Abstract
Purpose: :
To determine if treatment with OT-551 reduces progression of the the area of geographic atrophy (GA) in subjects with GA associated with age-related macular degeneration (AMD).
Methods: :
A randomized, double-masked, multi-center, placebo-controlled, clinical trial of OT-551 (0.3% & 0.45%) in 137 subjects with GA was performed. The study eye was required to have ≥1 discrete areas of GA of ≥1.3 mm2 (0.5 disc area [DA]) and a total GA area of 1.3 to 17.8 mm2 (0.5 - 7.0 DA) that is within 3000 microns of the foveal center. Topical OT-551 was administered to only one qualifying eye 4X daily for up to 2 years. Visits were scheduled at screening, baseline (BL), and at 1, 3, 6, 9, 12, 15, 18, 21 & 24 months. Efficacy outcomes included changes from BL in total area of GA and best-corrected visual acuity (BCVA) score. Safety measures were assessed by complete ophthalmologic examination and review of ocular and systemic adverse events (AEs).
Results: :
At BL, the mean (median) area of GA in study eyes from digital fluorescein angiograms was 6.17 (6.26) mm2 in the vehicle placebo group, 6.26 (5.72) mm2 in the OT-551 0.3% group, and 6.04 (5.11) mm2 in the OT-551 0.45% group. At month 18, mean (median) changes from BL of +3.55 (+3.08)mm2 in the placebo group, +3.01 (+2.91) mm2 in the OT-551 0.3% group, and +3.43 (+2.70) mm2 in the OT-551 0.45% group were observed. Mean (median) changes in BCVA at 18 months in study eyes were -4.9 (-3.0) letters in the placebo group, -8.9 (-6.0) letters in the OT-551 0.3% group, and -7.7 (-5.0) letters in the OT-551 0.45% group. The proportion of subjects losing ≥15 letters at month 18 was 16% in the placebo group, 20% in the OT-551 0.3% group and 21% in the OT-551 0.45% group. Most reported AEs were non-serious, mild in severity, and occurred at a low incidence (<5%). All serious AEs were non-ocular and none were related to the study drug.
Conclusions: :
While concentrations of OT-551 up to 0.45% appear to be safe when dosed 4X daily for up to two years, OT-551 does not appear to reduce the progression of the area of GA in subjects with AMD.
Clinical Trial: :
www.clinicaltrials.gov NCT00485394
Keywords: age-related macular degeneration • clinical (human) or epidemiologic studies: treatment/prevention assessment/controlled clinical trials • antioxidants