Effect of AIV007 by Periocular Administration in Subjects with Macular Edema Secondary to Neovascular Age-related Macular Degeneration (nAMD) and Diabetic Macular Edema (DME)

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).

AiViva BioPharma, Inc. (AiViva) has developed a novel, thermoresponsive gel suspension of AIV007 for periocular administration to form a durable depot. This monotherapy is in development for the treatment of retinal and choroidal vascular disease (i.e., neovascular age-related macular degeneration (nAMD) & diabetic macular edema (DME)). For preclinical and clinical (AIV007-E02) studies using periocular administration, AIV007 is injected outside the eyeball and the depot forms a soft mass, referred to as posterior juxtascleral depot (PJD) placement.

Inclusion criteria

General inclusion Criteria:

• Male or female subjects aged 21-90 years (inclusive) at screening
• BCVA in the study eye at screening and baseline/Day 1: ETDRS letter score ≤ 75 and ≥ 24 (20/32 to 20/330 Snellen equivalent)
• Subject must have received treatment within the 24 months before screening with intravitreal (IVT) injections of an anti-VEGF agent with the last anti-VEGF injection in the study eye being at least 6 weeks (42 days) before baseline/Day 1.
• Subject has documentation of anti-VEGF responsiveness
• Subject must provide written informed consent before any study-related procedures are performed
• Clear ocular media and adequate pupil dilation in both eyes to permit good-quality photographic imaging

nAMD subject

• The active CNV is confirmed by FA (evidence of leakage)
• Residual intraretinal or subretinal fluid based on SD-OCT
• CST ≥ 300 µm as assessed by SD-OCT
• Total lesion size < 10 disc areas (25.4 mm2)
• Absence of geographic atrophy within 200 µm of the fovea
• If subretinal hemorrhage is present, it must be < 50% of the total CNV lesion and/or not involve the fovea
• If fibrosis is present, it must be <50% of the total lesion area

DME subject

• Diagnosis of diabetes mellitus (Type 1 or Type 2)
• Subject has clinically significant DME with central involvement (CST≥300 μm by OCT)
• The decrease in vision in the study eye was determined by the investigator to be primarily the result of DME

Exclusion criteria

• Previous treatment for nAMD or DME in the study eye other than standard-of-care anti-VEGF IVT injection, e.g., cell therapy, brachytherapy, gene therapy
• Uncontrolled IOP, defined as an IOP > 25 mmHg
• Poorly controlled diabetes mellitus defined as hemoglobin A1c (HbA1c) >10% at screening visit
• The spherical equivalent for refractive error in the study eye of worse than 8.0 diopters of myopia (before cataract or refractive surgery) per the current prescription
• Any history of active bacterial, viral, fungal, or parasitic ocular or periocular infection, or intraocular inflammation in either eye within the 30 days before the screening Visit
• History of vitreous hemorrhage within 3 months before screening in the study eye
• Uncontrolled systemic disease or any other condition or therapy that would make the participant unsuitable for the study
• Participation in any investigational study within 60 days before the screening visit, or planned use of an investigational product or device during the study; any exposure to a prior investigational drug product must be fully washed out (at least 5 half-lives)
• History of allergy or hypersensitivity to constituents of the study treatment formulation, topical iodine, ocular antimicrobial solutions, or clinically relevant hypersensitivity to fluorescein