Trial Outcomes & Findings for Efficacy and Safety of Brolucizumab vs Aflibercept in Patients With Visual Impairment Due to Diabetic Macular Edema (NCT NCT03917472)

Last Updated: 2022-08-12

Results Overview

BCVA will be assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. Visual function of the study eye was assessed using the ETDRS protocol. Participants with a BCVA ETDRS letter score of 73 to 23 (per the inclusion criteria) (approximate Snellen equivalent of 20/40 to 20/320) in the study eye were included. Min and max possible scores are 0-100 respectively. A higher score represents better functioning. Last observation carried forward (LOCF) was used for the imputation of missing values.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

517 participants

Primary outcome timeframe

Baseline, Week 52

Results posted on

2022-08-12

Participant Flow

Study centers (no. of sites): Hungary (5), Israel (5), Slovakia (7), United States (78). Approximately, 495 subjects were planned to be randomized. Overall, 517 subjects were randomized either to brolucizumab 6 mg q4w arm (n=346) or aflibercept 2 mg q4w arm (n=171).

The study included a screening period of up to 2 weeks to assess eligibility, followed by a double-masked treatment period (Day 1 to Week 48). For all subjects, the last study assessment was performed at the Week 52/end of study (EOS) visit. All subjects had study visits q4w through Week 52. The primary analysis was performed at the EOS visit (Week 52).

Participant milestones

Participant milestones
Measure	Brolucizumab 6mg q4w Brolucizumab 6 mg/0.05 mL every 4 weeks.	Aflibercept 2mg q4w Aflibercept 2mg/0.05 mL every 4 weeks
Overall Study STARTED	346	171
Overall Study COMPLETED	311	156
Overall Study NOT COMPLETED	35	15

Reasons for withdrawal

Reasons for withdrawal
Measure	Brolucizumab 6mg q4w Brolucizumab 6 mg/0.05 mL every 4 weeks.	Aflibercept 2mg q4w Aflibercept 2mg/0.05 mL every 4 weeks
Overall Study Physician Decision	4	0
Overall Study Adverse Event	3	1
Overall Study Death	7	5
Overall Study Withdrawal by Subject	11	4
Overall Study Lost to Follow-up	10	5

Baseline Characteristics

Efficacy and Safety of Brolucizumab vs Aflibercept in Patients With Visual Impairment Due to Diabetic Macular Edema

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Brolucizumab 6mg q4w n=346 Participants Brolucizumab 6 mg/0.05 mL every 4 weeks.	Aflibercept 2mg q4w n=171 Participants Aflibercept 2mg/0.05 mL every 4 weeks	Total n=517 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Age, Categorical Between 18 and 65 years	208 Participants n=99 Participants	115 Participants n=107 Participants	323 Participants n=206 Participants
Age, Categorical >=65 years	138 Participants n=99 Participants	56 Participants n=107 Participants	194 Participants n=206 Participants
Age, Continuous	60.9 years STANDARD_DEVIATION 10.59 • n=99 Participants	60.2 years STANDARD_DEVIATION 9.31 • n=107 Participants	60.7 years STANDARD_DEVIATION 10.18 • n=206 Participants
Sex: Female, Male Female	152 Participants n=99 Participants	66 Participants n=107 Participants	218 Participants n=206 Participants
Sex: Female, Male Male	194 Participants n=99 Participants	105 Participants n=107 Participants	299 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants
Race (NIH/OMB) Asian	14 Participants n=99 Participants	7 Participants n=107 Participants	21 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants
Race (NIH/OMB) Black or African American	40 Participants n=99 Participants	15 Participants n=107 Participants	55 Participants n=206 Participants
Race (NIH/OMB) White	288 Participants n=99 Participants	145 Participants n=107 Participants	433 Participants n=206 Participants
Race (NIH/OMB) More than one race	2 Participants n=99 Participants	0 Participants n=107 Participants	2 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=99 Participants	3 Participants n=107 Participants	4 Participants n=206 Participants

PRIMARY outcome

Timeframe: Baseline, Week 52

Population: Full analysis set (FAS) - Last observation carried forward (LOCF)

Outcome measures

Outcome measures
Measure	Brolucizumab 6mg q4w n=346 Participants Brolucizumab 6 mg/0.05 mL every 4 weeks.	Aflibercept 2mg q4w n=171 Participants Aflibercept 2mg/0.05 mL every 4 weeks
Change From Baseline in Best-corrected Visual Acuity (BCVA) at Week 52	12.2 Scores on a scale Interval 11.2 to 13.2	11.0 Scores on a scale Interval 9.6 to 12.4

SECONDARY outcome

Timeframe: Baseline, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and 52

Population: Full analysis set (FAS) - Last observation carried forward (LOCF)

Central Subfield Thickness assessed by Spectral domain optical coherence tomography (SD-OCT) from the central reading center.

Outcome measures

Outcome measures
Measure	Brolucizumab 6mg q4w n=346 Participants Brolucizumab 6 mg/0.05 mL every 4 weeks.	Aflibercept 2mg q4w n=171 Participants Aflibercept 2mg/0.05 mL every 4 weeks
Change From Baseline in Central Subfield Thickness (CSFT) at Each Post-baseline Visit Week 4	-146.9 μm Interval -157.9 to -136.0	-119.5 μm Interval -135.1 to -103.9
Change From Baseline in Central Subfield Thickness (CSFT) at Each Post-baseline Visit Week 8	-174.4 μm Interval -185.3 to -163.4	-144.1 μm Interval -159.7 to -128.5
Change From Baseline in Central Subfield Thickness (CSFT) at Each Post-baseline Visit Week 12	-191.3 μm Interval -201.8 to -180.8	-156.7 μm Interval -171.7 to -141.8
Change From Baseline in Central Subfield Thickness (CSFT) at Each Post-baseline Visit Week 16	-200.5 μm Interval -211.0 to -189.9	-162.4 μm Interval -177.4 to -147.4
Change From Baseline in Central Subfield Thickness (CSFT) at Each Post-baseline Visit Week 20	-209.5 μm Interval -219.6 to -199.4	-168.7 μm Interval -183.1 to -154.2
Change From Baseline in Central Subfield Thickness (CSFT) at Each Post-baseline Visit Week 24	-217.5 μm Interval -227.3 to -207.6	-178.8 μm Interval -192.8 to -164.7
Change From Baseline in Central Subfield Thickness (CSFT) at Each Post-baseline Visit Week 28	-222.4 μm Interval -232.5 to -212.4	-183.6 μm Interval -197.8 to -169.3
Change From Baseline in Central Subfield Thickness (CSFT) at Each Post-baseline Visit Week 32	-227.2 μm Interval -237.2 to -217.1	-185.9 μm Interval -200.2 to -171.6
Change From Baseline in Central Subfield Thickness (CSFT) at Each Post-baseline Visit Week 36	-229.7 μm Interval -240.1 to -219.3	-186.7 μm Interval -201.5 to -172.0
Change From Baseline in Central Subfield Thickness (CSFT) at Each Post-baseline Visit Week 40	-233.6 μm Interval -243.7 to -223.6	-188.4 μm Interval -202.6 to -174.1
Change From Baseline in Central Subfield Thickness (CSFT) at Each Post-baseline Visit Week 44	-237.5 μm Interval -247.4 to -227.5	-188.1 μm Interval -202.3 to -173.9
Change From Baseline in Central Subfield Thickness (CSFT) at Each Post-baseline Visit Week 48	-237.7 μm Interval -247.7 to -227.6	-192.0 μm Interval -206.4 to -177.7
Change From Baseline in Central Subfield Thickness (CSFT) at Each Post-baseline Visit Week 52	-237.8 μm Interval -247.9 to -227.7	-196.5 μm Interval -210.8 to -182.1

