Reduction of LDL-C With PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder Study-2 (RUTHERFORD-2)

Study Description

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Brief Summary:

The primary objective was to evaluate the effect of 12 weeks of evolocumab subcutaneously once every 2 weeks (Q2W) and once monthly (QM), compared with placebo, on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in adults with heterozygous familial hypercholesterolemia (HeFH).

Condition or disease	Intervention/treatment	Phase
Hyperlipidemia	Biological: Evolocumab; Drug: Placebo	Phase 3

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	331 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate Safety, Tolerability and Efficacy of AMG 145 on LDL-C in Subjects With Heterozygous Familial Hypercholesterolemia
Study Start Date :	February 2013
Actual Primary Completion Date :	November 2013

Arms and Interventions

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Arm	Intervention/treatment
Placebo Comparator: Placebo Q2W; Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.	Drug: Placebo; Administered by subcutaneous injection
Placebo Comparator: Placebo QM; Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.	Drug: Placebo; Administered by subcutaneous injection
Experimental: Evolocumab Q2W; Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.	Biological: Evolocumab; Administered by subcutaneous injection; Other Names: AMG 145; Repatha
Experimental: Evolocumab QM; Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.	Biological: Evolocumab; Administered by subcutaneous injection; Other Names: AMG 145; Repatha

Outcome Measures

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Primary Outcome Measures :

1. Percent Change From Baseline in LDL-C at Week 12 [ Time Frame: Baseline and Week 12 ]
2. Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ]

Secondary Outcome Measures :

1. Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ]
2. Change From Baseline in LDL-C at Week 12 [ Time Frame: Baseline and Week 12 ]
3. Percentage of Participants With Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL (1.8 mmol/L) [ Time Frame: Weeks 10 and 12 ]
4. Percentage of Participants With LDL-C < 70 mg/dL (1.8 mmol/L) at Week 12 [ Time Frame: Week 12 ]
5. Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ]
6. Percent Change From Baseline in Non-HDL-C at Week 12 [ Time Frame: Baseline and Week 12 ]
7. Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ]
8. Percent Change From Baseline in Apolipoprotein B at Week 12 [ Time Frame: Baseline and Week 12 ]
9. Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ]
10. Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12 [ Time Frame: Baseline and Week 12 ]
11. Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ]
12. Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12 [ Time Frame: Baseline and Week 12 ]
13. Percent Change From Baseline in Lipoprotein (a) at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ]
14. Percent Change From Baseline in Lipoprotein (a) at Week 12 [ Time Frame: Baseline and Week 12 ]
15. Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ]
16. Percent Change From Baseline in Triglycerides at Week 12 [ Time Frame: Baseline and Week 12 ]
17. Percent Change From Baseline in HDL-C at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ]
18. Percent Change From Baseline in HDL-C at Week 12 [ Time Frame: Baseline and Week 12 ]
19. Percent Change From Baseline in Very Low-Density Lipoprotein Cholesterol (VLDL-C) at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ]
20. Percent Change From Baseline in VLDL-C at Week 12 [ Time Frame: Baseline and Week 12 ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 80 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Male or female ≥ 18 to ≤ 80 years of age
• Diagnosis of heterozygous familial hypercholesterolemia
• On a stable dose of an approved statin and lipid regulating medication
• Fasting LDL-C ≥ 100 mg/dL (2.6 mmol/L)
• Fasting triglycerides ≤ 400 mg/dL (4.5 mmol/L)

Exclusion Criteria:

• Homozygous familial hypercholesterolemia
• LDL or plasma apheresis
• New York Heart Association (NYHA) III or IV heart failure
• Uncontrolled cardiac arrhythmia
• Uncontrolled hypertension
• Type 1 diabetes, poorly controlled type 2 diabetes
• Uncontrolled hypothyroidism or hyperthyroidism

Contacts and Locations

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  Show 39 Study Locations

Sponsors and Collaborators

Amgen

Investigators

Study Director:	MD	Amgen

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

AmgenTrials clinical trials website 

Publications:

Raal FJ, Stein EA, Dufour R, Turner T, Civeira F, Burgess L, Langslet G, Scott R, Olsson AG, Sullivan D, Hovingh GK, Cariou B, Gouni-Berthold I, Somaratne R, Bridges I, Scott R, Wasserman SM, Gaudet D; RUTHERFORD-2 Investigators. PCSK9 inhibition with evolocumab (AMG 145) in heterozygous familial hypercholesterolaemia (RUTHERFORD-2): a randomised, double-blind, placebo-controlled trial. Lancet. 2015 Jan 24;385(9965):331-40. doi: 10.1016/S0140-6736(14)61399-4. Epub 2014 Oct 1.

Responsible Party:	Amgen
ClinicalTrials.gov Identifier:	NCT01763918 History of Changes
Other Study ID Numbers:	20110117; 2012-001365-32 ( EudraCT Number )
First Posted:	January 9, 2013
Results First Posted:	December 22, 2015
Last Update Posted:	March 15, 2017
Last Verified:	February 2017

Keywords provided by Amgen:

High cholesterol, Treatment for high cholesterol, Lowering cholesterol, Lowering high cholesterol, Hypercholesterolemia

Additional relevant MeSH terms:

Hypercholesterolemia; Hyperlipidemias; Hyperlipoproteinemias; Hyperlipoproteinemia Type II; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases	Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Antibodies, Monoclonal; Immunologic Factors; Physiological Effects of Drugs