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.

Study Overview

• Status: Recruiting
• Conditions: Neovascular (Wet) Age-related Macular Degeneration Without Polypoidal Choroidal Vasculopathy
• Intervention / Treatment: Drug: SMZ1; Drug: SMZ1 Placebo

• Study Type: Interventional
• Enrollment (Estimated): 266
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Nahyun Kang, Ph.D; Phone Number: +82 2-3489-6298; Email: nahyun.kang@sminnovation.com

Study Locations

• South Korea
  • Seoul
    • Seoul, Seoul, South Korea, 02447
      • Recruiting
      • Kyung Hee University Hospital
      • Contact: Gyeong-suk Yeo; Phone Number: +82 2-958-8461; Email: oplasik@hanmail.net

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SMZ1 Group; SMZ1 + Ranibizumab	Drug: SMZ1; Loading Phase (3 months): SMZ1 BID and Ranibizumab Monthly injection;; PRN Phase (9 months): SMZ1 BID and Ranibizumab PRN injection
Placebo Comparator: SMZ1 Placebo Group; SMZ1 Placebo + Ranibizumab	Drug: SMZ1 Placebo; Loading Phase (3 months): SMZ1 Placebo BID and Ranibizumab monthly injection;; PRN Phase (9 months): SMZ1 Placebo BID and Ranibizumab PRN injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best corrected visual acuity (BCVA) at Month 12	Change in BCVA score from baseline, at Month 12 after the administration of the investigational drug using early treatment diabetic retinopathy study (ETDRS) chart	Month 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Monthly BCVA	Change in BCVA score from baseline, at each month after the administration of the investigational drug for 11 months (excluding Month 12) using ETDRS chart	Monthly for 11 months
Central retinal thickness (CRT) every three months	Change in CRT from the screening visit, at Month 3, 6, and 12 after the administration of the investigational drug measured with optical coherence tomography (OCT)	Month 3, 6, and 12
Ranibizumab retreatment	Number of Ranibizumab retreatment through Month 4 and 12, following the Ranibizumab loading phase of 3 months	Through Month 4 and 12

Collaborators and Investigators

• Sponsor: SANGMYUNG innovation

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: June 26, 2026
• First Submitted That Met QC Criteria: July 5, 2026
• First Posted (Actual): July 10, 2026

Study Record Updates

• Last Update Posted (Actual): July 10, 2026
• Last Update Submitted That Met QC Criteria: July 5, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: SMZ1-301
• Other Study ID Numbers: SMZ1-301

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No