D'Haens Geert, Stardelova Kalina Grivcheva, Sadiku Edite, Kizlova Natallia, Skybalo Syitlana, Shehovtsova Yulia, Abramescu Mirela, Vitt Daniel, Kohlhof Hella, Muehler Andreas
Department of Gastroenterology, Amsterdam University Medical Centers, Amsterdam, the Netherlands.
University Clinic of Gastroenterohepatology, Skopje, North Macedonia.
Clin Transl Gastroenterol. 2025 Mar 1;16(3):e00813. doi: 10.14309/ctg.0000000000000813.
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).
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).
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.
VidoCa was safe, well-tolerated, and demonstrated proof-of-concept for dihydroorotate dehydrogenase inhibition to treat UC.
维多氟啶钙（VidoCa）是一种二氢乳清酸脱氢酶抑制剂，已在免疫相关疾病中显示出疗效。本研究评估了VidoCa在活动性溃疡性结肠炎（UC）患者中的安全性和有效性。
这项安慰剂对照的2期试验将中度至重度UC成人患者随机分为接受每日一次的VidoCa（10、30或45毫克）或安慰剂治疗10周（诱导期）；症状缓解的患者被重新随机分为每日一次的VidoCa 10毫克、30毫克或安慰剂，再治疗40周（维持期）。主要终点是第10周时的临床缓解。次要终点包括症状缓解、内镜愈合和症状反应。该研究已在ClinicalTrials.gov（NCT03341962）和EudraCT（2017-003703-22）注册。
263名患者被随机分配接受VidoCa（10毫克[n = 67]、30毫克[n = 66]和45毫克[n = 66]）或安慰剂（n = 64）的诱导治疗。接受VidoCa（30毫克或45毫克）治疗的16名（14%）患者达到主要终点，而接受安慰剂治疗的为8名（14%）。在未同时使用皮质类固醇的患者中，接受VidoCa治疗的7名（12%）患者在第10周时实现临床缓解，而接受安慰剂治疗的为1名（4%）。在第50周时，观察到临床缓解率（P = 0.0358）、无类固醇临床缓解率和内镜愈合率呈剂量依赖性增加。常见不良事件（AE）包括头痛（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VidoCa组的发生率相似。血尿（4例[6%]）是仅与45毫克VidoCa治疗相关的AE。严重AE的发生率较低。
VidoCa安全、耐受性良好，并证明了二氢乳清酸脱氢酶抑制治疗UC的概念验证。
