AdPEDF Therapy for Subfoveal Choroidal Neovascularization (CNV): Preliminary Phase I Results

Abstract

Abstract: : Purpose: To evaluate the safety and feasibility of intravitreous AdPEDF in patients with subfoveal CNV due to age–related macular degeneration (AMD). Methods: Open label, dose–escalation design with 8 dose levels (10⁶–10^9.5 pu in ½ log increments) in patients with subfoveal CNV ≤ 12 MPS disc areas and best corrected visual acuity of 20/200 or worse in study eye. After a single intravitreous injection of AdPEDF, 1 year follow–up consisted of periodic ocular exams, fluorescein angiograms, and laboratory evaluations including adenovirus neutralizing antibody titers and throat and urine cultures for adenovirus. Optical Coherence Tomography was performed as a substudy at 2 study sites. Results: Six of 8 dose cohorts have been fully enrolled (n=18), and accrual is ongoing. Intravitreous AdPEDF has been well–tolerated and there have been no dose limiting toxicities or related severe adverse events. Three patients (two at 10^7.5 and one at 10^8.5 pu) had mild transient inflammation and Grade 1 elevation in IOP thought to be probably or possibly related to the study drug. Neutralizing antibody titers did not increase at 3 months in 11 out of 12 patients and all adenoviral cultures were negative. Conclusions: Intravitreous injection of up to 10^8.5 pu of AdPEDF is well–tolerated and has not been associated with any serious short–term toxicity.

Keywords: age–related macular degeneration • gene transfer/gene therapy • adenovirus