Study to Evaluate the Safety and Effectiveness of Intravitreal Injections (IVI) of Brolucizumab in Patients With Neovascular Age-related Macular Degeneration (nAMD)

Study Overview
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Brief Summary
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The purpose of this study is to generate additional safety and effectiveness data in Indian neovascular age-related macular degeneration (nAMD) patients that more closely resemble the real-world population intended to be treated with brolucizumab. This study is being conducted as part of the post-marketing regulatory commitment to the Indian Health authority.

Detailed Description
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This is a prospective, multi-center, open-label, interventional phase IV clinical study. The study treatment i.e. brolucizumab will be prescribed in terms of the marketing authorization; the assignment of the patient to the therapy will be decided within the current practice and the medical indication, and will clearly be separated from the decision to include the patient in the study. All patients with nAMD who are planned to be treated with brolucizumab and have provided informed consent may be enrolled in this study. The treatment period for each patient will be 56 weeks after the start of brolucizumab treatment. Study visits will be scheduled at week 4, week 8, week 16, and thereafter at intervals of 8 weeks or 12 weeks after disease activity assessment at week 16. If the investigators require more frequent follow-up visits, it can be done according to their discretion and clinical judgment. Any patient who suffers from intra-ocular inflammation (IOI) during the study period would not be re-challenged with brolucizumab. Data originating from assessments and evaluations performed will be collected from the patient's medical records at Baseline (BL), i.e. start of brolucizumab treatment, week 4, week 8, week 16, week 20, week 24, week 32, week 40, week 44, week 48 and at week 56.

Official Title
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A Real-world, Prospective, Multi-center, Open-label, Phase IV Clinical Study to Evaluate the Safety and Effectiveness of Intravitreal Injections (IVI) of Brolucizumab in Patients With Neovascular Age-related Macular Degeneration (nAMD)

Conditions
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Neovascular Age-related Macular Degeneration (nAMD)

Intervention / Treatment
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* Biological: Injection Brolucizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female or male, treatment naïve patient with ≥50 years of age, with neovascular age-related macular degeneration (nAMD). Patient or legally acceptable representative (LAR) willing to voluntarily provide signed informed consent for participation in the study. Note: In case where both eyes are affected, data of only one eye ['study eye'] will be recorded. Selection of the eye to be considered for the purpose of the study [referred to as 'study eye'] will be as per the Investigator's discretion. Exclusion Criteria: Patients fulfilling any of the following criteria are not eligible for this study: Patient having other eye diseases that could compromise the VA. Patient with existing or suspected ocular or periocular infection in the study eye. Patient with an existing intraocular inflammation (IOI). Patient with uncontrolled glaucoma defined as intraocular pressure > 25 mmHg despite treatment with anti-glaucoma medication, or according to Investigator's judgment. Patient who has undergone intraocular surgery within 3 months prior to enrollment in this study. Patient having scar, fibrosis and atrophy involving the center of the fovea in the study eye.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 100 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Brolucizumab<br>Brolucizumab, formerly known as ESBA1008, is a humanized single-chain Fv (scFv) antibody fragment. Its Intravitreal injections. Brolucizumab 6 mg will be administered by IVT injection as per the Prescribing information (PI) and in line with the treating physician's clinical judgement. Patients will receive loading doses of brolucizumab at Day 0/Visit 1, Week 4/Visit 2 and Week 8/Visit 3. After the loading doses, at Week 16, disease activity assessment (DAA) will be performed based on BCVA and OCT to assess whether the patient will require q8w or q12w dosing. | Biological: Injection Brolucizumab<br>* Single-chain antibody fragment (scFv) Brolucizumab 6 mg will be administered by IVT injection as per the Prescribing information (PI) and in line with the treating physician's clinical judgement. Patients will receive loading doses of brolucizumab at Day 0/Visit 1, Week 4/Visit 2 and Week 8/Visit 3. After the loading doses, at Week 16, disease activity assessment (DAA) will be performed based on BCVA and OCT to assess whether the patient will require q8w or q12w dosing.<br>* Other names: Trade Names: Pagenax, Beovu, Vsiqq;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and characteristics of treatment-emergent adverse events during the 56 weeks of treatment with brolucizumab. | To evaluate ocular & non-ocular safety of intravitreal brolucizumab in real-world patients with nAMD. | Week 56 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change in BCVA from baseline to week 16 and week 56 as measured by Early Treatment Diabetic Retinopathy Study (ETDRS) letters. | To evaluate the effectiveness of brolucizumab in the management of nAMD in terms of change in best-corrected visual acuity (BCVA) from baseline to Week 56. | Week 56 | 
| Percentage (%) of patient eyes with gain in BCVA of 15/10/5 ETDRS letters or more from baseline to week 16 and week 56. | To evaluate the effectiveness of brolucizumab in the management of nAMD in terms of change in best-corrected visual acuity (BCVA) from baseline to Week 56. | Week 56 | 
| Percentage (%) of patient eyes with loss in BCVA of 15/10/5 ETDRS letters or more from baseline to week 16 and week 56. | To evaluate the effectiveness of brolucizumab in the management of nAMD in terms of change in best-corrected visual acuity (BCVA) from baseline to Week 56. | Week 56 | 
| Number of anti-VEGF injections, during the 56 weeks of treatment with brolucizumab. | Characterize the number of anti-VEGF injections during the 56 weeks of treatment with brolucizumab. | Week 56 | 
| Number of Non-injection visits during the 56 weeks of treatment with brolucizumab. | Characterize number of non-injection visits during the 56 weeks of treatment with brolucizumab. | 56 Weeks | 
| Total number of visits during the 56 weeks of treatment with brolucizumab. | Characterize the total number of visits during the 56 weeks of treatment with brolucizumab. | 56 Weeks | 
| Percentage (%) of patient eyes with at least one duration of interval between injections ≥ 8 weeks but <12 weeks. | Estimate the percentage (%) of patient eyes with anti-VEGF injection intervals q8w and q12w during the 56 weeks of treatment with brolucizumab. | Week 56 | 
| Percentage (%) of patient eyes with at least one duration of interval between injections ≥ 12 weeks. | Estimate the percentage (%) of patient eyes with anti-VEGF injection intervals q8w and q12w during the 56 weeks of treatment with brolucizumab. | Week 56 | 
| Absence of intra-retinal fluid from baseline to week 16 and week 56. | Estimate effect of brolucizumab on fluid (increased/reduced/unchanged) from baseline to week 16 and week 56 based on Optical Coherence Tomography Image Analysis. | Week 56 | 
| Absence of sub-retinal fluid from baseline to week 16 and week 56. | Estimate effect of brolucizumab on fluid from baseline to week 16 and week 56. | Week 56 | 
| Estimate CST change from baseline to week 16 and at week 56. | Estimate effect of brolucizumab on central subfield thickness (CST) from baseline to week 16 and week 56 as measured by Optical Coherence Tomography (in µm) | Week 56 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Macular degeneration, macula damage, age-related macular degeneration (ARMD), vision loss, retina damage, dry macular degeneration, wet macular degeneration, Subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration