Clinical trial NCT04774926: Study of Innovative Multimodal Imaging Biomarkers to Predict Anatomical Outcome in Naive Patients With wAMD Treated With Brolucizumab.
Official title: One Year, Single Arm, Open Label, Multicenter, Phase IV Study Using Multimodal Imaging to Guide Disease Activity Assessment Through Innovative Early Predictive Anatomical Biomarkers of Fluid Resolution in wAMD Patients Treated With Brolucizumab- IMAGINE Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Neovascular Age-related Macular Degeneration
Keywords: Neovascular age-related macular degeneration
anti-VEGF
brolucizumab
choroidal neovascularization
multimodal imaging biomarkers
fluid resolution
Macular degeneration
age-related macular degeneration (ARMD)
vision loss
macula damage
retina damage
dry macular degeneration
wet macular degeneration
AMD
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2021-03-01
Enrollment: 122
Sex: ALL
Minimum age (years): 50
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: The study is a one-year, open-label, single arm, multicenter, phase IV study in patients with wAMD.
Primary purpose: TREATMENT

Brief summary: The purpose of this study was to identify innovative early imaging parameters as predictors of the long-term clinical response to brolucizumab in terms of fluid resolution in patients with wet Age-related Macular Degeneration (wAMD) to evaluate their potential in supporting the choice of treatment regimen (q12w or q8w).

Detailed description: The study was a one-year, open-label, single arm, multicenter, phase IV study in patients with wAMD. The study planned to enroll approximately 263 (male and female) patients aged 50 years or older with untreated active subfoveal choroidal neovascularization (CNV) secondary to wAMD in the study eye from approximately 30 centers in Italy. The duration of the study treatment for enrolled patients was a maximum of 48 weeks, consisting of 8 weeks of three monthly loading doses and 40 weeks of maintenance regimen period (q8w or q12w) according to disease activity assessment.

Eligibility criteria: Inclusion Criteria:

* Signed written informed consent must be obtained prior to participation in the study
* Active choroidal neo-vascularization (CNV) secondary to AMD that affects the central subfield, including retinal angiomatous proliferation (RAP) with a CNV component, confirmed by presence of active leakage from CNV seen by fluorescein angiography (or other imaging modalities) and sequelae of CNV, e.g. pigment epithelial detachment (PED), subretinal or sub-retinal pigment epithelium (sub-RPE) hemorrhage, blocked fluorescence, macular edema in the study eye at Screening;
* Presence of intraretinal fluid (IRF) or subretinal fluid (SRF) affecting the central subfield (study eye), as seen by SD-OCT in the study eye at Screening;
* Best-corrected visual acuity (BCVA) score greater than or equal to 23 letters measured at 4-meters starting distance using Early Treatment Diabetic Retinopathy Study (EDTRS) visual acuity charts at both Screening and Baseline visits in the study eye.

Exclusion Criteria:

* Any active intraocular or periocular infection or active intraocular inflammation (e.g. infectious conjunctivitis, keratitis, scleritis, endophthalmitis, infectious blepharitis) in study eye at Screening or Baseline;
* Not interpretable OCTA and SD-OCT images according to Investigator's clinical judgment at Screening in the study eye;
* Concomitant conditions or ocular disorders in the study eye, at Screening or Baseline which, in the opinion of the Investigator, could prevent response to study treatment or may confound interpretation of study results, compromise visual acuity or require planned medical or surgical intervention during the course of the study;
* Uncontrolled glaucoma in the study eye defined as intraocular pressure (IOP) \> 25 mmHg on medication or according to Investigator's judgment at Screening or Baseline;
* Previous treatment with any anti-vascular endothelial growth factor (anti-Vascular endothelial growth factor (VEGF)) drugs or investigational drugs (other than vitamin supplements) in the study eye at any time prior to Screening;
* Systemic anti-VEGF therapy at any time;
* Stroke or myocardial infarction in the 6-month period prior to Baseline.

