Sirolimus Versus Anti-Vascular Endothelial Growth Factor (antiVEGF) for Wet AMD

Study Overview
=================
Brief Summary
-----------------
Phase 2 clinical trial, single site, randomized, subject-masked study to determine safety and efficacy of intravitreal injections of Sirolimus in subjects with wet Age-Related Macular Degeneration (wet AMD) with persistent intraretinal or subretinal edema due to neovascular AMD despite previous AntiVEGF treatment.

Detailed Description
-----------------
Forty subjects will be randomized to receive intravitreal Sirolimus or standard of care treatment in a 1:1 ratio. Over the course of the six month trial plus a 6 month optional extension, subjects will be evaluated monthly. Treatment with Sirolimus will be given at baseline, month 2 and month 4 with sham injections given at months 1, 3 and 5. For subjects in the extension Sirolimus will also be given at months 6, 8 and 10 with sham at month 7, 9, and 11. Subjects in the standard of care group will receive anti-VEGF injections or sham monthly. Retreatment criteria will be based upon continued subretinal edema, intraretinal edema or active chorioretinal neovascularization (CNV)

Official Title
-----------------
Sirolimus Versus AntiVEGF for Wet AMD

Conditions
-----------------
Age-Related Macular Degeneration

Intervention / Treatment
-----------------
* Drug: Sirolimus
* Drug: Standard of Care intravitreal injections of anti-VEGF


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: best corrected visual acuity of 5-65, inclusive, in study eye presence of choroid neovascularization secondary to AMD persistent edema despite at least 3 previous intravitreal anti-VEGF injections in the past 5 months Exclusion Criteria: greater than 100 micron decrease in central subfield thickness on Optical Coherence Topography (OCT) since last standard of care visit history of major ophthalmic surgery in the study eye in the past 3 months history of significant ocular disease or condition other than exudative AMD that may confound results

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sirolimus<br>Intravitreal Sirolimus | Drug: Sirolimus<br>* intravitreal injection<br>* Other names: DE-109;|
| Active Comparator: Standard of Care intravitreal anti-VEGF<br>anti-VEGF intravitreal injections | Drug: Standard of Care intravitreal injections of anti-VEGF<br>* intravitreal injections of anti-VEGF<br>* Other names: avastin,bevacizumab, eylea, aflibercept,;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Edema From Baseline to Month 6 Central Subfield Thickness ) on Heidelberg Optical Coherence Topography | Change in edema from baseline to month 6 as measured by mean difference in microns of central subfield thickness on Heidelberg optical coherence topography in each treatment group | Baseline to 6 months | 
| Visual Acuity | number of subjects with gain of 0-4 letters of visual acuity | Baseline to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Acuity (Best Corrected Visual Acuity) | number of subjects with gain of 5 or more letters of visual acuity | baseline to 6 months |