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

NCT03080935 | Terminated Phase 3 Results FDA Drug

• 2 other identifiers: 201602502016-004066-26
• Study Type: interventional
• Target: 1,600
• Locations: 7 countries
• Sites: 85

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).

Conditions

Dyslipidemia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit

  Baseline, 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

  Baseline, Week 12, Week 24, Week 48, Week 72, Week 96, Week 120, Week 144, Week 168, Week 192, Week 216, Week 260

Study Arms (1)

Evolocumab

EXPERIMENTAL

Single arm study administering Evolocumab.

Drug: Evolocumab

Interventions

Evolocumab DRUG

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

Also known as: AMG 145

Evolocumab

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Amgen: lead

Study Sites (85)

Algemeen Stedelijk Ziekenhuis Aalst

Aalst, 9300, Belgium

Location

Onze Lieve Vrouw Ziekenhuis Aalst

Aalst, 9300, Belgium

Location

Ziekenhuis Netwerk Antwerpen Middelheim

Antwerp, 2020, Belgium

Location

Ziekenhuis Netwerk Antwerpen Stuivenberg

Antwerp, 2060, Belgium

Location

Imelda Ziekenhuis vzw

Bonheiden, 2820, Belgium

Location

Centre Hospitalier Universitaire Brugmann

Brussels, 1020, Belgium

Location

Cliniques universitaires de Bruxelles Hopital Erasme

Brussels, 1070, Belgium

Location

Universite Catholique de Louvain Cliniques Universitaires Saint Luc

Brussels, 1200, Belgium

Location

Algemeen Ziekenhuis Sint Lucas

Ghent, 9000, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

Location

Medif sprl

Gozée, 6534, Belgium

Location

Centre Hospitalier Universitaire de Tivoli

La Louvière, 7100, Belgium

Location

Centres Hospitaliers Jolimont - Hopital de Jolimont

La Louvière, 7100, Belgium

Location

Centre Hospitalier Regional de la Citadelle

Liège, 4000, Belgium

Location

Centre Hospitalier Universitaire de Liege - Sart Tilman

Liège, 4000, Belgium

Location

Algemeen Ziekenhuis Turnhout

Turnhout, 2300, Belgium

Location

Aalborg Hospital

Aalborg, 9000, Denmark

Location

Center for Clinical and Basic Research Aalborg

Aalborg, 9000, Denmark

Location

Aarhus Universitetshospital

Aarhus N, 8200, Denmark

Location

Centre for Clinical and Basic Research Ballerup

Ballerup Municipality, 2750, Denmark

Location

Sydvestjysk Sygehus

Esbjerg, 6700, Denmark

Location

Frederiksberg/Bispebjerg Hospitaler

Frederiksberg, 2000, Denmark

Location

Glostrup Hospital

Glostrup Municipality, 2600, Denmark

Location

Hvidovre Hospital

Hvidovre, 2650, Denmark

Location

Amager Hospital

København S, 2300, Denmark

Location

Odense Universitetssygehus

Odense, 5000, Denmark

Location

Sjaellands Universitetshospital, Roskilde

Roskilde, 4000, Denmark

Location

Svendborg Sygehus

Svendborg, 5700, Denmark

Location

Center for Clinical and Basic Research Vejle

Vejle, 7100, Denmark

Location

Regionshospitalet Viborg

Viborg, 8800, Denmark

Location

Centre Hospitalier Regional Universitaire de Besancon, Hopital Jean Minjoz

Besançon, 25030, France

Location

Centre Hospitalier Régional Universitaire de Tours - Hôpital Trousseau

Chambray-lès-Tours, 37170, France

Location

Hopital Louis Pasteur

Le Coudray, 28630, France

Location

Centre Hospitalier Regional Universitaire de Montpellier - Hopital Arnaud de Villeneuve

