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

A One-year, Single-arm, Open-label, Multicenter Study Assessing the Effect of Brolucizumab on Disease Control in Adult Patients With Suboptimal Anatomically Controlled Neovascular Age-related Macular Degeneration (SWIFT)

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.

Study Overview

• Status: Completed
• Conditions: Neovascular Age-Related Macular Degeneration
• Intervention / Treatment: Drug: RTH258/Brolucizumab

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).

• Study Type: Interventional
• Enrollment (Actual): 295
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Aix en Provence, France, 13090
    • Novartis Investigative Site
  • Angers, France, 49044
    • Novartis Investigative Site
  • Avignon, France, 84000
    • Novartis Investigative Site
  • Bordeaux, France, 33000
    • Novartis Investigative Site
  • Bordeaux Cedex, France, 33076
    • Novartis Investigative Site
  • Caen, France, 14000
    • Novartis Investigative Site
  • Caen Cedex, France, 14033
    • Novartis Investigative Site
  • Colmar Cedex, France, 68024
    • Novartis Investigative Site
  • Creteil, France, 94000
    • Novartis Investigative Site
  • Dijon, France, 21034
    • Novartis Investigative Site
  • Grenoble, France, 38000
    • Novartis Investigative Site
  • La Rochelle, France, 17019
    • Novartis Investigative Site
  • La Valette Du Var, France, 83160
    • Novartis Investigative Site
  • Le Chesnay, France, 78157
    • Novartis Investigative Site
  • Lille, France, 59000
    • Novartis Investigative Site
  • Lyon, France, 69002
    • Novartis Investigative Site
  • Lyon, France, 69275
    • Novartis Investigative Site
  • Marseille, France, F 13008
    • Novartis Investigative Site
  • Marseille, France, 13015
    • Novartis Investigative Site
  • Melun, France, 77000
    • Novartis Investigative Site
  • Montargis, France, 45200
    • Novartis Investigative Site
  • Montauban, France, 82000
    • Novartis Investigative Site
  • Montpellier, France, 34000
    • Novartis Investigative Site
  • Montpellier, France, 34295
    • Novartis Investigative Site
  • Mulhouse cedex, France, 68070
    • Novartis Investigative Site
  • Nantes, France, 44300
    • Novartis Investigative Site
  • Nantes Cedex 1, France, 44093
    • Novartis Investigative Site
  • Paris, France, 75015
    • Novartis Investigative Site
  • Paris, France, 75007
    • Novartis Investigative Site
  • Paris, France, 75674
    • Novartis Investigative Site
  • Paris, France, 75001
    • Novartis Investigative Site
  • Paris 13, France, 75651
    • Novartis Investigative Site
  • Paris cedex 10, France, 75010
    • Novartis Investigative Site
  • Perpignan, France, 66000
    • Novartis Investigative Site
  • Plerin, France, 22190
    • Novartis Investigative Site
  • Poitiers, France, 86000
    • Novartis Investigative Site
  • Rouen, France, 76100
    • Novartis Investigative Site
  • Rueil Malmaison, France, 92500
    • Novartis Investigative Site
  • Saint Herblain, France, 44819
    • Novartis Investigative Site
  • Saint Jean, France, 31240
    • Novartis Investigative Site
  • Saint Jean de Vedas, France, 34430
    • Novartis Investigative Site
  • Saint Martin des Champs, France, 50300
    • Novartis Investigative Site
  • Strasbourg, France, 67000
    • Novartis Investigative Site
  • Toulouse Cedex 9, France, 31059
    • Novartis Investigative Site
  • Tours, France, 37000
    • Novartis Investigative Site
  • Vincennes, France, 94300
    • Novartis Investigative Site
  • Cedex1
    • Nice, Cedex1, France, 06001
      • Novartis Investigative Site
  • FRA
    • Rennes Cedex 9, FRA, France, 35033
      • Novartis Investigative Site
  • Indre Et Loire
    • Saint Cyr sur Loire, Indre Et Loire, France, 37540
      • Novartis Investigative Site
  • Rhone
    • Lyon cedex 04, Rhone, France, 69317
      • Novartis Investigative Site
  • Seine Saint Denis
    • Bobigny cedex, Seine Saint Denis, France, 93009
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients With no Disease Activity at Week 48 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 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.	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	Assessed by Spectral domain optical coherence tomography (SD-OCT) from the central reading center. At week 8, for 1 patient, the fluid assessment was performed, but result is unknown; at week 16, for 1 patient, the fluid assessment was performed, but result is unknown; at week 48, for 2 patients, the fluid assessment was performed, but result is unknown.	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	Assessed by Spectral domain optical coherence tomography (SD-OCT) from the central reading center.	Baseline, Weeks 4, 8, 16, 48
Distribution of the Last Interval With no Disease Activity up to Week 48 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.	Intervals of 0,4,5,6,7,8,9,10,11,12,13,14,15,16,17 Weeks
Distribution of the Maximal Intervals With no Disease Activity up to Week 48 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.	Intervals of 0,4,5,6,7,8,9,10,11,12,13,14,15,16,17 Weeks
Average Change in BCVA (Best-Corrected Visual Acuity) From Baseline up to Week 48 in the Study Eye	BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. Visual Function of the study eye was assessed using the ETDRS protocol. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.	Baseline, Weeks 4, 8, 16, 48
Summary of Treatment-emergent Adverse Events - Overall	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 clinical investigation participant after providing written informed consent for participation in the study.	Adverse events were reported from first dose of study treatment until Week 48, plus 30 days post treatment, up to a maximum duration of 52 weeks.
Summary of Treatment-emergent Adverse Events Regardless of Study Treatment Relationship by Primary System Organ Class, Preferred Term, and Maximum Severity - Ocular (Study Eye)	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 clinical investigation participant after providing written informed consent for participation in the study.	Adverse events were reported from first dose of study treatment until Week 48, plus 30 days post treatment, up to a maximum duration of 52 weeks.
Summary of Treatment-emergent Adverse Events Regardless of Study Treatment Relationship by Primary System Organ Class, Preferred Term, and Maximum Severity - Non-ocular	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 clinical investigation participant after providing written informed consent for participation in the study.	Adverse events were reported from first dose of study treatment until Week 48, plus 30 days post treatment, up to a maximum duration of 52 weeks.

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2020
• Primary Completion (Actual): October 5, 2022
• Study Completion (Actual): May 10, 2023

Study Registration Dates

• First Submitted: February 7, 2020
• First Submitted That Met QC Criteria: February 7, 2020
• First Posted (Actual): February 11, 2020

Study Record Updates

• Last Update Posted (Estimated): November 7, 2024
• Last Update Submitted That Met QC Criteria: September 6, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: diabetic macular edema; AMD; Macular degeneration; neovascular age-related macular degeneration; choroidal neovascularization; vision loss; retinal vein occlusion; RVO; DME; wet macular degeneration; age-related macular degeneration (ARMD); macula damage; retina damage; dry macular degeneration; nAMD; wetAMD; neovascular; disease control
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Diseases; Retinal Degeneration; Macular Degeneration; Wet Macular Degeneration
• Other Study ID Numbers: CRTH258AFR03; 2019-004145-33 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No