{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T02:29:03Z","timestamp":1792549743098,"version":"4.5.0"},"reference-count":32,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,11,5]],"date-time":"2020-11-05T00:00:00Z","timestamp":1604534400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Friedreich ataxia (FA) is a progressive genetic neurodegenerative disorder with no approved treatment. Omaveloxolone, an Nrf2 activator, improves mitochondrial function, restores redox balance, and reduces inflammation in models of FA. We investigated the safety and efficacy of omaveloxolone in patients with FA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted an international, double\u2010blind, randomized, placebo\u2010controlled, parallel\u2010group, registrational phase 2 trial at 11 institutions in the United States, Europe, and Australia (NCT02255435, EudraCT2015\u2010002762\u201023). Eligible patients, 16 to 40\u2009years of age with genetically confirmed FA and baseline modified Friedreich's Ataxia Rating Scale (mFARS) scores between 20 and 80, were randomized 1:1 to placebo or 150mg per day of omaveloxolone. The primary outcome was change from baseline in the mFARS score in those treated with omaveloxolone compared with those on placebo at 48\u2009weeks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      One hundred fifty\u2010five patients were screened, and 103 were randomly assigned to receive omaveloxolone (n = 51) or placebo (n = 52), with 40 omaveloxolone patients and 42 placebo patients analyzed in the full analysis set. Changes from baseline in mFARS scores in omaveloxolone (\u22121.55\u2009\u00b1\u20090.69) and placebo (0.85\u2009\u00b1\u20090.64) patients showed a difference between treatment groups of \u20132.40\u2009\u00b1\u20090.96 (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.014). Transient reversible increases in aminotransferase levels were observed with omaveloxolone without increases in total bilirubin or other signs of liver injury. Headache, nausea, and fatigue were also more common among patients receiving omaveloxolone.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>In the MOXIe trial, omaveloxolone significantly improved neurological function compared to placebo and was generally safe and well tolerated. It represents a potential therapeutic agent in FA. ANN NEUROL 2021;89:212\u2013225<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.25934","type":"journal-article","created":{"date-parts":[[2020,10,17]],"date-time":"2020-10-17T06:30:56Z","timestamp":1602916256000},"page":"212-225","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":345,"title":["Safety and Efficacy of Omaveloxolone in Friedreich Ataxia (\n                    <scp>MOXIe<\/scp>\n                    Study)"],"prefix":"10.1002","volume":"89","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7168-214X","authenticated-orcid":false,"given":"David R.","family":"Lynch","sequence":"first","affiliation":[{"name":"Division of Neurology Children's Hospital of Philadelphia  Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie P.","family":"Chin","sequence":"additional","affiliation":[{"name":"Reata Pharmaceuticals  Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin B.","family":"Delatycki","sequence":"additional","affiliation":[{"name":"Victorian Clinical Genetics Services, Murdoch Children's Research Institute  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8052-9240","authenticated-orcid":false,"given":"S. H.","family":"Subramony","sequence":"additional","affiliation":[{"name":"Department of Neurology McKnight Brain Institute, University of Florida Health System  Gainesville FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Corti","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Florida Health System  Gainesville FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Chad","family":"Hoyle","sequence":"additional","affiliation":[{"name":"Department of Neurology Ohio State University College of Medicine  Columbus OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia","family":"Boesch","sequence":"additional","affiliation":[{"name":"Department of Neurology Medical University Innsbruck  Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Nachbauer","sequence":"additional","affiliation":[{"name":"Department of Neurology Medical University Innsbruck  Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina","family":"Mariotti","sequence":"additional","affiliation":[{"name":"Istituto di Ricovero e Cura a Carattere Scientifico\u2013Carlo Besta Neurological Institute  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine D.","family":"Mathews","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Iowa Carver College of Medicine  Iowa City IA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Giunti","sequence":"additional","affiliation":[{"name":"University College London Hospital  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Wilmot","sequence":"additional","affiliation":[{"name":"Department of Neurology Emory University School of Medicine  Atlanta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa","family":"Zesiewicz","sequence":"additional","affiliation":[{"name":"Department of Neurology University of South Florida Ataxia Research Center  Tampa FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Perlman","sequence":"additional","affiliation":[{"name":"Department of Neurology University of California, Los Angeles  Los Angeles CA 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Poster presented at: American Society of Nephrology 44th Annual Meeting; November 8\u201313 2001; Philadelphia PA."},{"key":"e_1_2_9_30_1","article-title":"Effects of bardoxolone methyl on hepatic enzymes in patients with type 2 diabetes mellitus and stage 4 CKD","author":"Lewis JH","journal-title":"Clin Transl Sci"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10858-011-9481-9"},{"key":"e_1_2_9_32_1","first-page":"817","article-title":"The past and present of serum aminotransferases and the future of liver injury biomarkers","volume":"15","author":"McGill MR","year":"2016","journal-title":"EXCLI J"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v21.i3.711"}],"updated-by":[{"DOI":"10.1002\/ana.26808","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T00:00:00Z","timestamp":1696464000000}}],"container-title":["Annals of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ana.25934","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ana.25934","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ana.25934","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,27]],"date-time":"2023-08-27T23:50:45Z","timestamp":1693180245000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ana.25934"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,5]]},"references-count":32,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021,2]]}},"alternative-id":["10.1002\/ana.25934"],"URL":"https:\/\/doi.org\/10.1002\/ana.25934","archive":["Portico"],"relation":{},"ISSN":["0364-5134","1531-8249"],"issn-type":[{"value":"0364-5134","type":"print"},{"value":"1531-8249","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,5]]},"assertion":[{"value":"2020-07-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-10-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-11-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}