A Phase 3 interventional study of Brolucizumab and Aflibercept in Diabetic Macular Edema, sponsored by Novartis Pharmaceuticals. Completed at 24 sites in China. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-10-09.
Sponsored by Novartis Pharmaceuticals · Phase 3, Interventional, and Treatment
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.
The study is a randomized, double-masked, multi-center, active-controlled, 2-arm study in Chinese patients with Diabetic macular edema (DME). Approximately 335 Chinese patients were planned to be screened (20% screening failure rate expected) and approximately 268 (134 per arm) patients were planned to be randomized in approximately 25 centers.
Patients who met all the inclusion and none of the exclusion criteria were randomized in a 1:1 ratio to one of two treatment arms:
Disease activity assessments (DAAs) were conducted by the masked investigator for both treatment arms at Weeks 32, 36, and 48. In the brolucizumab arm, subjects who qualified for q12w during this initial q12w interval continued on a q12w treatment frequency unless disease activity was identified at the subsequent DAA visit at Week 48, in which case subjects were switched to a q8w treatment interval until Week 52.
308 studies on the registry are indexed under Vision Disorders; 81 are open to participants now.
This study's enrollment of 266 is above the median of 66 across 211 interventional studies indexed under Vision Disorders.
Browse Vision Disorders studies →Novartis Pharmaceuticals is the lead sponsor of 2,673 studies on the registry; 228 are open to participants now.
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Study Eye Visual impairment due to diabetic macular edema (DME) with:
Exclusion Criteria:
5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance
Drug: Brolucizumab
5 x every 4 weeks loading then every 8 weeks maintenance
Drug: Aflibercept
5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance
Also known as: RTH258
5 x every 4 weeks loading then every 8 weeks maintenance
Also known as: Eylea
Change From Baseline at Week 52 in Best-corrected Visual Acuity (BCVA) for the Study Eye.
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. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.
Time frame: Baseline to Week 52
Best-corrected Visual Acuity (BCVA) - Average Change From Baseline Over the Period Week 40 Through Week 52 for the Study Eye
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. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.
Time frame: Week 40 to Week 52
Change From Baseline by Visit up to Week 52 in Best-corrected Visual Acuity (BCVA) for the Study Eye
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. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.
Time frame: Baseline, Week 52
Best-corrected Visual Acuity (BCVA) - Average Change From Baseline Over the Period Week 4 Through Week 52 for the Study Eye
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. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.
Time frame: Week 4 to Week 52
Best-corrected Visual Acuity (BCVA) - Average Change From Baseline Over the Period Week 20 Through Week 52 for the Study Eye
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. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.
Time frame: Week 20 to Week 52
Best-corrected Visual Acuity (BCVA) - Average Change From Baseline Over the Period Week 28 Through Week 52 for the Study Eye
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. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.
Time frame: Week 28 to Week 52
Time-to-first q8w Treatment Need: Summary for Brolucizumab Subjects by Disease Activity Assessment Visit
The estimate for the proportion of subjects with a positive q12w treatment status was derived from Kaplan Meier time-to-event analyses for the event 'first q8w-need', applying a 'q8w-need' allocation in case of missing or confounded data attributable to lack of efficacy and/or lack of safety. As a result, the probability that subjects in brolucizumab arm do not need a q8w treatment (and therefore are maintained on a q12w treatment) up to the visit is reported in the table.
Time frame: Baseline (Week 0), Week 32, Week 36 and Week 48
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
The estimate for the proportion of subjects with a positive q12w treatment status was derived from Kaplan Meier time-to-event analyses for the event 'first q8w-need', applying a 'q8w-need' allocation in case of missing or confounded data attributable to lack of efficacy and/or lack of safety. As a result, the probability that subjects in brolucizumab arm do not need a q8w treatment (and therefore are maintained on a q12w treatment) up to the visit is reported in the table.
Time frame: Week 36 and Week 48
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
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. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.
Time frame: Baseline, Week 52
Time to Achieve Gain of >= 5 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain
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. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.
Time frame: Baseline up to Week 52
Time to Achieve Gain of >= 10 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain
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. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.
Time frame: Baseline up to Week 52
Time to Achieve Gain of >= 15 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain
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. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.
Time frame: Baseline up to Week 52
Number and Percentage of Patients Who Lost ≥5, ≥10 and ≥15 ETDRS Letters in BCVA From Baseline to Week 52 for the Study Eye
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. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.
Time frame: Baseline, Week 52
Proportion of Patients Who Have Absolute BCVA ≥73 ETDRS Letters at Each Post-baseline Visit for the Study Eye
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. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.
Time frame: Baseline up to Week 52
Number (%) of Subjects With q8w Treatment Need as Assessed by the Investigator at First Disease Activity Assessment (DAA) Visit - Week 32
To evaluate the efficacy related to dosing regimen of brolucizumab
Time frame: Week 32
Number (%) of Subjects With q8w Treatment Need as Assessed by the Investigator at Week 36, and Week 48
To evaluate the efficacy related to dosing regimen of brolucizumab
Time frame: Week 36, Week 48
Change From Baseline at Week 52 in Central Subfield Thickness (CSFT) for the Study Eye
Central Subfield Thickness Assessed by Spectral domain optical coherence tomography (SD-OCT) from the central reading center.
Time frame: Baseline, Week 52
Average Change From Baseline Over the Period Week 40 Through Week 52 in Central Subfield Thickness (CSFT) for the Study Eye
Central Subfield Thickness Assessed by Spectral domain optical coherence tomography (SD-OCT) from the central reading center.
Time frame: Baseline, over the period of Week 40 to Week 52
Average Change From Baseline Over the Period Week 4 Through Week 52 in Central Subfield Thickness (CSFT) for the Study Eye
Central Subfield Thickness Assessed by Spectral domain optical coherence tomography (SD-OCT) from the central reading center.
Time frame: Baseline, over the period of Week 4 to Week 52
Number and Percentage of Patients Who Have CSFT (<280 Microns) at Each Assessment Visit for the Study Eye
Central Subfield Thickness Assessed by Spectral domain optical coherence tomography (SD-OCT) from the central reading center.
Time frame: Baseline up to Week 52
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
As evaluated using the Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) score assessed by the Central Reading Center (CRC) based on color fundus photography images in the study eye. When the ETDRS-DR severities were evaluable, they were converted and categorized on a 12-level scale, from 1 (DR absent) to 12 (very advanced PDR). A lower score represents better visual functioning.
Time frame: Baseline, Week 52
Number (%) of Patients With Presence of Leakage in the Study Eye on Fluorescein Angiography (FA)
Assessed by angiography.
Time frame: Week 52
Number (%) of Patients With Presence of Subretinal Fluid (SRF), Intraretinal Fluid (IRF) in the Study Eye
To evaluate the efficacy of brolucizumab relative to aflibercept over the time period by assessing changes in anatomical parameters
Time frame: Baseline up to Week 52
Number of Patients With Presence of Subretinal Fluid (SRF) in the Study at Each Assessment Visit
Subretinal Fluid (SRF) status in the central subfield: proportion of subjects with presence of SRF in the study eye by visit
Time frame: Week 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48, 52
Number of Patients With Presence of Intraretinal Fluid (IRF) in the Study at Each Assessment Visit
Intraretinal Fluid (IRF) status in the central subfield: proportion of subjects with presence of IRF in the study eye by visit
Time frame: Week 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48, 52
Intraretinal Fluid (IRF) Status in the Central Subfield: Proportion of Subjects With Presence of IRF in the Study Eye by Visit
Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) status in the central subfield: proportion of subjects with presence of SRF and/or IRF in the study eye by visit
Time frame: Week 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48, 52
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
Severity of Diabetic Retinopathy (DR) was evaluated using the ETDRS DRSS score assessed by the Central Reading Center (CRC) based on color fundus photography images in the study eye. When the ETDRS-DR severities were evaluable, they were categorized on a 12-level scale, from 1 (DR absent) to 12 (very advanced PDR). A lower score represents better visual functioning.
Time frame: Baseline, Week 28 and Week 52
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
Severity of Diabetic Retinopathy (DR) was evaluated using the ETDRS DRSS score assessed by the Central Reading Center (CRC) based on color fundus photography images in the study eye. When the ETDRS-DR severities were evaluable, they were categorized on a 12-level scale, from 1 (DR absent) to 12 (very advanced PDR). A lower score represents better visual functioning.
Time frame: Baseline, Week 28 and Week 52
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
Severity of Diabetic Retinopathy (DR) was evaluated using the ETDRS DRSS score assessed by the Central Reading Center (CRC) based on color fundus photography images in the study eye. When the ETDRS-DR severities were evaluable, they were categorized on a 12-level scale, from 1 (DR absent) to 12 (very advanced PDR). A lower score represents better visual functioning.
Time frame: Baseline, Week 28 and Week 52
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
Severity of Diabetic Retinopathy (DR) was evaluated using the ETDRS DRSS score assessed by the Central Reading Center (CRC) based on color fundus photography images in the study eye. When the ETDRS-DR severities were evaluable, they were categorized on a 12-level scale, from 1 (DR absent) to 12 (very advanced PDR). A lower score represents better visual functioning.
Time frame: Baseline, Week 28 and Week 52
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
Severity of Diabetic Retinopathy (DR) was evaluated using the ETDRS DRSS score assessed by the Central Reading Center (CRC) based on color fundus photography images in the study eye. When the ETDRS-DR severities were evaluable, they were categorized on a 12-level scale, from 1 (DR absent) to 12 (very advanced PDR). A lower score represents better visual functioning.
Time frame: Baseline, Week 28 and Week 52
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
Severity of Diabetic Retinopathy (DR) was evaluated using the ETDRS DRSS score assessed by the Central Reading Center (CRC) based on color fundus photography images in the study eye. When the ETDRS-DR severities were evaluable, they were categorized on a 12-level scale, from 1 (DR absent) to 12 (very advanced PDR). A lower score represents better visual functioning.
Time frame: Baseline, Week 28 and Week 52
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
Severity of Diabetic Retinopathy (DR) was evaluated using the ETDRS DRSS score assessed by the Central Reading Center (CRC) based on color fundus photography images in the study eye. When the ETDRS-DR severities were evaluable, they were categorized on a 12-level scale, from 1 (DR absent) to 12 (very advanced PDR). A lower score represents better visual functioning.
Time frame: Baseline, Week 28 and Week 52
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
Severity of Diabetic Retinopathy (DR) was evaluated using the ETDRS DRSS score assessed by the Central Reading Center (CRC) based on color fundus photography images in the study eye. When the ETDRS-DR severities were evaluable, they were categorized on a 12-level scale, from 1 (DR absent) to 12 (very advanced PDR). A lower score represents better visual functioning.
Time frame: Baseline, Week 28 and Week 52
Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Overall Score
The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. A composite score is derived based on the average of the 11 subscales.
Time frame: Baseline, Week 28 and Week 52
Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - General Vision
The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. A composite score is derived based on the average of the 11 subscales.
Time frame: Baseline, Week 28 and Week 52
Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Ocular Pain
The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. A composite score is derived based on the average of the 11 subscales.
Time frame: Baseline, Week 28 and Week 52
Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Near Activities
The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. A composite score is derived based on the average of the 11 subscales.
Time frame: Baseline, Week 28 and Week 52
Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Distance Activities
The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. A composite score is derived based on the average of the 11 subscales.
Time frame: Baseline, Week 28 and Week 52
Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Social Functioning
The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. A composite score is derived based on the average of the 11 subscales.
