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

Dyslipidemia Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03080935
• Other study ID #: 20160250
• Secondary ID: 2016-004066-26
• Status: Terminated
• Phase: Phase 3
• Start date: March 13, 2017
• Est. completion date: March 4, 2022

Study information

• Verified date: March 2023
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1600
• Est. completion date: March 4, 2022
• Est. primary completion date: March 4, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Dyslipidemia
• Dyslipidemias

Intervention

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

Locations

Country	Name	City	State
Belgium	Algemeen Stedelijk Ziekenhuis Aalst	Aalst
Belgium	Onze Lieve Vrouw Ziekenhuis Aalst	Aalst
Belgium	Ziekenhuis Netwerk Antwerpen Middelheim	Antwerpen
Belgium	Ziekenhuis Netwerk Antwerpen Stuivenberg	Antwerpen
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	Bruxelles
Belgium	Algemeen Ziekenhuis Sint Lucas	Gent
Belgium	Universitair Ziekenhuis Gent	Gent
Belgium	Medif sprl	Gozee
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	Liege
Belgium	Algemeen Ziekenhuis Turnhout	Turnhout
Denmark	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
Denmark	Sydvestjysk Sygehus	Esbjerg
Denmark	Frederiksberg/Bispebjerg Hospitaler	Frederiksberg
Denmark	Glostrup Hospital	Glostrup
Denmark	Hvidovre Hospital	Hvidovre
Denmark	Amager Hospital	Kobenhavn 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
France	Centre Hospitalier Regional Universitaire de Besancon, Hopital Jean Minjoz	Besancon cedex
France	Centre Hospitalier Régional Universitaire de Tours - Hôpital Trousseau	Chambray les Tours
France	Hopital Louis Pasteur	Le Coudray
France	Centre Hospitalier Regional Universitaire de Montpellier - Hopital Arnaud de Villeneuve	Montpellier cedex 05
France	Centre Hospitalier Universitaire de Nantes - Hopital Guillaume et Rene Laennec	Nantes Cedex 1
France	Nouvelles Cliniques Nantaises	Nantes Cedex 2
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 Cedex 9
France	Centre Hospitalier Intercommunal Haute Saone	Vesoul
Germany	Universitaets-Herzzentrum Freiburg - Bad Krozingen	Bad Krozingen
Germany	Deutsches Herzzentrum Berlin	Berlin
Germany	Deutsches Rotes Kreuz Kliniken Berlin Köpenick	Berlin
Germany	Klinische Forschung Berlin GbR	Berlin
Germany	Vivantes Klinikum Neukölln	Berlin
Germany	Sankt-Johannes-Hospital	Dortmund
Germany	Gesellschaft fur Wissens und Technologietransfer der Technischen Uni Dresden	Dresden
Germany	Universitätsklinikum Köln	Köln
Germany	Ambulantes Herzzentrum Kassel	Kassel
Germany	Deutsches Herzzentrum München des Freistaates Bayern	München
Germany	Herz-Gefäß-Zentrum Nymphenburg am Klinikum Dritter Orden	München
Germany	Otto von Guericke Universität Magdeburg	Magdeburg
Germany	Johannes Gutenberg Universität Mainz	Mainz
Germany	Robert Bosch Krankenhaus	Stuttgart
Germany	Universitätsklinikum Ulm	Ulm
Germany	Forschungszentrum Ruhr	Witten
Germany	Helios Universitätsklinikum Wuppertal	Wuppertal
Italy	Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII	Bergamo
Italy	Azienda Ospedaliero Universitaria Careggi	Firenze
Italy	Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda	Milano
Italy	Centro Cardiologico Monzino	Milano
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
Portugal	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	Centro Hospitalar de Lisboa Ocidental, EPE - Hospital Sao Francisco Xavier	Lisboa
Portugal	Hospital Cuf Infante Santo	Lisboa
Portugal	Centro Hospitalar de Setubal EPE Hospital de Sao Bernardo	Setubal
Sweden	Falu Lasarett	Falun
Sweden	Helsingborgs Lasarett	Helsingborg
Sweden	Länssjukhuset Ryhov	Jönköping
Sweden	Sunderby Sjukhus	Lulea
Sweden	Capio Citykliniken	Lund
Sweden	Skanes Universitetssjukhus	Lund
Sweden	Universitetssjukhuset Ã-rebro	Orebro
Sweden	Ostersunds sjukhus	Ostersund
Sweden	Akardo MedSite	Stockholm
Sweden	Norrlands Universitetssjukhus	Umea

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

Belgium,  Denmark,  France,  Germany,  Italy,  Portugal,  Sweden, 

References & Publications (2)

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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

External Links

•   AmgenTrials clinical trials website