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临床试验/CTRI/2024/12/078284
CTRI/2024/12/078284进行中（未招募）2 期

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)

M/s KlinEra Global Services37 个研究点 分布在 1 个国家目标入组 225 人开始时间: 2025年1月7日最近更新:
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试验速览

阶段
2 期
状态
进行中（未招募）
发起方
入组人数
225
试验地点
37
主要终点
Percent relative change from Baseline in liver-fat content assessed by MRI-PDFF (Cohort A and Cohort B)
研究概览研究设计入排标准结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

CORT118335-862 is a Phase 2b, Randomized, Double-Blind, Placebo-Controlled Study in patients with biopsy confirmed or presumed non-cirrhotic MASH to evaluate the efficacy, safety, tolerability, and PK of miricorilant. The study will be conducted in 2 cohorts (Cohort A and Cohort B). Cohort A will include approximately 150 patients with biopsy-confirmed non-cirrhotic (F2-3) MASH. Cohort B will include approximately 75 patients with presumed non-cirrhotic MASH. The study will be conducted across 30 centers in India. The duration of study drug is 48 weeks for Cohort A subjects whereas it is maximum up to 24 weeks for Cohort B subjects. The drug (Miricorilant or Placebo Tablet) is administered orally twice weekly in the ratio of 2:1 in both Cohort A and B subjects.

研究设计

研究类型
Interventional
分配方式
Randomized
盲法
Participant and Investigator Blinded

入排标准

年龄范围
18.00 Year(s) 至 75.00 Year(s)（—）
性别
All

入选标准

  • •1 Have provided informed consent.
  • •Are adults greater than or equal to 18 to lesser than or equal to 75 years old.
  • •FibroScan liver stiffness measurement greater than or equal to 8 kPa and CAP greater than or equal to 280 dB/m.
  • •The FibroScan inclusion criterion does not apply to participants with an eligible historical liver biopsy performed within 6 months of Screening with reading confirmed by a consensus panel to meet inclusion criterion
  • •MRI-PDFF with greater than or equal to 8% steatosis, this assessment must be performed within 6 weeks of the Baseline visit (Day 1).
  • •Liver biopsy that meets the following criteria: A historical liver biopsy within 6 months of Screening with reading confirmed during the Screening period by a consensus panel is acceptable.
  • •Cohort A: Have a histological diagnosis of MASH with NAFLD Activity Score (NAS) greater than or equal to 4 (greater than or equal to 1 point in each subcomponent of steatosis, inflammation, and ballooning) and a NASH CRN fibrosis score of 2 or 3 based on the consensus method of histological assessment.
  • •Cohort B: Have a liver biopsy result that does not meet the criteria for inclusion in Cohort A and is consistent with one of the following scenarios based on the consensus method of histological assessment: i.
  • •NAS greater than or equal to 3 with greater than or equal to1 point in each subcomponent of steatosis, inflammation, and ballooning, and a NASH CRN fibrosis score of F1 OR ii.
  • •NAS greater than or equal to 2 with greater than or equal to 1 point in subcomponent of steatosis and greater than or equal to 1 point in subcomponent of ballooning or inflammation, and a NASH CRN fibrosis score of F2 or
  • •Have a stable weight since the liver biopsy was performed, defined by no more than a 5% loss of initial body weight.
  • •Agree to have a liver biopsy performed after 48 weeks of treatment (Cohort A)
  • •AST greater than 17 U/L for women and AST greater than 20 U/L for men.
  • •The AST inclusion criterion does not apply to participants with an eligible historical liver biopsy performed within 6 months of Screening with reading confirmed by a consensus panel to meet inclusion criterion
  • •Presence of at least 1 of the following metabolic syndromes that increase the risk of MASH: a.
  • •Diagnosis of type 2 diabetes OR b.
  • •Presence of 3 or more components of metabolic syndrome: i.
  • •Fasting blood glucose greater than or equal to 100 mg/dL (5.6 mmol/L) or treatment for elevated blood glucose ii.
  • •Systolic blood pressure greater than or equal to 130 mm Hg, diastolic blood pressure greater than or equal to 85 mm Hg, or treatment for hypertension iii.
  • •Serum triglycerides greater than or equal to 150 mg/dL (1.7 mmol/L) or drug treatment for elevated triglycerides iv.
  • •Serum high-density lipoprotein (HDL) cholesterol lesser than 40 mg/dL (1 mmol/L) in men and lesser than 50 mg/dL (1.3 mmol/L) in women or drug treatment for low HDL v.
  • •Overweight or obese (body mass index [BMI] greater than or equal to 25 kg/m2 [BMI greater than or equal to 23 kg/m2 in Asians]), or increased waist circumference greater than or equal to 102 cm (40 in) in men and greater than or equal to 88 cm (35 in) in women (men greater than or equal to 90 cm [35.4 in], women greater than or equal to 80 cm [31.5 in] in Asians)
  • •Male and female patients of childbearing potential must agree to use a protocol-specified method of contraception throughout the study, including the Screening period, and for at least 28 days after the last dose of assigned treatment.

