TY - JOUR
T1 - Randomized Phase IIb Study of Brimonidine Drug Delivery System Generation 2 for Geographic Atrophy in Age-Related Macular Degeneration
AU - BEACON Study Group
AU - Freeman, William R.
AU - Bandello, Francesco
AU - Souied, Eric
AU - Guymer, Robyn H.
AU - Garg, Sunir J.
AU - Chen, Fred K.
AU - Rich, Ryan
AU - Holz, Frank G.
AU - Patel, Sunil S.
AU - Kim, Kimmie
AU - López, Francisco J.
AU - Chen, Fred
AU - Korobelnik, Jean Francois
AU - Holz, Frank
AU - Ziemssen, Focke
AU - Campos, Emilio
AU - GrignoloEandi, Chiara
AU - Midena, Edoardo
AU - Peiretti, Enrico
AU - Staurenghi, Giovanni
AU - Viola, Francesco
AU - Bailey, Clare
AU - Esposti, Simona Degli
AU - Jackson, Timothy
AU - Menon, Geeta
AU - Pagliarini, Sergio
AU - Quhill, Fahd
AU - Antoszyk, Andrew
AU - Brooks, Logan
AU - Callanan, David
AU - Csaky, Karl
AU - Edwards, Albert
AU - Eichenbaum, David
AU - Freeman, William
AU - Garg, Sunir
AU - Ghuman, Avtar Thomas
AU - Gonzalez, Victor
AU - Gupta, Sunil
AU - Hamilton, Richard
AU - Khurana, Rahul
AU - Kunimoto, Derek
AU - Kuppermann, Baruch
AU - Lauer, Andreas
AU - Lee, Seong Young
AU - Maturi, Raj
AU - Patel, Sunil
AU - Reddy, Rahul
AU - Rivellese, Mark
AU - Rose, Steven
AU - Segal, Zachary
N1 - Publisher Copyright:
© 2023 American Academy of Ophthalmology
PY - 2023/7
Y1 - 2023/7
N2 - Purpose: To evaluate the safety and efficacy of repeat injections of Brimonidine Drug Delivery System (Brimo DDS) Generation 2 (Gen 2) containing 400-μg brimonidine in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD). Design: A phase IIb, randomized, multicenter, double-masked, sham-controlled, 30-month study (BEACON). Participants: Patients diagnosed with GA secondary to AMD and multifocal lesions with total area of > 1.25 mm2 and ≤ 18 mm2 in the study eye. Methods: Enrolled patients were randomized to treatment with intravitreal injections of 400-μg Brimo DDS (n = 154) or sham procedure (n = 156) in the study eye every 3 months from day 1 to month 21. Main Outcome Measures: The primary efficacy endpoint was GA lesion area change from baseline in the study eye, assessed with fundus autofluorescence imaging, at month 24. Results: The study was terminated early, at the time of the planned interim analysis, because of a slow GA progression rate (∼ 1.6 mm2/year) in the enrolled population. Least squares mean (standard error) GA area change from baseline at month 24 (primary endpoint) was 3.24 (0.13) mm2 with Brimo DDS (n = 84) versus 3.48 (0.13) mm2 with sham (n = 91), a reduction of 0.25 mm2 (7%) with Brimo DDS compared with sham (P = 0.150). At month 30, GA area change from baseline was 4.09 (0.15) mm2 with Brimo DDS (n = 49) versus 4.52 (0.15) mm2 with sham (n = 46), a reduction of 0.43 mm2 (10%) with Brimo DDS compared with sham (P = 0.033). Exploratory analysis showed numerically smaller loss over time in retinal sensitivity assessed with scotopic microperimetry with Brimo DDS than with sham (P = 0.053 at month 24). Treatment-related adverse events were usually related to the injection procedure. No implant accumulation was observed. Conclusions: Multiple intravitreal administrations of Brimo DDS (Gen 2) were well tolerated. The primary efficacy endpoint at 24 months was not met, but there was a numeric trend for reduction in GA progression at 24 months compared with sham treatment. The study was terminated early because of the lower-than-expected GA progression rate in the sham/control group. Financial Disclosure(s): Proprietary or commercial disclosures may be found after the references.
AB - Purpose: To evaluate the safety and efficacy of repeat injections of Brimonidine Drug Delivery System (Brimo DDS) Generation 2 (Gen 2) containing 400-μg brimonidine in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD). Design: A phase IIb, randomized, multicenter, double-masked, sham-controlled, 30-month study (BEACON). Participants: Patients diagnosed with GA secondary to AMD and multifocal lesions with total area of > 1.25 mm2 and ≤ 18 mm2 in the study eye. Methods: Enrolled patients were randomized to treatment with intravitreal injections of 400-μg Brimo DDS (n = 154) or sham procedure (n = 156) in the study eye every 3 months from day 1 to month 21. Main Outcome Measures: The primary efficacy endpoint was GA lesion area change from baseline in the study eye, assessed with fundus autofluorescence imaging, at month 24. Results: The study was terminated early, at the time of the planned interim analysis, because of a slow GA progression rate (∼ 1.6 mm2/year) in the enrolled population. Least squares mean (standard error) GA area change from baseline at month 24 (primary endpoint) was 3.24 (0.13) mm2 with Brimo DDS (n = 84) versus 3.48 (0.13) mm2 with sham (n = 91), a reduction of 0.25 mm2 (7%) with Brimo DDS compared with sham (P = 0.150). At month 30, GA area change from baseline was 4.09 (0.15) mm2 with Brimo DDS (n = 49) versus 4.52 (0.15) mm2 with sham (n = 46), a reduction of 0.43 mm2 (10%) with Brimo DDS compared with sham (P = 0.033). Exploratory analysis showed numerically smaller loss over time in retinal sensitivity assessed with scotopic microperimetry with Brimo DDS than with sham (P = 0.053 at month 24). Treatment-related adverse events were usually related to the injection procedure. No implant accumulation was observed. Conclusions: Multiple intravitreal administrations of Brimo DDS (Gen 2) were well tolerated. The primary efficacy endpoint at 24 months was not met, but there was a numeric trend for reduction in GA progression at 24 months compared with sham treatment. The study was terminated early because of the lower-than-expected GA progression rate in the sham/control group. Financial Disclosure(s): Proprietary or commercial disclosures may be found after the references.
KW - Age-related macular degeneration
KW - Brimonidine
KW - Geographic atrophy
KW - Implant
KW - Nonexudative
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U2 - 10.1016/j.oret.2023.03.001
DO - 10.1016/j.oret.2023.03.001
M3 - Article
C2 - 36906177
AN - SCOPUS:85153177511
SN - 2468-7219
VL - 7
SP - 573
EP - 585
JO - Ophthalmology Retina
JF - Ophthalmology Retina
IS - 7
ER -