P568 An open-label, multicenter, phase ib, pharmacokinetic (pk) and safety study of a fimh blocker, Sibofimloc (TAK-018/EB8018), in patients with Crohn’s disease (CD)
W. Reinisch1, X. Hébuterne2, A. Buisson3, S. Schreiber4, P. Desreumaux5, J.M. Paillarse6, C. Bonny7
1Medical University of Vienna, Gastroenterology and Hepatology, Vienna, Austria, 2CHU Nice and University Côte d’Azur, Gastroenterology, Nice, France, 3CHU, Gastroenterology, Clermont-Ferrand, France, 4University-Hospital Schleswig-Holstein, Internal medicine, Kiel, Germany, 5CHU Lille, Gastroenterology, Lille, France, 6Enterome Bioscience, Medical Department, Paris, France, 7Enterome Bioscience, Scientific Direction, Paris, France
Background
Sibofimloc (EB8018/TAK-018) is a gut-restricted orally administered, first-in-class, FimH blocker that targets FimH, a TLR4 receptor, expressed on
Methods
We conducted a multicenter open-label study to enrol 8 adult patients with active CD (faecal calprotectin (FCP) ≥150 µg/g and/or ulcers at colonoscopy). Pregnant women were excluded. This study was divided into two parts. 1)Two patients received a single dose of 3000 mg sibofimloc followed, after a wash-out period, by a 13 day-period with1500 mg twice daily. 2)After review of data from these two patients, the 6 remaining patients received 1500 mg sibofimloc twice daily for a 13 day period.
Results
Cmax values for the 2 initial patients (after single dose 3000 mg sibofimloc) were 51.3 and 348 ng/ml respectively and allowed part 2 of the study. The main safety and PK data of an interim analysis after the first 4 patients had been treated with sibofimloc 1500 mg twice daily are presented in the table.
| Nb of patients | 4 |
| Age in years (mean ± S.D.) | 31.8± 15.7 |
| Gender | 2 males; 2 females |
| Baseline fecal calprotectin: median [min-max] (µg/g) | 467[263–2500] |
| Nb of AE | 18 |
| Nb of related AE | 8 |
| Nb of serious AE | 0 |
| Nb of deaths | 0 |
| Nb of AE leading to drug discontinuation | 0 |
| Cmax at D13: median [min-max] (ng/ml) | 340.5[43.2–438] |
| Tmax at D13: median [min, max] (h) | 3.95[2.98–8] |
Nb:number;SD:standard deviation; AE:adverse event; D:Day; Cmax:maximum concentration; min:minimum; max:maximum; T max:time to reach Cmax.
In a previous study in 7 healthy subjects, after 14 days sibofimloc 1500 mg twice daily, median Cmax[min-max] at Day14 was 49[19.2–86.6]ng/ml.
Conclusion
These preliminary data confirmed that sibofimloc was well tolerated. In the small subset of patients analyzed, there was a slightly higher plasma exposure and interpatient variability compared with what has been seen earlier in healthy subjects. The safety and PK data allowed the continuation of the clinical development program with the initiation of a phase 2 trial for postoperative maintenance in patients with CD.