Significant reduction in ANGPLT3 levels is expected to reduce plasma LDL-C and TG levels and may lead to the reduction of risk of coronary heart disease and cardiovascular events associated with hypertriglyceridemia and LDL-C in subjects with persistent dyslipidemia. In this clinical study, the efficacy and safety of VSA003, an RNAi-based therapeutic targeting ANGPTL3, will be evaluated in subjects with HoFH.

Inclusion Criteria:

• Male or female aged ≥ 12 years and weighing ≥ 40 kg at the time of ICF signature;
• Patients with HoFH who meet genetic or clinical diagnosis;
• Willing to follow a daily low-fat diet for the duration of the study;
• Receiving stable and tolerable lipid-lowering therapy prior to LDL-C testing during the screening period;
• Fasting LDL-C ≥ 2.6 mmol/L.

Exclusion Criteria:

• Have received or are receiving targeted ANGPTL3 treatment within 5 months or 5 half-lives, whichever is longer, prior to screening;
• Fasting TG ≥ 4.5 mmol/L at screening;
• Presence of uncontrolled endocrine disease affecting lipids or lipoproteins;
• Weight change of more than 10% in the 4 weeks prior to randomisation;
• Initiation of a new dietary plan or significant differences from previous dietary structure and habits within 4 weeks prior to screening;
• Women who are pregnant (including planned pregnancies) or breastfeeding;
• Refusal to limit alcohol consumption to moderate limits and below during the study period, specifically no more than 14 units per week;
• Uncontrolled hypertension (blood pressure > 160/100 mmHg at screening);
• New York Heart Association (NYHA) class IV heart failure or left ventricular ejection fraction <30% within 12 months prior to screening;
• History of major surgery within 12 weeks prior to baseline, or planning to undergo major surgery during the study;
• Known allergy to any component of the study drug.