Evaluation of Miricorilant on Liver Fat in Patients With MASLD

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 \< 18 kg/m² or \> 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