Study to Evaluate Efficacy of Aflibercept in Neovascular Age-related Macular Degeneration Patients Non Responders to Anti-Vascular Endothelial Growth Factor

Study Overview
=================
Brief Summary
-----------------
Patients with neovascular age-related macular degeneration who do not respond to usual treatment with conventional medications may respond to a new drug of the same class which is designed to block a larger fraction of proangiogenic factors.

Official Title
-----------------
Phase IV Study to Evaluate the Efficacy of Aflibercept in Subjects With Neovascular Age-related Macular Degeneration (wAMD), Without Optimal Response to Repeated Monthly Intravitreal Injections of Anti Vascular Endothelial Growth Factor (Anti VEGF-A) Therapy.

Conditions
-----------------
Wet Macular Degeneration

Intervention / Treatment
-----------------
* Drug: 0.5mg aflibercept


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Signed Informed Consent Men and women ≥ 50 years of age. Any choroidal neovascular membranes (CNVM) lesion (occult, minimally classic or classic) secondary to age-related macular degeneration Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity of: 20/32 to 20/320 (letter score of 73 to 25) in the study eye. Able to return for ALL clinic visits and complete all study-related procedures. Absence of other ocular diseases that could affect visual acuity. Patients without optimal response to ranibizumab or bevacizumab defined as: Patient with significant persistent or recurrent fluid (intraretinal or subretinal) on OCT or any leakage on fluorescein angiography despite at least 4 injections within last 6 months, being the last OCT with presence of fluid within the 6 weeks after last treatment with ranibizumab or bevacizumab. Patient with significant persistent or recurrent fluid (intraretinal or subretinal) on OCT or any leakage on fluorescein angiography despite three monthly treatment with ranibizumab or bevacizumab. Exclusion Criteria: No scar, fibrosis, or atrophy involving the center of the fovea No retina pigment epithelium (RPE) rip/tear involving the central fovea Participation in another simultaneous interventional clinical trial Prior treatment with anti-VEGF or steroids therapy in the study eye within 28 days of baseline Prior treatment with photodynamic therapy (PDT) Intraocular surgery (including cataract surgery) in the study eye within 2 months preceding Baseline History of vitrectomy surgery, submacular surgery, or other surgical intervention for AMD in the study eye Active intraocular inflammation in the study eye History of cerebral vascular accident, myocardial infarction, transient ischemic attacks within 3 months of study enrollment. Unable to undergo fluorescein angiography or fundus photography because of uncontrolled allergies

Ages Eligible for Study
-----------------
Minimum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 0.5mg AFLIBERCEPT injection<br>Patients will receive intravitreal injection of aflibercept 0.5mg at baseline, week 4,8,16,24 and 32. Optionally, if intra or subretinal fluid persists at week 12, patients will receive an additional injection. | Drug: 0.5mg aflibercept<br>* 0.5mg aflibercept intravitreal injection will be performed every 4 weeks from baseline to week 8 (3 doses) and every 8 weeks until week 32.<br>* Other names: EYLEA;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with no fluid on Optical Coherence Tomography (OCT) after loading dose of aflibercept | At week 12 an OCT will be performed to evaluate the changes in intra or subretinal fluid and to determine the percentage of patients with no fluid after 3 doses of aflibercept injected on baseline visit, week 4 and week 8. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in best corrected visual acuity (BCVA)after loading dose |  | week 12 | 
| Changes in OCT central foveal thickness after loading dose |  | week 12 | 
| Anatomic and Visual Acuity outcomes maintained during (every 8 weeks) treatment. |  | week 40 | 
| Determine the time to resolution of any intra/sub retinal fluid on OCT |  | week 4,8,12,24,32,40 | 
| Describe safety of this cohort of patients | Describe the safety of aflibercept in study patients by determining ocular and non ocular adverse events classified according to type, frequency and severity during 40 weeks | baseline, week 4, 8, 12, 24, 32 and 40 |