MERLIN: Study of Safety and Efficacy of Brolucizumab 6 mg Dosed Every 4 Weeks Compared to Aflibercept 2 mg Dosed Every 4 Weeks in Patients With Retinal Fluid Despite Frequent Anti-VEGF Injections

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03710564
• Collaborator: (none)
• Enrollment: 535
• Locations: 61
• Arms: 2
• Actual Duration (Months): 32
• Patients Per Site: 8.8
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This clinical study was designed to compare the safety and efficacy of brolucizumab 6 mg dosed every 4 weeks to aflibercept 2 mg dosed every 4 weeks in those neovascular age-related macular degeneration (nAMD) patients with retinal fluid despite frequent anti-Vascular Endothelial Growth Factor (VEGF) injections.

Condition or Disease	Intervention/Treatment	Phase
Age-Related Macular Degeneration	Biological: Brolucizumab; Biological: Aflibercept	Phase 3

Detailed Description

This was a Phase III, multi-center, randomized, double-masked, parallel group study with 2 masked arms in which participants were randomized 2:1 to receive brolucizumab or aflibercept. All participants had study visits every 4 weeks through week 104.

The study consisted of three study periods:

Screening Period: The screening period lasted up to 2 weeks prior to administration of the first dose of study treatment, dependent upon confirmation of the patient meeting eligibility criteria.

Double-Masked Treatment Period: Participants meeting eligibility criteria entered the treatment period and were randomized in a 2:1 ratio into one of the following 2 masked treatment arms at the Baseline visit: Brolucizumab 6 mg injected every 4 weeks or Aflibercept 2 mg injected every 4 weeks. Treatment period lasted up to week 100.

Safety Follow up Period: Participants were followed up for safety during 4 weeks after the last dose of study treatment. Including the Screening Period, the total study duration for a participant was up to 106 weeks.

Some participants were eligible to continue into an extension study in order to receive treatment with brolucizumab (a) after completing the 104 -week double-masked treatment period, (b) upon meeting all inclusion/exclusion criteria for the extension study, and (c) based on Investigator's judgment that the participant was expected to benefit from treatment with brolucizumab.

Study Design

• Study Type: Interventional
• Actual Enrollment: 535 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: multicenter, randomized, double-maskedmulticenter, randomized, double-masked
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Double-masked Phase 3a Study to Assess Safety and Efficacy of Brolucizumab 6 mg q4 Weeks Compared to Aflibercept 2 mg q4 Weeks in Patients With Neovascular Age-related Macular Degeneration (nAMD) With Persistent Retinal Fluid (MERLIN)
• Actual Study Start Date: Oct 30, 2018
• Actual Primary Completion Date: Dec 21, 2020
• Actual Study Completion Date: Jul 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Brolucizumab Brolucizumab 6 mg dosed every 4 weeks was administered via intravitreal injection for 100 weeks.	Biological: Brolucizumab; 6 mg/0.05mL solution for intravitreal injection; Other Names: RTH258
Active Comparator: Aflibercept Aflibercept 2 mg dosed every 4 weeks was administered via intravitreal injection for 100 weeks.	Biological: Aflibercept; 2 mg/0.05mL solution for intravitreal injection; Other Names: EYLEA

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Best-Corrected Visual Acuity (BCVA) at Week 52 [Baseline, week 52]

   BCVA was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing protocol at an initial testing distance of 4 meters. BCVA min and max possible scores are 0-100 respectively and a higher score represents better functioning. A positive change from baseline represents better functioning. Baseline BCVA was defined as the last measurement on or prior to the baseline visit. BCVA assessments after start of alternative anti-VEGF treatment in the study eye were censored and imputed by the last value prior to start of alternative treatment. Last observation carried forward (LOCF) was used for the imputation of missing values.

Secondary Outcome Measures

1. Stable Visual Acuity (VA) or Improvement in VA at Week 52 and Week 104 [Baseline, weeks 52 and 104]

   Visual Acuity (VA) was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing protocol at an initial testing distance of 4 meters. VA min and max possible scores are 0-100 respectively and a higher score represents better functioning. The number of participants with no change or gain in VA compared to baseline was reported. VA stabilization or improvement is defined as a change from baseline no worse than 5 letters loss in VA compared to Baseline. Baseline VA was defined as the last measurement on or prior to the baseline visit. VA assessments after start of alternative anti-VEGF treatment in the study eye were censored and imputed by the last value prior to start of alternative treatment.

2. Loss in Best-Corrected Visual Acuity (BCVA) of 5 Letters or More [Baseline, weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100 and 104]

   BCVA was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing protocol at an initial testing distance of 4 meters. BCVA min and max possible scores are 0-100 respectively and a higher score represents better functioning. The number of subjects with loss in BCVA of 5 letters or more from baseline was reported for each post-baseline visit. Baseline BCVA was defined as the last measurement on or prior to the baseline visit. BCVA assessments after start of alternative anti-VEGF treatment in the study eye were censored and imputed by the last value prior to start of alternative treatment.

3. Loss in Best-Corrected Visual Acuity (BCVA) of 10 Letters or More [Baseline, weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100 and 104]

   BCVA was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing protocol at an initial testing distance of 4 meters. BCVA min and max possible scores are 0-100 respectively and a higher score represents better functioning. The number of subjects with loss in BCVA of 10 letters or more from baseline was reported for each post-baseline visit. Baseline BCVA was defined as the last measurement on or prior to the baseline visit. BCVA assessments after start of alternative anti-VEGF treatment in the study eye were censored and imputed by the last value prior to start of alternative treatment.

4. Loss in Best-Corrected Visual Acuity (BCVA) of 15 Letters or More [Baseline, weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100 and 104]

   BCVA was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing protocol at an initial testing distance of 4 meters. BCVA min and max possible scores are 0-100 respectively and a higher score represents better functioning. The number of subjects with loss in BCVA of 15 letters or more from baseline was reported for each post-baseline visit. Baseline BCVA was defined as the last measurement on or prior to the baseline visit. BCVA assessments after start of alternative anti-VEGF treatment in the study eye were censored and imputed by the last value prior to start of alternative treatment.

5. Gain in Best-Corrected Visual Acuity (BCVA) of 5 Letters or More [Baseline, weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100 and 104]

   BCVA was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing protocol at an initial testing distance of 4 meters. BCVA min and max possible scores are 0-100 respectively and a higher score represents better functioning. The number of subjects with gain in BCVA of 5 letters or more from baseline was reported for each post-baseline visit. Baseline BCVA was defined as the last measurement on or prior to the baseline visit. BCVA assessments after start of alternative anti-VEGF treatment in the study eye were censored and imputed by the last value prior to start of alternative treatment.

6. Gain in Best-Corrected Visual Acuity (BCVA) of 10 Letters or More [Baseline, weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100 and 104]

   BCVA was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing protocol at an initial testing distance of 4 meters. BCVA min and max possible scores are 0-100 respectively and a higher score represents better functioning. The number of subjects with gain in BCVA of 10 letters or more from baseline was reported for each post-baseline visit. Baseline BCVA was defined as the last measurement on or prior to the baseline visit. BCVA assessments after start of alternative anti-VEGF treatment in the study eye were censored and imputed by the last value prior to start of alternative treatment.

7. Gain in Best-Corrected Visual Acuity (BCVA) of 15 Letters or More [Baseline, weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100 and 104]

   BCVA was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing protocol at an initial testing distance of 4 meters. BCVA min and max possible scores are 0-100 respectively and a higher score represents better functioning. The number of subjects with gain in BCVA of 15 letters or more from baseline was reported for each post-baseline visit. Baseline BCVA was defined as the last measurement on or prior to the baseline visit. BCVA assessments after start of alternative anti-VEGF treatment in the study eye were censored and imputed by the last value prior to start of alternative treatment.

8. Change in Central Subfield Thickness (CST) From Baseline [Baseline, weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100 and 104]

   CST was assessed using Spectral Domain Optical Coherence Tomography (SD-OCT) images. A negative change from baseline is a favorable outcome. CST assessments after start of alternative anti-VEGF treatment in the study eye were censored and imputed by the last value prior to start of alternative treatment. These results were based on analysis using the Last observation carried forward (LOCF) approach for replacement/imputation of censored/missing values and observed data.

9. Number of Participants With Intraretinal Fluid (IRF) [Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100 and 104]

   IRF was assessed using Spectral Domain Optical Coherence Tomography (SD-OCT) images. The number of participants with presence of IRF was reported for each post-baseline visit. These results were based on analysis using the Last observation carried forward (LOCF) approach for replacement/imputation of censored/missing values and observed data.

10. Number of Participants With Subretinal Fluid (SRF) [Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100 and 104]

    SRF was assessed using Spectral Domain Optical Coherence Tomography (SD-OCT) images. The number of participants with presence of SRF was reported for each post-baseline visit. These results were based on analysis using the Last observation carried forward (LOCF) approach for replacement/imputation of censored/missing values and observed data.

11. Number of Participants With Sub-Retinal Pigment Epithelium (Sub-RPE) Fluid [Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100 and 104]

    Sub-RPE fluid was assessed using Spectral Domain Optical Coherence Tomography (SD-OCT) images. The number of participants with presence of sub-RPE fluid in participants with sub-RPE fluid at baseline was reported for each post-baseline visit. These results were based on analysis using the Last observation carried forward (LOCF) approach for replacement/imputation of censored/missing values and observed data.

12. Number of Participants With Fluid-free Status (no IRF, SRF or Sub-RPE Fluid) [Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100 and 104]

    Intraretinal fluid (IRF), Subretinal fluid (SRF) and Sub-Retinal Pigment Epithelium fluid (sub-RPE) were assessed using Spectral Domain Optical Coherence Tomography (SD-OCT) images. The number of participants with fluid-free status (simultaneous absence of IRF, SRF, and sub-RPE) was reported for each post-baseline visit. These results were based on analysis using the Last observation carried forward (LOCF) approach for replacement/imputation of censored/missing values and observed data.

