Fourier Open-label Extension Study in Subjects With Clinically Evident Cardiovascular Disease in Selected European Countries

NCT ID: NCT03080935

Last Updated: 2024-05-29

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 1600 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-13
• Study Completion Date: 2022-03-04

Brief Summary

This is a multicenter, open-label extension (OLE) study designed to assess the extended long-term safety of evolocumab in subjects who have completed the FOURIER trial (Study 20110118). Approximately 1600 subjects will be enrolled in this study. This study will continue for 260 weeks (approximately 5 years).

Detailed Description

This is a multicenter, open-label extension (OLE) study designed to assess the extended long-term safety of evolocumab in subjects who have completed the FOURIER trial (Study 20110118). FOURIER is a randomized placebo-controlled study of evolocumab, in patients with clinically evident atherosclerotic CVD on stable effective statin therapy. Subjects at sites participating in FOURIER OLE (Study 20160250) who are eligible and have signed the FOURIER OLE informed consent will be enrolled after completion of FOURIER.

The FOURIER OLE study requires laboratory assessments at day 1, week 12, and thereafter approximately every 6 months from day 1; the corresponding blood samples will be processed using a central laboratory.

Upon enrollment in FOURIER OLE study, subjects will receive evolocumab 140 mg every 2 weeks (Q2W) or 420 mg monthly (QM) according to their preference. Frequency and corresponding dose of administration can be changed at any scheduled time point where evolocumab is supplied to the subject, provided the appropriate supply is available. It is recommended that subjects continue the same background lipid-lowering therapy (LLT), including statin, as taken during FOURIER.

This study will continue for 260 weeks (approximately 5 years). Subjects ending administration of evolocumab should continue study assessments until the end of study. All subjects will be followed and complete procedures/assessments from enrollment through the date of study termination unless the subject has withdrawn consent, irrespective of whether the subject is continuing to receive treatment.

All deaths and cardiovascular events of interest will be reviewed by an independent external Clinical Events Committee (CEC), using standardized definitions.

Conditions

Dyslipidemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Evolocumab

Single arm study administering Evolocumab.

Group Type: EXPERIMENTAL

Evolocumab

Intervention Type: DRUG

Subjects will receive Evolocumab 140 mg every 2 weeks (Q2W) or 420 mg monthly (QM), according to the subject's preference.

Interventions

Evolocumab

Subjects will receive Evolocumab 140 mg every 2 weeks (Q2W) or 420 mg monthly (QM), according to the subject's preference.

Intervention Type: DRUG

Other Intervention Names

AMG 145

Eligibility Criteria

Inclusion Criteria

• Subject has provided informed consent prior to initiation of any study-specific activities/procedures.
• Subject had completed FOURIER (Study 20110118) while still receiving assigned Investigational Product.

Exclusion Criteria

• Permanent discontinuation of Investigational Product during FOURIER for any reason including an adverse event or serious adverse event.
• Currently receiving treatment in another investigational device or drug study, or less than 4 weeks since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded.
• Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the subject and investigator's knowledge.
• 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 known sensitivity to any of the active substances or excipients (eg, sodium acetate) to be administered during dosing.
• Females who are pregnant or breastfeeding or planning to become pregnant or breastfeed during treatment with evolocumab and for an additional 15 weeks after treatment with evolocumab discontinues.
• Female subjects of childbearing potential unwilling to use an acceptable method of effective contraception during treatment and for an additional 15 weeks after the last dose of protocol-required therapies.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MD

Role: STUDY_DIRECTOR

Amgen

Locations

Algemeen Stedelijk Ziekenhuis Aalst

Aalst, , Belgium

Onze Lieve Vrouw Ziekenhuis Aalst

Aalst, , Belgium

Ziekenhuis Netwerk Antwerpen Middelheim

Antwerp, , Belgium

Ziekenhuis Netwerk Antwerpen Stuivenberg

Antwerp, , Belgium

Imelda Ziekenhuis vzw

Bonheiden, , Belgium

Centre Hospitalier Universitaire Brugmann

Brussels, , Belgium

Cliniques universitaires de Bruxelles Hopital Erasme

Brussels, , Belgium

Universite Catholique de Louvain Cliniques Universitaires Saint Luc

Brussels, , Belgium

Algemeen Ziekenhuis Sint Lucas

Ghent, , Belgium

Universitair Ziekenhuis Gent

Ghent, , Belgium

Medif sprl

Gozée, , Belgium

Centre Hospitalier Universitaire de Tivoli

La Louvière, , Belgium

Centres Hospitaliers Jolimont - Hopital de Jolimont

La Louvière, , Belgium

Centre Hospitalier Regional de la Citadelle

Liège, , Belgium

Centre Hospitalier Universitaire de Liege - Sart Tilman

Liège, , Belgium

Algemeen Ziekenhuis Turnhout

Turnhout, , Belgium

Aalborg Hospital

Aalborg, , Denmark

Center for Clinical and Basic Research Aalborg

Aalborg, , Denmark

Aarhus Universitetshospital

Aarhus N, , Denmark

Centre for Clinical and Basic Research Ballerup

Ballerup Municipality, , Denmark

Sydvestjysk Sygehus

Esbjerg, , Denmark

Frederiksberg/Bispebjerg Hospitaler

Frederiksberg, , Denmark

Glostrup Hospital

Glostrup Municipality, , Denmark

Hvidovre Hospital

Hvidovre, , Denmark

Amager Hospital

København S, , Denmark

Odense Universitetssygehus

Odense, , Denmark

Sjaellands Universitetshospital, Roskilde

Roskilde, , Denmark

Svendborg Sygehus

Svendborg, , Denmark

Center for Clinical and Basic Research Vejle

Vejle, , Denmark

Regionshospitalet Viborg

Viborg, , Denmark

Centre Hospitalier Regional Universitaire de Besancon, Hopital Jean Minjoz

Besançon, , France

Centre Hospitalier Régional Universitaire de Tours - Hôpital Trousseau

Chambray-lès-Tours, , France

Hopital Louis Pasteur

Le Coudray, , France

Centre Hospitalier Regional Universitaire de Montpellier - Hopital Arnaud de Villeneuve

Montpellier, , France

Centre Hospitalier Universitaire de Nantes - Hopital Guillaume et Rene Laennec

Nantes, , France

Nouvelles Cliniques Nantaises

Nantes, , France

Centre Hospitalier Universitaire de Nice - Hopital Pasteur

Nice, , France

Hopital Lariboisiere

Paris, , France

Hopital Pitie-Salpetriere

Paris, , France

Centre Hospitalier de Pau - Hopital Francois Mitterrand

Pau, , France

Centre Hospitalier Universitaire de Reims - Hopital Robert Debre

Reims, , France

Centre Hospitalier Universitaire de Toulouse - Hopital Rangueil

Toulouse, , France

Centre Hospitalier Intercommunal Haute Saone

Vesoul, , France

Universitaets-Herzzentrum Freiburg - Bad Krozingen

Bad Krozingen, , Germany

Klinische Forschung Berlin GbR

Berlin, , Germany

Vivantes Klinikum Neukölln

Berlin, , Germany

Deutsches Rotes Kreuz Kliniken Berlin Köpenick

Berlin, , Germany

Deutsches Herzzentrum Berlin

Berlin, , Germany

Sankt-Johannes-Hospital

Dortmund, , Germany

Gesellschaft fur Wissens und Technologietransfer der Technischen Uni Dresden

Dresden, , Germany

Ambulantes Herzzentrum Kassel

Kassel, , Germany

Universitätsklinikum Köln

Köln, , Germany

Otto von Guericke Universität Magdeburg

Magdeburg, , Germany

Johannes Gutenberg Universität Mainz

Mainz, , Germany

Herz-Gefäß-Zentrum Nymphenburg am Klinikum Dritter Orden

München, , Germany

Deutsches Herzzentrum München des Freistaates Bayern

München, , Germany

Robert Bosch Krankenhaus

Stuttgart, , Germany

Universitätsklinikum Ulm

Ulm, , Germany

Forschungszentrum Ruhr

Witten, , Germany

Helios Universitätsklinikum Wuppertal

Wuppertal, , Germany

Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII

Bergamo, , Italy

Azienda Ospedaliero Universitaria Careggi

Florence, , Italy

Centro Cardiologico Monzino

Milan, , Italy

Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda

Milan, , Italy

Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello

Palermo, , Italy

Fondazione IRCCS Policlinico San Matteo

Pavia, , Italy

Azienda Ospedaliera di Perugia Ospedale Santa Maria della Misericordia

Perugia, , Italy

Fondazione Toscana Gabriele Monasterio, Stabilimento Ospedaliero di Pisa

Pisa, , Italy

Azienda Ospedaliera Universitaria Senese Policlinico Le Scotte

Siena, , Italy

Hospital Garcia de Orta, EPE

Almada, , Portugal

Centro Hospitalar e Universitario de Coimbra EPE

Coimbra, , Portugal

Centro Hospitalar Cova da Beira, EPE - Hospital Pero da Covilha

Covilha, , Portugal

Hospital Cuf Infante Santo

Lisbon, , Portugal

Centro Hospitalar de Lisboa Ocidental, EPE - Hospital Sao Francisco Xavier

Lisbon, , Portugal

Centro Hospitalar de Setubal EPE Hospital de Sao Bernardo

Setúbal, , Portugal

Falu Lasarett

Falun, , Sweden

Helsingborgs Lasarett

Helsingborg, , Sweden

Länssjukhuset Ryhov

Jönköping, , Sweden

Sunderby Sjukhus

Luleå, , Sweden

Skanes Universitetssjukhus

Lund, , Sweden

Capio Citykliniken

Lund, , Sweden

Universitetssjukhuset Ã-rebro

Örebro, , Sweden

Ostersunds sjukhus

Östersund, , Sweden

Akardo MedSite

Stockholm, , Sweden

Norrlands Universitetssjukhus

Umeå, , Sweden

Countries

Belgium; Denmark; France; Germany; Italy; Portugal; Sweden

References

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.

Reference Type: BACKGROUND

PMID: 36031810 (View on PubMed)

McClintick DJ, O'Donoghue ML, De Ferrari GM, Ferreira J, Ran X, Im K, Lopez JAG, Elliott-Davey M, Wang B, Monsalvo ML, Atar D, Keech A, Giugliano RP, Sabatine MS. Long-Term Efficacy of Evolocumab in Patients With or Without Multivessel Coronary Disease. J Am Coll Cardiol. 2024 Feb 13;83(6):652-664. doi: 10.1016/j.jacc.2023.11.029.

Reference Type: BACKGROUND

PMID: 38325990 (View on PubMed)

Katsiki N, Athyros VG, Mikhailidis DP, Mantzoros C. Proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors: Shaping the future after the further cardiovascular outcomes research with PCSK9 inhibition in subjects with elevated risk (FOURIER) trial. Metabolism. 2017 Sep;74:43-46. doi: 10.1016/j.metabol.2017.04.007. Epub 2017 Apr 20. No abstract available.

Reference Type: DERIVED

PMID: 28477848 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

2016-004066-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

20160250

Identifier Type: -

Identifier Source: org_study_id