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VIEW1: Vascular Endothelial Growth Factor VEGF Trap-Eye:Investigation of Efficacy and Safety in Wet Age-Related Macular Degeneration(AMD)

Sponsor
Regeneron Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT00509795
Collaborator
Bayer (Industry)
1,217
Enrollment
188
Locations
4
Arms
47
Duration (Months)
6.5
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is a phase 3, 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 the US and Canada.

Condition or Disease Intervention/Treatment Phase
  • Biological: ranibizumab
  • Biological: aflibercept injection (VEGF Trap-Eye, BAY86-5321)
  • Biological: aflibercept injection (VEGF Trap-Eye, BAY86-5321)
  • Biological: aflibercept injection (VEGF Trap-Eye, BAY86-5321)
 Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
1217 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 III Study of the Efficacy, Safety, and Tolerability of Repeated Doses of Intravitreal VEGF Trap in Subjects With Neovascular Age-Related Macular Degeneration
Study Start Date :
Aug 1, 2007
Actual Primary Completion Date :
Sep 1, 2010
Actual Study Completion Date :
Jul 1, 2011

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: ranibizumab 0.5mg Q4

Biological: ranibizumab
Participants received a 0.5mg dose of ranibizumab via intravitreal (IVT) injection 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.
Other Names:
  • Lucentis

    		•
    Experimental: aflibercept injection 2.0mg Q4

    Biological: aflibercept injection (VEGF Trap-Eye, BAY86-5321)
    Participants received a 2.0mg dose of aflibercept injection 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.
    Other Names:
  • VEGF Trap-Eye
  • BAY86-5321

    		•
    Experimental: aflibercept injection 0.5mg Q4

    Biological: aflibercept injection (VEGF Trap-Eye, BAY86-5321)
    Participants received a 0.5mg dose of aflibercept injection 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.
    Other Names:
  • VEGF Trap-Eye
  • BAY86-5321

    		•
    Experimental: aflibercept injection 2.0mg Q8

    Biological: aflibercept injection (VEGF Trap-Eye, BAY86-5321)
    Participants received a 2.0mg dose of aflibercept injection every 8 weeks (including one additional 2.0 mg dose at Week 4) for the first year and were to receive sham injections at interim monthly visits. Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks.
    Other Names:
  • VEGF Trap-Eye
  • BAY86-5321

    		•

    Outcome Measures

    Primary Outcome Measures

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

      Defined "maintenance of vision" as patients who lost fewer than 15 letters in Early Treatment Diabetic Retinopathy Study (ETDRS) letter score compared to baseline.

    Secondary Outcome Measures

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

      Defined study baseline range of ETDRS Best Corrected Visual Acuity of: letter score of 73 to 25 (20/40 to 20/320) in the study eye; a higher score represents better functioning.

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

      Defined study baseline range of ETDRS Best Corrected Visual Acuity of: letter score of 73 to 25 (20/40 to 20/320) in the study eye; a higher score represents better functioning.

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

      The NEI VFQ-25 total score ranges from 0-100 with a score of 0 being the worst outcome and 100 being the best outcome. The NEI VFQ questionnaire is organized as a collection of subscales which are all scored from 0-100. To reach the overall composite score, each sub-scale score is averaged in order to give each sub-scale equal weight.

    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 (mm^2); 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:

    1. Signed Informed Consent.

    2. Men and women ≥ 50 years of age.

    3. Active primary or recurrent subfoveal CNV lesions secondary to AMD, including juxtafoveal lesions that affect the fovea as evidenced by FA in the study eye.

    4. Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) of: letter score of 73 to 25 (20/40 to 20/320) in the study eye at 4 meters.

    5. Willing, committed, and able to return for ALL clinic visits and complete all study-related procedures.

    6. 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. See Appendix J.4) understand and willing to sign the informed consent form.

    Key

    Exclusion Criteria:

    1. Any prior ocular (in the study eye) or systemic treatment or surgery for neovascular AMD except dietary supplements or vitamins.

    2. Any prior or concomitant therapy with another investigational agent to treat neovascular AMD in the study eye, except dietary supplements or vitamins.

    3. Any prior treatment with anti-VEGF agents in the study eye.

    4. Total lesion size > 12 disc areas (30.5 mm^2, including blood, scars and neovascularization) as assessed by FA in the study eye.

    5. Subretinal hemorrhage 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 270 degrees by visible CNV.)

    6. Scar or fibrosis, making up > 50% of total lesion in the study eye.

    7. Scar, fibrosis, or atrophy involving the center of the fovea.

    8. Presence of retinal pigment epithelial tears or rips involving the macula in the study eye.

    9. History of any vitreous hemorrhage within 4 weeks prior to Visit 1 in the study eye.

    10. Presence of other causes of CNV in the study eye.

    11. History or clinical evidence of diabetic retinopathy, diabetic macular edema or any other vascular disease affecting the retina,other than AMD, in either eye.

    12. Prior vitrectomy in the study eye.

    13. History of retinal detachment or treatment or surgery for retinal detachment in the study eye.

    14. Any history of macular hole of stage 2 and above in the study eye.

    15. 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 its unlikely to interfere with the injection.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Birmingham Alabama United States 35205
    2 Birmingham Alabama United States 35223
    3 Phoenix Arizona United States 85014
    4 Phoenix Arizona United States 85020
    5 Tucson Arizona United States 85704
    6 Tucson Arizona United States 85710
    7 Beverly Hills California United States 90211
    8 Campbell California United States 95008
    9 Fullerton California United States 92835
    10 Glendale California United States 91203
    11 Irvine California United States 92697
    12 La Jolla California United States 92037
    13 Loma Linda California United States 92354
    14 Los Angeles California United States 90033
    15 Los Angeles California United States 90048
    16 Menlo Park California United States 94025
    17 Mountain View California United States 94040
    18 Oakland California United States 94609
    19 Palm Springs California United States 92262
    20 Pasadena California United States 91105
    21 Poway California United States 92064
    22 Sacramento California United States 95819
    23 San Diego California United States 92120
    24 San Francisco California United States 94107
    25 Santa Ana California United States 92705
    26 Torrance California United States 90503
    27 Ventura California United States 93003
    28 Westlake Village California United States 91361
    29 Yorba Linda California United States 92887
    30 Aurora Colorado United States 80045
    31 Denver Colorado United States 80205
    32 Denver Colorado United States 80230
    33 Bridgeport Connecticut United States 06606
    34 Hamden Connecticut United States 06518
    35 New Haven Connecticut United States 06510
    36 New London Connecticut United States 06320
    37 Altamonte Springs Florida United States 32701
    38 Boynton Beach Florida United States 33426
    39 Fort Myers Florida United States 33907
    40 Ft. Lauderdale Florida United States 33351
    41 Ft. Myers Florida United States 33912
    42 Gainesville Florida United States 32610
    43 Jacksonville Florida United States 32224
    44 Miami Florida United States 33136
    45 Miami Florida United States 33143
    46 Mount Dora Florida United States 32757
    47 Orlando Florida United States 32803
    48 Orlando Florida United States 32806
    49 Oscala Florida United States 34472
    50 Palm Beach Gardens Florida United States 33410
    51 Pensacola Florida United States 32503
    52 Sarasota Florida United States
    53 Stuart Florida United States 34994
    54 Tampa Florida United States 33612
    55 Winter Haven Florida United States 33880
    56 Augusta Georgia United States 30909
    57 Aiea Hawaii United States 96701
    58 Honolulu Hawaii United States 96813
    59 Oak Brook Illinois United States 60523
    60 Fort Wayne Indiana United States 46804
    61 Indianapolis Indiana United States 46202
    62 Indianapolis Indiana United States 46260
    63 Indianapolis Indiana United States 46280
    64 New Albany Indiana United States 47150
    65 Iowa City Iowa United States 52242-1091
    66 Wichita Kansas United States 67214
    67 Louisville Kentucky United States 40202
    68 Louisville Kentucky United States 40207
    69 Paducah Kentucky United States 42001
    70 New Orleans Louisiana United States 70115
    71 New Orleans Louisiana United States 70121
    72 Shreveport Louisiana United States 71105
    73 Bangor Maine United States 04401
    74 Portland Maine United States 04102
    75 Baltimore Maryland United States 21209
    76 Baltimore Maryland United States 21287
    77 Chevy Chase Maryland United States 20815
    78 Hagerstown Maryland United States 21740
    79 Towson Maryland United States 21204
    80 Boston Massachusetts United States 02111
    81 Boston Massachusetts United States 02114
    82 Boston Massachusetts United States 02215
    83 Boston Massachusetts United States
    84 Peabody Massachusetts United States 01960
    85 Ann Arbor Michigan United States 48105
    86 Battle Creek Michigan United States 49015
    87 Detroit Michigan United States 48202
    88 Grand Rapids Michigan United States 49525
    89 Jackson Michigan United States 49201
    90 Royal Oak Michigan United States 48073
    91 Southfield Michigan United States 48034
    92 West Bloomfield Michigan United States 48322
    93 Edina Minnesota United States 55435
    94 Minneapolis Minnesota United States 55404
    95 Rochester Minnesota United States 55905
    96 Florissant Missouri United States 63031
    97 Kansas City Missouri United States 64108
    98 Kansas City Missouri United States 64111
    99 Springfield Missouri United States 65804
    100 St. Louis Missouri United States 63110
    101 Missoula Montana United States 59801
    102 Lincoln Nebraska United States 68506
    103 Omaha Nebraska United States 68131
    104 Las Vegas Nevada United States 89144
    105 Lawrenceville New Jersey United States 08648
    106 New Brunswick New Jersey United States 08901
    107 Northfield New Jersey United States 08225
    108 Teaneck New Jersey United States 07666
    109 Toms River New Jersey United States 08753
    110 Albuquerque New Mexico United States 87106
    111 Albany New York United States 12206
    112 Brooklyn New York United States 11223
    113 Lynbrook New York United States 11563
    114 New York New York United States 10003
    115 New York New York United States 10021
    116 New York New York United States 10032
    117 Poughkeepsie New York United States 12601
    118 Rochester New York United States 14620
    119 Rochester New York United States 14642
    120 Slingerlands New York United States 12159
    121 Syracuse New York United States 13224
    122 Asheville North Carolina United States 28803
    123 Charlotte North Carolina United States 28210
    124 Raleigh North Carolina United States 27607
    125 Southern Pines North Carolina United States 28387
    126 Winston-Salem North Carolina United States 27157
    127 Cincinnati Ohio United States 45202
    128 Cincinnati Ohio United States 45242
    129 Columbus Ohio United States 43215
    130 Toledo Ohio United States 43608
    131 Oklahoma City Oklahoma United States 73104
    132 Ashland Oregon United States 97520
    133 Portland Oregon United States 97210
    134 Portland Oregon United States 97227
    135 Salem Oregon United States 97302
    136 Kingston Pennsylvania United States 18704
    137 Philadelphia Pennsylvania United States 19104
    138 Philadelphia Pennsylvania United States 19107
    139 Philadelphia Pennsylvania United States 19124
    140 Pittsberg Pennsylvania United States 15231
    141 Pittsburgh Pennsylvania United States 15212
    142 Pittsburgh Pennsylvania United States 15213
    143 West Mifflin Pennsylvania United States 15122
    144 Wyomissing Pennsylvania United States 19610
    145 Providence Rhode Island United States 02903-4928
    146 Charleston South Carolina United States 29414
    147 Columbia South Carolina United States 29223
    148 Greenville South Carolina United States 29605
    149 West Columbia South Carolina United States 29169
    150 Rapid City South Dakota United States 57701
    151 Memphis Tennessee United States 38119
    152 Memphis Tennessee United States 38120
    153 Nashville Tennessee United States 37203
    154 Abilene Texas United States 79606
    155 Austin Texas United States 78705
    156 Corpus Cristi Texas United States 78413
    157 Dallas Texas United States 75390
    158 DeSoto Texas United States 75115
    159 Ft. Worth Texas United States 76102
    160 Ft. Worth Texas United States 76104
    161 Galveston Texas United States 77555
    162 Houston Texas United States 77030
    163 McAllen Texas United States 78503
    164 Odessa Texas United States 79761
    165 San Antonio Texas United States 78240
    166 Salt Lake City Utah United States 84107
    167 Salt Lake City Utah United States 84132
    168 Burlington Vermont United States 05401
    169 Charlottesville Virginia United States 22908
    170 Fairfax Virginia United States 22031
    171 Richmond Virginia United States 23221
    172 Seattle Washington United States 98104
    173 Silverdale Washington United States 98383
    174 Madison Wisconsin United States 53715
    175 Madison Wisconsin United States 58705
    176 Milwaukee Wisconsin United States 53226
    177 Calgary Alberta Canada T3E 7MB
    178 Vancouver British Columbia Canada V5Z 3N9
    179 Victoria British Columbia Canada V8V 1B3
    180 Halifax Nova Scotia Canada B3H 2Y9
    181 London Ontario Canada N6A 4G5
    182 Mississauga Ontario Canada L4W 1W9
    183 Ottawa Ontario Canada K1H8L6
    184 Toronto Ontario Canada M4N3M5
    185 Toronto Ontario Canada M5C 2T2
    186 Montreal Quebec Canada H1T 2M4
    187 Montreal Quebec Canada H3A 1A1
    188 Regina Saskatchewan Canada S4T 1A5

    Sponsors and Collaborators

    • Regeneron Pharmaceuticals
    • Bayer

    Investigators

    • Study Director: Robert Vitti, MD, Regeneron Pharmaceuticals

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Regeneron Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT00509795
    Other Study ID Numbers:
    • VGFT-OD-0605
    First Posted:
    Aug 1, 2007
    Last Update Posted:
    Dec 28, 2012
    Last Verified:
    Dec 1, 2012
    Additional relevant MeSH terms:
    Macular Degeneration
    Ranibizumab
    Aflibercept

    Study Results

    Participant Flow

    Recruitment Details The study was conducted at 164 sites in the United States and Canada. Recruitment period: 02 Aug 2007 to 15 Sep 2009.
    Pre-assignment Detail 2063 patients were screened, 1217 randomized, and 1215 included in the Safety Analysis Set (SAF). The Full Analysis Set (FAS) included 1210 patients with at least 1 post-baseline assessment. The Per Protocol Set (PPS) included 1089 patients who received ≥ 9 doses of study drug and attended ≥ 9 scheduled visits during the first year.
    Arm/Group Title Ranibizumab 0.5mg Q4 IAI (EYLEA, VEGF Trap-Eye) 2.0mg Q4 IAI (EYLEA, VEGF Trap-Eye) 0.5mg Q4 IAI (EYLEA, VEGF Trap-Eye) 2.0mg Q8
    Arm/Group Description Patients received a 0.5mg dose of ranibizumab via intravitreal (IVT) injection every 4 weeks for the first year. Patients received a 2.0mg dose of Intravitreal Aflibercept Injection (IAI, EYLEA, VEGF Trap-Eye) every 4 weeks for the first year. Patients received a 0.5mg dose of Intravitreal Aflibercept Injection (IAI, EYLEA, VEGF Trap-Eye) every 4 weeks for the first year. Patients received a 2.0mg dose of Intravitreal Aflibercept Injection (IAI, EYLEA, VEGF Trap-Eye) every 8 weeks (including one additional 2.0 mg dose at Week 4) for the first year and received sham injections at interim monthly visits.
    Period Title: Overall Study
    STARTED 306 304 304 303
    Patients Received Treatment (SAF) 304 304 304 303
    Full Analysis Set (FAS) Population 304 304 301 301
    Per Protocol Set (PPS) Population 269 285 270 265
    COMPLETED 284 293 277 276
    NOT COMPLETED 22 11 27 27

    Baseline Characteristics

    Arm/Group Title Ranibizumab 0.5mg Q4 IAI (EYLEA, VEGF Trap-Eye) 2.0mg Q4 IAI (EYLEA, VEGF Trap-Eye) 0.5mg Q4 IAI (EYLEA, VEGF Trap-Eye) 2.0mg Q8 Total
    Arm/Group Description Patients received a 0.5mg dose of ranibizumab via IVT injection every 4 weeks for the first year. Patients received a 2.0mg dose of Intravitreal Aflibercept Injection (IAI, EYLEA, VEGF Trap-Eye) every 4 weeks for the first year. Patients received a 0.5mg dose of Intravitreal Aflibercept Injection (IAI, EYLEA, VEGF Trap-Eye) every 4 weeks for the first year. Patients received a 2.0mg dose of Intravitreal Aflibercept Injection (IAI, EYLEA, VEGF Trap-Eye) every 8 weeks (including one additional 2.0 mg dose at Week 4) for the first year and were to receive sham injections at interim monthly visits. Total of all reporting groups
    Overall Participants 304 304 304 303 1215
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    78.2
    (7.59)
    77.7
    (7.93)
    78.3
    (8.10)
    77.9
    (8.39)
    78.0
    (8.00)
    Sex: Female, Male (Count of Participants)
    Female
    172
    56.6%
    194
    63.8%
    169
    55.6%
    179
    59.1%
    714
    58.8%
    Male
    132
    43.4%
    110
    36.2%
    135
    44.4%
    124
    40.9%
    501
    41.2%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    7
    (0) 2.3%
    11
    (0) 3.6%
    11
    (0) 3.6%
    12
    (0) 4%
    41
    3.4%
    Not Hispanic or Latino
    297
    97.7%
    293
    96.4%
    293
    96.4%
    291
    96%
    1174
    96.6%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    2
    (0) 0.7%
    0
    (0) 0%
    2
    (0) 0.7%
    1
    (0) 0.3%
    5
    0.4%
    Asian
    0
    (0) 0%
    3
    (0) 1%
    5
    (0) 1.6%
    4
    (0) 1.3%
    12
    1%
    Native Hawaiian or Other Pacific Islander
    1
    (0) 0.3%
    0
    (0) 0%
    0
    (0) 0%
    1
    (0) 0.3%
    2
    0.2%
    Black or African American
    1
    (0) 0.3%
    1
    (0) 0.3%
    0
    (0) 0%
    1
    (0) 0.3%
    3
    0.2%
    White
    296
    (0) 97.4%
    295
    (0) 97%
    294
    (0) 96.7%
    289
    (0) 95.4%
    1174
    96.6%
    More than one race
    0
    (0) 0%
    0
    (0) 0%
    0
    (0) 0%
    1
    (0) 0.3%
    1
    0.1%
    Unknown or Not Reported
    4
    (0) 1.3%
    5
    (0) 1.6%
    3
    (0) 1%
    6
    (0) 2%
    18
    1.5%
    Baseline 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]
    71.7
    (17.29)
    70.4
    (16.60)
    71.1
    (17.72)
    69.5
    (16.82)
    70.7
    (17.11)
    Baseline Area of Choroidal Neovascularization (CNV) (mm^2) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mm^2]
    6.52
    (5.245)
    6.59
    (5.052)
    6.49
    (4.437)
    6.56
    (5.129)
    6.54
    (4.968)
    Baseline Lesion Type (patients) [Number]
    Occult
    115
    (0)
    110
    (0)
    123
    (0)
    118
    (0)
    466
    Minimally Classic
    101
    (0)
    105
    (0)
    97
    (0)
    112
    (0)
    415
    Predominantly Classic
    82
    (0)
    87
    (0)
    82
    (0)
    71
    (0)
    322
    Missing
    6
    (0)
    2
    (0)
    2
    (0)
    2
    (0)
    12
    Baseline Total Lesion Size (mm^2) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mm^2]
    6.99
    (5.491)
    6.98
    (5.388)
    6.96
    (4.711)
    6.88
    (5.214)
    6.95
    (5.202)
    Baseline Best Corrected Visual Acuity (BCVA) (letters read) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [letters read]
    54.0
    (13.43)
    55.2
    (13.15)
    55.5
    (13.12)
    55.7
    (12.84)
    55.1
    (13.14)

