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

NCT04774926 | Completed Phase 4 Results

• 2 other identifiers: CRTH258AIT042020-002452-20
• Study Type: interventional
• Target: 122
• Locations: 1 country
• Sites: 20

Brief Summary

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).

Conditions

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

Outcome Measures

Primary Outcomes (15)

• 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 Outcomes (27)

• Change in Optical Coherence Tomography (OCTA) Features Baseline up to Week 48 - Branching Vessels

  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)

  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 (%)

  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)

  Baseline, Week 16, Week 48

• Change in Optical Coherence Tomography (OCTA) Features Baseline up to Week 48 - Peripheral Anastomotic Arcades

  Baseline, Week 16, Week 48

Study Arms (1)

Brolucizumab 6 mg

EXPERIMENTAL

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

Drug: Brolucizumab

Interventions

Brolucizumab DRUG

120 mg/ml solution for intravitreal injection

Also known as: RTH258, Beovu

Brolucizumab 6 mg

Eligibility Criteria

• Age: 50 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (20)

Novartis Investigative Site

Ancona, AN, 60126, Italy

Location

Novartis Investigative Site

Acquaviva delle Fonti, BA, 70021, Italy

Location

Novartis Investigative Site

Bologna, BO, 40138, Italy

Location

Novartis Investigative Site

Cagliari, CA, 09124, Italy

Location

Novartis Investigative Site

Florence, FI, 50134, Italy

Location

Novartis Investigative Site

Monza, MB, 20900, Italy

Location

Novartis Investigative Site

Milan, MI, 20100, Italy

Location

Novartis Investigative Site

Milan, MI, 20122, Italy

Location

Novartis Investigative Site

Milan, MI, 20123, Italy

Location

Novartis Investigative Site

Milan, MI, 20132, Italy

Location

Novartis Investigative Site

Padua, PD, 35128, Italy

Location

Novartis Investigative Site

Roma, RM, 00133, Italy

Location

Novartis Investigative Site

Roma, RM, 00144, Italy

Location

Novartis Investigative Site

Roma, RM, 00168, Italy

Location

Novartis Investigative Site

Siena, SI, 53100, Italy

Location

Novartis Investigative Site

Torino, TO, 10126, Italy

Location

Novartis Investigative Site

Trieste, TS, 34129, Italy

Location

Novartis Investigative Site

Negrar, VR, 37024, Italy

Location

Novartis Investigative Site

Napoli, 80131, Italy

Location

Novartis Investigative Site

Napoli, 80138, Italy

Location

Related Publications (1)

• Lupidi M, Bandello F, Vujosevic S, Parravano M, Bacherini D, Minnella AM, Giansanti F, Ascardi C, Staurenghi G. Multimodal Imaging to Assess Disease Activity and Predict Fluid Resolution in Patients with wAMD Treated with Brolucizumab: The IMAGINE Study. Ophthalmol Ther. 2025 Oct;14(10):2497-2510. doi: 10.1007/s40123-025-01229-5. Epub 2025 Aug 20.

  PMID: 40833455 DERIVED

Related Links

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

MeSH Terms

Conditions

Choroidal Neovascularization; Macular Degeneration; Vision Disorders; Geographic Atrophy; Wet Macular Degeneration

Interventions

brolucizumab

Condition Hierarchy (Ancestors)

Choroid Diseases; Uveal Diseases; Eye Diseases; Neovascularization, Pathologic; Metaplasia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Retinal Degeneration; Retinal Diseases; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@Novartis.com

+ 1 862 778 8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

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

Study Record Dates

• First Submitted: February 25, 2021
• First Posted: March 1, 2021
• Study Start: October 15, 2021
• Primary Completion: October 4, 2023
• Study Completion: October 4, 2023
• Last Updated: May 16, 2025
• Results First Posted: February 24, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share

Locations

IT (20)