A Phase II Clinical Trial of Chiglitazar for NASH

Prior treatment

• Previous or planned ( during the study period) bariatric surgery;
• Liver transplantation history or planned liver transplantation;
• Weight loss of more than 5% in 6 months before screening;
• Donated blood or lost blood \>400 ml within 8 weeks before the first medication;
• Drugs cumulatively for more than 1 month in the previous 3 months before screening, such as obeticholic acid ( OCA ), berberine;
• Drugs that may cause liver damage for more than 2 weeks within 1 year before screening;
• Patients received the following medications unless they have received a stable dose for at least 1 month before screening :Beta-blockers, thiazide diuretics, statins, niacin, ezetimibe, thyroid hormone;
• Patient participating in other clinical trials of drugs or medical devices within 3 months prior to screening ;

Other illness

• Type 1 diabetes;
• Existing other liver diseases or history of liver diseases
• History of transient ischemic attack or cerebrovascular accident;
• History of myocardial infarction, or coronary angioplasty or coronary artery bypass surgery, unstable angina, heart failure (New York Heart Association NYHA grade III / IV ), or ECG signs of left ventricular hypertrophy, or serious arrhythmias ；
• History of edema of lower limbs or whole body;
• diagnosed as osteoporosis or any other known bone disease;
• In the past 5 years, there was a history of malignant tumors of any organ system;
• Human immunodeficiency virus ( HIV ) test is positive;
• History of drug abuse in 12 months;

Lab values

• Any of the following for type 2 diabetes:
  • HbA1c ≥ 8.5% during screening
  • At the time of screening, ≥ 2 oral hypoglycemic drugs combinations
  • Receiving any of the following medications at screening: Thiazolidinediones (TZD) drugs, fibrates, glucagon-like peptide-1 (GLP-1) receptor agonists, insulin
• The calculated eGFR \< 60 mL/(min\*1.73m\^2 );
• Low density lipoprotein cholesterol (LDL-C) ≥ 3.4 mmol/L during screening ;
• Platelet \< 100×10\^9 /L ;

Other

• During screening, blood pressure ≥ 160/100 mmHg ;
• Liver biopsy show liver cirrhosis or clinically diagnosed as cirrhosis;
• With MRI scan contraindications;
• Heavy drinking of alcohol for more than 3 months in a year;
• Heavy smoking \>30 per day within 1 year;
• There is clinical evidence of liver decompensation or severe liver damage;
• Pregnant or breastfeeding women.

• Before any evaluation, an informed consent form voluntarily signed by the patient must be obtained;
• 18 -75 years old (at the time of screening visit V1), male or female;
• MRI-PDFF ≥ 8% ;
• Liver stiffness value ( LSM ) 7.0-11.0kPa ;
• Triglyceride ( TG ) ≥1.7mmol/L and ≤5.6 mmol/L;
• HOMA-IR ≥ 2.5 ;
• Serum Alanine aminotransferease (ALT) ≥ the upper limit of normal during screening.