13. Time to First Dry Retina (no IRF or SRF) [Baseline, Up to Week 104 (assessments every 4 weeks)]

    Intraretinal fluid (IRF) and Subretinal fluid (SRF) were assessed using Spectral Domain Optical Coherence Tomography (SD-OCT) images. A dry retina is defined as no IRF or SRF at the respective visit. Kaplan-Meier method was used for estimate of percentiles with 95% CI based on methodology of Brookmeyer and Crowley. Data was censored at the last time when IRF/SRF assessments for fluid-free retina were available for participants who discontinued on/or prior to the time of the start of alternative anti-VEGF treatment. IRF and SRF assessments on unscheduled visits were considered.

14. Time to Sustained Dry Retina (no IRF or SRF at ≥ 2 Consecutive Visits) [Baseline, Up to Week 104 (assessments every 4 weeks)]

    Intraretinal fluid (IRF) and Subretinal fluid (SRF) were assessed using Spectral Domain Optical Coherence Tomography (SD-OCT) images. A sustained dry retina is defined as no IRF or SRF at 2 or more consecutive visits. Kaplan-Meier method was used for estimate of percentiles with 95% CI based on methodology of Brookmeyer and Crowley. Data was censored at the last time when IRF/SRF assessments for fluid-free retina were available for participants who discontinued on/or prior to the time of the start of alternative anti-VEGF treatment. IRF and SRF assessments on unscheduled visits were considered.

15. Number of Participants With Anti-drug Antibody (ADA) Negative Status [Baseline, weeks 4, 12, 24, 36, 52, 76 and 104]

    A blood sample was collected for anti-drug antibody assessment. ADA negative status = ADA negative result at the corresponding study visit. The baseline sample was collected prior to first dose of study treatment and the post-baseline assessments were taken at the scheduled timepoints. A negative Titer was used to assess the ADA status for the brolucizumab arm.

16. Free Brolucizumab Serum Concentration [pre-dose a baseline, weeks 4, 12, 24, 36, 52, 76 and 104]

    A blood sample was collected for Free Brolucizumab serum concentration assessment. This outcome measure was pre-specified for the brolucizumab arm only. The baseline sample was collected prior to first dose of study treatment and the post-baseline assessments. Values below the limit of quantification (BLQ) (<0.5 ng/mL) were replaced by one half of the LLOQ (0.25 ng/mL) in the calculation of the summary statistics. For the Mean score at each visit, if the calculated value was less than 0.5, then "NA" was displayed instead; meaning that the score is below the limit of quantitation (<0.5 ng/mL).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Signed informed consent

• Diagnosis of wet age-related macular degeneration (AMD)

• Currently receiving anti-VEGF injections

Exclusion Criteria:

• Active infection or inflammation in either eye

• Significant fibrosis in the study eye

• Recent ocular surgery

• Uncontrolled glaucoma

• Use of medications as specified in the protocol

• Pregnant, nursing

• Of child-bearing potential unless using highly effective method of contraception

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Phoenix	Arizona	United States	85016
2	Novartis Investigative Site	Phoenix	Arizona	United States	85020
3	Novartis Investigative Site	Phoenix	Arizona	United States	85053
4	Novartis Investigative Site	Beverly Hills	California	United States	90211
5	Novartis Investigative Site	Huntington Beach	California	United States	92647
6	Novartis Investigative Site	Mountain View	California	United States	94040
7	Novartis Investigative Site	Oakland	California	United States	94609
8	Novartis Investigative Site	Oxnard	California	United States	93036
9	Novartis Investigative Site	Palo Alto	California	United States	94303
10	Novartis Investigative Site	Redlands	California	United States	92374
11	Novartis Investigative Site	Sacramento	California	United States	95841
12	Novartis Investigative Site	San Francisco	California	United States	94107
13	Novartis Investigative Site	Santa Barbara	California	United States	93103
14	Novartis Investigative Site	Colorado Springs	Colorado	United States	80909
15	Novartis Investigative Site	Golden	Colorado	United States	80401
16	Novartis Investigative Site	Deerfield Beach	Florida	United States	33064
17	Novartis Investigative Site	Fort Lauderdale	Florida	United States	33308
18	Novartis Investigative Site	Fort Myers	Florida	United States	33912-7125
19	Novartis Investigative Site	Miami	Florida	United States	33136
20	Novartis Investigative Site	Mount Dora	Florida	United States	32757
21	Novartis Investigative Site	Pensacola	Florida	United States	32503
22	Novartis Investigative Site	Saint Petersburg	Florida	United States	33711
23	Novartis Investigative Site	Stuart	Florida	United States	34994
24	Novartis Investigative Site	Marietta	Georgia	United States	30060
25	Novartis Investigative Site	'Aiea	Hawaii	United States	96701
26	Novartis Investigative Site	Wheaton	Illinois	United States	60187
27	Novartis Investigative Site	West Des Moines	Iowa	United States	50266
28	Novartis Investigative Site	Lenexa	Kansas	United States	66215
29	Novartis Investigative Site	New Orleans	Louisiana	United States	70115-8139
30	Novartis Investigative Site	West Monroe	Louisiana	United States	71291
31	Novartis Investigative Site	Waldorf	Maryland	United States	20602
32	Novartis Investigative Site	Boston	Massachusetts	United States	02111
33	Novartis Investigative Site	Boston	Massachusetts	United States	02114
34	Novartis Investigative Site	Springfield	Massachusetts	United States	01107
35	Novartis Investigative Site	Royal Oak	Michigan	United States	48073
36	Novartis Investigative Site	Saint Louis	Missouri	United States	63110
37	Novartis Investigative Site	Las Vegas	Nevada	United States	89144
38	Novartis Investigative Site	Reno	Nevada	United States	89502
39	Novartis Investigative Site	Bloomfield	New Jersey	United States	07003
40	Novartis Investigative Site	Toms River	New Jersey	United States	08755
41	Novartis Investigative Site	Syracuse	New York	United States	13224
42	Novartis Investigative Site	Charlotte	North Carolina	United States	28210
43	Novartis Investigative Site	Cleveland	Ohio	United States	44122
44	Novartis Investigative Site	Fairfield	Ohio	United States	45014
45	Novartis Investigative Site	Eugene	Oregon	United States	97401
46	Novartis Investigative Site	Kingston	Pennsylvania	United States	95403
47	Novartis Investigative Site	Philadelphia	Pennsylvania	United States	19107
48	Novartis Investigative Site	Germantown	Tennessee	United States	38138
49	Novartis Investigative Site	Abilene	Texas	United States	79606
50	Novartis Investigative Site	Austin	Texas	United States	78705
51	Novartis Investigative Site	Austin	Texas	United States	78731
52	Novartis Investigative Site	Austin	Texas	United States	78793
53	Novartis Investigative Site	Fort Worth	Texas	United States	76102
54	Novartis Investigative Site	Fort Worth	Texas	United States	76104
55	Novartis Investigative Site	Harlingen	Texas	United States	78550
56	Novartis Investigative Site	Houston	Texas	United States	77030
57	Novartis Investigative Site	San Antonio	Texas	United States	78240
58	Novartis Investigative Site	Tyler	Texas	United States	75701
59	Novartis Investigative Site	Fairfax	Virginia	United States	22031
60	Novartis Investigative Site	Spokane	Washington	United States	99204
61	Novartis Investigative Site	Arecibo		Puerto Rico	00612

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

• Study Protocol - Jun 11, 2020
• Statistical Analysis Plan - Apr 30, 2021

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03710564
• Other Study ID Numbers: CRTH258AUS04
• First Posted: Oct 18, 2018
• Last Update Posted: Jul 22, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: neovascular age-related macular degeneration; nAMD; intravitreal injection; IVT; anti-VEGF; brolucizumab; aflibercept; EYLEA; double-masked; MERLIN; BEOVU
• Additional relevant MeSH terms: Macular Degeneration; Aflibercept

Study Results

Participant Flow

Arm/Group Title	Brolucizumab	Aflibercept
Arm/Group Description	Brolucizumab 6 mg dosed every 4 weeks was administered via intravitreal injection for 100 weeks.	Aflibercept 2 mg dosed every 4 weeks was administered via intravitreal injection for 100 weeks.
Period Title: Overall Study
STARTED	356	179
COMPLETED	172	86
NOT COMPLETED	184	93

Baseline Characteristics

Arm/Group Title	Brolucizumab	Aflibercept	Total
Arm/Group Description	Brolucizumab 6 mg dosed every 4 weeks was administered via intravitreal injection for 100 weeks.	Aflibercept 2 mg dosed every 4 weeks was administered via intravitreal injection for 100 weeks.	Total of all reporting groups
Overall Participants	356	179	535
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	76.4 (7.47)	76.1 (7.80)	76.3 (7.58)
Sex: Female, Male (Count of Participants)
Female	195 54.8%	107 59.8%	302 56.4%
Male	161 45.2%	72 40.2%	233 43.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	3 0.8%	2 1.1%	5 0.9%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	4 1.1%	0 0%	4 0.7%
White	347 97.5%	176 98.3%	523 97.8%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	2 0.6%	1 0.6%	3 0.6%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Best-Corrected Visual Acuity (BCVA) at Week 52
Description	BCVA was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing protocol at an initial testing distance of 4 meters. BCVA min and max possible scores are 0-100 respectively and a higher score represents better functioning. A positive change from baseline represents better functioning. Baseline BCVA was defined as the last measurement on or prior to the baseline visit. BCVA assessments after start of alternative anti-VEGF treatment in the study eye were censored and imputed by the last value prior to start of alternative treatment. Last observation carried forward (LOCF) was used for the imputation of missing values.
Time Frame	Baseline, week 52

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	Brolucizumab	Aflibercept
Arm/Group Description	Brolucizumab 6 mg dosed every 4 weeks was administered via intravitreal injection for 100 weeks.	Aflibercept 2 mg dosed every 4 weeks was administered via intravitreal injection for 100 weeks.
Measure Participants	356	179
Mean (Standard Deviation) [Score on a scale]	0.3 (9.02)	0.9 (6.51)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Brolucizumab, Aflibercept
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4537
	Comments
	Method	Pairwise ANOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -2.1 to 0.9
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.76
	Estimation Comments

2. Secondary Outcome

Title	Stable Visual Acuity (VA) or Improvement in VA at Week 52 and Week 104
Description	Visual Acuity (VA) was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing protocol at an initial testing distance of 4 meters. VA min and max possible scores are 0-100 respectively and a higher score represents better functioning. The number of participants with no change or gain in VA compared to baseline was reported. VA stabilization or improvement is defined as a change from baseline no worse than 5 letters loss in VA compared to Baseline. Baseline VA was defined as the last measurement on or prior to the baseline visit. VA assessments after start of alternative anti-VEGF treatment in the study eye were censored and imputed by the last value prior to start of alternative treatment.
Time Frame	Baseline, weeks 52 and 104

Outcome Measure Data

Analysis Population Description

The overall number of participants analyzed includes all randomized participants. The number analyzed per row represents participants with data at each time point.

Arm/Group Title	Brolucizumab	Aflibercept
Arm/Group Description	Brolucizumab 6 mg dosed every 4 weeks was administered via intravitreal injection for 100 weeks.	Aflibercept 2 mg dosed every 4 weeks was administered via intravitreal injection for 100 weeks.
Measure Participants	356	179
Week 52	232 65.2%	132 73.7%
Week 104	122 34.3%	63 35.2%

3. Secondary Outcome

Title	Loss in Best-Corrected Visual Acuity (BCVA) of 5 Letters or More
Description	BCVA was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing protocol at an initial testing distance of 4 meters. BCVA min and max possible scores are 0-100 respectively and a higher score represents better functioning. The number of subjects with loss in BCVA of 5 letters or more from baseline was reported for each post-baseline visit. Baseline BCVA was defined as the last measurement on or prior to the baseline visit. BCVA assessments after start of alternative anti-VEGF treatment in the study eye were censored and imputed by the last value prior to start of alternative treatment.
Time Frame	Baseline, weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100 and 104

Outcome Measure Data

Analysis Population Description

The overall number of participants analyzed includes all randomized participants. The number analyzed per row represents participants with data at each time point.

Arm/Group Title	Brolucizumab	Aflibercept
Arm/Group Description	Brolucizumab 6 mg dosed every 4 weeks was administered via intravitreal injection for 100 weeks.	Aflibercept 2 mg dosed every 4 weeks was administered via intravitreal injection for 100 weeks.
Measure Participants	356	179
Week 4	31 8.7%	16 8.9%
Week 8	38 10.7%	17 9.5%
Week 12	33 9.3%	22 12.3%
Week 16	34 9.6%	19 10.6%
Week 20	47 13.2%	15 8.4%
Week 24	40 11.2%	20 11.2%
Week 28	46 12.9%	24 13.4%
Week 32	45 12.6%	24 13.4%
Week 36	44 12.4%	24 13.4%
Week 40	46 12.9%	17 9.5%
Week 44	45 12.6%	17 9.5%
Week 48	46 12.9%	23 12.8%
Week 52	50 14%	24 13.4%
Week 56	46 12.9%	17 9.5%
Week 60	51 14.3%	23 12.8%
Week 64	47 13.2%	26 14.5%
Week 68	50 14%	28 15.6%
Week 72	59 16.6%	25 14%
Week 76	48 13.5%	31 17.3%
Week 80	49 13.8%	27 15.1%
Week 84	51 14.3%	27 15.1%
Week 88	37 10.4%	24 13.4%
Week 92	43 12.1%	24 13.4%
Week 96	42 11.8%	19 10.6%
Week 100	40 11.2%	19 10.6%
Week 104	40 11.2%	23 12.8%

4. Secondary Outcome

Title	Loss in Best-Corrected Visual Acuity (BCVA) of 10 Letters or More
Description	BCVA was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing protocol at an initial testing distance of 4 meters. BCVA min and max possible scores are 0-100 respectively and a higher score represents better functioning. The number of subjects with loss in BCVA of 10 letters or more from baseline was reported for each post-baseline visit. Baseline BCVA was defined as the last measurement on or prior to the baseline visit. BCVA assessments after start of alternative anti-VEGF treatment in the study eye were censored and imputed by the last value prior to start of alternative treatment.
Time Frame	Baseline, weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100 and 104

Outcome Measure Data

Analysis Population Description

The overall number of participants analyzed includes all randomized participants. The number analyzed per row represents participants with data at each time point.

Arm/Group Title	Brolucizumab	Aflibercept
Arm/Group Description	Brolucizumab 6 mg dosed every 4 weeks was administered via intravitreal injection for 100 weeks.	Aflibercept 2 mg dosed every 4 weeks was administered via intravitreal injection for 100 weeks.
Measure Participants	356	179
Week 4	4 1.1%	6 3.4%
Week 8	5 1.4%	5 2.8%
Week 12	9 2.5%	5 2.8%
Week 16	13 3.7%	4 2.2%
Week 20	14 3.9%	5 2.8%
Week 24	8 2.2%	6 3.4%
Week 28	14 3.9%	9 5%
Week 32	10 2.8%	8 4.5%
Week 36	9 2.5%	10 5.6%
Week 40	13 3.7%	5 2.8%
Week 44	17 4.8%	6 3.4%
Week 48	20 5.6%	9 5%
Week 52	24 6.7%	7 3.9%
Week 56	20 5.6%	5 2.8%
Week 60	21 5.9%	8 4.5%
Week 64	24 6.7%	10 5.6%
Week 68	20 5.6%	10 5.6%
Week 72	21 5.9%	11 6.1%
Week 76	24 6.7%	13 7.3%
Week 80	26 7.3%	13 7.3%
Week 84	20 5.6%	10 5.6%
Week 88	21 5.9%	14 7.8%
Week 92	20 5.6%	9 5%
Week 96	18 5.1%	8 4.5%
Week 100	15 4.2%	7 3.9%
Week 104	17 4.8%	7 3.9%

5. Secondary Outcome

Title	Loss in Best-Corrected Visual Acuity (BCVA) of 15 Letters or More
Description	BCVA was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing protocol at an initial testing distance of 4 meters. BCVA min and max possible scores are 0-100 respectively and a higher score represents better functioning. The number of subjects with loss in BCVA of 15 letters or more from baseline was reported for each post-baseline visit. Baseline BCVA was defined as the last measurement on or prior to the baseline visit. BCVA assessments after start of alternative anti-VEGF treatment in the study eye were censored and imputed by the last value prior to start of alternative treatment.
Time Frame	Baseline, weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100 and 104

Outcome Measure Data

Analysis Population Description

The overall number of participants analyzed includes all randomized participants. The number analyzed per row represents participants with data at each time point.

Arm/Group Title	Brolucizumab	Aflibercept
Arm/Group Description	Brolucizumab 6 mg dosed every 4 weeks was administered via intravitreal injection for 100 weeks.	Aflibercept 2 mg dosed every 4 weeks was administered via intravitreal injection for 100 weeks.
Measure Participants	356	179
Week 4	2 0.6%	1 0.6%
Week 8	2 0.6%	1 0.6%
Week 12	3 0.8%	2 1.1%
Week 16	4 1.1%	1 0.6%
Week 20	5 1.4%	1 0.6%
Week 24	3 0.8%	1 0.6%
Week 28	4 1.1%	3 1.7%
Week 32	6 1.7%	3 1.7%
Week 36	3 0.8%	4 2.2%
Week 40	5 1.4%	3 1.7%
Week 44	6 1.7%	3 1.7%
Week 48	10 2.8%	3 1.7%
Week 52	14 3.9%	2 1.1%
Week 56	13 3.7%	2 1.1%
Week 60	13 3.7%	3 1.7%
Week 64	10 2.8%	4 2.2%
Week 68	10 2.8%	4 2.2%
Week 72	10 2.8%	3 1.7%
Week 76	13 3.7%	4 2.2%
Week 80	12 3.4%	4 2.2%
Week 84	7 2%	6 3.4%
Week 88	10 2.8%	5 2.8%
Week 92	11 3.1%	4 2.2%
Week 96	9 2.5%	4 2.2%
Week 100	7 2%	5 2.8%
Week 104	10 2.8%	4 2.2%

6. Secondary Outcome

Title	Gain in Best-Corrected Visual Acuity (BCVA) of 5 Letters or More
Description	BCVA was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing protocol at an initial testing distance of 4 meters. BCVA min and max possible scores are 0-100 respectively and a higher score represents better functioning. The number of subjects with gain in BCVA of 5 letters or more from baseline was reported for each post-baseline visit. Baseline BCVA was defined as the last measurement on or prior to the baseline visit. BCVA assessments after start of alternative anti-VEGF treatment in the study eye were censored and imputed by the last value prior to start of alternative treatment.
Time Frame	Baseline, weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100 and 104

Outcome Measure Data

Analysis Population Description

The overall number of participants analyzed includes all randomized participants. The number analyzed per row represents participants with data at each time point.

Arm/Group Title	Brolucizumab	Aflibercept
Arm/Group Description	Brolucizumab 6 mg dosed every 4 weeks was administered via intravitreal injection for 100 weeks.	Aflibercept 2 mg dosed every 4 weeks was administered via intravitreal injection for 100 weeks.
Measure Participants	356	179
Week 4	94 26.4%	35 19.6%
Week 8	98 27.5%	43 24%
Week 12	113 31.7%	48 26.8%
Week 16	119 33.4%	53 29.6%
Week 20	123 34.6%	47 26.3%
Week 24	125 35.1%	57 31.8%
Week 28	129 36.2%	61 34.1%
Week 32	122 34.3%	57 31.8%
Week 36	108 30.3%	58 32.4%
Week 40	111 31.2%	62 34.6%
Week 44	103 28.9%	50 27.9%
Week 48	117 32.9%	54 30.2%
Week 52	108 30.3%	52 29.1%
Week 56	103 28.9%	48 26.8%
Week 60	108 30.3%	46 25.7%
Week 64	106 29.8%	51 28.5%
Week 68	96 27%	46 25.7%
Week 72	108 30.3%	46 25.7%
Week 76	107 30.1%	48 26.8%
Week 80	106 29.8%	50 27.9%
Week 84	102 28.7%	43 24%
Week 88	93 26.1%	42 23.5%
Week 92	79 22.2%	36 20.1%
Week 96	76 21.3%	31 17.3%
Week 100	70 19.7%	24 13.4%
Week 104	65 18.3%	28 15.6%

7. Secondary Outcome

Title	Gain in Best-Corrected Visual Acuity (BCVA) of 10 Letters or More
Description	BCVA was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing protocol at an initial testing distance of 4 meters. BCVA min and max possible scores are 0-100 respectively and a higher score represents better functioning. The number of subjects with gain in BCVA of 10 letters or more from baseline was reported for each post-baseline visit. Baseline BCVA was defined as the last measurement on or prior to the baseline visit. BCVA assessments after start of alternative anti-VEGF treatment in the study eye were censored and imputed by the last value prior to start of alternative treatment.
Time Frame	Baseline, weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100 and 104

Outcome Measure Data

Analysis Population Description

The overall number of participants analyzed includes all randomized participants. The number analyzed per row represents participants with data at each time point.

Arm/Group Title	Brolucizumab	Aflibercept
Arm/Group Description	Brolucizumab 6 mg dosed every 4 weeks was administered via intravitreal injection for 100 weeks.	Aflibercept 2 mg dosed every 4 weeks was administered via intravitreal injection for 100 weeks.
Measure Participants	356	179
Week 4	48 13.5%	18 10.1%
Week 8	49 13.8%	20 11.2%
Week 12	62 17.4%	20 11.2%
Week 16	64 18%	28 15.6%
Week 20	67 18.8%	26 14.5%
Week 24	77 21.6%	34 19%
Week 28	78 21.9%	36 20.1%
Week 32	75 21.1%	38 21.2%
Week 36	69 19.4%	38 21.2%
Week 40	65 18.3%	37 20.7%
Week 44	60 16.9%	31 17.3%
Week 48	66 18.5%	34 19%
Week 52	67 18.8%	32 17.9%
Week 56	71 19.9%	31 17.3%
Week 60	67 18.8%	26 14.5%
Week 64	72 20.2%	28 15.6%
Week 68	61 17.1%	31 17.3%
Week 72	62 17.4%	29 16.2%
Week 76	62 17.4%	24 13.4%
Week 80	66 18.5%	29 16.2%
Week 84	59 16.6%	29 16.2%
Week 88	53 14.9%	24 13.4%
Week 92	46 12.9%	21 11.7%
Week 96	50 14%	18 10.1%
Week 100	39 11%	15 8.4%
Week 104	42 11.8%	19 10.6%

8. Secondary Outcome

Title	Gain in Best-Corrected Visual Acuity (BCVA) of 15 Letters or More
Description	BCVA was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing protocol at an initial testing distance of 4 meters. BCVA min and max possible scores are 0-100 respectively and a higher score represents better functioning. The number of subjects with gain in BCVA of 15 letters or more from baseline was reported for each post-baseline visit. Baseline BCVA was defined as the last measurement on or prior to the baseline visit. BCVA assessments after start of alternative anti-VEGF treatment in the study eye were censored and imputed by the last value prior to start of alternative treatment.
Time Frame	Baseline, weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100 and 104

Outcome Measure Data

Analysis Population Description

The overall number of participants analyzed includes all randomized participants. The number analyzed per row represents participants with data at each time point.

Arm/Group Title	Brolucizumab	Aflibercept
Arm/Group Description	Brolucizumab 6 mg dosed every 4 weeks was administered via intravitreal injection for 100 weeks.	Aflibercept 2 mg dosed every 4 weeks was administered via intravitreal injection for 100 weeks.
Measure Participants	356	179
Week 4	43 12.1%	14 7.8%
Week 8	37 10.4%	16 8.9%
Week 12	51 14.3%	16 8.9%
Week 16	56 15.7%	23 12.8%
Week 20	51 14.3%	15 8.4%
Week 24	64 18%	25 14%
Week 28	63 17.7%	28 15.6%
Week 32	57 16%	25 14%
Week 36	50 14%	26 14.5%
Week 40	54 15.2%	26 14.5%
Week 44	47 13.2%	27 15.1%
Week 48	50 14%	22 12.3%
Week 52	50 14%	27 15.1%
Week 56	56 15.7%	22 12.3%
Week 60	56 15.7%	21 11.7%
Week 64	58 16.3%	22 12.3%
Week 68	50 14%	23 12.8%
Week 72	49 13.8%	19 10.6%
Week 76	54 15.2%	14 7.8%
Week 80	53 14.9%	20 11.2%
Week 84	44 12.4%	18 10.1%
Week 88	46 12.9%	18 10.1%
Week 92	42 11.8%	14 7.8%
Week 96	39 11%	11 6.1%
Week 100	30 8.4%	11 6.1%
Week 104	30 8.4%	14 7.8%

9. Secondary Outcome

Title	Change in Central Subfield Thickness (CST) From Baseline
Description	CST was assessed using Spectral Domain Optical Coherence Tomography (SD-OCT) images. A negative change from baseline is a favorable outcome. CST assessments after start of alternative anti-VEGF treatment in the study eye were censored and imputed by the last value prior to start of alternative treatment. These results were based on analysis using the Last observation carried forward (LOCF) approach for replacement/imputation of censored/missing values and observed data.
Time Frame	Baseline, weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100 and 104

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	Brolucizumab	Aflibercept
Arm/Group Description	Brolucizumab 6 mg dosed every 4 weeks was administered via intravitreal injection for 100 weeks.	Aflibercept 2 mg dosed every 4 weeks was administered via intravitreal injection for 100 weeks.
Measure Participants	356	178
Week 4	-55.1 (2.93)	-29.8 (4.15)
Week 8	-59.7 (3.16)	-35.4 (4.48)
Week 12	-62.3 (3.24)	-37.3 (4.59)
Week 16	-61.7 (3.36)	-39.2 (4.75)
Week 20	-64.6 (3.46)	-41.4 (4.90)
Week 24	-63.8 (3.61)	-40.8 (5.11)
Week 28	-64.3 (3.57)	-35.5 (5.05)
Week 32	-65.2 (3.70)	-40.4 (5.23)
Week 36	-64.0 (3.81)	-42.3 (5.39)
Week 40	-64.9 (3.76)	-38.2 (5.32)
Week 44	-66.7 (3.71)	-40.2 (5.24)
Week 48	-68.9 (3.76)	-40.7 (5.32)
Week 52	-69.0 (3.88)	-37.0 (5.50)
Week 56	-70.5 (3.85)	-43.9 (5.45)
Week 60	-70.0 (4.00)	-43.6 (5.66)
Week 64	-71.2 (3.99)	-41.5 (5.65)
Week 68	-71.3 (4.07)	-40.8 (5.77)
Week 72	-71.2 (4.08)	-42.6 (5.78)
Week 76	-71.4 (4.06)	-46.2 (5.76)
Week 80	-72.0 (4.13)	-45.3 (5.85)
Week 84	-71.3 (4.15)	-48.4 (5.88)
Week 88	-70.9 (4.14)	-44.6 (5.87)
Week 92	-69.1 (4.21)	-46.4 (5.97)
Week 96	-70.5 (4.13)	-43.5 (5.85)
Week 100	-69.8 (4.14)	-47.0 (5.87)
Week 104	-71.3 (4.16)	-48.3 (5.90)

10. Secondary Outcome

Title	Number of Participants With Intraretinal Fluid (IRF)
Description	IRF was assessed using Spectral Domain Optical Coherence Tomography (SD-OCT) images. The number of participants with presence of IRF was reported for each post-baseline visit. These results were based on analysis using the Last observation carried forward (LOCF) approach for replacement/imputation of censored/missing values and observed data.
Time Frame	Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100 and 104

Outcome Measure Data

Analysis Population Description

The overall number of participants analyzed includes all randomized participants. The number analyzed per row represents participants with evaluable data at each time point.

Arm/Group Title	Brolucizumab	Aflibercept
Arm/Group Description	Brolucizumab 6 mg dosed every 4 weeks was administered via intravitreal injection for 100 weeks.	Aflibercept 2 mg dosed every 4 weeks was administered via intravitreal injection for 100 weeks.
Measure Participants	356	179
Week 4	272 76.4%	132 73.7%
Week 8	276 77.5%	131 73.2%
Week 12	279 78.4%	125 69.8%
Week 16	274 77%	126 70.4%
Week 20	266 74.7%	124 69.3%
Week 24	266 74.7%	126 70.4%
Week 28	266 74.7%	128 71.5%
Week 32	262 73.6%	124 69.3%
Week 36	255 71.6%	124 69.3%
Week 40	255 71.6%	121 67.6%
Week 44	263 73.9%	122 68.2%
Week 48	265 74.4%	117 65.4%
Week 52	265 74.4%	120 67%
Week 56	268 75.3%	125 69.8%
Week 60	278 78.1%	125 69.8%
Week 64	276 77.5%	126 70.4%
Week 68	269 75.6%	127 70.9%
Week 72	271 76.1%	123 68.7%
Week 76	279 78.4%	122 68.2%
Week 80	280 78.7%	122 68.2%
Week 84	274 77%	124 69.3%
Week 88	270 75.8%	122 68.2%
Week 92	273 76.7%	123 68.7%
Week 96	270 75.8%	123 68.7%
Week 100	275 77.2%	126 70.4%
Week 104	273 76.7%	124 69.3%

11. Secondary Outcome

Title	Number of Participants With Subretinal Fluid (SRF)
Description	SRF was assessed using Spectral Domain Optical Coherence Tomography (SD-OCT) images. The number of participants with presence of SRF was reported for each post-baseline visit. These results were based on analysis using the Last observation carried forward (LOCF) approach for replacement/imputation of censored/missing values and observed data.
Time Frame	Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100 and 104

Outcome Measure Data

Analysis Population Description

The overall number of participants analyzed includes all randomized participants. The number analyzed per row represents participants with evaluable data at each time point.

Arm/Group Title	Brolucizumab	Aflibercept
Arm/Group Description	Brolucizumab 6 mg dosed every 4 weeks was administered via intravitreal injection for 100 weeks.	Aflibercept 2 mg dosed every 4 weeks was administered via intravitreal injection for 100 weeks.
Measure Participants	356	179
Week 4	161 45.2%	41 22.9%
Week 8	193 54.2%	47 26.3%
Week 12	205 57.6%	46 25.7%
Week 16	209 58.7%	60 33.5%
Week 20	200 56.2%	53 29.6%
Week 24	211 59.3%	59 33%
Week 28	207 58.1%	54 30.2%
Week 32	211 59.3%	55 30.7%
Week 36	200 56.2%	69 38.5%
Week 40	211 59.3%	59 33%
Week 44	211 59.3%	58 32.4%
Week 48	205 57.6%	62 34.6%
Week 52	203 57%	65 36.3%
Week 56	211 59.3%	65 36.3%
Week 60	207 58.1%	64 35.8%
Week 64	213 59.8%	63 35.2%
Week 68	212 59.6%	64 35.8%
Week 72	216 60.7%	72 40.2%
Week 76	220 61.8%	67 37.4%
Week 80	220 61.8%	66 36.9%
Week 84	228 64%	67 37.4%
Week 88	225 63.2%	73 40.8%
Week 92	222 62.4%	75 41.9%
Week 96	224 62.9%	73 40.8%
Week 100	223 62.6%	74 41.3%
Week 104	227 63.8%	79 44.1%

12. Secondary Outcome

Title	Number of Participants With Sub-Retinal Pigment Epithelium (Sub-RPE) Fluid
Description	Sub-RPE fluid was assessed using Spectral Domain Optical Coherence Tomography (SD-OCT) images. The number of participants with presence of sub-RPE fluid in participants with sub-RPE fluid at baseline was reported for each post-baseline visit. These results were based on analysis using the Last observation carried forward (LOCF) approach for replacement/imputation of censored/missing values and observed data.
Time Frame	Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100 and 104

Outcome Measure Data

Analysis Population Description

The overall number of participants analyzed includes all randomized participants. The number analyzed per row represents participants with evaluable data at each time point.

Arm/Group Title	Brolucizumab	Aflibercept
Arm/Group Description	Brolucizumab 6 mg dosed every 4 weeks was administered via intravitreal injection for 100 weeks.	Aflibercept 2 mg dosed every 4 weeks was administered via intravitreal injection for 100 weeks.
Measure Participants	356	179
Week 4	191 53.7%	89 49.7%
Week 8	213 59.8%	98 54.7%
Week 12	223 62.6%	98 54.7%
Week 16	235 66%	105 58.7%
Week 20	232 65.2%	99 55.3%
Week 24	231 64.9%	101 56.4%
Week 28	229 64.3%	95 53.1%
Week 32	237 66.6%	101 56.4%
Week 36	227 63.8%	101 56.4%
Week 40	238 66.9%	101 56.4%
Week 44	235 66%	103 57.5%
Week 48	228 64%	105 58.7%
Week 52	228 64%	113 63.1%
Week 56	240 67.4%	102 57%
Week 60	238 66.9%	107 59.8%
Week 64	235 66%	99 55.3%
Week 68	231 64.9%	98 54.7%
Week 72	236 66.3%	96 53.6%
Week 76	233 65.4%	96 53.6%
Week 80	234 65.7%	96 53.6%
Week 84	233 65.4%	100 55.9%
Week 88	234 65.7%	97 54.2%
Week 92	236 66.3%	94 52.5%
Week 96	237 66.6%	101 56.4%
Week 100	242 68%	104 58.1%
Week 104	237 66.6%	100 55.9%

13. Secondary Outcome

Title	Number of Participants With Fluid-free Status (no IRF, SRF or Sub-RPE Fluid)
Description	Intraretinal fluid (IRF), Subretinal fluid (SRF) and Sub-Retinal Pigment Epithelium fluid (sub-RPE) were assessed using Spectral Domain Optical Coherence Tomography (SD-OCT) images. The number of participants with fluid-free status (simultaneous absence of IRF, SRF, and sub-RPE) was reported for each post-baseline visit. These results were based on analysis using the Last observation carried forward (LOCF) approach for replacement/imputation of censored/missing values and observed data.
Time Frame	Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100 and 104

Outcome Measure Data

Analysis Population Description

The overall number of participants analyzed includes all randomized participants. The number analyzed per row represents participants with evaluable data at each time point.

Arm/Group Title	Brolucizumab	Aflibercept
Arm/Group Description	Brolucizumab 6 mg dosed every 4 weeks was administered via intravitreal injection for 100 weeks.	Aflibercept 2 mg dosed every 4 weeks was administered via intravitreal injection for 100 weeks.
Measure Participants	356	179
Week 4	82 23%	16 8.9%
Week 8	110 30.9%	24 13.4%
Week 12	120 33.7%	22 12.3%
Week 16	126 35.4%	23 12.8%
Week 20	114 32%	20 11.2%
Week 24	122 34.3%	28 15.6%
Week 28	124 34.8%	23 12.8%
Week 32	123 34.6%	24 13.4%
Week 36	111 31.2%	32 17.9%
Week 40	117 32.9%	23 12.8%
Week 44	122 34.3%	25 14%
Week 48	116 32.6%	27 15.1%
Week 52	107 30.1%	25 14%
Week 56	127 35.7%	28 15.6%
Week 60	125 35.1%	30 16.8%
Week 64	129 36.2%	28 15.6%
Week 68	124 34.8%	28 15.6%
Week 72	133 37.4%	31 17.3%
Week 76	133 37.4%	25 14%
Week 80	136 38.2%	26 14.5%
Week 84	135 37.9%	27 15.1%
Week 88	130 36.5%	32 17.9%
Week 92	128 36%	31 17.3%
Week 96	127 35.7%	32 17.9%
Week 100	130 36.5%	34 19%
Week 104	134 37.6%	38 21.2%

14. Secondary Outcome

Title	Time to First Dry Retina (no IRF or SRF)
Description	Intraretinal fluid (IRF) and Subretinal fluid (SRF) were assessed using Spectral Domain Optical Coherence Tomography (SD-OCT) images. A dry retina is defined as no IRF or SRF at the respective visit. Kaplan-Meier method was used for estimate of percentiles with 95% CI based on methodology of Brookmeyer and Crowley. Data was censored at the last time when IRF/SRF assessments for fluid-free retina were available for participants who discontinued on/or prior to the time of the start of alternative anti-VEGF treatment. IRF and SRF assessments on unscheduled visits were considered.
Time Frame	Baseline, Up to Week 104 (assessments every 4 weeks)

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	Brolucizumab	Aflibercept
Arm/Group Description	Brolucizumab 6 mg dosed every 4 weeks was administered via intravitreal injection for 100 weeks.	Aflibercept 2 mg dosed every 4 weeks was administered via intravitreal injection for 100 weeks.
Measure Participants	356	179
Median (95% Confidence Interval) [Days]	87.0	646.0

15. Secondary Outcome

Title	Time to Sustained Dry Retina (no IRF or SRF at ≥ 2 Consecutive Visits)
Description	Intraretinal fluid (IRF) and Subretinal fluid (SRF) were assessed using Spectral Domain Optical Coherence Tomography (SD-OCT) images. A sustained dry retina is defined as no IRF or SRF at 2 or more consecutive visits. Kaplan-Meier method was used for estimate of percentiles with 95% CI based on methodology of Brookmeyer and Crowley. Data was censored at the last time when IRF/SRF assessments for fluid-free retina were available for participants who discontinued on/or prior to the time of the start of alternative anti-VEGF treatment. IRF and SRF assessments on unscheduled visits were considered.
Time Frame	Baseline, Up to Week 104 (assessments every 4 weeks)

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	Brolucizumab	Aflibercept
Arm/Group Description	Brolucizumab 6 mg dosed every 4 weeks was administered via intravitreal injection for 100 weeks.	Aflibercept 2 mg dosed every 4 weeks was administered via intravitreal injection for 100 weeks.
Measure Participants	356	179
Median (95% Confidence Interval) [Days]	148.0	NA

16. Secondary Outcome

Title	Number of Participants With Anti-drug Antibody (ADA) Negative Status
Description	A blood sample was collected for anti-drug antibody assessment. ADA negative status = ADA negative result at the corresponding study visit. The baseline sample was collected prior to first dose of study treatment and the post-baseline assessments were taken at the scheduled timepoints. A negative Titer was used to assess the ADA status for the brolucizumab arm.
Time Frame	Baseline, weeks 4, 12, 24, 36, 52, 76 and 104

Outcome Measure Data

Analysis Population Description

The overall number of participants analyzed includes all randomized participants. The number analyzed per row represents participants with data at each time point. This outcome measure was pre-specified for the brolucizumab arm only.

Arm/Group Title	Brolucizumab
Arm/Group Description	Brolucizumab 6 mg dosed every 4 weeks was administered via intravitreal injection for 100 weeks.
Measure Participants	356
Baseline	77 21.6%
Week 4	121 34%
Week 12	122 34.3%
Week 24	118 33.1%
Week 36	117 32.9%
Week 52	106 29.8%
Week 76	100 28.1%
Week 104	101 28.4%

17. Secondary Outcome

Title	Free Brolucizumab Serum Concentration
Description	A blood sample was collected for Free Brolucizumab serum concentration assessment. This outcome measure was pre-specified for the brolucizumab arm only. The baseline sample was collected prior to first dose of study treatment and the post-baseline assessments. Values below the limit of quantification (BLQ) (<0.5 ng/mL) were replaced by one half of the LLOQ (0.25 ng/mL) in the calculation of the summary statistics. For the Mean score at each visit, if the calculated value was less than 0.5, then "NA" was displayed instead; meaning that the score is below the limit of quantitation (<0.5 ng/mL).
Time Frame	pre-dose a baseline, weeks 4, 12, 24, 36, 52, 76 and 104

Outcome Measure Data

Analysis Population Description

The overall number of participants analyzed includes all randomized participants. The number analyzed per row represents participants with data at each time point. This outcome measure was pre-specified for the brolucizumab arm only.

