Phase 3
N=263
To Compare Brolucizumab to Aflibercept in Chinese Patients With Visual Impairment Due to Diabetic Macular Edema
Diabetic Macular Edema
Bottom Line
View on ClinicalTrials.gov: NCT04058067 ↗Enrolled (actual)
263
Serious AEs
19.0%
Results posted
Sep 2024
Primary outcome: Primary: Change From Baseline at Week 52 in Best-corrected Visual Acuity (BCVA) for the Study Eye. — 10.6; 11.9 Scores on a scale — p=0.013
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
- Jan 2023
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline at Week 52 in Best-corrected Visual Acuity (BCVA) for the Study Eye. |
10.6; 11.9 | 0.013 sig |
| PRIMARY Best-corrected Visual Acuity (BCVA) - Average Change From Baseline Over the Period Week 40 Through Week 52 for the Study Eye |
10.1; 12.0 | 0.035 sig |
| SECONDARY Change From Baseline by Visit up to Week 52 in Best-corrected Visual Acuity (BCVA) for the Study Eye |
5.1; 4.4; 7.2; 6.6; 8.6; 8.0 | — |
| SECONDARY Best-corrected Visual Acuity (BCVA) - Average Change From Baseline Over the Period Week 4 Through Week 52 for the Study Eye |
9.0; 10.1 | — |
| SECONDARY Best-corrected Visual Acuity (BCVA) - Average Change From Baseline Over the Period Week 20 Through Week 52 for the Study Eye |
9.6; 11.5 | — |
| SECONDARY Best-corrected Visual Acuity (BCVA) - Average Change From Baseline Over the Period Week 28 Through Week 52 for the Study Eye |
9.6; 11.7 | — |
| SECONDARY Time-to-first q8w Treatment Need: Summary for Brolucizumab Subjects by Disease Activity Assessment Visit |
1; 0.733; 0.447; 0.417 | — |
| SECONDARY Time-to-first q8w Treatment Need: Summary for Brolucizumab Subjects by Disease Activity Assessment Visit, Within Those Subjects With no q8w-need During the Initial q12w Cycle |
1; 0.931 | — |
| SECONDARY Number and Percentage of Patients Who Gained in ≥5, ≥10 and ≥15 ETDRS Letters in BCVA From Baseline to Week 52 for the Study Eye |
102; 104; 74; 76; 44; 48 | — |
| SECONDARY Time to Achieve Gain of >= 5 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain |
0.136; 0.038; 0.508; 0.420; 0.720; 0.634 | — |
| SECONDARY Time to Achieve Gain of >= 10 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain |
0.061; 0.000; 0.227; 0.198; 0.394; 0.306 | — |
| SECONDARY Time to Achieve Gain of >= 15 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain |
0.008; 0.000; 0.083; 0.069; 0.152; 0.161 | — |
| SECONDARY Number and Percentage of Patients Who Lost ≥5, ≥10 and ≥15 ETDRS Letters in BCVA From Baseline to Week 52 for the Study Eye |
4; 4; 2; 1; 1; 1 | — |
| SECONDARY Proportion of Patients Who Have Absolute BCVA ≥73 ETDRS Letters at Each Post-baseline Visit for the Study Eye |
32; 34; 36; 46; 46; 55 | — |
| SECONDARY Number (%) of Subjects With q8w Treatment Need as Assessed by the Investigator at First Disease Activity Assessment (DAA) Visit - Week 32 |
34; 38 | — |
| SECONDARY Number (%) of Subjects With q8w Treatment Need as Assessed by the Investigator at Week 36, and Week 48 |
50; 32; 25; 32 | — |
| SECONDARY Change From Baseline at Week 52 in Central Subfield Thickness (CSFT) for the Study Eye |
-225.2; -215.0 | — |
| SECONDARY Average Change From Baseline Over the Period Week 40 Through Week 52 in Central Subfield Thickness (CSFT) for the Study Eye |
-215.1; -212.7 | — |
| SECONDARY Average Change From Baseline Over the Period Week 4 Through Week 52 in Central Subfield Thickness (CSFT) for the Study Eye |
-207.7; -199.2 | — |
| SECONDARY Number and Percentage of Patients Who Have CSFT (<280 Microns) at Each Assessment Visit for the Study Eye |
24; 17; 36; 22; 48; 29 | — |
| SECONDARY Number (%) of Patients With Progression to Proliferative Diabetic Retinopathy (PDR) as Assessed by ETDRS DRSS of at Least 61 by Week 52 for the Study Eye Among the Subset of Non-PDR Subjects at Screening |
1; 0 | — |
| SECONDARY Number (%) of Patients With Presence of Leakage in the Study Eye on Fluorescein Angiography (FA) |
110; 115 | — |
| SECONDARY Number (%) of Patients With Presence of Subretinal Fluid (SRF), Intraretinal Fluid (IRF) in the Study Eye |
87; 85 | — |
| SECONDARY Number of Patients With Presence of Subretinal Fluid (SRF) in the Study at Each Assessment Visit |
33; 37; 17; 28; 13; 20 | — |
| SECONDARY Number of Patients With Presence of Intraretinal Fluid (IRF) in the Study at Each Assessment Visit |
113; 115; 112; 110; 109; 112 | — |
| SECONDARY Intraretinal Fluid (IRF) Status in the Central Subfield: Proportion of Subjects With Presence of IRF in the Study Eye by Visit |
117; 118; 113; 114; 111; 114 | — |
| SECONDARY Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS): Number of Subjects With >=2-step Improvement From Baseline in the DRSS Score at Each Assessment Visit for the Study Eye - Number of Subjects |
45; 47; 62; 64 | — |
| SECONDARY Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS): Proportion of Subjects With >=2-step Improvement From Baseline in the DRSS Score at Each Assessment Visit for the Study Eye - Percentage Estimates |
33.9; 36.3; 46.7; 49.5 | — |
| SECONDARY Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS): Number of Subjects With >=3-step Improvement From Baseline in the DRSS Score at Each Assessment Visit for the Study Eye - Number of Subjects |
21; 15; 25; 25 | — |
| SECONDARY Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS): Proportion of Subjects With >=3-step Improvement From Baseline in the DRSS Score at Each Assessment Visit for the Study Eye - Percentage Estimates |
15.8; 11.6; 18.8; 19.3 | — |
| SECONDARY Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS): Number of Subjects With >=2-step Worsening From Baseline in the DRSS Score at Each Assessment Visit for the Study Eye - Number of Subjects |
1; 0; 0; 0 | — |
| SECONDARY Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS): Proportion of Subjects With >=2-step Worsening From Baseline in the DRSS Score at Each Assessment Visit for the Study Eye - Percentage Estimates |
0.8; 0.0 | — |
| SECONDARY Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS): Number of Subjects With >=3-step Worsening From Baseline in the DRSS Score at Each Assessment Visit for the Study Eye - Number of Subjects |
1; 0; 0; 0 | — |
| SECONDARY Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS): Proportion of Subjects With >=3-step Worsening From Baseline in the DRSS Score at Each Assessment Visit for the Study Eye - Percentage Estimates |
0.8; 0.0 | — |
| SECONDARY Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Overall Score |
5.3; 7.7; 5.4; 6.6 | — |
| SECONDARY Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - General Vision |
10.4; 9.5; 10.9; 11.5 | — |
| SECONDARY Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Ocular Pain |
5.1; 5.3; 3.5; 2.6 | — |
| SECONDARY Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Near Activities |
8.5; 9.7; 7.8; 8.0 | — |
| SECONDARY Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Distance Activities |
5.6; 7.6; 4.2; 6.5 | — |
| SECONDARY Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Social Functioning |
3.8; 5.2; 3.7; 5.8 | — |
| SECONDARY Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Mental Health |
7.2; 8.4; 7.4; 6.7 | — |
| SECONDARY Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Dependency |
3.3; 9.2; 5.2; 5.7 | — |
| SECONDARY Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Driving |
-3.4; 9.8; 0.1; 6.0 | — |
| SECONDARY Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Color Vision |
2.4; 3.0; 4.2; 3.3 | — |
| SECONDARY Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Peripheral Vision |
3.9; 7.5; 3.5; 7.7 | — |
| SECONDARY Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - General Health Rating |
3.1; 2.2; 4.2; -0.2 | — |
| SECONDARY Brolucizumab Serum Concentration |
21.1; 13.4 | — |
| SECONDARY Number (%) of Patients Who Have Positive Anti-drug Antibody (ADA) Status in Brolucizumab Arm |
35; 73; 16; 7 | — |
| SECONDARY Ocular Adverse Events (AEs) (>=2% in Any Treatment Arm) by Preferred Term for the Study Eye |
57; 47; 12; 6; 8; 9 | — |
| SECONDARY Number of Subjects With Non-ocular Adverse Events (AEs) (>=2% in Any Treatment Arm) |
94; 74 | — |
Summary
The purpose of this study was to evaluate the efficacy and safety of brolucizumab in treatment of Chinese patients with visual impairment due to Diabetic Macular Edema.
Eligibility Criteria
Inclusion Criteria
- Signed informed consent must be obtained prior to participation in the study.
- Patients ≥18 years of age at screening
- Patients with type 1 or type 2 diabetes mellitus (DM) and Hemoglobin A1c (HbA1c) of ≤10% at screening
- Medication for the management of diabetes must have been stable within 3 months prior to randomization and is expected to remain as stable as medically acceptable during the course of the study
- Study Eye Visual impairment due to diabetic macular edema (DME) with:
- Best-corrected visual acuity (BCVA) score between 78 and 23 letters, inclusive, using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) testing charts at a starting testing distance of 4 meters (approximate Snellen equivalent of 20/32 to 20/320) at screening and baseline
- DME involving the center of the macula, with central subfield retinal thickness (e.g. measured from retinal pigment epithelium (RPE) to the inner limiting membrane (ILM) inclusively) of ≥320 μm on Spectral domain optical coherence tomography (SD-OCT) at screening.
Exclusion Criteria
- Active Proliferative diabetic retinopathy (PDR) in the study eye as per 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 for the duration of the study (e.g. cataract, vitreous hemorrhage, retinal vascular occlusion, retinal detachment, macular hole, or choroidal neovascularization (CNV) 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 (ME), 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 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, affects visual acuity
- Previous treatment with any anti-vascular growth factor (VEGF) drug or investigational drugs in the study eye
Data sourced from ClinicalTrials.gov (NCT04058067). 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.