Systemic complement inhibition with eculizumab for geographic atrophy in age-related macular degeneration: the COMPLETE study

Abstract

Purpose: To evaluate the effect of eculizumab, a systemic inhibitor of complement component (C5), on the growth of geographic atrophy (GA) in patients with age-related macular degeneration (AMD).

Design: Prospective, double-masked, randomized clinical trial.

Participants: Patients with GA measuring from 1.25 to 18 mm(2) based on spectral-domain optical coherence tomography imaging.

Methods: Patients were randomized 2:1 to receive intravenous eculizumab or placebo over 6 months. In the eculizumab treatment arm, the first 10 patients received a low-dose regimen of 600 mg weekly for 4 weeks followed by 900 mg every 2 weeks until week 24, and the next 10 patients received a high-dose regimen of 900 mg weekly for 4 weeks followed by 1200 mg every 2 weeks until week 24. The placebo group was infused with saline. Patients were observed off treatment for an additional 26 weeks. Both normal-luminance and low-luminance visual acuities were measured throughout the study, and the low-luminance deficits were calculated as the difference between the letter scores.

Main outcome measures: Change in area of GA at 26 weeks.

Results: Thirty eyes of 30 patients were enrolled. Eighteen fellow eyes also met inclusion criteria and were analyzed as a secondary endpoint. For the 30 study eyes, mean square root of GA area measurements ± standard deviation at baseline were 2.55 ± 0.94 and 2.02 ± 0.74 mm in the eculizumab and placebo groups, respectively (P = 0.13). At 26 weeks, GA enlarged by a mean of 0.19 ± 0.12 and 0.18 ± 0.15 mm in the eculizumab and placebo groups, respectively (P = 0.96). At 52 weeks of follow-up, GA enlarged by a mean of 0.37 ± 0.22 mm in the eculizumab-treated eyes and by a mean of 0.37 ± 0.21 mm in the placebo group (P = 0.93, 2 sample t test). None of the eyes converted to wet AMD. No drug-related adverse events were identified.

Conclusions: Systemic complement inhibition with eculizumab was well tolerated through 6 months but did not decrease the growth rate of GA significantly. However, there was a statistically significant correlation between the low-luminance deficit at baseline and the progression of GA over 6 months.

Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

Graphs showing the growth of geographic atrophy over 52 weeks in patients receiving the eculizumab versus placebo. Outcomes (A and C) for the study eyes and (B and D) the pooled study eyes and fellow eyes, outcomes for (A and B) the placebo and all the active treatment arms, outcomes for (C and D) the low-dose and high-dose treatment arms, as well as the placebo arms, for study eyes and fellow eyes that met inclusion criteria.

Figure 2

Images from the left eye of a 73-year-old woman included in the low-dose group with growth in the area of geographic atrophy over 52 weeks. (A,D,G) Color fundus images obtained at baseline, 26 weeks, and 52 weeks, respectively. (B,E,H) Fundus autofluorescence images (Heidelberg Spectralis) obtained at baseline, 26 weeks, and 52 weeks, respectively. (C,F,I) Sub-retinal pigment epithelium slab en face image generated from spectral-domain optical coherence tomography datasets (Zeiss Cirrus) at baseline, 26 weeks, and 52 weeks, respectively. Area measurements were (C) 8.26 mm2 at baseline, (F) 9.47 mm2 at 26 weeks, and (I) 10.88 mm2 at 52 weeks.

Figure 4

Graph showing the relationship between low-luminance visual acuity deficit at baseline and growth of the square root of the area of geographic atrophy over (A) 26 weeks and (B) 52 weeks. Both study eyes (30 eyes) and fellow eyes (18 eyes) that met inclusion criteria are shown. For 26 weeks, r 0.38 and P ¼ 0.008; for 52 weeks, r = 0.41 and P = 0.004.