Clinical trial NCT01763866: LDL-C Assessment With PCSK9 Monoclonal Antibody Inhibition Combined With Statin Therapy-2
Official title: A Double-blind, Randomized, Placebo and Ezetimibe Controlled, Multicenter Study to Evaluate Safety, Tolerability and Efficacy of AMG 145 on LDL-C in Combination With Statin Therapy in Subjects With Primary Hypercholesterolemia and Mixed Dyslipidemia
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: 2067
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 administered subcutaneously every 2 weeks (Q2W) and monthly (QM) when used in combination with a statin, compared with placebo, on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in patients with primary hypercholesterolemia and mixed dyslipidemia.

Detailed description: Prior to the first randomization, participants entered a screening period to determine eligibility. During screening, all participants received subcutaneous placebo corresponding to the once monthly dose volume. Participants who completed the screening period and met eligibility criteria were randomized to 1 of 5 open-label statin cohorts (atorvastatin 10 mg or 80 mg, rosuvastatin 5 mg or 40 mg, or simvastatin 40 mg) for a 4 week lipid stabilization period based on statin therapy at the time of study entry (no statin use vs non-intensive statin use vs intensive statin use).

After the 4-week lipid-stabilization period, eligible patients taking rosuvastatin or simvastatin during the lipid-stabilization phase were then randomized to 1 of 4 treatment groups: evolocumab (140 mg, subcutaneous, every 2 weeks) or matching placebo (subcutaneous, every 2 weeks), or evolocumab (420 mg, subcutaneous, monthly) or matching placebo (subcutaneous, monthly). Patients taking atorvastatin during the lipid-stabilization phase were then randomized to 1 of 6 treatment groups: evolocumab (140 mg, subcutaneous, every 2 weeks) and placebo (oral, daily), evolocumab (420 mg, subcutaneous, monthly) and placebo (oral, daily), placebo (subcutaneous, every 2 weeks) and placebo (oral, daily) or ezetimibe (10 mg, oral, daily), or placebo (subcutaneous, monthly) and placebo (oral, daily) or ezetimibe (10 mg, oral, daily).

A participant was considered randomized into the study after successfully completing the screening period, meeting all inclusion/exclusion criteria, and undergoing both randomization procedures.

Participants randomized to simvastatin who were taking verapamil or diltiazem prior to randomization received simvastatin 10 mg once daily (QD) while participants who were taking amlodipine, amiodarone or ranolazine prior to randomization received simvastatin 20 mg QD. All other participants randomized to simvastatin received simvastatin 40 mg QD.

Eligibility criteria: Inclusion Criteria:

* Male or female ≥ 18 to ≤ 80 years of age
* Subjects not taking a statin must have fasting LDL-C of at least 150 mg/dL (4.0 mmol/L)
* Subjects already on a non-intensive statin must have fasting LDL-C at screening ≥ 100 mg/dL (2.6 mmol/L)
* Subjects already on a intensive statin must have fasting LDL-C at screening ≥ 80 mg/dL (2.1 mmol/L)
* Fasting triglycerides ≤ 400 mg/dL (4.5 mmol/L)

Exclusion Criteria:

* Statin intolerance
* New York Heart association (NYHA) III or IV heart failure
* Uncontrolled hypertension
* Uncontrolled cardiac arrhythmia
* Type 1 diabetes, poorly controlled type 2 diabetes
* Uncontrolled hypothyroidism or hyperthyroidism

