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

Study Overview
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Brief Summary
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To determine the efficacy of vascular endothelial growth factor (VEGF) Trap-Eye injected into the eye on vision function in subjects with macular edema as a consequence of central retinal vein occlusion

Official Title
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A Randomized, Double-masked, Sham-controlled Phase 3 Study of the Efficacy, Safety and Tolerability of Repeated Intravitreal Administration of VEGF Trap-Eye in Subjects With Macular Edema Secondary to Central Retinal Vein Occlusion (CRVO)

Conditions
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Retinal Vein Occlusion

Intervention / Treatment
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* Biological: Aflibercept Injection (EYLEA, VEGF Trap-Eye, BAY86-5321)
* Other: Sham treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Center-involved macular edema secondary to central retinal vein occlusion (CRVO) for no longer than 9 months with mean central subfield thickness ≥ 250 μm on optical coherence tomography (OCT) Adults ≥ 18 years Early treatment diabetic retinopathy study (ETDRS) best corrected visual acuity (BCVA) of 20/40 to 20/320 (73 to 24 letters) in the study eye Exclusion Criteria: Any prior treatment with anti-VEGF agents in the study eye (Pegaptanib sodium, anecortave acetate, bevacizumab, ranibizumab, etc.) or previous administration of systemic anti-angiogenic medications Prior panretinal laser photocoagulation or macular laser photocoagulation in the study eye CRVO disease duration > 9 months from date of diagnosis Previous use of intraocular corticosteroids in the study eye or use of periocular corticosteroids in the study eye within the 3 months prior to Day 1 Iris neovascularization, vitreous hemorrhage, traction retinal detachment, or preretinal fibrosis involving the macula in either the study eye or fellow eye

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aflibercept Injection (EYLEA, VEGF Trap-Eye, BAY86-5321)<br>Participants received a 2 mg dose of Intravitreal Aflibercept Injection (IAI) administered every 4 weeks from Day 1 through Week 20, later as often as every 4 weeks depending on the study retreatment criteria from Week 24 through Week 48. Follow-up phase: Participants on IAI, who continued the study, received 2 mg dose of IAI depending on the study retreatment criteria at Week 60 and 68. | Biological: Aflibercept Injection (EYLEA, VEGF Trap-Eye, BAY86-5321)<br>* Intravitreal injection. Weeks 0 to 20 of Aflibercept Injection every 4 weeks; Weeks 24 to 52 every 4 weeks PRN (pro re nata, on demand); plus additional on Week 60 and 68.<br>Other: Sham treatment<br>* Sham treatment. Weeks 0 to 52 sham treatment every 4 weeks; plus additional on Week 60 and 68.<br>|
| Sham Comparator: Sham treatment<br>Participants received sham treatment administered every 4 weeks from Day 1 through Week 52. Follow-up phase: Participants on sham treatment, who switched to Intravitreal Aflibercept Injection (IAI), received a 2 mg dose of IAI at week 52 and depending on the study retreatment criteria at Week 60 and 68. | Other: Sham treatment<br>* Sham treatment. Weeks 0 to 52 sham treatment every 4 weeks; plus additional on Week 60 and 68.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Gained at Least 15 Letters in BCVA as Measured by ETDRS Letter Score Compared With Baseline at Week 24 With Discontinued Participants Before Week 24 Evaluated as Failures | Defined study baseline range of Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score of 73 to 24 (= Acuity of 20/40 to 20/320) in the study eye; a higher score represents better functioning. Nominator = (Number of participants who maintained vision * 100); Denominator = Number of participants analyzed. | Baseline and Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in BCVA as Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score at Week 24 - Last Observation Carried Forward (LOCF) | 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. However, because this was assessed at the screening visit, subjects may have had a higher BCVA recorded at the baseline visit and would not have been excluded from the study. | Baseline and Week 24 | 
| Change From Baseline in Central Retinal Thickness (CRT) at Week 24 - LOCF |  | Baseline and Week 24 | 
| Percentage of Participants Who Developed Neovascularization During the First 24 Weeks | Formation of blood vessels in the anterior segment, optic disc, or elsewhere in the fundus up to Week 24 | From baseline until Week 24 | 
| Change From Baseline in National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25) 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 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 and Week 24 | 
| Change From Baseline in European Five-dimensional Health Scale (EQ-5D) Score at Week 24 - LOCF | EQ-5D is a quality of life questionnaire based on a scale from -0.594 (worst) to 1.00 (best). | Baseline and Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Macular Edema, Central Retinal Vein Occlusion, CRVO, VEGF Trap-Eye, best-corrected visual acuity