Trial Outcomes & Findings for Study to Assess the Efficacy and Safety of Brolucizumab 6mg Compared to Aflibercept 2 mg in a Treat-to-control Regimen (TALON) (NCT NCT04005352)

Last Updated: 2024-10-09

Results Overview

No disease activity is defined as no change in visual acuity and no change in other signs of the disease (e.g. Intraretinal Fluid (IRF), Subretinal Fluid (SRF), hemorrhage, leakage, etc.). Treatment interval distribution. Number (%) of subjects at 12/8/4-weeks intervals up to Week 32 for the study eye. If the study treatment is discontinued before Week 16, then the treatment interval is 4 weeks; otherwise. the last interval with no disease activity is used (if there was disease activity, the last interval is shortened by 4 weeks, down to a minimum of 4 weeks). If the duration of the last interval falls within the following ranges of (4-week, 8-week) or (8-week, 12-week) or ≥12-week then the floor value of these ranges was used.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

734 participants

Primary outcome timeframe

Up to Week 32

Results posted on

2024-10-09

Participant Flow

734 participants were treated.

Participant milestones

Participant milestones
Measure	Brolucizumab 6 mg Intra-vitreal injection	Aflibercept 2 mg Intra-vitreal injection
Overall Study STARTED	366	368
Overall Study COMPLETED	317	307
Overall Study NOT COMPLETED	49	61

Reasons for withdrawal

Reasons for withdrawal
Measure	Brolucizumab 6 mg Intra-vitreal injection	Aflibercept 2 mg Intra-vitreal injection
Overall Study Adverse Event	4	5
Overall Study Death	4	2
Overall Study Lost to Follow-up	6	2
Overall Study Physician Decision	7	13
Overall Study Protocol Violation	0	1
Overall Study Withdrawal by Subject	28	38

Baseline Characteristics

Study to Assess the Efficacy and Safety of Brolucizumab 6mg Compared to Aflibercept 2 mg in a Treat-to-control Regimen (TALON)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Brolucizumab 6 mg n=366 Participants Intra-vitreal injection	Aflibercept 2 mg n=368 Participants Intra-vitreal injection	Total n=734 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	32 Participants n=5 Participants	37 Participants n=7 Participants	69 Participants n=5 Participants
Age, Categorical >=65 years	334 Participants n=5 Participants	331 Participants n=7 Participants	665 Participants n=5 Participants
Age, Continuous	75.5 years STANDARD_DEVIATION 7.85 • n=5 Participants	75.5 years STANDARD_DEVIATION 8.41 • n=7 Participants	75.5 years STANDARD_DEVIATION 8.13 • n=5 Participants
Sex: Female, Male Female	216 Participants n=5 Participants	204 Participants n=7 Participants	420 Participants n=5 Participants
Sex: Female, Male Male	150 Participants n=5 Participants	164 Participants n=7 Participants	314 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	55 Participants n=5 Participants	55 Participants n=7 Participants	110 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	310 Participants n=5 Participants	312 Participants n=7 Participants	622 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to Week 32

Population: Full Analysis Set (Includes participants who were randomized and treated.)

Outcome measures

Outcome measures
Measure	Brolucizumab 6 mg n=366 Participants Intra-vitreal injection	Aflibercept 2 mg n=368 Participants Intra-vitreal injection
Distribution of the Last Interval With no Disease Activity up to Week 32 - Study Eye 12 weeks	141 Participants	73 Participants
Distribution of the Last Interval With no Disease Activity up to Week 32 - Study Eye 8 weeks	131 Participants	147 Participants
Distribution of the Last Interval With no Disease Activity up to Week 32 - Study Eye 4 weeks	94 Participants	148 Participants

PRIMARY outcome

Timeframe: Baseline, Week 28 and Week 32

Population: Full Analysis Set - Last observation carried forward (LOCF).

BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning. Least squares mean estimate - for weeks 28 and 32 combined.

