sibofimloc b.i.d. for 13 days. Blood was drawn for pharmacokinetic and biomarker analysis, and stool was collected for biomarker and microbiome analysis. Results: Eight patients with active ileal or ileocolonic CD were enrolled into the study. Systemic sibofimloc exposure was low. Sibofimloc was well tolerated with only grade 1-2 events observed. Several pro-inflammatory biomarkers, including IL-1β, IL-6, IL-8, TNF-α, IFN-γ, and calprotectin, were decreased in stool by end of study. Conclusions: This first study of the novel FimH blocker, sibofimloc, in patients with active CD demonstrated minimal systemic exposure with good tolerance, while decreasing several inflammatory biomarkers. EudraCT number: 2017-003279-70.
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Dates and versions

hal-03772988 , version 1 (08-09-2022)

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Walter Reinisch, Xavier Hebuterne, Anthony Buisson, Stefan Schreiber, Pierre Desreumaux, et al.. Safety, pharmacokinetic, and pharmacodynamic study of sibofimloc, a novel FimH blocker in patients with active Crohn's disease. Journal of Gastroenterology and Hepatology, 2022, 37 (5), pp.832-840. ⟨10.1111/jgh.15828⟩. ⟨hal-03772988⟩
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