A Study of HRS-5346 in Adult Participants With Elevated Lipoprotein(a) at High Risk for Cardiovascular Events

Inclusion Criteria:

1. Understanding the specific procedures of the trial, voluntarily participating inthis trial, and providing written informed consent;

2. Being at least 18 years of age on the day of signing the informed consent form;

3. Body Mass Index (BMI) within the range of 18.5 to 40 kg/m² (inclusive of boundaryvalues);

4. Participants must be at high risk of cardiovascular events, defined as individualsdiagnosed with Atherosclerotic Cardiovascular Disease (ASCVD) and those at high riskfor ASCVD.

5. Participants (including their partners) are willing to voluntarily use highlyeffective contraceptive measures from the time of signing the informed consent formuntil 6 months after the last administration of the study drug; female participantsmust have a negative blood pregnancy test and must not be breastfeeding;

6. Willing and able to comply with all the provisions of the protocol, includingdemonstrating the ability to adhere to study procedures prior to random assignment.

Exclusion Criteria:

• Medical History and Concomitant Medications

1. Occurrence of any of the following events within 3 months prior to screening, orbetween screening and randomization, or any other event deemed by the investigatorto indicate clinical instability: major cardiac or non-cardiac surgery, coronary,carotid, or peripheral artery revascularization, stroke or transient ischemicattack, myocardial infarction or unstable angina, acute limb ischemia;

2. Planned or anticipated cardiac, cerebrovascular, or peripheral artery surgery orcoronary revascularization or other major surgery after randomization;

3. History of hemorrhagic stroke or other significant bleeding events;

4. History of malignancy in any organ system (except well-treated basal cell carcinomaof the skin);

5. History of diseases that significantly affect lipid levels, such as nephroticsyndrome, severe liver disease, Cushing's syndrome, etc.;

6. Uncontrolled type 1 or type 2 diabetes within 6 months prior to screening (includingdiabetic ketoacidosis or hyperosmolar hyperglycemic state or HbA1c > 8.5% atscreening);

7. History of acute kidney injury within 12 months prior to screening;

8. Uncontrolled hyperthyroidism or hypothyroidism;

9. Active infection requiring systemic antiviral or antibiotic therapy prior torandomization;

10. New York Heart Association (NYHA) class III-IV heart function or most recent leftventricular ejection fraction (LVEF) < 30% at screening or prior to randomization;

11. Use of weight-loss medications or surgery leading to weight instability within 2months prior to screening;

12. Long-term continuous or repeated use of systemic corticosteroids within 3 monthsprior to screening (excluding local use, such as intra-articular, nasal, inhaled,topical, etc.; long-term continuous means ≥7 days; repeated means cumulative use ≥3times);

13. Lipoprotein apheresis treatment within 3 months prior to screening, or planned toundergo this treatment during the study;

14. Use of PCSK9 inhibitors within 12 months prior to screening;

15. Allergy to the active ingredient of HRS-5346 or any excipient. Laboratory and Other Tests

16. Uncontrolled hypertension at screening (sitting systolic blood pressure ≥160 mmHgand/or diastolic blood pressure ≥100 mmHg);

17. Severe renal insufficiency, defined as eGFR < 30 ml/min/1.73 m² (calculated usingthe CKD-EPI formula) at screening, or undergoing dialysis;

18. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) or γ-glutamyltransferase (GGT) more than 3 times the upper limit of normal (ULN), or totalbilirubin more than 2 times the ULN;

19. Positive test results for any of the following: human immunodeficiency virusantibody (HIV-Ab), hepatitis C virus antibody (HCV-Ab), Treponema pallidum antibody;positive hepatitis B virus surface antigen (HBsAg) with HBV-DNA ≥1000 copies/ml (or ≥200 IU/ml, if the lower limit of detection is higher than 1000 copies/ml or 200IU/ml, then HBV-DNA ≥ the lower limit of detection);

20. Creatine kinase (CK) more than 3 times the ULN;

21. Thyroid-stimulating hormone (TSH) below the lower limit of normal (LLN) or more than 1.5 times the ULN; Other Conditions

22. History of drug or alcohol abuse or dependence within the past 1 year;

23. Pregnant or breastfeeding women;

24. Participants in any drug or medical device clinical trial within 3 months prior toscreening (defined by the participant receiving the trial drug/device treatment), orwithin 5 half-lives of the trial drug prior to screening, whichever is longer;

25. Participants deemed by the investigator to have poor compliance or any factors thatmake them unsuitable for this trial, including but not limited to participationposing unacceptable risk to the participant or potentially interfering with studyresults.