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Trial record 1 of 1 for:    Panorama | Diabetic Retinopathy
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Study of the Efficacy and Safety of Intravitreal (IVT) Aflibercept for the Improvement of Moderately Severe to Severe Nonproliferative Diabetic Retinopathy (NPDR) (PANORAMA)

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: NCT02718326
Recruitment Status : Completed
First Posted : March 24, 2016
Results First Posted : November 21, 2019
Last Update Posted : July 30, 2020
Sponsor:
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 Nonproliferative Diabetic Retinopathy
Interventions Drug: Intravitreal aflibercept injection [IAI]
Drug: Sham
Enrollment 402
Recruitment Details Recruitment for this study was conducted in the following countries between 29 Mar 2016 and 07 Aug 2017: Germany, Hungary, Japan, the United Kingdom, and the United States. A total of 759 participants were screened.
Pre-assignment Details Out of 759, 402 participants were randomized to receive 1 of 3 treatment groups in a 1:1:1 ratio stratified based on their Diabetic Retinopathy Severity Scale (DRSS) score (level 47 vs. level 53). Only 1 eye was selected as the study eye.
Arm/Group Title Sham Treatment Intravitreal Aflibercept Injection (IAI) 2Q16 Intravitreal Aflibercept Injection (IAI) 2Q8
Hide Arm/Group Description All participants received sham injections in the study eye every 4 weeks (Q4) to week 16 (after 5 initial monthly sham injections), followed by sham injections Q8 to week 96. All participants received a 2 milligram (mg) Intravitreal Aflibercept Injection (IAI) in the study eye every 16 weeks (2Q16) (after 3 initial monthly doses and one 8-week interval) to week 96. All participants received 2 mg IAI in the study eye every 8 weeks (2Q8) from day 1 up to week 48 (after 5 initial monthly doses), followed by a flexible treatment regimen with IAI 2 mg to week 96.
Period Title: Overall Study
Number of participants Number of units (Eyes) Number of participants Number of units (Eyes) Number of participants Number of units (Eyes)
Started 133 133 135 135 134 134
Completed Week 52 109 109 122 122 124 124
Completed [1] 97 97 111 111 112 112
Not Completed 36 36 24 24 22 22
Reason Not Completed
Adverse Event             4                         9                         0            
Death             8                         1                         2            
Withdrawal by Subject             4                         9                         6            
Lost to Follow-up             18                         5                         14            
Protocol Deviation             1                         0                         0            
Pregnancy             1                         0                         0            
[1]
Week 100 (End of Study)
Arm/Group Title Sham Treatment Intravitreal Aflibercept Injection (IAI) 2Q16 Intravitreal Aflibercept Injection (IAI) 2Q8 Total
Hide Arm/Group Description All participants received sham injections in the study eye every 4 weeks (Q4) to week 16 (after 5 initial monthly sham injections), followed by sham injections Q8 to week 96. All participants received a 2 milligram (mg) Intravitreal Aflibercept Injection (IAI) in the study eye every 16 weeks (2Q16) (after 3 initial monthly doses and one 8-week interval) to week 96. All participants received 2 mg IAI in the study eye every 8 weeks (2Q8) from day 1 up to week 48 (after 5 initial monthly doses), followed by a flexible treatment regimen with IAI 2 mg to week 96. Total of all reporting groups
Overall Number of Baseline Participants 133 135 134 402
Hide Baseline Analysis Population Description
The full analysis set (FAS) included all randomized participants who received any study treatment as assigned at baseline (as randomized).
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 133 participants 135 participants 134 participants 402 participants
55.8  (10.31) 55.4  (11.13) 55.8  (10.19) 55.7  (10.53)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 133 participants 135 participants 134 participants 402 participants
Female
64
  48.1%
60
  44.4%
53
  39.6%
177
  44.0%
Male
69
  51.9%
75
  55.6%
81
  60.4%
225
  56.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 133 participants 135 participants 134 participants 402 participants
Hispanic or Latino
74
  55.6%
97
  71.9%
93
  69.4%
264
  65.7%
Not Hispanic or Latino
58
  43.6%
37
  27.4%
41
  30.6%
136
  33.8%
Unknown or Not Reported
1
   0.8%
1
   0.7%
0
   0.0%
2
   0.5%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 133 participants 135 participants 134 participants 402 participants
American Indian or Alaska Native
1
   0.8%
1
   0.7%
4
   3.0%
6
   1.5%
Asian
4
   3.0%
12
   8.9%
7
   5.2%
23
   5.7%
Native Hawaiian or Other Pacific Islander
0
   0.0%
1
   0.7%
1
   0.7%
2
   0.5%
Black or African American
13
   9.8%
16
  11.9%
12
   9.0%
41
  10.2%
White
107
  80.5%
99
  73.3%
104
  77.6%
310
  77.1%
More than one race
0
   0.0%
1
   0.7%
1
   0.7%
2
   0.5%
Unknown or Not Reported
8
   6.0%
5
   3.7%
5
   3.7%
18
   4.5%
Baseline Diabetic Retinopathy Severity Score (DRSS)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 133 participants 135 participants 134 participants 402 participants
Level 47 (Moderately Severe)
99
  74.4%
102
  75.6%
101
  75.4%
302
  75.1%
Level 53 (Severe)
34
  25.6%
33
  24.4%
33
  24.6%
100
  24.9%
[1]
Measure Description: The Diabetic Retinopathy Disease Severity Scale (DRSS) may be used to describe overall retinopathy severity as well as the change in severity over time. Severity range from level 10 (DR absent) to level 85 (advanced proliferative DR: posterior fundus obscured, or center of macula detached).
1.Primary Outcome
Title Percentage of Participants Who Improved by ≥2 Steps From Baseline in the Diabetic Retinopathy Disease Severity Scale (DRSS) Score at Week 24 in the Combined 2Q16 and 2Q8 Groups
Hide Description The Diabetic Retinopathy Disease Severity Scale (DRSS) may be used to describe overall retinopathy severity as well as the change in severity over time. Severity range from level 10 (DR absent) to level 85 (advanced proliferative DR: posterior fundus obscured, or center of macula detached). Here, DRSS describes severity level 47 (moderately severe NPDR) and level 53 (severe NPDR) at week 24 from baseline.
Time Frame At Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants who received any study treatment as assigned at baseline (as randomized). The missing data were imputed using last observation carried forward (LOCF) method.
