Reduction of LDL-C With PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder Study-2 - Full Text View

Purpose

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	Intervention	Phase
Hyperlipidemia	Biological: Evolocumab Drug: Placebo	Phase 3


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 Safety, Tolerability and Efficacy of AMG 145 on LDL-C in Subjects With Heterozygous Familial Hypercholesterolemia

Resource links provided by NLM:

Genetics Home Reference related topics: Chanarin-Dorfman syndrome cholesteryl ester storage disease hypercholesterolemia

MedlinePlus related topics: Cholesterol

Drug Information available for: Evolocumab

Genetic and Rare Diseases Information Center resources: Hyperlipoproteinemia Type 2

U.S. FDA Resources

Further study details as provided by Amgen:

Primary Outcome Measures:

Percent Change From Baseline in LDL-C at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ] [ Designated as safety issue: No ]
Change From Baseline in LDL-C at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
Percentage of Participants With LDL-C < 70 mg/dL (1.8 mmol/L) at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
Percent Change From Baseline in Non-HDL-C at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ] [ Designated as safety issue: No ]
Percent Change From Baseline in Apolipoprotein B at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
Percent Change From Baseline in Lipoprotein (a) at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ] [ Designated as safety issue: No ]
Percent Change From Baseline in Lipoprotein (a) at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ] [ Designated as safety issue: No ]
Percent Change From Baseline in Triglycerides at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
Percent Change From Baseline in HDL-C at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ] [ Designated as safety issue: No ]
Percent Change From Baseline in HDL-C at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
Percent Change From Baseline in VLDL-C at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]


Enrollment:	331
Study Start Date:	February 2013
Study Completion Date:	December 2013
Primary Completion Date:	November 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

Eligibility


Ages Eligible for Study:	18 Years to 80 Years (Adult, Senior)
Genders Eligible for Study:	Both
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

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: NCT01763918

Show 39 Study Locations

Sponsors and Collaborators

Amgen

Investigators


Study Director:	MD	Amgen

More Information

Additional Information:

AmgenTrials clinical trials website This link exits the ClinicalTrials.gov site

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
Study First Received:	January 7, 2013
Results First Received:	September 2, 2015
Last Updated:	November 18, 2015
Health Authority:	South Africa: Medicines Control Council United States: Food and Drug Administration Australia: Department of Health and Ageing Therapeutic Goods Administration France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) Germany: Paul-Ehrlich-Institut Netherlands: The Central Committee on Research Involving Human Subjects (CCMO) New Zealand: Medsafe Norway: Norwegian Medicines Agency Sweden: Medical Products Agency Switzerland: Swissmedic United Kingdom: Medicines and Healthcare Products Regulatory Agency Hong Kong: Department of Health Canada: Health Canada Spain: Agencia Española de Medicamentos y Productos Sanitarios

Keywords provided by Amgen:


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

Additional relevant MeSH terms:


Hypercholesterolemia Hyperlipidemias Hyperlipoproteinemia Type II Dyslipidemias Lipid Metabolism Disorders	Metabolic Diseases Lipid Metabolism, Inborn Errors Metabolism, Inborn Errors Genetic Diseases, Inborn Hyperlipoproteinemias

ClinicalTrials.gov processed this record on September 27, 2016

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