Clinical trial NCT01439880: Open Label Study of Long Term Evaluation Against LDL-C Trial
Official title: A Multicenter, Controlled, Open-label Extension (OLE) Study to Assess the Long-term Safety and Efficacy of AMG 145 (Evolocumab)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hypercholesterolemia
Keywords: High cholesterol
Raised cholesterol
Cholesterol
Elevated Cholesterol
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2011-09-23
Enrollment: 1324
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary clinical hypothesis is that long-term exposure of evolocumab (AMG 145) will be safe and well tolerated in adults with hypercholesterolemia.


Eligibility criteria: Inclusion Criteria:

* Complete a qualifying evolocumab (AMG 145) parent study protocol, including: 20101154 (NCT01375777), 20101155 (NCT01380730), 20090158 (NCT01375751), 20090159 (NCT01375764), and 20110231 (NCT01652703)

Exclusion Criteria:

* Experienced a treatment-related serious adverse event that led to investigational product (IP) discontinuation in the parent study
* Have an unstable medical condition, in the judgment of the investigator
* Known sensitivity to any of the products to be administered during dosing
* Currently enrolled in another investigational device or drug study (excluding evolocumab (AMG 145) parent study), or less than 30 days since ending another investigational device or drug study(s),or receiving other investigational agent(s)

Primary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: 52 weeks in the SOC-controlled period and up to 4 years in the All-IP period; actual median duration of treatment in the All-IP period was 46.9 months.
Secondary outcomes:
measure: Low-density Lipoprotein Cholesterol (LDL-C) Level at Week 24 and Week 52
timeFrame: Baseline of parent study and extension study weeks 24 and 52
measure: Non-high-density Lipoprotein Cholesterol (Non-HDL-C) Level at Week 24 and Week 52
timeFrame: Baseline of parent study and extension study weeks 24 and 52
measure: Apolipoprotein B Level at Week 24 and Week 52
timeFrame: Baseline of parent study and extension study weeks 24 and 52
measure: Total Cholesterol/HDL-C Ratio at Week 24 and Week 52
timeFrame: Baseline of parent study and extension study weeks 24 and 52
measure: Apolipoprotein B/Apolipoprotein A1 Ratio at Week 24 and Week 52
timeFrame: Baseline of parent study and extension study weeks 24 and 52
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Research Site
state: Alabama
city: Birmingham
country: United States
facility: Research Site
state: Alabama
city: Tucson
country: United States
facility: Research Site
state: Arizona
city: Little Rock
country: United States
facility: Research Site
state: Arkansas
city: Malvern
country: United States
facility: Research Site
state: Arkansas
city: Anaheim
country: United States
facility: Research Site
state: California
city: Carmichael
country: United States
facility: Research Site
state: California
city: Inglewood
country: United States
facility: Research Site
state: California
city: Mission Viejo
country: United States
facility: Research Site
state: California
city: Newport Beach
country: United States
facility: Research Site
state: California
city: Thousand Oaks
country: United States
facility: Research Site
state: California
city: Tustin
country: United States
facility: Research Site
state: California
city: Colorado Springs
country: United States
facility: Research Site
state: Colorado
city: Littleton
country: United States
facility: Research Site
state: Colorado
city: Daytona Beach
country: United States
facility: Research Site
state: Florida
city: DeLand
country: United States
facility: Research Site
state: Florida
city: Green Cove Springs
country: United States
facility: Research Site
state: Florida
city: Jacksonville
country: United States
facility: Research Site
state: Florida
city: Jacksonville
country: United States
facility: Research Site
state: Florida
city: Melbourne
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Ponte Vedra
country: United States
facility: Research Site
state: Florida
city: Port Charlotte
country: United States
facility: Research Site
state: Florida
city: Sanford
country: United States
facility: Research Site
state: Florida
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Savannah
country: United States
facility: Research Site
state: Georgia
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Indianapolis
country: United States
facility: Research Site
state: Indiana
city: Munster
country: United States
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state: Indiana
city: Iowa City
country: United States
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state: Iowa
city: Louisville
country: United States
facility: Research Site
state: Kentucky
city: Auburn
country: United States
facility: Research Site
state: Maine
city: Portland
country: United States
facility: Research Site
state: Maine
city: Bethesda
country: United States
facility: Research Site
state: Maryland
