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 (BLUE SKY)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Diabetic Macular Edema (DME); Neovascular Age-related Macular Degeneration (nAMD)
• Intervention / Treatment: Drug: brolucizumab

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.

• Study Type: Observational
• Enrollment (Actual): 573

Contacts and Locations

• Study Contact: Name: Novartis Pharmaceuticals; Phone Number: +41613241111; Email: novartis.email@novartis.com
• Study Contact Backup: Name: Novartis Pharmaceuticals

Study Locations

• Germany
  • Aschersleben, Germany, 06449
    • Novartis Investigative Site
  • Bayreuth, Germany, 95445
    • Novartis Investigative Site
  • Berlin, Germany, 10713
    • Novartis Investigative Site
  • Berlin, Germany, 14163
    • Novartis Investigative Site
  • Bonn, Germany, 53105
    • Novartis Investigative Site
  • Breisach am Rhein, Germany, 79206
    • Novartis Investigative Site
  • Chemnitz, Germany, 09113
    • Novartis Investigative Site
  • Dresden, Germany, 01307
    • Novartis Investigative Site
  • Dresden, Germany, 01067
    • Novartis Investigative Site
  • Dresden, Germany, 01324
    • Novartis Investigative Site
  • Esslingen, Germany, 73728
    • Novartis Investigative Site
  • Frankfurt, Germany, 60590
    • Novartis Investigative Site
  • Glauchau, Germany, 08371
    • Novartis Investigative Site
  • Gottingen, Germany, 37075
    • Novartis Investigative Site
  • Halle, Germany, 06118
    • Novartis Investigative Site
  • Homburg, Germany, 66421
    • Novartis Investigative Site
  • Hösbach, Germany, 63768
    • Novartis Investigative Site
  • Jena, Germany, 07740
    • Novartis Investigative Site
  • Kiel, Germany, 24103
    • Novartis Investigative Site
  • Koeln, Germany, 50968
    • Novartis Investigative Site
  • Leipzig, Germany, 04103
    • Novartis Investigative Site
  • Leipzig, Germany, 04106
    • Novartis Investigative Site
  • Magdeburg, Germany, 39104
    • Novartis Investigative Site
  • Marienberg, Germany, 09496
    • Novartis Investigative Site
  • Muenchen, Germany, 81377
    • Novartis Investigative Site
  • Muenster, Germany, 48145
    • Novartis Investigative Site
  • Neubrandenburg, Germany, 17036
    • Novartis Investigative Site
  • Neuburg, Germany, 86633
    • Novartis Investigative Site
  • Osnabrück, Germany, 49076
    • Novartis Investigative Site
  • Rostock, Germany, 18057
    • Novartis Investigative Site
  • Saarbruecken, Germany, 66111
    • Novartis Investigative Site
  • Schoenebeck, Germany, 39218
    • Novartis Investigative Site
  • Stralsund, Germany, 18435
    • Novartis Investigative Site
  • Sulzbach, Germany, 66280
    • Novartis Investigative Site
  • Torgau, Germany, 04860
    • Novartis Investigative Site
  • Waren, Germany, 17192
    • Novartis Investigative Site
  • Wuerzburg, Germany, 97080
    • Novartis Investigative Site
  • Bayern
    • Wuerzburg, Bayern, Germany, 97070
      • Novartis Investigative Site
  • RP
    • Trier, RP, Germany, 54296
      • Novartis Investigative Site
  • Sachsen
    • Schneeberg, Sachsen, Germany, 08289
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients being treated for nAMD or DME with brolucizumab will be enrolled in the study upon signing an informed consent.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
treatment naïve patients; Patients being the first time treated for nAMD or DME	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.
pre-treated patients; Patients already being treated for nAMD or DME	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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): November 5, 2020
• Primary Completion (Estimated): December 20, 2025
• Study Completion (Estimated): December 20, 2025

Study Registration Dates

• First Submitted: September 4, 2020
• First Submitted That Met QC Criteria: September 4, 2020
• First Posted (Actual): September 10, 2020

Study Record Updates

• Last Update Posted (Actual): March 28, 2024
• Last Update Submitted That Met QC Criteria: March 27, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: effectiveness; non-interventional trial; DME; fluid resolution; nAMD; Beovu; Brolucizumab; real world study; treatment intervals
• Additional Relevant MeSH Terms: Nervous System Diseases; Eye Diseases; Neurologic Manifestations; Retinal Degeneration; Retinal Diseases; Sensation Disorders; Macular Degeneration; Macular Edema; Edema; Wet Macular Degeneration; Vision, Low; Vision Disorders
• Other Study ID Numbers: CRTH258ADE02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No