Clinical trial NCT01763918: Reduction of LDL-C With PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder Study-2
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hyperlipidemia
Keywords: High cholesterol, Treatment for high cholesterol, Lowering cholesterol, Lowering high cholesterol, Hypercholesterolemia
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2013-01-09
Enrollment: 331
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility 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

Primary outcomes:
measure: Percent Change From Baseline in LDL-C at Week 12
timeFrame: Baseline and Week 12
measure: Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12
timeFrame: Baseline and Weeks 10 and 12
Secondary outcomes:
measure: Change From Baseline in LDL-C at the Mean of Weeks 10 and 12
timeFrame: Baseline and Weeks 10 and 12
measure: Change From Baseline in LDL-C at Week 12
timeFrame: Baseline and Week 12
measure: Percentage of Participants With Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL (1.8 mmol/L)
timeFrame: Weeks 10 and 12
measure: Percentage of Participants With LDL-C < 70 mg/dL (1.8 mmol/L) at Week 12
timeFrame: Week 12
measure: Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at the Mean of Weeks 10 and 12
timeFrame: Baseline and Weeks 10 and 12
measure: Percent Change From Baseline in Non-HDL-C at Week 12
timeFrame: Baseline and Week 12
measure: Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12
timeFrame: Baseline and Weeks 10 and 12
measure: Percent Change From Baseline in Apolipoprotein B at Week 12
timeFrame: Baseline and Week 12
measure: Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at the Mean of Weeks 10 and 12
timeFrame: Baseline and Weeks 10 and 12
measure: Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12
timeFrame: Baseline and Week 12
measure: Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at the Mean of Weeks 10 and 12
timeFrame: Baseline and Weeks 10 and 12
measure: Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12
timeFrame: Baseline and Week 12
measure: Percent Change From Baseline in Lipoprotein (a) at the Mean of Weeks 10 and 12
timeFrame: Baseline and Weeks 10 and 12
measure: Percent Change From Baseline in Lipoprotein (a) at Week 12
timeFrame: Baseline and Week 12
measure: Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12
timeFrame: Baseline and Weeks 10 and 12
measure: Percent Change From Baseline in Triglycerides at Week 12
timeFrame: Baseline and Week 12
measure: Percent Change From Baseline in HDL-C at the Mean of Weeks 10 and 12
timeFrame: Baseline and Weeks 10 and 12
measure: Percent Change From Baseline in HDL-C at Week 12
timeFrame: Baseline and Week 12
measure: Percent Change From Baseline in Very Low-Density Lipoprotein Cholesterol (VLDL-C) at the Mean of Weeks 10 and 12
timeFrame: Baseline and Weeks 10 and 12
measure: Percent Change From Baseline in VLDL-C at Week 12
timeFrame: Baseline and Week 12
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Research Site
state: Arizona
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Camperdown
country: Australia
facility: Research Site
state: New South Wales
city: Perth
country: Australia
facility: Research Site
state: Western Australia
city: Vancouver
country: Canada
facility: Research Site
state: British Columbia
city: London
country: Canada
facility: Research Site
state: Ontario
city: Chicoutimi
country: Canada
facility: Research Site
state: Quebec
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Bron
country: France
facility: Research Site
city: Nantes Cedex 1
country: France
facility: Research Site
city: Paris Cedex 13
country: France
facility: Research Site
city: Köln
country: Germany
facility: Research Site
city: New Territories
country: Hong Kong
facility: Research Site
city: Amersfoort
country: Netherlands
facility: Research Site
city: Amsterdam
country: Netherlands
facility: Research Site
city: Amsterdam
country: Netherlands
facility: Research Site
city: Gouda
country: Netherlands
facility: Research Site
city: Groningen
country: Netherlands
facility: Research Site
city: Hoorn
country: Netherlands
facility: Research Site
city: Tilburg
country: Netherlands
facility: Research Site
city: Utrecht
country: Netherlands
facility: Research Site
city: Christchurch
country: New Zealand
facility: Research Site
city: Oslo
country: Norway
facility: Research Site
city: Johannesburg
country: South Africa
facility: Research Site
state: Gauteng
city: Midrand
country: South Africa
facility: Research Site
state: Gauteng
city: Observatory
country: South Africa
facility: Research Site
state: Western Cape
city: Parow
country: South Africa
facility: Research Site
state: Western Cape
city: Cordoba
country: Spain
facility: Research Site
state: Andalucía
city: Zaragoza
country: Spain
facility: Research Site
state: Aragón
city: Reus
country: Spain
facility: Research Site
state: Cataluña
city: Madrid
country: Spain
facility: Research Site
city: Stockholm
country: Sweden
facility: Research Site
city: Stockholm
country: Sweden
facility: Research Site
city: Reinach
country: Switzerland
facility: Research Site
city: Coventry
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Toth PP, Descamps O, Genest J, Sattar N, Preiss D, Dent R, Djedjos C, Wu Y, Geller M, Uhart M, Somaratne R, Wasserman SM; PROFICIO Investigators. Pooled Safety Analysis of Evolocumab in Over 6000 Patients From Double-Blind and Open-Label Extension Studies. Circulation. 2017 May 9;135(19):1819-1831. doi: 10.1161/CIRCULATIONAHA.116.025233. Epub 2017 Mar 1.
citation: Kuchimanchi M, Grover A, Emery MG, Somaratne R, Wasserman SM, Gibbs JP, Doshi S. Population pharmacokinetics and exposure-response modeling and simulation for evolocumab in healthy volunteers and patients with hypercholesterolemia. J Pharmacokinet Pharmacodyn. 2018 Jun;45(3):505-522. doi: 10.1007/s10928-018-9592-y. Epub 2018 May 7.
citation: Kasichayanula S, Grover A, Emery MG, Gibbs MA, Somaratne R, Wasserman SM, Gibbs JP. Clinical Pharmacokinetics and Pharmacodynamics of Evolocumab, a PCSK9 Inhibitor. Clin Pharmacokinet. 2018 Jul;57(7):769-779. doi: 10.1007/s40262-017-0620-7.
citation: Wasserman SM, Sabatine MS, Koren MJ, Giugliano RP, Legg JC, Emery MG, Doshi S, Liu T, Somaratne R, Gibbs JP. Comparison of LDL-C Reduction Using Different Evolocumab Doses and Intervals: Biological Insights and Treatment Implications. J Cardiovasc Pharmacol Ther. 2018 Sep;23(5):423-432. doi: 10.1177/1074248418774043. Epub 2018 May 16.
citation: 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.
citation: Shapiro MD, Minnier J, Tavori H, Kassahun H, Flower A, Somaratne R, Fazio S. Relationship Between Low-Density Lipoprotein Cholesterol and Lipoprotein(a) Lowering in Response to PCSK9 Inhibition With Evolocumab. J Am Heart Assoc. 2019 Feb 19;8(4):e010932. doi: 10.1161/JAHA.118.010932.
citation: Stroes E, Robinson JG, Raal FJ, Dufour R, Sullivan D, Kassahun H, Ma Y, Wasserman SM, Koren MJ. Consistent LDL-C response with evolocumab among patient subgroups in PROFICIO: A pooled analysis of 3146 patients from phase 3 studies. Clin Cardiol. 2018 Oct;41(10):1328-1335. doi: 10.1002/clc.23049. Epub 2018 Oct 21.