Comparison of Rapid Aflibercept and Brolucizumab T&E in wAMD

Study Overview
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Brief Summary
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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.

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

Conditions
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Wet Age-related Macular Degeneration

Intervention / Treatment
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* Drug: Aflibercept
* Drug: Brolucizumab
* Procedure: early treat and extend (T&E)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: two-armed, randomized, double-blind
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Aflibercept ® rapid treatment extension (T&E)<br>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<br>* administration of anti-VEGF Aflibercept (Eylea)<br>Procedure: early treat and extend (T&E)<br>* extension of treatment intervals (T&E) from the beginning of treatment<br>|
| Active Comparator: Brolucizumab ® rapid treatment extension (T&E)<br>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. | Drug: Brolucizumab<br>* administration of anti-VEGF Brolucizumab (Beovu)<br>Procedure: early treat and extend (T&E)<br>* extension of treatment intervals (T&E) from the beginning of treatment<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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wAMD, Treat & Extend, Aflibercept, Brolucizumab, Loading-phase