title: The 1-year results of CLEAR-IT 2, a phase 2 study of vascular endothelial growth factor trap-eye dosed as-needed after 12-week fixed dosing.
abstract: OBJECTIVE
  To evaluate anatomic outcomes and vision, injection frequency, and safety during the as-needed (PRN) treatment phase of a study evaluating a 12-week fixed dosing period followed by PRN dosing to week 52 with vascular endothelial growth factor (VEGF) Trap-Eye for neovascular (wet) age-related macular degeneration (AMD).
  
  
  METHODS
  Multicenter, randomized, double-masked trial.
  
  
  METHODS
  We included 159 patients with subfoveal choroidal neovascularization (CNV) secondary to wet AMD.
  
  
  METHODS
  Patients were randomly assigned to 1 of 5 intravitreal VEGF Trap-Eye treatment groups: 0.5 mg or 2 mg every 4 weeks or 0.5, 2, or 4 mg every 12 weeks during the fixed-dosing period (weeks 1-12). From weeks 16 to 52, patients were evaluated monthly and were retreated PRN with their assigned dose (0.5, 2, or 4 mg).
  
  
  METHODS
  Change in central retinal/lesion thickness (CR/LT), change in total lesion and CNV size, mean change in best-corrected visual acuity (BCVA), proportion of patients with 15-letter loss or gain, time to first PRN injection, reinjection frequency, and safety at week 52.
  
  
  RESULTS
  The decrease in CR/LT at week 12 versus baseline remained significant at weeks 12 to 52 (-130 μm from baseline at week 52) and CNV size regressed from baseline by 2.21 mm(2) at 48 weeks. After achieving a significant improvement in BCVA during the 12-week, fixed-dosing phase for all groups combined, PRN dosing for 40 weeks maintained improvements in BCVA to 52 weeks (5.3-letter gain; P<0.0001). The most robust improvements and consistent maintenance of visual acuity generally occurred in patients initially dosed with 2 mg every 4 weeks for 12 weeks, demonstrating a gain of 9 letters at 52 weeks. Overall, a mean of 2 injections was administered after the 12-week fixed-dosing phase, and the mean time to first reinjection was 129 days; 19% of patients received no injections and 45% received 1 or 2 injections. Treatment with VEGF Trap-Eye was generally safe and well tolerated, with few ocular or systemic adverse events.
  
  
  CONCLUSIONS
  PRN dosing with VEGF Trap-Eye at weeks 16-52 maintained the significant anatomic and vision improvements established during the 12-week fixed-dosing phase with a low frequency of reinjections. Repeated dosing with VEGF Trap-Eye was well tolerated over 52 weeks of treatment.
  
  
  BACKGROUND
  Proprietary or commercial disclosure may be found after the references.
authors.affiliation: Ophthalmic Consultants of Boston, Boston, Massachusetts, USA.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Heier
authors.forename: David
authors.initials: D
authors.lastname: Boyer
authors.forename: Quan Dong
authors.initials: QD
authors.lastname: Nguyen
authors.forename: Dennis
authors.initials: D
authors.lastname: Marcus
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Roth
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: David M
authors.initials: DM
authors.lastname: Brown
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; 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; D009887:Ophthalmoscopy; D011446:Prospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage* / Q000627:therapeutic use; D014792:Visual Acuity; D057135:Wet Macular Degeneration / Q000150:complications* / Q000188:drug therapy / Q000473:pathology
chemical_list: D042461:Vascular Endothelial Growth Factor A