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

Sponsor
Bayer (Industry)
Overall Status
Completed
CT.gov ID
NCT00637377
Collaborator
Regeneron Pharmaceuticals (Industry)
1,240
Enrollment
189
Locations
4
Arms
40
Duration (Months)
6.6
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
  • 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)
 Phase 3

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 Design

Study Type:
Interventional
Actual Enrollment :
1240 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
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)
Study Start Date :
Apr 1, 2008
Actual Primary Completion Date :
Sep 1, 2010
Actual Study Completion Date :
Aug 1, 2011

Arms and Interventions

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.
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 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.
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 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.

Outcome Measures

Primary Outcome Measures

  1. Percentage of Participants Who Maintained Vision at Week 52 - Last Observation Carried Forward (LOCF) [At week 52]

    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.

Secondary Outcome Measures

  1. Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) as Measured by ETDRS Letter Score at Week 52 - LOCF [Baseline and at week 52]

    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.

  2. Percentage of Participants Who Gained at Least 15 Letters of Vision in the ETDRS Letter Score in the Study Eye at Week 52 - LOCF [At week 52]

    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.

  3. Mean Change From Baseline in National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25) Total Score at Week 52 - LOCF [Baseline and at week 52]

    The possible range of the NEI VFQ-25 total score is between 0 (worst possible) and 100 (best possible).

  4. Mean Change From Baseline in Choroidal Neovascularization (CNV) Area at Week 52 - LOCF [Baseline and at week 52]

    CNV area values measured in square millimeters; lower values represent better outcomes.

Eligibility Criteria

Criteria

Ages Eligible for Study:
50 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Buenos Aires Ciudad Auton. de Buenos Aires Argentina C1015ABO
2 Buenos Aires Ciudad Auton. de Buenos Aires Argentina C1023AAQ
3 Buenos Aires Ciudad Auton. de Buenos Aires Argentina C1122AAI
4 Buenos Aires Ciudad Auton. de Buenos Aires Argentina C1181ACH
5 Rosario Santa Fe Argentina S2000ANJ
6 Córdoba Argentina X5000IIT
7 Chatswood New South Wales Australia 2067
8 Sydney New South Wales Australia 2000
9 Westmead New South Wales Australia 2145
10 East Melbourne Victoria Australia 3002
11 Parkville Victoria Australia 3050
12 Nedlands Western Australia Australia 6009
13 Parramatta Australia 2150
14 Innsbruck Austria 6020
15 Linz Austria 4021
16 Wien Austria 1090
17 Liege Belgium 4000
18 Ribeirão Preto Sao Paulo Brazil 14048-900
19 São Paulo Sao Paulo Brazil 05651-901
20 Minas Gerais Brazil 30150-270
21 Sao Paulo Brazil 04023-062
22 Medellín Antioquia Colombia
23 Cali Cauca Colombia
24 Bogota Distrito Capital de Bogotá Colombia
25 Brno Czech Republic 63400
26 Olomouc Czech Republic 77520
27 Praha 10 Czech Republic 10034
28 Praha 4 Czech Republic 14000
29 Usti nad Labem Czech Republic 401 13
30 Paris Cedex 12 France 75557
31 Nantes Cedex 1 France 44093
32 Besancon France 25030
33 Bordeaux France 33000
34 Dijon France 21079
35 Lyon France 69003
36 Lyon France 69006
37 Marseille France 13008
38 Paris France 75010
39 Paris France 75015
40 Freiburg Baden-Württemberg Germany 79106
41 Heidelberg Baden-Württemberg Germany 69120
42 Tübingen Baden-Württemberg Germany 72076
43 München Bayern Germany 81675
44 Regensburg Bayern Germany 93053
45 Darmstadt Hessen Germany 64297
46 Aachen Nordrhein-Westfalen Germany 52074
47 Bonn Nordrhein-Westfalen Germany 53105
48 Essen Nordrhein-Westfalen Germany 45122
49 Köln Nordrhein-Westfalen Germany 50924
50 Münster Nordrhein-Westfalen Germany 48145
51 Ludwigshafen Rheinland-Pfalz Germany 67063
52 Mainz Rheinland-Pfalz Germany 55131
53 Homburg Saarland Germany 66421
54 Dresden Sachsen Germany 01307
55 Dresden Sachsen Germany 06067
56 Leipzig Sachsen Germany 04103
57 Kiel Schleswig-Holstein Germany 24105
58 Lübeck Schleswig-Holstein Germany 23538
59 Berlin Germany 12200
60 Hamburg Germany 20251
61 Budapest Hungary 1083
62 Budapest Hungary 1106
63 Budapest Hungary 1133
64 Veszprem Hungary 8200
65 Ahemedabad - 4 Gujrat India 380009
66 Wadala, Mumbai Maharashtra India 400031
67 Chennai Tamil Nadu India 600 006
68 Coimbatore Tamil Nadu India 641014
69 Madurai Tamil Nadu India 625 020
70 Pondicherry Tamil Nadu India 600007
71 Bangalore India 560010
72 Chandigarh India 160012
73 Hyderabad India 500 034
74 Kerala India 683572
75 Kolkata India 700073
76 Mumbai India 400 050
77 New Delhi India 110002
78 New Delhi India 110029
79 Orissa India 751 024
80 Afula Israel
81 Beer Sheva Israel
82 Haifa Israel 34362
83 Jerusalem Israel 91120
84 Kfar Saba Israel
85 Petach Tikva Israel 49100
86 Rehovot Israel 76100
87 Tel Aviv Israel 64239
88 Tel Hashomer Israel
89 Zrifin Israel 70300
90 Ancona Italy 60126
91 Bari Italy 70124
92 Catania Italy 95123
93 Genova Italy 16132
94 Milano Italy 20122
95 Milano Italy 20132
96 Milano Italy 20157
97 Padova Italy 35128
98 Roma Italy 00133
99 Roma Italy 00168
100 Roma Italy 00198
101 Torino Italy 10122
102 Udine Italy 33100
103 Varese Italy 21100
104 Verona Italy 37121
105 Nagoya Aichi Japan 466-8560
106 Nagoya Aichi Japan 467-8602
107 Urayasu Chiba Japan 279-0021
108 Maebashi Gunma Japan 371-8511
109 Sapporo Hokkaido Japan 060-8604
110 Kita Kagawa Japan 761-0793
111 Hirakata Osaka Japan 573-1191
112 Suita Osaka Japan 565-0871
113 Otsu Shiga Japan 520-2192
114 Chiyoda-ku Tokyo Japan 101-8309
115 Shinjuku-ku Tokyo Japan 160-8582
116 Fukuoka Japan 812-8582
117 Fukushima Japan 960-1295
118 Kagoshima Japan 890-8520
119 Kyoto Japan 606-8507
120 Seongnam Gyeonggido Korea, Republic of 463 707
121 Incheon Korea, Republic of 405-760
122 Seoul Korea, Republic of 110 744
123 Seoul Korea, Republic of 137 701
124 Seoul Korea, Republic of 138-736
125 Seoul Korea, Republic of 152-703
126 Riga Latvia 1002
127 Riga Latvia 1009
128 Riga Latvia 1050
129 Mexico City Distrito Federal Mexico 06800
130 Zapopan Jalisco Mexico 45060
131 Metepec México Mexico 52140
132 Monterrey Nuevo Leon Mexico 64060
133 Monterrey Nuevo Leon Mexico 64480
134 Chihuahua Mexico 31238
135 Mexico City Mexico 06030
136 México D.F. Mexico 04030
137 Leiden ZA Netherlands 2333
138 Amsterdam Netherlands 1100 DD
139 Groningen Netherlands 9713 GZ
140 Nijmegen Netherlands 6525 EX
141 Rotterdam Netherlands 3000 CA
142 Bydgoszcz Poland 85-631
143 Gdansk Poland 80-952
144 Katowice Poland 40-760
145 Poznan Poland 61-848
146 Warszaa Poland 02-005
147 Warszawa Poland 00-416
148 Wroclaw Poland 50-368
149 Coimbra Portugal 3000-548
150 Porto Portugal 4200-319
151 Singapore Singapore 119074
152 Singapore Singapore 159964
153 Singapore Singapore 168751
154 Singapore Singapore 308433
155 Banska Bystrica Slovakia 97517
156 Bratislava Slovakia 81369
157 Santiago de Compostela A Coruña Spain 15705
158 Oviedo Asturias Spain 33012
159 Pamplona Navarra Spain 31008
160 Alicante Spain 03016
161 Barcelona Spain 08017
162 Barcelona Spain 08022
163 Barcelona Spain 08035
164 Barcelona Spain 08036
165 Madrid Spain 28002
166 Madrid Spain 28046
167 Malaga Spain 29010
168 Sevilla Spain 41009
169 Sevilla Spain 41013
170 Valencia Spain 46014
171 Valencia Spain 46015
172 Valladolid Spain 47005
173 Linköping Sweden 58185
174 Stockholm Sweden 11282
175 Örebro Sweden 70185
176 Basel Switzerland 4031
177 Bern Switzerland 3010
178 Genève Switzerland 1211
179 Zürich Switzerland 8091
180 Southampton Hampshire United Kingdom SO16 6YD
181 Camberley Surrey United Kingdom GU16 5UJ
182 Aberdeen United Kingdom AB25 2ZN
183 Belfast United Kingdom BT12 6BA
184 Birmingham United Kingdom B4 7ET
185 Liverpool United Kingdom L7 8XP
186 London United Kingdom NW1 5QH
187 London United Kingdom SE5 9RS
188 Plymouth United Kingdom PL4 6PL
189 Torquay United Kingdom TQ2 7AA

Sponsors and Collaborators

  • Bayer
  • Regeneron Pharmaceuticals

Investigators

  • Study Director: Bayer Study Director, Bayer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Bayer
ClinicalTrials.gov Identifier:
NCT00637377
Other Study ID Numbers:
  • 91689
  • 2007-000583-25
First Posted:
Mar 18, 2008
Last Update Posted:
Dec 12, 2014
Last Verified:
Nov 1, 2014
Keywords provided by Bayer
Eye diseases
Vision Impairment and Blindness
Eyes and Vision
Seniors
Neovascular Age-Related Macular Degeneration (AMD)
Retinal Disease
Additional relevant MeSH terms:
Macular Degeneration
Ranibizumab
Aflibercept

Study Results

Participant Flow

Recruitment Details The study was conducted at 186 study centers in 26 countries. Recruitment period: 21 Apr 2008 - 4 Sep 2009.
Pre-assignment Detail 2031 participants were screened, 1240 were randomized and 1204 received at least 1 dose of study drug. 1204 participants were included in the Safety-Analysis Set (SAS). 1202 participants with at least 1 post-baseline measurement were included in the Full-Analysis Set (FAS).
Arm/Group Title Ranibizumab 0.5mg Q4 Aflibercept Injection (EYLEA, VEGF Trap-Eye) 2mg Q4 Aflibercept Injection (EYLEA, VEGF Trap-Eye) 0.5mg Q4 Aflibercept Injection (EYLEA, VEGF Trap-Eye) 2mg Q8
Arm/Group Description Participants received a dose of 0.5 mg Ranibizumab every 4 weeks for the first year (intravitreal [IVT] injection). Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks. Participants received a dose of 2.0 mg Aflibercept Injection every 4 weeks for the first year (intravitreal [IVT] injection). Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks. Participants received a dose of 0.5 mg Aflibercept Injection every 4 weeks for the first year (intravitreal [IVT] injection). Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks. Participants received a dose of 2.0 mg Aflibercept Injection every 8 weeks (including one additional 2.0 mg dose at Week 4) for the first year (IVT injection) and were to receive sham injections at interim monthly visits. During the second year, participants received 2.0 mg aflibercept as frequently as every 4 weeks, but no less frequently than every 12 weeks.
Period Title: Overall Study
STARTED 303 313 311 313
Participants Received Treatment 291 309 297 307
Participants Treated (FAS) 291 309 296 306
COMPLETED 276 281 274 284
NOT COMPLETED 27 32 37 29

Baseline Characteristics

Arm/Group Title Ranibizumab 0.5mg Q4 Aflibercept Injection (EYLEA, VEGF Trap-Eye) 2mg Q4 Aflibercept Injection (EYLEA, VEGF Trap-Eye) 0.5mg Q4 Aflibercept Injection (EYLEA, VEGF Trap-Eye) 2mg Q8 Total
Arm/Group Description Participants received a dose of 0.5 mg Ranibizumab every 4 weeks for the first year (intravitreal [IVT] injection). Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks. Participants received a dose of 2.0 mg Aflibercept Injection every 4 weeks for the first year (intravitreal [IVT] injection). Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks. Participants received a dose of 0.5 mg Aflibercept Injection every 4 weeks for the first year (intravitreal [IVT] injection). Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks. Participants received a dose of 2.0 mg Aflibercept Injection every 8 weeks (including one additional 2.0 mg dose at Week 4) for the first year (IVT injection) and were to receive sham injections at interim monthly visits. During the second year, participants received 2.0 mg aflibercept as frequently as every 4 weeks, but no less frequently than every 12 weeks. Total of all reporting groups
Overall Participants 291 309 296 306 1202
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
73.0
(9.0)
74.1
(8.5)
74.7
(8.6)
73.8
(8.6)
73.9
(8.7)
Sex: Female, Male (Count of Participants)
Female
169
58.1%
176
57%
147
49.7%
175
57.2%
667
55.5%
Male
122
41.9%
133
43%
149
50.3%
131
42.8%
535
44.5%
Ethnicity (participants) [Number]
Not Hispanic or Latino
239
82.1%
259
83.8%
241
81.4%
251
82%
990
82.4%
Hispanic or Latino
52
17.9%
50
16.2%
55
18.6%
55
18%
212
17.6%
Race (participants) [Number]
White
213
73.2%
226
73.1%
219
74%
217
70.9%
875
72.8%
Black or African American
1
0.3%
0
0%
1
0.3%
2
0.7%
4
0.3%
Asian
60
20.6%
67
21.7%
61
20.6%
69
22.5%
257
21.4%
Missing
17
5.8%
16
5.2%
15
5.1%
18
5.9%
66
5.5%
National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25) total score (scores on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [scores on a scale]
72.90
(19.09)
70.27
(19.41)
74.04
(18.22)
71.30
(19.06)
72.10
(18.99)
Area of Choroidal Neovascularization (CNV) (mm^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm^2]
7.59
(5.34)
8.25
(5.77)
7.70
(5.26)
7.75
(5.52)
7.83
(5.48)
Baseline lesion type (participants) [Number]
Predominantly classic
70
24.1%
72
23.3%
80
27%
88
28.8%
310
25.8%
Minimally classic
104
35.7%
112
36.2%
103
34.8%
106
34.6%
425
35.4%
Occult
116
39.9%
123
39.8%
113
38.2%
110
35.9%
462
38.4%
Missing
1
0.3%
2
0.6%
0
0%
2
0.7%
5
0.4%
Baseline total lesion size (mm^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm^2]
8.01
(5.74)
8.72
(6.14)
8.17
(5.51)
8.22
(5.87)
8.28
(5.82)
Best Corrected Visual Acuity (BCVA), assessed by ETDRS chart (Letters correctly read) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Letters correctly read]
53.8
(13.5)
52.8
(13.9)
51.6
(14.2)
51.6
(13.9)
52.4
(13.9)

Outcome Measures

1. Primary Outcome
Title Percentage of Participants Who Maintained Vision at Week 52 - Last Observation Carried Forward (LOCF)
Description 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.
Time Frame At week 52

Outcome Measure Data

Analysis Population Description
Per-Protocol Set (PPS); imputation technique: LOCF
Arm/Group Title Ranibizumab 0.5mg Q4 Aflibercept Injection (EYLEA, VEGF Trap-Eye) 2mg Q4 Aflibercept Injection (EYLEA, VEGF Trap-Eye) 0.5mg Q4 Aflibercept Injection (EYLEA, VEGF Trap-Eye) 2mg Q8
Arm/Group Description Participants received a dose of 0.5 mg Ranibizumab every 4 weeks for the first year (intravitreal [IVT] injection). Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks. Participants received a dose of 2.0 mg Aflibercept Injection every 4 weeks for the first year (intravitreal [IVT] injection). Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks. Participants received a dose of 0.5 mg Aflibercept Injection every 4 weeks for the first year (intravitreal [IVT] injection). Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks. Participants received a dose of 2.0 mg Aflibercept Injection every 8 weeks (including one additional 2.0 mg dose at Week 4) for the first year (IVT injection) and were to receive sham injections at interim monthly visits. During the second year, participants received 2.0 mg aflibercept as frequently as every 4 weeks, but no less frequently than every 12 weeks.
Measure Participants 269 274 268 270
Number [Percentage of participants]
94.42
32.4%
95.62
30.9%
96.27
32.5%
95.56
31.2%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ranibizumab 0.5mg Q4, Aflibercept Injection (EYLEA, VEGF Trap-Eye) 2mg Q4
Comments null hypothesis: pi ≤ pc-delta where pi is the probability that a participant maintained vision at week 52 under Aflibercept 2mg Q4, pc is the probability that a participant maintained vision at week 52 under Ranibizumab 0.5mg Q4 and delta is the non-inferiority margin. The null hypothesis is tested calculating a two-sided 95 % confidence using normal approximation of the difference of percentages of participants maintaining vision at week 52 (Ranibizumab 0.5mg Q4 minus Aflibercept 2mg Q4).
Type of Statistical Test Non-Inferiority or Equivalence
Comments The non-inferiority margin is set to 10. The power is 90 % according to the sample size estimation of the study protocol.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -1.20
Confidence Interval (2-Sided) 95%
-4.86 to 2.46
Parameter Dispersion Type:
Value:
Estimation Comments The difference is calculated as Ranibizumab minus Aflibercept. A negative value favors the Aflibercept 2mg Q4 group. As adjustment of multiple comparisons a conditional sequence of statistical hypotheses is used with alpha = 0.05.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ranibizumab 0.5mg Q4, Aflibercept Injection (EYLEA, VEGF Trap-Eye) 0.5mg Q4
Comments null hypothesis: pi ≤ pc-delta where pi is the probability that a participant maintained vision at week 52 under Aflibercept 0.5mg Q4, pc is the probability that a participant maintained vision at week 52 under Ranibizumab 0.5mg Q4 and delta is the non-inferiority margin. The null hypothesis is tested calculating a two-sided 95 % confidence using normal approximation of the difference of percentages of participants maintaining vision at week 52 (Ranibizumab 0.5mg Q4 minus Aflibercept 0.5mg Q4).
Type of Statistical Test Non-Inferiority or Equivalence
Comments The non-inferiority margin is set to 10. The power is 90 % according to the sample size estimation of the study protocol.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -1.84
Confidence Interval (2-Sided) 95%
-5.40 to 1.71
Parameter Dispersion Type:
Value:
Estimation Comments The difference is calculated as Ranibizumab minus Aflibercept. A negative value favors the Aflibercept 0.5mg Q4 group. As adjustment of multiple comparisons a conditional sequence of statistical hypotheses is used with alpha = 0.05.
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ranibizumab 0.5mg Q4, Aflibercept Injection (EYLEA, VEGF Trap-Eye) 2mg Q8
Comments null hypothesis: pi ≤ pc-delta where pi is the probability that a participant maintained vision at week 52 under Aflibercept 2mg Q8, pc is the probability that a participant maintained vision at week 52 under Ranibizumab 0.5mg Q4 and delta is the non-inferiority margin. The null hypothesis is tested calculating a two-sided 95 % confidence using normal approximation of the difference of percentages of participants maintaining vision at week 52 (Ranibizumab 0.5mg Q4 minus Aflibercept 2mg Q8).
Type of Statistical Test Non-Inferiority or Equivalence
Comments The non-inferiority margin is set to 10. The power is 90 % according to the sample size estimation of the study protocol.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -1.13
Confidence Interval (2-Sided) 95%
-4.81 to 2.55
Parameter Dispersion Type:
Value:
Estimation Comments The difference is calculated as Ranibizumab minus Aflibercept. A negative value favors the Aflibercept 2mg Q8 group. As adjustment of multiple comparisons a conditional sequence of statistical hypotheses is used with alpha = 0.05.
2. Secondary Outcome
Title Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) as Measured by ETDRS Letter Score at Week 52 - LOCF
Description 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.
Time Frame Baseline and at week 52

Outcome Measure Data

Analysis Population Description
Full-Analysis Set (FAS); imputation technique: LOCF
Arm/Group Title Ranibizumab 0.5mg Q4 Aflibercept Injection (EYLEA, VEGF Trap-Eye) 2mg Q4 Aflibercept Injection (EYLEA, VEGF Trap-Eye) 0.5mg Q4 Aflibercept Injection (EYLEA, VEGF Trap-Eye) 2mg Q8
Arm/Group Description Participants received a dose of 0.5 mg Ranibizumab every 4 weeks for the first year (intravitreal [IVT] injection). Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks. Participants received a dose of 2.0 mg Aflibercept Injection every 4 weeks for the first year (intravitreal [IVT] injection). Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks. Participants received a dose of 0.5 mg Aflibercept Injection every 4 weeks for the first year (intravitreal [IVT] injection). Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks. Participants received a dose of 2.0 mg Aflibercept Injection every 8 weeks (including one additional 2.0 mg dose at Week 4) for the first year (IVT injection) and were to receive sham injections at interim monthly visits. During the second year, participants received 2.0 mg aflibercept as frequently as every 4 weeks, but no less frequently than every 12 weeks.
Measure Participants 291 309 296 306
Mean (Standard Deviation) [Letters correctly read]
9.4
(13.5)
7.6
(12.6)
9.7
(14.1)
8.9
(14.4)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ranibizumab 0.5mg Q4, Aflibercept Injection (EYLEA, VEGF Trap-Eye) 2mg Q4
Comments The pairwise comparison is performed as contrast statement in the analysis of covariance model with treatment group as fixed factor (all 4 treatment groups) and the baseline ETDRS letter score as covariate. The null hypothesis is that both mean changes are equal.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.076
Comments as adjustment of multiple comparisons a conditional sequence of statistical hypotheses (a-priori ordered hypotheses) is used with alpha = 0.05.
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Differences in Least Squares means
Estimated Value -1.9484
Confidence Interval (2-Sided) 95%
-4.1009 to 0.2040
Parameter Dispersion Type:
Value:
Estimation Comments The difference is calculated as Aflibercept minus Ranibizumab. A positive value favors Aflibercept 2mg Q4.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ranibizumab 0.5mg Q4, Aflibercept Injection (EYLEA, VEGF Trap-Eye) 0.5mg Q4
Comments The pairwise comparison is performed as contrast statement in the analysis of covariance model with treatment group as fixed factor (all 4 treatment groups) and the baseline ETDRS letter score as covariate. The null hypothesis is that both mean changes are equal.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9555
Comments as adjustment of multiple comparisons a conditional sequence of statistical hypotheses (a-priori ordered hypotheses) is used with alpha = 0.05.
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Differences in Least Squares means
Estimated Value -0.0620
Confidence Interval (2-Sided) 95%
-2.2398 to 2.1158
Parameter Dispersion Type:
Value:
Estimation Comments The difference is calculated as Aflibercept minus Ranibizumab. A positive value favors Aflibercept 0.5mg Q4
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ranibizumab 0.5mg Q4, Aflibercept Injection (EYLEA, VEGF Trap-Eye) 2mg Q8
Comments The pairwise comparison is performed as contrast statement in the analysis of covariance model with treatment group as fixed factor (all 4 treatment groups) and the baseline ETDRS letter score as covariate. The null hypothesis is that both mean changes are equal.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.4131
Comments as adjustment of multiple comparisons a conditional sequence of statistical hypotheses (a-priori ordered hypotheses) is used with alpha = 0.05.
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Differences in Least Squares means
Estimated Value -0.9014
Confidence Interval (2-Sided) 95%
-3.0615 to 1.2587
Parameter Dispersion Type:
Value:
Estimation Comments The difference is calculated as Aflibercept minus Ranibizumab. A positive value favors the Aflibercept 2mg Q8 group
3. Secondary Outcome
Title Percentage of Participants Who Gained at Least 15 Letters of Vision in the ETDRS Letter Score in the Study Eye at Week 52 - LOCF
Description 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.
Time Frame At week 52

