Western University, London, Ontario, Canada.
Department of Internal Medicine I, University Hospital Schleswig-Holstein, Kiel University, Kiel, Germany.
Contemp Clin Trials. 2022 Nov;122:106958. doi: 10.1016/j.cct.2022.106958. Epub 2022 Oct 5.
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, and histological benefit in the phase 2 STEPSTONE trial for Crohn's disease (CD). We aim to describe the trial design of the YELLOWSTONE phase 3 program evaluating the safety and efficacy of ozanimod in patients with moderately to severely active CD.
The YELLOWSTONE program consists of phase 3, randomized, double-blind, placebo-controlled induction (NCT03440372 and NCT03440385) and maintenance (NCT03464097) trials and an open-label extension (OLE) study (NCT03467958). Patients with inadequate response or intolerance to ≥1 CD treatment are randomized to receive daily ozanimod 0.92 mg (equivalent to ozanimod HCl 1 mg) or placebo for 12 weeks during induction. Those who respond to ozanimod are rerandomized to continue ozanimod or placebo maintenance therapy for 52 weeks. Patients who do not meet criteria for maintenance, experience relapse during maintenance, or complete maintenance or ≥ 1 year of STEPSTONE are eligible for open-label treatment for up to 234 weeks. Efficacy endpoints include clinical, endoscopic, and histologic outcomes.
Expected 2023 (induction studies), 2024 (maintenance study), and 2026 (OLE).
YELLOWSTONE will provide pivotal phase 3 data on the safety and efficacy of ozanimod in patients with moderately to severely active CD using state-of-the-art methods, including centrally read endoscopic and histologic measurements, along with subjective assessments of symptom control based on the Crohn's Disease Activity Index. These studies could enable approval of ozanimod as a new CD therapy.
NCT03440372, NCT03440385, NCT03464097, NCT03467958.
奥扎莫德是一种口服鞘氨醇 1-磷酸受体调节剂，目前已被批准用于治疗中度至重度活动期溃疡性结肠炎和复发性多发性硬化症，在克罗恩病（CD）的 2 期 STEPSTONE 试验中显示出临床、内镜和组织学获益。我们旨在描述评估奥扎莫德在中度至重度活动期 CD 患者中的安全性和疗效的 YELLOWSTONE 3 期计划的试验设计。
YELLOWSTONE 计划包括 3 期、随机、双盲、安慰剂对照诱导（NCT03440372 和 NCT03440385）和维持（NCT03464097）试验以及开放标签扩展（OLE）研究（NCT03467958）。对≥1 种 CD 治疗反应不足或不耐受的患者进行随机分组，接受奥扎莫德 0.92mg（相当于奥扎莫德 HCl 1mg）或安慰剂治疗 12 周诱导期。对奥扎莫德有反应的患者再次随机分组，继续接受奥扎莫德或安慰剂维持治疗 52 周。不符合维持标准、维持期间复发或完成维持或≥1 年 STEPSTONE 的患者有资格接受奥扎莫德开放标签治疗，最长可达 234 周。疗效终点包括临床、内镜和组织学结果。
预计 2023 年（诱导研究）、2024 年（维持研究）和 2026 年（OLE）。
YELLOWSTONE 将使用最先进的方法提供奥扎莫德在中度至重度活动期 CD 患者中的安全性和疗效的关键性 3 期数据，包括中心读取的内镜和组织学测量，以及基于克罗恩病活动指数的症状控制的主观评估。这些研究可能使奥扎莫德获得批准成为一种新的 CD 治疗方法。
NCT03440372、NCT03440385、NCT03464097、NCT03467958。