Arm/Group Title Sham Treatment Intravitreal Aflibercept Injection (IAI) 2Q16 Intravitreal Aflibercept Injection (IAI) 2Q8 IAI 2 mg Groups Combined (2Q16 & 2Q8)
Hide Arm/Group Description:
All participants received sham injections in the study eye every 4 weeks (Q4) to week 16 (after 5 initial monthly sham injections), followed by sham injections Q8 to week 96.
All participants received a 2 milligram (mg) Intravitreal Aflibercept Injection (IAI) in the study eye every 16 weeks (2Q16) (after 3 initial monthly doses and one 8-week interval) to week 96.
All participants received 2 mg IAI in the study eye every 8 weeks (2Q8) from day 1 up to week 48 (after 5 initial monthly doses), followed by a flexible treatment regimen with IAI 2 mg to week 96.
IAI 2Q16: Participants received a 2 milligram (mg) Intravitreal Aflibercept Injection (IAI) in the study eye every 16 weeks (2Q16) (after 3 initial monthly doses and one 8-week interval) to week 96; IAI 2Q8: Participants received 2 mg IAI in the study eye every 8 weeks (2Q8) from day 1 up to week 48 (after 5 initial monthly doses), followed by a flexible treatment regimen with IAI 2 mg to week 96.
Overall Number of Participants Analyzed 133 135 134 269
Measure Type: Number
Unit of Measure: Percentage of participants
6.0 61.5 55.2 58.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sham Treatment, IAI 2 mg Groups Combined (2Q16 & 2Q8)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter percentage difference
Estimated Value 52.3
Confidence Interval (2-Sided) 95%
45.2 to 59.5
Estimation Comments [Not Specified]
2.Primary Outcome
Title Percentage of Participants With a ≥ 2-step Change at Week 52 in Diabetic Retinopathy Severity Scale (DRSS) From Baseline
Hide Description The Diabetic Retinopathy Disease Severity Scale (DRSS) may be used to describe overall retinopathy severity as well as the change in severity over time. Severity range from level 10 (DR absent) to level 85 (advanced proliferative DR: posterior fundus obscured, or center of macula detached). Here, DRSS describes severity level 47 (moderately severe NPDR) and level 53 (severe NPDR) at week 52 from baseline.
Time Frame At Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants who received any study treatment as assigned at baseline (as randomized). The missing data were imputed using LOCF method.
Arm/Group Title Sham Treatment Intravitreal Aflibercept Injection (IAI) 2Q16 Intravitreal Aflibercept Injection (IAI) 2Q8
Hide Arm/Group Description:
All participants received sham injections in the study eye every 4 weeks (Q4) to week 16 (after 5 initial monthly sham injections), followed by sham injections Q8 to week 96.
All participants received a 2 milligram (mg) Intravitreal Aflibercept Injection (IAI) in the study eye every 16 weeks (2Q16) (after 3 initial monthly doses and one 8-week interval) to week 96.
All participants received 2 mg IAI in the study eye every 8 weeks (2Q8) from day 1 up to week 48 (after 5 initial monthly doses), followed by a flexible treatment regimen with IAI 2 mg to week 96.
Overall Number of Participants Analyzed 133 135 134
Measure Type: Number
Unit of Measure: Percentage of participants
15.0 65.2 79.9
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sham Treatment, Intravitreal Aflibercept Injection (IAI) 2Q16
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter percentage difference
Estimated Value 50.1
Confidence Interval (2-Sided) 95%
40.1 to 60.1
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Sham Treatment, Intravitreal Aflibercept Injection (IAI) 2Q8
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter percentage difference
Estimated Value 64.8
Confidence Interval (2-Sided) 95%
55.8 to 73.9
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Participants Who Developed a Vision-Threatening Complication Due to Diabetic Retinopathy at Week 52
Hide Description Vision-threatening complications are defined as the composite outcome of proliferative diabetic retinopathy (PDR) (inclusive of participants who have vitreous hemorrhage or tractional retinal detachment believed to be due to PDR) and anterior segment neovascularization (ASNV) (participants with neovascularization of the iris [at least 2 cumulative clock hours], and/or definitive neovascularization of the iridocorneal angle).
Time Frame At Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants who received any study treatment as assigned at baseline (as randomized).
Arm/Group Title Sham Treatment Intravitreal Aflibercept Injection (IAI) 2Q16 Intravitreal Aflibercept Injection (IAI) 2Q8
Hide Arm/Group Description:
All participants received sham injections in the study eye every 4 weeks (Q4) to week 16 (after 5 initial monthly sham injections), followed by sham injections Q8 to week 96.
All participants received a 2 milligram (mg) Intravitreal Aflibercept Injection (IAI) in the study eye every 16 weeks (2Q16) (after 3 initial monthly doses and one 8-week interval) to week 96.
All participants received 2 mg IAI in the study eye every 8 weeks (2Q8) from day 1 up to week 48 (after 5 initial monthly doses), followed by a flexible treatment regimen with IAI 2 mg to week 96.
Overall Number of Participants Analyzed 133 135 134
Measure Type: Number
Unit of Measure: Percentage of participants
20.3 3.7 3.0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sham Treatment, Intravitreal Aflibercept Injection (IAI) 2Q8
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter percentage difference
Estimated Value -17.3
Confidence Interval (2-Sided) 95%
-24.7 to -9.9
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Sham Treatment, Intravitreal Aflibercept Injection (IAI) 2Q16
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter percentage difference
Estimated Value -16.6
Confidence Interval (2-Sided) 95%
-24.2 to -9.1
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Percentage of Participants Who Developed Central Involved-Diabetic Macular Edema (CI-DME) at Week 52
Hide Description The percentage of participants who developed CI-DME at week 52 were reported.
Time Frame At Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants who received any study treatment as assigned at baseline (as randomized).
Arm/Group Title Sham Treatment Intravitreal Aflibercept Injection (IAI) 2Q16 Intravitreal Aflibercept Injection (IAI) 2Q8
Hide Arm/Group Description:
All participants received sham injections in the study eye every 4 weeks (Q4) to week 16 (after 5 initial monthly sham injections), followed by sham injections Q8 to week 96.
All participants received a 2 milligram (mg) Intravitreal Aflibercept Injection (IAI) in the study eye every 16 weeks (2Q16) (after 3 initial monthly doses and one 8-week interval) to week 96.
All participants received 2 mg IAI in the study eye every 8 weeks (2Q8) from day 1 up to week 48 (after 5 initial monthly doses), followed by a flexible treatment regimen with IAI 2 mg to week 96.
