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 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).

Study Overview

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

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.

• 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 received 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
Number of Patients Classified as q12w Fluid-free or Not q12w Fluid-free	Early predictive factors of fluid-free response 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, As assessed by Spectral Domain Optical Coherence Tomography (SD-OCT). q12w fluid-free: pts completing the treatment and the study maintaining a stable q12w regimen assigned at Wk 16 up to Wk 48 and without the presence of IRF and SRF at Wk 48. not q12w fluid-free: Pt who completed treatment and the study with the presence of IRF or SRF at Wk 48; Pt who followed the q8w regimen of treatment at any time during the study (considering also who started with q12w regimen but then due to disease activity shifted to q8w regimen); Pt who discontinued treatment at any time after b/l since treatment disc. was considered as intercurrent event and a 'failure'.; Pt who dropped out at any time after b/l since study disc. was considered as intercurrent event and a 'failure'.	Up to Week 48
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	As assessed by Spectral Domain Optical Coherence Tomography (SD-OCT). Percentages were computed on Safety Population within 'No' and 'Yes' groups according to q12w fluid free. Type 1 neovascularization arises when CNV proliferation occurs below the Retinal Pigment Epithelium (RPE) and corresponds to occult CNV with a poorly defined pattern of leakage on fluorescein angiography (FA). Type 2 neovascularization refers to CNV proliferation above the RPE in the subretinal space and corresponds to classic CNV with intense fluorescein leakage. Type 3 neovascularization (or retinal angiomatous proliferation [RAP]) occurs when retinal circulation is involved, with an anastomosis between the choroidal and retinal circulations. Types 1-3 classification is a classification according to the type of anatomical lesion and is determined by multimodal imaging characteristics. Please note that by design, this is not a grading nor scores on a scale. PCV = Polypoidal Choroidal Vasculopathy	Baseline
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	As assessed by Spectral Domain Optical Coherence Tomography (SD-OCT). Percentages were computed on Safety Population within 'No' and 'Yes' groups according to q12w fluid free. Type 1 neovascularization arises when CNV proliferation occurs below the Retinal Pigment Epithelium (RPE) and corresponds to occult CNV with a poorly defined pattern of leakage on fluorescein angiography (FA). Type 2 neovascularization refers to CNV proliferation above the RPE in the subretinal space and corresponds to classic CNV with intense fluorescein leakage. Type 3 neovascularization (or retinal angiomatous proliferation [RAP]) occurs when retinal circulation is involved, with an anastomosis between the choroidal and retinal circulations. Types 1-3 classification is a classification according to the type of anatomical lesion and is determined by multimodal imaging characteristics. Please note that by design, this is not a grading nor scores on a scale. PCV = Polypoidal Choroidal Vasculopathy	Baseline
Potential Predictor Factors of Fluid-free Response: Sub-retinal Pigment Epithelium (Sub-RPE) Fluid - Patients Classified as Not q12w Fluid-free	As assessed by Spectral Domain Optical Coherence Tomography (SD-OCT). Percentages were computed on Safety Population within 'No' and 'Yes' groups according to q12w fluid free. Of note, the category 'Stable absent' is considered also for cases with baseline and last measurement collected equal to 'No' even if there are at least one 'Yes' in one of the other collected measurements. Similarly, the category 'Stable present' is considered also for cases with baseline and last measurement collected equal to 'Yes' even if there are at least one 'No' in one of the other collected measurements. Stable absent (i.e., all measurements 'No), Stable present (i.e., all measurements 'Yes'), Improved (i.e., last measurement collected as 'No' and baseline 'Yes'), Worsened (i.e., last measurement collected 'Yes' and baseline 'No').	Baseline to Week 16