Outcome Measure Data

Analysis Population Description
Full-Analysis Set; imputation technique: LOCF
Arm/Group Title Ranibizumab 0.5mg Q4 Aflibercept Injection (EYLEA, VEGF Trap-Eye) 2mg Q4 Aflibercept Injection (EYLEA, VEGF Trap-Eye) 0.5mg Q4 Aflibercept Injection (EYLEA, VEGF Trap-Eye) 2mg Q8
Arm/Group Description Participants received a dose of 0.5 mg Ranibizumab every 4 weeks for the first year (intravitreal [IVT] injection). Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks. Participants received a dose of 2.0 mg Aflibercept Injection every 4 weeks for the first year (intravitreal [IVT] injection). Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks. Participants received a dose of 0.5 mg Aflibercept Injection every 4 weeks for the first year (intravitreal [IVT] injection). Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks. Participants received a dose of 2.0 mg Aflibercept Injection every 8 weeks (including one additional 2.0 mg dose at Week 4) for the first year (IVT injection) and were to receive sham injections at interim monthly visits. During the second year, participants received 2.0 mg aflibercept as frequently as every 4 weeks, but no less frequently than every 12 weeks.
Measure Participants 291 309 296 306
Number [Percentage of participants]
34.02
11.7%
29.45
9.5%
34.80
11.8%
31.37
10.3%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ranibizumab 0.5mg Q4, Aflibercept Injection (EYLEA, VEGF Trap-Eye) 2mg Q4
Comments The null hypothesis is that the two proportions are equal.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.229
Comments as adjustment of multiple comparisons a conditional sequence of statistical hypotheses (a-priori ordered hypotheses) is used with alpha = 0.05.
Method Chi-squared
Comments
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -4.57
Confidence Interval (2-Sided) 95%
-12.02 to 2.88
Parameter Dispersion Type:
Value:
Estimation Comments The difference is calculated as Aflibercept minus Ranibizumab. A positive value favors the Aflibercept 2mg Q4 group
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ranibizumab 0.5mg Q4, Aflibercept Injection (EYLEA, VEGF Trap-Eye) 0.5mg Q4
Comments The null hypothesis is that the two proportions are equal.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.843
Comments as adjustment of multiple comparisons a conditional sequence of statistical hypotheses (a-priori ordered hypotheses) is used with alpha = 0.05.
Method Chi-squared
Comments
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 0.78
Confidence Interval (2-Sided) 95%
-6.91 to 8.46
Parameter Dispersion Type:
Value:
Estimation Comments The difference is calculated as Aflibercept minus Ranibizumab. A positive value favors the Aflibercept 0.5mg Q4 group
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ranibizumab 0.5mg Q4, Aflibercept Injection (EYLEA, VEGF Trap-Eye) 2mg Q8
Comments The null hypothesis is that the two proportions are equal.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.490
Comments as adjustment of multiple comparisons a conditional sequence of statistical hypotheses (a-priori ordered hypotheses) is used with alpha = 0.05.
Method Chi-squared
Comments
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -2.65
Confidence Interval (2-Sided) 95%
-10.18 to 4.88
Parameter Dispersion Type:
Value:
Estimation Comments The difference is calculated as Aflibercept minus Ranibizumab. A positive value favors the Aflibercept 2mg Q8 group
4. Secondary Outcome
Title Mean Change From Baseline in National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25) Total Score at Week 52 - LOCF
Description The possible range of the NEI VFQ-25 total score is between 0 (worst possible) and 100 (best possible).
Time Frame Baseline and at week 52

Outcome Measure Data

Analysis Population Description
Full-Analysis Set with assessment for this outcome measure; imputation technique: LOCF
Arm/Group Title Ranibizumab 0.5mg Q4 Aflibercept Injection (EYLEA, VEGF Trap-Eye) 2mg Q4 Aflibercept Injection (EYLEA, VEGF Trap-Eye) 0.5mg Q4 Aflibercept Injection (EYLEA, VEGF Trap-Eye) 2mg Q8
Arm/Group Description Participants received a dose of 0.5 mg Ranibizumab every 4 weeks for the first year (intravitreal [IVT] injection). Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks. Participants received a dose of 2.0 mg Aflibercept Injection every 4 weeks for the first year (intravitreal [IVT] injection). Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks. Participants received a dose of 0.5 mg Aflibercept Injection every 4 weeks for the first year (intravitreal [IVT] injection). Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks. Participants received a dose of 2.0 mg Aflibercept Injection every 8 weeks (including one additional 2.0 mg dose at Week 4) for the first year (IVT injection) and were to receive sham injections at interim monthly visits. During the second year, participants received 2.0 mg aflibercept as frequently as every 4 weeks, but no less frequently than every 12 weeks.
Measure Participants 287 304 290 299
Mean (Standard Deviation) [Scores on a scale]
6.3
(14.8)
4.5
(15.0)
5.1
(13.7)
4.9
(14.7)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ranibizumab 0.5mg Q4, Aflibercept Injection (EYLEA, VEGF Trap-Eye) 2mg Q4
Comments The pairwise comparison is performed as contrast statement in the analysis of covariance model with treatment group as fixed factor (all 4 treatment groups) and the baseline NEI VFQ-25 total score as covariate. The null hypothesis is that both mean changes are equal.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.0097
Comments as adjustment of multiple comparisons a conditional sequence of statistical hypotheses (a-priori ordered hypotheses) is used with alpha = 0.05.
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Differences in Least Squares means
Estimated Value -2.7885
Confidence Interval (2-Sided) 95%
-4.9012 to -0.6757
Parameter Dispersion Type:
Value:
Estimation Comments The difference is calculated as Aflibercept minus Ranibizumab. A positive value favors Aflibercept 2mg Q4.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ranibizumab 0.5mg Q4, Aflibercept Injection (EYLEA, VEGF Trap-Eye) 0.5mg Q4
Comments The pairwise comparison is performed as contrast statement in the analysis of covariance model with treatment group as fixed factor (all 4 treatment groups) and the baseline NEI VFQ-25 total score as covariate. The null hypothesis is that both mean changes are equal.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.3917
Comments as adjustment of multiple comparisons a conditional sequence of statistical hypotheses (a-priori ordered hypotheses) is used with alpha = 0.05.
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Differences in Least Squares means
Estimated Value -0.9320
Confidence Interval (2-Sided) 95%
-3.0658 to 1.2019
Parameter Dispersion Type:
Value:
Estimation Comments The difference is calculated as Aflibercept minus Ranibizumab. A positive value favors Aflibercept 0.5mg Q4.
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ranibizumab 0.5mg Q4, Aflibercept Injection (EYLEA, VEGF Trap-Eye) 2mg Q8
Comments The pairwise comparison is performed as contrast statement in the analysis of covariance model with treatment group as fixed factor (all 4 treatment groups) and the baseline NEI VFQ-25 total score as covariate. The null hypothesis is that both mean changes are equal.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.0717
Comments as adjustment of multiple comparisons a conditional sequence of statistical hypotheses (a-priori ordered hypotheses) is used with alpha = 0.05.
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Differences in Least Squares means
Estimated Value -1.9470
Confidence Interval (2-Sided) 95%
-4.0659 to 0.1718
Parameter Dispersion Type:
Value:
Estimation Comments The difference is calculated as Aflibercept minus Ranibizumab. A positive value favors Aflibercept 2mg Q8.
5. Secondary Outcome
Title Mean Change From Baseline in Choroidal Neovascularization (CNV) Area at Week 52 - LOCF
Description CNV area values measured in square millimeters; lower values represent better outcomes.
Time Frame Baseline and at week 52

Outcome Measure Data

Analysis Population Description
Full-Analysis Set with assessment for this outcome measure; imputation technique: LOCF
Arm/Group Title Ranibizumab 0.5mg Q4 Aflibercept Injection (EYLEA, VEGF Trap-Eye) 2mg Q4 Aflibercept Injection (EYLEA, VEGF Trap-Eye) 0.5mg Q4 Aflibercept Injection (EYLEA, VEGF Trap-Eye) 2mg Q8
Arm/Group Description Participants received a dose of 0.5 mg Ranibizumab every 4 weeks for the first year (intravitreal [IVT] injection). Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks. Participants received a dose of 2.0 mg Aflibercept Injection every 4 weeks for the first year (intravitreal [IVT] injection). Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks. Participants received a dose of 0.5 mg Aflibercept Injection every 4 weeks for the first year (intravitreal [IVT] injection). Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks. Participants received a dose of 2.0 mg Aflibercept Injection every 8 weeks (including one additional 2.0 mg dose at Week 4) for the first year (IVT injection) and were to receive sham injections at interim monthly visits. During the second year, participants received 2.0 mg aflibercept as frequently as every 4 weeks, but no less frequently than every 12 weeks.
Measure Participants 278 294 287 289
Mean (Standard Deviation) [mm^2]
-4.16
(5.90)
-5.95
(6.12)
-4.24
(6.13)
-5.16
(5.87)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ranibizumab 0.5mg Q4, Aflibercept Injection (EYLEA, VEGF Trap-Eye) 2mg Q4
Comments The pairwise comparison is performed as contrast statement in the analysis of covariance model with treatment group as fixed factor (all 4 treatment groups) and the baseline CNV area as covariate. The null hypothesis is that both mean changes are equal.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.0038
Comments as adjustment of multiple comparisons a conditional sequence of statistical hypotheses (a-priori ordered hypotheses) is used with alpha = 0.05.
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Differences in Least Squares means
Estimated Value -1.180
Confidence Interval (2-Sided) 95%
-1.979 to -0.382
Parameter Dispersion Type:
Value:
Estimation Comments The difference is calculated as Aflibercept minus Ranibizumab. A negative value favors Aflibercept 2mg Q4.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ranibizumab 0.5mg Q4, Aflibercept Injection (EYLEA, VEGF Trap-Eye) 0.5mg Q4
Comments The pairwise comparison is performed as contrast statement in the analysis of covariance model with treatment group as fixed factor (all 4 treatment groups) and the baseline CNV area as covariate. The null hypothesis is that both mean changes are equal.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.6784
Comments as adjustment of multiple comparisons a conditional sequence of statistical hypotheses (a-priori ordered hypotheses) is used with alpha = 0.05.
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Differences in Least Squares means
Estimated Value 0.170
Confidence Interval (2-Sided) 95%
-0.632 to 0.972
Parameter Dispersion Type:
Value:
Estimation Comments The difference is calculated as Aflibercept minus Ranibizumab. A negative value favors Aflibercept 0.5mg Q4.
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ranibizumab 0.5mg Q4, Aflibercept Injection (EYLEA, VEGF Trap-Eye) 2mg Q8
Comments The pairwise comparison is performed as contrast statement in the analysis of covariance model with treatment group as fixed factor (all 4 treatment groups) and the baseline CNV area as covariate. The null hypothesis is that both mean changes are equal.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.0727
Comments as adjustment of multiple comparisons a conditional sequence of statistical hypotheses (a-priori ordered hypotheses) is used with alpha = 0.05.
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Differences in Least Squares means
Estimated Value -0.733
Confidence Interval (2-Sided) 95%
-1.534 to 0.068
Parameter Dispersion Type:
Value:
Estimation Comments The difference is calculated as Aflibercept minus Ranibizumab. A negative value favors Aflibercept 2mg Q8.