Overall Number of Participants Analyzed 133 135 134
Measure Type: Number
Unit of Measure: Percentage of participants
25.6 6.7 8.2
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sham Treatment, Intravitreal Aflibercept Injection (IAI) 2Q8
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0002
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter percentage difference
Estimated Value -17.3
Confidence Interval (2-Sided) 95%
-26.2 to -8.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Sham Treatment, Intravitreal Aflibercept Injection (IAI) 2Q16
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter percentage difference
Estimated Value -18.9
Confidence Interval (2-Sided) 95%
-27.5 to -10.4
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Time to Development of Any Neovascular Vision Threatening Complication (PDR/ASNV) Through Week 52
Hide Description Vision-threatening complication (VTC) is defined as the composite outcome of proliferative diabetic retinopathy (PDR) (inclusive of participants who have vitreous hemorrhage or tractional retinal detachment believed to be due to PDR) and anterior segment neovascularization (ASNV) (participants with neovascularization of the iris [at least 2 cumulative clock hours], and/or definitive neovascularization of the iridocorneal angle). Vision Threatening Complications include PDR/ASNV identified by investigators and Diabetic Retinopathy Scale Score (DRSS) >61.
Time Frame Baseline through week 52 (day 365)
Hide Outcome Measure Data
Hide Analysis Population Description

FAS included all randomized participants who received any study treatment as assigned at baseline (as randomized). Participants who did not have an event were censored at their last visit at or before the week 52 visit.

Here, the value "NA" = Not evaluable due to small number of VTC events.

Arm/Group Title Sham Treatment Intravitreal Aflibercept Injection (IAI) 2Q16 Intravitreal Aflibercept Injection (IAI) 2Q8
Hide Arm/Group Description:
All participants received sham injections in the study eye every 4 weeks (Q4) to week 16 (after 5 initial monthly sham injections), followed by sham injections Q8 to week 96.
All participants received a 2 milligram (mg) Intravitreal Aflibercept Injection (IAI) in the study eye every 16 weeks (2Q16) (after 3 initial monthly doses and one 8-week interval) to week 96.
All participants received 2 mg IAI in the study eye every 8 weeks (2Q8) from day 1 up to week 48 (after 5 initial monthly doses), followed by a flexible treatment regimen with IAI 2 mg to week 96.
Overall Number of Participants Analyzed 133 135 134
Median (Inter-Quartile Range)
Unit of Measure: Days
NA [1] 
(371 to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
NA = Not evaluable due to small number of VTC events
6.Secondary Outcome
Title Time to Development of Central Involved-Diabetic Macular Edema (CI-DME) Through Week 52
Hide Description Time to develop Central Involved-Diabetic Macular Edema (CI-DME) through week 52 reported.
Time Frame Baseline through week 52 (day 365)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants who received any study treatment as assigned at baseline (as randomized). Participants who did not have an event were censored at their last visit, at or before the week 52 visit. Here, the value "NA" = Not evaluable due to small number of CI-DME events.
Arm/Group Title Sham Treatment Intravitreal Aflibercept Injection (IAI) 2Q16 Intravitreal Aflibercept Injection (IAI) 2Q8
Hide Arm/Group Description:
All participants received sham injections in the study eye every 4 weeks (Q4) to week 16 (after 5 initial monthly sham injections), followed by sham injections Q8 to week 96.
All participants received a 2 milligram (mg) Intravitreal Aflibercept Injection (IAI) in the study eye every 16 weeks (2Q16) (after 3 initial monthly doses and one 8-week interval) to week 96.
All participants received 2 mg IAI in the study eye every 8 weeks (2Q8) from day 1 up to week 48 (after 5 initial monthly doses), followed by a flexible treatment regimen with IAI 2 mg to week 96.
Overall Number of Participants Analyzed 133 135 134
Median (Inter-Quartile Range)
Unit of Measure: Days
NA [1] 
(333 to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
NA = Not evaluable due to small number of CI-DME events
7.Secondary Outcome
Title Percentage of Participants Who Received Panretinal Photocoagulation (PRP), Inclusive of Participants Undergoing Vitrectomy With Endolaser, at Week 52
Hide Description The percentage of participants who received panretinal photocoagulation (PRP), inclusive of participants undergoing vitrectomy with endolaser, at week 52 were reported.
Time Frame At Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants who received any study treatment as assigned at baseline (as randomized).
Arm/Group Title Sham Treatment Intravitreal Aflibercept Injection (IAI) 2Q16 Intravitreal Aflibercept Injection (IAI) 2Q8
Hide Arm/Group Description:
All participants received sham injections in the study eye every 4 weeks (Q4) to week 16 (after 5 initial monthly sham injections), followed by sham injections Q8 to week 96.
All participants received a 2 milligram (mg) Intravitreal Aflibercept Injection (IAI) in the study eye every 16 weeks (2Q16) (after 3 initial monthly doses and one 8-week interval) to week 96.
All participants received 2 mg IAI in the study eye every 8 weeks (2Q8) from day 1 up to week 48 (after 5 initial monthly doses), followed by a flexible treatment regimen with IAI 2 mg to week 96.
Overall Number of Participants Analyzed 133 135 134
Measure Type: Number
Unit of Measure: Percentage of participants
6.8 0.7 0.7
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sham Treatment, Intravitreal Aflibercept Injection (IAI) 2Q8
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0096
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter percentage difference
Estimated Value -6.0
Confidence Interval (2-Sided) 95%
-10.5 to -1.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Sham Treatment, Intravitreal Aflibercept Injection (IAI) 2Q16
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0089
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter percentage difference
Estimated Value -6.0
Confidence Interval (2-Sided) 95%
-10.5 to -1.6
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Area Under the Curve (AUC) for Change From Baseline in Best Corrected Visual Acuity (BCVA) at Week 52
Hide Description The area under the curve (AUC) is the area under the best corrected visual acuity (BCVA) versus time curve from baseline to week 52. Visual function of the study eye was assessed at a distance of 4 meters at every study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. BCVA scale range is 0 (worst) to 100 (best).
Time Frame At week 52
Hide Outcome Measure Data
Hide Analysis Population Description
AUC was calculated as a weighted average based on total AUC (using the trapezoidal rule) divided by total duration in days. FAS included all randomized participants who received any study treatment as assigned at baseline (as randomized).