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Patients Who Maintained Vision at Week 52 - Last Observation Carried Forward (LOCF)
    Description Defined "maintenance of vision" as patients who lost fewer than 15 letters in Early Treatment Diabetic Retinopathy Study (ETDRS) letter score compared to baseline.
    Time Frame Baseline and at week 52

    Outcome Measure Data

    Analysis Population Description
    PPS population used for analysis.
    Arm/Group Title Ranibizumab 0.5mg Q4 IAI (EYLEA, VEGF Trap-Eye) 2.0mg Q4 IAI (EYLEA, VEGF Trap-Eye) 0.5mg Q4 IAI (EYLEA, VEGF Trap-Eye) 2.0mg Q8 Total
    Arm/Group Description Patients received a 0.5mg dose of ranibizumab via IVT injection every 4 weeks for the first year. Patients received a 2.0mg dose of Intravitreal Aflibercept Injection (IAI, EYLEA, VEGF Trap-Eye) every 4 weeks for the first year. Patients received a 0.5mg dose of Intravitreal Aflibercept Injection (IAI, EYLEA, VEGF Trap-Eye) every 4 weeks for the first year. Patients received a 2.0mg dose of Intravitreal Aflibercept Injection (IAI, EYLEA, VEGF Trap-Eye) every 8 weeks (including one additional 2.0 mg dose at Week 4) for the first year and were to receive sham injections at interim monthly visits.
    Measure Participants 269 285 270 265 1089
    Number [percentage of patients]
    94.4
    (0)
    95.1
    (0)
    95.9
    (0)
    95.1
    (0)
    95.1
    (0)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ranibizumab 0.5mg Q4, IAI (EYLEA, VEGF Trap-Eye) 2.0mg Q4
    Comments The statistical approach included a conditional sequence of calculations of the 95.1% CI using normal approximation of the difference between the proportion of patients with maintained vision at Week 52 for the group treated with 0.5 mg ranibizumab and the proportion of patients with maintained vision for each of the groups treated with IAI.
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments The non-inferiority margin was set at 10%. The power is 90% according to the sample size estimation of the study protocol. Although not in the analysis plan for the study, in a separate communication, the FDA further explained that, whereas the 10% non-inferiority margin would be used to assess non-inferiority, a 5% non-inferiority margin would be used to assess clinical equivalence.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value -0.7
    Confidence Interval (2-Sided) 95.1%
    -4.4 to 3.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments The difference is calculated as ranibizumab minus IAI. A positive value favors IAI 2.0Q4. As adjustment of multiple comparisons as conditional sequence of statistical hypotheses is used with alpha = 0.049.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Ranibizumab 0.5mg Q4, IAI (EYLEA, VEGF Trap-Eye) 0.5mg Q4
    Comments The statistical approach included a conditional sequence of calculations of the 95.1% CI using normal approximation of the difference between the proportion of patients with maintained vision at Week 52 for the group treated with 0.5 mg ranibizumab and the proportion of patients with maintained vision for each of the groups treated with IAI (EYLEA, VEGF Trap-Eye).
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments The non-inferiority margin was set at 10%. The power is 90% according to the sample size estimation of the study protocol. Although not in the analysis plan for the study, in a separate communication, the FDA further explained that, whereas the 10% non-inferiority margin would be used to assess non-inferiority, a 5% non-inferiority margin would be used to assess clinical equivalence.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value -1.5
    Confidence Interval (2-Sided) 95.1%
    -5.1 to 2.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments The difference is calculated as ranibizumab minus IAI. A negative value favors the IAI 0.5Q4 group. As adjustment of multiple comparisons as conditional sequence of statistical hypotheses is used with alpha = 0.049.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Ranibizumab 0.5mg Q4, IAI (EYLEA, VEGF Trap-Eye) 2.0mg Q8
    Comments The statistical approach included a conditional sequence of calculations of the 95.1% CI using normal approximation of the difference between the proportion of patients with maintained vision at Week 52 for the group treated with 0.5 mg ranibizumab and the proportion of patients with maintained vision for each of the groups treated with IAI (EYLEA, VEGF Trap-Eye).
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments The non-inferiority margin was set at 10%. The power is 90% according to the sample size estimation of the study protocol. Although not in the analysis plan for the study, in a separate communication, the FDA further explained that, whereas the 10% non-inferiority margin would be used to assess non-inferiority, a 5% non-inferiority margin would be used to assess clinical equivalence.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value -0.7
    Confidence Interval (2-Sided) 95.1%
    -4.5 to 3.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments The difference is calculated as ranibizumab minus IAI. A negative value favors the IAI 2.0Q8 group. As adjustment of multiple comparisons as conditional sequence of statistical hypotheses is used with alpha = 0.049.
    2. Secondary Outcome
    Title Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) as Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score at Week 52 - LOCF
    Description Defined study baseline range of ETDRS Best Corrected Visual Acuity of: letter score of 73 to 25 (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
    FAS population used for analysis.
    Arm/Group Title Ranibizumab 0.5mg Q4 IAI (EYLEA, VEGF Trap-Eye) 2.0mg Q4 IAI (EYLEA, VEGF Trap-Eye) 0.5mg Q4 IAI (EYLEA, VEGF Trap-Eye) 2.0mg Q8 Total
    Arm/Group Description Patients received a 0.5mg dose of ranibizumab via IVT injection every 4 weeks for the first year. Patients received a 2.0mg dose of Intravitreal Aflibercept Injection (IAI, EYLEA, VEGF Trap-Eye) every 4 weeks for the first year. Patients received a 0.5mg dose of Intravitreal Aflibercept Injection (IAI, EYLEA, VEGF Trap-Eye) every 4 weeks for the first year. Patients received a 2.0mg dose of Intravitreal Aflibercept Injection (IAI, EYLEA, VEGF Trap-Eye) every 8 weeks (including one additional 2.0 mg dose at Week 4) for the first year and were to receive sham injections at interim monthly visits.
    Measure Participants 304 304 301 301 1210
    Mean (Standard Deviation) [letters read]
    8.1
    (15.25)
    10.9
    (13.77)
    6.9
    (13.41)
    7.9
    (15.00)
    8.5
    (14.44)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ranibizumab 0.5mg Q4, IAI (EYLEA, VEGF Trap-Eye) 2.0mg 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 measure 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 0.0054
    Comments As adjustment of multiple comparisons, a conditional sequence of statistical hypotheses is used with alpha = 0.049
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Differences in Least Squares means
    Estimated Value 3.15
    Confidence Interval (2-Sided) 95.1%
    0.92 to 5.37
    Parameter Dispersion Type:
    Value:
    Estimation Comments The difference is calculated as IAI minus ranibizumab. A positive value favors IAI 2.0Q4.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Ranibizumab 0.5mg Q4, IAI (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 measure 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 0.4793
    Comments As adjustment of multiple comparisons, a conditional sequence of statistical hypotheses is used with alpha = 0.049
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Differences in Least Squares means
    Estimated Value 0.80
    Confidence Interval (2-Sided) 95.1%
    -3.03 to 1.43
    Parameter Dispersion Type:
    Value:
    Estimation Comments The difference is calculated as IAI minus ranibizumab. A positive value favors IAI 0.5Q4.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Ranibizumab 0.5mg Q4, IAI (EYLEA, VEGF Trap-Eye) 2.0mg 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 measure 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 0.8179
    Comments As adjustment of multiple comparisons, a conditional sequence of statistical hypotheses is used with alpha = 0.049
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Differences in Least Squares Means
    Estimated Value 0.26
    Confidence Interval (2-Sided) 95.1%
    -1.97 to 2.49
    Parameter Dispersion Type:
    Value:
    Estimation Comments The difference is calculated as IAI minus ranibizumab. A positive value favors IAI 2.0Q8.
    3. Secondary Outcome
    Title Percentage of Patients 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 of: letter score of 73 to 25 (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
    FAS population used for analysis.
    Arm/Group Title Ranibizumab 0.5mg Q4 IAI (EYLEA, VEGF Trap-Eye) 2.0mg Q4 IAI (EYLEA, VEGF Trap-Eye) 0.5mg Q4 IAI (EYLEA, VEGF Trap-Eye) 2.0mg Q8 Total
    Arm/Group Description Patients received a 0.5mg dose of ranibizumab via IVT injection every 4 weeks for the first year. Patients received a 2.0mg dose of Intravitreal Aflibercept Injection (IAI, EYLEA, VEGF Trap-Eye) every 4 weeks for the first year. Patients received a 0.5mg dose of Intravitreal Aflibercept Injection (IAI, EYLEA, VEGF Trap-Eye) every 4 weeks for the first year. Patients received a 2.0mg dose of Intravitreal Aflibercept Injection (IAI, EYLEA, VEGF Trap-Eye) every 8 weeks (including one additional 2.0 mg dose at Week 4) for the first year and were to receive sham injections at interim monthly visits.
    Measure Participants 304 304 301 301 1210
    Number [percentage of patients]
    30.9
    (0)
    37.5
    (0)
    24.9
    (0)
    30.6
    (0)
    31.1
    (0)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ranibizumab 0.5mg Q4, IAI (EYLEA, VEGF Trap-Eye) 2.0mg Q4
    Comments The null hypothesis is that both percentages are equal.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.1042
    Comments As adjustment of multiple comparisons, a conditional sequence of statistical hypotheses is used with alpha = 0.049.
    Method Chi-squared
    Comments
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value 6.6
    Confidence Interval (2-Sided) 95.1%
    -1.0 to 14.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments The difference is calculated as IAI minus ranibizumab. A positive value favors IAI 2.0Q4.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Ranibizumab 0.5mg Q4, IAI (EYLEA, VEGF Trap-Eye) 0.5mg Q4
    Comments The null hypothesis is that both percentages are equal.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.1037
    Comments As adjustment of multiple comparisons, a conditional sequence of statistical hypotheses is used with alpha = 0.049.
    Method Chi-squared
    Comments
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value -6.0
    Confidence Interval (2-Sided) 95.1%
    -13.2 to 1.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments The difference is calculated as IAI minus ranibizumab. A positive value favors IAI 0.5Q4.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Ranibizumab 0.5mg Q4, IAI (EYLEA, VEGF Trap-Eye) 2.0mg Q8
    Comments The pairwise The null hypothesis is that both percentages are equal.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.93
    Comments As adjustment of multiple comparisons, a conditional sequence of statistical hypotheses is used with alpha = 0.049.
    Method Chi-squared
    Comments
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value -0.4
    Confidence Interval (2-Sided) 95.1%
    -7.7 to 7.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments The difference is calculated as VEGF Trap-Eye minus ranibizumab. A positive value favors VEGF Trap-Eye 2.0Q8.
    4. Secondary Outcome
    Title Mean Change From Baseline in National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25) Total Score at Week 52 - LOCF
    Description The NEI VFQ-25 total score ranges from 0-100 with a score of 0 being the worst outcome and 100 being the best outcome. The NEI VFQ questionnaire is organized as a collection of subscales which are all scored from 0-100. To reach the overall composite score, each sub-scale score is averaged in order to give each sub-scale equal weight.
    Time Frame Baseline and at Week 52

