Efficacy and Safety of Two Different Brolucizumab 6 mg Dosing Regimens in Neovascular Age-related Macular Degeneration (FALCON)

Novartis

Status and phase: Completed; Phase 4

Conditions: Age-related Macular Degeneration

Treatments: Biological: Brolucizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT04679935

CRTH258ADE01

2019-004767-53 (EudraCT Number)

Details and patient eligibility

About

The purpose of this study was to evaluate the efficacy and safety of two different brolucizumab 6 mg dosing regimens in patients with visual impairment due to age-related macular degeneration (AMD) who have previously received anti-VEGF (vascular endothelial growth factor) treatment.

Full description

This study was a 52-week randomized, open-label, multi-center, two-arm study for pretreated patients with suboptimal anatomically controlled nAMD. Patients who consented were screened to evaluate eligibility. Eligible patients were randomized in a 1:1 ratio to one of the two treatment arms:

• Brolucizumab 6 mg "loading arm": 1 loading injection every 4 weeks for 3 consecutive injections (baseline, weeks 4 and 8) followed by an injection every 12 weeks.
• Brolucizumab 6 mg "non-loading arm": one initial injection followed by an injection every 12 weeks

There were three periods in this study:

• Screening period: from day -14 to baseline
• Open-label treatment period: from baseline (day 1) to week 48
• Post-treatment follow-up period: from week 48 to week 52

In both study arms, treatment intervals after the initiation phase were either 8 weeks or 12 weeks depending on disease activity status. More frequent injections, i.e., treatment intervals of < 8 weeks were not allowed after the initiation phase.

Enrollment: 52 patients

Sex: All

Ages: 50 to 99 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male or female patients ≥ 50 years of age at screening
• Active choroidal neovascularization (CNV) secondary to AMD that affects the central subfield, including retinal angiomatous proliferation (RAP) with a CNV component, confirmed by presence of active leakage from CNV seen by fluorescein angiography and sequellae of CNV, e.g. pigment epithelial detachment (PED), subretinal or sub-retinal pigment epithelium (sub-RPE) hemorrhage, blocked fluorescence, macular edema (intraretinal fluid (IRF) and/or subretinal fluid (SRF) and/or sub-retinal pigment epithelium (sub-RPE) fluid that affects the central subfield, as seen by spectral domain optical coherence tomography (SD-OCT)) at screening, as confirmed by central reading center (study eye). If active CNV according to the above explained activity criteria is not detectable in screening image data (no IRF and no SRF), presence of residual and/or recurrent fluid (IRF and / or SRF) within the last 6 months before baseline visit is also considered eligible. In this case, historical images must be submitted for analysis by the central reading center.
• Pretreatment with any anti-VEGF drug for a maximum of five years (60 months). Patients should have shown functional and/or anatomical treatment response to the pretreatment(s), prior to participating in this study.
• The treatment initiation phase with the current anti-VEGF must have been completed for at least 6 months with continuous treatment in a ≥ q4w to ≤ q12w injection interval (±2-day window, i.e., 26 to 86 days inclusive) before the baseline visit. At least 4 weeks (minimum 26 days) must have passed between the last anti-VEGF pretreatment and baseline.
• Best-corrected visual acuity (BCVA) score between 83 and 38 letters, inclusive, using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts at both screening and baseline visit (study eye)

Exclusion criteria

• Any active intraocular or periocular infection or active intraocular inflammation, at screening or baseline (study eye)
• Uncontrolled glaucoma defined as intraocular pressure (IOP) > 25 mmHg on medication, or according to investigator's judgement, at screening or baseline (study eye)
• Presence of amblyopia, amaurosis or ocular disorders in the fellow eye with BCVA <20/200 at screening (except when due to conditions whose surgery may improve VA, e.g. cataract)
• Ocular treatments: treatment with anti-VEGF drugs for > 5 years in the study eye, pretreatment with brolucizumab at any time in the study eye, previous treatment with investigational drugs in the last 6 months, intraocular or periocular steroids at any time, macular laser photocoagulation or photodynamic therapy at any time, peripheral laser photocoagulation within 3 months prior to baseline, intraocular surgery within 3 months prior to baseline, vitreoretinal surgery at any time, aphakia with the absence of posterior capsule (study eye)
• Stroke or myocardial infarction during the 6 month period prior to baseline
• Systemic anti-VEGF therapy during the 3-month period prior to baseline

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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52 participants in 2 patient groups

Brolucizumab 6 mg non-loading

Experimental group

Description:

One initial injection followed by treatment every 12 weeks.

Treatment:

Biological: Brolucizumab

Brolucizumab 6 mg loading

Experimental group

Description:

3 x 4-weekly injections followed by treatment every 12 weeks.

Treatment:

Biological: Brolucizumab