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

Sponsor

Berner Augenklinik am Lindenhofspital (Other)

Overall Status

Enrolling by invitation

CT.gov ID

NCT04932980

Collaborator

medignition AG (Other)

Enrollment

Location

Arms

39.8

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Wet Age-related Macular Degeneration	Drug: Aflibercept Drug: Brolucizumab Procedure: early treat and extend (T&E)	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

80 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

two-armed, randomized, double-blindtwo-armed, randomized, double-blind

Masking:

Double (Participant, Investigator)

Masking Description:

double-blind

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

May 9, 2022

Anticipated Primary Completion Date :

Dec 1, 2024

Anticipated Study Completion Date :

Sep 1, 2025

Arms and Interventions

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.	Drug: Brolucizumab administration of anti-VEGF Brolucizumab (Beovu) Procedure: early treat and extend (T&E) extension of treatment intervals (T&E) from the beginning of treatment

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.

Drug: Brolucizumab

administration of anti-VEGF Brolucizumab (Beovu)

Procedure: early treat and extend (T&E)

extension of treatment intervals (T&E) from the beginning of treatment

Outcome Measures

Primary Outcome Measures

Number of injections given until week 52 [52 weeks]
number injections received by patient

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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