A First-in-human Trial of SZN-8141 in Diabetic Macular Edema

DUET (Cl-8141-1001) is a first-in-human clinical trial evaluating the safety, tolerability, pharmacokinetics (how the body processes the study drug), and preliminary biological activity of SZN-8141 in people with diabetic macular edema (DME). In this study, small groups of participants with DME (approximately three participants per dose group) will receive a single injection of SZN-8141 into the eye and will be followed for approximately 3 months. During the trial, participants will undergo regular assessments to monitor their overall health and eye condition. These assessments include eye examinations, vision testing, retinal imaging, laboratory testing, and blood sample collection to measure levels of SZN-8141 in the bloodstream and to assess whether the body develops anti-drug antibodies. The trial uses an ascending-dose design, in which successive groups of participants receive increasing dose levels of SZN-8141. Safety and tolerability data from each dose group will be reviewed before the next higher dose level is evaluated.

Inclusion Criteria: * Be willing and able to understand the study procedures and the risks involved and provide written informed consent before the first study-related activity * Age ≥18 years and ≤90 years old * Documented diagnosis of diabetes mellitus (type 1 or 2), as defined by the American Diabetes Association or per World Health Organization (WHO) criteria * Hemoglobin A1C (HbA1c) of ≤12% for ≤60 days before Day 1 * Macular thickening secondary to DME involving the center of the fovea with CST ≥325 μm on OCT as determined by the central reading center at the screening visit * Adequately clear ocular media and adequate pupillary dilation to allow acquisition of good quality retinal images * BCVA of 73-25 ETDRS letters inclusive (20/40-20/200 approximate Snellen equivalent), using the ETDRS protocol at the initial testing distance of 4 m on Day 1 * Treatment naïve and previously treated participants with protocol specified drug washout Exclusion Criteria: * Be pregnant or breastfeeding * Active cancer within the past 12 months * Stroke (cerebral vascular accident) or myocardial infarction \