A Study to Evaluate the Safety, Efficacy of SYH2053 in Chinese Participants With Non-familial Hypercholesterolemia and Mixed Hyperlipidemia

Inclusion

• Age of 18 - 75 years (inclusive);
• Participants with primary hypercholesterolemia or mixed dyslipidemia who have maintained a low-fat diet for at least 4 weeks prior to screening. Additionally, meet one of the following criteria:

A stable dose of lipid-lowering therapy (statin or statin intolerance with other lipid-lowering therapy) ≥4 weeks, or no use of lipid-lowering therapy for ≥4 weeks;

• According to local laboratory results, low-density lipoprotein cholesterol (LDL-C) level ≥100 mg/dL(2.6 mmol/L) and fasting triglycerides ≤400 mg/dL (4.5 mmol/L);
• Participants must understand of the study protocol, including the nature of the intervention and potential adverse events, and must provide voluntary, written informed consent before enrollment;
• Participants are able to establish good communication with the investigator and complete the trial in accordance with the protocol.

Exclusion

• Participants with severe allergic diseases or an allergic constitution (allergies to three or more drugs or foods) or allergic to oligonucleotide drugs；
• History of treatment with PCSK9-targeted antibody therapies or PCSK9-targeted oligonucleotide therapies;
• History of malignancy within 5 years (excluding treated basal cell carcinoma of the skin), or presence of a suspected malignancy currently being evaluated by the investigator;
• Systolic blood pressure (SBP) > 180 mmHg or diastolic blood pressure (DBP) > 110 mmHg during the Screening Period or prior to Randomization (repeat measurement allowed once);
• History of severe cardiovascular or cerebrovascular disease (e.g., hypertensive encephalopathy, acute stroke, transient ischemic attack, acute myocardial infarction, severe arrhythmia, etc.) within 6 months prior to Screening or prior to Randomization; or presence of severe aortic or peripheral vascular disease; or presence of conditions requiring surgical intervention; history of major surgery within 6 months prior to Screening or prior to Randomization; or plans for major surgery during the study period;
• History of heart failure with NYHA Class III-IV, or LVEF < 40% at Screening Period;
• eGFR < 30 mL/min/1.73 m² at Screening Period;
• Presence of severe thyroid disease (except for subjects on a stable dose of thyroid hormone replacement therapy or anti-thyroid medication for at least 6 months prior to Screening or Randomization);
• Thyroid Stimulating Hormone (TSH) > 1.5 × ULN at Screening Period (a single repeat measurement is permitted within 1 week);
• Creatine Kinase(CK) > 3 × ULN at Screening Period (a single repeat measurement is permitted within 1 week);
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 × ULN at Screening Period (a single repeat measurement is permitted within 1 week); or any one of Total Bilirubin (TBIL), gamma-glutamyl transferase (GGT), or alkaline phosphatase (ALP) > 1.5 × ULN (a single repeat measurement is permitted within 1 week);
• Prolonged QT/QTcF interval at Screening Period or prior to Randomization (QTcF > 450 ms for males, > 470 ms for females)
• Positive result for any one of hepatitis B surface antigen (HBsAg), Hepatitis C virus (HCV) antibody, syphilis antibody, or Human Immunodeficiency Virus (HIV) antibody;
• HbA1c > 8.5% at screening Period; or unstable anti-diabetic treatment within 3 months prior to Screening for patients with Type 2 diabetes;
• History of drug abuse within 5 years, including the recurrent use of dependence-producing drugs or substances unrelated to medical purposes in large quantities, including addictive and habituating drugs that cause physical and psychological dependence;
• History of alcohol abuse within 1 year (defined as consuming more than 14 units of alcohol per week [1 unit = 360 mL of beer with 5% alcohol content, or 45 mL of spirits with 40% alcohol content, or 150 mL of wine with 12% alcohol content]);
• Body weight change (gain or loss) ≥ 10% within 3 months prior to Screening;
• Participation in any other clinical trial involving the administration of an investigational drug within 3 months prior to Screening or within 5 half-lives of the other investigational drug (whichever is longer), or plans to participate in any other clinical trial during the study period;
• Any condition that, in the Investigator's opinion, may interfere with the conduct of the study, including but not limited to: a. presence of any disease within 6 months prior to Screening through the study period that may interfere with study results; b. any other reason that would prevent the subject from completing the study or that makes them inappropriate for inclusion;
• Pregnant or lactating women; or women of childbearing potential and male participants who plan to father a child (including sperm or egg donation) during the study period and/or who refuse to use effective contraceptive methods.