Vascular Endothelial Growth Factor VEGF Trap-Eye:Investigation of Efficacy and Safety in Wet Age-Related Macular Degeneration(AMD)

Study Overview
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Brief Summary
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This study is a phase 3, double-masked, randomized, study of the efficacy and safety of VEGF Trap-Eye in patients with neovascular age-related macular degeneration. Approximately 1200 patients will be randomized in the US and Canada.

Official Title
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A Randomized, Double Masked, Active Controlled Phase III Study of the Efficacy, Safety, and Tolerability of Repeated Doses of Intravitreal VEGF Trap in Subjects With Neovascular Age-Related Macular Degeneration

Conditions
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Macular Degeneration

Intervention / Treatment
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* Biological: ranibizumab
* Biological: aflibercept injection (VEGF Trap-Eye, BAY86-5321)
* Biological: aflibercept injection (VEGF Trap-Eye, BAY86-5321)
* Biological: aflibercept injection (VEGF Trap-Eye, BAY86-5321)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed Informed Consent. Men and women ≥ 50 years of age. Active primary or recurrent subfoveal CNV lesions secondary to AMD, including juxtafoveal lesions that affect the fovea as evidenced by FA in the study eye. Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) of: letter score of 73 to 25 (20/40 to 20/320) in the study eye at 4 meters. Willing, committed, and able to return for ALL clinic visits and complete all study-related procedures. Able to read, (or, if unable to read due to visual impairment, be read to verbatim by the person administering the informed consent or a family member. See Appendix J.4) understand and willing to sign the informed consent form. Key Exclusion Criteria: Any prior ocular (in the study eye) or systemic treatment or surgery for neovascular AMD except dietary supplements or vitamins. Any prior or concomitant therapy with another investigational agent to treat neovascular AMD in the study eye, except dietary supplements or vitamins. Any prior treatment with anti-VEGF agents in the study eye. Total lesion size > 12 disc areas (30.5 mm^2, including blood, scars and neovascularization) as assessed by FA in the study eye. Subretinal hemorrhage that is either 50% or more of the total lesion area, or if the blood is under the fovea and is 1 or more disc areas in size in the study eye. (If the blood is under the fovea, then the fovea must be surrounded 270 degrees by visible CNV.) Scar or fibrosis, making up > 50% of total lesion in the study eye. Scar, fibrosis, or atrophy involving the center of the fovea. Presence of retinal pigment epithelial tears or rips involving the macula in the study eye. History of any vitreous hemorrhage within 4 weeks prior to Visit 1 in the study eye. Presence of other causes of CNV in the study eye. History or clinical evidence of diabetic retinopathy, diabetic macular edema or any other vascular disease affecting the retina,other than AMD, in either eye. Prior vitrectomy in the study eye. History of retinal detachment or treatment or surgery for retinal detachment in the study eye. Any history of macular hole of stage 2 and above in the study eye. Any intraocular or periocular surgery within 3 months of Day 1 on the study eye, except lid surgery, which may not have taken place within 1 month of day 1, as long as its unlikely to interfere with the injection.

Ages Eligible for Study
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Minimum Age: 50 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ranibizumab 0.5mg Q4<br> | Biological: ranibizumab<br>* Participants received a 0.5mg dose of ranibizumab via intravitreal (IVT) injection every 4 weeks for the first year. Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks.<br>* Other names: Lucentis;|
| Experimental: aflibercept injection 2.0mg Q4<br> | Biological: aflibercept injection (VEGF Trap-Eye, BAY86-5321)<br>* Participants received a 2.0mg dose of aflibercept injection every 4 weeks for the first year. Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks.<br>* Other names: BAY86-5321;|
| Experimental: aflibercept injection 0.5mg Q4<br> | Biological: aflibercept injection (VEGF Trap-Eye, BAY86-5321)<br>* Participants received a 0.5mg dose of aflibercept injection every 4 weeks for the first year. Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks.<br>* Other names: BAY86-5321;|
| Experimental: aflibercept injection 2.0mg Q8<br> | Biological: aflibercept injection (VEGF Trap-Eye, BAY86-5321)<br>* Participants received a 2.0mg dose of aflibercept injection every 8 weeks (including one additional 2.0 mg dose at Week 4) for the first year and were to receive sham injections at interim monthly visits. Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks.<br>* Other names: BAY86-5321;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients Who Maintained Vision at Week 52 - Last Observation Carried Forward (LOCF) | Defined maintenance of vision as patients who lost fewer than 15 letters in Early Treatment Diabetic Retinopathy Study (ETDRS) letter score compared to baseline. | Baseline and at week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) as Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score at Week 52 - LOCF | Defined study baseline range of ETDRS Best Corrected Visual Acuity of: letter score of 73 to 25 (20/40 to 20/320) in the study eye; a higher score represents better functioning. | Baseline and at week 52 | 
| Percentage of Patients Who Gained at Least 15 Letters of Vision in the ETDRS Letter Score in the Study Eye at Week 52 - LOCF. | Defined study baseline range of ETDRS Best Corrected Visual Acuity of: letter score of 73 to 25 (20/40 to 20/320) in the study eye; a higher score represents better functioning. | Baseline and at week 52 | 
| Mean Change From Baseline in National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25) Total Score 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 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 at Week 52 | 
| Mean Change From Baseline in Choroidal Neovascularization (CNV) Area at Week 52 (LOCF) | CNV area values measured in square millimeters (mm^2); lower values represent better outcomes. | Baseline and at week 52 |