Branch Retinal Vein Occlusion
Conditions
Brief summary
This is a phase III, double-masked, randomized, active-controlled, parallel-group, 52-week study to assess the efficacy and safety of Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) compared to laser treatment in patients with macular edema secondary to BRVO.
Interventions
PROCEDUREMacular Laser Photocoagulation
DRUGIntravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321)
Sponsors
Bayer
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
The following inclusion criteria include, but are not limited to: 1. Adults ≥ 18 years of age with foveal center-involved macular edema (ME) secondary to BRVO diagnosed within 12 months before the screening visit 2. ETDRS BCVA: letter score of 73 to 24 (20/40 to 20/320) in the study eye at screening and at day 1 3. Provide signed informed consent
Exclusion criteria
The following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participants Who Gained at Least 15 Letters in Best Corrected Visual Acuity (BCVA) at Week 24 - LOCF | Baseline to week 24 | Best corrected visual acuity (BCVA) was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol at every visit from baseline through week 24. Last observation carried forward (LOCF) method was used to impute missing data. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 24 in BCVA Score - LOCF | Baseline to Week 24 | Best corrected visual acuity (BCVA) was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol at every visit from baseline through week 24 - Last observation carried forward (LOCF) method was used to impute missing data. |
| Change From Baseline in Central Retinal Thickness (CRT) at Week 24 - LOCF | Baseline to week 24 | CRT was evaluated at every visit from baseline through week 24 using spectral domain Optical Coherence Tomography (OCT). |
| Change From Baseline in the National Eye Institute Visual Function Questionnaire - 25 (NEI VFQ-25) Questionnaire Total Score at Week 24 - LOCF | Baseline to week 24 | 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. |
Countries
Canada, Japan, United States
Participant flow
Recruitment details
Participants with macular edema secondary to branch retinal vein occlusion (BRVO) involving the center of the macula in the study eye were eligible to participate in the study.
Pre-assignment details
Of 281 participants who were screened for inclusion in the study, 183 were enrolled (started) and 183 received treatment.
Participants by arm
| Arm | Count |
|---|---|
| Macular Laser Photocoagulation Treatment (Control) Participants received macular laser treatment at Baseline and then according to laser re-treatment criteria up to week 24. Participants received treatment with Intravitreal Aflibercept Injection (IAI) starting at week 24 if they met rescue criteria. Treatment with IAI once initiated was 3 initial monthly doses followed by Q8 week dosing. | 90 |
| Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) Participants received 2 mg Intravitreal Aflibercept Injection (IAI) every 4 weeks (2Q4) through week 24 followed by injections every 8 weeks (2Q8) through week 48. Participants in this group could receive laser rescue at week 36. | 91 |
| Total | 181 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 4 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Lost to Follow-up | 3 | 1 |
| Overall Study | Other | 1 | 2 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 9 | 11 |
Baseline characteristics
| Characteristic | Macular Laser Photocoagulation Treatment (Control) | Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) | Total |
|---|---|---|---|
| Age, Continuous | 63.9 years STANDARD_DEVIATION 11.37 | 67.0 years STANDARD_DEVIATION 10.41 | 65.5 years STANDARD_DEVIATION 10.98 |
| Sex: Female, Male Female | 36 Participants | 47 Participants | 83 Participants |
| Sex: Female, Male Male | 54 Participants | 44 Participants | 98 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 30 / 92 | 25 / 91 |
| serious Total, serious adverse events | 10 / 92 | 13 / 91 |
Outcome results
Primary
Participants Who Gained at Least 15 Letters in Best Corrected Visual Acuity (BCVA) at Week 24 - LOCF
Best corrected visual acuity (BCVA) was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol at every visit from baseline through week 24. Last observation carried forward (LOCF) method was used to impute missing data.
Time frame: Baseline to week 24
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Macular Laser Photocoagulation Treatment (Control) | Participants Who Gained at Least 15 Letters in Best Corrected Visual Acuity (BCVA) at Week 24 - LOCF | 24 participants |
| Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) | Participants Who Gained at Least 15 Letters in Best Corrected Visual Acuity (BCVA) at Week 24 - LOCF | 48 participants |
p-value: 0.000395% CI: [13, 40.1]Cochran-Mantel-Haenszel
Secondary
Change From Baseline in Central Retinal Thickness (CRT) at Week 24 - LOCF
CRT was evaluated at every visit from baseline through week 24 using spectral domain Optical Coherence Tomography (OCT).
Time frame: Baseline to week 24
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Macular Laser Photocoagulation Treatment (Control) | Change From Baseline in Central Retinal Thickness (CRT) at Week 24 - LOCF | -128.0 microns | Standard Deviation 195.02 |
| Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) | Change From Baseline in Central Retinal Thickness (CRT) at Week 24 - LOCF | -280.5 microns | Standard Deviation 189.7 |
Comparison: Difference was IAI group minus laser group; P-value, Point estimate, and 95% CI, were based on an ANCOVA model with baseline measurement as covariate and treatment group, region, and baseline Best Corrected Visual Acuity (BCVA ≤20/200 and BCVA \>20/200) as fixed factors.p-value: <0.000195% CI: [-179.8, -117.4]ANCOVA
Secondary
Change From Baseline in the National Eye Institute Visual Function Questionnaire - 25 (NEI VFQ-25) Questionnaire Total Score at Week 24 - 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 to week 24
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Macular Laser Photocoagulation Treatment (Control) | Change From Baseline in the National Eye Institute Visual Function Questionnaire - 25 (NEI VFQ-25) Questionnaire Total Score at Week 24 - LOCF | 6.3 scores on a scale | Standard Deviation 12.34 |
| Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) | Change From Baseline in the National Eye Institute Visual Function Questionnaire - 25 (NEI VFQ-25) Questionnaire Total Score at Week 24 - LOCF | 7.7 scores on a scale | Standard Deviation 11.08 |
Comparison: Difference was IAI group minus laser group; P-value, Point estimate, and 95% CI, were based on an ANCOVA model with baseline measurement as covariate and treatment group, region, and baseline Best Corrected Visual Acuity (BCVA ≤20/200 and BCVA \>20/200) as fixed factors.p-value: 0.083395% CI: [-0.3, 5.5]ANCOVA
Secondary
Change From Baseline to Week 24 in BCVA Score - LOCF
Best corrected visual acuity (BCVA) was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol at every visit from baseline through week 24 - Last observation carried forward (LOCF) method was used to impute missing data.
Time frame: Baseline to Week 24
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Macular Laser Photocoagulation Treatment (Control) | Change From Baseline to Week 24 in BCVA Score - LOCF | 6.9 letters correctly read | Standard Deviation 12.91 |
| Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) | Change From Baseline to Week 24 in BCVA Score - LOCF | 17.0 letters correctly read | Standard Deviation 11.88 |
Comparison: Difference was IAI group minus laser group. P-value, Point estimate and 95% confidence interval (CI) were based on an analysis of covariance (ANCOVA) model with baseline measurement as covariate and treatment group, region, and baseline Best Corrected Visual Acuity (BCVA ≤20/200 and BCVA \>20/200) as fixed factors.p-value: <0.000195% CI: [7.1, 14]ANCOVA