Neovascular Age-related Macular Degeneration (nAMD)BLUE SKYNCT04543331
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
An observational study of Neovascular Age-related Macular Degeneration (nAMD) and Diabetic Macular Edema (DME), run by Novartis Pharmaceuticals at 41 sites in Germany.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Neovascular Age-related Macular Degeneration (nAMD), Diabetic Macular Edema (DME)
- What is being tested?
- brolucizumab
- How many people
- 572 participants
- Where
- 41 sitesGermany
- Study dates
- 5 Nov 2020to 17 Nov 2025
- Phase
- Observational
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 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients being treated for nAMD or DME with brolucizumab will be enrolled in the study upon signing an informed consent.
Who may be able to join
- 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
Who cannot join
- 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)
Show all 12Show fewer
- 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
Trial locations and contacts
41 sites in 1 country.
41 sites in 1 country
Germany41 sites
Novartis Investigative Site
Aschersleben, 06449
Novartis Investigative Site
Bayreuth, 95445
Novartis Investigative Site
Berlin, 10713
Novartis Investigative Site
Berlin, 14163
Novartis Investigative Site
Bonn, 53105
Novartis Investigative Site
Breisach, 79206
Novartis Investigative Site
Chemnitz, 09113
Novartis Investigative Site
Cologne, 50968
Novartis Investigative Site
Dresden, Saxony, 01307
Novartis Investigative Site
Dresden, 01067
Novartis Investigative Site
Dresden, 01324
Novartis Investigative Site
Esslingen am Neckar, 73728
Novartis Investigative Site
Frankfurt am Main, Hesse, 60590
Novartis Investigative Site
Glauchau, 08371
Novartis Investigative Site
Göttingen, Lower Saxony, 37075
Novartis Investigative Site
Halle, Saxony-Anhalt, 06118
Novartis Investigative Site
Homburg, 66421
Novartis Investigative Site
Hösbach, 63768
Novartis Investigative Site
Jena, Thuringia, 07740
Novartis Investigative Site
Kiel, 24103
Novartis Investigative Site
Leipzig, Saxony, 04103
Novartis Investigative Site
Leipzig, 04106
Novartis Investigative Site
Magdeburg, 39104
Novartis Investigative Site
Marienberg, 09496
Novartis Investigative Site
Munich, Bavaria, 81377
Novartis Investigative Site
Münster, 48145
Novartis Investigative Site
Neubrandenburg, 17036
Novartis Investigative Site
Neuburg A.d. Donau, Bavaria, 86633
Novartis Investigative Site
Osnabrück, Lower Saxony, 49076
Novartis Investigative Site
Rostock, Mecklenburg-Vorpommern, 18057
Novartis Investigative Site
Saarbrücken, Saarland, 66111
Novartis Investigative Site
Schneeberg, Saxony, 08289
Novartis Investigative Site
Schönebeck, 39218
Novartis Investigative Site
Stralsund, 18435
Novartis Investigative Site
Sulzbach, 66280
Novartis Investigative Site
Torgau, 04860
Novartis Investigative Site
Trier, Rhineland-Palatinate, 54296
Novartis Investigative Site
Waren, 17192
Novartis Investigative Site
Würzburg, Bavaria, 97070
Novartis Investigative Site
Würzburg, Bavaria, 97080
Novartis Investigative Site
Würzburg, 97080
About this study
Official title: 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
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.
Read the detailed description
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.
- Being tested
- brolucizumab
- Keywords
- Beovu, Brolucizumab, nAMD, DME, non-interventional trial, effectiveness, fluid resolution, treatment intervals, real world study
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
brolucizumabDrug
There is no treatment allocation. Patients administered Brolucizumab by prescription that have started before inclusion of the patient into the study will be enrolled.
| Study group | Role | What they receive |
|---|---|---|
| treatment naïve patients | Patients being the first time treated for nAMD or DME Receives: Drug: brolucizumab | |
| pre-treated patients | Patients already being treated for nAMD or DME Receives: Drug: brolucizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline, month 12
Secondary outcomes (21)
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
Measured: Baseline
Evaluate anatomical parameters during treatment with brolucizumab
nAMD patients. Detailed Outcome Measure will be defined in the Statistical Analysis Plan.
Measured: 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.
Measured: 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
Measured: 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
Measured: Baseline, month 6
Estimate discontinuation rate and time to discontinuation
nAMD patients. Detailed Outcome Measure will be defined in the Statistical Analysis Plan
Measured: Month 1-12 and 13-24
Assess retreatment criteria
nAMD patients. Detailed Outcome Measure will be defined in the Statistical Analysis Plan
Measured: Up to month 24
Estimate the number of OCT
nAMD patients. Detailed Outcome Measure will be defined in the Statistical Analysis Plan
Measured: Month 1-12 and 13-24
Assess the safety of brolucizumab
nAMD patients. Detailed Outcome Measure will be defined in the Statistical Analysis Plan
Measured: Up to month 24
Evaluate anatomical effectiveness
naive nAMD patients. Detailed Outcome Measure will be defined in the Statistical Analysis Plan
Measured: Up to month 24
Evaluate treatment intervals
naive nAMD patients. Detailed Outcome Measure will be defined in the Statistical Analysis Plan
Measured: 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
Measured: 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
Measured: 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
Measured: Month 12
Evaluate anatomical parameters during treatment with brolucizumab
DME patients. Detailed Outcome Measure will be defined in the Statistical Analysis Plan
Measured: 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
Measured: 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
Measured: Baseline, month 12
Estimate time to discontinuation (persistence)
DME patients. Detailed Outcome Measure will be defined in the Statistical Analysis Plan
Measured: Up to month 24
Estimate the treatment burden
DME patients. Detailed Outcome Measure will be defined in the Statistical Analysis Plan
Measured: 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.
Measured: Month 1-12 and 13-24
Assess safety of brolucizumab
DME patients. Detailed Outcome Measure will be defined in the Statistical Analysis Plan.
Measured: Up to month 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2020
- Study start5 Nov 2020
- Primary completion17 Nov 2025
- Study completion17 Nov 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neovascular Age-related Macular Degeneration (nAMD)Studies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 572 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04543331
- Sponsor's protocol ID
- CRTH258ADE02
- Acronym
- BLUE SKY
- Status last verified
- Jul 2026
- First submitted
- 4 Sep 2020
- Last updated
- 29 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No