Integrated results from the COPERNICUS and GALILEO studies

Abstract

Objectives

To report on the efficacy and safety of intravitreal aflibercept in patients with macular edema secondary to central retinal vein occlusion (CRVO) in an integrated analysis of COPERNICUS and GALILEO.

Patients and methods

Patients were randomized to receive intravitreal aflibercept 2 mg every 4 weeks or sham injections until week 24. From week 24 to week 52, all intravitreal aflibercept-treated patients in both studies and sham-treated patients in COPERNICUS were eligible to receive intravitreal aflibercept based on prespecified criteria. In GALILEO, sham-treated patients continued to receive sham treatment through week 52.

Results

At week 24, mean gain in best-corrected visual acuity and mean reduction in central retinal thickness were greater for intravitreal aflibercept-treated patients compared with sham, consistent with individual trial results. At week 52, after 6 months of intravitreal aflibercept as-needed treatment in COPERNICUS, patients originally randomized to sham group experienced visual and anatomic improvements but did not improve to the extent of those initially treated with intravitreal aflibercept, while the sham group in GALILEO did not improve over week 24 mean best-corrected visual acuity scores. Ocular serious adverse events occurred in <10% of patients.

Conclusion

This analysis of integrated data from COPERNICUS and GALILEO confirmed that intravitreal aflibercept is an effective treatment for macular edema following CRVO.

Keywords:

• macular edema
• central retinal vein occlusion
• anti-vascular endothelial growth factor
• aflibercept
• COPERNICUS
• GALILEO

Supplementary material

List of Institutional Review Boards and Ethic Committees for COPERNICUS and GALILEO sites

COPERNICUS

USA: Copernicus Group IRB, UCSD Human Research Protection Program, Cleveland Clinic IRB, IRB, OPRS; Canada: The University of British Columbia Office of Research Services Clinical Research Ethics Board, IRB Services, Capital District Health Authority Research Ethics Board, University of Western Ontario Health Sciences Research Ethics Board, Research Ethics Research and Development Vancouver Island Health Authority, Sunnybrook Research Ethics Board; India: Regional Institute of Ophthalmology; Ethics Committee Hyderabad Eye Research Foundation, Narayana Nethralaya Institutional Ethics Committee; Israel: Helsinki Committee of Tel Aviv, Helsinki Committee of Rabin Medical Center, Helsinki Committee of Kaplan Medical Center, Helsinki Committee of Meir Medical Center; Colombia: Instituto Nacional de Investigacion en Oftalmologia – INIO, Comite de etica en Investigacion de Fundacion Oftalmological Nacional – FUNDONAL.

GALILEO

Australia: Bellberry Human Research Ethics Committee, Royal Prince Alfred Hospital, The Royal Victorian Eye & Ear Hospital; Austria: Ethikkommission der Medizinischen Universität Wien und des AKH, Ethikkommission des Landes Oberösterreich, Ethikkommission des KH Barmherzige Brüder Linz; France: Comite de Protection des Personnes sud ouest et Outremer III; Germany: Ethikkommission an der Medizinischen Fakultät Rheinische Friedrich-Wilhelms-Universität Bonn, Bereich Humanmed. d. Georg-August-Universität Göttingen Medizinische Fakultät Ethik-Kommission, Ethik-Kommission bei der Ärztekammer des Saarlandes, Ethik-Kommission bei der Ärztekammer Hamburg, Ethik-Kommission bei der Landesärztekammer Hessen, Ethik-kommission der Ärztekammer Westfalen-Lippe, Ethik-Kommission der Landesärztekammer Rheinland-Pfalz, Ethik-Kommission der Sächssischen Landesärztekammer, Klinikum der Christian-Albrechts-Universität Ethik-Kommission, Ethik-Kommision der Medizinischen Fakultät der Eberhard-Karls-Universität und am Universitätsklinikum Tübingen, Ethikkommission des Fachbereichs Humanmedizin, Klinikum rechts der Isar Fakultät für Medizin Ethik-Kommission, Ethikkommission an der Medizinischen Fakultät Rheinische Friedrich-Wilhelms-Universität Bonn, Ethik-Kommission der Technischen Universität Dresden, Ethik-Kommission der Medizinischen Fakultät der Universität zu Köln, Ethik-Kommission der Medizinischen Fakultät der Universität Leipzig, Universitätsklinik Gießen und Marburg GmbH Standort Marburg Ethik Kommission, Universitätsklinikum Aachen Ethik-Kommission an der Medizinischen Fakultät, Ethik-Kommission der Medizinischen Fakultät der Universität Duisburg-Essen, Universitätsklinikum Freiburg Ethik-Kommission, Ethikkommission der Med. Fakultät Heidelberg, Universitätsklinikum Regensburg Ethikkom-mission der medizinischen Fakultät, Universitätsklinikum Schleswig-Holstein/AÖR Ethikkommission; Hungary: ETT Klinikai Farmakológiai Etikai Bizottság, ETT Klinikai Farmakológiai Etikai Bizottság; Italy: Comitato etico per la sperimentazione clinica dei medicinali dell’ A.O.U. Careggi, Comitato Etico A.O.U. Ospedali Riuniti Umberto I-Lancisi-Salesi, Comitato Etico A.O.U. Policlinico Consorziale di Bari, Comitato Bioetico dell Azienda Ospedaliero-Universitaria Policlinico di Catania, Comitato Etico Indipendente Presso la Fondazione PTV Policlinico Tor Vergata, Comitato Etico della ASL RM/A di Roma, Comitato Etico ASL TO/2 di Torino, Comitato Etico IRCCS Fondazione S.Raffaele del Monte Tabor di Milano, Comitato di Etica Fondazione Irccs Ca’Granda Ospedale Maggiore Policlinico; Japan: Juntendo University Urayasu Hospital IRB, Kyoto University Hospital IRB, Nagoya City University Hospital IRB, Nagoya University Hospital IRB, Osaka University Hospital IRB, Surugadai Nihon University Hospital IRB; South Korea: Asan Medical Center, Gachon University Gil Medical Center, Seoul National University Bundang Hospital IRB, Seoul National University Hospital IRB, Severance Hospital Institutional Review Board, St Mary Hospital IRB; Latvia: Ethics Committee for Clinical Trials; Singapore: NHG Domain Specific Review Boards (DSRB), Singhealth Centralised Institutional Review Board.

Acknowledgments

The authors wish to thank the COPERNICUS and GALILEO study investigators. Medical writing assistance was provided by Corey Eagan, MPH, of PAREXEL and was funded by Bayer. COPERNICUS and GALILEO were sponsored by Bayer and Regeneron Pharmaceuticals, Inc.

Disclosure

Amelie Pielen has received research funding from Novartis, Bayer, Roche, Genentech, and Théa Pharm and has been a lecturer and consultant for Novartis, Allergan, and Bayer Pharmaceuticals. W Lloyd Clark is a consultant for Genentech, Ohr Pharmaceuticals, Regeneron Pharmaceuticals, Inc., Roche, and Santen; offers research support for Allergan, Genentech, Regeneron Pharmaceuticals, Inc., Roche, and Santen; and has equity in VERSYL, Inc. David S Boyer is a consultant for Aerpio, Alcon, Alimera, Allegro, Allergan, Bausch & Lomb, Bayer, CoDa Therapeutics, Foresight Biotherapeutics, Genentech, GenSight Biologics, GrayBug Vision, GlaxoSmithKline, Neurotech, Notal Vision, Novartis, Ophthotech, Ohr, Optos, Regeneron Pharmaceuticals, RetroSense, Regulus Therapeutics, Sun Pharmaceuticals, StemCells, and ThromboGenics; is a lecturer for Alcon and Allergan; and holds minor equity in Allegro, Neutotech, Ohr, and Ophthotech. Yuichiro Ogura is a consultant to Alcon, Janssen Pharma, and Wakamoto and has received financial support from Bausch & Lomb, Bayer, Kissei Pharma, Kowa, Novartis, Santen, Sanwa Kagaku, Senju, and Topcon. Frank G Holz is a consultant to Acucela, Genentech/Roche, Novartis, Bayer, Alcon, OPTOS, Heidelberg Engineering, Carl Zeiss Meditec, Allergan, and Pfizer and has received financial support from OPTOS, Heidelberg Engineering, Carl Zeiss Meditec, Alcon, Genentech/Roche, Bayer, and Novartis. Jean-Francois Korobelnik is a consultant to Alcon, Alimera, Allergan, Bayer, Horus, Novartis, Roche, Thea, and Zeiss. Brigitte Stemper, Friedrich Asmus, Kay D Rittenhouse, and Christiane Ahlers are employees of Bayer. Robert Vitti and Namrata Saroj are employees of Regeneron Pharmaceuticals, Inc. Oliver Zeitz is a former employee of and consultant to Bayer. Julia A Haller is a consultant to KalVista, Merck, Janssen, Novartis, and Thrombogenics and a board member of Celgene. The authors report no other conflicts of interest in this work.