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

Age-related Macular Degeneration Clinical Trial

— FALCON  

Official title:

A 52-week, Two Arm, Randomized, Open-label, Multicenter Study Assessing the Efficacy and Safety of Two Different Brolucizumab 6 mg Dosing Regimens for Patients With Suboptimal Anatomically Controlled Neovascular Age-related Macular Degeneration

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04679935
• Other study ID #: CRTH258ADE01
• Secondary ID: 2019-004767-53
• Status: Completed
• Phase: Phase 4
• Start date: July 13, 2021
• Est. completion date: January 31, 2024

Study information

• Verified date: April 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is 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.

Description:

The study is a 52-week, two arm, randomized, open-label, multicenter study in patients with suboptimal anatomically controlled neovascular age-related macular degeneration. Patients who consent will undergo screening assessments to evaluate their eligibility based on the inclusion and exclusion criteria. Afterwards, patients will be randomized in a 1:1 ratio to one of the two treatment arms and attend 15 planned visits. Subjects in the loading arm will receive 3x monthly loading doses followed by treatment every 12 weeks. Subjects in the non-loading arm receive one initial injection followed by treatment every 12 weeks.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: January 31, 2024
• Est. primary completion date: January 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 99 Years

Eligibility

Inclusion Criteria:

• Signed informed consent must be obtained prior to participation in the study

• 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:

• Concomitant conditions or ocular disorders in the study eye at screening or baseline which could, in the opinion of the investigator, prevent response to study treatment or may confound interpretation of study results, compromise visual acuity or require planned medical or surgical intervention during the 52-week study period, atrophy or fibrosis at the center of the fovea as confirmed by central reading center or structural damage of the fovea (study eye)

• 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

Other protocol-defined inclusion/exclusion criteria may apply

Related Conditions & MeSH terms

• Age-related Macular Degeneration
• Macular Degeneration
• Wet Macular Degeneration

Intervention

Biological:
• Brolucizumab
Intravitreal injection

Locations

Country	Name	City	State
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Bonn
Germany	Novartis Investigative Site	Duesseldorf
Germany	Novartis Investigative Site	Frankfurt Main	Hessen
Germany	Novartis Investigative Site	Gottingen
Germany	Novartis Investigative Site	Hannover
Germany	Novartis Investigative Site	Homburg
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Luebeck
Germany	Novartis Investigative Site	Magdeburg
Germany	Novartis Investigative Site	Mainz
Germany	Novartis Investigative Site	Marburg
Germany	Novartis Investigative Site	Muenster
Germany	Novartis Investigative Site	Neubrandenburg
Germany	Novartis Investigative Site	Regensburg	Bavaria
Germany	Novartis Investigative Site	Ulm
Switzerland	Novartis Investigative Site	Bern
Switzerland	Novartis Investigative Site	Lausanne	CHE
Switzerland	Novartis Investigative Site	Zuerich

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Germany,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean change in best-corrected visual acuity	Visual acuity test (the assumed patient number necessary for analysis of the primary objective will not be achieved. Therefore, the primary endpoint and all analyses will now be performed in a purely descriptive manner.); BCVA will be assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts.	Baseline, Week 40 to Week 52
Secondary	Mean treatment interval	Treatment interval distribution	-24 Weeks, Baseline, Week 52
Secondary	Rate of patients with prolonged interval	Treatment interval distribution	-24 Weeks, Baseline, Week 52
Secondary	Proportion of patients maintained at a every 12 weeks interval	Treatment interval distribution	every 12 weeks up to week 52
Secondary	Distribution of patients at every 8 weeks/ every 12 weeks intervals	Treatment interval distribution	Baseline and every 8 or 12 weeks, up to Week 52
Secondary	Mean change in best-corrected visual acuity	BCVA will be assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts.	Baseline, Week 52
Secondary	Proportions of patients with best-corrected visual acuity improvements of >= 5, >= 10 and >= 15 letters	BCVA will be assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts.	Baseline, Week 52
Secondary	Proportion of patients with best-corrected visual acuity >= 69 letters	BCVA will be assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts.	At Week 52
Secondary	Mean change in best-corrected visual acuity	BCVA will be assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts.	Baseline, Week 16 to Week 28
Secondary	Change in central subfield thickness	Change in central subfield thickness will be measured by Spectral domain optical coherence tomography.	Baseline, Week 52
Secondary	Absence of intraretinal fluid, subretinal fluid, and sub-retinal pigment epithelium fluid in the central subfield	Change in fluids will be measured by Spectral domain optical coherence tomography.	Up to Week 52
Secondary	Presence of active choroidal neovascularization leakage	Presence of active choroidal neovascularization leakage will be measured by Fluorescein angiography.	At Week 52
Secondary	Incidence of ocular and non-ocular adverse events	An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign (including abnormal laboratory findings), symptom or disease) in a subject or clinical investigation subject after providing written informed consent for participation in the study.	Up to Week 52