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)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 175
- 试验地点
- 154
- 主要终点
- Percent relative change from Baseline in liver-fat content assessed by MRI-PDFF (Cohort A and Cohort B)
研究概览
简要总结
A Phase 2b, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Miricorilant in Adult Patients with Nonalcoholic Steatohepatitis (MONARCH)
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Double Blinded
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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:
- •Diagnosis of type 2 diabetes OR
- •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
排除标准
- •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
研究组 & 干预措施
Placebo (Cohort A)
Patients who meet the entry criteria for study CORT118335-862 (Cohort A) will be enrolled to receive a matching placebo twice a week for 48 weeks.
干预措施: Placebo (Cohort A) (Drug)
Placebo (Cohort B)
Patients who meet the entry criteria for study CORT118335-862 (Cohort B) will be enrolled to receive a matching placebo twice a week for 24 weeks.
干预措施: Placebo (Cohort B) (Drug)
Experimental (Cohort A)
Patients who meet the entry criteria for study CORT118335-862 (Cohort A) will be enrolled to receive 100 mg of miricorilant, twice a week for 48 weeks.
干预措施: Miricorilant (Cohort A) (Drug)
Experimental (Cohort B)
Patients who meet the entry criteria for study CORT118335-862 (Cohort B) will be enrolled to receive 100 mg of miricorilant, twice a week for 6 weeks. Dose will be escalated to 200 mg of miricorilant, twice a week for 18 weeks.
干预措施: Miricorilant (Cohort B) (Drug)
结局指标
主要结局
Percent relative change from Baseline in liver-fat content assessed by MRI-PDFF (Cohort A and Cohort B)
时间窗: Week 24
次要结局
- 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)(Week 24 and 48)
- Change in HbA1c (Cohort A and B at Week 24, Cohort A at Week 48)(Week 24 and 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)(Week 24 and 48)
- Change in absolute body weight (Cohort A and B at Week 24, Cohort A at Week 48)(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)(Week 6, 24 and 48)
- Change in HOMA-IR (Cohort A and B at Week 24, Cohort A at Week 48)(Week 24 and 48)
- Change in plasma glucose (Cohort A and B at Week 24, Cohort A at Week 48)(Week 24 and 48)
- Change in ELF, Pro-C3 and other markers of liver fibrosis (Cohort A and B at Week 24, Cohort A at Week 48)(Week 24 and 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)(Week 6, 24, Week 48)
- 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)(Week 6 and 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).(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).(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).(Week 48)