city: Chevy Chase
country: United States
facility: Research Site
state: Maryland
city: Brockton
country: United States
facility: Research Site
state: Massachusetts
city: Marquette
country: United States
facility: Research Site
state: Michigan
city: Brooklyn Center
country: United States
facility: Research Site
state: Minnesota
city: Tupelo
country: United States
facility: Research Site
state: Mississippi
city: Great Falls
country: United States
facility: Research Site
state: Montana
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: Cortlandt Manor
country: United States
facility: Research Site
state: New York
city: Endwell
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: Williamsville
country: United States
facility: Research Site
state: New York
city: Raleigh
country: United States
facility: Research Site
state: North Carolina
city: Raleigh
country: United States
facility: Research Site
state: North Carolina
city: Winston-Salem
country: United States
facility: Research Site
state: North Carolina
city: Fargo
country: United States
facility: Research Site
state: North Dakota
city: Akron
country: United States
facility: Research Site
state: Ohio
city: Cadiz
country: United States
facility: Research Site
state: Ohio
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Cincinnati
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: Dayton
country: United States
facility: Research Site
state: Ohio
city: Norman
country: United States
facility: Research Site
state: Oklahoma
city: Oklahoma City
country: United States
facility: Research Site
state: Oklahoma
city: Camp Hill
country: United States
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state: Pennsylvania
city: Duncansville
country: United States
facility: Research Site
state: Pennsylvania
city: Pittsburgh
country: United States
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state: Pennsylvania
city: York
country: United States
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state: Pennsylvania
city: Mount Pleasant
country: United States
facility: Research Site
state: South Carolina
city: Rapid City
country: United States
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state: South Dakota
city: Rapid City
country: United States
facility: Research Site
state: South Dakota
city: Bristol
country: United States
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state: Tennessee
city: Arlington
country: United States
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state: Texas
city: Houston
country: United States
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state: Texas
city: Houston
country: United States
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state: Texas
city: San Antonio
country: United States
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state: Texas
city: Norfolk
country: United States
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state: Virginia
city: Richmond
country: United States
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state: Virginia
city: Renton
country: United States
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state: Washington
city: Seattle
country: United States
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state: Washington
city: Tacoma
country: United States
facility: Research Site
state: Washington
city: Camperdown
country: Australia
facility: Research Site
state: New South Wales
city: Maroubra
country: Australia
facility: Research Site
state: New South Wales
city: Sydney
country: Australia
facility: Research Site
state: New South Wales
city: Perth
country: Australia
facility: Research Site
state: Western Australia
city: Anthée
country: Belgium
facility: Research Site
city: Bruxelles
country: Belgium
facility: Research Site
city: Gozee
country: Belgium
facility: Research Site
city: Gribomont
country: Belgium
facility: Research Site
city: Halen
country: Belgium
facility: Research Site
city: Ham
country: Belgium
facility: Research Site
city: Linkebeek
country: Belgium
facility: Research Site
city: Ukkel
country: Belgium
facility: Research Site
city: Kelowna
country: Canada
facility: Research Site
state: British Columbia
city: Bay Roberts
country: Canada
facility: Research Site
state: Newfoundland and Labrador
city: Mount Pearl
country: Canada
facility: Research Site
state: Newfoundland and Labrador
city: St. John's
country: Canada
facility: Research Site
state: Newfoundland and Labrador
city: Cambridge
country: Canada
facility: Research Site
state: Ontario
city: London
country: Canada
facility: Research Site
state: Ontario
city: London
country: Canada
facility: Research Site
state: Ontario
city: Newmarket
country: Canada
facility: Research Site
state: Ontario
city: Sarnia
country: Canada
facility: Research Site
state: Ontario
city: Sudbury
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Woodstock
country: Canada
facility: Research Site
state: Ontario
city: Chicoutimi
country: Canada
facility: Research Site
state: Quebec
city: Gatineau
country: Canada
facility: Research Site
