PURPOSE: Geographic atrophy (GA), a late stage of age-related macular 
degeneration (AMD), is a major cause of blindness. Even while central visual 
acuity remains relatively well preserved, GA often causes considerable 
compromise of visual function and quality of life. No treatment currently 
exists. We evaluated the safety and efficacy of pegcetacoplan, a complement C3 
inhibitor, for treatment of GA.
DESIGN: Prospective, multicenter, randomized, sham-controlled phase 2 study.
PARTICIPANTS: Two hundred forty-six patients with GA.
METHODS: Patients with GA were assigned randomly in a 2:2:1:1 ratio to receive 
intravitreal injections of 15 mg pegcetacoplan monthly or every other month 
(EOM) or sham intravitreal injections monthly or EOM for 12 months with 
follow-up at months 15 and 18. Area and growth of GA were measured using fundus 
autofluorescence imaging.
MAIN OUTCOME MEASURES: The primary efficacy end point was mean change in square 
root GA lesion area from baseline to month 12. Secondary outcome measures 
included mean change from baseline in GA lesion area without the square root 
transformation, distance of GA lesion from the fovea, best-corrected visual 
acuity (BCVA), low-luminance BCVA, and low-luminance visual acuity deficit. The 
primary safety end point was the number and severity of treatment-emergent 
adverse events.
RESULTS: In patients receiving pegcetacoplan monthly or EOM, the GA growth rate 
was reduced by 29% (95% confidence interval [CI], 9-49; P = 0.008) and 20% (95% 
CI, 0-40; P = 0.067) compared with the sham treatment group. Post hoc analysis 
showed that the effect was greater in the second 6 months of treatment, with 
observed reductions of 45% (P = 0.0004) and 33% (P = 0.009) for pegcetacoplan 
monthly and EOM, respectively. Two cases of culture-positive endophthalmitis and 
1 case of culture-negative endophthalmitis occurred in the pegcetacoplan monthly 
group. New-onset investigator-determined exudative AMD was reported more 
frequently in pegcetacoplan-treated eyes (18/86 eyes [20.9%] and 7/79 eyes 
[8.9%] in monthly and EOM groups, respectively) than in sham-treated eyes (1/81 
eyes [1.2%]).
CONCLUSIONS: Local C3 inhibition with pegcetacoplan resulted in statistically 
significant reductions in the growth of GA compared with sham treatment. Phase 3 
studies will define the efficacy and safety profile further.