排除标准

  • •Have participated in another clinical trial within the last 3 months of Screening where the patient received active treatment for 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.
  • •Have participated in another study with miricorilant within 3 months prior to Screening.
  • •Women who are pregnant, planning to become pregnant, or are lactating.
  • •Have a BMI lesser than 18 kg/m2 or greater than 45 kg/m
  • •Are currently using any medications prohibited due to the potential for drug-drug interactions (DDI) with study treatments.
  • •Prohibited medications (see Section 5.4.2) must be discontinued at least 5 half-lives prior to a patient receiving their first study treatment.
  • •Have had a successful weight-loss surgery within 2 years prior to Screening or are planning weight-loss surgery during the study.
  • •Have a greater than 5% weight change within 3 months prior to Screening.
  • •Have significant alcohol consumption, defined as more than 2 drink units per day (equivalent to 20 g of ethanol) in women and 3 drink units per day (equivalent to 30 g of ethanol) in men for greater than or equal to 3 consecutive months within 1 year prior to Screening, inability to reliably quantify alcohol intake, or score a value greater than or equal to 8 on the Alcohol Use Disorders Identification Test (AUDIT) questionnaire.
  • •Have phosphatidylethanol (PEth) greater than
  • •Use of drugs associated with MASLD (eg, amiodarone, methotrexate, tamoxifen, estrogens at doses greater than those used for hormone replacement or contraception, anabolic steroids, or valproic acid) for more than 4 weeks in the 2 months prior to enrollment.
  • •Have been treated with resmetirom within 3 months prior to Screening.
  • •Are currently on pioglitazone, or high-dose Vitamin E (greater than 800 IU/day) unless on stable dose for at least 6 months prior to Baseline visit; maximum dose of pioglitazone allowed is 15 mg a day; patients on Vitamin E doses lesser than or equal to 800 IU/day for any duration are eligible to participate in the study.
  • •Are on lipid-modifying therapies unless on a stable dose for at least 6 weeks prior to Baseline visit (and at least 4 weeks prior to screening MRI-PDFF), maximum dose of rosuvastatin allowed is 10 mg a day.
  • •Are on glucagon-like peptide-1 (GLP-1) agonists or other anti-obesity compounds unless on a stable dose for at least 6 months prior to Baseline visit.
  • •Are using a medication such as digoxin with an increased risk for toxicity in the event of electrolyte changes.
  • •Have had liver transplantation or plan to have liver transplantation during the study.
  • •Have type 1 diabetes.
  • •Have poorly controlled type 2 diabetes with an HbA1c greater than or equal to 9.5%, an insulin dose adjustment greater than 20% within 60 days prior to Baseline visit, are on GLP-1 agonists unless on a stable dose for at least 6 months prior to Baseline visit, or are on other diabetes medication unless on a stable dose for at least 3 months prior to and during Screening.
  • •Have abnormal screening laboratories, a.
  • •AST greater than 5 × ULN b.
  • •ALT greater than 5 × ULN c.
  • •Creatine kinase greater than 3 × ULN
  • •Have known or suspected cirrhosis based on the opinion of the Investigator.
  • •A patient who presents with possible signs of suspected cirrhosis listed below will be excluded from the study, a.
  • •Physical exam findings, i.
  • •Jaundice b.
  • •Laboratory findings, i.
  • •Direct bilirubin greater than 0.3 mg/dL.
  • •Note, For patients who have Gilbert’s syndrome see exclusion criterion 23.f ii.
  • •Evidence of a nodular liver with splenomegaly d.
  • •Endoscopy, i.
  • •Evidence of esophageal varices
  • •Have hepatic decompensation defined as the presence of any of the following, a.
  • •Serum albumin lesser than 3.5 g/dL b.
  • •International normalized ratio (INR) greater than 1.3 (unless due to therapeutic anticoagulants) c.
  • •Total bilirubin greater than 1.3 mg/dL.
  • •Note for patients who have Gilbert’s syndrome see exclusion criterion 23.f d.
  • •History of esophageal or gastric variceal bleedings, ascites, or hepatic encephalopathy
  • •Hepatitis C as defined by presence of hepatitis C virus (HCV) antibody and positive HCV RNA.
  • •Documented cured HCV infection is acceptable if greater than 3 years from Screening visit c.
  • •History or evidence of current active autoimmune hepatitis d.
  • •History or evidence of primary biliary cholangitis e.
  • •History or evidence of primary sclerosing cholangitis f.
  • •History or evidence of Gilbert’s syndrome if direct bilirubin is greater than 0.3 mg/dL and total bilirubin greater than or equal to 2mg/dL or evidence of hemolysis contributing to elevated total bilirubin g.
  • •History or evidence of Wilson’s disease h.
  • •History or evidence of alpha-1-antitrypsin deficiency i.
  • •History or evidence of hemochromatosis j.
  • •History or evidence of drug-induced liver disease, as defined on the basis of typical exposure and history k.
  • 另有 15 项未显示

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 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 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 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 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)
  • 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)
  • 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)

研究者

发起方
M/s KlinEra Global Services
申办方类型
Contract research organization
责任方
Principal Investigator

研究点 (37)

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