Arm/Group Title Sham Treatment Intravitreal Aflibercept Injection (IAI) 2Q16 Intravitreal Aflibercept Injection (IAI) 2Q8
Hide Arm/Group Description:
All participants received sham injections in the study eye every 4 weeks (Q4) to week 16 (after 5 initial monthly sham injections), followed by sham injections Q8 to week 96.
All participants received a 2 milligram (mg) Intravitreal Aflibercept Injection (IAI) in the study eye every 16 weeks (2Q16) (after 3 initial monthly doses and one 8-week interval) to week 96.
All participants received 2 mg IAI in the study eye every 8 weeks (2Q8) from day 1 up to week 48 (after 5 initial monthly doses), followed by a flexible treatment regimen with IAI 2 mg to week 96.
Overall Number of Participants Analyzed 133 135 134
Mean (Standard Deviation)
Unit of Measure: scores on a scale
0.5  (3.01) 1.7  (3.50) 1.3  (3.49)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sham Treatment, Intravitreal Aflibercept Injection (IAI) 2Q8
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0529
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimate for contrast
Estimated Value 0.80
Confidence Interval (2-Sided) 95%
-0.01 to 1.60
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Sham Treatment, Intravitreal Aflibercept Injection (IAI) 2Q16
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0057
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimate for contrast
Estimated Value 1.14
Confidence Interval (2-Sided) 95%
0.33 to 1.94
Estimation Comments [Not Specified]
Time Frame All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product
Adverse Event Reporting Description Reported adverse events are treatment-emergent adverse events (TEAEs) which are AEs that developed/worsened from baseline (day1) up to end of study (week 100).
 
Arm/Group Title Sham Treatment Intravitreal Aflibercept Injection (IAI) 2Q16 Intravitreal Aflibercept Injection (IAI) 2Q8 IAI 2 mg Groups Combined (2Q16 & 2Q8)
Hide Arm/Group Description All participants received sham injections in the study eye every 4 weeks (Q4) to week 16 (after 5 initial monthly sham injections), followed by sham injections Q8 to week 96. All participants received a 2 milligram (mg) Intravitreal Aflibercept Injection (IAI) in the study eye every 16 weeks (2Q16) (after 3 initial monthly doses and one 8-week interval) to week 96. All participants received 2 mg IAI in the study eye every 8 weeks (2Q8) from day 1 up to week 48 (after 5 initial monthly doses), followed by a flexible treatment regimen with IAI 2 mg to week 96. IAI 2Q16: Participants received a 2 milligram (mg) Intravitreal Aflibercept Injection (IAI) in the study eye every 16 weeks (2Q16) (after 3 initial monthly doses and one 8-week interval) to week 96; IAI 2Q8: Participants received 2 mg IAI in the study eye every 8 weeks (2Q8) from day 1 up to week 48 (after 5 initial monthly doses), followed by a flexible treatment regimen with IAI 2 mg to week 96.
All-Cause Mortality
Sham Treatment Intravitreal Aflibercept Injection (IAI) 2Q16 Intravitreal Aflibercept Injection (IAI) 2Q8 IAI 2 mg Groups Combined (2Q16 & 2Q8)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   8/133 (6.02%)      1/135 (0.74%)      3/134 (2.24%)      4/269 (1.49%)    
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Sham Treatment Intravitreal Aflibercept Injection (IAI) 2Q16 Intravitreal Aflibercept Injection (IAI) 2Q8 IAI 2 mg Groups Combined (2Q16 & 2Q8)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   38/133 (28.57%)      38/135 (28.15%)      47/134 (35.07%)      85/269 (31.60%)    
Blood and lymphatic system disorders         
Anaemia  1  0/133 (0.00%)  0 2/135 (1.48%)  2 0/134 (0.00%)  0 2/269 (0.74%)  2
Cardiac disorders         
Coronary artery disease  1  1/133 (0.75%)  1 5/135 (3.70%)  5 4/134 (2.99%)  4 9/269 (3.35%)  9
Cardiac failure congestive  1  1/133 (0.75%)  1 2/135 (1.48%)  2 3/134 (2.24%)  3 5/269 (1.86%)  5
Myocardial infarction  1  1/133 (0.75%)  1 2/135 (1.48%)  2 1/134 (0.75%)  1 3/269 (1.12%)  3
Acute myocardial infarction  1  2/133 (1.50%)  2 2/135 (1.48%)  2 0/134 (0.00%)  0 2/269 (0.74%)  2
Cardiac failure acute  1  0/133 (0.00%)  0 1/135 (0.74%)  2 1/134 (0.75%)  1 2/269 (0.74%)  3
Coronary artery stenosis  1  0/133 (0.00%)  0 2/135 (1.48%)  2 0/134 (0.00%)  0 2/269 (0.74%)  2
