Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 6 of 81 for:    CRVO - Central Retinal Vein Occlusion

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00943072
Recruitment Status : Completed
First Posted : July 21, 2009
Results First Posted : May 27, 2013
Last Update Posted : May 27, 2013
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
Regeneron Pharmaceuticals

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Macular Edema Secondary to Central Retinal Vein Occlusion
Interventions Biological: VEGF Trap-Eye 2.0mg
Drug: Sham
Enrollment 189
Recruitment Details The study was conducted at 55 study centers in the United States, Canada, Columbia, India, and Israel. The recruitment period occurred between 08 Jul 2009 and 29 Apr 2010.
Pre-assignment Details 273 participants were screened, 189 randomized, and 188 were included in the Safety Analysis Set (SAF). The Full Analysis Set (FAS) included 187 participants with at least one post-baseline assessment.
Arm/Group Title Intravitreal Aflibercept Injection (EYLEA, VEGF Trap-Eye) Sham Treatment
Hide Arm/Group Description

Participants received a 2 mg Intravitreal Aflibercept Injection (IAI) every 4 weeks (2Q4) from Baseline (Day 1) to Week 24.

Starting at week 24 through week 52, participants were evaluated monthly to receive either the 2 mg IAI PRN or sham injection according to the protocol re-treatment criteria as assessed by the masked physician. If none of the re-treatment criteria were met, participants received a sham injection.

From Week 52 to 100, participants were evaluated every three months, but could receive injections of IAI up to monthly if re-treatment criteria were met; sham injections were not given. Participants were observed from Week 24 to Week 100. Participants in the safety population that completed Week 24 were at risk.

Participants received sham treatment every 4 weeks from Baseline (Day 1) to Week 24.

Starting at week 24 through week 52, participants were eligible for active treatment and were evaluated monthly to receive either 2 mg IAI PRN or sham injection according to the protocol re-treatment criteria as assessed by the masked physician.

From Week 52 to 100, participants were evaluated every three months, but could receive injections of IAI up to monthly if re-treatment criteria were met; sham injections were not given.

Period Title: Overall Study
Started 115 74
Participants Received Treatment 114 [1] 74
Full Analysis Set (FAS) Population 114 [2] 73
Completed 110 [3] 60 [4]
Not Completed 5 14
Reason Not Completed
Adverse Event             0             3
Death             0             2
Withdrawal by Subject             3             1
Protocol Violation             0             1
Lost to Follow-up             1             2
Lack of Efficacy             0             4
Other             1             1
[1]
Safety population (SAF)
[2]
FAS population used for analysis of Primary and Secondary Outcome Measures
[3]
110 Participants completed Week 24, From FAS; 102 Participants completed up to Week 100, From SAF
[4]
60 Participants completed Week 24, From FAS; 50 Participants completed up to Week 100, From SAF
Arm/Group Title Intravitreal Aflibercept Injection (EYLEA, VEGF Trap-Eye) Sham Treatment Total
Hide Arm/Group Description Participants received a 2 mg Intravitreal Aflibercept Injection (IAI) every 4 weeks (2Q4) from Baseline (Day 1) to Week 24. Participants received sham treatment every 4 weeks from Baseline (Day 1) to Week 24. Total of all reporting groups
Overall Number of Baseline Participants 114 74 188
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 114 participants 74 participants 188 participants
65.5  (13.57) 67.5  (14.22) 66.3  (13.83)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 114 participants 74 participants 188 participants
Female
45
  39.5%
35
  47.3%
80
  42.6%
Male
69
  60.5%
39
  52.7%
108
  57.4%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 114 participants 74 participants 188 participants
Hispanic or Latino
18
  15.8%
12
  16.2%
30
  16.0%
Not Hispanic or Latino
96
  84.2%
62
  83.8%
158
  84.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 114 participants 74 participants 188 participants
American Indian or Alaska Native
2
   1.8%
0
   0.0%
2
   1.1%
Asian
7
   6.1%
2
   2.7%
9
   4.8%
Native Hawaiian or Other Pacific Islander
0
   0.0%
1
   1.4%
1
   0.5%
Black or African American
5
   4.4%
5
   6.8%
10
   5.3%
White
88
  77.2%
60
  81.1%
148
  78.7%
More than one race
12
  10.5%
6
   8.1%
18
   9.6%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Baseline Retinal Thickness by Optical Coherence Tomography (OCT)  
Mean (Standard Deviation)
Unit of measure:  Microns
Number Analyzed 114 participants 74 participants 188 participants
661.7  (237.37) 678.4  (248.66) 668.1  (241.23)
Baseline National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25) Total Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Scores on a scale
Number Analyzed 114 participants 74 participants 188 participants
77.67  (15.96) 78.01  (16.26) 77.81  (16.04)
[1]
Measure 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.
Baseline Intraocular Pressure  
Mean (Standard Deviation)
Unit of measure:  Millimeters of mercury (mmHg)
Number Analyzed 114 participants 74 participants 188 participants
15.1  (3.26) 15.0  (2.83) 15.1  (3.09)
Number of Participants with Retinal Perfusion at Baseline   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 114 participants 74 participants 188 participants
Perfused 77 50 127
Non-Perfused 17 12 29
Indeterminate 20 12 32
[1]
Measure Description:

Retinal Perfusion defined as less than 10 disc areas of capillary non-perfusion using fluorescein angiography (FA).

