Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk Open-label Extension (FOURIER OLE)

A Multicenter, Open-label, Single-arm, Extension Study to Assess Long-term Safety of Evolocumab Therapy in Patients With Clinically Evident Cardiovascular Disease

The primary clinical hypothesis is that long-term exposure of evolocumab will be safe and well tolerated in subjects with clinically evident atherosclerotic cardiovascular disease (CVD).

Study Overview

• Status: Completed
• Conditions: Dyslipidemia
• Intervention / Treatment: Biological: Evolocumab

Detailed Description

This is a multicenter, open-label extension study designed to assess the long-term safety of evolocumab in subjects who completed the FOURIER study,which is a randomized placebo-controlled study of evolocumab in subjects with clinically evident atherosclerotic CVD on stable effective statin therapy. Eligible subjects at sites participating in FOURIER OLE who have signed the FOURIER OLE informed consent may be enrolled at the completion of FOURIER study.

• Study Type: Interventional
• Enrollment (Actual): 5035
• Phase: Phase 3

Contacts and Locations

Study Locations

• Czechia
  • Brno, Czechia, 625 00
    • Research Site
  • Brno, Czechia, 603 00
    • Research Site
  • Brno, Czechia, 638 00
    • Research Site
  • Jihlava, Czechia, 586 33
    • Research Site
  • Liberec, Czechia, 460 63
    • Research Site
  • Mohelnice, Czechia, 789 85
    • Research Site
  • Ostrava, Czechia, 728 80
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  • Ostrava-Dubina, Czechia, 700 30
    • Research Site
  • Praha 2, Czechia, 128 08
    • Research Site
  • Prerov, Czechia, 750 02
    • Research Site
  • Pribram VIII, Czechia, 261 01
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  • Znojmo, Czechia, 669 02
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• Hungary
  • Bekescsaba, Hungary, 5600
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  • Miskolc, Hungary, 3529
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  • Nyiregyhaza, Hungary, 4400
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• Poland
  • Bielsko-Biala, Poland, 43-316
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  • Bydgoszcz, Poland, 85-094
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  • Gdansk, Poland, 80-542
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  • Gdynia, Poland, 81-402
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  • Gdynia, Poland, 81-472
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  • Gizycko, Poland, 11-500
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  • Katowice, Poland, 40-084
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  • Kielce, Poland, 25-020
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  • Krakow, Poland, 31-202
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  • Krakow, Poland, 30-082
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  • Krakow, Poland, 31-216
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  • Lodz, Poland, 91-347
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  • Lublin, Poland, 20-857
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  • Nysa, Poland, 48-300
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  • Olsztyn, Poland, 10-010
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  • Plock, Poland, 09-402
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  • Poznan, Poland, 61-853
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  • Pszczyna, Poland, 43-200
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  • Pulawy, Poland, 24-100
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  • Ruda Slaska, Poland, 41-709
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  • Skierniewice, Poland, 96-100
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  • Staszow, Poland, 28-200
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  • Swidnik, Poland, 21-040
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  • Tarnow, Poland, 33-100
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  • Torun, Poland, 87-100
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  • Warszawa, Poland, 02-097
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  • Warszawa, Poland, 02-507
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  • Warszawa, Poland, 04-628
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  • Wloclawek, Poland, 87-800
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  • Wroclaw, Poland, 50-349
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  • Zamosc, Poland, 22-400
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• Russian Federation
  • Moscow, Russian Federation, 129090
    • Research Site
  • Saint-Petersburg, Russian Federation, 197022
    • Research Site
  • Saint-Petersburg, Russian Federation, 199106
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  • Saint-Petersburg, Russian Federation, 192289
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  • Saratov, Russian Federation, 410054
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• Slovakia
  • Kosice, Slovakia, 040 22
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  • Svidnik, Slovakia, 089 01
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• Ukraine
  • Zaporizhzhya, Ukraine, 69600
    • Research Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
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    • Huntsville, Alabama, United States, 35801
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  • Arizona
    • Phoenix, Arizona, United States, 85018
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  • California
    • Banning, California, United States, 92220
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    • Long Beach, California, United States, 90807
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    • Oceanside, California, United States, 92056