Adverse Events

Time Frame
Adverse Event Reporting Description
Arm/Group Title Ranibizumab 0.5mg Q4 Aflibercept Injection (EYLEA, VEGF Trap-Eye) 2mg Q4 Aflibercept Injection (EYLEA, VEGF Trap-Eye) 0.5mg Q4 Aflibercept Injection (EYLEA, VEGF Trap-Eye) 2mg Q8
Arm/Group Description Participants received a dose of 0.5 mg Ranibizumab every 4 weeks for the first year (intravitreal [IVT] injection). Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks. Participants received a dose of 2.0 mg Aflibercept Injection every 4 weeks for the first year (intravitreal [IVT] injection). Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks. Participants received a dose of 0.5 mg Aflibercept Injection every 4 weeks for the first year (intravitreal [IVT] injection). Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks. Participants received a dose of 2.0 mg Aflibercept Injection every 8 weeks (including one additional 2.0 mg dose at Week 4) for the first year (IVT injection) and were to receive sham injections at interim monthly visits. During the second year, participants received 2.0 mg aflibercept as frequently as every 4 weeks, but no less frequently than every 12 weeks.
All Cause Mortality
Ranibizumab 0.5mg Q4 Aflibercept Injection (EYLEA, VEGF Trap-Eye) 2mg Q4 Aflibercept Injection (EYLEA, VEGF Trap-Eye) 0.5mg Q4 Aflibercept Injection (EYLEA, VEGF Trap-Eye) 2mg Q8
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total / (NaN) / (NaN) / (NaN) / (NaN)
Serious Adverse Events
Ranibizumab 0.5mg Q4 Aflibercept Injection (EYLEA, VEGF Trap-Eye) 2mg Q4 Aflibercept Injection (EYLEA, VEGF Trap-Eye) 0.5mg Q4 Aflibercept Injection (EYLEA, VEGF Trap-Eye) 2mg Q8
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 65/291 (22.3%) 81/309 (26.2%) 72/297 (24.2%) 81/307 (26.4%)
Blood and lymphatic system disorders
Anaemia 0/291 (0%) 2/309 (0.6%) 1/297 (0.3%) 0/307 (0%)
Febrile neutropenia 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Cardiac disorders
Acute myocardial infarction 1/291 (0.3%) 0/309 (0%) 0/297 (0%) 2/307 (0.7%)
Angina pectoris 1/291 (0.3%) 1/309 (0.3%) 1/297 (0.3%) 0/307 (0%)
Angina unstable 1/291 (0.3%) 0/309 (0%) 1/297 (0.3%) 0/307 (0%)
Aortic valve stenosis 1/291 (0.3%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Arrhythmia 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Arteriosclerosis coronary artery 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Atrial fibrillation 2/291 (0.7%) 2/309 (0.6%) 2/297 (0.7%) 3/307 (1%)
Atrial flutter 0/291 (0%) 2/309 (0.6%) 1/297 (0.3%) 1/307 (0.3%)
Atrioventricular block 0/291 (0%) 0/309 (0%) 1/297 (0.3%) 0/307 (0%)
Bradycardia 1/291 (0.3%) 0/309 (0%) 0/297 (0%) 0/307 (0%)
Cardiac arrest 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Cardiac failure 1/291 (0.3%) 0/309 (0%) 1/297 (0.3%) 1/307 (0.3%)
Cardiac failure congestive 1/291 (0.3%) 1/309 (0.3%) 0/297 (0%) 1/307 (0.3%)
Cardio-respiratory arrest 1/291 (0.3%) 0/309 (0%) 0/297 (0%) 0/307 (0%)
Cardiogenic shock 1/291 (0.3%) 0/309 (0%) 0/297 (0%) 0/307 (0%)
Coronary artery disease 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Coronary artery thrombosis 1/291 (0.3%) 0/309 (0%) 0/297 (0%) 0/307 (0%)
Mitral valve incompetence 1/291 (0.3%) 0/309 (0%) 0/297 (0%) 0/307 (0%)
Myocardial infarction 4/291 (1.4%) 3/309 (1%) 3/297 (1%) 4/307 (1.3%)
Myocardial ischaemia 0/291 (0%) 0/309 (0%) 0/297 (0%) 2/307 (0.7%)
Palpitations 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Pericarditis 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Sinus bradycardia 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Supraventricular tachycardia 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Ventricular arrhythmia 0/291 (0%) 0/309 (0%) 1/297 (0.3%) 0/307 (0%)
Ventricular tachycardia 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Left ventricular dysfunction 0/291 (0%) 0/309 (0%) 1/297 (0.3%) 0/307 (0%)
Cardiopulmonary failure 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Acute coronary syndrome 1/291 (0.3%) 2/309 (0.6%) 2/297 (0.7%) 2/307 (0.7%)
Cardiac disorder 0/291 (0%) 0/309 (0%) 1/297 (0.3%) 0/307 (0%)
Mitral valve disease 1/291 (0.3%) 0/309 (0%) 0/297 (0%) 0/307 (0%)
Cardiovascular insufficiency 0/291 (0%) 0/309 (0%) 0/297 (0%) 2/307 (0.7%)
Ear and labyrinth disorders
Vertigo 0/291 (0%) 0/309 (0%) 1/297 (0.3%) 0/307 (0%)
Tympanic membrane disorder 1/291 (0.3%) 0/309 (0%) 0/297 (0%) 0/307 (0%)
Eye disorders
Blindness 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Cataract 5/291 (1.7%) 4/309 (1.3%) 4/297 (1.3%) 4/307 (1.3%)
Cataract cortical 1/291 (0.3%) 0/309 (0%) 0/297 (0%) 0/307 (0%)
Cataract nuclear 0/291 (0%) 1/309 (0.3%) 1/297 (0.3%) 0/307 (0%)
Cataract subcapsular 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Choroidal detachment 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Hyphaema 1/291 (0.3%) 0/309 (0%) 0/297 (0%) 0/307 (0%)
Iridocyclitis 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Macular cyst 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Macular degeneration 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 3/307 (1%)
Maculopathy 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Posterior capsule opacification 2/291 (0.7%) 0/309 (0%) 0/297 (0%) 0/307 (0%)
Retinal degeneration 1/291 (0.3%) 0/309 (0%) 0/297 (0%) 0/307 (0%)
Retinal detachment 3/291 (1%) 0/309 (0%) 1/297 (0.3%) 0/307 (0%)
Retinal haemorrhage 4/291 (1.4%) 3/309 (1%) 4/297 (1.3%) 2/307 (0.7%)
Retinal pigment epitheliopathy 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Retinal vein occlusion 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Visual acuity reduced 3/291 (1%) 5/309 (1.6%) 1/297 (0.3%) 7/307 (2.3%)
Vitreous detachment 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Vitreous haemorrhage 1/291 (0.3%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Macular hole 0/291 (0%) 0/309 (0%) 1/297 (0.3%) 0/307 (0%)
Ocular retrobulbar haemorrhage 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Choroidal neovascularisation 1/291 (0.3%) 1/309 (0.3%) 0/297 (0%) 2/307 (0.7%)
Retinal pigment epithelial tear 1/291 (0.3%) 0/309 (0%) 1/297 (0.3%) 2/307 (0.7%)
Macular scar 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Age-related macular degeneration 0/291 (0%) 3/309 (1%) 0/297 (0%) 1/307 (0.3%)
Gastrointestinal disorders
Abdominal mass 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Abdominal pain 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 1/307 (0.3%)
Abdominal pain upper 0/291 (0%) 0/309 (0%) 1/297 (0.3%) 0/307 (0%)
Abnormal faeces 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Anal fistula 0/291 (0%) 0/309 (0%) 1/297 (0.3%) 0/307 (0%)
Colitis 1/291 (0.3%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Colonic polyp 2/291 (0.7%) 0/309 (0%) 1/297 (0.3%) 1/307 (0.3%)
Constipation 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Diverticulum 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Diverticulum intestinal 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Femoral hernia 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Femoral hernia, obstructive 1/291 (0.3%) 0/309 (0%) 0/297 (0%) 0/307 (0%)
Gastric ulcer 0/291 (0%) 0/309 (0%) 1/297 (0.3%) 0/307 (0%)
Gastritis 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Gastritis erosive 0/291 (0%) 0/309 (0%) 1/297 (0.3%) 1/307 (0.3%)
Inguinal hernia 0/291 (0%) 1/309 (0.3%) 1/297 (0.3%) 1/307 (0.3%)
Intestinal obstruction 0/291 (0%) 0/309 (0%) 1/297 (0.3%) 0/307 (0%)
Large intestine perforation 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Nausea 1/291 (0.3%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Pancreatitis 0/291 (0%) 0/309 (0%) 1/297 (0.3%) 0/307 (0%)
Pancreatitis acute 0/291 (0%) 0/309 (0%) 1/297 (0.3%) 1/307 (0.3%)
Rectal polyp 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Rectal prolapse 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Small intestinal obstruction 0/291 (0%) 0/309 (0%) 1/297 (0.3%) 0/307 (0%)
Lower gastrointestinal haemorrhage 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Enterovesical fistula 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Bowel movement irregularity 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
General disorders
Asthenia 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Chest pain 3/291 (1%) 1/309 (0.3%) 1/297 (0.3%) 1/307 (0.3%)
Chills 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Death 0/291 (0%) 0/309 (0%) 1/297 (0.3%) 0/307 (0%)
Hernia 0/291 (0%) 0/309 (0%) 1/297 (0.3%) 0/307 (0%)
Malaise 1/291 (0.3%) 0/309 (0%) 0/297 (0%) 0/307 (0%)
Multi-organ failure 1/291 (0.3%) 0/309 (0%) 0/297 (0%) 0/307 (0%)
