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

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

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.

Study Overview

• Status: Completed
• Conditions: Age-related Macular Degeneration
• Intervention / Treatment: Biological: Brolucizumab

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 13353
    • Novartis Investigative Site
  • Bonn, Germany, 53105
    • Novartis Investigative Site
  • Duesseldorf, Germany, 40225
    • Novartis Investigative Site
  • Gottingen, Germany, 37075
    • Novartis Investigative Site
  • Hannover, Germany, 30625
    • Novartis Investigative Site
  • Homburg, Germany, 66421
    • Novartis Investigative Site
  • Leipzig, Germany, 04103
    • Novartis Investigative Site
  • Luebeck, Germany, 23538
    • Novartis Investigative Site
  • Magdeburg, Germany, 39120
    • Novartis Investigative Site
  • Mainz, Germany, 55131
    • Novartis Investigative Site
  • Marburg, Germany, 35039
    • Novartis Investigative Site
  • Muenster, Germany, 48149
    • Novartis Investigative Site
  • Neubrandenburg, Germany, 17036
    • Novartis Investigative Site
  • Ulm, Germany, 89075
    • Novartis Investigative Site
  • Bavaria
    • Regensburg, Bavaria, Germany, 93053
      • Novartis Investigative Site
  • Hessen
    • Frankfurt Main, Hessen, Germany, 60549
      • Novartis Investigative Site
• Switzerland
  • Bern, Switzerland, 3007
    • Novartis Investigative Site
  • Zuerich, Switzerland, 8063
    • Novartis Investigative Site
  • CHE
    • Lausanne, CHE, Switzerland, 1000
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Brolucizumab 6 mg non-loading; One initial injection followed by treatment every 12 weeks.	Biological: Brolucizumab; Intravitreal injection; Other Names: RTH258
Experimental: Brolucizumab 6 mg loading; 3 x 4-weekly injections followed by treatment every 12 weeks.	Biological: Brolucizumab; Intravitreal injection; Other Names: RTH258

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean treatment interval	Treatment interval distribution	-24 Weeks, Baseline, Week 52
Rate of patients with prolonged interval	Treatment interval distribution	-24 Weeks, Baseline, Week 52
Proportion of patients maintained at a every 12 weeks interval	Treatment interval distribution	every 12 weeks up to week 52
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
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
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
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
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
Change in central subfield thickness	Change in central subfield thickness will be measured by Spectral domain optical coherence tomography.	Baseline, Week 52
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
Presence of active choroidal neovascularization leakage	Presence of active choroidal neovascularization leakage will be measured by Fluorescein angiography.	At Week 52
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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Holz FG, Schmitz-Valckenberg S, Wolf A, Agostini H, Lorenz K, Pielen A, Feltgen N, Guthoff R, Quiering C, Clemens A, Jaeger K. A randomized, open-label, multicenter study of switching to brolucizumab with or without a loading dose for patients with suboptimal anatomically controlled neovascular age-related macular degeneration-the FALCON study. Graefes Arch Clin Exp Ophthalmol. 2022 Aug;260(8):2695-2702. doi: 10.1007/s00417-022-05591-z. Epub 2022 Feb 21.

Study record dates

Study Major Dates

• Study Start (Actual): July 13, 2021
• Primary Completion (Actual): January 31, 2024
• Study Completion (Actual): January 31, 2024

Study Registration Dates

• First Submitted: December 3, 2020
• First Submitted That Met QC Criteria: December 21, 2020
• First Posted (Actual): December 22, 2020

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Eye Diseases; anti-VEGF; Macular degeneration; neovascular age-related macular degeneration; choroidal neovascularization; vision loss; Retinal Diseases; Retinal Degeneration; wet macular degeneration; brolucizumab; age-related macular degeneration (ARMD); macula damage; retina damage; dry macular degeneration; Subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration; loading vs. non-loading
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Wet Macular Degeneration
• Other Study ID Numbers: CRTH258ADE01; 2019-004767-53 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on ww.clinicalstudydatarequest.com.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No