Trial Evaluating PCSK9 Antibody in Subjects With LDL Receptor Abnormalities

2-part, Phase 2/3 Study to Assess the Safety, Tolerability and Efficacy of AMG 145 in Subjects With Homozygous Familial Hypercholesterolemia. Part A - Open-label, Single-arm, Multicenter Pilot Study to Evaluate Safety, Tolerability and Efficacy of AMG 145 in Subjects With Homozygous Familial Hypercholesterolemia. Part B - Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate Safety, Tolerability and Efficacy of AMG 145 in Subjects With Homozygous Familial Hypercholesterolemia

A study to determine the safety, tolerability, and efficacy of evolocumab (AMG 145) in patients with homozygous familial hypercholesterolemia (HoFH).

Study Masking:

Part A: Open Label Part B: Double Blind

Inclusion Criteria:

• Males and females ≥ 12 to ≤ 80 years of age
• Diagnosis of homozygous familial hypercholesterolemia
• Stable lipid-lowering therapies for at least 4 weeks
• LDL cholesterol ≥ 130 mg/dl (3.4 mmol/L)
• Triglyceride ≤ 400 mg/dL (4.5 mmol/L)
• Bodyweight of ≥ 40 kg at screening.

Exclusion Criteria:

• LDL or plasma apheresis within 8 weeks prior to randomization
• New York Heart Association (NYHA) class III or IV or last known left ventricular ejection fraction < 30%
• Myocardial infarction, unstable angina, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) or stroke within 3 months of randomization
• Planned cardiac surgery or revascularization
• Uncontrolled cardiac arrhythmia
• Uncontrolled hypertension