Diabetic Macular Edema
Conditions
Keywords
Diabetic Macular Edema, Diabetic Retinopathy
Brief summary
The purpose of this study is to determine the efficacy of Intravitreal Aflibercept Injection (IAI; EYLEA®; BAY86-5321) on the best corrected visual acuity (BCVA) assessed by the early treatment diabetic retinopathy study (ETDRS) chart in patients with diabetic macular edema (DME) with central involvement.
Interventions
DRUGIntravitreal Aflibercept Injection (IAI; EYLEA®; BAY86-5321)
PROCEDUREMacular Laser Photocoagulation
Laser therapy
Sponsors
Bayer
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
The following is an abbreviated list of inclusion criteria: * Adults ≥ 18 years with type 1 or 2 diabetes mellitus * Decrease in vision determined to be primarily the result of DME in the study eye * BCVA ETDRS letter score of 73 to 24 (20/40 to 20/320) in the study eye
Exclusion criteria
The following is an abbreviated list of
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Best Corrected Visual Acuity (BCVA) as Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score at Week 52 - Last Observation Carried Forward (LOCF) | Baseline and Week 52 | Visual function of the study eye was assessed using the ETDRS protocol. Participants with a BCVA ETDRS letter score of 73 to 24 (= Acuity of 20/40 to 20/320) in the study eye were included; a higher score represents better functioning. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Gained at Least 15 Letters in BCVA as Measured by ETDRS Letter Score Compared With Baseline at Week 52 - LOCF | Baseline and Week 52 | — |
| Percentage of Participants With a ≥2-step Improvement From Baseline in the ETDRS DRSS (Diabetic Retinopathy Severity Score) as Assessed by FP (Fundus Photography) at Week 52 - LOCF | Baseline and Week 52 | Baseline ETDRS DRSS: None (level 10); Mild to moderate nonproliferative DR (levels 14, 15, 20, 35, and 43); Moderately severe/severe nonproliferative DR (levels 47 and 53); Mild/moderate/high-risk/advanced proliferative DR (levels 61, 65, 71,75, 81, and 85) |
| Percentage of Participants Who Gained at Least 10 Letters in BCVA as Measured by ETDRS Letter Score Compared With Baseline at Week 52 - LOCF | Baseline and Week 52 | — |
| Change From Baseline in National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25) Near Activities Subscale at Week 52 - LOCF | Baseline and Week 52 | The NEI VFQ-25 total score ranges from 0-100 with a score of 0 being the worst outcome and 100 being the best outcome. The NEI VFQ questionnaire is organized as a collection of subscales that are all scored from 0-100. Near activities are defined as reading ordinary print in newspapers, performing work or hobbies requiring near vision, or finding something on a crowded shelf. |
| Change From Baseline in National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25) Distance Activities Subscale at Week 52 - LOCF | Baseline and Week 52 | The NEI VFQ-25 total score ranges from 0-100 with a score of 0 being the worst outcome and 100 being the best outcome. The NEI VFQ questionnaire is organized as a collection of subscales that are all scored from 0-100. Distance activities are defined as reading street signs or names on stores, and going down stairs, steps, or curbs. |
| Change From Baseline in Central Retinal Thickness (CRT) at Week 52 as Assessed on Optical Coherence Tomography (OCT) - LOCF | Baseline and Week 52 | — |
Countries
United States
Participant flow
Recruitment details
Participants with diabetic macular edema (DME) secondary to diabetes mellitus involving the center of the macula in the study eye could participate in the study.
Pre-assignment details
Of 687 participants who were screened for inclusion in the study, 466 were enrolled (started) and 461 received treatment.
Participants by arm
| Arm | Count |
|---|---|
| Control Participants received macular laser treatment at baseline and as-needed at visits at which laser re-treatment criteria were met, but no more frequently than every 12 weeks. | 154 |
| Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2Q4 Participants received 2mg Intravitreal aflibercept injection (IAI) every 4 weeks. | 155 |
| Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2Q8 Participants received 2mg Intravitreal aflibercept injection (IAI) every 4 weeks for 5 visits followed by injections every 8 weeks. | 152 |
| Total | 461 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 5 | 4 | 4 |
| Overall Study | Death | 3 | 7 | 5 |
| Overall Study | Lost to Follow-up | 2 | 4 | 5 |
| Overall Study | Other | 4 | 5 | 2 |
| Overall Study | Withdrawal by Subject | 9 | 11 | 11 |
Baseline characteristics
| Characteristic | Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2Q4 | Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2Q8 | Total | Control |
|---|---|---|---|---|
| Age, Continuous | 62 years STANDARD_DEVIATION 11.16 | 63.1 years STANDARD_DEVIATION 9.36 | 62.2 years STANDARD_DEVIATION 9.7 | 61.7 years STANDARD_DEVIATION 8.65 |
| Sex: Female, Male Female | 68 Participants | 73 Participants | 210 Participants | 69 Participants |
| Sex: Female, Male Male | 87 Participants | 79 Participants | 251 Participants | 85 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 91 / 154 | 90 / 155 | 76 / 152 | 134 / 154 | 137 / 155 | 136 / 152 |
| serious Total, serious adverse events | 67 / 154 | 67 / 155 | 56 / 152 | 84 / 154 | 85 / 155 | 75 / 152 |
Outcome results
Primary
Change From Baseline in Best Corrected Visual Acuity (BCVA) as Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score at Week 52 - Last Observation Carried Forward (LOCF)
Visual function of the study eye was assessed using the ETDRS protocol. Participants with a BCVA ETDRS letter score of 73 to 24 (= Acuity of 20/40 to 20/320) in the study eye were included; a higher score represents better functioning.
Time frame: Baseline and Week 52
Population: The Primary efficacy endpoint was analyzed using the full analysis set (FAS). The FAS included all 'Participants received Treatment' and had a baseline and at least 1 post-baseline assessment of Best Corrected Visual Acuity (BCVA).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Control | Change From Baseline in Best Corrected Visual Acuity (BCVA) as Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score at Week 52 - Last Observation Carried Forward (LOCF) | .10 letters correctly read | Standard Error 1.03 |
| Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2Q4 | Change From Baseline in Best Corrected Visual Acuity (BCVA) as Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score at Week 52 - Last Observation Carried Forward (LOCF) | 12.3 letters correctly read | Standard Error 0.76 |
| Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2Q8 | Change From Baseline in Best Corrected Visual Acuity (BCVA) as Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score at Week 52 - Last Observation Carried Forward (LOCF) | 10.6 letters correctly read | Standard Error 0.69 |
p-value: <0.000197.5% CI: [9.35, 15.04]ANCOVA
p-value: <0.000197.5% CI: [7.73, 13.17]ANCOVA
Secondary
Change From Baseline in Central Retinal Thickness (CRT) at Week 52 as Assessed on Optical Coherence Tomography (OCT) - LOCF
Time frame: Baseline and Week 52
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Control | Change From Baseline in Central Retinal Thickness (CRT) at Week 52 as Assessed on Optical Coherence Tomography (OCT) - LOCF | -73.3 microns | Standard Error 12.09 |
| Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2Q4 | Change From Baseline in Central Retinal Thickness (CRT) at Week 52 as Assessed on Optical Coherence Tomography (OCT) - LOCF | -184.1 microns | Standard Error 6.57 |
| Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2Q8 | Change From Baseline in Central Retinal Thickness (CRT) at Week 52 as Assessed on Optical Coherence Tomography (OCT) - LOCF | -186.8 microns | Standard Error 6.9 |
p-value: <0.000197.5% CI: [-141.3, -80.22]ANCOVA
p-value: <0.000197.5% CI: [-144.2, -82.75]ANCOVA
Secondary
Change From Baseline in National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25) Distance Activities Subscale at Week 52 - LOCF
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 that are all scored from 0-100. Distance activities are defined as reading street signs or names on stores, and going down stairs, steps, or curbs.
Time frame: Baseline and Week 52
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Control | Change From Baseline in National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25) Distance Activities Subscale at Week 52 - LOCF | 4.9 scores on a scale | Standard Error 1.44 |
| Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2Q4 | Change From Baseline in National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25) Distance Activities Subscale at Week 52 - LOCF | 7.7 scores on a scale | Standard Error 1.57 |
| Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2Q8 | Change From Baseline in National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25) Distance Activities Subscale at Week 52 - LOCF | 6.5 scores on a scale | Standard Error 1.48 |
p-value: 0.170297.5% CI: [-1.82, 7.54]ANCOVA
p-value: 0.406797.5% CI: [-2.83, 6.13]ANCOVA
Secondary
Change From Baseline in National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25) Near Activities Subscale at Week 52 - LOCF
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 that are all scored from 0-100. Near activities are defined as reading ordinary print in newspapers, performing work or hobbies requiring near vision, or finding something on a crowded shelf.
Time frame: Baseline and Week 52
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Control | Change From Baseline in National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25) Near Activities Subscale at Week 52 - LOCF | 3.7 scores on a scale | Standard Error 1.55 |
| Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2Q4 | Change From Baseline in National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25) Near Activities Subscale at Week 52 - LOCF | 8.9 scores on a scale | Standard Error 1.58 |
| Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2Q8 | Change From Baseline in National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25) Near Activities Subscale at Week 52 - LOCF | 8.1 scores on a scale | Standard Error 1.44 |
p-value: 0.016897.5% CI: [0.33, 10.04]ANCOVA
p-value: 0.032397.5% CI: [-0.21, 8.93]ANCOVA
Secondary
Percentage of Participants Who Gained at Least 10 Letters in BCVA as Measured by ETDRS Letter Score Compared With Baseline at Week 52 - LOCF
Time frame: Baseline and Week 52
Population: All secondary efficacy endpoints were analyzed using the full analysis set (FAS). The FAS included all 'Participants received Treatment' and had a baseline and at least 1 post-baseline assessment of Best Corrected Visual Acuity (BCVA).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control | Percentage of Participants Who Gained at Least 10 Letters in BCVA as Measured by ETDRS Letter Score Compared With Baseline at Week 52 - LOCF | 30 percentage of participants |
| Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2Q4 | Percentage of Participants Who Gained at Least 10 Letters in BCVA as Measured by ETDRS Letter Score Compared With Baseline at Week 52 - LOCF | 100 percentage of participants |
| Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2Q8 | Percentage of Participants Who Gained at Least 10 Letters in BCVA as Measured by ETDRS Letter Score Compared With Baseline at Week 52 - LOCF | 88 percentage of participants |
p-value: 0.000197.5% CI: [34.7, 57]Cochran-Mantel-Haenszel
p-value: 0.000197.5% CI: [27.2, 50.3]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Gained at Least 15 Letters in BCVA as Measured by ETDRS Letter Score Compared With Baseline at Week 52 - LOCF
Time frame: Baseline and Week 52
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control | Percentage of Participants Who Gained at Least 15 Letters in BCVA as Measured by ETDRS Letter Score Compared With Baseline at Week 52 - LOCF | 12 percentage of participants |
| Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2Q4 | Percentage of Participants Who Gained at Least 15 Letters in BCVA as Measured by ETDRS Letter Score Compared With Baseline at Week 52 - LOCF | 64 percentage of participants |
| Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2Q8 | Percentage of Participants Who Gained at Least 15 Letters in BCVA as Measured by ETDRS Letter Score Compared With Baseline at Week 52 - LOCF | 47 percentage of participants |
p-value: <0.000197.5% CI: [24.1, 44.4]Cochran-Mantel-Haenszel
p-value: <0.000197.5% CI: [13.5, 33.1]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With a ≥2-step Improvement From Baseline in the ETDRS DRSS (Diabetic Retinopathy Severity Score) as Assessed by FP (Fundus Photography) at Week 52 - LOCF
Baseline ETDRS DRSS: None (level 10); Mild to moderate nonproliferative DR (levels 14, 15, 20, 35, and 43); Moderately severe/severe nonproliferative DR (levels 47 and 53); Mild/moderate/high-risk/advanced proliferative DR (levels 61, 65, 71,75, 81, and 85)
Time frame: Baseline and Week 52
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control | Percentage of Participants With a ≥2-step Improvement From Baseline in the ETDRS DRSS (Diabetic Retinopathy Severity Score) as Assessed by FP (Fundus Photography) at Week 52 - LOCF | 22 percentage of participants |
| Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2Q4 | Percentage of Participants With a ≥2-step Improvement From Baseline in the ETDRS DRSS (Diabetic Retinopathy Severity Score) as Assessed by FP (Fundus Photography) at Week 52 - LOCF | 52 percentage of participants |
| Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2Q8 | Percentage of Participants With a ≥2-step Improvement From Baseline in the ETDRS DRSS (Diabetic Retinopathy Severity Score) as Assessed by FP (Fundus Photography) at Week 52 - LOCF | 44 percentage of participants |
p-value: <0.000197.5% CI: [9, 30.4]Cochran-Mantel-Haenszel
p-value: 0.001797.5% CI: [4.4, 25.4]Cochran-Mantel-Haenszel