Primary outcomes:
measure: Number of Patients Classified as q12w Fluid-free or Not q12w Fluid-free
timeFrame: Up to Week 48
measure: Potential Predictor Factors of Fluid-free Response: Type of Predominant Basal Choroidal Neovascularization (CNV) Lesion Type, as Assessed by SD-OCT at Baseline - Patients Classified as Not q12w Fluid-free
timeFrame: Baseline
measure: Potential Predictor Factors of Fluid-free Response: Type of Predominant Basal Choroidal Neovascularization (CNV) Lesion Type, as Assessed by SD-OCT at Baseline - Patients Classified as q12w Fluid-free
timeFrame: Baseline
measure: Potential Predictor Factors of Fluid-free Response: Sub-retinal Pigment Epithelium (Sub-RPE) Fluid - Patients Classified as Not q12w Fluid-free
timeFrame: Baseline to Week 16
measure: Potential Predictor Factors of Fluid-free Response: Sub-retinal Pigment Epithelium (Sub-RPE) Fluid - Patients Classified as q12w Fluid-free
timeFrame: Baseline to Week 16
measure: Potential Predictor Factors of Fluid-free Response: Subretinal Hyperreflective Material (SHRM) - Patients Classified as Not q12w Fluid-free
timeFrame: Baseline to Week 16
measure: Potential Predictor Factors of Fluid-free Response: Subretinal Hyperreflective Material (SHRM) - Patients Classified as q12w Fluid-free
timeFrame: Baseline to Week 16
measure: Potential Predictor Factors of Fluid-free Response: Outer Retinal Tubulation (ORT) - Patients Classified as Not q12w Fluid-free
timeFrame: Baseline to Week 16
measure: Potential Predictor Factors of Fluid-free Response: Outer Retinal Tubulation (ORT) - Patients Classified as q12w Fluid-free
timeFrame: Baseline to Week 16
measure: Potential Predictor Factors of Fluid-free Response: External Limiting Membrane (ELM) Integrity Loss in Center 1 mm - Patients Classified as Not q12w Fluid-free
timeFrame: Baseline to Week 16
measure: Potential Predictor Factors of Fluid-free Response: External Limiting Membrane (ELM) Integrity Loss in Center 1 mm - Patients Classified as q12w Fluid-free
timeFrame: Baseline to Week 16
measure: Potential Predictor Factors of Fluid-free Response: Type of Pigment Epithelium Detachment (PED) - Patients Classified as Not q12w Fluid-free
timeFrame: Baseline to Week 16
measure: Potential Predictor Factors of Fluid-free Response: Type of Pigment Epithelium Detachment (PED) - Patients Classified as q12w Fluid-free
timeFrame: Baseline to Week 16
measure: Potential Predictor Factors of Fluid-free Response: Percentage Changes in Central Subfield Thickness (CST) From Baseline at Week 16 - Patients Classified as q12w Fluid-free
timeFrame: Baseline, Week 16
measure: Potential Predictor Factors of Fluid-free Response: Percentage Changes in Central Subfield Thickness (CST) From Baseline at Week 16 - Patients Classified as Not q12w Fluid-free
timeFrame: Baseline, Week 16
Secondary outcomes:
measure: Change in Optical Coherence Tomography (OCTA) Features Baseline up to Week 48 - Branching Vessels
timeFrame: Baseline, Week 16, Week 48
measure: Change in Optical Coherence Tomography (OCTA) Features Baseline up to Week 48 - Change From Baseline of Total CNV Lesion Area (mm*2)
timeFrame: Baseline, Week 16, Week 48
measure: Change in Optical Coherence Tomography (OCTA) Features Baseline up to Week 48 - Change From Baseline of Choroidal Neovascularization (CNV) Vascular Density (%)
timeFrame: Baseline, Week 16, Week 48
measure: Change in Optical Coherence Tomography (OCTA) Features Baseline up to Week 48 - Change From Baseline of Lesion Greatest Linear Diameter (mm)
timeFrame: Baseline, Week 16, Week 48
measure: Change in Optical Coherence Tomography (OCTA) Features Baseline up to Week 48 - Peripheral Anastomotic Arcades
timeFrame: Baseline, Week 16, Week 48
measure: Change in Optical Coherence Tomography (OCTA) Features Baseline up to Week 48 - Vascular Loops
timeFrame: Baseline, Week 16, Week 48
measure: Change in Optical Coherence Tomography (OCTA) Features Baseline up to Week 48 - Dark Halo
timeFrame: Baseline, Week 16, Week 48
measure: Spectral Domain Optical Coherence Tomography (SD-OCT) Features Baseline up to Week 48 - Pigment Epithelial Detachment (PED)
timeFrame: Baseline, Week 16, Week 48
