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

Study Overview
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Brief Summary
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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).

Official Title
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A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate Tolerability and Efficacy of AMG 145 on LDL-C in Subject With Heterozygous Familial Hypercholesterolemia

Conditions
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Hypercholesterolemia, Familial

Intervention / Treatment
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* Biological: Evolocumab
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants received placebo subcutaneous injection once every 4 weeks for 12 weeks. | Biological: Placebo<br>* d by subcutaneous injection<br>|
| Experimental: Evolocumab 350 mg<br>Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. | Biological: Evolocumab<br>* Administered by subcutaneous injection<br>* Other names: Repatha;|
| Experimental: Evolocumab 420 mg<br>Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. | Biological: Evolocumab<br>* Administered by subcutaneous injection<br>* Other names: Repatha;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12 | LDL-C was measured using ultracentrifugation. | Baseline and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change From Baseline in LDL-C at Week 12 | LDL-C was measured using ultracentrifugation. | 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 Apolipoprotein B 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heterozygous Familial Hypercholesterolemia, Proprotein convertase subtilisin/kexin type 9 (PCSK9)