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

NCT01375751 | Completed Phase 2 Results DMC

• 1 other identifier: 20090158
• Study Type: interventional
• Target: 168
• Locations: 0 countries
• Sites: N/A

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).

Conditions

Hypercholesterolemia, Familial

Keywords

Heterozygous Familial Hypercholesterolemia; Proprotein convertase subtilisin/kexin type 9 (PCSK9)

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Absolute Change From Baseline in LDL-C 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 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

Study Arms (3)

Placebo

PLACEBO COMPARATOR

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

Biological: Placebo

Evolocumab 350 mg

EXPERIMENTAL

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

Biological: Evolocumab

Evolocumab 420 mg

EXPERIMENTAL

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

Biological: Evolocumab

Interventions

Evolocumab BIOLOGICAL

Administered by subcutaneous injection

Also known as: AMG 145, Repatha

Evolocumab 350 mg; Evolocumab 420 mg

Placebo BIOLOGICAL

d by subcutaneous injection

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Amgen: lead

Related 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.

  PMID: 23129602 BACKGROUND

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Hyperlipoproteinemia Type II; Hypercholesterolemia, Autosomal Dominant, 3

Interventions

evolocumab

Condition Hierarchy (Ancestors)

Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2011
• First Posted: June 17, 2011
• Study Start: August 2, 2011
• Primary Completion: May 16, 2012
• Study Completion: May 16, 2012
• Last Updated: November 15, 2022
• Results First Posted: September 29, 2015

Record last verified: 2022-11