evaluation of miricorilant on liver fat in patients with masld

Conditions: Nonalcoholic Steatohepatitis (NASH); Metabolic Dysfunction-Associated Steatohepatitis (MASH); Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD); Non-alcoholic Fatty Liver Disease (NAFLD)

Summary: a phase 1, open-label study evaluating the effect of miricorilant on hepatic lipids in patients with presumed metabolic dysfunction-associated steatohepatitis (mash)

approximately 8 patients who are eligible for participation in the study will be assigned to a single dose cohort receiving 100 mg of miricorilant daily. the total duration of participation for each patient is expected to be up to 14 weeks, comprising a 6-week screening period, a 4-week treatment phase, and a 4-week follow-up period.

Eligibility criteria:
inclusion criteria: * evidence of liver fibrosis with either fibroscan liver stiffness measurement ≥ 8 kpa and cap ≥ 280 db/m or historical biopsy within 12 months of screening that meets the following criteria: 1. nafld activity score (nas) ≥ 3 with ≥ 1 point in each subcomponent of steatosis, inflammation, and ballooning, and a nash crn fibrosis score of f1 or 2. nas ≥ 2 with ≥ 1 point in subcomponent of steatosis and ≥ 1 point in subcomponent of ballooning or inflammation, and a nash crn fibrosis score of f2 or 3 * ast \> 17 u/l for women and ast \> 20 u/l for men. the ast inclusion criterion does not apply to participants with an eligible historical liver biopsy performed within 12 months of screening. * fib-4 score of ≥ 1.3. the fib-4 inclusion criterion does not apply to participants with an eligible historical liver biopsy performed within 12 months of screening. * mri-pdff with ≥ 8% steatosis; this assessment must be performed within 4 weeks of the baseline visit. * have a stable weight within the last 6 months, defined by no more than a 5% loss of initial body weight. * presence of at least 1 of the following metabolic syndrome characteristics that increase the risk of mash: a. diagnosis of type 2 diabetes managed with diet alone or diet and metformin (metformin dose must be stable for at least 1 month prior to screening) or b. presence of 3 or more components of metabolic syndrome: i. fasting blood glucose ≥ 100 mg/dl (5.6 mmol/l) or treatment for elevated blood glucose with metformin ii. systolic blood pressure ≥ 130 mm hg, diastolic blood pressure ≥ 85 mm hg, or treatment for hypertension iii. serum tg ≥ 150 mg/dl (1.7 mmol/l) iv. serum high-density lipoprotein cholesterol (hdl) \< 40 mg/dl (1 mmol/l) in men and \< 50 mg/dl (1.3 mmol/l) in women or drug treatment for low hdl v. having overweight or obesity (body mass index \[bmi\] ≥ 25 kg/m2 \[bmi * 23 kg/m2 in asians\]), or increased waist circumference ≥ 102 cm (40 in) in men and ≥ 88 cm (35 in) in women (men ≥ 90 cm \[35.4 in\]; women ≥ 80 cm \[31.5 in\] in asians). other inclusion criteria may apply exclusion criteria: * participation in another clinical trial for mash or weight loss (e.g., glp-1 receptor agonists) within the last 3 months. * participation in any other clinical trial within the last 3 months or 5 half-lives of the treatment, whichever is longer. * women who are pregnant, planning to become pregnant, or lactating. * bmi \ 45 kg/m². * significant alcohol consumption exceeding 20 g/day for women or 30 g/day for men within 1 year prior to screening. * positive urine drug screen for amphetamines, cocaine, opiates, or cannabinoids. * known or suspected cirrhosis or signs of hepatic decompensation. * other chronic liver diseases such as hepatitis b or c, autoimmune hepatitis, primary biliary cholangitis, or wilson's disease. * history of myocardial infarction, unstable angina, or stroke within 3 months prior to screening. * uncontrolled hypertension (systolic \> 160 mm hg or diastolic \> 100 mm hg). * current use of medications prohibited due to potential drug-drug interactions with study treatment. * contraindications to magnetic resonance imaging (mri). other exclusion criteria may apply

Keywords: nonalcoholic fatty liver disease (nafld) nonalcoholic steatohepatitis (nash) metabolic dysfunction-associated steatohepatitis (mash) metabolic dysfunction-associated steatosis liver disease (masld)