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Clinical Trial Results:
A two-year, three-arm, randomized, double masked, multicenter, phase III study assessing the efficacy and safety of brolucizumab versus aflibercept in adult patients with visual impairment due to diabetic macular edema (KESTREL)

Summary
EudraCT number	2017-004742-23
Trial protocol	NL AT ES PT GB IT
Global end of trial date	18 Oct 2021

Results information
Results version number	v2(current)
This version publication date	15 Dec 2022
First version publication date	13 Aug 2022
Other versions	v1
Version creation reason	Correction of full data set Updated results to match updates to CTGOV results per NIH QA comments

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

CRTH258B2301

ISRCTN number

US NCT number

NCT03481634

WHO universal trial number (UTN)

Sponsor organisation name

Novartis Pharma AG

Sponsor organisation address

Novartis Campus, Basel, Switzerland,

Public contact

Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@Novartis.com

Scientific contact

Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@Novartis.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

18 Oct 2021

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

18 Oct 2021

Was the trial ended prematurely?

Main objective of the trial

To demonstrate that brolucizumab is non-inferior to aflibercept with respect to the visual outcome after the first year of treatment. Due to EudraCT system limitations, which EMA is aware of, data using 999 as data points in this record are not an accurate representation of the clinical trial results. Please use https://www.novctrd.com for complete trial results.

Protection of trial subjects

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.

Background therapy

Evidence for comparator

Actual start date of recruitment

23 Jul 2018

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Argentina: 43

Country: Number of subjects enrolled

Australia: 27

Country: Number of subjects enrolled

Austria: 17

Country: Number of subjects enrolled

Canada: 16

Country: Number of subjects enrolled

Colombia: 17

Country: Number of subjects enrolled

United Kingdom: 19

Country: Number of subjects enrolled

Israel: 53

Country: Number of subjects enrolled

Italy: 17

Country: Number of subjects enrolled

Japan: 59

Country: Number of subjects enrolled

Netherlands: 8

Country: Number of subjects enrolled

Portugal: 44

Country: Number of subjects enrolled

Spain: 63

Country: Number of subjects enrolled

United States: 183

Worldwide total number of subjects

566

EEA total number of subjects

149

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

294

From 65 to 84 years

267

85 years and over

Subject disposition

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Recruitment details

Screening details

Of a total of 873 subjects who were screened,566 subjects were randomized in a 1:1:1 ratio to the brolucizumab 6 mg (n=189) or 3 mg (n=190) arms, or to the aflibercept 2 mg arm (n=187) between 30-Jul-2018 and 14-Nov-2019, and 307 subjects were not randomized due to screen failures.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Investigator, Monitor, Carer, Subject

Are arms mutually exclusive

Yes

Brolucizumab 3 mg

Arm description

Brolucizumab 3 mg/0.05 mL, 5 loading doses, with subsequent doses per protocol-specified maintenance schedule

Arm type

Experimental

Investigational medicinal product name

Brolucizumab

Investigational medicinal product code

RTH258

Other name

Beovu

Pharmaceutical forms

Solution for injection

Routes of administration

Intravitreal use

Dosage and administration details

3 mg/0.05 mL administered 5xq6w during loading phase then q12w/q8w during maintenance phase.

Brolucizumab 6 mg

Arm description

Brolucizumab 6 mg/0.05 mL, 5 loading doses, with subsequent doses per protocol-specified maintenance schedule

Arm type

Experimental

Investigational medicinal product name

Brolucizumab

Investigational medicinal product code

RTH258

Other name

Beovu

Pharmaceutical forms

Solution for injection

Routes of administration

Intravitreal use

Dosage and administration details

6 mg/0.05 mL administered 5xq6w during loading phase then q12w/q8w during maintenance phase.

Aflibercept 2 mg

Arm description

Aflibercept 2 mg/0.05 mL, as labeled, 5 loading doses, with subsequent doses every 8 weeks

Arm type

Active comparator

Investigational medicinal product name

Aflibercept

Investigational medicinal product code

Other name

EYLEA

Pharmaceutical forms

Solution for injection

Routes of administration

Intravitreal use

Dosage and administration details

2 mg/0.05 mL administered 5xq4w during loading phase then q8w during maintenance phase.

Number of subjects in period 1	Brolucizumab 3 mg	Brolucizumab 6 mg	Aflibercept 2 mg
Started	190	189	187
Completed	157	154	153
Not completed	33	35	34
Adverse event, serious fatal	4	8	7
Physician decision	3	-	1
Adverse event, non-fatal	6	3	7
Subject decision	16	19	14
Lost to follow-up	3	4	4
Progressive disease	-	1	-
Protocol deviation	1	-	1

Baseline characteristics

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Reporting group title

Brolucizumab 3 mg

Reporting group description

Brolucizumab 3 mg/0.05 mL, 5 loading doses, with subsequent doses per protocol-specified maintenance schedule

Reporting group title

Brolucizumab 6 mg

Reporting group description

Brolucizumab 6 mg/0.05 mL, 5 loading doses, with subsequent doses per protocol-specified maintenance schedule

Reporting group title

Aflibercept 2 mg

Reporting group description

Aflibercept 2 mg/0.05 mL, as labeled, 5 loading doses, with subsequent doses every 8 weeks

Reporting group values	Brolucizumab 3 mg	Brolucizumab 6 mg	Aflibercept 2 mg	Total
Number of subjects	190	189	187	566
Age Categorical
Units: Participants
<=18 years	0	0	0	0
Between 18 and 65 years	97	104	93	294
>=65 years	93	85	94	272
Age Continuous
Units: years
arithmetic mean (standard deviation)	64.4 ± 9.76	62.4 ± 10.14	63.9 ± 10.09	-
Sex: Female, Male
Units: Participants
Female	71	79	61	211
Male	119	110	126	355
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	1	0	1	2
Asian	25	25	26	76
Native Hawaiian or Other Pacific Islander	0	2	0	2
Black or African American	13	4	7	24
White	151	158	152	461
More than one race	0	0	1	1
Unknown or Not Reported	0	0	0	0

End points

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Reporting group title

Brolucizumab 3 mg

Reporting group description

Brolucizumab 3 mg/0.05 mL, 5 loading doses, with subsequent doses per protocol-specified maintenance schedule

Reporting group title

Brolucizumab 6 mg

Reporting group description

Brolucizumab 6 mg/0.05 mL, 5 loading doses, with subsequent doses per protocol-specified maintenance schedule

Reporting group title

Aflibercept 2 mg

Reporting group description

Aflibercept 2 mg/0.05 mL, as labeled, 5 loading doses, with subsequent doses every 8 weeks

Primary: Change from baseline in best-corrected visual acuity (BCVA) at Week 52

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End point title

Change from baseline in best-corrected visual acuity (BCVA) at Week 52

End point description

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. Participants with a BCVA ETDRS letter score of 78 to 23 (approximate Snellen equivalent of 20/32 to 20/320) in the study eye were included. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning. This endpoint was analyzed via the pairwise ANOVA method where the 2 dose groups of Brolucizumab are compared to Aflibercept.

End point type

Primary

End point timeframe

Baseline, Week 52

End point values	Brolucizumab 3 mg	Brolucizumab 6 mg	Aflibercept 2 mg
Number of subjects analysed	190	189	187
Units: Scores on a scale
least squares mean (standard error)
Brolucizumab 3 mg v Aflibercept 2 mg	7.3 ± 0.66	999 ± 999	10.6 ± 0.67
Brolucizumab 6 mg v Aflibercept 2 mg	999 ± 999	9.2 ± 0.57	10.5 ± 0.57

Brolucizumab 6 mg v Aflibercept 2 mg

Comparison groups

Brolucizumab 6 mg v Aflibercept 2 mg

Number of subjects included in analysis

376

Analysis specification

Pre-specified

Analysis type

^[1]

P-value

< 0.001 ^[2]

Method

ANOVA

Parameter type

LS mean difference

Point estimate

-1.3

Confidence interval

level

95%

sides

2-sided

lower limit

-2.9

upper limit

0.3

Variability estimate

Standard error of the mean

Dispersion value

0.81

Notes
[1] - Non-inferiority (4-letter margin)
[2] - 1-sided p-value

Brolucizumab 3 mg v Aflibercept 2 mg

Comparison groups

Brolucizumab 3 mg v Aflibercept 2 mg

Number of subjects included in analysis

377

Analysis specification

Pre-specified

Analysis type

^[3]

P-value

= 0.227 ^[4]

Method

ANOVA

Parameter type

LS mean difference

Point estimate

-3.3

Confidence interval

level

95%

sides

2-sided

lower limit

-5.1

upper limit

-1.4

Variability estimate

Standard error of the mean

Dispersion value

0.94

Notes
[3] - Non-inferiority (4-letter margin)
[4] - 1-sided p-value

Secondary: Average change from baseline in BCVA over the period Week 40 through Week 52

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End point title

Average change from baseline in BCVA over the period Week 40 through Week 52

End point description

BCVA will be assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. Visual function of the study eye was assessed using the ETDRS protocol. Participants with a BCVA ETDRS letter score of 78 to 23 (per the inclusion criteria) (approximate Snellen equivalent of 20/32 to 20/320) in the study eye were included. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning. This endpoint was analyzed via the pairwise ANOVA method where the 2 dose groups of Brolucizumab are compared to Aflibercept.

End point type

Secondary

End point timeframe

Baseline and Week 40 through Week 52 (average)

End point values	Brolucizumab 3 mg	Brolucizumab 6 mg	Aflibercept 2 mg
Number of subjects analysed	190	189	187
Units: Scores on a scale
least squares mean (standard error)
Brolucizumab 3 mg v Aflibercept 2 mg	7.0 ± 0.63	999 ± 999	10.5 ± 0.64
Brolucizumab 6 mg v Aflibercept 2 mg	999 ± 999	9.0 ± 0.53	10.5 ± 0.53

Brolucizumab 3 mg v Aflibercept 2 mg

Comparison groups

Brolucizumab 3 mg v Aflibercept 2 mg

Number of subjects included in analysis

377

Analysis specification

Pre-specified

Analysis type

^[5]

Method

ANOVA

Parameter type

Mean difference (net)

Point estimate

-3.5

Confidence interval

level

95%

sides

2-sided

lower limit

-5.2

upper limit

-1.7

Variability estimate

Standard error of the mean

Dispersion value

0.9

Notes
[5] - Non-inferiority (4-letter margin)

Brolucizumab 6 mg v Aflibercept 2 mg

Comparison groups

Brolucizumab 6 mg v Aflibercept 2 mg

Number of subjects included in analysis

376

Analysis specification

Pre-specified

Analysis type

^[6]

P-value

< 0.001 ^[7]

Method

ANOVA

Parameter type

Mean difference (net)

Point estimate

-1.5

Confidence interval

level

95%

sides

2-sided

lower limit

-3

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.75

Notes
[6] - Non-inferiority (4-letter margin)
[7] - (1-sided)

Secondary: Patients maintained at q12w - Probability of maintaining on q12w

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End point title

Patients maintained at q12w - Probability of maintaining on q12w ^[8]

End point description

Positive treatment status is defined as intravitreal (IVT) injections per planned dosing regimen [every 12 weeks (q12w)]. This outcome measure is pre-specified for brolucizumab treatment arms only.

End point type

Secondary

End point timeframe

Baseline (Week 0), Weeks 32, 36 and 48

Notes
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint does not apply to all treatment arms.

End point values	Brolucizumab 3 mg	Brolucizumab 6 mg
Number of subjects analysed	190	189
Units: Probability
number (confidence interval 95%)
Prob. of maintaining on q12w (survival)- Week 0	1 (-999 to 999)	1 (-999 to 999)
Prob. of maintaining on q12w (survival)- Week 32	0.758 (0.685 to 0.816)	0.801 (0.732 to 0.854)
Prob. of maintaining on q12w (survival)- Week 36	0.545 (0.463 to 0.619)	0.628 (0.548 to 0.698)
Prob. of maintaining on q12w (survival)- Week 48	0.474 (0.393 to 0.551)	0.551 (0.469 to 0.625)

No statistical analyses for this end point

Secondary: Patients maintained at q12w (for those patients who qualified for q12w at week 36) - probability of maintaining on q12w

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End point title

Patients maintained at q12w (for those patients who qualified for q12w at week 36) - probability of maintaining on q12w ^[9]

End point description

Positive treatment status is defined as intravitreal (IVT) injections per planned dosing regimen [every 8 weeks (q8w)]. This outcome measure is pre-specified for brolucizumab treatment arms only.

End point type

Secondary

End point timeframe

Weeks 36 and 48

Notes
[9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint does not apply to all treatment arms.

End point values	Brolucizumab 3 mg	Brolucizumab 6 mg
Number of subjects analysed	190	189
Units: Probability
number (confidence interval 95%)
Prob. of maintaining on q12w (survival) - Week 36	1 (-999 to 999)	1 (-999 to 999)
Prob. of maintaining on q12w (survival) - Week 48	0.870 (0.772 to 0.928)	0.876 (0.788 to 0.930)

No statistical analyses for this end point

Secondary: Change from baseline in BCVA at each visit up to Week 52

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End point title

Change from baseline in BCVA at each visit up to Week 52

End point description

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. Participants with a BCVA ETDRS letter score of 78 to 23 (approximate Snellen equivalent of 20/32 to 20/320) in the study eye were included. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.

End point type

Secondary

End point timeframe

Baseline (Week 0), Weeks 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48, and 52

End point values	Brolucizumab 3 mg	Brolucizumab 6 mg	Aflibercept 2 mg
Number of subjects analysed	190	189	187
Units: Scores on a scale
arithmetic mean (standard deviation)
Week 4 (n=187, 186, 185)	4.0 ± 5.02	4.5 ± 5.22	5.1 ± 6.74
Week 6 (n=185,186,180)	5.1 ± 5.86	6.0 ± 6.22	6.8 ± 6.80
Week 8 (n=183,184,181)	5.6 ± 5.90	6.6 ± 6.54	7.1 ± 7.57
Week 12 (n=183,186,182)	6.7 ± 5.93	7.3 ± 6.57	8.1 ± 7.63
Week 16 (n=173,179,179)	7.0 ± 7.00	7.5 ± 6.83	8.5 ± 7.36
Week 18 (n=175,181,172)	7.6 ± 6.35	8.0 ± 6.84	8.8 ± 7.27
Week 20 (n=176,177,176)	7.8 ± 7.59	8.3 ± 7.51	9.8 ± 7.47
Week 24 (n=174,178,177)	8.1 ± 6.42	9.3 ± 7.08	9.2 ± 7.84
Week 28 (n=170,175,170)	8.2 ± 6.58	9.6 ± 7.40	10.3 ± 7.26
Week 32 (n=155,161,162)	8.2 ± 7.76	9.2 ± 7.20	9.9 ± 7.89
Week 36 (n=154,166,165)	6.9 ± 8.10	8.6 ± 8.15	10.2 ± 7.84
Week 40 (n=160,163,163)	7.3 ± 10.47	9.5 ± 7.99	10.0 ± 8.28
Week 44 (n=156,157,163)	7.5 ± 10.92	9.6 ± 7.66	10.7 ± 8.25
Week 48 (n=155,154,159)	7.2 ± 11.53	10.0 ± 7.63	11.1 ± 8.75
Week 52 (n=156,153,160)	7.8 ± 10.72	10.2 ± 7.66	10.7 ± 8.87

No statistical analyses for this end point

Secondary: BCVA (letters read): ANOVA results for average change from baseline over the period Week 88 through Week 100 for the study eye (FAS - LOCF)

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End point title

BCVA (letters read): ANOVA results for average change from baseline over the period Week 88 through Week 100 for the study eye (FAS - LOCF)

End point description

Assessed with ETDRS visual acuity testing charts

End point type

Secondary

End point timeframe

Baseline, and Week 88 through Week 100 (average)

End point values	Brolucizumab 3 mg	Brolucizumab 6 mg	Aflibercept 2 mg
Number of subjects analysed	190	189	187
Units: BCVA letters read
least squares mean (standard error)
Brolucizumab 3mg vAflibercept 2mg (n=190, 0, 187)	6.7 ± 0.77	999 ± 999	10.6 ± 0.78
Brolucizumab 6mg v Aflibercept 2mg) (n=0, 189,187)	999 ± 999	8.6 ± 0.72	10.6 ± 0.73

Brolucizumab 3 mg v Aflibercept 2 mg

Comparison groups

Brolucizumab 3 mg v Aflibercept 2 mg

Number of subjects included in analysis

377

Analysis specification

Pre-specified

Analysis type

^[10]

Method

ANOVA

Parameter type

LS mean difference

Point estimate

-3.8

Confidence interval

level

95%

sides

2-sided

lower limit

-6

upper limit

-1.7

Variability estimate

Standard error of the mean

Dispersion value

1.09

Notes
[10] - Descriptive

Brolucizumab 6 mg v Aflibercept 2 mg

Comparison groups

Brolucizumab 6 mg v Aflibercept 2 mg

Number of subjects included in analysis

376

Analysis specification

Pre-specified

Analysis type

^[11]

Method

ANOVA

Parameter type

LS mean difference

Point estimate

-2

Confidence interval

level

95%

sides

2-sided

lower limit

-4

upper limit

0.1

Variability estimate

Standard error of the mean

Dispersion value

1.03

Notes
[11] - Descriptive

Secondary: Patients maintained at q12w up to Week 64 (after three q12w- treatment intervals) and Week 100 - Probability of maintaining on q12w (survival)

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End point title

Patients maintained at q12w up to Week 64 (after three q12w- treatment intervals) and Week 100 - Probability of maintaining on q12w (survival)

End point description

This outcome measure is pre-specified for brolucizumab treatment arms only

End point type

Secondary

End point timeframe

Baseline (Week 0), Weeks 32, 36, 48, 60, 72, 84, and 96

End point values	Brolucizumab 3 mg	Brolucizumab 6 mg	Aflibercept 2 mg
Number of subjects analysed	190	189	0 ^[12]
Units: Probability
number (confidence interval 95%)
Prob. of maintaining on q12w (survival)-Week 0	1 (-999 to 999)	1 (-999 to 999)	( to )
Prob. of maintaining on q12w (survival)-Week 32	0.758 (0.685 to 0.816)	0.807 (0.739 to 0.860)	( to )
Prob. of maintaining on q12w (survival)-Week 36	0.545 (0.463 to 0.619)	0.628 (0.548 to 0.698)	( to )
Prob. of maintaining on q12w (survival)-Week 48	0.474 (0.393 to 0.551)	0.550 (0.468 to 0.625)	( to )
Prob. of maintaining on q12w (survival)-Week 60	0.403 (0.323 to 0.482)	0.520 (0.437 to 0.596)	( to )
Prob. of maintaining on q12w (survival)-Week 72	0.394 (0.314 to 0.473)	0.487 (0.404 to 0.565)	( to )
Prob. of maintaining on q12w (survival)-Week 84	0.365 (0.285 to 0.445)	0.460 (0.376 to 0.539)	( to )
Prob. of maintaining on q12w (survival)-Week 96	0.334 (0.254 to 0.415)	0.441 (0.357 to 0.521)	( to )

Notes
[12] - Does not apply to the Aflibercept 2 mg arm

No statistical analyses for this end point

Secondary: Secondary: Patients maintained at q12w up to Week 64 (after three q12w- treatment intervals) and Week 100, within those patients that qualified for q12w at Week 36 - Probability of maintaining on q12w (survival)

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End point title

Secondary: Patients maintained at q12w up to Week 64 (after three q12w- treatment intervals) and Week 100, within those patients that qualified for q12w at Week 36 - Probability of maintaining on q12w (survival)

End point description

This outcome measure is pre-specified for brolucizumab treatment arms only

End point type

Secondary

End point timeframe

Baseline (Week 0), Weeks 32, 36, 48, 60, 72, 84, and 96

End point values	Brolucizumab 3 mg	Brolucizumab 6 mg	Aflibercept 2 mg
Number of subjects analysed	190	189	0 ^[13]
Units: Probability
number (confidence interval 95%)
Prob. of maintaining on q12w (survival)-Week 0	1 (-999 to 999)	1 (-999 to 999)	( to )
Prob. of maintaining on q12w (survival)-Week 32	1 (-999 to 999)	1 (-999 to 999)	( to )
Prob. of maintaining on q12w (survival)-Week 36	1 (-999 to 999)	1 (-999 to 999)	( to )
Prob. of maintaining on q12w (survival)-Week 48	0.870 (0.772 to 0.928)	0.876 (0.788 to 0.930)	( to )
Prob. of maintaining on q12w (survival)-Week 60	0.740 (0.622 to 0.826)	0.828 (0.730 to 0.892)	( to )
Prob. of maintaining on q12w (survival)-Week 72	0.723 (0.603 to 0.812)	0.775 (0.670 to 0.851)	( to )
Prob. of maintaining on q12w (survival)-Week 84	0.670 (0.544 to 0.769)	0.732 (0.621 to 0.816)	( to )
Prob. of maintaining on q12w (survival)-Week 96	0.613 (0.482 to 0.720)	0.702 (0.587 to 0.791)	( to )

Notes
[13] - Does not apply to the Aflibercept 2 mg arm

No statistical analyses for this end point

Secondary: Change from baseline in central subfield thickness (CSFT) at each visit up to week 52 - Pairwise ANOVA results

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End point title

Change from baseline in central subfield thickness (CSFT) at each visit up to week 52 - Pairwise ANOVA results

End point description

Central Subfield Thickness Assessed by Spectral domain optical coherence tomography (SD-OCT) from the central reading center. Afliber = Aflibercept; Wk = Week

End point type

Secondary

End point timeframe

Baseline up to week 52

End point values	Brolucizumab 3 mg	Brolucizumab 6 mg	Aflibercept 2 mg
Number of subjects analysed	190	189	187
Units: μm
least squares mean (standard error)
Brolucizumab 3mg v Afliber 2mg-Wk4 (n=190, 0, 187)	-104.7 ± 6.11	999 ± 999	-104.1 ± 6.15
Brolucizumab 6mg v Afliber 2mg-Wk4 (n=0, 189, 187)	999 ± 999	-105.6 ± 5.92	-103.4 ± 5.95
Brolucizumab 3mg v Afliber 2mg-Wk6 (n=190, 0, 187)	-107.1 ± 6.24	999 ± 999	-119.3 ± 6.29
Brolucizumab 6mg v Afliber 2mg-Wk6 (n=0, 189, 187)	999 ± 999	-116.1 ± 5.89	-118.6 ± 5.92
Brolucizumab 3mg vAfliber 2mg-Wk8 (n=190, 0, 187)	-125.1 ± 6.06	999 ± 999	-126.1 ± 6.11
Brolucizumab 6mg v Afliber 2mg-Wk8 (n=0, 189, 187)	999 ± 999	-128.9 ± 5.82	-125.6 ± 5.86
Brolucizumab 3mg v Afliber2mg-Wk12 (n=190, 0, 187)	-131.0 ± 6.14	999 ± 999	-137.4 ± 6.19
Brolucizumab6mg v Afliber2mg-Wk12 (n=0, 189, 187)	999 ± 999	-134.5 ± 6.22	-137.3 ± 6.26
Brolucizumab3mg v Afliber2mg-Wk16 (n=190, 0, 187)	-142.3 ± 5.98	999 ± 999	-143.3 ± 6.02
Brolucizumab6mg v Afliber2mg-Wk16 (n=0, 189, 187)	999 ± 999	-146.5 ± 5.83	-143.1 ± 5.86
Brolucizumab3mg v Afliber2mg-Wk18 (n=190, 0, 187)	-138.1 ± 6.27	999 ± 999	-147.0 ± 6.32
Brolucizumab6mg v Afliber2mg-Wk18 (n=0, 189, 187)	999 ± 999	-144.2 ± 5.96	-146.8 ± 5.99
Brolucizumab3mg v Afliber2mg-Wk20 (n=190, 0, 187)	-151.8 ± 6.01	999 ± 999	-148.3 ± 6.06
Brolucizumab6mg v Afliber2mg-Wk20 (n=0, 189, 187)	999 ± 999	-153.8 ± 5.71	-148.0 ± 5.74
Brolucizumab3mg v Afliber2mg-Wk24 (n=190, 0, 187)	-152.6 ± 6.37	999 ± 999	-138.7 ± 6.42
Brolucizumab6mg v Afliber2mg-Wk24 (n=0, 189, 187)	999 ± 999	-156.2 ± 6.30	-138.4 ± 6.33
Brolucizumab3mg v Afliber2mg-Wk28 (n=190, 0, 187)	-163.4 ± 5.81	999 ± 999	-154.6 ± 5.85
Brolucizumab6mg v Afliber2mg-Wk28 (n=0, 189, 187)	999 ± 999	-163.3 ± 5.97	-154.6 ± 6.00
Brolucizumab3mg v Afliber2mg-Wk32 (n=190, 0, 187)	-147.4 ± 6.68	999 ± 999	-144.3 ± 6.73
Brolucizumab6mg v Afliber2mg-Wk32 (n=0, 189, 187)	999 ± 999	-156.0 ± 6.35	-144.2 ± 6.38
Brolucizumab3mg v Afliber2mg-Wk36 (n=190, 0, 187)	-119.8 ± 7.74	999 ± 999	-156.0 ± 7.81
Brolucizumab6mg v Afliber2mg-Wk36 (n=0, 189, 187)	999 ± 999	-135.1 ± 7.01	-155.5 ± 7.05
Brolucizumab3mg v Afliber2mg-Wk40 (n=190, 0, 187)	-155.8 ± 6.46	999 ± 999	-149.7 ± 6.51
Brolucizumab6mg v Afliber2mg-Wk40 (n=0, 189, 187)	999 ± 999	-156.9 ± 6.68	-150.4 ± 6.72
Brolucizumab3mg v Afliber2mg-Wk44 (n=190, 0, 187)	-155.4 ± 6.56	999 ± 999	-163.4 ± 6.62
Brolucizumab6mg v Afliber2mg-Wk44 (n=0, 189, 187)	999 ± 999	-162.2 ± 6.17	-163.3 ± 6.21
Brolucizumab3mg v Afliber2mg-Wk48 (n=190, 0, 187)	-144.2 ± 6.92	999 ± 999	-157.8 ± 6.98
Brolucizumab6mg v Afliber2mg-Wk48 (n=0, 189, 187)	999 ± 999	-153.5 ± 6.52	-158.2 ± 6.55
Brolucizumab3mg v Afliber2mg-Wk52 (n=190, 0, 187)	-156.4 ± 6.70	999 ± 999	-160.7 ± 6.75
Brolucizumab6mg v Afliber2mg-Wk52 (n=0, 189, 187)	999 ± 999	-165.5 ± 6.17	-160.4 ± 6.21

Brolucizumab 3 mg v Aflibercept 2 mg

Statistical analysis description

Week 4

Comparison groups

Brolucizumab 3 mg v Aflibercept 2 mg

Number of subjects included in analysis

377

Analysis specification

Pre-specified

Analysis type

^[14]

Method

ANOVA

Parameter type

LS mean difference

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-17.7

upper limit

16.4

Variability estimate

Standard error of the mean

Dispersion value

8.68

Notes
[14] - Descriptive

Brolucizumab 6 mg v Aflibercept 2 mg

Statistical analysis description

Week 4

Comparison groups

Brolucizumab 6 mg v Aflibercept 2 mg

Number of subjects included in analysis

376

Analysis specification

Pre-specified

Analysis type

^[15]

Method

ANOVA

Parameter type

LS mean difference

Point estimate

-2.1

Confidence interval

level

95%

sides

2-sided

lower limit

-18.7

upper limit

14.4

Variability estimate

Standard error of the mean

Dispersion value

8.41

Notes
[15] - Descriptive

Brolucizumab 3 mg Aflibercept 2 mg

Statistical analysis description

Week 6 v

Comparison groups

Brolucizumab 3 mg v Aflibercept 2 mg

Number of subjects included in analysis

377

Analysis specification

Pre-specified

Analysis type

^[16]

Method

ANOVA

Parameter type

LS mean difference

Point estimate

12.2

Confidence interval

level

95%

sides

2-sided

lower limit

-5.2

upper limit

29.7

Variability estimate

Standard error of the mean

Dispersion value

8.87

Notes
[16] - Descriptive

Brolucizumab 3 mg v Aflibercept 2 mg

Statistical analysis description

Week 8

Comparison groups

Brolucizumab 3 mg v Aflibercept 2 mg

Number of subjects included in analysis

377

Analysis specification

Pre-specified

Analysis type

^[17]

Method

ANOVA

Parameter type

LS mean difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-16

upper limit

17.9

Variability estimate

Standard error of the mean

Dispersion value

8.61

Notes
[17] - Descriptive

Brolucizumab 6 mg v Aflibercept 2 mg

Statistical analysis description

Week 6

Comparison groups

Brolucizumab 6 mg v Aflibercept 2 mg

Number of subjects included in analysis

376

Analysis specification

Pre-specified

Analysis type

^[18]

Method

ANOVA

Parameter type

LS mean difference

Point estimate

2.4

Confidence interval

level

95%

sides

2-sided

lower limit

-14

upper limit

18.9

Variability estimate

Standard error of the mean

Dispersion value

8.38

Notes
[18] - Descriptive

Brolucizumab 6 mg v Aflibercept 2 mg

Statistical analysis description

Week 8

Comparison groups

Brolucizumab 6 mg v Aflibercept 2 mg

Number of subjects included in analysis

376

Analysis specification

Pre-specified

Analysis type

^[19]

Method

ANOVA

Parameter type

LS mean difference

Point estimate

-3.4

Confidence interval

level

95%

sides

2-sided

lower limit

-19.6

upper limit

12.9

Variability estimate

Standard error of the mean

Dispersion value

8.28

Notes
[19] - Descriptive

Brolucizumab 3 mg v Aflibercept 2 mg

Statistical analysis description

Week 12

Comparison groups

Brolucizumab 3 mg v Aflibercept 2 mg

Number of subjects included in analysis

377

Analysis specification

Pre-specified

Analysis type

^[20]