Potential Predictor Factors of Fluid-free Response: Sub-retinal Pigment Epithelium (Sub-RPE) Fluid - Patients Classified as q12w Fluid-free	As assessed by Spectral Domain Optical Coherence Tomography (SD-OCT). Percentages were computed on Safety Population within 'No' and 'Yes' groups according to q12w fluid free. Of note, the category 'Stable absent' is considered also for cases with baseline and last measurement collected equal to 'No' even if there are at least one 'Yes' in one of the other collected measurements. Similarly, the category 'Stable present' is considered also for cases with baseline and last measurement collected equal to 'Yes' even if there are at least one 'No' in one of the other collected measurements. Stable absent (i.e., all measurements 'No), Stable present (i.e., all measurements 'Yes'), Improved (i.e., last measurement collected as 'No' and baseline 'Yes'), Worsened (i.e., last measurement collected 'Yes' and baseline 'No').	Baseline to Week 16
Potential Predictor Factors of Fluid-free Response: Subretinal Hyperreflective Material (SHRM) - Patients Classified as Not q12w Fluid-free	As assessed by Spectral Domain Optical Coherence Tomography (SD-OCT). Percentages were computed on Safety Population within 'No' and 'Yes' groups according to q12w fluid free. Of note, the category 'Stable absent' is considered also for cases with baseline and last measurement collected equal to 'No' even if there are at least one 'Yes' in one of the other collected measurements. Similarly, the category 'Stable present' is considered also for cases with baseline and last measurement collected equal to 'Yes' even if there are at least one 'No' in one of the other collected measurements. Stable absent (i.e., all measurements 'No), Stable present (i.e., all measurements 'Yes'), Improved (i.e., last measurement collected as 'No' and baseline 'Yes'), Worsened (i.e., last measurement collected 'Yes' and baseline 'No').	Baseline to Week 16
Potential Predictor Factors of Fluid-free Response: Subretinal Hyperreflective Material (SHRM) - Patients Classified as q12w Fluid-free	As assessed by Spectral Domain Optical Coherence Tomography (SD-OCT). Percentages were computed on Safety Population within 'No' and 'Yes' groups according to q12w fluid free. Of note, the category 'Stable absent' is considered also for cases with baseline and last measurement collected equal to 'No' even if there are at least one 'Yes' in one of the other collected measurements. Similarly, the category 'Stable present' is considered also for cases with baseline and last measurement collected equal to 'Yes' even if there are at least one 'No' in one of the other collected measurements. Stable absent (i.e., all measurements 'No), Stable present (i.e., all measurements 'Yes'), Improved (i.e., last measurement collected as 'No' and baseline 'Yes'), Worsened (i.e., last measurement collected 'Yes' and baseline 'No').	Baseline to Week 16
Potential Predictor Factors of Fluid-free Response: Outer Retinal Tubulation (ORT) - Patients Classified as Not q12w Fluid-free	As assessed by Spectral Domain Optical Coherence Tomography (SD-OCT). Percentages were computed on Safety Population within 'No' and 'Yes' groups according to q12w fluid free. Of note, the category 'Stable absent' is considered also for cases with baseline and last measurement collected equal to 'No' even if there are at least one 'Yes' in one of the other collected measurements. Similarly, the category 'Stable present' is considered also for cases with baseline and last measurement collected equal to 'Yes' even if there are at least one 'No' in one of the other collected measurements. Stable absent (i.e., all measurements 'No), Stable present (i.e., all measurements 'Yes'), Improved (i.e., last measurement collected as 'No' and baseline 'Yes'), Worsened (i.e., last measurement collected 'Yes' and baseline 'No').	Baseline to Week 16
