Inclusion Criteria:  Fasting LDL-C >100 mg/dL at Screening Weight of ≥ 30 kg and body mass index ≥ 16 and ≤ 40 kg/m2 Diagnosis of HoFH based on a supportive genetic test On stable maximally tolerated lipid lowering therapy Willing to abide by stable low-fat, low-cholesterol, heart-healthy diet for at least 4 weeks prior to Day 1 Participants of childbearing potential (males & females) must agree to use highly-effective contraception during the study and for at least 24 weeks from the last dose of study medication. Women of childbearing potential must have a negative pregnancy test and cannot be breastfeeding Women of childbearing potential on hormonal contraceptives must be stable on the medications for ≥ 2 menstrual cycles prior to Day 1 Willing to provide written informed consent and to comply with study requirements  Exclusion Criteria:  Current use or use within 365 days from Day 1 of any hepatocyte targeted small interfering RNA oligonucleotides (siRNA) or antisense oligonucleoside molecule Use of evinacumab (some exceptions apply) Fasting TG > 300 mg/dL at Screening Presence of any clinically significant uncontrolled endocrine disease known to influence serum lipids or lipoproteins Newly diagnosed (within 3 months prior to informed consent) or poorly controlled diabetes (Hemoglobin A1c > 9%) Use of systemic corticosteroids (some exceptions apply) Symptoms of myocardial ischemia or severe left ventricular dysfunction History of malignancy within 3 years of Day 1 (some exceptions apply) Planned cardiac procedure/surgery such as coronary artery bypass graft (CABG) surgery, percutaneous coronary intervention (PCI), carotid surgery or stenting, or carotid revascularization  Note: additional inclusion/exclusion criteria may apply per protocol