NEWTON: Aflibercept Injection for Previously Treated Macular Edema Associated With Central Retinal Vein Occlusions

Study Overview
=================
Brief Summary
-----------------
The purpose of the study is to determine the effect of Intravitreal Aflibercept Injection (IAI) on previously treated Central Retinal Vein Occlusions (CRVOs) with other Anti-VEGF agents.

Detailed Description
-----------------
This prospective, open-label, single-center, nonrandomized, investigator-sponsored clinical study seeks to investigate the visual outcomes of a treat and extend dosing regimen of intravitreal aflibercept injection for macular edema following CRVO. All patients will receive IAI 2 mg at baseline and Week 4. If the pre-defined extension criteria are met at the 4-week visit, and at any follow up visit, the patient will receive a mandated treatment, and the next visit will be extended by two weeks. If the extension criteria are not met on a follow-up visit, the treatment interval will be continued to be reduced by 1 week. If criteria are still not met despite treatment at the reduced interval, treatment will be administered as usual and follow up interval will continue to be reduced by 1 week until the criteria are met or a 4-week interval is reached. Treatment of IAI is rendered at every visit.

Official Title
-----------------
NEWTON: A Single-center Open Label Study Evaluating Intravitreal Aflibercept Injection (IAI) for Previously Treated Macular Edema Associated With Central Retinal Vein Occlusions

Conditions
-----------------
Macular Edema With Central Retinal Vein Occlusions

Intervention / Treatment
-----------------
* Drug: Aflibercept (2.0 mg)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients aged 18 and above with documented history of center-involved macular edema secondary to CRVO. Patients must have received treatment for at least 6 months before baseline, with 3 initial loading doses, and evidence of recurrence of edema when extended beyond 4 weeks. Protocol refracted ETDRS BCVA of 20/25 to 20/320 (73-24 letters). Willing and able to comply with clinic visits and study-related procedures. Provide signed informed consent. Exclusion Criteria: Prior panretinal or macular laser photocoagulation Previous use of intraocular corticosteroids or use of periocular corticosteroids within the 3 months prior to day 1 Prior treatment with systemic anti-VEGF agents Presence of iris neovascularization Vitreous hemorrhage in the Study Eye Traction retinal detachment, or preretinal fibrosis involving the macula Diabetic macular edema or diabetic retinopathy, defined as eyes of diabetic patients with more than 1 microaneurysm outside the area of the vein occlusion. Infectious blepharitis, keratitis, scleritis, or conjunctivitis. Active intraocular inflammation (grade trace or above) in the study eye, or history of idiopathic or autoimmune-associated uveitis in either eye. Uncontrolled glaucoma in the study eye (defined as intraocular pressure equal or greater than 30mmHg despite treatment with anti-glaucoma medication) Concurrent eye disease in the study eye that could compromise visual acuity (e.g. advanced glaucoma, age-related macular degeneration, etc) Any concurrent intraocular condition in the study eye (e.g. glaucoma) that, in the opinion of the investigator, could either require medical or surgical intervention during the 52 weeks study period to prevent or treat visual loss that might result from that condition. Pregnant or breast-feeding women Sexually active men* or women of childbearing potential** who are unwilling to practice adequate contraception during the study (adequate contraceptive measures include stable use of oral contraceptives or other prescription pharmaceutical contraceptives for 2 or more menstrual cycles prior to screening; intrauterine device [IUD]; bilateral tubal ligation; vasectomy; condom plus, contraceptive sponge, foam or jelly, or diaphragm) *Contraception is not required for men with documented vasectomy. **Postmenopausal women must be amenorrheic for at least 12 months in order not to be considered of child bearing potential. Pregnancy testing and contraception are not required for women with documented hysterectomy or tubal ligation.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 100 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: Aflibercept (2.0 mg)<br>Intravitreal Aflibercept (2.0 mg) | Drug: Aflibercept (2.0 mg)<br>* Intravitreal Aflibercept (2.0 mg)<br>* Other names: VEGF Trap-EYE;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Intravitreal Aflibercept on Treatment Interval | Mean number of weeks between each injection where there is no macular edema | 52 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Visual Acuity | Mean change in EDTRS BCVA | 52 Weeks | 
| Retinal Thickness | Mean change in Central Subfoveal Thickness by OCT | 52 Weeks | 
| Adverse Events | Incidence and severity of ocular and systemic AE's | 52 Weeks | 
| Number of Treatments | Mean number of Intravitreal Injections | 52 Weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Macular Edema, Central Retinal Vein Occlusion, CRVO, Aflibercept, VEGF Trap-Eye, Eylea, Ranibizumab, Bevacizumab