NCT04239027

Brief Summary

Neovascular age-related macular degeneration (nAMD) is characterized by the presence of choroidal neovascularization (CNV). Choroidal neovascularization consists of abnormal blood vessels originating from the choroid and can lead to hemorrhage, fluid exudation, and fibrosis, resulting in photoreceptor damage and vision loss. The safety and efficacy of brolucizumab has been demonstrated in 2 randomized, multicenter, double-masked, active controlled Phase 3 studies in nAMD patients (RTH258-C001 and RTH258-C002). Anatomical changes were evaluated in these studies using spectral domain optical coherence tomography (SD-OCT), which relied on indirect parameters for the diagnosis of active CNV. The OCT-angiography (OCT A) that directly visualize retinal circulation and image CNV and vascular diseases of the retina was not included in previous brolucizumab studies. This single-arm, open-label, multicenter study was performed to evaluate the efficacy and safety of brolucizumab 6 mg in patients with nAMD. OCT-A was used in this study to assess the morphological response of patients to brolucizumab in terms of percentage change in CNV lesion area in the short term (i.e. at Week 12) and in the long term (i.e. at Week 48), as well as changes in other OCT-A features up to Week 48.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
210

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started Jan 2021

Geographic Reach
1 country

40 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 21, 2020

Completed
2 days until next milestone

First Posted

Study publicly available on registry

January 23, 2020

Completed
1 year until next milestone

Study Start

First participant enrolled

January 26, 2021

Completed
1.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 23, 2022

Completed
9 months until next milestone

Study Completion

Last participant's last visit for all outcomes

February 2, 2023

Completed
1.3 years until next milestone

Results Posted

Study results publicly available

June 4, 2024

Completed
Last Updated

October 9, 2024

Status Verified

October 1, 2024

Enrollment Period

1.3 years

First QC Date

January 21, 2020

Results QC Date

April 28, 2023

Last Update Submit

October 7, 2024

Conditions

Keywords

age-related macular degeneration, wetAMD, nAMD, neovascular, choroidal neovascularization, CNV, OCT-angiography

Outcome Measures

Primary Outcomes (1)

  • Percentage Change in Choroidal Neovascularization (CNV) Lesion Area Measured by Optical Coherence Tomography-Angiograph (OCT-A) From Baseline to Week 12

    OCT-A is a dye-less angiographic procedure based on split-spectrum-decorrelation-amplitude angiography. It enables the capture of scattered intra-vessel particles (mainly erythrocyte cells) at all levels of the retinal and inner-choroidal vasculature, thus providing 3-D imaging of the retinal circulation. The literature suggests that OCT-A is a good marker for assessing anti-VEGF therapeutic response, especially lesion size. Inter-Quartile Range = q1 - q3.

    Baseline, Week 12

Secondary Outcomes (12)

  • Percentage Change in Choroidal Neovascularization (CNV) Lesion Area Measured by Optical Coherence Tomography-Angiograph (OCT-A) From Baseline to Week 48

    Baseline, Weeks 4, 8, 48

  • Change in Choroidal Neovascularization (CNV) Lesion Area Measured by Optical Coherence Tomography-Angiograph (OCT-A) From Baseline to Week 48

    Baseline, Weeks 4, 8, 12, 48

  • Presence of Choroidal Neovascularization (CNV) Lesion Area Measured by Optical Coherence Tomography-Angiograph (OCT-A) From Baseline to Week 48

    Baseline, Week 48

  • Change in Best Corrected Visual Acuity (BCVA) From Baseline up to Week 48

    Baseline, Weeks 4, 8, 12, 48

  • Percentage of Patients Who Are Maintained on an Exclusive Treatment Interval Every 12 Weeks (q12w) Following the Loading Phase to Week 48

    Weeks 20, 32, 44, 48

  • +7 more secondary outcomes

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 maintenance treatment from Week 16/Week 20 up to Week 40/Week 44.

Drug: RTH258/Brolucizumab

Interventions

Brolucizumab is a new generation of anti-VEGF (vascular endothelial growth factor). All patients were treated with brolucizumab 6mg: 3 loading injections (at Screening/Baseline, Week 4 and Week 8), followed by maintenance treatment every 8 weeks (Q8W) or every 12 weeks (Q12W) depending on disease activity from Week 16/Week20 to Week 40/Week 44. Brolucizumab was administered by an intravitreal (IVT) injection to the study. eye.