Outcome measures

Outcome measures
Measure	Brolucizumab 6 mg n=366 Participants Intra-vitreal injection	Aflibercept 2 mg n=368 Participants Intra-vitreal injection
Average Change From Baseline at Week 28 and Week 32 in Best-corrected Visual Acuity (BCVA) - Study Eye	5.2 Scores on a scale Standard Error 0.51	5.1 Scores on a scale Standard Error 0.51

SECONDARY outcome

Timeframe: Up to Week 64

Population: Full Analysis Set

No disease activity is defined as no change in visual acuity and no change in other signs of the disease (e.g. IRF, SRF, hemorrhage, leakage, etc.). Treatment interval distribution. The number of subjects at 16/12/8/4-weeks intervals as the last interval with no disease activity. If the study treatment is discontinued before Week 16, then the treatment interval is 4 weeks; otherwise. the last interval with no disease activity is used (if there was disease activity, the last interval is shortened by 4 weeks, down to a minimum of 4 weeks). If the duration of the last interval falls within the following ranges of (4-week, 8-week) or (8-week, 12-week) or (12-weeks, 16-weeks) or ≥16-week then the floor value of these ranges was used.

Outcome measures

Outcome measures
Measure	Brolucizumab 6 mg n=366 Participants Intra-vitreal injection	Aflibercept 2 mg n=368 Participants Intra-vitreal injection
Distribution of the Last Interval With no Disease Activity up to Week 64 - Study Eye 8 Weeks	95 Participants	81 Participants
Distribution of the Last Interval With no Disease Activity up to Week 64 - Study Eye 4 Weeks	85 Participants	154 Participants
Distribution of the Last Interval With no Disease Activity up to Week 64 - Study Eye 16 Weeks	104 Participants	45 Participants
Distribution of the Last Interval With no Disease Activity up to Week 64 - Study Eye 12 Weeks	82 Participants	88 Participants

SECONDARY outcome

Timeframe: Up to Week 64

Population: Full Analysis Set

No disease activity is defined as no change in visual acuity and no change in other signs of the disease (e.g. IRF, SRF, hemorrhage, leakage, etc.). Maximal interval distribution. Number of subjects at 16/12/8/4-weeks intervals as the last interval with no disease activity. If the study treatment is discontinued before Week 16 included, then the treatment interval is 4 weeks; otherwise, the last interval with no disease activity is used (if there was disease activity, the last interval is shortened by 4 weeks, down to a minimum of 4 weeks). If the duration of the maximal interval falls within the following ranges of \[4-weeks, 8-weeks) or \[8-weeks, 12-weeks) or \[12-weeks, 16-weeks\] or ≥16-weeks then the floor value of these ranges is used.

Outcome measures

Outcome measures
Measure	Brolucizumab 6 mg n=366 Participants Intra-vitreal injection	Aflibercept 2 mg n=368 Participants Intra-vitreal injection
Distribution of the Maximal Intervals With no Disease Activity up to Week 64 - Study Eye 16 Weeks	117 Participants	57 Participants
Distribution of the Maximal Intervals With no Disease Activity up to Week 64 - Study Eye 12 Weeks	96 Participants	92 Participants
Distribution of the Maximal Intervals With no Disease Activity up to Week 64 - Study Eye 8 Weeks	94 Participants	114 Participants
Distribution of the Maximal Intervals With no Disease Activity up to Week 64 - Study Eye 4 Weeks	59 Participants	105 Participants

SECONDARY outcome

Timeframe: Weeks 14 and 16

Population: Full Analysis Set. Note that the number analyzed is reduced because the Week 14 visit was conducted at the investigator's discretion, and because some patients had already stopped treatment by Week 16.

Disease activity assessment as determined by visual acuity and assessment of other signs of the disease (e.g. IRF, SRF, hemorrhage, leakage, etc.).

Outcome measures

Outcome measures
Measure	Brolucizumab 6 mg n=301 Participants Intra-vitreal injection	Aflibercept 2 mg n=296 Participants Intra-vitreal injection
Number of Participants With no Disease Activity - Study Eye Week 14 (n=118, 137)	87 Participants	88 Participants
Number of Participants With no Disease Activity - Study Eye Week 16 (n=301,296)	260 Participants	211 Participants

SECONDARY outcome

Timeframe: Up to Week 64

Population: Full Analysis Set - subjects with no important protocol deviations with impact

Intraretinal fluid (IRF) and subretinal fluid (SRF) were assessed by Spectral Domain Optical Coherence Tomography (SD-OCT) (study eye). Please note that this endpoint can be impacted by the optional disease activity assessment visits and the flexible dosing regimen, in addition to the randomized treatment. Hence, the observed treatment effect may be confounded by the study design artifacts.

