A Phase II Study to Evaluate the Safety and Efficacy of SAL003 Combined With Atorvastatin in Hypercholesterolemia and Mixed Dyslipidemia

Prior treatment

• Route 1: The medication compliance of atorvastatin during the induction period is less than 80% or more than 120%; Route 2: The medication compliance of atorvastatin within 28 days before screening is less than 80% or more than 120%;
• Within 3 months before screening, there is heart failure (NYHA cardiac function classification of grade III and IV), acute coronary syndrome, percutaneous coronary intervention, or other serious heart diseases \[such as cardiogenic shock, grade II-III atrioventricular block, bradycardia (heart rate \< 50 beats/minute), other serious arrhythmias, etc.\];
• Within 3 months before screening, there is a serious cerebrovascular disease (hypertensive encephalopathy, cerebral vascular injury, stroke, transient ischemic attack, etc.), or there is a serious aortic or peripheral vascular lesion, or there are indications for surgical intervention;
• Within 3 months before screening, there is a major surgical history or plans to undergo major surgery during the study period;
• Within 3 months before screening, blood donation or significant blood loss (\> 400 mL), or those diagnosed with insufficient blood volume;
• Within 30 days before the administration of the study drug, use of any known substances that can affect lipid metabolism, tonics (such as fish oil \> 1000 mg/day, drugs containing red yeast rice components or health supplements), or other cholesterol-lowering drugs other than statins;
• Within 3 months before screening, participated in other drug or device clinical trials, or within 6 months before screening received any treatment targeting the proprotein convertase subtilisin/kexin type 9 (PCSK9) target;
• Within 6 months before screening had a history of drug abuse or alcoholism (14 units of alcohol per week: 1 unit = 285 mL of beer, or 25 mL of spirits, or 100 mL of wine);

Other illness

• Suffering from homozygous familial hypercholesterolemia (HoFH); Other diseases that may cause secondary increase of LDL-C: Cushing's syndrome, nephrotic syndrome, myeloma, glycogen storage disease, systemic lupus erythematosus, acute intermittent porphyria;
• Patients with poorly controlled hypertension (SBP ≥ 160 mm Hg or DBP ≥ 100 mm Hg);
• Active malignant tumors, or patients with a history of malignant tumors within 5 years before screening (excluding skin basal cell carcinoma or cervical carcinoma in situ);
• Patients known to be allergic to the test drug or any component of the test drug, or who have had a severe allergic reaction to other antibody-based drugs;
• Patients with a history of organ transplantation;

Lab values

• Diabetic patients with the following conditions known: 1) Type 1 diabetic patients; 2) Type 2 diabetic patients with poor blood sugar control (HbA1c \> 8.0%);
• Patients with active viral hepatitis (including hepatitis B and hepatitis C), other severe liver diseases, or liver dysfunction (ALT or AST \> 2.5 times the upper limit of normal, TBIL \> 2 times the upper limit of normal);
• Glomerular filtration rate (eGFR) \< 30 ml/min/1.73m2 during the screening period;
• Female subjects during the screening period or during the trial are breastfeeding or have a positive serum pregnancy result;

Other

• Patients with abnormal thyroid function (thyroid stimulating hormone TSH exceeds the normal range of the center);
• CK \> 3 times the upper limit of normal during the screening period;
• Positive for AIDS or syphilis tests;
• The subject or the subject's spouse or partner has a pregnancy plan or refuses to adopt an acceptable effective contraceptive method from the time of signing the informed consent form to the end of the last administration;
• The subject and his/her spouse or partner have a pregnancy plan or refuse to adopt an acceptable effective contraceptive method from the time of signing the informed consent form to the end of the last administration within 6 months;
• Patients considered not suitable for participating in the clinical trial by the investigator.

• Subjects aged 18 to 75 years.
• Diagnosis of hypercholesterolemia and/or mixed dyslipidemia per the 2016 Chinese guidelines.
• On a stable statin regimen as defined by the two pathways:
  • Pathway 1: On other statins or irregular atorvastatin, willing to switch to/stabilize on atorvastatin.
  • Pathway 2: On stable, regular atorvastatin (Lipitor) for ≥4 weeks.
• Fasting LDL-C must be above target:
  • With ASCVD history: ≥1.8 mmol/L (70 mg/dL)
  • Without ASCVD history: ≥2.6 mmol/L (100 mg/dL)
• Fasting triglycerides (TG) ≤ 5.6 mmol/L (500 mg/dL) at screening.
• Provide signed informed consent.