Treatment of Recalcitrant Neovascular AMD Using Brolocizumab With Immediate T&E

Study Overview
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Brief Summary
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The investigator propose to conduct a randomized clinical trial, investigating the safety and efficacy of brolucizumab for treatment of nAMD patients with CNV, and plans to specifically target those who are not responding to standard Treat and Extend (T&E) treatment. A randomised omized study will be conducted with 2 arms, one with the new drug (brolocizumab) and novel treatment protocol versus a second arm using the current gold standard of aflibercept and the T&E protocol

Detailed Description
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In addition, there will also be a rescue option for those in the aflibercept arm who are not responding well to also switch to brolucizumab. The primary outcome is the change in central macular thickness, since we expect the new treatment to be effective in reducing intraretinal and subretinal fluids, which in effect are indicators of disease activity. In addition, investigator will look at the improvement of visual acuity, the reduction of treatment intervals, total number of injections over 1 year, recurrence rate and safety profiles of both drugs.

Official Title
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Treatment of Recalcitrant Neovascular AMD Using Brolocizumab With a Novel Treat and Extend Protocol - a Randomized Controlled Prospective Study

Conditions
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Age-Related Macular Degeneration

Intervention / Treatment
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* Drug: Brolucizumab
* Drug: Aflibercept


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 50 and above Diagnosis of exudative age-related macular degeneration (subfoveal CNV) as shown on optical coherence tomography (OCT) - presence of intraretinal fluid, subretinal fluid or subretinal hyperreflective material and/or FFA (leakage classified as subfoveal or as juxtafoveal or extrafoveal) Actively treated with aflibercept and given 3 monthly loading doses followed by treat and extend Maximal interval period is less than or equal to 8 weekly injections Patients must understand and sign the ethics board approved consent form Exclusion Criteria: Ocular criteria: Co-existing retinal and/or macular disease (DME, RVO, high myopia of 8 diopters or more, retinal detachment, macular hole stage 2 or above, significant vitreomacular traction or epiretinal membrane, etc.) Co-existing ocular disease (glaucoma, uveitis etc.) History of uveitis or intraocular inflammation, scleritis, or episcleritis History of corneal transplant, pars planar vitrectomy or aphakia History of therapeutic radiation to the region of the study eye Media opacity obstructing investigation or assessment (cataract, corneal scar, vitreous hemorrhage) Treat and extend period beyond 8 weeks Any intravitreal injection of steroid within 3 months before randomization Systemic criteria: Poorly controlled systemic disease including hypertension and diabetes Any acute coronary event or stroke within 6 months before randomization Malignancy within 5 years Systemic anti-VEGF treatment Allergy or sensitivity to investigational product, including fluoresceine dye, anesthetics, aflibercept or brolucizumab

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel interventional arms with option of rescue treatment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Brolucizumab<br>new drug (brolocizumab) and novel treatment protocol | Drug: Brolucizumab<br>* Intravitreal injection<br>* Other names: Beovu;|
| Active Comparator: Aflibercept<br>aflibercept and continuing on the traditional T&E protocol. There will also be a rescue option for those in the aflibercept arm who are not responding well to also switch to brolocizumab | Drug: Aflibercept<br>* Intravitreal injection<br>* Other names: Eylea;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Central Macular thickness | Measurement of the change in macular thickness (um) | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual acuity | Change in best corrected visual acuity (BCVA), LogMAR | 1 year | 
| Treatment interval | Change in the duration of the treatment interval between each injection (weeks) | 1 year | 
| Complications | Relating to the drug (eg. Inflammation), relating to the procedure (glaucoma, cataract, retinal detachment, haemorrhage etc) | 1 year | 
| Optical Coherence Tomography features | Changes and presence of OCT features during every follow up visit (sub retinal fluid, intraretinal fluid, pigmented epithelial defect) | 1 year |