A Randomized Phase II Study of Efmarodocokin Alfa, an interleukin-22 Agonist, Versus Vedolizumab in Patients With Ulcerative Colitis.

IF 11.6 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Clinical Gastroenterology and Hepatology Pub Date : 2024-12-16 DOI:10.1016/j.cgh.2024.11.013

Silvio Danese, Michael E Rothenberg, Jeremy J Lim, Han Ting Ding, Jacqueline M McBride, Yiling Chen, Ajit Dash, Jordan S Mar, Mary Keir, Laurent Peyrin-Biroulet, Julian Panes, Jean-Frederic Colombel, Brian Feagan, John F Valentine, Stefan Schreiber

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引用次数: 0

Abstract

Background & aims: Efmarodocokin alfa is an interleukin (IL)-22 agonist, with favorable pharmacokinetic properties and an acceptable safety profile. This study further explored the therapeutic potential of efmarodocokin alfa compared with vedolizumab in patients with ulcerative colitis (UC).

Methods: This randomized phase II trial evaluated the efficacy, safety, pharmacokinetics, and pharmacodynamics of 3 doses of efmarodocokin alfa administered intravenously every 4 weeks (30 μg/kg [n = 43], 60 μg/kg [n = 44], and 90 μg/kg [n = 43]) compared with placebo (n = 22) and with vedolizumab (n = 43) in the treatment of moderate to severe UC. Key clinical outcomes were assessed through the modified Mayo Clinic Score, and endoscopic evaluations by a central reader.

Results: Efmarodocokin alfa was adequately tolerated with an acceptable safety profile. Although efmarodocokin alfa did not show statistically significant improvement in clinical remission, clinical response, endoscopic healing, or endoscopic remission at week 8 compared with placebo, vedolizumab demonstrated some efficacy. Clinical remission was achieved by 12%, 9%, and 12% of patients in the 30, 60, and 90 μg/kg dose arms, respectively, compared with 9% and 26% of patients in the placebo and vedolizumab arms at week 8. Similarly, endoscopic healing at week 8 was achieved by 14%, 14%, and 12% of patients in the 30, 60, and 90 μg/kg dose arms, respectively, compared with 14% and 33% of patients in the placebo and vedolizumab arms. A dose-dependent increase in pharmacodynamic biomarkers was observed (regenerating islet-derived protein 3-alpha and C-reactive protein levels).

Conclusion: Efmarodocokin alfa did not demonstrate efficacy compared with placebo, and this phase II study was ended early for futility; however, there was evidence of target engagement (skin adverse events, regenerating islet-derived protein 3-alpha levels).

Clinicaltrials: gov, Number: NCT03558152.

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一项随机2期研究，一种IL-22激动剂efmarodocokin alfa与vedolizumab在溃疡性结肠炎患者中的疗效。

背景和目的：Efmarodocokin α是一种白细胞介素(IL)-22激动剂，具有良好的药代动力学（PK）特性和可接受的安全性。本研究进一步探讨了efmarodocokin与vedolizumab在溃疡性结肠炎（UC）患者中的治疗潜力。方法：这项随机2期试验评估了3个剂量的efmarodocokin alfa（每4周静脉注射30 μg/kg [n=43], 60 μg/kg [n=44]和90 μg/kg [n=43]）与安慰剂（n=22）和vedolizumab （n=43）治疗中重度UC的疗效、安全性、PK和药效学。主要临床结果通过修改后的梅奥临床评分进行评估，并由中心阅读器进行内窥镜评估。结果：Efmarodocokin α具有足够的耐受性和可接受的安全性。虽然与安慰剂相比，efmarodocokin在第8周的临床缓解、临床反应、内窥镜愈合或内窥镜缓解方面没有统计学意义上的显著改善，但vedolizumab显示出一定的疗效。在30、60和90 μg/kg剂量组中，分别有12%、9%和12%的患者达到临床缓解，而在第8周时，安慰剂组和维多单抗组中分别有9%和26%的患者达到临床缓解。同样，在30、60和90 μg/kg剂量组中，第8周内窥镜下愈合的患者分别为14%、14%和12%，而安慰剂组和vedolizumab组的这一比例分别为14%和33%。观察到药效学生物标志物（REG3A和CRP水平）的剂量依赖性增加。结论：与安慰剂相比，Efmarodocokin α没有显示出疗效，该2期研究因无效而提前结束；然而，有证据表明目标接触（皮肤ae， REG3A水平）；NCT03558152。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical Gastroenterology and Hepatology 医学-胃肠肝病学

CiteScore

16.90

自引率

4.80%

发文量

903

审稿时长

22 days

期刊介绍： Clinical Gastroenterology and Hepatology (CGH) is dedicated to offering readers a comprehensive exploration of themes in clinical gastroenterology and hepatology. Encompassing diagnostic, endoscopic, interventional, and therapeutic advances, the journal covers areas such as cancer, inflammatory diseases, functional gastrointestinal disorders, nutrition, absorption, and secretion. As a peer-reviewed publication, CGH features original articles and scholarly reviews, ensuring immediate relevance to the practice of gastroenterology and hepatology. Beyond peer-reviewed content, the journal includes invited key reviews and articles on endoscopy/practice-based technology, health-care policy, and practice management. Multimedia elements, including images, video abstracts, and podcasts, enhance the reader's experience. CGH remains actively engaged with its audience through updates and commentary shared via platforms such as Facebook and Twitter.