Arm/Group Title	Brolucizumab
Arm/Group Description	Brolucizumab 6 mg dosed every 4 weeks was administered via intravitreal injection for 100 weeks.
Measure Participants	356
Baseline	NA (NA)
Week 4	0.69 (2.47)
Week 12	0.81 (2.33)
Week 24	0.69 (2.10)
Week 36	0.54 (1.32)
Week 52	NA (NA)
Week 76	NA (NA)
Week 104	NA (NA)

Adverse Events

Time Frame	Adverse events were reported from the start of treatment to 4 weeks after end of treatment, assessed up to maximum duration of 104 weeks.
Adverse Event Reporting Description	Any sign or symptom that occurs during the study treatment plus the 30 days post treatment
Arm/Group Title	Brolucizumab 6mg		Aflibercept 2mg		Overall
Arm/Group Description	Brolucizumab 6mg		Aflibercept 2mg		Overall
All Cause Mortality
	Brolucizumab 6mg		Aflibercept 2mg		Overall
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/356 (2.8%)		4/179 (2.2%)		14/535 (2.6%)
Serious Adverse Events
	Brolucizumab 6mg		Aflibercept 2mg		Overall
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	75/356 (21.1%)		45/179 (25.1%)		120/535 (22.4%)
Blood and lymphatic system disorders
Anaemia	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Cardiac disorders
Acute left ventricular failure	0/356 (0%)		1/179 (0.6%)		1/535 (0.2%)
Angina pectoris	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Angina unstable	2/356 (0.6%)		0/179 (0%)		2/535 (0.4%)
Atrial fibrillation	1/356 (0.3%)		3/179 (1.7%)		4/535 (0.7%)
Cardiac arrest	1/356 (0.3%)		1/179 (0.6%)		2/535 (0.4%)
Cardiac failure congestive	2/356 (0.6%)		1/179 (0.6%)		3/535 (0.6%)
Left ventricular failure	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Myocardial infarction	2/356 (0.6%)		0/179 (0%)		2/535 (0.4%)
Sinus node dysfunction	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Stress cardiomyopathy	0/356 (0%)		1/179 (0.6%)		1/535 (0.2%)
Ventricular extrasystoles	0/356 (0%)		1/179 (0.6%)		1/535 (0.2%)
Eye disorders
Angle closure glaucoma - Study eye	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Anterior chamber cell - Study eye	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Anterior chamber flare - Study eye	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Cataract - Fellow eye	0/356 (0%)		1/179 (0.6%)		1/535 (0.2%)
Cataract - Study eye	1/356 (0.3%)		1/179 (0.6%)		2/535 (0.4%)
Glaucoma - Study eye	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Iridocyclitis - Study eye	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Neovascular age-related macular degeneration - Fellow eye	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Posterior capsule opacification - Study eye	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Retinal artery occlusion - Study eye	2/356 (0.6%)		0/179 (0%)		2/535 (0.4%)
Retinal haemorrhage - Study eye	1/356 (0.3%)		1/179 (0.6%)		2/535 (0.4%)
Retinal vasculitis - Study eye	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Retinal vein occlusion - Study eye	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Uveitis - Study eye	4/356 (1.1%)		0/179 (0%)		4/535 (0.7%)
Visual acuity reduced - Study eye	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Vitreal cells - Study eye	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Vitreous haze - Study eye	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Vitritis - Study eye	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Gastrointestinal disorders
Abdominal hernia	1/356 (0.3%)		1/179 (0.6%)		2/535 (0.4%)
Constipation	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Diarrhoea	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Dysphagia	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Gastric ulcer	0/356 (0%)		1/179 (0.6%)		1/535 (0.2%)
Gastrointestinal ulcer	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Hiatus hernia	0/356 (0%)		1/179 (0.6%)		1/535 (0.2%)
Impaired gastric emptying	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Intestinal obstruction	1/356 (0.3%)		1/179 (0.6%)		2/535 (0.4%)
Peptic ulcer haemorrhage	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Small intestinal obstruction	1/356 (0.3%)		1/179 (0.6%)		2/535 (0.4%)
Upper gastrointestinal haemorrhage	0/356 (0%)		1/179 (0.6%)		1/535 (0.2%)
General disorders
Chest pain	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Drowning	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Pyrexia	0/356 (0%)		1/179 (0.6%)		1/535 (0.2%)
Systemic inflammatory response syndrome	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Hepatobiliary disorders
Hepatic cyst	0/356 (0%)		1/179 (0.6%)		1/535 (0.2%)
Infections and infestations
Anal abscess	0/356 (0%)		1/179 (0.6%)		1/535 (0.2%)
Bronchitis	0/356 (0%)		2/179 (1.1%)		2/535 (0.4%)
COVID-19	2/356 (0.6%)		1/179 (0.6%)		3/535 (0.6%)
COVID-19 pneumonia	2/356 (0.6%)		1/179 (0.6%)		3/535 (0.6%)
Clostridium difficile colitis	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Diverticulitis	1/356 (0.3%)		1/179 (0.6%)		2/535 (0.4%)
Endophthalmitis - Study eye	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Infective exacerbation of bronchiectasis	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Influenza	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Pneumonia	5/356 (1.4%)		1/179 (0.6%)		6/535 (1.1%)
Pneumonia aspiration	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Postoperative wound infection	0/356 (0%)		1/179 (0.6%)		1/535 (0.2%)
Sepsis	2/356 (0.6%)		0/179 (0%)		2/535 (0.4%)
Septic shock	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Urinary tract infection	2/356 (0.6%)		0/179 (0%)		2/535 (0.4%)
Urosepsis	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Injury, poisoning and procedural complications
Corneal abrasion - Study eye	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Face injury	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Femur fracture	0/356 (0%)		1/179 (0.6%)		1/535 (0.2%)
Foot fracture	0/356 (0%)		1/179 (0.6%)		1/535 (0.2%)
Hip fracture	0/356 (0%)		2/179 (1.1%)		2/535 (0.4%)
Pelvic fracture	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Postoperative respiratory failure	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Rib fracture	0/356 (0%)		1/179 (0.6%)		1/535 (0.2%)
Road traffic accident	0/356 (0%)		1/179 (0.6%)		1/535 (0.2%)
Upper limb fracture	1/356 (0.3%)		1/179 (0.6%)		2/535 (0.4%)
Wrist fracture	0/356 (0%)		1/179 (0.6%)		1/535 (0.2%)
Investigations
Streptococcus test positive - Study eye	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Metabolism and nutrition disorders
Dehydration	2/356 (0.6%)		0/179 (0%)		2/535 (0.4%)
Hypoglycaemia	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Hyponatraemia	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Musculoskeletal and connective tissue disorders
Intervertebral disc degeneration	0/356 (0%)		1/179 (0.6%)		1/535 (0.2%)
Lumbar spinal stenosis	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Osteoarthritis	0/356 (0%)		1/179 (0.6%)		1/535 (0.2%)
Pathological fracture	0/356 (0%)		1/179 (0.6%)		1/535 (0.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of colon	1/356 (0.3%)		1/179 (0.6%)		2/535 (0.4%)
Bone cancer	1/356 (0.3%)		1/179 (0.6%)		2/535 (0.4%)
Breast cancer	2/356 (0.6%)		0/179 (0%)		2/535 (0.4%)
Choroid neoplasm - Fellow eye	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Hepatic cancer	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Lung adenocarcinoma	0/356 (0%)		1/179 (0.6%)		1/535 (0.2%)
