Sirolimus in Conjunction With Eylea vs Eylea Alone for Exudative AMD

Study Overview
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Brief Summary
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To determine safety and efficacy of intravitreal injections of Sirolimus with adjunct EYLEA in subjects with exudative age related macular degeneration (AMD) with persistent intraretinal or subretinal edema due to neovascular AMD despite previous intravitreal anti-vascular endothelial growth factor (antiVEGF) treatment.

Detailed Description
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This study is a single-center, masked, randomized, 36 week study, designed to evaluate the safety and treatment efficacy of intravitreal Sirolimus with adjunct EYLEA® (aflibercept) in patients with persistent edema due to neovascular AMD versus EYLEA® (aflibercept) alone. Twenty (20) patients will be randomized to receive study medication in a 1:1 ratio. Study treatment will be administered by intravitreal injections. The sham injections given in the EYLEA® alone group are needleless and they are given in order to help preserve the masking of those subjects in that treatment group.

Official Title
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Sirolimus in Conjunction With EYLEA® (Aflibercept) Versus EYLEA® Alone for Exudative AMD

Conditions
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Exudative Age Related Macular Degeneration

Intervention / Treatment
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* Drug: Sirolimus
* Drug: EYLEA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients, 50 years of age or older at baseline Patient has completed/signed an informed consent prior to any study-related procedures and is able to follow study instructions and likely to complete all required visits. • Ocular Inclusion Criteria (Study eye only): BCVA 5 - 75 (20/800-20/30), inclusive, in study eye; if both eyes are eligible, the eye with the best potential visual improvement as determined by the investigator will be selected for treatment. Presence of choroidal neovascularization secondary to AMD At least 3 previous intravitreal anti-VEGF injections in the past 6 months Injection of antiVEGF may be deferred for at least 4 weeks from randomization based on clinical assessment of AMD by the investigator. Clear ocular media and adequate pupil dilation to permit good quality photographic imaging - Exclusion Criteria: Females who are pregnant, nursing, planning a pregnancy or who are of childbearing potential not using a reliable method of contraception. History or current evidence of hypersensitivity to any components of the study medication or fluorescein, as assessed by the investigator. Participation in any investigational drug or device study within 30 days prior to baseline History or current evidence of a medical condition that may, in the opinion of the investigator, preclude the safe administration of study medication or affect the results of the study. • Ocular Exclusion Criteria (Study eye only): Decrease of greater than 150 microns in central subfield thickness as measured by OCT since the last intravitreal injection in the study eye Aphakia History of pars plana vitrectomy in the study eye History of major ophthalmic surgery in the study eye in the past 3 months and any ophthalmic surgery in the study eye within the past 30 days History of significant ocular disease or condition other than exudative AMD that may confound results Uncontrolled glaucoma (defined as intraocular pressure >21mm Hg despite treatment with two or more ocular hypotensive medications at baseline) No active ocular or periocular infections, or ocular malignancy including lymphoma Presence of significant epiretinal membrane Significant vitreoretinal traction -

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 99 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: Group 1<br>Sirolimus 440ug for intravitreal injection will be provided in sterile single-use glass vials. One single-dose vial will be packaged in a box for each patient injection. Sirolimus injections will be given at baseline, week 4, 12, 20 and 28. EYLEA® (aflibercept) intravitreal injections will be given at week 1, 8, 16, 24 and 32. | Drug: Sirolimus<br> <br> * Other names: DE-109;Drug: EYLEA<br> <br> * Other names: aflibercept;|
| Active Comparator: Group 2<br>Intravitreal injection of EYLEA® (aflibercept) will be given at baseline, week 8, 16, 24 and 32. Sham injections will be given at week 1, 4, 12, 20, and 28 in order to maintain masking of patient to treatment assignment | Drug: EYLEA<br> <br> * Other names: aflibercept;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Central Subfield Thickness on OCT From Baseline to Week 36 | the amount of change in intraretinal and subretinal fluid as measured by microns of central subfield thickness (CST) on Heidelberg Optical Coherence Tomography (OCT) | baseline to week 36 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Best Corrected Visual Acuity (BCVA) From Baseline to Week 36 |  | baseline to week 36 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AMD