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

NCT07249216 | Recruiting DMC

• 1 other identifier: 2025-0319
• Study Type: interventional
• Target: 117
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Age Related Macular Degeneration

Outcome Measures

Primary Outcomes (1)

• Difference in vitreous biomarker concentrations between responders and non-responders

  Comparison of inflammatory and angiogenic biomarkers in vitreous humor measured at baseline, week 12, and week 24

  24 weeks

Secondary Outcomes (2)

• Change in concentration of inflammatory and angiogenic biomarkers in vitreous humor from baseline to week 24 (including IL-6, IL-8, MCP-1, TNF-α, VEGF-A, PlGF, ANG-2, MMP-2, MMP-9, and complement pathway proteins)

  24 weeks

• Proportion of eyes classified as suboptimal responders at Week 12

  24 weeks

Study Arms (2)

Ranibizumab

OTHER

Drug: Ranibizumab

Faricimab

OTHER

Drug: Faricimab; Drug: Ranibizumab

Interventions

Faricimab DRUG

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.

Faricimab

Ranibizumab DRUG

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.

Faricimab; Ranibizumab

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged ≥ 50 years old at the time of informed consent
• Willing and able to provide informed consent
• Willingness and ability to comply with all scheduled visits and study procedures
• Female subjects must be of non-childbearing potential or show a negative pregnancy test at screening and must agree to use appropriate methods of contraception during the study and for one month after the last dose.
• Confirmed diagnosis of symptomatic nAMD based on optical coherence tomography (OCT), fluorescein fundus angiography (FFA), and indocyanine green angiography (ICG-A)
• nAMD characteristics:
• Subfoveal CNV/PCV
• Juxtafoveal/extrafoveal CNV/PCV with a subfoveal component related to the exudative activity.
• Treatment naïve- NO previous treatment with intravitreal anti-VEGF agents, regardless of the indication, NO previous thermal laser in the macular region, or verteporfin photodynamic therapy (vPDT), regardless of indication
• BCVA of 24-78 letters as measured by an Early Treatment Diabetic Retinopathy Study (ETDRS) chart (Snellen equivalent 20/32-20/320)

You may not qualify if:

• CNV or retinal exudation due to causes other than typical AMD, such as vitelliform dystrophy, ocular histoplasmosis, trauma, pathological myopia, angioid streaks, choroidal rupture, or uveitis
• Active intraocular inflammation or suspected or active intraocular or periocular infection (eg, infectious conjunctivitis, keratitis, scleritis, endophthalmitis, infectious blepharitis) in either eye at Baseline
• Any history or evidence of a concurrent intraocular condition in the study eye, including retinal diseases other than neovascular AMD, that, in the judgment of the Investigator, could either require medical or surgical intervention during the course of the study to prevent or treat visual loss that might result from that condition or that limits the potential to gain visual acuity upon treatment with the investigational product
• History of cataract surgery within 6 months prior to recruitment
• Cataract surgery during the study period is not permitted.
• Retinal pigment epithelium (RPE) rip/tear in the study eye at Baseline
• Current vitreous hemorrhage or history of vitreous hemorrhage in the study eye within 4 weeks prior to Baseline
• History of rhegmatogenous retinal detachment, stage 3/4 macular hole, or any retinal break unless adequate repair has been performed
• History of the following in the study eye:
• Previous pars plana vitrectomy
• Previous photodynamic therapy (PDT)
• Intraocular or refractive surgery within the 6 months period prior to Baseline
• Previous penetrating keratoplasty or vitrectomy
• Previous pan retinal photocoagulation
• Previous submacular surgery or macular laser treatment

Sponsors & Collaborators

• Singapore National Eye Centre: lead

Study Sites (1)

Singapore National Eye Centre/Singapore Eye Research Institute

Singapore, Singapore

RECRUITING

MeSH Terms

Conditions

Macular Degeneration

Interventions

faricimab; Ranibizumab

Condition Hierarchy (Ancestors)

Retinal Degeneration; Retinal Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Gemmy Cheung

CONTACT

63227460; gemmy.cheung.c.m@singhealth.com.sg

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 14, 2025
• First Posted: November 25, 2025
• Study Start: July 18, 2025
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): July 1, 2029
• Last Updated: November 25, 2025

Record last verified: 2025-11

Locations

SG (1)