title: Systemic complement inhibition with eculizumab for geographic atrophy in age-related macular degeneration: the COMPLETE study.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  Prospective, double-masked, randomized clinical trial.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Zohar
authors.initials: Z
authors.lastname: Yehoshua
authors.affiliation: Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida; Department of Ophthalmology, Federal University of Säo Paulo, UNIFESP, São Paulo, Brazil.
authors.forename: Carlos Alexandre
authors.initials: CA
authors.lastname: de Amorim Garcia Filho
authors.affiliation: Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Renata Portella
authors.initials: RP
authors.lastname: Nunes
authors.affiliation: Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Gregori
authors.affiliation: Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida; Department of Ophthalmology, Federal University of Säo Paulo, UNIFESP, São Paulo, Brazil.
authors.forename: Fernando M
authors.initials: FM
authors.lastname: Penha
authors.affiliation: Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Moshfeghi
authors.affiliation: Institute for Genomic Medicine and Shiley Eye Center, University of California, San Diego, La Jolla, California.
authors.forename: Kang
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Doheny Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, California.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Sadda
authors.affiliation: Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: William
authors.initials: W
authors.lastname: Feuer
authors.affiliation: Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida. Electronic address: prosenfeld@med.miami.edu.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Rosenfeld
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000378:metabolism; D003182:Complement C5 / Q000037:antagonists & inhibitors*; D003404:Creatinine / Q000097:blood; D018450:Disease Progression; D004311:Double-Blind Method; D005136:Eye Proteins / Q000235:genetics; D005260:Female; D005451:Fluorescein Angiography; D057092:Geographic Atrophy / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D041623:Tomography, Optical Coherence; D016896:Treatment Outcome; D014792:Visual Acuity / Q000502:physiology
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D003182:Complement C5; D005136:Eye Proteins; D002097:C-Reactive Protein; C481642:eculizumab; D003404:Creatinine