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: July 9, 2014
Last verified: July 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
Biological: evolocumab (AMG 145)
Other: 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)
Biological: evolocumab (AMG 145)
Dose 1 every 4 weeks
Experimental: Group 2
evolocumab (AMG 145)
Biological: evolocumab (AMG 145)
Dose 2 every 4 weeks
Placebo Comparator: PLACEBO
PLACEBO
Other: 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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: July 9, 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 August 01, 2014