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    • Oxnard, California, United States, 93030
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    • Palm Springs, California, United States, 92262
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    • Roseville, California, United States, 95661
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    • San Diego, California, United States, 92161
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    • San Pedro, California, United States, 90732
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    • Tarzana, California, United States, 91356
      • Research Site
    • Torrance, California, United States, 90502
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    • Valley Village, California, United States, 91607
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  • Colorado
    • Aurora, Colorado, United States, 80012
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    • Colorado Springs, Colorado, United States, 80909
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    • Denver, Colorado, United States, 80218
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    • Littleton, Colorado, United States, 80120
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  • Florida
    • Boynton Beach, Florida, United States, 33472
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    • Clearwater, Florida, United States, 33756
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    • Crystal River, Florida, United States, 34429
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    • Daytona Beach, Florida, United States, 32117
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    • Hollywood, Florida, United States, 33021
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    • Hollywood, Florida, United States, 33024
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    • Jacksonville, Florida, United States, 32216
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    • Largo, Florida, United States, 33777
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    • Miami, Florida, United States, 33173
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    • New Port Richey, Florida, United States, 34653
      • Research Site
    • Pensacola, Florida, United States, 32501
      • Research Site
    • Ponte Vedra Beach, Florida, United States, 32081
      • Research Site
    • Port Charlotte, Florida, United States, 33952
      • Research Site
    • Saint Petersburg, Florida, United States, 33713
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    • Sarasota, Florida, United States, 34232
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    • Sarasota, Florida, United States, 34239
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  • Georgia
    • Athens, Georgia, United States, 30606
      • Research Site
    • Atlanta, Georgia, United States, 30342
      • Research Site
    • Augusta, Georgia, United States, 30909
      • Research Site
    • Dunwoody, Georgia, United States, 30338
      • Research Site
    • Gainesville, Georgia, United States, 30501
      • Research Site
    • Savannah, Georgia, United States, 31406
      • Research Site
    • Suwanee, Georgia, United States, 30024
      • Research Site
  • Idaho
    • Coeur d'Alene, Idaho, United States, 83814
      • Research Site
    • Meridian, Idaho, United States, 83642
      • Research Site
  • Illinois
    • Addison, Illinois, United States, 60101
      • Research Site
    • Belleville, Illinois, United States, 62220
      • Research Site
    • Chicago, Illinois, United States, 60616
      • Research Site
    • Jerseyville, Illinois, United States, 62052
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  • Indiana
    • Evansville, Indiana, United States, 47714
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    • Munster, Indiana, United States, 46321
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  • Iowa
    • Iowa City, Iowa, United States, 52242
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    • Waterloo, Iowa, United States, 50702
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  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Research Site
    • Wichita, Kansas, United States, 67203
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  • Kentucky
    • Lexington, Kentucky, United States, 40503
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  • Louisiana
    • Hammond, Louisiana, United States, 70403
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    • Metairie, Louisiana, United States, 70006
      • Research Site
    • Monroe, Louisiana, United States, 71201
      • Research Site
    • Natchitoches, Louisiana, United States, 71457
      • Research Site
    • Slidell, Louisiana, United States, 70458
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  • Maine
    • Auburn, Maine, United States, 04210
      • Research Site
    • Bangor, Maine, United States, 04401
      • Research Site
    • Biddeford, Maine, United States, 04005
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  • Maryland
    • Baltimore, Maryland, United States, 21204
      • Research Site
    • Columbia, Maryland, United States, 21044
      • Research Site
    • Salisbury, Maryland, United States, 21804
      • Research Site
  • Massachusetts
    • Haverhill, Massachusetts, United States, 01830
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    • Newton, Massachusetts, United States, 02459
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  • Michigan
    • Grandville, Michigan, United States, 49418
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    • Lansing, Michigan, United States, 48912
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    • Muskegon, Michigan, United States, 49444
