A Phase I Study of GenSci148 Intravitreal Injection for Neovascular Age-related Macular Degeneration, Diabetic Macular Edema and Retinal Vein Occlusion

This is a Phase I, multicenter, open-label, dose-escalation study conducted in 2 parts to evaluate the safety, tolerability, PK and PD profiles, and immunogenicity, as well as the preliminary efficacy of intravitreal injection of GenSci148 in participants with nAMD, DME and RVO.

Part 1 (Single Ascending Dose, SAD): Conducted in participants with nAMD. Four dose levels (1 mg/eye, 3 mg/eye, 7 mg/eye, and 10 mg/eye) are planned, administered via a single IVT injection. Dose escalation is determined by the Safety Review Committee (SRC) based on safety, tolerability, PK, PD, and other available data.

Part 2 (Multiple Ascending Dose, MAD): Conducted in participants with nAMD, DME, and RVO. Three dose levels (low, medium, and high) are planned. Participants will receive multiple IVT injections according to the study schedule. Disease activity assessment will be performed during follow-up, and participants meeting retreatment criteria may receive additional doses of GenSci148.

Safety assessments include adverse events, physical examinations, laboratory tests, vital signs, ECG, and ophthalmic examinations (BCVA, IOP, slit-lamp examination, , etc.). PK/PD and immunogenicity samples are collected at predefined time points.

Inclusion criteria

• Able to understand the study and provide written informed consent prior to any study-related procedures.
• Willing and able to comply with scheduled visits, treatment plan, and study procedures.
• Best corrected visual acuity (BCVA) of 24 to 78 letters (inclusive) in the study eye, and BCVA ≥ 24 letters in the fellow eye.

Exclusion criteria

• Prior or current contraindicated ophthalmic treatments in study or fellow eye per protocol.
• Refractive error > ±8.0 diopters in the study eye.
• Anterior segment neovascularization or vitreous hemorrhage in the study eye.