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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT01375751
First received: June 16, 2011
Last updated: January 24, 2014
Last verified: January 2014
  Purpose

The primary hypothesis is that a dose of evolocumab (AMG 145) every-4-weeks (Q4W) subcutaneous (SC) will be well tolerated and will result in greater lowering of Low-Density Lipoprotein Cholesterol (LDL-C) at week 12 than placebo in subjects with heterozygous familial hypercholesterolemia


Condition Intervention Phase
Hypercholesterolemia, Familial
Drug: evolocumab (AMG 145)
Drug: PLACEBO
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate Tolerability and Efficacy of AMG 145 on Low-Density Lipoprotein Cholesterol (LDL-C) in Subject With Heterozygous Familial Hypercholesterolemia

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • The percent change from baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at week 12 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Absolute change from baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at week 12 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Percent change from baseline in non-High Density Lipoprotein Cholesterol (HDL-C) at week 12 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Percent change from baseline in Apolipoprotein B (ApoB) at week 12 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Percent change from baseline in the total cholesterol/High Density Lipoprotein Cholesterol (HDL-C) at week 12 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Percent change from baseline in Apolipoprotein B (ApoB)/Apolipoprotein A-1 (ApoA1) ratio at week 12 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Enrollment: 168
Study Start Date: July 2011
Study Completion Date: July 2012
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1
evolocumab (AMG 145)
Drug: evolocumab (AMG 145)
Dose 1 every 4 weeks
Experimental: Group 2
evolocumab (AMG 145)
Drug: evolocumab (AMG 145)
Dose 2 every 4 weeks
Placebo Comparator: PLACEBO
PLACEBO
Drug: PLACEBO
Every 4 weeks

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01375751

Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
No publications provided by Amgen

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01375751     History of Changes
Other Study ID Numbers: 20090158
Study First Received: June 16, 2011
Last Updated: January 24, 2014
Health Authority: Hong Kong: Department of Health
Netherlands:Centrale Commissie Mensgebonden Onderzoek (CCMO)
Norway: Norwegian Medicines Agency
Singapore: Health Science Authority
South Africa: Medicines Control Council
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Sweden: Medical Products Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration
Canada: Health Canada
Germany: Paul_Ehrlich-Institut Bundesamt fur Sera und Impfstoffe

Keywords provided by Amgen:
Heterozygous Familial Hypercholesterolemia

Additional relevant MeSH terms:
Hypercholesterolemia
Hyperlipoproteinemia Type II
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Hyperlipoproteinemias

ClinicalTrials.gov processed this record on April 15, 2014