Atrial fibrillation  1  0/133 (0.00%)  0 0/135 (0.00%)  0 1/134 (0.75%)  1 1/269 (0.37%)  1
Atrial flutter  1  0/133 (0.00%)  0 1/135 (0.74%)  1 0/134 (0.00%)  0 1/269 (0.37%)  1
Cardiac arrest  1  0/133 (0.00%)  0 0/135 (0.00%)  0 1/134 (0.75%)  1 1/269 (0.37%)  1
Cardiac failure chronic  1  0/133 (0.00%)  0 1/135 (0.74%)  1 0/134 (0.00%)  0 1/269 (0.37%)  1
Myocardial ischaemia  1  0/133 (0.00%)  0 0/135 (0.00%)  0 1/134 (0.75%)  1 1/269 (0.37%)  1
Supraventricular tachycardia  1  0/133 (0.00%)  0 1/135 (0.74%)  1 0/134 (0.00%)  0 1/269 (0.37%)  1
Acute coronary syndrome  1  1/133 (0.75%)  1 0/135 (0.00%)  0 0/134 (0.00%)  0 0/269 (0.00%)  0
Cardiac failure  1  1/133 (0.75%)  1 0/135 (0.00%)  0 0/134 (0.00%)  0 0/269 (0.00%)  0
Ischaemic cardiomyopathy  1  1/133 (0.75%)  1 0/135 (0.00%)  0 0/134 (0.00%)  0 0/269 (0.00%)  0
Left ventricular dysfunction  1  1/133 (0.75%)  1 0/135 (0.00%)  0 0/134 (0.00%)  0 0/269 (0.00%)  0
Left ventricular failure  1  2/133 (1.50%)  2 0/135 (0.00%)  0 0/134 (0.00%)  0 0/269 (0.00%)  0
Pulseless electrical activity  1  1/133 (0.75%)  1 0/135 (0.00%)  0 0/134 (0.00%)  0 0/269 (0.00%)  0
Eye disorders         
Visual acuity reduced Fellow Eye  1  1/133 (0.75%)  1 0/135 (0.00%)  0 3/134 (2.24%)  3 3/269 (1.12%)  3
Diabetic retinal oedema Fellow Eye  1  0/133 (0.00%)  0 0/135 (0.00%)  0 1/134 (0.75%)  1 1/269 (0.37%)  1
Macular fibrosis Fellow Eye  1  0/133 (0.00%)  0 0/135 (0.00%)  0 1/134 (0.75%)  1 1/269 (0.37%)  1
Macular hole Fellow Eye  1  0/133 (0.00%)  0 0/135 (0.00%)  0 1/134 (0.75%)  1 1/269 (0.37%)  1
Retinal vein occlusion Fellow Eye  1  0/133 (0.00%)  0 1/135 (0.74%)  1 0/134 (0.00%)  0 1/269 (0.37%)  1
Visual impairment Fellow Eye  1  0/133 (0.00%)  0 0/135 (0.00%)  0 1/134 (0.75%)  1 1/269 (0.37%)  1
Vitreous adhesions Fellow Eye  1  0/133 (0.00%)  0 0/135 (0.00%)  0 1/134 (0.75%)  1 1/269 (0.37%)  1
Vitreous haemorrhage Fellow Eye  1  1/133 (0.75%)  1 1/135 (0.74%)  1 0/134 (0.00%)  0 1/269 (0.37%)  1
Cataract Fellow Eye  1  1/133 (0.75%)  1 0/135 (0.00%)  0 0/134 (0.00%)  0 0/269 (0.00%)  0
Iris neovascularisation Fellow Eye  1  2/133 (1.50%)  2 0/135 (0.00%)  0 0/134 (0.00%)  0 0/269 (0.00%)  0
Cystoid macular oedema Study Eye  1  0/133 (0.00%)  0 0/135 (0.00%)  0 1/134 (0.75%)  2 1/269 (0.37%)  2
Visual acuity reduced Study Eye  1  0/133 (0.00%)  0 0/135 (0.00%)  0 1/134 (0.75%)  1 1/269 (0.37%)  1
Vitreous haemorrhage Study Eye  1  0/133 (0.00%)  0 0/135 (0.00%)  0 1/134 (0.75%)  1 1/269 (0.37%)  1
Diabetic retinopathy Study Eye  1  1/133 (0.75%)  2 0/135 (0.00%)  0 0/134 (0.00%)  0 0/269 (0.00%)  0
Iris neovascularisation Study Eye  1  1/133 (0.75%)  1 0/135 (0.00%)  0 0/134 (0.00%)  0 0/269 (0.00%)  0
Retinal neovascularisation Study Eye  1  1/133 (0.75%)  1 0/135 (0.00%)  0 0/134 (0.00%)  0 0/269 (0.00%)  0
Gastrointestinal disorders         
Diabetic gastroparesis  1  0/133 (0.00%)  0 0/135 (0.00%)  0 1/134 (0.75%)  1 1/269 (0.37%)  1
Dysphagia  1  0/133 (0.00%)  0 0/135 (0.00%)  0 1/134 (0.75%)  1 1/269 (0.37%)  1
Faecaloma  1  0/133 (0.00%)  0 0/135 (0.00%)  0 1/134 (0.75%)  1 1/269 (0.37%)  1
Impaired gastric emptying  1  0/133 (0.00%)  0 0/135 (0.00%)  0 1/134 (0.75%)  5 1/269 (0.37%)  5
Small intestinal obstruction  1  0/133 (0.00%)  0 0/135 (0.00%)  0 1/134 (0.75%)  1 1/269 (0.37%)  1
Upper gastrointestinal haemorrhage  1  0/133 (0.00%)  0 1/135 (0.74%)  1 0/134 (0.00%)  0 1/269 (0.37%)  1
Vomiting  1  1/133 (0.75%)  1 0/135 (0.00%)  0 1/134 (0.75%)  1 1/269 (0.37%)  1
Gastrointestinal haemorrhage  1  1/133 (0.75%)  1 0/135 (0.00%)  0 0/134 (0.00%)  0 0/269 (0.00%)  0
Ileus  1  1/133 (0.75%)  1 0/135 (0.00%)  0 0/134 (0.00%)  0 0/269 (0.00%)  0
Nausea  1  1/133 (0.75%)  1 0/135 (0.00%)  0 0/134 (0.00%)  0 0/269 (0.00%)  0
General disorders         
Chest pain  1  0/133 (0.00%)  0 1/135 (0.74%)  1 0/134 (0.00%)  0 1/269 (0.37%)  1
Non-cardiac chest pain  1  0/133 (0.00%)  0 0/135 (0.00%)  0 1/134 (0.75%)  1 1/269 (0.37%)  1
Asthenia  1  1/133 (0.75%)  1 0/135 (0.00%)  0 0/134 (0.00%)  0 0/269 (0.00%)  0
Generalised oedema  1  1/133 (0.75%)  1 0/135 (0.00%)  0 0/134 (0.00%)  0 0/269 (0.00%)  0
Pyrexia  1  1/133 (0.75%)  1 0/135 (0.00%)  0 0/134 (0.00%)  0 0/269 (0.00%)  0
Hepatobiliary disorders         
Cholecystitis  1  1/133 (0.75%)  1 0/135 (0.00%)  0 1/134 (0.75%)  1 1/269 (0.37%)  1
