Primary endpoint results of a phase II study of vascular endothelial growth factor trap-eye in wet age-related macular degeneration

Ophthalmology. 2011 Jun;118(6):1089-97. doi: 10.1016/j.ophtha.2011.02.039.

Abstract

Objective: To evaluate the biologic effects and safety of vascular endothelial growth factor (VEGF) Trap-Eye during a 12-week fixed-dosing period in patients with neovascular (wet) age-related macular degeneration (AMD).

Design: Multicenter, prospective, randomized, double-masked clinical trial with initial 12-week fixed dosing period. Data were analyzed to week 16.

Participants: We included 159 patients with subfoveal choroidal neovascularization secondary to wet AMD.

Methods: Patients were randomized 1:1:1:1:1 to VEGF Trap-Eye during the fixed-dosing phase (day 1 to week 12): 0.5 or 2 mg every 4 weeks (0.5 mg q4wk, 2 mg q4wk) on day 1 and at weeks 4, 8, and 12; or 0.5, 2, or 4 mg every 12 weeks (0.5 mg q12wk, 2 mg q12wk, or 4 mg q12wk) on day 1 and at week 12.

Main outcome measures: The primary endpoint was change from baseline in central retinal/lesion thickness (CR/LT) at week 12; secondary outcomes included change in best-corrected visual acuity (BCVA), proportion of patients with a gain of ≥ 15 letters, proportion of patients with a loss of >15 letters, and safety.

Results: At week 12, treatment with VEGF Trap-Eye resulted in a significant mean decrease in CR/LT of 119 μm from baseline in all groups combined (P<0.0001). The reduction in CR/LT with the 2 mg q4wk and 0.5mg q4wk regimens was significantly greater than each of the quarterly dosing regimens. The BCVA increased significantly by a mean of 5.7 letters at 12 weeks in the combined group (P<0.0001), with the greatest mean gain of >8 letters in the monthly dosing groups. At 8 weeks, BCVA improvements were similar with 2 mg q4wk and 2 mg q12wk dosing. After the last required dose at week 12, CR/LT and visual acuity were maintained or further improved at week 16 in all treatment groups. Ocular adverse events were mild and consistent with safety profiles reported for other intraocular anti-VEGF treatments.

Conclusions: Repeated monthly intravitreal dosing of VEGF Trap-Eye over 12 weeks demonstrated significant reductions in retinal thickness and improvements in visual acuity, and was well-tolerated in patients with neovascular AMD.

Financial disclosure(s): Proprietary or commercial disclosure may be found after the references.

Publication types

  • Clinical Trial, Phase II
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Choroidal Neovascularization / diagnosis
  • Choroidal Neovascularization / etiology
  • Choroidal Neovascularization / prevention & control*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • Fovea Centralis / drug effects
  • Fovea Centralis / pathology*
  • Humans
  • Intravitreal Injections
  • Male
  • Middle Aged
  • Prospective Studies
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / administration & dosage*
  • Vascular Endothelial Growth Factor A / therapeutic use
  • Visual Acuity
  • Wet Macular Degeneration / complications
  • Wet Macular Degeneration / diagnosis
  • Wet Macular Degeneration / drug therapy*

Substances

  • Vascular Endothelial Growth Factor A