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

Introduction: Vidofludimus calcium (VidoCa) is a dihydroorotate dehydrogenase (DHODH) 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-severe UC to receive once-daily VidoCa (10, 30, or 45 mg) or placebo for 10 weeks (induction); patients with symptomatic remission were re-randomized 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: 263 patients were randomized to induction treatment with VidoCa (10 mg [n=67)], 30 mg [n=66], 45 mg [n=66]) or placebo (n=64). Sixteen (14%) patients treated with VidoCa (30 mg or 45 mg) achieved the primary endpoint compared to 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.

Conclusions: VidoCa was safe, well-tolerated, and demonstrated proof-of-concept for DHODH inhibition to treat UC.