Oedema peripheral 1/291 (0.3%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Pyrexia 0/291 (0%) 2/309 (0.6%) 0/297 (0%) 1/307 (0.3%)
Disease progression 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Device malfunction 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Device dislocation 1/291 (0.3%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Hepatobiliary disorders
Bile duct stone 0/291 (0%) 0/309 (0%) 1/297 (0.3%) 0/307 (0%)
Cholecystitis 1/291 (0.3%) 2/309 (0.6%) 0/297 (0%) 0/307 (0%)
Cholecystitis acute 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Cholelithiasis 0/291 (0%) 2/309 (0.6%) 2/297 (0.7%) 0/307 (0%)
Jaundice cholestatic 0/291 (0%) 0/309 (0%) 1/297 (0.3%) 0/307 (0%)
Infections and infestations
Appendicitis 1/291 (0.3%) 0/309 (0%) 0/297 (0%) 0/307 (0%)
Bronchitis 1/291 (0.3%) 1/309 (0.3%) 1/297 (0.3%) 1/307 (0.3%)
Diverticulitis 1/291 (0.3%) 0/309 (0%) 0/297 (0%) 0/307 (0%)
Endophthalmitis 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Escherichia sepsis 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Gastroenteritis 1/291 (0.3%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Gastroenteritis salmonella 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Herpes zoster 1/291 (0.3%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Herpes zoster ophthalmic 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Liver abscess 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Peridiverticular abscess 1/291 (0.3%) 0/309 (0%) 0/297 (0%) 0/307 (0%)
Pneumonia 1/291 (0.3%) 4/309 (1.3%) 2/297 (0.7%) 6/307 (2%)
Pneumonia pneumococcal 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Postoperative wound infection 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Pyelonephritis 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Septic shock 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Urinary tract infection 2/291 (0.7%) 2/309 (0.6%) 1/297 (0.3%) 0/307 (0%)
Urosepsis 0/291 (0%) 0/309 (0%) 1/297 (0.3%) 0/307 (0%)
Dysentery 1/291 (0.3%) 0/309 (0%) 0/297 (0%) 0/307 (0%)
Respiratory tract infection 1/291 (0.3%) 0/309 (0%) 0/297 (0%) 0/307 (0%)
Gastroenteritis norovirus 1/291 (0.3%) 0/309 (0%) 0/297 (0%) 0/307 (0%)
Injury, poisoning and procedural complications
Accident 0/291 (0%) 1/309 (0.3%) 1/297 (0.3%) 0/307 (0%)
Ankle fracture 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 1/307 (0.3%)
Burns second degree 0/291 (0%) 0/309 (0%) 1/297 (0.3%) 0/307 (0%)
Cerebral haemorrhage traumatic 0/291 (0%) 0/309 (0%) 1/297 (0.3%) 0/307 (0%)
Clavicle fracture 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Concussion 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Fall 2/291 (0.7%) 1/309 (0.3%) 1/297 (0.3%) 3/307 (1%)
Femoral neck fracture 0/291 (0%) 0/309 (0%) 1/297 (0.3%) 0/307 (0%)
Femur fracture 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Head injury 0/291 (0%) 1/309 (0.3%) 1/297 (0.3%) 0/307 (0%)
Hip fracture 2/291 (0.7%) 1/309 (0.3%) 1/297 (0.3%) 0/307 (0%)
Injury 0/291 (0%) 0/309 (0%) 1/297 (0.3%) 0/307 (0%)
Jaw fracture 1/291 (0.3%) 0/309 (0%) 0/297 (0%) 0/307 (0%)
Joint dislocation 1/291 (0.3%) 0/309 (0%) 0/297 (0%) 0/307 (0%)
Patella fracture 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Radius fracture 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Rib fracture 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Road traffic accident 0/291 (0%) 1/309 (0.3%) 1/297 (0.3%) 1/307 (0.3%)
Skull fractured base 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Subdural haematoma 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Traumatic haematoma 0/291 (0%) 0/309 (0%) 1/297 (0.3%) 0/307 (0%)
Ulna fracture 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Wrist fracture 1/291 (0.3%) 0/309 (0%) 0/297 (0%) 0/307 (0%)
Lumbar vertebral fracture 1/291 (0.3%) 0/309 (0%) 0/297 (0%) 2/307 (0.7%)
Contusion 0/291 (0%) 0/309 (0%) 1/297 (0.3%) 0/307 (0%)
Graft thrombosis 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Wound haemorrhage 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Meniscus lesion 0/291 (0%) 0/309 (0%) 0/297 (0%) 2/307 (0.7%)
Post procedural complication 0/291 (0%) 0/309 (0%) 1/297 (0.3%) 0/307 (0%)
Traumatic brain injury 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Joint injury 1/291 (0.3%) 0/309 (0%) 0/297 (0%) 0/307 (0%)
Eye injury 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Upper limb fracture 2/291 (0.7%) 1/309 (0.3%) 3/297 (1%) 0/307 (0%)
Lower limb fracture 0/291 (0%) 0/309 (0%) 2/297 (0.7%) 0/307 (0%)
Spinal column injury 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Investigations
Blood osmolarity decreased 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Electrocardiogram QT prolonged 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Haematocrit decreased 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Haemoglobin decreased 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Intraocular pressure increased 0/291 (0%) 0/309 (0%) 1/297 (0.3%) 2/307 (0.7%)
Mean cell haemoglobin decreased 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Mean cell volume decreased 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Red blood cell count decreased 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Investigation 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Metabolism and nutrition disorders
Dehydration 2/291 (0.7%) 1/309 (0.3%) 0/297 (0%) 1/307 (0.3%)
Diabetes mellitus 1/291 (0.3%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Gout 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Hyperglycaemia 1/291 (0.3%) 0/309 (0%) 0/297 (0%) 0/307 (0%)
Hypokalaemia 0/291 (0%) 0/309 (0%) 1/297 (0.3%) 0/307 (0%)
Hyponatraemia 0/291 (0%) 0/309 (0%) 2/297 (0.7%) 0/307 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Arthritis 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Back pain 1/291 (0.3%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Dupuytren's contracture 1/291 (0.3%) 0/309 (0%) 0/297 (0%) 0/307 (0%)
Lumbar spinal stenosis 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Neck pain 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Osteoarthritis 0/291 (0%) 0/309 (0%) 3/297 (1%) 1/307 (0.3%)
Rheumatoid arthritis 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Rotator cuff syndrome 0/291 (0%) 0/309 (0%) 1/297 (0.3%) 0/307 (0%)
Sjogren's syndrome 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Spinal column stenosis 0/291 (0%) 0/309 (0%) 1/297 (0.3%) 0/307 (0%)
Synovitis 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Intervertebral disc protrusion 1/291 (0.3%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Foot deformity 0/291 (0%) 0/309 (0%) 1/297 (0.3%) 1/307 (0.3%)
Intervertebral disc degeneration 0/291 (0%) 0/309 (0%) 1/297 (0.3%) 0/307 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Basal cell carcinoma 1/291 (0.3%) 0/309 (0%) 2/297 (0.7%) 0/307 (0%)
Benign salivary gland neoplasm 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Bladder cancer 0/291 (0%) 0/309 (0%) 1/297 (0.3%) 0/307 (0%)
Bladder cancer recurrent 0/291 (0%) 0/309 (0%) 1/297 (0.3%) 0/307 (0%)
Bladder cancer stage 0, with cancer in situ 0/291 (0%) 0/309 (0%) 1/297 (0.3%) 0/307 (0%)
Bladder neoplasm 0/291 (0%) 0/309 (0%) 1/297 (0.3%) 0/307 (0%)
Breast cancer 1/291 (0.3%) 0/309 (0%) 3/297 (1%) 1/307 (0.3%)
Carcinoid tumour 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Colon cancer 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Colon cancer recurrent 1/291 (0.3%) 0/309 (0%) 0/297 (0%) 0/307 (0%)
Gastric cancer 0/291 (0%) 0/309 (0%) 1/297 (0.3%) 1/307 (0.3%)
Glioblastoma multiforme 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Lung carcinoma cell type unspecified stage IV 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Lymphoma 1/291 (0.3%) 0/309 (0%) 0/297 (0%) 0/307 (0%)
Meningioma 0/291 (0%) 0/309 (0%) 1/297 (0.3%) 0/307 (0%)
Metastases to bone 0/291 (0%) 0/309 (0%) 1/297 (0.3%) 0/307 (0%)
Metastases to ovary 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Myelodysplastic syndrome 0/291 (0%) 0/309 (0%) 1/297 (0.3%) 0/307 (0%)
Oesophageal carcinoma 1/291 (0.3%) 0/309 (0%) 0/297 (0%) 0/307 (0%)
Ovarian cancer 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Pancreatic carcinoma 0/291 (0%) 0/309 (0%) 1/297 (0.3%) 0/307 (0%)
Prostate cancer metastatic 0/291 (0%) 0/309 (0%) 1/297 (0.3%) 0/307 (0%)
Squamous cell carcinoma 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Uterine leiomyoma 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Lung cancer metastatic 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Colon cancer metastatic 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Lung neoplasm malignant 0/291 (0%) 0/309 (0%) 2/297 (0.7%) 1/307 (0.3%)
