Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine Graduate School of Medicine, Yokohama, Kanagawa, Japan.
Department of Gastroenterology, National Hospital Organisation Yokohama Medical Center, Yokohama, Japan.
BMJ Open. 2024 Nov 24;14(11):e088862. doi: 10.1136/bmjopen-2024-088862.
Non-alcoholic fatty liver disease, now known as metabolic dysfunction-associated steatotic liver disease (MASLD), is a phenotype of the metabolic syndrome in the liver and is clearly associated with metabolic abnormalities such as hyperglycaemia and dyslipidaemia. Although the prevalence of MASLD is increasing worldwide, there is currently no consensus on the efficacy and safety of the drugs used to treat MASLD/metabolic dysfunction-associated steatohepatitis (MASH). Pemafibrate, a selective peroxisome proliferator-activated receptor alpha modulator, was designed to have higher peroxisome proliferator-activated receptor alfa (PPARα) agonist activity and selectivity than existing PPARα agonists, and in development trials, without increasing creatinine levels, lipid parameters and alanine aminotransferase (ALT) were significantly improved. Thus, pemafibrate may effectively ameliorate the pathogenesis and metabolic abnormalities in MASLD/MASH. In this trial, we evaluated the efficacy and safety of pemafibrate in patients with MASLD/MASH.
This trial was designed as an open-label, three-arm, randomised controlled study. After obtaining informed consent, patients aged 20-80 years who met the selection criteria were enrolled. Patients were randomised to receive pemafibrate 0.4 mg/day, 0.2 mg/day or fenofibrate (n=120 per group). The duration of treatment was 48 weeks. The primary endpoint was a change in ALT levels after 24 weeks of administration. Secondary endpoints included changes from baseline in liver fibrosis markers (fibrosis-4 index, type IV collagen 7s, enhanced liver fibrosis and Mac-2 binding protein glycosylation isomer) at 48 weeks as well as changes in liver fat mass and liver stiffness measured by MRI and ultrasound (US) at centres equipped with MRI and US capabilities.
Ethical approval was obtained from the Yokohama City University Certified Institutional Review Board before participant enrolment (CRB20-014). The results of this study will be submitted for publication in international peer-reviewed journals and the key findings will be presented at international scientific conferences. Participants wishing to understand the results of this study will be contacted directly on data publication.
This trial was registered in the Japan Registry of Clinical Trials (number: jRCTs031200280).
V.1.9, 23 November 2023.
非酒精性脂肪性肝病，现称为代谢相关脂肪性肝病（MASLD），是肝脏代谢综合征的一种表型，与高血糖和血脂异常等代谢异常明显相关。尽管全球 MASLD 的患病率正在上升，但目前尚无共识认为用于治疗 MASLD/代谢相关脂肪性肝炎（MASH）的药物有效且安全。Pemafibrate 是一种选择性过氧化物酶体增殖物激活受体 α 调节剂，其设计目的是具有比现有过氧化物酶体增殖物激活受体 α（PPARα）激动剂更高的 PPARα 激动活性和选择性，并且在开发试验中，没有增加肌酐水平，脂质参数和丙氨酸氨基转移酶（ALT）显著改善。因此，Pemafibrate 可能有效改善 MASLD/MASH 的发病机制和代谢异常。在这项试验中，我们评估了 Pemafibrate 治疗 MASLD/MASH 患者的疗效和安全性。
本试验设计为开放标签、三臂、随机对照研究。获得知情同意后，符合入选标准的 20-80 岁患者入组。患者被随机分为接受 Pemafibrate 0.4mg/天、0.2mg/天或非诺贝特（每组 120 人）。治疗持续 48 周。主要终点是治疗 24 周后 ALT 水平的变化。次要终点包括 48 周时肝纤维化标志物（纤维化 4 指数、IV 型胶原 7s、增强型肝纤维化和 Mac-2 结合蛋白糖基化异构体）的基线变化以及 MRI 和超声（US）在配备 MRI 和 US 功能的中心测量的肝脂肪量和肝硬度的变化。
在参与者入组前，横滨市立大学认证机构审查委员会（CRB20-014）获得了伦理批准。本研究的结果将提交给国际同行评议期刊发表，并将在国际科学会议上报告主要研究结果。希望了解本研究结果的参与者将在数据发布后直接联系。
本试验在日本临床试验注册处（注册号：jRCTs031200280）注册。
V.1.9，2023 年 11 月 23 日。
