A Study on Efficacy and Safety of HST101 in Chinese Patients with Hypercholesterolemia

Prior treatment

• Serious arrhythmia, MI, unstable angina pectoris, PCI, CABG, implantable cardioverter defibrillator, aortic valve surgery or stroke within 3 months prior to the first dose;
• LDL apheresis or plasma exchange within 2 months prior to the first dose;
• History of prescription drug abuse, illicit drug use or alcohol abuse within 6 months prior to screening;
• Participate another clinical trial within 30 days or less than 5 half-lifes (drug) before screening, whichever is longer

Other illness

• Documented history of homozygous familial hypercholesterolemia (HoFH);
• Poorly controlled thyroid disorder including hypothyroidism or hyperthyroidism;
• Planned cardiac surgery or revascularization during the study period;
• New York Heart Association (NYHA) Class III-IV heart failure;
• Poorly controlled hypertension (SBP≥160 mmHg or DBP≥100 mmHg in a sitting position)
• History of any major drug allergy, including allergy to protein biologics;

Lab values

• Estimated glomerular filtration rate (eGFR)\<30 mL/min/1.73m2;
• Active liver disease or hepatic dysfunction, history of liver transplant, and/or ALT or AST \>2.5 × ULN at screening;
• Poorly controlled Type 1 or Type 2 diabetes mellitus defined as fasting blood glucose ≥11.0 mmol/L (200 mg/dL) and glycosylated hemoglobin (HbA1c) ≥ 9%;
• Unexplained creatine kinase (CK) \> 5 x ULN (retested once is needed if suspected to be related to excessive exercise or abnormal activity);
• HIV, Treponema pallidum, or HCV antibody test positive, or HBV-DNA \>ULN at screening;

Other

• Pregnant or lactating women;

• Provision of written and signed informed consent form prior to any study-specific procedure;
• Male or female participants ≥18 years of age at the screening visit;
• Body weight ≥ 40 kg and body mass index (BMI) ≥18 and ≤35 kg/m2;
• On a stable diet and lipid-lowering oral drugs (such as statins, ezetimibe or Hybutimibe, omega-3 compounds, fenofibrate, nicotinic acid, etc.) for at least 4 weeks prior to the first drug administration
• LDL-C≥1.8 mmol/L (70 mg/dL) and TG≤4.52 mmol/L (400 mg/dL) at screening for ASCVD patients or those at very (ultra)-high risk for ASCVD, including patients with HeFH; LDL-C ≥ 2.6 mmol/L (100 mg/dL) and TG ≤ 4.52 mmol/L (400 mg/dL) at screening for patients at high-risk for ASCVD including patients with HeFH;
• Patients on a PCSK9 mAb at a dose of 75 mg, 140 mg, or 150 mg Q2W must undergo a washout period of ≥6 weeks after the last dose; for those on 300 mg or 420 mg Q4W, the washout period is ≥10 weeks following last dose;
• Female of childbearing potential must have a negative pregnancy test at the last screening visit and consent to use highly effective contraceptives during the trial and 3 months after the last dose of investigational drug.