{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T17:12:15Z","timestamp":1788455535174,"version":"build-2803163510"},"reference-count":27,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2024,10,26]],"date-time":"2024-10-26T00:00:00Z","timestamp":1729900800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Biocity Biopharmaceuticals"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"published-print":{"date-parts":[[2025,4]]},"abstract":"\n Key Points<\/jats:title>\n \n \n \n Patients with IgA nephropathy and significant proteinuria are at high risk of progressive kidney function loss and kidney failure.<\/jats:p>\n <\/jats:list-item>\n \n We report the results of a clinical trial assessing the selective endothelin receptor antagonist SC0062 for the treatment of IgA nephropathy.<\/jats:p>\n <\/jats:list-item>\n \n SC0062 led to clinically meaningful improvements in proteinuria and did not increase risk of peripheral edema at higher doses.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>\n \n Background<\/jats:title>\n Endothelin receptor type A activation contributes to kidney injury in patients with IgA nephropathy. SC0062 is a novel selective endothelin receptor type A antagonist. We report the results of a phase 2 dose-finding trial to characterize the efficacy and safety of SC0062 in patients with IgA nephropathy.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We conducted a randomized, placebo-controlled, double-blind, clinical trial in adults with biopsy-proven IgA nephropathy and eGFR \u226530 ml\/min per 1.73 m\n 2<\/jats:sup>\n with urine protein-creatinine ratio (UPCR) \u22650.75 g\/g or proteinuria \u22651 g\/24 hour despite using maximum tolerated doses of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Patients were randomized 1:1:1:1 to 24-week treatment with SC0062 5, 10, and 20 mg or matching placebo once daily. The primary efficacy outcome was percent change from baseline in UPCR in 24-hour urine samples after 12 weeks of treatment. Secondary end points included changes in eGFR. Safety outcomes including treatment-emergent adverse events and serious adverse events were recorded.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Overall, 131 patients (mean age 42 years [SD 11]; mean eGFR 72 ml\/min per 1.73 m\n 2<\/jats:sup>\n [SD 24] and median 24-hour UPCR 1.2 g\/g [25th\u201375th percentile, 0.9\u20131.5 g\/g]) were randomized to placebo (\n n<\/jats:italic>\n =34) or SC0062 5 mg (\n n<\/jats:italic>\n =33), 10 mg (\n n<\/jats:italic>\n =32), or 20 mg (\n n<\/jats:italic>\n =32). All SC0062 doses reduced UPCR versus placebo throughout treatment. At week 12, placebo-corrected geometric mean changes (95% confidence interval) from baseline in UPCR with SC0062 5, 10, and 20 mg were\u221227.6% (\u221243.0 to \u22128.2), \u221220.5% (\u221237.4 to 1.0), and \u221238.1% (\u221251.4 to \u221221.0), respectively, and at week 24 they were\u221222.4% (\u221242.2 to 4.3), \u221230.9% (\u221248.6 to \u22127.0), and \u221251.6% (\u221264.2 to \u221234.6), respectively. No differences in eGFR were observed among treatment groups. The proportion of participants with treatment-emergent adverse events or serious adverse events was balanced among treatment groups. Peripheral edema was reported by two (6%), one (3%), one (3%) participants in the 5, 10, and 20 mg SC0062-treated groups, respectively, compared with five (15%) in the placebo group.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n In patients with IgA nephropathy, SC0062 reduced proteinuria and did not increase risk of peripheral edema.<\/jats:p>\n <\/jats:sec>\n \n Clinical Trial registry name and registration number:<\/jats:title>\n A Study to Evaluate the Efficacy and Safety of SC0062 in the Treatment of CKD, NCT05687890.<\/jats:p>\n <\/jats:sec>\n \n Podcast<\/jats:title>\n This article contains a podcast at https:\/\/dts.podtrac.com\/redirect.mp3\/www.asn-online.org\/media\/podcast\/JASN\/2024_10_26_KTS_October2024.mp3<\/jats:p>\n <\/jats:sec>","DOI":"10.1681\/asn.0000000538","type":"journal-article","created":{"date-parts":[[2024,10,27]],"date-time":"2024-10-27T13:00:08Z","timestamp":1730034008000},"page":"657-667","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":26,"title":["The Selective Endothelin Receptor Antagonist SC0062 in IgA Nephropathy"],"prefix":"10.1681","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3126-3730","authenticated-orcid":false,"given":"Hiddo J.L.","family":"Heerspink","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands"},{"name":"The George Institute for Global Health, Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5891-0215","authenticated-orcid":false,"given":"Xiaoying","family":"Du","sequence":"additional","affiliation":[{"name":"Kidney Disease Center, The First Affiliated Hospital of Zhejiang University, Hangzhou, China"},{"name":"National Key Clinical Department of Kidney Diseases, Hangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanning","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, General Hospital of Northern Theater Command, Shenyang, 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