Clinical trial NCT04679935: Efficacy and Safety of Two Different Brolucizumab 6 mg Dosing Regimens in Neovascular Age-related Macular Degeneration
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
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
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2020-12-22
Enrollment: 52
Sex: ALL
Minimum age (years): 50
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: two arm, multicenter
Primary purpose: TREATMENT

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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Week 40 to Week 52: LS Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye
timeFrame: Baseline, Week 40 to Week 52
Secondary outcomes:
measure: Treatment Intervals Before and During the Study
timeFrame: -24 Weeks, Baseline, Week 52
measure: Number of Patients With Prolonged Interval
timeFrame: Baseline, Week 52
measure: Proportion of Patients Who Maintained on q12w Regimen.
timeFrame: Up to week 52
measure: Distribution of Patients at Every 8 Weeks / Every 12 Weeks Intervals - Frequency of Switches in Treatment Intervals Between Baseline and Week 52
timeFrame: Up to Week 52
measure: Mean Change in Best-corrected Visual Acuity
timeFrame: Baseline, Weeks 16 to 28, Week 52
measure: Number of Patients With Best-corrected Visual Acuity Improvements of >= 5, >= 10 and >= 15 Letters
timeFrame: Baseline, up to Week 52
measure: Number of Patients With Best-corrected Visual Acuity >= 69 Letters
timeFrame: Baseline, up to Week 52
measure: LS Mean Change in Best-corrected Visual Acuity From Baseline at Week 52
timeFrame: Baseline, Week 52
measure: Change in Central Subfield Thickness From Baseline at Weeks 12, 16, 28 and 52
timeFrame: Baseline, Weeks 12, 16, 28 and 52
measure: Absence of Intraretinal Fluid in the Central Subfield
timeFrame: Every 4 weeks from baseline up to Week 52
measure: Absence of Subretinal Fluid in the Central Subfield
timeFrame: Every 4 weeks from baseline up to Week 52
measure: Absence of Sub-retinal Pigment Epithelium Fluid in the Central Subfield
timeFrame: Every 4 weeks from baseline up to Week 52
measure: Presence of Active Choroidal Neovascularization Leakage
timeFrame: At Week 52
measure: Overview of TEAEs
timeFrame: Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of approximately 52 weeks.
measure: Ocular TEAEs in the Study Eye by Primary System Organ Class
timeFrame: Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of approximately 52 weeks.
measure: Ocular TEAEs in the Study Eye by Preferred Term (at Least 5% in Any Group)
timeFrame: Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of approximately 52 weeks.
measure: Non-ocular TEAEs - Total
timeFrame: Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of approximately 52 weeks.
measure: Ocular TEAEs in the Study Eye of Moderate or Severe Intensity
timeFrame: Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of approximately 52 weeks.
Other outcomes:
Locations:
city: Regensburg
country: Germany
facility: Novartis Investigative Site
state: Bavaria
city: Frankfurt Main
country: Germany
facility: Novartis Investigative Site
state: Hessen
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Bonn
country: Germany
facility: Novartis Investigative Site
city: Duesseldorf
country: Germany
facility: Novartis Investigative Site
city: Gottingen
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Homburg
country: Germany
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
city: Luebeck
country: Germany
facility: Novartis Investigative Site
city: Magdeburg
country: Germany
facility: Novartis Investigative Site
city: Mainz
country: Germany
facility: Novartis Investigative Site
city: Marburg
country: Germany
facility: Novartis Investigative Site
city: Muenster
country: Germany
facility: Novartis Investigative Site
city: Neubrandenburg
country: Germany
facility: Novartis Investigative Site
city: Ulm
country: Germany
facility: Novartis Investigative Site
city: Lausanne
country: Switzerland
facility: Novartis Investigative Site
state: CHE
city: Bern
country: Switzerland
facility: Novartis Investigative Site
city: Zuerich
country: Switzerland
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: 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.