A Phase 3 Safety and Efficacy Study of Fovista® (E10030) Intravitreous Administration in Combination With Lucentis® Compared to Lucentis® Monotherapy

Study Overview
=================
Brief Summary
-----------------
The objectives of this study are to evaluate the safety and efficacy of intravitreal administration of Fovista® administered in combination with Lucentis® compared to Lucentis® monotherapy in subjects with subfoveal choroidal neovascularization secondary to age-related macular degeneration (AMD).

Detailed Description
-----------------
Subjects will be randomized in a 1:1 ratio to the following dose groups: Fovista® 1.5 mg/eye + Lucentis® 0.5 mg/eye Fovista® sham + Lucentis® 0.5 mg/eye Subjects will be treated for a total of 24 months with active Fovista® or sham in combination with Lucentis® with the primary endpoint at 12 months. Primary Efficacy Endpoint: The primary efficacy endpoint is the mean change in visual acuity (ETDRS letters) from baseline at the month 12 visit. Safety Endpoints: Safety endpoints include adverse events, vital signs, ophthalmic variables [ophthalmic examination, intraocular pressure (IOP), fluorescein angiogram (FA), optical coherence tomography (OCT)], ECG, and laboratory variables. Approximately 622 subjects will be randomized into one of the two treatment cohorts (311 patients per dose group).

Official Title
-----------------
A Phase 3 Randomized, Double-masked, Controlled Trial to Establish the Safety and Efficacy of Intravitreous Administration of Fovista® (Anti PDGF-B Pegylated Aptamer) Administered in Combination With Lucentis® Compared to Lucentis® Monotherapy in Subjects With Subfoveal Neovascular Age-related Macular Degeneration.

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

Intervention / Treatment
-----------------
* Drug: E10030
* Drug: ranibizumab
* Drug: E10030 sham intravitreal injection


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects of either gender aged ≥ 50 years Active subfoveal choroidal neovascularization (CNV) secondary to AMD Presence of sub-retinal hyper-reflective material (SD-OCT) Exclusion Criteria: Any prior treatment for AMD in the study eye prior to the Day 1 visit, except oral supplements of vitamins and minerals Any prior intravitreal treatment in the study eye prior to the Day 1 visit, regardless of indication (including intravitreal corticosteroids) Any intraocular surgery or thermal laser within three (3) months of trial entry. Any prior thermal laser in the macular region, regardless of indication Subjects with subfoveal scar or subfoveal atrophy are excluded Diabetes mellitus

Ages Eligible for Study
-----------------
Minimum Age: 50 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: E10030 + ranibizumab<br>E10030 1.5 mg intravitreal injection + ranibizumab 0.5 mg intravitreal injection | Drug: E10030<br> <br> * Other names: Fovista®;Drug: ranibizumab<br> <br> * Other names: Lucentis®;|
| Active Comparator: Sham + ranibizumab<br>E10030 sham intravitreal injection + ranibizumab 0.5 mg intravitreal injection | Drug: ranibizumab<br> <br> * Other names: Lucentis®;Drug: E10030 sham intravitreal injection<br>* Pressure on the eye with a syringe with no needle<br>* Other names: Sham;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change in Visual Acuity From Baseline to 12 Months | The primary efficacy endpoint is the mean change in visual acuity (ETDRS letters) from baseline to the month 12 visit. Higher ETDRS letters represents higher vision and a higher change in ETDRS letters represents better functioning. | 12 Months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Wet AMD, choroidal neovascularization, Fovista®, E10030, Lucentis®