A Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of CS0159 in Subjects With NASH

Prior treatment

• Use of other investigational drugs within 5 half-lives of enrollment, or within 30 days, whichever is longer.
• Previous exposure to farnesoid X receptor (FXR) agonists 3 months prior to the first dosing.
• Current or within 6 months of screening use of drugs associated with steatosis, including but not limited to eg, methotrexate, amiodarone, high-dose estrogen, tamoxifen, long term systemic steroids, anabolic steroids, valproic acid.
• Weight changes \>10% in 6 months prior to screening, or weight changes \>5% from the screening MRI-PDFF to randomization or from the time of the diagnostic liver biopsy to randomization, whichever is longer.

Other illness

• Poorly controlled hypertension (systolic \>160 mm Hg, or diastolic blood pressure \>100 mm Hg - mean of 3 measurements).

Lab values

• Total bilirubin \>upper limit of normal (ULN; except for patients with Gilbert's syndrome with a normal direct bilirubin value and normal reticulocyte count).
  • Platelet count \<140 000/mm³, absolute neutrophil count \<1500 cells/mm3, or total
• white blood cells \<3000 cells/mm3.
• Alanine aminotransferase and aspartate aminotransferase (AST) \>5 × ULN, or alkaline phosphatase (ALP) \>1.5 × ULN.
• Uncontrolled diabetes mellitus (hemoglobin A1c \>10.0% during screening).

Other

• Prothrombin time international normalized ratio \>1.3, unless due to therapeutic anticoagulation.

• Patients who meet the diagnosis of NASH.
• Evidence of metabolic syndrome, except for those patients with biopsy-proven NASH.
• Body mass index (BMI) \>25 kg/m2, NOTE: for Asian-Americans BMI \>23 kg/m2.
• Stable use of other antidiabetic, weight loss, or lipid-modifying medications for at least 12 weeks prior to randomization.