Comparison of Rapid Aflibercept and Brolucizumab T&E in wAMD (SPARROW)

Study Comparing Early Extension of Aflibercept and Brolucizumab in Wet AMD (SPARROW)

The currently widely established and preferred protocol for the treatment of wet age-related macular degeneration includes a loading phase of three monthly injections without interim adaptation or treatment according to disease activity, thereafter following a T&E strategy with treatment adaptation in increments of 2-4 weeks according to disease activity. Based on pharmacological considerations regarding the vitreal half-life of the drugs, the aim of this prospective explorative study is to test whether an early extension of treatment intervals without a loading phase is an option without compromising functional outcomes. Based on a superiority of Afl compared to Ran with regard to achieving a dry retina after one year and based on studies, but in the absence of real-life experience with Bro, it seems of interest to test how far Afl and Bro are comparable in terms of their potential to extend the treatment intervals over 12 months, the time to dryness of the retina, and number of injections. Also, it is of high clinical relevance to demonstrate efficacy with longer initial treatment intervals compared to the current possibly over-treating loading-phase with three four-weekly injections.

Study Overview

• Status: Enrolling by invitation
• Conditions: Wet Age-related Macular Degeneration
• Intervention / Treatment: Drug: Aflibercept; Procedure: early treat and extend (T&E); Drug: Brolucizumab

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Bern, Switzerland, 3007
    • Berner Augenklinik

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Active MNV secondary to nAMD, going along with clinically significant vision loss
• Patients aged 50 years or older of all sexes
• Presence of IRF and/or SRF and/or subretinal hyperreflective material affecting the central subfield of the study eye on OCT
• signed informed consent for this study prior to the screening visit
• If possible: availability of a smartphone and willingness to perform self-testing with the Alleye app (soft criteria)

Exclusion Criteria:

• Any other cause of macular oedema
• Structural damage to the macula precluding a visual potential
• Optical media opacities not allowing an accurate performance of the protocol examinations
• Any intraocular surgery within three months prior to inclusion and history of any vitreoretinal surgery
• Advanced diabetic retinopathy potentially requiring any treatment within six months following inclusion or history of vitreal haemorrhage
• Presence of vitreoretinal traction or tractive epiretinal membrane affecting the fovea
• History of IVT with anti-VEGF or corticosteroids at any time in the study eye
• Inability to follow the procedures of the study, e.g., due to language problems, psychological disorders, dementia, etc.
• Significantly worse functional prognosis in the other eye or only eye
• Women of childbearing potential not willing to use an effective method of contraception during treatment and until at least 3 months after the last treatment
• Pregnant or lactating women
• Any systemic auto-inflammatory and auto-immune disease requiring treatment
• Treatment with high-dose corticosteroids (Prednisone equivalent >5mg/day), immunosuppressive or immunomodulatory or anti-proliferative agents for any reason
• Inability or contraindications to undergo the investigated intervention

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Aflibercept ® rapid treatment extension (T&E); Early treat and extend (T&E) with Aflibercept ®. First IVT followed by control after 3 weeks and 2nd IVT after 6 weeks (= shortest treatment interval). Treatment will be adjusted according to morphologic response by adaptation of treatment intervals in +/- two-week increments.	Drug: Aflibercept; administration of anti-VEGF Aflibercept (Eylea); Procedure: early treat and extend (T&E); extension of treatment intervals (T&E) from the beginning of treatment
Active Comparator: Brolucizumab ® rapid treatment extension (T&E); Early treat and extend (T&E) with Brolucizumab ®. First IVT followed by control after 3 weeks and 2nd IVT after 6 weeks (= shortest treatment interval). Treatment will be adjusted according to morphologic response by adaptation of treatment intervals in +/- two-week increments.	Procedure: early treat and extend (T&E); extension of treatment intervals (T&E) from the beginning of treatment; Drug: Brolucizumab; administration of anti-VEGF Brolucizumab (Beovu)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of injections given until week 52	number injections received by patient	52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Injections until week 104	number injections received by patient	104 weeks
Number of treatment failures	number with treatment demand of less than 6 weeks at any time point	52 weeks
Number of treatment failures	number with treatment demand of less than 6 weeks at any time point	104 weeks
Time until drying of retina	mean interval until absence of intra- and subretinal fluid	52 weeks
Time until drying of retina	mean interval until absence of intra- and subretinal fluid	104 weeks
portion of eyes without disease activity	% patients with absence of intra- and subretinal fluid	52 weeks
portion of eyes without disease activity	% patients with absence of intra- and subretinal fluid	104 weeks
eyes under treatment intervals of ≥12 weeks	portion of eyes with stable disease under treatment intervals of ≥12 weeks	52 weeks
eyes under treatment intervals of ≥12 weeks	portion of eyes with stable disease under treatment intervals of ≥12 weeks	104 weeks
Change in visual acuity	change of VA in logRAD from baseline to week 52	52 weeks
Change in visual acuity	change of VA in logRAD from baseline to week 104	104 weeks
Change in central subfield thickness (CST)	change from baseline to week 52	52 weeks
Change in central subfield thickness (CST)	change from baseline to week 104	104 weeks
Portion of eyes gaining and loosing ≥5, ≥10, and ≥15 letters	change from baseline to week 52	52 weeks
Portion of eyes gaining and loosing ≥5, ≥10, and ≥15 letters	change from baseline to week 104	104 weeks
Maximal treatment interval extension	mean treatment interval extension	52 weeks
Maximal treatment interval extension	mean treatment interval extension	104 weeks

Collaborators and Investigators

• Sponsor: Berner Augenklinik
• Collaborators: medignition AG
• Investigators: Principal Investigator: Justus G. Garweg, Prof. Dr. med., Berner Augenklinik

Publications and helpful links

General Publications

• Fauser S, Schwabecker V, Muether PS. Suppression of intraocular vascular endothelial growth factor during aflibercept treatment of age-related macular degeneration. Am J Ophthalmol. 2014 Sep;158(3):532-6. doi: 10.1016/j.ajo.2014.05.025. Epub 2014 May 28.
• Garweg JG, Gerhardt C. Disease stability and extended dosing under anti-VEGF treatment of exudative age-related macular degeneration (AMD) - a meta-analysis. Graefes Arch Clin Exp Ophthalmol. 2021 Aug;259(8):2181-2192. doi: 10.1007/s00417-020-05048-1. Epub 2021 Feb 2.

Study record dates

Study Major Dates

• Study Start (Actual): May 9, 2022
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): March 1, 2028

Study Registration Dates

• First Submitted: June 6, 2021
• First Submitted That Met QC Criteria: June 18, 2021
• First Posted (Actual): June 21, 2021

Study Record Updates

• Last Update Posted (Actual): April 24, 2024
• Last Update Submitted That Met QC Criteria: April 23, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Aflibercept; wAMD; Brolucizumab; Treat & Extend; Loading-phase
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Aflibercept
• Other Study ID Numbers: SPARROW 2021-01236

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