Pinnacle Clinical Research, San Antonio, TX, USA.
Madrigal Pharmaceuticals, Conshohocken, PA, USA.
Nat Med. 2023 Nov;29(11):2919-2928. doi: 10.1038/s41591-023-02603-1. Epub 2023 Oct 16.
Nonalcoholic steatohepatitis (NASH) is a progressive liver disease with no approved treatment. MAESTRO-NAFLD-1 was a 52-week randomized, double-blind, placebo-controlled phase 3 trial evaluating the safety of resmetirom in adults with nonalcoholic fatty liver disease and presumed NASH. Patients were randomized to three double-blind arms (100 mg resmetirom (n = 325), 80 mg resmetirom (n = 327) or placebo (n = 320)) or open-label 100 mg resmetirom (n = 171). The primary end point was incidence of treatment-emergent adverse events (TEAEs) over 52 weeks and key secondary end points were LDL-C, apoB, triglycerides (over 24 weeks), hepatic fat (over 16 and 52 weeks) and liver stiffness (over 52 weeks). Resmetirom was safe and well tolerated. TEAEs occurred in 86.5% (open-label 100 mg resmetirom), 86.1% (100 mg resmetirom), 88.4% (80 mg resmetirom) and 81.8% (placebo) of patients. TEAEs in excess of placebo included diarrhea and nausea at the initiation of treatment. Key secondary end points included least square means difference from placebo at 80 mg, 100 mg resmetirom: LDL-C (-11.1%, -12.6%), apoB (-15.6%, -18.0%), triglycerides (-15.4%, -20.4%), 16-week hepatic fat (-34.9%, -38.6%), (P < 0.0001) and liver stiffness (-1.02, -1.70) and 52-week hepatic fat (-28.8, -33.9). These findings demonstrate resmetirom was safe and well tolerated in adults with presumed NASH, supporting a role for further clinical development. (ClinicalTrials.gov identifier NCT04197479 ).
非酒精性脂肪性肝炎（NASH）是一种进展性肝病，目前尚无获批的治疗方法。MAESTRO-NAFLD-1 是一项为期 52 周的随机、双盲、安慰剂对照的 3 期临床试验，旨在评估 resmetirom 在非酒精性脂肪性肝病和推定的 NASH 成人患者中的安全性。患者被随机分配至三个双盲治疗组（100mg resmetirom（n=325）、80mg resmetirom（n=327）或安慰剂（n=320））或开放标签 100mg resmetirom（n=171）组。主要终点是 52 周内治疗出现的不良事件（TEAEs）发生率，关键次要终点是 LDL-C、载脂蛋白 B（apoB）、甘油三酯（24 周时）、肝内脂肪（16 和 52 周时）和肝硬度（52 周时）。Resmetirom 安全且耐受良好。TEAEs 发生率分别为 86.5%（开放标签 100mg resmetirom）、86.1%（100mg resmetirom）、88.4%（80mg resmetirom）和 81.8%（安慰剂）。治疗起始时，TEAEs 发生率高于安慰剂的有腹泻和恶心。关键次要终点包括 80mg 和 100mg resmetirom 与安慰剂相比的最小平方均数差值：LDL-C（-11.1%，-12.6%）、apoB（-15.6%，-18.0%）、甘油三酯（-15.4%，-20.4%）、16 周肝内脂肪（-34.9%，-38.6%）（均 P<0.0001）和肝硬度（-1.02，-1.70）以及 52 周肝内脂肪（-28.8%，-33.9%）。这些结果表明，resmetirom 在推定的 NASH 成人患者中安全且耐受良好，支持进一步开展临床开发。（临床试验.gov 标识符 NCT04197479）。
