Design, Rationale and Baseline Characteristics of the Randomized Double-blind Phase II Clinical Trial of Vidofludimus calcium (IMU-838) in Relapsing-Remitting Multiple Sclerosis (4558)

Objective: To present the design and participant baseline characteristics of the MRI Trial to exPlore the efficAcy and Safety of IMU-838 in Relapsing Remitting Multiple Sclerosis (EMPhASIS) study (NCT03846219). Background: Vidofludimus calcium/IMU-838 belongs to a novel chemical class of orally available dihydroorotate dehydrogenase (DHODH) inhibitors. By inhibiting DHODH, a key enzyme of pyrimidine de novo biosynthesis, activated T and B cells experience metabolic stress, and the release of Th1 and Th17 key cytokines (IL-17A, IL-17F and IFNg) is attenuated. Considering these selective immunomodulatory effects and a more favorable safety profile than first generation DHODH inhibitors based on a serum half life time of only 30 hours and a comparable safety profile as placebo in a phase II trial for rheumatoid arthritis (NCT01010581), IMU-838 has been considered therapeutically promising for various autoimmune disorders including multiple sclerosis (MS). Design/Methods: EMPhASIS is an ongoing multicenter, double-blind, placebo-controlled, randomized, parallel-group trial to assess the efficacy and safety of 2 once-daily oral doses of IMU-838 in patients with relapsing-remitting MS. The trial consists of a blinded, 24-week main treatment period and an optional initially blinded, then open-label extended treatment period of up to 9.5 years. Inclusion criteria were age 18–55 years, active relapsing remitting MS, and EDSS 0–4. Patients were randomized 1:1:1 to treatment with 30 mg/day or 45 mg/day IMU-838, or placebo in the main treatment period. The primary endpoint is the cumulative number of combined unique active MRI lesions at 24 weeks. Results: Enrollment occurred from February 2019 to October 2019. As of 10th October 2019, EMPhASIS randomized 210 patients (65% women). Mean age at baseline was 36.8 years (standard deviation 8.8). Further details of study design and baseline demographics will be presented. Conclusions: EMPhASIS is a Phase II trial investigating the efficacy and safety of the second generation DHODH inhibitor in patients with relapsing remitting MS. Disclosure: Dr. Fox has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Robert Fox has received compensation for serving as a consultant or speaker from Actelion, Biogen, Celgene, EMD Serono, Genentech, Immunic, Novartis, and Teva. He, or the institution he works for, has received research support from Novartis.. Dr. Fox has received research support from He, or the institution he works for, has received research support from Novartis..Dr. Wiendl has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Abbvie, Actelion, Alexion, Biogen, Cognomed, Evgen, F. Hoffmann-La Roche Ltd, Genzyme, Johnson & Johnson, MedDay Pharmaceuticals, Merck Serono, Novartis, Roche Pharma AG, Sanofi-Aventis, TEVA, and WebMD Global. Dr. Wiendl has received research support from Biogen, GlaxoSmithKline GmbH, Roche Pharma AG, and Sanofi-Genzyme.Dr. De Stefano has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with A consultant for Schering, Biogen-Idec, Teva, Novartis, Sanofi-Genzyme, Roche and Merck-Serono; is on the speakers’ bureaus of Biogen-Idec, Teva, Novartis, Sanofi-Genzyme, Roche, and Merck-Serono. Dr. De Stefano has received research support from Has grants or grants pending from FISM and Roche. He contributed to studies sponsored by Merck KGaA, Darmstadt, Germany. Dr. Sellner has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Bayer, Biogen, Merck, Novartis, Roche, Sanofi, Teva, Gerot-Lannach. Dr. Sellner has received research support from Biogen, Merck, Roche. Dr. Muehler has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Immunic Therapeutics. Dr. Muehler has received compensation for serving on the Board of Directors of Immunic Therapeutics. Dr. Muehler has received royalty, license fees, or contractual rights payments from Immunic Therapeutics. Dr. Muehler holds stock and/or stock options in Immunic Therapeutics which sponsored research in which Dr. Muehler was involved as an investigator.