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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Age-related Macular Degeneration

Intervention / Treatment
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* Biological: Brolucizumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: two arm, multicenter
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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