To Compare Brolucizumab to Aflibercept in Chinese Patients With Visual Impairment Due to Diabetic Macular Edema

Phase 3

Completed

Conditions: Diabetic Macular Edema

Interventions: Drug: Brolucizumab
Drug: Aflibercept

Registration Number: NCT04058067

Lead Sponsor: Novartis Pharmaceuticals

Brief Summary: The purpose of this study is 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 263

Inclusion Criteria

Patients with type 1 or type 2 diabetes mellitus
Visual impairment due to Diabetic Macular Edema

Exclusion Criteria

Any active intraocular or periocular infection or active intraocular inflammation
Structural damage of the fovea
Uncontrolled glaucoma
Neovascularization of the iris

Other protocol-defined inclusion/exclusion criteria may apply.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Brolucizumab 6 mg	Brolucizumab	5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance
Aflibercept 2 mg	Aflibercept	5 x every 4 weeks loading then every 8 weeks maintenance

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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.
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.
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
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
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 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.
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