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

Am J Ophthalmol. 2021 Jul:227:116-124. doi: 10.1016/j.ajo.2021.02.031. Epub 2021 Mar 3.

Abstract

Purpose: To evaluate the effect of select baseline characteristics on geographic atrophy (GA) progression in eyes receiving intravitreal pegcetacoplan or sham.

Design: Phase 2 multicenter, randomized, single-masked, sham-controlled trial.

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.

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) with GA progression. Monthly and EOM pegcetacoplan significantly reduced progression (P < .05) when controlling for these risk factors.

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.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Complement C3 / antagonists & inhibitors*
  • Complement Inactivating Agents / therapeutic use*
  • Disease Progression
  • Female
  • Geographic Atrophy / diagnosis
  • Geographic Atrophy / drug therapy*
  • Geographic Atrophy / physiopathology
  • Humans
  • Intravitreal Injections
  • Male
  • Middle Aged
  • Peptides, Cyclic / therapeutic use*
  • Prospective Studies
  • Single-Blind Method
  • Treatment Outcome
  • Vision Disorders / physiopathology
  • Visual Acuity / physiology

Substances

  • C3 protein, human
  • Complement C3
  • Complement Inactivating Agents
  • Peptides, Cyclic
  • pegcetacoplan