Time frame: Baseline, Week 28 and Week 52
Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Mental Health
The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. A composite score is derived based on the average of the 11 subscales.
Time frame: Baseline, Week 28 and Week 52
Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Dependency
The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. A composite score is derived based on the average of the 11 subscales.
Time frame: Baseline, Week 28 and Week 52
Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Driving
The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. A composite score is derived based on the average of the 11 subscales.
Time frame: Baseline, Week 28 and Week 52
Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Color Vision
The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. A composite score is derived based on the average of the 11 subscales.
Time frame: Baseline, Week 28 and Week 52
Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Peripheral Vision
The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. A composite score is derived based on the average of the 11 subscales.
Time frame: Baseline, Week 28 and Week 52
Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - General Health Rating
The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. A composite score is derived based on the average of the 11 subscales.
Time frame: Baseline, Week 28 and Week 52
Brolucizumab Serum Concentration
To confirm the systemic brolucizumab exposure in a subset of patients.
Time frame: Approximately 24 hours post Day 1 treatment and approximately 24 hours post Week 24 treatment
Number (%) of Patients Who Have Positive Anti-drug Antibody (ADA) Status in Brolucizumab Arm
To assess the immunogenicity of brolucizumab
Time frame: Up to Week 52
Ocular Adverse Events (AEs) (>=2% in Any Treatment Arm) by Preferred Term for the 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
Time frame: Adverse events are reported from first dose of study treatment until end of study treatment plus 30days post treatment, up to a maximum duration of approximately 52 weeks.
Number of Subjects With Non-ocular Adverse Events (AEs) (>=2% in Any Treatment Arm)
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
Time frame: Adverse events are reported from first dose of study treatment until end of study treatment plus 30days post treatment, up to a maximum duration of approximately 52 weeks.
| Milestone | Brolucizumab 6 mg | Aflibercept 2 mg |
|---|---|---|
| Started | 132 | 131 |
| Completed | 120 | 120 |
| Not completed | 12 | 11 |
| Withdrew: Adverse event | 2 | 0 |
| Withdrew: Death | 0 | 1 |
| Withdrew: Physician decision | 3 | 1 |
| Withdrew: Protocol violation | 0 | 1 |
| Withdrew: Withdrawal by subject | 7 | 8 |
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. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.
| Scores on a scale | Brolucizumab 6 mg | Aflibercept 2 mg |
|---|---|---|
| Change From Baseline at Week 52 in Best-corrected Visual Acuity (BCVA) for the Study Eye. | 10.6 ± 0.85 | 11.9 ± 0.85 |
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. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.
| Scores on a scale | Brolucizumab 6 mg | Aflibercept 2 mg |
|---|---|---|
| Best-corrected Visual Acuity (BCVA) - Average Change From Baseline Over the Period Week 40 Through Week 52 for the Study Eye | 10.1 ± 0.81 | 12.0 ± 0.82 |
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. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.
| Scores on a scale | Brolucizumab 6 mg | Aflibercept 2 mg |
|---|---|---|
| Week 4 (n=129,123) | 5.1 ± 6.58 | 4.4 ± 6.75 |
| Week 6 (n=125,122) | 7.2 ± 7.49 | 6.6 ± 7.50 |
| Week 8 (n=128,125) | 8.6 ± 8.43 | 8.0 ± 8.56 |
| Week 12 (n=119,122) | 9.2 ± 8.77 | 9.0 ± 9.67 |
| Week 16 (n=115,118) | 10.0 ± 9.83 | 10.4 ± 9.86 |
| Week 18 (n=113,115) | 9.8 ± 9.19 | 10.7 ± 10.25 |
| Week 20 (n=109,114) | 10.0 ± 9.36 | 11.3 ± 9.57 |
| Week 24 (n=109,116) | 9.9 ± 10.48 | 10.5 ± 9.80 |
| Week 28 (n=111,111) | 10.5 ± 9.62 | 10.9 ± 10.13 |
| Week 32 (n=107,116) | 10.1 ± 10.29 | 11.3 ± 10.12 |
| Week 36 (n=105,114) | 9.1 ± 10.86 | 11.8 ± 10.62 |
| Week 40 (n=101,110) | 10.1 ± 10.24 | 11.7 ± 10.02 |
| Week 44 (n=102,110) | 11.2 ± 9.86 | 12.2 ± 9.79 |
| Week 48 (n=103,105) | 10.9 ± 9.91 | 12.2 ± 10.71 |
| Week 52 (n=105,105) | 11.3 ± 9.21 | 12.1 ± 10.92 |
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. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.
| Scores on a scale | Brolucizumab 6 mg | Aflibercept 2 mg |
|---|---|---|
| Best-corrected Visual Acuity (BCVA) - Average Change From Baseline Over the Period Week 4 Through Week 52 for the Study Eye | 9.0 ± 0.68 | 10.1 ± 0.68 |
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. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.
| Scores on a scale | Brolucizumab 6 mg | Aflibercept 2 mg |
|---|---|---|
| Best-corrected Visual Acuity (BCVA) - Average Change From Baseline Over the Period Week 20 Through Week 52 for the Study Eye | 9.6 ± 0.77 | 11.5 ± 0.77 |
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. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.
| Scores on a scale | Brolucizumab 6 mg | Aflibercept 2 mg |
|---|---|---|
| Best-corrected Visual Acuity (BCVA) - Average Change From Baseline Over the Period Week 28 Through Week 52 for the Study Eye | 9.6 ± 0.80 | 11.7 ± 0.80 |
The estimate for the proportion of subjects with a positive q12w treatment status was derived from Kaplan Meier time-to-event analyses for the event 'first q8w-need', applying a 'q8w-need' allocation in case of missing or confounded data attributable to lack of efficacy and/or lack of safety. As a result, the probability that subjects in brolucizumab arm do not need a q8w treatment (and therefore are maintained on a q12w treatment) up to the visit is reported in the table.