Potential Predictor Factors of Fluid-free Response: Outer Retinal Tubulation (ORT) - Patients Classified as q12w Fluid-free	As assessed by Spectral Domain Optical Coherence Tomography (SD-OCT). Percentages were computed on Safety Population within 'No' and 'Yes' groups according to q12w fluid free. Of note, the category 'Stable absent' is considered also for cases with baseline and last measurement collected equal to 'No' even if there are at least one 'Yes' in one of the other collected measurements. Similarly, the category 'Stable present' is considered also for cases with baseline and last measurement collected equal to 'Yes' even if there are at least one 'No' in one of the other collected measurements. Stable absent (i.e., all measurements 'No), Stable present (i.e., all measurements 'Yes'), Improved (i.e., last measurement collected as 'No' and baseline 'Yes'), Worsened (i.e., last measurement collected 'Yes' and baseline 'No').	Baseline to Week 16
Potential Predictor Factors of Fluid-free Response: External Limiting Membrane (ELM) Integrity Loss in Center 1 mm - Patients Classified as Not q12w Fluid-free	As assessed by Spectral Domain Optical Coherence Tomography (SD-OCT). Percentages were computed on Safety Population within 'No' and 'Yes' groups according to q12w fluid free. Of note, the category 'Stable absent' is considered also for cases with baseline and last measurement collected equal to 'No' even if there are at least one 'Yes' in one of the other collected measurements. Similarly, the category 'Stable present' is considered also for cases with baseline and last measurement collected equal to 'Yes' even if there are at least one 'No' in one of the other collected measurements. Stable absent (i.e., all measurements 'No), Stable present (i.e., all measurements 'Yes'), Improved (i.e., last measurement collected as 'No' and baseline 'Yes'), Worsened (i.e., last measurement collected 'Yes' and baseline 'No').	Baseline to Week 16
Potential Predictor Factors of Fluid-free Response: External Limiting Membrane (ELM) Integrity Loss in Center 1 mm - Patients Classified as q12w Fluid-free	As assessed by Spectral Domain Optical Coherence Tomography (SD-OCT). Percentages were computed on Safety Population within 'No' and 'Yes' groups according to q12w fluid free. Of note, the category 'Stable absent' is considered also for cases with baseline and last measurement collected equal to 'No' even if there are at least one 'Yes' in one of the other collected measurements. Similarly, the category 'Stable present' is considered also for cases with baseline and last measurement collected equal to 'Yes' even if there are at least one 'No' in one of the other collected measurements. Stable absent (i.e., all measurements 'No), Stable present (i.e., all measurements 'Yes'), Improved (i.e., last measurement collected as 'No' and baseline 'Yes'), Worsened (i.e., last measurement collected 'Yes' and baseline 'No').	Baseline to Week 16
Potential Predictor Factors of Fluid-free Response: Type of Pigment Epithelium Detachment (PED) - Patients Classified as Not q12w Fluid-free	As assessed by Spectral Domain Optical Coherence Tomography (SD-OCT). Percentages were computed on Safety Population within 'No' and 'Yes' groups according to q12w fluid free.; Stable Fibrovascular only (i.e., all measurements 'Fibrovascular only').; Stable not only fibrovascular (i.e., all measurements 'Predominantly fibrovascular' or 'Predominantly serous' or 'Drusenoid Pigment Epithelial Detachment (PED)').; From not only fibrovascular to Fibrovascular only (i.e., last measurement collected 'Fibrovascular only' and baseline 'Predominantly fibrovascular' or 'Predominantly serous' or 'Drusenoid PED').; From Fibrovascular only to not only fibrovascular (i.e., last measurement collected 'Predominantly fibrovascular' or 'Predominantly serous' or 'Drusenoid PED' and baseline 'Fibrovascular only').	Baseline to Week 16
Potential Predictor Factors of Fluid-free Response: Type of Pigment Epithelium Detachment (PED) - Patients Classified as q12w Fluid-free	As assessed by Spectral Domain Optical Coherence Tomography (SD-OCT). Percentages were computed on Safety Population within 'No' and 'Yes' groups according to q12w fluid free.; Stable Fibrovascular only (i.e., all measurements 'Fibrovascular only').; Stable not only fibrovascular (i.e., all measurements 'Predominantly fibrovascular' or 'Predominantly serous' or 'Drusenoid Pigment Epithelial Detachment (PED)').; From not only fibrovascular to Fibrovascular only (i.e., last measurement collected 'Fibrovascular only' and baseline 'Predominantly fibrovascular' or 'Predominantly serous' or 'Drusenoid PED').; From Fibrovascular only to not only fibrovascular (i.e., last measurement collected 'Predominantly fibrovascular' or 'Predominantly serous' or 'Drusenoid PED' and baseline 'Fibrovascular only').	Baseline to Week 16
