Safety and Efficacy Evaluation of SMZ1 With Ranibizumab in Patients With Neovascular Age-related Macular Degeneration Without Polypoidal Choroidal Vasculopathy

A 12-month, Randomization, Double-blind, Placebo-controlled, Parallel, Multicenter-Phase 3 Trial to Evaluate the Safety and Efficacy of SMZ1 Tablet in Combination With Ranibizumab in Patients With Neovascular Age-related Macular Degeneration Without Polypoidal Choroidal Vasculopathy

The purpose of this study is to evaluate the efficacy and safety of SMZ1 tablets in combination with Ranibizumab compared with placebo in combination with Ranibizumab in subjects with neovascular (wet) age-related macular degeneration (nAMD) without polypoidal choroidal vasculopathy (PCV). The primary objective is to demonstrate the superiority of SMZ1 tablets over placebo with respect to improvement in best-corrected visual acuity at Month 12.

Inclusion Criteria:

• 50 years of age or older

• A study eye satisfying all of the following criteria after screening

  ① Active* submacular choroidal neovascularization due to nAMD confirmed by fluorescein angiography (FAG) and optical coherence tomography (OCT)

  *Fluorescence leakage confirmed via FAG and intraretinal or subretinal fluid confirmed via OCT

  ② Absence of active polypoidal lesions due to polypoidal choroidal vasculopathy (PCV) confirmed by indocyanine green angiography (ICGA)

• A study eye with fibrosis covering less than 50% of the total lesion area

• A study eye with ETDRS best corrected visual acuity (BCVA) score range of 73-24 at a distance of 4m (equivalent to 20/40-20/320 of Snellen)

• A study eye with a neovascular lesion area of less than 12 optic-disk areas (For an optic nerve head diameter set to 1.8mm, the corresponding optic-disk area is 2.45mm2)

• Provided written informed consent voluntarily after receiving a full explanation of the clinical trial.

Exclusion Criteria:

• History of ocular treatment, systemic therapies, or surgical procedures, such as photodynamic therapy (PDT) and laser photocoagulation, for the treatment of wet nAMD (supplements and vitamins excluded)
• History of anti-VEGF treatment (e.g., ranibizumab, bevacizumab, aflibercept 2mg, or biosimilars) or combination therapy in the study eye for the treatment of wet nAMD
• A study eye with scarring or fibrosis covering more than 50% of the total lesion area
• A study eye with vitreous hemorrhage occurring within 1 month prior to the Screening Visit
• A study eye with intraocular pressure (IOP) ≥ 25mmHg, including glaucoma with IOP ≥ 25mmHg despite medical treatment
• A study eye with a total lesion area (including vessels, scar tissue, and neovascularization) greater than 12 optic-disk areas (>30.5mm2), as measured by FAG