Trial Outcomes & Findings for Treatment of Diabetic Macular Edema With Aflibercept in Subjects Previously Treated With Ranibizumab or Bevacizumab (NCT NCT02559180)
NCT ID: NCT02559180
Last Updated: 2023-03-30
Results Overview
Subjects were evaluated for efficacy by the change in best corrected visual acuity from baseline. Best Corrected Visual Acuity (BCVA) was measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) letter score starting at 4 meters. More letters read correctly results in a higher letter score, which represents better visual acuity.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
20 participants
Primary outcome timeframe
Baseline and 12 months
Results posted on
2023-03-30
Participant Flow
Participant milestones
| Measure |
Single Arm
Aflibercept 2mg given intravitreally every month until resolution of fluid in retina and then continued every 2 months for a total of 24 months of treatment
|
|---|---|
|
Overall Study
STARTED
|
20
|
|
Overall Study
COMPLETED
|
16
|
|
Overall Study
NOT COMPLETED
|
4
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Treatment of Diabetic Macular Edema With Aflibercept in Subjects Previously Treated With Ranibizumab or Bevacizumab
Baseline characteristics by cohort
| Measure |
Single Arm
n=20 Participants
Aflibercept 2mg given intravitreally every month until resolution of fluid in retina and then continued every 2 months for a total of 24 months of treatment
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
7 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
13 Participants
n=5 Participants
|
|
Age, Continuous
|
63.7 years
STANDARD_DEVIATION 13.5 • n=5 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
5 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
15 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
20 participants
n=5 Participants
|
|
Early Treatment Diabetic Retinopathy Study (ETDRS) letters scores
Study Eye
|
69.95 letters
n=5 Participants
|
|
Early Treatment Diabetic Retinopathy Study (ETDRS) letters scores
Fellow Eye
|
73.65 letters
n=5 Participants
|
|
Optical Coherence Tomography (OCT) - Central Subfield Thickness (CST)
|
419 µm
n=5 Participants
|
|
OCT - Cube Volume
|
11.5 mm3
n=5 Participants
|
|
OCT - Average Thickness
|
300.2 µm
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and 12 monthsSubjects were evaluated for efficacy by the change in best corrected visual acuity from baseline. Best Corrected Visual Acuity (BCVA) was measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) letter score starting at 4 meters. More letters read correctly results in a higher letter score, which represents better visual acuity.
Outcome measures
| Measure |
Single Arm
n=20 Eyes
Aflibercept 2mg given intravitreally every month until resolution of fluid in retina and then continued every 2 months for a total of 24 months of treatment
|
|---|---|
|
Efficacy of Treatment Outcomes by Change in Visual Acuity From Baseline
Baseline
|
69.95 letters
Interval 60.0 to 81.0
|
|
Efficacy of Treatment Outcomes by Change in Visual Acuity From Baseline
12 Months
|
74 letters
Interval 56.0 to 85.0
|
PRIMARY outcome
Timeframe: Baseline and 12 monthsMean absolute Central Foveal Thickness change from baseline at month 12 as measured by Spectral Domain Optical Coherence Tomography (SD-OCT), defined as the average thickness within the central 1 mm subfield of the central retina. Thicker measures can represent more macular edema
Outcome measures
| Measure |
Single Arm
n=20 Eyes
Aflibercept 2mg given intravitreally every month until resolution of fluid in retina and then continued every 2 months for a total of 24 months of treatment
|
|---|---|
|
Mean Absolute Change on Central Foveal Thickness
Baseline
|
419.7 μm
Standard Deviation 92
|
|
Mean Absolute Change on Central Foveal Thickness
12 months
|
287.2 μm
Standard Deviation 80.2
|
SECONDARY outcome
Timeframe: Baseline, 6 months, 12 months, 24 monthsPopulation: A total of 20 participants were enrolled; 20 completed 6 and 12 months and 16 completed the study (24 months)
The mean change from baseline in best-corrected visual acuity score at months 6,12 and 24. Best Corrected Visual Acuity was measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) letter score starting at 4 meters. More letters read correctly results in a higher letter score, which represents better visual acuity.
