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

Jeffrey S. Heier, David Boyer, Quan Dong Nguyen, Dennis Marcus, Daniel B. Roth, George Yancopoulos, Neil Stahl, Avner Ingerman, Robert Vitti, Alyson J. Berliner, Ke Yang, David M. Brown

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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). Design: Multicenter, randomized, double-masked trial. Participants: 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). Main Outcome Measures: 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 mm2 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. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Original languageEnglish (US)
Pages (from-to)1098-1106
Number of pages9
JournalOphthalmology
Volume118
Issue number6
DOIs
StatePublished - Jun 1 2011

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

ASJC Scopus subject areas

  • Ophthalmology

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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. / Heier, Jeffrey S.; Boyer, David; Nguyen, Quan Dong; Marcus, Dennis; Roth, Daniel B.; Yancopoulos, George; Stahl, Neil; Ingerman, Avner; Vitti, Robert; Berliner, Alyson J.; Yang, Ke; Brown, David M.

In: Ophthalmology, Vol. 118, No. 6, 01.06.2011, p. 1098-1106.

Research output: Contribution to journalArticle

Heier, JS, Boyer, D, Nguyen, QD, Marcus, D, Roth, DB, Yancopoulos, G, Stahl, N, Ingerman, A, Vitti, R, Berliner, AJ, Yang, K & Brown, DM 2011, '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', Ophthalmology, vol. 118, no. 6, pp. 1098-1106. https://doi.org/10.1016/j.ophtha.2011.03.020
Heier, Jeffrey S. ; Boyer, David ; Nguyen, Quan Dong ; Marcus, Dennis ; Roth, Daniel B. ; Yancopoulos, George ; Stahl, Neil ; Ingerman, Avner ; Vitti, Robert ; Berliner, Alyson J. ; Yang, Ke ; Brown, David M. / 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. In: Ophthalmology. 2011 ; Vol. 118, No. 6. pp. 1098-1106.
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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). Design: Multicenter, randomized, double-masked trial. Participants: 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). Main Outcome Measures: 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 mm2 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. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.",
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T1 - 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

AU - Heier, Jeffrey S.

AU - Boyer, David

AU - Nguyen, Quan Dong

AU - Marcus, Dennis

AU - Roth, Daniel B.

AU - Yancopoulos, George

AU - Stahl, Neil

AU - Ingerman, Avner

AU - Vitti, Robert

AU - Berliner, Alyson J.

AU - Yang, Ke

AU - Brown, David M.

PY - 2011/6/1

Y1 - 2011/6/1

N2 - 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). Design: Multicenter, randomized, double-masked trial. Participants: 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). Main Outcome Measures: 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 mm2 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. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

AB - 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). Design: Multicenter, randomized, double-masked trial. Participants: 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). Main Outcome Measures: 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 mm2 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. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

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