Effect of Intravitreally Administered AIV007 in Subjects With Neovascular Age-Related Macular Degeneration

AIV007 is a multiple kinase inhibitor of vascular endothelial growth factor receptors (VEGFR 1, -2 & -3); fibroblast growth factor receptors (FGFR-1, -2, -3 & -4); and platelet-derived growth factor receptors (PDGFR-α & β)1. Lenvatinib is the active pharmaceutical ingredient in AIV007 formulation that is FDA-approved for oral administration for patients with advanced renal cell carcinoma (RCC), differentiated thyroid cancer (DTC), unresectable hepatocellular carcinoma (HCC), and advanced endometrial carcinoma (Lenvima USPI 2021; NDA 206947). AIV007 is a novel, thermoresponsive gel suspension for intravitreal administration proposed to form a durable depot inside the eye. This monotherapy is being evaluated for the treatment of retinal and choroidal vascular disease. A single intravitreal treatment in 3 subjects was evaluated using 2 doses to evaluate depot formation, safety and biological activity by measuring visual acuity, reduction in retinal fluids associated with vision and effects of fibrosis.

Inclusion criteria

• Male or female subjects aged ≥ 50 years
• Subjects must provide written informed consent before any study-related procedures are performed
• Active subfoveal CNV in the study eye secondary to AMD that has previously been treated with at least 3 intravitreal injections of an anti-VEGF agent
• BCVA in the study eye

• Sentinel subjects only: 65 ETDRS letters (20/50 Snellen equivalent) or worse
• All other subjects: 78 to 35 ETDRS letters (20/32 to 20/200 Snellen equivalent)
• Clear ocular media and adequate pupil dilation in both eyes to permit good quality photographic imaging

Exclusion criteria

• Previous treatment for nAMD in the study eye, other than standard-of-care anti- VEGF IVT injection, eg, cell therapy, brachytherapy, gene therapy
• Treatment with anti-VEGF in the non-study eye 2 weeks prior to baseline
• Presence of diabetic retinopathy or glaucoma in either eye
• Spherical equivalent for refractive error in the study eye of worse than 8.0 diopters of myopia (prior to cataract or refractive surgery)
• Presence of active infection or inflammation within 30 days prior to screening
• Presence of contraindications to anti-VEGF treatment, including myocardial infarction, any cardiac event requiring hospitalization, treatment for acute congestive heart failure, transient ischemic attack, or stroke within the last 3 months of baseline
• Uncontrolled hypertension or diabetes mellitus