Outcome measures
| Measure |
Single Arm
n=20 Eyes
Aflibercept 2mg given intravitreally every month until resolution of fluid in retina and then continued every 2 months for a total of 24 months of treatment
|
|---|---|
|
Mean Change on Visual Acuity Score
Baseline
|
69.95 letters
Interval 66.0 to 74.0
|
|
Mean Change on Visual Acuity Score
6 months
|
71.5 letters
Interval 54.0 to 83.0
|
|
Mean Change on Visual Acuity Score
12 months
|
74 letters
Interval 56.0 to 85.0
|
|
Mean Change on Visual Acuity Score
24 months
|
75 letters
Interval 71.0 to 80.0
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, 12 months,and 24 monthsPopulation: A total of 20 participants were enrolled; 20 completed the 12 months and 16 completed the study (24 months). 15 OCT angiography out of 16 that completed the study were available for the 24-month analysis.
Change in macular OCT perfusion (whole deep capillary perfusion density) at months 12 and 24 by OCT angiography
Outcome measures
| Measure |
Single Arm
n=20 Eyes
Aflibercept 2mg given intravitreally every month until resolution of fluid in retina and then continued every 2 months for a total of 24 months of treatment
|
|---|---|
|
Optical Coherence Tomography (OCT) Perfusion
Baseline
|
50.82 percentage perfusion density
Interval 48.63 to 53.01
|
|
Optical Coherence Tomography (OCT) Perfusion
12 months
|
47.6 percentage perfusion density
Interval 45.38 to 49.87
|
|
Optical Coherence Tomography (OCT) Perfusion
24 months
|
46.40 percentage perfusion density
Interval 43.88 to 48.92
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, 6 months, and 12 monthsThe diabetic retinopathy severity changes from baseline at months 6 and 12. DR severity was judged clinically at the fundus examination.
Outcome measures
| Measure |
Single Arm
n=20 Participants
Aflibercept 2mg given intravitreally every month until resolution of fluid in retina and then continued every 2 months for a total of 24 months of treatment
|
|---|---|
|
Number of Participants With Diabetic Retinopathy (DR) Classified by Severity
Baseline · Mild nonproliferative diabetic retinopathy (NPDR)
|
0 Participants
|
|
Number of Participants With Diabetic Retinopathy (DR) Classified by Severity
Baseline · Moderate NPDR
|
9 Participants
|
|
Number of Participants With Diabetic Retinopathy (DR) Classified by Severity
Baseline · Severe NPDR
|
5 Participants
|
|
Number of Participants With Diabetic Retinopathy (DR) Classified by Severity
Baseline · Proliferative diabetic retinopathy (PDR)
|
6 Participants
|
|
Number of Participants With Diabetic Retinopathy (DR) Classified by Severity
6 Months · Mild nonproliferative diabetic retinopathy (NPDR)
|
0 Participants
|
|
Number of Participants With Diabetic Retinopathy (DR) Classified by Severity
6 Months · Moderate NPDR
|
9 Participants
|
|
Number of Participants With Diabetic Retinopathy (DR) Classified by Severity
6 Months · Severe NPDR
|
5 Participants
|
|
Number of Participants With Diabetic Retinopathy (DR) Classified by Severity
6 Months · Proliferative diabetic retinopathy (PDR)
|
6 Participants
|
|
Number of Participants With Diabetic Retinopathy (DR) Classified by Severity
12 Months · Mild nonproliferative diabetic retinopathy (NPDR)
|
2 Participants
|
|
Number of Participants With Diabetic Retinopathy (DR) Classified by Severity
12 Months · Moderate NPDR
|
7 Participants
|
|
Number of Participants With Diabetic Retinopathy (DR) Classified by Severity
12 Months · Severe NPDR
|
5 Participants
|
|
Number of Participants With Diabetic Retinopathy (DR) Classified by Severity
12 Months · Proliferative diabetic retinopathy (PDR)
|
6 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, 12 months, and 24 monthsPopulation: A total of 20 participants were enrolled; 20 completed the 12 months and 16 completed the study (24 months). 15 OCT angiography out of 16 that completed the study were available for the 24-month analysis.
Capillary Perfusion Density change at month 12 and month 24 by OCT angiography.
Outcome measures
| Measure |
Single Arm
n=20 Eyes
Aflibercept 2mg given intravitreally every month until resolution of fluid in retina and then continued every 2 months for a total of 24 months of treatment
|
|---|---|
|
Retinal Vascular Changes by OCT Angiography
Baseline : Super - Whole
|
45.98 percentage perfusion density
Interval 43.76 to 48.21
|
|
Retinal Vascular Changes by OCT Angiography
Baseline : Super - Fovea
|
31.15 percentage perfusion density
Interval 28.03 to 34.26
|
|
Retinal Vascular Changes by OCT Angiography
Baseline : Super - Parafovea
|
47.34 percentage perfusion density
Interval 44.89 to 49.0
|
|
Retinal Vascular Changes by OCT Angiography
Baseline : Deep - Whole
|
50.82 percentage perfusion density
Interval 48.63 to 53.01
|
|
Retinal Vascular Changes by OCT Angiography
Baseline : Deep - Fovea
|
24.56 percentage perfusion density
Interval 20.34 to 28.77
|
|
Retinal Vascular Changes by OCT Angiography
Baseline : Deep - Parafovea
|
53.71 percentage perfusion density
Interval 51.3 to 56.11
|
|
Retinal Vascular Changes by OCT Angiography
12 Months : Super - Whole
|
43.56 percentage perfusion density
Interval 41.29 to 45.83
|
|
Retinal Vascular Changes by OCT Angiography
12 Months : Super - Fovea
|
24.30 percentage perfusion density
Interval 21.11 to 27.49
|
|
Retinal Vascular Changes by OCT Angiography
12 Months : Super - Parafovea
|
45.08 percentage perfusion density
Interval 42.58 to 47.58
|
|
Retinal Vascular Changes by OCT Angiography
12 Months : Deep - Whole
|
47.63 percentage perfusion density
Interval 45.38 to 49.87
|
|
Retinal Vascular Changes by OCT Angiography
12 Months : Deep - Fovea
|
24.92 percentage perfusion density
Interval 20.61 to 29.24
|
|
Retinal Vascular Changes by OCT Angiography
12 Months : Deep - Parafovea
|
49.88 percentage perfusion density
Interval 47.42 to 52.35
|
|
Retinal Vascular Changes by OCT Angiography
24 Months : Super - Whole
|
40.68 percentage perfusion density
Interval 38.17 to 43.19
|
|
Retinal Vascular Changes by OCT Angiography
24 Months : Super - Fovea
|
18.51 percentage perfusion density
Interval 14.94 to 22.08
|
|
Retinal Vascular Changes by OCT Angiography
24 Months : Super - Parafovea
|
42.93 percentage perfusion density
Interval 40.24 to 45.61
|
|
Retinal Vascular Changes by OCT Angiography
24 Months : Deep - Whole
|
46.40 percentage perfusion density
Interval 43.88 to 48.92
|
|
Retinal Vascular Changes by OCT Angiography
24 Months : Deep - Fovea
|
23.69 percentage perfusion density
Interval 18.87 to 28.5
|
|
Retinal Vascular Changes by OCT Angiography
24 Months : Deep - Parafovea
|
48.83 percentage perfusion density
Interval 46.08 to 51.58
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, 12 months, and 24 monthsPopulation: A total of 20 participants were enrolled; 20 completed the 12 months and 16 completed the study (24 months). 15 OCT angiography out of 16 that completed the study were available for the 24-month analysis.
FAZ Area change at month 12 and month 24 by OCT angiography.
Outcome measures
| Measure |
Single Arm
n=20 Eyes
Aflibercept 2mg given intravitreally every month until resolution of fluid in retina and then continued every 2 months for a total of 24 months of treatment
|
|---|---|
|
Foveal Avascular Zone (FAZ) Changes
Baseline
|
0.30 mm2
Interval 0.22 to 0.37
|
|
Foveal Avascular Zone (FAZ) Changes
12 Months
|
0.34 mm2
Interval 0.27 to 0.41
|
|
Foveal Avascular Zone (FAZ) Changes
24 Months
|
0.40 mm2
Interval 0.33 to 0.48
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, 6 months, and 12 monthsThe percentage of participants that were considered anatomically 'dry' by SDOCT at months 6 and 12 and transitioned to the every-8-weeks treatment regimen.
