Randomized Phase IIb Study of Brimonidine Drug Delivery System Generation 2 for Geographic Atrophy in Age-Related Macular Degeneration
Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:7 |
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| Enthalten in: |
Ophthalmology. Retina - 7(2023), 7 vom: 12. Juli, Seite 573-585 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Freeman, William R [VerfasserIn] |
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| Links: |
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| Themen: |
Age-related macular degeneration |
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| Anmerkungen: |
Date Completed 10.07.2023 Date Revised 16.11.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.oret.2023.03.001 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM354118064 |
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| 100 | 1 | |a Freeman, William R |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Randomized Phase IIb Study of Brimonidine Drug Delivery System Generation 2 for Geographic Atrophy in Age-Related Macular Degeneration |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Completed 10.07.2023 | ||
| 500 | |a Date Revised 16.11.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a 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) | ||
| 520 | |a DESIGN: A phase IIb, randomized, multicenter, double-masked, sham-controlled, 30-month study (BEACON) | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosures may be found after the references | ||
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a Clinical Trial, Phase II | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Age-related macular degeneration | |
| 650 | 4 | |a Brimonidine | |
| 650 | 4 | |a Geographic atrophy | |
| 650 | 4 | |a Implant | |
| 650 | 4 | |a Nonexudative | |
| 700 | 1 | |a Bandello, Francesco |e verfasserin |4 aut | |
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| 700 | 1 | |a Patel, Sunil S |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Kimmie |e verfasserin |4 aut | |
| 700 | 1 | |a López, Francisco J |e verfasserin |4 aut | |
| 700 | 0 | |a BEACON Study Group |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Fred |e investigator |4 oth | |
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| 700 | 1 | |a Souied, Eric |e investigator |4 oth | |
| 700 | 1 | |a Holz, Frank |e investigator |4 oth | |
| 700 | 1 | |a Ziemssen, Focke |e investigator |4 oth | |
| 700 | 1 | |a Bandello, Francesco |e investigator |4 oth | |
| 700 | 1 | |a Campos, Emilio |e investigator |4 oth | |
| 700 | 1 | |a GrignoloEandi, Chiara |e investigator |4 oth | |
| 700 | 1 | |a Midena, Edoardo |e investigator |4 oth | |
| 700 | 1 | |a Peiretti, Enrico |e investigator |4 oth | |
| 700 | 1 | |a Staurenghi, Giovanni |e investigator |4 oth | |
| 700 | 1 | |a Viola, Francesco |e investigator |4 oth | |
| 700 | 1 | |a Bailey, Clare |e investigator |4 oth | |
| 700 | 1 | |a Esposti, Simona Degli |e investigator |4 oth | |
| 700 | 1 | |a Jackson, Timothy |e investigator |4 oth | |
| 700 | 1 | |a Menon, Geeta |e investigator |4 oth | |
| 700 | 1 | |a Pagliarini, Sergio |e investigator |4 oth | |
| 700 | 1 | |a Quhill, Fahd |e investigator |4 oth | |
| 700 | 1 | |a Antoszyk, Andrew |e investigator |4 oth | |
| 700 | 1 | |a Brooks, Logan |e investigator |4 oth | |
| 700 | 1 | |a Callanan, David |e investigator |4 oth | |
| 700 | 1 | |a Csaky, Karl |e investigator |4 oth | |
| 700 | 1 | |a Edwards, Albert |e investigator |4 oth | |
| 700 | 1 | |a Eichenbaum, David |e investigator |4 oth | |
| 700 | 1 | |a Freeman, William |e investigator |4 oth | |
| 700 | 1 | |a Garg, Sunir |e investigator |4 oth | |
| 700 | 1 | |a Ghuman, Avtar Thomas |e investigator |4 oth | |
| 700 | 1 | |a Gonzalez, Victor |e investigator |4 oth | |
| 700 | 1 | |a Gupta, Sunil |e investigator |4 oth | |
| 700 | 1 | |a Hamilton, Richard |e investigator |4 oth | |
| 700 | 1 | |a Khurana, Rahul |e investigator |4 oth | |
| 700 | 1 | |a Kunimoto, Derek |e investigator |4 oth | |
| 700 | 1 | |a Kuppermann, Baruch |e investigator |4 oth | |
| 700 | 1 | |a Lauer, Andreas |e investigator |4 oth | |
| 700 | 1 | |a Lee, Seong Young |e investigator |4 oth | |
| 700 | 1 | |a Maturi, Raj |e investigator |4 oth | |
| 700 | 1 | |a Patel, Sunil |e investigator |4 oth | |
| 700 | 1 | |a Reddy, Rahul |e investigator |4 oth | |
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| 700 | 1 | |a Rivellese, Mark |e investigator |4 oth | |
| 700 | 1 | |a Rose, Steven |e investigator |4 oth | |
| 700 | 1 | |a Segal, Zachary |e investigator |4 oth | |
| 700 | 1 | |a Wong, Robert |e investigator |4 oth | |
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