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

Subjects will be randomized in a 1:1 ratio to the following two arms per study design:

* Fovista® 1.5 mg/eye + Avastin® 1.25 mg/eye or Eylea® 2 mg/eye
* Fovista® sham + Avastin® 1.25 mg/eye or Eylea® 2 mg/eye

Subjects will be treated for up to 24 months with active Fovista® or sham, in combination with either Avastin® or Eylea® with the primary endpoint at 12 months.

Approximately 622 subjects will be randomized into one of the two treatment groups (311 patients per dose group), and the efficacy analysis will be based on the data from these two groups as per the SAP

• E10030 (Drug), also known as Fovista®
• bevacizumab or aflibercept (Drug), also known as Avastin®, Eylea®: Patients are randomized to receive either bevacizumab or aflibercept
• E10030 sham injection (Drug), also known as Sham: Pressure on the eye with a syringe with no needle

Primary outcomes

• Mean Change in Visual Acuity (Measured at Baseline and at the Month 12 Visit) [12 months]: The primary efficacy endpoint is the mean change in visual acuity (ETDRS letters) measured at baseline and at the month 12 visit. Higher ETDRS letters represents higher vision and a higher change in ETDRS letters represents better functioning.

Sex: All, ages: 50 Years to any

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

Participant flow

Outcome results

• Mean Change in Visual Acuity (Measured at Baseline and at the Month 12 Visit) (Primary), Mean, letters: E10030 + Bevacizumab or Aflibercept 9.42 +/- 0.85; Sham + Bevacizumab or Aflibercept 9.04 +/- 0.85

Adverse events

Time frame: All-Cause Mortality data was collected for up to 2 years, and Adverse events (AEs) were collected for up to 12 months of exposure (Year 1) for the 2 pre-specified treatment groups (E10030 + Bevacizumab or Aflibercept vs. Sham + Bevacizumab or Aflibercept), per the study design and the SAP.

Serious adverse events by term

34 more terms not shown.

Other adverse events by term

107 more sites not listed.

• Results publication: Park EJ, Choi J, Lee KC, Na DH. Emerging PEGylated non-biologic drugs. Expert Opin Emerg Drugs. 2019 Jun;24(2):107-119. doi: 10.1080/14728214.2019.1604684. Epub 2019 Apr 19. PMID 30957581

• Study Protocol (PDF, 2014-03-06)
• Statistical Analysis Plan (PDF, 2017-03-21)