A Phase 2b, Study Evaluating Miricorilant in Adult Patients With Nonalcoholic Steatohepatitis (MONARCH)

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

Detailed Description
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Approximately 150 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.

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

Conditions
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Nonalcoholic Steatohepatitis (NASH), Metabolic Dysfunction-associated Steatohepatitis (MASH)

Intervention / Treatment
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* Drug: Miricorilant
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a diagnosis of NASH based on a biopsy obtained within the last year OR Have a diagnosis of presumed NASH based on blood tests and scans FibroScan® liver stiffness measurement ≥ 8 kPa and CAP ≥ 300 dB/m. MRI-PDFF with ≥ 8% steatosis Histological diagnosis of NASH 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. Presence of at least 1 of the following metabolic syndromes that increase the risk of NASH: Diagnosis of type 2 diabetes OR 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 ii. Systolic blood pressure ≥ 130, diastolic blood pressure ≥ 85, 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 year and received active treatment for NASH Have participated in another clinical trial for any other indication within the last 3 months Are pregnant or lactating women Have a BMI <18 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental<br>Patients who meet the entry criteria for study CORT118335-862 will be enrolled to receive 100 mg of miricorilant, twice a week for 48 weeks. | Drug: Miricorilant<br>* Miricorilant 100 mg for oral dosing<br>* Other names: CORT118335;|
| Placebo Comparator: Placebo<br>Patients who meet the entry criteria for study CORT118335-862 will be enrolled to receive a matching placebo twice a week for 48 weeks. | Drug: Placebo<br>* Matching placebo for oral dosing<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent relative change from Baseline in liver-fat content assessed by MRI-PDFF. |  | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with at least 2 points reduction from Baseline in the NAS (NAFLD activity score) without worsening of liver fibrosis at Week 48 assessed by biopsy, with at least a 1-point reduction in ballooning or inflammation. |  | Week 48 | 
| Improvement in liver fibrosis stage by at least 1-point (NASH CRN fibrosis score) from Baseline and no worsening of steatohepatitis at Week 48 assessed by biopsy. |  | Week 48 | 
| Change in liver stiffness and Controlled Attenuation Parameter (CAP) by FibroScan. |  | Week 24 and 48 | 
| Change in absolute body weight |  | Week 24 and 48 | 
| Change in lipids - total cholesterol, HDL, LDL, VLDL, TG, serum free fatty acids, apolipoproteins |  | Week 24 and 48 | 
| Change in Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) |  | Week 24 and 48 | 
| Change in ELF, Pro-C3 and other markers of liver fibrosis |  | Week 24 and 48 | 
| Change in HbA1c |  | Week 24 and 48 | 
| Change in HOMA-IR |  | Week 24 and 48 | 
| Change in plasma glucose |  | Week 24 and 48 | 
| Percent relative change from Baseline in liver-fat content by MRI-PDFF. |  | Week 6, Week 48 | 
| Absolute change from Baseline in liver-fat content by MRI-PDFF. |  | Week 6, 24, Week 48 | 
| Resolution of steatohepatitis (defined as a ballooning grade of 0 and a lobular inflammation grade of ≤ 1) and no worsening of liver fibrosis at Week 48 assessed by biopsy. |  | Week 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nonalcoholic Fatty Liver Disease (NAFLD), Metabolic dysfunction-Associated Steatohepatitis (MASH), Nonalcoholic Steatohepatitis (NASH), Metabolic dysfunction-Associated Steatosis Liver Disease (MASLD)