Clinical trial NCT06108219: A Phase 2b, Study Evaluating Miricorilant in Adult Patients With Nonalcoholic Steatohepatitis/Metabolic Dysfunction-Associated Steatohepatitis (MONARCH)
Official title: A Phase 2b, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Miricorilant in Adult Patients With Nonalcoholic Steatohepatitis/Metabolic Dysfunction-Associated Steatohepatitis (MONARCH)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Nonalcoholic Steatohepatitis (NASH)
Metabolic Dysfunction-associated Steatohepatitis (MASH)
Keywords: Nonalcoholic Steatohepatitis (NASH)
Nonalcoholic Fatty Liver Disease (NAFLD)
Metabolic dysfunction-Associated Steatohepatitis (MASH)
Metabolic dysfunction-Associated Steatosis Liver Disease (MASLD)
Lead sponsor: Corcept Therapeutics
Sponsor class: INDUSTRY
First posted: 2023-10-30
Enrollment: 195
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: Approximately 120 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 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 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).

Eligibility criteria: 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

Primary outcomes:
measure: Percent relative change from Baseline in liver-fat content assessed by MRI-PDFF (Cohort A and Cohort B)
timeFrame: Week 24
Secondary outcomes:
measure: Change in liver stiffness and Controlled Attenuation Parameter (CAP) by FibroScan. (Cohort A and Cohort B at Week 24, Cohort A at Week 48)
timeFrame: Week 24 and 48
measure: Change in absolute body weight (Cohort A and B at Week 24, Cohort A at Week 48)
timeFrame: Week 24 and 48
measure: Change in lipids - total cholesterol, HDL, LDL, VLDL, TG, serum free fatty acids, apolipoproteins (Cohort A and Cohort B at Week 24, Cohort A at Week 48)
timeFrame: Week 24 and 48
measure: Change in Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) (Cohort A and Cohort B at Week 6 and 24, Cohort A at Week 48)
timeFrame: Week 6, 24 and 48
measure: Change in ELF, Pro-C3 and other markers of liver fibrosis (Cohort A and B at Week 24, Cohort A at Week 48)
timeFrame: Week 24 and 48
measure: Change in HbA1c (Cohort A and B at Week 24, Cohort A at Week 48)
timeFrame: Week 24 and 48
measure: Change in HOMA-IR (Cohort A and B at Week 24, Cohort A at Week 48)
timeFrame: Week 24 and 48
measure: Change in plasma glucose (Cohort A and B at Week 24, Cohort A at Week 48)
timeFrame: Week 24 and 48
measure: 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)
timeFrame: Week 6 and 24, Week 48
measure: 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)
timeFrame: Week 6, 24, Week 48
measure: 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).
timeFrame: Week 48
measure: 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).
timeFrame: Week 48
measure: 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).
timeFrame: Week 48
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Site #207
state: Arizona
city: Tucson
country: United States
facility: Site #209
state: Arizona
city: Huntington Park
country: United States
facility: Site #378
state: California
city: Lancaster
country: United States
facility: Site #439
state: California
city: Long Beach
country: United States
facility: Site #469
state: California
city: Los Angeles
country: United States
facility: Site #373
state: California
city: Panorama City
country: United States
facility: Site #214
state: California
city: Santa Ana
country: United States
facility: Site #233
state: California
city: Boca Raton
country: United States
facility: Site #452
state: Florida
city: Hallandale Beach
country: United States
facility: Site #465
state: Florida
city: Hialeah Gardens
country: United States
facility: Site #430
state: Florida
city: Lakewood Ranch
country: United States
facility: Site #458
state: Florida
city: Largo
country: United States
facility: Site #475
state: Florida
city: Miami Lakes
country: United States
facility: Site #438
state: Florida
city: Viera
country: United States
facility: Site #460
state: Florida
city: Houma
country: United States
facility: Site #453
state: Louisiana
city: Marrero
country: United States
facility: Site #451
state: Louisiana
city: Metairie
country: United States
facility: Site #061
state: Louisiana
city: Rockville
country: United States
facility: Site #440
state: Maryland
city: Saint Paul
country: United States
facility: Site #442
state: Minnesota
city: Kansas City
country: United States
facility: Site #228
state: Missouri
city: Jackson
country: United States
facility: Site #455
state: New Jersey
city: East Syracuse
country: United States
facility: Site #445
state: New York
city: New York
country: United States
facility: Site #454
state: New York
city: Morehead City
country: United States
facility: Site #464
state: North Carolina
city: Beavercreek
country: United States
facility: Site #447
state: Ohio
city: Columbus
country: United States
facility: Site #470
state: Ohio
city: Dayton
country: United States
facility: Site #448
state: Ohio
city: Westlake
country: United States
facility: Site #437
state: Ohio
city: Cordova
country: United States
facility: Site #461
state: Tennessee
city: Austin
country: United States
facility: Site #211
state: Texas
city: Brownsville
country: United States
facility: Site #432
state: Texas
city: Dallas
country: United States
facility: Site #370
state: Texas
city: Edinburg
country: United States
facility: Site #213
state: Texas
city: Edinburg
country: United States
facility: Site #215
state: Texas
city: Georgetown
country: United States
facility: Site #431
state: Texas
city: Houston
country: United States
facility: Site #305
state: Texas
city: Katy
country: United States
facility: Site #459
state: Texas
city: San Antonio
country: United States
facility: Site #433
state: Texas
city: San Antonio
country: United States
facility: Site #212
state: Texas
city: Waco
country: United States
facility: Site #434
state: Texas
city: West Jordan
country: United States
facility: Site #441
state: Utah
city: Manassas
country: United States
facility: Site #463
state: Virginia
city: Seattle
country: United States
facility: Site #226
state: Washington
city: San Juan
country: Puerto Rico
facility: Site #457
Study officials:
affiliation: Corcept Therapeutics
name: Kavita Juneja, MD
role: STUDY_DIRECTOR
References: