Clinical trial NCT04932980: Comparison of Rapid Aflibercept and Brolucizumab T&E in wAMD
Official title: Study Comparing Early Extension of Aflibercept and Brolucizumab in Wet AMD (SPARROW)
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: NA
Conditions: Wet Age-related Macular Degeneration
Keywords: wAMD
Treat & Extend
Aflibercept
Brolucizumab
Loading-phase
Lead sponsor: Berner Augenklinik
Sponsor class: OTHER
Collaborators: name: medignition AG
First posted: 2021-06-21
Enrollment: 80
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: two-armed, randomized, double-blind
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of injections given until week 52
timeFrame: 52 weeks
Secondary outcomes:
measure: Injections until week 104
timeFrame: 104 weeks
measure: Number of treatment failures
timeFrame: 52 weeks
measure: Number of treatment failures
timeFrame: 104 weeks
measure: Time until drying of retina
timeFrame: 52 weeks
measure: Time until drying of retina
timeFrame: 104 weeks
measure: portion of eyes without disease activity
timeFrame: 52 weeks
measure: portion of eyes without disease activity
timeFrame: 104 weeks
measure: eyes under treatment intervals of ≥12 weeks
timeFrame: 52 weeks
measure: eyes under treatment intervals of ≥12 weeks
timeFrame: 104 weeks
measure: Change in visual acuity
timeFrame: 52 weeks
measure: Change in visual acuity
timeFrame: 104 weeks
measure: Change in central subfield thickness (CST)
timeFrame: 52 weeks
measure: Change in central subfield thickness (CST)
timeFrame: 104 weeks
measure: Portion of eyes gaining and loosing ≥5, ≥10, and ≥15 letters
timeFrame: 52 weeks
measure: Portion of eyes gaining and loosing ≥5, ≥10, and ≥15 letters
timeFrame: 104 weeks
measure: Maximal treatment interval extension
timeFrame: 52 weeks
measure: Maximal treatment interval extension
timeFrame: 104 weeks
Other outcomes:
Locations:
city: Bern
country: Switzerland
facility: Berner Augenklinik
Study officials:
affiliation: Berner Augenklinik
name: Justus G. Garweg, Prof. Dr. med.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.