Ozanimod as a novel oral small molecule therapy for the treatment of Crohn's disease: The YELLOWSTONE clinical trial program

• DOI: 10.1016/j.cct.2022.106958
• Publication Date: 2022-10-05T23:16:04Z
• Authors: Brian G. Feagan; Stefan Schreiber; Anita Afzali; Florian Rieder; Jeffrey Hyams; Kanthi Kollengode; Jared Pearlman; Vladimir Son; Cecilia Marta; Douglas C. Wolf; Geert G. D'Haens
• Keywords: Maintenance therapy

Ozanimod, an oral sphingosine 1-phosphate receptor modulator currently approved for the treatment of moderately to severely active ulcerative colitis and relapsing multiple sclerosis, showed clinical, endoscopic, histological benefit in phase 2 STEPSTONE trial Crohn's disease (CD). We aim describe design YELLOWSTONE 3 program evaluating safety efficacy ozanimod patients with CD.The consists 3, randomized, double-blind, placebo-controlled induction (NCT03440372 NCT03440385) maintenance (NCT03464097) trials open-label extension (OLE) study (NCT03467958). Patients inadequate response or intolerance ≥1 CD are randomized receive daily 0.92 mg (equivalent HCl 1 mg) placebo 12 weeks during induction. Those who respond rerandomized continue therapy 52 weeks. do not meet criteria maintenance, experience relapse complete ≥ year eligible up 234 Efficacy endpoints include histologic outcomes.Expected 2023 (induction studies), 2024 (maintenance study), 2026 (OLE).YELLOWSTONE will provide pivotal data on using state-of-the-art methods, including centrally read endoscopic measurements, along subjective assessments symptom control based Disease Activity Index. These studies could enable approval as a new therapy.NCT03440372, NCT03440385, NCT03464097, NCT03467958.