Clinical trial NCT04264819: Study of Brolucizumab in Adult Patients With Suboptimal Anatomically Controlled Neovascular Age-related Macular Degeneration
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
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
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2020-02-11
Enrollment: 295
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single-arm, open-label study
Primary purpose: TREATMENT

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).

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.

Primary outcomes:
measure: Number of Patients With no Disease Activity at Week 16 in the Study Eye
timeFrame: Week 16
Secondary outcomes:
measure: Number of Patients With no Disease Activity at Week 48 in the Study Eye
timeFrame: Week 48
measure: 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
timeFrame: Baseline, Weeks 4,8,16, 48
measure: 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
timeFrame: Baseline, Week 4, 8, 16, 48
measure: Number of Patients With a Dry Retina (Neither IRF Nor SRF) up to Week 48 in the Study Eye
timeFrame: Baseline, Weeks 4, 8, 16, 48
measure: Distribution of the Last Interval With no Disease Activity up to Week 48 in the Study Eye
timeFrame: Intervals of 0,4,5,6,7,8,9,10,11,12,13,14,15,16,17 Weeks
measure: Distribution of the Maximal Intervals With no Disease Activity up to Week 48 in the Study Eye
timeFrame: Intervals of 0,4,5,6,7,8,9,10,11,12,13,14,15,16,17 Weeks
measure: Average Change in BCVA (Best-Corrected Visual Acuity) From Baseline up to Week 48 in the Study Eye
timeFrame: Baseline, Weeks 4, 8, 16, 48
measure: Summary of Treatment-emergent Adverse Events - Overall
timeFrame: 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.
measure: Summary of Treatment-emergent Adverse Events Regardless of Study Treatment Relationship by Primary System Organ Class, Preferred Term, and Maximum Severity - Ocular (Study Eye)
timeFrame: 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.
measure: Summary of Treatment-emergent Adverse Events Regardless of Study Treatment Relationship by Primary System Organ Class, Preferred Term, and Maximum Severity - Non-ocular
timeFrame: 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.
Other outcomes:
Locations:
city: Nice
country: France
facility: Novartis Investigative Site
state: Cedex1
city: Rennes Cedex 9
country: France
facility: Novartis Investigative Site
state: FRA
city: Saint Cyr sur Loire
country: France
facility: Novartis Investigative Site
state: Indre Et Loire
city: Lyon cedex 04
country: France
facility: Novartis Investigative Site
state: Rhone
city: Bobigny cedex
country: France
facility: Novartis Investigative Site
state: Seine Saint Denis
city: Aix en Provence
country: France
facility: Novartis Investigative Site
city: Angers
country: France
facility: Novartis Investigative Site
city: Avignon
country: France
facility: Novartis Investigative Site
city: Bordeaux Cedex
country: France
facility: Novartis Investigative Site
city: Bordeaux
country: France
facility: Novartis Investigative Site
city: Caen Cedex
country: France
facility: Novartis Investigative Site
city: Caen
country: France
facility: Novartis Investigative Site
city: Colmar Cedex
country: France
facility: Novartis Investigative Site
city: Creteil
country: France
facility: Novartis Investigative Site
city: Dijon
country: France
facility: Novartis Investigative Site
city: Grenoble
country: France
facility: Novartis Investigative Site
city: La Rochelle
country: France
facility: Novartis Investigative Site
city: La Valette Du Var
country: France
facility: Novartis Investigative Site
city: Le Chesnay
country: France
facility: Novartis Investigative Site
city: Lille
country: France
facility: Novartis Investigative Site
city: Lyon
country: France
facility: Novartis Investigative Site
city: Lyon
country: France
facility: Novartis Investigative Site
city: Marseille
country: France
facility: Novartis Investigative Site
city: Marseille
country: France
facility: Novartis Investigative Site
city: Melun
country: France
facility: Novartis Investigative Site
city: Montargis
country: France
facility: Novartis Investigative Site
city: Montauban
country: France
facility: Novartis Investigative Site
city: Montpellier
country: France
facility: Novartis Investigative Site
city: Montpellier
country: France
facility: Novartis Investigative Site
city: Mulhouse cedex
country: France
facility: Novartis Investigative Site
city: Nantes Cedex 1
country: France
facility: Novartis Investigative Site
city: Nantes
country: France
facility: Novartis Investigative Site
city: Paris 13
country: France
facility: Novartis Investigative Site
city: Paris cedex 10
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Perpignan
country: France
facility: Novartis Investigative Site
city: Plerin
country: France
facility: Novartis Investigative Site
city: Poitiers
country: France
facility: Novartis Investigative Site
city: Rouen
country: France
facility: Novartis Investigative Site
city: Rueil Malmaison
country: France
facility: Novartis Investigative Site
city: Saint Herblain
country: France
facility: Novartis Investigative Site
city: Saint Jean de Vedas
country: France
facility: Novartis Investigative Site
city: Saint Jean
country: France
facility: Novartis Investigative Site
city: Saint Martin des Champs
country: France
facility: Novartis Investigative Site
city: Strasbourg
country: France
facility: Novartis Investigative Site
city: Toulouse Cedex 9
country: France
facility: Novartis Investigative Site
city: Tours
country: France
facility: Novartis Investigative Site
city: Vincennes
country: France
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: