A double‐blind, randomized, placebo‐controlled phase 2 trial evaluating the selective dihydroorotate dehydrogenase inhibitor vidofludimus calcium in relapsing‐remitting multiple sclerosis
Abstract Objective Inhibition of dihydroorotate dehydrogenase suppresses magnetic resonance imaging brain lesions and disease activity in multiple sclerosis but has limiting tolerability. We assessed the safety and efficacy of vidofludimus calcium, a novel, selective dihydroorotate dehydrogenase inh...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022-07-01
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| Series: | Annals of Clinical and Translational Neurology |
| Online Access: | https://doi.org/10.1002/acn3.51574 |
| _version_ | 1828463044972249088 |
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| author | Robert J. Fox Heinz Wiendl Christian Wolf Nicola De Stefano Johann Sellner Viktoriia Gryb Konrad Rejdak Plamen Stoyanov Bozhinov Nataliya Tomakh Iryna Skrypchenko Andreas R. Muehler |
| author_facet | Robert J. Fox Heinz Wiendl Christian Wolf Nicola De Stefano Johann Sellner Viktoriia Gryb Konrad Rejdak Plamen Stoyanov Bozhinov Nataliya Tomakh Iryna Skrypchenko Andreas R. Muehler |
| author_sort | Robert J. Fox |
| collection | DOAJ |
| description | Abstract Objective Inhibition of dihydroorotate dehydrogenase suppresses magnetic resonance imaging brain lesions and disease activity in multiple sclerosis but has limiting tolerability. We assessed the safety and efficacy of vidofludimus calcium, a novel, selective dihydroorotate dehydrogenase inhibitor, in patients with relapsing‐remitting multiple sclerosis. Methods This double‐blind, 24 weeks, placebo‐controlled, phase 2 trial (EMPhASIS) enrolled patients 18–55 years with relapsing‐remitting multiple sclerosis. Eligible patients were randomly assigned (1:1:1) to once‐daily vidofludimus calcium (30 mg or 45 mg) or placebo. The primary endpoint was the cumulative number of combined unique active lesions to week 24 between vidofludimus calcium 45 mg and placebo (clinicalTrials.gov number NCT03846219; EudraCT 2018–001896‐19). Results After 24 weeks, the mean cumulative number of combined unique active lesions was 6.4 (95% CI: 2.8–13.9) with placebo compared to 2.4 (95% CI: 1.1–4.9) with vidofludimus calcium 45 mg (rate ratio 0.38, 95% CI: 0.22–0.64; p = 0.0002); the rate ratio between vidofludimus calcium 30 mg and placebo was 0.30 (95% CI: 0.17–0.53; p < 0.0001). Treatment‐emergent adverse events occurred in 30 (44%) of patients assigned placebo and 60 (43%) of patients assigned vidofludimus calcium. Serious adverse events occurred in one (1%) assigned placebo and two (1%) assigned vidofludimus calcium. No increased incidence of infectious, hepatic, or renal treatment‐emergent adverse events or serious adverse events was observed. Interpretation Treatment with vidofludimus calcium led to a reduction in new magnetic resonance imaging lesions in patients with relapsing‐remitting multiple sclerosis and was well tolerated with a favorable safety profile. Assessment in longer, larger trials is justified. |
| first_indexed | 2024-12-11T02:46:59Z |
| format | Article |
| id | doaj.art-20b5a8195d66471c8d36116775ea8d4f |
| institution | Directory Open Access Journal |
| issn | 2328-9503 |
| language | English |
| last_indexed | 2024-12-11T02:46:59Z |
| publishDate | 2022-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Annals of Clinical and Translational Neurology |
| spelling | doaj.art-20b5a8195d66471c8d36116775ea8d4f2022-12-22T01:23:23ZengWileyAnnals of Clinical and Translational Neurology2328-95032022-07-019797798710.1002/acn3.51574A double‐blind, randomized, placebo‐controlled phase 2 trial evaluating the selective dihydroorotate dehydrogenase inhibitor vidofludimus calcium in relapsing‐remitting multiple sclerosisRobert J. Fox0Heinz Wiendl1Christian Wolf2Nicola De Stefano3Johann Sellner4Viktoriia Gryb5Konrad Rejdak6Plamen Stoyanov Bozhinov7Nataliya Tomakh8Iryna Skrypchenko9Andreas R. Muehler10Mellen Center for Multiple Sclerosis Cleveland Clinic Cleveland Ohio USADepartment of Neurology with Institute of Translational Neurology University of Münster Münster GermanyLycalis sprl Brussels BelgiumDepartment