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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01439880




Registration number
NCT01439880
Ethics application status
Date submitted
22/09/2011
Date registered
23/09/2011
Date last updated
21/09/2022

Titles & IDs
Public title
Open Label Study of Long Term Evaluation Against LDL-C Trial
Scientific title
A Multicenter, Controlled, Open-label Extension (OLE) Study to Assess the Long-term Safety and Efficacy of AMG 145 (Evolocumab)
Secondary ID [1] 0 0
2011-001915-29
Secondary ID [2] 0 0
20110110
Universal Trial Number (UTN)
Trial acronym
OSLER
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hypercholesterolemia 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Evolocumab
Other interventions - Standard of care

Active Comparator: Standard of Care - Participants received standard of care (SOC) treatment for the first year of the study (SOC-controlled period). At week 52 participants began treatment with evolocumab 420 mg once a month (QM) for 4 years during the all-investigational product [all-IP] period.

Experimental: Evolocumab + SOC - Participants received evolocumab 420 mg once a month plus standard of care for the first year of the study (SOC-controlled period). At week 52 participants continued treatment with evolocumab 420 mg QM for another 4 years during the all-IP period.


Other interventions: Evolocumab
Administered by subcutaneous injection

Other interventions: Standard of care
Standard of care therapy as per local practices. This could include prescribed therapies and/or dietary/exercise regimes
Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Adverse Events
Timepoint [1] 0 0
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 outcome [1] 0 0
Low-density Lipoprotein Cholesterol (LDL-C) Level at Week 24 and Week 52
Timepoint [1] 0 0
Baseline of parent study and extension study weeks 24 and 52
Secondary outcome [2] 0 0
Non-high-density Lipoprotein Cholesterol (Non-HDL-C) Level at Week 24 and Week 52
Timepoint [2] 0 0
Baseline of parent study and extension study weeks 24 and 52
Secondary outcome [3] 0 0
Apolipoprotein B Level at Week 24 and Week 52
Timepoint [3] 0 0
Baseline of parent study and extension study weeks 24 and 52
Secondary outcome [4] 0 0
Total Cholesterol/HDL-C Ratio at Week 24 and Week 52
Timepoint [4] 0 0
Baseline of parent study and extension study weeks 24 and 52
Secondary outcome [5] 0 0
Apolipoprotein B/Apolipoprotein A1 Ratio at Week 24 and Week 52
Timepoint [5] 0 0
Baseline of parent study and extension study weeks 24 and 52

Eligibility
Key inclusion criteria
- Complete a qualifying evolocumab (AMG 145) parent study protocol, including: 20101154
(NCT01375777), 20101155 (NCT01380730), 20090158 (NCT01375751), 20090159 (NCT01375764),
and 20110231 (NCT01652703)
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
7/10/2011
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
20/06/2018
Sample size
Target
Accrual to date
Final
1324
Recruitment in Australia
Recruitment state(s)
NSW,WA
Recruitment hospital [1] 0 0
Research Site - Camperdown
Recruitment hospital [2] 0 0
Research Site - Maroubra
Recruitment hospital [3] 0 0
Research Site - Sydney
Recruitment hospital [4] 0 0
Research Site - Perth
Recruitment postcode(s) [1] 0 0
2015 - Camperdown
Recruitment postcode(s) [2] 0 0
2035 - Maroubra
Recruitment postcode(s) [3] 0 0
2022 - Sydney
Recruitment postcode(s) [4] 0 0
6000 - Perth
Recruitment outside Australia
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United States of America
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Alabama
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Arizona
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Arkansas
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California
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Colorado
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Florida
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Georgia
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Illinois
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Indiana
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Iowa
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Kentucky
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Maine
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Maryland
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Massachusetts
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Michigan
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Minnesota
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Mississippi
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Montana
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Nevada
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New York
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North Carolina
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North Dakota
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Ohio
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Oklahoma
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Pennsylvania
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South Carolina
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South Dakota
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Tennessee
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Texas
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Virginia
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Washington
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Belgium
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Anthée
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Belgium
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Bruxelles
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Belgium
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Gozee
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Belgium
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Gribomont
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Belgium
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Halen
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Belgium
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Ham
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Belgium
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Linkebeek
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Belgium
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Ukkel
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Canada
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British Columbia
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Canada
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Newfoundland and Labrador
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Canada
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Ontario
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Canada
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Quebec
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Czechia
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Brno
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Czechia
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Olomouc
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Czechia
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Praha 2
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Czechia
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Praha 4
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Czechia
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Slany
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Czechia
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Svitavy
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Czechia
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Usti nad Orlici
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Czechia
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Znojmo
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Denmark
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Aalborg
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Denmark
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Ballerup
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Vejle
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Finland
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Helsinki
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Finland
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OYS
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Germany
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Berlin
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Germany
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Köln
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Hong Kong
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New Territories
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Hungary
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Budapest
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Hungary
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Debrecen
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Hungary
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Dunaujvaros
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Hungary
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Gyula
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Hungary
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Kecskemet
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Hungary
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Komarom
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Hungary
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Szolnok
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Hungary
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Zalaegerszeg
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Japan
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Aichi
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Japan
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Fukui
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Japan
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Fukuoka
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Japan
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Gunma
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Japan
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Hyogo
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Japan
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Ibaraki
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Japan
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Ishikawa
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Japan
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Kagawa
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Japan
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Kochi
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Japan
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Kyoto
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Japan
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Nagano
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Japan
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Osaka
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Japan
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Saitama
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Japan
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Tokyo
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Netherlands
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Amsterdam
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Netherlands
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Hoorn
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Netherlands
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Utrecht
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Norway
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Oslo
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Singapore
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Singapore
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South Africa
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Gauteng
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South Africa
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Western Cape
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Spain
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Andalucía
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Spain
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Aragón
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Spain
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Cataluña
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Spain
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Madrid
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Sweden
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Göteborg
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Sweden
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Lund
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Sweden
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Stockholm
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United Kingdom
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London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Amgen
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01439880
Trial related presentations / publications
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
MD
Address 0 0
Amgen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01439880