Method

ANOVA

Parameter type

LS mean difference

Point estimate

6.4

Confidence interval

level

95%

sides

2-sided

lower limit

-10.7

upper limit

23.6

Variability estimate

Standard error of the mean

Dispersion value

8.73

Notes
[20] - Descriptive

Brolucizumab 6 mg v Aflibercept 2 mg

Statistical analysis description

Week 12

Comparison groups

Brolucizumab 6 mg v Aflibercept 2 mg

Number of subjects included in analysis

376

Analysis specification

Pre-specified

Analysis type

^[21]

Method

ANOVA

Parameter type

LS mean difference

Point estimate

2.8

Confidence interval

level

95%

sides

2-sided

lower limit

-14.6

upper limit

20.2

Variability estimate

Standard error of the mean

Dispersion value

8.85

Notes
[21] - Descriptive

Brolucizumab 3 mg v Aflibercept 2 mg

Statistical analysis description

Week 16

Comparison groups

Brolucizumab 3 mg v Aflibercept 2 mg

Number of subjects included in analysis

377

Analysis specification

Pre-specified

Analysis type

^[22]

Method

ANOVA

Parameter type

LS mean difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-15.7

upper limit

17.8

Variability estimate

Standard error of the mean

Dispersion value

8.5

Notes
[22] - Descriptive

Brolucizumab 6 mg v Aflibercept 2 mg

Statistical analysis description

Week 16

Comparison groups

Brolucizumab 6 mg v Aflibercept 2 mg

Number of subjects included in analysis

376

Analysis specification

Pre-specified

Analysis type

^[23]

Method

ANOVA

Parameter type

LS mean difference

Point estimate

-3.4

Confidence interval

level

95%

sides

2-sided

lower limit

-19.7

upper limit

12.9

Variability estimate

Standard error of the mean

Dispersion value

8.29

Notes
[23] - Descriptive

Brolucizumab 3 mg v Aflibercept 2 mg

Statistical analysis description

Week 18

Comparison groups

Brolucizumab 3 mg v Aflibercept 2 mg

Number of subjects included in analysis

377

Analysis specification

Pre-specified

Analysis type

^[24]

Method

ANOVA

Parameter type

LS mean difference

Point estimate

8.9

Confidence interval

level

95%

sides

2-sided

lower limit

-8.6

upper limit

26.5

Variability estimate

Standard error of the mean

Dispersion value

8.92

Notes
[24] - Descriptive

Brolucizumab 6 mg v Aflibercept 2 mg

Statistical analysis description

Week 18

Comparison groups

Brolucizumab 6 mg v Aflibercept 2 mg

Number of subjects included in analysis

376

Analysis specification

Pre-specified

Analysis type

^[25]

Method

ANOVA

Parameter type

LS mean difference

Point estimate

2.6

Confidence interval

level

95%

sides

2-sided

lower limit

-14.1

upper limit

19.2

Variability estimate

Standard error of the mean

Dispersion value

8.47

Notes
[25] - Descriptive

Brolucizumab 3 mg v Aflibercept 2 mg

Statistical analysis description

Week 20

Comparison groups

Brolucizumab 3 mg v Aflibercept 2 mg

Number of subjects included in analysis

377

Analysis specification

Pre-specified

Analysis type

^[26]

Method

ANOVA

Parameter type

LS mean difference

Point estimate

-3.4

Confidence interval

level

95%

sides

2-sided

lower limit

-20.2

upper limit

13.4

Variability estimate

Standard error of the mean

Dispersion value

8.55

Notes
[26] - Descriptive

Brolucizumab 6 mg v Aflibercept 2 mg

Statistical analysis description

Week 20

Comparison groups

Brolucizumab 6 mg v Aflibercept 2 mg

Number of subjects included in analysis

376

Analysis specification

Pre-specified

Analysis type

^[27]

Method

ANOVA

Parameter type

LS mean difference

Point estimate

-5.8

Confidence interval

level

95%

sides

2-sided

lower limit

-21.7

upper limit

10.2

Variability estimate

Standard error of the mean

Dispersion value

8.12

Notes
[27] - Descriptive

Brolucizumab 3 mg v Aflibercept 2 mg

Statistical analysis description

Week 24

Comparison groups

Brolucizumab 3 mg v Aflibercept 2 mg

Number of subjects included in analysis

377

Analysis specification

Pre-specified

Analysis type

^[28]

Method

ANOVA

Parameter type

LS mean difference

Point estimate

-13.9

Confidence interval

level

95%

sides

2-sided

lower limit

-31.7

upper limit

3.9

Variability estimate

Standard error of the mean

Dispersion value

9.06

Notes
[28] - Descriptive

Brolucizumab 6 mg v Aflibercept 2 mg

Statistical analysis description

Week 24

Comparison groups

Brolucizumab 6 mg v Aflibercept 2 mg

Number of subjects included in analysis

376

Analysis specification

Pre-specified

Analysis type

^[29]

Method

ANOVA

Parameter type

LS mean difference

Point estimate

-17.8

Confidence interval

level

95%

sides

2-sided

lower limit

-35.4

upper limit

-0.2

Variability estimate

Standard error of the mean

Dispersion value

8.95

Notes
[29] - Descriptive

Brolucizumab 3 mg v Aflibercept 2 mg

Statistical analysis description

Week 28

Comparison groups

Brolucizumab 3 mg v Aflibercept 2 mg

Number of subjects included in analysis

377

Analysis specification

Pre-specified

Analysis type

^[30]

Method

ANOVA

Parameter type

LS mean difference

Point estimate

-8.7

Confidence interval

level

95%

sides

2-sided

lower limit

-25

upper limit

7.5

Variability estimate

Standard error of the mean

Dispersion value

8.26

Notes
[30] - Descriptive

Brolucizumab 6 mg v Aflibercept 2 mg

Statistical analysis description

Week 28

Comparison groups

Brolucizumab 6 mg v Aflibercept 2 mg

Number of subjects included in analysis

376

Analysis specification

Pre-specified

Analysis type

^[31]

Method

ANOVA

Parameter type

LS mean difference

Point estimate

-8.7

Confidence interval

level

95%

sides

2-sided

lower limit

-25.4

upper limit

Variability estimate

Standard error of the mean

Dispersion value

8.49

Notes
[31] - Descriptive

Brolucizumab 3 mg v Aflibercept 2 mg

Statistical analysis description

Week 32

Comparison groups

Brolucizumab 3 mg v Aflibercept 2 mg

Number of subjects included in analysis

377

Analysis specification

Pre-specified

Analysis type

^[32]

Method

ANOVA

Parameter type

LS mean difference

Point estimate

-3.2

Confidence interval

level

95%

sides

2-sided

lower limit

-21.8

upper limit

15.5

Variability estimate

Standard error of the mean

Dispersion value

9.49

Notes
[32] - Descriptive

Brolucizumab 6 mg v Aflibercept 2 mg

Statistical analysis description

Week 32

Comparison groups

Brolucizumab 6 mg v Aflibercept 2 mg

Number of subjects included in analysis

376

Analysis specification

Pre-specified

Analysis type

^[33]

Method

ANOVA

Parameter type

LS mean difference

Point estimate

-11.7

Confidence interval

level

95%

sides

2-sided

lower limit

-29.5

upper limit

Variability estimate

Standard error of the mean

Dispersion value

9.02

Notes
[33] - Descriptive

Brolucizumab 3 mg v Aflibercept 2 mg

Statistical analysis description

Week 36

Comparison groups

Brolucizumab 3 mg v Aflibercept 2 mg

Number of subjects included in analysis

377

Analysis specification

Pre-specified

Analysis type

^[34]

Method

ANOVA

Parameter type

LS mean difference

Point estimate

36.3

Confidence interval

level

95%

sides

2-sided

lower limit

14.6

upper limit

57.9

Variability estimate

Standard error of the mean

Dispersion value

11.01

Notes
[34] - Descriptive

Brolucizumab 6 mg v Aflibercept 2 mg

Statistical analysis description

Week 36

Comparison groups

Brolucizumab 6 mg v Aflibercept 2 mg

Number of subjects included in analysis

376

Analysis specification

Pre-specified

Analysis type

^[35]

Method

ANOVA

Parameter type

LS mean difference

Point estimate

20.4

Confidence interval

level

95%

sides

2-sided

lower limit

0.7

upper limit

Variability estimate

Standard error of the mean

Dispersion value

9.97

Notes
[35] - Descriptive

Brolucizumab 3 mg v Aflibercept 2 mg

Statistical analysis description

Week 40

Comparison groups

Brolucizumab 3 mg v Aflibercept 2 mg

Number of subjects included in analysis

377

Analysis specification

Pre-specified

Analysis type

^[36]

Method

ANOVA

Parameter type

LS mean difference

Point estimate

-6.1

Confidence interval

level

95%

sides

2-sided

lower limit

-24.2

upper limit

11.9

Variability estimate

Standard error of the mean

Dispersion value

9.19

Notes
[36] - Descriptive

Brolucizumab 6 mg v Aflibercept 2 mg

Statistical analysis description

Week 40

Comparison groups

Brolucizumab 6 mg v Aflibercept 2 mg

Number of subjects included in analysis

376

Analysis specification

Pre-specified

Analysis type

^[37]

Method

ANOVA

Parameter type

LS mean difference

Point estimate

-6.5

Confidence interval

level

95%

sides

2-sided

lower limit

-25.2

upper limit

12.2

Variability estimate

Standard error of the mean

Dispersion value

9.5

Notes
[37] - Descriptive

Brolucizumab 3 mg v Aflibercept 2 mg

Statistical analysis description

Week 44

Comparison groups

Brolucizumab 3 mg v Aflibercept 2 mg

Number of subjects included in analysis

377

Analysis specification

Pre-specified

Analysis type

^[38]

Method

ANOVA

Parameter type

LS mean difference

Point estimate

7.9

Confidence interval

level

95%

sides

2-sided

lower limit

-10.4

upper limit

26.3

Variability estimate

Standard error of the mean

Dispersion value

9.33

Notes
[38] - Descriptive

Brolucizumab 6 mg v Aflibercept 2 mg

Statistical analysis description

Week 44

Comparison groups

Brolucizumab 6 mg v Aflibercept 2 mg

Number of subjects included in analysis

376

Analysis specification

Pre-specified

Analysis type

^[39]

Method

ANOVA

Parameter type

LS mean difference

Point estimate

1.1

Confidence interval

level

95%

sides

2-sided

lower limit

-16.2

upper limit

18.3

Variability estimate

Standard error of the mean

Dispersion value

8.78

Notes
[39] - Descriptive

Brolucizumab 6 mg v Aflibercept 2 mg

Statistical analysis description

Week 48

Comparison groups

Brolucizumab 6 mg v Aflibercept 2 mg

Number of subjects included in analysis

376

Analysis specification

Pre-specified

Analysis type

^[40]

Method

ANOVA

Parameter type

LS mean difference

Point estimate

4.7

Confidence interval

level

95%

sides

2-sided

lower limit

-13.5

upper limit

Variability estimate

Standard error of the mean

Dispersion value

9.26

Notes
[40] - Descriptive

Brolucizumab 3 mg v Aflibercept 2 mg

Statistical analysis description

Week 48

Comparison groups

Brolucizumab 3 mg v Aflibercept 2 mg

Number of subjects included in analysis

377

Analysis specification

Pre-specified

Analysis type

^[41]

Method

ANOVA

Parameter type

LS mean difference

Point estimate

13.6

Confidence interval

level

95%

sides

2-sided

lower limit

-5.8

upper limit

32.9

Variability estimate

Standard error of the mean

Dispersion value

9.84

Notes
[41] - Descriptive

Brolucizumab 3 mg v Aflibercept 2 mg

Statistical analysis description

Week 52

Comparison groups

Brolucizumab 3 mg v Aflibercept 2 mg

Number of subjects included in analysis

377

Analysis specification

Pre-specified

Analysis type

^[42]

Method

ANOVA

Parameter type

LS mean difference

Point estimate

4.3

Confidence interval

level

95%

sides

2-sided

lower limit

-14.5

upper limit

Variability estimate

Standard error of the mean

Dispersion value

9.52

Notes
[42] - Descriptive

Brolucizumab 6 mg v Aflibercept 2 mg

Statistical analysis description

Week 52

Comparison groups

Brolucizumab 6 mg v Aflibercept 2 mg

Number of subjects included in analysis

376

Analysis specification

Pre-specified

Analysis type

^[43]

Method

ANOVA

Parameter type

LS mean difference

Point estimate

-5.1

Confidence interval

level

95%

sides

2-sided

lower limit

-22.3

upper limit

12.2

Variability estimate

Standard error of the mean

Dispersion value

8.78

Notes
[43] - Descriptive

Secondary: Central subfield thickness (CSFT) (micrometers): ANOVA results for average change from baseline over the period Week 88 through Week 100 for the study eye (Full Analysis Set – LOCF)

Top of page

End point title

Central subfield thickness (CSFT) (micrometers): ANOVA results for average change from baseline over the period Week 88 through Week 100 for the study eye (Full Analysis Set – LOCF)

End point description

Central subfield thickness (average thickness of circular 1mm area centered around fovea measured from RPE to ILM, inclusively). Assessed with Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts

End point type

Secondary

End point timeframe

Baseline, and Week 88 through Week 100 (average)

End point values	Brolucizumab 3 mg	Brolucizumab 6 mg	Aflibercept 2 mg
Number of subjects analysed	190	189	187
Units: micrometers
least squares mean (standard error)
Brolucizumab 3mg v Aflibercept 2mg (n=190, 0, 187)	-167.1 ± 6.54	999 ± 999	-168.8 ± 6.59
Brolucizumab 6mg vAflibercept 2mg (n=0, 189,187)	999 ± 999	-171.9 ± 6.18	-168.5 ± 6.22

Brolucizumab 6 mg v Aflibercept 2 mg

Comparison groups

Brolucizumab 6 mg v Aflibercept 2 mg

Number of subjects included in analysis

376

Analysis specification

Pre-specified

Analysis type

^[44]

Method

ANOVA

Parameter type

LS mean difference

Point estimate

-3.5

Confidence interval

level

95%

sides

2-sided

lower limit

-20.7

upper limit

13.8

Variability estimate

Standard error of the mean

Dispersion value

8.79

Notes
[44] - Descriptive

Brolucizumab 3 mg v Aflibercept 2 mg

Comparison groups

Brolucizumab 3 mg v Aflibercept 2 mg

Number of subjects included in analysis

377

Analysis specification

Pre-specified

Analysis type

^[45]

Method

ANOVA

Parameter type

LS mean difference

Point estimate

1.7

Confidence interval

level

95%

sides

2-sided

lower limit

-16.6

upper limit

Variability estimate

Standard error of the mean

Dispersion value

9.3

Notes
[45] - Descriptive

Secondary: Number and percentage of patients with presence of subretinal fluid (SRF) at each assessment visit

