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).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
175
Miricorilant 100 mg for oral dosing
Matching placebo for oral dosing for 48 Weeks
Miricorilant 100 mg for oral dosing Miricorilant 200 mg for oral dosing
Percent relative change from Baseline in liver-fat content assessed by MRI-PDFF (Cohort A and Cohort B)
Time frame: Week 24
Percent relative change from Baseline in liver-fat content by MRI-PDFF (Cohort A and B at Week 6 and 24, Cohort A at Week 48)
Time frame: Week 6 and 24, Week 48
Absolute change from Baseline in liver-fat content by MRI-PDFF (Cohort A and B at Week 6 and 24, Cohort A at Week 48)
Time frame: 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 (Cohort A).
Time frame: Week 48
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 (Cohort A).
Time frame: 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 (Cohort A).
Time frame: Week 48
Change in liver stiffness and Controlled Attenuation Parameter (CAP) by FibroScan. (Cohort A and Cohort B at Week 24, Cohort A at Week 48)
Time frame: Week 24 and 48
Change in absolute body weight (Cohort A and B at Week 24, Cohort A at Week 48)
Time frame: Week 24 and 48
Change in lipids - total cholesterol, HDL, LDL, VLDL, TG, serum free fatty acids, (Cohort A and Cohort B at Week 24, Cohort A at Week 48)
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Matching placebo for oral dosing for 24 Weeks
Site #207
Chandler, Arizona, United States
Site #209
Tucson, Arizona, United States
Site #378
Huntington Park, California, United States
Site #439
Lancaster, California, United States
Site #469
Long Beach, California, United States
Site #373
Los Angeles, California, United States
Site #214
Panorama City, California, United States
Site #233
Santa Ana, California, United States
Site #452
Boca Raton, Florida, United States
Site # 101
Gainesville, Florida, United States
...and 67 more locations
Time frame: Week 24 and 48
Change in Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) (Cohort A and Cohort B at Week 6 and 24, Cohort A at Week 48)
Time frame: Week 6, 24 and 48
Proportion of patients with Baseline ALT > 30 U/L achieving a reduction from Baseline in ALT ≥ 17 U/L at Week 24 (Cohort A and Cohort B) and Week 48 (Cohort A).
Time frame: Week 24, Week 48
Change in ELF, (Cohort A and B at Week 24, Cohort A at Week 48)
Time frame: Week 24 and 48
Change in HbA1c (Cohort A and B at Week 24, Cohort A at Week 48)
Time frame: Week 24 and 48
Change in HOMA-IR (Cohort A and B at Week 24, Cohort A at Week 48)
Time frame: Week 24 and 48
Change in plasma glucose (Cohort A and B at Week 24, Cohort A at Week 48)
Time frame: Week 24 and 48