Safety and Efficacy of AGN208397 in the Treatment of Macular Edema Associated With Retinal Vein Occlusion (RVO)

Study Overview
=================
Brief Summary
-----------------
This study will evaluate the safety and efficacy of a single intravitreal injection of AGN208397 to treat Macular Edema associated with Retinal Vein Occlusion. This study is being conducted in two stages: Stage 1 will enroll approximately 21 subjects who will receive a single open label intravitreal injection of either 75 ug, 300 ug, 600 ug or 900 ug of AGN208397 and be followed for 12 months post treatment; based on Stage 1 results, Stage 2 will enroll approximately 96 subjects who will receive a single masked intravitreal injection of one of three doses of AGN208397 or Ozurdex® and be followed for 12 months post treatment.

Conditions
-----------------
Macular Edema, Retinal Vein Occlusion

Intervention / Treatment
-----------------
* Drug: AGN208397 intravitreal injection
* Drug: dexamethasone intravitreal implant


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: macular edema due to retinal vein occlusion visual acuity in the study eye between 20/320 to 20/40 Exclusion Criteria: cataract surgery or Lasik within 3 months prior to study Day 1 or anticipated need for cataract surgery during study period (12 months) use of injectable drugs in the study eye within 2 months prior to day 1 active eye infection in either eye visual acuity in the non-study eye of 20/200 or worse

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Stage 1 Cohort 1<br>AGN208397 intravitreal injection 75 ug on Day 1. | Drug: AGN208397 intravitreal injection<br>* AGN208397 intravitreal injection on Day 1.<br>|
| Experimental: Stage 1 Cohort 2<br>AGN208397 intravitreal injection 300 ug on Day 1. | Drug: AGN208397 intravitreal injection<br>* AGN208397 intravitreal injection on Day 1.<br>|
| Experimental: Stage 1 Cohort 3<br>AGN208397 intravitreal injection 600 ug on Day 1. | Drug: AGN208397 intravitreal injection<br>* AGN208397 intravitreal injection on Day 1.<br>|
| Experimental: Stage 1 Cohort 4<br>AGN208397 intravitreal injection 900 ug on Day 1. | Drug: AGN208397 intravitreal injection<br>* AGN208397 intravitreal injection on Day 1.<br>|
| Experimental: Stage 2 Arm 1<br>AGN208397 intravitreal injection 600 ug on Day 1. | Drug: AGN208397 intravitreal injection<br>* AGN208397 intravitreal injection on Day 1.<br>|
| Experimental: Stage 2 Arm 2<br>AGN208397 intravitreal injection 450 ug on Day 1. | Drug: AGN208397 intravitreal injection<br>* AGN208397 intravitreal injection on Day 1.<br>|
| Experimental: Stage 2 Arm 3<br>AGN208397 intravitreal injection 300 ug on Day 1. | Drug: AGN208397 intravitreal injection<br>* AGN208397 intravitreal injection on Day 1.<br>|
| Active Comparator: Stage 2 Arm 4<br>Dexamethasone 700 ug intravitreal implant on Day 1. | Drug: dexamethasone intravitreal implant<br>* Dexamethasone 700 ug intravitreal implant on Day 1.<br>* Other names: Ozurdex®;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline at Month 1 in Retinal Thickness in the Study Eye During Stage 1 | Retinal thickness is assessed by optical coherence tomography (OCT) in the study eye. The retina is the light-sensitive part of the eye. OCT is a laser-based, noninvasive, diagnostic system providing high-resolution, three-dimensional images of the retina. A negative change from baseline indicates an improvement. | Baseline, Month 1 | 
| Change From Baseline at Month 1 in Retinal Thickness in the Study Eye During Stage 2 | Retinal thickness is assessed by OCT in the study eye. The retina is the light-sensitive part of the eye. OCT is a laser-based, noninvasive, diagnostic system providing high-resolution, three-dimensional images of the retina. A negative change from baseline indicates an improvement. | Baseline, Month 1 | 
| Change From Baseline at Month 1 in Best Corrected Visual Acuity (BCVA) in the Study Eye During Stage 1 | BCVA is measured using an eye chart and is reported as the number of letters read correctly (ranging from 0 to 100 letters). The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved. | Baseline, Month 1 | 
| Change From Baseline at Month 1 in BCVA in the Study Eye During Stage 2 | BCVA is measured using an eye chart and is reported as the number of letters read correctly (ranging from 0 to 100 letters). The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved. | Baseline, Month 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline at Month 12 in Retinal Thickness in the Study Eye During Stage 1 | Retinal thickness is assessed by OCT in the study eye. The retina is the light-sensitive part of the eye. OCT is a laser-based, noninvasive, diagnostic system providing high-resolution, three-dimensional images of the retina. A negative change from baseline indicates an improvement. | Baseline, Month 12 | 
| Change From Baseline at Month 12 in Retinal Thickness in the Study Eye During Stage 2 | Retinal thickness is assessed by OCT in the study eye. The retina is the light-sensitive part of the eye. OCT is a laser-based, noninvasive, diagnostic system providing high-resolution, three-dimensional images of the retina. A negative change from baseline indicates an improvement. | Baseline, Month 12 | 
| Change From Baseline at Month 12 in BCVA in the Study Eye During Stage 1 | BCVA is measured using an eye chart and is reported as the number of letters read correctly (ranging from 0 to 100 letters). The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved. | Baseline, Month 12 | 
| Change From Baseline at Month 12 in BCVA in the Study Eye During Stage 2 | BCVA is measured using an eye chart and is reported as the number of letters read correctly (ranging from 0 to 100 letters). The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved. | Baseline, Month 12 |