Nervous system disorders
Cerebral infarction 0/291 (0%) 0/309 (0%) 1/297 (0.3%) 0/307 (0%)
Cerebrovascular accident 2/291 (0.7%) 2/309 (0.6%) 1/297 (0.3%) 2/307 (0.7%)
Dementia Alzheimer's type 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Epilepsy 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Headache 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 1/307 (0.3%)
Hypertensive encephalopathy 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Normal pressure hydrocephalus 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Petit mal epilepsy 0/291 (0%) 0/309 (0%) 1/297 (0.3%) 0/307 (0%)
Presyncope 1/291 (0.3%) 0/309 (0%) 0/297 (0%) 0/307 (0%)
Sciatica 0/291 (0%) 0/309 (0%) 1/297 (0.3%) 0/307 (0%)
Subarachnoid haemorrhage 1/291 (0.3%) 1/309 (0.3%) 0/297 (0%) 1/307 (0.3%)
Syncope 1/291 (0.3%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Transient ischaemic attack 1/291 (0.3%) 2/309 (0.6%) 0/297 (0%) 0/307 (0%)
Brain oedema 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
VIIth nerve paralysis 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Lumbar radiculopathy 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Lacunar infarction 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Ischaemic stroke 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Nerve root compression 1/291 (0.3%) 0/309 (0%) 0/297 (0%) 0/307 (0%)
Psychiatric disorders
Confusional state 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Depression 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Renal and urinary disorders
Nephrolithiasis 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Renal failure 0/291 (0%) 3/309 (1%) 0/297 (0%) 2/307 (0.7%)
Renal failure acute 0/291 (0%) 0/309 (0%) 1/297 (0.3%) 0/307 (0%)
Urinary retention 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Urinary tract obstruction 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Cystitis noninfective 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Reproductive system and breast disorders
Benign prostatic hyperplasia 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Ovarian cyst 0/291 (0%) 0/309 (0%) 1/297 (0.3%) 0/307 (0%)
Uterine haemorrhage 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Vaginal prolapse 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema 2/291 (0.7%) 0/309 (0%) 0/297 (0%) 0/307 (0%)
Asthma 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Chronic obstructive pulmonary disease 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 1/307 (0.3%)
Cough 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Dyspnoea 1/291 (0.3%) 1/309 (0.3%) 0/297 (0%) 1/307 (0.3%)
Lung disorder 1/291 (0.3%) 0/309 (0%) 0/297 (0%) 0/307 (0%)
Pleurisy 0/291 (0%) 0/309 (0%) 1/297 (0.3%) 0/307 (0%)
Pneumothorax 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Pulmonary hypertension 1/291 (0.3%) 0/309 (0%) 0/297 (0%) 0/307 (0%)
Sleep apnoea syndrome 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Respiratory tract congestion 0/291 (0%) 0/309 (0%) 1/297 (0.3%) 0/307 (0%)
Skin and subcutaneous tissue disorders
Dermal cyst 0/291 (0%) 0/309 (0%) 1/297 (0.3%) 0/307 (0%)
Dermatitis allergic 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Erythema multiforme 0/291 (0%) 0/309 (0%) 1/297 (0.3%) 0/307 (0%)
Pemphigus 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Rash 0/291 (0%) 2/309 (0.6%) 0/297 (0%) 0/307 (0%)
Skin necrosis 1/291 (0.3%) 0/309 (0%) 0/297 (0%) 0/307 (0%)
Skin ulcer 1/291 (0.3%) 0/309 (0%) 0/297 (0%) 0/307 (0%)
Urticaria 1/291 (0.3%) 0/309 (0%) 0/297 (0%) 0/307 (0%)
Surgical and medical procedures
Blepharoplasty 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Strangulated hernia repair 0/291 (0%) 0/309 (0%) 1/297 (0.3%) 0/307 (0%)
Surgery 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Hip surgery 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Haematoma evacuation 1/291 (0.3%) 0/309 (0%) 0/297 (0%) 0/307 (0%)
Vaginal operation 1/291 (0.3%) 0/309 (0%) 0/297 (0%) 0/307 (0%)
Vascular disorders
Circulatory collapse 0/291 (0%) 1/309 (0.3%) 1/297 (0.3%) 1/307 (0.3%)
Haematoma 1/291 (0.3%) 0/309 (0%) 0/297 (0%) 0/307 (0%)
Hypertension 0/291 (0%) 0/309 (0%) 1/297 (0.3%) 1/307 (0.3%)
Hypertensive crisis 1/291 (0.3%) 1/309 (0.3%) 0/297 (0%) 2/307 (0.7%)
Varicose vein 1/291 (0.3%) 0/309 (0%) 0/297 (0%) 0/307 (0%)
Deep vein thrombosis 0/291 (0%) 0/309 (0%) 1/297 (0.3%) 0/307 (0%)
Peripheral artery aneurysm 0/291 (0%) 0/309 (0%) 0/297 (0%) 1/307 (0.3%)
Venous thrombosis limb 0/291 (0%) 1/309 (0.3%) 0/297 (0%) 0/307 (0%)
Peripheral arterial occlusive disease 1/291 (0.3%) 0/309 (0%) 0/297 (0%) 0/307 (0%)
Other (Not Including Serious) Adverse Events
Ranibizumab 0.5mg Q4 Aflibercept Injection (EYLEA, VEGF Trap-Eye) 2mg Q4 Aflibercept Injection (EYLEA, VEGF Trap-Eye) 0.5mg Q4 Aflibercept Injection (EYLEA, VEGF Trap-Eye) 2mg Q8
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 254/291 (87.3%) 259/309 (83.8%) 251/297 (84.5%) 260/307 (84.7%)
Cardiac disorders
Atrioventricular block first degree 16/291 (5.5%) 25/309 (8.1%) 23/297 (7.7%) 22/307 (7.2%)
Eye disorders
Cataract 29/291 (10%) 36/309 (11.7%) 34/297 (11.4%) 32/307 (10.4%)
Conjunctival haemorrhage 34/291 (11.7%) 33/309 (10.7%) 46/297 (15.5%) 35/307 (11.4%)
Conjunctivitis 19/291 (6.5%) 14/309 (4.5%) 8/297 (2.7%) 21/307 (6.8%)
Dry eye 14/291 (4.8%) 12/309 (3.9%) 15/297 (5.1%) 16/307 (5.2%)
Eye pain 28/291 (9.6%) 36/309 (11.7%) 25/297 (8.4%) 24/307 (7.8%)
Macular cyst 18/291 (6.2%) 8/309 (2.6%) 9/297 (3%) 9/307 (2.9%)
Macular degeneration 37/291 (12.7%) 35/309 (11.3%) 42/297 (14.1%) 51/307 (16.6%)
Macular oedema 17/291 (5.8%) 16/309 (5.2%) 23/297 (7.7%) 22/307 (7.2%)
Maculopathy 13/291 (4.5%) 16/309 (5.2%) 18/297 (6.1%) 10/307 (3.3%)
Ocular hyperaemia 20/291 (6.9%) 18/309 (5.8%) 17/297 (5.7%) 10/307 (3.3%)
Retinal cyst 13/291 (4.5%) 20/309 (6.5%) 17/297 (5.7%) 13/307 (4.2%)
Retinal degeneration 33/291 (11.3%) 37/309 (12%) 27/297 (9.1%) 23/307 (7.5%)
Retinal haemorrhage 82/291 (28.2%) 84/309 (27.2%) 70/297 (23.6%) 82/307 (26.7%)
Retinal oedema 34/291 (11.7%) 32/309 (10.4%) 31/297 (10.4%) 40/307 (13%)
Retinal pigment epitheliopathy 28/291 (9.6%) 23/309 (7.4%) 20/297 (6.7%) 28/307 (9.1%)
Visual acuity reduced 46/291 (15.8%) 44/309 (14.2%) 55/297 (18.5%) 60/307 (19.5%)
Vitreous detachment 22/291 (7.6%) 30/309 (9.7%) 17/297 (5.7%) 24/307 (7.8%)
Conjunctival hyperaemia 18/291 (6.2%) 8/309 (2.6%) 11/297 (3.7%) 5/307 (1.6%)
Detachment of retinal pigment epithelium 38/291 (13.1%) 37/309 (12%) 33/297 (11.1%) 31/307 (10.1%)
Choroidal neovascularisation 28/291 (9.6%) 25/309 (8.1%) 28/297 (9.4%) 23/307 (7.5%)
Age-related macular degeneration 26/291 (8.9%) 28/309 (9.1%) 26/297 (8.8%) 38/307 (12.4%)
Gastrointestinal disorders
Diarrhoea 14/291 (4.8%) 9/309 (2.9%) 16/297 (5.4%) 16/307 (5.2%)
General disorders
Pyrexia 19/291 (6.5%) 12/309 (3.9%) 19/297 (6.4%) 8/307 (2.6%)
Infections and infestations
Bronchitis 13/291 (4.5%) 17/309 (5.5%) 20/297 (6.7%) 12/307 (3.9%)
Influenza 14/291 (4.8%) 19/309 (6.1%) 12/297 (4%) 23/307 (7.5%)
Nasopharyngitis 39/291 (13.4%) 25/309 (8.1%) 32/297 (10.8%) 26/307 (8.5%)
Investigations
Blood glucose increased 9/291 (3.1%) 17/309 (5.5%) 14/297 (4.7%) 18/307 (5.9%)
Intraocular pressure increased 37/291 (12.7%) 38/309 (12.3%) 24/297 (8.1%) 29/307 (9.4%)
Musculoskeletal and connective tissue disorders
Arthralgia 11/291 (3.8%) 8/309 (2.6%) 15/297 (5.1%) 7/307 (2.3%)
Back pain 17/291 (5.8%) 19/309 (6.1%) 12/297 (4%) 16/307 (5.2%)
Nervous system disorders
Dizziness 15/291 (5.2%) 8/309 (2.6%) 4/297 (1.3%) 5/307 (1.6%)
Headache 14/291 (4.8%) 12/309 (3.9%) 16/297 (5.4%) 20/307 (6.5%)
Vascular disorders
Hypertension 42/291 (14.4%) 41/309 (13.3%) 33/297 (11.1%) 34/307 (11.1%)

Limitations/Caveats

The conditional sequence of hypothesis testing had to stop after testing the first superiority hypothesis. Therefore, all further statistical tests are exploratory tests.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Confidentiality agreement with sponsor, contract with the sponsor via the CRO (Clinical research organization), set up based on local legal requirements, changes addressed+confirmed with local responsible persons; PIs interested in presenting the study on meetings, contacted the sponsor and received slides and approval to do so either by the Clinical Lead or the Medical Affairs department

Results Point of Contact

Name/Title Therapeutic Area Head
Organization BAYER
Phone
Email clinical-trials-contact@bayerhealthcare.com
Responsible Party:
Bayer
ClinicalTrials.gov Identifier:
NCT00637377
Other Study ID Numbers:
  • 91689
  • 2007-000583-25
First Posted:
Mar 18, 2008
Last Update Posted:
Dec 12, 2014
Last Verified:
Nov 1, 2014