{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T09:23:43Z","timestamp":1790760223186,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T00:00:00Z","timestamp":1696204800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100020152","name":"Madrigal Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100020152","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Non\u2010alcoholic steatohepatitis (NASH) is a progressive form of non\u2010alcoholic fatty liver disease (NAFLD) associated with steatosis, hepatocellular injury, inflammation and fibrosis. In a Phase 2 trial in adults with NASH (NCT02912260), resmetirom, an orally administered, liver\u2010targeted thyroid hormone receptor\u2010\u03b2 selective agonist, significantly reduced hepatic fat (via imaging) and resolved NASH without worsening fibrosis (via liver biopsy) in a significant number of patients compared with placebo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>To present the design of the Phase 3 MAESTRO clinical programme evaluating resmetirom for treatment of NASH (MAESTRO\u2010NAFLD\u20101 [NCT04197479], MAESTRO\u2010NAFLD\u2010OLE [NCT04951219], MAESTRO\u2010NASH [NCT03900429], MAESTRO\u2010NASH\u2010OUTCOMES [NCT05500222]).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>MAESTRO\u2010NASH is a pivotal serial biopsy trial in up to 2000 adults with biopsy\u2010confirmed at\u2010risk NASH. Patients are randomised to a once\u2010daily oral placebo, 80\u2009mg resmetirom, or 100\u2009mg resmetirom. Liver biopsies are conducted at screening, week 52 and month 54. MAESTRO\u2010NAFLD\u20101 is a 52\u2010week safety trial in ~1400 adults with NAFLD\/presumed NASH (based on non\u2010invasive testing); ~700 patients from MAESTRO\u2010NAFLD\u20101 are enrolled in MAESTRO\u2010NAFLD\u2010OLE, a 52\u2010week active treatment extension to further evaluate safety. MAESTRO\u2010NASH\u2010OUTCOMES is enrolling 700 adults with well\u2010compensated NASH cirrhosis to evaluate the potential for resmetirom to slow progression to hepatic decompensation events. Non\u2010invasive tests (biomarkers, imaging) are assessed longitudinally throughout, in addition to validated patient\u2010reported outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The MAESTRO clinical programme was designed in conjunction with regulatory authorities to support approval of resmetirom for treatment of NASH. The surrogate endpoints, based on week 52 liver biopsy, serum biomarkers and imaging, are confirmed by long\u2010term clinical liver\u2010related outcomes in MAESTRO\u2010NASH (month 54) and MAESTRO\u2010NASH\u2010OUTCOMES (time to event).<\/jats:p><\/jats:sec>","DOI":"10.1111\/apt.17734","type":"journal-article","created":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T06:09:15Z","timestamp":1696313355000},"page":"51-63","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":91,"title":["Design of the phase 3 <scp>MAESTRO<\/scp> clinical program to evaluate resmetirom for the treatment of nonalcoholic steatohepatitis"],"prefix":"10.1111","volume":"59","author":[{"given":"Stephen A.","family":"Harrison","sequence":"first","affiliation":[{"name":"Pinnacle Clinical Research Center  San Antonio Texas USA"},{"name":"Radcliffe Department of Medicine University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3051-0111","authenticated-orcid":false,"given":"Vlad","family":"Ratziu","sequence":"additional","affiliation":[{"name":"Sorbonne University  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9518-0088","authenticated-orcid":false,"given":"Quentin M.","family":"Anstee","sequence":"additional","affiliation":[{"name":"Translational &amp; Clinical Research Institute, Faculty of Medical Sciences Newcastle University  Newcastle\u2010Upon\u2010Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mazen","family":"Noureddin","sequence":"additional","affiliation":[{"name":"Houston Research Institute Houston Methodist Hospital  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8682-5748","authenticated-orcid":false,"given":"Arun J.","family":"Sanyal","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Virginia Commonwealth University  Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4224-4703","authenticated-orcid":false,"given":"J\u00f6rn M.","family":"Schattenberg","sequence":"additional","affiliation":[{"name":"Metabolic Liver Research Program, I. 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