A Phase 2b, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Miricorilant in Adult Patients with Nonalcoholic Steatohepatitis (MONARCH)

Approximately 75 patients who are eligible for participation in the study will be randomized on Day 1 in a 2:1 ratio to 100 mg miricorilant or placebo twice weekly, for 48 weeks of treatment (Cohort A).

Approximately 90 patients who are eligible for participation in the study will be randomized on Day 1 in a 2:1 ratio to 100 mg miricorilant twice a week for 6 weeks of treatment, followed by a dose escalation to 200 mg miricorilant or placebo twice weekly for an additional 18 weeks which resulting in a total treatment duration of 24 weeks, or to placebo for 24 weeks. (Cohort B).

Inclusion Criteria:

• Cohort A: Histological diagnosis of NASH/MASH with NAS ≥ 4 (≥ 1 point in each subcomponent of steatosis, inflammation, and ballooning) and NASH-CRN fibrosis score of 2 or 3 based on the consensus method of histological assessment. A historical liver biopsy within 6 months of Screening with reading confirmed during the Screening period by a consensus panel is acceptable.

• Cohort B: Have a liver biopsy result that does not meet with the criteria for inclusion in Cohort A and is consistent with one of the following based on the consensus method of histological assessment:

  • NAS ≥ 3 with ≥1 point in each subcomponent of steatosis, inflammation, and ballooning, and a NASH-CRN fibrosis score of F1 or
  • 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.

• FibroScan® liver stiffness measurement ≥ 8 kPa and CAP ≥ 280 dB/m.

• MRI-PDFF with ≥ 8% steatosis

• Presence of at least 1 of the following metabolic syndromes that increase the risk of NASH/MASH:

  1. Diagnosis of type 2 diabetes OR
  2. Presence of 2 or more components of metabolic syndrome:

  i. Fasting blood glucose ≥ 100 mg/dL (5.6 mmol/L) or treatment for elevated blood glucose ii. Systolic blood pressure ≥ 130mmHg, diastolic blood pressure ≥ 85mmHg, or treatment for hypertension iii. Serum triglycerides ≥ 150 mg/dL (1.7 mmol/L) or drug treatment for elevated triglycerides iv. Serum high-density lipoprotein (HDL) cholesterol < 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. Overweight or obese (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 (male ≥ 90 cm [35.4 in]; women ≥ 80 cm [31.5 in] in

• Other inclusion criteria may apply

Exclusion Criteria:

• Have participated in another clinical trial within the last 3 months of Screening where the patient received active treatment for NASH/MASH.
• Have participated in a clinical trial for any other indication within the last 3 months or 5 half-lives of the treatment, whichever is longer.
• Are pregnant or lactating women
• Have a BMI < 18 kg/m2 or > 45 kg/m2.• Have had liver transplantation or plan to have liver transplantation during the study
• Have type 1 diabetes or poorly controlled type 2 diabetes.
• Are pregnant or lactating women
• Have a BMI < 18 kg/m2 or > 45 kg/m2
• Have had successful weight-loss surgery within 2 years prior to Screening or are planning weight-loss surgery during the study.
• Have a >5% weight change within 3 months prior to Screening.
• Have significant alcohol consumption of more than 20 g per day for women and 30 g per day for men within 1 year prior to screening or score of ≥8 on AUDIT questionnaire
• Have any other chronic liver disease
• History of cirrhosis or evidence of cirrhosis by clinical, imaging, or liver biopsy evaluation
• Have hepatic decompensation
• Other exclusion criteria may apply

Double Blinded