state: Quebec
city: Granby
country: Canada
facility: Research Site
state: Quebec
city: Lachine
country: Canada
facility: Research Site
state: Quebec
city: Pointe-Claire
country: Canada
facility: Research Site
state: Quebec
city: Quebec
country: Canada
facility: Research Site
city: Brno
country: Czechia
facility: Research Site
city: Brno
country: Czechia
facility: Research Site
city: Brno
country: Czechia
facility: Research Site
city: Olomouc
country: Czechia
facility: Research Site
city: Praha 2
country: Czechia
facility: Research Site
city: Praha 4
country: Czechia
facility: Research Site
city: Slany
country: Czechia
facility: Research Site
city: Svitavy
country: Czechia
facility: Research Site
city: Usti nad Orlici
country: Czechia
facility: Research Site
city: Znojmo
country: Czechia
facility: Research Site
city: Aalborg
country: Denmark
facility: Research Site
city: Ballerup
country: Denmark
facility: Research Site
city: Vejle
country: Denmark
facility: Research Site
city: Helsinki
country: Finland
facility: Research Site
city: OYS
country: Finland
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Köln
country: Germany
facility: Research Site
city: New Territories
country: Hong Kong
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Debrecen
country: Hungary
facility: Research Site
city: Dunaujvaros
country: Hungary
facility: Research Site
city: Gyula
country: Hungary
facility: Research Site
city: Kecskemet
country: Hungary
facility: Research Site
city: Komarom
country: Hungary
facility: Research Site
city: Szolnok
country: Hungary
facility: Research Site
city: Zalaegerszeg
country: Hungary
facility: Research Site
city: Nagoya-shi
country: Japan
facility: Research Site
state: Aichi
city: Nagoya-shi
country: Japan
facility: Research Site
state: Aichi
city: Nagoya-shi
country: Japan
facility: Research Site
state: Aichi
city: Fukui-shi
country: Japan
facility: Research Site
state: Fukui
city: Kasuga-shi
country: Japan
facility: Research Site
state: Fukuoka
city: Fujioka-shi
country: Japan
facility: Research Site
state: Gunma
city: Maebashi-shi
country: Japan
facility: Research Site
state: Gunma
city: Maebashi-shi
country: Japan
facility: Research Site
state: Gunma
city: Takasaki-shi
country: Japan
facility: Research Site
state: Gunma
city: Kawanishi-shi
country: Japan
facility: Research Site
state: Hyogo
city: Kobe-shi
country: Japan
facility: Research Site
state: Hyogo
city: Hitachi-shi
country: Japan
facility: Research Site
state: Ibaraki
city: Koga-shi
country: Japan
facility: Research Site
state: Ibaraki
city: Mito-shi
country: Japan
facility: Research Site
state: Ibaraki
city: Komatsu-shi
country: Japan
facility: Research Site
state: Ishikawa
city: Takamatsu-shi
country: Japan
facility: Research Site
state: Kagawa
city: Kochi-shi
country: Japan
facility: Research Site
state: Kochi
city: Kyoto-shi
country: Japan
facility: Research Site
state: Kyoto
city: Kyoto-shi
country: Japan
facility: Research Site
state: Kyoto
city: Ina-shi
country: Japan
facility: Research Site
state: Nagano
city: Matsumoto-shi
country: Japan
facility: Research Site
state: Nagano
city: Suwa-shi
country: Japan
facility: Research Site
state: Nagano
city: Ibaraki-shi
country: Japan
facility: Research Site
state: Osaka
city: Toyonaka-shi
country: Japan
facility: Research Site
state: Osaka
city: Hanyu-shi
country: Japan
facility: Research Site
state: Saitama
city: Sayama-shi
country: Japan
facility: Research Site
state: Saitama
city: Toda-shi
country: Japan
facility: Research Site
state: Saitama
city: Chiyoda-ku
country: Japan
facility: Research Site
state: Tokyo
city: Hachioji-shi
country: Japan
facility: Research Site
state: Tokyo
city: Itabashi-ku
country: Japan
facility: Research Site
state: Tokyo
city: Shinagawa-ku
country: Japan
facility: Research Site
state: Tokyo
city: Toshima-ku
country: Japan
facility: Research Site
state: Tokyo
city: Amsterdam
country: Netherlands
facility: Research Site
city: Hoorn
country: Netherlands
facility: Research Site
city: Utrecht
country: Netherlands
facility: Research Site
city: Oslo
country: Norway
facility: Research Site
city: Singapore
country: Singapore
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: Barcelona
country: Spain
facility: Research Site
state: Cataluña
city: Reus
country: Spain
facility: Research Site
state: Cataluña
city: Madrid
country: Spain
facility: Research Site
city: Göteborg
country: Sweden
facility: Research Site
city: Lund
country: Sweden
facility: Research Site
city: Stockholm
country: Sweden
facility: Research Site
city: Stockholm
country: Sweden
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Koren MJ, Sabatine MS, Giugliano RP, Langslet G, Wiviott SD, Kassahun H, Ruzza A, Ma Y, Somaratne R, Raal FJ. Long-term Low-Density Lipoprotein Cholesterol-Lowering Efficacy, Persistence, and Safety of Evolocumab in Treatment of Hypercholesterolemia: Results Up to 4 Years From the Open-Label OSLER-1 Extension Study. JAMA Cardiol. 2017 Jun 1;2(6):598-607. doi: 10.1001/jamacardio.2017.0747.
