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Safety, pharmacokinetic, and pharmacodynamic study of sibofimloc, a novel FimH blocker in patients with active Crohn's disease
- Source :
- Journal of Gastroenterology and Hepatology, Journal of Gastroenterology and Hepatology, 2022, 37 (5), pp.832-840. ⟨10.1111/jgh.15828⟩
- Publication Year :
- 2022
- Publisher :
- Wiley, 2022.
-
Abstract
- Essai clinique - Phase I; International audience; 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.
- Subjects :
- Adult
clinical trials
Adhesins, Escherichia coli
Hepatology
FimH receptor
microbiology
Gastroenterology
microbiome
[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology
basic science
adherent-invasive E. coli
Anti-Bacterial Agents
Crohn's disease
Crohn Disease
FimH blocker
experimental models and pathophysiology
Escherichia coli
sibofimloc
Humans
Fimbriae Proteins
Biomarkers
Subjects
Details
- ISSN :
- 14401746 and 08159319
- Volume :
- 37
- Database :
- OpenAIRE
- Journal :
- Journal of Gastroenterology and Hepatology
- Accession number :
- edsair.doi.dedup.....5532cb9801c671ed3dab0cf7db3b0c0f
- Full Text :
- https://doi.org/10.1111/jgh.15828