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

NCT04264819 | Completed Phase 3 Results

• 2 other identifiers: CRTH258AFR032019-004145-33
• Study Type: interventional
• Target: 295
• Locations: 1 country
• Sites: 51

Brief Summary

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.

Conditions

Neovascular Age-Related Macular Degeneration

Keywords

Macular degeneration; age-related macular degeneration (ARMD); vision loss; macula damage; retina damage; dry macular degeneration; wet macular degeneration; AMD; diabetic macular edema; DME; neovascular age-related macular degeneration; nAMD; retinal vein occlusion; RVO; wetAMD; neovascular; choroidal neovascularization; disease control

Outcome Measures

Primary Outcomes (1)

• 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.

  Week 16

Secondary Outcomes (10)

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

  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

  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

  Baseline, Week 4, 8, 16, 48

• Number of Patients With a Dry Retina (Neither IRF Nor SRF) up to Week 48 in the Study Eye

  Baseline, Weeks 4, 8, 16, 48

• Distribution of the Last Interval With no Disease Activity up to Week 48 in the Study Eye

  Intervals of 0,4,5,6,7,8,9,10,11,12,13,14,15,16,17 Weeks

Study Arms (1)

RTH258/Brolucizumab

EXPERIMENTAL

This is a single arm study in which all patients will be treated with brolucizumab 6mg; 3 loading injections (at Screening/Baseline, week 4 and week 8) followed by treat-to-control phase with adjustable treatment frequency based on disease activity from every 8 to up to 16 weeks; last treatment at week 44/46 based on the treatment regimen.

Drug: RTH258/Brolucizumab

Interventions

RTH258/Brolucizumab DRUG

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.

RTH258/Brolucizumab

Eligibility Criteria

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

You may qualify if:

• Patients must provide written informed consent before any study-related procedures are performed.
• Patients must be 50 years of age or older at Screening/Baseline.
• Study eye:
• 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.
• 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.
• Presence of residual fluid (IRF or SRF that affects the central subfield under, as seen by OCT)
• 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.

You may not qualify if:

• Ocular conditions
• 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.
• 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).
• Medical history of intraocular inflammation and/or retinal vascular occlusion within 12 months prior to Screening/Baseline
• Study eye
• Poor quality of OCT image at Screening/Baseline.
• Atrophy or fibrosis involving the center of the fovea in the study eye, as assessed by CFP and fundus autofluorescence (FAF).
• The total area of fibrosis or subretinal blood affecting the foveal center point comprising ≥ 50% of the lesion area in the study eye.
• 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.
• 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.
• Current vitreous hemorrhage or history of vitreous hemorrhage in the study eye within 4 weeks prior to Screening/Baseline.
• Uncontrolled glaucoma in the study eye defined as IOP \> 25 mmHg on medication or according to the Investigator's judgment, at Screening/Baseline.
• Aphakia and/or absence of the posterior capsule in the study eye. Ocular treatments (study eye)
• Patient has received any investigational treatment for nAMD (other than vitamin supplements) in the study eye at any time.
• Previous use of intraocular or periocular of corticosteroids in the study eye within the 6 month period prior to Screening/Baseline.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (51)

Novartis Investigative Site

Nice, Cedex1, 06001, France

Location

Novartis Investigative Site

Rennes, FRA, 35033, France

Location

Novartis Investigative Site

Saint-Cyr-sur-Loire, Indre Et Loire, 37540, France

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Novartis Investigative Site

Lyon, Rhone, 69317, France

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Novartis Investigative Site

Bobigny, Seine Saint Denis, 93009, France

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Novartis Investigative Site

Aix-en-Provence, 13090, France

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Novartis Investigative Site

Angers, 49044, France

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Novartis Investigative Site

Avignon, 84000, France

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Novartis Investigative Site

Bordeaux, 33000, France

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Novartis Investigative Site

Bordeaux, 33076, France

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Novartis Investigative Site

Caen, 14000, France

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Novartis Investigative Site

Caen, 14033, France

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Novartis Investigative Site

Colmar, 68024, France

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Novartis Investigative Site

Créteil, 94000, France

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Novartis Investigative Site

Dijon, 21034, France

Location

Novartis Investigative Site

Grenoble, 38000, France

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Novartis Investigative Site

La Rochelle, 17019, France

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Novartis Investigative Site

La Valette-du-Var, 83160, France

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Novartis Investigative Site

Le Chesnay, 78157, France

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Novartis Investigative Site

Lille, 59000, France

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Novartis Investigative Site

Lyon, 69002, France

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Novartis Investigative Site

Lyon, 69275, France

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Novartis Investigative Site

Marseille, 13015, France

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Novartis Investigative Site

Marseille, F 13008, France

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Novartis Investigative Site

Melun, 77000, France

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Novartis Investigative Site

Montargis, 45200, France

Location

Novartis Investigative Site

Montauban, 82000, France

Location

Novartis Investigative Site

Montpellier, 34000, France

Location

Novartis Investigative Site

Montpellier, 34295, France

Location

Novartis Investigative Site

Mulhouse, 68070, France

Location

Novartis Investigative Site

Nantes, 44093, France

Location

Novartis Investigative Site

Nantes, 44300, France

Location

Novartis Investigative Site

Paris, 75001, France

Location

Novartis Investigative Site

Paris, 75007, France

Location

Novartis Investigative Site

Paris, 75010, France

Location

Novartis Investigative Site

Paris, 75015, France

Location

Novartis Investigative Site

Paris, 75651, France

Location

Novartis Investigative Site

Paris, 75674, France

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Novartis Investigative Site

Perpignan, 66000, France

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Novartis Investigative Site

Plérin, 22190, France

Location

Novartis Investigative Site

Poitiers, 86000, France

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Novartis Investigative Site

Rouen, 76100, France

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Novartis Investigative Site

Rueil-Malmaison, 92500, France

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Novartis Investigative Site

Saint-Herblain, 44819, France

Location

Novartis Investigative Site

Saint-Jean, 31240, France

Location

Novartis Investigative Site

Saint-Jean-de-Védas, 34430, France

Location

Novartis Investigative Site

Saint-Martin-des-Champs, 50300, France

Location

Novartis Investigative Site

Strasbourg, 67000, France

Location

Novartis Investigative Site

Toulouse, 31059, France

Location

Novartis Investigative Site

Tours, 37000, France

Location

Novartis Investigative Site

Vincennes, 94300, France

Location

Related Publications (1)

• Bodaghi B, Souied EH, Tadayoni R, Weber M, Ponthieux A, Kodjikian L. Detection and Management of Intraocular Inflammation after Brolucizumab Treatment for Neovascular Age-Related Macular Degeneration. Ophthalmol Retina. 2023 Oct;7(10):879-891. doi: 10.1016/j.oret.2023.06.009. Epub 2023 Jun 19.

  PMID: 37343623 DERIVED

MeSH Terms

Conditions

Macular Degeneration; Vision Disorders; Geographic Atrophy; Wet Macular Degeneration; Retinal Vein Occlusion; Choroidal Neovascularization

Interventions

brolucizumab

Condition Hierarchy (Ancestors)

Retinal Degeneration; Retinal Diseases; Eye Diseases; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Venous Thrombosis; Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Choroid Diseases; Uveal Diseases; Neovascularization, Pathologic; Metaplasia; Pathologic Processes

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 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single-arm, open-label study

Study Record Dates

• First Submitted: February 7, 2020
• First Posted: February 11, 2020
• Study Start: December 14, 2020
• Primary Completion: October 5, 2022
• Study Completion: May 10, 2023
• Last Updated: November 7, 2024
• Results First Posted: November 7, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will share

Locations

FR (51)