Randomized Phase IIb Study of Brimonidine Drug Delivery System Generation 2 for Geographic Atrophy in Age-Related Macular Degeneration.

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 mm and ≤ 18 mm 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 mm/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) mm with Brimo DDS (n = 84) versus 3.48 (0.13) mm with sham (n = 91), a reduction of 0.25 mm (7%) with Brimo DDS compared with sham (P = 0.150). At month 30, GA area change from baseline was 4.09 (0.15) mm with Brimo DDS (n = 49) versus 4.52 (0.15) mm with sham (n = 46), a reduction of 0.43 mm (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.