Hypercholesterolemia Clinical Trial
— OSLEROfficial title:
A Multicenter, Controlled, Open-label Extension (OLE) Study to Assess the Long-term Safety and Efficacy of AMG 145 (Evolocumab)
| Verified date | September 2022 |
| Source | Amgen |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
The primary clinical hypothesis is that long-term exposure of evolocumab (AMG 145) will be safe and well tolerated in adults with hypercholesterolemia.
| Status | Completed |
| Enrollment | 1324 |
| Est. completion date | June 20, 2018 |
| Est. primary completion date | June 20, 2018 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 75 Years |
| Eligibility | 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) |
| Country | Name | City | State |
|---|---|---|---|
| Australia | Research Site | Camperdown | New South Wales |
| Australia | Research Site | Maroubra | New South Wales |
| Australia | Research Site | Perth | Western Australia |
| Australia | Research Site | Sydney | New South Wales |
| Belgium | Research Site | Anthée | |
| Belgium | Research Site | Bruxelles | |
| Belgium | Research Site | Gozee | |
| Belgium | Research Site | Gribomont | |
| Belgium | Research Site | Halen | |
| Belgium | Research Site | Ham | |
| Belgium | Research Site | Linkebeek | |
| Belgium | Research Site | Ukkel | |
| Canada | Research Site | Bay Roberts | Newfoundland and Labrador |
| Canada | Research Site | Cambridge | Ontario |
| Canada | Research Site | Chicoutimi | Quebec |
| Canada | Research Site | Gatineau | Quebec |
| Canada | Research Site | Granby | Quebec |
| Canada | Research Site | Kelowna | British Columbia |
| Canada | Research Site | Lachine | Quebec |
| Canada | Research Site | London | Ontario |
| Canada | Research Site | London | Ontario |
| Canada | Research Site | Mount Pearl | Newfoundland and Labrador |
| Canada | Research Site | Newmarket | Ontario |
| Canada | Research Site | Pointe-Claire | Quebec |
| Canada | Research Site | Quebec | |
| Canada | Research Site | Sarnia | Ontario |
| Canada | Research Site | St. John's | Newfoundland and Labrador |
| Canada | Research Site | Sudbury | Ontario |
| Canada | Research Site | Toronto | Ontario |
| Canada | Research Site | Toronto | Ontario |
| Canada | Research Site | Toronto | Ontario |
| Canada | Research Site | Woodstock | Ontario |
| Czechia | Research Site | Brno | |
| Czechia | Research Site | Brno | |
| Czechia | Research Site | Brno | |
| Czechia | Research Site | Olomouc | |
| Czechia | Research Site | Praha 2 | |
| Czechia | Research Site | Praha 4 | |
| Czechia | Research Site | Slany | |
| Czechia | Research Site | Svitavy | |
| Czechia | Research Site | Usti nad Orlici | |
| Czechia | Research Site | Znojmo | |
| Denmark | Research Site | Aalborg | |
| Denmark | Research Site | Ballerup | |
| Denmark | Research Site | Vejle | |
| Finland | Research Site | Helsinki | |
| Finland | Research Site | OYS | |
| Germany | Research Site | Berlin | |
| Germany | Research Site | Köln | |
| Hong Kong | Research Site | New Territories | |
| Hungary | Research Site | Budapest | |
| Hungary | Research Site | Debrecen | |
| Hungary | Research Site | Dunaujvaros | |
| Hungary | Research Site | Gyula | |
| Hungary | Research Site | Kecskemet | |
| Hungary | Research Site | Komarom | |
| Hungary | Research Site | Szolnok | |
| Hungary | Research Site | Zalaegerszeg | |
| Japan | Research Site | Chiyoda-ku | Tokyo |
| Japan | Research Site | Fujioka-shi | Gunma |
| Japan | Research Site | Fukui-shi | Fukui |
| Japan | Research Site | Hachioji-shi | Tokyo |
| Japan | Research Site | Hanyu-shi | Saitama |
| Japan | Research Site | Hitachi-shi | Ibaraki |
| Japan | Research Site | Ibaraki-shi | Osaka |
| Japan | Research Site | Ina-shi | Nagano |
| Japan | Research Site | Itabashi-ku | Tokyo |
| Japan | Research Site | Kasuga-shi | Fukuoka |
| Japan | Research Site | Kawanishi-shi | Hyogo |
| Japan | Research Site | Kobe-shi | Hyogo |
| Japan | Research Site | Kochi-shi | Kochi |
| Japan | Research Site | Koga-shi | Ibaraki |
| Japan | Research Site | Komatsu-shi | Ishikawa |
| Japan | Research Site | Kyoto-shi | Kyoto |
| Japan | Research Site | Kyoto-shi | Kyoto |
| Japan | Research Site | Maebashi-shi | Gunma |
| Japan | Research Site | Maebashi-shi | Gunma |
| Japan | Research Site | Matsumoto-shi | Nagano |
| Japan | Research Site | Mito-shi | Ibaraki |
| Japan | Research Site | Nagoya-shi | Aichi |
| Japan | Research Site | Nagoya-shi | Aichi |
| Japan | Research Site | Nagoya-shi | Aichi |
| Japan | Research Site | Sayama-shi | Saitama |
| Japan | Research Site | Shinagawa-ku | Tokyo |
| Japan | Research Site | Suwa-shi | Nagano |
| Japan | Research Site | Takamatsu-shi | Kagawa |
| Japan | Research Site | Takasaki-shi | Gunma |
| Japan | Research Site | Toda-shi | Saitama |
| Japan | Research Site | Toshima-ku | Tokyo |
| Japan | Research Site | Toyonaka-shi | Osaka |
| Netherlands | Research Site | Amsterdam | |
| Netherlands | Research Site | Hoorn | |
| Netherlands | Research Site | Utrecht | |
| Norway | Research Site | Oslo | |
| Singapore | Research Site | Singapore | |
| South Africa | Research Site | Johannesburg | Gauteng |
| South Africa | Research Site | Midrand | Gauteng |
| South Africa | Research Site | Observatory | Western Cape |
| South Africa | Research Site | Parow | Western Cape |
| Spain | Research Site | Barcelona | Cataluña |
| Spain | Research Site | Cordoba | Andalucía |
| Spain | Research Site | Madrid | |
| Spain | Research Site | Reus | Cataluña |
| Spain | Research Site | Zaragoza | Aragón |
| Sweden | Research Site | Göteborg | |
| Sweden | Research Site | Lund | |
| Sweden | Research Site | Stockholm | |
| Sweden | Research Site | Stockholm | |
| United Kingdom | Research Site | London | |
| United States | Research Site | Akron | Ohio |
| United States | Research Site | Anaheim | California |
| United States | Research Site | Arlington | Texas |
| United States | Research Site | Atlanta | Georgia |
| United States | Research Site | Auburn | Maine |
| United States | Research Site | Bethesda | Maryland |
| United States | Research Site | Birmingham | Alabama |
| United States | Research Site | Birmingham | Alabama |
| United States | Research Site | Bristol | Tennessee |
| United States | Research Site | Brockton | Massachusetts |
| United States | Research Site | Brooklyn Center | Minnesota |
| United States | Research Site | Cadiz | Ohio |
| United States | Research Site | Camp Hill | Pennsylvania |
| United States | Research Site | Carmichael | California |
| United States | Research Site | Chevy Chase | Maryland |
| United States | Research Site | Chicago | Illinois |
| United States | Research Site | Cincinnati | Ohio |
| United States | Research Site | Cincinnati | Ohio |
| United States | Research Site | Cincinnati | Ohio |
| United States | Research Site | Cleveland | Ohio |
| United States | Research Site | Colorado Springs | Colorado |
| United States | Research Site | Cortlandt Manor | New York |
| United States | Research Site | Dayton | Ohio |
| United States | Research Site | Daytona Beach | Florida |
| United States | Research Site | DeLand | Florida |
| United States | Research Site | Duncansville | Pennsylvania |
| United States | Research Site | Endwell | New York |
| United States | Research Site | Fargo | North Dakota |
| United States | Research Site | Great Falls | Montana |
| United States | Research Site | Green Cove Springs | Florida |
| United States | Research Site | Henderson | Nevada |
| United States | Research Site | Houston | Texas |
| United States | Research Site | Houston | Texas |
| United States | Research Site | Indianapolis | Indiana |
| United States | Research Site | Inglewood | California |
| United States | Research Site | Iowa City | Iowa |
| United States | Research Site | Jacksonville | Florida |
| United States | Research Site | Jacksonville | Florida |
| United States | Research Site | Las Vegas | Nevada |
| United States | Research Site | Las Vegas | Nevada |
| United States | Research Site | Little Rock | Arkansas |
| United States | Research Site | Littleton | Colorado |
| United States | Research Site | Louisville | Kentucky |
| United States | Research Site | Malvern | Arkansas |
| United States | Research Site | Marquette | Michigan |
| United States | Research Site | Melbourne | Florida |
| United States | Research Site | Miami | Florida |
| United States | Research Site | Miami | Florida |
| United States | Research Site | Mission Viejo | California |
| United States | Research Site | Mount Pleasant | South Carolina |
| United States | Research Site | Munster | Indiana |
| United States | Research Site | New York | New York |
| United States | Research Site | Newport Beach | California |
| United States | Research Site | Norfolk | Virginia |
| United States | Research Site | Norman | Oklahoma |
| United States | Research Site | Oklahoma City | Oklahoma |
| United States | Research Site | Pittsburgh | Pennsylvania |
| United States | Research Site | Ponte Vedra | Florida |
| United States | Research Site | Port Charlotte | Florida |
| United States | Research Site | Portland | Maine |
| United States | Research Site | Raleigh | North Carolina |
| United States | Research Site | Raleigh | North Carolina |
| United States | Research Site | Rapid City | South Dakota |
| United States | Research Site | Rapid City | South Dakota |
| United States | Research Site | Renton | Washington |
| United States | Research Site | Richmond | Virginia |
| United States | Research Site | San Antonio | Texas |
| United States | Research Site | Sanford | Florida |
| United States | Research Site | Savannah | Georgia |
| United States | Research Site | Seattle | Washington |
| United States | Research Site | Tacoma | Washington |
| United States | Research Site | Thousand Oaks | California |
| United States | Research Site | Tucson | Arizona |
| United States | Research Site | Tupelo | Mississippi |
| United States | Research Site | Tustin | California |
| United States | Research Site | Williamsville | New York |
| United States | Research Site | Winston-Salem | North Carolina |
| United States | Research Site | York | Pennsylvania |
| Lead Sponsor | Collaborator |
|---|---|
| Amgen |
United States, Australia, Belgium, Canada, Czechia, Denmark, Finland, Germany, Hong Kong, Hungary, Japan, Netherlands, Norway, Singapore, South Africa, Spain, Sweden, United Kingdom,
Daviglus ML, Ferdinand KC, López 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. — View 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. — View 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. — View 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. Review. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation
Toth PP, Jones SR, Monsalvo ML, Elliott-Davey M, López 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. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Number of Participants With Adverse Events | Adverse event (AE) severity assessments were made using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) grading, version 4.03, where grade 1 = mild AE, grade 2 = moderate AE, Grade 3 = severe AE, grade 4 = life-threatening AE and Grade 5 = death due to AE. | 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 | Low-density Lipoprotein Cholesterol (LDL-C) Level at Week 24 and Week 52 | Baseline of parent study and extension study weeks 24 and 52 | ||
| Secondary | Non-high-density Lipoprotein Cholesterol (Non-HDL-C) Level at Week 24 and Week 52 | Baseline of parent study and extension study weeks 24 and 52 | ||
| Secondary | Apolipoprotein B Level at Week 24 and Week 52 | Baseline of parent study and extension study weeks 24 and 52 | ||
| Secondary | Total Cholesterol/HDL-C Ratio at Week 24 and Week 52 | Baseline of parent study and extension study weeks 24 and 52 | ||
| Secondary | Apolipoprotein B/Apolipoprotein A1 Ratio at Week 24 and Week 52 | Baseline of parent study and extension study weeks 24 and 52 |
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