Phase 4
N=122
Study of Innovative Multimodal Imaging Biomarkers to Predict Anatomical Outcome in Naive Patients With wAMD Treated With Brolucizumab.
Neovascular Age-related Macular Degeneration
Bottom Line
View on ClinicalTrials.gov: NCT04774926 ↗Enrolled (actual)
122
Serious AEs
11.5%
Results posted
Feb 2025
Primary outcome: Primary: Number of Patients Classified as q12w Fluid-free or Not q12w Fluid-free — 93; 27 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 4
- Interventions
- Brolucizumab (Drug)
- Age
- Adult, Older Adult · 50+ yrs
- Sex
- All
- Sponsor
- Novartis Pharmaceuticals
- Primary completion
- Oct 2023
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Patients Classified as q12w Fluid-free or Not q12w Fluid-free |
93; 27 | — |
| PRIMARY 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 |
61; 21; 5; 6 | — |
| PRIMARY 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 |
19; 4; 3; 1 | — |
| PRIMARY Potential Predictor Factors of Fluid-free Response: Sub-retinal Pigment Epithelium (Sub-RPE) Fluid - Patients Classified as Not q12w Fluid-free |
39; 32; 20; 2 | — |
| PRIMARY Potential Predictor Factors of Fluid-free Response: Sub-retinal Pigment Epithelium (Sub-RPE) Fluid - Patients Classified as q12w Fluid-free |
12; 7; 8; 0 | — |
| PRIMARY Potential Predictor Factors of Fluid-free Response: Subretinal Hyperreflective Material (SHRM) - Patients Classified as Not q12w Fluid-free |
41; 33; 7; 12 | — |
| PRIMARY Potential Predictor Factors of Fluid-free Response: Subretinal Hyperreflective Material (SHRM) - Patients Classified as q12w Fluid-free |
11; 7; 4; 5 | — |
| PRIMARY Potential Predictor Factors of Fluid-free Response: Outer Retinal Tubulation (ORT) - Patients Classified as Not q12w Fluid-free |
84; 1; 3; 5 | — |
| PRIMARY Potential Predictor Factors of Fluid-free Response: Outer Retinal Tubulation (ORT) - Patients Classified as q12w Fluid-free |
25; 2; 0; 0 | — |
| PRIMARY Potential Predictor Factors of Fluid-free Response: External Limiting Membrane (ELM) Integrity Loss in Center 1 mm - Patients Classified as Not q12w Fluid-free |
25; 43; 11; 14 | — |
| PRIMARY Potential Predictor Factors of Fluid-free Response: External Limiting Membrane (ELM) Integrity Loss in Center 1 mm - Patients Classified as q12w Fluid-free |
8; 13; 3; 3 | — |
| PRIMARY Potential Predictor Factors of Fluid-free Response: Type of Pigment Epithelium Detachment (PED) - Patients Classified as Not q12w Fluid-free |
38; 28; 24; 3 | — |
| PRIMARY Potential Predictor Factors of Fluid-free Response: Type of Pigment Epithelium Detachment (PED) - Patients Classified as q12w Fluid-free |
13; 7; 7; 0 | — |
| PRIMARY 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 |
-36.4 | — |
| PRIMARY 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 |
-31.7 | — |
| SECONDARY Change in Optical Coherence Tomography (OCTA) Features Baseline up to Week 48 - Branching Vessels |
11; 4; 2; 11; 26; 20 | — |
| SECONDARY Change in Optical Coherence Tomography (OCTA) Features Baseline up to Week 48 - Change From Baseline of Total CNV Lesion Area (mm*2) |
0.476; 0.533 | — |
| SECONDARY Change in Optical Coherence Tomography (OCTA) Features Baseline up to Week 48 - Change From Baseline of Choroidal Neovascularization (CNV) Vascular Density (%) |
1.326; 29.900 | — |
| SECONDARY Change in Optical Coherence Tomography (OCTA) Features Baseline up to Week 48 - Change From Baseline of Lesion Greatest Linear Diameter (mm) |
-0.211; -0.147 | — |
| SECONDARY Change in Optical Coherence Tomography (OCTA) Features Baseline up to Week 48 - Peripheral Anastomotic Arcades |
14; 1; 4; 6; 7; 2 | — |
| SECONDARY Change in Optical Coherence Tomography (OCTA) Features Baseline up to Week 48 - Vascular Loops |
12; 1; 3; 10; 4; 3 | — |
| SECONDARY Change in Optical Coherence Tomography (OCTA) Features Baseline up to Week 48 - Dark Halo |
9; 2; 0; 4; 6; 5 | — |
| SECONDARY Spectral Domain Optical Coherence Tomography (SD-OCT) Features Baseline up to Week 48 - Pigment Epithelial Detachment (PED) |
120; 114; 92; 1 | — |
| SECONDARY Spectral Domain Optical Coherence Tomography (SD-OCT) Features Baseline up to Week 48 - Central Subfield Thickness (CST) (μm) |
482.6; 309.2; 307.9 | — |
| SECONDARY Change in Spectral Domain Optical Coherence Tomography (SD-OCT) Features From Baseline up to Week 48 |
-188.4; -197.6 | — |
| SECONDARY Change in Spectral Domain Optical Coherence Tomography (SD-OCT) Features From Baseline up to Week 48 - Intraretinal Fluid (IRF) Cystoid Edema |
46; 38; 4; 26; 40; 30 | — |
| SECONDARY Change in Spectral Domain Optical Coherence Tomography (SD-OCT) Features From Baseline up to Week 48 - Subretinal Fluid (SRF) |
7; 75; 1; 31; 6; 57 | — |
| SECONDARY Change in Spectral Domain Optical Coherence Tomography (SD-OCT) Features From Baseline up to Week 48 - Sub Retinal Pigment Epithelium (Sub RPE) Fluid |
49; 26; 1; 38; 36; 26 | — |
| SECONDARY Change in Spectral Domain Optical Coherence Tomography (SD-OCT) Features From Baseline up to Week 48 - Subretinal Hyperreflective Material (SHRM) |
50; 11; 16; 37; 45; 14 | — |
| SECONDARY Change in Spectral Domain Optical Coherence Tomography (SD-OCT) Features From Baseline up to Week 48 - Outer Retinal Tubulation (ORT) |
103; 3; 5; 3; 77; 3 | — |
| SECONDARY Change in Spectral Domain Optical Coherence Tomography (SD-OCT) Features From Baseline up to Week 48 - External Limiting Membrane (ELM) Integrity Loss |
30; 14; 15; 54; 24; 9 | — |
| SECONDARY Change in Best-corrected Visual Acuity (BCVA) From Baseline up to Week 48 |
4.0; 5.5 | — |
| SECONDARY Number of Patients With Fluid Resolution of the Study Eye |
64; 49; 18; 19; 12; 49 | — |
| SECONDARY Sustained Dryness of the Study Eye - Kaplan-Meier Estimates - Median Time to the Achievement of Sustained Dryness |
16.43 | — |
| SECONDARY Cumulative Incidence of Patients With Sustained Dryness of the Study Eye |
36; 54; 64; 68; 68; 68 | — |
| SECONDARY Determinants in the Investigator's Choice of Brolucizumab Dosing Regimen (q8w) at Week 16 |
17; 21; 15; 13; 4; 4 | — |
| SECONDARY Determinants in the Investigator's Choice of Brolucizumab Dosing Regimen (q12w) at Week 16 |
46; 41; 35; 29; 26; 26 | — |
| SECONDARY Change in Hospital Anxiety and Depression Scale (HADS) Scores |
-0.78; -0.10 | — |
| SECONDARY Change in European Quality of Life-5D-5L (EQ-5D-5L) Scores |
0.00 | — |
| SECONDARY Treatment Emergent Adverse Events |
59; 14; 33; 40; 13; 4 | — |
| SECONDARY Ocular Treatment Emergent Adverse Events - Study Eye |
25; 1; 11; 3; 1; 10 | — |
| SECONDARY Ocular Treatment Emergent Adverse Events - by System Organ Class (SOC) and Preferred Term (PT) |
30; 3; 1; 1; 2; 1 | — |
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).
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.
Data sourced from ClinicalTrials.gov (NCT04774926). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.