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

Amgen

Status and phase: Completed; Phase 2

Conditions: Hypercholesterolemia, Familial

Treatments: Biological: Evolocumab; Biological: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01375751

20090158

Details and patient eligibility

About

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).

Enrollment: 168 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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168 participants in 3 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Participants received placebo subcutaneous injection once every 4 weeks for 12 weeks.

Treatment:

Biological: Placebo

Evolocumab 350 mg

Experimental group

Description:

Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.

Treatment:

Biological: Evolocumab

Evolocumab 420 mg

Experimental group

Description:

Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.

Treatment:

Biological: Evolocumab