Study of ARO-ANG3 in Participants With Homozygous Familial Hypercholesterolemia (HOFH)

Participants with documented homozygous familial hypercholesterolemia (HoFH) who have provided informed consent will receive 2 open-label doses of ARO-ANG3 and be evaluated for safety and efficacy parameters through 36 weeks. Participants who complete the first 36 week treatment period may opt to continue in an additional 24-month extension period during which they will receive up to 8 doses open-label doses of ARO-ANG3.

Inclusion Criteria: * Fasting LDL-C \>100 mg/dL at Screening * Weight of ≥ 40 kg and body mass index ≥ 18.5 and ≤ 40 kg/m2 * Diagnosis of HoFH based on a supportive genetic test or clinical diagnosis * 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 metastatic 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