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

NCT04679935 | Completed Phase 4 Results

• 2 other identifiers: CRTH258ADE012019-004767-53
• Study Type: interventional
• Target: 52
• Locations: 2 countries
• Sites: 19

Brief Summary

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.

Conditions

Age-related Macular Degeneration

Keywords

neovascular age-related macular degeneration; anti-VEGF; choroidal neovascularization; brolucizumab; loading vs. non-loading; Macular degeneration; age-related macular degeneration (ARMD); vision loss; macula damage; retina damage; dry macular degeneration; wet macular degeneration; Subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration; Retinal Degeneration; Retinal Diseases; Eye Diseases

Outcome Measures

Primary Outcomes (1)

• Week 40 to Week 52: LS Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye

  BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. Visual function of the study eye was assessed using the ETDRS protocol. Participants with a BCVA ETDRS letter score between 78 and 23 ETDRS letters (inclusive) at Screening and Baseline in the study eye were included. Min and max possible scores are 0-100 respectively. A higher score represents better functioning.

  Baseline, Week 40 to Week 52

Secondary Outcomes (18)

• Treatment Intervals Before and During the Study

  -24 Weeks, Baseline, Week 52

• Number of Patients With Prolonged Interval

  Baseline, Week 52

• Proportion of Patients Who Maintained on q12w Regimen.

  Up to week 52

• Distribution of Patients at Every 8 Weeks / Every 12 Weeks Intervals - Frequency of Switches in Treatment Intervals Between Baseline and Week 52

  Up to Week 52

• Mean Change in Best-corrected Visual Acuity

  Baseline, Weeks 16 to 28, Week 52

Study Arms (2)

Brolucizumab 6 mg non-loading

EXPERIMENTAL

One initial injection followed by treatment every 12 weeks.

Biological: Brolucizumab

Brolucizumab 6 mg loading

EXPERIMENTAL

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

Biological: Brolucizumab

Interventions

Brolucizumab BIOLOGICAL

Intravitreal injection

Also known as: RTH258, Beovu

Brolucizumab 6 mg loading; Brolucizumab 6 mg non-loading

Eligibility Criteria

• Age: 50 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (19)

Novartis Investigative Site

Regensburg, Bavaria, 93053, Germany

Location

Novartis Investigative Site

Frankfurt am Main, Hesse, 60549, Germany

Location

Novartis Investigative Site

Berlin, 13353, Germany

Location

Novartis Investigative Site

Bonn, 53105, Germany

Location

Novartis Investigative Site

Düsseldorf, 40225, Germany

Location

Novartis Investigative Site

Göttingen, 37075, Germany

Location

Novartis Investigative Site

Hanover, 30625, Germany

Location

Novartis Investigative Site

Homburg, 66421, Germany

Location

Novartis Investigative Site

Leipzig, 04103, Germany

Location

Novartis Investigative Site

Lübeck, 23538, Germany

Location

Novartis Investigative Site

Magdeburg, 39120, Germany

Location

Novartis Investigative Site

Mainz, 55131, Germany

Location

Novartis Investigative Site

Marburg, 35039, Germany

Location

Novartis Investigative Site

Münster, 48149, Germany

Location

Novartis Investigative Site

Neubrandenburg, 17036, Germany

Location

Novartis Investigative Site

Ulm, 89075, Germany

Location

Novartis Investigative Site

Lausanne, CHE, 1000, Switzerland

Location

Novartis Investigative Site

Bern, 3007, Switzerland

Location

Novartis Investigative Site

Zurich, 8063, Switzerland

Location

Related Publications (1)

• 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.

  PMID: 35188581 DERIVED

Related Links

• A Plain Language Trial Summary is available on www.novctrd.com

MeSH Terms

Conditions

Macular Degeneration; Choroidal Neovascularization; Vision Disorders; Geographic Atrophy; Wet Macular Degeneration; Retinal Degeneration; Retinal Diseases; Eye Diseases

Interventions

brolucizumab

Condition Hierarchy (Ancestors)

Choroid Diseases; Uveal Diseases; Neovascularization, Pathologic; Metaplasia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Eye Diseases, Hereditary

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@Novartis.com

+ 1 862 778 8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: open-label
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: two arm, multicenter

Study Record Dates

• First Submitted: December 3, 2020
• First Posted: December 22, 2020
• Study Start: July 13, 2021
• Primary Completion: January 31, 2024
• Study Completion: January 31, 2024
• Last Updated: September 26, 2025
• Results First Posted: January 27, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

DE (16); CH (3)