Trial Outcomes & Findings for To Compare Brolucizumab to Aflibercept in Chinese Patients With Visual Impairment Due to Diabetic Macular Edema (NCT NCT04058067)

NCT ID: NCT04058067

Last Updated: 2024-10-09

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 266 participants
• Primary outcome timeframe: Baseline to Week 52
• Results posted on: 2024-10-09

Participant Flow

Participant milestones

Measure	Brolucizumab 6 mg 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2 mg 5 x every 4 weeks loading then every 8 weeks maintenance
Overall Study STARTED	132	131
Overall Study COMPLETED	120	120
Overall Study NOT COMPLETED	12	11

Reasons for withdrawal

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

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

Baseline characteristics by cohort

Measure	Brolucizumab 6 mg n=132 Participants 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2 mg n=131 Participants 5 x every 4 weeks loading then every 8 weeks maintenance	Total n=263 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	85 Participants n=5 Participants	88 Participants n=7 Participants	173 Participants n=5 Participants
Age, Categorical >=65 years	47 Participants n=5 Participants	43 Participants n=7 Participants	90 Participants n=5 Participants
Age, Continuous	60.5 Years STANDARD_DEVIATION 9.20 • n=5 Participants	58.7 Years STANDARD_DEVIATION 9.92 • n=7 Participants	59.6 Years STANDARD_DEVIATION 9.59 • n=5 Participants
Sex: Female, Male Female	62 Participants n=5 Participants	60 Participants n=7 Participants	122 Participants n=5 Participants
Sex: Female, Male Male	70 Participants n=5 Participants	71 Participants n=7 Participants	141 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	132 Participants n=5 Participants	131 Participants n=7 Participants	263 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to Week 52

Population: Full Analysis Set- last observation carried forward (FAS - LOCF)

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.

Outcome measures

Measure	Brolucizumab 6 mg n=132 Participants 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2 mg n=131 Participants 5 x every 4 weeks loading then every 8 weeks maintenance
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	11.9 Scores on a scale Standard Error 0.85

PRIMARY outcome

Timeframe: Week 40 to Week 52

Population: Full Analysis Set- last observation carried forward (FAS - LOCF)

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.

Outcome measures

Measure	Brolucizumab 6 mg n=132 Participants 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2 mg n=131 Participants 5 x every 4 weeks loading then every 8 weeks maintenance
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	12.0 Scores on a scale Standard Error 0.82

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Brolucizumab 6 mg n=132 Participants 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2 mg n=131 Participants 5 x every 4 weeks loading then every 8 weeks maintenance
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	11.3 Scores on a scale Standard Deviation 10.12
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	4.4 Scores on a scale Standard Deviation 6.75
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	6.6 Scores on a scale Standard Deviation 7.50
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	8.0 Scores on a scale Standard Deviation 8.56
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	9.0 Scores on a scale Standard Deviation 9.67
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	10.4 Scores on a scale Standard Deviation 9.86
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	10.7 Scores on a scale Standard Deviation 10.25
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	11.3 Scores on a scale Standard Deviation 9.57
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	10.5 Scores on a scale Standard Deviation 9.80
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	10.9 Scores on a scale Standard Deviation 10.13
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	11.8 Scores on a scale Standard Deviation 10.62
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	11.7 Scores on a scale Standard Deviation 10.02
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	12.2 Scores on a scale Standard Deviation 9.79
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	12.2 Scores on a scale Standard Deviation 10.71
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	12.1 Scores on a scale Standard Deviation 10.92

SECONDARY outcome

Timeframe: Week 4 to Week 52

Population: Full Analysis Set- last observation carried forward (FAS - LOCF)

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.

Outcome measures

Measure	Brolucizumab 6 mg n=132 Participants 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2 mg n=131 Participants 5 x every 4 weeks loading then every 8 weeks maintenance
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	10.1 Scores on a scale Standard Error 0.68

SECONDARY outcome

Timeframe: Week 20 to Week 52

Population: Full Analysis Set- last observation carried forward (FAS - LOCF)

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.

Outcome measures

Measure	Brolucizumab 6 mg n=132 Participants 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2 mg n=131 Participants 5 x every 4 weeks loading then every 8 weeks maintenance
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	11.5 Scores on a scale Standard Error 0.77

SECONDARY outcome

Timeframe: Week 28 to Week 52

Population: Full Analysis Set- last observation carried forward (FAS - LOCF)

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.

Outcome measures

Measure	Brolucizumab 6 mg n=132 Participants 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2 mg n=131 Participants 5 x every 4 weeks loading then every 8 weeks maintenance
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 0.80	11.7 Scores on a scale Standard Error 0.80

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 32, Week 36 and Week 48

Population: FAS - Efficacy/Safety approach

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.

Outcome measures

Measure	Brolucizumab 6 mg n=132 Participants 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2 mg 5 x every 4 weeks loading then every 8 weeks maintenance
Time-to-first q8w Treatment Need: Summary for Brolucizumab Subjects by Disease Activity Assessment Visit Week 0	1 Probability Not applicable for probability of 1	—
Time-to-first q8w Treatment Need: Summary for Brolucizumab Subjects by Disease Activity Assessment Visit Week 32 (n=86,0)	0.733 Probability Interval 0.626 to 0.813	—
Time-to-first q8w Treatment Need: Summary for Brolucizumab Subjects by Disease Activity Assessment Visit Week36 (n=59,0)	0.447 Probability Interval 0.338 to 0.55	—
Time-to-first q8w Treatment Need: Summary for Brolucizumab Subjects by Disease Activity Assessment Visit Week48 (n=30,0)	0.417 Probability Interval 0.309 to 0.522	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Brolucizumab 6 mg n=35 Participants 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2 mg 5 x every 4 weeks loading then every 8 weeks maintenance
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 Interval 0.751 to 0.982	—
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 Not applicable for probability of 1	—

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Full Analysis Set- last observation carried forward (FAS - LOCF)

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.

Outcome measures

Measure	Brolucizumab 6 mg n=132 Participants 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2 mg n=131 Participants 5 x every 4 weeks loading then every 8 weeks maintenance
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	76 Participants
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	104 Participants
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	48 Participants

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: Full Analysis Set

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.

