{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T09:17:17Z","timestamp":1791623837215,"version":"4.3.4"},"reference-count":38,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,5,15]],"date-time":"2023-05-15T00:00:00Z","timestamp":1684108800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Primary biliary cholangitis (PBC) is a rare liver disease with significant unmet need for second\u2010line\/add\u2010on treatments. Setanaxib, a NOX1\/4 inhibitor, has shown anti\u2010fibrotic effects in\n                      <jats:italic>in vitro<\/jats:italic>\n                      and animal studies. This phase 2, randomized, multicentre study investigated the efficacy and safety of setanaxib in patients with PBC.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients with \u22656\u2009months of ursodeoxycholic acid (UDCA) treatment were randomized 1:1:1 to oral setanaxib 400\u2009mg once daily (OD), twice daily (BID), or placebo, in addition to UDCA for 24\u2009weeks. Other inclusion criteria included alkaline phosphatase (ALP) \u22651.5\u2009\u00d7\u2009ULN and gamma\u2010glutamyl transferase (GGT) \u22651.5\u2009\u00d7\u2009ULN. The primary endpoint was percentage change from baseline in GGT at Week 24; secondary endpoints included change from baseline in ALP, liver stiffness (LS; via transient elastography), fatigue at Week 24, and safety outcomes. p values compare setanaxib 400\u2009mg BID and placebo groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of patients randomized (setanaxib 400\u2009mg OD and BID: 38, and 36; placebo: 37), 104\/111 completed Week 24. Mean (standard deviation [SD]) change in GGT to Week 24 was \u22124.9% (59.6%) for setanaxib 400\u2009mg OD, \u221219.0% (28.9%) for setanaxib 400\u2009mg BID, and\u2009\u22128.4% (21.5%) for placebo;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u2009.31. Patients treated with setanaxib 400\u2009mg OD and BID showed decreased serum ALP levels from baseline to Week 24 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u2009.002: setanaxib BID versus placebo). Patients treated with setanaxib 400\u2009mg OD and BID showed mean (SD) percentage increases in LS to Week 24 of 3.3% (35.0%) and 7.9% (43.7%), versus 10.1% (33.1%) for placebo (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u2009.65). Changes in mean (SD) PBC\u201040 fatigue domain scores to Week 24 were +0.3% (24.9%) for setanaxib 400\u2009mg OD, \u22129.9% (19.8%) for setanaxib 400\u2009mg BID and +2.4% (23.1%) for placebo,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u2009.027. Two patients (one placebo, one setanaxib 400\u2009mg BID) experienced serious treatment\u2010emergent adverse events, deemed unrelated to study drug.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The primary endpoint was not met. However, the secondary endpoints provide preliminary evidence for potential anti\u2010cholestatic and anti\u2010fibrotic effects in PBC, supporting the further evaluation of setanaxib in a future phase 2b\/3 trial.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.15596","type":"journal-article","created":{"date-parts":[[2023,5,15]],"date-time":"2023-05-15T03:26:23Z","timestamp":1684121183000},"page":"1507-1522","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":75,"title":["Setanaxib, a first\u2010in\u2010class selective NADPH oxidase 1\/4 inhibitor for primary biliary cholangitis: A randomized, placebo\u2010controlled, phase 2 trial"],"prefix":"10.1111","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3262-1998","authenticated-orcid":false,"given":"Pietro","family":"Invernizzi","sequence":"first","affiliation":[{"name":"Division of Gastroenterology Centre for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano\u2010Bicocca  Monza Italy"},{"name":"European Reference Network on Hepatological Diseases (ERN RARE\u2010LIVER) IRCCS Fondazione San Gerardo dei Tintori  Monza Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1445-0443","authenticated-orcid":false,"given":"Marco","family":"Carbone","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology Centre for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano\u2010Bicocca  Monza Italy"},{"name":"European Reference Network on Hepatological Diseases (ERN RARE\u2010LIVER) IRCCS Fondazione San Gerardo dei Tintori  Monza Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Jones","sequence":"additional","affiliation":[{"name":"Newcastle University Medical School  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5498-6037","authenticated-orcid":false,"given":"Cynthia","family":"Levy","sequence":"additional","affiliation":[{"name":"Schiff Center for Liver Diseases University of Miami  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Little","sequence":"additional","affiliation":[{"name":"Calliditas Therapeutics AB  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Wiesel","sequence":"additional","affiliation":[{"name":"Genkyotex  Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederik","family":"Nevens","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology University Hospital, KU Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the study investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,5,15]]},"reference":[{"key":"e_1_2_15_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41395-018-0390-3"},{"key":"e_1_2_15_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-021-01545-7"},{"key":"e_1_2_15_4_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v21.i25.7683"},{"key":"e_1_2_15_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.03.022"},{"key":"e_1_2_15_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2017-315259"},{"key":"e_1_2_15_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(19)30343-7"},{"key":"e_1_2_15_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2020.06.062"},{"key":"e_1_2_15_9_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2014.08.029"},{"key":"e_1_2_15_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2020.08.006"},{"key":"e_1_2_15_11_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2014.12.005"},{"key":"e_1_2_15_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1509840"},{"key":"e_1_2_15_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2019.09.050"},{"key":"e_1_2_15_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2018.11.004"},{"key":"e_1_2_15_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhepr.2019.05.005"},{"key":"e_1_2_15_16_1","unstructured":"Electronic Medicines Compendium.Fibrazate XL 400 mg Modified Release Tablets.2021[November 2022]. 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