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Carlos Alexandre A. Garcia Filho, Zohar Yehoshua, Giovanni Gregori, Ying Li, William Feuer, Fernando M. Penha, Srinivas R. Sadda, Li Zhang, Kang Zhang, Philip J. Rosenfeld; Efficacy Of The Systemic Complement Inhibitor Eculizumab In AMD Patients With Drusen: The COMPLETE Study. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2045.
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Aberrant regulation of the complement system has been implicated as a cause of AMD and complement components have been localized within drusen. The COMPLement Inhibition with Eculizumab for the Treatment of Non-Exudative Age-Related Macular Degeneration (COMPLETE) Study was designed to prospectively evaluate the effect of eculizumab, a systemic inhibitor of complement component 5 (C5), on drusen area and volume in patients with age-related macular degeneration (AMD).
In this prospective, double-masked study, patients with drusen in the absence of geographic atrophy were randomized 2:1 to intravenous (IV) eculizumab or placebo in a double masked fashion. 50% of patients in the eculizumab group received a low dose regimen of 600 mg weekly for 4 weeks followed by a maintenance period of 900 mg every two weeks until week 26. The other 50% received a high dose of 900 mg weekly for 4 weeks followed by 1200 mg every two weeks until week 26. The placebo group was infused with saline. Study eyes contained drusen with a volume of at least 0.03 mm3 within a 3 mm diameter circle centered on the fovea using SDOCT imaging. SDOCT drusen volume maps were obtained using the Cirrus instrument (Carl Zeiss Meditec Inc., Dublin, CA), the 200x200 scan pattern, and a proprietary algorithm. Ophthalmologic exams, ETDRS visual acuity, and SDOCT were performed at baseline and at follow-up visits at months 3, 6, 9, and 12. The primary endpoint was the change in drusen volume within a 3mm diameter circle centered on the fovea at 6 months. The study was designed with 80% power to detect a 70% greater incidence of drusen volume decreases at 26 weeks in eyes of patients receiving active treatment. Statistical analyses were performed with two-sample t-tests and ANOVA. Only one eye of each patient was designated as a study eye.
30 eyes of 30 patients were enrolled in the study, and randomized 10:10:10 into each group. 13 fellow eyes met entry criteria and were analyzed as a secondary endpoint. For the 30 study eyes, the mean (SD) drusen areas at baseline in the central 3 mm were 2.1 (1.0) mm2, and 1.9 (SD=0.7) mm2 for eculizumab and placebo groups, respectively (p=0.71). Mean drusen volumes at baseline in the central 3 mm were 0.15 (0.17) mm3 and 0.12 (SD=0.08) mm3 in the eculizumab and placebo groups, respectively (p=0.53). Through 6 months, no drug-related adverse events were identified.
The COMPLETE Study is the first use of systemic complement inhibition for the treatment of dry AMD, and systemic complement inhibition with eculizumab was well tolerated through 6 months. The 6-month outcome data are currently being analyzed and will be presented.
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