Top of page

End point title

Number and percentage of patients with presence of subretinal fluid (SRF) at each assessment visit

End point description

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

End point type

Secondary

End point timeframe

Baseline up to Week 52 (primary analysis) and Week 100 (final analysis)

End point values	Brolucizumab 3 mg	Brolucizumab 6 mg	Aflibercept 2 mg
Number of subjects analysed	190	189	187
Units: Participants
Week 4	26	23	27
Week 6	20	17	17
Week 8	10	9	12
Week 12	11	8	8
Week16	6	6	7
Week18	7	4	6
Week 20	5	4	6
Week 24	7	3	6
Week 28	5	2	3
Week 32	11	1	6
Week 36	16	14	4
Week 40	8	5	6
Week 44	4	4	4
Week 48	7	8	3
Week 52	4	4	4
Week 56	9	3	5
Week 60	9	5	5
Week 64	6	4	5
Week 68	6	4	3
Week 72	5	4	4
Week 76	4	4	4
Week 80	5	4	5
Week 84	6	3	3
Week 88	7	2	4
Week 92	4	2	4
Week 96	5	3	5
Week 100	3	2	2

No statistical analyses for this end point

Secondary: Number and percentage of patients with presence of intraretinal fluid (IRF) at each assessment visit

Top of page

End point title

Number and percentage of patients with presence of intraretinal fluid (IRF) at each assessment visit

End point description

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

End point type

Secondary

End point timeframe

Baseline, up to Week 52 (primary analysis) and Week 100 (final analysis)

End point values	Brolucizumab 3 mg	Brolucizumab 6 mg	Aflibercept 2 mg
Number of subjects analysed	190	189	187
Units: Participants
Week 4	176	169	169
Week 6	177	169	169
Week 8	166	161	164
Week 12	167	162	165
Week 16	155	150	156
Week 18	152	149	154
Week 20	142	147	145
Week 24	142	140	153
Week 28	139	130	144
Week 32	143	131	156
Week 36	153	141	144
Week 40	129	114	150
Week 44	127	118	135
Week 48	132	123	147
Week 52	113	114	137
Week 56	111	103	138
Week 60	119	115	126
Week 64	102	105	131
Week 68	109	98	118
Week 72	107	103	126
Week 76	98	96	118
Week 80	96	85	120
Week 84	102	92	108
Week 88	89	85	114
Week 92	91	86	105
Week 96	92	90	107
Week 100	87	79	101

No statistical analyses for this end point

Secondary: Number and percentage of patients with presence of SRF and/or IRF in the study eye by visit

Top of page

End point title

Number and percentage of patients with presence of SRF and/or IRF in the study eye by visit

End point description

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

End point type

Secondary

End point timeframe

Baseline, up to Week 52 (primary analysis) and Week 100 (final analysis)

End point values	Brolucizumab 3 mg	Brolucizumab 6 mg	Aflibercept 2 mg
Number of subjects analysed	190	189	187
Units: Participants
Week 4	177	172	171
Week 6	177	173	169
Week 8	166	162	164
Week 12	168	162	165
Week 16	156	150	156
Week 18	153	149	154
Week 20	142	147	145
Week 24	142	140	153
Week 28	139	130	144
Week 32	143	131	156
Week 36	153	141	144
Week 40	129	114	150
Week 44	127	118	135
Week 48	132	123	147
Week 52	113	114	137
Week 56	111	103	138
Week 60	120	115	126
Week 64	102	105	131
Week 68	109	98	118
Week 72	107	103	126
Week 76	98	96	118
Week 80	96	85	120
Week 84	102	92	108
Week 88	89	85	114
Week 92	91	86	105
Week 96	92	90	107
Week 100	87	79	101

No statistical analyses for this end point

Secondary: Number and percentage of patients with presence of leakage on fluorescein angiography (FA) at Week 52 (Primary Analysis)

Top of page

End point title

Number and percentage of patients with presence of leakage on fluorescein angiography (FA) at Week 52 (Primary Analysis)

End point description

Assessed by angiography.

End point type

Secondary

End point timeframe

Week 52 (Primary Analysis)

End point values	Brolucizumab 3 mg	Brolucizumab 6 mg	Aflibercept 2 mg
Number of subjects analysed	189	188	186
Units: Participants	114	108	140

No statistical analyses for this end point

Secondary: Number and percentage of patients with presence of leakage on fluorescein angiography (FA) at Week 100 (Final Analysis)

Top of page

End point title

Number and percentage of patients with presence of leakage on fluorescein angiography (FA) at Week 100 (Final Analysis)

End point description

Assessed by angiography.

End point type

Secondary

End point timeframe

Week 100 (Final Analysis)

End point values	Brolucizumab 3 mg	Brolucizumab 6 mg	Aflibercept 2 mg
Number of subjects analysed	190	188	186
Units: Participants	94	80	104

No statistical analyses for this end point

Secondary: Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) : proportion of subjects with >=2-step improvement from baseline in the DRSS score at each assessment visit for the study eye - Number of subjects

Top of page

End point title

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 - Number of subjects

End point description

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 the original scale with scores varying from 10 (DR absent) to 85 (very advanced PDR). All DRSS values were then converted into a 12-level scale, allowing the derivation of the ≥2-step and ≥3-step change from baseline for each post-baseline assessment”. A lower score represents better visual functioning.

End point type

Secondary

End point timeframe

Baseline, Weeks 28, 52, 76, 100

End point values	Brolucizumab 3 mg	Brolucizumab 6 mg	Aflibercept 2 mg
Number of subjects analysed	185	186	184
Units: Participants
Week 28 Proportion of subjects	44	49	39
Week 52 Proportion of subjects	53	55	40
Week 76 Proportion of subjects	59	55	51
Week 100 Proportion of subjects	60	61	54

No statistical analyses for this end point

Secondary: Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) : proportion of subjects with >=2-step improvement from baseline in the DRSS score at each assessment visit for the study eye - Proportion estimates (%)

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End point title

End point description

End point type

Secondary

End point timeframe

Baseline, Weeks 28, 52, 76, 100

End point values	Brolucizumab 3 mg	Brolucizumab 6 mg	Aflibercept 2 mg
Number of subjects analysed	185	186	184
Units: Proportion estimates (%)
number (not applicable)
Brolucizumab3mg v Afliber2mg Wk28 (n=185,0, 184)	23.3	999	21.7
Brolucizumab6mg v Afliber2mg Wk28 (n=0, 186, 184)	999	25.8	21.7
Brolucizumab3mg v Afliber2mg Wk52 (n=185,0, 184)	28.0	999	22.3
Brolucizumab6mg v Afliber2mg Wk52 (n=0, 186, 184)	999	29.0	22.2
Brolucizumab3mg v Afliber2mg Wk76 (n=185,0, 184)	31.2	999	28.4
Brolucizumab6mg v Afliber2mg Wk76 (n=0, 186, 184)	999	29.0	28.3
Brolucizumab3mg v Afliber2mg Wk100 (n=185,0,184)	31.7	999	30.1
Brolucizumab6mg v Afliber2mg Wk 100 (n=0,186,184)	999	32.1	30.0

Brolucizumab 3 mg v Aflibercept 2 mg

Comparison groups

Brolucizumab 3 mg v Aflibercept 2 mg

Number of subjects included in analysis

369

Analysis specification

Pre-specified

Analysis type

^[46]

Method

Clopper-Pearson exact method

Parameter type

Difference - %

Point estimate

1.6

Confidence interval

level

95%

sides

2-sided

lower limit

-5.3

upper limit

8.4

Notes
[46] - Descriptive; Week 28

Brolucizumab 6 mg v Aflibercept 2 mg

Comparison groups

Brolucizumab 6 mg v Aflibercept 2 mg

Number of subjects included in analysis

370

Analysis specification

Pre-specified

Analysis type

^[47]

Method

Clopper-Pearson exact method

Parameter type

Difference - %

Point estimate

4.1

Confidence interval

level

95%

sides

2-sided

lower limit

-2.1

upper limit

10.3

Notes
[47] - Descriptive; Week 28

Brolucizumab 3 mg v Aflibercept 2 mg

Comparison groups

Brolucizumab 3 mg v Aflibercept 2 mg

Number of subjects included in analysis

369

Analysis specification

Pre-specified

Analysis type

^[48]

Method

Clopper-Pearson exact method

Parameter type

Difference - %

Point estimate

5.8

Confidence interval

level

95%

sides

2-sided

lower limit

-1.2

upper limit

12.4

Notes
[48] - Descriptive; Week 52

Brolucizumab 6 mg v Aflibercept 2 mg

Comparison groups

Brolucizumab 6 mg v Aflibercept 2 mg

Number of subjects included in analysis

370

Analysis specification

Pre-specified

Analysis type

^[49]

Method

Clopper-Pearson exact method

Parameter type

Difference - %

Point estimate

6.7

Confidence interval

level

95%

sides

2-sided

lower limit

0.6

upper limit

12.9

Notes
[49] - Descriptive; Week 52

Brolucizumab 3 mg v Aflibercept 2 mg

Comparison groups

Brolucizumab 3 mg v Aflibercept 2 mg

Number of subjects included in analysis

369

Analysis specification

Pre-specified

Analysis type

^[50]

Method

Clopper-Pearson exact method

Parameter type

Difference - %

Point estimate

2.8

Confidence interval

level

95%

sides

2-sided

lower limit

-3.9

upper limit

9.4

Notes
[50] - Descriptive: Week 76

Brolucizumab 6 mg v Aflibercept 2 mg

Comparison groups

Brolucizumab 6 mg v Aflibercept 2 mg

Number of subjects included in analysis

370

Analysis specification

Pre-specified

Analysis type

^[51]

Method

Clopper-Pearson exact method

Parameter type

Difference - %

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-5.7

upper limit

Notes
[51] - Descriptive: Week 76

Brolucizumab 3 mg v Aflibercept 2 mg

Comparison groups

Brolucizumab 3 mg v Aflibercept 2 mg

Number of subjects included in analysis

369

Analysis specification

Pre-specified

Analysis type

^[52]

Method

Clopper-Pearson exact method

Parameter type

Difference - %

Point estimate

1.7

Confidence interval

level

95%

sides

2-sided

lower limit

-5

upper limit

8.1

Notes
[52] - Descriptive: Week 100

Brolucizumab 6 mg v Aflibercept 2 mg

Comparison groups

Brolucizumab 6 mg v Aflibercept 2 mg

Number of subjects included in analysis

370

Analysis specification

Pre-specified

Analysis type

^[53]

Method

Clopper-Pearson exact method

Parameter type

Difference - %

Point estimate

2.2

Confidence interval

level

95%

sides

2-sided

lower limit

-4

upper limit

8.4

Notes
[53] - Descriptive: Week 100

Secondary: Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS): proportion of subjects with >=3-step improvement from baseline in the DRSS score at each assessment visit for the study eye - Number of subjects

Top of page

End point title

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 - Number of subjects

End point description

End point type

Secondary

End point timeframe

Baseline, Weeks 28, 52, 76, 100

End point values	Brolucizumab 3 mg	Brolucizumab 6 mg	Aflibercept 2 mg
Number of subjects analysed	185	186	184
Units: Participants
Week 28 Proportion of subjects	23	32	22
Week 52 Proportion of subjects	24	39	30
Week 76 Proportion of subjects	27	40	42
Week 100 Proportion of subjects	29	44	41

No statistical analyses for this end point

Secondary: Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS): proportion of subjects with >=3-step improvement from baseline in the DRSS score at each assessment visit for the study eye - Proportion estimates (%)

Top of page

End point title

End point description

End point type

Secondary

End point timeframe

Baseline, Weeks 28, 52, 76, 100

End point values	Brolucizumab 3 mg	Brolucizumab 6 mg	Aflibercept 2 mg
Number of subjects analysed	185	186	184
Units: Proportion estimates (%)
number (not applicable)
Brolucizumab3mg v Afliber2mg Wk28 (n=185, 0,184)	12.1	999	12.3
Brolucizumab6mg v Afliber2mg Wk28 (n=0, 186, 184)	999	16.8	12.2
Brolucizumab3mg v Afliber2mg Wk52(n=185, 0,184)	12.6	999	16.8
Brolucizumab6mg v. Afliber2mg Wk52(n=0, 186,184)	999	20.5	16.7
Brolucizumab3mg v Afliber2mg Wk76 (n=185, 0,184)	14.2	999	23.4
Brolucizumab6mg v Afliber2mg Wk76 (n=0, 186, 184)	999	21.1	23.3
Brolucizumab3mg v Afliber2mg Wk100 (n=185, 0, 84)	15.2	999	22.9
Brolucizumab6mg v Afliber2mg Wk100 (n=0,186,184)	999	23.2	22.8

Brolucizumab 3 mg v Aflibercept 2 mg

Comparison groups

Brolucizumab 3 mg v Aflibercept 2 mg

Number of subjects included in analysis

369

Analysis specification

Pre-specified

Analysis type

^[54]

Method

Clopper-Pearson exact method

Parameter type

Difference - %

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-6.4

upper limit

5.8

Notes
[54] - Descriptive; Week 28

Brolucizumab 6 mg v Aflibercept 2 mg

Comparison groups

Brolucizumab 6 mg v Aflibercept 2 mg

Number of subjects included in analysis

370

Analysis specification

Pre-specified

Analysis type

^[55]

Method

Clopper-Pearson exact method

Parameter type

Difference - %

Point estimate

4.6

Confidence interval

level

95%

sides

2-sided

lower limit

-1.3

upper limit

Notes
[55] - Descriptive; Week 28

Brolucizumab 3 mg v Aflibercept 2 mg

Comparison groups

Brolucizumab 3 mg v Aflibercept 2 mg

Number of subjects included in analysis

369

Analysis specification

Pre-specified

Analysis type

^[56]

Method

Clopper-Pearson exact method

Parameter type

Difference - %

Point estimate

-4.2

Confidence interval

level

95%

sides

2-sided

lower limit

-10.2

upper limit

2.2

Notes
[56] - Descriptive; Week 52

Brolucizumab 6 mg v Aflibercept 2 mg

Comparison groups

Brolucizumab 6 mg v Aflibercept 2 mg

Number of subjects included in analysis

370

Analysis specification

Pre-specified

Analysis type

^[57]

Method

Clopper-Pearson exact method

Parameter type

Difference - %

Point estimate

3.9

Confidence interval

level

95%

sides

2-sided

lower limit

-2.2

upper limit

10.5

Notes
[57] - Descriptive; Week 52

Brolucizumab 3 mg v Aflibercept 2 mg

Comparison groups

Brolucizumab 3 mg v Aflibercept 2 mg

Number of subjects included in analysis

369

Analysis specification

Pre-specified

Analysis type

^[58]

Method

Clopper-Pearson exact method

Parameter type

Difference - %

Point estimate

-9.2

Confidence interval

level

95%

sides

2-sided

lower limit

-15.5

upper limit

-2.8

Notes
[58] - Descriptive; Week 72

Brolucizumab 6 mg v Aflibercept 2 mg

Comparison groups

Brolucizumab 6 mg v Aflibercept 2 mg

Number of subjects included in analysis

370

Analysis specification

Pre-specified

Analysis type

^[59]

