Study of YKYY032 Injection in Adults With Hyperlipoproteinemia (a)

1. Before starting any research on a specific activity/program, a written informed consent must be provided;
2. For both males and females, the age at signing the Informed Consent Form (ICF) should be between 18 and 80 years;
3. The body mass index should be within the range of 18.5 - 40 kg/㎡ (including the boundary values);
4. During the pre-screening period (if any) and the screening period, the fasting Lp(a) measured in the central laboratory of the trial participants should be ≥ 150 nmol/L;

5. According to one of the following criteria, the participants are clinically diagnosed with ASCVD, including but not limited to:

   1. Having a history of coronary artery revascularization through percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG);
   2. Diagnosed with coronary artery disease, with or without a previous myocardial infarction;
   3. Diagnosed with atherosclerotic cerebrovascular disease;
   4. Diagnosed with peripheral artery disease; or without a clinical history of ASCVD, but meeting the definition of high-risk individuals for ASCVD in the overall risk assessment flowchart for ASCVD in Chinese lipid management guidelines (2023) (see Appendix 16.1 for the overall risk assessment flowchart for ASCVD in Chinese adults);

6. For the trial participants who receive the following drug treatments, their treatment plans must be stable for at least 4 weeks before signing the screening ICF, and are expected to remain stable until the end of the follow-up period after the last administration of the trial drug:

   1. Lipid-lowering drugs (statins, ezetimibe, PCSK9 inhibitors, niacin, fibrates, fish oil or other products containing ω-3 fatty acids, including over-the-counter drugs [OTC]);
   2. Testosterone, estrogen, anti-estrogen, progesterone, progestin, selective estrogen receptor modulators and growth hormone.
7. Female trial participants are not pregnant or breastfeeding; fertile female and male trial participants must have an acceptable contraceptive method from the time of signing the ICF until 12 months after the last administration of the trial drug (see Appendix 16.2 for the requirements for trial participants' contraception); males are not allowed to donate sperm, and females are not allowed to donate eggs;
8. They are willing to follow the research procedures stipulated in this protocol (including follow-up) and are willing to cooperate fully with the researchers.

Exclusion Criteria:

1. Clinical evidence of active liver disease or liver dysfunction in the past or currently exists, defined as AST or ALT ≥ 2 times the upper limit of normal (ULN) or total bilirubin (TBIL) ≥ 1.5 times the ULN at the screening period (except for participants diagnosed with Gilbert syndrome);
2. Estimated glomerular filtration rate (eGFR) calculated using the Chronic Kidney Disease - Epidemiology Collaboration (CKD-EPI) creatinine clearance formula is \< 60 mL/min/1.73 ㎡ during the screening period;
3. Any recent major cardiovascular event (ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction, unstable angina pectoris, coronary or peripheral artery revascularization, major cardiac surgery, stroke or transient ischemic attack, acute limb ischemia) or non-cardiac major surgery within 6 months before randomization;
4. Any planned cardiac surgery, PCI or carotid artery stenting procedure during the study period, or planned non-cardiac major surgery;
5. Moderate to severe heart failure (NYHA functional class III or IV at the screening period) or previously known left ventricular ejection fraction \< 50%;
6. Uncontrolled hypertension (systolic blood pressure [SBP] ≥ 160 mmHg or diastolic blood pressure [DBP] ≥ 100 mmHg);
7. Presence of uncontrolled arrhythmia within 3 months before randomization, defined as recurrent and symptomatic ventricular tachycardia, atrial fibrillation with rapid ventricular response, or drug-uncontrolled supraventricular tachycardia;
8. Any malignancy within 5 years before randomization (successfully treated non-melanoma skin cancer, cervical carcinoma in situ, breast duct carcinoma, or stage 1 prostate cancer excluded);
9. Any hereditary or other bleeding disorders;
10. Fasting triglycerides ≥ 500 mg/dL (5.65 mmol/L) at the screening period;
11. Fasting LDL-C ≥ 4.9 mmol/L (190 mg/dL) at the screening period;
12. Presence of type 1 diabetes or poorly controlled type 2 diabetes (defined as requiring hospitalization for ketoacidosis or hyperosmolar hyperglycemic state, or glycated hemoglobin [HbA1c] ≥ 8.5% at the screening period, or hospitalization due to poor glycemic control) within 3 months before randomization;
13. Uncontrolled hyperthyroidism or hypothyroidism (stable treatment with abnormal thyroid hormone or unrelieved clinical symptoms);
14. Any active infection or major hematological, renal, metabolic, gastrointestinal or endocrine dysfunction requiring systemic antiviral or antimicrobial treatment by the investigator's judgment before randomization;
15. Evidence of acute or chronic hepatitis B or hepatitis C at the screening period (positive for hepatitis B surface antigen [HBsAg]; or positive for hepatitis C antibody [HCV-Ab]), or human immunodeficiency virus (HIV) infection (positive for HIV antibody), or active syphilis infection (positive for Treponema pallidum antibody);
16. Any ASO, small interfering RNA (siRNA) treatment (such as Inclisiran sodium injection) or any experimental treatment targeting Lp(a) within 12 months before randomization;
17. Stable use of immunosuppressants, or stable use of corticosteroids (excluding topical/inhaled use) within 3 months before randomization (continuous use >14 days is considered stable use); or regular systemic corticosteroid use within 4 weeks before the first dose; or expected need for prednisone >20 mg/day or equivalent;
18. Currently receiving, or having received lipoprotein apheresis within 3 months before randomization, or planning to receive lipoprotein apheresis during the study;
19. Have homozygous familial hypercholesterolemia (HoFH) or have received lomitapide within 12 months prior to randomization;
20. Are known to be allergic to any component of YKYY032 injection, or have a history or current severe allergic reaction;
21. Have participated in or plan to participate in a drug clinical trial within 3 months prior to screening, or within the trial period (excluding non-interventional studies and those who only signed the ICF but did not receive study intervention);
22. Have had or currently have drug abuse or alcoholism (for men, an average weekly alcohol intake of more than 14 units, for women, more than 7 units [1 unit = 360 mL beer; or 150 mL wine; or 45 mL distilled spirits]);
23. Have received any known herbal medicine (including but not limited to: hawthorn, salvia miltiorrhiza), vitamin (including but not limited to: niacin), or supplement (including but not limited to: red yeast rice, omega-3 fatty acids) within 30 days prior to randomization, except for those who have been using lipid-lowering drugs stably for 4 weeks prior to screening (see item 6 of the inclusion criteria);
24. Have had or currently have any underlying disease or mental condition that the investigator considers may affect the safety of the study participants during the study, or interfere with the participation or completion of the study, or affect the interpretation of data.