Safety and Efficacy of Vidofludimus Calcium in Patients Hospitalized with COVID-19: A Double-Blind, Randomized, Placebo-Controlled, Phase 2 Trial

DOI record: { "DOI": "10.1007/s40121-022-00690-0", "ISSN": [ "2193-8229", "2193-6382" ], "URL": "http://dx.doi.org/10.1007/s40121-022-00690-0", "alternative-id": [ "690" ], "assertion": [ { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "Received", "name": "received", "order": 1, "value": "3 June 2022" }, { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "Accepted", "name": "accepted", "order": 2, "value": "17 August 2022" }, { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "First Online", "name": "first_online", "order": 3, "value": "15 October 2022" } ], "author": [ { "ORCID": "https://orcid.org/0000-0003-0446-3224", "affiliation": [], "authenticated-orcid": false, "family": "Vehreschild", "given": "Maria J. G. T.", "sequence": "first" }, { "ORCID": "https://orcid.org/0000-0001-7338-0751", "affiliation": [], "authenticated-orcid": false, "family": "Atanasov", "given": "Petar", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0002-1226-5431", "affiliation": [], "authenticated-orcid": false, "family": "Yurko", "given": "Kateryna", "sequence": "additional" }, { "affiliation": [], "family": "Oancea", "given": "Cristian", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0003-2867-1124", "affiliation": [], "authenticated-orcid": false, "family": "Popov", "given": "Georgi", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0003-0627-2843", "affiliation": [], "authenticated-orcid": false, "family": "Smesnoi", "given": "Valentina", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0001-5964-1572", "affiliation": [], "authenticated-orcid": false, "family": "Placinta", "given": "Gheorghe", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0001-8279-5203", "affiliation": [], "authenticated-orcid": false, "family": "Kohlhof", "given": "Hella", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0003-4741-0317", "affiliation": [], "authenticated-orcid": false, "family": "Vitt", "given": "Daniel", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0002-9332-1801", "affiliation": [], "authenticated-orcid": false, "family": "Peelen", "given": "Evelyn", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0002-9787-0226", "affiliation": [], "authenticated-orcid": false, "family": "Mihajlović", "given": "Jelena", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0001-5811-5976", "affiliation": [], "authenticated-orcid": false, "family": "Muehler", "given": "Andreas R.", "sequence": "additional" } ], "container-title": "Infectious Diseases and Therapy", "container-title-short": "Infect Dis Ther", "content-domain": { "crossmark-restriction": false, "domain": [ "link.springer.com" ] }, "created": { "date-parts": [ [ 2022, 10, 15 ] ], "date-time": "2022-10-15T05:02:29Z", "timestamp": 1665810149000 }, "deposited": { "date-parts": [ [ 2024, 10, 5 ] ], "date-time": "2024-10-05T21:14:00Z", "timestamp": 1728162840000 }, "funder": [ { "name": "Immunic Therapeutics" } ], "indexed": { "date-parts": [ [ 2025, 3, 28 ] ], "date-time": "2025-03-28T11:26:55Z", "timestamp": 1743161215970, "version": "3.37.3" }, "is-referenced-by-count": 10, "issue": "6", "issued": { "date-parts": [ [ 2022, 10, 15 ] ] }, "journal-issue": { "issue": "6", "published-print": { "date-parts": [ [ 2022, 12 ] ] } }, "language": "en", "license": [ { "URL": "https://creativecommons.org/licenses/by-nc/4.0", "content-version": "tdm", "delay-in-days": 0, "start": { "date-parts": [ [ 2022, 10, 15 ] ], "date-time": "2022-10-15T00:00:00Z", "timestamp": 1665792000000 } }, { "URL": "https://creativecommons.org/licenses/by-nc/4.0", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2022, 10, 15 ] ], "date-time": "2022-10-15T00:00:00Z", "timestamp": 1665792000000 } } ], "link": [ { "URL": "https://link.springer.com/content/pdf/10.1007/s40121-022-00690-0.pdf", "content-type": "application/pdf", "content-version": "vor", "intended-application": "text-mining" }, { "URL": "https://link.springer.com/article/10.1007/s40121-022-00690-0/fulltext.html", "content-type": "text/html", "content-version": "vor", "intended-application": "text-mining" }, { "URL": "https://link.springer.com/content/pdf/10.1007/s40121-022-00690-0.pdf", "content-type": "application/pdf", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "297", "original-title": [], "page": "2159-2176", "prefix": "10.1007", "published": { "date-parts": [ [ 2022, 10, 15 ] ] }, "published-online": { "date-parts": [ [ 2022, 10, 15 ] ] }, "published-print": { "date-parts": [ [ 2022, 12 ] ] }, "publisher": "Springer Science and Business Media LLC", "reference": [ { "DOI": "10.1056/NEJMoa2100433", "author": "AC Gordan", "doi-asserted-by": "publisher", "first-page": "1491", "issue": "16", "journal-title": "N Engl J Med", "key": "690_CR1", "unstructured": "Gordan AC, Mouncey PR, Al-Beidh F, et al. Interleukin-6 receptor antagonists in critically ill patients with Covid-19. N Engl J Med. 2021;384(16):1491–502.", "volume": "384", "year": "2021" }, { "DOI": "10.1016/S0140-6736(21)00676-0", "author": "RECOVERY Collaborative Group", "doi-asserted-by": "publisher", "first-page": "1637", "issue": "10285", "journal-title": "Lancet", "key": "690_CR2", "unstructured": "RECOVERY Collaborative Group. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet. 2021;397(10285):1637–45.", "volume": "397", "year": "2021" }, { "DOI": "10.1056/NEJMoa2028836", "author": "JH Stone", "doi-asserted-by": "publisher", "first-page": "2333", "issue": "24", "journal-title": "N Engl J Med", "key": "690_CR3", "unstructured": "Stone JH, Frigault MJ, Serling-Boyd NJ, et al. Efficacy of tocilizumab in patients hospitalized with Covid-19. N Engl J Med. 2020;383(24):2333–44.", "volume": "383", "year": "2020" }, { "DOI": "10.1056/NEJMoa2116044", "author": "AJ Bernal", "doi-asserted-by": "publisher", "first-page": "509", "journal-title": "N Engl J Med", "key": "690_CR4", "unstructured": "Bernal AJ, Gomes da Silva MM, Musungaie DB, et al. Molnupiravir for oral treatment of covid-19 in nonhospitalized patients. N Engl J Med. 2022;386:509–20.", "volume": "386", "year": "2022" }, { "key": "690_CR5", "unstructured": "Paxlovid [package insert]. New York: Pfizer; 2021. https://www.fda.gov/media/155050/download. Accessed June 30, 2022." }, { "DOI": "10.1056/NEJMoa2007764", "author": "JH Beigel", "doi-asserted-by": "publisher", "first-page": "1813", "issue": "19", "journal-title": "N Engl J Med", "key": "690_CR6", "unstructured": "Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the treatment of Covid-19—final report. N Engl J Med. 2020;383(19):1813–26.", "volume": "383", "year": "2020" }, { "DOI": "10.1016/j.it.2020.11.003", "author": "V Feuillet", "doi-asserted-by": "publisher", "first-page": "31", "issue": "1", "journal-title": "Trends Immunol", "key": "690_CR7", "unstructured": "Feuillet V, Canard B, Trautmann A. Combining antivirals and immunomodulators to fight COVID-19. Trends Immunol. 