The Selective Endothelin Receptor Antagonist SC0062 in IgA Nephropathy

作者：Hiddo J.L. Heerspink, Xiaoying Du, Yan Xu, Yanning Zhang, Bin Liu, Guangyu Bi, Changping Xu, Qun Luo, Henglan Wu, Jianxin Wan, Liou Cao, Rong Wang, Qiuling Fan, Hong Cheng, Lixia Xu, Jiyi Huang, Aimin Zhong, Qingfeng Peng, Yong-Jiang Hei, Yiwei Wang, Bo Zhou, Liqin Zhang, Jianghua Chen · 发表于：Journal of the American Society of Nephrology · 年份：2024 · DOI：10.1681/asn.0000000538 · 被引用次数：25 · 研究领域：Renal Diseases and Glomerulopathies、Chronic Kidney Disease and Diabetes、Ion Transport and Channel Regulation

Key Points Patients with IgA nephropathy and significant proteinuria are at high risk of progressive kidney function loss and kidney failure. We report the results of a clinical trial assessing the selective endothelin receptor antagonist SC0062 for the treatment of IgA nephropathy. SC0062 led to clinically meaningful improvements in proteinuria and did not increase risk of peripheral edema at higher doses. Background 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. Methods We conducted a randomized, placebo-controlled, double-blind, clinical trial in adults with biopsy-proven IgA nephropathy and eGFR ≥30 ml/min per 1.73 m 2 with urine protein-creatinine ratio (UPCR) ≥0.75 g/g or proteinuria ≥1 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. Results Overall, 131 pati...