    Outcome Measure Data

    Analysis Population Description
    FAS population used for analysis.
    Arm/Group Title Ranibizumab 0.5mg Q4 IAI (EYLEA, VEGF Trap-Eye) 2.0mg Q4 IAI (EYLEA, VEGF Trap-Eye) 0.5mg Q4 IAI (EYLEA, VEGF Trap-Eye) 2.0mg Q8 Total
    Arm/Group Description Patients received a 0.5mg dose of ranibizumab via IVT injection every 4 weeks for the first year. Patients received a 2.0mg dose of Intravitreal Aflibercept Injection (IAI, EYLEA, VEGF Trap-Eye) every 4 weeks for the first year. Patients received a 0.5mg dose of Intravitreal Aflibercept Injection (IAI, EYLEA, VEGF Trap-Eye) every 4 weeks for the first year. Patients received a 2.0mg dose of Intravitreal Aflibercept Injection (IAI, EYLEA, VEGF Trap-Eye) every 8 weeks (including one additional 2.0 mg dose at Week 4) for the first year and were to receive sham injections at interim monthly visits.
    Measure Participants 304 304 301 301 1210
    Mean (Standard Deviation) [scores on a scale]
    4.9
    (14.01)
    6.7
    (13.50)
    4.5
    (11.87)
    5.1
    (14.74)
    5.3
    (13.59)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ranibizumab 0.5mg Q4, IAI (EYLEA, VEGF Trap-Eye) 2.0mg 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 measure 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 0.2090
    Comments As adjustment of multiple comparisons, a conditional sequence of statistical hypotheses is used with alpha = 0.049
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Differences Least Squares means
    Estimated Value 1.28
    Confidence Interval (2-Sided) 95.1%
    -0.73 to 3.28
    Parameter Dispersion Type:
    Value:
    Estimation Comments The difference is calculated as IAI minus ranibizumab. A positive value favors IAI 2.0Q4.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Ranibizumab 0.5mg Q4, IAI (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 measure 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 0.5128
    Comments As adjustment of multiple comparisons, a conditional sequence of statistical hypotheses is used with alpha = 0.049
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Differences in Least Squares means
    Estimated Value -0.67
    Confidence Interval (2-Sided) 95.1%
    -2.69 to 1.35
    Parameter Dispersion Type:
    Value:
    Estimation Comments The difference is calculated as IAI minus ranibizumab. A positive value favors IAI 0.5Q4.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Ranibizumab 0.5mg Q4, IAI (EYLEA, VEGF Trap-Eye) 2.0mg 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 measure 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 0.5579
    Comments As adjustment of multiple comparisons, a conditional sequence of statistical hypotheses is used with alpha = 0.049
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Differences in Least Squares means
    Estimated Value -0.60
    Confidence Interval (2-Sided) 95.1%
    -2.61 to 1.42
    Parameter Dispersion Type:
    Value:
    Estimation Comments The difference is calculated as IAI minus ranibizumab. A positive value favors IAI 2.0Q8.
    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 (mm^2); lower values represent better outcomes.
    Time Frame Baseline and at week 52

    Outcome Measure Data

    Analysis Population Description
    FAS population used for analysis.
    Arm/Group Title Ranibizumab 0.5mg Q4 IAI (EYLEA, VEGF Trap-Eye) 2.0mg Q4 IAI (EYLEA, VEGF Trap-Eye) 0.5mg Q4 IAI (EYLEA, VEGF Trap-Eye) 2.0mg Q8 Total
    Arm/Group Description Patients received a 0.5mg dose of ranibizumab via IVT injection every 4 weeks for the first year. Patients received a 2.0mg dose of Intravitreal Aflibercept Injection (IAI, EYLEA, VEGF Trap-Eye) every 4 weeks for the first year. Patients received a 0.5mg dose of Intravitreal Aflibercept Injection (IAI, EYLEA, VEGF Trap-Eye) every 4 weeks for the first year. Patients received a 2.0mg dose of Intravitreal Aflibercept Injection (IAI, EYLEA, VEGF Trap-Eye) every 8 weeks (including one additional 2.0 mg dose at Week 4) for the first year and were to receive sham injections at interim monthly visits.
    Measure Participants 304 304 301 301 1210
    Mean (Standard Deviation) [mm^2]
    -4.2
    (5.59)
    -4.6
    (5.47)
    -3.5
    (5.27)
    -3.4
    (6.02)
    -3.9
    (5.61)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ranibizumab 0.5mg Q4, IAI (EYLEA, VEGF Trap-Eye) 2.0mg 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 measure 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 0.3575
    Comments As adjustment of multiple comparisons, a conditional sequence of statistical hypotheses is used with alpha = 0.049
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Differences in Least Squares means
    Estimated Value -0.33
    Confidence Interval (2-Sided) 95.1%
    -1.04 to 0.38
    Parameter Dispersion Type:
    Value:
    Estimation Comments The difference is calculated as IAI minus ranibizumab. A negative value favors IAI 2.0Q4
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Ranibizumab 0.5mg Q4, IAI (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 measure 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 0.0507
    Comments As adjustment of multiple comparisons, a conditional sequence of statistical hypotheses is used with alpha = 0.049
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Differences in Least Squares means
    Estimated Value 0.71
    Confidence Interval (2-Sided) 95.1%
    -0.01 to 1.42
    Parameter Dispersion Type:
    Value:
    Estimation Comments The difference is calculated as IAI minus ranibizumab. A negative value favors IAI 0.5Q4
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Ranibizumab 0.5mg Q4, IAI (EYLEA, VEGF Trap-Eye) 2.0mg 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 measure 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 0.0173
    Comments As adjustment of multiple comparisons, a conditional sequence of statistical hypotheses is used with alpha = 0.049
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Differences in Least Squares means
    Estimated Value 0.86
    Confidence Interval (2-Sided) 95.1%
    0.15 to 1.58
    Parameter Dispersion Type:
    Value:
    Estimation Comments The difference is calculated as IAI minus ranibizumab. A negative value favors IAI 2.0Q8