| Probability | Brolucizumab 6 mg | Aflibercept 2 mg |
|---|---|---|
| Week 0 | 1 (NA to NA) | — |
| Week 32 (n=86,0) | 0.733 (0.626 to 0.813) | — |
| Week36 (n=59,0) | 0.447 (0.338 to 0.550) | — |
| Week48 (n=30,0) | 0.417 (0.309 to 0.522) | — |
The estimate for the proportion of subjects with a positive q12w treatment status was derived from Kaplan Meier time-to-event analyses for the event 'first q8w-need', applying a 'q8w-need' allocation in case of missing or confounded data attributable to lack of efficacy and/or lack of safety. As a result, the probability that subjects in brolucizumab arm do not need a q8w treatment (and therefore are maintained on a q12w treatment) up to the visit is reported in the table.
| Probability | Brolucizumab 6 mg | Aflibercept 2 mg |
|---|---|---|
| Week36 (n=35,0) | 1 (NA to NA) | — |
| Week48 (n=29,0) | 0.931 (0.751 to 0.982) | — |
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. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.
| Participants | Brolucizumab 6 mg | Aflibercept 2 mg |
|---|---|---|
| N (%) of subjects with ≥5 letters gain from baseline or reached BCVA of ≥84 letters at Week 52 | 102 | 104 |
| N (%) of subjects with ≥10 letters gain from baseline or reached BCVA of ≥84 letters at Week 52 | 74 | 76 |
| N (%) of subjects with ≥15 letters gain from baseline or reached BCVA of ≥84 letters at Week 52 | 44 | 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. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.
| Probability of BCVA gain | Brolucizumab 6 mg | Aflibercept 2 mg |
|---|---|---|
| Week 4 | 0.136 (0.084 to 0.201) | 0.038 (0.014 to 0.081) |
| Week 6 (n=114,126) | 0.508 (0.419 to 0.589) | 0.420 (0.334 to 0.503) |
| Week 8 (n=65, 76) | 0.720 (0.634 to 0.789) | 0.634 (0.544 to 0.710) |
| Week 12 (n=37, 48) | 0.780 (0.699 to 0.842) | 0.725 (0.639 to 0.794) |
| Week 16 (n=29, 36) | 0.818 (0.740 to 0.875) | 0.780 (0.697 to 0.842) |
| Week 18 (n=24, 28) | 0.818 (0.740 to 0.875) | 0.843 (0.766 to 0.896) |
| Week 20 (n=24,20) | 0.841 (0.765 to 0.894) | 0.866 (0.793 to 0.915) |
| Week 24 (n=21,17) | 0.856 (0.782 to 0.906) | 0.874 (0.802 to 0.921) |
| Week 28 (n=19,15) | 0.864 (0.791 to 0.913) | 0.882 (0.811 to 0.928) |
| Week 32 (n=17,14) | 0.888 (0.818 to 0.932) | 0.882 (0.811 to 0.928) |
| Week 36 (n=14,14,) | 0.888 (0.818 to 0.932) | 0.882 (0.811 to 0.928) |
| Week 40 (n=14,14) | 0.888 (0.818 to 0.932) | 0.908 (0.840 to 0.948) |
| Week 44 (n=14,11) | 0.896 (0.828 to 0.938) | 0.908 (0.840 to 0.948) |
| Week 48 (n=13,10) | 0.912 (0.846 to 0.951) | 0.917 (0.850 to 0.955) |
| Week 52 (n=11,9) | 0.957 (0.880 to 0.985) | 0.926 (0.860 to 0.962) |
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. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.
| Probability of BCVA gain | Brolucizumab 6 mg | Aflibercept 2 mg |
|---|---|---|
| Week 4 | 0.061 (0.028 to 0.110) | 0.000 (NA to NA) |
| Week 6 (n=124,131) | 0.227 (0.160 to 0.302) | 0.198 (0.135 to 0.271) |
| Week 8 (n=102,105) | 0.394 (0.310 to 0.476) | 0.306 (0.229 to 0.386) |
| Week 12 (n=80,90) | 0.508 (0.419 to 0.590) | 0.439 (0.352 to 0.523) |
| Week 16 (n=64,71) | 0.562 (0.472 to 0.642) | 0.527 (0.436 to 0.609) |
| Week 18 (n=55,59) | 0.594 (0.504 to 0.673) | 0.551 (0.460 to 0.633) |
| Week 20 (n=50,56) | 0.618 (0.528 to 0.696) | 0.591 (0.500 to 0.671) |
| Week 24 (n=47,51) | 0.643 (0.553 to 0.719) | 0.664 (0.573 to 0.739) |
| Week 28 (n=44,41) | 0.659 (0.570 to 0.735) | 0.680 (0.590 to 0.754) |
| Week 32 (n=41,38) | 0.676 (0.587 to 0.750) | 0.705 (0.616 to 0.777) |
| Week 36 (n=39,35) | 0.693 (0.604 to 0.766) | 0.722 (0.634 to 0.793) |
| Week 40 (n=35,33) | 0.710 (0.622 to 0.782) | 0.730 (0.642 to 0.800) |
| Week 44 (n=33,32) | 0.728 (0.640 to 0.798) | 0.739 (0.652 to 0.808) |
| Week 48 (n=31,28) | 0.754 (0.667 to 0.822) | 0.749 (0.661 to 0.817) |
| Week 52 (n=28,27) | 0.899 (0.416 to 0.987) | 1 (NA to NA) |
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. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.
| Probability of BCVA gain | Brolucizumab 6 mg | Aflibercept 2 mg |
|---|---|---|
| Week 4 | 0.008 (0.001 to 0.038) | 0.000 (NA to NA) |
| Week 6 (n=131,131) | 0.083 (0.044 to 0.138) | 0.069 (0.034 to 0.121) |
| Week 8 (n=121,122) | 0.152 (0.096 to 0.218) | 0.161 (0.104 to 0.229) |
| Week 12 (n=112,109) | 0.227 (0.160 to 0.302) | 0.216 (0.149 to 0.290) |
| Week 16 (n=101,100) | 0.266 (0.193 to 0.343) | 0.255 (0.183 to 0.333) |
| Week 18 (n=94,94) | 0.313 (0.235 to 0.393) | 0.319 (0.240 to 0.401) |
| Week 20 (n=87,85) | 0.344 (0.264 to 0.426) | 0.359 (0.276 to 0.442) |
| Week 24 (n=82,80) | 0.409 (0.323 to 0.492) | 0.399 (0.313 to 0.483) |
| Week 28 (n=72,74) | 0.425 (0.338 to 0.509) | 0.432 (0.344 to 0.516) |
| Week 32 (n=67,69) | 0.459 (0.370 to 0.544) | 0.456 (0.367 to 0.541) |
| Week 36 (n=63,66) | 0.485 (0.395 to 0.570) | 0.481 (0.391 to 0.566) |
| Week 40 (n=58,63) | 0.494 (0.403 to 0.579) | 0.506 (0.415 to 0.590) |
| Week 44 (n=57,60) | 0.512 (0.420 to 0.596) | 0.531 (0.439 to 0.614) |
| Week 48 (n=55,54) | 0.539 (0.446 to 0.622) | 0.540 (0.447 to 0.623) |
| Week 52 (n=52,53) | 0.623 (0.436 to 0.763) | 1 (NA to NA) |
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. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.
| Participants | Brolucizumab 6 mg | Aflibercept 2 mg |
|---|---|---|
| N (%) of subjects with ≥5 letters loss from baseline or reached BCVA of ≥84 letters at Week 52 | 4 | 4 |
| N (%) of subjects with ≥10 letters loss from baseline or reached BCVA of ≥84 letters at Week 52 | 2 | 1 |
| N (%) of subjects with ≥15 letters loss from baseline or reached BCVA of ≥84 letters at Week 52 | 1 | 1 |
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. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.
| Participants | Brolucizumab 6 mg | Aflibercept 2 mg |
|---|---|---|
| Week 4 | 32 | 34 |
| Week 6 | 36 | 46 |
| Week 8 | 46 | 55 |
| Week 12 | 50 | 63 |
| Week 16 | 50 | 67 |
| Week 18 | 51 | 68 |
| Week 20 | 54 | 65 |
| Week 24 | 53 | 74 |
| Week 28 | 52 | 72 |
| Week 32 | 51 | 74 |
| Week 36 | 49 | 77 |
| Week 40 | 53 | 81 |
| Week 44 | 53 | 76 |
| Week 48 | 57 | 78 |
| Week 52 | 55 | 75 |
To evaluate the efficacy related to dosing regimen of brolucizumab
| Participants | Brolucizumab 6 mg | Aflibercept 2 mg |
|---|---|---|
| Number (%) of Subjects With q8w Treatment Need as Assessed by the Investigator at First Disease Activity Assessment (DAA) Visit - Week 32 | 34 | 38 |
To evaluate the efficacy related to dosing regimen of brolucizumab
| Participants | Brolucizumab 6 mg | Aflibercept 2 mg |
|---|---|---|
| Week 36 (n=105,113) | 50 | 32 |
| Week 48 (n=102,104) | 25 | 32 |
Central Subfield Thickness Assessed by Spectral domain optical coherence tomography (SD-OCT) from the central reading center.
| micrometer | Brolucizumab 6 mg | Aflibercept 2 mg |
|---|---|---|
| Change From Baseline at Week 52 in Central Subfield Thickness (CSFT) for the Study Eye | -225.2 ± 9.71 | -215.0 ± 9.75 |
Central Subfield Thickness Assessed by Spectral domain optical coherence tomography (SD-OCT) from the central reading center.
| micrometer | Brolucizumab 6 mg | Aflibercept 2 mg |
|---|---|---|
| Average Change From Baseline Over the Period Week 40 Through Week 52 in Central Subfield Thickness (CSFT) for the Study Eye | -215.1 ± 8.69 | -212.7 ± 8.73 |
Central Subfield Thickness Assessed by Spectral domain optical coherence tomography (SD-OCT) from the central reading center.
| micrometer | Brolucizumab 6 mg | Aflibercept 2 mg |
|---|---|---|
| Average Change From Baseline Over the Period Week 4 Through Week 52 in Central Subfield Thickness (CSFT) for the Study Eye | -207.7 ± 7.77 | -199.2 ± 7.80 |
Central Subfield Thickness Assessed by Spectral domain optical coherence tomography (SD-OCT) from the central reading center.
| Participants | Brolucizumab 6 mg | Aflibercept 2 mg |
|---|---|---|
| Week 4 | 24 | 17 |
| Week 6 | 36 | 22 |
| Week 8 | 48 | 29 |
| Week 12 | 52 | 33 |
| Week 16 | 63 | 41 |
| Week 18 | 61 | 41 |
| Week 20 | 67 | 46 |
| Week 24 | 65 | 40 |
| Week 28 | 71 | 49 |
| Week 32 | 63 | 47 |
| Week 36 | 59 | 51 |
| Week 40 | 67 | 47 |
| Week 44 | 74 | 56 |
| Week 48 | 68 | 52 |
| Week 52 | 79 | 56 |
As evaluated using the Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) score assessed by the Central Reading Center (CRC) based on color fundus photography images in the study eye. When the ETDRS-DR severities were evaluable, they were converted and categorized on a 12-level scale, from 1 (DR absent) to 12 (very advanced PDR). A lower score represents better visual functioning.
| Participants | Brolucizumab 6 mg | Aflibercept 2 mg |
|---|---|---|
| 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 |
Assessed by angiography.
| Participants | Brolucizumab 6 mg | Aflibercept 2 mg |
|---|---|---|
| Number (%) of Patients With Presence of Leakage in the Study Eye on Fluorescein Angiography (FA) | 110 | 115 |
To evaluate the efficacy of brolucizumab relative to aflibercept over the time period by assessing changes in anatomical parameters
| Participants | Brolucizumab 6 mg | Aflibercept 2 mg |
|---|---|---|
| Number (%) of Patients With Presence of Subretinal Fluid (SRF), Intraretinal Fluid (IRF) in the Study Eye | 87 | 85 |
Subretinal Fluid (SRF) status in the central subfield: proportion of subjects with presence of SRF in the study eye by visit
| Participants | Brolucizumab 6 mg | Aflibercept 2 mg |
|---|---|---|
| Week 4 | 33 | 37 |
| Week 6 | 17 | 28 |
| Week 8 | 13 | 20 |
| Week 12 | 7 | 14 |
| Week 16 | 6 | 9 |
| Week 18 | 6 | 4 |
| Week 20 | 6 | 2 |
| Week 24 | 5 | 2 |
| Week 28 | 5 | 5 |
| Week 32 | 8 | 7 |
| Week 36 | 13 | 8 |
| Week 40 | 7 | 6 |
| Week 44 | 7 | 3 |
| Week 48 | 10 | 4 |
| Week 52 | 9 | 4 |
Intraretinal Fluid (IRF) status in the central subfield: proportion of subjects with presence of IRF in the study eye by visit
| Participants | Brolucizumab 6 mg | Aflibercept 2 mg |
|---|---|---|
| Week 4 | 113 | 115 |
| Week 6 | 112 | 110 |
| Week 8 | 109 | 112 |
| Week 12 | 100 | 110 |
| Week 16 | 99 | 109 |
| Week 18 | 98 | 110 |
| Week 20 | 94 | 102 |
| Week 24 | 90 | 102 |
| Week 28 | 87 | 100 |
| Week 32 | 88 | 99 |
| Week 36 | 98 | 98 |
| Week 40 | 89 | 101 |
| Week 44 | 84 | 94 |
| Week 48 | 89 | 94 |
| Week 52 | 87 | 85 |
Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) status in the central subfield: proportion of subjects with presence of SRF and/or IRF in the study eye by visit
| Participants | Brolucizumab 6 mg | Aflibercept 2 mg |
|---|---|---|
| Week 4 | 117 | 118 |
| Week 6 | 113 | 114 |
| Week 8 | 111 | 114 |
| Week 12 | 100 | 110 |
| Week 16 | 99 | 110 |
| Week 18 | 98 | 110 |
| Week 20 | 94 | 102 |
| Week 24 | 90 | 102 |
| Week 28 | 87 | 100 |
| Week 32 | 88 | 99 |
| Week 36 | 98 | 98 |
| Week 40 | 89 | 101 |
| Week 44 | 84 | 94 |
| Week 48 | 89 | 94 |
| Week 52 | 87 | 85 |
Severity of Diabetic Retinopathy (DR) was evaluated using the ETDRS DRSS score assessed by the Central Reading Center (CRC) based on color fundus photography images in the study eye. When the ETDRS-DR severities were evaluable, they were categorized on a 12-level scale, from 1 (DR absent) to 12 (very advanced PDR). A lower score represents better visual functioning.
| Participants | Brolucizumab 6 mg | Aflibercept 2 mg |
|---|---|---|
| Week 28 | 45 | 47 |
| Week 52 | 62 | 64 |
Severity of Diabetic Retinopathy (DR) was evaluated using the ETDRS DRSS score assessed by the Central Reading Center (CRC) based on color fundus photography images in the study eye. When the ETDRS-DR severities were evaluable, they were categorized on a 12-level scale, from 1 (DR absent) to 12 (very advanced PDR). A lower score represents better visual functioning.
| Percentage estimates | Brolucizumab 6 mg | Aflibercept 2 mg |
|---|---|---|
| Week 28 | 33.9 | 36.3 |
| Week 52 | 46.7 | 49.5 |
Severity of Diabetic Retinopathy (DR) was evaluated using the ETDRS DRSS score assessed by the Central Reading Center (CRC) based on color fundus photography images in the study eye. When the ETDRS-DR severities were evaluable, they were categorized on a 12-level scale, from 1 (DR absent) to 12 (very advanced PDR). A lower score represents better visual functioning.
| Participants | Brolucizumab 6 mg | Aflibercept 2 mg |
|---|---|---|
| Week 28 | 21 | 15 |
| Week 52 | 25 | 25 |
Severity of Diabetic Retinopathy (DR) was evaluated using the ETDRS DRSS score assessed by the Central Reading Center (CRC) based on color fundus photography images in the study eye. When the ETDRS-DR severities were evaluable, they were categorized on a 12-level scale, from 1 (DR absent) to 12 (very advanced PDR). A lower score represents better visual functioning.
| Percentage estimates | Brolucizumab 6 mg | Aflibercept 2 mg |
|---|---|---|
| Week 28 | 15.8 | 11.6 |
| Week 52 | 18.8 | 19.3 |
Severity of Diabetic Retinopathy (DR) was evaluated using the ETDRS DRSS score assessed by the Central Reading Center (CRC) based on color fundus photography images in the study eye. When the ETDRS-DR severities were evaluable, they were categorized on a 12-level scale, from 1 (DR absent) to 12 (very advanced PDR). A lower score represents better visual functioning.
| Participants | Brolucizumab 6 mg | Aflibercept 2 mg |
|---|---|---|
| Week 28 | 1 | 0 |
| Week 52 | 0 | 0 |
Severity of Diabetic Retinopathy (DR) was evaluated using the ETDRS DRSS score assessed by the Central Reading Center (CRC) based on color fundus photography images in the study eye. When the ETDRS-DR severities were evaluable, they were categorized on a 12-level scale, from 1 (DR absent) to 12 (very advanced PDR). A lower score represents better visual functioning.
| Percentage estimates | Brolucizumab 6 mg | Aflibercept 2 mg |
|---|---|---|
| Week 28 | 0.8 | 0.0 |
Severity of Diabetic Retinopathy (DR) was evaluated using the ETDRS DRSS score assessed by the Central Reading Center (CRC) based on color fundus photography images in the study eye. When the ETDRS-DR severities were evaluable, they were categorized on a 12-level scale, from 1 (DR absent) to 12 (very advanced PDR). A lower score represents better visual functioning.
| Participants | Brolucizumab 6 mg | Aflibercept 2 mg |
|---|---|---|
| Week 28 | 1 | 0 |
| Week 52 | 0 | 0 |
Severity of Diabetic Retinopathy (DR) was evaluated using the ETDRS DRSS score assessed by the Central Reading Center (CRC) based on color fundus photography images in the study eye. When the ETDRS-DR severities were evaluable, they were categorized on a 12-level scale, from 1 (DR absent) to 12 (very advanced PDR). A lower score represents better visual functioning.
| Percentage estimates | Brolucizumab 6 mg | Aflibercept 2 mg |
|---|---|---|
| Week 28 | 0.8 | 0.0 |
The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. A composite score is derived based on the average of the 11 subscales.
| Scores on a Scale | Brolucizumab 6 mg | Aflibercept 2 mg |
|---|---|---|
| Week 28 | 5.3 ± 11.97 | 7.7 ± 15.98 |
| Week 52 (n=101,101) | 5.4 ± 13.87 | 6.6 ± 16.50 |
The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. A composite score is derived based on the average of the 11 subscales.
| Scores on a Scale | Brolucizumab 6 mg | Aflibercept 2 mg |
|---|---|---|
| Week 28 (n=96,103) | 10.4 ± 18.80 | 9.5 ± 18.75 |
| Week 52 (n=101,101) | 10.9 ± 18.23 | 11.5 ± 17.74 |
The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. A composite score is derived based on the average of the 11 subscales.
| Scores on a Scale | Brolucizumab 6 mg | Aflibercept 2 mg |
|---|---|---|
| Week 28 (n=96,103) | 5.1 ± 20.16 | 5.3 ± 24.23 |
| Week 52 (n=101,101) | 3.5 ± 22.51 | 2.6 ± 25.27 |
The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. A composite score is derived based on the average of the 11 subscales.
| Scores on a Scale | Brolucizumab 6 mg | Aflibercept 2 mg |
|---|---|---|
| Week 28 (n=96,103) | 8.5 ± 20.79 | 9.7 ± 24.15 |
| Week 52 (n=100,101) | 7.8 ± 22.12 | 8.0 ± 25.25 |
The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. A composite score is derived based on the average of the 11 subscales.
| Scores on a Scale | Brolucizumab 6 mg | Aflibercept 2 mg |
|---|---|---|
| Week 28 (n=96,103) | 5.6 ± 17.54 | 7.6 ± 22.34 |
| Week 52 (n=101,101) | 4.2 ± 18.42 | 6.5 ± 22.43 |
The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. A composite score is derived based on the average of the 11 subscales.
| Scores on a Scale | Brolucizumab 6 mg | Aflibercept 2 mg |
|---|---|---|
| Week 28 (n=96,103) | 3.8 ± 14.86 | 5.2 ± 18.98 |
| Week 52 (n=101,101) | 3.7 ± 15.47 | 5.8 ± 17.73 |
The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. A composite score is derived based on the average of the 11 subscales.
| Scores on a Scale | Brolucizumab 6 mg | Aflibercept 2 mg |
|---|---|---|
| Week 28 (n=96,103) | 7.2 ± 23.94 | 8.4 ± 26.85 |
| Week 52 (n=101,101) | 7.4 ± 27.94 | 6.7 ± 27.84 |
The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. A composite score is derived based on the average of the 11 subscales.
| Scores on a Scale | Brolucizumab 6 mg | Aflibercept 2 mg |
|---|---|---|
| Week 28 (n=96,103) | 3.3 ± 27.90 | 9.2 ± 29.86 |
| Week 52 (n=101,101) | 5.2 ± 30.77 | 5.7 ± 33.73 |
The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. A composite score is derived based on the average of the 11 subscales.
| Scores on a Scale | Brolucizumab 6 mg | Aflibercept 2 mg |
|---|---|---|
| Week 28 (n=22,22) | -3.4 ± 11.69 | 9.8 ± 23.09 |
| Week 52 (n=28,21) | 0.1 ± 10.91 | 6.0 ± 23.59 |
The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. A composite score is derived based on the average of the 11 subscales.
| Scores on a Scale | Brolucizumab 6 mg | Aflibercept 2 mg |
|---|---|---|
| Week 28 (n=94,100) | 2.4 ± 17.22 | 3.0 ± 19.87 |
| Week 52 (n=96,92) | 4.2 ± 17.27 | 3.3 ± 17.47 |
The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. A composite score is derived based on the average of the 11 subscales.
| Scores on a Scale | Brolucizumab 6 mg | Aflibercept 2 mg |
|---|---|---|
| Week 28 (n=96,103) | 3.9 ± 14.20 | 7.5 ± 20.96 |
| Week 52 (n=101,101) | 3.5 ± 19.69 | 7.7 ± 19.92 |
The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. A composite score is derived based on the average of the 11 subscales.
| Scores on a Scale | Brolucizumab 6 mg | Aflibercept 2 mg |
|---|---|---|
| Week 28 (n=96,103) | 3.1 ± 26.47 | 2.2 ± 26.91 |
| Week 52 (n=101,101) | 4.2 ± 26.24 | -0.2 ± 26.34 |
To confirm the systemic brolucizumab exposure in a subset of patients.
