IBI306 Monotherapy in Non-Familial Hypercholesterolemia and Mixed Hyperlipidemia

Inclusion criteria

• Male or female, ≥18 and ≤75 years of age on the day of signing informed consent.
• Fasting LDL-C ≥ 2.6 mmol/L and < 4.9 mmol/L measured in a local laboratory at screening and randomization.
• Fasting triglyceride (TG) ≤ 5.64 mmol/L measured in a local laboratory at screening and randomization.
• According to the 2023 Chinese Guidelines for the Management of Blood Lipids, the 10-year risk of atherosclerotic cardiovascular disease is assessed as low or moderate (< 10%).
• Understand the study-related procedures and methods, and voluntarily participate in the study and sign the informed consent form.

Exclusion criteria

• History of any of the following medical or treatment conditions:

• Known allergies to the study drugs or their components, or severe allergic reactions to other antibody drugs.
• Previously diagnosed as ASCVD, including acute coronary syndrome, stable coronary heart disease, post-revascularization, ischemic cardiomyopathy, ischemic stroke, transient ischemic attack, peripheral atherosclerotic disease, etc.
• Confirmed or suspected familial hypercholesterolaemia according to UK Simon Broome criteria.
• History of acute or chronic heart failure with New York Heart Association (NYHA) class III or IV, or left ventricular ejection fraction < 40% within 3 months prior to screening.
• Previous diagnosis of severe arrhythmia, such as recurrent and symptomatic ventricular tachycardia, atrial fibrillation with rapid ventricular rate, or supraventricular tachycardia poorly controlled by medication, etc.
• Poorly controlled hypertension, defined as sitting systolic blood pressure (SBP) ≥ 160 mmHg or diastolic blood pressure (DBP) ≥ 100 mmHg at screening or randomization.
• Previous diagnosis of nephrotic syndrome, severe liver disease, Cushing's syndrome, and other diseases that significantly affect blood lipid levels.
• History of type 1 diabetes mellitus, or type 2 diabetes mellitus with one of the following: (1) glycosylated hemoglobin (HbA1c) ≥ 8.5% at screening; (2) severe hypoglycemia within 6 months prior to screening; (3) insulin injection ≥ 2 times per day prior to screening.
• History of malignancy within 5 years prior to screening.
• Treatment with a PCSK9 monoclonal antibody within 6 months prior to screening or treatment with inclisiran prior to screening.
• Participation in a clinical study of any medical device or other drug within 3 months prior to screening (except for screening failure), or less than 5 half-lives from the most recent dose of the investigational drug at screening.
• Treatment with systemic cyclosporine within 3 months prior to screening.
• Long-term continuous (≥ 7 days) or multiple (≥ 3 times) systemic glucocorticoid therapy within 3 months prior to screening (except for topical, intraocular, intranasal, inhaled, or intra-articular injection).
• Treatment with weight-loss drugs or bariatric surgery within 3 months prior to screening.
• History of drug or alcohol abuse prior to screening. Average weekly alcohol intake: more than 21 units for males and more than 14 units for females (1 unit = 360 mL of beer, or 150 mL of red wine, or 45 mL of distilled spirits/white wine).

• Paricipants whose laboratory test parameters meet any of the following criteria at screening or randomization:

• Estimated glomerular filtration rate ( eGFR) < 30 mL/min/1.73 m 2 using the MDRD formula.
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 × upper limit of normal (ULN), or total bilirubin > 1.5 × ULN.
• Creatine kinase (CK) > 3 × ULN.
• Hypothyroidism or hyperthyroidism, defined as thyroid-stimulating hormone (TSH) below the lower limit of normal or exceeding 1.5 times the ULN, respectively.
• Positive for hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibody (HBcAb) and HBV DNA copy number ≥ 1.0 × 10 3 /mL, or positive for hepatitis C antibody ( except for those who have received complete anti-hepatitis C treatment and whose HCV RNA is below the lower limit of detection ).
• Positive for human immunodeficiency virus (HIV) antibodies or syphilis-specific antibodies.

• Female participants of childbearing potential who did not use contraception within 4 weeks prior to screening, or male or female participants who did not agree to use contraception as specified in this protocol throughout the study and for 15 weeks after the last treatment.

• Female participants who are pregnant or lactating. 5. The investigator believes that the subject has poor compliance, or there are factors that may bring unacceptable safety risks or affect the study results.