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

Hypercholesterolemia, Familial Clinical Trial

— RUTHERFORD  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01375751
• Other study ID #: 20090158
• Status: Completed
• Phase: Phase 2
• Start date: August 2, 2011
• Est. completion date: May 16, 2012

Study information

• Verified date: November 2022
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 168
• Est. completion date: May 16, 2012
• Est. primary completion date: May 16, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Hypercholesterolemia
• Hypercholesterolemia, Familial
• Hyperlipoproteinemia Type II

Intervention

Biological:
• Evolocumab
Administered by subcutaneous injection
• Placebo
d by subcutaneous injection

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Absolute Change From Baseline in LDL-C at Week 12	LDL-C was measured using ultracentrifugation.	Baseline and Week 12
Secondary	Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (HDL-C) at Week 12		Baseline and Week 12
Secondary	Percent Change From Baseline in Apolipoprotein B at Week 12		Baseline and Week 12
Secondary	Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12		Baseline and Week 12
Secondary	Percent Change From Baseline in Apolipoprotein B /Apolipoprotein A-1 Ratio at Week 12		Baseline and Week 12

External Links

•   AmgenTrials clinical trials website