Abstract
Purpose: :
Currently, no effective treatment is available for vision loss associated with geographic atrophy. NT-501 protects photoreceptors in a number of animal models. The purpose of the present study is to evaluate the safety and efficacy of NT-501 in a multi-center, double-masked, controlled, dose-ranging and randomized phase 2 trial for geographic atrophy associated with dry AMD.
Methods: :
The CNTF study consists of 48 participants that were randomized in a 2:1:1 ratio to receive an intravitreal high or low dose CNTF implant, or to sham surgery, respectively. BCVA was measured by an Electronic Visual Acuity Tester (EVA) using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol, retinal thickness was measured by time domain optical coherence tomography (OCT) at 4, 6, and 12, and 18 mos. and lesion size was measured by fundus photography at 12 and 18 mos. following implant placement. CNTF release from explanted implants was measured by ELISA.
Results: :
Visual function was stabilized, as measured by 15-letter loss, in the high dose-treated group compared to sham and low dose groups at 12 and 18 months. Among eyes with starting BCVA 20/63, the mean BCVA in the high dose group was 10.5 and 10.0 letters greater than the low dose/sham group at 12 months and 18 months respectively, a difference that was statistically significant at 12 months (p=0.03). Stabilized visual acuity was accompanied by corresponding structural changes; CNTF treatment resulted in a dose-dependent increase in retinal thickness as early as 4 months post-implant and this increase was maintained through 6, 12 and 18 months (p<0.001). GA lesion area growth rate was reduced in treated eyes compared to fellow eyes at 12 and 18 months. Both the NT-501 implant and the implant procedure were well tolerated; no serious adverse events associated with the implant or implantation procedure were reported. The explanted devices showed healthy cells and stable CNTF output up to 18 months.
Conclusions: :
CNTF delivered by intraocular ECT implant stabilized visual acuity and increased retinal thickness without serious adverse events, in eyes with geographic atrophy associated with non-neovascular AMD. These data support next stage clinical studies in a larger patient population.
Clinical Trial: :
www.clinicaltrials.gov NCT00447954
Keywords: age-related macular degeneration • clinical (human) or epidemiologic studies: treatment/prevention assessment/controlled clinical trials