Efficacy Of The Systemic Complement Inhibitor Eculizumab In AMD Patients With Drusen: The COMPLETE Study

Abstract

 

Purpose:

 

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).

 

Methods:

 

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.

 

Results:

 

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.

 

Conclusions:

 

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.

 

Clinical Trial:

 

http://www.clinicaltrials.gov NCT00935883

 

Keywords: age-related macular degeneration • clinical (human) or epidemiologic studies: treatment/prevention assessment/controlled clinical trials