Safety and Tolerability of Intravitreal Carotuximab (DE-122) in Patients With Persistent Exudative Age-Related Macular Degeneration: A Phase I Study

PURPOSE: Carotuximab (DE-122) is a novel endoglin antibody that exhibits potent anti-angiogenic activity. The aim of this study was to evaluate the safety and tolerability of a single intravitreal injection of four ascending doses of carotuximab in patients with persistent exudative age-related macular degeneration (AMD). METHODS: In an open-label, dose-escalating, sequential cohort study, patients with persistent exudative AMD were assigned to an intravitreal injection of carotuximab 0.5 mg, 1.0 mg, 2.0 mg, or 4.0 mg (n = 3 per group). Safety and change in central subfield thickness (CST), as measured by spectral domain–optical coherence tomography, were assessed from baseline until day 90. Rescue therapy with an anti-vascular endothelial growth factor medication was allowed on days 8, 30, and 60. RESULTS: Seven patients (58%) experienced at least one adverse event (AE), including five patients (41.7%) who experienced one or more AEs in the study eye and two patients (16.7%) who experienced one or more non-ocular AEs. Posterior eye deposits were reported in one patient 2 days after receiving 1.0 mg, but they resolved spontaneously by day 43. A >50-µm reduction in CST on two consecutive visits was observed in four patients (33%), including one patient in each dose cohort. CONCLUSIONS: In this study, carotuximab was generally well tolerated, with no serious AEs reported, when administered as a single intravitreal injection to patients with persistent exudative AMD. TRANSLATIONAL RELEVANCE: Further characterization of the safety and efficacy of carotuximab will be needed to determine what role it may have in the treatment of exudative AMD.