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

Diabetic Macular Edema (DME) Clinical Trial

— BLUE SKY  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04543331
• Other study ID #: CRTH258ADE02
• Status: Active, not recruiting
• Start date: November 5, 2020
• Est. completion date: December 20, 2025

Study information

• Verified date: May 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical 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 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 573
• Est. completion date: December 20, 2025
• Est. primary completion date: December 20, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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:

1. Diagnosis of nAMD or visual impairment due to DME

2. Male and Female nAMD and DME patients with =18 years of age at index

3. Decision to treat with brolucizumab at baseline visit

4. Signed written informed consent

5. Patients for whom a therapy with brolucizumab is medically indicated

6. Intraretinal and/or subretinal fluid affecting the central subfield of the study eye at Screening

Exclusion Criteria:

1. Patients that have any contraindication or are not eligible for treatment with brolucizumab as according to the SmPC

2. Patients treated for RVO or CNV other than nAMD

3. Receipt of any anti-VEGF treatment other than brolucizumab in the study eye at index date

4. Central subfield of the study eye affected by fibrosis or geographic atrophy or total area of fibrosis >50% of the total lesion (nAMD)

5. Any active intraocular or periocular infection or active intraocular inflammation in either eye at index date

6. Patients who have been on anti-VEGF treatment for longer than 3 years (before index date)

7. Any medical or psychological condition in the treating physician's opinion which may prevent the patient from the 24 months study participation

8. Patients participating in parallel in an interventional clinical trial

9. Patients participating in parallel in any other NIS generating primary data for an anti-VEGF drug

10. Laser photocoagulation (focal/grid or panretinal) in the study eye during the 3-month period prior to baseline

11. Prior use of intraocular or periocular corticosteroids in the study eye provided at least 4 months prior to baseline

12. Pregnancy and breast-feeding

Related Conditions & MeSH terms

• Diabetic Macular Edema (DME)
• Edema
• Macular Degeneration
• Macular Edema
• Neovascular Age-related Macular Degeneration (nAMD)
• Vision Disorders
• Vision, Low
• Wet Macular Degeneration

Intervention

Drug:
• brolucizumab
There is no treatment allocation. Patients administered Brolucizumab by prescription that have started before inclusion of the patient into the study will be enrolled.

Locations

Country	Name	City	State
Germany	Novartis Investigative Site	Aschersleben
Germany	Novartis Investigative Site	Bayreuth
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Bonn
Germany	Novartis Investigative Site	Breisach am Rhein
Germany	Novartis Investigative Site	Chemnitz
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Esslingen
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Glauchau
Germany	Novartis Investigative Site	Gottingen
Germany	Novartis Investigative Site	Halle
Germany	Novartis Investigative Site	Homburg
Germany	Novartis Investigative Site	Hösbach
Germany	Novartis Investigative Site	Jena
Germany	Novartis Investigative Site	Kiel
Germany	Novartis Investigative Site	Koeln
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Magdeburg
Germany	Novartis Investigative Site	Marienberg
Germany	Novartis Investigative Site	Muenchen
Germany	Novartis Investigative Site	Muenster
Germany	Novartis Investigative Site	Neubrandenburg
Germany	Novartis Investigative Site	Neuburg
Germany	Novartis Investigative Site	Osnabrück
Germany	Novartis Investigative Site	Rostock
Germany	Novartis Investigative Site	Saarbruecken
Germany	Novartis Investigative Site	Schneeberg	Sachsen
Germany	Novartis Investigative Site	Schoenebeck
Germany	Novartis Investigative Site	Stralsund
Germany	Novartis Investigative Site	Sulzbach
Germany	Novartis Investigative Site	Torgau
Germany	Novartis Investigative Site	Trier	RP
Germany	Novartis Investigative Site	Waren
Germany	Novartis Investigative Site	Wuerzburg
Germany	Novartis Investigative Site	Wuerzburg	Bayern

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	Evaluate anatomical parameters during treatment with brolucizumab	nAMD patients. Detailed Outcome Measure will be defined in the Statistical Analysis Plan.	Up to month 24
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Assess retreatment criteria	nAMD patients. Detailed Outcome Measure will be defined in the Statistical Analysis Plan	Up to month 24
Secondary	Estimate the number of OCT	nAMD patients. Detailed Outcome Measure will be defined in the Statistical Analysis Plan	Month 1-12 and 13-24
Secondary	Assess the safety of brolucizumab	nAMD patients. Detailed Outcome Measure will be defined in the Statistical Analysis Plan	Up to month 24
Secondary	Evaluate anatomical effectiveness	naive nAMD patients. Detailed Outcome Measure will be defined in the Statistical Analysis Plan	Up to month 24
Secondary	Evaluate treatment intervals	naive nAMD patients. Detailed Outcome Measure will be defined in the Statistical Analysis Plan	Up to month 24
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Estimate time to discontinuation (persistence)	DME patients. Detailed Outcome Measure will be defined in the Statistical Analysis Plan	Up to month 24
Secondary	Estimate the treatment burden	DME patients. Detailed Outcome Measure will be defined in the Statistical Analysis Plan	Month 1-12 and 13-24
Secondary	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
Secondary	Assess safety of brolucizumab	DME patients. Detailed Outcome Measure will be defined in the Statistical Analysis Plan.	Up to month 24