Impact of Baseline Characteristics on Geographic Atrophy Progression in the FILLY Trial Evaluating the Complement C3 Inhibitor Pegcetacoplan

center dot PURPOSE: To evaluate the effect of select baseline characteristics on geographic atrophy (GA) progression in eyes receiving intravitreal pegcetacoplan or sham. center dot DESIGN: Phase 2 multicenter, randomized, single masked, sham-controlled trial. center dot METHODS: Patients with GA received 15 mg pegcetacoplan monthly or every other month (EOM), or sham injection monthly or EOM for 12 months. Primary efficacy endpoint was change in GA lesion size (square root) from baseline. Post hoc analysis evaluated the effects of age; gender; lesion size, focality, and location (extrafoveal vs foveal); pseudodrusen status; best-corrected visual acuity (BCVA); and low-luminance deficit (LLD) on GA progression at Month 12. center dot RESULTS: Of 246 randomized patients, 192 with 12 month data were included in this analysis. Overall mean (standard deviation) change in lesion size (mm) was 0.26 (0.17) ( P < .01), 0.27 (0.27) ( P < .05), and 0.36 (0.21) in the monthly pegcetacoplan (n = 67), EOM pegcetacoplan (n = 58), and sham (n = 67) groups, respectively. In univariate analysis, patients with extrafoveal lesions ( P < .001), BCVA >20/60 ( P = .001), and larger LLD ( P = .002) had greater mean changes in lesion size. Multivariate analysis confirmed significant association of extrafoveal lesions ( P = .001) and larger LLD ( P = .023)& nbsp; with GA progression. Monthly and EOM pegcetacoplan significantly reduced progression ( P < .05) when controlling for these risk factors. center dot CONCLUSIONS: Extrafoveal lesions and larger LLD are potential risk factors for GA progression. Pegcetacoplan treatment significantly controlled GA progression even after accounting for these risk factors. (Am J Ophthalmol 2021;227: 116-124. (c) 2021 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC ND license ( http://creativecommons.org/licenses/by-ncnd/4.0/ ))