measure: Spectral Domain Optical Coherence Tomography (SD-OCT) Features Baseline up to Week 48 - Central Subfield Thickness (CST) (μm)
timeFrame: Baseline, Week 16, Week 48
measure: Change in Spectral Domain Optical Coherence Tomography (SD-OCT) Features From Baseline up to Week 48
timeFrame: Baseline, Week 16, Week 48
measure: Change in Spectral Domain Optical Coherence Tomography (SD-OCT) Features From Baseline up to Week 48 - Intraretinal Fluid (IRF) Cystoid Edema
timeFrame: Baseline, Week 16, Week 48
measure: Change in Spectral Domain Optical Coherence Tomography (SD-OCT) Features From Baseline up to Week 48 - Subretinal Fluid (SRF)
timeFrame: Baseline, Week 16, Week 48
measure: Change in Spectral Domain Optical Coherence Tomography (SD-OCT) Features From Baseline up to Week 48 - Sub Retinal Pigment Epithelium (Sub RPE) Fluid
timeFrame: Baseline, Week 16, Week 48
measure: Change in Spectral Domain Optical Coherence Tomography (SD-OCT) Features From Baseline up to Week 48 - Subretinal Hyperreflective Material (SHRM)
timeFrame: Baseline, Week 16, Week 48
measure: Change in Spectral Domain Optical Coherence Tomography (SD-OCT) Features From Baseline up to Week 48 - Outer Retinal Tubulation (ORT)
timeFrame: Baseline, Week 16, Week 48
measure: Change in Spectral Domain Optical Coherence Tomography (SD-OCT) Features From Baseline up to Week 48 - External Limiting Membrane (ELM) Integrity Loss
timeFrame: Baseline, Week 16, Week 48
measure: Change in Best-corrected Visual Acuity (BCVA) From Baseline up to Week 48
timeFrame: Baseline, Week 16, Week 48
measure: Number of Patients With Fluid Resolution of the Study Eye
timeFrame: Week 16, Week 48
measure: Sustained Dryness of the Study Eye - Kaplan-Meier Estimates - Median Time to the Achievement of Sustained Dryness
timeFrame: Up to Week 48
measure: Cumulative Incidence of Patients With Sustained Dryness of the Study Eye
timeFrame: Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48
measure: Determinants in the Investigator's Choice of Brolucizumab Dosing Regimen (q8w) at Week 16
timeFrame: Up to Week 16
measure: Determinants in the Investigator's Choice of Brolucizumab Dosing Regimen (q12w) at Week 16
timeFrame: Up to Week 16
measure: Change in Hospital Anxiety and Depression Scale (HADS) Scores
timeFrame: Up to Week 48
measure: Change in European Quality of Life-5D-5L (EQ-5D-5L) Scores
timeFrame: Baseline, Week 48
measure: Treatment Emergent Adverse Events
timeFrame: AEs are reported from first dose of study treatment until 4 weeks after last treatment, for a maximum time frame of approx. 48 weeks.
measure: Ocular Treatment Emergent Adverse Events - Study Eye
timeFrame: AEs are reported from first dose of study treatment until 4 weeks after last treatment, for a maximum time frame of approx. 48 weeks.
measure: Ocular Treatment Emergent Adverse Events - by System Organ Class (SOC) and Preferred Term (PT)
timeFrame: AEs are reported from first dose of study treatment until 4 weeks after last treatment, for a maximum time frame of approx. 48 weeks.
Other outcomes:
Locations:
city: Ancona
country: Italy
facility: Novartis Investigative Site
state: AN
city: Acquaviva delle Fonti
country: Italy
facility: Novartis Investigative Site
state: BA
city: Bologna
country: Italy
facility: Novartis Investigative Site
state: BO
city: Cagliari
country: Italy
facility: Novartis Investigative Site
state: CA
city: Firenze
country: Italy
facility: Novartis Investigative Site
state: FI
city: Monza
country: Italy
facility: Novartis Investigative Site
state: MB
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Padova
country: Italy
facility: Novartis Investigative Site
state: PD
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Siena
country: Italy
facility: Novartis Investigative Site
state: SI
city: Torino
country: Italy
facility: Novartis Investigative Site
state: TO
city: Trieste
country: Italy
facility: Novartis Investigative Site
state: TS
city: Negrar
country: Italy
facility: Novartis Investigative Site
state: VR
city: Napoli
country: Italy
facility: Novartis Investigative Site
city: Napoli
country: Italy
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: