Treatment of Diabetic Macular Edema With Aflibercept in Subjects Previously Treated With Ranibizumab or Bevacizumab

Study Overview
=================
Brief Summary
-----------------
Treatment of diabetic macular edema with intravitreal aflibercept in subjects previously treated with intravitreal anti-Vascular endothelial growth factor (VEGF) agents (ranibizumab or bevacizumab)

Detailed Description
-----------------
This study is an investigator initiated interventional study for subjects with diabetic macular edema (DME) that have been previously treated with bevacizumab or ranibizumab. Intravitreal aflibercept 2mg will be given until OCT (ocular coherence tomography) demonstrates an absence of fluid. Continued intravitreal aflibercept 2mg will then take place every 2 months for a total of 24 months of treatment. This study is an interventional, single arm, investigator initiated study. Subjects will be given 2 mg (0.05 mL or 50 microliters) of intravitreal aflibercept injection (IAI) administered monthly until OCT demonstrates no evidence of fluid as defined by the protocol, followed by 2 mg (0.05 mL) once every 2 months. Each subject will be evaluated for 24 months. Thus, the study duration will be 24 months plus the recruitment period. Subjects will be evaluated for safety, efficacy as measured by Spectral Domain Optical Coherence Tomography (SDOCT) and best corrected visual acuity (BCVA) using the Electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS) protocol. In additional, fundus photography, fluorescein angiography, and OCT angiography will be performed at baseline, month 6, month 12 and at the final visit. Only one eye per subject may be enrolled in the study. If a subject's fellow (non-study) eye requires treatment for at study entry, or during the subject's participation in the study, the fellow eye can receive IAI for DME.

Official Title
-----------------
Investigator Initiated Observational Study of Intravitreal Aflibercept Injection in Subjects With Diabetic Macular Edema Previously Treated With Ranibizumab or Bevacizumab

Conditions
-----------------
Diabetic Retinopathy, Macular Edema

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Men and women ≥ 18 years of age. Foveal-involving retinal edema secondary to DME based on investigator review of clinical exam and SDOCT with central subfield thickness value of 325 microns by Zeiss Cirrus SD-OCT. E-ETDRS best-corrected visual acuity of: 20/25 to 20/400 in the study eye. History of previous treatment with anti-VEGF with at least 4 injections over the last 6 months. 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 or concomitant therapy with another investigational agent to treat DME in the study eye. Prior panretinal photocoagulation in the study eye within the past 3 months. Prior intravitreal anti-VEGF therapy in the study eye within 30 days of enrollment. Prior systemic anti-VEGF therapy, investigational or FDA-approved, is only allowed up to 3 months prior to first dose, and will not be allowed during the study. Previous treatment with intravitreal aflibercept injection Significant vitreous hemorrhage obscuring view to the macula or the retinal periphery as determined by the investigator on clinical exam Presence of other causes of macular edema, including pathologic myopia (spherical equivalent of -8 diopters or more negative, or axial length of 25 mm or more), ocular histoplasmosis syndrome, angioid streaks, choroidal rupture, choroidal neovascularization, age-related macular degeneration or multifocal choroiditis in the study eye. Presence of macula-threatening traction retinal detachment. 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's unlikely to interfere with the injection. Uncontrolled glaucoma at baseline evaluation Active intraocular inflammation in either eye. Active ocular or periocular infection in either eye. Any ocular or periocular infection within the last 2 weeks prior to Screening in either eye. Any history of uveitis in either eye. History of corneal transplant or corneal dystrophy in the study eye. Significant media opacities, including cataract, in the study eye which might interfere with visual acuity, assessment of safety, or fundus photography. Any concurrent intraocular condition in the study eye (e.g. cataract) that, in the opinion of the investigator, could require either medical or surgical intervention during the 52 week study period. Any concurrent ocular condition in the study eye which, in the opinion of the investigator, could either increase the risk to the subject beyond what is to be expected from standard procedures of intraocular injection, or which otherwise may interfere with the injection procedure or with evaluation of efficacy or safety. Participation as a subject in any clinical study within the 12 weeks prior to Day 1. Any systemic therapy with an investigational agent in the past 3 months prior to Day 1. Any history of allergy to povidone iodine. Pregnant or breast-feeding women Women of childbearing potential who are unwilling to practice adequate contraception during the study -

Ages Eligible for Study
-----------------
Minimum Age: 18 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: Single Arm<br>aflibercept 2mg given intravitreally every month until resolution of fluid in retina and then continued every 2 months for a total of 24 months of treatment | Drug: aflibercept<br>* aflibercept 2mg given intravitreally every month until resolution of fluid in retina and then continued every 2 months for a total of 24 months of treatment<br>* Other names: Eylea;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of Treatment Outcomes by Change in Visual Acuity From Baseline | Subjects were evaluated for efficacy by the change in best corrected visual acuity from baseline. Best Corrected Visual Acuity (BCVA) was measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) letter score starting at 4 meters. More letters read correctly results in a higher letter score, which represents better visual acuity. | Baseline and 12 months | 
| Mean Absolute Change on Central Foveal Thickness | Mean absolute Central Foveal Thickness change from baseline at month 12 as measured by Spectral Domain Optical Coherence Tomography (SD-OCT), defined as the average thickness within the central 1 mm subfield of the central retina. Thicker measures can represent more macular edema | Baseline and 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change on Visual Acuity Score | The mean change from baseline in best-corrected visual acuity score at months 6,12 and 24. Best Corrected Visual Acuity was measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) letter score starting at 4 meters. More letters read correctly results in a higher letter score, which represents better visual acuity. | Baseline, 6 months, 12 months, 24 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Diabetes, Macular Edema, Diabetic Retinopathy