Clinical trial NCT01375751: Reduction of Low-Density Lipoprotein Cholesterol (LDL-C) With PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder Study
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hypercholesterolemia, Familial
Keywords: Heterozygous Familial Hypercholesterolemia
Proprotein convertase subtilisin/kexin type 9 (PCSK9)
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2011-06-17
Enrollment: 168
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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

Primary outcomes:
measure: Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12
timeFrame: Baseline and Week 12
Secondary outcomes:
measure: Absolute Change From Baseline in LDL-C at Week 12
timeFrame: Baseline and Week 12
measure: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (HDL-C) at Week 12
timeFrame: Baseline and Week 12
measure: Percent Change From Baseline in Apolipoprotein B at Week 12
timeFrame: Baseline and Week 12
measure: Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12
timeFrame: Baseline and Week 12
measure: Percent Change From Baseline in Apolipoprotein B /Apolipoprotein A-1 Ratio at Week 12
timeFrame: Baseline and Week 12
Other outcomes:
Locations:
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Raal F, Scott R, Somaratne R, Bridges I, Li G, Wasserman SM, Stein EA. Low-density lipoprotein cholesterol-lowering effects of AMG 145, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 serine protease in patients with heterozygous familial hypercholesterolemia: the Reduction of LDL-C with PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder (RUTHERFORD) randomized trial. Circulation. 2012 Nov 13;126(20):2408-17. doi: 10.1161/CIRCULATIONAHA.112.144055. Epub 2012 Nov 5.