of Medicine, Surgery and Neuroscience University of Siena Siena ItalyDepartment of Neurology Landesklinikum Mistelbach‐Gänserndorf 2130 Mistelbach AustriaRegional Clinical Hospital Department of Vascular Neurology Ivano‐Frankivsk UkraineMedical University of Lublin Department of Neurology Jaczewskiego 8 20‐954 Lublin PolandMedical University of Pleven 1 Saint Kliment Ohridski Street 5800 Pleven BulgariaLLC “INET‐09” 32 Zhabotinskogo Leonida Street Zaporozhye UkraineKharkiv Regional Clinical Hospital Department of Neurology Kharkiv UkraineImmunic AG Lochhamer Schlage 21 82166 Gräfelfing GermanyAbstract Objective Inhibition of dihydroorotate dehydrogenase suppresses magnetic resonance imaging brain lesions and disease activity in multiple sclerosis but has limiting tolerability. We assessed the safety and efficacy of vidofludimus calcium, a novel, selective dihydroorotate dehydrogenase inhibitor, in patients with relapsing‐remitting multiple sclerosis. Methods This double‐blind, 24 weeks, placebo‐controlled, phase 2 trial (EMPhASIS) enrolled patients 18–55 years with relapsing‐remitting multiple sclerosis. Eligible patients were randomly assigned (1:1:1) to once‐daily vidofludimus calcium (30 mg or 45 mg) or placebo. The primary endpoint was the cumulative number of combined unique active lesions to week 24 between vidofludimus calcium 45 mg and placebo (clinicalTrials.gov number NCT03846219; EudraCT 2018–001896‐19). Results After 24 weeks, the mean cumulative number of combined unique active lesions was 6.4 (95% CI: 2.8–13.9) with placebo compared to 2.4 (95% CI: 1.1–4.9) with vidofludimus calcium 45 mg (rate ratio 0.38, 95% CI: 0.22–0.64; p = 0.0002); the rate ratio between vidofludimus calcium 30 mg and placebo was 0.30 (95% CI: 0.17–0.53; p < 0.0001). Treatment‐emergent adverse events occurred in 30 (44%) of patients assigned placebo and 60 (43%) of patients assigned vidofludimus calcium. Serious adverse events occurred in one (1%) assigned placebo and two (1%) assigned vidofludimus calcium. No increased incidence of infectious, hepatic, or renal treatment‐emergent adverse events or serious adverse events was observed. Interpretation Treatment with vidofludimus calcium led to a reduction in new magnetic resonance imaging lesions in patients with relapsing‐remitting multiple sclerosis and was well tolerated with a favorable safety profile. Assessment in longer, larger trials is justified.https://doi.org/10.1002/acn3.51574 |
| spellingShingle | Robert J. Fox Heinz Wiendl Christian Wolf Nicola De Stefano Johann Sellner Viktoriia Gryb Konrad Rejdak Plamen Stoyanov Bozhinov Nataliya Tomakh Iryna Skrypchenko Andreas R. Muehler A double‐blind, randomized, placebo‐controlled phase 2 trial evaluating the selective dihydroorotate dehydrogenase inhibitor vidofludimus calcium in relapsing‐remitting multiple sclerosis Annals of Clinical and Translational Neurology |
| title | A double‐blind, randomized, placebo‐controlled phase 2 trial evaluating the selective dihydroorotate dehydrogenase inhibitor vidofludimus calcium in relapsing‐remitting multiple sclerosis |
| title_full | A double‐blind, randomized, placebo‐controlled phase 2 trial evaluating the selective dihydroorotate dehydrogenase inhibitor vidofludimus calcium in relapsing‐remitting multiple sclerosis |
| title_fullStr | A double‐blind, randomized, placebo‐controlled phase 2 trial evaluating the selective dihydroorotate dehydrogenase inhibitor vidofludimus calcium in relapsing‐remitting multiple sclerosis |
| title_full_unstemmed | A double‐blind, randomized, placebo‐controlled phase 2 trial evaluating the selective dihydroorotate dehydrogenase inhibitor vidofludimus calcium in relapsing‐remitting multiple sclerosis |
| title_short | A double‐blind, randomized, placebo‐controlled phase 2 trial evaluating the selective dihydroorotate dehydrogenase inhibitor vidofludimus calcium in relapsing‐remitting multiple sclerosis |
| title_sort | double blind randomized placebo controlled phase 2 trial evaluating the selective dihydroorotate dehydrogenase inhibitor vidofludimus calcium in relapsing remitting multiple sclerosis |
| url | https://doi.org/10.1002/acn3.51574 |
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