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

Study Description

Go to 

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

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

Go to 

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

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

Go to 

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

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

Go to 

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

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

Go to 

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

Ages Eligible for Study:	18 Years to 80 Years (Adult, Older Adult)
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

Go to 

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

  Show 39 Study Locations

Sponsors and Collaborators

Amgen

Investigators

Study Director:	MD	Amgen

More Information

Go to 

Top of Page 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