Systemic Complement Inhibition With Eculizumab For The Treatment Of Geographic Atrophy In AMD Patients: The Complete Study

Abstract

 

Purpose:

 

Aberrant regulation of the complement system has been implicated as a cause of AMD. 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 the growth of geographic atrophy (GA) in patients with age-related macular degeneration (AMD).

 

Methods:

 

Patients with GA measuring from 1.25 mm² to 18 mm² were randomized 2:1 to receive intravenous (IV) eculizumab or a saline placebo. Half of the patients in the eculizumab group received the low dose of eculizumab (600 mg via IV infusion for 4 weeks followed by 900 mg every two weeks until week 26), while the other half received the high dose (900 mg eculizumab via IV infusion for 4 weeks followed by 1200 mg every two weeks until week 26). After 26 weeks, patients were followed without treatment every 3 months for an additional 6 months. Ophthalmologic exam, normal and low luminance ETDRS visual acuity testing, and imaging studies were performed at baseline and months 3, 6, 9, and 12. Primary endpoint was the change in area of GA at 6 months as measured by SDOCT, autofluorescence, and fluorescein angiography. The study was designed with 80% power to detect a 75% reduction in mean enlargement rate at 26 weeks in eyes of patients receiving active treatment. Statistical analyses were performed using two-sample t-tests and ANOVA. Only one eye of each patient was included.

 

Results:

 

30 study eyes of 30 patients were enrolled in the study and randomized 10:10:10 to the low dose: high dose: placebo groups. 19 fellow eyes met entry criteria and were analyzed as a secondary endpoint. At baseline, the mean (SD) lesion areas by SDOCT for the study eyes was 7.3 mm² (4.8) and 4.7 mm² (3.6) in the eculizumab and placebo groups, respectively (p=0.13). Baseline mean (SD) ETDRS acuity was 71.3 (7.8) and 78.6 (5.2) letters for the eculizumab and placebo groups, respectively (p=0.01). Low and high dose eculizumab groups had similar SDOCT areas (p=0.36), but high dose patients read 7 fewer letters (p=0.040). At baseline, the mean (SD) low luminance acuities were 56.1 (11.7) and 48.1 (15.4) letters for the eculizumab and placebo groups, respectively (p=0.16). 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 • imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound)