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 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

Baseline characteristics.

BackgroundVitreous hemorrhage from proliferative diabetic retinopathy can cause severe vision loss. DRCR Retina Network Protocol AB was a randomized clinical trial comparing intravitreal aflibercept versus vitrectomy with panretinal photocoagulation and found no difference in the average rate of visual recovery over 104 weeks. Herein, we describe patient-reported outcome measures from Protocol AB.MethodsSecondary analysis of a multicenter (39 sites) randomized clinical trial. The Work Productivity and Activity Impairment Questionnaire was administered at 4, 12, 24, 36, 52, 68, 84, and 104 weeks. Main outcomes were mean change in activity impairment and work productivity loss over 24 and 104 weeks (area under the curve).ResultsMean (SD) activity impairment at baseline was 58% (27%) in the aflibercept group (N = 99) and 56% (30%) in the vitrectomy group (N = 105). The mean reduction in activity impairment from baseline over 24 weeks was 21% (25%) in the aflibercept group and 27% (31%) in the vitrectomy group (adjusted difference = -6.8% [95% CI, -12.7% to -0.9%], P = .02); over 104 weeks, the adjusted mean difference was -3.1% (95% CI, -9.2% to 3.0%, P = .31). Mean work productivity loss at baseline was 51% (28%) in the aflibercept group (N = 44) and 58% (30%) in the vitrectomy group (N = 43). The mean reduction in work productivity loss from baseline over 24 weeks (area under the curve) was 19% (23%) in the aflibercept group and 31% (24%) in the vitrectomy group (adjusted difference = -8.3% [95% CI, -16.8% to 0.2%], P = .06); over 104 weeks, the adjusted mean difference was -9.1% (95% CI, -18.4% to 0.2%, P = .05).ConclusionsParticipants with vitreous hemorrhage from proliferative diabetic retinopathy had less activity impairment over 24 weeks when treated initially with vitrectomy and panretinal photocoagulation versus intravitreal aflibercept. The trend was similar for work productivity but not statistically significant. By 104 weeks, the improvements were similar in the two treatment groups.Trial registrationClinicalTrials.gov NCT02858076.</div

Activity impairment by visual acuity in the better-seeing eye at baseline.

Mean change in activity impairment from baseline over 104 weeks by baseline visual acuity in the better-seeing eye. Error bars represent 95% confidence intervals.</p

Change in activity impairment and work productivity loss from baseline by treatment group over 104 weeks.

Mean change in activity impairment (A) and work productivity loss (B) by treatment group. Error bars represent 95% confidence intervals.</p

Changes in activity impairment and work productivity after treatment for vitreous hemorrhage due to proliferative diabetic retinopathy: Secondary outcomes from a randomized controlled trial (DRCR Retina Network Protocol AB).

BackgroundVitreous hemorrhage from proliferative diabetic retinopathy can cause severe vision loss. DRCR Retina Network Protocol AB was a randomized clinical trial comparing intravitreal aflibercept versus vitrectomy with panretinal photocoagulation and found no difference in the average rate of visual recovery over 104 weeks. Herein, we describe patient-reported outcome measures from Protocol AB.MethodsSecondary analysis of a multicenter (39 sites) randomized clinical trial. The Work Productivity and Activity Impairment Questionnaire was administered at 4, 12, 24, 36, 52, 68, 84, and 104 weeks. Main outcomes were mean change in activity impairment and work productivity loss over 24 and 104 weeks (area under the curve).ResultsMean (SD) activity impairment at baseline was 58% (27%) in the aflibercept group (N = 99) and 56% (30%) in the vitrectomy group (N = 105). The mean reduction in activity impairment from baseline over 24 weeks was 21% (25%) in the aflibercept group and 27% (31%) in the vitrectomy group (adjusted difference = -6.8% [95% CI, -12.7% to -0.9%], P = .02); over 104 weeks, the adjusted mean difference was -3.1% (95% CI, -9.2% to 3.0%, P = .31). Mean work productivity loss at baseline was 51% (28%) in the aflibercept group (N = 44) and 58% (30%) in the vitrectomy group (N = 43). The mean reduction in work productivity loss from baseline over 24 weeks (area under the curve) was 19% (23%) in the aflibercept group and 31% (24%) in the vitrectomy group (adjusted difference = -8.3% [95% CI, -16.8% to 0.2%], P = .06); over 104 weeks, the adjusted mean difference was -9.1% (95% CI, -18.4% to 0.2%, P = .05).ConclusionsParticipants with vitreous hemorrhage from proliferative diabetic retinopathy had less activity impairment over 24 weeks when treated initially with vitrectomy and panretinal photocoagulation versus intravitreal aflibercept. The trend was similar for work productivity but not statistically significant. By 104 weeks, the improvements were similar in the two treatment groups.Trial registrationClinicalTrials.gov NCT02858076