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

Tracking Information
First Submitted Date ICMJE	June 16, 2011
First Posted Date ICMJE	June 17, 2011
Results First Submitted Date	August 28, 2015
Results First Posted Date	September 29, 2015
Last Update Posted Date	September 29, 2015
Study Start Date ICMJE	August 2011
Actual Primary Completion Date	May 2012 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: August 28, 2015)	Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12 [ Time Frame: Baseline and Week 12 ]; LDL-C was measured using ultracentrifugation.
Original Primary Outcome Measures ICMJE; (submitted: June 16, 2011)	The percent change from baseline in LDL-C at week 12 [ Time Frame: 12 weeks ]
Change History	Complete list of historical versions of study NCT01375751 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: August 28, 2015)	Absolute Change From Baseline in LDL-C at Week 12 [ Time Frame: Baseline and Week 12 ]LDL-C was measured using ultracentrifugation.; Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (HDL-C) at Week 12 [ Time Frame: Baseline and Week 12 ]; Percent Change From Baseline in Apolipoprotein B at Week 12 [ Time Frame: Baseline and Week 12 ]; Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12 [ Time Frame: Baseline and Week 12 ]; Percent Change From Baseline in Apolipoprotein B /Apolipoprotein A-1 Ratio at Week 12 [ Time Frame: Baseline and Week 12 ]
Original Secondary Outcome Measures ICMJE; (submitted: June 16, 2011)	Absolute change from baseline in LDL-C at week 12 [ Time Frame: 12 weeks ]; Percent change from baseline in non-HDL-C at week 12 [ Time Frame: 12 weeks ]; Percent change from baseline in ApoB at week 12 [ Time Frame: 12 weeks ]; Percent change from baseline in the total cholesterol/HDL-C at week 12 [ Time Frame: 12 weeks ]; Percent change from baseline in ApoB/ApoA1 ratio at week 12 [ Time Frame: 12 weeks ]
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Reduction of Low-Density Lipoprotein Cholesterol (LDL-C) With PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder Study
Official Title ICMJE	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
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).
Detailed Description	Not Provided
Study Type ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition ICMJE	Hypercholesterolemia, Familial
Intervention ICMJE	Biological: Evolocumab Administered by subcutaneous injection Other Names: AMG 145 Repatha; Biological: Placebo d by subcutaneous injection
Study Arms	Placebo Comparator: Placebo Participants received placebo subcutaneous injection once every 4 weeks for 12 weeks. Intervention: Biological: Placebo; Experimental: Evolocumab 350 mg Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. Intervention: Biological: Evolocumab; Experimental: Evolocumab 420 mg Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. Intervention: Biological: Evolocumab
Publications *	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.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: February 19, 2013)	168
Original Estimated Enrollment ICMJE; (submitted: June 16, 2011)	150
Actual Study Completion Date	May 2012
Actual Primary Completion Date	May 2012 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years to 75 Years (Adult, Older Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Not Provided
Removed Location Countries	Canada, Germany, Hong Kong, Netherlands, Norway, Singapore, South Africa, Spain, Sweden, United Kingdom, United States
Administrative Information
NCT Number ICMJE	NCT01375751
Other Study ID Numbers ICMJE	20090158
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Amgen
Study Sponsor ICMJE	Amgen
Collaborators ICMJE	Not Provided
Investigators ICMJE	Study Director: MD Amgen
PRS Account	Amgen
Verification Date	August 2015
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP