Diabetic Macular Edema
Conditions
Keywords
Diabetic Macular edema (DME), Intravitreal injection, brolucizumab, aflibercept, macular edema, diabetic retinopathy
Brief 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.
Detailed description
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: * Brolucizumab 6 mg: 5 × every 6 weeks (q6w) loading then every 12 weeks (q12w) or every 8 weeks (q8w) maintenance * Aflibercept 2 mg: 5 × every 4 weeks (q4w) loading then q8w maintenance 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.
Interventions
DRUGBrolucizumab
5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance
DRUGAflibercept
5 x every 4 weeks loading then every 8 weeks maintenance
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Signed informed consent must be obtained prior to participation in the study. 2. Patients ≥18 years of age at screening 3. Patients with type 1 or type 2 diabetes mellitus (DM) and Hemoglobin A1c (HbA1c) of ≤10% at screening 4. 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 5. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline at Week 52 in Best-corrected Visual Acuity (BCVA) for the Study Eye. | Baseline to Week 52 | 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. |
| Best-corrected Visual Acuity (BCVA) - Average Change From Baseline Over the Period Week 40 Through Week 52 for the Study Eye | Week 40 to Week 52 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Best-corrected Visual Acuity (BCVA) - Average Change From Baseline Over the Period Week 20 Through Week 52 for the Study Eye | Week 20 to Week 52 | 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. |
| Best-corrected Visual Acuity (BCVA) - Average Change From Baseline Over the Period Week 28 Through Week 52 for the Study Eye | Week 28 to Week 52 | 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-to-first q8w Treatment Need: Summary for Brolucizumab Subjects by Disease Activity Assessment Visit | Baseline (Week 0), Week 32, Week 36 and Week 48 | 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-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 | Week 36 and Week 48 | 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. |
| 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 | Baseline, Week 52 | 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 to Achieve Gain of >= 5 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Baseline up to Week 52 | 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 to Achieve Gain of >= 10 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Baseline up to Week 52 | 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. |
| Number of Patients With Presence of Intraretinal Fluid (IRF) in the Study at Each Assessment Visit | 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 |
| Time to Achieve Gain of >= 15 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Baseline up to Week 52 | 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. |
| Number and Percentage of Patients Who Lost ≥5, ≥10 and ≥15 ETDRS Letters in BCVA From Baseline to Week 52 for the Study Eye | Baseline, Week 52 | 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. |
| Proportion of Patients Who Have Absolute BCVA ≥73 ETDRS Letters at Each Post-baseline Visit for the Study Eye | Baseline up to Week 52 | 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. |
| Number (%) of Subjects With q8w Treatment Need as Assessed by the Investigator at First Disease Activity Assessment (DAA) Visit - Week 32 | Week 32 | To evaluate the efficacy related to dosing regimen of brolucizumab |
| Number (%) of Subjects With q8w Treatment Need as Assessed by the Investigator at Week 36, and Week 48 | Week 36, Week 48 | To evaluate the efficacy related to dosing regimen of brolucizumab |
| Change From Baseline at Week 52 in Central Subfield Thickness (CSFT) for the Study Eye | Baseline, Week 52 | Central Subfield Thickness Assessed by Spectral domain optical coherence tomography (SD-OCT) from the central reading center. |
| Average Change From Baseline Over the Period Week 40 Through Week 52 in Central Subfield Thickness (CSFT) for the Study Eye | Baseline, over the period of Week 40 to Week 52 | Central Subfield Thickness Assessed by Spectral domain optical coherence tomography (SD-OCT) from the central reading center. |
| Average Change From Baseline Over the Period Week 4 Through Week 52 in Central Subfield Thickness (CSFT) for the Study Eye | Baseline, over the period of Week 4 to Week 52 | Central Subfield Thickness Assessed by Spectral domain optical coherence tomography (SD-OCT) from the central reading center. |
| Number and Percentage of Patients Who Have CSFT (<280 Microns) at Each Assessment Visit for the Study Eye | Baseline up to Week 52 | Central Subfield Thickness Assessed by Spectral domain optical coherence tomography (SD-OCT) from the central reading center. |
| 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 | Baseline, Week 52 | 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. |
| Number (%) of Patients With Presence of Leakage in the Study Eye on Fluorescein Angiography (FA) | Week 52 | Assessed by angiography. |
| Number (%) of Patients With Presence of Subretinal Fluid (SRF), Intraretinal Fluid (IRF) in the Study Eye | Baseline up to Week 52 | To evaluate the efficacy of brolucizumab relative to aflibercept over the time period by assessing changes in anatomical parameters |
| Number of Patients With Presence of Subretinal Fluid (SRF) in the Study at Each Assessment Visit | Week 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48, 52 | Subretinal Fluid (SRF) status in the central subfield: proportion of subjects with presence of SRF in the study eye by visit |
| Intraretinal Fluid (IRF) Status in the Central Subfield: Proportion of Subjects With Presence of IRF in the Study Eye by Visit | Week 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48, 52 | 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 |
| 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 | Baseline, Week 28 and Week 52 | 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. |
| 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 | Baseline, Week 28 and Week 52 | 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. |
| 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 | Baseline, Week 28 and Week 52 | 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. |
| 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 | Baseline, Week 28 and Week 52 | 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. |
| 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 | Baseline, Week 28 and Week 52 | 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. |
| 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 | Baseline, Week 28 and Week 52 | 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. |
| 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 | Baseline, Week 28 and Week 52 | 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. |
| 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 | Baseline, Week 28 and Week 52 | 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. |
| Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Overall Score | Baseline, Week 28 and Week 52 | 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. |
| Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - General Vision | Baseline, Week 28 and Week 52 | 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. |
| Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Ocular Pain | Baseline, Week 28 and Week 52 | 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. |
| Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Near Activities | Baseline, Week 28 and Week 52 | 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. |
| Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Distance Activities | Baseline, Week 28 and Week 52 | 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. |
| Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Social Functioning | Baseline, Week 28 and Week 52 | 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. |
| Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Mental Health | Baseline, Week 28 and Week 52 | 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. |
| Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Dependency | Baseline, Week 28 and Week 52 | 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. |
| Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Driving | Baseline, Week 28 and Week 52 | 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. |
| Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Color Vision | Baseline, Week 28 and Week 52 | 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. |
| Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Peripheral Vision | Baseline, Week 28 and Week 52 | 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. |
| Change From Baseline by Visit up to Week 52 in Best-corrected Visual Acuity (BCVA) for the Study Eye | Baseline, Week 52 | 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. |
| Brolucizumab Serum Concentration | Approximately 24 hours post Day 1 treatment and approximately 24 hours post Week 24 treatment | To confirm the systemic brolucizumab exposure in a subset of patients. |
| Number (%) of Patients Who Have Positive Anti-drug Antibody (ADA) Status in Brolucizumab Arm | Up to Week 52 | To assess the immunogenicity of brolucizumab |
| Ocular Adverse Events (AEs) (>=2% in Any Treatment Arm) by Preferred Term for the Study Eye | 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. | 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 |
| Number of Subjects With Non-ocular Adverse Events (AEs) (>=2% in Any Treatment Arm) | 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. | 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 |
| Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - General Health Rating | Baseline, Week 28 and Week 52 | 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. |
| Best-corrected Visual Acuity (BCVA) - Average Change From Baseline Over the Period Week 4 Through Week 52 for the Study Eye | Week 4 to Week 52 | 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. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Brolucizumab 6 mg 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance | 132 |
| Aflibercept 2 mg 5 x every 4 weeks loading then every 8 weeks maintenance | 131 |
| Total | 263 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | Death | 0 | 1 |
| Overall Study | Physician Decision | 3 | 1 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 7 | 8 |
Baseline characteristics
| Characteristic | Brolucizumab 6 mg | Aflibercept 2 mg | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 47 Participants | 43 Participants | 90 Participants |
| Age, Categorical Between 18 and 65 years | 85 Participants | 88 Participants | 173 Participants |
| Age, Continuous | 60.5 Years STANDARD_DEVIATION 9.2 | 58.7 Years STANDARD_DEVIATION 9.92 | 59.6 Years STANDARD_DEVIATION 9.59 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 132 Participants | 131 Participants | 263 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 62 Participants | 60 Participants | 122 Participants |
| Sex: Female, Male Male | 70 Participants | 71 Participants | 141 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 132 | 1 / 131 | 1 / 263 |
| other Total, other adverse events | 92 / 132 | 84 / 131 | 176 / 263 |
| serious Total, serious adverse events | 28 / 132 | 22 / 131 | 50 / 263 |
Outcome results
Primary
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
Population: Full Analysis Set- last observation carried forward (FAS - LOCF)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Brolucizumab 6 mg | Best-corrected Visual Acuity (BCVA) - Average Change From Baseline Over the Period Week 40 Through Week 52 for the Study Eye | 10.1 Scores on a scale | Standard Error 0.81 |
| Aflibercept 2 mg | Best-corrected Visual Acuity (BCVA) - Average Change From Baseline Over the Period Week 40 Through Week 52 for the Study Eye | 12.0 Scores on a scale | Standard Error 0.82 |
p-value: 0.03595% CI: [-4.2, 0.4]ANOVA
Primary
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
Population: Full Analysis Set- last observation carried forward (FAS - LOCF)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Brolucizumab 6 mg | Change From Baseline at Week 52 in Best-corrected Visual Acuity (BCVA) for the Study Eye. | 10.6 Scores on a scale | Standard Error 0.85 |
| Aflibercept 2 mg | Change From Baseline at Week 52 in Best-corrected Visual Acuity (BCVA) for the Study Eye. | 11.9 Scores on a scale | Standard Error 0.85 |
p-value: 0.01395% CI: [-3.7, 1.1]ANOVA
Secondary
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
Population: Full Analysis Set- last observation carried forward (FAS - LOCF)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Brolucizumab 6 mg | Average Change From Baseline Over the Period Week 40 Through Week 52 in Central Subfield Thickness (CSFT) for the Study Eye | -215.1 micrometer | Standard Error 8.69 |
| Aflibercept 2 mg | Average Change From Baseline Over the Period Week 40 Through Week 52 in Central Subfield Thickness (CSFT) for the Study Eye | -212.7 micrometer | Standard Error 8.73 |
95% CI: [-26.8, 21.9]ANOVA
Secondary
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
Population: Full Analysis Set- last observation carried forward (FAS - LOCF)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Brolucizumab 6 mg | Average Change From Baseline Over the Period Week 4 Through Week 52 in Central Subfield Thickness (CSFT) for the Study Eye | -207.7 micrometer | Standard Error 7.77 |
| Aflibercept 2 mg | Average Change From Baseline Over the Period Week 4 Through Week 52 in Central Subfield Thickness (CSFT) for the Study Eye | -199.2 micrometer | Standard Error 7.8 |
95% CI: [-30.3, 13.2]ANOVA
Secondary
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
Population: Full Analysis Set- last observation carried forward (FAS - LOCF)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Brolucizumab 6 mg | Best-corrected Visual Acuity (BCVA) - Average Change From Baseline Over the Period Week 20 Through Week 52 for the Study Eye | 9.6 Scores on a scale | Standard Error 0.77 |
| Aflibercept 2 mg | Best-corrected Visual Acuity (BCVA) - Average Change From Baseline Over the Period Week 20 Through Week 52 for the Study Eye | 11.5 Scores on a scale | Standard Error 0.77 |
95% CI: [-4, 0.2]ANOVA
Secondary
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
Population: Full Analysis Set- last observation carried forward (FAS - LOCF)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Brolucizumab 6 mg | Best-corrected Visual Acuity (BCVA) - Average Change From Baseline Over the Period Week 28 Through Week 52 for the Study Eye | 9.6 Scores on a scale | Standard Error 0.8 |
| Aflibercept 2 mg | Best-corrected Visual Acuity (BCVA) - Average Change From Baseline Over the Period Week 28 Through Week 52 for the Study Eye | 11.7 Scores on a scale | Standard Error 0.8 |
95% CI: [-4.3, 0.2]ANOVA
Secondary
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
Population: Full Analysis Set- last observation carried forward (FAS - LOCF)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Brolucizumab 6 mg | Best-corrected Visual Acuity (BCVA) - Average Change From Baseline Over the Period Week 4 Through Week 52 for the Study Eye | 9.0 Scores on a scale | Standard Error 0.68 |
| Aflibercept 2 mg | Best-corrected Visual Acuity (BCVA) - Average Change From Baseline Over the Period Week 4 Through Week 52 for the Study Eye | 10.1 Scores on a scale | Standard Error 0.68 |
95% CI: [-3, 0.8]ANOVA
Secondary
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
Population: Safety Set. Patients in the Safety set with a valid value for the outcome measure.~Analysis for Weeks 4, 12, 24, 36 and 52 were below the level of quantification (BLQ).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Brolucizumab 6 mg | Brolucizumab Serum Concentration | Day 2 | 21.1 ng/mL | Geometric Coefficient of Variation 4.4 |
| Brolucizumab 6 mg | Brolucizumab Serum Concentration | Week 24 + 1 Day (n=7,0) | 13.4 ng/mL | Geometric Coefficient of Variation 4.81 |
Secondary
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
Population: Full Analysis Set - Observed
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Brolucizumab 6 mg | Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Color Vision | Week 28 (n=94,100) | 2.4 Scores on a Scale | Standard Deviation 17.22 |
| Brolucizumab 6 mg | Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Color Vision | Week 52 (n=96,92) | 4.2 Scores on a Scale | Standard Deviation 17.27 |
| Aflibercept 2 mg | Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Color Vision | Week 28 (n=94,100) | 3.0 Scores on a Scale | Standard Deviation 19.87 |
| Aflibercept 2 mg | Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Color Vision | Week 52 (n=96,92) | 3.3 Scores on a Scale | Standard Deviation 17.47 |
Secondary
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
Population: Full Analysis Set - Observed
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Brolucizumab 6 mg | Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Dependency | Week 28 (n=96,103) | 3.3 Scores on a Scale | Standard Deviation 27.9 |
| Brolucizumab 6 mg | Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Dependency | Week 52 (n=101,101) | 5.2 Scores on a Scale | Standard Deviation 30.77 |
| Aflibercept 2 mg | Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Dependency | Week 28 (n=96,103) | 9.2 Scores on a Scale | Standard Deviation 29.86 |
| Aflibercept 2 mg | Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Dependency | Week 52 (n=101,101) | 5.7 Scores on a Scale | Standard Deviation 33.73 |
Secondary
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
Population: Full Analysis Set - Observed
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Brolucizumab 6 mg | Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Distance Activities | Week 28 (n=96,103) | 5.6 Scores on a Scale | Standard Deviation 17.54 |
| Brolucizumab 6 mg | Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Distance Activities | Week 52 (n=101,101) | 4.2 Scores on a Scale | Standard Deviation 18.42 |
| Aflibercept 2 mg | Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Distance Activities | Week 28 (n=96,103) | 7.6 Scores on a Scale | Standard Deviation 22.34 |
| Aflibercept 2 mg | Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Distance Activities | Week 52 (n=101,101) | 6.5 Scores on a Scale | Standard Deviation 22.43 |
Secondary
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
Population: Full Analysis Set - Observed
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Brolucizumab 6 mg | Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Driving | Week 28 (n=22,22) | -3.4 Scores on a Scale | Standard Deviation 11.69 |
| Brolucizumab 6 mg | Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Driving | Week 52 (n=28,21) | 0.1 Scores on a Scale | Standard Deviation 10.91 |
| Aflibercept 2 mg | Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Driving | Week 28 (n=22,22) | 9.8 Scores on a Scale | Standard Deviation 23.09 |
| Aflibercept 2 mg | Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Driving | Week 52 (n=28,21) | 6.0 Scores on a Scale | Standard Deviation 23.59 |
Secondary
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
Population: Full Analysis Set - Observed
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Brolucizumab 6 mg | Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - General Health Rating | Week 28 (n=96,103) | 3.1 Scores on a Scale | Standard Deviation 26.47 |
| Brolucizumab 6 mg | Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - General Health Rating | Week 52 (n=101,101) | 4.2 Scores on a Scale | Standard Deviation 26.24 |
| Aflibercept 2 mg | Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - General Health Rating | Week 28 (n=96,103) | 2.2 Scores on a Scale | Standard Deviation 26.91 |
| Aflibercept 2 mg | Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - General Health Rating | Week 52 (n=101,101) | -0.2 Scores on a Scale | Standard Deviation 26.34 |
Secondary
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
Population: Full Analysis Set - Observed
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Brolucizumab 6 mg | Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - General Vision | Week 28 (n=96,103) | 10.4 Scores on a Scale | Standard Deviation 18.8 |
| Brolucizumab 6 mg | Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - General Vision | Week 52 (n=101,101) | 10.9 Scores on a Scale | Standard Deviation 18.23 |
| Aflibercept 2 mg | Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - General Vision | Week 28 (n=96,103) | 9.5 Scores on a Scale | Standard Deviation 18.75 |
| Aflibercept 2 mg | Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - General Vision | Week 52 (n=101,101) | 11.5 Scores on a Scale | Standard Deviation 17.74 |
Secondary
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
Population: Full Analysis Set - Observed
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Brolucizumab 6 mg | Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Mental Health | Week 28 (n=96,103) | 7.2 Scores on a Scale | Standard Deviation 23.94 |
| Brolucizumab 6 mg | Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Mental Health | Week 52 (n=101,101) | 7.4 Scores on a Scale | Standard Deviation 27.94 |
| Aflibercept 2 mg | Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Mental Health | Week 28 (n=96,103) | 8.4 Scores on a Scale | Standard Deviation 26.85 |
| Aflibercept 2 mg | Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Mental Health | Week 52 (n=101,101) | 6.7 Scores on a Scale | Standard Deviation 27.84 |
Secondary
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
Population: Full Analysis Set - Observed
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Brolucizumab 6 mg | Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Near Activities | Week 28 (n=96,103) | 8.5 Scores on a Scale | Standard Deviation 20.79 |
| Brolucizumab 6 mg | Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Near Activities | Week 52 (n=100,101) | 7.8 Scores on a Scale | Standard Deviation 22.12 |
| Aflibercept 2 mg | Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Near Activities | Week 28 (n=96,103) | 9.7 Scores on a Scale | Standard Deviation 24.15 |
| Aflibercept 2 mg | Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Near Activities | Week 52 (n=100,101) | 8.0 Scores on a Scale | Standard Deviation 25.25 |
Secondary
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
Population: Full Analysis Set - Observed
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Brolucizumab 6 mg | Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Ocular Pain | Week 28 (n=96,103) | 5.1 Scores on a Scale | Standard Deviation 20.16 |
| Brolucizumab 6 mg | Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Ocular Pain | Week 52 (n=101,101) | 3.5 Scores on a Scale | Standard Deviation 22.51 |
| Aflibercept 2 mg | Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Ocular Pain | Week 28 (n=96,103) | 5.3 Scores on a Scale | Standard Deviation 24.23 |
| Aflibercept 2 mg | Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Ocular Pain | Week 52 (n=101,101) | 2.6 Scores on a Scale | Standard Deviation 25.27 |
Secondary
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
Population: Full Analysis Set - Observed
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Brolucizumab 6 mg | Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Overall Score | Week 28 | 5.3 Scores on a Scale | Standard Deviation 11.97 |
| Brolucizumab 6 mg | Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Overall Score | Week 52 (n=101,101) | 5.4 Scores on a Scale | Standard Deviation 13.87 |
| Aflibercept 2 mg | Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Overall Score | Week 28 | 7.7 Scores on a Scale | Standard Deviation 15.98 |
| Aflibercept 2 mg | Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Overall Score | Week 52 (n=101,101) | 6.6 Scores on a Scale | Standard Deviation 16.5 |
Comparison: Week 2895% CI: [-4.1, 2.3]ANCOVA
Comparison: Week 5295% CI: [-3.1, 3.3]ANCOVA
Secondary
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
Population: Full Analysis Set - Observed
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Brolucizumab 6 mg | Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Peripheral Vision | Week 28 (n=96,103) | 3.9 Scores on a Scale | Standard Deviation 14.2 |
| Brolucizumab 6 mg | Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Peripheral Vision | Week 52 (n=101,101) | 3.5 Scores on a Scale | Standard Deviation 19.69 |
| Aflibercept 2 mg | Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Peripheral Vision | Week 28 (n=96,103) | 7.5 Scores on a Scale | Standard Deviation 20.96 |
| Aflibercept 2 mg | Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Peripheral Vision | Week 52 (n=101,101) | 7.7 Scores on a Scale | Standard Deviation 19.92 |
Secondary
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
Population: Full Analysis Set - Observed
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Brolucizumab 6 mg | Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Social Functioning | Week 28 (n=96,103) | 3.8 Scores on a Scale | Standard Deviation 14.86 |
| Brolucizumab 6 mg | Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Social Functioning | Week 52 (n=101,101) | 3.7 Scores on a Scale | Standard Deviation 15.47 |
| Aflibercept 2 mg | Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Social Functioning | Week 28 (n=96,103) | 5.2 Scores on a Scale | Standard Deviation 18.98 |
| Aflibercept 2 mg | Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Social Functioning | Week 52 (n=101,101) | 5.8 Scores on a Scale | Standard Deviation 17.73 |
Secondary
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
Population: Full Analysis Set- last observation carried forward (FAS - LOCF)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Brolucizumab 6 mg | Change From Baseline at Week 52 in Central Subfield Thickness (CSFT) for the Study Eye | -225.2 micrometer | Standard Error 9.71 |
| Aflibercept 2 mg | Change From Baseline at Week 52 in Central Subfield Thickness (CSFT) for the Study Eye | -215.0 micrometer | Standard Error 9.75 |
95% CI: [-37.3, 17]ANOVA
Secondary
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
Population: Full Analysis Set- observed. All randomized subjects who received at least one intravitreal treatment (IVT) injection of the study treatment and had a valid value of the outcome measure at each timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Brolucizumab 6 mg | Change From Baseline by Visit up to Week 52 in Best-corrected Visual Acuity (BCVA) for the Study Eye | Week 4 (n=129,123) | 5.1 Scores on a scale | Standard Deviation 6.58 |
| Brolucizumab 6 mg | Change From Baseline by Visit up to Week 52 in Best-corrected Visual Acuity (BCVA) for the Study Eye | Week 6 (n=125,122) | 7.2 Scores on a scale | Standard Deviation 7.49 |
| Brolucizumab 6 mg | Change From Baseline by Visit up to Week 52 in Best-corrected Visual Acuity (BCVA) for the Study Eye | Week 8 (n=128,125) | 8.6 Scores on a scale | Standard Deviation 8.43 |
| Brolucizumab 6 mg | Change From Baseline by Visit up to Week 52 in Best-corrected Visual Acuity (BCVA) for the Study Eye | Week 12 (n=119,122) | 9.2 Scores on a scale | Standard Deviation 8.77 |
| Brolucizumab 6 mg | Change From Baseline by Visit up to Week 52 in Best-corrected Visual Acuity (BCVA) for the Study Eye | Week 16 (n=115,118) | 10.0 Scores on a scale | Standard Deviation 9.83 |
| Brolucizumab 6 mg | Change From Baseline by Visit up to Week 52 in Best-corrected Visual Acuity (BCVA) for the Study Eye | Week 18 (n=113,115) | 9.8 Scores on a scale | Standard Deviation 9.19 |
| Brolucizumab 6 mg | Change From Baseline by Visit up to Week 52 in Best-corrected Visual Acuity (BCVA) for the Study Eye | Week 24 (n=109,116) | 9.9 Scores on a scale | Standard Deviation 10.48 |
| Brolucizumab 6 mg | Change From Baseline by Visit up to Week 52 in Best-corrected Visual Acuity (BCVA) for the Study Eye | Week 28 (n=111,111) | 10.5 Scores on a scale | Standard Deviation 9.62 |
| Brolucizumab 6 mg | Change From Baseline by Visit up to Week 52 in Best-corrected Visual Acuity (BCVA) for the Study Eye | Week 32 (n=107,116) | 10.1 Scores on a scale | Standard Deviation 10.29 |
| Brolucizumab 6 mg | Change From Baseline by Visit up to Week 52 in Best-corrected Visual Acuity (BCVA) for the Study Eye | Week 36 (n=105,114) | 9.1 Scores on a scale | Standard Deviation 10.86 |
| Brolucizumab 6 mg | Change From Baseline by Visit up to Week 52 in Best-corrected Visual Acuity (BCVA) for the Study Eye | Week 40 (n=101,110) | 10.1 Scores on a scale | Standard Deviation 10.24 |
| Brolucizumab 6 mg | Change From Baseline by Visit up to Week 52 in Best-corrected Visual Acuity (BCVA) for the Study Eye | Week 44 (n=102,110) | 11.2 Scores on a scale | Standard Deviation 9.86 |
| Brolucizumab 6 mg | Change From Baseline by Visit up to Week 52 in Best-corrected Visual Acuity (BCVA) for the Study Eye | Week 48 (n=103,105) | 10.9 Scores on a scale | Standard Deviation 9.91 |
| Brolucizumab 6 mg | Change From Baseline by Visit up to Week 52 in Best-corrected Visual Acuity (BCVA) for the Study Eye | Week 52 (n=105,105) | 11.3 Scores on a scale | Standard Deviation 9.21 |
| Brolucizumab 6 mg | Change From Baseline by Visit up to Week 52 in Best-corrected Visual Acuity (BCVA) for the Study Eye | Week 20 (n=109,114) | 10.0 Scores on a scale | Standard Deviation 9.36 |
| Aflibercept 2 mg | Change From Baseline by Visit up to Week 52 in Best-corrected Visual Acuity (BCVA) for the Study Eye | Week 28 (n=111,111) | 10.9 Scores on a scale | Standard Deviation 10.13 |
| Aflibercept 2 mg | Change From Baseline by Visit up to Week 52 in Best-corrected Visual Acuity (BCVA) for the Study Eye | Week 4 (n=129,123) | 4.4 Scores on a scale | Standard Deviation 6.75 |
| Aflibercept 2 mg | Change From Baseline by Visit up to Week 52 in Best-corrected Visual Acuity (BCVA) for the Study Eye | Week 44 (n=102,110) | 12.2 Scores on a scale | Standard Deviation 9.79 |
| Aflibercept 2 mg | Change From Baseline by Visit up to Week 52 in Best-corrected Visual Acuity (BCVA) for the Study Eye | Week 6 (n=125,122) | 6.6 Scores on a scale | Standard Deviation 7.5 |
| Aflibercept 2 mg | Change From Baseline by Visit up to Week 52 in Best-corrected Visual Acuity (BCVA) for the Study Eye | Week 32 (n=107,116) | 11.3 Scores on a scale | Standard Deviation 10.12 |
| Aflibercept 2 mg | Change From Baseline by Visit up to Week 52 in Best-corrected Visual Acuity (BCVA) for the Study Eye | Week 8 (n=128,125) | 8.0 Scores on a scale | Standard Deviation 8.56 |
| Aflibercept 2 mg | Change From Baseline by Visit up to Week 52 in Best-corrected Visual Acuity (BCVA) for the Study Eye | Week 52 (n=105,105) | 12.1 Scores on a scale | Standard Deviation 10.92 |
| Aflibercept 2 mg | Change From Baseline by Visit up to Week 52 in Best-corrected Visual Acuity (BCVA) for the Study Eye | Week 36 (n=105,114) | 11.8 Scores on a scale | Standard Deviation 10.62 |
| Aflibercept 2 mg | Change From Baseline by Visit up to Week 52 in Best-corrected Visual Acuity (BCVA) for the Study Eye | Week 16 (n=115,118) | 10.4 Scores on a scale | Standard Deviation 9.86 |
| Aflibercept 2 mg | Change From Baseline by Visit up to Week 52 in Best-corrected Visual Acuity (BCVA) for the Study Eye | Week 48 (n=103,105) | 12.2 Scores on a scale | Standard Deviation 10.71 |
| Aflibercept 2 mg | Change From Baseline by Visit up to Week 52 in Best-corrected Visual Acuity (BCVA) for the Study Eye | Week 18 (n=113,115) | 10.7 Scores on a scale | Standard Deviation 10.25 |
| Aflibercept 2 mg | Change From Baseline by Visit up to Week 52 in Best-corrected Visual Acuity (BCVA) for the Study Eye | Week 20 (n=109,114) | 11.3 Scores on a scale | Standard Deviation 9.57 |
| Aflibercept 2 mg | Change From Baseline by Visit up to Week 52 in Best-corrected Visual Acuity (BCVA) for the Study Eye | Week 40 (n=101,110) | 11.7 Scores on a scale | Standard Deviation 10.02 |
| Aflibercept 2 mg | Change From Baseline by Visit up to Week 52 in Best-corrected Visual Acuity (BCVA) for the Study Eye | Week 24 (n=109,116) | 10.5 Scores on a scale | Standard Deviation 9.8 |
| Aflibercept 2 mg | Change From Baseline by Visit up to Week 52 in Best-corrected Visual Acuity (BCVA) for the Study Eye | Week 12 (n=119,122) | 9.0 Scores on a scale | Standard Deviation 9.67 |
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
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
Population: FAS - LOCF. For subjects with an assessment of the criterion.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brolucizumab 6 mg | 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 | Week 28 | 45 Participants |
| Brolucizumab 6 mg | 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 | Week 52 | 62 Participants |
| Aflibercept 2 mg | 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 | Week 28 | 47 Participants |
| Aflibercept 2 mg | 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 | Week 52 | 64 Participants |
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
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
Population: FAS - LOCF. For subjects with an assessment of the criterion.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brolucizumab 6 mg | 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 | Week 28 | 1 Participants |
| Brolucizumab 6 mg | 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 | Week 52 | 0 Participants |
| Aflibercept 2 mg | 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 | Week 28 | 0 Participants |
| Aflibercept 2 mg | 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 | Week 52 | 0 Participants |
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
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
Population: FAS - LOCF. For subjects with an assessment of the criterion.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brolucizumab 6 mg | 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 | Week 28 | 21 Participants |
| Brolucizumab 6 mg | 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 | Week 52 | 25 Participants |
| Aflibercept 2 mg | 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 | Week 28 | 15 Participants |
| Aflibercept 2 mg | 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 | Week 52 | 25 Participants |
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
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
Population: FAS - LOCF. For subjects with an assessment of the criterion.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brolucizumab 6 mg | 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 | Week 28 | 1 Participants |
| Brolucizumab 6 mg | 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 | Week 52 | 0 Participants |
| Aflibercept 2 mg | 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 | Week 28 | 0 Participants |
| Aflibercept 2 mg | 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 | Week 52 | 0 Participants |
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
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
Population: FAS - LOCF. For subjects with an assessment of the criterion.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Brolucizumab 6 mg | 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 | Week 28 | 33.9 Percentage estimates |
| Brolucizumab 6 mg | 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 | Week 52 | 46.7 Percentage estimates |
| Aflibercept 2 mg | 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 | Week 28 | 36.3 Percentage estimates |
| Aflibercept 2 mg | 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 | Week 52 | 49.5 Percentage estimates |
Comparison: Week 2895% CI: [-13.9, 8.8]Clopper-Pearson exact method
Comparison: Week 5295% CI: [-14.1, 9]Clopper-Pearson exact method
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
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
Population: FAS - LOCF. For subjects with an assessment of the criterion.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Brolucizumab 6 mg | 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 | Week 28 | 0.8 Percentage estimates |
| Aflibercept 2 mg | 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 | Week 28 | 0.0 Percentage estimates |
Comparison: Week 2895% CI: [0.7, 2.9]Clopper-Pearson exact method
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
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
Population: FAS - LOCF. For subjects with an assessment of the criterion.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Brolucizumab 6 mg | 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 | Week 28 | 15.8 Percentage estimates |
| Brolucizumab 6 mg | 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 | Week 52 | 18.8 Percentage estimates |
| Aflibercept 2 mg | 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 | Week 28 | 11.6 Percentage estimates |
| Aflibercept 2 mg | 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 | Week 52 | 19.3 Percentage estimates |
Comparison: Week 2895% CI: [-4.1, 12.6]Clopper-Pearson exact method
Comparison: Week 5295% CI: [-10.5, 9.3]Clopper-Pearson exact method
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
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
Population: FAS - LOCF. For subjects with an assessment of the criterion.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Brolucizumab 6 mg | 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 | Week 28 | 0.8 Percentage estimates |
| Aflibercept 2 mg | 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 | Week 28 | 0.0 Percentage estimates |
Comparison: Week 2895% CI: [0.7, 2.9]Clopper-Pearson exact method
Secondary
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
Population: Full Analysis Set - LOCF
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brolucizumab 6 mg | Intraretinal Fluid (IRF) Status in the Central Subfield: Proportion of Subjects With Presence of IRF in the Study Eye by Visit | Week 16 | 99 Participants |
| Brolucizumab 6 mg | Intraretinal Fluid (IRF) Status in the Central Subfield: Proportion of Subjects With Presence of IRF in the Study Eye by Visit | Week 28 | 87 Participants |
| Brolucizumab 6 mg | Intraretinal Fluid (IRF) Status in the Central Subfield: Proportion of Subjects With Presence of IRF in the Study Eye by Visit | Week 6 | 113 Participants |
| Brolucizumab 6 mg | Intraretinal Fluid (IRF) Status in the Central Subfield: Proportion of Subjects With Presence of IRF in the Study Eye by Visit | Week 32 | 88 Participants |
| Brolucizumab 6 mg | Intraretinal Fluid (IRF) Status in the Central Subfield: Proportion of Subjects With Presence of IRF in the Study Eye by Visit | Week 18 | 98 Participants |
| Brolucizumab 6 mg | Intraretinal Fluid (IRF) Status in the Central Subfield: Proportion of Subjects With Presence of IRF in the Study Eye by Visit | Week 36 | 98 Participants |
| Brolucizumab 6 mg | Intraretinal Fluid (IRF) Status in the Central Subfield: Proportion of Subjects With Presence of IRF in the Study Eye by Visit | Week 12 | 100 Participants |
| Brolucizumab 6 mg | Intraretinal Fluid (IRF) Status in the Central Subfield: Proportion of Subjects With Presence of IRF in the Study Eye by Visit | Week 40 | 89 Participants |
| Brolucizumab 6 mg | Intraretinal Fluid (IRF) Status in the Central Subfield: Proportion of Subjects With Presence of IRF in the Study Eye by Visit | Week 20 | 94 Participants |
| Brolucizumab 6 mg | Intraretinal Fluid (IRF) Status in the Central Subfield: Proportion of Subjects With Presence of IRF in the Study Eye by Visit | Week 44 | 84 Participants |
| Brolucizumab 6 mg | Intraretinal Fluid (IRF) Status in the Central Subfield: Proportion of Subjects With Presence of IRF in the Study Eye by Visit | Week 8 | 111 Participants |
| Brolucizumab 6 mg | Intraretinal Fluid (IRF) Status in the Central Subfield: Proportion of Subjects With Presence of IRF in the Study Eye by Visit | Week 48 | 89 Participants |
| Brolucizumab 6 mg | Intraretinal Fluid (IRF) Status in the Central Subfield: Proportion of Subjects With Presence of IRF in the Study Eye by Visit | Week 24 | 90 Participants |
| Brolucizumab 6 mg | Intraretinal Fluid (IRF) Status in the Central Subfield: Proportion of Subjects With Presence of IRF in the Study Eye by Visit | Week 52 | 87 Participants |
| Brolucizumab 6 mg | Intraretinal Fluid (IRF) Status in the Central Subfield: Proportion of Subjects With Presence of IRF in the Study Eye by Visit | Week 4 | 117 Participants |
| Aflibercept 2 mg | Intraretinal Fluid (IRF) Status in the Central Subfield: Proportion of Subjects With Presence of IRF in the Study Eye by Visit | Week 52 | 85 Participants |
| Aflibercept 2 mg | Intraretinal Fluid (IRF) Status in the Central Subfield: Proportion of Subjects With Presence of IRF in the Study Eye by Visit | Week 4 | 118 Participants |
| Aflibercept 2 mg | Intraretinal Fluid (IRF) Status in the Central Subfield: Proportion of Subjects With Presence of IRF in the Study Eye by Visit | Week 6 | 114 Participants |
| Aflibercept 2 mg | Intraretinal Fluid (IRF) Status in the Central Subfield: Proportion of Subjects With Presence of IRF in the Study Eye by Visit | Week 8 | 114 Participants |
| Aflibercept 2 mg | Intraretinal Fluid (IRF) Status in the Central Subfield: Proportion of Subjects With Presence of IRF in the Study Eye by Visit | Week 12 | 110 Participants |
| Aflibercept 2 mg | Intraretinal Fluid (IRF) Status in the Central Subfield: Proportion of Subjects With Presence of IRF in the Study Eye by Visit | Week 16 | 110 Participants |
| Aflibercept 2 mg | Intraretinal Fluid (IRF) Status in the Central Subfield: Proportion of Subjects With Presence of IRF in the Study Eye by Visit | Week 18 | 110 Participants |
| Aflibercept 2 mg | Intraretinal Fluid (IRF) Status in the Central Subfield: Proportion of Subjects With Presence of IRF in the Study Eye by Visit | Week 20 | 102 Participants |
| Aflibercept 2 mg | Intraretinal Fluid (IRF) Status in the Central Subfield: Proportion of Subjects With Presence of IRF in the Study Eye by Visit | Week 24 | 102 Participants |
| Aflibercept 2 mg | Intraretinal Fluid (IRF) Status in the Central Subfield: Proportion of Subjects With Presence of IRF in the Study Eye by Visit | Week 28 | 100 Participants |
| Aflibercept 2 mg | Intraretinal Fluid (IRF) Status in the Central Subfield: Proportion of Subjects With Presence of IRF in the Study Eye by Visit | Week 32 | 99 Participants |
| Aflibercept 2 mg | Intraretinal Fluid (IRF) Status in the Central Subfield: Proportion of Subjects With Presence of IRF in the Study Eye by Visit | Week 36 | 98 Participants |
| Aflibercept 2 mg | Intraretinal Fluid (IRF) Status in the Central Subfield: Proportion of Subjects With Presence of IRF in the Study Eye by Visit | Week 40 | 101 Participants |
| Aflibercept 2 mg | Intraretinal Fluid (IRF) Status in the Central Subfield: Proportion of Subjects With Presence of IRF in the Study Eye by Visit | Week 44 | 94 Participants |
| Aflibercept 2 mg | Intraretinal Fluid (IRF) Status in the Central Subfield: Proportion of Subjects With Presence of IRF in the Study Eye by Visit | Week 48 | 94 Participants |
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
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
Population: Full Analysis Set- last observation carried forward (FAS - LOCF)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brolucizumab 6 mg | 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 | N (%) of subjects with ≥5 letters gain from baseline or reached BCVA of ≥84 letters at Week 52 | 102 Participants |
| Brolucizumab 6 mg | 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 | N (%) of subjects with ≥10 letters gain from baseline or reached BCVA of ≥84 letters at Week 52 | 74 Participants |
| Brolucizumab 6 mg | 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 | N (%) of subjects with ≥15 letters gain from baseline or reached BCVA of ≥84 letters at Week 52 | 44 Participants |
| Aflibercept 2 mg | 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 | N (%) of subjects with ≥5 letters gain from baseline or reached BCVA of ≥84 letters at Week 52 | 104 Participants |
| Aflibercept 2 mg | 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 | N (%) of subjects with ≥10 letters gain from baseline or reached BCVA of ≥84 letters at Week 52 | 76 Participants |
| Aflibercept 2 mg | 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 | N (%) of subjects with ≥15 letters gain from baseline or reached BCVA of ≥84 letters at Week 52 | 48 Participants |
Comparison: Proportion of subjects with ≥5 letters gain from baseline or reached BCVA of ≥84 letters at Week 5295% CI: [-13.7, 6.7]Regression, Logistic
Comparison: Proportion of subjects with ≥10 letters gain from baseline or reached BCVA of ≥84 letters at Week 5295% CI: [-14.7, 9.4]Regression, Logistic
Comparison: Proportion of subjects with ≥15 letters gain from baseline or reached BCVA of ≥84 letters at Week 5295% CI: [-15.5, 6.9]Regression, Logistic
Secondary
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
Population: Full Analysis Set - LOCF
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brolucizumab 6 mg | Number and Percentage of Patients Who Have CSFT (<280 Microns) at Each Assessment Visit for the Study Eye | Week 32 | 63 Participants |
| Brolucizumab 6 mg | Number and Percentage of Patients Who Have CSFT (<280 Microns) at Each Assessment Visit for the Study Eye | Week 6 | 36 Participants |
| Brolucizumab 6 mg | Number and Percentage of Patients Who Have CSFT (<280 Microns) at Each Assessment Visit for the Study Eye | Week 40 | 67 Participants |
| Brolucizumab 6 mg | Number and Percentage of Patients Who Have CSFT (<280 Microns) at Each Assessment Visit for the Study Eye | Week 44 | 74 Participants |
| Brolucizumab 6 mg | Number and Percentage of Patients Who Have CSFT (<280 Microns) at Each Assessment Visit for the Study Eye | Week 18 | 61 Participants |
| Brolucizumab 6 mg | Number and Percentage of Patients Who Have CSFT (<280 Microns) at Each Assessment Visit for the Study Eye | Week 48 | 68 Participants |
| Brolucizumab 6 mg | Number and Percentage of Patients Who Have CSFT (<280 Microns) at Each Assessment Visit for the Study Eye | Week 12 | 52 Participants |
| Brolucizumab 6 mg | Number and Percentage of Patients Who Have CSFT (<280 Microns) at Each Assessment Visit for the Study Eye | Week 52 | 79 Participants |
| Brolucizumab 6 mg | Number and Percentage of Patients Who Have CSFT (<280 Microns) at Each Assessment Visit for the Study Eye | Week 20 | 67 Participants |
| Brolucizumab 6 mg | Number and Percentage of Patients Who Have CSFT (<280 Microns) at Each Assessment Visit for the Study Eye | Week 4 | 24 Participants |
| Brolucizumab 6 mg | Number and Percentage of Patients Who Have CSFT (<280 Microns) at Each Assessment Visit for the Study Eye | Week 28 | 71 Participants |
| Brolucizumab 6 mg | Number and Percentage of Patients Who Have CSFT (<280 Microns) at Each Assessment Visit for the Study Eye | Week 8 | 48 Participants |
| Brolucizumab 6 mg | Number and Percentage of Patients Who Have CSFT (<280 Microns) at Each Assessment Visit for the Study Eye | Week 24 | 65 Participants |
| Brolucizumab 6 mg | Number and Percentage of Patients Who Have CSFT (<280 Microns) at Each Assessment Visit for the Study Eye | Week 36 | 59 Participants |
| Brolucizumab 6 mg | Number and Percentage of Patients Who Have CSFT (<280 Microns) at Each Assessment Visit for the Study Eye | Week 16 | 63 Participants |
| Aflibercept 2 mg | Number and Percentage of Patients Who Have CSFT (<280 Microns) at Each Assessment Visit for the Study Eye | Week 40 | 47 Participants |
| Aflibercept 2 mg | Number and Percentage of Patients Who Have CSFT (<280 Microns) at Each Assessment Visit for the Study Eye | Week 6 | 22 Participants |
| Aflibercept 2 mg | Number and Percentage of Patients Who Have CSFT (<280 Microns) at Each Assessment Visit for the Study Eye | Week 8 | 29 Participants |
| Aflibercept 2 mg | Number and Percentage of Patients Who Have CSFT (<280 Microns) at Each Assessment Visit for the Study Eye | Week 12 | 33 Participants |
| Aflibercept 2 mg | Number and Percentage of Patients Who Have CSFT (<280 Microns) at Each Assessment Visit for the Study Eye | Week 16 | 41 Participants |
| Aflibercept 2 mg | Number and Percentage of Patients Who Have CSFT (<280 Microns) at Each Assessment Visit for the Study Eye | Week 18 | 41 Participants |
| Aflibercept 2 mg | Number and Percentage of Patients Who Have CSFT (<280 Microns) at Each Assessment Visit for the Study Eye | Week 20 | 46 Participants |
| Aflibercept 2 mg | Number and Percentage of Patients Who Have CSFT (<280 Microns) at Each Assessment Visit for the Study Eye | Week 24 | 40 Participants |
| Aflibercept 2 mg | Number and Percentage of Patients Who Have CSFT (<280 Microns) at Each Assessment Visit for the Study Eye | Week 36 | 51 Participants |
| Aflibercept 2 mg | Number and Percentage of Patients Who Have CSFT (<280 Microns) at Each Assessment Visit for the Study Eye | Week 44 | 56 Participants |
| Aflibercept 2 mg | Number and Percentage of Patients Who Have CSFT (<280 Microns) at Each Assessment Visit for the Study Eye | Week 48 | 52 Participants |
| Aflibercept 2 mg | Number and Percentage of Patients Who Have CSFT (<280 Microns) at Each Assessment Visit for the Study Eye | Week 52 | 56 Participants |
| Aflibercept 2 mg | Number and Percentage of Patients Who Have CSFT (<280 Microns) at Each Assessment Visit for the Study Eye | Week 28 | 49 Participants |
| Aflibercept 2 mg | Number and Percentage of Patients Who Have CSFT (<280 Microns) at Each Assessment Visit for the Study Eye | Week 32 | 47 Participants |
| Aflibercept 2 mg | Number and Percentage of Patients Who Have CSFT (<280 Microns) at Each Assessment Visit for the Study Eye | Week 4 | 17 Participants |
Comparison: Week 495% CI: [-3.3, 13.5]Clopper-Pearson exact method
Comparison: Week 695% CI: [1.4, 20.6]Clopper-Pearson exact method
Comparison: Week 895% CI: [3.9, 25.3]Clopper-Pearson exact method
Comparison: Week 1295% CI: [2.8, 24.9]Clopper-Pearson exact method
Comparison: Week 1695% CI: [5.1, 28.6]Clopper-Pearson exact method
Comparison: Week 1895% CI: [3.1, 26.6]Clopper-Pearson exact method
Comparison: Week 2095% CI: [3.5, 27.1]Clopper-Pearson exact method
Comparison: Week 2495% CI: [7.2, 30.2]Clopper-Pearson exact method
Comparison: Week 2895% CI: [4.9, 27.9]Clopper-Pearson exact method
Comparison: Week 3295% CI: [0.4, 24.4]Clopper-Pearson exact method
Comparison: Week 3695% CI: [-5.9, 18]Clopper-Pearson exact method
Comparison: Week 4095% CI: [3.3, 26.1]Clopper-Pearson exact method
Comparison: Week 4495% CI: [1.9, 25.7]Clopper-Pearson exact method
Comparison: Week 4895% CI: [-0.8, 23.6]Clopper-Pearson exact method
Comparison: Week 5295% CI: [5.8, 30.5]Clopper-Pearson exact method
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
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
Population: Full Analysis Set- last observation carried forward (FAS - LOCF)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brolucizumab 6 mg | Number and Percentage of Patients Who Lost ≥5, ≥10 and ≥15 ETDRS Letters in BCVA From Baseline to Week 52 for the Study Eye | N (%) of subjects with ≥5 letters loss from baseline or reached BCVA of ≥84 letters at Week 52 | 4 Participants |
| Brolucizumab 6 mg | Number and Percentage of Patients Who Lost ≥5, ≥10 and ≥15 ETDRS Letters in BCVA From Baseline to Week 52 for the Study Eye | N (%) of subjects with ≥10 letters loss from baseline or reached BCVA of ≥84 letters at Week 52 | 2 Participants |
| Brolucizumab 6 mg | Number and Percentage of Patients Who Lost ≥5, ≥10 and ≥15 ETDRS Letters in BCVA From Baseline to Week 52 for the Study Eye | N (%) of subjects with ≥15 letters loss from baseline or reached BCVA of ≥84 letters at Week 52 | 1 Participants |
| Aflibercept 2 mg | Number and Percentage of Patients Who Lost ≥5, ≥10 and ≥15 ETDRS Letters in BCVA From Baseline to Week 52 for the Study Eye | N (%) of subjects with ≥5 letters loss from baseline or reached BCVA of ≥84 letters at Week 52 | 4 Participants |
| Aflibercept 2 mg | Number and Percentage of Patients Who Lost ≥5, ≥10 and ≥15 ETDRS Letters in BCVA From Baseline to Week 52 for the Study Eye | N (%) of subjects with ≥10 letters loss from baseline or reached BCVA of ≥84 letters at Week 52 | 1 Participants |
| Aflibercept 2 mg | Number and Percentage of Patients Who Lost ≥5, ≥10 and ≥15 ETDRS Letters in BCVA From Baseline to Week 52 for the Study Eye | N (%) of subjects with ≥15 letters loss from baseline or reached BCVA of ≥84 letters at Week 52 | 1 Participants |
Comparison: Proportion of subjects with ≥5 letters loss from baseline at Week 5295% CI: [-4.2, 4.4]Regression, Logistic
Comparison: Proportion of subjects with ≥10 letters loss from baseline at Week 5295% CI: [-1.6, 3.8]Regression, Logistic
Comparison: Proportion of subjects with ≥15 letters loss from baseline at Week 5295% CI: [-2.2, 2.3]Regression, Logistic
Secondary
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
Population: Safety Set. Patients in the Safety set with a valid value for the outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brolucizumab 6 mg | Number (%) of Patients Who Have Positive Anti-drug Antibody (ADA) Status in Brolucizumab Arm | ADA negative (ADA Negative or titer value of 40 at pre-dose) (n=64,0) | 35 Participants |
| Brolucizumab 6 mg | Number (%) of Patients Who Have Positive Anti-drug Antibody (ADA) Status in Brolucizumab Arm | ADA positive with no boost (ADA Positive at pre-dose) (n=85,0) | 73 Participants |
| Brolucizumab 6 mg | Number (%) of Patients Who Have Positive Anti-drug Antibody (ADA) Status in Brolucizumab Arm | Boosted (ADA Positive at pre-dose) (n=85,0) | 7 Participants |
| Brolucizumab 6 mg | Number (%) of Patients Who Have Positive Anti-drug Antibody (ADA) Status in Brolucizumab Arm | Induced (ADA Negative at pre-dose) (n=46,0) | 16 Participants |
Secondary
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
Population: Full Analysis Set - LOCF
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brolucizumab 6 mg | Number of Patients With Presence of Intraretinal Fluid (IRF) in the Study at Each Assessment Visit | Week 16 | 99 Participants |
| Brolucizumab 6 mg | Number of Patients With Presence of Intraretinal Fluid (IRF) in the Study at Each Assessment Visit | Week 28 | 87 Participants |
| Brolucizumab 6 mg | Number of Patients With Presence of Intraretinal Fluid (IRF) in the Study at Each Assessment Visit | Week 6 | 112 Participants |
| Brolucizumab 6 mg | Number of Patients With Presence of Intraretinal Fluid (IRF) in the Study at Each Assessment Visit | Week 32 | 88 Participants |
| Brolucizumab 6 mg | Number of Patients With Presence of Intraretinal Fluid (IRF) in the Study at Each Assessment Visit | Week 18 | 98 Participants |
| Brolucizumab 6 mg | Number of Patients With Presence of Intraretinal Fluid (IRF) in the Study at Each Assessment Visit | Week 36 | 98 Participants |
| Brolucizumab 6 mg | Number of Patients With Presence of Intraretinal Fluid (IRF) in the Study at Each Assessment Visit | Week 12 | 100 Participants |
| Brolucizumab 6 mg | Number of Patients With Presence of Intraretinal Fluid (IRF) in the Study at Each Assessment Visit | Week 40 | 89 Participants |
| Brolucizumab 6 mg | Number of Patients With Presence of Intraretinal Fluid (IRF) in the Study at Each Assessment Visit | Week 20 | 94 Participants |
| Brolucizumab 6 mg | Number of Patients With Presence of Intraretinal Fluid (IRF) in the Study at Each Assessment Visit | Week 44 | 84 Participants |
| Brolucizumab 6 mg | Number of Patients With Presence of Intraretinal Fluid (IRF) in the Study at Each Assessment Visit | Week 8 | 109 Participants |
| Brolucizumab 6 mg | Number of Patients With Presence of Intraretinal Fluid (IRF) in the Study at Each Assessment Visit | Week 48 | 89 Participants |
| Brolucizumab 6 mg | Number of Patients With Presence of Intraretinal Fluid (IRF) in the Study at Each Assessment Visit | Week 24 | 90 Participants |
| Brolucizumab 6 mg | Number of Patients With Presence of Intraretinal Fluid (IRF) in the Study at Each Assessment Visit | Week 52 | 87 Participants |
| Brolucizumab 6 mg | Number of Patients With Presence of Intraretinal Fluid (IRF) in the Study at Each Assessment Visit | Week 4 | 113 Participants |
| Aflibercept 2 mg | Number of Patients With Presence of Intraretinal Fluid (IRF) in the Study at Each Assessment Visit | Week 52 | 85 Participants |
| Aflibercept 2 mg | Number of Patients With Presence of Intraretinal Fluid (IRF) in the Study at Each Assessment Visit | Week 4 | 115 Participants |
| Aflibercept 2 mg | Number of Patients With Presence of Intraretinal Fluid (IRF) in the Study at Each Assessment Visit | Week 6 | 110 Participants |
| Aflibercept 2 mg | Number of Patients With Presence of Intraretinal Fluid (IRF) in the Study at Each Assessment Visit | Week 8 | 112 Participants |
| Aflibercept 2 mg | Number of Patients With Presence of Intraretinal Fluid (IRF) in the Study at Each Assessment Visit | Week 12 | 110 Participants |
| Aflibercept 2 mg | Number of Patients With Presence of Intraretinal Fluid (IRF) in the Study at Each Assessment Visit | Week 16 | 109 Participants |
| Aflibercept 2 mg | Number of Patients With Presence of Intraretinal Fluid (IRF) in the Study at Each Assessment Visit | Week 18 | 110 Participants |
| Aflibercept 2 mg | Number of Patients With Presence of Intraretinal Fluid (IRF) in the Study at Each Assessment Visit | Week 20 | 102 Participants |
| Aflibercept 2 mg | Number of Patients With Presence of Intraretinal Fluid (IRF) in the Study at Each Assessment Visit | Week 24 | 102 Participants |
| Aflibercept 2 mg | Number of Patients With Presence of Intraretinal Fluid (IRF) in the Study at Each Assessment Visit | Week 28 | 100 Participants |
| Aflibercept 2 mg | Number of Patients With Presence of Intraretinal Fluid (IRF) in the Study at Each Assessment Visit | Week 32 | 99 Participants |
| Aflibercept 2 mg | Number of Patients With Presence of Intraretinal Fluid (IRF) in the Study at Each Assessment Visit | Week 36 | 98 Participants |
| Aflibercept 2 mg | Number of Patients With Presence of Intraretinal Fluid (IRF) in the Study at Each Assessment Visit | Week 40 | 101 Participants |
| Aflibercept 2 mg | Number of Patients With Presence of Intraretinal Fluid (IRF) in the Study at Each Assessment Visit | Week 44 | 94 Participants |
| Aflibercept 2 mg | Number of Patients With Presence of Intraretinal Fluid (IRF) in the Study at Each Assessment Visit | Week 48 | 94 Participants |
Secondary
Number (%) of Patients With Presence of Leakage in the Study Eye on Fluorescein Angiography (FA)
Assessed by angiography.
Time frame: Week 52
Population: Full Analysis Set - LOCF
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Brolucizumab 6 mg | Number (%) of Patients With Presence of Leakage in the Study Eye on Fluorescein Angiography (FA) | 110 Participants |
| Aflibercept 2 mg | Number (%) of Patients With Presence of Leakage in the Study Eye on Fluorescein Angiography (FA) | 115 Participants |
95% CI: [-13.2, 4.6]Clopper-Pearson exact method
Secondary
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
Population: Full Analysis Set - LOCF
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brolucizumab 6 mg | Number of Patients With Presence of Subretinal Fluid (SRF) in the Study at Each Assessment Visit | Week 4 | 33 Participants |
| Brolucizumab 6 mg | Number of Patients With Presence of Subretinal Fluid (SRF) in the Study at Each Assessment Visit | Week 6 | 17 Participants |
| Brolucizumab 6 mg | Number of Patients With Presence of Subretinal Fluid (SRF) in the Study at Each Assessment Visit | Week 8 | 13 Participants |
| Brolucizumab 6 mg | Number of Patients With Presence of Subretinal Fluid (SRF) in the Study at Each Assessment Visit | Week 12 | 7 Participants |
| Brolucizumab 6 mg | Number of Patients With Presence of Subretinal Fluid (SRF) in the Study at Each Assessment Visit | Week 18 | 6 Participants |
| Brolucizumab 6 mg | Number of Patients With Presence of Subretinal Fluid (SRF) in the Study at Each Assessment Visit | Week 20 | 6 Participants |
| Brolucizumab 6 mg | Number of Patients With Presence of Subretinal Fluid (SRF) in the Study at Each Assessment Visit | Week 24 | 5 Participants |
| Brolucizumab 6 mg | Number of Patients With Presence of Subretinal Fluid (SRF) in the Study at Each Assessment Visit | Week 32 | 8 Participants |
| Brolucizumab 6 mg | Number of Patients With Presence of Subretinal Fluid (SRF) in the Study at Each Assessment Visit | Week 36 | 13 Participants |
| Brolucizumab 6 mg | Number of Patients With Presence of Subretinal Fluid (SRF) in the Study at Each Assessment Visit | Week 44 | 7 Participants |
| Brolucizumab 6 mg | Number of Patients With Presence of Subretinal Fluid (SRF) in the Study at Each Assessment Visit | Week 48 | 10 Participants |
| Brolucizumab 6 mg | Number of Patients With Presence of Subretinal Fluid (SRF) in the Study at Each Assessment Visit | Week 52 | 9 Participants |
| Brolucizumab 6 mg | Number of Patients With Presence of Subretinal Fluid (SRF) in the Study at Each Assessment Visit | Week 16 | 6 Participants |
| Brolucizumab 6 mg | Number of Patients With Presence of Subretinal Fluid (SRF) in the Study at Each Assessment Visit | Week 28 | 5 Participants |
| Brolucizumab 6 mg | Number of Patients With Presence of Subretinal Fluid (SRF) in the Study at Each Assessment Visit | Week 40 | 7 Participants |
| Aflibercept 2 mg | Number of Patients With Presence of Subretinal Fluid (SRF) in the Study at Each Assessment Visit | Week 32 | 7 Participants |
| Aflibercept 2 mg | Number of Patients With Presence of Subretinal Fluid (SRF) in the Study at Each Assessment Visit | Week 4 | 37 Participants |
| Aflibercept 2 mg | Number of Patients With Presence of Subretinal Fluid (SRF) in the Study at Each Assessment Visit | Week 52 | 4 Participants |
| Aflibercept 2 mg | Number of Patients With Presence of Subretinal Fluid (SRF) in the Study at Each Assessment Visit | Week 6 | 28 Participants |
| Aflibercept 2 mg | Number of Patients With Presence of Subretinal Fluid (SRF) in the Study at Each Assessment Visit | Week 40 | 6 Participants |
| Aflibercept 2 mg | Number of Patients With Presence of Subretinal Fluid (SRF) in the Study at Each Assessment Visit | Week 8 | 20 Participants |
| Aflibercept 2 mg | Number of Patients With Presence of Subretinal Fluid (SRF) in the Study at Each Assessment Visit | Week 36 | 8 Participants |
| Aflibercept 2 mg | Number of Patients With Presence of Subretinal Fluid (SRF) in the Study at Each Assessment Visit | Week 12 | 14 Participants |
| Aflibercept 2 mg | Number of Patients With Presence of Subretinal Fluid (SRF) in the Study at Each Assessment Visit | Week 44 | 3 Participants |
| Aflibercept 2 mg | Number of Patients With Presence of Subretinal Fluid (SRF) in the Study at Each Assessment Visit | Week 18 | 4 Participants |
| Aflibercept 2 mg | Number of Patients With Presence of Subretinal Fluid (SRF) in the Study at Each Assessment Visit | Week 16 | 9 Participants |
| Aflibercept 2 mg | Number of Patients With Presence of Subretinal Fluid (SRF) in the Study at Each Assessment Visit | Week 20 | 2 Participants |
| Aflibercept 2 mg | Number of Patients With Presence of Subretinal Fluid (SRF) in the Study at Each Assessment Visit | Week 48 | 4 Participants |
| Aflibercept 2 mg | Number of Patients With Presence of Subretinal Fluid (SRF) in the Study at Each Assessment Visit | Week 28 | 5 Participants |
| Aflibercept 2 mg | Number of Patients With Presence of Subretinal Fluid (SRF) in the Study at Each Assessment Visit | Week 24 | 2 Participants |
Secondary
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
Population: Full Analysis Set- last observation carried forward (FAS - LOCF)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Brolucizumab 6 mg | Number (%) of Patients With Presence of Subretinal Fluid (SRF), Intraretinal Fluid (IRF) in the Study Eye | 87 Participants |
| Aflibercept 2 mg | Number (%) of Patients With Presence of Subretinal Fluid (SRF), Intraretinal Fluid (IRF) in the Study Eye | 85 Participants |
95% CI: [-10.5, 12.4]Clopper-Pearson exact method
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
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
Population: Full Analysis Set - LOCF. Subset of non-Proliferative diabetic retinopathy (PDR) subjects at screening
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Brolucizumab 6 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 Participants |
| 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 | 0 Participants |
95% CI: [0.8, 3.6]Clopper-Pearson exact method
Secondary
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.
Population: Safety Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Brolucizumab 6 mg | Number of Subjects With Non-ocular Adverse Events (AEs) (>=2% in Any Treatment Arm) | 94 Participants |
| Aflibercept 2 mg | Number of Subjects With Non-ocular Adverse Events (AEs) (>=2% in Any Treatment Arm) | 74 Participants |
Secondary
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
Population: Full Analysis Set - Observed (Patients with a valid observed value for the outcome measure.)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Brolucizumab 6 mg | Number (%) of Subjects With q8w Treatment Need as Assessed by the Investigator at First Disease Activity Assessment (DAA) Visit - Week 32 | 34 Participants |
| Aflibercept 2 mg | Number (%) of Subjects With q8w Treatment Need as Assessed by the Investigator at First Disease Activity Assessment (DAA) Visit - Week 32 | 38 Participants |
95% CI: [-13.6, 11.2]Clopper-Pearson exact method
Secondary
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
Population: Full Analysis Set - Observed
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brolucizumab 6 mg | Number (%) of Subjects With q8w Treatment Need as Assessed by the Investigator at Week 36, and Week 48 | Week 36 (n=105,113) | 50 Participants |
| Brolucizumab 6 mg | Number (%) of Subjects With q8w Treatment Need as Assessed by the Investigator at Week 36, and Week 48 | Week 48 (n=102,104) | 25 Participants |
| Aflibercept 2 mg | Number (%) of Subjects With q8w Treatment Need as Assessed by the Investigator at Week 36, and Week 48 | Week 36 (n=105,113) | 32 Participants |
| Aflibercept 2 mg | Number (%) of Subjects With q8w Treatment Need as Assessed by the Investigator at Week 36, and Week 48 | Week 48 (n=102,104) | 32 Participants |
Secondary
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.
Population: Safety Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brolucizumab 6 mg | Ocular Adverse Events (AEs) (>=2% in Any Treatment Arm) by Preferred Term for the Study Eye | Intraocular pressure increased | 8 Participants |
| Brolucizumab 6 mg | Ocular Adverse Events (AEs) (>=2% in Any Treatment Arm) by Preferred Term for the Study Eye | Dry eye | 3 Participants |
| Brolucizumab 6 mg | Ocular Adverse Events (AEs) (>=2% in Any Treatment Arm) by Preferred Term for the Study Eye | Cataract | 8 Participants |
| Brolucizumab 6 mg | Ocular Adverse Events (AEs) (>=2% in Any Treatment Arm) by Preferred Term for the Study Eye | Epiretinal membrane | 3 Participants |
| Brolucizumab 6 mg | Ocular Adverse Events (AEs) (>=2% in Any Treatment Arm) by Preferred Term for the Study Eye | Visual acuity reduced | 12 Participants |
| Brolucizumab 6 mg | Ocular Adverse Events (AEs) (>=2% in Any Treatment Arm) by Preferred Term for the Study Eye | Eye pruritus | 3 Participants |
| Brolucizumab 6 mg | Ocular Adverse Events (AEs) (>=2% in Any Treatment Arm) by Preferred Term for the Study Eye | Conjunctival haemorrhage | 7 Participants |
| Brolucizumab 6 mg | Ocular Adverse Events (AEs) (>=2% in Any Treatment Arm) by Preferred Term for the Study Eye | Uveitis | 3 Participants |
| Brolucizumab 6 mg | Ocular Adverse Events (AEs) (>=2% in Any Treatment Arm) by Preferred Term for the Study Eye | Meibomian gland dysfunction | 8 Participants |
| Brolucizumab 6 mg | Ocular Adverse Events (AEs) (>=2% in Any Treatment Arm) by Preferred Term for the Study Eye | Vitreous haemorrhage | 3 Participants |
| Brolucizumab 6 mg | Ocular Adverse Events (AEs) (>=2% in Any Treatment Arm) by Preferred Term for the Study Eye | Vitreous opacities | 4 Participants |
| Brolucizumab 6 mg | Ocular Adverse Events (AEs) (>=2% in Any Treatment Arm) by Preferred Term for the Study Eye | Xerophthalmia | 2 Participants |
| Brolucizumab 6 mg | Ocular Adverse Events (AEs) (>=2% in Any Treatment Arm) by Preferred Term for the Study Eye | Number of subjects with at least one AE | 57 Participants |
| Aflibercept 2 mg | Ocular Adverse Events (AEs) (>=2% in Any Treatment Arm) by Preferred Term for the Study Eye | Xerophthalmia | 5 Participants |
| Aflibercept 2 mg | Ocular Adverse Events (AEs) (>=2% in Any Treatment Arm) by Preferred Term for the Study Eye | Number of subjects with at least one AE | 47 Participants |
| Aflibercept 2 mg | Ocular Adverse Events (AEs) (>=2% in Any Treatment Arm) by Preferred Term for the Study Eye | Visual acuity reduced | 6 Participants |
| Aflibercept 2 mg | Ocular Adverse Events (AEs) (>=2% in Any Treatment Arm) by Preferred Term for the Study Eye | Intraocular pressure increased | 9 Participants |
| Aflibercept 2 mg | Ocular Adverse Events (AEs) (>=2% in Any Treatment Arm) by Preferred Term for the Study Eye | Meibomian gland dysfunction | 9 Participants |
| Aflibercept 2 mg | Ocular Adverse Events (AEs) (>=2% in Any Treatment Arm) by Preferred Term for the Study Eye | Cataract | 3 Participants |
| Aflibercept 2 mg | Ocular Adverse Events (AEs) (>=2% in Any Treatment Arm) by Preferred Term for the Study Eye | Conjunctival haemorrhage | 5 Participants |
| Aflibercept 2 mg | Ocular Adverse Events (AEs) (>=2% in Any Treatment Arm) by Preferred Term for the Study Eye | Vitreous opacities | 0 Participants |
| Aflibercept 2 mg | Ocular Adverse Events (AEs) (>=2% in Any Treatment Arm) by Preferred Term for the Study Eye | Dry eye | 3 Participants |
| Aflibercept 2 mg | Ocular Adverse Events (AEs) (>=2% in Any Treatment Arm) by Preferred Term for the Study Eye | Epiretinal membrane | 2 Participants |
| Aflibercept 2 mg | Ocular Adverse Events (AEs) (>=2% in Any Treatment Arm) by Preferred Term for the Study Eye | Eye pruritus | 1 Participants |
| Aflibercept 2 mg | Ocular Adverse Events (AEs) (>=2% in Any Treatment Arm) by Preferred Term for the Study Eye | Uveitis | 0 Participants |
| Aflibercept 2 mg | Ocular Adverse Events (AEs) (>=2% in Any Treatment Arm) by Preferred Term for the Study Eye | Vitreous haemorrhage | 5 Participants |
Secondary
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
Population: Full Analysis Set - LOCF
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brolucizumab 6 mg | Proportion of Patients Who Have Absolute BCVA ≥73 ETDRS Letters at Each Post-baseline Visit for the Study Eye | Week 16 | 50 Participants |
| Brolucizumab 6 mg | Proportion of Patients Who Have Absolute BCVA ≥73 ETDRS Letters at Each Post-baseline Visit for the Study Eye | Week 28 | 52 Participants |
| Brolucizumab 6 mg | Proportion of Patients Who Have Absolute BCVA ≥73 ETDRS Letters at Each Post-baseline Visit for the Study Eye | Week 6 | 36 Participants |
| Brolucizumab 6 mg | Proportion of Patients Who Have Absolute BCVA ≥73 ETDRS Letters at Each Post-baseline Visit for the Study Eye | Week 32 | 51 Participants |
| Brolucizumab 6 mg | Proportion of Patients Who Have Absolute BCVA ≥73 ETDRS Letters at Each Post-baseline Visit for the Study Eye | Week 36 | 49 Participants |
| Brolucizumab 6 mg | Proportion of Patients Who Have Absolute BCVA ≥73 ETDRS Letters at Each Post-baseline Visit for the Study Eye | Week 18 | 51 Participants |
| Brolucizumab 6 mg | Proportion of Patients Who Have Absolute BCVA ≥73 ETDRS Letters at Each Post-baseline Visit for the Study Eye | Week 40 | 53 Participants |
| Brolucizumab 6 mg | Proportion of Patients Who Have Absolute BCVA ≥73 ETDRS Letters at Each Post-baseline Visit for the Study Eye | Week 12 | 50 Participants |
| Brolucizumab 6 mg | Proportion of Patients Who Have Absolute BCVA ≥73 ETDRS Letters at Each Post-baseline Visit for the Study Eye | Week 44 | 53 Participants |
| Brolucizumab 6 mg | Proportion of Patients Who Have Absolute BCVA ≥73 ETDRS Letters at Each Post-baseline Visit for the Study Eye | Week 20 | 54 Participants |
| Brolucizumab 6 mg | Proportion of Patients Who Have Absolute BCVA ≥73 ETDRS Letters at Each Post-baseline Visit for the Study Eye | Week 48 | 57 Participants |
| Brolucizumab 6 mg | Proportion of Patients Who Have Absolute BCVA ≥73 ETDRS Letters at Each Post-baseline Visit for the Study Eye | Week 8 | 46 Participants |
| Brolucizumab 6 mg | Proportion of Patients Who Have Absolute BCVA ≥73 ETDRS Letters at Each Post-baseline Visit for the Study Eye | Week 52 | 55 Participants |
| Brolucizumab 6 mg | Proportion of Patients Who Have Absolute BCVA ≥73 ETDRS Letters at Each Post-baseline Visit for the Study Eye | Week 24 | 53 Participants |
| Brolucizumab 6 mg | Proportion of Patients Who Have Absolute BCVA ≥73 ETDRS Letters at Each Post-baseline Visit for the Study Eye | Week 4 | 32 Participants |
| Aflibercept 2 mg | Proportion of Patients Who Have Absolute BCVA ≥73 ETDRS Letters at Each Post-baseline Visit for the Study Eye | Week 32 | 74 Participants |
| Aflibercept 2 mg | Proportion of Patients Who Have Absolute BCVA ≥73 ETDRS Letters at Each Post-baseline Visit for the Study Eye | Week 4 | 34 Participants |
| Aflibercept 2 mg | Proportion of Patients Who Have Absolute BCVA ≥73 ETDRS Letters at Each Post-baseline Visit for the Study Eye | Week 6 | 46 Participants |
| Aflibercept 2 mg | Proportion of Patients Who Have Absolute BCVA ≥73 ETDRS Letters at Each Post-baseline Visit for the Study Eye | Week 8 | 55 Participants |
| Aflibercept 2 mg | Proportion of Patients Who Have Absolute BCVA ≥73 ETDRS Letters at Each Post-baseline Visit for the Study Eye | Week 12 | 63 Participants |
| Aflibercept 2 mg | Proportion of Patients Who Have Absolute BCVA ≥73 ETDRS Letters at Each Post-baseline Visit for the Study Eye | Week 16 | 67 Participants |
| Aflibercept 2 mg | Proportion of Patients Who Have Absolute BCVA ≥73 ETDRS Letters at Each Post-baseline Visit for the Study Eye | Week 18 | 68 Participants |
| Aflibercept 2 mg | Proportion of Patients Who Have Absolute BCVA ≥73 ETDRS Letters at Each Post-baseline Visit for the Study Eye | Week 20 | 65 Participants |
| Aflibercept 2 mg | Proportion of Patients Who Have Absolute BCVA ≥73 ETDRS Letters at Each Post-baseline Visit for the Study Eye | Week 24 | 74 Participants |
| Aflibercept 2 mg | Proportion of Patients Who Have Absolute BCVA ≥73 ETDRS Letters at Each Post-baseline Visit for the Study Eye | Week 28 | 72 Participants |
| Aflibercept 2 mg | Proportion of Patients Who Have Absolute BCVA ≥73 ETDRS Letters at Each Post-baseline Visit for the Study Eye | Week 36 | 77 Participants |
| Aflibercept 2 mg | Proportion of Patients Who Have Absolute BCVA ≥73 ETDRS Letters at Each Post-baseline Visit for the Study Eye | Week 40 | 81 Participants |
| Aflibercept 2 mg | Proportion of Patients Who Have Absolute BCVA ≥73 ETDRS Letters at Each Post-baseline Visit for the Study Eye | Week 44 | 76 Participants |
| Aflibercept 2 mg | Proportion of Patients Who Have Absolute BCVA ≥73 ETDRS Letters at Each Post-baseline Visit for the Study Eye | Week 48 | 78 Participants |
| Aflibercept 2 mg | Proportion of Patients Who Have Absolute BCVA ≥73 ETDRS Letters at Each Post-baseline Visit for the Study Eye | Week 52 | 75 Participants |
Comparison: Week 495% CI: [-7.9, 8.6]Clopper-Pearson exact method
Comparison: Week 695% CI: [-14.3, 2.9]Clopper-Pearson exact method
Comparison: Week 895% CI: [-13.3, 4.4]Clopper-Pearson exact method
Comparison: Week 1295% CI: [-16.4, 2.3]Clopper-Pearson exact method
Comparison: Week 1695% CI: [-19.2, 0]Clopper-Pearson exact method
Comparison: Week 1895% CI: [-19, 0]Clopper-Pearson exact method
Comparison: Week 2095% CI: [-15.8, 3.9]Clopper-Pearson exact method
Comparison: Week 2495% CI: [-23.9, -3.1]Clopper-Pearson exact method
Comparison: Week 2895% CI: [-22, -2.1]Clopper-Pearson exact method
Comparison: Week 3295% CI: [-26, -4.8]Clopper-Pearson exact method
Comparison: Week 3695% CI: [-29.5, -8.9]Clopper-Pearson exact method.
Comparison: Week 4095% CI: [-28.7, -8.6]Clopper-Pearson exact method
Comparison: Week 4495% CI: [-25.6, -4.4]Clopper-Pearson exact method
Comparison: Week 4895% CI: [-23.6, -3.4]Clopper-Pearson exact method
Comparison: Week 5295% CI: [-23.5, -2.9]Clopper-Pearson exact method
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
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
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Brolucizumab 6 mg | Time to Achieve Gain of >= 10 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 16 (n=64,71) | 0.562 Probability of BCVA gain |
| Brolucizumab 6 mg | Time to Achieve Gain of >= 10 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 28 (n=44,41) | 0.659 Probability of BCVA gain |
| Brolucizumab 6 mg | Time to Achieve Gain of >= 10 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 6 (n=124,131) | 0.227 Probability of BCVA gain |
| Brolucizumab 6 mg | Time to Achieve Gain of >= 10 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 36 (n=39,35) | 0.693 Probability of BCVA gain |
| Brolucizumab 6 mg | Time to Achieve Gain of >= 10 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 18 (n=55,59) | 0.594 Probability of BCVA gain |
| Brolucizumab 6 mg | Time to Achieve Gain of >= 10 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 40 (n=35,33) | 0.710 Probability of BCVA gain |
| Brolucizumab 6 mg | Time to Achieve Gain of >= 10 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 12 (n=80,90) | 0.508 Probability of BCVA gain |
| Brolucizumab 6 mg | Time to Achieve Gain of >= 10 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 44 (n=33,32) | 0.728 Probability of BCVA gain |
| Brolucizumab 6 mg | Time to Achieve Gain of >= 10 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 20 (n=50,56) | 0.618 Probability of BCVA gain |
| Brolucizumab 6 mg | Time to Achieve Gain of >= 10 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 48 (n=31,28) | 0.754 Probability of BCVA gain |
| Brolucizumab 6 mg | Time to Achieve Gain of >= 10 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 8 (n=102,105) | 0.394 Probability of BCVA gain |
| Brolucizumab 6 mg | Time to Achieve Gain of >= 10 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 52 (n=28,27) | 0.899 Probability of BCVA gain |
| Brolucizumab 6 mg | Time to Achieve Gain of >= 10 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 24 (n=47,51) | 0.643 Probability of BCVA gain |
| Brolucizumab 6 mg | Time to Achieve Gain of >= 10 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 32 (n=41,38) | 0.676 Probability of BCVA gain |
| Brolucizumab 6 mg | Time to Achieve Gain of >= 10 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 4 | 0.061 Probability of BCVA gain |
| Aflibercept 2 mg | Time to Achieve Gain of >= 10 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 32 (n=41,38) | 0.705 Probability of BCVA gain |
| Aflibercept 2 mg | Time to Achieve Gain of >= 10 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 4 | 0.000 Probability of BCVA gain |
| Aflibercept 2 mg | Time to Achieve Gain of >= 10 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 6 (n=124,131) | 0.198 Probability of BCVA gain |
| Aflibercept 2 mg | Time to Achieve Gain of >= 10 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 8 (n=102,105) | 0.306 Probability of BCVA gain |
| Aflibercept 2 mg | Time to Achieve Gain of >= 10 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 12 (n=80,90) | 0.439 Probability of BCVA gain |
| Aflibercept 2 mg | Time to Achieve Gain of >= 10 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 16 (n=64,71) | 0.527 Probability of BCVA gain |
| Aflibercept 2 mg | Time to Achieve Gain of >= 10 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 18 (n=55,59) | 0.551 Probability of BCVA gain |
| Aflibercept 2 mg | Time to Achieve Gain of >= 10 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 20 (n=50,56) | 0.591 Probability of BCVA gain |
| Aflibercept 2 mg | Time to Achieve Gain of >= 10 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 24 (n=47,51) | 0.664 Probability of BCVA gain |
| Aflibercept 2 mg | Time to Achieve Gain of >= 10 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 28 (n=44,41) | 0.680 Probability of BCVA gain |
| Aflibercept 2 mg | Time to Achieve Gain of >= 10 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 36 (n=39,35) | 0.722 Probability of BCVA gain |
| Aflibercept 2 mg | Time to Achieve Gain of >= 10 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 40 (n=35,33) | 0.730 Probability of BCVA gain |
| Aflibercept 2 mg | Time to Achieve Gain of >= 10 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 44 (n=33,32) | 0.739 Probability of BCVA gain |
| Aflibercept 2 mg | Time to Achieve Gain of >= 10 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 48 (n=31,28) | 0.749 Probability of BCVA gain |
| Aflibercept 2 mg | Time to Achieve Gain of >= 10 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 52 (n=28,27) | 1 Probability of BCVA gain |
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
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
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Brolucizumab 6 mg | Time to Achieve Gain of >= 15 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 16 (n=101,100) | 0.266 Probability of BCVA gain |
| Brolucizumab 6 mg | Time to Achieve Gain of >= 15 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 28 (n=72,74) | 0.425 Probability of BCVA gain |
| Brolucizumab 6 mg | Time to Achieve Gain of >= 15 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 6 (n=131,131) | 0.083 Probability of BCVA gain |
| Brolucizumab 6 mg | Time to Achieve Gain of >= 15 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 32 (n=67,69) | 0.459 Probability of BCVA gain |
| Brolucizumab 6 mg | Time to Achieve Gain of >= 15 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 18 (n=94,94) | 0.313 Probability of BCVA gain |
| Brolucizumab 6 mg | Time to Achieve Gain of >= 15 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 36 (n=63,66) | 0.485 Probability of BCVA gain |
| Brolucizumab 6 mg | Time to Achieve Gain of >= 15 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 12 (n=112,109) | 0.227 Probability of BCVA gain |
| Brolucizumab 6 mg | Time to Achieve Gain of >= 15 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 40 (n=58,63) | 0.494 Probability of BCVA gain |
| Brolucizumab 6 mg | Time to Achieve Gain of >= 15 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 20 (n=87,85) | 0.344 Probability of BCVA gain |
| Brolucizumab 6 mg | Time to Achieve Gain of >= 15 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 44 (n=57,60) | 0.512 Probability of BCVA gain |
| Brolucizumab 6 mg | Time to Achieve Gain of >= 15 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 8 (n=121,122) | 0.152 Probability of BCVA gain |
| Brolucizumab 6 mg | Time to Achieve Gain of >= 15 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 48 (n=55,54) | 0.539 Probability of BCVA gain |
| Brolucizumab 6 mg | Time to Achieve Gain of >= 15 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 24 (n=82,80) | 0.409 Probability of BCVA gain |
| Brolucizumab 6 mg | Time to Achieve Gain of >= 15 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 52 (n=52,53) | 0.623 Probability of BCVA gain |
| Brolucizumab 6 mg | Time to Achieve Gain of >= 15 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 4 | 0.008 Probability of BCVA gain |
| Aflibercept 2 mg | Time to Achieve Gain of >= 15 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 52 (n=52,53) | 1 Probability of BCVA gain |
| Aflibercept 2 mg | Time to Achieve Gain of >= 15 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 4 | 0.000 Probability of BCVA gain |
| Aflibercept 2 mg | Time to Achieve Gain of >= 15 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 6 (n=131,131) | 0.069 Probability of BCVA gain |
| Aflibercept 2 mg | Time to Achieve Gain of >= 15 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 8 (n=121,122) | 0.161 Probability of BCVA gain |
| Aflibercept 2 mg | Time to Achieve Gain of >= 15 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 12 (n=112,109) | 0.216 Probability of BCVA gain |
| Aflibercept 2 mg | Time to Achieve Gain of >= 15 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 16 (n=101,100) | 0.255 Probability of BCVA gain |
| Aflibercept 2 mg | Time to Achieve Gain of >= 15 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 18 (n=94,94) | 0.319 Probability of BCVA gain |
| Aflibercept 2 mg | Time to Achieve Gain of >= 15 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 20 (n=87,85) | 0.359 Probability of BCVA gain |
| Aflibercept 2 mg | Time to Achieve Gain of >= 15 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 24 (n=82,80) | 0.399 Probability of BCVA gain |
| Aflibercept 2 mg | Time to Achieve Gain of >= 15 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 28 (n=72,74) | 0.432 Probability of BCVA gain |
| Aflibercept 2 mg | Time to Achieve Gain of >= 15 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 32 (n=67,69) | 0.456 Probability of BCVA gain |
| Aflibercept 2 mg | Time to Achieve Gain of >= 15 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 36 (n=63,66) | 0.481 Probability of BCVA gain |
| Aflibercept 2 mg | Time to Achieve Gain of >= 15 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 40 (n=58,63) | 0.506 Probability of BCVA gain |
| Aflibercept 2 mg | Time to Achieve Gain of >= 15 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 44 (n=57,60) | 0.531 Probability of BCVA gain |
| Aflibercept 2 mg | Time to Achieve Gain of >= 15 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 48 (n=55,54) | 0.540 Probability of BCVA gain |
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
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
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Brolucizumab 6 mg | Time to Achieve Gain of >= 5 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 16 (n=29, 36) | 0.818 Probability of BCVA gain |
| Brolucizumab 6 mg | Time to Achieve Gain of >= 5 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 28 (n=19,15) | 0.864 Probability of BCVA gain |
| Brolucizumab 6 mg | Time to Achieve Gain of >= 5 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 6 (n=114,126) | 0.508 Probability of BCVA gain |
| Brolucizumab 6 mg | Time to Achieve Gain of >= 5 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 32 (n=17,14) | 0.888 Probability of BCVA gain |
| Brolucizumab 6 mg | Time to Achieve Gain of >= 5 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 18 (n=24, 28) | 0.818 Probability of BCVA gain |
| Brolucizumab 6 mg | Time to Achieve Gain of >= 5 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 36 (n=14,14,) | 0.888 Probability of BCVA gain |
| Brolucizumab 6 mg | Time to Achieve Gain of >= 5 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 12 (n=37, 48) | 0.780 Probability of BCVA gain |
| Brolucizumab 6 mg | Time to Achieve Gain of >= 5 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 40 (n=14,14) | 0.888 Probability of BCVA gain |
| Brolucizumab 6 mg | Time to Achieve Gain of >= 5 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 20 (n=24,20) | 0.841 Probability of BCVA gain |
| Brolucizumab 6 mg | Time to Achieve Gain of >= 5 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 44 (n=14,11) | 0.896 Probability of BCVA gain |
| Brolucizumab 6 mg | Time to Achieve Gain of >= 5 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 8 (n=65, 76) | 0.720 Probability of BCVA gain |
| Brolucizumab 6 mg | Time to Achieve Gain of >= 5 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 48 (n=13,10) | 0.912 Probability of BCVA gain |
| Brolucizumab 6 mg | Time to Achieve Gain of >= 5 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 24 (n=21,17) | 0.856 Probability of BCVA gain |
| Brolucizumab 6 mg | Time to Achieve Gain of >= 5 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 52 (n=11,9) | 0.957 Probability of BCVA gain |
| Brolucizumab 6 mg | Time to Achieve Gain of >= 5 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 4 | 0.136 Probability of BCVA gain |
| Aflibercept 2 mg | Time to Achieve Gain of >= 5 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 52 (n=11,9) | 0.926 Probability of BCVA gain |
| Aflibercept 2 mg | Time to Achieve Gain of >= 5 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 4 | 0.038 Probability of BCVA gain |
| Aflibercept 2 mg | Time to Achieve Gain of >= 5 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 6 (n=114,126) | 0.420 Probability of BCVA gain |
| Aflibercept 2 mg | Time to Achieve Gain of >= 5 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 8 (n=65, 76) | 0.634 Probability of BCVA gain |
| Aflibercept 2 mg | Time to Achieve Gain of >= 5 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 12 (n=37, 48) | 0.725 Probability of BCVA gain |
| Aflibercept 2 mg | Time to Achieve Gain of >= 5 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 16 (n=29, 36) | 0.780 Probability of BCVA gain |
| Aflibercept 2 mg | Time to Achieve Gain of >= 5 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 18 (n=24, 28) | 0.843 Probability of BCVA gain |
| Aflibercept 2 mg | Time to Achieve Gain of >= 5 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 20 (n=24,20) | 0.866 Probability of BCVA gain |
| Aflibercept 2 mg | Time to Achieve Gain of >= 5 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 24 (n=21,17) | 0.874 Probability of BCVA gain |
| Aflibercept 2 mg | Time to Achieve Gain of >= 5 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 28 (n=19,15) | 0.882 Probability of BCVA gain |
| Aflibercept 2 mg | Time to Achieve Gain of >= 5 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 32 (n=17,14) | 0.882 Probability of BCVA gain |
| Aflibercept 2 mg | Time to Achieve Gain of >= 5 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 36 (n=14,14,) | 0.882 Probability of BCVA gain |
| Aflibercept 2 mg | Time to Achieve Gain of >= 5 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 40 (n=14,14) | 0.908 Probability of BCVA gain |
| Aflibercept 2 mg | Time to Achieve Gain of >= 5 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 44 (n=14,11) | 0.908 Probability of BCVA gain |
| Aflibercept 2 mg | Time to Achieve Gain of >= 5 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain | Week 48 (n=13,10) | 0.917 Probability of BCVA gain |
Secondary
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
Population: FAS - Efficacy/Safety approach
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Brolucizumab 6 mg | Time-to-first q8w Treatment Need: Summary for Brolucizumab Subjects by Disease Activity Assessment Visit | Week 0 | 1 Probability |
| Brolucizumab 6 mg | Time-to-first q8w Treatment Need: Summary for Brolucizumab Subjects by Disease Activity Assessment Visit | Week 32 (n=86,0) | 0.733 Probability |
| Brolucizumab 6 mg | Time-to-first q8w Treatment Need: Summary for Brolucizumab Subjects by Disease Activity Assessment Visit | Week36 (n=59,0) | 0.447 Probability |
| Brolucizumab 6 mg | Time-to-first q8w Treatment Need: Summary for Brolucizumab Subjects by Disease Activity Assessment Visit | Week48 (n=30,0) | 0.417 Probability |
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
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
Population: FAS - Efficacy/Safety approach. Participants in the Full Analysis Set with no identified q8w-need at Week 32 and Week 36.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Brolucizumab 6 mg | 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 | Week36 (n=35,0) | 1 Probability |
| Brolucizumab 6 mg | 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 | Week48 (n=29,0) | 0.931 Probability |
Post Hoc
All Collected Deaths
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.
Time frame: On-treatment - up to 52 weeks; Post-treatment - greater than 30 days after last treatment, until study completion, up to Week 52
Population: Safety Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brolucizumab 6 mg | All Collected Deaths | On-Treatment Deaths | 0 Participants |
| Brolucizumab 6 mg | All Collected Deaths | Post-Treatment Deaths | 0 Participants |
| Brolucizumab 6 mg | All Collected Deaths | All Deaths | 0 Participants |
| Aflibercept 2 mg | All Collected Deaths | On-Treatment Deaths | 0 Participants |
| Aflibercept 2 mg | All Collected Deaths | Post-Treatment Deaths | 1 Participants |
| Aflibercept 2 mg | All Collected Deaths | All Deaths | 1 Participants |