Inclusion Criteria:
1. Age ≥18 years old, male or female, and weight ≥40 kg.
2. Genetic diagnosis or clinical diagnosis of HoFH.
3. Receiving stable and tolerable lipid-lowering treatment or other drugs for chronic disease treatment for certain periods before the study, and maintaining the stable -treatments throughout the study.
4. Fasting serum LDL-C ≥2.6 mmol/L.
5. Fasting TG during screening is ≤5.6 mmol/L
6. BMI\< 40 kg/m ² during screening
7. Understand the study procedures, voluntarily participate, and sign the informed consent form.
Exclusion Criteria:
1. The genetic diagnosis was for heterozygous familial hypercholesterolemia;
2. During the screening process, the participant has uncontrolled other diseases that affect blood lipids or lipoproteins (such as nephrotic syndrome, severe liver diseases, glycogen storage disease, systemic lupus erythematosus, Cushing's syndrome, etc.) that the researchers believed would interfere with the accurate assessment of the study validity;
3. The participant has received or is receiving monoclonal antibodies targeting ANGPTL3 within 5 months or 5 half-lives (whichever is longer) before the LDL-C test during the screening period;
4. Within 12 months before the LDL-C test during the screening period, use of any ASO or siRNA type drugs;
5. Those who used any of the following treatments within the specified time limit before the LDL-C test: 1) mipomersen (within 5 months); 2) bepatide acid (within 4 weeks); 3) lipid purification or plasma exchange (within 8 weeks); 4) liver transplantation or CRISPR-based gene editing treatment (at any time);
6. During the screening period, within 5 months or 5 half-lives (whichever is longer) prior to the LDL-C test, the subject had received significant medications other than lipid-lowering drugs that affected LDL-C levels (such as oral or intravenous glucocorticoids, tacrolimus, cyclosporine, sirolimus, estrogens, vitamin A derivatives, antidepressants, etc.);
7. At the time of screening, the subject was using medications for thyroid disorders and the use of thyroid disorder medications was stable for less than 12 weeks before the LDL-C test;
8. History of allergic or suspected allergic reactions to oligonucleotide drugs or excipients of investigational drugs;
9. History of having a serious adverse cardiovascular event within 180 days before randomization (such as myocardial infarction, stroke or cerebrovascular event, unstable angina pectoris, deterioration of heart failure or hospitalization);
10. History of having uncontrolled (after drug or ablation therapy) or severe arrhythmias (such as atrial fibrillation with rapid ventricular rate, recurrent or persistent supraventricular or ventricular tachycardia) within 180 days before randomization;
11. History of having NYHA class Ⅲ-Ⅳ grade heart failure or left ventricular ejection fraction \<30% within 1 year before randomization or at the time of screening;
12. History of having type 1 diabetes at the time of screening, or had type 2 diabetes and was using hypoglycemic drugs, and the use of hypoglycemic drugs was stable for less than 12 weeks before the LDL-C test.
13. History of malignancy (except for cured skin basal cell cancer, etc.) or potential malignancy within the previous 5 years before randomization or at the time of screening;
14. Major surgery (including CABG, etc.) was performed within 180 days before randomization or was planned to be performed during the study period;
15. History of drug abuse or alcohol abuse within 1 year before randomization;
16. Within 90 days before LDL-C testing during the screening period or within 5 half-lives (whichever is longer), the participant has received or plans to receive other clinical research treatments (drugs or devices) during the study period;
17. During the screening period, the participant met any of the following criteria:
SBP ≥ 160 mmHg, or DBP ≥ 100 mmHg (untreated or after drug stabilization treatment); ALT or AST \> 3.0 × ULN, or total bilirubin \> 1.5 × ULN; CK \> 2.5 × ULN; QTcF interval: male \> 450 ms, female \> 470 ms; eGFR \< 30 mL/min/1.73 m2 (CKD-EPI formula, see Appendix 13.6); HBsAg positive and HBV DNA positive; or HCV antibody positive and HCV RNA positive; or positive for HIV antibody, anti-Neisseria meningitidis antibody; TSH \< LLN, or TSH \> 1.5 ULN; HbA1c \> 9%;
18. Female participants with reproductive capacity who were in pregnancy or lactation at the time of screening, or had a positive pregnancy test result before randomization; or male and female participants with reproductive capacity who had a fertility plan (including sperm donation, egg donation) and/or were unable to take effective contraceptive measures during the study period until after the end of treatment;
19. Other situations considered by the investigator as not suitable for participating in this trial (including poor compliance, etc.).
