Vidofludimus Calcium in Patients With Moderate-to-Severe Ulcerative Colitis: A Randomized, Placebo-Controlled, Phase 2 Trial.

IF 3 3区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Clinical and Translational Gastroenterology Pub Date : 2025-01-10 DOI:10.14309/ctg.0000000000000813

Geert D'Haens, Kalina Grivcheva Stardelova, Edite Sadiku, Natallia Kizlova, Syitlana Skybalo, Yulia Shehovtsova, Mirela Abramescu, Daniel Vitt, Hella Kohlhof, Andreas Muehler

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引用次数: 0

Abstract

Introduction: Vidofludimus calcium (VidoCa) is a dihydroorotate dehydrogenase inhibitor that demonstrated efficacy in immune-related diseases. This study assessed the safety and efficacy of VidoCa in patients with active ulcerative colitis (UC).

Methods: This placebo-controlled, phase 2 trial randomized adults with moderate-to-severe UC to receive once-daily VidoCa (10, 30, or 45 mg) or placebo for 10 weeks (induction); patients with symptomatic remission were rerandomized to VidoCa 10, 30 mg, or placebo once daily for an additional 40 weeks (maintenance). The primary endpoint was clinical remission at week 10. Secondary endpoints included symptomatic remission, endoscopic healing, and symptomatic response. The study is registered with ClinicalTrials.gov (NCT03341962) and EudraCT (2017-003703-22).

Results: Two hundred sixty-three patients were randomized to induction treatment with VidoCa (10 mg [n = 67], 30 mg [n = 66], and 45 mg [n = 66]) or placebo (n = 64). Sixteen (14%) patients treated with VidoCa (30 mg or 45 mg) achieved the primary endpoint compared with 8 (14%) with placebo. In patients without concomitant corticosteroids, 7 (12%) treated with VidoCa achieved clinical remission at week 10 vs 1 (4%) with placebo. At week 50, dose-dependent increases in the rate of clinical remission ( P = 0.0358), steroid-free clinical remission, and endoscopic healing were observed. Common adverse events (AEs) were headache (4 [6%]), anemia (3 [6%]), vomiting (3 [5%]), and hypertension (3 [5%]) with incidence similar between placebo and VidoCa. Hematuria (4 [6%]) was a treatment-related AE with VidoCa 45 mg only. The incidence of serious AEs was low.

Discussion: VidoCa was safe, well-tolerated, and demonstrated proof-of-concept for dihydroorotate dehydrogenase inhibition to treat UC.

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Vidofludimus钙治疗中重度溃疡性结肠炎：一项随机、安慰剂对照的2期试验

简介：Vidofludimus calcium （VidoCa）是一种二氢酸脱氢酶（DHODH）抑制剂，在免疫相关疾病中表现出疗效。本研究评估了VidoCa治疗活动性溃疡性结肠炎（UC）患者的安全性和有效性。方法：这项安慰剂对照的2期试验随机选择患有中重度UC的成年人，每天接受一次维多卡（10、30或45毫克）或安慰剂，持续10周（诱导）；症状缓解的患者重新随机分配到维多卡10、30毫克或安慰剂组，每天一次，持续40周（维持）。主要终点是第10周的临床缓解。次要终点包括症状缓解、内镜下愈合和症状反应。该研究已在ClinicalTrials.gov （NCT03341962）和EudraCT（2017-003703-22）注册。结果：263例患者随机分为VidoCa诱导组（10 mg [n=67）， 30 mg [n=66], 45 mg [n=66])和安慰剂组（n=64）。16例（14%）患者使用VidoCa （30mg或45mg）治疗达到主要终点，而8例（14%）患者使用安慰剂。在未同时使用皮质类固醇的患者中，7例（12%）使用VidoCa治疗在第10周达到临床缓解，而1例（4%）使用安慰剂治疗。在第50周，观察到临床缓解率、无类固醇临床缓解率和内窥镜愈合率的剂量依赖性增加（p=0.0358）。常见不良事件（ae）为头痛（4例[6%]）、贫血（3例[6%]）、呕吐（3例[5%]）和高血压（3例[5%]），安慰剂组和维多卡组发生率相似。血尿（4[6%]）是仅使用VidoCa 45 mg治疗相关的AE。严重不良反应发生率低。结论：VidoCa是安全的，耐受性良好，并且证明了DHODH抑制治疗UC的概念。

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 and Translational Gastroenterology GASTROENTEROLOGY & HEPATOLOGY-

CiteScore

7.00

自引率

0.00%

发文量

114

审稿时长

16 weeks

期刊介绍： Clinical and Translational Gastroenterology (CTG), published on behalf of the American College of Gastroenterology (ACG), is a peer-reviewed open access online journal dedicated to innovative clinical work in the field of gastroenterology and hepatology. CTG hopes to fulfill an unmet need for clinicians and scientists by welcoming novel cohort studies, early-phase clinical trials, qualitative and quantitative epidemiologic research, hypothesis-generating research, studies of novel mechanisms and methodologies including public health interventions, and integration of approaches across organs and disciplines. CTG also welcomes hypothesis-generating small studies, methods papers, and translational research with clear applications to human physiology or disease. Colon and small bowel Endoscopy and novel diagnostics Esophagus Functional GI disorders Immunology of the GI tract Microbiology of the GI tract Inflammatory bowel disease Pancreas and biliary tract Liver Pathology Pediatrics Preventative medicine Nutrition/obesity Stomach.