Efficacy and Safety of Recombinant Human FGF21-Fc Fusion Protein for Injection (TQA2225/AP025) in Adult Subjects With Non-alcoholic Steatohepatitis (NASH)

Prior treatment

• History of weight loss surgery within 5 years (inclusive) prior to screening
• A major surgery was performed 3 months prior to signing the Informed Consent Form (ICF), or planned during the study period.
• Have experienced any bone trauma, fracture, or bone surgery within ≤ 2 months prior to screening.
• Patient participating in other clinical trials of drugs or medical devices within 3 months prior to screening.
• Liver transplantation history or planned liver transplantation

Other illness

• Documented causes of chronic liver disease other than NASH
• Uncontrolled hypertension at Screening (values ≥160/100 mm Hg)
• Subjects with any type of active malignancy or a history of malignancy (except cervical cancer or non-metastatic cutaneous squamous cell carcinoma, basal cell carcinoma and papillary thyroid carcinoma) that has been cured for more than 5 years prior to the screening period;
• Any other condition which, in the opinion of the Investigator, would impede compliance, hinder completion of the study, compromise the well-being of the patient, or interfere with the study outcomes.

Lab values

• Type 1 diabetes or uncontrolled Type 2 diabetes defined as:Hemoglobin A1c ≥9% at screening，Fasting blood glucose≥13.9mmol/l
• Abnormal laboratory test values：ALT or AST \>5 × ULN；Serum ALP≥2× ULN；eGFR\<60mL/min；INR\>1.3× ULN；platelets \< LLN.

Age

• Recent history of drug abuse (defined as ≤ 2 years).

Other

• History or presence of cirrhosis
• Unable or unwilling to undergo liver biopsy according to research requirements.
• When screening, according to the results of dual energy X-ray absorptiometry (DXA) examination, it meets the criteria for osteoporosis: T≤ -2.5
• Pregnant or breastfeeding women.
• Contraindications for MRI examination

• Must be willing to participate in the study and provide written informed consent.
• Male or female aged 18 ≤ age \< 75 at the time of signing the informed consent.
• Must have had prior liver biopsy within 180 days of randomization with fibrosis stage 1 to 3 and a NAS of ≥4 with at least a score of 1 in each of the lobular inflammation and ballooning degeneration.
• Confirmation of ≥10% liver fat content on Magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF).
• Weight changes≤5% in the 6 weeks prior to randomization.
• No qualitative change in dose for the drugs listed below:
  • Antidiabetic treatment if glucagon-like peptide-1 receptor agonists (GLP1 receptor agonists) or sodium-glucose co-transporter-2 inhibitors (SGLT2 inhibitors): for at least 3 months
  • Vitamin E (if at a dose ≥400 IU/day): for at least 6 months
  • Statins: for at least 3 months
• Females of childbearing potential must practice a consistent and proper use of highly effective method of contraception throughout the study and for 6 month after treatment discontinuation.