2021;42(1):31.", "volume": "42", "year": "2021" }, { "DOI": "10.1016/S2666-5247(21)00114-2", "author": "LYC Chen", "doi-asserted-by": "publisher", "issue": "6", "journal-title": "Lancet Microbe", "key": "690_CR8", "unstructured": "Chen LYC, Quach TTT. Combining immunomodulators and antivirals for COVID-19. Lancet Microbe. 2021;2(6): e233.", "volume": "2", "year": "2021" }, { "DOI": "10.1056/NEJMoa2031994", "author": "AC Kalil", "doi-asserted-by": "publisher", "first-page": "795", "issue": "9", "journal-title": "N Engl J Med", "key": "690_CR9", "unstructured": "Kalil AC, Patterson TF, Mehta AK, et al. Baricitinib plus remdesivir for hospitalized adults with Covid-19. N Engl J Med. 2021;384(9):795–807.", "volume": "384", "year": "2021" }, { "DOI": "10.1073/pnas.82.8.2473", "author": "KK Biron", "doi-asserted-by": "publisher", "first-page": "2473", "issue": "8", "journal-title": "Proc Natl Acad Sci USA", "key": "690_CR10", "unstructured": "Biron KK, Stanat SC, Sorrell JB, et al. Metabolic activation of the nucleoside analog 9-[(2-hydroxy-1-(hydroxymethyl)ethoxy]methyl)guanine in human diploid fibroblasts infected with human cytomegalovirus. Proc Natl Acad Sci USA. 1985;82(8):2473.", "volume": "82", "year": "1985" }, { "DOI": "10.1073/pnas.1017142108", "author": "A Bonavia", "doi-asserted-by": "publisher", "first-page": "6739", "issue": "17", "journal-title": "Proc Natl Acad Sci USA", "key": "690_CR11", "unstructured": "Bonavia A, Franti M, Keaney EP, et al. Identification of broad-spectrum antiviral compounds and assessment of the druggability of their target for efficacy against respiratory syncytial virus (RSV). Proc Natl Acad Sci USA. 2011;108(17):6739–44.", "volume": "108", "year": "2011" }, { "DOI": "10.3390/v12080821", "author": "YJ Kim", "doi-asserted-by": "publisher", "first-page": "821", "issue": "8", "journal-title": "Viruses", "key": "690_CR12", "unstructured": "Kim YJ, Cubitt B, Cai Y, et al. Novel dihydroorotate dehydrogenase inhibitors with potent interferon-independent antiviral activity against mammarenaviruses in vitro. Viruses. 2020;12(8):821.", "volume": "12", "year": "2020" }, { "DOI": "10.1007/s13238-020-00768-w", "author": "R Xiong", "doi-asserted-by": "publisher", "first-page": "723", "issue": "10", "journal-title": "Protein Cell", "key": "690_CR13", "unstructured": "Xiong R, Zhang L, Li S, et al. Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2. Protein Cell. 2020;11(10):723–39.", "volume": "11", "year": "2020" }, { "DOI": "10.3390/v12121394", "author": "F Hahn", "doi-asserted-by": "publisher", "first-page": "1394", "issue": "12", "journal-title": "Viruses", "key": "690_CR14", "unstructured": "Hahn F, Wangen C, Häge S, et al. IMU-838, a developmental DHODH inhibitor in phase II for autoimmune disease, shows anti-SARS-CoV-2 and broad-spectrum antiviral efficacy in vitro. Viruses. 