title: Primary endpoint results of a phase II study of vascular endothelial growth factor trap-eye in wet age-related macular degeneration.
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).
  
  
  METHODS
  Multicenter, prospective, randomized, double-masked clinical trial with initial 12-week fixed dosing period. Data were analyzed to week 16.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  BACKGROUND
  Proprietary or commercial disclosure may be found after the references.
authors.affiliation: Retina Consultants of Houston, The Methodist Hospital, Houston, Texas, USA. dmbmd@houstonretina.com
authors.forename: David M
authors.initials: DM
authors.lastname: Brown
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Heier
authors.forename: Thomas
authors.initials: T
authors.lastname: Ciulla
authors.forename: Matthew
authors.initials: M
authors.lastname: Benz
authors.forename: Prema
authors.initials: P
authors.lastname: Abraham
authors.forename: George
authors.initials: G
authors.lastname: Yancopoulos
authors.forename: Neil
authors.initials: N
authors.lastname: Stahl
authors.forename: Avner
authors.initials: A
authors.lastname: Ingerman
authors.forename: Robert
authors.initials: R
authors.lastname: Vitti
authors.forename: Alyson J
authors.initials: AJ
authors.lastname: Berliner
authors.forename: Ke
authors.initials: K
authors.lastname: Yang
authors.forename: Quan Dong
authors.initials: QD
authors.lastname: Nguyen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020256:Choroidal Neovascularization / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D005584:Fovea Centralis / Q000187:drug effects / Q000473:pathology*; D006801:Humans; D058449:Intravitreal Injections; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage* / Q000627:therapeutic use; D014792:Visual Acuity; D057135:Wet Macular Degeneration / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*
chemical_list: D042461:Vascular Endothelial Growth Factor A