A Study of Chiglitazar in Patients With Metabolic Dysfunction-associated Steatohepatitis and Type 2 Diabetes Mellitus

Prior treatment

• Any of the following cardiovascular conditions within 6 months prior to screening:
  • acute myocardial infarction (MI),
  • cerebrovascular accident (stroke),
  • unstable angina,
  • hospitalization due to congestive heart failure (CHF)
  • New York Heart Association Functional Classification IV CHF
• Known clinically significant gastric emptying abnormality (for example, severe diabetic gastroparesis or gastric outlet obstruction) or chronically take drugs that directly affect gastrointestinal motility.
• A transplanted organ (corneal transplants allowed) or awaiting an organ transplant.
• Use of drugs associated with hepatic steatosis (e.g., amiodarone, methotrexate, tamoxifen) for more than 2 weeks in the 3 months prior to screening.
• Current use of medication is associated with weight gain, except when on stable dose for at least 3 months prior to screening and remaining on stable dose during the study.
• Receiving or having received (within 3 months of screening) chronic (\>2 weeks) systemic glucocorticoid therapy.
• Use of treatment targeting MASH for more than 2 weeks in the 3 months prior to screening (GLP-1 receptor agonists or PPAR pan agonists).

Other illness

• Evidence of other forms of chronic liver disease:
  • Alcoholic liver disease,
  • Hepatitis B as defined by presence of hepatitis B surface antigen (HBsAg) or hepatitis B DNA,
  • Hepatitis C as defined by presence of hepatitis C virus (HCV) RNA or positive hepatitis C antibody (anti-HCV),
  • Evidence of autoimmune liver disease as defined by compatible liver histology,
  • Current drug-induced liver disease as defined on the basis of typical exposure and history,
  • Suspected or proven liver cancer,
  • Any other type of liver disease other than MASH.
• Patients with T2DM who have a history of diabetic ketoacidosis, proliferative diabetic retinopathy, diabetic maculopathy or severe non-proliferative diabetic retinopathy that requires acute treatment.
• History of an active or untreated malignancy or are in remission from a clinically significant malignancy (other than basal or squamous cell skin cancer, in situ carcinomas of the cervix, or in situ prostate cancer) for less than 5 years.
• Uncontrolled hypertension (systolic blood pressure ≥160 mm Hg and/or diastolic blood pressure ≥ 100 mm Hg).
• Any other condition which in the opinion of investigator would impede compliance or hinder completion of the study.

Lab values

• Uncontrolled T2DM defined as HbA1c \>9.5% at time of screening or Type 1 diabetes mellitus (T1DM).
• Renal impairment measured as estimated glomerular filtration rate (eGFR) \<30 mL/min/1.73 m2.
• Evidence of untreated hypothyroidism or hyperthyroidism based on clinical or laboratory evaluation.

Other

• Alcohol consumption \>20g ethyl alcohol/day for women and \>40g ethyl alcohol/day for men.
• Have a known self or family history (first-degree relative) of multiple endocrine neoplasia type 2A or type 2B, thyroid C-cell hyperplasia, or medullary thyroid carcinoma (MTC).
• Women of childbearing potential: positive pregnancy test during screening or at randomization or unwillingness to use an effective form of birth control during the trial (at least include one barrier contraceptive method) and breast feeding.

• Men and women aged at least 18 years and under 75 years (inclusive) at the time of obtaining consent.
• Participants must be diagnosed as T2DM and HbA1c ≤ 9.5% at time of screening.
• Participants must take Fibroscan examination with the result of CAP ≥ 238 dB/m and LSM\>8.5 kPa.
• Diagnosis of MASH by liver biopsy, with NAFLD Activity Score (NAS) ≥4 with ≥1 point for each component, and fibrosis stage 1b or more over according to the NASH Clinical Research Network (CRN) scoring system. (or liver biopsy not more than 6 months prior to screening)
• Stable body weight (≤10% body weight change) for at least 3 months.
• Possess good understanding and behavior and be able to take the medication daily as required by the trial.
• Willing to sign the informed consent.