Cholecystitis chronic  1  0/133 (0.00%)  0 0/135 (0.00%)  0 1/134 (0.75%)  1 1/269 (0.37%)  1
Cholelithiasis  1  1/133 (0.75%)  1 0/135 (0.00%)  0 1/134 (0.75%)  1 1/269 (0.37%)  1
Infections and infestations         
Cellulitis  1  1/133 (0.75%)  1 2/135 (1.48%)  2 5/134 (3.73%)  6 7/269 (2.60%)  8
Pneumonia  1  2/133 (1.50%)  2 3/135 (2.22%)  3 3/134 (2.24%)  5 6/269 (2.23%)  8
Diabetic foot infection  1  0/133 (0.00%)  0 3/135 (2.22%)  3 0/134 (0.00%)  0 3/269 (1.12%)  3
Sepsis  1  1/133 (0.75%)  1 0/135 (0.00%)  0 3/134 (2.24%)  3 3/269 (1.12%)  3
Abscess limb  1  0/133 (0.00%)  0 0/135 (0.00%)  0 2/134 (1.49%)  2 2/269 (0.74%)  2
Arthritis bacterial  1  0/133 (0.00%)  0 0/135 (0.00%)  0 1/134 (0.75%)  1 1/269 (0.37%)  1
Enterococcal bacteraemia  1  0/133 (0.00%)  0 0/135 (0.00%)  0 1/134 (0.75%)  1 1/269 (0.37%)  1
Gastroenteritis viral  1  0/133 (0.00%)  0 0/135 (0.00%)  0 1/134 (0.75%)  1 1/269 (0.37%)  1
Influenza  1  1/133 (0.75%)  1 0/135 (0.00%)  0 1/134 (0.75%)  1 1/269 (0.37%)  1
Osteomyelitis  1  4/133 (3.01%)  4 1/135 (0.74%)  1 0/134 (0.00%)  0 1/269 (0.37%)  1
Osteomyelitis acute  1  0/133 (0.00%)  0 0/135 (0.00%)  0 1/134 (0.75%)  1 1/269 (0.37%)  1
Pneumonia bacterial  1  0/133 (0.00%)  0 0/135 (0.00%)  0 1/134 (0.75%)  1 1/269 (0.37%)  1
Sepsis syndrome  1  0/133 (0.00%)  0 1/135 (0.74%)  1 0/134 (0.00%)  0 1/269 (0.37%)  1
Staphylococcal infection  1  0/133 (0.00%)  0 1/135 (0.74%)  1 0/134 (0.00%)  0 1/269 (0.37%)  1
Staphylococcal osteomyelitis  1  0/133 (0.00%)  0 0/135 (0.00%)  0 1/134 (0.75%)  1 1/269 (0.37%)  1
Staphylococcal skin infection  1  0/133 (0.00%)  0 0/135 (0.00%)  0 1/134 (0.75%)  1 1/269 (0.37%)  1
Urinary tract infection  1  0/133 (0.00%)  0 1/135 (0.74%)  2 0/134 (0.00%)  0 1/269 (0.37%)  2
Appendicitis  1  1/133 (0.75%)  1 0/135 (0.00%)  0 0/134 (0.00%)  0 0/269 (0.00%)  0
Diabetic gangrene  1  1/133 (0.75%)  1 0/135 (0.00%)  0 0/134 (0.00%)  0 0/269 (0.00%)  0
Infected skin ulcer  1  1/133 (0.75%)  1 0/135 (0.00%)  0 0/134 (0.00%)  0 0/269 (0.00%)  0
Septic shock  1  1/133 (0.75%)  1 0/135 (0.00%)  0 0/134 (0.00%)  0 0/269 (0.00%)  0
Injury, poisoning and procedural complications         
Anaemia postoperative  1  0/133 (0.00%)  0 0/135 (0.00%)  0 1/134 (0.75%)  1 1/269 (0.37%)  1
Ankle fracture  1  0/133 (0.00%)  0 1/135 (0.74%)  1 0/134 (0.00%)  0 1/269 (0.37%)  1
Fall  1  0/133 (0.00%)  0 1/135 (0.74%)  1 0/134 (0.00%)  0 1/269 (0.37%)  1
Femur fracture  1  0/133 (0.00%)  0 0/135 (0.00%)  0 1/134 (0.75%)  1 1/269 (0.37%)  1
Fibula fracture  1  0/133 (0.00%)  0 0/135 (0.00%)  0 1/134 (0.75%)  1 1/269 (0.37%)  1
Meniscus injury  1  0/133 (0.00%)  0 1/135 (0.74%)  1 0/134 (0.00%)  0 1/269 (0.37%)  1
Postoperative respiratory failure  1  0/133 (0.00%)  0 0/135 (0.00%)  0 1/134 (0.75%)  1 1/269 (0.37%)  1
Postoperative thoracic procedure complication  1  0/133 (0.00%)  0 1/135 (0.74%)  1 0/134 (0.00%)  0 1/269 (0.37%)  1
Radius fracture  1  0/133 (0.00%)  0 0/135 (0.00%)  0 1/134 (0.75%)  1 1/269 (0.37%)  1
Skin laceration  1  0/133 (0.00%)  0 0/135 (0.00%)  0 1/134 (0.75%)  1 1/269 (0.37%)  1
Tibia fracture  1  0/133 (0.00%)  0 0/135 (0.00%)  0 1/134 (0.75%)  1 1/269 (0.37%)  1
Traumatic arthropathy  1  0/133 (0.00%)  0 1/135 (0.74%)  1 0/134 (0.00%)  0 1/269 (0.37%)  1
Ulna fracture  1  0/133 (0.00%)  0 0/135 (0.00%)  0 1/134 (0.75%)  1 1/269 (0.37%)  1
Limb injury  1  1/133 (0.75%)  1 0/135 (0.00%)  0 0/134 (0.00%)  0 0/269 (0.00%)  0
Pneumocephalus  1  1/133 (0.75%)  1 0/135 (0.00%)  0 0/134 (0.00%)  0 0/269 (0.00%)  0
Subdural haematoma  1  1/133 (0.75%)  1 0/135 (0.00%)  0 0/134 (0.00%)  0 0/269 (0.00%)  0
Traumatic fracture Study Eye  1  0/133 (0.00%)  0 0/135 (0.00%)  0 1/134 (0.75%)  1 1/269 (0.37%)  1
Investigations         
Blood glucose increased  1  0/133 (0.00%)  0 0/135 (0.00%)  0 1/134 (0.75%)  1 1/269 (0.37%)  1
Blood sodium decreased  1  0/133 (0.00%)  0 0/135 (0.00%)  0 1/134 (0.75%)  1 1/269 (0.37%)  1
Metabolism and nutrition disorders         
Dehydration  1  1/133 (0.75%)  1 0/135 (0.00%)  0 3/134 (2.24%)  3 3/269 (1.12%)  3
Diabetic ketoacidosis  1  0/133 (0.00%)  0 2/135 (1.48%)  2 0/134 (0.00%)  0 2/269 (0.74%)  2
Hypoglycaemia  1  0/133 (0.00%)  0 2/135 (1.48%)  2 0/134 (0.00%)  0 2/269 (0.74%)  2
Diabetes mellitus  1  0/133 (0.00%)  0 0/135 (0.00%)  0 1/134 (0.75%)  1 1/269 (0.37%)  1
Gout  1  0/133 (0.00%)  0 1/135 (0.74%)  1 0/134 (0.00%)  0 1/269 (0.37%)  1
