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

NCT ID: NCT04264819

Last Updated: 2024-11-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 295 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-14
• Study Completion Date: 2023-05-10

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.

Detailed Description

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).

Conditions

Neovascular Age-Related Macular Degeneration

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

RTH258/Brolucizumab

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.

Group Type: EXPERIMENTAL

RTH258/Brolucizumab

Intervention Type: 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.

Interventions

RTH258/Brolucizumab

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.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Investigative Site

Nice, Cedex1, France

Novartis Investigative Site

Rennes, FRA, France

Novartis Investigative Site

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

Novartis Investigative Site

Lyon, Rhone, France

Novartis Investigative Site

Bobigny, Seine Saint Denis, France

Novartis Investigative Site

Aix-en-Provence, , France

Novartis Investigative Site

Angers, , France

Novartis Investigative Site

Avignon, , France

Novartis Investigative Site

Bordeaux, , France

Novartis Investigative Site

Bordeaux, , France

Novartis Investigative Site

Caen, , France

Novartis Investigative Site

Caen, , France

Novartis Investigative Site

Colmar, , France

Novartis Investigative Site

Créteil, , France

Novartis Investigative Site

Dijon, , France

Novartis Investigative Site

Grenoble, , France

Novartis Investigative Site

La Rochelle, , France

Novartis Investigative Site

La Valette-du-Var, , France

Novartis Investigative Site

Le Chesnay, , France

Novartis Investigative Site

Lille, , France

Novartis Investigative Site

Lyon, , France

Novartis Investigative Site

Lyon, , France

Novartis Investigative Site

Marseille, , France

Novartis Investigative Site

Marseille, , France

Novartis Investigative Site

Melun, , France

Novartis Investigative Site

Montargis, , France

Novartis Investigative Site

Montauban, , France

Novartis Investigative Site

Montpellier, , France

Novartis Investigative Site

Montpellier, , France

Novartis Investigative Site

Mulhouse, , France

Novartis Investigative Site

Nantes, , France

Novartis Investigative Site

Nantes, , France

Novartis Investigative Site

Paris, , France

Novartis Investigative Site

Paris, , France

Novartis Investigative Site

Paris, , France

Novartis Investigative Site

Paris, , France

Novartis Investigative Site

Paris, , France

Novartis Investigative Site

Paris, , France

Novartis Investigative Site

Perpignan, , France

Novartis Investigative Site

Plérin, , France

Novartis Investigative Site

Poitiers, , France

Novartis Investigative Site

Rouen, , France

Novartis Investigative Site

Rueil-Malmaison, , France

Novartis Investigative Site

Saint-Herblain, , France

Novartis Investigative Site

Saint-Jean, , France

Novartis Investigative Site

Saint-Jean-de-Védas, , France

Novartis Investigative Site

Saint-Martin-des-Champs, , France

Novartis Investigative Site

Strasbourg, , France

Novartis Investigative Site

Toulouse, , France

Novartis Investigative Site

Tours, , France

Novartis Investigative Site

Vincennes, , France

Countries

France

References

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.

Reference Type: DERIVED

PMID: 37343623 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2019-004145-33

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CRTH258AFR03

Identifier Type: -

Identifier Source: org_study_id