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. 2024 Nov 24;14(11):e088862.
doi: 10.1136/bmjopen-2024-088862.

Pemafibrate for treating MASLD complicated by hypertriglyceridaemia: a multicentre, open-label, randomised controlled trial study protocol

Michihiro Iwaki  1 , Takashi Kobayashi  1 , Asako Nogami  1 , Yuji Ogawa  2 , Kento Imajo  3 , Eiji Sakai  4 , Yoshinobu Nakada  5 , Satoshi Koyama  6 , Takeo Kurihashi  7 , Noriko Oza  8 , Toshikazu Kohira  9 , Michiaki Okada  10 , Yuki Yamaguchi  11 , Shinji Iwane  12 , Fujito Kageyama  13 , Yuzo Sasada  14 , Masahiro Matsushita  15 , Akimitsu Tadauchi  16 , Gou Murohisa  17 , Masamichi Nagasawa  17 , Shuichi Sato  18 , Kazuhisa Maeda  19 , Koichiro Furuta  20 , Ryuta Shigefuku  21 , Yuya Seko  22 , Hiroshi Tobita  23 , Kazuhito Kawata  24 , Miwa Kawanaka  25 , Takaaki Sugihara  26 , Nobuharu Tamaki  27 , Motoh Iwasa  21 , Takumi Kawaguchi  28 , Yoshito Itoh  22 , Atsushi Kawaguchi  29 , Hirokazu Takahashi  30 , Atsushi Nakajima  1 , Masato Yoneda  31
Affiliations

Pemafibrate for treating MASLD complicated by hypertriglyceridaemia: a multicentre, open-label, randomised controlled trial study protocol

Michihiro Iwaki et al. BMJ Open. .

Abstract

Introduction: 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.

Methods and analysis: 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.

Ethics and dissemination: 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.

Trial registration number: This trial was registered in the Japan Registry of Clinical Trials (number: jRCTs031200280).

Protocol version: V.1.9, 23 November 2023.

Keywords: Hepatology; Lipid disorders; Other metabolic, e.g. iron, porphyria.

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Conflict of interest statement

Competing interests: ANa received grants and research support from Gilead, Mylan EPD, EA Pharma, Kowa, Taisho and Biofermin. ANa is a consulting advisor for Gilead, Boehringer Ingelheim, BMS, Kowa, Astellas, EA Pharma and Mylan EPD. The other authors declare no conflict of interest.

Figures

Figure 1
Figure 1. Study design. aN = 360 enrolled. MASLD, metabolic dysfunction-associated steatotic liver disease.
See this image and copyright information in PMC

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