Back to resultsReduction of Low-Density Lipoprotein Cholesterol (LDL-C) With PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder Study (RUTHERFORD)
Primary Purpose
Hypercholesterolemia, Familial
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Evolocumab
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Hypercholesterolemia, Familial focused on measuring Heterozygous Familial Hypercholesterolemia, Proprotein convertase subtilisin/kexin type 9 (PCSK9)
Eligibility 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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Placebo Comparator
Experimental
Experimental
Arm Label
Placebo
Evolocumab 350 mg
Evolocumab 420 mg
Arm Description
Participants received placebo subcutaneous injection once every 4 weeks for 12 weeks.
Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Outcomes
Primary Outcome Measures
Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12
LDL-C was measured using ultracentrifugation.
Secondary Outcome Measures
Absolute Change From Baseline in LDL-C at Week 12
LDL-C was measured using ultracentrifugation.
Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (HDL-C) at Week 12
Percent Change From Baseline in Apolipoprotein B at Week 12
Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12
Percent Change From Baseline in Apolipoprotein B /Apolipoprotein A-1 Ratio at Week 12
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01375751
Brief Title
Reduction of Low-Density Lipoprotein Cholesterol (LDL-C) With PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder Study
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Completed
Study Start Date
August 2, 2011 (Actual)
Primary Completion Date
May 16, 2012 (Actual)
Study Completion Date
May 16, 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypercholesterolemia, Familial
Keywords
Heterozygous Familial Hypercholesterolemia, Proprotein convertase subtilisin/kexin type 9 (PCSK9)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
168 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants received placebo subcutaneous injection once every 4 weeks for 12 weeks.
Arm Title
Evolocumab 350 mg
Arm Type
Experimental
Arm Description
Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Arm Title
Evolocumab 420 mg
Arm Type
Experimental
Arm Description
Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Intervention Type
Biological
Intervention Name(s)
Evolocumab
Other Intervention Name(s)
AMG 145, Repatha
Intervention Description
Administered by subcutaneous injection
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
d by subcutaneous injection
Primary Outcome Measure Information:
Title
Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12
Description
LDL-C was measured using ultracentrifugation.
Time Frame
Baseline and Week 12
Secondary Outcome Measure Information:
Title
Absolute Change From Baseline in LDL-C at Week 12
Description
LDL-C was measured using ultracentrifugation.
Time Frame
Baseline and Week 12
Title
Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (HDL-C) at Week 12
Time Frame
Baseline and Week 12
Title
Percent Change From Baseline in Apolipoprotein B at Week 12
Time Frame
Baseline and Week 12
Title
Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12
Time Frame
Baseline and Week 12
Title
Percent Change From Baseline in Apolipoprotein B /Apolipoprotein A-1 Ratio at Week 12
Time Frame
Baseline and Week 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Amgen
Official's Role
Study Director
12. IPD Sharing Statement
Citations:
PubMed Identifier
23129602
Citation
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.
Results Reference
background
Links:
URL
http://www.amgentrials.com
Description
AmgenTrials clinical trials website
Learn more about this trial
Reduction of Low-Density Lipoprotein Cholesterol (LDL-C) With PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder Study
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