Non-Perfused defined as greater than or equal to 10 disc areas of non-perfusion.

Indeterminate defined as not able to be determined by the reading center; for the purposes of analysis, indeterminate patients were considered non-perfused.

Baseline Best Corrected Visual Acuity (BCVA) Letter Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Letters correctly read
Number Analyzed 114 participants 74 participants 188 participants
50.7  (13.90) 48.7  (14.41) 49.9  (14.10)
[1]
Measure Description: Only participants with an ETDRS (Early Treatment Diabetic Retinopathy Study) Best Corrected Visual Acuity letter score of 73 to 25 (= Acuity of 20/40 to 20/320) in the study eye at 4 meters were included; a higher score represents better functioning.
Time Since Central Retinal Vein Occlusion (CRVO) Diagnosis  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 114 participants 74 participants 188 participants
</= 2 Months 64 53 117
> 2 Months 49 21 70
Missing 1 0 1
1.Primary Outcome
Title Percentage of Participants Who Gained at Least 15 Letters in BCVA at Week 24 as Measured by ETDRS Letter Score
Hide Description

Percentage values indicate the number of subjects in each arm who were able to read an additional 15 letters or more at Week 24 compared to baseline.

Defined study baseline range of ETDRS Best Corrected Visual Acuity letter score of 73 to 24 letters (= Acuity of 20/40 to 20/320) in the study eye; a higher score represents better functioning.

Time Frame Baseline and at Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Intravitreal Aflibercept Injection (EYLEA, VEGF Trap-Eye) Sham Treatment
Hide Arm/Group Description:
Participants received a 2 mg Intravitreal Aflibercept Injection (IAI) every 4 weeks (2Q4) from Baseline (Day 1) to Week 24.
Participants received sham treatment every 4 weeks from Baseline (Day 1) to Week 24.
Overall Number of Participants Analyzed 114 73
Measure Type: Number
Unit of Measure: percentage of participants
64 9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Intravitreal Aflibercept Injection (EYLEA, VEGF Trap-Eye), Sham Treatment
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-value for the primary endpoint was calculated using 2-sided Cochran-Mantel-Haenszel test adjusted by regions (North America vs. Rest of World) and baseline BCVA (BCVA > 20/200 and BCVA ≤ 20/200)
Method Cochran-Mantel-Haenszel
Comments CMH adjusted difference
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 44.8
Confidence Interval (2-Sided) 95%
33.0 to 56.6
Estimation Comments The Risk Difference (RD) indicates the difference between the IAI (EYLEA, VEGF Trap-Eye) Treatment group minus the Sham Treatment group.
2.Secondary Outcome
Title Change From Baseline in BCVA as Measured by ETDRS Letter Score at Week 24 - Last Observation Carried Forward (LOCF)
Hide Description Defined study baseline range of ETDRS Best Corrected Visual Acuity letter score of 73 to 24 (= Acuity of 20/40 to 20/320) in the study eye; a higher score represents better functioning.
Time Frame Baseline and at Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Intravitreal Aflibercept Injection (EYLEA, VEGF Trap-Eye) Sham Treatment
Hide Arm/Group Description:
Participants received a 2 mg Intravitreal Aflibercept Injection (IAI) every 4 weeks (2Q4) from Baseline (Day 1) to Week 24.
Participants received sham treatment every 4 weeks from Baseline (Day 1) to Week 24.
Overall Number of Participants Analyzed 114 73
Mean (Standard Deviation)
Unit of Measure: letters correctly read
17.3  (12.78) -4.0  (17.96)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Intravitreal Aflibercept Injection (EYLEA, VEGF Trap-Eye), Sham Treatment
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 21.70
Confidence Interval (2-Sided) 95%
17.36 to 26.04
Estimation Comments RD is the IAI group minus sham group. 95% confidence interval is for the RD.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Intravitreal Aflibercept Injection (EYLEA, VEGF Trap-Eye), Sham Treatment
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean
Estimated Value 16.36
Estimation Comments LS Mean indicates is the IAI (EYLEA, VEGF Trap-Eye) Treatment group minus the Sham Treatment group.
3.Secondary Outcome
Title Change From Baseline in Central Retinal Thickness (CRT) at Week 24 - LOCF
Hide Description [Not Specified]
Time Frame Baseline and at Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Intravitreal Aflibercept Injection (EYLEA, VEGF Trap-Eye) Sham Treatment
Hide Arm/Group Description:
Participants received a 2 mg Intravitreal Aflibercept Injection (IAI) every 4 weeks (2Q4) from Baseline (Day 1) to Week 24.
Participants received sham treatment every 4 weeks from Baseline (Day 1) to Week 24.
Overall Number of Participants Analyzed 114 73
Mean (Standard Deviation)
Unit of Measure: microns
-457.2  (238.21) -144.8  (291.07)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Intravitreal Aflibercept Injection (EYLEA, VEGF Trap-Eye), Sham Treatment
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -311.9
Confidence Interval (2-Sided) 95%
-389.4 to -234.4
Estimation Comments The Risk Difference (RD) indicates the difference between the IAI (EYLEA, VEGF Trap-Eye) Treatment group minus the Sham Treatment group. 95% confidence interval is for the RD.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Intravitreal Aflibercept Injection (EYLEA, VEGF Trap-Eye), Sham Treatment
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean
Estimated Value -487.1
Estimation Comments The Least Square Mean indicates the difference between the IAI (EYLEA, VEGF Trap-Eye) Treatment group minus the Sham Treatment group.
4.Secondary Outcome
Title Percentage of Participants Progressing to Any of the Following: Anterior Segment Neovascularization, New Vessels of the Disc (NVD) or New Vessels Elsewhere (NVE) During the First 24 Weeks
Hide Description [Not Specified]
Time Frame Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Intravitreal Aflibercept Injection (EYLEA, VEGF Trap-Eye) Sham Treatment
Hide Arm/Group Description:
Participants received a 2 mg Intravitreal Aflibercept Injection (IAI) every 4 weeks (2Q4) from Baseline (Day 1) to Week 24.
Participants received sham treatment every 4 weeks from Baseline (Day 1) to Week 24.
Overall Number of Participants Analyzed 114 73
Measure Type: Number
Unit of Measure: percentage of participants
Any neovascularization 0 6.8
Anterior segment neovascularization 0 6.8
Neovascularization of the optic disc (NVD) 0 0
Neovascularization elsewhere in the fundus (NVE) 0 0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Intravitreal Aflibercept Injection (EYLEA, VEGF Trap-Eye), Sham Treatment
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0059
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments CMH adjusted difference
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -6.6
Confidence Interval (2-Sided) 95%
-12.2 to -1.1
Estimation Comments The Risk Difference (RD) indicates the difference between the IAI (EYLEA, VEGF Trap-Eye) Treatment group minus the Sham Treatment group. 95% confidence interval is for the RD.
5.Secondary Outcome
Title Change From Baseline in the NEI VFQ-25 in Total Score at Week 24 (LOCF)
Hide Description The NEI VFQ-25 assesses visual function and quality of life. 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 24
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Intravitreal Aflibercept Injection (EYLEA, VEGF Trap-Eye) Sham Treatment
Hide Arm/Group Description:
Participants received a 2 mg Intravitreal Aflibercept Injection (IAI) every 4 weeks (2Q4) from Baseline (Day 1) to Week 24.
Participants received sham treatment every 4 weeks from Baseline (Day 1) to Week 24.
Overall Number of Participants Analyzed 114 73
Mean (Standard Deviation)
Unit of Measure: scores on a scale
7.2  (12.11) 0.8  (9.79)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Intravitreal Aflibercept Injection (EYLEA, VEGF Trap-Eye), Sham Treatment
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0009
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 6.26
Confidence Interval (2-Sided) 95%
2.61 to 9.91
Estimation Comments The Risk Difference (RD) indicates the difference between the IAI (EYLEA, VEGF Trap-Eye) Treatment group minus the Sham Treatment group. 95% confidence interval is for the RD.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Intravitreal Aflibercept Injection (EYLEA, VEGF Trap-Eye), Sham Treatment
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean
Estimated Value 8.80
Estimation Comments Least Square Mean indicates the difference between the IAI (EYLEA, VEGF Trap-Eye) Treatment group minus the Sham Treatment group.
Time Frame Baseline to Week 24; Week 24 to Week 100
Adverse Event Reporting Description Adverse event data were collected from the sites during the time period from Baseline through Week 24 or/and Week 100. For analysis, adverse events with a start date on or after the Week 24 visit date are summarized in the Week 24 to Week 100 time period.
 
Arm/Group Title Intravitreal Aflibercept Injection (IAI) (Baseline to Week 24) Sham Treatment (Baseline to Week 24) IAI to IAI (Week 24 to Week 100) Sham Treatment to IAI (Week 24 to Week 100)
Hide Arm/Group Description

Participants received a 2 mg Intravitreal Aflibercept Injection (IAI) every 4 weeks (2Q4) from Baseline (Day 1) to Week 20. Participants were observed until Week 24.

Participants in the safety population were at risk.

Participants received sham treatment every 4 weeks from Baseline (Day 1) to Week 20. Participants were observed until Week 24. Participants in the safety population were at risk.

Starting at week 24 through week 52, participants were evaluated monthly to receive either the 2 mg Intravitreal Aflibercept Injection (IAI) PRN or sham injection according to the protocol re-treatment criteria as assessed by the masked physician. If none of the re-treatment criteria were met, participants received a sham injection.

From Week 52 to 100, participants were evaluated every three months, but could receive injections of IAI up to monthly if re-treatment criteria were met; sham injections were not given. Participants were observed from Week 24 to Week 100. Participants in the safety population that completed Week 24 were at risk.

Starting at week 24 through week 52, participants were eligible for active treatment and were evaluated monthly to receive either 2 mg Intravitreal Aflibercept Injection (IAI) PRN or sham injection according to the protocol re-treatment criteria as assessed by the masked physician.

From Week 52 to 100, participants were evaluated every three months, but could receive injections of IAI up to monthly if re-treatment criteria were met; sham injections were not given.

All-Cause Mortality
Intravitreal Aflibercept Injection (IAI) (Baseline to Week 24) Sham Treatment (Baseline to Week 24) IAI to IAI (Week 24 to Week 100) Sham Treatment to IAI (Week 24 to Week 100)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Intravitreal Aflibercept Injection (IAI) (Baseline to Week 24) Sham Treatment (Baseline to Week 24) IAI to IAI (Week 24 to Week 100) Sham Treatment to IAI (Week 24 to Week 100)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   6/114 (5.26%)   6/74 (8.11%)   20/110 (18.18%)   14/60 (23.33%) 
Blood and lymphatic system disorders         
Anaemia * 1  1/114 (0.88%)  0/74 (0.00%)  0/110 (0.00%)  1/60 (1.67%) 
Neutropenia * 1  0/114 (0.00%)  0/74 (0.00%)  0/110 (0.00%)  1/60 (1.67%) 
Pernicious anaemia * 1  0/114 (0.00%)  0/74 (0.00%)  0/110 (0.00%)  1/60 (1.67%) 
Cardiac disorders         
Acute myocardial infarction * 1  0/114 (0.00%)  1/74 (1.35%)  0/110 (0.00%)  0/60 (0.00%) 
Aortic valve stenosis * 1  0/114 (0.00%)  0/74 (0.00%)  1/110 (0.91%)  0/60 (0.00%) 
Atrial fibrillation * 1  1/114 (0.88%)  0/74 (0.00%)  1/110 (0.91%)  1/60 (1.67%) 
Atrial tachycardia * 1  0/114 (0.00%)  0/74 (0.00%)  1/110 (0.91%)  0/60 (0.00%) 
Atrioventricular block * 1  0/114 (0.00%)  0/74 (0.00%)  1/110 (0.91%)  0/60 (0.00%) 
Cardiac failure acute * 1  0/114 (0.00%)  0/74 (0.00%)  1/110 (0.91%)  0/60 (0.00%) 
Coronary artery disease * 1  0/114 (0.00%)  0/74 (0.00%)  1/110 (0.91%)  0/60 (0.00%) 
Coronary artery stenosis * 1  0/114 (0.00%)  0/74 (0.00%)  2/110 (1.82%)  0/60 (0.00%) 
Myocardial infarction * 1  0/114 (0.00%)  0/74 (0.00%)  1/110 (0.91%)  0/60 (0.00%) 
Supraventricular tachycardia * 1  0/114 (0.00%)  0/74 (0.00%)  1/110 (0.91%)  0/60 (0.00%) 
Ventricular extrasystoles * 1  0/114 (0.00%)  0/74 (0.00%)  1/110 (0.91%)  0/60 (0.00%) 
Eye disorders         
Cataract * 1 [1]  0/114 (0.00%)  0/74 (0.00%)  1/110 (0.91%)  0/60 (0.00%) 
Conjunctival haemorrhage * 1 [1]  0/114 (0.00%)  0/74 (0.00%)  1/110 (0.91%)  0/60 (0.00%) 
Cystoid macular oedema * 1 [2]  0/114 (0.00%)  0/74 (0.00%)  2/110 (1.82%)  0/60 (0.00%) 
Dry eye * 1 [2]  0/114 (0.00%)  0/74 (0.00%)  0/110 (0.00%)  0/60 (0.00%) 
Eye irritation * 1 [2]  0/114 (0.00%)  0/74 (0.00%)  0/110 (0.00%)  0/60 (0.00%) 
Eye pain * 1 [2]  0/114 (0.00%)  0/74 (0.00%)  0/110 (0.00%)  0/60 (0.00%) 
Glaucoma * 1 [2]  0/114 (0.00%)  2/74 (2.70%)  0/110 (0.00%)  1/60 (1.67%) 
Iris neovascularisation * 1 [2]  0/114 (0.00%)  2/74 (2.70%)  0/110 (0.00%)  0/60 (0.00%) 
Lacrimation increased * 1 [2]  0/114 (0.00%)  0/74 (0.00%)  0/110 (0.00%)  0/60 (0.00%) 
Macular fibrosis * 1 [1]  0/114 (0.00%)  0/74 (0.00%)  1/110 (0.91%)  0/60 (0.00%) 
Macular oedema * 1 [2]  0/114 (0.00%)  0/74 (0.00%)  1/110 (0.91%)  0/60 (0.00%) 
Maculopathy * 1 [2]  0/114 (0.00%)  0/74 (0.00%)  0/110 (0.00%)  0/60 (0.00%) 
Optic disc vascular disorder * 1 [2]  0/114 (0.00%)  0/74 (0.00%)  0/110 (0.00%)  0/60 (0.00%) 
Posterior capsule opacification * 1 [1]  0/114 (0.00%)  0/74 (0.00%)  1/110 (0.91%)  0/60 (0.00%) 
Retinal artery occlusion * 1 [2]  1/114 (0.88%)  0/74 (0.00%)  0/110 (0.00%)  0/60 (0.00%) 
Retinal exudates * 1 [2]  0/114 (0.00%)  0/74 (0.00%)  0/110 (0.00%)  0/60 (0.00%) 
Retinal haemorrhage * 1 [1]  0/114 (0.00%)  0/74 (0.00%)  0/110 (0.00%)  0/60 (0.00%) 
Retinal pigment epitheliopathy * 1 [2]  0/114 (0.00%)  0/74 (0.00%)  0/110 (0.00%)  0/60 (0.00%) 
Retinal tear * 1 [2]  0/114 (0.00%)  1/74 (1.35%)  0/110 (0.00%)  1/60 (1.67%) 
Retinal vascular disorder * 1 [2]  0/114 (0.00%)  0/74 (0.00%)  1/110 (0.91%)  0/60 (0.00%) 
Retinal vein occlusion * 1 [2]  0/114 (0.00%)  1/74 (1.35%)  1/110 (0.91%)  0/60 (0.00%) 
Visual acuity reduced * 1 [2]  1/114 (0.88%)  1/74 (1.35%)  1/110 (0.91%)  0/60 (0.00%) 
Vitreous detachment * 1 [2]  0/114 (0.00%)  0/74 (0.00%)  0/110 (0.00%)  0/60 (0.00%) 
Vitreous floaters * 1 [2]  0/114 (0.00%)  0/74 (0.00%)  0/110 (0.00%)  0/60 (0.00%) 
Vitreous haemorrhage * 1 [1]  0/114 (0.00%)  0/74 (0.00%)  1/110 (0.91%)  0/60 (0.00%) 
Gastrointestinal disorders         
Abdominal adhesions * 1  1/114 (0.88%)  0/74 (0.00%)  0/110 (0.00%)  0/60 (0.00%) 
Colitis * 1  0/114 (0.00%)  0/74 (0.00%)  0/110 (0.00%)  1/60 (1.67%) 
Dysphagia * 1  1/114 (0.88%)  0/74 (0.00%)  0/110 (0.00%)  1/60 (1.67%) 
Gastrointestinal motility disorder * 1  0/114 (0.00%)  0/74 (0.00%)  0/110 (0.00%)  1/60 (1.67%) 
Inguinal hernia * 1  0/114 (0.00%)  0/74 (0.00%)  2/110 (1.82%)  0/60 (0.00%) 
Intestinal ischaemia * 1  0/114 (0.00%)  0/74 (0.00%)  0/110 (0.00%)  1/60 (1.67%) 
Intestinal obstruction * 1  0/114 (0.00%)  0/74 (0.00%)  0/110 (0.00%)  1/60 (1.67%) 
Pancreatitis * 1  0/114 (0.00%)  1/74 (1.35%)  0/110 (0.00%)  1/60 (1.67%) 
Small intestinal obstruction * 1  0/114 (0.00%)  0/74 (0.00%)  0/110 (0.00%)  1/60 (1.67%) 
General disorders         
Adhesion * 1  0/114 (0.00%)  0/74 (0.00%)  0/110 (0.00%)  1/60 (1.67%) 
Chest discomfort * 1  0/114 (0.00%)  0/74 (0.00%)  1/110 (0.91%)  0/60 (0.00%) 
Chest pain * 1  0/114 (0.00%)  0/74 (0.00%)  1/110 (0.91%)  0/60 (0.00%) 
Generalised oedema * 1  0/114 (0.00%)  0/74 (0.00%)  1/110 (0.91%)  0/60 (0.00%) 
Hepatobiliary disorders         
Bile duct stone * 1  0/114 (0.00%)  0/74 (0.00%)  0/110 (0.00%)  1/60 (1.67%) 
Cholecystitis * 1  0/114 (0.00%)  1/74 (1.35%)  0/110 (0.00%)  0/60 (0.00%) 
Infections and infestations         
Arthritis bacterial * 1  0/114 (0.00%)  0/74 (0.00%)  1/110 (0.91%)  0/60 (0.00%) 
Bacteriuria * 1  0/114 (0.00%)  0/74 (0.00%)  1/110 (0.91%)  0/60 (0.00%) 
Bronchitis * 1  0/114 (0.00%)  0/74 (0.00%)  0/110 (0.00%)  1/60 (1.67%) 
Bronchitis viral * 1  1/114 (0.88%)  0/74 (0.00%)  0/110 (0.00%)  0/60 (0.00%) 
Cellulitis * 1  0/114 (0.00%)  1/74 (1.35%)  1/110 (0.91%)  0/60 (0.00%) 
Clostridial infection * 1  0/114 (0.00%)  1/74 (1.35%)  0/110 (0.00%)  0/60 (0.00%) 
Endophthalmitis * 1 [2]  1/114 (0.88%)  0/74 (0.00%)  0/110 (0.00%)  0/60 (0.00%) 
Herpes oesophagitis * 1  0/114 (0.00%)  0/74 (0.00%)  0/110 (0.00%)  1/60 (1.67%) 
Influenza * 1  0/114 (0.00%)  0/74 (0.00%)  0/110 (0.00%)  0/60 (0.00%) 
Nasopharyngitis * 1  0/114 (0.00%)  0/74 (0.00%)  0/110 (0.00%)  0/60 (0.00%) 
Periorbital cellulitis * 1 [1]  0/114 (0.00%)  0/74 (0.00%)  0/110 (0.00%)  1/60 (1.67%) 
Pneumonia * 1  0/114 (0.00%)  1/74 (1.35%)  0/110 (0.00%)  3/60 (5.00%) 
Upper respiratory tract infection * 1  0/114 (0.00%)  0/74 (0.00%)  0/110 (0.00%)  0/60 (0.00%) 
Urinary tract infection * 1  0/114 (0.00%)  0/74 (0.00%)  2/110 (1.82%)  0/60 (0.00%) 
Injury, poisoning and procedural complications         
Accident * 1  0/114 (0.00%)  0/74 (0.00%)  1/110 (0.91%)  1/60 (1.67%) 
Brain contusion * 1  0/114 (0.00%)  0/74 (0.00%)  1/110 (0.91%)  0/60 (0.00%) 
Corneal abrasion * 1 [2]  1/114 (0.88%)  0/74 (0.00%)  0/110 (0.00%)  0/60 (0.00%) 
Craniocerebral injury * 1  0/114 (0.00%)  0/74 (0.00%)  1/110 (0.91%)  0/60 (0.00%) 
Facial bones fracture * 1 [1]  0/114 (0.00%)  0/74 (0.00%)  1/110 (0.91%)  0/60 (0.00%) 
Fall * 1  0/114 (0.00%)  0/74 (0.00%)  0/110 (0.00%)  1/60 (1.67%) 
Femur fracture * 1  0/114 (0.00%)  0/74 (0.00%)  0/110 (0.00%)  1/60 (1.67%) 
In-stent coronary artery restenosis * 1  0/114 (0.00%)  0/74 (0.00%)  1/110 (0.91%)  0/60 (0.00%) 
Radius fracture * 1  0/114 (0.00%)  0/74 (0.00%)  1/110 (0.91%)  0/60 (0.00%) 
Renal haematoma * 1  0/114 (0.00%)  0/74 (0.00%)  1/110 (0.91%)  0/60 (0.00%) 
Skull fracture * 1  0/114 (0.00%)  0/74 (0.00%)  1/110 (0.91%)  0/60 (0.00%) 
Spinal column injury * 1  0/114 (0.00%)  0/74 (0.00%)  1/110 (0.91%)  0/60 (0.00%) 
Investigations         
Blood pressure systolic increased * 1  0/114 (0.00%)  0/74 (0.00%)  0/110 (0.00%)  0/60 (0.00%) 
Blood urine present * 1  0/114 (0.00%)  0/74 (0.00%)  0/110 (0.00%)  0/60 (0.00%) 
Intraocular pressure increased * 1 [1]  0/114 (0.00%)  0/74 (0.00%)  1/110 (0.91%)  0/60 (0.00%) 
Protein urine present * 1  0/114 (0.00%)  0/74 (0.00%)  0/110 (0.00%)  0/60 (0.00%) 
Metabolism and nutrition disorders         
Abnormal loss of weight * 1  1/114 (0.88%)  0/74 (0.00%)  0/110 (0.00%)  0/60 (0.00%) 
Dehydration * 1  0/114 (0.00%)  0/74 (0.00%)  0/110 (0.00%)  1/60 (1.67%) 
Hypokalaemia * 1  0/114 (0.00%)  0/74 (0.00%)  0/110 (0.00%)  1/60 (1.67%) 
Musculoskeletal and connective tissue disorders         
Arthritis * 1  0/114 (0.00%)  0/74 (0.00%)  1/110 (0.91%)  1/60 (1.67%) 
Intervertebral disc degeneration * 1  0/114 (0.00%)  0/74 (0.00%)  0/110 (0.00%)  1/60 (1.67%) 
Intervertebral disc protrusion * 1  0/114 (0.00%)  0/74 (0.00%)  1/110 (0.91%)  0/60 (0.00%) 
Osteoarthritis * 1  1/114 (0.88%)  0/74 (0.00%)  0/110 (0.00%)  1/60 (1.67%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Colon cancer * 1  0/114 (0.00%)  1/74 (1.35%)  0/110 (0.00%)  1/60 (1.67%) 
Mantle cell lymphoma * 1  0/114 (0.00%)  0/74 (0.00%)  0/110 (0.00%)  1/60 (1.67%) 
Metastatic renal cell carcinoma * 1  0/114 (0.00%)  0/74 (0.00%)  1/110 (0.91%)  0/60 (0.00%) 
Non-small cell lung cancer * 1  1/114 (0.88%)  0/74 (0.00%)  0/110 (0.00%)  0/60 (0.00%) 
Oesophageal adenocarcinoma stage IV * 1  0/114 (0.00%)  1/74 (1.35%)  0/110 (0.00%)  0/60 (0.00%) 
Prostate cancer * 1  0/114 (0.00%)  1/74 (1.35%)  0/110 (0.00%)  0/60 (0.00%) 
Squamous cell carcinoma of skin * 1  0/114 (0.00%)  0/74 (0.00%)  1/110 (0.91%)  0/60 (0.00%) 
Thyroid cancer * 1  0/114 (0.00%)  1/74 (1.35%)  0/110 (0.00%)  0/60 (0.00%) 
Nervous system disorders         
Carotid artery stenosis * 1  0/114 (0.00%)  1/74 (1.35%)  0/110 (0.00%)  0/60 (0.00%) 
Convulsion * 1  0/114 (0.00%)  0/74 (0.00%)  1/110 (0.91%)  0/60 (0.00%) 
Dementia * 1  0/114 (0.00%)  0/74 (0.00%)  1/110 (0.91%)  0/60 (0.00%) 
Encephalopathy * 1  0/114 (0.00%)  0/74 (0.00%)  1/110 (0.91%)  0/60 (0.00%) 
Haemorrhagic cerebral infarction * 1  0/114 (0.00%)  0/74 (0.00%)  1/110 (0.91%)  0/60 (0.00%) 
Loss of consciousness * 1  0/114 (0.00%)  0/74 (0.00%)  1/110 (0.91%)  0/60 (0.00%) 
Subarachnoid haemorrhage * 1  0/114 (0.00%)  0/74 (0.00%)  1/110 (0.91%)  0/60 (0.00%) 
Syncope * 1  0/114 (0.00%)  0/74 (0.00%)  1/110 (0.91%)  0/60 (0.00%) 
Psychiatric disorders         
Mental status changes * 1  0/114 (0.00%)  1/74 (1.35%)  0/110 (0.00%)  0/60 (0.00%) 
Renal and urinary disorders         
Haematuria * 1  0/114 (0.00%)  0/74 (0.00%)  1/110 (0.91%)  0/60 (0.00%) 
Obstructive uropathy * 1  0/114 (0.00%)  0/74 (0.00%)  1/110 (0.91%)  0/60 (0.00%) 
Renal failure acute * 1  0/114 (0.00%)  0/74 (0.00%)  1/110 (0.91%)  2/60 (3.33%) 
Renal failure chronic * 1  0/114 (0.00%)  1/74 (1.35%)  0/110 (0.00%)  0/60 (0.00%) 
Reproductive system and breast disorders         
Benign prostatic hyperplasia * 1  0/114 (0.00%)  0/74 (0.00%)  1/110 (0.91%)  0/60 (0.00%) 
Cystocele * 1  0/114 (0.00%)  0/74 (0.00%)  0/110 (0.00%)  1/60 (1.67%) 
Rectocele * 1  0/114 (0.00%)  0/74 (0.00%)  0/110 (0.00%)  1/60 (1.67%) 
Respiratory, thoracic and mediastinal disorders         
Apnoea * 1  0/114 (0.00%)  1/74 (1.35%)  0/110 (0.00%)  0/60 (0.00%) 
Asthma * 1  0/114 (0.00%)  0/74 (0.00%)  1/110 (0.91%)  0/60 (0.00%) 
Epistaxis * 1  0/114 (0.00%)  0/74 (0.00%)  1/110 (0.91%)  0/60 (0.00%) 
Pneumonia aspiration * 1  0/114 (0.00%)  0/74 (0.00%)  1/110 (0.91%)  0/60 (0.00%) 
Pneumothorax * 1  1/114 (0.88%)  0/74 (0.00%)  0/110 (0.00%)  0/60 (0.00%) 
Respiratory failure * 1  0/114 (0.00%)  0/74 (0.00%)  0/110 (0.00%)  1/60 (1.67%) 
Skin and subcutaneous tissue disorders         
Dermatitis contact * 1  0/114 (0.00%)  0/74 (0.00%)  1/110 (0.91%)  0/60 (0.00%) 
Vascular disorders         
Hypertension * 1  0/114 (0.00%)  0/74 (0.00%)  0/110 (0.00%)  0/60 (0.00%) 
Hypotension * 1  0/114 (0.00%)  0/74 (0.00%)  1/110 (0.91%)  0/60 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA Version 13.1
[1]
Ocular AE Fellow Eye
[2]
Ocular AE Study Eye
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Intravitreal Aflibercept Injection (IAI) (Baseline to Week 24) Sham Treatment (Baseline to Week 24) IAI to IAI (Week 24 to Week 100) Sham Treatment to IAI (Week 24 to Week 100)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   57/114 (50.00%)   34/74 (45.95%)   76/110 (69.09%)   50/60 (83.33%) 
Eye disorders         
Cataract * 1 [1]  0/114 (0.00%)  0/74 (0.00%)  6/110 (5.45%)  0/60 (0.00%) 
Cystoid macular oedema * 1 [2]  0/114 (0.00%)  0/74 (0.00%)  14/110 (12.73%)  4/60 (6.67%) 
Dry eye * 1 [2]  0/114 (0.00%)  0/74 (0.00%)  0/110 (0.00%)  4/60 (6.67%) 
Eye irritation * 1 [2]  6/114 (5.26%)  0/74 (0.00%)  0/110 (0.00%)  0/60 (0.00%) 
Eye pain * 1 [2]  16/114 (14.04%)  4/74 (5.41%)  9/110 (8.18%)  4/60 (6.67%) 
Iris neovascularisation * 1 [2]  0/114 (0.00%)  4/74 (5.41%)  0/110 (0.00%)  0/60 (0.00%) 
Lacrimation increased * 1 [2]  0/114 (0.00%)  0/74 (0.00%)  0/110 (0.00%)  4/60 (6.67%) 
Macular oedema * 1 [2]  0/114 (0.00%)  0/74 (0.00%)  20/110 (18.18%)  0/60 (0.00%) 
Maculopathy * 1 [2]  10/114 (8.77%)  0/74 (0.00%)  6/110 (5.45%)  0/60 (0.00%) 
Optic disc vascular disorder * 1 [2]  8/114 (7.02%)  0/74 (0.00%)  6/110 (5.45%)  5/60 (8.33%) 
Retinal exudates * 1 [2]  7/114 (6.14%)  0/74 (0.00%)  0/110 (0.00%)  5/60 (8.33%) 
Retinal haemorrhage * 1 [1]  0/114 (0.00%)  0/74 (0.00%)  6/110 (5.45%)  4/60 (6.67%) 
Retinal pigment epitheliopathy * 1 [2]  0/114 (0.00%)  0/74 (0.00%)  0/110 (0.00%)  12/60 (20.00%) 
Retinal vascular disorder * 1 [2]  6/114 (5.26%)  4/74 (5.41%)  8/110 (7.27%)  0/60 (0.00%) 
Visual acuity reduced * 1 [2]  7/114 (6.14%)  12/74 (16.22%)  27/110 (24.55%)  8/60 (13.33%) 
Vitreous detachment * 1 [2]  0/114 (0.00%)  5/74 (6.76%)  8/110 (7.27%)  0/60 (0.00%) 
Vitreous floaters * 1 [2]  6/114 (5.26%)  0/74 (0.00%)  0/110 (0.00%)  0/60 (0.00%) 
Infections and infestations         
Influenza * 1  0/114 (0.00%)  0/74 (0.00%)  7/110 (6.36%)  0/60 (0.00%) 
Nasopharyngitis * 1  0/114 (0.00%)  4/74 (5.41%)  6/110 (5.45%)  0/60 (0.00%) 
Upper respiratory tract infection * 1  6/114 (5.26%)  0/74 (0.00%)  6/110 (5.45%)  0/60 (0.00%) 
Investigations         
Blood pressure systolic increased * 1  0/114 (0.00%)  0/74 (0.00%)  0/110 (0.00%)  4/60 (6.67%) 
Blood urine present * 1  0/114 (0.00%)  0/74 (0.00%)  0/110 (0.00%)  4/60 (6.67%) 
Intraocular pressure increased * 1 [1]  0/114 (0.00%)  0/74 (0.00%)  0/110 (0.00%)  4/60 (6.67%) 
Protein urine present * 1  0/114 (0.00%)  0/74 (0.00%)  0/110 (0.00%)  5/60 (8.33%) 
Vascular disorders         
Hypertension * 1  10/114 (8.77%)  4/74 (5.41%)  13/110 (11.82%)  9/60 (15.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA Version 13.1
[1]
Ocular AE Fellow Eye
[2]
Ocular AE Study Eye
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The only disclosure restriction on the PI, after completion of the trial and multi-center publication, is that the sponsor can review results communications prior to public release & may have the right to embargo communications regarding results for a period between 60 & 180 days from the time submitted to the sponsor for review; provided that the sponsor can remove confidential/proprietary information. 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: 914 847 5385
Responsible Party: Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00943072     History of Changes
Other Study ID Numbers: VGFT-OD-0819
First Submitted: July 10, 2009
First Posted: July 21, 2009
Results First Submitted: October 19, 2012
Results First Posted: May 27, 2013
Last Update Posted: May 27, 2013