Safety, pharmacokinetic, and pharmacodynamic study of sibofimloc, a novel FimH blocker in patients with active Crohn's disease.
J Gastroenterol Hepatol
; 37(5): 832-840, 2022 May.
Article
in En
| MEDLINE
| ID: mdl-35266174
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-1ß, 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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Crohn Disease
Type of study:
Clinical_trials
Limits:
Adult
/
Humans
Language:
En
Journal:
J Gastroenterol Hepatol
Journal subject:
GASTROENTEROLOGIA
Year:
2022
Document type:
Article
Affiliation country: