Vascular Endothelial Growth Factor (VEGF) Trap-Eye: Investigation of Efficacy and Safety in Wet Age-Related Macular Degeneration (AMD) (VIEW 2)

A Randomized, Double Masked, Active Controlled, Phase 3 Study of the Efficacy, Safety, and Tolerability of Repeated Doses of Intravitreal VEGF Trap in Subjects With Neovascular Age-related Macular Degeneration (AMD)

This study is a phase III, double-masked, randomized, study of the efficacy and safety of VEGF Trap-Eye in patients with neovascular age-related macular degeneration. Approximately 1200 patients will be randomized in Europe, Asia, Japan, Australia and South America.

Study Overview

• Status: Completed
• Conditions: Macular Degeneration
• Intervention / Treatment: Drug: Ranibizumab; Biological: Aflibercept Injection (EYLEA, VEGF Trap-Eye, BAY86-5321); Biological: Aflibercept Injection (EYLEA, VEGF Trap-Eye, BAY86-5321); Biological: Aflibercept Injection (EYLEA, VEGF Trap-Eye, BAY86-5321)

Detailed Description

Data of this trial ("VIEW 2") was pooled with data of a sister trial ("VIEW 1", NCT00509795), and an integrated analyses of the combined data was performed.

• Study Type: Interventional
• Enrollment (Actual): 1240
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Córdoba, Argentina, X5000IIT
  • Ciudad Auton. de Buenos Aires
    • Buenos Aires, Ciudad Auton. de Buenos Aires, Argentina, C1181ACH
    • Buenos Aires, Ciudad Auton. de Buenos Aires, Argentina, C1015ABO
    • Buenos Aires, Ciudad Auton. de Buenos Aires, Argentina, C1023AAQ
    • Buenos Aires, Ciudad Auton. de Buenos Aires, Argentina, C1122AAI
  • Santa Fe
    • Rosario, Santa Fe, Argentina, S2000ANJ
• Australia
  • Parramatta, Australia, 2150
  • New South Wales
    • Chatswood, New South Wales, Australia, 2067
    • Sydney, New South Wales, Australia, 2000
    • Westmead, New South Wales, Australia, 2145
  • Victoria
    • East Melbourne, Victoria, Australia, 3002
    • Parkville, Victoria, Australia, 3050
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
• Austria
  • Innsbruck, Austria, 6020
  • Linz, Austria, 4021
  • Wien, Austria, 1090
• Belgium
  • Liege, Belgium, 4000
• Brazil
  • Minas Gerais, Brazil, 30150-270
  • Sao Paulo, Brazil, 04023-062
  • Sao Paulo
    • Ribeirão Preto, Sao Paulo, Brazil, 14048-900
    • São Paulo, Sao Paulo, Brazil, 05651-901
• Colombia
  • Antioquia
    • Medellín, Antioquia, Colombia
  • Cauca
    • Cali, Cauca, Colombia
  • Distrito Capital de Bogotá
    • Bogota, Distrito Capital de Bogotá, Colombia
• Czech Republic
  • Brno, Czech Republic, 63400
  • Olomouc, Czech Republic, 77520
  • Praha 10, Czech Republic, 10034
  • Praha 4, Czech Republic, 14000
  • Usti nad Labem, Czech Republic, 401 13
• France
  • Besancon, France, 25030
  • Bordeaux, France, 33000
  • Dijon, France, 21079
  • Lyon, France, 69003
  • Lyon, France, 69006
  • Marseille, France, 13008
  • Paris, France, 75015
  • Paris, France, 75010
  • Cedex 1
    • Nantes, Cedex 1, France, 44093
  • Cedex 12
    • Paris, Cedex 12, France, 75557
• Germany
  • Berlin, Germany, 12200
  • 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
  • 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
    • 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, 1083
  • Budapest, Hungary, 1106
  • Budapest, Hungary, 1133
  • Veszprem, Hungary, 8200
• India
  • Bangalore, India, 560010
  • Chandigarh, India, 160012
  • Hyderabad, India, 500 034
  • Kerala, India, 683572
  • Kolkata, India, 700073
  • Mumbai, India, 400 050
  • New Delhi, India, 110002
  • New Delhi, India, 110029
  • Orissa, India, 751 024
  • Gujrat
    • Ahemedabad - 4, Gujrat, India, 380009
  • Maharashtra
    • Wadala, Mumbai, Maharashtra, India, 400031
  • Tamil Nadu
    • Chennai, Tamil Nadu, India, 600 006
    • Coimbatore, Tamil Nadu, India, 641014
    • Madurai, Tamil Nadu, India, 625 020
    • Pondicherry, Tamil Nadu, India, 600007
• Israel
  • Afula, Israel
  • Beer Sheva, Israel
  • Haifa, Israel, 34362
  • Jerusalem, Israel, 91120
  • Kfar Saba, Israel
  • Petach Tikva, Israel, 49100
  • Rehovot, Israel, 76100
  • Tel Aviv, Israel, 64239
  • Tel Hashomer, Israel
  • Zrifin, Israel, 70300
• Italy
  • Ancona, Italy, 60126
  • Bari, Italy, 70124
  • Catania, Italy, 95123
  • Genova, Italy, 16132
  • Milano, Italy, 20122
  • Milano, Italy, 20132
  • Milano, Italy, 20157
  • Padova, Italy, 35128
  • Roma, Italy, 00168
  • Roma, Italy, 00133
  • Roma, Italy, 00198
  • Torino, Italy, 10122
  • Udine, Italy, 33100
  • Varese, Italy, 21100
  • Verona, Italy, 37121
• Japan
  • Fukuoka, Japan, 812-8582
  • Fukushima, Japan, 960-1295
  • Kagoshima, Japan, 890-8520
  • Kyoto, Japan, 606-8507
  • Aichi
    • Nagoya, Aichi, Japan, 466-8560
    • Nagoya, Aichi, Japan, 467-8602
  • Chiba
    • Urayasu, Chiba, Japan, 279-0021
  • Gunma
    • Maebashi, Gunma, Japan, 371-8511
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060-8604
  • Kagawa
    • Kita, Kagawa, Japan, 761-0793
  • Osaka
    • Hirakata, Osaka, Japan, 573-1191
    • Suita, Osaka, Japan, 565-0871
  • Shiga
    • Otsu, Shiga, Japan, 520-2192
  • Tokyo
    • Chiyoda-ku, Tokyo, Japan, 101-8309
    • Shinjuku-ku, Tokyo, Japan, 160-8582
• Korea, Republic of
  • Incheon, Korea, Republic of, 405-760
  • Seoul, Korea, Republic of, 138-736
  • Seoul, Korea, Republic of, 137 701
  • Seoul, Korea, Republic of, 152-703
  • Seoul, Korea, Republic of, 110 744
  • Gyeonggido
    • Seongnam, Gyeonggido, Korea, Republic of, 463 707
• Latvia
  • Riga, Latvia, 1002
  • Riga, Latvia, 1009
  • Riga, Latvia, 1050
• Mexico
  • Chihuahua, Mexico, 31238
  • Mexico City, Mexico, 06030
  • México D.F., Mexico, 04030
  • Distrito Federal
    • Mexico City, Distrito Federal, Mexico, 06800
  • Jalisco
    • Zapopan, Jalisco, Mexico, 45060
  • México
    • Metepec, México, Mexico, 52140
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64060
    • Monterrey, Nuevo Leon, Mexico, 64480
• Netherlands
  • Amsterdam, Netherlands, 1100 DD
  • Groningen, Netherlands, 9713 GZ
  • Nijmegen, Netherlands, 6525 EX
  • Rotterdam, Netherlands, 3000 CA
  • ZA
    • Leiden, ZA, Netherlands, 2333
• Poland
  • Bydgoszcz, Poland, 85-631
  • Gdansk, Poland, 80-952
  • Katowice, Poland, 40-760
  • Poznan, Poland, 61-848
  • Warszaa, Poland, 02-005
  • Warszawa, Poland, 00-416
  • Wroclaw, Poland, 50-368
• Portugal
  • Coimbra, Portugal, 3000-548
  • Porto, Portugal, 4200-319
• Singapore
  • Singapore, Singapore, 119074
  • Singapore, Singapore, 308433
  • Singapore, Singapore, 168751
  • Singapore, Singapore, 159964
• Slovakia
  • Banska Bystrica, Slovakia, 97517
  • Bratislava, Slovakia, 81369
• Spain
  • Alicante, Spain, 03016
  • Barcelona, Spain, 08036
  • Barcelona, Spain, 08035
  • Barcelona, Spain, 08022
  • Barcelona, Spain, 08017
  • Madrid, Spain, 28046
  • Madrid, Spain, 28002
  • Malaga, Spain, 29010
  • Sevilla, Spain, 41013
  • Sevilla, Spain, 41009
  • Valencia, Spain, 46014
  • Valencia, Spain, 46015
  • Valladolid, Spain, 47005
  • A Coruña
    • Santiago de Compostela, A Coruña, Spain, 15705
  • Asturias
    • Oviedo, Asturias, Spain, 33012
  • Navarra
    • Pamplona, Navarra, Spain, 31008
• Sweden
  • Linköping, Sweden, 58185
  • Stockholm, Sweden, 11282
  • Örebro, Sweden, 70185
• Switzerland
  • Basel, Switzerland, 4031
  • Bern, Switzerland, 3010
  • Genève, Switzerland, 1211
  • Zürich, Switzerland, 8091
• United Kingdom
  • Aberdeen, United Kingdom, AB25 2ZN
  • Belfast, United Kingdom, BT12 6BA
  • Birmingham, United Kingdom, B4 7ET
  • Liverpool, United Kingdom, L7 8XP
  • London, United Kingdom, SE5 9RS
  • London, United Kingdom, NW1 5QH
  • Plymouth, United Kingdom, PL4 6PL
  • Torquay, United Kingdom, TQ2 7AA
  • Hampshire
    • Southampton, Hampshire, United Kingdom, SO16 6YD
  • Surrey
    • Camberley, Surrey, United Kingdom, GU16 5UJ

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Signed informed consent.
• Men and women >/=50 years of age.
• Active primary or recurrent subfoveal CNV lesions secondary to AMD, including juxtafoveal lesions that affect the fovea as evidenced by Fluorescein angiography (FA) in the study eye.
• ETDRS Best-Corrected Visual Acuity letter score of 73 to 25 (= Acuity of 20/40 to 20/320) in the study eye at 4 meters.
• Willing, committed, and able to return for ALL clinic visits and complete all study-related procedures.
• Able to read, (or, if unable to read due to visual impairment, be read to verbatim by the person administering the informed consent or a family member) understand and willing to sign the informed consent form.

Exclusion Criteria:

• Any prior ocular (in the study eye) or systemic treatment or surgery for neovascular AMD, except dietary supplements or vitamins.
• Any prior or concomitant therapy with another investigational agent to treat neovascular AMD in the study eye.
• Any prior treatment with anti-VEGF agents in the study eye.
• Total lesion size >12 disc areas (30.5 mm, including blood, scars and neovascularization) as assessed by FA in the study eye.
• Subretinal hemorrhages that is either 50% or more of the total lesion area, or if the blood is under the fovea and is 1 or more disc areas in size in the study eye (if the blood is under the fovea, then the fovea must be surrounded by 270 degrees by visible CNV).
• Scar or fibrosis making up >50% of the total lesion in the study eye.
• Scar, fibrosis, or atrophy involving the center of the fovea in the study eye.
• Presence of retinal pigment epithelial tears or rips involving the macula in the study eye.
• History of any vitreous hemorrhage within 4 weeks prior to Visit 1 in the study eye.
• Presence of other causes of CNV in the study eye.
• Prior vitrectomy in the study eye.
• History of retinal detachment or treatment or surgery for retinal detachment in the study eye.
• Any history of macular hole of stage 2 and above in the study eye.
• Any intraocular or periocular surgery within 3 months of Day 1 on the study eye, except lid surgery, which may not have taken place within 1 month of Day 1, as long as it is unlikely to interfere with the injection.
• History or clinical evidence of diabetic retinopathy, diabetic macular edema or any retinal vascular disease other than AMD in either eye.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ranibizumab 0.5mg Q4; Participants received a 0.5 mg dose of Ranibizumab via intravitreal (IVT) injection administered every 4 weeks for the first year. Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks.	Drug: Ranibizumab; Participants received a 0.5 mg dose of Ranibizumab via intravitreal (IVT) injection administered every 4 weeks for the first year. Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks.
Experimental: Aflibercept Injection (EYLEA, VEGF Trap-Eye) 2mg Q4; Participants received a 2.0 mg dose of Aflibercept Injection administered every 4 weeks for the first year. Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks.	Biological: Aflibercept Injection (EYLEA, VEGF Trap-Eye, BAY86-5321); Participants received a 2.0 mg dose of Aflibercept Injection administered every 4 weeks for the first year. Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks.; Biological: Aflibercept Injection (EYLEA, VEGF Trap-Eye, BAY86-5321); Participants received a 0.5 mg dose of Aflibercept Injection administered every 4 weeks for the first year. Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks.; Biological: Aflibercept Injection (EYLEA, VEGF Trap-Eye, BAY86-5321); Participants received a 2.0 mg dose of Aflibercept Injection administered every 8 weeks (including one additional 2,0 mg dose at Week 4) for the first year. Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks.
Experimental: Aflibercept Injection (EYLEA, VEGF Trap-Eye) 0.5mg Q4; Participants received a 0.5 mg dose of Aflibercept Injection administered every 4 weeks for the first year. Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks.	Biological: Aflibercept Injection (EYLEA, VEGF Trap-Eye, BAY86-5321); Participants received a 2.0 mg dose of Aflibercept Injection administered every 4 weeks for the first year. Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks.; Biological: Aflibercept Injection (EYLEA, VEGF Trap-Eye, BAY86-5321); Participants received a 0.5 mg dose of Aflibercept Injection administered every 4 weeks for the first year. Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks.; Biological: Aflibercept Injection (EYLEA, VEGF Trap-Eye, BAY86-5321); Participants received a 2.0 mg dose of Aflibercept Injection administered every 8 weeks (including one additional 2,0 mg dose at Week 4) for the first year. Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks.
Experimental: Aflibercept Injection (EYLEA, VEGF Trap-Eye) 2mg Q8; Participants received a 2.0 mg dose of Aflibercept Injection administered every 8 weeks (including one additional 2,0 mg dose at Week 4) for the first year. Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks.	Biological: Aflibercept Injection (EYLEA, VEGF Trap-Eye, BAY86-5321); Participants received a 2.0 mg dose of Aflibercept Injection administered every 4 weeks for the first year. Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks.; Biological: Aflibercept Injection (EYLEA, VEGF Trap-Eye, BAY86-5321); Participants received a 0.5 mg dose of Aflibercept Injection administered every 4 weeks for the first year. Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks.; Biological: Aflibercept Injection (EYLEA, VEGF Trap-Eye, BAY86-5321); Participants received a 2.0 mg dose of Aflibercept Injection administered every 8 weeks (including one additional 2,0 mg dose at Week 4) for the first year. Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Maintained Vision at Week 52 - Last Observation Carried Forward (LOCF)	Maintenance of vision was defined as a loss of < 15 letters in the ETDRS (Early Treatment Diabetic Retinopathy Study) letter score (defined study baseline range of ETDRS Best Corrected Visual Acuity letter score of 73 to 25 (= 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.	At week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) as Measured by ETDRS Letter Score at Week 52 - LOCF	Defined study baseline range of ETDRS Best Corrected Visual Acuity letter score of 73 to 25 (= Acuity of 20/40 to 20/320) in the study eye; a higher score represents better functioning.	Baseline and at week 52
Percentage of Participants Who Gained at Least 15 Letters of Vision in the ETDRS Letter Score in the Study Eye at Week 52 - LOCF	Defined study baseline range of ETDRS Best Corrected Visual Acuity letter score of 73 to 25 (= 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.	At week 52
Mean Change From Baseline in National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25) Total Score at Week 52 - LOCF	The possible range of the NEI VFQ-25 total score is between 0 (worst possible) and 100 (best possible).	Baseline and at week 52
Mean Change From Baseline in Choroidal Neovascularization (CNV) Area at Week 52 - LOCF	CNV area values measured in square millimeters; lower values represent better outcomes.	Baseline and at week 52

Collaborators and Investigators

• Sponsor: Bayer
• Collaborators: Regeneron Pharmaceuticals

Publications and helpful links

General Publications

• Heier JS, Brown DM, Chong V, Korobelnik JF, Kaiser PK, Nguyen QD, Kirchhof B, Ho A, Ogura Y, Yancopoulos GD, Stahl N, Vitti R, Berliner AJ, Soo Y, Anderesi M, Groetzbach G, Sommerauer B, Sandbrink R, Simader C, Schmidt-Erfurth U; VIEW 1 and VIEW 2 Study Groups. Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. Ophthalmology. 2012 Dec;119(12):2537-48. doi: 10.1016/j.ophtha.2012.09.006. Epub 2012 Oct 17. Erratum In: Ophthalmology. 2013 Jan;120(1):209-10.
• Schmidt-Erfurth U, Kaiser PK, Korobelnik JF, Brown DM, Chong V, Nguyen QD, Ho AC, Ogura Y, Simader C, Jaffe GJ, Slakter JS, Yancopoulos GD, Stahl N, Vitti R, Berliner AJ, Soo Y, Anderesi M, Sowade O, Zeitz O, Norenberg C, Sandbrink R, Heier JS. Intravitreal aflibercept injection for neovascular age-related macular degeneration: ninety-six-week results of the VIEW studies. Ophthalmology. 2014 Jan;121(1):193-201. doi: 10.1016/j.ophtha.2013.08.011. Epub 2013 Sep 29.
• Moshfeghi DM, Thompson D, Saroj N. Changes in neovascular activity following fixed dosing with an anti-vascular endothelial growth factor agent over 52 weeks in the phase III VIEW 1 and VIEW 2 studies. Br J Ophthalmol. 2020 Sep;104(9):1223-1227. doi: 10.1136/bjophthalmol-2019-315021. Epub 2019 Dec 11.
• Yuzawa M, Fujita K, Wittrup-Jensen KU, Norenberg C, Zeitz O, Adachi K, Wang EC, Heier J, Kaiser P, Chong V, Korobelnik JF. Improvement in vision-related function with intravitreal aflibercept: data from phase 3 studies in wet age-related macular degeneration. Ophthalmology. 2015 Mar;122(3):571-8. doi: 10.1016/j.ophtha.2014.09.024. Epub 2014 Nov 6.
• Ogura Y, Terasaki H, Gomi F, Yuzawa M, Iida T, Honda M, Nishijo K, Sowade O, Komori T, Schmidt-Erfurth U, Simader C, Chong V; VIEW 2 Investigators. Efficacy and safety of intravitreal aflibercept injection in wet age-related macular degeneration: outcomes in the Japanese subgroup of the VIEW 2 study. Br J Ophthalmol. 2015 Jan;99(1):92-7. doi: 10.1136/bjophthalmol-2014-305076. Epub 2014 Aug 8.

Helpful Links

• Click here to find information about studies related to Bayer Healthcare products conducted in Europe
• Click here to view the data of the twin trial conducted by the collaboration partner.

Study record dates

Study Major Dates

• Study Start: April 1, 2008
• Primary Completion (Actual): September 1, 2010
• Study Completion (Actual): August 1, 2011

Study Registration Dates

• First Submitted: March 12, 2008
• First Submitted That Met QC Criteria: March 17, 2008
• First Posted (Estimate): March 18, 2008

Study Record Updates

• Last Update Posted (Estimate): December 12, 2014
• Last Update Submitted That Met QC Criteria: November 28, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Keywords: Eye diseases; Vision Impairment and Blindness; Eyes and Vision; Seniors; Neovascular Age-Related Macular Degeneration (AMD); Retinal Disease
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Ranibizumab; Aflibercept
• Other Study ID Numbers: 91689; 2007-000583-25 (EudraCT Number)