2020;12(12):1394.", "volume": "12", "year": "2020" }, { "DOI": "10.1371/journal.ppat.1003678", "author": "M Lucas-Hourani", "doi-asserted-by": "publisher", "issue": "10", "journal-title": "PLoS Pathog", "key": "690_CR15", "unstructured": "Lucas-Hourani M, Dauzonne D, Jorda P, et al. Inhibition of pyrimidine biosynthesis pathway suppresses viral growth through innate immunity. PLoS Pathog. 2013;9(10): e1003678.", "volume": "9", "year": "2013" }, { "DOI": "10.1016/j.ejmech.2019.111855", "author": "S Hayek", "doi-asserted-by": "publisher", "journal-title": "Eur J Med Chem", "key": "690_CR16", "unstructured": "Hayek S, Pietrancosta N, Hovhannisyan AA, et al. Cerpegin-derived furo[3,4-c]pyridine-3,4(1H,5H)-diones enhance cellular response to interferons by de novo pyrimidine biosynthesis inhibition. Eur J Med Chem. 2020;186: 111855.", "volume": "186", "year": "2020" }, { "DOI": "10.1016/j.msard.2020.102129", "author": "A Muehler", "doi-asserted-by": "publisher", "journal-title": "Mult Scler Relat Disord", "key": "690_CR17", "unstructured": "Muehler A, Peelen E, Kohlhof H, Gröppel M, Vitt D. Vidofludimus calcium, a next generation DHODH inhibitor for the treatment of relapsing-remitting multiple sclerosis. Mult Scler Relat Disord. 2020;43: 102129.", "volume": "43", "year": "2020" }, { "DOI": "10.1002/ibd.21264", "author": "LR Fitzpatrick", "doi-asserted-by": "publisher", "first-page": "1763", "issue": "10", "journal-title": "Inflamm Bowel Dis", "key": "690_CR18", "unstructured": "Fitzpatrick LR, Deml L, Hofmann C, et al. 4SC-101, a novel immunosuppressive drug, inhibits IL-17 and attenuates colitis in two murine models of inflammatory bowel disease. Inflamm Bowel Dis. 2010;16(10):1763–77.", "volume": "16", "year": "2010" }, { "key": "690_CR19", "unstructured": "Phase 2 dose-finding IMU-838 for ulcerative colitis (CALDOSE-1). ClinicalTrials.gov Identifier NCT03341962. Updated February 24, 2021. https://clinicaltrials.gov/ct2/show/NCT03341962. Accessed March 21, 2019." }, { "key": "690_CR20", "unstructured": "Vidofludimus calcium for primary sclerosing cholangitis (PSC). ClinicalTrials.gov Identifier NCT03722576. Updated November 25, 2020. https://clinicaltrials.gov/ct2/show/NCT03722576. Accessed March 21, 2019." }, { "DOI": "10.1007/s40268-019-00286-z", "author": "A Muehler", "doi-asserted-by": "publisher", "first-page": "351", "issue": "4", "journal-title": "Drugs R D", "key": "690_CR21", "unstructured": "Muehler A, Kohlhof H, Groeppel M, Vitt D. The selective oral immunomodulator vidofludimus in patients with active rheumatoid arthritis: safety results from the COMPONENT study. Drugs R D. 2019;19(4):351–66. https://doi.org/10.1007/s40268-019-00286-z.", "volume": "19", "year": "2019" }, { "DOI": "10.1212/WNL.96.15_supplement.2872", "author": "RJ Fox", "doi-asserted-by": "crossref", "first-page": "2872", "issue": "15 Suppl", "journal-title": "Neurology", "key": "690_CR22", "unstructured": "Fox RJ, Wiendl H, de Stefano N, Sellner J, Muehler A. Safety and tolerability of IMU-838, a next-generation DHODH inhibitor in EMPhASIS: a randomized, placebo-controlled phase 2 trial in relapsing multiple sclerosis. Neurology. 