    Adverse Events

    Time Frame AEs reported from Day 1 to Wk 96. Yr 1 of tx (Day 1 to Wk 52): 21-day screening period followed by administration of study drug every 4 or 8 wks including sham injections at interim study visits (when study drug was not administered) for 48 wks.
    Adverse Event Reporting Description Yr 2 of tx (Wk 52 to Wk 96): Pts evaluated every 4 wks and received IVT injections of study drug (sham injections were not given) at intervals determined by specific re-treatment criteria. During this period, injections were given as frequently as every 4 weeks, but no less frequently than every 12 wks.
    Arm/Group Title Ranibizumab 0.5mg Q4 IAI (EYLEA, VEGF Trap-Eye) 2.0mg Q4 IAI (EYLEA, VEGF Trap-Eye) 0.5mg Q4 IAI (EYLEA, VEGF Trap-Eye) 2.0mg Q8
    Arm/Group Description Patients received a 0.5mg dose of ranibizumab via intravitreal (IVT) injection every 4 weeks for the first year. During the second year of treatment, patients were evaluated every 4 weeks and received IVT injections of ranibizumab (sham injections were not given) at intervals determined by specific re-treatment criteria. During this period, injections were given as frequently as every 4 weeks, but no less frequently than every 12 weeks. Patients received a 2.0mg dose of Intravitreal Aflibercept Injection (IAI, EYLEA, VEGF Trap-Eye) every 4 weeks for the first year. During the second year of treatment, patients were evaluated every 4 weeks and received IVT injections of Intravitreal Aflibercept Injection (IAI, EYLEA, VEGF Trap-Eye) (sham injections were not given) at intervals determined by specific re-treatment criteria. During this period, injections were given as frequently as every 4 weeks, but no less frequently than every 12 weeks. Patients received a 0.5mg dose of Intravitreal Aflibercept Injection (IAI, EYLEA, VEGF Trap-Eye) every 4 weeks for the first year. During the second year of treatment, patients were evaluated every 4 weeks and received IVT injections of Intravitreal Aflibercept Injection (IAI, EYLEA, VEGF Trap-Eye) (sham injections were not given) at intervals determined by specific re-treatment criteria. During this period, injections were given as frequently as every 4 weeks, but no less frequently than every 12 weeks. Patients received a 2.0mg dose of Intravitreal Aflibercept Injection (IAI, EYLEA, VEGF Trap-Eye) every 8 weeks (including one additional 2.0 mg dose at Week 4) for the first year and were to receive sham injections at interim monthly visits. During the second year of treatment, patients were evaluated every 4 weeks and received IVT injections of Intravitreal Aflibercept Injection (IAI, EYLEA, VEGF Trap-Eye) (sham injections were not given) at intervals determined by specific re-treatment criteria. During this period, injections were given as frequently as every 4 weeks, but no less frequently than every 12 weeks.
    All Cause Mortality
    Ranibizumab 0.5mg Q4 IAI (EYLEA, VEGF Trap-Eye) 2.0mg Q4 IAI (EYLEA, VEGF Trap-Eye) 0.5mg Q4 IAI (EYLEA, VEGF Trap-Eye) 2.0mg 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 IAI (EYLEA, VEGF Trap-Eye) 2.0mg Q4 IAI (EYLEA, VEGF Trap-Eye) 0.5mg Q4 IAI (EYLEA, VEGF Trap-Eye) 2.0mg Q8
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 94/304 (30.9%) 70/304 (23%) 88/304 (28.9%) 90/303 (29.7%)
    Blood and lymphatic system disorders
    ANAEMIA 2/304 (0.7%) 0/304 (0%) 1/304 (0.3%) 2/303 (0.7%)
    COAGULOPATHY 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    Congenital, familial and genetic disorders
    ARTERIOVENOUS MALFORMATION 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    Ear and labyrinth disorders
    MENIERE'S DISEASE 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    VERTIGO 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 2/303 (0.7%)
    ACUTE CORONARY SYNDROME 0/304 (0%) 1/304 (0.3%) 1/304 (0.3%) 0/303 (0%)
    ACUTE MYOCARDIAL INFARCTION 1/304 (0.3%) 2/304 (0.7%) 2/304 (0.7%) 1/303 (0.3%)
    ANGINA UNSTABLE 3/304 (1%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    AORTIC VALVE STENOSIS 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    ARRHYTHMIA 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 0/303 (0%)
    ARTERIOSCLEROSIS CORONARY ARTERY 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 0/303 (0%)
    ATRIAL FIBRILLATION 3/304 (1%) 2/304 (0.7%) 7/304 (2.3%) 7/303 (2.3%)
    ATRIOVENTRICULAR BLOCK FIRST DEGREE 0/304 (0%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    BRADYCARDIA 2/304 (0.7%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    CARDIAC ARREST 0/304 (0%) 1/304 (0.3%) 1/304 (0.3%) 0/303 (0%)
    CARDIAC FAILURE ACUTE 1/304 (0.3%) 0/304 (0%) 2/304 (0.7%) 0/303 (0%)
    CARDIAC FAILURE CHRONIC 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    CARDIAC FAILURE CONGESTIVE 4/304 (1.3%) 2/304 (0.7%) 4/304 (1.3%) 8/303 (2.6%)
    CARDIO-RESPIRATORY ARREST 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    CARDIOMYOPATHY 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    CORONARY ARTERY DISEASE 5/304 (1.6%) 0/304 (0%) 6/304 (2%) 1/303 (0.3%)
    CORONARY ARTERY OCCLUSION 1/304 (0.3%) 2/304 (0.7%) 0/304 (0%) 0/303 (0%)
    CORONARY ARTERY STENOSIS 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    INTRACARDIAC THROMBUS 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    MITRAL VALVE INCOMPETENCE 0/304 (0%) 0/304 (0%) 2/304 (0.7%) 0/303 (0%)
    MYOCARDIAL INFARCTION 6/304 (2%) 1/304 (0.3%) 5/304 (1.6%) 2/303 (0.7%)
    MYOCARDIAL ISCHAEMIA 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    PERICARDIAL EFFUSION 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 0/303 (0%)
    SICK SINUS SYNDROME 2/304 (0.7%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    SUPRAVENTRICULAR TACHYCARDIA 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    TACHYARRHYTHMIA 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    TACHYCARDIA 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    VENTRICULAR FIBRILLATION 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    VENTRICULAR TACHYCARDIA 0/304 (0%) 2/304 (0.7%) 0/304 (0%) 0/303 (0%)
    Eye disorders
    AGE-RELATED MACULAR DEGENERATION 0/304 (0%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    BLEPHARITIS 0/304 (0%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    CATARACT 0/304 (0%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    CHOROIDAL NEOVASCULARISATION 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    CONJUNCTIVAL HAEMORRHAGE 0/304 (0%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    CONJUNCTIVITIS 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    MACULAR DEGENERATION 0/304 (0%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    MACULOPATHY 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    POSTERIOR CAPSULE OPACIFICATION 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    RETINAL DETACHMENT 0/304 (0%) 0/304 (0%) 2/304 (0.7%) 0/303 (0%)
    RETINAL HAEMORRHAGE 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    RETINAL OEDEMA 0/304 (0%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    RETINAL TEar and labyrinth disorders 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    UVEITIS 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    VISUAL ACUITY REDUCED 1/304 (0.3%) 1/304 (0.3%) 3/304 (1%) 0/303 (0%)
    VITREOUS DETACHMENT 0/304 (0%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    ANGLE CLOSURE GLAUCOMA 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 0/303 (0%)
    BLINDNESS TRANSIENT 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    CHOROIDAL HAEMORRHAGE 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    DRY Eye disorders 0/304 (0%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    Eye disorders IRRITATION 0/304 (0%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    Eye disorders PAIN 0/304 (0%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    Eye disorders PRURITUS 0/304 (0%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    FOREIGN BODY SENSATION IN Eye disordersS 0/304 (0%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    KERATITIS 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 0/303 (0%)
    LACRIMATION INCREASED 0/304 (0%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    MACULAR HOLE 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    PSEUDOENDOPHTHALMITIS 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    RETINAL DEGENERATION 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 0/303 (0%)
    RETINAL PIGMENT EPITHELIAL TEar and labyrinth disorders 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    RETINAL PIGMENT EPITHELIOPATHY 0/304 (0%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    VISION BLURRED 0/304 (0%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    VITREOUS FLOATERS 0/304 (0%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    VITREOUS HAEMORRHAGE 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    Gastrointestinal disorders
    ABDOMINAL HERNIA 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    ABDOMINAL HERNIA OBSTRUCTIVE 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    COLITIS 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    COLITIS ISCHAEMIC 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    COLONIC POLYP 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    CONSTIPATION 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    DIARRHOEA 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    DUODENAL ULCER HAEMORRHAGE 2/304 (0.7%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    DYSPHAGIA 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    FOOD POISONING 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    GASTRIC HAEMORRHAGE 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    GASTRIC ULCER 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    GASTRITIS 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 1/303 (0.3%)
    GASTRITIS EROSIVE 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    GASTROINTESTINAL DISORDER 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    GASTROINTESTINAL MOTILITY DISORDER 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    GASTROINTESTINAL OBSTRUCTION 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    GASTROOESOPHAGEAL REFLUX DISEASE 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 0/303 (0%)
    HAEMATOCHEZIA 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 0/303 (0%)
    HAEMORRHOIDS 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    HIATUS HERNIA 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    ILEUS 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 0/303 (0%)
    INGUINAL HERNIA 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    INTESTINAL OBSTRUCTION 2/304 (0.7%) 0/304 (0%) 1/304 (0.3%) 1/303 (0.3%)
    LOWER GASTROINTESTINAL HAEMORRHAGE 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    NAUSEA 0/304 (0%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    OESOPHAGEAL ULCER 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    PANCREATITIS 0/304 (0%) 0/304 (0%) 2/304 (0.7%) 1/303 (0.3%)
    SMALL INTESTINAL OBSTRUCTION 2/304 (0.7%) 0/304 (0%) 2/304 (0.7%) 1/303 (0.3%)
    ASTHENIA 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    CATHETER SITE HAEMATOMA 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    CHEST PAIN 2/304 (0.7%) 1/304 (0.3%) 2/304 (0.7%) 0/303 (0%)
    DEATH 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 0/303 (0%)
    DEVICE DISLOCATION 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 0/303 (0%)
    DRUG WITHDRAWAL SYNDROME 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    NON-CARDIAC CHEST PAIN 1/304 (0.3%) 1/304 (0.3%) 0/304 (0%) 0/303 (0%)
    PYREXIA 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    Hepatobiliary disorders
    BILE DUCT STONE 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    CHOLANGITIS 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 0/303 (0%)
    CHOLECYSTITIS 0/304 (0%) 0/304 (0%) 0/304 (0%) 2/303 (0.7%)
    CHOLECYSTITIS ACUTE 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    CHOLECYSTITIS CHRONIC 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 0/303 (0%)
    CHOLELITHIASIS 1/304 (0.3%) 1/304 (0.3%) 2/304 (0.7%) 0/303 (0%)
    PORTAL HYPERTENSION 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    PORTAL VEIN THROMBOSIS 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    Immune system disorders
    DRUG HYPERSENSITIVITY 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    Infections and infestations
    ANAL ABSCESS 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    ANORECTAL CELLULITIS 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    ARTHRITIS BACTERIAL 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    BACTERIAL DISEASE CARRIER 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    BRONCHITIS 0/304 (0%) 0/304 (0%) 2/304 (0.7%) 3/303 (1%)
    CELLULITIS 3/304 (1%) 3/304 (1%) 2/304 (0.7%) 0/303 (0%)
    CLOSTRIDIAL Infections and infestationsION 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 2/303 (0.7%)
    CLOSTRIDIUM DIFFICILE COLITIS 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    DEVICE RELATED Infections and infestationsION 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    DIVERTICULITIS 1/304 (0.3%) 1/304 (0.3%) 0/304 (0%) 1/303 (0.3%)
    ENCEPHALITIS VIRAL 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    ENDOCARDITIS 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    ESCHERICHIA URINARY TRACT Infections and infestationsION 1/304 (0.3%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    GASTROENTERITIS 1/304 (0.3%) 1/304 (0.3%) 0/304 (0%) 2/303 (0.7%)
    GASTROENTERITIS VIRAL 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 1/303 (0.3%)
    INFLUENZA 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    KLEBSIELLA BACTERAEMIA 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    LABYRINTHITIS 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    LOBAR PNEUMONIA 2/304 (0.7%) 0/304 (0%) 0/304 (0%) 2/303 (0.7%)
    LUNG Infections and infestationsION 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    NASOPHARYNGITIS 0/304 (0%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    PHARYNGITIS 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    PNEUMONIA 14/304 (4.6%) 6/304 (2%) 5/304 (1.6%) 8/303 (2.6%)
    PYELONEPHRITIS 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 1/303 (0.3%)
    SCROTAL ABSCESS 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    SEPSIS 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    SEPTIC SHOCK 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 1/303 (0.3%)
    SINUSITIS 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    SINUSITIS FUNGAL 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    STAPHYLOCOCCAL BACTERAEMIA 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 1/303 (0.3%)
    UPPER RESPIRATORY TRACT Infections and infestationsION 0/304 (0%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    URINARY TRACT Infections and infestationsION 1/304 (0.3%) 3/304 (1%) 0/304 (0%) 0/303 (0%)
    URINARY TRACT Infections and infestationsION BACTERIAL 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    URINARY TRACT Infections and infestationsION STAPHYLOCOCCAL 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    UROSEPSIS 1/304 (0.3%) 0/304 (0%) 1/304 (0.3%) 1/303 (0.3%)
    VESTIBULAR NEURONITIS 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    VIRAL Infections and infestationsION 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    VIRAL PERICARDITIS 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    WOUND Infections and infestationsION BACTERIAL 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 0/303 (0%)
    ENDOPHTHALMITIS 1/304 (0.3%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    Injury, poisoning and procedural complications
    ACCIDENT 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    CERVICAL VERTEBRAL FRACTURE 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    CONCUSSION 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    FALL 8/304 (2.6%) 13/304 (4.3%) 7/304 (2.3%) 16/303 (5.3%)
    FEMORAL NECK FRACTURE 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 0/303 (0%)
    FEMUR FRACTURE 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 2/303 (0.7%)
    FIBULA FRACTURE 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    FOOT FRACTURE 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    HEAD Injury, poisoning and procedural complications 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    HIP FRACTURE 1/304 (0.3%) 4/304 (1.3%) 2/304 (0.7%) 1/303 (0.3%)
    HUMERUS FRACTURE 0/304 (0%) 1/304 (0.3%) 3/304 (1%) 0/303 (0%)
    INCISIONAL HERNIA, OBSTRUCTIVE 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    JOINT DISLOCATION 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 0/303 (0%)
    JOINT Injury, poisoning and procedural complications 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    LUMBAR VERTEBRAL FRACTURE 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    MENISCUS LESION 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    POST LAMINECTOMY SYNDROME 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 0/303 (0%)
    PROCEDURAL PAIN 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    PUBIS FRACTURE 1/304 (0.3%) 2/304 (0.7%) 0/304 (0%) 0/303 (0%)
    RIB FRACTURE 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 1/303 (0.3%)
    ROAD TRAFFIC ACCIDENT 1/304 (0.3%) 1/304 (0.3%) 0/304 (0%) 1/303 (0.3%)
    SNAKE BITE 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    SPINAL COMPRESSION FRACTURE 0/304 (0%) 0/304 (0%) 2/304 (0.7%) 1/303 (0.3%)
    SPINAL FRACTURE 2/304 (0.7%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    STERNAL FRACTURE 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 0/303 (0%)
    SUBCUTANEOUS HAEMATOMA 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    SUBDURAL HAEMATOMA 2/304 (0.7%) 0/304 (0%) 1/304 (0.3%) 2/303 (0.7%)
    TIBIA FRACTURE 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    TRAUMATIC BRAIN Injury, poisoning and procedural complications 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 0/303 (0%)
    UPPER LIMB FRACTURE 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 1/303 (0.3%)
    VASCULAR PSEUDOANEURYSM 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 0/303 (0%)
    INCORRECT DOSE ADMINISTERED 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    Investigations
    Blood and lymphatic system disorders GLUCOSE INCREASED 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 0/303 (0%)
    Blood and lymphatic system disorders PRESSURE INCREASED 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    Blood and lymphatic system disorders PRESSURE ORTHOSTATIC ABNORMAL 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    INTRAOCULAR PRESSURE INCREASED 0/304 (0%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    Metabolism and nutrition disorders
    DEHYDRATION 0/304 (0%) 1/304 (0.3%) 1/304 (0.3%) 1/303 (0.3%)
    DIABETES MELLITUS 0/304 (0%) 0/304 (0%) 2/304 (0.7%) 0/303 (0%)
    DIABETES MELLITUS INADEQUATE CONTROL 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    ELECTROLYTE IMBALANCE 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 0/303 (0%)
    HYPERKALAEMIA 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    HYPOGLYCAEMIA 0/304 (0%) 2/304 (0.7%) 1/304 (0.3%) 0/303 (0%)
    HYPOKALAEMIA 2/304 (0.7%) 1/304 (0.3%) 0/304 (0%) 0/303 (0%)
    HYPONATRAEMIA 2/304 (0.7%) 1/304 (0.3%) 1/304 (0.3%) 1/303 (0.3%)
    MALNUTRITION 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 0/303 (0%)
    SHOCK HYPOGLYCAEMIC 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 0/303 (0%)
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA 0/304 (0%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    ARTHRITIS 1/304 (0.3%) 1/304 (0.3%) 0/304 (0%) 1/303 (0.3%)
    ARTHROPATHY 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    BACK PAIN 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    CERVICAL SPINAL STENOSIS 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 0/303 (0%)
    INTERVERTEBRAL DISC DEGENERATION 0/304 (0%) 1/304 (0.3%) 1/304 (0.3%) 1/303 (0.3%)
    INTERVERTEBRAL DISC PROTRUSION 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 0/303 (0%)
    LUMBAR SPINAL STENOSIS 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    OSTEOARTHRITIS 4/304 (1.3%) 1/304 (0.3%) 3/304 (1%) 1/303 (0.3%)
    OSTEONECROSIS 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    PAIN IN EXTREMITY 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    RHABDOMYOLYSIS 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 1/303 (0.3%)
    SPINAL COLUMN STENOSIS 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    SPINAL OSTEOARTHRITIS 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    SPONDYLOLISTHESIS 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    ATYPICAL FIBROXANTHOMA 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    B-CELL LYMPHOMA 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    BASAL CELL CARCINOMA 0/304 (0%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    BLADDER TRANSITIONAL CELL CARCINOMA 0/304 (0%) 1/304 (0.3%) 2/304 (0.7%) 1/303 (0.3%)
    BLADDER TRANSITIONAL CELL CARCINOMA RECURRENT 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 0/303 (0%)
    BRAIN NEOPLASM 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    BREAST Neoplasms benign, malignant and unspecified (incl cysts and polyps) 0/304 (0%) 0/304 (0%) 2/304 (0.7%) 2/303 (0.7%)
    BREAST Neoplasms benign, malignant and unspecified (incl cysts and polyps) IN SITU 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    BRONCHIOLOALVEOLAR CARCINOMA 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 0/303 (0%)
    CARDIAC MYXOMA 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    CHRONIC LYMPHOCYTIC LEUKAEMIA 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 0/303 (0%)
    COLON Neoplasms benign, malignant and unspecified (incl cysts and polyps) 1/304 (0.3%) 1/304 (0.3%) 0/304 (0%) 0/303 (0%)
    COLON Neoplasms benign, malignant and unspecified (incl cysts and polyps) RECURRENT 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    ENDOMETRIAL Neoplasms benign, malignant and unspecified (incl cysts and polyps) 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    HEPATIC Neoplasms benign, malignant and unspecified (incl cysts and polyps) METASTATIC 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    HEPATIC NEOPLASM MALIGNANT 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    LEUKAEMIA 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    LUNG NEOPLASM 1/304 (0.3%) 1/304 (0.3%) 0/304 (0%) 0/303 (0%)
    LUNG NEOPLASM MALIGNANT 2/304 (0.7%) 0/304 (0%) 0/304 (0%) 2/303 (0.7%)
    LUNG SQUAMOUS CELL CARCINOMA STAGE II 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    MALIGNANT MELANOMA 1/304 (0.3%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    METASTASES TO CENTRAL NERVOUS SYSTEM 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    METASTASES TO Hepatobiliary disorders 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    METASTASES TO LUNG 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    METASTASES TO LYMPH NODES 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    METASTATIC NEOPLASM 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    NEOPLASM MALIGNANT 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 0/303 (0%)
    NON-SMALL CELL LUNG Neoplasms benign, malignant and unspecified (incl cysts and polyps) METASTATIC 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    NON-SMALL CELL LUNG Neoplasms benign, malignant and unspecified (incl cysts and polyps) STAGE IV 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    OESOPHAGEAL ADENOCARCINOMA 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    PROSTATE Neoplasms benign, malignant and unspecified (incl cysts and polyps) 1/304 (0.3%) 0/304 (0%) 2/304 (0.7%) 1/303 (0.3%)
    PROSTATE Neoplasms benign, malignant and unspecified (incl cysts and polyps) METASTATIC 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 1/303 (0.3%)
    RECTAL Neoplasms benign, malignant and unspecified (incl cysts and polyps) STAGE III 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    RECTOSIGMOID Neoplasms benign, malignant and unspecified (incl cysts and polyps) 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    RENAL CELL CARCINOMA 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 1/303 (0.3%)
    SALIVARY GLAND Neoplasms benign, malignant and unspecified (incl cysts and polyps) RECURRENT 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    SMALL CELL LUNG Neoplasms benign, malignant and unspecified (incl cysts and polyps) METASTATIC 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 0/303 (0%)
    SMALL CELL LUNG Neoplasms benign,malignant & unspecified(incl cysts and polyps)STAGE UNSPECIFIED 1/304 (0.3%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    SQUAMOUS CELL CARCINOMA 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    SQUAMOUS CELL CARCINOMA OF Skin and subcutaneous tissue disorders 5/304 (1.6%) 3/304 (1%) 2/304 (0.7%) 4/303 (1.3%)
    THYROID Neoplasms benign, malignant and unspecified (incl cysts and polyps) 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    TONGUE NEOPLASM MALIGNANT STAGE UNSPECIFIED 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    TONSIL Neoplasms benign, malignant and unspecified (incl cysts and polyps) 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 0/303 (0%)
    TRANSITIONAL CELL CARCINOMA 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    TUMOUR HAEMORRHAGE 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    WALDENSTROM'S MACROGLOBULINAEMIA 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    Nervous system disorders
    APHASIA 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 0/303 (0%)
    BALANCE DISORDER 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    CAROTID ARTERY DISEASE 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    CAROTID ARTERY STENOSIS 0/304 (0%) 2/304 (0.7%) 0/304 (0%) 0/303 (0%)
    CEREBELLAR INFARCTION 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    CEREBRAL ARTERY THROMBOSIS 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 0/303 (0%)
    CEREBRAL HAEMORRHAGE 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    CEREBRAL INFARCTION 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    CEREBROVASCULAR ACCIDENT 2/304 (0.7%) 3/304 (1%) 1/304 (0.3%) 5/303 (1.7%)
    COMA 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    CONVULSION 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    DEMENTIA 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    DIZZINESS 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 1/303 (0.3%)
    EMBOLIC STROKE 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    HEADACHE 0/304 (0%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    ISCHAEMIC CEREBRAL INFARCTION 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 0/303 (0%)
    LACUNAR INFARCTION 1/304 (0.3%) 1/304 (0.3%) 0/304 (0%) 0/303 (0%)
    LOSS OF CONSCIOUSNESS 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 0/303 (0%)
    METABOLIC ENCEPHALOPATHY 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    PRESYNCOPE 0/304 (0%) 1/304 (0.3%) 1/304 (0.3%) 1/303 (0.3%)
    SPINAL CORD COMPRESSION 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    SUBARACHNOID HAEMORRHAGE 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 1/303 (0.3%)
    SYNCOPE 3/304 (1%) 1/304 (0.3%) 3/304 (1%) 1/303 (0.3%)
    TRANSIENT GLOBAL AMNESIA 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    TRANSIENT ISCHAEMIC ATTACK 0/304 (0%) 3/304 (1%) 7/304 (2.3%) 5/303 (1.7%)
    Psychiatric disorders
    CONFUSIONAL STATE 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    MENTAL STATUS CHANGES 2/304 (0.7%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    Psychiatric disordersOTIC DISORDER 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    Renal and urinary disorders
    CALCULUS BLADDER 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    CALCULUS URETERIC 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    HAEMATURIA 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    HYDRONEPHROSIS 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    RENAL FAILURE 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 0/303 (0%)
    RENAL FAILURE ACUTE 0/304 (0%) 3/304 (1%) 2/304 (0.7%) 2/303 (0.7%)
    RENAL FAILURE CHRONIC 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    Reproductive system and breast disorders
    CYSTOCELE 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 0/303 (0%)
    RECTOCELE 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 0/303 (0%)
    Respiratory, thoracic and mediastinal disorders
    ACUTE RESPIRATORY FAILURE 1/304 (0.3%) 0/304 (0%) 1/304 (0.3%) 2/303 (0.7%)
    APNOEIC ATTACK 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    ASTHMA 1/304 (0.3%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    CHRONIC OBSTRUCTIVE PULMONARY DISEASE 3/304 (1%) 3/304 (1%) 6/304 (2%) 6/303 (2%)
    COUGH 0/304 (0%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    DYSPNOEA 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    EMPHYSEMA 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    PLEURAL EFFUSION 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 0/303 (0%)
    PNEUMONIA ASPIRATION 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 2/303 (0.7%)
    PNEUMONITIS 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 1/303 (0.3%)
    PULMONARY EMBOLISM 0/304 (0%) 2/304 (0.7%) 1/304 (0.3%) 2/303 (0.7%)
    PULMONARY FIBROSIS 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 0/303 (0%)
    PULMONARY MASS 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    PULMONARY OEDEMA 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 0/303 (0%)
    RESPIRATORY DISTRESS 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    RESPIRATORY FAILURE 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    RESTRICTIVE PULMONARY DISEASE 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    TRACHEAL MASS 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    Skin and subcutaneous tissue disorders
    ANGIOEDEMA 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    Surgical and medical procedures
    CHOLECYSTECTOMY 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 0/303 (0%)
    MICROGRAPHIC Skin and subcutaneous tissue disorders SURGERY 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    Vascular disorders
    AORTIC ANEURYSM 1/304 (0.3%) 2/304 (0.7%) 1/304 (0.3%) 0/303 (0%)
    AORTIC ANEURYSM RUPTURE 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    AORTIC STENOSIS 1/304 (0.3%) 1/304 (0.3%) 2/304 (0.7%) 1/303 (0.3%)
    ARTERIOSCLEROSIS 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    DEEP VEIN THROMBOSIS 1/304 (0.3%) 1/304 (0.3%) 1/304 (0.3%) 2/303 (0.7%)
    FEMORAL ARTERY ANEURYSM 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    HAEMATOMA 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 0/303 (0%)
    HYPERTENSION 2/304 (0.7%) 0/304 (0%) 3/304 (1%) 0/303 (0%)
    HYPOTENSION 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 0/303 (0%)
    ILIAC ARTERY OCCLUSION 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    LYMPHATIC FISTULA 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    LYMPHOCELE 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 0/303 (0%)
    ORTHOSTATIC HYPOTENSION 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    PERIPHERAL ARTERY ANEURYSM 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 0/303 (0%)
    PERIPHERAL VASCULAR DISORDER 1/304 (0.3%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    PHLEBITIS 0/304 (0%) 0/304 (0%) 1/304 (0.3%) 0/303 (0%)
    PHLEBITIS DEEP 0/304 (0%) 1/304 (0.3%) 0/304 (0%) 0/303 (0%)
    SHOCK HAEMORRHAGIC 0/304 (0%) 0/304 (0%) 0/304 (0%) 1/303 (0.3%)
    Other (Not Including Serious) Adverse Events
    Ranibizumab 0.5mg Q4 IAI (EYLEA, VEGF Trap-Eye) 2.0mg Q4 IAI (EYLEA, VEGF Trap-Eye) 0.5mg Q4 IAI (EYLEA, VEGF Trap-Eye) 2.0mg Q8
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 261/304 (85.9%) 254/304 (83.6%) 262/304 (86.2%) 258/303 (85.1%)
    Ear and labyrinth disorders
    ATRIOVENTRICULAR BLOCK FIRST DEGREE 16/304 (5.3%) 18/304 (5.9%) 8/304 (2.6%) 9/303 (3%)
    Eye disorders
    AGE-RELATED MACULAR DEGENERATION 21/304 (6.9%) 16/304 (5.3%) 12/304 (3.9%) 15/303 (5%)
    BLEPHARITIS 16/304 (5.3%) 18/304 (5.9%) 14/304 (4.6%) 14/303 (4.6%)
    CATARACT 10/304 (3.3%) 17/304 (5.6%) 10/304 (3.3%) 10/303 (3.3%)
    CHOROIDAL NEOVASCULARISATION 17/304 (5.6%) 10/304 (3.3%) 13/304 (4.3%) 9/303 (3%)
    CONJUNCTIVAL HAEMORRHAGE 16/304 (5.3%) 17/304 (5.6%) 16/304 (5.3%) 19/303 (6.3%)
    MACULAR DEGENERATION 22/304 (7.2%) 14/304 (4.6%) 21/304 (6.9%) 14/303 (4.6%)
    RETINAL HAEMORRHAGE 43/304 (14.1%) 36/304 (11.8%) 36/304 (11.8%) 22/303 (7.3%)
    RETINAL OEDEMA 18/304 (5.9%) 8/304 (2.6%) 12/304 (3.9%) 11/303 (3.6%)
    VISUAL ACUITY REDUCED 27/304 (8.9%) 10/304 (3.3%) 20/304 (6.6%) 19/303 (6.3%)
    VITREOUS DETACHMENT 16/304 (5.3%) 24/304 (7.9%) 25/304 (8.2%) 24/303 (7.9%)
    DRY Eye disorders 12/304 (3.9%) 16/304 (5.3%) 10/304 (3.3%) 14/303 (4.6%)
    Eye disorders IRRITATION 19/304 (6.3%) 13/304 (4.3%) 15/304 (4.9%) 16/303 (5.3%)
    Eye disorders PAIN 34/304 (11.2%) 39/304 (12.8%) 35/304 (11.5%) 31/303 (10.2%)
    Eye disorders PRURITUS 11/304 (3.6%) 16/304 (5.3%) 10/304 (3.3%) 6/303 (2%)
    FOREIGN BODY SENSATION IN Eye disordersS 9/304 (3%) 10/304 (3.3%) 10/304 (3.3%) 19/303 (6.3%)
    LACRIMATION INCREASED 11/304 (3.6%) 11/304 (3.6%) 15/304 (4.9%) 16/303 (5.3%)
    RETINAL PIGMENT EPITHELIOPATHY 14/304 (4.6%) 18/304 (5.9%) 17/304 (5.6%) 14/303 (4.6%)
    VISION BLURRED 12/304 (3.9%) 18/304 (5.9%) 17/304 (5.6%) 13/303 (4.3%)
    VITREOUS FLOATERS 47/304 (15.5%) 49/304 (16.1%) 30/304 (9.9%) 29/303 (9.6%)
    Gastrointestinal disorders
    DIARRHOEA 18/304 (5.9%) 18/304 (5.9%) 8/304 (2.6%) 9/303 (3%)
    NAUSEA 15/304 (4.9%) 16/304 (5.3%) 15/304 (4.9%) 15/303 (5%)
    Infections and infestations
    BRONCHITIS 23/304 (7.6%) 19/304 (6.3%) 16/304 (5.3%) 24/303 (7.9%)
    NASOPHARYNGITIS 36/304 (11.8%) 46/304 (15.1%) 41/304 (13.5%) 39/303 (12.9%)
    SINUSITIS 18/304 (5.9%) 13/304 (4.3%) 17/304 (5.6%) 14/303 (4.6%)
    UPPER RESPIRATORY TRACT Infections and infestationsION 18/304 (5.9%) 18/304 (5.9%) 19/304 (6.3%) 26/303 (8.6%)
    URINARY TRACT Infections and infestationsION 26/304 (8.6%) 22/304 (7.2%) 25/304 (8.2%) 23/303 (7.6%)
    Injury, poisoning and procedural complications
    FALL 19/304 (6.3%) 13/304 (4.3%) 15/304 (4.9%) 21/303 (6.9%)
    Investigations
    Blood and lymphatic system disorders GLUCOSE INCREASED 13/304 (4.3%) 12/304 (3.9%) 17/304 (5.6%) 16/303 (5.3%)
    INTRAOCULAR PRESSURE INCREASED 16/304 (5.3%) 8/304 (2.6%) 15/304 (4.9%) 15/303 (5%)
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA 17/304 (5.6%) 18/304 (5.9%) 17/304 (5.6%) 8/303 (2.6%)
    BACK PAIN 11/304 (3.6%) 14/304 (4.6%) 13/304 (4.3%) 16/303 (5.3%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    BASAL CELL CARCINOMA 5/304 (1.6%) 11/304 (3.6%) 15/304 (4.9%) 17/303 (5.6%)
    Nervous system disorders
    HEADACHE 21/304 (6.9%) 14/304 (4.6%) 16/304 (5.3%) 15/303 (5%)
    Respiratory, thoracic and mediastinal disorders
    COUGH 16/304 (5.3%) 13/304 (4.3%) 10/304 (3.3%) 13/303 (4.3%)
    Vascular disorders
    HYPERTENSION 35/304 (11.5%) 30/304 (9.9%) 32/304 (10.5%) 33/303 (10.9%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    After completion of the trial, the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days from the time submitted to the sponsor for review; provided that the sponsor can remove confidential or proprietary information from such communications. The sponsor cannot require other changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Clinical Trials Administrator
    Organization Regeneron Pharmaceuticals
    Phone
    Email clinicaltrials@regeneron.com
    Responsible Party:
    Regeneron Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT00509795
    Other Study ID Numbers:
    • VGFT-OD-0605
    First Posted:
    Aug 1, 2007
    Last Update Posted:
    Dec 28, 2012
    Last Verified:
    Dec 1, 2012