Reduction of Low-Density Lipoprotein Cholesterol (LDL-C) With PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder Study (RUTHERFORD)

• Absolute Change From Baseline in LDL-C at Week 12 [ Time Frame: Baseline and Week 12 ]
  LDL-C was measured using ultracentrifugation.
• Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (HDL-C) at Week 12 [ Time Frame: Baseline and Week 12 ]
• Percent Change From Baseline in Apolipoprotein B at Week 12 [ Time Frame: Baseline and Week 12 ]
• Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12 [ Time Frame: Baseline and Week 12 ]
• Percent Change From Baseline in Apolipoprotein B /Apolipoprotein A-1 Ratio at Week 12 [ Time Frame: Baseline and Week 12 ]

• Absolute change from baseline in LDL-C at week 12 [ Time Frame: 12 weeks ]
• Percent change from baseline in non-HDL-C at week 12 [ Time Frame: 12 weeks ]
• Percent change from baseline in ApoB at week 12 [ Time Frame: 12 weeks ]
• Percent change from baseline in the total cholesterol/HDL-C at week 12 [ Time Frame: 12 weeks ]
• Percent change from baseline in ApoB/ApoA1 ratio at week 12 [ Time Frame: 12 weeks ]

• Biological: Evolocumab
  Administered by subcutaneous injection
  Other Names:

  • AMG 145
  • Repatha
• Biological: Placebo
  d by subcutaneous injection

• Placebo Comparator: Placebo
  Participants received placebo subcutaneous injection once every 4 weeks for 12 weeks.
  Intervention: Biological: Placebo
• Experimental: Evolocumab 350 mg
  Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
  Intervention: Biological: Evolocumab
• Experimental: Evolocumab 420 mg
  Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
  Intervention: Biological: Evolocumab

Inclusion Criteria:

• Male or female ≥ 18 to ≤ 75 years of age
• Diagnosis of heterozygous familial hypercholesterolemia by having met the diagnostic criteria outlined by the Simon Broome Register Group (Scientific Steering Committee 1991)
• On an approved statin, with or without ezetimibe, with stable dose(s) for at least 4 weeks
• Fasting Low-Density Lipoprotein Cholesterol (LDL-C) ≥ 100 mg/dL
• Fasting triglycerides ≤ 400 mg/dL

Exclusion Criteria:

• Homozygous familial hypercholesterolemia
• Low-Density Lipoprotein (LDL) or plasma apheresis within 12 months prior to randomization
• New York Heart Association (NYHA) III or IV heart failure, or known left ventricular ejection fraction < 30%
• Uncontrolled cardiac arrhythmia
• Myocardial infarction, unstable angina, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) or stroke within 3 months prior to randomization
• Type 1 diabetes; newly diagnosed or poorly controlled type 2 diabetes (HbA1c > 8.5%)
• Uncontrolled hypertension