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	As assessed by Spectral Domain Optical Coherence Tomography (SD-OCT). Mean (SD) was computed on the Safety Population within 'No' and 'Yes' groups according to q12w fluid free.	Baseline, Week 16
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	As assessed by Spectral Domain Optical Coherence Tomography (SD-OCT). Mean (SD) was computed on the Safety Population within 'No' and 'Yes' groups according to q12w fluid free.	Baseline, Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Optical Coherence Tomography (OCTA) Features Baseline up to Week 48 - Branching Vessels	Evaluate the effect of brolucizumab on the evolution of qualitative and quantitative OCTA parameters of wet Age-related Macular Degeneration (wAMD) The morphology of the Neovascularization (CNV) complex was evaluated qualitatively by assessing the presence/absence of branching vessels. The presence of tiny vessels branching from bigger vessels is indicative of an active CNV lesion. UNG/P = Ungradable due to pathology UNG/Q = Ungradable due to Quality	Baseline, Week 16, Week 48
Change in Optical Coherence Tomography (OCTA) Features Baseline up to Week 48 - Change From Baseline of Total CNV Lesion Area (mm*2)	Evaluate the effect of brolucizumab on the evolution of qualitative and quantitative OCTA parameters of wet Age-related Macular Degeneration (wAMD). The total Basal Choroidal Neovascularization (CNV) lesion area (mm^2) and greatest linear diameter of lesion (mm) are the parameters related to CNV flow size.	Baseline, Week 16, Week 48
Change in Optical Coherence Tomography (OCTA) Features Baseline up to Week 48 - Change From Baseline of Choroidal Neovascularization (CNV) Vascular Density (%)	Evaluate the effect of brolucizumab on the evolution of qualitative and quantitative OCTA parameters of wet Age-related Macular Degeneration (wAMD). The Choroidal Neovascularization (CNV) vascular density (%) is calculated as a ratio of the area occupied by vessels and the total area of the lesion and multiplied by 100.	Baseline, Week 16, Week 48
Change in Optical Coherence Tomography (OCTA) Features Baseline up to Week 48 - Change From Baseline of Lesion Greatest Linear Diameter (mm)	Evaluate the effect of brolucizumab on the evolution of qualitative and quantitative OCTA parameters of wet Age-related Macular Degeneration (wAMD). The total Basal Choroidal Neovascularization (CNV) lesion area (mm^2) and greatest linear diameter of lesion (mm) are the parameters related to CNV flow size.	Baseline, Week 16, Week 48
Change in Optical Coherence Tomography (OCTA) Features Baseline up to Week 48 - Peripheral Anastomotic Arcades	Evaluate the effect of brolucizumab on the evolution of qualitative and quantitative OCTA parameters of wet Age-related Macular Degeneration (wAMD). The morphology of the Choroidal Neovascularization (CNV) complex was evaluated qualitatively by assessing the peripheral anastomotic arcades. The presence of peripheral anastomotic arcades at the vessel termini is indicative of an active CNV lesion.	Baseline, Week 16, Week 48
Change in Optical Coherence Tomography (OCTA) Features Baseline up to Week 48 - Vascular Loops	Evaluate the effect of brolucizumab on the evolution of qualitative and quantitative OCTA parameters of wet Age-related Macular Degeneration (wAMD). The morphology of the Choroidal Neovascularization (CNV) complex was evaluated qualitatively by assessing the vascular loops. The presence of vascular loops is indicative of an active CNV lesion.	Baseline, Week 16, Week 48
Change in Optical Coherence Tomography (OCTA) Features Baseline up to Week 48 - Dark Halo	Evaluate the effect of brolucizumab on the evolution of qualitative and quantitative OCTA parameters of wet Age-related Macular Degeneration (wAMD). The morphology of the Choroidal Neovascularization (CNV) complex was evaluated qualitatively by assessing the dark halo. The presence of dark halo is considered a region of choriocapillaris alteration corresponding to local flow impairment and is indicative of an active CNV lesion.	Baseline, Week 16, Week 48
Spectral Domain Optical Coherence Tomography (SD-OCT) Features Baseline up to Week 48 - Pigment Epithelial Detachment (PED)	Evaluate the effect of brolucizumab on the evolution of qualitative and quantitative SCD-OCT parameters of wet Age-related Macular Degeneration (wAMD)	Baseline, Week 16, Week 48
Spectral Domain Optical Coherence Tomography (SD-OCT) Features Baseline up to Week 48 - Central Subfield Thickness (CST) (μm)	Evaluate the effect of brolucizumab on the evolution of qualitative and quantitative SCD-OCT parameters of wet Age-related Macular Degeneration (wAMD). The central retina thickness (CRT) evaluated in this study represents the average retinal thickness of the circular area within 1 mm diameter around the foveal center and was called Center Subfield Thickness (CST), also known as foveal thickness.	Baseline, Week 16, Week 48
Change in Spectral Domain Optical Coherence Tomography (SD-OCT) Features From 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)	Baseline, Week 16, Week 48
Change in Spectral Domain Optical Coherence Tomography (SD-OCT) Features From Baseline up to Week 48 - Intraretinal Fluid (IRF) Cystoid Edema	Evaluate the effect of brolucizumab on the evolution of qualitative and quantitative SCD-OCT parameters of wet Age-related Macular Degeneration (wAMD). IRF is the fluid that accumulates within the neurosensory retina due to the disruption of the external limiting membrane (ELM)-photoreceptor complex in the outer retina by the active Choroidal Neovascularization (CNV) membrane.	Baseline, Week 16, Week 48
Change in Spectral Domain Optical Coherence Tomography (SD-OCT) Features From Baseline up to Week 48 - Subretinal Fluid (SRF)	Evaluate the effect of brolucizumab on the evolution of qualitative and quantitative SCD-OCT parameters of wet Age-related Macular Degeneration (wAMD). SRF is the fluid that commonly accumulates between the neurosensory retina and the retinal pigment epithelium (RPE) due to the profuse leakage from blood vessels of the Choroidal Neovascularization (CNV) complex.	Baseline, Week 16, Week 48
Change in Spectral Domain Optical Coherence Tomography (SD-OCT) Features From Baseline up to Week 48 - Sub Retinal Pigment Epithelium (Sub RPE) Fluid	Evaluate the effect of brolucizumab on the evolution of qualitative and quantitative SCD-OCT parameters of wet Age-related Macular Degeneration (wAMD). Sub-RPE fluid, i.e., the fluid that accumulates under the RPE, thus often leading to Pigment Epithelial Detachments (PEDs).	Baseline, Week 16, Week 48
Change in Spectral Domain Optical Coherence Tomography (SD-OCT) Features From Baseline up to Week 48 - Subretinal Hyperreflective Material (SHRM)	Evaluate the effect of brolucizumab on the evolution of qualitative and quantitative SCD-OCT parameters of wet Age-related Macular Degeneration (wAMD). SHRM, i.e., a poorly defined, medium-to-hyperreflective mass between the neurosensory layers and the sub retinal pigment epithelium (RPE) on SD-OCT, which is indicative of the neurovascular membrane, particularly in type II Choroidal Neovascularization (CNV) lesions, and of disciform scar formation	Baseline, Week 16, Week 48
Change in Spectral Domain Optical Coherence Tomography (SD-OCT) Features From Baseline up to Week 48 - Outer Retinal Tubulation (ORT)	Evaluate the effect of brolucizumab on the evolution of qualitative and quantitative SCD-OCT parameters of wet Age-related Macular Degeneration (wAMD). ORT, i.e., branching tubular structures located in the outer nuclear layer of the retina, which seems to be indicative of a rearrangement of degenerating photoreceptors in a variety of retinal diseases, including wAMD. On SD-OCT, ORT appears as well-defined round or ovoid hyporeflective spaces with hyperreflective borders.	Baseline, Week 16, Week 48
Change in Spectral Domain Optical Coherence Tomography (SD-OCT) Features From Baseline up to Week 48 - External Limiting Membrane (ELM) Integrity Loss	Evaluate the effect of brolucizumab on the evolution of qualitative and quantitative SCD-OCT parameters of wet Age-related Macular Degeneration (wAMD). Status of the ELM as an indicator of retinal integrity was evaluated focusing on ELM integrity loss in center 1 mm (i.e., considering the central 1 x 1-mm subfield).	Baseline, Week 16, Week 48
Change in Best-corrected Visual Acuity (BCVA) From Baseline up to Week 48	BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. Visual function of the study eye was assessed using the ETDRS protocol. Participants with a BCVA ETDRS letter score of >= 34 ETDRS letters (Snellen equivalent 20/200) at Screening / Baseline in the study eye were included. Min and max possible scores are 0-100 respectively. A higher score represents better functioning. Last observation carried forward (LOCF) was used for the imputation of missing values.	Baseline, Week 16, Week 48
Number of Patients With Fluid Resolution of the Study Eye	Evaluate the effect of brolucizumab on sustained dryness from Baseline to Week 48. Among patients with fluid present at Baseline, patients with fluid resolution were identified in case of absence of IRF and SRF and patients without fluid resolution were categorized in 'only IRF present', 'only SRF present', 'both IRF and SRF present' at each post-baseline timepoint. IRF = Intraretinal Fluid SRF = Subretinal Fluid	Week 16, Week 48
Sustained Dryness of the Study Eye - Kaplan-Meier Estimates - Median Time to the Achievement of Sustained Dryness	Evaluate the effect of brolucizumab on sustained dryness from Baseline to Week 48. Patients who achieved sustained dryness were identified considering those with fluid resolution for at least 2/3 consecutive visits. Median time to the achievement of sustained dryness was calculated by the Kaplan-Meier method. Sustained dryness of the study eye, is defined by the absence of IRF and SRF for at least 2 consecutive visits and for at least 3 consecutive visits. IRF = Intraretinal Fluid SRF = Subretinal Fluid	Up to Week 48
Cumulative Incidence of Patients With Sustained Dryness of the Study Eye	Evaluate the effect of brolucizumab on sustained dryness from Baseline to Week 48. Sustained dryness of the study eye, is defined by the absence of IRF and SRF for at least 2 consecutive visits and for at least 3 consecutive visits. IRF = Intraretinal Fluid SRF = Subretinal Fluid	Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48
Determinants in the Investigator's Choice of Brolucizumab Dosing Regimen (q8w) at Week 16	Evaluate the reasons underlying the Investigators' choice of brolucizumab treatment regimen (q8w) BVCA=Best-Corrected Visual Acuity, CFP=Color Fundus Photography; CNV=Choroidal Neovascularization; FA=Fluorescein Angiography; ICGA=IndoCyanine Green Angiography; OCTA=Optical Coherence Tomography Angiography; SD-OCT=Spectral Domain Optical Coherence Tomography	Up to Week 16
Determinants in the Investigator's Choice of Brolucizumab Dosing Regimen (q12w) at Week 16	Evaluate the reasons underlying the Investigators' choice of brolucizumab treatment regimen (q12w) BVCA=Best-Corrected Visual Acuity, CFP=Color Fundus Photography; CNV=Choroidal Neovascularization; FA=Fluorescein Angiography; ICGA=IndoCyanine Green Angiography; OCTA=Optical Coherence Tomography Angiography; SD-OCT=Spectral Domain Optical Coherence Tomography	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. 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.	Baseline, Week 48
Treatment Emergent Adverse Events	An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a subject or clinical investigation subject	AEs are reported from first dose of study treatment until 4 weeks after last treatment, for a maximum time frame of approx. 48 weeks.
Ocular Treatment Emergent Adverse Events - Study Eye	An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a subject or clinical investigation subject	AEs are reported from first dose of study treatment until 4 weeks after last treatment, for a maximum time frame of approx. 48 weeks.
Ocular Treatment Emergent Adverse Events - by System Organ Class (SOC) and Preferred Term (PT)	An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a subject or clinical investigation subject	AEs are reported from first dose of study treatment until 4 weeks after last treatment, for a maximum time frame of approx. 48 weeks.

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• A Plain Language Trial Summary is available on www.novctrd.com

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): May 16, 2025
• Last Update Submitted That Met QC Criteria: May 14, 2025
• Last Verified: May 1, 2025

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 Diseases; Retinal Degeneration; 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