A Phase 1, Open-Label, Dose-Escalation Trial to Investigate Safety and Tolerability of Single Intravitreous Injections of ICON-1 Targeting Tissue Factor in Wet AMD.

ABSTRACT

BACKGROUND AND OBJECTIVE: This phase 1 study evaluated the safety and tolerability of single intravitreous injections (IVIs) of ICON-1 (Iconic Therapeutics, South San Francisco, CA) in patients with neovascular age-related macular degeneration (nAMD). ICON-1 is a modified factor VIIa protein linked with the Fc portion of a human immunoglobulin G1. The molecule binds tissue factor overexpressed on choroidal neovascularization (CNV) in AMD. PATIENTS AND METHODS: Open-label, interventional, dose-escalation trial in 18 patients with CNV due to AMD, with six patients per dose cohort. Patients received a single IVI of ICON-1 at baseline in one of three escalating doses 60 µg, 150 µg, or 300 µg. Standard anti-vascular endothelial growth factor treatment was allowed at the investigator's discretion at least 2 weeks after the ICON-1 injection; patients were followed up to 24 weeks. Dose escalation was based on the absence of significant safety events. At each study visit, best-corrected visual acuity (BCVA), ophthalmic examination (intraocular pressure, slit-lamp, and dilated fundus examination), and ophthalmic imaging (color fundus photography, fluorescein angiography, and optical coherence tomography) assessments were performed. The systemic pharmacokinetics of ICON-1 and presence of anti-ICON-1 antibodies were also assessed. RESULTS: ICON-1 was safe and well-tolerated up to the highest dose administered, which was 300 µg. Commonly reported adverse events were considered related to the IVI procedure or to the underlying nAMD. No significant systemic levels of ICON-1 or anti-ICON-1 antibodies were detected. Preliminary evidence of biological activity (improved BCVA, reduced central retinal thickness, decreased CNV size, and leakage) was most evident with the 300 µg dose at 1 to 2 weeks after the single ICON-1 injection. CONCLUSION: Intravitreous administration of ICON-1 in single doses up to 300 µg in eyes with neovascular AMD was safe and well-tolerated. [Ophthalmic Surg Lasers Imaging Retina. 2018;49336-345.].