Montpellier, 34295, France

Location

Centre Hospitalier Universitaire de Nantes - Hopital Guillaume et Rene Laennec

Nantes, 44093, France

Location

Nouvelles Cliniques Nantaises

Nantes, 44202, France

Location

Centre Hospitalier Universitaire de Nice - Hopital Pasteur

Nice, 06000, France

Location

Hopital Lariboisiere

Paris, 75010, France

Location

Hopital Pitie-Salpetriere

Paris, 75013, France

Location

Centre Hospitalier de Pau - Hopital Francois Mitterrand

Pau, 64000, France

Location

Centre Hospitalier Universitaire de Reims - Hopital Robert Debre

Reims, 51100, France

Location

Centre Hospitalier Universitaire de Toulouse - Hopital Rangueil

Toulouse, 31059, France

Location

Centre Hospitalier Intercommunal Haute Saone

Vesoul, 70014, France

Location

Universitaets-Herzzentrum Freiburg - Bad Krozingen

Bad Krozingen, 79189, Germany

Location

Klinische Forschung Berlin GbR

Berlin, 10787, Germany

Location

Vivantes Klinikum Neukölln

Berlin, 12351, Germany

Location

Deutsches Rotes Kreuz Kliniken Berlin Köpenick

Berlin, 12559, Germany

Location

Deutsches Herzzentrum Berlin

Berlin, 13353, Germany

Location

Sankt-Johannes-Hospital

Dortmund, 44137, Germany

Location

Gesellschaft fur Wissens und Technologietransfer der Technischen Uni Dresden

Dresden, 01307, Germany

Location

Ambulantes Herzzentrum Kassel

Kassel, 34121, Germany

Location

Universitätsklinikum Köln

Köln, 50937, Germany

Location

Otto von Guericke Universität Magdeburg

Magdeburg, 39120, Germany

Location

Johannes Gutenberg Universität Mainz

Mainz, 55131, Germany

Location

Herz-Gefäß-Zentrum Nymphenburg am Klinikum Dritter Orden

München, 80333, Germany

Location

Deutsches Herzzentrum München des Freistaates Bayern

München, 80636, Germany

Location

Robert Bosch Krankenhaus

Stuttgart, 70376, Germany

Location

Universitätsklinikum Ulm

Ulm, 89081, Germany

Location

Forschungszentrum Ruhr

Witten, 58455, Germany

Location

Helios Universitätsklinikum Wuppertal

Wuppertal, 42117, Germany

Location

Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII

Bergamo, 24127, Italy

Location

Azienda Ospedaliero Universitaria Careggi

Florence, 50139, Italy

Location

Centro Cardiologico Monzino

Milan, 20138, Italy

Location

Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda

Milan, 20162, Italy

Location

Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello

Palermo, 90146, Italy

Location

Fondazione IRCCS Policlinico San Matteo

Pavia, 27100, Italy

Location

Azienda Ospedaliera di Perugia Ospedale Santa Maria della Misericordia

Perugia, 06129, Italy

Location

Fondazione Toscana Gabriele Monasterio, Stabilimento Ospedaliero di Pisa

Pisa, 56124, Italy

Location

Azienda Ospedaliera Universitaria Senese Policlinico Le Scotte

Siena, 53100, Italy

Location

Hospital Garcia de Orta, EPE

Almada, 2801-951, Portugal

Location

Centro Hospitalar e Universitario de Coimbra EPE

Coimbra, 3000-075, Portugal

Location

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

Covilha, 6200-251, Portugal

Location

Hospital Cuf Infante Santo

Lisbon, 1350-352, Portugal

Location

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

Lisbon, 1449-005, Portugal

Location

Centro Hospitalar de Setubal EPE Hospital de Sao Bernardo

Setúbal, 2910-446, Portugal

Location

Falu Lasarett

Falun, 791 82, Sweden

Location

Helsingborgs Lasarett

Helsingborg, 252 47, Sweden

Location

Länssjukhuset Ryhov

Jönköping, 551 85, Sweden

Location

Sunderby Sjukhus

Luleå, 971 80, Sweden

Location

Skanes Universitetssjukhus

Lund, 221 85, Sweden

Location

Capio Citykliniken

Lund, 222 21, Sweden

Location

Universitetssjukhuset Ã-rebro

Örebro, 701 85, Sweden

Location

Ostersunds sjukhus

Östersund, 831 83, Sweden

Location

Akardo MedSite

Stockholm, 117 27, Sweden

Location

Norrlands Universitetssjukhus

Umeå, 901 85, Sweden

Location

Related Publications (3)

• 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.

  PMID: 36031810 BACKGROUND

• 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.

  PMID: 38325990 BACKGROUND

• 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.

  PMID: 28477848 DERIVED

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Dyslipidemias

Interventions

evolocumab

Condition Hierarchy (Ancestors)

Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Limitations and Caveats

This study was terminated to coincide with the completion of study 20130295 (NCT02867813). The study was not terminated due to any safety findings.

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Masking Details: Open label
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 10, 2017
• First Posted: March 15, 2017
• Study Start: March 13, 2017
• Primary Completion: March 4, 2022
• Study Completion: March 4, 2022
• Last Updated: May 29, 2024
• Results First Posted: January 11, 2023

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.
• 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.

Locations

IT (9); BE (16); SE (10); FR (13); PT (6); DE (17); DK (14)