Outcome measures
| Measure |
Single Arm
n=20 Participants
Aflibercept 2mg given intravitreally every month until resolution of fluid in retina and then continued every 2 months for a total of 24 months of treatment
|
|---|---|
|
Number of Participants With Absence of Retinal Fluid as Measured by OCT
Baseline · every-4-weeks regimen
|
20 Participants
|
|
Number of Participants With Absence of Retinal Fluid as Measured by OCT
Baseline · every-8-weeks regimen
|
0 Participants
|
|
Number of Participants With Absence of Retinal Fluid as Measured by OCT
6 Months · every-4-weeks regimen
|
13 Participants
|
|
Number of Participants With Absence of Retinal Fluid as Measured by OCT
6 Months · every-8-weeks regimen
|
7 Participants
|
|
Number of Participants With Absence of Retinal Fluid as Measured by OCT
12 Months · every-4-weeks regimen
|
5 Participants
|
|
Number of Participants With Absence of Retinal Fluid as Measured by OCT
12 Months · every-8-weeks regimen
|
15 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 12 monthsThe percentage of participants who gained or lost 5, 10, and 15 letters or more of vision at month 12. Visual Acuity (BCVA) was measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) letter score starting at 4 meters.
Outcome measures
| Measure |
Single Arm
n=20 Participants
Aflibercept 2mg given intravitreally every month until resolution of fluid in retina and then continued every 2 months for a total of 24 months of treatment
|
|---|---|
|
Number of Participants That Gained or Lost Letters of Visual Acuity.
Lost 15 letters
|
5 percentage of participants
|
|
Number of Participants That Gained or Lost Letters of Visual Acuity.
Lost 14 to 10 letters
|
5 percentage of participants
|
|
Number of Participants That Gained or Lost Letters of Visual Acuity.
Lost 9 to 5 letters
|
10 percentage of participants
|
|
Number of Participants That Gained or Lost Letters of Visual Acuity.
Lost 1 to 4 letters
|
5 percentage of participants
|
|
Number of Participants That Gained or Lost Letters of Visual Acuity.
Gained 0 to 4 letters
|
30 percentage of participants
|
|
Number of Participants That Gained or Lost Letters of Visual Acuity.
Gained 5 to 9 letters
|
10 percentage of participants
|
|
Number of Participants That Gained or Lost Letters of Visual Acuity.
Gained 10 to 14 letters
|
25 percentage of participants
|
|
Number of Participants That Gained or Lost Letters of Visual Acuity.
Gained more than 15 letters
|
10 percentage of participants
|
Adverse Events
Single Arm
Serious events: 4 serious events
Other events: 0 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Single Arm
n=20 participants at risk
Aflibercept 2mg given intravitreally every month until resolution of fluid in retina and then continued every 2 months for a total of 24 months of treatment
|
|---|---|
|
General disorders
Hypertension and Hyperglycemia
|
5.0%
1/20 • Number of events 1 • 24 months
Safety evaluations included ocular and non-ocular events reported by patients during or between study visits. Adverse Events (AE) could also be detected through assessment and were recorded in case report forms. AEs were categorized according to severity (mild, moderate or severe) and relationship to study drug (related/not related).
|
|
Cardiac disorders
Chest pain
|
5.0%
1/20 • 24 months
Safety evaluations included ocular and non-ocular events reported by patients during or between study visits. Adverse Events (AE) could also be detected through assessment and were recorded in case report forms. AEs were categorized according to severity (mild, moderate or severe) and relationship to study drug (related/not related).
|
|
Infections and infestations
Bilateral lower limb cellulitis
|
5.0%
1/20 • 24 months
Safety evaluations included ocular and non-ocular events reported by patients during or between study visits. Adverse Events (AE) could also be detected through assessment and were recorded in case report forms. AEs were categorized according to severity (mild, moderate or severe) and relationship to study drug (related/not related).
|
|
General disorders
Death of unknown cause
|
5.0%
1/20 • 24 months
Safety evaluations included ocular and non-ocular events reported by patients during or between study visits. Adverse Events (AE) could also be detected through assessment and were recorded in case report forms. AEs were categorized according to severity (mild, moderate or severe) and relationship to study drug (related/not related).
|
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60