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

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

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).

Study Overview

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

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 122
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Napoli, Italy, 80131
    • Novartis Investigative Site
  • Napoli, Italy, 80138
    • Novartis Investigative Site
  • AN
    • Ancona, AN, Italy, 60126
      • Novartis Investigative Site
  • BA
    • Acquaviva delle Fonti, BA, Italy, 70021
      • Novartis Investigative Site
  • BO
    • Bologna, BO, Italy, 40138
      • Novartis Investigative Site
  • CA
    • Cagliari, CA, Italy, 09124
      • Novartis Investigative Site
  • FI
    • Firenze, FI, Italy, 50134
      • Novartis Investigative Site
  • MB
    • Monza, MB, Italy, 20900
      • Novartis Investigative Site
  • MI
    • Milano, MI, Italy, 20132
      • Novartis Investigative Site
    • Milano, MI, Italy, 20122
      • Novartis Investigative Site
    • Milano, MI, Italy, 20123
      • Novartis Investigative Site
    • Milano, MI, Italy, 20100
      • Novartis Investigative Site
  • PD
    • Padova, PD, Italy, 35128
      • Novartis Investigative Site
  • RM
    • Roma, RM, Italy, 00168
      • Novartis Investigative Site
    • Roma, RM, Italy, 00144
      • Novartis Investigative Site
    • Roma, RM, Italy, 00133
      • Novartis Investigative Site
  • SI
    • Siena, SI, Italy, 53100
      • Novartis Investigative Site
  • TO
    • Torino, TO, Italy, 10126
      • Novartis Investigative Site
  • TS
    • Trieste, TS, Italy, 34129
      • Novartis Investigative Site
  • VR
    • Negrar, VR, Italy, 37024
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

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: Brolucizumab 6 mg; Participants will receive 3 monthly ocular injections followed by a q12w or q8w maintenance phase based on patient's disease activity (DA).	Drug: Brolucizumab; 120 mg/ml solution for intravitreal injection; Other Names: RTH258, Beovu

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
Incidence of Ocular and Non-ocular Adverse Events throughout the study	Assess the safety and tolerability of brolucizumab	Up to Week 48

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2021
• Primary Completion (Actual): October 4, 2023
• Study Completion (Actual): October 4, 2023

Study Registration Dates

• First Submitted: February 25, 2021
• First Submitted That Met QC Criteria: February 25, 2021
• First Posted (Actual): March 1, 2021

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: AMD; anti-VEGF; Macular degeneration; choroidal neovascularization; vision loss; Neovascular age-related macular degeneration; wet macular degeneration; brolucizumab; multimodal imaging biomarkers; fluid resolution; age-related macular degeneration (ARMD); macula damage; retina damage; dry macular degeneration
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Wet Macular Degeneration
• Other Study ID Numbers: CRTH258AIT04; 2020-002452-20 (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 https://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