Outcome measures

Measure	Brolucizumab 6 mg n=132 Participants 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2 mg n=131 Participants 5 x every 4 weeks loading then every 8 weeks maintenance
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 Interval 0.084 to 0.201	0.038 Probability of BCVA gain Interval 0.014 to 0.081
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 Interval 0.419 to 0.589	0.420 Probability of BCVA gain Interval 0.334 to 0.503
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 Interval 0.634 to 0.789	0.634 Probability of BCVA gain Interval 0.544 to 0.71
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 Interval 0.699 to 0.842	0.725 Probability of BCVA gain Interval 0.639 to 0.794
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 Interval 0.74 to 0.875	0.780 Probability of BCVA gain Interval 0.697 to 0.842
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 Interval 0.74 to 0.875	0.843 Probability of BCVA gain Interval 0.766 to 0.896
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 Interval 0.765 to 0.894	0.866 Probability of BCVA gain Interval 0.793 to 0.915
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 Interval 0.782 to 0.906	0.874 Probability of BCVA gain Interval 0.802 to 0.921
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 Interval 0.791 to 0.913	0.882 Probability of BCVA gain Interval 0.811 to 0.928
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 Interval 0.818 to 0.932	0.882 Probability of BCVA gain Interval 0.811 to 0.928
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 Interval 0.818 to 0.932	0.882 Probability of BCVA gain Interval 0.811 to 0.928
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 Interval 0.818 to 0.932	0.908 Probability of BCVA gain Interval 0.84 to 0.948
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 Interval 0.828 to 0.938	0.908 Probability of BCVA gain Interval 0.84 to 0.948
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 Interval 0.846 to 0.951	0.917 Probability of BCVA gain Interval 0.85 to 0.955
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 Interval 0.88 to 0.985	0.926 Probability of BCVA gain Interval 0.86 to 0.962

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: Full Analysis Set

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.

Outcome measures

Measure	Brolucizumab 6 mg n=132 Participants 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2 mg n=131 Participants 5 x every 4 weeks loading then every 8 weeks maintenance
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 Interval 0.028 to 0.11	0.000 Probability of BCVA gain CI is NA when probability is 0.
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 Interval 0.553 to 0.719	0.664 Probability of BCVA gain Interval 0.573 to 0.739
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 Interval 0.57 to 0.735	0.680 Probability of BCVA gain Interval 0.59 to 0.754
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 Interval 0.16 to 0.302	0.198 Probability of BCVA gain Interval 0.135 to 0.271
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 Interval 0.31 to 0.476	0.306 Probability of BCVA gain Interval 0.229 to 0.386
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 Interval 0.419 to 0.59	0.439 Probability of BCVA gain Interval 0.352 to 0.523
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 Interval 0.472 to 0.642	0.527 Probability of BCVA gain Interval 0.436 to 0.609
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 Interval 0.504 to 0.673	0.551 Probability of BCVA gain Interval 0.46 to 0.633
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 Interval 0.528 to 0.696	0.591 Probability of BCVA gain Interval 0.5 to 0.671
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 Interval 0.587 to 0.75	0.705 Probability of BCVA gain Interval 0.616 to 0.777
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 Interval 0.604 to 0.766	0.722 Probability of BCVA gain Interval 0.634 to 0.793
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 Interval 0.622 to 0.782	0.730 Probability of BCVA gain Interval 0.642 to 0.8
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 Interval 0.64 to 0.798	0.739 Probability of BCVA gain Interval 0.652 to 0.808
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 Interval 0.667 to 0.822	0.749 Probability of BCVA gain Interval 0.661 to 0.817
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 Interval 0.416 to 0.987	1 Probability of BCVA gain CI is NA when probability = 1.

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: Full Analysis Set

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.

Outcome measures

Measure	Brolucizumab 6 mg n=132 Participants 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2 mg n=131 Participants 5 x every 4 weeks loading then every 8 weeks maintenance
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 Interval 0.16 to 0.302	0.216 Probability of BCVA gain Interval 0.149 to 0.29
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 Interval 0.193 to 0.343	0.255 Probability of BCVA gain Interval 0.183 to 0.333
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 Interval 0.001 to 0.038	0.000 Probability of BCVA gain CI is NA when probability = 0.
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 Interval 0.044 to 0.138	0.069 Probability of BCVA gain Interval 0.034 to 0.121
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 Interval 0.096 to 0.218	0.161 Probability of BCVA gain Interval 0.104 to 0.229
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 Interval 0.235 to 0.393	0.319 Probability of BCVA gain Interval 0.24 to 0.401
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 Interval 0.264 to 0.426	0.359 Probability of BCVA gain Interval 0.276 to 0.442
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 Interval 0.323 to 0.492	0.399 Probability of BCVA gain Interval 0.313 to 0.483
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 Interval 0.338 to 0.509	0.432 Probability of BCVA gain Interval 0.344 to 0.516
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 Interval 0.37 to 0.544	0.456 Probability of BCVA gain Interval 0.367 to 0.541
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 Interval 0.395 to 0.57	0.481 Probability of BCVA gain Interval 0.391 to 0.566
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 Interval 0.403 to 0.579	0.506 Probability of BCVA gain Interval 0.415 to 0.59
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 Interval 0.42 to 0.596	0.531 Probability of BCVA gain Interval 0.439 to 0.614
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 Interval 0.446 to 0.622	0.540 Probability of BCVA gain Interval 0.447 to 0.623
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 Interval 0.436 to 0.763	1 Probability of BCVA gain CI is NA when probability = 1.

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Full Analysis Set- last observation carried forward (FAS - LOCF)

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.

Outcome measures

Measure	Brolucizumab 6 mg n=132 Participants 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2 mg n=131 Participants 5 x every 4 weeks loading then every 8 weeks maintenance
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	4 Participants
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	1 Participants
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	1 Participants

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: Full Analysis Set - LOCF

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.

Outcome measures

Measure	Brolucizumab 6 mg n=132 Participants 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2 mg n=131 Participants 5 x every 4 weeks loading then every 8 weeks maintenance
Proportion of Patients Who Have Absolute BCVA ≥73 ETDRS Letters at Each Post-baseline Visit for the Study Eye Week 16	50 Participants	67 Participants
Proportion of Patients Who Have Absolute BCVA ≥73 ETDRS Letters at Each Post-baseline Visit for the Study Eye Week 44	53 Participants	76 Participants
Proportion of Patients Who Have Absolute BCVA ≥73 ETDRS Letters at Each Post-baseline Visit for the Study Eye Week 52	55 Participants	75 Participants
Proportion of Patients Who Have Absolute BCVA ≥73 ETDRS Letters at Each Post-baseline Visit for the Study Eye Week 32	51 Participants	74 Participants
Proportion of Patients Who Have Absolute BCVA ≥73 ETDRS Letters at Each Post-baseline Visit for the Study Eye Week 36	49 Participants	77 Participants
Proportion of Patients Who Have Absolute BCVA ≥73 ETDRS Letters at Each Post-baseline Visit for the Study Eye Week 40	53 Participants	81 Participants
Proportion of Patients Who Have Absolute BCVA ≥73 ETDRS Letters at Each Post-baseline Visit for the Study Eye Week 48	57 Participants	78 Participants
Proportion of Patients Who Have Absolute BCVA ≥73 ETDRS Letters at Each Post-baseline Visit for the Study Eye Week 4	32 Participants	34 Participants
Proportion of Patients Who Have Absolute BCVA ≥73 ETDRS Letters at Each Post-baseline Visit for the Study Eye Week 6	36 Participants	46 Participants
Proportion of Patients Who Have Absolute BCVA ≥73 ETDRS Letters at Each Post-baseline Visit for the Study Eye Week 8	46 Participants	55 Participants
Proportion of Patients Who Have Absolute BCVA ≥73 ETDRS Letters at Each Post-baseline Visit for the Study Eye Week 12	50 Participants	63 Participants
Proportion of Patients Who Have Absolute BCVA ≥73 ETDRS Letters at Each Post-baseline Visit for the Study Eye Week 18	51 Participants	68 Participants
Proportion of Patients Who Have Absolute BCVA ≥73 ETDRS Letters at Each Post-baseline Visit for the Study Eye Week 20	54 Participants	65 Participants
Proportion of Patients Who Have Absolute BCVA ≥73 ETDRS Letters at Each Post-baseline Visit for the Study Eye Week 24	53 Participants	74 Participants
Proportion of Patients Who Have Absolute BCVA ≥73 ETDRS Letters at Each Post-baseline Visit for the Study Eye Week 28	52 Participants	72 Participants

SECONDARY outcome

Timeframe: Week 32

Population: Full Analysis Set - Observed (Patients with a valid observed value for the outcome measure.)

To evaluate the efficacy related to dosing regimen of brolucizumab

Outcome measures

Measure	Brolucizumab 6 mg n=107 Participants 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2 mg n=115 Participants 5 x every 4 weeks loading then every 8 weeks maintenance
Number (%) of Subjects With q8w Treatment Need as Assessed by the Investigator at First Disease Activity Assessment (DAA) Visit - Week 32	34 Participants	38 Participants

SECONDARY outcome

Timeframe: Week 36, Week 48

Population: Full Analysis Set - Observed

To evaluate the efficacy related to dosing regimen of brolucizumab

Outcome measures

Measure	Brolucizumab 6 mg n=105 Participants 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2 mg n=113 Participants 5 x every 4 weeks loading then every 8 weeks maintenance
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	32 Participants
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	32 Participants

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Full Analysis Set- last observation carried forward (FAS - LOCF)

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

Outcome measures

Measure	Brolucizumab 6 mg n=132 Participants 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2 mg n=131 Participants 5 x every 4 weeks loading then every 8 weeks maintenance
Change From Baseline at Week 52 in Central Subfield Thickness (CSFT) for the Study Eye	-225.2 micrometer Standard Error 9.71	-215.0 micrometer Standard Error 9.75

SECONDARY outcome

Timeframe: Baseline, over the period of Week 40 to Week 52

Population: Full Analysis Set- last observation carried forward (FAS - LOCF)

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

Outcome measures

Measure	Brolucizumab 6 mg n=132 Participants 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2 mg n=131 Participants 5 x every 4 weeks loading then every 8 weeks maintenance
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	-212.7 micrometer Standard Error 8.73

SECONDARY outcome

Timeframe: Baseline, over the period of Week 4 to Week 52

Population: Full Analysis Set- last observation carried forward (FAS - LOCF)

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

Outcome measures

Measure	Brolucizumab 6 mg n=132 Participants 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2 mg n=131 Participants 5 x every 4 weeks loading then every 8 weeks maintenance
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	-199.2 micrometer Standard Error 7.80

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: Full Analysis Set - LOCF

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

Outcome measures

Measure	Brolucizumab 6 mg n=132 Participants 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2 mg n=131 Participants 5 x every 4 weeks loading then every 8 weeks maintenance
Number and Percentage of Patients Who Have CSFT (<280 Microns) at Each Assessment Visit for the Study Eye Week 52	79 Participants	56 Participants
Number and Percentage of Patients Who Have CSFT (<280 Microns) at Each Assessment Visit for the Study Eye Week 48	68 Participants	52 Participants
Number and Percentage of Patients Who Have CSFT (<280 Microns) at Each Assessment Visit for the Study Eye Week 4	24 Participants	17 Participants
Number and Percentage of Patients Who Have CSFT (<280 Microns) at Each Assessment Visit for the Study Eye Week 6	36 Participants	22 Participants
Number and Percentage of Patients Who Have CSFT (<280 Microns) at Each Assessment Visit for the Study Eye Week 8	48 Participants	29 Participants
Number and Percentage of Patients Who Have CSFT (<280 Microns) at Each Assessment Visit for the Study Eye Week 12	52 Participants	33 Participants
Number and Percentage of Patients Who Have CSFT (<280 Microns) at Each Assessment Visit for the Study Eye Week 16	63 Participants	41 Participants
Number and Percentage of Patients Who Have CSFT (<280 Microns) at Each Assessment Visit for the Study Eye Week 18	61 Participants	41 Participants
Number and Percentage of Patients Who Have CSFT (<280 Microns) at Each Assessment Visit for the Study Eye Week 20	67 Participants	46 Participants
Number and Percentage of Patients Who Have CSFT (<280 Microns) at Each Assessment Visit for the Study Eye Week 24	65 Participants	40 Participants
Number and Percentage of Patients Who Have CSFT (<280 Microns) at Each Assessment Visit for the Study Eye Week 28	71 Participants	49 Participants
Number and Percentage of Patients Who Have CSFT (<280 Microns) at Each Assessment Visit for the Study Eye Week 32	63 Participants	47 Participants
Number and Percentage of Patients Who Have CSFT (<280 Microns) at Each Assessment Visit for the Study Eye Week 36	59 Participants	51 Participants
Number and Percentage of Patients Who Have CSFT (<280 Microns) at Each Assessment Visit for the Study Eye Week 40	67 Participants	47 Participants
Number and Percentage of Patients Who Have CSFT (<280 Microns) at Each Assessment Visit for the Study Eye Week 44	74 Participants	56 Participants

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Full Analysis Set - LOCF. Subset of non-Proliferative diabetic retinopathy (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.

Outcome measures

Measure	Brolucizumab 6 mg n=106 Participants 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2 mg n=107 Participants 5 x every 4 weeks loading then every 8 weeks maintenance
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	0 Participants

SECONDARY outcome

Timeframe: Week 52

Population: Full Analysis Set - LOCF

Assessed by angiography.

Outcome measures

Measure	Brolucizumab 6 mg n=132 Participants 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2 mg n=131 Participants 5 x every 4 weeks loading then every 8 weeks maintenance
Number (%) of Patients With Presence of Leakage in the Study Eye on Fluorescein Angiography (FA)	110 Participants	115 Participants

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: Full Analysis Set- last observation carried forward (FAS - LOCF)

To evaluate the efficacy of brolucizumab relative to aflibercept over the time period by assessing changes in anatomical parameters

Outcome measures

Measure	Brolucizumab 6 mg n=132 Participants 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2 mg n=131 Participants 5 x every 4 weeks loading then every 8 weeks maintenance
Number (%) of Patients With Presence of Subretinal Fluid (SRF), Intraretinal Fluid (IRF) in the Study Eye	87 Participants	85 Participants

SECONDARY outcome

Timeframe: Week 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48, 52

Population: Full Analysis Set - LOCF

Subretinal Fluid (SRF) status in the central subfield: proportion of subjects with presence of SRF in the study eye by visit

Outcome measures

Measure	Brolucizumab 6 mg n=132 Participants 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2 mg n=131 Participants 5 x every 4 weeks loading then every 8 weeks maintenance
Number of Patients With Presence of Subretinal Fluid (SRF) in the Study at Each Assessment Visit Week 52	9 Participants	4 Participants
Number of Patients With Presence of Subretinal Fluid (SRF) in the Study at Each Assessment Visit Week 6	17 Participants	28 Participants
Number of Patients With Presence of Subretinal Fluid (SRF) in the Study at Each Assessment Visit Week 8	13 Participants	20 Participants
Number of Patients With Presence of Subretinal Fluid (SRF) in the Study at Each Assessment Visit Week 4	33 Participants	37 Participants
Number of Patients With Presence of Subretinal Fluid (SRF) in the Study at Each Assessment Visit Week 12	7 Participants	14 Participants
Number of Patients With Presence of Subretinal Fluid (SRF) in the Study at Each Assessment Visit Week 16	6 Participants	9 Participants
Number of Patients With Presence of Subretinal Fluid (SRF) in the Study at Each Assessment Visit Week 18	6 Participants	4 Participants
Number of Patients With Presence of Subretinal Fluid (SRF) in the Study at Each Assessment Visit Week 20	6 Participants	2 Participants
Number of Patients With Presence of Subretinal Fluid (SRF) in the Study at Each Assessment Visit Week 24	5 Participants	2 Participants
Number of Patients With Presence of Subretinal Fluid (SRF) in the Study at Each Assessment Visit Week 28	5 Participants	5 Participants
Number of Patients With Presence of Subretinal Fluid (SRF) in the Study at Each Assessment Visit Week 32	8 Participants	7 Participants
Number of Patients With Presence of Subretinal Fluid (SRF) in the Study at Each Assessment Visit Week 36	13 Participants	8 Participants
Number of Patients With Presence of Subretinal Fluid (SRF) in the Study at Each Assessment Visit Week 40	7 Participants	6 Participants
Number of Patients With Presence of Subretinal Fluid (SRF) in the Study at Each Assessment Visit Week 44	7 Participants	3 Participants
Number of Patients With Presence of Subretinal Fluid (SRF) in the Study at Each Assessment Visit Week 48	10 Participants	4 Participants

SECONDARY outcome

Timeframe: Week 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48, 52

Population: Full Analysis Set - LOCF

Intraretinal Fluid (IRF) status in the central subfield: proportion of subjects with presence of IRF in the study eye by visit

Outcome measures

Measure	Brolucizumab 6 mg n=132 Participants 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2 mg n=131 Participants 5 x every 4 weeks loading then every 8 weeks maintenance
Number of Patients With Presence of Intraretinal Fluid (IRF) in the Study at Each Assessment Visit Week 4	113 Participants	115 Participants
Number of Patients With Presence of Intraretinal Fluid (IRF) in the Study at Each Assessment Visit Week 6	112 Participants	110 Participants
Number of Patients With Presence of Intraretinal Fluid (IRF) in the Study at Each Assessment Visit Week 8	109 Participants	112 Participants
Number of Patients With Presence of Intraretinal Fluid (IRF) in the Study at Each Assessment Visit Week 12	100 Participants	110 Participants
Number of Patients With Presence of Intraretinal Fluid (IRF) in the Study at Each Assessment Visit Week 16	99 Participants	109 Participants
Number of Patients With Presence of Intraretinal Fluid (IRF) in the Study at Each Assessment Visit Week 18	98 Participants	110 Participants
Number of Patients With Presence of Intraretinal Fluid (IRF) in the Study at Each Assessment Visit Week 20	94 Participants	102 Participants
Number of Patients With Presence of Intraretinal Fluid (IRF) in the Study at Each Assessment Visit Week 24	90 Participants	102 Participants
Number of Patients With Presence of Intraretinal Fluid (IRF) in the Study at Each Assessment Visit Week 28	87 Participants	100 Participants
Number of Patients With Presence of Intraretinal Fluid (IRF) in the Study at Each Assessment Visit Week 32	88 Participants	99 Participants
Number of Patients With Presence of Intraretinal Fluid (IRF) in the Study at Each Assessment Visit Week 36	98 Participants	98 Participants
Number of Patients With Presence of Intraretinal Fluid (IRF) in the Study at Each Assessment Visit Week 40	89 Participants	101 Participants
Number of Patients With Presence of Intraretinal Fluid (IRF) in the Study at Each Assessment Visit Week 44	84 Participants	94 Participants
Number of Patients With Presence of Intraretinal Fluid (IRF) in the Study at Each Assessment Visit Week 48	89 Participants	94 Participants
Number of Patients With Presence of Intraretinal Fluid (IRF) in the Study at Each Assessment Visit Week 52	87 Participants	85 Participants

SECONDARY outcome

Timeframe: Week 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48, 52

Population: Full Analysis Set - LOCF

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

Outcome measures

Measure	Brolucizumab 6 mg n=132 Participants 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2 mg n=131 Participants 5 x every 4 weeks loading then every 8 weeks maintenance
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	118 Participants
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	114 Participants
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	114 Participants
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	110 Participants
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	110 Participants
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	110 Participants
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	102 Participants
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	102 Participants
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	100 Participants
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	99 Participants
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	98 Participants
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	101 Participants
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	94 Participants
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	94 Participants
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	85 Participants

SECONDARY outcome

Timeframe: Baseline, Week 28 and Week 52

Population: FAS - LOCF. For subjects with an assessment of the criterion.

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.

Outcome measures

Measure	Brolucizumab 6 mg n=132 Participants 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2 mg n=130 Participants 5 x every 4 weeks loading then every 8 weeks maintenance
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	47 Participants
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	64 Participants

SECONDARY outcome

Timeframe: Baseline, Week 28 and Week 52

Population: FAS - LOCF. For subjects with an assessment of the criterion.

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.

Outcome measures

Measure	Brolucizumab 6 mg n=132 Participants 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2 mg n=130 Participants 5 x every 4 weeks loading then every 8 weeks maintenance
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	36.3 Percentage estimates
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	49.5 Percentage estimates

SECONDARY outcome

Timeframe: Baseline, Week 28 and Week 52

Population: FAS - LOCF. For subjects with an assessment of the criterion.

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.

Outcome measures

Measure	Brolucizumab 6 mg n=132 Participants 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2 mg n=130 Participants 5 x every 4 weeks loading then every 8 weeks maintenance
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	15 Participants
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	25 Participants

SECONDARY outcome

Timeframe: Baseline, Week 28 and Week 52

Population: FAS - LOCF. For subjects with an assessment of the criterion.

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.

Outcome measures

Measure	Brolucizumab 6 mg n=132 Participants 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2 mg n=130 Participants 5 x every 4 weeks loading then every 8 weeks maintenance
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	11.6 Percentage estimates
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	19.3 Percentage estimates

SECONDARY outcome

Timeframe: Baseline, Week 28 and Week 52

Population: FAS - LOCF. For subjects with an assessment of the criterion.

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.

Outcome measures

Measure	Brolucizumab 6 mg n=132 Participants 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2 mg n=130 Participants 5 x every 4 weeks loading then every 8 weeks maintenance
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	0 Participants
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	0 Participants

SECONDARY outcome

Timeframe: Baseline, Week 28 and Week 52

Population: FAS - LOCF. For subjects with an assessment of the criterion.

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.

Outcome measures

Measure	Brolucizumab 6 mg n=132 Participants 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2 mg n=130 Participants 5 x every 4 weeks loading then every 8 weeks maintenance
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	0.0 Percentage estimates

SECONDARY outcome

Timeframe: Baseline, Week 28 and Week 52

Population: FAS - LOCF. For subjects with an assessment of the criterion.

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.

Outcome measures

Measure	Brolucizumab 6 mg n=132 Participants 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2 mg n=130 Participants 5 x every 4 weeks loading then every 8 weeks maintenance
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	0 Participants
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	0 Participants

SECONDARY outcome

Timeframe: Baseline, Week 28 and Week 52

Population: FAS - LOCF. For subjects with an assessment of the criterion.

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.

Outcome measures

Measure	Brolucizumab 6 mg n=132 Participants 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2 mg n=130 Participants 5 x every 4 weeks loading then every 8 weeks maintenance
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	0.0 Percentage estimates

SECONDARY outcome

Timeframe: Baseline, Week 28 and Week 52

Population: Full Analysis Set - Observed

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.

Outcome measures

Measure	Brolucizumab 6 mg n=101 Participants 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2 mg n=103 Participants 5 x every 4 weeks loading then every 8 weeks maintenance
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	7.7 Scores on a Scale Standard Deviation 15.98
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	6.6 Scores on a Scale Standard Deviation 16.50

SECONDARY outcome

Timeframe: Baseline, Week 28 and Week 52

Population: Full Analysis Set - Observed

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.

Outcome measures

Measure	Brolucizumab 6 mg n=101 Participants 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2 mg n=103 Participants 5 x every 4 weeks loading then every 8 weeks maintenance
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 18.80	9.5 Scores on a Scale Standard Deviation 18.75
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	11.5 Scores on a Scale Standard Deviation 17.74

SECONDARY outcome

Timeframe: Baseline, Week 28 and Week 52

Population: Full Analysis Set - Observed

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.

Outcome measures

Measure	Brolucizumab 6 mg n=101 Participants 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2 mg n=103 Participants 5 x every 4 weeks loading then every 8 weeks maintenance
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	2.6 Scores on a Scale Standard Deviation 25.27
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	5.3 Scores on a Scale Standard Deviation 24.23

SECONDARY outcome

Timeframe: Baseline, Week 28 and Week 52

Population: Full Analysis Set - Observed

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.

Outcome measures

Measure	Brolucizumab 6 mg n=100 Participants 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2 mg n=103 Participants 5 x every 4 weeks loading then every 8 weeks maintenance
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	9.7 Scores on a Scale Standard Deviation 24.15
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	8.0 Scores on a Scale Standard Deviation 25.25

SECONDARY outcome

Timeframe: Baseline, Week 28 and Week 52

Population: Full Analysis Set - Observed

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.

Outcome measures

Measure	Brolucizumab 6 mg n=101 Participants 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2 mg n=103 Participants 5 x every 4 weeks loading then every 8 weeks maintenance
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	7.6 Scores on a Scale Standard Deviation 22.34
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	6.5 Scores on a Scale Standard Deviation 22.43

SECONDARY outcome

Timeframe: Baseline, Week 28 and Week 52

Population: Full Analysis Set - Observed

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.

Outcome measures

Measure	Brolucizumab 6 mg n=101 Participants 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2 mg n=103 Participants 5 x every 4 weeks loading then every 8 weeks maintenance
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	5.2 Scores on a Scale Standard Deviation 18.98
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	5.8 Scores on a Scale Standard Deviation 17.73

SECONDARY outcome

Timeframe: Baseline, Week 28 and Week 52

Population: Full Analysis Set - Observed

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.

Outcome measures

Measure	Brolucizumab 6 mg n=101 Participants 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2 mg n=103 Participants 5 x every 4 weeks loading then every 8 weeks maintenance
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	8.4 Scores on a Scale Standard Deviation 26.85
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	6.7 Scores on a Scale Standard Deviation 27.84

SECONDARY outcome

Timeframe: Baseline, Week 28 and Week 52

Population: Full Analysis Set - Observed

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.

Outcome measures

Measure	Brolucizumab 6 mg n=101 Participants 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2 mg n=103 Participants 5 x every 4 weeks loading then every 8 weeks maintenance
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 27.90	9.2 Scores on a Scale Standard Deviation 29.86
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	5.7 Scores on a Scale Standard Deviation 33.73

SECONDARY outcome

Timeframe: Baseline, Week 28 and Week 52

Population: Full Analysis Set - Observed

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.

Outcome measures

Measure	Brolucizumab 6 mg n=28 Participants 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2 mg n=22 Participants 5 x every 4 weeks loading then every 8 weeks maintenance
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	9.8 Scores on a Scale Standard Deviation 23.09
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	6.0 Scores on a Scale Standard Deviation 23.59

SECONDARY outcome

Timeframe: Baseline, Week 28 and Week 52

Population: Full Analysis Set - Observed

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.

Outcome measures

Measure	Brolucizumab 6 mg n=101 Participants 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2 mg n=103 Participants 5 x every 4 weeks loading then every 8 weeks maintenance
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	3.0 Scores on a Scale Standard Deviation 19.87
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	3.3 Scores on a Scale Standard Deviation 17.47

SECONDARY outcome

Timeframe: Baseline, Week 28 and Week 52

Population: Full Analysis Set - Observed

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.

Outcome measures

Measure	Brolucizumab 6 mg n=101 Participants 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2 mg n=103 Participants 5 x every 4 weeks loading then every 8 weeks maintenance
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 14.20	7.5 Scores on a Scale Standard Deviation 20.96
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	7.7 Scores on a Scale Standard Deviation 19.92

SECONDARY outcome

Timeframe: Baseline, Week 28 and Week 52

Population: Full Analysis Set - Observed

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.

Outcome measures

Measure	Brolucizumab 6 mg n=101 Participants 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2 mg n=103 Participants 5 x every 4 weeks loading then every 8 weeks maintenance
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	2.2 Scores on a Scale Standard Deviation 26.91
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	-0.2 Scores on a Scale Standard Deviation 26.34

SECONDARY outcome

Timeframe: 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).

To confirm the systemic brolucizumab exposure in a subset of patients.

Outcome measures

Measure	Brolucizumab 6 mg n=13 Participants 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2 mg 5 x every 4 weeks loading then every 8 weeks maintenance
Brolucizumab Serum Concentration Day 2	21.1 ng/mL Geometric Coefficient of Variation 4.40	—
Brolucizumab Serum Concentration Week 24 + 1 Day (n=7,0)	13.4 ng/mL Geometric Coefficient of Variation 4.81	—

SECONDARY outcome

Timeframe: Up to Week 52

Population: Safety Set. Patients in the Safety set with a valid value for the outcome measure.

To assess the immunogenicity of brolucizumab

Outcome measures

Measure	Brolucizumab 6 mg n=85 Participants 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2 mg 5 x every 4 weeks loading then every 8 weeks maintenance
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	—
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	—
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	—
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	—

SECONDARY outcome

Timeframe: 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

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

Outcome measures

Measure	Brolucizumab 6 mg n=132 Participants 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2 mg n=131 Participants 5 x every 4 weeks loading then every 8 weeks maintenance
Ocular Adverse Events (AEs) (>=2% in Any Treatment Arm) by Preferred Term for the Study Eye Uveitis	3 Participants	0 Participants
Ocular Adverse Events (AEs) (>=2% in Any Treatment Arm) by Preferred Term for the Study Eye Vitreous haemorrhage	3 Participants	5 Participants
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	47 Participants
Ocular Adverse Events (AEs) (>=2% in Any Treatment Arm) by Preferred Term for the Study Eye Visual acuity reduced	12 Participants	6 Participants
Ocular Adverse Events (AEs) (>=2% in Any Treatment Arm) by Preferred Term for the Study Eye Intraocular pressure increased	8 Participants	9 Participants
Ocular Adverse Events (AEs) (>=2% in Any Treatment Arm) by Preferred Term for the Study Eye Meibomian gland dysfunction	8 Participants	9 Participants
Ocular Adverse Events (AEs) (>=2% in Any Treatment Arm) by Preferred Term for the Study Eye Cataract	8 Participants	3 Participants
Ocular Adverse Events (AEs) (>=2% in Any Treatment Arm) by Preferred Term for the Study Eye Conjunctival haemorrhage	7 Participants	5 Participants
Ocular Adverse Events (AEs) (>=2% in Any Treatment Arm) by Preferred Term for the Study Eye Vitreous opacities	4 Participants	0 Participants
Ocular Adverse Events (AEs) (>=2% in Any Treatment Arm) by Preferred Term for the Study Eye Dry eye	3 Participants	3 Participants
Ocular Adverse Events (AEs) (>=2% in Any Treatment Arm) by Preferred Term for the Study Eye Epiretinal membrane	3 Participants	2 Participants
Ocular Adverse Events (AEs) (>=2% in Any Treatment Arm) by Preferred Term for the Study Eye Eye pruritus	3 Participants	1 Participants
Ocular Adverse Events (AEs) (>=2% in Any Treatment Arm) by Preferred Term for the Study Eye Xerophthalmia	2 Participants	5 Participants

SECONDARY outcome

Timeframe: 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

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

Outcome measures

Measure	Brolucizumab 6 mg n=132 Participants 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2 mg n=131 Participants 5 x every 4 weeks loading then every 8 weeks maintenance
Number of Subjects With Non-ocular Adverse Events (AEs) (>=2% in Any Treatment Arm)	94 Participants	74 Participants

POST_HOC outcome

Timeframe: 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

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.

Outcome measures

Measure	Brolucizumab 6 mg n=132 Participants 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2 mg n=131 Participants 5 x every 4 weeks loading then every 8 weeks maintenance
All Collected Deaths On-Treatment Deaths	0 Participants	0 Participants
All Collected Deaths Post-Treatment Deaths	0 Participants	1 Participants
All Collected Deaths All Deaths	0 Participants	1 Participants

Adverse Events

Brolucizumab 6mg

Serious events: 28 serious events

Other events: 92 other events

Deaths: 0 deaths

Aflibercept 2mg

Serious events: 22 serious events

Other events: 84 other events

Deaths: 1 deaths

Overall

Serious events: 50 serious events

Other events: 176 other events

Deaths: 1 deaths

Serious adverse events

Measure	Brolucizumab 6mg n=132 participants at risk 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2mg n=131 participants at risk 5 x every 4 weeks loading then every 8 weeks maintenance	Overall n=263 participants at risk Overall
Cardiac disorders Angina unstable	0.00% 0/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.76% 1/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.38% 1/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Cardiac disorders Arteriosclerosis coronary artery	0.76% 1/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.00% 0/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.38% 1/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Cardiac disorders Atrial flutter	0.00% 0/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.76% 1/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.38% 1/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Cardiac disorders Cardiac failure	0.76% 1/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.00% 0/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.38% 1/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Cardiac disorders Coronary artery disease	0.76% 1/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.00% 0/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.38% 1/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Endocrine disorders Thyroid mass	1.5% 2/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.00% 0/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.76% 2/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Eye disorders Cataract - Fellow eye	3.8% 5/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.76% 1/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	2.3% 6/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Eye disorders Cataract - Study eye	1.5% 2/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	1.5% 2/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	1.5% 4/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Eye disorders Cataract nuclear - Study eye	0.00% 0/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.76% 1/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.38% 1/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Eye disorders Diabetic retinal oedema - Fellow eye	0.00% 0/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.76% 1/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.38% 1/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Eye disorders Retinal artery occlusion - Study eye	0.76% 1/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.00% 0/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.38% 1/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Eye disorders Vitreous haemorrhage - Study eye	0.00% 0/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.76% 1/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.38% 1/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Gastrointestinal disorders Diabetic gastroparesis	0.76% 1/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.00% 0/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.38% 1/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Gastrointestinal disorders Large intestine polyp	0.76% 1/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.00% 0/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.38% 1/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Gastrointestinal disorders Oesophageal varices haemorrhage	0.00% 0/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.76% 1/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.38% 1/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Hepatobiliary disorders Hepatic cirrhosis	0.00% 0/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.76% 1/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.38% 1/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Immune system disorders Contrast media allergy	0.00% 0/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.76% 1/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.38% 1/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Infections and infestations Endophthalmitis - Study eye	0.76% 1/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.00% 0/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.38% 1/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Infections and infestations Pneumonia bacterial	0.76% 1/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.00% 0/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.38% 1/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Injury, poisoning and procedural complications Comminuted fracture	0.76% 1/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.00% 0/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.38% 1/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Injury, poisoning and procedural complications Craniocerebral injury	0.76% 1/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.76% 1/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.76% 2/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Injury, poisoning and procedural complications Femur fracture	0.00% 0/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.76% 1/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.38% 1/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Injury, poisoning and procedural complications Traumatic intracranial haematoma	0.76% 1/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.00% 0/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.38% 1/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Metabolism and nutrition disorders Diabetes mellitus inadequate control	0.76% 1/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.00% 0/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.38% 1/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Metabolism and nutrition disorders Type 2 diabetes mellitus	0.00% 0/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.76% 1/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.38% 1/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Musculoskeletal and connective tissue disorders Bone cyst	0.00% 0/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.76% 1/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.38% 1/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.76% 1/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.00% 0/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.38% 1/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.76% 1/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.00% 0/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.38% 1/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colorectal adenoma	0.00% 0/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.76% 1/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.38% 1/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma	0.00% 0/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.76% 1/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.38% 1/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Nervous system disorders Cerebral infarction	1.5% 2/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	1.5% 2/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	1.5% 4/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Nervous system disorders Cerebrovascular insufficiency	0.76% 1/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.00% 0/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.38% 1/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Nervous system disorders Diabetic neuropathy	1.5% 2/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.00% 0/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.76% 2/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Nervous system disorders Neuritis	0.76% 1/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.00% 0/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.38% 1/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Nervous system disorders Vertebrobasilar insufficiency	0.00% 0/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.76% 1/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.38% 1/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Renal and urinary disorders Chronic kidney disease	2.3% 3/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.00% 0/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	1.1% 3/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Renal and urinary disorders Diabetic nephropathy	0.76% 1/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	2.3% 3/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	1.5% 4/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Renal and urinary disorders End stage renal disease	0.00% 0/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.76% 1/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.38% 1/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Renal and urinary disorders Renal failure	0.00% 0/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.76% 1/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.38% 1/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.76% 1/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.38% 1/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.76% 1/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.00% 0/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.38% 1/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Vascular disorders Blood pressure inadequately controlled	0.00% 0/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.76% 1/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.38% 1/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Vascular disorders Hypertension	0.00% 0/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.76% 1/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.38% 1/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Vascular disorders Subclavian artery stenosis	0.76% 1/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.00% 0/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.38% 1/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.

Other adverse events

Measure	Brolucizumab 6mg n=132 participants at risk 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Aflibercept 2mg n=131 participants at risk 5 x every 4 weeks loading then every 8 weeks maintenance	Overall n=263 participants at risk Overall
Investigations Blood creatinine increased	1.5% 2/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	3.1% 4/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	2.3% 6/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Investigations Blood pressure increased	4.5% 6/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	2.3% 3/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	3.4% 9/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Investigations Blood triglycerides increased	2.3% 3/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	1.5% 2/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	1.9% 5/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Investigations Blood urea nitrogen/creatinine ratio increased	2.3% 3/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	1.5% 2/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	1.9% 5/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Investigations Blood uric acid increased	3.0% 4/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	2.3% 3/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	2.7% 7/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Investigations Gamma-glutamyltransferase increased	2.3% 3/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.76% 1/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	1.5% 4/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Investigations Haemoglobin decreased	2.3% 3/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	1.5% 2/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	1.9% 5/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Investigations Intraocular pressure increased - Fellow eye	2.3% 3/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	1.5% 2/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	1.9% 5/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Investigations Intraocular pressure increased - Study eye	6.1% 8/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	6.9% 9/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	6.5% 17/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Investigations Protein urine present	4.5% 6/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	2.3% 3/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	3.4% 9/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Investigations White blood cells urine positive	3.0% 4/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	3.1% 4/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	3.0% 8/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Metabolism and nutrition disorders Hypercholesterolaemia	2.3% 3/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.00% 0/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	1.1% 3/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Metabolism and nutrition disorders Hyperkalaemia	5.3% 7/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	3.1% 4/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	4.2% 11/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Metabolism and nutrition disorders Hyperlipidaemia	7.6% 10/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	6.9% 9/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	7.2% 19/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Metabolism and nutrition disorders Hyperuricaemia	2.3% 3/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	4.6% 6/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	3.4% 9/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Metabolism and nutrition disorders Hypocalcaemia	3.0% 4/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.00% 0/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	1.5% 4/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Metabolism and nutrition disorders Hypokalaemia	2.3% 3/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	2.3% 3/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	2.3% 6/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Metabolism and nutrition disorders Hypoproteinaemia	2.3% 3/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	3.1% 4/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	2.7% 7/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Blood and lymphatic system disorders Anaemia	3.0% 4/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	3.1% 4/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	3.0% 8/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Cardiac disorders Arteriosclerosis coronary artery	2.3% 3/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	4.6% 6/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	3.4% 9/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Endocrine disorders Thyroid mass	1.5% 2/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	3.1% 4/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	2.3% 6/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Eye disorders Cataract - Fellow eye	3.8% 5/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.00% 0/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	1.9% 5/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Eye disorders Cataract - Study eye	4.5% 6/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	1.5% 2/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	3.0% 8/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Eye disorders Conjunctival haemorrhage - Fellow eye	2.3% 3/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.00% 0/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	1.1% 3/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Eye disorders Conjunctival haemorrhage - Study eye	5.3% 7/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	3.8% 5/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	4.6% 12/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Eye disorders Diabetic retinal oedema - Fellow eye	3.0% 4/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	8.4% 11/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	5.7% 15/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Eye disorders Diabetic retinopathy - Fellow eye	3.0% 4/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.76% 1/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	1.9% 5/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Eye disorders Dry eye - Fellow eye	1.5% 2/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	2.3% 3/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	1.9% 5/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Eye disorders Dry eye - Study eye	2.3% 3/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	2.3% 3/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	2.3% 6/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Eye disorders Epiretinal membrane - Study eye	2.3% 3/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	1.5% 2/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	1.9% 5/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Eye disorders Eye pruritus - Fellow eye	2.3% 3/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.00% 0/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	1.1% 3/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Eye disorders Eye pruritus - Study eye	2.3% 3/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.76% 1/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	1.5% 4/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Eye disorders Macular oedema - Fellow eye	2.3% 3/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.76% 1/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	1.5% 4/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Eye disorders Meibomian gland dysfunction - Fellow eye	6.1% 8/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	6.9% 9/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	6.5% 17/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Eye disorders Meibomian gland dysfunction - Study eye	6.1% 8/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	6.9% 9/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	6.5% 17/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Eye disorders Uveitis - Study eye	2.3% 3/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.00% 0/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	1.1% 3/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Eye disorders Visual acuity reduced - Fellow eye	7.6% 10/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	6.1% 8/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	6.8% 18/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Eye disorders Visual acuity reduced - Study eye	9.1% 12/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	4.6% 6/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	6.8% 18/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Eye disorders Vitreous haemorrhage - Study eye	2.3% 3/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	3.1% 4/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	2.7% 7/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Eye disorders Vitreous opacities - Fellow eye	3.0% 4/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.00% 0/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	1.5% 4/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Eye disorders Vitreous opacities - Study eye	3.0% 4/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.00% 0/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	1.5% 4/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Eye disorders Xerophthalmia - Fellow eye	1.5% 2/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	6.1% 8/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	3.8% 10/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Eye disorders Xerophthalmia - Study eye	1.5% 2/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	3.8% 5/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	2.7% 7/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Gastrointestinal disorders Chronic gastritis	3.0% 4/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.76% 1/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	1.9% 5/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Gastrointestinal disorders Constipation	1.5% 2/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	3.8% 5/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	2.7% 7/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Gastrointestinal disorders Diarrhoea	2.3% 3/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.76% 1/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	1.5% 4/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
General disorders Pyrexia	2.3% 3/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	1.5% 2/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	1.9% 5/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Hepatobiliary disorders Hepatic cyst	0.00% 0/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	2.3% 3/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	1.1% 3/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Infections and infestations COVID-19	3.8% 5/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.76% 1/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	2.3% 6/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Infections and infestations Herpes zoster	3.0% 4/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.76% 1/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	1.9% 5/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Infections and infestations Nasopharyngitis	2.3% 3/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.76% 1/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	1.5% 4/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Infections and infestations Pneumonia	0.00% 0/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	3.8% 5/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	1.9% 5/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Infections and infestations Upper respiratory tract infection	6.8% 9/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	6.9% 9/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	6.8% 18/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Infections and infestations Urinary tract infection	2.3% 3/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	3.1% 4/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	2.7% 7/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Investigations Alanine aminotransferase increased	2.3% 3/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.00% 0/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	1.1% 3/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Investigations Bacterial test positive	2.3% 3/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.00% 0/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	1.1% 3/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Investigations Blood cholesterol increased	0.76% 1/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	2.3% 3/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	1.5% 4/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Musculoskeletal and connective tissue disorders Pain in extremity	3.0% 4/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.00% 0/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	1.5% 4/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Nervous system disorders Carotid arteriosclerosis	3.0% 4/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	3.1% 4/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	3.0% 8/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Nervous system disorders Cerebral infarction	0.76% 1/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	2.3% 3/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	1.5% 4/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Nervous system disorders Diabetic neuropathy	3.0% 4/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	3.1% 4/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	3.0% 8/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Nervous system disorders Headache	3.0% 4/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.76% 1/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	1.9% 5/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Renal and urinary disorders Diabetic nephropathy	3.0% 4/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	5.3% 7/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	4.2% 11/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Renal and urinary disorders Renal cyst	3.0% 4/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	1.5% 2/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	2.3% 6/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Renal and urinary disorders Renal failure	3.8% 5/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.76% 1/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	2.3% 6/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Renal and urinary disorders Renal impairment	3.8% 5/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.76% 1/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	2.3% 6/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Reproductive system and breast disorders Benign prostatic hyperplasia	2.3% 3/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.76% 1/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	1.5% 4/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Respiratory, thoracic and mediastinal disorders Cough	3.0% 4/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.76% 1/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	1.9% 5/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Respiratory, thoracic and mediastinal disorders Pleural effusion	2.3% 3/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.76% 1/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	1.5% 4/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Respiratory, thoracic and mediastinal disorders Pulmonary mass	3.0% 4/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	5.3% 7/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	4.2% 11/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Skin and subcutaneous tissue disorders Dermatitis allergic	2.3% 3/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.76% 1/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	1.5% 4/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Skin and subcutaneous tissue disorders Eczema	3.0% 4/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.76% 1/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	1.9% 5/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Vascular disorders Aortic arteriosclerosis	2.3% 3/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	0.76% 1/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	1.5% 4/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Vascular disorders Hypertension	5.3% 7/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	9.2% 12/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	7.2% 19/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.
Vascular disorders Peripheral arterial occlusive disease	2.3% 3/132 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	2.3% 3/131 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.	2.3% 6/263 • Adverse events are reported from first dose of study treatment until end of study, up to a maximum duration of approximately 52 weeks.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: + 1 862 778 8300

Email: Novartis.email@Novartis.com

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