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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04774926

Collaborator

(none)

263

Enrollment

Locations

Arm

23.6

Anticipated Duration (Months)

13.8

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

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).

Condition or Disease	Intervention/Treatment	Phase
Neovascular Age-related Macular Degeneration	Drug: Brolucizumab	Phase 4

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 Design

Study Type:

Interventional

Anticipated Enrollment :

263 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

The study is a one-year, open-label, single arm, multicenter, phase IV study in patients with wAMD.The study is a one-year, open-label, single arm, multicenter, phase IV study in patients with wAMD.

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Oct 15, 2021

Anticipated Primary Completion Date :

Oct 2, 2023

Anticipated Study Completion Date :

Oct 2, 2023

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Predictive value of early anatomical parameters measured by multimodal imaging. [Up to Week 48]
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 [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 [Up to Week 48]
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 [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 [Up to Week 48]
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 [Up to 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 [Up to Week 48]
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 [Up to Week 48]
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 [Up to Week 48]
Assess the safety and tolerability of brolucizumab

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years to 100 Years

Sexes Eligible for Study:

All

Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Ancona	AN	Italy	60126
2	Novartis Investigative Site	Acquaviva delle Fonti	BA	Italy	70021
3	Novartis Investigative Site	Bologna	BO	Italy	40138
4	Novartis Investigative Site	Cagliari	CA	Italy	09124
5	Novartis Investigative Site	Firenze	FI	Italy	50134
6	Novartis Investigative Site	Monza	MB	Italy	20900
7	Novartis Investigative Site	Milano	MI	Italy	20100
8	Novartis Investigative Site	Milano	MI	Italy	20122
9	Novartis Investigative Site	Milano	MI	Italy	20123
10	Novartis Investigative Site	Milano	MI	Italy	20132
11	Novartis Investigative Site	Reggio Emilia	RE	Italy	42123
12	Novartis Investigative Site	Roma	RM	Italy	00133
13	Novartis Investigative Site	Roma	RM	Italy	00168
14	Novartis Investigative Site	Roma	RM	Italy	00198
15	Novartis Investigative Site	Siena	SI	Italy	53100
16	Novartis Investigative Site	Trieste	TS	Italy	34129
17	Novartis Investigative Site	Negrar	VR	Italy	37024
18	Novartis Investigative Site	Napoli		Italy	80131
19	Novartis Investigative Site	Napoli		Italy	80138