Intravitreal Aflibercept Injection for Radiation Retinopathy

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety of intravitreal aflibercept injection - in the treatment of macular edema associated with retinopathy secondary to previous radiation therapy.

Detailed Description
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Radiation retinopathy can cause decreased vision in patients who have received either external beam radiation or local plaque therapy to the eye. An early manifestation of radiation retinopathy is macular edema, which represents fluid within the retina that affects central vision. There is currently no approved treatment for this disease, although there have been anecdotal reports of benefit with laser photocoagulation, intravitreal anti-VEGF agents, or intravitreal steroid use. This is a phase 1 study to evaluate aflibercept for the treatment of macular edema associated with retinopathy secondary to previous radiation treatment.

Official Title
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Treatment of Radiation Retinopathy With Intravitreal Aflibercept Injection 2.0mg

Conditions
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Radiation Retinopathy, Macular Edema

Intervention / Treatment
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* Drug: Aflibercept every 2 months
* Drug: Aflibercept monthly


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Retinopathy associated with previous I-125 brachytherapy for uveal melanoma (85 Gy over 96 hours) at least 6 months prior to enrollment Ability to provide written informed consent and comply with study assessments for the full duration of the study Age > 18 years Center involved macular edema > 300µm in thickness on SD-OCT Best corrected visual acuity of 20/40- 20/400 Birth control therapy for females of child-bearing age Exclusion Criteria: Pre-existing retinopathy due to other disorders Vision decrease is considered to be due to ischemic radiation retinopathy without macular edema or optic neuropathy Presence of metastasis Pregnancy (positive pregnancy test) or lactation Premenopausal women not using adequate contraception. The following are considered effective means of contraception: surgical sterilization or use of oral contraceptives, barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel, an IUD, or contraceptive hormone implant or patch. Prior enrollment in any study with intravitreal aflibercept injection Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated Uncontrolled glaucoma in the study eye (defined as IOP ≥ 30 mmHg despite treatment with anti-glaucoma medication) History of cerebral vascular accident, myocardial infarction, transient ischemic attacks within 4 months of study enrollment. Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye Any concurrent intraocular condition in the study eye (e.g., cataract or diabetic retinopathy) that, in the opinion of the investigator, could either require medical or surgical intervention during the study period to prevent or treat visual loss that might result from that condition, or if allowed to progress untreated, could likely contribute to loss of at least 2 Snellen equivalent lines of BCVA over the 6-month study period Presence of significant subfoveal fibrosis or atrophy Intraocular surgery (including cataract surgery) in the study eye within 2 months of enrollment Active intraocular inflammation (grade trace or above) in the study eye History of allergy to fluorescein, ICG or iodine, not amenable to treatment Prior/Concomitant Treatment: Panretinal photocoagulation treatment Previous intraocular steroids or PDT within 3 months Previous participation in any studies of investigational drugs within 30 days preceding Day 0 (excluding vitamins and minerals) Previous treatment with intravitreally (in either eye) or intravenously administered Avastin (bevacizumab) within 60 days or concomitant use in either eye outside the scope of this study Previous use of Eylea, Macugen or Lucentis in study eye within 60 days or concomitant use in either eye outside the scope of this study Prior submacular or vitreous surgery

Ages Eligible for Study
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Minimum Age: 18 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: aflibercept every 2 months<br> | Drug: Aflibercept every 2 months<br>* 2.0 mg aflibercept intravitreal injections once per month for the first 3 months (M0, M1, M2), then every 2 months (M4, M6, M8, M10)<br>* Other names: VEGF Trap-Eye;|
| Experimental: aflibercept monthly<br> | Drug: Aflibercept monthly<br>* 2.0mg aflibercept intravitreal injections every month (M0-11)<br>* Other names: VEGF Trap-Eye;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events |  | 12 months | 
| Severity of adverse events |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change in best corrected visual acuity from baseline |  | 12 months | 
| Mean change in central foveal thickness by optical coherence tomography (OCT) from baseline |  | 12 months | 
| Mean visual acuity |  | 12 months | 
| Mean central foveal thickness |  | 12 months | 
| Proportion of patients gaining 3 lines of vision |  | 12 months | 
| Mean change in lesion characteristics (lesion size, leakage) |  | 12 months | 
| Proportion of patients with no fluid on OCT |  | 12 months | 
| Mean change in macular volume |  | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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radiation, retinopathy, macular edema, anti-VEGF, VEGF-Trap, aflibercept