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    • Saginaw, Michigan, United States, 48601
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  • Minnesota
    • Saint Cloud, Minnesota, United States, 56303
      • Research Site
    • Saint Paul, Minnesota, United States, 55102
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  • Mississippi
    • Tupelo, Mississippi, United States, 38801
      • Research Site
  • Missouri
    • Kansas City, Missouri, United States, 64128
      • Research Site
    • Saint Louis, Missouri, United States, 63128
      • Research Site
  • Montana
    • Kalispell, Montana, United States, 59901
      • Research Site
  • Nebraska
    • Lincoln, Nebraska, United States, 68506
      • Research Site
  • Nevada
    • Las Vegas, Nevada, United States, 89148
      • Research Site
  • New Jersey
    • Voorhees, New Jersey, United States, 08043
      • Research Site
  • New York
    • Brooklyn, New York, United States, 11206
      • Research Site
    • Cortlandt Manor, New York, United States, 10567
      • Research Site
    • New Hyde Park, New York, United States, 11042
      • Research Site
    • New Windsor, New York, United States, 12553
      • Research Site
    • New York, New York, United States, 10029
      • Research Site
    • Rochester, New York, United States, 14609
      • Research Site
    • West Seneca, New York, United States, 14224
      • Research Site
    • Williamsville, New York, United States, 14221
      • Research Site
  • North Carolina
    • Calabash, North Carolina, United States, 28467
      • Research Site
    • Charlotte, North Carolina, United States, 28204
      • Research Site
    • Greensboro, North Carolina, United States, 27408
      • Research Site
    • Hickory, North Carolina, United States, 28601
      • Research Site
    • High Point, North Carolina, United States, 27262
      • Research Site
    • Mooresville, North Carolina, United States, 28117
      • Research Site
    • Statesville, North Carolina, United States, 28625
      • Research Site
    • Tabor City, North Carolina, United States, 28463
      • Research Site
    • Wilmington, North Carolina, United States, 28401
      • Research Site
    • Winston-Salem, North Carolina, United States, 27103
      • Research Site
  • North Dakota
    • Fargo, North Dakota, United States, 58122
      • Research Site
  • Ohio
    • Canton, Ohio, United States, 44710
      • Research Site
    • Cincinnati, Ohio, United States, 45219
      • Research Site
    • Columbus, Ohio, United States, 43215
      • Research Site
    • Columbus, Ohio, United States, 43201
      • Research Site
    • Dayton, Ohio, United States, 45414
      • Research Site
    • Elyria, Ohio, United States, 44035
      • Research Site
    • Marion, Ohio, United States, 43302
      • Research Site
    • Sandusky, Ohio, United States, 44870
      • Research Site
    • Springfield, Ohio, United States, 45505
      • Research Site
    • Toledo, Ohio, United States, 43615
      • Research Site
    • Willoughby, Ohio, United States, 44094
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  • Oklahoma
    • Pryor, Oklahoma, United States, 74361
      • Research Site
    • Tulsa, Oklahoma, United States, 74133
      • Research Site
  • Oregon
    • Portland, Oregon, United States, 97225
      • Research Site
  • Pennsylvania
    • Camp Hill, Pennsylvania, United States, 17011
      • Research Site
    • Chambersburg, Pennsylvania, United States, 17201
      • Research Site
    • Philadelphia, Pennsylvania, United States, 19152
      • Research Site
    • Pittsburgh, Pennsylvania, United States, 15206
      • Research Site
  • Rhode Island
    • Pawtucket, Rhode Island, United States, 02860
      • Research Site
  • South Carolina
    • Charleston, South Carolina, United States, 29407
      • Research Site
    • Indian Land, South Carolina, United States, 29707
      • Research Site
    • Moncks Corner, South Carolina, United States, 29461
      • Research Site
    • North Myrtle Beach, South Carolina, United States, 29582
      • Research Site
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Research Site
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Research Site
    • Memphis, Tennessee, United States, 38104
      • Research Site
    • Nashville, Tennessee, United States, 37203
      • Research Site
    • Tullahoma, Tennessee, United States, 37388
      • Research Site
  • Texas
    • Austin, Texas, United States, 78758
      • Research Site
    • Houston, Texas, United States, 77030
      • Research Site
    • Houston, Texas, United States, 77025
      • Research Site
    • Kerrville, Texas, United States, 78028
      • Research Site
    • Plano, Texas, United States, 75024
      • Research Site
    • Plano, Texas, United States, 75023
      • Research Site
    • San Antonio, Texas, United States, 78229
      • Research Site
    • Wichita Falls, Texas, United States, 76301
      • Research Site
  • Utah
    • Layton, Utah, United States, 84041
      • Research Site
    • West Jordan, Utah, United States, 84088
      • Research Site
  • Virginia
    • Burke, Virginia, United States, 22015
      • Research Site
    • Falls Church, Virginia, United States, 22042
      • Research Site
    • Richmond, Virginia, United States, 23294
      • Research Site
    • Suffolk, Virginia, United States, 23435
      • Research Site
  • Washington
    • Federal Way, Washington, United States, 98003
      • Research Site
    • Seattle, Washington, United States, 98195
      • Research Site
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54301
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject has provided informed consent before initiation of any study-specific activities/procedures
• Subject has completed FOURIER (Study 20110118) while still receiving assigned investigational product.

Exclusion Criteria:

• Investigational product was permanently discontinued during FOURIER for any reason, including an adverse event or serious adverse event
• Subject is currently receiving treatment in another investigational device or drug study, or ended treatment on another investigational device or drug study(ies) within less than 4 weeks. Other investigational procedures while participating in this study are excluded
• Subject is not likely to be available to complete protocol-required study visits or procedures and/or to comply with required study procedures to the best of the subject's and investigator's knowledge
• Subject has a history or evidence of any other clinically significant disorder, condition, or disease that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion
• Subject has a known sensitivity to any of the active substances or excipients (eg, sodium acetate) to be administered during dosing
• Female subject is pregnant or breastfeeding or is planning to become pregnant or planning to breastfeed during treatment with evolocumab and within 15 weeks after the end of treatment with evolocumab
• Female subjects of childbearing potential who are not willing to use an acceptable method(s) of effective birth control during treatment with evolocumab and for an additional 15 weeks after the end of treatment with evolocumab are excluded

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: evolocumab (AMG 145); All subjects are randomized to a single arm and will receive evolocumab 140mg every two weeks (Q2W) or 420mg monthly (QM) according to subject's preference.	Biological: Evolocumab; subjects will receive evolocumab 140 mg every 2 weeks (Q2W) or 420 mg monthly (QM), according to the subject's preference.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Experienced an Adverse Event	All adverse event summaries for the primary analysis of the primary endpoint (OLE study period only) included all treatment-emergent events reported on the Event electronic case report form (eCRF), including CEC positively reviewed events and disease-related events.	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit	Week 12, Week 24, Week 48, Week 72, Week 96, Week 120, Week 144, Week 168, Week 192, Week 216, Week 260
Percentage of Participants Who Achieved an LDL-C Level < 40 mg/dL	Week 12, Week 24, Week 48, Week 72, Week 96, Week 120, Week 144, Week 168, Week 192, Week 216, Week 260

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

General Publications

• O'Donoghue ML, Giugliano RP, Wiviott SD, Atar D, Keech A, Kuder JF, Im K, Murphy SA, Flores-Arredondo JH, Lopez JAG, Elliott-Davey M, Wang B, Monsalvo ML, Abbasi S, Sabatine MS. Long-Term Evolocumab in Patients With Established Atherosclerotic Cardiovascular Disease. Circulation. 2022 Oct 11;146(15):1109-1119. doi: 10.1161/CIRCULATIONAHA.122.061620. Epub 2022 Aug 29.
• Gaba P, O'Donoghue ML, Park JG, Wiviott SD, Atar D, Kuder JF, Im K, Murphy SA, De Ferrari GM, Gaciong ZA, Toth K, Gouni-Berthold I, Lopez-Miranda J, Schiele F, Mach F, Flores-Arredondo JH, Lopez JAG, Elliott-Davey M, Wang B, Monsalvo ML, Abbasi S, Giugliano RP, Sabatine MS. Association Between Achieved Low-Density Lipoprotein Cholesterol Levels and Long-Term Cardiovascular and Safety Outcomes: An Analysis of FOURIER-OLE. Circulation. 2023 Feb 13. doi: 10.1161/CIRCULATIONAHA.122.063399. Online ahead of print.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): September 2, 2016
• Primary Completion (Actual): March 21, 2022
• Study Completion (Actual): March 21, 2022

Study Registration Dates

• First Submitted: July 20, 2016
• First Submitted That Met QC Criteria: August 11, 2016
• First Posted (Estimate): August 16, 2016

Study Record Updates

• Last Update Posted (Actual): April 7, 2023
• Last Update Submitted That Met QC Criteria: April 5, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Hypercholesterolemia; High Cholesterol; Lowering cholesterol; Treatment for high cholesterol; Lowering high cholesterol
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Dyslipidemias; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Evolocumab
• Other Study ID Numbers: 20130295; 2015-004780-36 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
• IPD Sharing Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR