Phase 3
N=360
A Study of the Efficacy and Safety of Brolucizumab vs. Aflibercept in Patients With Visual Impairment Due to Diabetic Macular Edema
Diabetic Macular Edema
Bottom Line
View on ClinicalTrials.gov: NCT03481660 ↗Enrolled (actual)
360
Serious AEs
31.4%
Results posted
Jan 2024
Primary outcome: Primary: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) at Week 52 for the Study Eye — 10.6; 9.4 Scores on a scale — p=<0.001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Brolucizumab (Drug); Aflibercept (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Novartis Pharmaceuticals
- Primary completion
- Jun 2020
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) at Week 52 for the Study Eye |
10.6; 9.4 | <0.001 sig |
| SECONDARY Average Mean Change From Baseline in BCVA Over the Period Week 40 Through Week 52 for the Study Eye |
10.3; 9.4 | <0.001 sig |
| SECONDARY (Brolucizumab Treatment Arm Only): Percentage of Participants Maintained at q12w up to Week 52 and up to q12w/q16w up to Week 100. |
50.3; 36.8 | — |
| SECONDARY (Brolucizumab Treatment Arm Only): Percentage of Participants Maintained at q12w up to Week 52 Within Those Patients That Qualified for q12w at Week 36 |
95.1 | — |
| SECONDARY (Brolucizumab Treatment Arm Only): Percentage of Participants Maintained at q12w/q16w up to Week 100, Within Those Patients That Qualified for q12w at Week 36 |
69.6 | — |
| SECONDARY (Brolucizumab Treatment Arm Only): Percentage of Participants Maintained on q16w up to Week 100 Within the Patients on q12w at Week 68 and on q16w at Week 76 |
87.9 | — |
| SECONDARY (Brolucizumab Treatment Arm Only): Percentage of Participants Re-assigned and Maintained on q12w up to Week 100 Within the Patients on q8w at Week 68 and on q12w at Week 80 |
73.1 | — |
| SECONDARY (Brolucizumab Treatment Arm Only): Number of Participants With Injections Per Planned Dosing Regimen (Every 8, 12 or 16 Weeks) |
74; 32; 35 | — |
| SECONDARY Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) at Each Visit up to Week 100 for the Study Eye |
5.1; 4.2; 6.8; 5.9; 7.8; 6.7 | — |
| SECONDARY Average Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Over the Period Week 4 to Week 52/100 for the Study Eye |
9.1; 8.4; 9.8; 8.7 | — |
| SECONDARY Average Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Over the Period Week 20 to Week 52/100 and Week 28 to Week 52/100 for the Study Eye |
10.1; 9.3; 10.4; 9.2; 10.1; 9.4 | — |
| SECONDARY Average Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Over the Period Week 88 to 100 for the Study Eye |
10.8; 8.7 | — |
| SECONDARY Percentage of Participants Who Gained >= 5 Letters in BCVA From Baseline or Reached BCVA >= 84 Letters at Each Post-baseline Visit for the Study Eye |
49.2; 46.4; 62.0; 62.4; 67.6; 63.5 | — |
| SECONDARY Percentage of Participants Who Gained >= 10 Letters in BCVA From Baseline or Reached BCVA >= 84 Letters at Each Post-baseline Visit for the Study Eye |
22.9; 23.8; 34.6; 31.5; 39.7; 36.5 | — |
| SECONDARY Percentage of Participants Who Gained >= 15 Letters in BCVA From Baseline or Reached BCVA >= 84 Letters at Each Post-baseline Visit for the Study Eye |
12.3; 9.4; 13.4; 13.8; 25.1; 16.0 | — |
| SECONDARY Percentage of Participants Who Lost >= 5 ETDRS Letters in Best Corrected Visual Acuity (BCVA) From Baseline at Each Post-baseline Visit for the Study Eye |
3.4; 4.4; 1.7; 3.3; 1.1; 2.8 | — |
| SECONDARY Percentage of Participants Who Lost >= 10 ETDRS Letters in Best Corrected Visual Acuity (BCVA) From Baseline at Each Post-baseline Visit for the Study Eye |
NA; 1.1; 1.1; 0.6; 1.1; NA | — |
| SECONDARY Percentage of Participants Who Lost >= 15 ETDRS Letters in Best Corrected Visual Acuity (BCVA) From Baseline at Each Post-baseline Visit for the Study Eye |
NA; 0.6; 1.1; NA; 0.6; NA | — |
| SECONDARY Percentage of Participants With an Absolute Best Corrected Visual Acuity (BCVA) >= 73 ETDRS Letters at Each Post-baseline Visit for the Study Eye |
55.3; 42.5; 64.8; 49.7; 66.5; 50.8 | — |
| SECONDARY Mean Change From Baseline in Central Subfield Thickness (CSFT) at Each Post-baseline Visit for the Study Eye |
-128.2; -113.9; -136.9; -126.0; -155.4; -130.8 | — |
| SECONDARY Average Mean Change From Baseline in Central Subfield Thickness (CSFT) Over the Period Week 40 Through Week 52 / Week 88 Through Week 100 for the Study Eye |
-187.1; -157.7; -196.6; -173.4 | <0.003 sig |
| SECONDARY Average Mean Change From Baseline in CSFT Over the Period Week 4 to Week 52 / 100 for the Study Eye |
-172.8; -145.4; -181.8; -156.1 | — |
| SECONDARY Percentage of Participants With Normal CSFT Thickness (<280 Micrometers) at Each Post-baseline Visit for the Study Eye |
12.8; 13.3; 16.8; 14.4; 22.9; 16.7 | — |
| SECONDARY Percentage of Patients With Presence of Subretinal Fluid (SRF) in the Study Eye at Each Post-baseline Visit |
12.3; 19.3; 10.1; 13.8; 5.6; 12.2 | — |
| SECONDARY Percentage of Patients With Presence of Intraretinal Fluid (IRF) in the Study Eye at Each Post-baseline Visit |
88.3; 89.0; 85.5; 86.2; 87.2; 84.5 | — |
| SECONDARY Percentage of Patients With Presence of Subretinal Fluid (SRF) and/or Intraretinal Fluid (IRF) in the Study Eye at Each Post-baseline Visit |
90.5; 90.6; 86.6; 88.4; 87.2; 85.6 | — |
| SECONDARY Percentage of Participants With Presence of Leakage on Fluorescein Angiography (FA) at Weeks 52 and 100 |
54.7; 79.4; 46.9; 65.6 | — |
| SECONDARY Percentage of Participants With With >=2-step Improvement From Baseline in ETDRS Diabetic Retinopathy Severity Scale (ETDRS-DRSS) Score |
25.0; 20.9; 29.0; 27.7; 30.1; 30.5 | — |
| SECONDARY Percentage of Participants With With >=3-step Improvement From Baseline in ETDRS Diabetic Retinopathy Severity Scale (ETDRS-DRSS) Score |
13.1; 11.3; 14.8; 15.3; 18.8; 15.3 | — |
| SECONDARY Percentage of Participants With With >=2-step Worsening From Baseline in ETDRS Diabetic Retinopathy Severity Scale (ETDRS-DRSS) Score |
2.3; 0.6; 1.7; 0.6; 3.4; 0.6 | — |
| SECONDARY Percentage of Participants With With >=3-step Worsening From Baseline in ETDRS Diabetic Retinopathy Severity Scale (ETDRS-DRSS) Score |
0.6; NA; 0.6; NA; 0.6; NA | — |
| SECONDARY Percentage of Participants With Progression to Proliferative Diabetic Retinopathy (PDR) as Assessed by ETDRS-DRSS Score of at Least 61 by Week 100 |
0.6; 0.6 | — |
| SECONDARY Number of Participants With Ocular and Non-ocular Adverse Events (AEs) |
52; 47; 15; 23; 6; 4 | — |
| SECONDARY Change From Baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25): Composite Score |
5.7; 6.3; 8.9; 6.7; 9.8; 7.6 | — |
| SECONDARY Change From Baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25): Subscale Score - General Vision |
9.0; 10.2; 11.2; 10.5; 12.4; 12.0 | — |
| SECONDARY Change From Baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25): Subscale Score - Ocular Pain |
4.1; 4.6; 4.6; 4.4; 6.2; 4.6 | — |
| SECONDARY Change From Baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25): Subscale Score - Near Activities |
6.4; 6.3; 10.5; 9.3; 11.0; 9.2 | — |
| SECONDARY Change From Baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25): Subscale Score - Distance Activities |
6.2; 5.6; 11.7; 8.2; 12.1; 8.1 | — |
| SECONDARY Change From Baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25): Subscale Score - Social Functioning |
3.3; 4.4; 7.1; 4.9; 6.3; 5.0 | — |
| SECONDARY Change From Baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25): Subscale Score - Mental Health |
7.9; 10.1; 12.6; 10.1; 13.5; 13.1 | — |
| SECONDARY Change From Baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25): Subscale Score - Role Difficulties |
6.9; 9.4; 12.2; 8.7; 14.0; 11.4 | — |
| SECONDARY Change From Baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25): Subscale Score - Dependency |
5.5; 3.6; 7.6; 3.9; 7.3; 5.6 | — |
| SECONDARY Change From Baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25): Subscale Score - Driving |
1.4; 4.8; 6.4; 4.2; 8.9; 2.8 | — |
| SECONDARY Change From Baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25): Subscale Score - Color Vision |
3.5; 4.2; 5.8; 3.6; 5.2; 3.9 | — |
| SECONDARY Change From Baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25): Subscale Score - Peripheral Vision |
5.3; 4.0; 7.2; 3.2; 9.3; 4.3 | — |
| SECONDARY Change From Baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25): General Health Rating |
3.9; 4.3; 5.8; 4.8; 8.9; 7.1 | — |
| SECONDARY Systemic Brolucizumab Concentration |
56.2; 0.760; NA; NA; 41.5 | — |
| SECONDARY Distribution of Integrated Anti-Drug Antibody (ADA) Status in the Brolucizumab Arm |
146; 27; 6 | — |
| SECONDARY Distribution of Integrated Anti-Drug Antibody (ADA) Status in the Brolucizumab Arm - Adjusted for Pre-existing ADA Status |
53; 93; 14; 13 | — |
| SECONDARY Pre-existing ADA Status and Incidence of Adverse Event of Special Interest (AESI) in the Study Eye |
1; 63; 5; 105 | — |
| SECONDARY Integrated ADA Status up to Week 100 and Incidence of Adverse Event of Special Interest (AESI) in the Study Eye. |
4; 142; 2; 25 | — |
Summary
This was a Phase III, randomized, double-masked, multi-center, active-controlled, two-arm study designed to evaluate the efficacy and safety of brolucizumab 6 mg compared to the active control, aflibercept 2 mg used per authorized label, in subjects with visual impairment due to diabetic macular edema (DME).
Eligibility Criteria
Key Inclusion Criteria
General
- Patients must give written informed consent before any study related assessments are performed
- Patients with type 1 or type 2 diabetes mellitus and HbA1c of = = 320 micrometers (μm) on SD-OCT at screening If both eyes are eligible, the eye with the worse visual acuity will be selected for study eye. However, the investigator may select the eye with better visual acuity, based on medical reasons or local ethical requirements.
Key Exclusion Criteria
- Previous treatment with any anti-VEGF drugs or investigational drugs in the study eye
- Active proliferative diabetic retinopathy in the study eye as per the investigator
- Concomitant conditions or ocular disorders in the study eye at screening or baseline which could, in the opinion of the investigator, prevent response to study treatment or may confound interpretation of study results, compromise visual acuity or require medical or surgical intervention during the first 12-month study period (e.g., cataract, vitreous hemorrhage, retinal vascular occlusion, retinal detachment, macular hole, or choroidal neovascularization of any cause)
- Any active intraocular or periocular infection or active intraocular inflammation (e.g., infectious conjunctivitis, keratitis, scleritis, endophthalmitis, infectious blepharitis, uveitis) in study eye at screening or baseline
- Structural damage of the fovea in the study eye at screening likely to preclude improvement in visual acuity following the resolution of macular edema, including atrophy of the retinal pigment epithelium, subretinal fibrosis, laser scar(s), epiretinal membrane involving fovea or organized hard exudate plaques
- Uncontrolled glaucoma in the study eye defined as intraocular pressure (IOP) > 25 millimeters mercury (mmHg) on medication or according to investigator's judgment, at screening or baseline
- Neovascularization of the iris in the study eye at screening or baseline
- Evidence of vitreomacular traction in the study eye at screening or baseline which, in the opinion of the investigator, affect visual acuity
Data sourced from ClinicalTrials.gov (NCT03481660). 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.