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

Phase 2

Completed

• Conditions: Hypercholesterolemia, Familial
• Interventions: Biological: Placebo; Biological: Evolocumab

• Registration Number: NCT01375751
• Lead Sponsor: Amgen

Brief Summary

The primary objective of this study was to evaluate the effect of 12 weeks of subcutaneous evolocumab (AMG 145), compared with placebo, on percent change from baseline in LDL-C in adults with heterozygous familial hypercholesterolemia (HeFH).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-06-16
• Study First Submitted QC: 2011-06-16
• Study First Posted: 2011-06-17
• Study Start: 2011-08-02
• Primary Completion: 2012-05-16
• Study Completion: 2012-05-16
• Disposition First Submitted: 2013-04-02
• Disposition First Submitted QC: 2013-04-02
• Disposition First Posted: 2013-04-09
• Results First Submitted: 2015-08-28
• Results First Submitted QC: 2015-08-28
• Results First Posted: 2015-09-29
• Status Verified: 2022-11
• Last Update Submitted: 2022-11-10
• Last Update Posted: 2022-11-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 168

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Participants received placebo subcutaneous injection once every 4 weeks for 12 weeks.
Evolocumab 420 mg	Evolocumab	Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Evolocumab 350 mg	Evolocumab	Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.

Primary Outcome Measures

Name	Time	Method
Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12	Baseline and Week 12	LDL-C was measured using ultracentrifugation.

Secondary Outcome Measures

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