Study of Innovative Multimodal Imaging Biomarkers to Predict Anatomical Outcome in Naive Patients With wAMD Treated With Brolucizumab.

Neovascular Age-related Macular Degeneration Clinical Trial

— IMAGINE  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04774926
• Other study ID #: CRTH258AIT04
• Secondary ID: 2020-002452-20
• Status: Completed
• Phase: Phase 4
• Start date: October 15, 2021
• Est. completion date: October 4, 2023

Study information

• Verified date: April 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this phase IV study is 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) with the purpose to evaluate their potential in supporting the treatment regimen choice (q12w or q8w).

Description:

This is a one-year, open-label, single arm, multicenter, phase IV study in patients with untreated active subfoveal Choroidal Neovascularization (CNV) secondary to wAMD The study consists of a screening period of up to 2 weeks and a treatment period with brolucizumab from Baseline (Day 1) up to Week 48.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 122
• Est. completion date: October 4, 2023
• Est. primary completion date: October 4, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 100 Years

Eligibility

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.

Related Conditions & MeSH terms

• Macular Degeneration
• Neovascular Age-related Macular Degeneration
• Wet Macular Degeneration

Intervention

Drug:
• Brolucizumab
120 mg/ml solution for intravitreal injection

Locations

Country	Name	City	State
Italy	Novartis Investigative Site	Acquaviva delle Fonti	BA
Italy	Novartis Investigative Site	Ancona	AN
Italy	Novartis Investigative Site	Bologna	BO
Italy	Novartis Investigative Site	Cagliari	CA
Italy	Novartis Investigative Site	Firenze	FI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Monza	MB
Italy	Novartis Investigative Site	Napoli
Italy	Novartis Investigative Site	Napoli
Italy	Novartis Investigative Site	Negrar	VR
Italy	Novartis Investigative Site	Padova	PD
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Siena	SI
Italy	Novartis Investigative Site	Torino	TO
Italy	Novartis Investigative Site	Trieste	TS

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Predictive value of early anatomical parameters measured by multimodal imaging.	Early predictive factors of fluid-free response, which is defined as the absence of retinal fluid at Week 48 in patients with a stable q12w treatment regimen up to Week 48 after the loading phase.	Up to Week 48
Secondary	Change in Optical Coherence Tomography (OCTA) features Baseline up to Week 48	Evaluate the effect of brolucizumab on the evolution of qualitative and quantitative OCTA parameters of wet Age-related Macular Degeneration (wAMD)	up to Week 48
Secondary	Change in Spectral Domain Optical Coherence Tomography (SD-OCT) features	Evaluate the effect of brolucizumab on the evolution of qualitative and quantitative SD-OCT parameters of wAMD from Baseline to Week 48. Change in SD-OCT features as assessed by qualitative (Intraretinal Fluid (IRF), Subretinal Fluid (SRF), sub- Retinal Pigment Epithelium (RPE) fluid, status of External Limiting Membrane (ELM), Subretinal Hyperreflective Material (SHRM ) and outer retinal tubulation) and quantitative criteria (Central Retinal Thickness (CRT) and Pigment Epithelium Detachment (PED) volume).	Up to Week 48
Secondary	Change in Best-corrected visual acuity (BCVA) from Baseline up to Week 48	Evaluate the effect of brolucizumab on the evolution of functional parameters of wAMD from Baseline to Week 48	up to Week 48
Secondary	Time to reach sustained dryness of the study eye	Evaluate the effect of brolucizumab on sustained dryness from Baseline to Week 48	Up to Week 48
Secondary	Determinants in the Investigator's choice of brolucizumab dosing regimen (q12w or q8w) at Week 16	Evaluate the reasons underlying the Investigators' choice of brolucizumab treatment regimen (q12w or q8w)	Up to Week 16
Secondary	Change in Hospital Anxiety and Depression Scale (HADS) scores	Evaluate anxiety/depression in patients with wAMD treated with brolucizumab. The Hospital Anxiety and Depression Scale (HADS) is a fourteen-item scale that generates ordinal data. Seven items relate to anxiety and seven relate to depression. This patient-reported outcome measure was specifically developed to avoid reliance on anxiety/depression aspects which are also common somatic symptoms of illness, such as fatigue and insomnia or hypersomnia. Calculations of scores: each item is rated on a 4-point scale. The HADS consists of two sub-scores: the HAD-A for anxiety and HAD-D for depression. Each sub-score ranges from 0 to 21 points: scores =11 indicate the presence of an anxious or depressive disorder, scores between 8-10 points are borderline abnormal, and scores =7 indicate that an anxious or depressive disorder is not present.	Up to Week 48
Secondary	Change in European Quality of Life-5D-5L (EQ-5D-5L) scores	Evaluate quality of life in patients with wAMD treated with brolucizumab. CRTH258AIT04. The EQ-5D-5L is a standardized widely used instrument for measuring generic health status. It comprises the following five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels. i.e. no problems, slight problems, moderate problems, severe problems and extreme problems, corresponding to digit numbers ranging from 1 to 5. The EQ-5D-5L total score is determined through a Visual Analogue Scale (VAS) and ranges from 0 to 100 with higher scores indicative of a better health status.	Up to Week 48
Secondary	Incidence of Ocular and Non-ocular Adverse Events throughout the study	Assess the safety and tolerability of brolucizumab	Up to Week 48