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

David M. Brown, Jeffrey S. Heier, Thomas Ciulla, Matthew Benz, Prema Abraham, George Yancopoulos, Neil Stahl, Avner Ingerman, Robert Vitti, Alyson J. Berliner, Ke Yang, Quan Dong Nguyen

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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.

Original languageEnglish (US)
Pages (from-to)1089-1097
Number of pages9
JournalOphthalmology
Volume118
Issue number6
DOIs
StatePublished - Jun 1 2011

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Macular Degeneration
Vascular Endothelial Growth Factor A
Visual Acuity
Disclosure
Safety
Choroidal Neovascularization
Therapeutics
Outcome Assessment (Health Care)
Clinical Trials

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Brown, D. M., Heier, J. S., Ciulla, T., Benz, M., Abraham, P., Yancopoulos, G., ... Nguyen, Q. D. (2011). Primary endpoint results of a phase II study of vascular endothelial growth factor trap-eye in wet age-related macular degeneration. Ophthalmology, 118(6), 1089-1097. https://doi.org/10.1016/j.ophtha.2011.02.039

Primary endpoint results of a phase II study of vascular endothelial growth factor trap-eye in wet age-related macular degeneration. / Brown, David M.; Heier, Jeffrey S.; Ciulla, Thomas; Benz, Matthew; Abraham, Prema; Yancopoulos, George; Stahl, Neil; Ingerman, Avner; Vitti, Robert; Berliner, Alyson J.; Yang, Ke; Nguyen, Quan Dong.

In: Ophthalmology, Vol. 118, No. 6, 01.06.2011, p. 1089-1097.

Research output: Contribution to journalArticle

Brown, DM, Heier, JS, Ciulla, T, Benz, M, Abraham, P, Yancopoulos, G, Stahl, N, Ingerman, A, Vitti, R, Berliner, AJ, Yang, K & Nguyen, QD 2011, 'Primary endpoint results of a phase II study of vascular endothelial growth factor trap-eye in wet age-related macular degeneration', Ophthalmology, vol. 118, no. 6, pp. 1089-1097. https://doi.org/10.1016/j.ophtha.2011.02.039
Brown, David M. ; Heier, Jeffrey S. ; Ciulla, Thomas ; Benz, Matthew ; Abraham, Prema ; Yancopoulos, George ; Stahl, Neil ; Ingerman, Avner ; Vitti, Robert ; Berliner, Alyson J. ; Yang, Ke ; Nguyen, Quan Dong. / Primary endpoint results of a phase II study of vascular endothelial growth factor trap-eye in wet age-related macular degeneration. In: Ophthalmology. 2011 ; Vol. 118, No. 6. pp. 1089-1097.
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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.",
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T1 - Primary endpoint results of a phase II study of vascular endothelial growth factor trap-eye in wet age-related macular degeneration

AU - Brown, David M.

AU - Heier, Jeffrey S.

AU - Ciulla, Thomas

AU - Benz, Matthew

AU - Abraham, Prema

AU - Yancopoulos, George

AU - Stahl, Neil

AU - Ingerman, Avner

AU - Vitti, Robert

AU - Berliner, Alyson J.

AU - Yang, Ke

AU - Nguyen, Quan Dong

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N2 - 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.

AB - 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.

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