{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:08:57Z","timestamp":1790791737949,"version":"4.1.0"},"reference-count":23,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","license":[{"start":{"date-parts":[[2022,10,22]],"date-time":"2022-10-22T00:00:00Z","timestamp":1666396800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatol Commun"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Rencofilstat (RCF) demonstrated antifibrotic effects in preclinical models and was safe and well tolerated in Phase 1 studies. The aim of this Phase 2a study was safety, tolerability, pharmacokinetics, and exploration of efficacy biomarkers in subjects with nonalcoholic steatohepatitis (NASH). This Phase 2a, multicenter, single\u2010blind, placebo\u2010controlled study randomized 49 presumed F2\/F3 subjects to RCF 75\u2009mg once daily (QD), RCF 225\u2009mg QD, or placebo for 28\u2009days. Primary safety and tolerability endpoints were explored using descriptive statistics with <jats:italic toggle=\"yes\">post hoc<\/jats:italic> analyses comparing active to placebo groups. Pharmacokinetics were evaluated using population pharmacokinetics methods. Efficacy was explored using biomarkers, transcriptomics, and lipidomics. RCF was safe and well tolerated, with no safety signals identified. The most frequently reported treatment\u2010emergent adverse events were constipation, diarrhea, back pain, dizziness, and headache. No clinically significant changes in laboratory parameters were observed, and RCF pharmacokinetics were unchanged in subjects with NASH. Alanine transaminase (ALT) reduction was greater in active subjects than in placebo groups. Nonparametric analysis suggested that ALT reductions were statistically different in the 225\u2010mg cohort compared with matching placebo: \u221216.3\u2009\u00b1\u200925.5% versus \u22120.7\u2009\u00b1\u200913.4%, respectively. ProC3 and C6M reduction was statistically significant in groups having baseline ProC3\u2009&gt;\u200915.0\u2009ng\/ml. RCF was safe and well tolerated after 28\u2009days in subjects with presumed F2\/F3 NASH. Presence of NASH did not alter its pharmacokinetics. Reductions in ALT, ProC3, and C6M suggest direct antifibrotic effects with longer treatment duration. Reductions in key collagen genes support a mechanism of action via suppression and\/or regression of collagen deposition. <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>: These results support advancement of rencofilstat into a larger and longer Phase 2b study.<\/jats:p>","DOI":"10.1002\/hep4.2100","type":"journal-article","created":{"date-parts":[[2022,10,22]],"date-time":"2022-10-22T12:59:11Z","timestamp":1666443551000},"page":"3379-3392","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":29,"title":["Rencofilstat, a cyclophilin inhibitor: A phase 2a, multicenter, single\u2010blind, placebo\u2010controlled study in F2\/F3 NASH"],"prefix":"10.1097","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8285-2204","authenticated-orcid":false,"given":"Stephen A.","family":"Harrison","sequence":"first","affiliation":[{"name":"Radcliffe Department of Medicine,University of Oxford, Pinnacle Clinical Research,Live Oak,Texas,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6350-5258","authenticated-orcid":false,"given":"Patrick R.","family":"Mayo","sequence":"additional","affiliation":[{"name":"Research and Development,Hepion Pharmaceuticals, Inc.,Edmonton,Alberta,Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3060-5492","authenticated-orcid":false,"given":"Todd M.","family":"Hobbs","sequence":"additional","affiliation":[{"name":"Clinical, Medical and Regulatory,Hepion Pharmaceuticals, Inc.,Edison,New Jersey,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0903-7013","authenticated-orcid":false,"given":"Carlos","family":"Canizares","sequence":"additional","affiliation":[{"name":"Clinical, Medical and Regulatory,Hepion Pharmaceuticals, Inc.,Edison,New Jersey,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1896-2289","authenticated-orcid":false,"given":"Erin P.","family":"Foster","sequence":"additional","affiliation":[{"name":"Research and Development,Hepion Pharmaceuticals, Inc.,Edmonton,Alberta,Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7859-9947","authenticated-orcid":false,"given":"Caroline","family":"Zhao","sequence":"additional","affiliation":[{"name":"Research and Development,Hepion Pharmaceuticals, Inc.,Edmonton,Alberta,Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8762-6062","authenticated-orcid":false,"given":"Daren R.","family":"Ure","sequence":"additional","affiliation":[{"name":"Research and Development,Hepion Pharmaceuticals, Inc.,Edmonton,Alberta,Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3151-5467","authenticated-orcid":false,"given":"Daniel J.","family":"Trepanier","sequence":"additional","affiliation":[{"name":"Research and Development,Hepion Pharmaceuticals, Inc.,Edmonton,Alberta,Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7488-9637","authenticated-orcid":false,"given":"Jill A.","family":"Greytok","sequence":"additional","affiliation":[{"name":"Clinical, Medical and Regulatory,Hepion Pharmaceuticals, Inc.,Edison,New Jersey,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6847-6409","authenticated-orcid":false,"given":"Robert T.","family":"Foster","sequence":"additional","affiliation":[{"name":"Research and Development,Hepion Pharmaceuticals, 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