Clinical trial NCT03080935: Fourier Open-label Extension Study in Subjects With Clinically Evident Cardiovascular Disease in Selected European Countries
Official title: A Multicenter, Open-label, Single-arm, Extension Study to Assess Long-term Safety of Evolocumab Therapy in Subjects With Clinically Evident Cardiovascular Disease in Selected European Countries
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Dyslipidemia
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2017-03-15
Enrollment: 1600
Sex: ALL
Minimum age (years): 40
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Number of Participants Who Experienced an Adverse Event
timeFrame: Up to 5 years
Secondary outcomes:
measure: Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit
timeFrame: Baseline, Week 12, Week 24, Week 48, Week 72, Week 96, Week 120, Week 144, Week 168, Week 192, Week 216, Week 260
measure: Percentage of Participants Who Achieved an LDL-C Level < 40 mg/dL
timeFrame: Baseline, Week 12, Week 24, Week 48, Week 72, Week 96, Week 120, Week 144, Week 168, Week 192, Week 216, Week 260
Other outcomes:
Locations:
city: Aalst
country: Belgium
facility: Algemeen Stedelijk Ziekenhuis Aalst
city: Aalst
country: Belgium
facility: Onze Lieve Vrouw Ziekenhuis Aalst
city: Antwerpen
country: Belgium
facility: Ziekenhuis Netwerk Antwerpen Middelheim
city: Antwerpen
country: Belgium
facility: Ziekenhuis Netwerk Antwerpen Stuivenberg
city: Bonheiden
country: Belgium
facility: Imelda Ziekenhuis vzw
city: Brussels
country: Belgium
facility: Centre Hospitalier Universitaire Brugmann
city: Brussels
country: Belgium
facility: Cliniques universitaires de Bruxelles Hopital Erasme
city: Bruxelles
country: Belgium
facility: Universite Catholique de Louvain Cliniques Universitaires Saint Luc
city: Gent
country: Belgium
facility: Algemeen Ziekenhuis Sint Lucas
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Gozee
country: Belgium
facility: Medif sprl
city: La LouviÃ¨re
country: Belgium
facility: Centre Hospitalier Universitaire de Tivoli
city: La LouviÃ¨re
country: Belgium
facility: Centres Hospitaliers Jolimont - Hopital de Jolimont
city: Liege
country: Belgium
facility: Centre Hospitalier Universitaire de Liege - Sart Tilman
city: LiÃ¨ge
country: Belgium
facility: Centre Hospitalier Regional de la Citadelle
city: Turnhout
country: Belgium
facility: Algemeen Ziekenhuis Turnhout
city: Aalborg
country: Denmark
facility: Aalborg Hospital
city: Aalborg
country: Denmark
facility: Center for Clinical and Basic Research Aalborg
city: Aarhus N
country: Denmark
facility: Aarhus Universitetshospital
city: Ballerup
country: Denmark
facility: Centre for Clinical and Basic Research Ballerup
city: Esbjerg
country: Denmark
facility: Sydvestjysk Sygehus
city: Frederiksberg
country: Denmark
facility: Frederiksberg/Bispebjerg Hospitaler
city: Glostrup
country: Denmark
facility: Glostrup Hospital
city: Hvidovre
country: Denmark
facility: Hvidovre Hospital
city: Kobenhavn S
country: Denmark
facility: Amager Hospital
city: Odense
country: Denmark
facility: Odense Universitetssygehus
city: Roskilde
country: Denmark
facility: Sjaellands Universitetshospital, Roskilde
city: Svendborg
country: Denmark
facility: Svendborg Sygehus
city: Vejle
country: Denmark
facility: Center for Clinical and Basic Research Vejle
city: Viborg
country: Denmark
facility: Regionshospitalet Viborg
city: Besancon cedex
country: France
facility: Centre Hospitalier Regional Universitaire de Besancon, Hopital Jean Minjoz
city: Chambray les Tours
country: France
facility: Centre Hospitalier RÃ©gional Universitaire de Tours - HÃ´pital Trousseau
city: Le Coudray
country: France
facility: Hopital Louis Pasteur
city: Montpellier cedex 05
country: France
facility: Centre Hospitalier Regional Universitaire de Montpellier - Hopital Arnaud de Villeneuve
city: Nantes Cedex 1
country: France
facility: Centre Hospitalier Universitaire de Nantes - Hopital Guillaume et Rene Laennec
city: Nantes Cedex 2
country: France
facility: Nouvelles Cliniques Nantaises
city: Nice
country: France
facility: Centre Hospitalier Universitaire de Nice - Hopital Pasteur
city: Paris
country: France
facility: Hopital Lariboisiere
city: Paris
country: France
facility: Hopital Pitie-Salpetriere
city: Pau
country: France
facility: Centre Hospitalier de Pau - Hopital Francois Mitterrand
city: Reims
country: France
facility: Centre Hospitalier Universitaire de Reims - Hopital Robert Debre
city: Toulouse Cedex 9
country: France
facility: Centre Hospitalier Universitaire de Toulouse - Hopital Rangueil
city: Vesoul
country: France
facility: Centre Hospitalier Intercommunal Haute Saone
city: Bad Krozingen
country: Germany
facility: Universitaets-Herzzentrum Freiburg - Bad Krozingen
city: Berlin
country: Germany
facility: Klinische Forschung Berlin GbR
city: Berlin
country: Germany
facility: Vivantes Klinikum NeukÃ¶lln
city: Berlin
country: Germany
facility: Deutsches Rotes Kreuz Kliniken Berlin KÃ¶penick
city: Berlin
country: Germany
facility: Deutsches Herzzentrum Berlin
city: Dortmund
country: Germany
facility: Sankt-Johannes-Hospital
city: Dresden
country: Germany
facility: Gesellschaft fur Wissens und Technologietransfer der Technischen Uni Dresden
city: Kassel
country: Germany
facility: Ambulantes Herzzentrum Kassel
city: KÃ¶ln
country: Germany
facility: UniversitÃ¤tsklinikum KÃ¶ln
city: Magdeburg
country: Germany
facility: Otto von Guericke UniversitÃ¤t Magdeburg
city: Mainz
country: Germany
facility: Johannes Gutenberg UniversitÃ¤t Mainz
city: MÃ¼nchen
country: Germany
facility: Herz-GefÃ¤ÃŸ-Zentrum Nymphenburg am Klinikum Dritter Orden
city: MÃ¼nchen
country: Germany
facility: Deutsches Herzzentrum MÃ¼nchen des Freistaates Bayern
city: Stuttgart
country: Germany
facility: Robert Bosch Krankenhaus
city: Ulm
country: Germany
facility: UniversitÃ¤tsklinikum Ulm
city: Witten
country: Germany
facility: Forschungszentrum Ruhr
city: Wuppertal
country: Germany
facility: Helios UniversitÃ¤tsklinikum Wuppertal
city: Bergamo
country: Italy
facility: Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII
city: Firenze
country: Italy
facility: Azienda Ospedaliero Universitaria Careggi
city: Milano
country: Italy
facility: Centro Cardiologico Monzino
city: Milano
country: Italy
facility: Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
city: Palermo
country: Italy
facility: Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
city: Perugia
country: Italy
facility: Azienda Ospedaliera di Perugia Ospedale Santa Maria della Misericordia
city: Pisa
country: Italy
facility: Fondazione Toscana Gabriele Monasterio, Stabilimento Ospedaliero di Pisa
city: Siena
country: Italy
facility: Azienda Ospedaliera Universitaria Senese Policlinico Le Scotte
city: Almada
country: Portugal
facility: Hospital Garcia de Orta, EPE
city: Coimbra
country: Portugal
facility: Centro Hospitalar e Universitario de Coimbra EPE
city: Covilha
country: Portugal
facility: Centro Hospitalar Cova da Beira, EPE - Hospital Pero da Covilha
city: Lisboa
country: Portugal
facility: Hospital Cuf Infante Santo
city: Lisboa
country: Portugal
facility: Centro Hospitalar de Lisboa Ocidental, EPE - Hospital Sao Francisco Xavier
city: Setubal
country: Portugal
facility: Centro Hospitalar de Setubal EPE Hospital de Sao Bernardo
city: Falun
country: Sweden
facility: Falu Lasarett
city: Helsingborg
country: Sweden
facility: Helsingborgs Lasarett
city: JÃ¶nkÃ¶ping
country: Sweden
facility: LÃ¤nssjukhuset Ryhov
city: Lulea
country: Sweden
facility: Sunderby Sjukhus
city: Lund
country: Sweden
facility: Skanes Universitetssjukhus
city: Lund
country: Sweden
facility: Capio Citykliniken
city: Orebro
country: Sweden
facility: Universitetssjukhuset Ã-rebro
city: Ostersund
country: Sweden
facility: Ostersunds sjukhus
city: Stockholm
country: Sweden
facility: Akardo MedSite
city: Umea
country: Sweden
facility: Norrlands Universitetssjukhus
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.