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

Ophthalmology. 2014 Mar;121(3):693-701. doi: 10.1016/j.ophtha.2013.09.044. Epub 2013 Nov 26.


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.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • C-Reactive Protein / metabolism
  • Complement C5 / antagonists & inhibitors*
  • Creatinine / blood
  • Disease Progression
  • Double-Blind Method
  • Eye Proteins / genetics
  • Female
  • Fluorescein Angiography
  • Geographic Atrophy / diagnosis
  • Geographic Atrophy / drug therapy*
  • Geographic Atrophy / genetics
  • Humans
  • Infusions, Intravenous
  • Male
  • Polymorphism, Single Nucleotide
  • Prospective Studies
  • Tomography, Optical Coherence
  • Treatment Outcome
  • Visual Acuity / physiology


  • Antibodies, Monoclonal, Humanized
  • Complement C5
  • Eye Proteins
  • C-Reactive Protein
  • eculizumab
  • Creatinine