Method

Clopper-Pearson exact method

Parameter type

Difference - %

Point estimate

-2.3

Confidence interval

level

95%

sides

2-sided

lower limit

-8.4

upper limit

4.4

Notes
[59] - Descriptive; Week 72

Brolucizumab 3 mg v Aflibercept 2 mg

Comparison groups

Brolucizumab 3 mg v Aflibercept 2 mg

Number of subjects included in analysis

369

Analysis specification

Pre-specified

Analysis type

^[60]

Method

Clopper-Pearson exact method

Parameter type

Difference - %

Point estimate

-7.7

Confidence interval

level

95%

sides

2-sided

lower limit

-14

upper limit

-1.6

Notes
[60] - Descriptive; Week 100

Brolucizumab 6 mg v Aflibercept 2 mg

Comparison groups

Brolucizumab 6 mg v Aflibercept 2 mg

Number of subjects included in analysis

370

Analysis specification

Pre-specified

Analysis type

^[61]

Method

Clopper-Pearson exact method

Parameter type

Difference - %

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-5.7

upper limit

6.8

Notes
[61] - Descriptive; Week 100

Secondary: Change from baseline in patient reported outcomes Visual Functioning Questionnaire-25 (VFQ-25) total and subscale scores up to Week 52 (Primary Analysis) and Week 100 (Final Analysis)

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End point title

Change from baseline in patient reported outcomes Visual Functioning Questionnaire-25 (VFQ-25) total and subscale scores up to Week 52 (Primary Analysis) and Week 100 (Final Analysis)

End point description

The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. A composite score is derived based on the average of the 11 subscales. Change from baseline in the composite and subscale scores are summarized. Abbreviation: Afliber = Aflibercept; Wk = Week

End point type

Secondary

End point timeframe

Baseline, Weeks 28, 52, 76, 100

End point values	Brolucizumab 3 mg	Brolucizumab 6 mg	Aflibercept 2 mg
Number of subjects analysed	165	173	168
Units: overall scores
least squares mean (confidence interval 95%)
Wk 28 Brolucizumab3mg v Afliber2mg (n=165,0,168)	6.2 (-999 to 999)	999 (-999 to 999)	7.1 (-999 to 999)
Wk28 Brolucizumab6mg v Afliber2mg (n=0,173,168)	999 (999 to 999)	5.9 (-999 to 999)	7.9 (-999 to 999)
Wk52 Brolucizumab3mg v Afliber2mg(n=151,0,157)	5.4 (-999 to 999)	999 (-999 to 999)	7.7 (-999 to 999)
Wk52 Brolucizumab6mg v Afliber2mg (n=0,148,157)	999 (999 to 999)	7.1 (-999 to 999)	8.1 (-999 to 999)
Wk76 Brolucizumab3mg v Afliber2mg (n=133, 0,143)	7.2 (-999 to 999)	999 (999 to 999)	6.6 (-999 to 999)
Wk76 Brolucizumab6mg v Afliber2mg (n=0,138,143)	999 (999 to 999)	5.6 (-999 to 999)	7.3 (-999 to 999)
Wk100 Brolucizumab3mg v Afliber2mg (n=140, 0,142)	7.0 (-999 to 999)	999 (999 to 999)	5.8 (-999 to 999)
Wk100 Brolucizumab6mg v Afliber2mg(n=0,141,142)	999 (999 to 999)	6.2 (-999 to 999)	6.4 (-999 to 999)

Brolucizumab 6 mg v Aflibercept 2 mg

Statistical analysis description

Week 28

Comparison groups

Brolucizumab 6 mg v Aflibercept 2 mg

Number of subjects included in analysis

341

Analysis specification

Pre-specified

Analysis type

^[62]

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

-1.9

Confidence interval

level

95%

sides

2-sided

lower limit

-4.2

upper limit

0.3

Notes
[62] - Descriptive

Brolucizumab 3 mg v Aflibercept 2 mg

Statistical analysis description

Week 28

Comparison groups

Brolucizumab 3 mg v Aflibercept 2 mg

Number of subjects included in analysis

333

Analysis specification

Pre-specified

Analysis type

^[63]

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

-0.9

Confidence interval

level

95%

sides

2-sided

lower limit

-3

upper limit

1.2

Notes
[63] - Descriptive

Brolucizumab 6 mg v Aflibercept 2 mg

Statistical analysis description

Week 52

Comparison groups

Brolucizumab 6 mg v Aflibercept 2 mg

Number of subjects included in analysis

341

Analysis specification

Pre-specified

Analysis type

^[64]

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-3.4

upper limit

1.4

Notes
[64] - Descriptive

Brolucizumab 3 mg v Aflibercept 2 mg

Statistical analysis description

Week 52

Comparison groups

Brolucizumab 3 mg v Aflibercept 2 mg

Number of subjects included in analysis

333

Analysis specification

Pre-specified

Analysis type

^[65]

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

-2.3

Confidence interval

level

95%

sides

2-sided

lower limit

-4.7

upper limit

0.1

Notes
[65] - Descriptive

Brolucizumab 6 mg v Aflibercept 2 mg

Statistical analysis description

Week 76

Comparison groups

Brolucizumab 6 mg v Aflibercept 2 mg

Number of subjects included in analysis

341

Analysis specification

Pre-specified

Analysis type

^[66]

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

3.1

Notes
[66] - Descriptive

Brolucizumab 3 mg v Aflibercept 2 mg

Statistical analysis description

Week 76

Comparison groups

Brolucizumab 3 mg v Aflibercept 2 mg

Number of subjects included in analysis

333

Analysis specification

Pre-specified

Analysis type

^[67]

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

-1.7

Confidence interval

level

95%

sides

2-sided

lower limit

-4.5

upper limit

1.1

Notes
[67] - Descriptive

Brolucizumab 6 mg v Aflibercept 2 mg

Statistical analysis description

Week 100

Comparison groups

Brolucizumab 6 mg v Aflibercept 2 mg

Number of subjects included in analysis

341

Analysis specification

Pre-specified

Analysis type

^[68]

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

1.2

Confidence interval

level

95%

sides

2-sided

lower limit

-1.6

upper limit

4.1

Notes
[68] - Descriptive

Brolucizumab 3 mg v Aflibercept 2 mg

Statistical analysis description

Week 100

Comparison groups

Brolucizumab 3 mg v Aflibercept 2 mg

Number of subjects included in analysis

333

Analysis specification

Pre-specified

Analysis type

^[69]

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-2.9

upper limit

2.6

Notes
[69] - Descriptive

Secondary: Ocular Adverse Events (AEs) (>=2% in any treatment arm) by preferred term for the study eye

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End point title

Ocular Adverse Events (AEs) (>=2% in any treatment arm) by preferred term for the study eye

End point description

End point type

Secondary

End point timeframe

Adverse events were reported from first dose of study treatment until Week 96, plus 30 days post treatment, up to a maximum duration of 100 weeks.

End point values	Brolucizumab 3 mg	Brolucizumab 6 mg	Aflibercept 2 mg
Number of subjects analysed	190	189	187
Units: Participants
Number of subjects with at least one AE	103	92	94
Cataract	17	16	13
Conjunctival haemorrhage	19	16	19
Intraocular pressure increased	14	11	3
Vitreous detachment	9	10	3
Vitreous floaters	7	10	6
Diabetic retinal oedema	12	9	4
Conjunctivitis	4	6	1
Dry eye	10	6	5
Eye pain	3	6	5
Posterior capsule opacification	3	6	3
Eye irritation	3	5	4
Blepharitis	3	4	4
Keratitis	0	4	3
Vitreous haemorrhage	2	4	3
Punctate keratitis	8	3	1
Vision blurred	6	3	1
Visual acuity reduced	7	3	9
Iridocyclitis	4	2	0
Ocular hypertension	4	2	2
Uveitis	4	2	0
Corneal abrasion	3	1	4
Retinal exudates	7	1	3
Cataract subcapsular	1	0	4
Conjunctival hyperaemia	4	0	1
Vitreoretinal traction syndrome	1	0	5

No statistical analyses for this end point

Secondary: Number of subjects with non-ocular Adverse Events (AEs) (>=2% in any treatment arm)

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End point title

Number of subjects with non-ocular Adverse Events (AEs) (>=2% in any treatment arm)

End point description

End point type

Secondary

End point timeframe

Adverse events were reported from first dose of study treatment until Week 96, plus 30 days post treatment, up to a maximum duration of 100 weeks.

End point values	Brolucizumab 3 mg	Brolucizumab 6 mg	Aflibercept 2 mg
Number of subjects analysed	190	189	187
Units: Participants	146	146	143

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Adverse events were reported from first dose of study treatment until Week 96, plus 30 days post treatment, up to a maximum duration of 100 weeks.

Adverse event reporting additional description

Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events field “number of deaths resulting from adverse events” all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

24.1

Reporting group title

Brolucizumab 3mg

Reporting group description

Brolucizumab 3mg

Reporting group title

Aflibercept 2mg

Reporting group description

Aflibercept 2mg

Reporting group title

Overall

Reporting group description

Overall

Reporting group title

Brolucizumab 6mg

Reporting group description

Brolucizumab 6mg

Serious adverse events	Brolucizumab 3mg	Aflibercept 2mg	Overall	Brolucizumab 6mg
Total subjects affected by serious adverse events
subjects affected / exposed	58 / 190 (30.53%)	63 / 187 (33.69%)	180 / 566 (31.80%)	59 / 189 (31.22%)
number of deaths (all causes)	4	7	19	8
number of deaths resulting from adverse events	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Brain neoplasm
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	1 / 566 (0.18%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
Breast cancer metastatic
subjects affected / exposed	0 / 190 (0.00%)	1 / 187 (0.53%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Colon cancer
subjects affected / exposed	1 / 190 (0.53%)	0 / 187 (0.00%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Endometrial cancer
subjects affected / exposed	0 / 190 (0.00%)	1 / 187 (0.53%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatocellular carcinoma
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	1 / 566 (0.18%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Intraductal proliferative breast lesion
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	1 / 566 (0.18%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lung neoplasm malignant
subjects affected / exposed	1 / 190 (0.53%)	0 / 187 (0.00%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ovarian cancer metastatic
subjects affected / exposed	0 / 190 (0.00%)	1 / 187 (0.53%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pancreatic carcinoma
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	2 / 566 (0.35%)	2 / 189 (1.06%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
Prostate cancer
subjects affected / exposed	0 / 190 (0.00%)	1 / 187 (0.53%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Thyroid cancer
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	1 / 566 (0.18%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
Vascular disorders
Accelerated hypertension
subjects affected / exposed	0 / 190 (0.00%)	1 / 187 (0.53%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Deep vein thrombosis
subjects affected / exposed	0 / 190 (0.00%)	1 / 187 (0.53%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Dry gangrene
subjects affected / exposed	1 / 190 (0.53%)	0 / 187 (0.00%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Embolism venous
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	1 / 566 (0.18%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Extremity necrosis
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	1 / 566 (0.18%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Haematoma
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	1 / 566 (0.18%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypertension
subjects affected / exposed	2 / 190 (1.05%)	0 / 187 (0.00%)	2 / 566 (0.35%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypertensive crisis
subjects affected / exposed	0 / 190 (0.00%)	1 / 187 (0.53%)	3 / 566 (0.53%)	2 / 189 (1.06%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 3	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypertensive emergency
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	1 / 566 (0.18%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypertensive urgency
subjects affected / exposed	0 / 190 (0.00%)	2 / 187 (1.07%)	2 / 566 (0.35%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypotension
subjects affected / exposed	1 / 190 (0.53%)	1 / 187 (0.53%)	2 / 566 (0.35%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Orthostatic hypotension
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	2 / 566 (0.35%)	2 / 189 (1.06%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 3	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Peripheral arterial occlusive disease
subjects affected / exposed	1 / 190 (0.53%)	0 / 187 (0.00%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pregnancy, puerperium and perinatal conditions
Pre-eclampsia
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	1 / 566 (0.18%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Death
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	1 / 566 (0.18%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
Generalised oedema
subjects affected / exposed	0 / 190 (0.00%)	2 / 187 (1.07%)	2 / 566 (0.35%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 3	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Oedema peripheral
subjects affected / exposed	1 / 190 (0.53%)	0 / 187 (0.00%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	1 / 190 (0.53%)	1 / 187 (0.53%)	2 / 566 (0.35%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Sudden death
subjects affected / exposed	1 / 190 (0.53%)	1 / 187 (0.53%)	2 / 566 (0.35%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 1	0 / 2	0 / 0
Reproductive system and breast disorders
Benign prostatic hyperplasia
subjects affected / exposed	1 / 190 (0.53%)	0 / 187 (0.00%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Prostatic disorder
subjects affected / exposed	0 / 190 (0.00%)	1 / 187 (0.53%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome
subjects affected / exposed	0 / 190 (0.00%)	1 / 187 (0.53%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Acute respiratory failure
subjects affected / exposed	1 / 190 (0.53%)	0 / 187 (0.00%)	3 / 566 (0.53%)	2 / 189 (1.06%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 4	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Asthma
subjects affected / exposed	0 / 190 (0.00%)	1 / 187 (0.53%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Chronic obstructive pulmonary disease
subjects affected / exposed	1 / 190 (0.53%)	0 / 187 (0.00%)	2 / 566 (0.35%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 3	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Haemothorax
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	1 / 566 (0.18%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pleural effusion
subjects affected / exposed	1 / 190 (0.53%)	2 / 187 (1.07%)	4 / 566 (0.71%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 5	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary congestion
subjects affected / exposed	1 / 190 (0.53%)	0 / 187 (0.00%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	0 / 190 (0.00%)	1 / 187 (0.53%)	3 / 566 (0.53%)	2 / 189 (1.06%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 3	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary oedema
subjects affected / exposed	1 / 190 (0.53%)	0 / 187 (0.00%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory failure
subjects affected / exposed	0 / 190 (0.00%)	1 / 187 (0.53%)	3 / 566 (0.53%)	2 / 189 (1.06%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 3	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
Psychiatric disorders
Confusional state
subjects affected / exposed	0 / 190 (0.00%)	1 / 187 (0.53%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
Hepatitis C antibody positive
subjects affected / exposed	0 / 190 (0.00%)	1 / 187 (0.53%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
International normalised ratio increased
subjects affected / exposed	1 / 190 (0.53%)	0 / 187 (0.00%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Intraocular pressure increased - Study eye
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	1 / 566 (0.18%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Ankle fracture
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	1 / 566 (0.18%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cataract operation complication - Fellow eye
subjects affected / exposed	0 / 190 (0.00%)	1 / 187 (0.53%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Facial bones fracture
subjects affected / exposed	0 / 190 (0.00%)	1 / 187 (0.53%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Femur fracture
subjects affected / exposed	0 / 190 (0.00%)	2 / 187 (1.07%)	2 / 566 (0.35%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hand fracture
subjects affected / exposed	0 / 190 (0.00%)	1 / 187 (0.53%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Head injury
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	1 / 566 (0.18%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hip fracture
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	1 / 566 (0.18%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Laryngeal injury
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	1 / 566 (0.18%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pelvic fracture
subjects affected / exposed	0 / 190 (0.00%)	2 / 187 (1.07%)	2 / 566 (0.35%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Peripheral artery restenosis
subjects affected / exposed	1 / 190 (0.53%)	0 / 187 (0.00%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Skin flap necrosis
subjects affected / exposed	1 / 190 (0.53%)	0 / 187 (0.00%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Subdural haematoma
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	1 / 566 (0.18%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Toxicity to various agents
subjects affected / exposed	0 / 190 (0.00%)	1 / 187 (0.53%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ulna fracture
subjects affected / exposed	1 / 190 (0.53%)	0 / 187 (0.00%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Acute coronary syndrome
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	1 / 566 (0.18%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Acute left ventricular failure
subjects affected / exposed	0 / 190 (0.00%)	1 / 187 (0.53%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Acute myocardial infarction
subjects affected / exposed	0 / 190 (0.00%)	2 / 187 (1.07%)	3 / 566 (0.53%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Angina pectoris
subjects affected / exposed	2 / 190 (1.05%)	1 / 187 (0.53%)	3 / 566 (0.53%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 1	1 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Arrhythmia
subjects affected / exposed	1 / 190 (0.53%)	0 / 187 (0.00%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Atrial fibrillation
subjects affected / exposed	0 / 190 (0.00%)	2 / 187 (1.07%)	3 / 566 (0.53%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Atrioventricular block
subjects affected / exposed	1 / 190 (0.53%)	0 / 187 (0.00%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bradycardia
subjects affected / exposed	0 / 190 (0.00%)	1 / 187 (0.53%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac arrest
subjects affected / exposed	1 / 190 (0.53%)	0 / 187 (0.00%)	2 / 566 (0.35%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
Cardiac failure
subjects affected / exposed	1 / 190 (0.53%)	1 / 187 (0.53%)	4 / 566 (0.71%)	2 / 189 (1.06%)
occurrences causally related to treatment / all	0 / 1	1 / 1	1 / 4	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
Cardiac failure chronic
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	1 / 566 (0.18%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac failure congestive
subjects affected / exposed	5 / 190 (2.63%)	5 / 187 (2.67%)	12 / 566 (2.12%)	2 / 189 (1.06%)
occurrences causally related to treatment / all	0 / 5	0 / 5	0 / 12	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiorenal syndrome
subjects affected / exposed	0 / 190 (0.00%)	1 / 187 (0.53%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiovascular disorder
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	1 / 566 (0.18%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Coronary artery disease
subjects affected / exposed	1 / 190 (0.53%)	3 / 187 (1.60%)	6 / 566 (1.06%)	2 / 189 (1.06%)
occurrences causally related to treatment / all	0 / 1	0 / 3	0 / 6	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Coronary artery stenosis
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	1 / 566 (0.18%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ischaemic cardiomyopathy
subjects affected / exposed	0 / 190 (0.00%)	1 / 187 (0.53%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Mitral valve disease mixed
subjects affected / exposed	1 / 190 (0.53%)	0 / 187 (0.00%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Mitral valve incompetence
subjects affected / exposed	0 / 190 (0.00%)	1 / 187 (0.53%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Myocardial infarction
subjects affected / exposed	2 / 190 (1.05%)	3 / 187 (1.60%)	8 / 566 (1.41%)	3 / 189 (1.59%)
occurrences causally related to treatment / all	1 / 2	0 / 3	1 / 8	0 / 3
deaths causally related to treatment / all	0 / 1	0 / 2	0 / 3	0 / 0
Myocardial ischaemia
subjects affected / exposed	1 / 190 (0.53%)	0 / 187 (0.00%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Carotid artery occlusion
subjects affected / exposed	0 / 190 (0.00%)	2 / 187 (1.07%)	2 / 566 (0.35%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cerebral atrophy
subjects affected / exposed	0 / 190 (0.00%)	1 / 187 (0.53%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cerebral haemorrhage
subjects affected / exposed	1 / 190 (0.53%)	1 / 187 (0.53%)	2 / 566 (0.35%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
Cerebrovascular accident
subjects affected / exposed	3 / 190 (1.58%)	4 / 187 (2.14%)	11 / 566 (1.94%)	4 / 189 (2.12%)
occurrences causally related to treatment / all	0 / 3	1 / 4	2 / 11	1 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Encephalopathy
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	1 / 566 (0.18%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Epilepsy
subjects affected / exposed	0 / 190 (0.00%)	1 / 187 (0.53%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 3	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ischaemic stroke
subjects affected / exposed	0 / 190 (0.00%)	1 / 187 (0.53%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lacunar stroke
subjects affected / exposed	0 / 190 (0.00%)	1 / 187 (0.53%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Migraine
subjects affected / exposed	0 / 190 (0.00%)	1 / 187 (0.53%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Optic neuritis - Study eye
subjects affected / exposed	1 / 190 (0.53%)	0 / 187 (0.00%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Subarachnoid haemorrhage
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	1 / 566 (0.18%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Syncope
subjects affected / exposed	0 / 190 (0.00%)	1 / 187 (0.53%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Transient ischaemic attack
subjects affected / exposed	0 / 190 (0.00%)	1 / 187 (0.53%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	1 / 566 (0.18%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Microcytic anaemia
subjects affected / exposed	0 / 190 (0.00%)	1 / 187 (0.53%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
Amaurosis fugax - Fellow eye
subjects affected / exposed	1 / 190 (0.53%)	0 / 187 (0.00%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cataract - Fellow eye
subjects affected / exposed	0 / 190 (0.00%)	4 / 187 (2.14%)	7 / 566 (1.24%)	3 / 189 (1.59%)
occurrences causally related to treatment / all	0 / 0	0 / 4	0 / 7	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cataract - Study eye
subjects affected / exposed	1 / 190 (0.53%)	3 / 187 (1.60%)	9 / 566 (1.59%)	5 / 189 (2.65%)
occurrences causally related to treatment / all	0 / 1	0 / 3	0 / 9	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Conjunctival cyst - Study eye
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	1 / 566 (0.18%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diabetic retinal oedema - Study eye
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	1 / 566 (0.18%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diabetic retinopathy - Fellow eye
subjects affected / exposed	0 / 190 (0.00%)	1 / 187 (0.53%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Epiretinal membrane - Study eye
subjects affected / exposed	1 / 190 (0.53%)	0 / 187 (0.00%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Glaucoma - Fellow eye
subjects affected / exposed	0 / 190 (0.00%)	1 / 187 (0.53%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Glaucoma - Study eye
subjects affected / exposed	1 / 190 (0.53%)	0 / 187 (0.00%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Macular oedema - Study eye
subjects affected / exposed	1 / 190 (0.53%)	0 / 187 (0.00%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Posterior capsule opacification - Study eye
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	1 / 566 (0.18%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pterygium - Study eye
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	1 / 566 (0.18%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Retinal artery occlusion - Fellow eye
subjects affected / exposed	1 / 190 (0.53%)	0 / 187 (0.00%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Retinal artery occlusion - Study eye
subjects affected / exposed	1 / 190 (0.53%)	0 / 187 (0.00%)	2 / 566 (0.35%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 1	0 / 0	1 / 2	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Retinal detachment - Study eye
subjects affected / exposed	1 / 190 (0.53%)	1 / 187 (0.53%)	2 / 566 (0.35%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Retinal occlusive vasculitis - Study eye
subjects affected / exposed	1 / 190 (0.53%)	0 / 187 (0.00%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Retinal vasculitis - Study eye
subjects affected / exposed	2 / 190 (1.05%)	0 / 187 (0.00%)	2 / 566 (0.35%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Retinal vein thrombosis - Study eye
subjects affected / exposed	1 / 190 (0.53%)	0 / 187 (0.00%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Uveitis - Study eye
subjects affected / exposed	1 / 190 (0.53%)	0 / 187 (0.00%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Visual acuity reduced - Study eye
subjects affected / exposed	0 / 190 (0.00%)	1 / 187 (0.53%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vitreous floaters - Study eye
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	1 / 566 (0.18%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vitreous haemorrhage - Fellow eye
subjects affected / exposed	2 / 190 (1.05%)	0 / 187 (0.00%)	3 / 566 (0.53%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vitritis - Study eye
subjects affected / exposed	1 / 190 (0.53%)	0 / 187 (0.00%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Duodenal ulcer
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	1 / 566 (0.18%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Dysphagia
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	1 / 566 (0.18%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastric polyps
subjects affected / exposed	1 / 190 (0.53%)	0 / 187 (0.00%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrooesophageal reflux disease
subjects affected / exposed	1 / 190 (0.53%)	0 / 187 (0.00%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Haematemesis
subjects affected / exposed	1 / 190 (0.53%)	0 / 187 (0.00%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hiatus hernia
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	1 / 566 (0.18%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Inguinal hernia
subjects affected / exposed	1 / 190 (0.53%)	0 / 187 (0.00%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Mechanical ileus
subjects affected / exposed	1 / 190 (0.53%)	0 / 187 (0.00%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Mesenteric vein thrombosis
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	1 / 566 (0.18%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Obstructive pancreatitis
subjects affected / exposed	0 / 190 (0.00%)	1 / 187 (0.53%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pancreatitis
subjects affected / exposed	1 / 190 (0.53%)	0 / 187 (0.00%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Proctitis ulcerative
subjects affected / exposed	0 / 190 (0.00%)	1 / 187 (0.53%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 3	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Rectal polyp
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	1 / 566 (0.18%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ulcerative gastritis
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	1 / 566 (0.18%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Upper gastrointestinal haemorrhage
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	1 / 566 (0.18%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Bile duct stone
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	2 / 566 (0.35%)	2 / 189 (1.06%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cholecystitis acute
subjects affected / exposed	0 / 190 (0.00%)	1 / 187 (0.53%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cholelithiasis
subjects affected / exposed	0 / 190 (0.00%)	1 / 187 (0.53%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gallbladder disorder
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	1 / 566 (0.18%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatitis acute
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	1 / 566 (0.18%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Decubitus ulcer
subjects affected / exposed	0 / 190 (0.00%)	1 / 187 (0.53%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diabetic foot
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	1 / 566 (0.18%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	1 / 190 (0.53%)	2 / 187 (1.07%)	5 / 566 (0.88%)	2 / 189 (1.06%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 5	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bladder pain
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	1 / 566 (0.18%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Chronic kidney disease
subjects affected / exposed	1 / 190 (0.53%)	0 / 187 (0.00%)	2 / 566 (0.35%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diabetic nephropathy
subjects affected / exposed	1 / 190 (0.53%)	1 / 187 (0.53%)	3 / 566 (0.53%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
End stage renal disease
subjects affected / exposed	0 / 190 (0.00%)	1 / 187 (0.53%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nephropathy
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	1 / 566 (0.18%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal failure
subjects affected / exposed	1 / 190 (0.53%)	4 / 187 (2.14%)	6 / 566 (1.06%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 1	0 / 5	0 / 7	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urinary bladder rupture
subjects affected / exposed	0 / 190 (0.00%)	1 / 187 (0.53%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urinary retention
subjects affected / exposed	0 / 190 (0.00%)	1 / 187 (0.53%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Endocrine disorders
Goitre
subjects affected / exposed	0 / 190 (0.00%)	1 / 187 (0.53%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	1 / 190 (0.53%)	0 / 187 (0.00%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Exostosis
subjects affected / exposed	0 / 190 (0.00%)	1 / 187 (0.53%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Muscular weakness
subjects affected / exposed	0 / 190 (0.00%)	1 / 187 (0.53%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Periarthritis
subjects affected / exposed	1 / 190 (0.53%)	0 / 187 (0.00%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Rhabdomyolysis
subjects affected / exposed	0 / 190 (0.00%)	2 / 187 (1.07%)	2 / 566 (0.35%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Rotator cuff syndrome
subjects affected / exposed	0 / 190 (0.00%)	1 / 187 (0.53%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Acute sinusitis
subjects affected / exposed	0 / 190 (0.00%)	1 / 187 (0.53%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Appendicitis
subjects affected / exposed	1 / 190 (0.53%)	0 / 187 (0.00%)	2 / 566 (0.35%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 3	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bacteraemia
subjects affected / exposed	1 / 190 (0.53%)	0 / 187 (0.00%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
COVID-19
subjects affected / exposed	2 / 190 (1.05%)	2 / 187 (1.07%)	7 / 566 (1.24%)	3 / 189 (1.59%)
occurrences causally related to treatment / all	0 / 2	0 / 2	0 / 7	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 2	0 / 1
COVID-19 pneumonia
subjects affected / exposed	0 / 190 (0.00%)	1 / 187 (0.53%)	2 / 566 (0.35%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 3	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
Cellulitis
subjects affected / exposed	2 / 190 (1.05%)	2 / 187 (1.07%)	5 / 566 (0.88%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 2	0 / 4	0 / 7	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Clostridium difficile colitis
subjects affected / exposed	1 / 190 (0.53%)	0 / 187 (0.00%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diabetic foot infection
subjects affected / exposed	2 / 190 (1.05%)	0 / 187 (0.00%)	3 / 566 (0.53%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Encephalitis
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	1 / 566 (0.18%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Endophthalmitis - Study eye
subjects affected / exposed	2 / 190 (1.05%)	1 / 187 (0.53%)	3 / 566 (0.53%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 1	1 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Fungal sepsis
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	1 / 566 (0.18%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gas gangrene
subjects affected / exposed	1 / 190 (0.53%)	0 / 187 (0.00%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis viral
subjects affected / exposed	0 / 190 (0.00%)	1 / 187 (0.53%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infective exacerbation of chronic obstructive airways disease
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	1 / 566 (0.18%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Localised infection
subjects affected / exposed	1 / 190 (0.53%)	0 / 187 (0.00%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Osteomyelitis
subjects affected / exposed	1 / 190 (0.53%)	3 / 187 (1.60%)	6 / 566 (1.06%)	2 / 189 (1.06%)
occurrences causally related to treatment / all	0 / 1	0 / 5	0 / 8	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Osteomyelitis acute
subjects affected / exposed	1 / 190 (0.53%)	0 / 187 (0.00%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Periodontitis
subjects affected / exposed	0 / 190 (0.00%)	1 / 187 (0.53%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	1 / 190 (0.53%)	1 / 187 (0.53%)	4 / 566 (0.71%)	2 / 189 (1.06%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 4	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia fungal
subjects affected / exposed	1 / 190 (0.53%)	0 / 187 (0.00%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
Postoperative abscess
subjects affected / exposed	1 / 190 (0.53%)	0 / 187 (0.00%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary sepsis
subjects affected / exposed	1 / 190 (0.53%)	0 / 187 (0.00%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory tract infection
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	1 / 566 (0.18%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Sepsis
subjects affected / exposed	2 / 190 (1.05%)	0 / 187 (0.00%)	4 / 566 (0.71%)	2 / 189 (1.06%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 4	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
Septic shock
subjects affected / exposed	1 / 190 (0.53%)	0 / 187 (0.00%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
Staphylococcal infection
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	1 / 566 (0.18%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	0 / 190 (0.00%)	1 / 187 (0.53%)	2 / 566 (0.35%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection bacterial
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	1 / 566 (0.18%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urosepsis
subjects affected / exposed	0 / 190 (0.00%)	1 / 187 (0.53%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Viral upper respiratory tract infection
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	1 / 566 (0.18%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Wound infection
subjects affected / exposed	0 / 190 (0.00%)	1 / 187 (0.53%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	1 / 190 (0.53%)	0 / 187 (0.00%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diabetes mellitus
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	3 / 566 (0.53%)	3 / 189 (1.59%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 3	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diabetic ketoacidosis
subjects affected / exposed	0 / 190 (0.00%)	1 / 187 (0.53%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diabetic metabolic decompensation
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	1 / 566 (0.18%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hyperglycaemia
subjects affected / exposed	2 / 190 (1.05%)	0 / 187 (0.00%)	3 / 566 (0.53%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hyperkalaemia
subjects affected / exposed	1 / 190 (0.53%)	0 / 187 (0.00%)	1 / 566 (0.18%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypoglycaemia
subjects affected / exposed	1 / 190 (0.53%)	1 / 187 (0.53%)	2 / 566 (0.35%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hyponatraemia
subjects affected / exposed	0 / 190 (0.00%)	2 / 187 (1.07%)	2 / 566 (0.35%)	0 / 189 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypovolaemia
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	1 / 566 (0.18%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ketoacidosis
subjects affected / exposed	0 / 190 (0.00%)	0 / 187 (0.00%)	1 / 566 (0.18%)	1 / 189 (0.53%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 2%

Non-serious adverse events	Brolucizumab 3mg	Aflibercept 2mg	Overall	Brolucizumab 6mg
Total subjects affected by non serious adverse events
subjects affected / exposed	146 / 190 (76.84%)	137 / 187 (73.26%)	431 / 566 (76.15%)	148 / 189 (78.31%)
Vascular disorders
Hypertension
subjects affected / exposed	22 / 190 (11.58%)	24 / 187 (12.83%)	67 / 566 (11.84%)	21 / 189 (11.11%)
occurrences all number	25	30	76	21
General disorders and administration site conditions
Oedema peripheral
subjects affected / exposed	4 / 190 (2.11%)	5 / 187 (2.67%)	14 / 566 (2.47%)	5 / 189 (2.65%)
occurrences all number	5	5	15	5
Pyrexia
subjects affected / exposed	1 / 190 (0.53%)	3 / 187 (1.60%)	12 / 566 (2.12%)	8 / 189 (4.23%)
occurrences all number	1	3	12	8
Immune system disorders
Seasonal allergy
subjects affected / exposed	2 / 190 (1.05%)	4 / 187 (2.14%)	10 / 566 (1.77%)	4 / 189 (2.12%)
occurrences all number	2	4	10	4
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	7 / 190 (3.68%)	10 / 187 (5.35%)	28 / 566 (4.95%)	11 / 189 (5.82%)
occurrences all number	7	11	30	12
Dyspnoea
subjects affected / exposed	0 / 190 (0.00%)	2 / 187 (1.07%)	8 / 566 (1.41%)	6 / 189 (3.17%)
occurrences all number	0	3	9	6
Psychiatric disorders
Depression
subjects affected / exposed	0 / 190 (0.00%)	3 / 187 (1.60%)	7 / 566 (1.24%)	4 / 189 (2.12%)
occurrences all number	0	3	7	4
Investigations
Blood glucose increased
subjects affected / exposed	2 / 190 (1.05%)	1 / 187 (0.53%)	7 / 566 (1.24%)	4 / 189 (2.12%)
occurrences all number	2	1	8	5
Blood pressure increased
subjects affected / exposed	6 / 190 (3.16%)	3 / 187 (1.60%)	13 / 566 (2.30%)	4 / 189 (2.12%)
occurrences all number	6	4	14	4
Glucose urine present
subjects affected / exposed	1 / 190 (0.53%)	2 / 187 (1.07%)	7 / 566 (1.24%)	4 / 189 (2.12%)
occurrences all number	1	2	7	4
Glycosylated haemoglobin increased
subjects affected / exposed	4 / 190 (2.11%)	4 / 187 (2.14%)	9 / 566 (1.59%)	1 / 189 (0.53%)
occurrences all number	4	5	10	1
Intraocular pressure increased - Fellow eye
subjects affected / exposed	5 / 190 (2.63%)	3 / 187 (1.60%)	8 / 566 (1.41%)	0 / 189 (0.00%)
occurrences all number	5	4	9	0
Intraocular pressure increased - Study eye
subjects affected / exposed	14 / 190 (7.37%)	3 / 187 (1.60%)	28 / 566 (4.95%)	11 / 189 (5.82%)
occurrences all number	14	5	36	17
Injury, poisoning and procedural complications
Corneal abrasion - Study eye
subjects affected / exposed	3 / 190 (1.58%)	4 / 187 (2.14%)	8 / 566 (1.41%)	1 / 189 (0.53%)
occurrences all number	3	4	8	1
Fall
subjects affected / exposed	5 / 190 (2.63%)	2 / 187 (1.07%)	12 / 566 (2.12%)	5 / 189 (2.65%)
occurrences all number	9	3	23	11
Limb injury
subjects affected / exposed	4 / 190 (2.11%)	1 / 187 (0.53%)	6 / 566 (1.06%)	1 / 189 (0.53%)
occurrences all number	4	1	6	1
Cardiac disorders
Atrial fibrillation
subjects affected / exposed	8 / 190 (4.21%)	1 / 187 (0.53%)	10 / 566 (1.77%)	1 / 189 (0.53%)
occurrences all number	9	1	11	1
Cardiac failure congestive
subjects affected / exposed	2 / 190 (1.05%)	3 / 187 (1.60%)	9 / 566 (1.59%)	4 / 189 (2.12%)
occurrences all number	2	3	9	4
Nervous system disorders
Dizziness
subjects affected / exposed	5 / 190 (2.63%)	3 / 187 (1.60%)	12 / 566 (2.12%)	4 / 189 (2.12%)
occurrences all number	5	3	12	4
Headache
subjects affected / exposed	3 / 190 (1.58%)	3 / 187 (1.60%)	16 / 566 (2.83%)	10 / 189 (5.29%)
occurrences all number	3	4	18	11
Migraine
subjects affected / exposed	1 / 190 (0.53%)	5 / 187 (2.67%)	8 / 566 (1.41%)	2 / 189 (1.06%)
occurrences all number	1	5	10	4
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	6 / 190 (3.16%)	9 / 187 (4.81%)	24 / 566 (4.24%)	9 / 189 (4.76%)
occurrences all number	6	10	26	10
Ear and labyrinth disorders
Vertigo
subjects affected / exposed	2 / 190 (1.05%)	5 / 187 (2.67%)	10 / 566 (1.77%)	3 / 189 (1.59%)
occurrences all number	2	5	11	4
Eye disorders
Blepharitis - Fellow eye
subjects affected / exposed	4 / 190 (2.11%)	4 / 187 (2.14%)	13 / 566 (2.30%)	5 / 189 (2.65%)
occurrences all number	4	5	14	5
Blepharitis - Study eye
subjects affected / exposed	3 / 190 (1.58%)	4 / 187 (2.14%)	11 / 566 (1.94%)	4 / 189 (2.12%)
occurrences all number	3	5	12	4
Cataract - Fellow eye
subjects affected / exposed	11 / 190 (5.79%)	5 / 187 (2.67%)	28 / 566 (4.95%)	12 / 189 (6.35%)
occurrences all number	11	5	28	12
Cataract - Study eye
subjects affected / exposed	17 / 190 (8.95%)	10 / 187 (5.35%)	39 / 566 (6.89%)	12 / 189 (6.35%)
occurrences all number	17	10	39	12
Cataract subcapsular - Study eye
subjects affected / exposed	1 / 190 (0.53%)	4 / 187 (2.14%)	5 / 566 (0.88%)	0 / 189 (0.00%)
occurrences all number	1	4	5	0
Conjunctival haemorrhage - Fellow eye
subjects affected / exposed	2 / 190 (1.05%)	7 / 187 (3.74%)	14 / 566 (2.47%)	5 / 189 (2.65%)
occurrences all number	2	7	15	6
Conjunctival haemorrhage - Study eye
subjects affected / exposed	19 / 190 (10.00%)	19 / 187 (10.16%)	54 / 566 (9.54%)	16 / 189 (8.47%)
occurrences all number	22	25	65	18
Conjunctival hyperaemia - Study eye
subjects affected / exposed	4 / 190 (2.11%)	1 / 187 (0.53%)	5 / 566 (0.88%)	0 / 189 (0.00%)
occurrences all number	4	2	6	0
Conjunctivitis allergic - Fellow eye
subjects affected / exposed	3 / 190 (1.58%)	4 / 187 (2.14%)	9 / 566 (1.59%)	2 / 189 (1.06%)
occurrences all number	3	5	10	2
Diabetic retinal oedema - Fellow eye
subjects affected / exposed	17 / 190 (8.95%)	12 / 187 (6.42%)	41 / 566 (7.24%)	12 / 189 (6.35%)
occurrences all number	19	15	48	14
Diabetic retinal oedema - Study eye
subjects affected / exposed	12 / 190 (6.32%)	4 / 187 (2.14%)	25 / 566 (4.42%)	9 / 189 (4.76%)
occurrences all number	17	6	35	12
Diabetic retinopathy - Fellow eye
subjects affected / exposed	6 / 190 (3.16%)	8 / 187 (4.28%)	20 / 566 (3.53%)	6 / 189 (3.17%)
occurrences all number	6	9	21	6
Dry eye - Fellow eye
subjects affected / exposed	9 / 190 (4.74%)	5 / 187 (2.67%)	19 / 566 (3.36%)	5 / 189 (2.65%)
occurrences all number	9	6	20	5
Dry eye - Study eye
subjects affected / exposed	11 / 190 (5.79%)	5 / 187 (2.67%)	22 / 566 (3.89%)	6 / 189 (3.17%)
occurrences all number	11	6	23	6
Eye irritation - Fellow eye
subjects affected / exposed	0 / 190 (0.00%)	2 / 187 (1.07%)	8 / 566 (1.41%)	6 / 189 (3.17%)
occurrences all number	0	2	8	6
Eye irritation - Study eye
subjects affected / exposed	3 / 190 (1.58%)	4 / 187 (2.14%)	12 / 566 (2.12%)	5 / 189 (2.65%)
occurrences all number	3	4	12	5
Eye pain - Fellow eye
subjects affected / exposed	2 / 190 (1.05%)	4 / 187 (2.14%)	8 / 566 (1.41%)	2 / 189 (1.06%)
occurrences all number	2	4	8	2
Eye pain - Study eye
subjects affected / exposed	3 / 190 (1.58%)	5 / 187 (2.67%)	14 / 566 (2.47%)	6 / 189 (3.17%)
occurrences all number	3	7	18	8
Iridocyclitis - Study eye
subjects affected / exposed	4 / 190 (2.11%)	0 / 187 (0.00%)	6 / 566 (1.06%)	2 / 189 (1.06%)
occurrences all number	8	0	10	2
Keratitis - Study eye
subjects affected / exposed	0 / 190 (0.00%)	3 / 187 (1.60%)	7 / 566 (1.24%)	4 / 189 (2.12%)
occurrences all number	0	3	7	4
Macular oedema - Fellow eye
subjects affected / exposed	5 / 190 (2.63%)	2 / 187 (1.07%)	13 / 566 (2.30%)	6 / 189 (3.17%)
occurrences all number	5	2	14	7
Ocular hypertension - Fellow eye
subjects affected / exposed	2 / 190 (1.05%)	2 / 187 (1.07%)	9 / 566 (1.59%)	5 / 189 (2.65%)
occurrences all number	2	2	9	5
Ocular hypertension - Study eye
subjects affected / exposed	4 / 190 (2.11%)	2 / 187 (1.07%)	8 / 566 (1.41%)	2 / 189 (1.06%)
occurrences all number	7	2	11	2
Posterior capsule opacification - Study eye
subjects affected / exposed	3 / 190 (1.58%)	3 / 187 (1.60%)	11 / 566 (1.94%)	5 / 189 (2.65%)
occurrences all number	3	3	11	5
Punctate keratitis - Study eye
subjects affected / exposed	8 / 190 (4.21%)	1 / 187 (0.53%)	12 / 566 (2.12%)	3 / 189 (1.59%)
occurrences all number	8	1	13	4
Retinal exudates - Fellow eye
subjects affected / exposed	5 / 190 (2.63%)	3 / 187 (1.60%)	11 / 566 (1.94%)	3 / 189 (1.59%)
occurrences all number	5	3	11	3
Retinal exudates - Study eye
subjects affected / exposed	7 / 190 (3.68%)	3 / 187 (1.60%)	11 / 566 (1.94%)	1 / 189 (0.53%)
occurrences all number	7	3	11	1
Retinal haemorrhage - Fellow eye
subjects affected / exposed	5 / 190 (2.63%)	1 / 187 (0.53%)	8 / 566 (1.41%)	2 / 189 (1.06%)
occurrences all number	5	1	8	2
Retinal haemorrhage - Study eye
subjects affected / exposed	4 / 190 (2.11%)	2 / 187 (1.07%)	6 / 566 (1.06%)	0 / 189 (0.00%)
occurrences all number	4	2	6	0
Vision blurred - Study eye
subjects affected / exposed	6 / 190 (3.16%)	1 / 187 (0.53%)	10 / 566 (1.77%)	3 / 189 (1.59%)
occurrences all number	6	1	10	3
Visual acuity reduced - Fellow eye
subjects affected / exposed	4 / 190 (2.11%)	3 / 187 (1.60%)	10 / 566 (1.77%)	3 / 189 (1.59%)
occurrences all number	4	3	10	3
Visual acuity reduced - Study eye
subjects affected / exposed	7 / 190 (3.68%)	8 / 187 (4.28%)	18 / 566 (3.18%)	3 / 189 (1.59%)
occurrences all number	7	11	21	3
Vitreoretinal traction syndrome - Study eye
subjects affected / exposed	1 / 190 (0.53%)	5 / 187 (2.67%)	6 / 566 (1.06%)	0 / 189 (0.00%)
occurrences all number	1	5	6	0
Vitreous detachment - Fellow eye
subjects affected / exposed	5 / 190 (2.63%)	4 / 187 (2.14%)	14 / 566 (2.47%)	5 / 189 (2.65%)
occurrences all number	5	4	14	5
Vitreous detachment - Study eye
subjects affected / exposed	9 / 190 (4.74%)	3 / 187 (1.60%)	22 / 566 (3.89%)	10 / 189 (5.29%)
occurrences all number	9	3	22	10
Vitreous floaters - Fellow eye
subjects affected / exposed	7 / 190 (3.68%)	5 / 187 (2.67%)	17 / 566 (3.00%)	5 / 189 (2.65%)
occurrences all number	8	5	18	5
Vitreous floaters - Study eye
subjects affected / exposed	7 / 190 (3.68%)	6 / 187 (3.21%)	23 / 566 (4.06%)	10 / 189 (5.29%)
occurrences all number	10	6	27	11
Vitreous haemorrhage - Fellow eye
subjects affected / exposed	4 / 190 (2.11%)	5 / 187 (2.67%)	13 / 566 (2.30%)	4 / 189 (2.12%)
occurrences all number	5	6	16	5
Vitreous haemorrhage - Study eye
subjects affected / exposed	2 / 190 (1.05%)	3 / 187 (1.60%)	9 / 566 (1.59%)	4 / 189 (2.12%)
occurrences all number	2	3	9	4
Gastrointestinal disorders
Constipation
subjects affected / exposed	4 / 190 (2.11%)	5 / 187 (2.67%)	13 / 566 (2.30%)	4 / 189 (2.12%)
occurrences all number	4	5	13	4
Diarrhoea
subjects affected / exposed	5 / 190 (2.63%)	6 / 187 (3.21%)	21 / 566 (3.71%)	10 / 189 (5.29%)
occurrences all number	5	6	23	12
Nausea
subjects affected / exposed	2 / 190 (1.05%)	3 / 187 (1.60%)	10 / 566 (1.77%)	5 / 189 (2.65%)
occurrences all number	2	3	10	5
Vomiting
subjects affected / exposed	5 / 190 (2.63%)	2 / 187 (1.07%)	14 / 566 (2.47%)	7 / 189 (3.70%)
occurrences all number	6	2	15	7
Skin and subcutaneous tissue disorders
Skin ulcer
subjects affected / exposed	4 / 190 (2.11%)	2 / 187 (1.07%)	10 / 566 (1.77%)	4 / 189 (2.12%)
occurrences all number	4	2	10	4
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	1 / 190 (0.53%)	3 / 187 (1.60%)	8 / 566 (1.41%)	4 / 189 (2.12%)
occurrences all number	1	3	8	4
Chronic kidney disease
subjects affected / exposed	1 / 190 (0.53%)	7 / 187 (3.74%)	15 / 566 (2.65%)	7 / 189 (3.70%)
occurrences all number	1	7	16	8
Renal failure
subjects affected / exposed	5 / 190 (2.63%)	3 / 187 (1.60%)	10 / 566 (1.77%)	2 / 189 (1.06%)
occurrences all number	5	3	10	2
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	12 / 190 (6.32%)	5 / 187 (2.67%)	23 / 566 (4.06%)	6 / 189 (3.17%)
occurrences all number	16	6	28	6
Back pain
subjects affected / exposed	4 / 190 (2.11%)	6 / 187 (3.21%)	15 / 566 (2.65%)	5 / 189 (2.65%)
occurrences all number	4	6	15	5
Muscle spasms
subjects affected / exposed	4 / 190 (2.11%)	2 / 187 (1.07%)	6 / 566 (1.06%)	0 / 189 (0.00%)
occurrences all number	5	2	7	0
Infections and infestations
Bronchitis
subjects affected / exposed	5 / 190 (2.63%)	4 / 187 (2.14%)	14 / 566 (2.47%)	5 / 189 (2.65%)
occurrences all number	6	4	15	5
COVID-19
subjects affected / exposed	8 / 190 (4.21%)	7 / 187 (3.74%)	22 / 566 (3.89%)	7 / 189 (3.70%)
occurrences all number	8	7	22	7
Cellulitis
subjects affected / exposed	0 / 190 (0.00%)	4 / 187 (2.14%)	6 / 566 (1.06%)	2 / 189 (1.06%)
occurrences all number	0	4	6	2
Conjunctivitis - Fellow eye
subjects affected / exposed	3 / 190 (1.58%)	4 / 187 (2.14%)	13 / 566 (2.30%)	6 / 189 (3.17%)
occurrences all number	3	5	16	8
Conjunctivitis - Study eye
subjects affected / exposed	4 / 190 (2.11%)	1 / 187 (0.53%)	11 / 566 (1.94%)	6 / 189 (3.17%)
occurrences all number	4	1	14	9
Ear infection
subjects affected / exposed	4 / 190 (2.11%)	2 / 187 (1.07%)	6 / 566 (1.06%)	0 / 189 (0.00%)
occurrences all number	6	2	8	0
Herpes zoster
subjects affected / exposed	5 / 190 (2.63%)	0 / 187 (0.00%)	5 / 566 (0.88%)	0 / 189 (0.00%)
occurrences all number	5	0	5	0
Influenza
subjects affected / exposed	6 / 190 (3.16%)	7 / 187 (3.74%)	21 / 566 (3.71%)	8 / 189 (4.23%)
occurrences all number	6	9	23	8
Lower respiratory tract infection
subjects affected / exposed	4 / 190 (2.11%)	0 / 187 (0.00%)	5 / 566 (0.88%)	1 / 189 (0.53%)
occurrences all number	4	0	5	1
Nasopharyngitis
subjects affected / exposed	20 / 190 (10.53%)	16 / 187 (8.56%)	54 / 566 (9.54%)	18 / 189 (9.52%)
occurrences all number	29	18	71	24
Pneumonia
subjects affected / exposed	3 / 190 (1.58%)	4 / 187 (2.14%)	11 / 566 (1.94%)	4 / 189 (2.12%)
occurrences all number	3	4	11	4
Sinusitis
subjects affected / exposed	4 / 190 (2.11%)	4 / 187 (2.14%)	13 / 566 (2.30%)	5 / 189 (2.65%)
occurrences all number	5	5	15	5
Tooth infection
subjects affected / exposed	1 / 190 (0.53%)	4 / 187 (2.14%)	5 / 566 (0.88%)	0 / 189 (0.00%)
occurrences all number	1	4	5	0
Upper respiratory tract infection
subjects affected / exposed	6 / 190 (3.16%)	5 / 187 (2.67%)	16 / 566 (2.83%)	5 / 189 (2.65%)
occurrences all number	7	6	19	6
Urinary tract infection
subjects affected / exposed	17 / 190 (8.95%)	8 / 187 (4.28%)	45 / 566 (7.95%)	20 / 189 (10.58%)
occurrences all number	30	12	70	28
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	2 / 190 (1.05%)	0 / 187 (0.00%)	8 / 566 (1.41%)	6 / 189 (3.17%)
occurrences all number	2	0	8	6
Diabetes mellitus
subjects affected / exposed	7 / 190 (3.68%)	7 / 187 (3.74%)	18 / 566 (3.18%)	4 / 189 (2.12%)
occurrences all number	7	7	18	4
Diabetes mellitus inadequate control
subjects affected / exposed	4 / 190 (2.11%)	3 / 187 (1.60%)	10 / 566 (1.77%)	3 / 189 (1.59%)
occurrences all number	4	3	10	3
Dyslipidaemia
subjects affected / exposed	2 / 190 (1.05%)	2 / 187 (1.07%)	8 / 566 (1.41%)	4 / 189 (2.12%)
occurrences all number	2	2	8	4
Hyperglycaemia
subjects affected / exposed	2 / 190 (1.05%)	1 / 187 (0.53%)	7 / 566 (1.24%)	4 / 189 (2.12%)
occurrences all number	2	1	7	4
Type 2 diabetes mellitus
subjects affected / exposed	3 / 190 (1.58%)	3 / 187 (1.60%)	12 / 566 (2.12%)	6 / 189 (3.17%)
occurrences all number	4	3	15	8

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Were there any global substantial amendments to the protocol? Yes

23 May 2018

Definition of “personal data” was added and WOC was updated. Added clarification on the framework of analysis on study information collected from withdrawn subjects.

11 Feb 2020

Purpose and timing of interim analyses/design adaptations were updated for the primary analysis to be conducted when the first 534 randomized subjects have completed their Week 52 visit or terminated the study prior to Week 52. Clarification that data for the additional subjects randomized in Japan beyond the study target of 534 subjects was to be analyzed once these subjects had completed their Week 52 visit or terminated the study prior to Week 52. Details were added regarding the primary Week 52 analysis and additional analyses to allow for consistency assessment of data between Japanese and non-Japanese subjects. Clarification was added regarding treatment masking. Aflibercept was removed from ADA and systemic exposure.

12 Jun 2020

Changes in relation to emerging safety issue are: Information was added to describe a new safety signal from post-marketing case reports. Additional guidance was added emphasizing that if any sign of intraocular inflammation is present, an IVT injection must not be performed and subjects should be treated for intraocular inflammation according to clinical practice. Additional examination and assessments included to fully characterize cases of intraocular inflammation were made. Modifications were made to include importance of estimands per ICH E9(R1) guidance. Changes were incorporated to address the COVID- 19 pandemic. Other changes incorporated in this amendment: Three endpoints were moved from Secondary to Exploratory. Clarifications were added regarding unmasked investigator/site personnel, injection procedure, IOP measurement procedure, and SAE reporting period

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

Due to EudraCT system limitations, which EMA is aware of, data using 999 as data points in this record are not an accurate representation of the clinical trial results. Please use https://www.novctrd.com for complete trial results.

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Clinical trials

Clinical Trial Results: A two-year, three-arm, randomized, double masked, multicenter, phase III study assessing the efficacy and safety of brolucizumab versus aflibercept in adult patients with visual impairment due to diabetic macular edema (KESTREL)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change from baseline in best-corrected visual acuity (BCVA) at Week 52

Primary: Change from baseline in best-corrected visual acuity (BCVA) at Week 52

Secondary: Average change from baseline in BCVA over the period Week 40 through Week 52

Secondary: Average change from baseline in BCVA over the period Week 40 through Week 52

Secondary: Patients maintained at q12w - Probability of maintaining on q12w

Secondary: Patients maintained at q12w - Probability of maintaining on q12w

Secondary: Patients maintained at q12w (for those patients who qualified for q12w at week 36) - probability of maintaining on q12w

Secondary: Patients maintained at q12w (for those patients who qualified for q12w at week 36) - probability of maintaining on q12w

Secondary: Change from baseline in BCVA at each visit up to Week 52

Secondary: Change from baseline in BCVA at each visit up to Week 52

Secondary: BCVA (letters read): ANOVA results for average change from baseline over the period Week 88 through Week 100 for the study eye (FAS - LOCF)

Secondary: BCVA (letters read): ANOVA results for average change from baseline over the period Week 88 through Week 100 for the study eye (FAS - LOCF)

Secondary: Patients maintained at q12w up to Week 64 (after three q12w- treatment intervals) and Week 100 - Probability of maintaining on q12w (survival)

Secondary: Patients maintained at q12w up to Week 64 (after three q12w- treatment intervals) and Week 100 - Probability of maintaining on q12w (survival)

Secondary: Secondary: Patients maintained at q12w up to Week 64 (after three q12w- treatment intervals) and Week 100, within those patients that qualified for q12w at Week 36 - Probability of maintaining on q12w (survival)

Secondary: Secondary: Patients maintained at q12w up to Week 64 (after three q12w- treatment intervals) and Week 100, within those patients that qualified for q12w at Week 36 - Probability of maintaining on q12w (survival)

Secondary: Change from baseline in central subfield thickness (CSFT) at each visit up to week 52 - Pairwise ANOVA results

Secondary: Change from baseline in central subfield thickness (CSFT) at each visit up to week 52 - Pairwise ANOVA results

Secondary: Central subfield thickness (CSFT) (micrometers): ANOVA results for average change from baseline over the period Week 88 through Week 100 for the study eye (Full Analysis Set – LOCF)

Secondary: Central subfield thickness (CSFT) (micrometers): ANOVA results for average change from baseline over the period Week 88 through Week 100 for the study eye (Full Analysis Set – LOCF)

Secondary: Number and percentage of patients with presence of subretinal fluid (SRF) at each assessment visit

Secondary: Number and percentage of patients with presence of subretinal fluid (SRF) at each assessment visit

Secondary: Number and percentage of patients with presence of intraretinal fluid (IRF) at each assessment visit

Secondary: Number and percentage of patients with presence of intraretinal fluid (IRF) at each assessment visit

Secondary: Number and percentage of patients with presence of SRF and/or IRF in the study eye by visit

Secondary: Number and percentage of patients with presence of SRF and/or IRF in the study eye by visit

Secondary: Number and percentage of patients with presence of leakage on fluorescein angiography (FA) at Week 52 (Primary Analysis)

Secondary: Number and percentage of patients with presence of leakage on fluorescein angiography (FA) at Week 52 (Primary Analysis)

Secondary: Number and percentage of patients with presence of leakage on fluorescein angiography (FA) at Week 100 (Final Analysis)

Secondary: Number and percentage of patients with presence of leakage on fluorescein angiography (FA) at Week 100 (Final Analysis)

Secondary: Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) : proportion of subjects with >=2-step improvement from baseline in the DRSS score at each assessment visit for the study eye - Number of subjects

Secondary: Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) : proportion of subjects with >=2-step improvement from baseline in the DRSS score at each assessment visit for the study eye - Number of subjects

Secondary: Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) : proportion of subjects with >=2-step improvement from baseline in the DRSS score at each assessment visit for the study eye - Proportion estimates (%)

Secondary: Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) : proportion of subjects with >=2-step improvement from baseline in the DRSS score at each assessment visit for the study eye - Proportion estimates (%)

Secondary: Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS): proportion of subjects with >=3-step improvement from baseline in the DRSS score at each assessment visit for the study eye - Number of subjects

Secondary: Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS): proportion of subjects with >=3-step improvement from baseline in the DRSS score at each assessment visit for the study eye - Number of subjects

Secondary: Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS): proportion of subjects with >=3-step improvement from baseline in the DRSS score at each assessment visit for the study eye - Proportion estimates (%)

Secondary: Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS): proportion of subjects with >=3-step improvement from baseline in the DRSS score at each assessment visit for the study eye - Proportion estimates (%)

Secondary: Change from baseline in patient reported outcomes Visual Functioning Questionnaire-25 (VFQ-25) total and subscale scores up to Week 52 (Primary Analysis) and Week 100 (Final Analysis)

Secondary: Change from baseline in patient reported outcomes Visual Functioning Questionnaire-25 (VFQ-25) total and subscale scores up to Week 52 (Primary Analysis) and Week 100 (Final Analysis)

Secondary: Ocular Adverse Events (AEs) (>=2% in any treatment arm) by preferred term for the study eye

Secondary: Ocular Adverse Events (AEs) (>=2% in any treatment arm) by preferred term for the study eye

Secondary: Number of subjects with non-ocular Adverse Events (AEs) (>=2% in any treatment arm)

Secondary: Number of subjects with non-ocular Adverse Events (AEs) (>=2% in any treatment arm)

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A two-year, three-arm, randomized, double masked, multicenter, phase III study assessing the efficacy and safety of brolucizumab versus aflibercept in adult patients with visual impairment due to diabetic macular edema (KESTREL)