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 III, 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 Europe, Asia, Japan, Australia and South America.

Detailed Description
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Data of this trial (VIEW 2) was pooled with data of a sister trial (VIEW 1, NCT00509795), and an integrated analyses of the combined data was performed.

Official Title
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A Randomized, Double Masked, Active Controlled, Phase 3 Study of the Efficacy, Safety, and Tolerability of Repeated Doses of Intravitreal VEGF Trap in Subjects With Neovascular Age-related Macular Degeneration (AMD)

Conditions
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Macular Degeneration

Intervention / Treatment
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* Drug: Ranibizumab
* Biological: Aflibercept Injection (EYLEA, VEGF Trap-Eye, BAY86-5321)
* Biological: Aflibercept Injection (EYLEA, VEGF Trap-Eye, BAY86-5321)
* Biological: Aflibercept Injection (EYLEA, 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 Fluorescein angiography (FA) in the study eye. ETDRS Best-Corrected Visual Acuity letter score of 73 to 25 (= Acuity of 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) understand and willing to sign the informed consent form. 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. Any prior treatment with anti-VEGF agents in the study eye. Total lesion size >12 disc areas (30.5 mm, including blood, scars and neovascularization) as assessed by FA in the study eye. Subretinal hemorrhages 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 by 270 degrees by visible CNV). Scar or fibrosis making up >50% of the total lesion in the study eye. Scar, fibrosis, or atrophy involving the center of the fovea in the study eye. 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. 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 it is unlikely to interfere with the injection. History or clinical evidence of diabetic retinopathy, diabetic macular edema or any retinal vascular disease other than AMD in either eye.

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>Participants received a 0.5 mg dose of Ranibizumab via intravitreal (IVT) injection administered 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. | Drug: Ranibizumab<br>* Participants received a 0.5 mg dose of Ranibizumab via intravitreal (IVT) injection administered 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>|
| Experimental: Aflibercept Injection (EYLEA, VEGF Trap-Eye) 2mg Q4<br>Participants received a 2.0 mg dose of Aflibercept Injection administered 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. | Biological: Aflibercept Injection (EYLEA, VEGF Trap-Eye, BAY86-5321)<br>* Participants received a 2.0 mg dose of Aflibercept Injection administered 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>|
| Experimental: Aflibercept Injection (EYLEA, VEGF Trap-Eye) 0.5mg Q4<br>Participants received a 0.5 mg dose of Aflibercept Injection administered 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. | Biological: Aflibercept Injection (EYLEA, VEGF Trap-Eye, BAY86-5321)<br>* Participants received a 0.5 mg dose of Aflibercept Injection administered 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>|
| Experimental: Aflibercept Injection (EYLEA, VEGF Trap-Eye) 2mg Q8<br>Participants received a 2.0 mg dose of Aflibercept Injection administered every 8 weeks (including one additional 2,0 mg dose at Week 4) for the first year. Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks. | Biological: Aflibercept Injection (EYLEA, VEGF Trap-Eye, BAY86-5321)<br>* Participants received a 2.0 mg dose of Aflibercept Injection administered every 8 weeks (including one additional 2,0 mg dose at Week 4) 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>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Maintained Vision at Week 52 - Last Observation Carried Forward (LOCF) | Maintenance of vision was defined as a loss of < 15 letters in the ETDRS (Early Treatment Diabetic Retinopathy Study) letter score (defined study baseline range of ETDRS Best Corrected Visual Acuity letter score of 73 to 25 (= 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. | 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 ETDRS Letter Score at Week 52 - LOCF | Defined study baseline range of ETDRS Best Corrected Visual Acuity letter score of 73 to 25 (= Acuity of 20/40 to 20/320) in the study eye; a higher score represents better functioning. | Baseline and at week 52 | 
| Percentage of Participants 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 letter score of 73 to 25 (= 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. | At week 52 | 
| Mean Change From Baseline in National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25) Total Score at Week 52 - LOCF | The possible range of the NEI VFQ-25 total score is between 0 (worst possible) and 100 (best possible). | 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; lower values represent better outcomes. | Baseline and at week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Eye diseases, Vision Impairment and Blindness, Eyes and Vision, Seniors, Neovascular Age-Related Macular Degeneration (AMD), Retinal Disease