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 and aims: Efmarodocokin alfa is an interleukin (IL)-22 agonist, with favorable pharmacokinetic (PK) properties and an acceptable safety profile. This study further explored the therapeutic potential of efmarodocokin alfa compared to vedolizumab in patients with ulcerative colitis (UC).
Methods: This randomized phase 2 trial evaluated the efficacy, safety, PK, 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 to 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 (REG3A and CRP levels).
Conclusion: Efmarodocokin alfa did not demonstrate efficacy compared to placebo and this phase 2 study was ended early for futility; however, there was evidence of target engagement (skin AEs, REG3A levels); NCT03558152.
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.