2021;96(15 Suppl):2872.", "volume": "96", "year": "2021" }, { "key": "690_CR23", "unstructured": "World Health Organization (WHO) WHO R&D Blueprint—COVID-19 Therapeutic Trial Synopsis. https://www.who.int/blueprint/priority-diseases/key-action/COVID-19_Treatment_Trial_Design_Master_Protocol_synopsis_Final_18022020.pdf. Accessed Dec 4, 2021." }, { "DOI": "10.1056/NEJMc2010419", "author": "P Goyal", "doi-asserted-by": "publisher", "first-page": "2372", "issue": "24", "journal-title": "N Engl J Med", "key": "690_CR24", "unstructured": "Goyal P, Choi JJ, Pinheiro LC, et al. Clinical characteristics of Covid-19 in New York City. N Engl J Med. 2020;382(24):2372–4.", "volume": "382", "year": "2020" }, { "DOI": "10.1001/jamanetworkopen.2021.3071", "author": "BT Garibaldi", "doi-asserted-by": "publisher", "issue": "3", "journal-title": "JAMA Netw Open", "key": "690_CR25", "unstructured": "Garibaldi BT, Wang K, Robinson ML, et al. Comparison of time to clinical improvement with vs without remdesivir treatment in hospitalized patients with COVID-19. JAMA Netw Open. 2021;4(3): e213071.", "volume": "4", "year": "2021" }, { "DOI": "10.1016/j.dsx.2021.102329", "author": "AK Singh", "doi-asserted-by": "publisher", "issue": "6", "journal-title": "Diabetes Metab Syndr", "key": "690_CR26", "unstructured": "Singh AK, Singh A, Singh R, Misra A. Molnupiravir in COVID-19: a systematic review of literature. Diabetes Metab Syndr. 2021;15(6): 102329.", "volume": "15", "year": "2021" }, { "DOI": "10.1007/s13318-020-00623-7", "author": "A Muehler", "doi-asserted-by": "publisher", "first-page": "557", "issue": "5", "journal-title": "Eur J Drug Metab Pharmacokinet", "key": "690_CR27", "unstructured": "Muehler A, Kohlhof H, Groeppel M, Vitt D. Safety, tolerability and pharmacokinetics of vidofludimus calcium (IMU-838) after single and multiple ascending oral doses in healthy male subjects. Eur J Drug Metab Pharmacokinet. 2020;45(5):557–73.", "volume": "45", "year": "2020" }, { "DOI": "10.1016/j.crohns.2012.09.016", "author": "KR Herrlinger", "doi-asserted-by": "publisher", "first-page": "636", "issue": "8", "journal-title": "J Crohns Colitis", "key": "690_CR28", "unstructured": "Herrlinger KR, Diculescu M, Fellermann K, et al. Efficacy, safety and tolerability of vidofludimus in patients with inflammatory bowel disease: the ENTRANCE study. J Crohns Colitis. 2013;7(8):636–43.", "volume": "7", "year": "2013" }, { "DOI": "10.1002/acn3.51574", "author": "RJ Fox", "doi-asserted-by": "publisher", "journal-title": "Ann Clin Transl Neurol", "key": "690_CR29", "unstructured": "Fox RJ, Wiendl H, Wolf C, et al. A double-blind, randomized, placebo-controlled phase 2 trial evaluating the selective dihydroorotate dehydrogenase inhibitor vidofludimus calcium in relapsing-remitting multiple sclerosis. Ann Clin Transl Neurol. 2022. https://doi.org/10.1002/acn3.51574.", "year": "2022" }, { "DOI": "10.1002/hep4.1926", "author": "EJ Carey", "doi-asserted-by": "publisher", "first-page": "1589", "issue": "7", "journal-title": "Hepatol Commun", "key": "690_CR30", "unstructured": "Carey EJ, Eaton J, Clayton M, et al. A pilot study of vidofludimus calcium for treatment of primary sclerosing cholangitis. Hepatol Commun. 