NCT07249216

Identification of Molecular Signals in Vitreous Humor Associated With Suboptimal Response to Vascular Endothelial Growth Factor (VEGF) Inhibition in Neovascular Age-related Macular Degeneration (nAMD) Within a Clinical Trial Setting

Identification of Molecular Signals in Vitreous Humor Associated With Suboptimal Response to VEGF Inhibition in nAMD Within a Clinical Trial Setting

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 117 (estimated)
• Sponsor: Singapore National Eye Centre · Other Government
• Sex: All
• Age: 50 Years
• Healthy volunteers: Not accepted

Summary

Neovascular age-related macular degeneration (nAMD), also called wet AMD, can cause serious vision loss. While anti-VEGF (anti Vascular Endothelial Growth Factor) treatments such as ranibizumab help many patients, about 20 40% have a suboptimal response. In this study, the investigators want to identify other factors (beyond VEGF) that might be driving the disease in these non-responding patients. By looking at samples from inside the eye (vitreous humor) and comparing "good responders" to "suboptimal responders", the investigators hope to find potential new treatment approaches or biomarkers for nAMD.

Detailed description

Neovascular age-related macular degeneration (nAMD) is a leading cause of severe vision loss worldwide. Although intravitreal anti-VEGF injections have markedly improved outcomes, 20-40% of patients show a suboptimal response, indicating the involvement of additional molecular pathways. This study investigates whether profiling the vitreous humor can reveal alternative angiogenic pathways-beyond VEGF-that drive persistent disease. If such pathways are identified, switching from anti-VEGF monotherapy (ranibizumab) to a bispecific anti-VEGF/anti-Ang2 agent (faricimab) may improve disease control and provide better vision outcomes for patients with inadequate response to standard therapy. Additionally, the dosage regimens (monthly injections over 24 weeks), and selection of treatment-naïve nAMD patients will minimize confounding variables. This approach ensures a clear comparison between good responders and suboptimal responders. By correlating clinical/imaging outcomes with vitreous biomarker profiles, the investigators aim to develop personalized treatment strategies for nAMD.

Conditions

• Age Related Macular Degeneration

Interventions

Type	Name	Description
DRUG	Faricimab	All study eyes will start on the intravitreal ranibizumab loading phase, with the initial injection given within two weeks of the screening visit and overall of x 3 monthly injections. At week 12, patients will be evaluated for their response following the loading phase. Patients who show an absence of IRF, absence of or ≤100µm subretinal fluid (SRF), and no new hemorrhage will be categorized as good responders and will continue with four further monthly intravitreal ranibizumab. Suboptimal responders (defined as the presence of subretinal fluid \> 100 µm, any intraretinal fluid (IRF), or a new hemorrhage) will switch to four doses of monthly intravitreal faricimab.
DRUG	Ranibizumab	All study eyes will start on the intravitreal ranibizumab loading phase, with the initial injection given within two weeks of the screening visit and overall of x 3 monthly injections. At week 12, patients will be evaluated for their response following the loading phase. Patients who show an absence of IRF, absence of or ≤100µm SRF, and no new hemorrhage will be categorized as good responders and will continue with four further monthly intravitreal ranibizumab. Suboptimal responders (defined as the presence of subretinal fluid \> 100 µm, any intraretinal fluid (IRF), or a new hemorrhage) will switch to four doses of monthly intravitreal faricimab.

Timeline

• Start date: 2025-07-18
• Primary completion: 2029-06-01
• Completion: 2029-07-01
• First posted: 2025-11-25
• Last updated: 2025-11-25

Locations

1 site across 1 country: Singapore