Observational Study to Evaluate Fluid Resolution and Effectiveness in Patients Receiving Beovu in Neovascular Age-related Macular Degeneration and Visual Impairment Due to Diabetic Macular Edema

Study Overview
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Brief Summary
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This study is a prospective, non-interventional, multicenter, open-label study in nAMD and DME patients being treated with brolucizumab according to the EU SmPC. An observational study design, without a strict, mandated visit schedule or mandated treatment regimen was chosen as the most appropriate to collect available data in a real life setting. For that reason, this NIS does not impose a therapy protocol, diagnostic/therapeutic procedure or a visit schedule. The diagnostic or monitoring procedures are only those ordinarily applied to the therapeutic strategy and to routine clinical care and will take place as per investigator's discretion. This includes e.g. visit frequency, injection frequency and types of assessments performed - only data from routine medical practice will be collected as part of the study.

Detailed Description
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BLUE SKY consists of the nAMD-related module BIRL (Brolucizumab In Real Life) and two general, indication-related study modules BLUE SKY AMD and BLUE SKY DME. Patients will be enrolled at approximately 55 centers, which will be representatively distributed amongst the 16 German federal states. This will ensure to reflect all state-specific health insurance laws and guidelines. Naïve and pre-treated patients will be included after decision to start treatment with brolucizumab and consent is given. All patients will be documented either in the AMD or DME-module (Full Analysis Set). For the BIRL module, only naïve nAMD patients enrolled in approximately 7 selected centers will be documented. All these centers are equipped with the Zeiss PlexElite OCT-A, needed to assess and analyze BIRL specific objectives in a comparable setting. Only images from routine medical practice will be collected as part of the study. The study eye will be defined as the first eye treated during the study, the other eye will be considered as fellow eye. If both eyes are treated at baseline, the eye with the worse VA will be chosen as the study eye (if VA is measured equal, the treating ophthalmologist defines the study eye upon his discretion). The prospective observation period per patient will be up to 24 months.

Official Title
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OBservationaL stUdy to Evaluate Fluid reSolution and Effectiveness in Patients Receiving Beovu (Brolucizumab) Under KeY Treatment Schemes in Neovascular Age-related Macular Degeneration and Visual Impairment Due to Diabetic Macular Edema

Conditions
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Neovascular Age-related Macular Degeneration (nAMD), Diabetic Macular Edema (DME)

Intervention / Treatment
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* Drug: brolucizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The unit of analysis is patient-eye, i.e. all criteria should be applied to the study eye, unless otherwise specified. Patients will be included in the study if they fulfil the following requisites: Diagnosis of nAMD or visual impairment due to DME Male and Female nAMD and DME patients with ≥18 years of age at index Decision to treat with brolucizumab at baseline visit Signed written informed consent Patients for whom a therapy with brolucizumab is medically indicated Intraretinal and/or subretinal fluid affecting the central subfield of the study eye at Screening Exclusion Criteria: Patients that have any contraindication or are not eligible for treatment with brolucizumab as according to the SmPC Patients treated for RVO or CNV other than nAMD Receipt of any anti-VEGF treatment other than brolucizumab in the study eye at index date Central subfield of the study eye affected by fibrosis or geographic atrophy or total area of fibrosis >50% of the total lesion (nAMD) Any active intraocular or periocular infection or active intraocular inflammation in either eye at index date Patients who have been on anti-VEGF treatment for longer than 3 years (before index date) Any medical or psychological condition in the treating physician's opinion which may prevent the patient from the 24 months study participation Patients participating in parallel in an interventional clinical trial Patients participating in parallel in any other NIS generating primary data for an anti-VEGF drug Laser photocoagulation (focal/grid or panretinal) in the study eye during the 3-month period prior to baseline Prior use of intraocular or periocular corticosteroids in the study eye provided at least 4 months prior to baseline Pregnancy and breast-feeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| treatment naïve patients<br>Patients being the first time treated for nAMD or DME | Drug: brolucizumab<br>* There is no treatment allocation. Patients administered Brolucizumab by prescription that have started before inclusion of the patient into the study will be enrolled.<br>|
| pre-treated patients<br>Patients already being treated for nAMD or DME | Drug: brolucizumab<br>* There is no treatment allocation. Patients administered Brolucizumab by prescription that have started before inclusion of the patient into the study will be enrolled.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients' eyes that are absent of subretinal fluid (SRF) and intra-retinal fluid (IRF) | This outcome measure is part of the BLUE SKY AMD module. This primary study objective will be addressed considering treatment naïve and pre-treated patient eyes, analyzed as two independent groups (naïve and switch). | Month 12 | 
| Mean change in visual actuity (VA) under clinic specific routine treatment schemes | This outcome measure is part of the BIRL module. This primary study objective will be addressed considering treatment naïve patient eyes. Index date (Baseline): defined as the date of the first anti-VEGF injection (brolucizumab) in patient eye. | Baseline, month 12 | 
| Morphological CNV-Changes under clinic specific routine treatment schemes | This outcome measure is part of the BIRL module. This primary study objective will be addressed considering treatment naïve patient eyes. Index date (Baseline): defined as the date of the first anti-VEGF injection (brolucizumab) in patient eye. | Baseline, month 12 | 
| Percent of patients maintained on q12w dosing after loading through Week 52 | This outcome measure is part of the BLUE SKY DME module. This primary study objective will be addressed considering treatment naïve patient eyes included in the study. | After loading, month 12 | 
| Change in interval length from last interval before switch (baseline) to last interval at end of follow-up (12 months) | This outcome measure is part of the BLUE SKY DME module. This primary study objective will be addressed considering pre-treated patient eyes. Index date (Baseline): defined as the date of the first anti-VEGF injection (brolucizumab) in patient eyes. | Baseline, month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Characterize nAMD patients who initiated treatment with brolucizumab with the respect to baseline characteristics | nAMD patients. Detailed Outcome Measure will be defined in the Statistical Analysis Plan | Baseline | 
| Evaluate anatomical parameters during treatment with brolucizumab | nAMD patients. Detailed Outcome Measure will be defined in the Statistical Analysis Plan. | Up to month 24 | 
| Evaluate VA change from baseline during treatment with brolucizumab | nAMD patients. Detailed Outcome Measure will be defined in the Statistical Analysis Plan. | Baseline, month 24 | 
| Estimate number of anti-VEGF injections, visits and injection intervals | nAMD patients. Detailed Outcome Measure will be defined in the Statistical Analysis Plan | Up to month 24 | 
| Estimate percentage of switchers during first 6 months and characterize switchers | nAMD patients. Detailed Outcome Measure will be defined in the Statistical Analysis Plan | Baseline, month 6 | 
| Estimate discontinuation rate and time to discontinuation | nAMD patients. Detailed Outcome Measure will be defined in the Statistical Analysis Plan | Month 1-12 and 13-24 | 
| Assess retreatment criteria | nAMD patients. Detailed Outcome Measure will be defined in the Statistical Analysis Plan | Up to month 24 | 
| Estimate the number of OCT | nAMD patients. Detailed Outcome Measure will be defined in the Statistical Analysis Plan | Month 1-12 and 13-24 | 
| Assess the safety of brolucizumab | nAMD patients. Detailed Outcome Measure will be defined in the Statistical Analysis Plan | Up to month 24 | 
| Evaluate anatomical effectiveness | naive nAMD patients. Detailed Outcome Measure will be defined in the Statistical Analysis Plan | Up to month 24 | 
| Evaluate treatment intervals | naive nAMD patients. Detailed Outcome Measure will be defined in the Statistical Analysis Plan | Up to month 24 | 
| Describe implementation of treatment schemes into clinical practice | naive nAMD patients. Detailed Outcome Measure will be defined in the Statistical Analysis Plan | Up to month 24 | 
| Evaluate morphological changes under brolucizumab treatment using multimodal imaging | naive nAMD patients. Detailed Outcome Measure will be defined in the Statistical Analysis Plan | Up to month 24 | 
| Percentage of patient's eyes with absence of IRF and/or SRF at month 12 (naive and switch) | DME patients. Detailed Outcome Measure will be defined in the Statistical Analysis Plan | Month 12 | 
| Evaluate anatomical parameters during treatment with brolucizumab | DME patients. Detailed Outcome Measure will be defined in the Statistical Analysis Plan | Month 1-12 and 13-24 | 
| Characterize VA change from baseline during treatment with brolucizumab | DME patients. Detailed Outcome Measure will be defined in the Statistical Analysis Plan | Month 1-12 and 13-24 | 
| Estimate discontinuation rate during first year of brolucizumab treatment | DME patients. Detailed Outcome Measure will be defined in the Statistical Analysis Plan | Baseline, month 12 | 
| Estimate time to discontinuation (persistence) | DME patients. Detailed Outcome Measure will be defined in the Statistical Analysis Plan | Up to month 24 | 
| Estimate the treatment burden | DME patients. Detailed Outcome Measure will be defined in the Statistical Analysis Plan | Month 1-12 and 13-24 | 
| Estimate the number of OCT and the number of visits with/without OCT | DME patients. Detailed Outcome Measure will be defined in the Statistical Analysis Plan. | Month 1-12 and 13-24 | 
| Assess safety of brolucizumab | DME patients. Detailed Outcome Measure will be defined in the Statistical Analysis Plan. | Up to month 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Beovu, Brolucizumab, nAMD, DME, non-interventional trial, effectiveness, fluid resolution, treatment intervals, real world study