Safety and Efficacy of Repeated Intravitreal Administration of Vascular Endothelial Growth Factor (VEGF) Trap in Patients With Wet Age-Related Macular Degeneration (AMD)

Study Overview
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Brief Summary
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This study examines the effect of intravitreally administered VEGF Trap in patients with wet AMD. The purpose of this trial is to assess the ocular and systemic safety and tolerability of repeated intravitreal doses of VEGF Trap in patients with subfoveal choroidal neovascularization (CNV) due to AMD.

Detailed Description
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This is a double masked, prospective, randomized study in which five groups of approximately 30 patients meeting the eligibility criteria will be randomly assigned in a balanced ratio to receive a series of intravitreal (IVT) injections of VEGF Trap into the study eye at 4- or 12 -week intervals over a 12-week period. After Week 12, patients will be evaluated every 4 weeks. Patients will remain on study or may be eligible to enter a long-term extension study, in which they will continue to receive VEGF Trap.

Official Title
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A Randomized, Controlled Study of the Safety, Tolerability and Biological Effect of Repeated Intravitreal Administration of VEGF Trap in Patients With Neovascular Age-Related Macular Degeneration

Conditions
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Macular Degeneration

Intervention / Treatment
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* Biological: aflibercept injection (VEGF Trap-Eye, BAY86-5321)
* Biological: aflibercept injection (VEGF Trap-Eye, BAY86-5321)
* 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: Subfoveal CNV secondary to AMD. Central retinal (including lesion) thickness ≥ 300 µm as measured by Optical Coherence Tomography (OCT). Early Treatment of Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity of 73 letters to 34 letters. Exclusion Criteria: History of any vitreous hemorrhage within 4 weeks prior to Day 1. Aphakia. Significant subfoveal atrophy or scarring. Prior treatment with the following in the study eye: Subfoveal thermal laser therapy. Submacular surgery or other surgical intervention for the treatment of AMD. Extrafoveal laser coagulation treatment within 12 weeks prior to Day 1. Photodynamic therapy (PDT) within 12 weeks prior to Visit 2 (Day 1). Pegaptanib sodium (Macugen) within 8 weeks of Visit 2 (Day 1). Juxtascleral steroids or anecortave acetate within 24 weeks (6 months) prior to Visit 2 (Day 1). Intravitreal administration of triamcinolone acetonide or other steroids within 24 weeks prior to Visit 2 (Day 1), unless no visible residue of drug substance can be seen in the vitreous cavity using indirect ophthalmoscopy. Prior systemic or intravitreal treatment with VEGF Trap, ranibizumab (Lucentis) or bevacizumab (Avastin). Presence of any other condition or laboratory abnormality, which, in the opinion of the Investigator, would interfere with the assessment of disease status/progression or jeopardize the patient's appropriate participation in this Phase II study.

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: aflibercept injection (VEGF Trap-Eye, BAY86-5321) 0.5mg q4<br> | Biological: aflibercept injection (VEGF Trap-Eye, BAY86-5321)<br>* Participants received 0.5 mg of aflibercept injection (VEGF Trap-Eye, BAY86-5321) at 4 week intervals through Week 12<br>* Other names: BAY86-5321;|
| Experimental: aflibercept injection (VEGF Trap-Eye, BAY86-5321) 0.5mg q12<br> | Biological: aflibercept injection (VEGF Trap-Eye, BAY86-5321)<br>* Participants received 0.5 mg of aflibercept injection (VEGF Trap-Eye, BAY86-5321) at 12 week intervals through Week 12.<br>* Other names: BAY86-5321;|
| Experimental: aflibercept injection (VEGF Trap-Eye, BAY86-5321) 2.0mg q4<br> | Biological: aflibercept injection (VEGF Trap-Eye, BAY86-5321)<br>* Participants received 2.0 mg of aflibercept injection (VEGF Trap-Eye, BAY86-5321) at 4 week intervals through Week 12<br>* Other names: BAY86-5321;|
| Experimental: aflibercept injection (VEGF Trap-Eye, BAY86-5321) 2.0mg q12<br> | Biological: aflibercept injection (VEGF Trap-Eye, BAY86-5321)<br>* Participants received 2.0 mg of aflibercept injection (VEGF Trap-Eye, BAY86-5321) at 12 week intervals through Week 12.<br>* Other names: BAY86-5321;|
| Experimental: aflibercept injection (VEGF Trap-Eye, BAY86-5321) 4.0mg q12<br> | Biological: aflibercept injection (VEGF Trap-Eye, BAY86-5321)<br>* Participants received 4.0 mg of aflibercept injection (VEGF Trap-Eye, BAY86-5321) at 12 week intervals through Week 12.<br>* Other names: BAY86-5321;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change of CR/LT From Baseline at Week 12 | CR/LT measured in micrometers (µm); lower individual values represent better outcomes. | Baseline and at Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Percent Change of CR/LT From Baseline at Week 12 | CR/LT measured in micrometers (µm); a more negative percentage represents a better outcome | Baseline and at Week 12 | 
| Mean Change in Best Corrected Visual Acuity (BCVA) as Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) From Baseline at Week 12 | 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 12 | 
| Percentage of Participants Who Gained at Least 15 Letters of Vision in the ETDRS Letter Score From Baseline at Week 12 | 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 | At Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neovascular Age-Related Macular Degeneration