Hyperglycaemia  1  0/133 (0.00%)  0 0/135 (0.00%)  0 1/134 (0.75%)  1 1/269 (0.37%)  1
Hypokalaemia  1  1/133 (0.75%)  1 0/135 (0.00%)  0 0/134 (0.00%)  0 0/269 (0.00%)  0
Hypomagnesaemia  1  1/133 (0.75%)  1 0/135 (0.00%)  0 0/134 (0.00%)  0 0/269 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Musculoskeletal chest pain  1  0/133 (0.00%)  0 0/135 (0.00%)  0 1/134 (0.75%)  1 1/269 (0.37%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Cervix carcinoma stage 0  1  0/133 (0.00%)  0 0/135 (0.00%)  0 1/134 (0.75%)  1 1/269 (0.37%)  1
Gastric cancer  1  0/133 (0.00%)  0 1/135 (0.74%)  1 0/134 (0.00%)  0 1/269 (0.37%)  1
Malignant melanoma  1  0/133 (0.00%)  0 0/135 (0.00%)  0 1/134 (0.75%)  1 1/269 (0.37%)  1
Pancreatic carcinoma  1  0/133 (0.00%)  0 0/135 (0.00%)  0 1/134 (0.75%)  1 1/269 (0.37%)  1
Transitional cell carcinoma metastatic  1  0/133 (0.00%)  0 0/135 (0.00%)  0 1/134 (0.75%)  1 1/269 (0.37%)  1
Uterine leiomyoma  1  0/133 (0.00%)  0 0/135 (0.00%)  0 1/134 (0.75%)  1 1/269 (0.37%)  1
Basal cell carcinoma  1  1/133 (0.75%)  1 0/135 (0.00%)  0 0/134 (0.00%)  0 0/269 (0.00%)  0
Papillary thyroid cancer  1  1/133 (0.75%)  2 0/135 (0.00%)  0 0/134 (0.00%)  0 0/269 (0.00%)  0
Squamous cell carcinoma of skin  1  1/133 (0.75%)  1 0/135 (0.00%)  0 0/134 (0.00%)  0 0/269 (0.00%)  0
Nervous system disorders         
Cerebrovascular accident  1  0/133 (0.00%)  0 3/135 (2.22%)  3 1/134 (0.75%)  1 4/269 (1.49%)  4
Brain stem stroke  1  0/133 (0.00%)  0 1/135 (0.74%)  1 0/134 (0.00%)  0 1/269 (0.37%)  1
Cerebral infarction  1  0/133 (0.00%)  0 1/135 (0.74%)  1 0/134 (0.00%)  0 1/269 (0.37%)  1
Hepatic encephalopathy  1  0/133 (0.00%)  0 0/135 (0.00%)  0 1/134 (0.75%)  1 1/269 (0.37%)  1
Hypoglycaemic unconsciousness  1  1/133 (0.75%)  1 0/135 (0.00%)  0 0/134 (0.00%)  0 0/269 (0.00%)  0
Ischaemic stroke  1  3/133 (2.26%)  3 0/135 (0.00%)  0 0/134 (0.00%)  0 0/269 (0.00%)  0
Psychiatric disorders         
Bipolar disorder  1  0/133 (0.00%)  0 1/135 (0.74%)  1 0/134 (0.00%)  0 1/269 (0.37%)  1
Renal and urinary disorders         
Acute kidney injury  1  2/133 (1.50%)  2 1/135 (0.74%)  1 3/134 (2.24%)  3 4/269 (1.49%)  4
Chronic kidney disease  1  0/133 (0.00%)  0 1/135 (0.74%)  1 0/134 (0.00%)  0 1/269 (0.37%)  1
End stage renal disease  1  0/133 (0.00%)  0 0/135 (0.00%)  0 1/134 (0.75%)  1 1/269 (0.37%)  1
Urge incontinence  1  0/133 (0.00%)  0 1/135 (0.74%)  1 0/134 (0.00%)  0 1/269 (0.37%)  1
Urinary retention  1  1/133 (0.75%)  1 1/135 (0.74%)  1 0/134 (0.00%)  0 1/269 (0.37%)  1
Respiratory, thoracic and mediastinal disorders         
Acute respiratory failure  1  1/133 (0.75%)  1 0/135 (0.00%)  0 2/134 (1.49%)  2 2/269 (0.74%)  2
Pleural effusion  1  2/133 (1.50%)  2 1/135 (0.74%)  1 1/134 (0.75%)  1 2/269 (0.74%)  2
Chronic obstructive pulmonary disease  1  1/133 (0.75%)  1 0/135 (0.00%)  0 1/134 (0.75%)  1 1/269 (0.37%)  1
Pulmonary arterial hypertension  1  0/133 (0.00%)  0 0/135 (0.00%)  0 1/134 (0.75%)  1 1/269 (0.37%)  1
Respiratory acidosis  1  0/133 (0.00%)  0 1/135 (0.74%)  1 0/134 (0.00%)  0 1/269 (0.37%)  1
Respiratory failure  1  0/133 (0.00%)  0 1/135 (0.74%)  1 0/134 (0.00%)  0 1/269 (0.37%)  1
Pulmonary congestion  1  1/133 (0.75%)  1 0/135 (0.00%)  0 0/134 (0.00%)  0 0/269 (0.00%)  0
Pulmonary hypertension  1  2/133 (1.50%)  2 0/135 (0.00%)  0 0/134 (0.00%)  0 0/269 (0.00%)  0
Skin and subcutaneous tissue disorders         
Diabetic foot  1  0/133 (0.00%)  0 1/135 (0.74%)  1 2/134 (1.49%)  2 3/269 (1.12%)  3
Photosensitivity reaction  1  1/133 (0.75%)  1 0/135 (0.00%)  0 0/134 (0.00%)  0 0/269 (0.00%)  0
Vascular disorders         
Peripheral ischaemia  1  0/133 (0.00%)  0 0/135 (0.00%)  0 1/134 (0.75%)  1 1/269 (0.37%)  1
Arteriosclerosis  1  1/133 (0.75%)  1 0/135 (0.00%)  0 0/134 (0.00%)  0 0/269 (0.00%)  0
Hypotension  1  1/133 (0.75%)  1 0/135 (0.00%)  0 0/134 (0.00%)  0 0/269 (0.00%)  0
1
Term from vocabulary, MedDRA (22.0)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Sham Treatment Intravitreal Aflibercept Injection (IAI) 2Q16 Intravitreal Aflibercept Injection (IAI) 2Q8 IAI 2 mg Groups Combined (2Q16 & 2Q8)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   104/133 (78.20%)      104/135 (77.04%)      106/134 (79.10%)      210/269 (78.07%)    
Eye disorders         
Blepharitis Fellow Eye  1  1/133 (0.75%)  1 3/135 (2.22%)  3 7/134 (5.22%)  7 10/269 (3.72%)  10
Cataract Fellow Eye  1  4/133 (3.01%)  4 9/135 (6.67%)  9 4/134 (2.99%)  4 13/269 (4.83%)  13
Conjunctival haemorrhage Fellow Eye  1  6/133 (4.51%)  7 5/135 (3.70%)  14 8/134 (5.97%)  14 13/269 (4.83%)  28
Diabetic retinal oedema Fellow Eye  1  19/133 (14.29%)  25 17/135 (12.59%)  24 23/134 (17.16%)  27 40/269 (14.87%)  51
Diabetic retinopathy Fellow Eye  1  12/133 (9.02%)  13 13/135 (9.63%)  14 10/134 (7.46%)  10 23/269 (8.55%)  24
Macular oedema Fellow Eye  1  4/133 (3.01%)  4 7/135 (5.19%)  7 6/134 (4.48%)  6 13/269 (4.83%)  13
Retinal exudates Fellow Eye  1  8/133 (6.02%)  9 2/135 (1.48%)  2 6/134 (4.48%)  7 8/269 (2.97%)  9
Vitreous haemorrhage Fellow Eye  1  4/133 (3.01%)  4 8/135 (5.93%)  12 3/134 (2.24%)  3 11/269 (4.09%)  15
Blepharitis Study Eye  1  1/133 (0.75%)  1 2/135 (1.48%)  2 7/134 (5.22%)  7 9/269 (3.35%)  9
Cataract Study Eye  1  5/133 (3.76%)  5 8/135 (5.93%)  8 8/134 (5.97%)  8 16/269 (5.95%)  16
Conjunctival haemorrhage Study Eye  1  8/133 (6.02%)  14 18/135 (13.33%)  27 25/134 (18.66%)  34 43/269 (15.99%)  61
Diabetic retinal oedema Study Eye  1  43/133 (32.33%)  54 14/135 (10.37%)  22 19/134 (14.18%)  25 33/269 (12.27%)  47
Diabetic retinopathy Study Eye  1  22/133 (16.54%)  25 3/135 (2.22%)  4 5/134 (3.73%)  5 8/269 (2.97%)  9
Eye pain Study Eye  1  6/133 (4.51%)  8 11/135 (8.15%)  13 5/134 (3.73%)  5 16/269 (5.95%)  18
Retinal exudates Study Eye  1  6/133 (4.51%)  7 5/135 (3.70%)  5 9/134 (6.72%)  9 14/269 (5.20%)  14
Vitreous detachment Study Eye  1  4/133 (3.01%)  4 7/135 (5.19%)  7 7/134 (5.22%)  9 14/269 (5.20%)  16
Vitreous floaters Study Eye  1  3/133 (2.26%)  3 7/135 (5.19%)  8 13/134 (9.70%)  13 20/269 (7.43%)  21
Gastrointestinal disorders         
Constipation  1  3/133 (2.26%)  3 5/135 (3.70%)  5 7/134 (5.22%)  7 12/269 (4.46%)  12
Nausea  1  8/133 (6.02%)  9 5/135 (3.70%)  5 6/134 (4.48%)  14 11/269 (4.09%)  19
Infections and infestations         
Bronchitis  1  7/133 (5.26%)  7 9/135 (6.67%)  10 5/134 (3.73%)  5 14/269 (5.20%)  15
Cellulitis  1  6/133 (4.51%)  6 5/135 (3.70%)  10 7/134 (5.22%)  7 12/269 (4.46%)  17
Influenza  1  8/133 (6.02%)  8 10/135 (7.41%)  12 4/134 (2.99%)  4 14/269 (5.20%)  16
Nasopharyngitis  1  15/133 (11.28%)  16 11/135 (8.15%)  16 11/134 (8.21%)  12 22/269 (8.18%)  28
Urinary tract infection  1  16/133 (12.03%)  22 12/135 (8.89%)  13 11/134 (8.21%)  13 23/269 (8.55%)  26
Injury, poisoning and procedural complications         
Fall  1  5/133 (3.76%)  5 5/135 (3.70%)  7 8/134 (5.97%)  11 13/269 (4.83%)  18
Investigations         
Blood glucose increased  1  7/133 (5.26%)  8 3/135 (2.22%)  3 7/134 (5.22%)  7 10/269 (3.72%)  10
Glycosylated haemoglobin increased  1  7/133 (5.26%)  7 9/135 (6.67%)  9 9/134 (6.72%)  9 18/269 (6.69%)  18
Metabolism and nutrition disorders         
Diabetes mellitus  1  13/133 (9.77%)  15 11/135 (8.15%)  11 8/134 (5.97%)  8 19/269 (7.06%)  19
Nervous system disorders         
Headache  1  2/133 (1.50%)  2 7/135 (5.19%)  9 8/134 (5.97%)  8 15/269 (5.58%)  17
Vascular disorders         
Hypertension  1  25/133 (18.80%)  28 28/135 (20.74%)  32 20/134 (14.93%)  23 48/269 (17.84%)  55
1
Term from vocabulary, MedDRA (22.0)
Indicates events were collected by systematic assessment
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 investigator has the right to independently publish study results from the investigator's site after a multi-center publication, or a defined period after the completion of the study by all sites. The investigator must provide the sponsor a copy of any such publication derived from the study for review and comment in advance of any submission, and delay publication, if requested, to allow the Sponsor to preserve its proprietary rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Clinical Trial Management
Organization: Regeneron Pharmaceuticals, Inc.
Phone: 844-734-6643
EMail: clinicaltrials@regeneron.com
Layout table for additonal information
Responsible Party: Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02718326    
Other Study ID Numbers: VGFTe-OD-1411
2016-002639-14 ( EudraCT Number )
First Submitted: March 20, 2016
First Posted: March 24, 2016
Results First Submitted: August 6, 2019
Results First Posted: November 21, 2019
Last Update Posted: July 30, 2020