{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:13:04Z","timestamp":1791267184525,"version":"4.1.0"},"reference-count":23,"publisher":"Wiley","issue":"11-12","license":[{"start":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T00:00:00Z","timestamp":1634688000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Namodenoson, an A3 adenosine receptor (A3AR) agonist, improved liver function\/pathology in non\u2010alcoholic steatohepatitis (NASH) preclinical models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To evaluate the efficacy and safety of namodenoson for the treatment of non\u2010alcoholic fatty liver disease (NAFLD) with or without NASH<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This phase 2 study included 60 patients with NAFLD (ALT \u226560\u00a0IU\/L) who were randomised (1:1:1) to oral namodenoson 12.5\u00a0mg b.d. (n\u00a0=\u00a021), 25\u00a0mg b.d. (n\u00a0=\u00a019), or placebo (n\u00a0=\u00a020) for 12\u00a0weeks (total follow\u2010up: 16\u00a0weeks). The main efficacy endpoint involved serum ALT after 12\u00a0weeks of treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Serum ALT decreased over time with namodenoson in a dose\u2010dependent manner. The difference between change from baseline (CFB) for ALT in the namodenoson 25\u00a0mg b.d. arm vs placebo trended towards significance at 12\u00a0weeks (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.066). Serum AST levels also decreased with namodenoson in a dose\u2010dependent manner; at 12\u00a0weeks, the CFB for 25\u00a0mg b.d. vs placebo was significant (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.03). At Week 12, 31.6% in the namodenoson 25\u00a0mg b.d. arm and 20.0% in the placebo arm achieved ALT normalisation (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.405). At week 16, the respective rates were 36.8% and 10.0% (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.038). A3AR expression levels were stable over time across study arms. Both doses of namodenoson were well tolerated with no drug\u2010emergent severe adverse events, drug\u2010drug interactions, hepatotoxicity, or deaths. Three adverse events were considered possibly related to study treatment: myalgia (12.5\u00a0mg b.d. arm), muscular weakness (25\u00a0mg b.d. arm), and headache (25\u00a0mg b.d. arm).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>A3AR is a valid target; namodenoson 25\u00a0mg b.d. was safe and demonstrated efficacy signals (ClinicalTrials.gov #NCT02927314).<\/jats:p><\/jats:sec>","DOI":"10.1111\/apt.16664","type":"journal-article","created":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T14:09:15Z","timestamp":1634825355000},"page":"1405-1415","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Randomised clinical trial: A phase 2 double\u2010blind study of namodenoson in non\u2010alcoholic fatty liver disease and steatohepatitis"],"prefix":"10.1111","volume":"54","author":[{"given":"Rifaat","family":"Safadi","sequence":"first","affiliation":[{"name":"The Liver Unit Hadassah Medical Organization Hadassah Hebrew University Medical Centre Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marius","family":"Braun","sequence":"additional","affiliation":[{"name":"The Liver Institute Rabin Medical Centre Beilinson Hospital Petah\u2010Tikva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adi","family":"Francis","sequence":"additional","affiliation":[{"name":"Cardiology Department Holy Family Hospital Nazareth Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yael","family":"Milgrom","sequence":"additional","affiliation":[{"name":"The Liver Unit Hadassah Medical Organization Hadassah Hebrew University Medical Centre Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Massarwa","sequence":"additional","affiliation":[{"name":"The Liver Unit Hadassah Medical Organization Hadassah Hebrew University Medical Centre Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Hakimian","sequence":"additional","affiliation":[{"name":"The Liver Unit Hadassah Medical Organization Hadassah Hebrew University Medical Centre Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wadi","family":"Hazou","sequence":"additional","affiliation":[{"name":"The Liver Unit Hadassah Medical Organization Hadassah Hebrew University Medical Centre Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Assaf","family":"Issachar","sequence":"additional","affiliation":[{"name":"The Liver Institute Rabin Medical Centre Beilinson Hospital Petah\u2010Tikva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zivit","family":"Harpaz","sequence":"additional","affiliation":[{"name":"Can\u2010Fite BioPharma Ltd Petah\u2010Tikva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motti","family":"Farbstein","sequence":"additional","affiliation":[{"name":"Can\u2010Fite BioPharma Ltd Petah\u2010Tikva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inbal","family":"Itzhak","sequence":"additional","affiliation":[{"name":"Can\u2010Fite BioPharma Ltd Petah\u2010Tikva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naama","family":"Lev\u2010Cohain","sequence":"additional","affiliation":[{"name":"The Radiology Dep. 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