citation: Koren MJ, Giugliano RP, Raal FJ, Sullivan D, Bolognese M, Langslet G, Civeira F, Somaratne R, Nelson P, Liu T, Scott R, Wasserman SM, Sabatine MS; OSLER Investigators. Efficacy and safety of longer-term administration of evolocumab (AMG 145) in patients with hypercholesterolemia: 52-week results from the Open-Label Study of Long-Term Evaluation Against LDL-C (OSLER) randomized trial. Circulation. 2014 Jan 14;129(2):234-43. doi: 10.1161/CIRCULATIONAHA.113.007012. Epub 2013 Nov 19.
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: Hovingh GK, Raal FJ, Dent R, Stefanutti C, Descamps O, Masana L, Lira A, Bridges I, Coll B, Sullivan D. Long-term safety, tolerability, and efficacy of evolocumab in patients with heterozygous familial hypercholesterolemia. J Clin Lipidol. 2017 Nov-Dec;11(6):1448-1457. doi: 10.1016/j.jacl.2017.09.003. Epub 2017 Sep 22.
citation: Koren MJ, Sabatine MS, Giugliano RP, Langslet G, Wiviott SD, Ruzza A, Ma Y, Hamer AW, Wasserman SM, Raal FJ. Long-Term Efficacy and Safety of Evolocumab in Patients With Hypercholesterolemia. J Am Coll Cardiol. 2019 Oct 29;74(17):2132-2146. doi: 10.1016/j.jacc.2019.08.1024.
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: Sattar N, Toth PP, Blom DJ, Koren MJ, Soran H, Uhart M, Elliott M, Cyrille M, Somaratne R, Preiss D. Effect of the Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor Evolocumab on Glycemia, Body Weight, and New-Onset Diabetes Mellitus. Am J Cardiol. 2017 Nov 1;120(9):1521-1527. doi: 10.1016/j.amjcard.2017.07.047. Epub 2017 Jul 31.
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: Schludi B, Giugliano RP, Sabatine MS, Raal FJ, Teramoto T, Koren MJ, Stein EA, Wang H, Monsalvo ML. Time-averaged low-density lipoprotein cholesterol lowering with evolocumab: Pooled analysis of phase 2 trials. J Clin Lipidol. 2022 Jul-Aug;16(4):538-543. doi: 10.1016/j.jacl.2022.05.069. Epub 2022 Jun 6.
citation: Hirayama A, Yamashita S, Ruzza A, Inomata H, Cyrille M, Lu C, Hamer AW, Yoshida M, Kiyosue A, Teramoto T. Long-Term Treatment With Evolocumab Among Japanese Patients - Final Report of the OSLER Open-Label Extension Studies. Circ J. 2019 Apr 25;83(5):971-977. doi: 10.1253/circj.CJ-19-0139. Epub 2019 Mar 29.
citation: Sabatine MS, Giugliano RP, Wiviott SD, Raal FJ, Blom DJ, Robinson J, Ballantyne CM, Somaratne R, Legg J, Wasserman SM, Scott R, Koren MJ, Stein EA; Open-Label Study of Long-Term Evaluation against LDL Cholesterol (OSLER) Investigators. Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015 Apr 16;372(16):1500-9. doi: 10.1056/NEJMoa1500858. Epub 2015 Mar 15.