Lung cancer metastatic	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Lung neoplasm malignant	3/356 (0.8%)		0/179 (0%)		3/535 (0.6%)
Malignant peritoneal neoplasm	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Non-small cell lung cancer metastatic	0/356 (0%)		1/179 (0.6%)		1/535 (0.2%)
Oropharyngeal squamous cell carcinoma	0/356 (0%)		1/179 (0.6%)		1/535 (0.2%)
Prostate cancer	1/356 (0.3%)		2/179 (1.1%)		3/535 (0.6%)
Renal cancer metastatic	0/356 (0%)		1/179 (0.6%)		1/535 (0.2%)
Squamous cell carcinoma	0/356 (0%)		1/179 (0.6%)		1/535 (0.2%)
Nervous system disorders
Cerebral haemorrhage	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Cerebral infarction	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Cerebrovascular accident	1/356 (0.3%)		1/179 (0.6%)		2/535 (0.4%)
Haemorrhagic cerebral infarction	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Intracranial aneurysm	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Loss of consciousness	0/356 (0%)		1/179 (0.6%)		1/535 (0.2%)
Migraine	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Presyncope	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Seizure	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Syncope	2/356 (0.6%)		2/179 (1.1%)		4/535 (0.7%)
Transient ischaemic attack	0/356 (0%)		2/179 (1.1%)		2/535 (0.4%)
Renal and urinary disorders
Acute kidney injury	2/356 (0.6%)		1/179 (0.6%)		3/535 (0.6%)
Haematuria	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Nephrolithiasis	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	1/356 (0.3%)		1/179 (0.6%)		2/535 (0.4%)
Asphyxia	0/356 (0%)		1/179 (0.6%)		1/535 (0.2%)
Chronic obstructive pulmonary disease	2/356 (0.6%)		0/179 (0%)		2/535 (0.4%)
Dyspnoea	1/356 (0.3%)		1/179 (0.6%)		2/535 (0.4%)
Haemoptysis	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Pleural effusion	0/356 (0%)		1/179 (0.6%)		1/535 (0.2%)
Pleuritic pain	0/356 (0%)		1/179 (0.6%)		1/535 (0.2%)
Pulmonary embolism	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Pulmonary hypertension	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Pulmonary mass	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Respiratory failure	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Skin and subcutaneous tissue disorders
Skin ulcer	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Stasis dermatitis	0/356 (0%)		1/179 (0.6%)		1/535 (0.2%)
Vascular disorders
Aortic stenosis	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Hypotension	1/356 (0.3%)		0/179 (0%)		1/535 (0.2%)
Peripheral arterial occlusive disease	0/356 (0%)		1/179 (0.6%)		1/535 (0.2%)
Shock	0/356 (0%)		1/179 (0.6%)		1/535 (0.2%)
Other (Not Including Serious) Adverse Events
	Brolucizumab 6mg		Aflibercept 2mg		Overall
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	287/356 (80.6%)		149/179 (83.2%)		436/535 (81.5%)
Blood and lymphatic system disorders
Anaemia	4/356 (1.1%)		6/179 (3.4%)		10/535 (1.9%)
Cardiac disorders
Arrhythmia	1/356 (0.3%)		2/179 (1.1%)		3/535 (0.6%)
Arteriosclerosis coronary artery	1/356 (0.3%)		2/179 (1.1%)		3/535 (0.6%)
Atrial fibrillation	9/356 (2.5%)		10/179 (5.6%)		19/535 (3.6%)
Tachycardia	4/356 (1.1%)		0/179 (0%)		4/535 (0.7%)
Ear and labyrinth disorders
Ear pain	0/356 (0%)		2/179 (1.1%)		2/535 (0.4%)
Vertigo	8/356 (2.2%)		1/179 (0.6%)		9/535 (1.7%)
Endocrine disorders
Hypothyroidism	5/356 (1.4%)		3/179 (1.7%)		8/535 (1.5%)
Eye disorders
Blepharitis - Fellow eye	10/356 (2.8%)		4/179 (2.2%)		14/535 (2.6%)
Blepharitis - Study eye	13/356 (3.7%)		5/179 (2.8%)		18/535 (3.4%)
Cataract - Fellow eye	13/356 (3.7%)		3/179 (1.7%)		16/535 (3%)
Cataract - Study eye	23/356 (6.5%)		4/179 (2.2%)		27/535 (5%)
Cataract nuclear - Fellow eye	4/356 (1.1%)		1/179 (0.6%)		5/535 (0.9%)
Cataract nuclear - Study eye	8/356 (2.2%)		1/179 (0.6%)		9/535 (1.7%)
Cataract subcapsular - Study eye	16/356 (4.5%)		6/179 (3.4%)		22/535 (4.1%)
Chalazion - Study eye	4/356 (1.1%)		2/179 (1.1%)		6/535 (1.1%)
Conjunctival haemorrhage - Fellow eye	6/356 (1.7%)		7/179 (3.9%)		13/535 (2.4%)
Conjunctival haemorrhage - Study eye	32/356 (9%)		14/179 (7.8%)		46/535 (8.6%)
Corneal disorder - Study eye	2/356 (0.6%)		2/179 (1.1%)		4/535 (0.7%)
Corneal oedema - Study eye	3/356 (0.8%)		2/179 (1.1%)		5/535 (0.9%)
Diabetic retinopathy - Study eye	2/356 (0.6%)		2/179 (1.1%)		4/535 (0.7%)
Diplopia - Study eye	5/356 (1.4%)		1/179 (0.6%)		6/535 (1.1%)
Dry age-related macular degeneration - Fellow eye	5/356 (1.4%)		0/179 (0%)		5/535 (0.9%)
Dry age-related macular degeneration - Study eye	10/356 (2.8%)		4/179 (2.2%)		14/535 (2.6%)
Dry eye - Fellow eye	10/356 (2.8%)		3/179 (1.7%)		13/535 (2.4%)
Dry eye - Study eye	19/356 (5.3%)		4/179 (2.2%)		23/535 (4.3%)
Eye irritation - Study eye	4/356 (1.1%)		0/179 (0%)		4/535 (0.7%)
Eye pain - Study eye	9/356 (2.5%)		4/179 (2.2%)		13/535 (2.4%)
Iridocyclitis - Fellow eye	1/356 (0.3%)		2/179 (1.1%)		3/535 (0.6%)
Iridocyclitis - Study eye	17/356 (4.8%)		3/179 (1.7%)		20/535 (3.7%)
Iritis - Study eye	6/356 (1.7%)		2/179 (1.1%)		8/535 (1.5%)
Lacrimation increased - Study eye	4/356 (1.1%)		2/179 (1.1%)		6/535 (1.1%)
Meibomian gland dysfunction - Study eye	1/356 (0.3%)		2/179 (1.1%)		3/535 (0.6%)
Neovascular age-related macular degeneration - Fellow eye	19/356 (5.3%)		13/179 (7.3%)		32/535 (6%)
Neovascular age-related macular degeneration - Study eye	9/356 (2.5%)		5/179 (2.8%)		14/535 (2.6%)
Ocular hypertension - Fellow eye	1/356 (0.3%)		2/179 (1.1%)		3/535 (0.6%)
Ocular hypertension - Study eye	3/356 (0.8%)		2/179 (1.1%)		5/535 (0.9%)
Optic disc haemorrhage - Study eye	2/356 (0.6%)		2/179 (1.1%)		4/535 (0.7%)
Posterior capsule opacification - Fellow eye	9/356 (2.5%)		4/179 (2.2%)		13/535 (2.4%)
Posterior capsule opacification - Study eye	8/356 (2.2%)		8/179 (4.5%)		16/535 (3%)
Punctate keratitis - Fellow eye	7/356 (2%)		2/179 (1.1%)		9/535 (1.7%)
Punctate keratitis - Study eye	9/356 (2.5%)		5/179 (2.8%)		14/535 (2.6%)
Retinal artery embolism - Study eye	4/356 (1.1%)		0/179 (0%)		4/535 (0.7%)
Retinal haemorrhage - Fellow eye	9/356 (2.5%)		6/179 (3.4%)		15/535 (2.8%)
Retinal haemorrhage - Study eye	16/356 (4.5%)		5/179 (2.8%)		21/535 (3.9%)
Subretinal fluid - Fellow eye	4/356 (1.1%)		2/179 (1.1%)		6/535 (1.1%)
Subretinal fluid - Study eye	3/356 (0.8%)		2/179 (1.1%)		5/535 (0.9%)
Uveitis - Study eye	8/356 (2.2%)		3/179 (1.7%)		11/535 (2.1%)
Vision blurred - Study eye	7/356 (2%)		1/179 (0.6%)		8/535 (1.5%)
Visual acuity reduced - Fellow eye	4/356 (1.1%)		0/179 (0%)		4/535 (0.7%)
Visual acuity reduced - Study eye	22/356 (6.2%)		6/179 (3.4%)		28/535 (5.2%)
Vitreal cells - Study eye	3/356 (0.8%)		4/179 (2.2%)		7/535 (1.3%)
Vitreous detachment - Fellow eye	6/356 (1.7%)		3/179 (1.7%)		9/535 (1.7%)
Vitreous detachment - Study eye	18/356 (5.1%)		5/179 (2.8%)		23/535 (4.3%)
Vitreous floaters - Fellow eye	4/356 (1.1%)		2/179 (1.1%)		6/535 (1.1%)
Vitreous floaters - Study eye	21/356 (5.9%)		10/179 (5.6%)		31/535 (5.8%)
Vitreous haemorrhage - Study eye	6/356 (1.7%)		2/179 (1.1%)		8/535 (1.5%)
Vitritis - Study eye	9/356 (2.5%)		3/179 (1.7%)		12/535 (2.2%)
Gastrointestinal disorders
Constipation	3/356 (0.8%)		2/179 (1.1%)		5/535 (0.9%)
Dental caries	9/356 (2.5%)		1/179 (0.6%)		10/535 (1.9%)
Diarrhoea	6/356 (1.7%)		4/179 (2.2%)		10/535 (1.9%)
