Vascular Endothelial Growth Factor (VEGF) Trap-Eye: Investigation of Efficacy and Safety in Central Retinal Vein Occlusion (CRVO) (GALILEO)

A Randomized, Double-masked, Sham-controlled Phase 3 Study of the Efficacy, Safety and Tolerability of Repeated Intravitreal Administration of VEGF Trap-Eye in Subjects With Macular Edema Secondary to Central Retinal Vein Occlusion (CRVO)

To determine the efficacy of vascular endothelial growth factor (VEGF) Trap-Eye injected into the eye on vision function in subjects with macular edema as a consequence of central retinal vein occlusion

Study Overview

• Status: Completed
• Conditions: Retinal Vein Occlusion
• Intervention / Treatment: Biological: Aflibercept Injection (EYLEA, VEGF Trap-Eye, BAY86-5321); Other: Sham treatment

• Study Type: Interventional
• Enrollment (Actual): 177
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Chatswood, New South Wales, Australia, 2067
    • Parramatta, New South Wales, Australia, 2150
    • Sydney, New South Wales, Australia, 2000
    • Westmead, New South Wales, Australia, 2145
  • Victoria
    • East Melbourne, Victoria, Australia, 3002
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
• Austria
  • Innsbruck, Austria, 6020
  • Linz, Austria, 4021
  • Wien, Austria, 1090
• France
  • Bordeaux, France, 33000
  • Dijon, France, 21033
  • Marseille, France, 13008
  • Paris, France, 75015
  • Cedex 1
    • Nantes, Cedex 1, France, 44093
  • Cedex 12
    • Paris, Cedex 12, France, 75557
• Germany
  • Berlin, Germany, 13353
  • Hamburg, Germany, 20251
  • Baden-Württemberg
    • Freiburg, Baden-Württemberg, Germany, 79106
    • Heidelberg, Baden-Württemberg, Germany, 69120
    • Tübingen, Baden-Württemberg, Germany, 72076
  • Bayern
    • München, Bayern, Germany, 81675
    • Regensburg, Bayern, Germany, 93053
  • Hessen
    • Darmstadt, Hessen, Germany, 64297
    • Frankfurt, Hessen, Germany, 60596
    • Marburg, Hessen, Germany, 35037
  • Niedersachsen
    • Göttingen, Niedersachsen, Germany, 37075
  • Nordrhein-Westfalen
    • Aachen, Nordrhein-Westfalen, Germany, 52074
    • Bonn, Nordrhein-Westfalen, Germany, 53105
    • Essen, Nordrhein-Westfalen, Germany, 45122
    • Köln, Nordrhein-Westfalen, Germany, 50924
    • Münster, Nordrhein-Westfalen, Germany, 48145
  • Rheinland-Pfalz
    • Ludwigshafen, Rheinland-Pfalz, Germany, 67063
    • Mainz, Rheinland-Pfalz, Germany, 55131
  • Saarland
    • Homburg, Saarland, Germany, 66421
  • Sachsen
    • Chemnitz, Sachsen, Germany, 09116
    • Dresden, Sachsen, Germany, 01307
    • Dresden, Sachsen, Germany, 06067
    • Leipzig, Sachsen, Germany, 04103
  • Schleswig-Holstein
    • Kiel, Schleswig-Holstein, Germany, 24105
    • Lübeck, Schleswig-Holstein, Germany, 23538
• Hungary
  • Budapest, Hungary, 1106
  • Budapest, Hungary, 1133
  • Budapest, Hungary, 1089
  • Debrecen, Hungary, 4032
  • Veszprem, Hungary, 8200
  • Zalaegerszeg, Hungary, H-8900
• Italy
  • Ancona, Italy, 60126
  • Bari, Italy, 70124
  • Catania, Italy, 95123
  • Firenze, Italy, 50134
  • Milano, Italy, 20122
  • Milano, Italy, 20132
  • Milano, Italy, 20157
  • Padova, Italy, 35128
  • Roma, Italy, 00133
  • Roma, Italy, 00198
  • Torino, Italy, 10122
• Japan
  • Kyoto, Japan, 606-8507
  • Aichi
    • Nagoya, Aichi, Japan, 466-8560
    • Nagoya, Aichi, Japan, 467-8602
  • Chiba
    • Urayasu, Chiba, Japan, 279-0021
  • Osaka
    • Suita, Osaka, Japan, 565-0871
  • Tokyo
    • Chiyoda-ku, Tokyo, Japan, 101-8309
• Korea, Republic of
  • Incheon, Korea, Republic of, 405-760
  • Seoul, Korea, Republic of, 137-701
  • Seoul, Korea, Republic of
  • Seoul, Korea, Republic of, 138-736
  • Seoul, Korea, Republic of, 110 744
  • Gyeonggido
    • Seongnam-si, Gyeonggido, Korea, Republic of, 463-707
• Latvia
  • Riga, Latvia, 1002
  • Riga, Latvia, 1050
• Singapore
  • Singapore, Singapore, 119074
  • Singapore, Singapore, 168751

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Center-involved macular edema secondary to central retinal vein occlusion (CRVO) for no longer than 9 months with mean central subfield thickness ≥ 250 μm on optical coherence tomography (OCT)
• Adults ≥ 18 years
• Early treatment diabetic retinopathy study (ETDRS) best corrected visual acuity (BCVA) of 20/40 to 20/320 (73 to 24 letters) in the study eye

Exclusion Criteria:

• Any prior treatment with anti-VEGF agents in the study eye (Pegaptanib sodium, anecortave acetate, bevacizumab, ranibizumab, etc.) or previous administration of systemic anti-angiogenic medications
• Prior panretinal laser photocoagulation or macular laser photocoagulation in the study eye
• CRVO disease duration > 9 months from date of diagnosis
• Previous use of intraocular corticosteroids in the study eye or use of periocular corticosteroids in the study eye within the 3 months prior to Day 1
• Iris neovascularization, vitreous hemorrhage, traction retinal detachment, or preretinal fibrosis involving the macula in either the study eye or fellow eye

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aflibercept Injection (EYLEA, VEGF Trap-Eye, BAY86-5321); Participants received a 2 mg dose of Intravitreal Aflibercept Injection (IAI) administered every 4 weeks from Day 1 through Week 20, later as often as every 4 weeks depending on the study retreatment criteria from Week 24 through Week 48. Follow-up phase: Participants on IAI, who continued the study, received 2 mg dose of IAI depending on the study retreatment criteria at Week 60 and 68.	Biological: Aflibercept Injection (EYLEA, VEGF Trap-Eye, BAY86-5321); Intravitreal injection. Weeks 0 to 20 of Aflibercept Injection every 4 weeks; Weeks 24 to 52 every 4 weeks PRN (pro re nata, on demand); plus additional on Week 60 and 68.; Other: Sham treatment; Sham treatment. Weeks 0 to 52 sham treatment every 4 weeks; plus additional on Week 60 and 68.
Sham Comparator: Sham treatment; Participants received sham treatment administered every 4 weeks from Day 1 through Week 52. Follow-up phase: Participants on sham treatment, who switched to Intravitreal Aflibercept Injection (IAI), received a 2 mg dose of IAI at week 52 and depending on the study retreatment criteria at Week 60 and 68.	Other: Sham treatment; Sham treatment. Weeks 0 to 52 sham treatment every 4 weeks; plus additional on Week 60 and 68.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Gained at Least 15 Letters in BCVA as Measured by ETDRS Letter Score Compared With Baseline at Week 24 With Discontinued Participants Before Week 24 Evaluated as Failures	Defined study baseline range of Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score of 73 to 24 (= Acuity of 20/40 to 20/320) in the study eye; a higher score represents better functioning. Nominator = (Number of participants who maintained vision * 100); Denominator = Number of participants analyzed.	Baseline and Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in BCVA as Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score at Week 24 - Last Observation Carried Forward (LOCF)	Defined study baseline range of ETDRS Best Corrected Visual Acuity letter score of 73 to 24 (= Acuity of 20/40 to 20/320) in the study eye; a higher score represents better functioning. However, because this was assessed at the screening visit, subjects may have had a higher BCVA recorded at the baseline visit and would not have been excluded from the study.	Baseline and Week 24
Change From Baseline in Central Retinal Thickness (CRT) at Week 24 - LOCF		Baseline and Week 24
Percentage of Participants Who Developed Neovascularization During the First 24 Weeks	Formation of blood vessels in the anterior segment, optic disc, or elsewhere in the fundus up to Week 24	From baseline until Week 24
Change From Baseline in National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25) Total Score at Week 24 - LOCF	The NEI VFQ-25 total score ranges from 0-100 with a score of 0 being the worst outcome and 100 being the best outcome. The NEI VFQ questionnaire is organized as a collection of subscales which are all scored from 0-100. To reach the overall composite score, each sub-scale score is averaged in order to give each sub-scale equal weight	Baseline and Week 24
Change From Baseline in European Five-dimensional Health Scale (EQ-5D) Score at Week 24 - LOCF	EQ-5D is a quality of life questionnaire based on a scale from -0.594 (worst) to 1.00 (best).	Baseline and Week 24

Collaborators and Investigators

• Sponsor: Bayer
• Collaborators: Regeneron Pharmaceuticals

Publications and helpful links

General Publications

• Holz FG, Roider J, Ogura Y, Korobelnik JF, Simader C, Groetzbach G, Vitti R, Berliner AJ, Hiemeyer F, Beckmann K, Zeitz O, Sandbrink R. VEGF Trap-Eye for macular oedema secondary to central retinal vein occlusion: 6-month results of the phase III GALILEO study. Br J Ophthalmol. 2013 Mar;97(3):278-84. doi: 10.1136/bjophthalmol-2012-301504. Epub 2013 Jan 7. Erratum In: Br J Ophthalmol. 2015 Dec;99(12):1746.
• Korobelnik JF, Holz FG, Roider J, Ogura Y, Simader C, Schmidt-Erfurth U, Lorenz K, Honda M, Vitti R, Berliner AJ, Hiemeyer F, Stemper B, Zeitz O, Sandbrink R; GALILEO Study Group. Intravitreal Aflibercept Injection for Macular Edema Resulting from Central Retinal Vein Occlusion: One-Year Results of the Phase 3 GALILEO Study. Ophthalmology. 2014 Jan;121(1):202-208. doi: 10.1016/j.ophtha.2013.08.012. Epub 2013 Sep 29.

Helpful Links

• Click here to find information about studies related to Bayer Healthcare products conducted in Europe

Study record dates

Study Major Dates

• Study Start: October 1, 2009
• Primary Completion (Actual): February 1, 2011
• Study Completion (Actual): February 1, 2012

Study Registration Dates

• First Submitted: October 30, 2009
• First Submitted That Met QC Criteria: November 12, 2009
• First Posted (Estimate): November 13, 2009

Study Record Updates

• Last Update Posted (Estimate): November 2, 2014
• Last Update Submitted That Met QC Criteria: October 27, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: CRVO; Central Retinal Vein Occlusion; Macular Edema; VEGF Trap-Eye; best-corrected visual acuity
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Eye Diseases; Retinal Diseases; Embolism and Thrombosis; Venous Thrombosis; Thrombosis; Retinal Vein Occlusion; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Aflibercept
• Other Study ID Numbers: 14130; 2009-010973-19 (EudraCT Number)