Age Related Macular DegenerationM-VIVANCT07249216
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
A study testing Faricimab and Ranibizumab in people with Age Related Macular Degeneration, run by Singapore National Eye Centre at 1 site in Singapore.
Trial 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. Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Age Related Macular Degeneration
- What is being tested?
- Faricimab and Ranibizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 117 participants
- Where
- 1 siteSingapore
- Study dates
- 18 Jul 2025to Jul 2029
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
Show all 12Show fewer
- Subfoveal CNV/PCV
- Juxtafoveal/extrafoveal CNV/PCV with a subfoveal component related to the exudative activity.
- Either:
- 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.
- Eyes that have received 3 prior monthly intravitreal ranibizumab injections within 3 months prior to enrolment for nAMD indication only; and no previous treatment with other intravitreal anti-VEGF agents, 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)
Who cannot join
- 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
Show all 27Show fewer
- 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
- Uncontrolled glaucoma or ocular hypertension in the study eye defined as intraocular pressure (IOP) > 25 mmHg on medication or according to the investigator's judgment at baseline
- Intra- or periocular use of corticosteroids in the study eye during the 6-month period prior to baseline:
- Use of topical ocular corticosteroids in the study eye for 60 or more consecutive days within the 90-day period prior to baseline
- Use of systemic corticosteroids for 30 or more consecutive days within the 90 days prior to baseline, with the exception of low stable doses of corticosteroids (defined as ≤10 mg prednisolone or equivalent dose used for 90 days or more). Inhaled, nasal or dermal steroids are also permitted
- Previous therapeutic radiation near the region of the study eye
- History of a medical condition (disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding) that, in the judgment of the investigator, would preclude scheduled study visits, completion of the study, or a safe administration of the investigational product
- History of hypersensitivity to any component of the test article or clinically relevant sensitivity to fluorescein dye (or indocyanine green), as assessed by the Investigator
- Participation in an investigational drug, biologic, or device study within 30 days or the duration of 5 half-lives of the investigational product (whichever is longer) prior to baseline Note: observational clinical studies solely involving over-the-counter vitamins, supplements, or diets are not exclusionary
- Systemic anti-vascular endothelial growth factor (VEGF) therapy within the 90-day period prior to baseline
- Stroke or myocardial infarction in the 90-day period prior to baseline
- Uncontrolled blood pressure defined as a systolic value ≥ 180 mmHg and/or diastolic value ≥ 100 mmHg at screening
- Medical or psychiatric conditions that, in the opinion of the investigator, make consistent follow-up over the study period unlikely, or in general a poor medical risk because of other systemic diseases or active uncontrolled infections
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Singapore1 site, 1 recruiting
- Recruiting
Singapore National Eye Centre/Singapore Eye Research Institute
Singapore
Gemmy Cheung, +65 63227460, gemmy.cheung.c.m@singhealth.com.sg
About this study
Official title: Identification of Molecular Signals in Vitreous Humor Associated With Suboptimal Response to VEGF Inhibition in nAMD Within a Clinical Trial Setting
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.
Read the 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
- Being tested
- Faricimab, Ranibizumab
- Medical subject headings
- Macular Degeneration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FaricimabDrug
All treatment-naïve 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. Previously treated eyes will not undergo an in-study loading phase (baseline, week 4 and week 8 visits), as pre-enrolment injections will be considered equivalent.
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.
RanibizumabDrug
All treatment naive 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. Previously treated eyes will not undergo an in-study loading phase (baseline, week 4 and week 8 visits), as pre-enrolment injections will be considered equivalent.
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.
| Study group | Role | What they receive |
|---|---|---|
| Ranibizumab | Other | Not described Receives: Drug: Ranibizumab |
| Faricimab | Other | Not described Receives: Drug: Faricimab; Drug: Ranibizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in vitreous biomarker concentrations between responders and non-responders
Comparison of inflammatory and angiogenic biomarkers in vitreous humor measured at baseline and week 12.
Measured: 12 weeks
Secondary outcomes (2)
Change in concentration of inflammatory and angiogenic biomarkers in vitreous humor from baseline to week 12 (including IL-6, IL-8, MCP-1, TNF-α, VEGF-A, PlGF, ANG-2, MMP-2, MMP-9, and complement pathway proteins)
Picograms per milliliter (pg/mL)
Measured: 12 weeks
Proportion of eyes classified as suboptimal responders at Week 12
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2025
- Study start18 Jul 2025
- Primary completionJun 2029 (estimated)
- Study completionJul 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Age Related Macular DegenerationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 117 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Singapore National Eye Centre
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Gemmy Cheung Chui Ming, Singapore Eye Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07249216
- Sponsor's protocol ID
- 2025-0319
- Acronym
- M-VIVA
- Status last verified
- Sep 2026
- First submitted
- 14 Nov 2025
- Last updated
- 16 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Identification of Molecular Signals in Vitreous Humor Associated With Suboptimal Response to VEGF Inhibition in nAMD Within a Clinical Trial Setting
- ClinicalTrials.gov ID
- NCT07249216
- Acronym / sponsor ID
- M-VIVA / 2025-0319
- Conditions
- Age Related Macular Degeneration
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 117 participants (estimated)
- Lead sponsor
- Singapore National Eye CentreOther government
- Study start
- 18 Jul 2025 (actual)
- Primary completion
- Jun 2029 (estimated)
- Study completion
- Jul 2029 (estimated)
- First posted
- 25 Nov 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ranibizumab | Other | Drug: Ranibizumab |
| Faricimab | Other | Drug: Faricimab, Drug: Ranibizumab |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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)
Key exclusion criteria (27 listed)
- 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
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FaricimabAll treatment-naïve 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. Previously treated eyes will not undergo an in-study loading phase (baseline, week 4 and week 8 visits), as pre-enrolment injections will be considered equivalent. 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 | Faricimab |
| RanibizumabAll treatment naive 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. Previously treated eyes will not undergo an in-study loading phase (baseline, week 4 and week 8 visits), as pre-enrolment injections will be considered equivalent. 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. | Drug | Faricimab, Ranibizumab |
Primary outcome
Difference in vitreous biomarker concentrations between responders and non-responders
Time frame: 12 weeks
Comparison of inflammatory and angiogenic biomarkers in vitreous humor measured at baseline and week 12.
2 secondary outcomes
Change in concentration of inflammatory and angiogenic biomarkers in vitreous humor from baseline to week 12 (including IL-6, IL-8, MCP-1, TNF-α, VEGF-A, PlGF, ANG-2, MMP-2, MMP-9, and complement pathway proteins)
Time frame: 12 weeks
Proportion of eyes classified as suboptimal responders at Week 12
Time frame: 12 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Sep 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Faricimab and Ranibizumab in people with Age Related Macular Degeneration, run by Singapore National Eye Centre at 1 site in Singapore.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 16 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Gemmy Cheung (63227460, gemmy.cheung.c.m@singhealth.com.sg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Difference in vitreous biomarker concentrations between responders and non-responders (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Sep 2026.