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

Purpose

The primary hypothesis is that dosing regimens of Evolocumab (AMG 145) will be well tolerated and will result in a greater reduction of Low Density Lipoprotein-Cholesterol (LDL-C) in subjects with heterozygous familial hypercholesterolemia.

Condition	Intervention	Phase
Hyperlipidemia	Biological: Evolocumab (AMG 145) Other: 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

Genetic and Rare Diseases Information Center resources: Hyperlipoproteinemia Type 2 Sphingolipidosis

U.S. FDA Resources

Further study details as provided by Amgen:

Primary Outcome Measures:

Mean percent change from baseline in low density lipoprotein-cholesterol [ Time Frame: 10 and 12 Weeks ] [ Designated as safety issue: No ]
Mean percent change from baseline in low density lipoprotein-cholesterol
Percent change from baseline in low density lipoprotein-cholesterol [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
Percent change from baseline in low density lipoprotein-cholesterol

Secondary Outcome Measures:

Mean change from baseline in low density lipoprotein-cholesterol [ Time Frame: 10 and 12 Weeks ] [ Designated as safety issue: No ]
Mean change from baseline in low density lipoprotein-cholesterol
Change from baseline in low density lipoprotein-cholesterol [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
Change from baseline in low density lipoprotein-cholesterol
Mean low density lipoprotein-cholesterol response (low density lipoprotein-cholesterol < 70 mg/dL [1.8 mmol/L]) [ Time Frame: 10 and 12 Weeks ] [ Designated as safety issue: No ]
Mean low density lipoprotein-cholesterol response (low density lipoprotein-cholesterol < 70 mg/dL [1.8 mmol/L])
Low density lipoprotein-cholesterol response (low density lipoprotein-cholesterol < 70 mg/dL [1.8 mmol/L]) [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
Low density lipoprotein-cholesterol response (low density lipoprotein-cholesterol < 70 mg/dL [1.8 mmol/L])
Mean percent change from baseline in non-high density lipoprotein-cholesterol [ Time Frame: 10 and 12 Weeks ] [ Designated as safety issue: No ]
Mean percent change from baseline non-high density lipoprotein-cholesterol
Percent change from baseline in non-high density lipoprotein-cholesterol [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
Percent change from baseline non-high density lipoprotein-cholesterol
Mean percent change from baseline in apolipoprotein B [ Time Frame: 10 and 12 Weeks ] [ Designated as safety issue: No ]
Mean percent change from baseline in apolipoprotein B
Percent change from baseline in apolipoprotein B [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
Percent change from baseline in apolipoprotein B
Mean percent change from baseline in the total cholesterol/high density lipoprotein-cholesterol ratio [ Time Frame: 10 and 12 Weeks ] [ Designated as safety issue: No ]
Mean percent change from baseline in the total cholesterol/high density lipoprotein-cholesterol ratio
Percent change from baseline in the total cholesterol/high density lipoprotein-cholesterol ratio [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
Percent change from baseline in the total cholesterol/high density lipoprotein-cholesterol ratio
Mean percent change from baseline in apolipoprotein B/apolipoprotein A1 ratio [ Time Frame: 10 and 12 Weeks ] [ Designated as safety issue: No ]
Mean percent change from baseline in apolipoprotein B/apolipoprotein A1 ratio
Percent change from baseline in apolipoprotein B/apolipoprotein A1 ratio [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
Percent change from baseline in apolipoprotein B/apolipoprotein A1 ratio
Mean percent change from baseline in lipoprotein (a) [ Time Frame: 10 and 12 Weeks ] [ Designated as safety issue: No ]
Mean percent change from baseline in lLipoprotein (a)
Percent change from baseline in lipoprotein (a) [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
Percent change from baseline in lipoprotein (a)
Mean percent change from baseline in triglycerides [ Time Frame: 10 and 12 Weeks ] [ Designated as safety issue: No ]
Mean percent change from baseline in triglycerides
Percent change from baseline in triglycerides [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
Percent change from baseline in triglycerides
Mean percent change from baseline in high density lipoprotein-cholesterol [ Time Frame: 10 and 12 Weeks ] [ Designated as safety issue: No ]
Mean percent change from baseline in high density lipoprotein-cholesterol
Percent change from baseline in high density lipoprotein-cholesterol [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
Percent change from baseline in high density lipoprotein-cholesterol
Mean percent change from baseline in very low-density lipoprotein cholesterol [ Time Frame: 10 and 12 Weeks ] [ Designated as safety issue: No ]
Mean percent change from baseline in very low-density lipoprotein cholesterol
Percent change from baseline in very low-density lipoprotein cholesterol [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
Percent change from baseline in very low-density lipoprotein cholesterol


Enrollment:	329
Study Start Date:	January 2013
Study Completion Date:	January 2014
Primary Completion Date:	December 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Arm 1 Dose 1 of subcutaneous Evolocumab (AMG 145) every 2 weeks	Biological: Evolocumab (AMG 145) Patients will receive Evolocumab (AMG 145) every 2 weeks or monthly
Experimental: Arm 2 Dose 2 of subcutaneous Evolocumab (AMG 145) monthly	Biological: Evolocumab (AMG 145) Patients will receive Evolocumab (AMG 145) every 2 weeks or monthly
Placebo Comparator: Arm 3 Dose 3 of subcutaneous placebo every 2 weeks	Other: Placebo Patients will receive placebo every 2 weeks or monthly. All patients at screening will participate in placebo-run in element of the trial.
Placebo Comparator: Arm 4 Dose 4 of subcutaneous placebo monthly	Other: Placebo Patients will receive placebo every 2 weeks or monthly. All patients at screening will participate in placebo-run in element of the trial.

Eligibility


Ages Eligible for Study:	18 Years to 80 Years
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
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

No publications provided by Amgen

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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
Study First Received:	January 7, 2013
Last Updated:	January 28, 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 Hyperlipoproteinemia Type II Dyslipidemias Genetic Diseases, Inborn Hyperlipidemias	Hyperlipoproteinemias Lipid Metabolism Disorders Lipid Metabolism, Inborn Errors Metabolic Diseases Metabolism, Inborn Errors

ClinicalTrials.gov processed this record on February 27, 2015

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