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

Primary Purpose

Neovascular Age-related Macular Degeneration

Status
Active
Phase
Phase 4
Locations
Italy
Study Type
Interventional
Intervention
Brolucizumab
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neovascular Age-related Macular Degeneration focused on measuring 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

Eligibility Criteria

50 Years - 100 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Brolucizumab 6 mg

Arm Description

Participants will receive 3 monthly ocular injections followed by a q12w or q8w maintenance phase based on patient's disease activity (DA).

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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)
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).
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
Time to reach sustained dryness of the study eye
Evaluate the effect of brolucizumab on sustained dryness from Baseline 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)
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.
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.
Incidence of Ocular and Non-ocular Adverse Events throughout the study
Assess the safety and tolerability of brolucizumab

Full Information

First Posted
February 25, 2021
Last Updated
July 12, 2023
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT04774926
Brief Title
Study of Innovative Multimodal Imaging Biomarkers to Predict Anatomical Outcome in Naive Patients With wAMD Treated With Brolucizumab.
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
October 15, 2021 (Actual)
Primary Completion Date
October 2, 2023 (Anticipated)
Study Completion Date
October 2, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Model Description
The study is a one-year, open-label, single arm, multicenter, phase IV study in patients with wAMD.
Masking
None (Open Label)
Allocation
N/A
Enrollment
122 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Brolucizumab 6 mg
Arm Type
Experimental
Arm Description
Participants will receive 3 monthly ocular injections followed by a q12w or q8w maintenance phase based on patient's disease activity (DA).
Intervention Type
Drug
Intervention Name(s)
Brolucizumab
Other Intervention Name(s)
RTH258, Beovu
Intervention Description
120 mg/ml solution for intravitreal injection
Primary Outcome Measure Information:
Title
Predictive value of early anatomical parameters measured by multimodal imaging.
Description
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.
Time Frame
Up to Week 48
Secondary Outcome Measure Information:
Title
Change in Optical Coherence Tomography (OCTA) features Baseline up to Week 48
Description
Evaluate the effect of brolucizumab on the evolution of qualitative and quantitative OCTA parameters of wet Age-related Macular Degeneration (wAMD)
Time Frame
up to Week 48
Title
Change in Spectral Domain Optical Coherence Tomography (SD-OCT) features
Description
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).
Time Frame
Up to Week 48
Title
Change in Best-corrected visual acuity (BCVA) from Baseline up to Week 48
Description
Evaluate the effect of brolucizumab on the evolution of functional parameters of wAMD from Baseline to Week 48
Time Frame
up to Week 48
Title
Time to reach sustained dryness of the study eye
Description
Evaluate the effect of brolucizumab on sustained dryness from Baseline to Week 48
Time Frame
Up to Week 48
Title
Determinants in the Investigator's choice of brolucizumab dosing regimen (q12w or q8w) at Week 16
Description
Evaluate the reasons underlying the Investigators' choice of brolucizumab treatment regimen (q12w or q8w)
Time Frame
Up to Week 16
Title
Change in Hospital Anxiety and Depression Scale (HADS) scores
Description
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.
Time Frame
Up to Week 48
Title
Change in European Quality of Life-5D-5L (EQ-5D-5L) scores
Description
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.
Time Frame
Up to Week 48
Title
Incidence of Ocular and Non-ocular Adverse Events throughout the study
Description
Assess the safety and tolerability of brolucizumab
Time Frame
Up to Week 48

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Ancona
State/Province
AN
ZIP/Postal Code
60126
Country
Italy
Facility Name
Novartis Investigative Site
City
Acquaviva delle Fonti
State/Province
BA
ZIP/Postal Code
70021
Country
Italy
Facility Name
Novartis Investigative Site
City
Bologna
State/Province
BO
ZIP/Postal Code
40138
Country
Italy
Facility Name
Novartis Investigative Site
City
Cagliari
State/Province
CA
ZIP/Postal Code
09124
Country
Italy
Facility Name
Novartis Investigative Site
City
Firenze
State/Province
FI
ZIP/Postal Code
50134
Country
Italy
Facility Name
Novartis Investigative Site
City
Monza
State/Province
MB
ZIP/Postal Code
20900
Country
Italy
Facility Name
Novartis Investigative Site
City
Milano
State/Province
MI
ZIP/Postal Code
20100
Country
Italy
Facility Name
Novartis Investigative Site
City
Milano
State/Province
MI
ZIP/Postal Code
20122
Country
Italy
Facility Name
Novartis Investigative Site
City
Milano
State/Province
MI
ZIP/Postal Code
20123
Country
Italy
Facility Name
Novartis Investigative Site
City
Milano
State/Province
MI
ZIP/Postal Code
20132
Country
Italy
Facility Name
Novartis Investigative Site
City
Padova
State/Province
PD
ZIP/Postal Code
35128
Country
Italy
Facility Name
Novartis Investigative Site
City
Roma
State/Province
RM
ZIP/Postal Code
00133
Country
Italy
Facility Name
Novartis Investigative Site
City
Roma
State/Province
RM
ZIP/Postal Code
00144
Country
Italy
Facility Name
Novartis Investigative Site
City
Roma
State/Province
RM
ZIP/Postal Code
00168
Country
Italy
Facility Name
Novartis Investigative Site
City
Siena
State/Province
SI
ZIP/Postal Code
53100
Country
Italy
Facility Name
Novartis Investigative Site
City
Torino
State/Province
TO
ZIP/Postal Code
10126
Country
Italy
Facility Name
Novartis Investigative Site
City
Trieste
State/Province
TS
ZIP/Postal Code
34129
Country
Italy
Facility Name
Novartis Investigative Site
City
Negrar
State/Province
VR
ZIP/Postal Code
37024
Country
Italy
Facility Name
Novartis Investigative Site
City
Napoli
ZIP/Postal Code
80131
Country
Italy
Facility Name
Novartis Investigative Site
City
Napoli
ZIP/Postal Code
80138
Country
Italy

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.
IPD Sharing URL
https://www.clinicalstudydatarequest.com/

Learn more about this trial

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

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