RTH258/Brolucizumab

Eligibility Criteria

Age50 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (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 AMD that affect 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 hemorrhage or sub-retinal pigment epithelium (sub-RPE) hemorrhage, blocked fluorescence, macular edema.
  • Intra- and/or subretinal fluid affecting the central subfield of the study eye at Screening/Baseline.
  • BCVA between 83 and 23 letters, inclusive, in the study eye at Screening/Baseline using early treatment diabetic retinopathy study (ETDRS) at an initial testing distance of 4 meters.

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 (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-A and SD-OCT images at Screening/Baseline.
  • Atrophy or fibrosis involving the center of the fovea in the study eye, as assessed by color fundus photography and fundus autofluorescence (FAF) at Screening/Baseline.
  • The total area of fibrosis or subretinal blood affecting the foveal center point comprising ≥ 50% of the lesion area in the study eye at Screening/Baseline.
  • 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, retinal pigment epithelium (RPE) rip/tear scar, laser burn, at the time of Screening 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 at Screening/Baseline.
  • Ocular treatments (study eye):
  • Patient has received any approved or investigational treatment for nAMD (other than vitamin supplements) in the study eye at any time.
  • +19 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (40)

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

Location

Novartis Investigative Site

Lyon, Rhone, 69317, France

Location

Novartis Investigative Site

Bobigny, Seine Saint Denis, 93009, France

Location

Novartis Investigative Site

Aix-en-Provence, 13090, France

Location

Novartis Investigative Site

Angers, 49044, France

Location

Novartis Investigative Site

Avignon, 84000, France

Location

Novartis Investigative Site

Bordeaux, 33000, France

Location

Novartis Investigative Site

Boulogne-sur-Mer, 62321, France

Location

Novartis Investigative Site

Caen, 14000, France

Location

Novartis Investigative Site

Caen, 14033, France

Location

Novartis Investigative Site

Créteil, 94000, France

Location

Novartis Investigative Site

Dijon, 21034, France

Location

Novartis Investigative Site

Floirac, 33270, France

Location

Novartis Investigative Site

Grenoble, 38000, France

Location

Novartis Investigative Site

La Rochelle, 17019, France

Location

Novartis Investigative Site

Lagord, 17140, France

Location

Novartis Investigative Site

Le Chesnay, 78157, France

Location

Novartis Investigative Site

Lille, 59000, France

Location

Novartis Investigative Site

Lyon, 69002, France

Location

Novartis Investigative Site

Marseille, F 13008, France

Location

Novartis Investigative Site

Montargis, 45200, France

Location

Novartis Investigative Site

Montauban, 82000, France

Location

Novartis Investigative Site

Montpellier, 34000, 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, 75007, France

Location

Novartis Investigative Site

Paris, 75010, France

Location

Novartis Investigative Site

Perpignan, 66000, France

Location

Novartis Investigative Site

Plérin, 22190, France

Location

Novartis Investigative Site

Poitiers, 86021, France

Location

Novartis Investigative Site

Rouen, 76100, France

Location

Novartis Investigative Site

Royan, 17200, France

Location

Novartis Investigative Site

Rueil-Malmaison, 92500, France

Location

Novartis Investigative Site

Saint-Herblain, 44819, 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

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.

Related Links

MeSH Terms

Conditions

Macular DegenerationChoroidal Neovascularization

Interventions

brolucizumab

Condition Hierarchy (Ancestors)

Retinal DegenerationRetinal DiseasesEye DiseasesChoroid DiseasesUveal DiseasesNeovascularization, PathologicMetaplasiaPathologic ProcessesPathological Conditions, Signs and Symptoms

Results Point of Contact

Title
Study Director
Organization
Novartis Pharmaceuticals

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
Model Details: Single-arm, open-label study
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 21, 2020

First Posted

January 23, 2020

Study Start

January 26, 2021

Primary Completion

May 23, 2022

Study Completion

February 2, 2023

Last Updated

October 9, 2024

Results First Posted

June 4, 2024

Record last verified: 2024-10

Data Sharing

IPD Sharing
Will share

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

More information

Locations