A Safety and Efficacy Study of E10030 (Anti-PDGF Pegylated Aptamer) Plus Lucentis for Neovascular Age-Related Macular Degeneration

• •The proportion of subjects gaining 15 or more ETDRS letters from baseline at the Week 24 visit [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  •The proportion of subjects gaining 15 or more ETDRS letters from baseline at the Week 24 visit
• Change in area of choroidal neovascularization (CNV) [ Time Frame: 24 Weeks ] [ Designated as safety issue: No ]
  • The mean change in area of choroidal neovascularization from baseline at Week 24 (by fluorescein angiogram)
• Number of patients with Adverse Events [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]

• Change in visual acuity [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • The mean change in visual acuity from baseline at Week 12
• Change in area of choroidal neovascularization (CNV) [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
  • The mean change in area of choroidal neovascularization from baseline at Week 12 (by fluorescein angiogram)
• Change in retinal thickness [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • The mean change in central subfield retinal thickness from baseline at Week 12
• Number of patients with Adverse Events [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]

The objectives of this study are to evaluate the safety and efficacy of E10030 intravitreous injection when administered in combination with Lucentis® against a control of Lucentis® alone in subjects with subfoveal choroidal neovascularization secondary to age-related macular degeneration (AMD).

Subjects will be randomized in a 1:1:1 ratio to the following dose groups:

• E10030 0.3 mg/eye + Lucentis® 0. 5 mg/eye
• E10030 1.5 mg/eye + Lucentis® 0. 5 mg/eye
• E10030 sham + Lucentis® 0. 5 mg/eye

Subjects will be treated with active E10030 or sham E10030 in combination with Lucentis® at Day 0, Week 4, Week 8, Week 12, Week 16 and Week 20.

Primary Efficacy Endpoint:

The primary efficacy endpoint is mean change in visual acuity from baseline at the Week 24 visit

Safety Endpoints:

Safety endpoints include adverse events, vital signs, ophthalmic variables [visual acuity, intraocular pressure (IOP), ophthalmic examination, color fundus photography, fluorescein angiograms (FA), optical coherence tomography (OCT)], and laboratory variables.

Approximately 444 subjects will be randomized into one of the three treatment cohorts (approximately 148 patients per dose group).

• Drug: E10030 plus Lucentis
  once a month intravitreal injection
• Drug: Lucentis
  10 mg/mL intravitreal injection monthly

• Active Comparator: Lucentis
  Intervention: Drug: E10030 plus Lucentis
• Experimental: E10030 low dose plus Lucentis
  Intervention: Drug: Lucentis
• Experimental: E10030 high dose plus Lucentis
  Intervention: Drug: Lucentis

Inclusion Criteria:

• Subfoveal choroidal neovascularization (CNV) due to AMD

Exclusion Criteria:

Any of the following underlying diseases including:

• Diabetes mellitus
• History or evidence of severe cardiac disease (e.g., NYHA Functional Class III or IV - see Appendix 19.6), history or clinical evidence of unstable angina, acute coronary syndrome, myocardial infarction or coronary artery revascularization within 6 months, or ventricular tachyarrhythmias requiring ongoing treatment.
• Clinically significant impaired renal or hepatic function.
• Stroke (within 12 months of trial entry).
• Any major surgical procedure within one month of trial entry.
• Known serious allergies to the fluorescein dye used in angiography (mild allergy amenable to treatment is allowable), to the components of the ranibizumab (Lucentis) formulation, or to the components of the E10030 formulation