| ng/mL | Brolucizumab 6 mg | Aflibercept 2 mg |
|---|---|---|
| Day 2 | 21.1 ± 4.40 | — |
| Week 24 + 1 Day (n=7,0) | 13.4 ± 4.81 | — |
To assess the immunogenicity of brolucizumab
| Participants | Brolucizumab 6 mg | Aflibercept 2 mg |
|---|---|---|
| ADA negative (ADA Negative or titer value of 40 at pre-dose) (n=64,0) | 35 | — |
| ADA positive with no boost (ADA Positive at pre-dose) (n=85,0) | 73 | — |
| Induced (ADA Negative at pre-dose) (n=46,0) | 16 | — |
| Boosted (ADA Positive at pre-dose) (n=85,0) | 7 | — |
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
| Participants | Brolucizumab 6 mg | Aflibercept 2 mg |
|---|---|---|
| Number of subjects with at least one AE | 57 | 47 |
| Visual acuity reduced | 12 | 6 |
| Intraocular pressure increased | 8 | 9 |
| Meibomian gland dysfunction | 8 | 9 |
| Cataract | 8 | 3 |
| Conjunctival haemorrhage | 7 | 5 |
| Vitreous opacities | 4 | 0 |
| Dry eye | 3 | 3 |
| Epiretinal membrane | 3 | 2 |
| Eye pruritus | 3 | 1 |
| Uveitis | 3 | 0 |
| Vitreous haemorrhage | 3 | 5 |
| Xerophthalmia | 2 | 5 |
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
| Participants | Brolucizumab 6 mg | Aflibercept 2 mg |
|---|---|---|
| Number of Subjects With Non-ocular Adverse Events (AEs) (>=2% in Any Treatment Arm) | 94 | 74 |
On-treatment deaths are reported from first dose of study treatment until end of study treatment plus 4 weeks post treatment, up to a maximum timeframe of approximately 52 weeks. Post-treatment deaths are reported for the timeframe of greater than 30 days after last treatment, until study completion, up to Week 52. All deaths refer to the sum of on-treatment and post-treatment deaths.
| Participants | Brolucizumab 6 mg | Aflibercept 2 mg |
|---|---|---|
| On-Treatment Deaths | 0 | 0 |
| Post-Treatment Deaths | 0 | 1 |
| All Deaths | 0 | 1 |
Collected over Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.. Non-serious events are listed at a 2% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Brolucizumab 6mg | 0/132 (0%) | 28/132 (21.2%) | 92/132 (69.7%) |
| Aflibercept 2mg | 1/131 (0.8%) | 22/131 (16.8%) | 84/131 (64.1%) |
| Overall | 1/263 (0.4%) | 50/263 (19%) | 176/263 (66.9%) |
| Event | Brolucizumab 6mg | Aflibercept 2mg | Overall |
|---|---|---|---|
| Cataract - Fellow eyeEye disorders | 5/132 | 1/131 | 6/263 |
| Diabetic nephropathyRenal and urinary disorders | 1/132 | 3/131 | 4/263 |
| Chronic kidney diseaseRenal and urinary disorders | 3/132 | 0/131 | 3/263 |
| Cataract - Study eyeEye disorders | 2/132 | 2/131 | 4/263 |
| Cerebral infarctionNervous system disorders | 2/132 | 2/131 | 4/263 |
| Thyroid massEndocrine disorders | 2/132 | 0/131 | 2/263 |
| Diabetic neuropathyNervous system disorders | 2/132 | 0/131 | 2/263 |
| Angina unstableCardiac disorders | 0/132 | 1/131 | 1/263 |
| Atrial flutterCardiac disorders | 0/132 | 1/131 | 1/263 |
| Cataract nuclear - Study eyeEye disorders | 0/132 | 1/131 | 1/263 |
| Event | Brolucizumab 6mg | Aflibercept 2mg | Overall |
|---|---|---|---|
| HypertensionVascular disorders | 7/132 | 12/131 | 19/263 |
| Visual acuity reduced - Study eyeEye disorders | 12/132 | 6/131 | 18/263 |
| Diabetic retinal oedema - Fellow eyeEye disorders | 4/132 | 11/131 | 15/263 |
| Visual acuity reduced - Fellow eyeEye disorders | 10/132 | 8/131 | 18/263 |
| HyperlipidaemiaMetabolism and nutrition disorders | 10/132 | 9/131 | 19/263 |
| Meibomian gland dysfunction - Fellow eyeEye disorders | 8/132 | 9/131 | 17/263 |
| Meibomian gland dysfunction - Study eyeEye disorders | 8/132 | 9/131 | 17/263 |
| Upper respiratory tract infectionInfections and infestations | 9/132 | 9/131 | 18/263 |
| Intraocular pressure increased - Study eyeInvestigations | 8/132 | 9/131 | 17/263 |
| Xerophthalmia - Fellow eyeEye disorders | 2/132 | 8/131 | 10/263 |
| Age, Categorical(Participants) | Brolucizumab 6 mg | Aflibercept 2 mg | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 85 | 88 | 173 |
| >=65 years | 47 | 43 | 90 |
| Age, Continuous(Years) | Brolucizumab 6 mg | Aflibercept 2 mg | Total |
|---|---|---|---|
| Mean | 60.5 ± 9.20 | 58.7 ± 9.92 | 59.6 ± 9.59 |
| Sex: Female, Male(Participants) | Brolucizumab 6 mg | Aflibercept 2 mg | Total |
|---|---|---|---|
| Female | 62 | 60 | 122 |
| Male | 70 | 71 | 141 |
| Race (NIH/OMB)(Participants) | Brolucizumab 6 mg | Aflibercept 2 mg | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 132 | 131 | 263 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 |
| White | 0 | 0 | 0 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
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Plan to share: Yes — 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 www.clinicalstudydatarequest.com
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