Dyspepsia	0/356 (0%)		2/179 (1.1%)		2/535 (0.4%)
Food poisoning	0/356 (0%)		2/179 (1.1%)		2/535 (0.4%)
Gastrooesophageal reflux disease	6/356 (1.7%)		4/179 (2.2%)		10/535 (1.9%)
Hiatus hernia	3/356 (0.8%)		3/179 (1.7%)		6/535 (1.1%)
Large intestine polyp	0/356 (0%)		3/179 (1.7%)		3/535 (0.6%)
Nausea	6/356 (1.7%)		3/179 (1.7%)		9/535 (1.7%)
Toothache	2/356 (0.6%)		3/179 (1.7%)		5/535 (0.9%)
General disorders
Fatigue	4/356 (1.1%)		0/179 (0%)		4/535 (0.7%)
Oedema peripheral	9/356 (2.5%)		6/179 (3.4%)		15/535 (2.8%)
Immune system disorders
Drug hypersensitivity	1/356 (0.3%)		2/179 (1.1%)		3/535 (0.6%)
Seasonal allergy	12/356 (3.4%)		8/179 (4.5%)		20/535 (3.7%)
Infections and infestations
Bronchitis	15/356 (4.2%)		8/179 (4.5%)		23/535 (4.3%)
COVID-19	8/356 (2.2%)		7/179 (3.9%)		15/535 (2.8%)
Cellulitis	4/356 (1.1%)		2/179 (1.1%)		6/535 (1.1%)
Chorioretinitis - Study eye	9/356 (2.5%)		1/179 (0.6%)		10/535 (1.9%)
Conjunctivitis - Study eye	4/356 (1.1%)		0/179 (0%)		4/535 (0.7%)
Cystitis	2/356 (0.6%)		3/179 (1.7%)		5/535 (0.9%)
Diverticulitis	2/356 (0.6%)		3/179 (1.7%)		5/535 (0.9%)
Ear infection	4/356 (1.1%)		3/179 (1.7%)		7/535 (1.3%)
Fungal infection	4/356 (1.1%)		3/179 (1.7%)		7/535 (1.3%)
Gastroenteritis viral	2/356 (0.6%)		3/179 (1.7%)		5/535 (0.9%)
Herpes zoster	2/356 (0.6%)		2/179 (1.1%)		4/535 (0.7%)
Hordeolum - Fellow eye	5/356 (1.4%)		3/179 (1.7%)		8/535 (1.5%)
Hordeolum - Study eye	4/356 (1.1%)		2/179 (1.1%)		6/535 (1.1%)
Influenza	7/356 (2%)		2/179 (1.1%)		9/535 (1.7%)
Localised infection	4/356 (1.1%)		1/179 (0.6%)		5/535 (0.9%)
Nasopharyngitis	12/356 (3.4%)		10/179 (5.6%)		22/535 (4.1%)
Pharyngitis	1/356 (0.3%)		2/179 (1.1%)		3/535 (0.6%)
Pneumonia	9/356 (2.5%)		1/179 (0.6%)		10/535 (1.9%)
Sinusitis	11/356 (3.1%)		11/179 (6.1%)		22/535 (4.1%)
Tooth abscess	4/356 (1.1%)		1/179 (0.6%)		5/535 (0.9%)
Tooth infection	4/356 (1.1%)		1/179 (0.6%)		5/535 (0.9%)
Upper respiratory tract infection	17/356 (4.8%)		6/179 (3.4%)		23/535 (4.3%)
Urinary tract infection	36/356 (10.1%)		16/179 (8.9%)		52/535 (9.7%)
Injury, poisoning and procedural complications
Arthropod bite	2/356 (0.6%)		2/179 (1.1%)		4/535 (0.7%)
Bone contusion	1/356 (0.3%)		2/179 (1.1%)		3/535 (0.6%)
Fall	23/356 (6.5%)		6/179 (3.4%)		29/535 (5.4%)
Foreign body in eye - Study eye	11/356 (3.1%)		2/179 (1.1%)		13/535 (2.4%)
Hand fracture	1/356 (0.3%)		2/179 (1.1%)		3/535 (0.6%)
Ligament sprain	4/356 (1.1%)		3/179 (1.7%)		7/535 (1.3%)
Meniscus injury	0/356 (0%)		2/179 (1.1%)		2/535 (0.4%)
Muscle strain	5/356 (1.4%)		1/179 (0.6%)		6/535 (1.1%)
Posterior capsule rupture - Study eye	0/356 (0%)		2/179 (1.1%)		2/535 (0.4%)
Skin laceration	4/356 (1.1%)		1/179 (0.6%)		5/535 (0.9%)
Investigations
Amylase increased	1/356 (0.3%)		3/179 (1.7%)		4/535 (0.7%)
Blood alkaline phosphatase increased	0/356 (0%)		2/179 (1.1%)		2/535 (0.4%)
Blood cholesterol increased	3/356 (0.8%)		4/179 (2.2%)		7/535 (1.3%)
Blood creatinine increased	3/356 (0.8%)		2/179 (1.1%)		5/535 (0.9%)
Blood glucose increased	5/356 (1.4%)		1/179 (0.6%)		6/535 (1.1%)
Blood lactate dehydrogenase increased	3/356 (0.8%)		2/179 (1.1%)		5/535 (0.9%)
Blood phosphorus increased	0/356 (0%)		2/179 (1.1%)		2/535 (0.4%)
Blood potassium increased	2/356 (0.6%)		2/179 (1.1%)		4/535 (0.7%)
Blood pressure increased	6/356 (1.7%)		3/179 (1.7%)		9/535 (1.7%)
Blood triglycerides increased	4/356 (1.1%)		2/179 (1.1%)		6/535 (1.1%)
Blood urea increased	0/356 (0%)		2/179 (1.1%)		2/535 (0.4%)
Intraocular pressure increased - Fellow eye	2/356 (0.6%)		2/179 (1.1%)		4/535 (0.7%)
Intraocular pressure increased - Study eye	19/356 (5.3%)		7/179 (3.9%)		26/535 (4.9%)
Lipase increased	2/356 (0.6%)		2/179 (1.1%)		4/535 (0.7%)
Mean cell volume increased	1/356 (0.3%)		2/179 (1.1%)		3/535 (0.6%)
Monocyte count increased	2/356 (0.6%)		2/179 (1.1%)		4/535 (0.7%)
Optic nerve cup/disc ratio increased - Study eye	0/356 (0%)		2/179 (1.1%)		2/535 (0.4%)
Red blood cell count decreased	5/356 (1.4%)		1/179 (0.6%)		6/535 (1.1%)
Urine analysis abnormal	4/356 (1.1%)		2/179 (1.1%)		6/535 (1.1%)
White blood cell count increased	2/356 (0.6%)		2/179 (1.1%)		4/535 (0.7%)
Metabolism and nutrition disorders
Dehydration	5/356 (1.4%)		0/179 (0%)		5/535 (0.9%)
Hypercalcaemia	0/356 (0%)		2/179 (1.1%)		2/535 (0.4%)
Hypercholesterolaemia	6/356 (1.7%)		4/179 (2.2%)		10/535 (1.9%)
Hyperlipidaemia	6/356 (1.7%)		1/179 (0.6%)		7/535 (1.3%)
Hypertriglyceridaemia	0/356 (0%)		3/179 (1.7%)		3/535 (0.6%)
Hyponatraemia	4/356 (1.1%)		0/179 (0%)		4/535 (0.7%)
Type 2 diabetes mellitus	4/356 (1.1%)		3/179 (1.7%)		7/535 (1.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	15/356 (4.2%)		6/179 (3.4%)		21/535 (3.9%)
Arthritis	4/356 (1.1%)		3/179 (1.7%)		7/535 (1.3%)
Back pain	13/356 (3.7%)		3/179 (1.7%)		16/535 (3%)
Dupuytren's contracture	0/356 (0%)		2/179 (1.1%)		2/535 (0.4%)
Intervertebral disc degeneration	1/356 (0.3%)		2/179 (1.1%)		3/535 (0.6%)
Muscle spasms	4/356 (1.1%)		4/179 (2.2%)		8/535 (1.5%)
Osteoarthritis	11/356 (3.1%)		3/179 (1.7%)		14/535 (2.6%)
Osteoporosis	0/356 (0%)		2/179 (1.1%)		2/535 (0.4%)
Pain in extremity	2/356 (0.6%)		4/179 (2.2%)		6/535 (1.1%)
Rheumatoid arthritis	3/356 (0.8%)		3/179 (1.7%)		6/535 (1.1%)
Rotator cuff syndrome	0/356 (0%)		3/179 (1.7%)		3/535 (0.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	7/356 (2%)		0/179 (0%)		7/535 (1.3%)
Squamous cell carcinoma	5/356 (1.4%)		2/179 (1.1%)		7/535 (1.3%)
Squamous cell carcinoma of skin	4/356 (1.1%)		0/179 (0%)		4/535 (0.7%)
Nervous system disorders
Amnesia	2/356 (0.6%)		2/179 (1.1%)		4/535 (0.7%)
Carotid artery stenosis	4/356 (1.1%)		1/179 (0.6%)		5/535 (0.9%)
Dizziness	2/356 (0.6%)		2/179 (1.1%)		4/535 (0.7%)
Headache	6/356 (1.7%)		7/179 (3.9%)		13/535 (2.4%)
Nerve compression	1/356 (0.3%)		2/179 (1.1%)		3/535 (0.6%)
Neuropathy peripheral	2/356 (0.6%)		2/179 (1.1%)		4/535 (0.7%)
Sciatica	2/356 (0.6%)		3/179 (1.7%)		5/535 (0.9%)
Psychiatric disorders
Anxiety	5/356 (1.4%)		4/179 (2.2%)		9/535 (1.7%)
Depression	4/356 (1.1%)		3/179 (1.7%)		7/535 (1.3%)
Insomnia	4/356 (1.1%)		1/179 (0.6%)		5/535 (0.9%)
Renal and urinary disorders
Acute kidney injury	4/356 (1.1%)		2/179 (1.1%)		6/535 (1.1%)
Haematuria	7/356 (2%)		1/179 (0.6%)		8/535 (1.5%)
Nephrolithiasis	3/356 (0.8%)		3/179 (1.7%)		6/535 (1.1%)
Proteinuria	12/356 (3.4%)		5/179 (2.8%)		17/535 (3.2%)
Reproductive system and breast disorders
Prostatomegaly	3/356 (0.8%)		2/179 (1.1%)		5/535 (0.9%)
Respiratory, thoracic and mediastinal disorders
Asthma	2/356 (0.6%)		2/179 (1.1%)		4/535 (0.7%)
Chronic obstructive pulmonary disease	7/356 (2%)		2/179 (1.1%)		9/535 (1.7%)
Cough	11/356 (3.1%)		5/179 (2.8%)		16/535 (3%)
Dyspnoea	4/356 (1.1%)		2/179 (1.1%)		6/535 (1.1%)
Pulmonary mass	5/356 (1.4%)		0/179 (0%)		5/535 (0.9%)
Skin and subcutaneous tissue disorders
Decubitus ulcer	1/356 (0.3%)		2/179 (1.1%)		3/535 (0.6%)
Psoriasis	0/356 (0%)		2/179 (1.1%)		2/535 (0.4%)
Rash	3/356 (0.8%)		7/179 (3.9%)		10/535 (1.9%)
Urticaria	0/356 (0%)		2/179 (1.1%)		2/535 (0.4%)
Vascular disorders
Arteriosclerosis	2/356 (0.6%)		3/179 (1.7%)		5/535 (0.9%)
Deep vein thrombosis	0/356 (0%)		2/179 (1.1%)		2/535 (0.4%)
Hypertension	28/356 (7.9%)		23/179 (12.8%)		51/535 (9.5%)
Hypotension	3/356 (0.8%)		3/179 (1.7%)		6/535 (1.1%)
Peripheral arterial occlusive disease	2/356 (0.6%)		2/179 (1.1%)		4/535 (0.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.