Clinical trial NCT01763905: Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects -2
Official title: A Double-blind, Randomized, Multicenter Study to Evaluate Safety and Efficacy of AMG 145, Compared With Ezetimibe, in Hypercholesterolemic Subjects Unable to Tolerate an Effective Dose of a HMG-CoA Reductase Inhibitor
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: 307
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 subcutaneous (SC) evolocumab every 2 weeks (Q2W) and monthly (QM), compared with ezetimibe, on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in hypercholesterolemic adults unable to tolerate an effective dose of a statin (HMG-CoA (5-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitors).


Eligibility criteria: Inclusion Criteria:

* Male or female ≥ 18 to ≤ 80 years of age
* Not on a statin or on a low dose statin with stable dose for at least 4 weeks
* History of intolerance to at least 2 statins
* Subject not at LDL-C goal
* Lipid lowering therapy has been stable prior to enrolment for at least 4 weeks.
* Fasting triglycerides ≤ 400 mg/dL

Exclusion Criteria:

* 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-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/High Density Lipoprotein Cholesterol 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/High Density Lipoprotein Cholesterol 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 High-Density Lipoprotein Cholesterol (HDL-C) at the Mean of Weeks 10 and 12
timeFrame: Baseline and Weeks 10 and 12
measure: Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Week 12
timeFrame: Baseline and Week 12
measure: Percent Change From Baseline in Very Low-Density Lipoprotein Cholesterol at the Mean of Weeks 10 and 12
timeFrame: Baseline and Weeks 10 and 12
measure: Percent Change From Baseline in Very Low-Density Lipoprotein Cholesterol at Week 12
timeFrame: Baseline and Week 12
Other outcomes:
Locations:
city: Carmichael
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Mission Viejo
country: United States
facility: Research Site
state: California
city: Thousand Oaks
country: United States
facility: Research Site
state: California
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Savannah
country: United States
facility: Research Site
state: Georgia
city: Auburn
country: United States
facility: Research Site
state: Maine
city: Traverse City
country: United States
facility: Research Site
state: Michigan
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: Henderson
country: United States
facility: Research Site
state: Nevada
city: Las Vegas
country: United States
facility: Research Site
state: Nevada
city: Las Vegas
country: United States
facility: Research Site
state: Nevada
city: New York
country: United States
facility: Research Site
state: New York
city: Raleigh
country: United States
facility: Research Site
state: North Carolina
city: Akron
country: United States
facility: Research Site
state: Ohio
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Cleveland
country: United States
facility: Research Site
state: Ohio
city: Norman
country: United States
facility: Research Site
state: Oklahoma
city: Houston
country: United States
facility: Research Site
state: Texas
city: Camperdown
country: Australia
facility: Research Site
state: New South Wales
city: Milton
country: Australia
facility: Research Site
state: Queensland
city: Melbourne
country: Australia
facility: Research Site
state: Victoria
city: Perth
country: Australia
facility: Research Site
state: Western Australia
city: Brussels
country: Belgium
facility: Research Site
city: Gent
country: Belgium
facility: Research Site
city: La Louvière
country: Belgium
facility: Research Site
city: Newmarket
country: Canada
facility: Research Site
state: Ontario
city: Lachine
country: Canada
facility: Research Site
state: Quebec
city: Pointe-Claire
country: Canada
facility: Research Site
state: Quebec
city: Aalborg
country: Denmark
facility: Research Site
city: Ballerup
country: Denmark
facility: Research Site
city: Vejle
country: Denmark
facility: Research Site
city: Lille Cedex
country: France
facility: Research Site
city: Paris Cedex 13
country: France
facility: Research Site
city: Vénissieux
country: France
facility: Research Site
city: Bad Krozingen
country: Germany
facility: Research Site
city: Dresden
country: Germany
facility: Research Site
city: Heppenheim
country: Germany
facility: Research Site
city: Hong Kong
country: Hong Kong
facility: Research Site
city: New Territories
country: Hong Kong
facility: Research Site
city: Alkmaar
country: Netherlands
facility: Research Site
city: Amsterdam
country: Netherlands
facility: Research Site
city: Groningen
country: Netherlands
facility: Research Site
city: Lodz
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Midrand
country: South Africa
facility: Research Site
state: Gauteng
city: Observatory
country: South Africa
facility: Research Site
state: Western Cape
city: Somerset West
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: Lugano
country: Switzerland
facility: Research Site
city: Reinach
country: Switzerland
facility: Research Site
city: Liverpool
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Telford
country: United Kingdom
facility: Research Site
city: West Bromwich
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: Cho L, Dent R, Stroes ESG, Stein EA, Sullivan D, Ruzza A, Flower A, Somaratne R, Rosenson RS. Persistent Safety and Efficacy of Evolocumab in Patients with Statin Intolerance: a Subset Analysis of the OSLER Open-Label Extension Studies. Cardiovasc Drugs Ther. 2018 Aug;32(4):365-372. doi: 10.1007/s10557-018-6817-7.
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: Cho L, Rocco M, Colquhoun D, Sullivan D, Rosenson RS, Dent R, Xue A, Scott R, Wasserman SM, Stroes E. Design and rationale of the GAUSS-2 study trial: a double-blind, ezetimibe-controlled phase 3 study of the efficacy and tolerability of evolocumab (AMG 145) in subjects with hypercholesterolemia who are intolerant of statin therapy. Clin Cardiol. 2014 Mar;37(3):131-9. doi: 10.1002/clc.22248. Epub 2014 Jan 29.
citation: Stroes E, Colquhoun D, Sullivan D, Civeira F, Rosenson RS, Watts GF, Bruckert E, Cho L, Dent R, Knusel B, Xue A, Scott R, Wasserman SM, Rocco M; GAUSS-2 Investigators. Anti-PCSK9 antibody effectively lowers cholesterol in patients with statin intolerance: the GAUSS-2 randomized, placebo-controlled phase 3 clinical trial of evolocumab. J Am Coll Cardiol. 2014 Jun 17;63(23):2541-2548. doi: 10.1016/j.jacc.2014.03.019. Epub 2014 Mar 30.
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.
citation: Toth PP, Jones SR, Monsalvo ML, Elliott-Davey M, Lopez JAG, Banach M. Effect of Evolocumab on Non-High-Density Lipoprotein Cholesterol, Apolipoprotein B, and Lipoprotein(a): A Pooled Analysis of Phase 2 and Phase 3 Studies. J Am Heart Assoc. 2020 Mar 3;9(5):e014129. doi: 10.1161/JAHA.119.014129. Epub 2020 Mar 2.
citation: Koren MJ, Jones PH, Robinson JG, Sullivan D, Cho L, Hucko T, Lopez JAG, Fleishman AN, Somaratne R, Stroes E. A Comparison of Ezetimibe and Evolocumab for Atherogenic Lipid Reduction in Four Patient Populations: A Pooled Efficacy and Safety Analysis of Three Phase 3 Studies. Cardiol Ther. 2020 Dec;9(2):447-465. doi: 10.1007/s40119-020-00181-8. Epub 2020 Jun 20.