SECONDARY outcome

Timeframe: Baseline, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and 52

Population: Full analysis set (FAS) - Last observation carried forward (LOCF).

Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) status in the central subfield: proportion of subjects with simultaneous absence of SRF and IRF in the study eye by visit. Events and censoring after 52 weeks are included in week 52 row.

Outcome measures

Outcome measures
Measure	Brolucizumab 6mg q4w n=346 Participants Brolucizumab 6 mg/0.05 mL every 4 weeks.	Aflibercept 2mg q4w n=171 Participants Aflibercept 2mg/0.05 mL every 4 weeks
Number and Percentage of Participants With Fluid-free Macula in the Study Eye at Each Post-baseline Visit Week 4	23 Participants	4 Participants
Number and Percentage of Participants With Fluid-free Macula in the Study Eye at Each Post-baseline Visit Week 8	31 Participants	4 Participants
Number and Percentage of Participants With Fluid-free Macula in the Study Eye at Each Post-baseline Visit Week 12	38 Participants	10 Participants
Number and Percentage of Participants With Fluid-free Macula in the Study Eye at Each Post-baseline Visit Week 16	48 Participants	11 Participants
Number and Percentage of Participants With Fluid-free Macula in the Study Eye at Each Post-baseline Visit Week 20	54 Participants	9 Participants
Number and Percentage of Participants With Fluid-free Macula in the Study Eye at Each Post-baseline Visit Week 24	84 Participants	19 Participants
Number and Percentage of Participants With Fluid-free Macula in the Study Eye at Each Post-baseline Visit Week 28	65 Participants	13 Participants
Number and Percentage of Participants With Fluid-free Macula in the Study Eye at Each Post-baseline Visit Week 32	76 Participants	17 Participants
Number and Percentage of Participants With Fluid-free Macula in the Study Eye at Each Post-baseline Visit Week 36	91 Participants	21 Participants
Number and Percentage of Participants With Fluid-free Macula in the Study Eye at Each Post-baseline Visit Week 40	96 Participants	23 Participants
Number and Percentage of Participants With Fluid-free Macula in the Study Eye at Each Post-baseline Visit Week 44	96 Participants	20 Participants
Number and Percentage of Participants With Fluid-free Macula in the Study Eye at Each Post-baseline Visit week 48	92 Participants	23 Participants
Number and Percentage of Participants With Fluid-free Macula in the Study Eye at Each Post-baseline Visit Week 52	144 Participants	38 Participants

SECONDARY outcome

Timeframe: Baseline, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and 52

Population: Full analysis set (FAS) - Last observation carried forward (LOCF)

Central Subfield Thickness Assessed by Spectral domain optical coherence tomography (SD-OCT) from the central reading center.

Outcome measures

Outcome measures
Measure	Brolucizumab 6mg q4w n=346 Participants Brolucizumab 6 mg/0.05 mL every 4 weeks.	Aflibercept 2mg q4w n=171 Participants Aflibercept 2mg/0.05 mL every 4 weeks
Number and Percentage of Participants With Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) at Each Post-baseline Visit for the Study Eye Week 4	61 Participants	9 Participants
Number and Percentage of Participants With Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) at Each Post-baseline Visit for the Study Eye Week 8	93 Participants	24 Participants
Number and Percentage of Participants With Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) at Each Post-baseline Visit for the Study Eye Week 12	124 Participants	33 Participants
Number and Percentage of Participants With Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) at Each Post-baseline Visit for the Study Eye Week 16	147 Participants	42 Participants
Number and Percentage of Participants With Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) at Each Post-baseline Visit for the Study Eye Week 20	167 Participants	47 Participants
Number and Percentage of Participants With Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) at Each Post-baseline Visit for the Study Eye Week 24	177 Participants	52 Participants
Number and Percentage of Participants With Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) at Each Post-baseline Visit for the Study Eye Week 28	186 Participants	57 Participants
Number and Percentage of Participants With Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) at Each Post-baseline Visit for the Study Eye Week 32	195 Participants	62 Participants
Number and Percentage of Participants With Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) at Each Post-baseline Visit for the Study Eye Week 36	206 Participants	63 Participants
Number and Percentage of Participants With Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) at Each Post-baseline Visit for the Study Eye Week 40	211 Participants	65 Participants
Number and Percentage of Participants With Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) at Each Post-baseline Visit for the Study Eye Week 44	216 Participants	69 Participants
Number and Percentage of Participants With Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) at Each Post-baseline Visit for the Study Eye Week 48	222 Participants	68 Participants
Number and Percentage of Participants With Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) at Each Post-baseline Visit for the Study Eye Week 52	229 Participants	71 Participants

SECONDARY outcome

Timeframe: Baseline, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and 52

Population: Full Analysis Set. Time to first fluid-free macula analysis is based on the subset of subjects with fluid present at baseline and at least one post-baseline assessment.

Central Subfield Thickness Assessed by Spectral domain optical coherence tomography (SD-OCT) from the central reading center. Fluid status assessments after start of alternative DME treatment in the study eye are censored. Time to first fluid-free macula analysis is based on the subset of subjects with fluid present at baseline and at least one post-baseline assessment. Time (week) was calculated by (study day / 7). Events and censoring after 52 weeks were included in week 52 row.

Outcome measures

Outcome measures
Measure	Brolucizumab 6mg q4w n=344 Participants Brolucizumab 6 mg/0.05 mL every 4 weeks.	Aflibercept 2mg q4w n=170 Participants Aflibercept 2mg/0.05 mL every 4 weeks
Time to First Fluid-free Macula - Time-to-first Absence of Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) in the Study Eye - Number of Subjects With Absence of SRF / IRF and Number of Subjects Censored by Visit Number of subjects with absence of SRF / IRF at Week 0 (n=344,170)	0 Participants	0 Participants
Time to First Fluid-free Macula - Time-to-first Absence of Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) in the Study Eye - Number of Subjects With Absence of SRF / IRF and Number of Subjects Censored by Visit Number of subjects with absence of SRF / IRF at Week 4 (n=344,170)	6 Participants	1 Participants
Time to First Fluid-free Macula - Time-to-first Absence of Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) in the Study Eye - Number of Subjects With Absence of SRF / IRF and Number of Subjects Censored by Visit Number of subjects with absence of SRF / IRF at Week 8 (n=335,168)	18 Participants	3 Participants
Time to First Fluid-free Macula - Time-to-first Absence of Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) in the Study Eye - Number of Subjects With Absence of SRF / IRF and Number of Subjects Censored by Visit Number of subjects with absence of SRF / IRF at Week 12 (n=314, 165)	13 Participants	2 Participants
Time to First Fluid-free Macula - Time-to-first Absence of Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) in the Study Eye - Number of Subjects With Absence of SRF / IRF and Number of Subjects Censored by Visit Number of subjects with absence of SRF / IRF at Week 16 (n=297, 161)	17 Participants	4 Participants
Time to First Fluid-free Macula - Time-to-first Absence of Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) in the Study Eye - Number of Subjects With Absence of SRF / IRF and Number of Subjects Censored by Visit Number of subjects with absence of SRF / IRF at Week 20 (n=277, 156)	8 Participants	6 Participants
Time to First Fluid-free Macula - Time-to-first Absence of Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) in the Study Eye - Number of Subjects With Absence of SRF / IRF and Number of Subjects Censored by Visit Number of subjects with absence of SRF / IRF at Week 24 (n=265,150)	16 Participants	2 Participants
Time to First Fluid-free Macula - Time-to-first Absence of Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) in the Study Eye - Number of Subjects With Absence of SRF / IRF and Number of Subjects Censored by Visit Number of subjects with absence of SRF / IRF at Week 28 (n=246,146)	18 Participants	7 Participants
Time to First Fluid-free Macula - Time-to-first Absence of Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) in the Study Eye - Number of Subjects With Absence of SRF / IRF and Number of Subjects Censored by Visit Number of subjects with absence of SRF / IRF at Week 32 (n=224,139)	3 Participants	1 Participants
Time to First Fluid-free Macula - Time-to-first Absence of Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) in the Study Eye - Number of Subjects With Absence of SRF / IRF and Number of Subjects Censored by Visit Number of subjects with absence of SRF / IRF at Week 36 (n=220,138)	8 Participants	2 Participants
Time to First Fluid-free Macula - Time-to-first Absence of Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) in the Study Eye - Number of Subjects With Absence of SRF / IRF and Number of Subjects Censored by Visit Number of subjects with absence of SRF / IRF at Week 40 (n=211, 134)	16 Participants	4 Participants
Time to First Fluid-free Macula - Time-to-first Absence of Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) in the Study Eye - Number of Subjects With Absence of SRF / IRF and Number of Subjects Censored by Visit Number of subjects with absence of SRF / IRF at Week 44 (194, 129)	11 Participants	2 Participants
Time to First Fluid-free Macula - Time-to-first Absence of Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) in the Study Eye - Number of Subjects With Absence of SRF / IRF and Number of Subjects Censored by Visit Number of subjects with absence of SRF / IRF at Week 48 (n=181, 125)	3 Participants	0 Participants
Time to First Fluid-free Macula - Time-to-first Absence of Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) in the Study Eye - Number of Subjects With Absence of SRF / IRF and Number of Subjects Censored by Visit Number of subjects with absence of SRF / IRF at Week 52 (n=177, 122)	30 Participants	12 Participants
Time to First Fluid-free Macula - Time-to-first Absence of Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) in the Study Eye - Number of Subjects With Absence of SRF / IRF and Number of Subjects Censored by Visit Number of subjects censored at Week 0 (n=344, 170)	0 Participants	0 Participants
Time to First Fluid-free Macula - Time-to-first Absence of Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) in the Study Eye - Number of Subjects With Absence of SRF / IRF and Number of Subjects Censored by Visit Number of subjects censored at Week 4 (n-344, 170)	3 Participants	1 Participants
Time to First Fluid-free Macula - Time-to-first Absence of Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) in the Study Eye - Number of Subjects With Absence of SRF / IRF and Number of Subjects Censored by Visit Number of subjects censored at Week 8 (n=335,168)	3 Participants	0 Participants
Time to First Fluid-free Macula - Time-to-first Absence of Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) in the Study Eye - Number of Subjects With Absence of SRF / IRF and Number of Subjects Censored by Visit Number of subjects censored at Week 12 (n=314, 165)	4 Participants	2 Participants
Time to First Fluid-free Macula - Time-to-first Absence of Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) in the Study Eye - Number of Subjects With Absence of SRF / IRF and Number of Subjects Censored by Visit Number of subjects censored at Week 16 (n=297, 161)	3 Participants	1 Participants
Time to First Fluid-free Macula - Time-to-first Absence of Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) in the Study Eye - Number of Subjects With Absence of SRF / IRF and Number of Subjects Censored by Visit Number of subjects censored at Week 20 (n=277, 156)	4 Participants	0 Participants
Time to First Fluid-free Macula - Time-to-first Absence of Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) in the Study Eye - Number of Subjects With Absence of SRF / IRF and Number of Subjects Censored by Visit Number of subjects censored at Week 24 (n=265, 150)	3 Participants	2 Participants
Time to First Fluid-free Macula - Time-to-first Absence of Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) in the Study Eye - Number of Subjects With Absence of SRF / IRF and Number of Subjects Censored by Visit Number of subjects censored at Week 28 (n=246, 146)	4 Participants	0 Participants
Time to First Fluid-free Macula - Time-to-first Absence of Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) in the Study Eye - Number of Subjects With Absence of SRF / IRF and Number of Subjects Censored by Visit Number of subjects censored at Week 32 (n=224,139)	1 Participants	0 Participants
Time to First Fluid-free Macula - Time-to-first Absence of Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) in the Study Eye - Number of Subjects With Absence of SRF / IRF and Number of Subjects Censored by Visit Number of subjects censored at Week 36 (220, 138)	1 Participants	2 Participants
Time to First Fluid-free Macula - Time-to-first Absence of Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) in the Study Eye - Number of Subjects With Absence of SRF / IRF and Number of Subjects Censored by Visit Number of subjects censored at Week 40 (n=211,134)	1 Participants	1 Participants
Time to First Fluid-free Macula - Time-to-first Absence of Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) in the Study Eye - Number of Subjects With Absence of SRF / IRF and Number of Subjects Censored by Visit Number of subjects censored at Week 44 (n=194,129)	2 Participants	2 Participants
Time to First Fluid-free Macula - Time-to-first Absence of Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) in the Study Eye - Number of Subjects With Absence of SRF / IRF and Number of Subjects Censored by Visit Number of subjects censored at Week 48 (n=181, 125)	1 Participants	3 Participants
Time to First Fluid-free Macula - Time-to-first Absence of Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) in the Study Eye - Number of Subjects With Absence of SRF / IRF and Number of Subjects Censored by Visit Number of subjects censored at Week 52 (n=177, 122)	147 Participants	110 Participants

SECONDARY outcome

Timeframe: Baseline, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and 52

Population: Full Analysis Set. Time to first fluid-free macula analysis is based on the subset of subjects with fluid present at baseline and at least one post-baseline assessment.

Outcome measures

Outcome measures
Measure	Brolucizumab 6mg q4w n=344 Participants Brolucizumab 6 mg/0.05 mL every 4 weeks.	Aflibercept 2mg q4w n=170 Participants Aflibercept 2mg/0.05 mL every 4 weeks
Time to First Fluid-free Macula - Time-to-first Absence of Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) in the Study Eye - Kaplan-Meier Analysis - Probability of Absence of SRF/IRF by Visit Probability of absence of SRF/IRF at Week 0 (n=344,170)	0.000 Probability of absence of SRF/IRF CIs are not applicable for probability = 0.	0.000 Probability of absence of SRF/IRF CIs are not applicable for probability = 0.
Time to First Fluid-free Macula - Time-to-first Absence of Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) in the Study Eye - Kaplan-Meier Analysis - Probability of Absence of SRF/IRF by Visit Probability of absence of SRF/IRF at Week 4 (n=344,170)	0.018 Probability of absence of SRF/IRF Interval 0.007 to 0.036	0.006 Probability of absence of SRF/IRF Interval 0.001 to 0.03
Time to First Fluid-free Macula - Time-to-first Absence of Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) in the Study Eye - Kaplan-Meier Analysis - Probability of Absence of SRF/IRF by Visit Probability of absence of SRF/IRF at Week 8 (n=335,168)	0.071 Probability of absence of SRF/IRF Interval 0.047 to 0.101	0.024 Probability of absence of SRF/IRF Interval 0.008 to 0.056
Time to First Fluid-free Macula - Time-to-first Absence of Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) in the Study Eye - Kaplan-Meier Analysis - Probability of Absence of SRF/IRF by Visit Probability of absence of SRF/IRF at Week 12 (n=314, 165)	0.109 Probability of absence of SRF/IRF Interval 0.079 to 0.145	0.036 Probability of absence of SRF/IRF Interval 0.015 to 0.072
Time to First Fluid-free Macula - Time-to-first Absence of Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) in the Study Eye - Kaplan-Meier Analysis - Probability of Absence of SRF/IRF by Visit Probability of absence of SRF/IRF at Week 16 (n=297, 161)	0.161 Probability of absence of SRF/IRF Interval 0.124 to 0.202	0.060 Probability of absence of SRF/IRF Interval 0.03 to 0.103
Time to First Fluid-free Macula - Time-to-first Absence of Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) in the Study Eye - Kaplan-Meier Analysis - Probability of Absence of SRF/IRF by Visit Probability of absence of SRF/IRF at Week 20 (n=277, 156)	0.185 Probability of absence of SRF/IRF Interval 0.145 to 0.228	0.096 Probability of absence of SRF/IRF Interval 0.057 to 0.146
Time to First Fluid-free Macula - Time-to-first Absence of Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) in the Study Eye - Kaplan-Meier Analysis - Probability of Absence of SRF/IRF by Visit Probability of absence of SRF/IRF at Week 24 (n=265,150)	0.234 Probability of absence of SRF/IRF Interval 0.19 to 0.281	0.108 Probability of absence of SRF/IRF Interval 0.067 to 0.161
Time to First Fluid-free Macula - Time-to-first Absence of Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) in the Study Eye - Kaplan-Meier Analysis - Probability of Absence of SRF/IRF by Visit Probability of absence of SRF/IRF at Week 28 (n=246,146)	0.291 Probability of absence of SRF/IRF Interval 0.243 to 0.341	0.151 Probability of absence of SRF/IRF Interval 0.101 to 0.21
Time to First Fluid-free Macula - Time-to-first Absence of Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) in the Study Eye - Kaplan-Meier Analysis - Probability of Absence of SRF/IRF by Visit Probability of absence of SRF/IRF at Week 32 (n=224,139)	0.300 Probability of absence of SRF/IRF Interval 0.252 to 0.351	0.157 Probability of absence of SRF/IRF Interval 0.106 to 0.217
Time to First Fluid-free Macula - Time-to-first Absence of Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) in the Study Eye - Kaplan-Meier Analysis - Probability of Absence of SRF/IRF by Visit Probability of absence of SRF/IRF at Week 36 (n=220,138)	0.326 Probability of absence of SRF/IRF Interval 0.275 to 0.377	0.169 Probability of absence of SRF/IRF Interval 0.116 to 0.23
Time to First Fluid-free Macula - Time-to-first Absence of Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) in the Study Eye - Kaplan-Meier Analysis - Probability of Absence of SRF/IRF by Visit Probability of absence of SRF/IRF at Week 40 (n=211, 134)	0.377 Probability of absence of SRF/IRF Interval 0.324 to 0.43	0.194 Probability of absence of SRF/IRF Interval 0.137 to 0.258
Time to First Fluid-free Macula - Time-to-first Absence of Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) in the Study Eye - Kaplan-Meier Analysis - Probability of Absence of SRF/IRF by Visit Probability of absence of SRF/IRF at Week 44 (194, 129)	0.412 Probability of absence of SRF/IRF Interval 0.358 to 0.466	0.206 Probability of absence of SRF/IRF Interval 0.148 to 0.271
Time to First Fluid-free Macula - Time-to-first Absence of Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) in the Study Eye - Kaplan-Meier Analysis - Probability of Absence of SRF/IRF by Visit Probability of absence of SRF/IRF at Week 48 (n=181, 125)	0.422 Probability of absence of SRF/IRF Interval 0.368 to 0.476	0.206 Probability of absence of SRF/IRF Interval 0.148 to 0.271
Time to First Fluid-free Macula - Time-to-first Absence of Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) in the Study Eye - Kaplan-Meier Analysis - Probability of Absence of SRF/IRF by Visit Probability of absence of SRF/IRF at Week 52 (n=177, 122)	0.653 Probability of absence of SRF/IRF Interval 0.54 to 0.745	0.328 Probability of absence of SRF/IRF Interval 0.234 to 0.426

SECONDARY outcome

Timeframe: Baseline, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and 52

Population: Full Analysis Set

Central Subfield Thickness Assessed by Spectral domain optical coherence tomography (SD-OCT) from the central reading center. CSFT assessments after start of alternative DME treatment in the study eye are censored. Time to first absence of DME based on subjects with valid baseline and at least one post-baseline CSFT assessment. Time (week) was calculated by (study day / 7). Events and censoring after 52 weeks were included in week 52 row.

Outcome measures

Outcome measures
Measure	Brolucizumab 6mg q4w n=346 Participants Brolucizumab 6 mg/0.05 mL every 4 weeks.	Aflibercept 2mg q4w n=171 Participants Aflibercept 2mg/0.05 mL every 4 weeks
Time to First Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) in the Study Eye at Each Post-baseline Visit - Number of Subjects With Probability of Absence of DME and Number Censored by Visit Number censored at Week 24 (n=174,120)	1 Participants	1 Participants
Time to First Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) in the Study Eye at Each Post-baseline Visit - Number of Subjects With Probability of Absence of DME and Number Censored by Visit Number censored at Week 28 (n=161,115)	2 Participants	1 Participants
Time to First Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) in the Study Eye at Each Post-baseline Visit - Number of Subjects With Probability of Absence of DME and Number Censored by Visit Number censored at Week 32 (n=146,107)	2 Participants	0 Participants
Time to First Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) in the Study Eye at Each Post-baseline Visit - Number of Subjects With Probability of Absence of DME and Number Censored by Visit Number censored at Week 36 (n=135,102)	0 Participants	2 Participants
Time to First Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) in the Study Eye at Each Post-baseline Visit - Number of Subjects With Probability of Absence of DME and Number Censored by Visit Number censored at Week 40 (n=125, 98)	1 Participants	1 Participants
Time to First Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) in the Study Eye at Each Post-baseline Visit - Number of Subjects With Probability of Absence of DME and Number Censored by Visit Number censored at Week 44 (117, 96)	0 Participants	2 Participants
Time to First Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) in the Study Eye at Each Post-baseline Visit - Number of Subjects With Probability of Absence of DME and Number Censored by Visit Number of subjects with Probability of absence of DME at Week 0 (n=346,171)	0 Participants	0 Participants
Time to First Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) in the Study Eye at Each Post-baseline Visit - Number of Subjects With Probability of Absence of DME and Number Censored by Visit Number of subjects with Probability of absence of DME at Week 4 (n=346,171)	14 Participants	1 Participants
Time to First Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) in the Study Eye at Each Post-baseline Visit - Number of Subjects With Probability of Absence of DME and Number Censored by Visit Number of subjects with Probability of absence of DME at Week 8 (n=329,169)	54 Participants	12 Participants
Time to First Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) in the Study Eye at Each Post-baseline Visit - Number of Subjects With Probability of Absence of DME and Number Censored by Visit Number of subjects with Probability of absence of DME at Week 12 (n=272, 157)	32 Participants	13 Participants
Time to First Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) in the Study Eye at Each Post-baseline Visit - Number of Subjects With Probability of Absence of DME and Number Censored by Visit Number of subjects with Probability of absence of DME at Week 16 (n=239, 142)	33 Participants	11 Participants
Time to First Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) in the Study Eye at Each Post-baseline Visit - Number of Subjects With Probability of Absence of DME and Number Censored by Visit Number of subjects with Probability of absence of DME at Week 20 (n=204, 130)	26 Participants	10 Participants
Time to First Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) in the Study Eye at Each Post-baseline Visit - Number of Subjects With Probability of Absence of DME and Number Censored by Visit Number of subjects with Probability of absence of DME at Week 24 (n=174,120)	12 Participants	4 Participants
Time to First Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) in the Study Eye at Each Post-baseline Visit - Number of Subjects With Probability of Absence of DME and Number Censored by Visit Number of subjects with Probability of absence of DME at Week 28 (n=161,115)	13 Participants	7 Participants
Time to First Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) in the Study Eye at Each Post-baseline Visit - Number of Subjects With Probability of Absence of DME and Number Censored by Visit Number of subjects with Probability of absence of DME at Week 32 (n=146,107)	9 Participants	5 Participants
Time to First Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) in the Study Eye at Each Post-baseline Visit - Number of Subjects With Probability of Absence of DME and Number Censored by Visit Number of subjects with Probability of absence of DME at Week 36 (n=135,102)	10 Participants	2 Participants
Time to First Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) in the Study Eye at Each Post-baseline Visit - Number of Subjects With Probability of Absence of DME and Number Censored by Visit Number of subjects with Probability of absence of DME at Week 40 (n=125, 98)	7 Participants	1 Participants
Time to First Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) in the Study Eye at Each Post-baseline Visit - Number of Subjects With Probability of Absence of DME and Number Censored by Visit Number of subjects with Probability of absence of DME at Week 44 (117, 96)	11 Participants	2 Participants
Time to First Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) in the Study Eye at Each Post-baseline Visit - Number of Subjects With Probability of Absence of DME and Number Censored by Visit Number of subjects with Probability of absence of DME at Week 48 (n=106, 92)	6 Participants	3 Participants
Time to First Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) in the Study Eye at Each Post-baseline Visit - Number of Subjects With Probability of Absence of DME and Number Censored by Visit Number of subjects with Probability of absence of DME at Week 52 (n=99, 88)	13 Participants	4 Participants
Time to First Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) in the Study Eye at Each Post-baseline Visit - Number of Subjects With Probability of Absence of DME and Number Censored by Visit Number censored at Week 0 (n=346,171)	0 Participants	0 Participants
Time to First Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) in the Study Eye at Each Post-baseline Visit - Number of Subjects With Probability of Absence of DME and Number Censored by Visit Number censored at Week 4 (n=346,171)	3 Participants	1 Participants
Time to First Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) in the Study Eye at Each Post-baseline Visit - Number of Subjects With Probability of Absence of DME and Number Censored by Visit Number censored at Week 8 (n=329,169)	3 Participants	0 Participants
Time to First Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) in the Study Eye at Each Post-baseline Visit - Number of Subjects With Probability of Absence of DME and Number Censored by Visit Number censored at Week 12 (n=272, 157)	1 Participants	2 Participants
Time to First Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) in the Study Eye at Each Post-baseline Visit - Number of Subjects With Probability of Absence of DME and Number Censored by Visit Number censored at Week 16 (n=239, 142)	2 Participants	1 Participants
Time to First Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) in the Study Eye at Each Post-baseline Visit - Number of Subjects With Probability of Absence of DME and Number Censored by Visit Number censored at Week 20 (n=204, 130)	4 Participants	0 Participants
Time to First Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) in the Study Eye at Each Post-baseline Visit - Number of Subjects With Probability of Absence of DME and Number Censored by Visit Number censored at Week 48 (n=106, 92)	1 Participants	1 Participants
Time to First Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) in the Study Eye at Each Post-baseline Visit - Number of Subjects With Probability of Absence of DME and Number Censored by Visit Number censored at Week 52 (n=99, 88)	86 Participants	84 Participants

SECONDARY outcome

Timeframe: Baseline, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and 52

Population: Full Analysis Set

Outcome measures

Outcome measures
Measure	Brolucizumab 6mg q4w n=346 Participants Brolucizumab 6 mg/0.05 mL every 4 weeks.	Aflibercept 2mg q4w n=171 Participants Aflibercept 2mg/0.05 mL every 4 weeks
Time to First Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) in the Study Eye at Each Post-baseline Visit - Kaplan-Meier Analysis - Probability of Absence of DME by Visit Probability of absence of DME at Week 0 (n=346,171)	0.000 Probability of absence of DME CIs are not applicable when the probability = 0.	0.000 Probability of absence of DME CIs are not applicable when the probability = 0.
Time to First Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) in the Study Eye at Each Post-baseline Visit - Kaplan-Meier Analysis - Probability of Absence of DME by Visit Probability of absence of DME at Week 4 (n=346,171)	0.041 Probability of absence of DME Interval 0.023 to 0.066	0.006 Probability of absence of DME Interval 0.001 to 0.03
Time to First Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) in the Study Eye at Each Post-baseline Visit - Kaplan-Meier Analysis - Probability of Absence of DME by Visit Probability of absence of DME at Week 8 (n=329,169)	0.199 Probability of absence of DME Interval 0.158 to 0.243	0.076 Probability of absence of DME Interval 0.043 to 0.123
Time to First Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) in the Study Eye at Each Post-baseline Visit - Kaplan-Meier Analysis - Probability of Absence of DME by Visit Probability of absence of DME at Week 12 (n=272, 157)	0.293 Probability of absence of DME Interval 0.246 to 0.342	0.153 Probability of absence of DME Interval 0.104 to 0.212
Time to First Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) in the Study Eye at Each Post-baseline Visit - Kaplan-Meier Analysis - Probability of Absence of DME by Visit Probability of absence of DME at Week 16 (n=239, 142)	0.391 Probability of absence of DME Interval 0.339 to 0.443	0.219 Probability of absence of DME Interval 0.16 to 0.284
Time to First Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) in the Study Eye at Each Post-baseline Visit - Kaplan-Meier Analysis - Probability of Absence of DME by Visit Probability of absence of DME at Week 20 (n=204, 130)	0.470 Probability of absence of DME Interval 0.416 to 0.522	0.279 Probability of absence of DME Interval 0.213 to 0.348
Time to First Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) in the Study Eye at Each Post-baseline Visit - Kaplan-Meier Analysis - Probability of Absence of DME by Visit Probability of absence of DME at Week 24 (n=174,120)	0.506 Probability of absence of DME Interval 0.452 to 0.559	0.303 Probability of absence of DME Interval 0.235 to 0.374
Time to First Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) in the Study Eye at Each Post-baseline Visit - Kaplan-Meier Analysis - Probability of Absence of DME by Visit Probability of absence of DME at Week 28 (n=161,115)	0.547 Probability of absence of DME Interval 0.491 to 0.598	0.346 Probability of absence of DME Interval 0.274 to 0.418
Time to First Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) in the Study Eye at Each Post-baseline Visit - Kaplan-Meier Analysis - Probability of Absence of DME by Visit Probability of absence of DME at Week 32 (n=146,107)	0.575 Probability of absence of DME Interval 0.52 to 0.626	0.376 Probability of absence of DME Interval 0.303 to 0.45
Time to First Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) in the Study Eye at Each Post-baseline Visit - Kaplan-Meier Analysis - Probability of Absence of DME by Visit Probability of absence of DMEE at Week 36 (n=135,102)	0.606 Probability of absence of DME Interval 0.551 to 0.657	0.389 Probability of absence of DME Interval 0.314 to 0.462
Time to First Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) in the Study Eye at Each Post-baseline Visit - Kaplan-Meier Analysis - Probability of Absence of DME by Visit Probability of absence of DME at Week 40 (n=125, 98)	0.628 Probability of absence of DME Interval 0.574 to 0.678	0.395 Probability of absence of DME Interval 0.32 to 0.468
Time to First Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) in the Study Eye at Each Post-baseline Visit - Kaplan-Meier Analysis - Probability of Absence of DME by Visit Probability of absence of DME at Week 44 (117, 96)	0.663 Probability of absence of DME Interval 0.609 to 0.712	0.408 Probability of absence of DME Interval 0.332 to 0.482
Time to First Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) in the Study Eye at Each Post-baseline Visit - Kaplan-Meier Analysis - Probability of Absence of DME by Visit Probability of absence of DME at Week 48 (n=106, 92)	0.682 Probability of absence of DME Interval 0.629 to 0.73	0.427 Probability of absence of DME Interval 0.351 to 0.501
Time to First Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) in the Study Eye at Each Post-baseline Visit - Kaplan-Meier Analysis - Probability of Absence of DME by Visit Probability of absence of DME at Week 52 (n=99, 88)	0.866 Probability of absence of DME Interval 0.302 to 0.983	0.516 Probability of absence of DME Interval 0.357 to 0.654

SECONDARY outcome

Timeframe: Baseline, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and 52

Population: Full analysis set (FAS) - Last observation carried forward (LOCF)

Outcome measures

Outcome measures
Measure	Brolucizumab 6mg q4w n=346 Participants Brolucizumab 6 mg/0.05 mL every 4 weeks.	Aflibercept 2mg q4w n=171 Participants Aflibercept 2mg/0.05 mL every 4 weeks
Best Corrected Visual Acuity (Letters Read): Change From Baseline in Best-corrected Visual Acuity (BCVA) at Each Post-baseline Visit for the Study Eye Week 4	5.7 scores on a scale Interval 5.1 to 6.4	5.4 scores on a scale Interval 4.5 to 6.4
Best Corrected Visual Acuity (Letters Read): Change From Baseline in Best-corrected Visual Acuity (BCVA) at Each Post-baseline Visit for the Study Eye Week 8	7.7 scores on a scale Interval 6.9 to 8.5	7.4 scores on a scale Interval 6.4 to 8.5
Best Corrected Visual Acuity (Letters Read): Change From Baseline in Best-corrected Visual Acuity (BCVA) at Each Post-baseline Visit for the Study Eye Week 12	9.1 scores on a scale Interval 8.3 to 9.9	8.0 scores on a scale Interval 6.9 to 9.1
Best Corrected Visual Acuity (Letters Read): Change From Baseline in Best-corrected Visual Acuity (BCVA) at Each Post-baseline Visit for the Study Eye Week 16	9.6 scores on a scale Interval 8.8 to 10.4	8.5 scores on a scale Interval 7.3 to 9.7
Best Corrected Visual Acuity (Letters Read): Change From Baseline in Best-corrected Visual Acuity (BCVA) at Each Post-baseline Visit for the Study Eye Week 20	10.2 scores on a scale Interval 9.3 to 11.1	9.2 scores on a scale Interval 7.9 to 10.5
Best Corrected Visual Acuity (Letters Read): Change From Baseline in Best-corrected Visual Acuity (BCVA) at Each Post-baseline Visit for the Study Eye Week 24	10.7 scores on a scale Interval 9.8 to 11.6	9.6 scores on a scale Interval 8.3 to 10.9
Best Corrected Visual Acuity (Letters Read): Change From Baseline in Best-corrected Visual Acuity (BCVA) at Each Post-baseline Visit for the Study Eye Week 28	10.9 scores on a scale Interval 10.0 to 11.8	10.7 scores on a scale Interval 9.3 to 12.0
Best Corrected Visual Acuity (Letters Read): Change From Baseline in Best-corrected Visual Acuity (BCVA) at Each Post-baseline Visit for the Study Eye Week 32	11.5 scores on a scale Interval 10.6 to 12.5	10.5 scores on a scale Interval 9.2 to 11.9
Best Corrected Visual Acuity (Letters Read): Change From Baseline in Best-corrected Visual Acuity (BCVA) at Each Post-baseline Visit for the Study Eye Week 36	11.6 scores on a scale Interval 10.6 to 12.6	10.8 scores on a scale Interval 9.4 to 12.2
Best Corrected Visual Acuity (Letters Read): Change From Baseline in Best-corrected Visual Acuity (BCVA) at Each Post-baseline Visit for the Study Eye Week 40	11.7 scores on a scale Interval 10.7 to 12.6	10.7 scores on a scale Interval 9.4 to 12.1
Best Corrected Visual Acuity (Letters Read): Change From Baseline in Best-corrected Visual Acuity (BCVA) at Each Post-baseline Visit for the Study Eye Week 44	12.0 scores on a scale Interval 11.0 to 13.0	10.6 scores on a scale Interval 9.2 to 12.0
Best Corrected Visual Acuity (Letters Read): Change From Baseline in Best-corrected Visual Acuity (BCVA) at Each Post-baseline Visit for the Study Eye Week 48	12.2 scores on a scale Interval 11.2 to 13.2	10.7 scores on a scale Interval 9.3 to 12.1
Best Corrected Visual Acuity (Letters Read): Change From Baseline in Best-corrected Visual Acuity (BCVA) at Each Post-baseline Visit for the Study Eye Week 52	12.2 scores on a scale Interval 11.2 to 13.2	11.0 scores on a scale Interval 9.6 to 12.4

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Full analysis set (FAS) - Last observation carried forward (LOCF)

Outcome measures

Outcome measures
Measure	Brolucizumab 6mg q4w n=346 Participants Brolucizumab 6 mg/0.05 mL every 4 weeks.	Aflibercept 2mg q4w n=171 Participants Aflibercept 2mg/0.05 mL every 4 weeks
Gain in Best-corrected Visual Acuity (BCVA) (Letters Read): Number (%) of Subjects Who Gained ≥ 5, 10, or 15 Letters in BCVA From Baseline or Reached BCVA ≥ 84 Letters in the Study Eye at Week 52 ≥ 15 letters gain from baseline or BCVA ≥ 84 letters at Week 52	151 Participants Interval 38.3 to 49.0	69 Participants Interval 32.9 to 48.1
Gain in Best-corrected Visual Acuity (BCVA) (Letters Read): Number (%) of Subjects Who Gained ≥ 5, 10, or 15 Letters in BCVA From Baseline or Reached BCVA ≥ 84 Letters in the Study Eye at Week 52 ≥ 5 letters gain from baseline or BCVA ≥ 84 letters at Week 52	286 Participants Interval 78.2 to 86.5	127 Participants Interval 67.0 to 80.6
Gain in Best-corrected Visual Acuity (BCVA) (Letters Read): Number (%) of Subjects Who Gained ≥ 5, 10, or 15 Letters in BCVA From Baseline or Reached BCVA ≥ 84 Letters in the Study Eye at Week 52 ≥ 10 letters gain from baseline or BCVA ≥ 84 letters at Week 52	211 Participants Interval 55.6 to 66.2	95 Participants Interval 47.8 to 63.1

SECONDARY outcome

Timeframe: Baseline, Weeks 12, 24 and 52

Population: Full analysis set (FAS) - Last observation carried forward (LOCF). Subjects who had full/partial panretinal photocoagulation or local photocoagulation for new vessel (DRSS score 60) at any visit were excluded from analysis. DRSS scores after start of alternative DME treatment in the study eye are censored and replaced by the last value prior to start of this alternative treatment.

The Diabetic Retinopathy Disease Severity Scale measures the 5 levels of diabetic retinopathy - none, mild, moderate, severe, and proliferative. Severity of Diabetic retinopathy was evaluated using the ETDRS DRSS score assessed by the Central Reading Center based on color fundus photography images in the study eye. When the ETDRS-DR severities were evaluable, they were categorized on the original scale with scores varying from 10 (DR absent) to 85 (very advanced PDR). All DRSS values were then converted into a 12-level scale, allowing the derivation of the ≥2-step and ≥3-step change from baseline for each post-baseline assessment". A lower score represents better functioning. Subjects who had full/partial panretinal photocoagulation or local photocoagulation for new vessel (DRSS score 60) at any visit were excluded. DRSS scores after start of alternative DME treatment in the study eye are censored and replaced by the last value prior to start of this alternative treatment.

Outcome measures

Outcome measures
Measure	Brolucizumab 6mg q4w n=221 Participants Brolucizumab 6 mg/0.05 mL every 4 weeks.	Aflibercept 2mg q4w n=118 Participants Aflibercept 2mg/0.05 mL every 4 weeks
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 Week 12	56 Participants	21 Participants
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 Week 24	82 Participants	38 Participants
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 Week 52	95 Participants	45 Participants

SECONDARY outcome

Timeframe: Baseline, Weeks 12, 24 and 52

Outcome measures

Outcome measures
Measure	Brolucizumab 6mg q4w n=221 Participants Brolucizumab 6 mg/0.05 mL every 4 weeks.	Aflibercept 2mg q4w n=118 Participants Aflibercept 2mg/0.05 mL every 4 weeks
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 Week 12	18 Participants	8 Participants
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 Week 24	33 Participants	16 Participants
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 Week 52	40 Participants	18 Participants

SECONDARY outcome

Timeframe: Baseline

Population: Safety Set

Outcome measures

Outcome measures
Measure	Brolucizumab 6mg q4w n=342 Participants Brolucizumab 6 mg/0.05 mL every 4 weeks.	Aflibercept 2mg q4w Aflibercept 2mg/0.05 mL every 4 weeks
Anti-Drug Antibody (ADA): Frequency Distribution of Pre-existing ADA Status in the Brolucizumab Arm Negative	112 Participants	—
Anti-Drug Antibody (ADA): Frequency Distribution of Pre-existing ADA Status in the Brolucizumab Arm Positive	230 Participants	—

SECONDARY outcome

Timeframe: Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 52 weeks.

Population: Safety Set

Outcome measures

Outcome measures
Measure	Brolucizumab 6mg q4w n=346 Participants Brolucizumab 6 mg/0.05 mL every 4 weeks.	Aflibercept 2mg q4w n=171 Participants Aflibercept 2mg/0.05 mL every 4 weeks
Ocular AEs (Greater Than or Equal to 2% in Any Treatment Arm) by Preferred Term in the Study Eye Vitreous floaters	8 Participants	5 Participants
Ocular AEs (Greater Than or Equal to 2% in Any Treatment Arm) by Preferred Term in the Study Eye Dry eye	7 Participants	4 Participants
Ocular AEs (Greater Than or Equal to 2% in Any Treatment Arm) by Preferred Term in the Study Eye Eye pain	6 Participants	5 Participants
Ocular AEs (Greater Than or Equal to 2% in Any Treatment Arm) by Preferred Term in the Study Eye Corneal abrasion	0 Participants	5 Participants
Ocular AEs (Greater Than or Equal to 2% in Any Treatment Arm) by Preferred Term in the Study Eye Diabetic retinal oedema	0 Participants	4 Participants
Ocular AEs (Greater Than or Equal to 2% in Any Treatment Arm) by Preferred Term in the Study Eye Number of subjects with at least one AE	105 Participants	59 Participants
Ocular AEs (Greater Than or Equal to 2% in Any Treatment Arm) by Preferred Term in the Study Eye Vitreous detachment	10 Participants	7 Participants
Ocular AEs (Greater Than or Equal to 2% in Any Treatment Arm) by Preferred Term in the Study Eye Cataract	9 Participants	6 Participants
Ocular AEs (Greater Than or Equal to 2% in Any Treatment Arm) by Preferred Term in the Study Eye Conjunctival haemorrhage	9 Participants	7 Participants
Ocular AEs (Greater Than or Equal to 2% in Any Treatment Arm) by Preferred Term in the Study Eye Punctate keratitis	9 Participants	2 Participants
Ocular AEs (Greater Than or Equal to 2% in Any Treatment Arm) by Preferred Term in the Study Eye Uveitis	8 Participants	1 Participants

SECONDARY outcome

Timeframe: Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 52 weeks.

Population: Safety Set

Outcome measures

Outcome measures
Measure	Brolucizumab 6mg q4w n=346 Participants Brolucizumab 6 mg/0.05 mL every 4 weeks.	Aflibercept 2mg q4w n=171 Participants Aflibercept 2mg/0.05 mL every 4 weeks
Number of Subjects With Non-ocular AEs (Greater Than or Equal to 2% in Any Treatment Arm)	209 Participants	96 Participants

Adverse Events

Brolucizumab 6mg

Serious events: 74 serious events

Other events: 144 other events

Deaths: 7 deaths

Aflibercept 2mg

Serious events: 36 serious events

Other events: 92 other events

Deaths: 5 deaths

Overall

Serious events: 110 serious events

Other events: 236 other events

Deaths: 12 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: + 1 862 778 8300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER