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

A Phase Ⅱ Randomized, Parallel-group, Placebo-controlled, Active-controlled Trial to Assess the Efficacy, Safety of the SYH2053 Subcutaneous Injection in Participants With Primary Hypercholesterolemia or Mixed Dyslipidemia

The purpose of this study is to compare the effectiveness, safety of SYH2053 in Participants with primary hypercholesterolemia or mixed dyslipidemia.

A total of 156 Participants were actually enrolled

Inclusion

1. Age of 18 - 75 years (inclusive);

2. 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;

3. 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);

4. 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;

5. Participants are able to establish good communication with the investigator and complete the trial in accordance with the protocol.

Exclusion

1. Participants with severe allergic diseases or an allergic constitution (allergies to three or more drugs or foods) or allergic to oligonucleotide drugs；
2. History of treatment with PCSK9-targeted antibody therapies or PCSK9-targeted oligonucleotide therapies;
3. 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;
4. 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);
5. 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;
6. History of heart failure with NYHA Class III-IV, or LVEF < 40% at Screening Period;
7. eGFR < 30 mL/min/1.73 m² at Screening Period;
8. 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);
9. Thyroid Stimulating Hormone (TSH) > 1.5 × ULN at Screening Period (a single repeat measurement is permitted within 1 week);
10. Creatine Kinase(CK) > 3 × ULN at Screening Period (a single repeat measurement is permitted within 1 week);
11. 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);
12. Prolonged QT/QTcF interval at Screening Period or prior to Randomization (QTcF > 450 ms for males, > 470 ms for females)
13. Positive result for any one of hepatitis B surface antigen (HBsAg), Hepatitis C virus (HCV) antibody, syphilis antibody, or Human Immunodeficiency Virus (HIV) antibody;
14. HbA1c > 8.5% at screening Period; or unstable anti-diabetic treatment within 3 months prior to Screening for patients with Type 2 diabetes;
15. 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;
16. 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]);
17. Body weight change (gain or loss) ≥ 10% within 3 months prior to Screening;
18. 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;
19. 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;
20. 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.