IAI Versus Sham as Prophylaxis Against Conversion to Neovascular AMD

Study Overview
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Brief Summary
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This is a prospective, single-blind, randomized study to evaluate intravitreal aflibercept injection (IAI) versus sham as prophylaxis against conversion to neovascular age-related macular degeneration (AMD) in high-risk subjects.

Detailed Description
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128 subjects will be enrolled in the trial and randomized in a 1:1 ratio to receive either IAI every three months for 24 months or sham injections. Enrollment will be stratified in order to ensure a balance between the two treatment groups for subjects who were diagnosed with exudative AMD within the past two years versus those diagnosed more than two years prior to Baseline. Study assessments will be conducted at required visits every three months and include manifest refraction and ETDRS visual acuity testing, slit lamp exam and dilated fundus exam, spectral-domain optical coherence tomography (SD-OCT) using Avanti device, and OCT angiography using Avanti AngioVueTM, and fluorescein angiography. Fundus photography will also be performed at Baseline, Month 12 and Month 24 visits. In the event of conversion to neovascular AMD in the study eye at any point during the study, the Investigator will treat the subject with IAI at a frequency per his/her discretion.

Official Title
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A Prospective, Single-Blind, Randomized Study to Evaluate Intravitreal Aflibercept Injection (IAI) Versus Sham as PROphylaxis Against CONversion to Neovascular Age-Related Macular Degeneration (AMD) in High-Risk Eyes

Conditions
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Age-Related Macular Degeneration

Intervention / Treatment
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* Drug: Intravitreal aflibercept injection
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Study eye must have a diagnosis of non-exudative age-related degeneration characterized by the presence of many intermediate sized drusen, 1 or more large drusen, and/or hyperpigmentary changes. Fellow (non-study) eye must have CNV lesion (i.e., leakage on fluorescein angiography and/or subretinal, intraretinal, or sub-RPE fluid on OCT) secondary to age-related macular degeneration OR history of CNV lesion secondary to age-related macular degeneration, as confirmed by current or past treatment or current or past diagnostic imaging. Subject must be willing and able to comply with clinic visits and study-related procedures. Subject must provide signed informed consent. Subject must be able to understand and complete study-related questionnaires. In order to participate in the home monitoring sub-study, subjects must have an approved wireless device (i.e. iPhone, iPad, or iPod running iOS 6.0 or later) or be willing to use a loaned device and have access to a wireless Internet connection for the duration of the study. Exclusion Criteria: Evidence of neovascular AMD in the study eye at time of enrollment or anytime in the past. The reading center must confirm that there is no evidence of neovascular AMD in the study eye prior to enrollment. Serous PED of any size in the study eye, as determined by the reading center. Previous treatment with verteporfin PDT, anti-VEGF therapy, laser, external beam radiation or other AMD therapy in the study eye. History of macular hole in study eye. History of vitrectomy in study eye. Lens extraction or implantation within the last 3 months. Capsulotomy within the last 1 month. Lens or other media opacity that would preclude good fundus photography or angiography within the next 2 years. Macular edema or signs of diabetic retinopathy more severe than 10 red dots (microaneurysms or blot hemorrhages). Retinal changes related to high myopia and/or myopic correction greater than 8.00 diopters spherical equivalent. Any progressive ocular disease that would affect visual acuity within the next 2 years. Previous participation in any studies of investigational drugs likely to have ocular effects within 30 days preceding the initial study treatment. Concurrent use of systemic anti-VEGF agents. Active or recent (within 4 weeks) intraocular inflammation (grade trace or above) in the study eye. Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye. For subjects who have undergone prior refractive or cataract surgery in the study eye, the preoperative refractive error in the study eye cannot exceed 8 diopters of myopia. Uncontrolled glaucoma in the study eye (defined as intraocular pressure greater than 25 mmHg) despite treatment with anti-glaucoma medication). Subjects who are unable to be photographed to document CNV due to known allergy to fluorescein dye, lack of venous access or cataract obscuring the CNV. Subjects with other ocular diseases that can compromise the visual acuity of the study eye such as amblyopia and anterior ischemic optic neuropathy. Current treatment for active systemic infection. Evidence of significant uncontrolled concomitant diseases such as cardiovascular disease, nervous system, pulmonary, renal, hepatic, endocrine, or gastrointestinal disorders. History of recurrent significant infections or bacterial infections. Inability to comply with study or follow-up procedures. Pregnancy (positive pregnancy test) or lactation
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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intravitreal aflibercept injection<br>Subjects will be randomized to receive intravitreal aflibercept injection every three months for 24 months. | Drug: Intravitreal aflibercept injection<br>* Intravitreal aflibercept injection<br>* Other names: Eylea;|
| Placebo Comparator: Placebo<br>Subjects will be randomized to receive sham injection every three months for 24 months. | Drug: Placebo<br>* Sham injection<br>* Other names: Sham injection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects converting to neovascular AMD at 24 months, characterized by the development of choroidal neovascularization (CNV). |  | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change in visual acuity at 24 months compared to baseline |  | 24 months | 
| Percentage of subjects losing less than 15 ETDRS letters at 24 months compared to baseline |  | 24 months | 
| Incidence and severity of potential ocular side effects including endophthamitis, retinal detachment, cataract, and intraocular inflammation |  | up to Month 24 | 
| Incidence and severity of systemic side effects |  | up to Month 24 |