Primary outcomes:
measure: Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (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 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: 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: Percentage of Participants Who Achieved a Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL
timeFrame: Weeks 10 and 12
measure: Percentage of Participants Who Achieved LDL-C < 70 mg/dL at Week 12
timeFrame: 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 Very Low-Density Cholesterol (VLDL-C) at the Mean of Weeks 10 and 12
timeFrame: Baseline and Weeks 10 and 12
measure: Percent Change From Baseline in Very Low-Density Cholesterol (VLDL-C) 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
Other outcomes:
Locations:
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city: Heidelberg Heights
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city: Richmond
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facility: Research Site
city: Hasselt
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country: Belgium
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city: Tremelo
country: Belgium
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country: Canada
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state: British Columbia
city: Kelowna
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city: Surrey
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state: British Columbia
city: Saint Johnâ€™s
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state: Newfoundland and Labrador
city: Cambridge
country: Canada
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state: Ontario
city: Hamilton
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city: London
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city: Newmarket
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city: Scarborough
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city: Toronto
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state: Ontario
city: Woodstock
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state: Quebec
city: Greenfield Park
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city: Lachine
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city: Montreal
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city: Brno
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country: Czechia
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city: Moravske Budejovice
country: Czechia
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country: Hungary
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country: Hungary
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city: Bologna
country: Italy
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city: Suwon-si
country: Korea, Republic of
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facility: Research Site
city: Mexico
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state: Distrito Federal
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city: Guadalajara
country: Mexico
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country: Mexico
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country: Mexico
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city: Tampico
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state: Tamaulipas
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facility: Research Site
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country: Netherlands
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country: Netherlands
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country: Netherlands
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city: Waalwijk
country: Netherlands
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city: Barnaul
country: Russian Federation
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city: Kemerovo
country: Russian Federation
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city: Moscow
country: Russian Federation
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city: Moscow
country: Russian Federation
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country: Russian Federation
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country: Russian Federation
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country: Russian Federation
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country: Russian Federation
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city: Saint Petersburg
country: Russian Federation
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city: Saint-Petersburg
country: Russian Federation
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country: Russian Federation
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country: South Africa
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state: Gauteng
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country: South Africa
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country: South Africa
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country: South Africa
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city: Kuils River
country: South Africa
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state: Western Cape
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country: South Africa
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state: Western Cape
city: Bloemfontein
country: South Africa
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city: Cape Town
country: South Africa
facility: Research Site
city: Almeria
country: Spain
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state: AndalucÃ-a
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country: Spain
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state: AndalucÃ-a
city: Barcelona
country: Spain
facility: Research Site
state: CataluÃ±a
city: Barcelona
country: Spain
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state: CataluÃ±a
city: L'Hospitalet de Llobregat
country: Spain
facility: Research Site
state: CataluÃ±a
city: Valencia
country: Spain
facility: Research Site
state: Comunidad Valenciana
city: Pozuelo de Alarcon
country: Spain
facility: Research Site
state: Madrid
city: Pozuelo De AlarcÃ³n
country: Spain
facility: Research Site
state: Madrid
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: GÃ¶teborg
country: Sweden
facility: Research Site
city: Lund
country: Sweden
facility: Research Site
city: Lund
country: Sweden
facility: Research Site
city: Stockholm
country: Sweden
facility: Research Site
city: Uddevalla
country: Sweden
facility: Research Site
city: Ã-rebro
country: Sweden
facility: Research Site
city: Bellinzona
country: Switzerland
facility: Research Site
city: Geneva 14
country: Switzerland
facility: Research Site
city: Lausanne
country: Switzerland
facility: Research Site
city: Muensterlingen
country: Switzerland
facility: Research Site
city: St. Gallen
country: Switzerland
facility: Research Site
city: Zurich
country: Switzerland
facility: Research Site
city: Kaohsiung
country: Taiwan
facility: Research Site
city: Kaohsiung
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Birmingham
country: United Kingdom
facility: Research Site
city: Blackpool
country: United Kingdom
facility: Research Site
city: Cardiff
country: United Kingdom
facility: Research Site
city: Chesterfield
country: United Kingdom
facility: Research Site
city: Chorley
country: United Kingdom
facility: Research Site
city: Doncaster
country: United Kingdom
facility: Research Site
city: Glasgow
country: United Kingdom
facility: Research Site
city: Glasgow
country: United Kingdom
facility: Research Site
city: Harrow
country: United Kingdom
facility: Research Site
city: Liverpool
country: United Kingdom
facility: Research Site
city: Liverpool
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
city: Reading
country: United Kingdom
facility: Research Site
city: Reading
country: United Kingdom
facility: Research Site
city: Scunthorpe
country: United Kingdom
facility: Research Site
city: Wakefield
country: United Kingdom
facility: Research Site
city: Whitby
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Robinson JG, Nedergaard BS, Rogers WJ, Fialkow J, Neutel JM, Ramstad D, Somaratne R, Legg JC, Nelson P, Scott R, Wasserman SM, Weiss R; LAPLACE-2 Investigators. Effect of evolocumab or ezetimibe added to moderate- or high-intensity statin therapy on LDL-C lowering in patients with hypercholesterolemia: the LAPLACE-2 randomized clinical trial. JAMA. 2014 May 14;311(18):1870-82. doi: 10.1001/jama.2014.4030.
citation: Robinson JG, Rogers WJ, Nedergaard BS, Fialkow J, Neutel JM, Ramstad D, Somaratne R, Legg JC, Nelson P, Scott R, Wasserman SM, Weiss R. Rationale and design of LAPLACE-2: a phase 3, randomized, double-blind, placebo- and ezetimibe-controlled trial evaluating the efficacy and safety of evolocumab in subjects with hypercholesterolemia on background statin therapy. Clin Cardiol. 2014 Apr;37(4):195-203. doi: 10.1002/clc.22252. Epub 2014 Jan 30.
citation: Daviglus ML, Ferdinand KC, Lopez JAG, Wu Y, Monsalvo ML, Rodriguez CJ. Effects of Evolocumab on Low-Density Lipoprotein Cholesterol, Non-High Density Lipoprotein Cholesterol, Apolipoprotein B, and Lipoprotein(a) by Race and Ethnicity: A Meta-Analysis of Individual Participant Data From Double-Blind and Open-Label Extension Studies. J Am Heart Assoc. 2021 Jan 5;10(1):e016839. doi: 10.1161/JAHA.120.016839. Epub 2020 Dec 16.
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.
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: 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, 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: 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: 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: May HT, Muhlestein JB, Ma Y, Lopez JAG, Coll B, Nelson J. Effects of Evolocumab on the ApoA1 Remnant Ratio: A Pooled Analysis of Phase 3 Studies. Cardiol Ther. 2019 Jun;8(1):91-102. doi: 10.1007/s40119-019-0133-6. Epub 2019 Mar 9.