Study of Brolucizumab in Adult Patients With Suboptimal Anatomically Controlled Neovascular Age-related Macular Degeneration

Novartis Pharmaceuticals295 enrolled

Overview

Neovascular age-related macular degeneration is characterized by the presence of choroidal neovascularization (CNV), which consists of abnormal blood vessels originating from the choroid that can lead to hemorrhage, fluid exudation, and fibrosis, resulting in photoreceptor damage and vision loss.

This is a prospective, single-arm, open-label, multicenter study to evaluate the efficacy and safety of brolucizumab 6 mg in pretreated suboptimal anatomically controlled patients with neovascular age-related macular degeneration (nAMD).

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

295

Conditions

Neovascular Age-Related Macular Degeneration

Interventions

RTH258/BrolucizumabDRUG

Brolucizumab is a new generation of anti-VEGF (vascular endothelial growth factor). All patients will be treated with brolucizumab 6mg: 3 loading injections (at Screening/Baseline, Week 4 and Week 8), followed by Treat-to-Control regimen up to Week 44/46.

Eligibility

Sex: ALLMin age: 50 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Patients must provide written informed consent before any study-related procedures are performed. 2. Patients must be 50 years of age or older at Screening/Baseline. Study eye: 3. Active CNV lesions secondary to nAMD diagnosed \< 18 months prior to Screening/Baseline that affect the central subfield, including retinal angiomatous proliferation (RAP) with a CNV component, confirmed by presence of active leakage from CNV seen by FA and sequelae of CNV, e.g. pigment epithelial detachment (PED), subretinal hemorrhage or sub RPE hemorrhage, blocked fluorescence, or macular edema. 4. Previous treatment with only one licensed anti-VEGF drug (i.e. Lucentis®, Eylea®) with a ≥ Q4 and ≤ Q8 treatment (treatment interval of 26 to 62 days inclusive) with licensed anti-VEGF (a minimal washout period of at least 4 weeks / 26 days is required). Patients must have received at least 3 injections of this anti-VEGF in the 6 months prior to Screening/Baseline. 5. Presence of residual fluid (IRF or SRF that affects the central subfield under, as seen by OCT) 6. BCVA score must be ≤ 83 and ≥ 38 letters at an initial testing distance of 4 meters starting distance using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity charts at Screening/Baseline. Exclusion Criteria: Ocular conditions 1. Any active intraocular or periocular infection or active intraocular inflammation (e.g. infectious conjunctivitis, keratitis, scleritis, endophthalmitis, infectious blepharitis), in either eye at Screening/Baseline. 2. Presence of amblyopia, amaurosis, or ocular disorders in the fellow eye with BCVA \< 35 ETDRS letters at Screening/Baseline (except when due to conditions whose surgery may improve visual acuity, e.g. cataract). 3. Medical history of intraocular inflammation and/or retinal vascular occlusion within 12 months prior to Screening/Baseline Study eye 4. Poor quality of OCT image at Screening/Baseline. 5. Atrophy or fibrosis involving the center of the fovea in the study eye, as assessed by CFP and fundus autofluorescence (FAF). 6. The total area of fibrosis or subretinal blood affecting the foveal center point comprising ≥ 50% of the lesion area in the study eye. 7. Concomitant conditions or ocular disorders in the study eye, including retinal diseases other than nAMD, that, in the judgment of the Investigator, could require medical or surgical intervention during the course of the study to prevent or treat visual loss that might result from that condition, or that limits the potential to gain visual acuity upon treatment with the investigational product. 8. Structural damage within 0.5 disc diameter of the center of the macula in the study eye, e.g. vitreomacular traction, epiretinal membrane, RPE rip/tear scar, laser burn, at the time of Screening/Baseline that in the Investigator's opinion could preclude visual function improvement with treatment. 9. Current vitreous hemorrhage or history of vitreous hemorrhage in the study eye within 4 weeks prior to Screening/Baseline. 10. Uncontrolled glaucoma in the study eye defined as IOP \> 25 mmHg on medication or according to the Investigator's judgment, at Screening/Baseline. 11. Aphakia and/or absence of the posterior capsule in the study eye. Ocular treatments (study eye) 12. Patient has received any investigational treatment for nAMD (other than vitamin supplements) in the study eye at any time. 13. Previous use of intraocular or periocular of corticosteroids in the study eye within the 6 month period prior to Screening/Baseline. 14. Previous penetrating keratoplasty or vitrectomy at any time prior to Screening/Baseline. 15. History or evidence of the following in the study eye within the 90-day period prior to Screening/Baseline: * Intraocular or refractive surgery. * Previous panretinal and peripheral laser photocoagulation. * Previous macular surgery or other intraocular surgical intervention 16. Previous laser treatment for nAMD including photodynamic therapy (PDT) laser at any time prior to Screening/Baseline. 17. Previous treatment with investigational drugs.

Locations (51)

Outcomes

Primary Outcomes

Number of Patients With no Disease Activity at Week 16 in the Study Eye

Disease activity criteria were assessed by the Investigator based on whether neovascular age-related macular degeneration (nAMD) was still active or had been re-activated. The disease was defined as active if at least one of the following criteria was observed: * Best-corrected visual acuity (BCVA) decrease ≥ 5 letters from the best value since Baseline due to disease activity * Any significant increase in central retinal thickness (CRT) * Retinal hemorrhage * Intraretinal fluid or sub-retinal fluid (SRF) due to disease activity (degenerative cysts allowed) * Increase of sub-retinal pigmented epithelium (RPE) fluid These criteria were for guidance only, Investigators could define disease activity based on their own assessment.

Time frame: Week 16

Secondary Outcomes

Number of Patients With no Disease Activity at Week 48 in the Study Eye

Time frame: Week 48

Change From Baseline in CFST (Central Sub-Field Retinal Thickness) as Assessed by OCT (Optical Coherence Tomography) Over Time up to Week 48 in the Study Eye

Central Subfield Thickness Assessed by Spectral domain optical coherence tomography (SD-OCT) from the central reading center.

Time frame: Baseline, Weeks 4,8,16, 48

Absence of IRF (Intraretinal Fluid), SRF (Subretinal Fluid), and Sub-RPE (Retinal Pigmented Epithelium) Fluid as Assessed by OCT Over Time up to Week 48 in the Study Eye

Data from ClinicalTrials.gov

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