2022;6(7):1589–97.", "volume": "6", "year": "2022" }, { "DOI": "10.1056/NEJMoa1014656", "author": "P O’Connor", "doi-asserted-by": "publisher", "first-page": "1293", "issue": "14", "journal-title": "N Engl J Med", "key": "690_CR31", "unstructured": "O’Connor P, Wolinsky JS, Confavreux C, et al. Randomized trial of oral teriflunomide for relapsing multiple sclerosis. N Engl J Med. 2011;365(14):1293–303.", "volume": "365", "year": "2011" }, { "DOI": "10.1016/S1474-4422(13)70308-9", "author": "C Confavreux", "doi-asserted-by": "publisher", "first-page": "247", "issue": "3", "journal-title": "Lancet Neurol", "key": "690_CR32", "unstructured": "Confavreux C, O’Connor P, Comi G, et al. Oral teriflunomide for patients with relapsing multiple sclerosis (TOWER): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Neurol. 2014;13(3):247–56.", "volume": "13", "year": "2014" }, { "DOI": "10.1212/WNL.0b013e31829e6fbf", "author": "A Bar-Or", "doi-asserted-by": "publisher", "first-page": "552", "issue": "6", "journal-title": "Neurology", "key": "690_CR33", "unstructured": "Bar-Or A, Freedman MS, Kremenchutzky M, et al. Teriflunomide effect on immune response to influenza vaccine in patients with multiple sclerosis. Neurology. 2013;81(6):552.", "volume": "81", "year": "2013" }, { "DOI": "10.1212/NXI.0000000000000070", "author": "A Bar-Or", "doi-asserted-by": "publisher", "issue": "2", "journal-title": "Neurol Neuroimmunol Neuroinflamm", "key": "690_CR34", "unstructured": "Bar-Or A, Wiendl H, Miller B, et al. Randomized study of teriflunomide effects on immune responses to neoantigen and recall antigens. Neurol Neuroimmunol Neuroinflamm. 2015;2(2): e70.", "volume": "2", "year": "2015" }, { "DOI": "10.3390/pathogens10060763", "author": "JE Gold", "doi-asserted-by": "publisher", "first-page": "763", "issue": "6", "journal-title": "Pathogens", "key": "690_CR35", "unstructured": "Gold JE, Okyay RA, Licht WE, Hurley DJ. Investigation of long COVID prevalence and its relationship to Epstein–Barr virus reactivation. Pathogens. 2021;10(6):763.", "volume": "10", "year": "2021" }, { "DOI": "10.1093/ecco-jcc/jjab232.193", "doi-asserted-by": "crossref", "key": "690_CR36", "unstructured": "Marschall M, Peelen P, Müller R, et al. IMU-838, a small molecule DHODH inhibitor in phase 2 clinical trial for multiple sclerosis, shows potent anti-EBV activity in cell-culture-based systems: potential additional benefits in multiple sclerosis treatment. ECTRIMS, Poster P37; 2021." }, { "DOI": "10.1002/jmv.26129", "author": "T Yu", "doi-asserted-by": "publisher", "first-page": "2675", "issue": "11", "journal-title": "J Med Virol", "key": "690_CR37", "unstructured": "Yu T, Tian C, Chu S, et al. COVID-19 patients benefit from early antiviral treatment: a comparative, retrospective study. J Med Virol. 2020;92(11):2675–83.", "volume": "92", "year": "2020" }, { "DOI": "10.1056/NEJMoa2116846", "author": "RL Gottlieb", "doi-asserted-by": "publisher", "first-page": "305", "journal-title": "N Engl J Med", "key": "690_CR38", "unstructured": "Gottlieb RL, Vaca CE, Paredes R, et al. Early remdesivir to prevent progression to severe Covid-19 in outpatients. N Engl J Med. 2022;386:305–15.", "volume": "386", "year": "2022" } ], "reference-count": 38, "references-count": 38, "relation": {}, "resource": { "primary": { "URL": "https://link.springer.com/10.1007/s40121-022-00690-0" } }, "score": 1, "short-title": [], "source": "Crossref", "subject": [], "subtitle": [], "title": "Safety and Efficacy of Vidofludimus Calcium in Patients Hospitalized with COVID-19: A Double-Blind, Randomized, Placebo-Controlled, Phase 2 Trial", "type": "journal-article", "update-policy": "https://doi.org/10.1007/springer_crossmark_policy", "volume": "11" }