Outcome measures

Outcome measures
Measure	Brolucizumab 6 mg n=366 Participants Intra-vitreal injection	Aflibercept 2 mg n=368 Participants Intra-vitreal injection
Time From Last Loading Injection to First Visit With No Disease Activity (Weeks) - 75th Percentile - Study Eye	9.1 weeks Interval 8.9 to 10.6	12.1 weeks Interval 11.3 to 12.9

SECONDARY outcome

Timeframe: Up to Week 64

Population: Full Analysis Set - subjects with no important protocol deviations with impact

Intraretinal fluid (IRF) and subretinal fluid (SRF) were assessed by Spectral Domain Optical Coherence Tomography (SD-OCT) (study eye).

Outcome measures

Outcome measures
Measure	Brolucizumab 6 mg n=330 Participants Intra-vitreal injection	Aflibercept 2 mg n=337 Participants Intra-vitreal injection
Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye 32 Week	20 Participants	25 Participants
Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye 36 Week	20 Participants	23 Participants
Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye 56 Week	17 Participants	20 Participants
Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye 60 Week	11 Participants	14 Participants
Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye 64 Week	0 Participants	0 Participants
Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye 0 Week	330 Participants	337 Participants
Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye 4 Week	144 Participants	138 Participants
Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye 8 Week	70 Participants	86 Participants
Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye 12 Week	70 Participants	86 Participants
Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye 16 Week	37 Participants	67 Participants
Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye 20 Week	34 Participants	55 Participants
Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye 24 Week	30 Participants	47 Participants
Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye 28 Week	28 Participants	38 Participants
Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye 40 Week	18 Participants	22 Participants
Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye 44 Week	18 Participants	22 Participants
Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye 48 Week	17 Participants	20 Participants
Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye 52 Week	17 Participants	20 Participants

SECONDARY outcome

Timeframe: Baseline, Week 60 and Week 64

Population: Full Analysis Set - LOCF

Outcome measures

Outcome measures
Measure	Brolucizumab 6 mg n=366 Participants Intra-vitreal injection	Aflibercept 2 mg n=368 Participants Intra-vitreal injection
Average Change From Baseline at Week 60 and Week 64 in Best-corrected Visual Acuity (BCVA) - Study Eye	4.7 Scores on a scale Standard Error 0.60	4.9 Scores on a scale Standard Error 0.60

SECONDARY outcome

Timeframe: Baseline, Week 32, and Week 64

Population: Full Analysis Set - LOCF

Outcome measures

Outcome measures
Measure	Brolucizumab 6 mg n=366 Participants Intra-vitreal injection	Aflibercept 2 mg n=368 Participants Intra-vitreal injection
Number of Participants With Best-corrected Visual Acuity Improvements of ≥ 15 Letters in BCVA From Baseline or Reached BCVA ≥ 84 Letters up to Week 32/64 Per Treatment Arm - Study Eye Week 32	88 Participants	92 Participants
Number of Participants With Best-corrected Visual Acuity Improvements of ≥ 15 Letters in BCVA From Baseline or Reached BCVA ≥ 84 Letters up to Week 32/64 Per Treatment Arm - Study Eye Week 64	89 Participants	91 Participants

SECONDARY outcome

Timeframe: Week 32 and Week 64

Population: Full Analysis Set - LOCF

Outcome measures

Outcome measures
Measure	Brolucizumab 6 mg n=366 Participants Intra-vitreal injection	Aflibercept 2 mg n=368 Participants Intra-vitreal injection
Number of Participants With Best-corrected Visual Acuity ≥ 69 Letters - Study Eye Week 64	240 Participants	219 Participants
Number of Participants With Best-corrected Visual Acuity ≥ 69 Letters - Study Eye Week 32	244 Participants	228 Participants

SECONDARY outcome

Timeframe: Baseline, Weeks 28 and 32 and at Weeks 60 and 64

Population: Full Analysis Set - LOCF

CSFT was measured by Spectral Domain Optical Coherence Tomography

Outcome measures

Outcome measures
Measure	Brolucizumab 6 mg n=366 Participants Intra-vitreal injection	Aflibercept 2 mg n=368 Participants Intra-vitreal injection
Average Change From Baseline in Central Subfield Thickness (CSFT) - Study Eye Weeks 28 and 32 (average)	-166.9 micrometers Standard Error 6.97	-140.0 micrometers Standard Error 6.96
Average Change From Baseline in Central Subfield Thickness (CSFT) - Study Eye Weeks 60 and 64 (average)	-182.9 micrometers Standard Error 7.72	-167.5 micrometers Standard Error 8.16

SECONDARY outcome

Timeframe: At Weeks 28, 32, 60 and 64

Population: Full Analysis Set

Intraretinal Fluid and/or Subretinal Fluid status was measured by Spectral Domain Optical Coherence Tomography (SD-OCT).

Outcome measures

Outcome measures
Measure	Brolucizumab 6 mg n=286 Participants Intra-vitreal injection	Aflibercept 2 mg n=289 Participants Intra-vitreal injection
Number of Participants With Presence of Intraretinal Fluid and/or Subretinal Fluid in the Central Subfield - Study Eye Week 28 (n=285,289)	175 Participants	198 Participants
Number of Participants With Presence of Intraretinal Fluid and/or Subretinal Fluid in the Central Subfield - Study Eye Week 32 (n=286, 267)	144 Participants	152 Participants
Number of Participants With Presence of Intraretinal Fluid and/or Subretinal Fluid in the Central Subfield - Study Eye Week 60 (n=269,244)	60 Participants	69 Participants
Number of Participants With Presence of Intraretinal Fluid and/or Subretinal Fluid in the Central Subfield - Study Eye Week 64 (n=271, 241)	72 Participants	83 Participants

SECONDARY outcome

Timeframe: At Weeks 28, 32, 60 and 64

Population: Full Analysis Set

Sub-Retinal Pigment Epithelium fluid status was measured by Spectral Domain Optical Coherence Tomography (SD-OCT).

Outcome measures

Outcome measures
Measure	Brolucizumab 6 mg n=288 Participants Intra-vitreal injection	Aflibercept 2 mg n=289 Participants Intra-vitreal injection
Number of Participants With Presence of Sub-Retinal Pigment Epithelium Fluid in the Central Subfield - Study Eye Week 28 (n=288,289)	173 Participants	208 Participants
Number of Participants With Presence of Sub-Retinal Pigment Epithelium Fluid in the Central Subfield - Study Eye Week 32 (n=288, 266)	156 Participants	175 Participants
Number of Participants With Presence of Sub-Retinal Pigment Epithelium Fluid in the Central Subfield - Study Eye Week 60 (n=271,244)	27 Participants	31 Participants
Number of Participants With Presence of Sub-Retinal Pigment Epithelium Fluid in the Central Subfield - Study Eye Week 64 (n=271, 242)	34 Participants	43 Participants

SECONDARY outcome

Timeframe: Baseline, Week 32, and Week 64

Population: Full Analysis Set

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. Each subscale score has a range of 0 to 100 inclusive and will be calculated from the re-scaled raw data. A composite score is derived based on the average of the 11 subscales.

Outcome measures

Outcome measures
Measure	Brolucizumab 6 mg n=278 Participants Intra-vitreal injection	Aflibercept 2 mg n=261 Participants Intra-vitreal injection
Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Composite Scores - Study Eye Week 32 (n-278, 261)	4.09 Scores on a scale Standard Error 0.20	3.72 Scores on a scale Standard Error 0.21
Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Composite Scores - Study Eye Week 64 (n=248, 224)	2.8 Scores on a scale Standard Error 0.69	4.7 Scores on a scale Standard Error 0.73

SECONDARY outcome

Timeframe: Baseline, Week 32, and Week 64

Population: Full Analysis Set

Outcome measures

Outcome measures
Measure	Brolucizumab 6 mg n=278 Participants Intra-vitreal injection	Aflibercept 2 mg n=261 Participants Intra-vitreal injection
Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - General Vision - Study Eye Week 32 (n-278, 261)	7.94 Scores on a scale Standard Error 0.86	5.79 Scores on a scale Standard Error 0.89
Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - General Vision - Study Eye Week 64 (n=248, 224)	7.3 Scores on a scale Standard Error 0.87	8.0 Scores on a scale Standard Error 0.92

SECONDARY outcome

Timeframe: Baseline, Week 32, and Week 64

Population: Full Analysis Set

Outcome measures

Outcome measures
Measure	Brolucizumab 6 mg n=278 Participants Intra-vitreal injection	Aflibercept 2 mg n=261 Participants Intra-vitreal injection
Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Ocular Pain - Study Eye Week 32 (n-278, 261)	3.55 Scores on a scale Standard Error 0.92	2.78 Scores on a scale Standard Error 0.94
Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Ocular Pain - Study Eye Week 64 (n=248, 224)	3.1 Scores on a scale Standard Error 0.89	5.0 Scores on a scale Standard Error 0.94

SECONDARY outcome

Timeframe: Baseline, Week 32, and Week 64

Population: Full Analysis Set

Outcome measures

Outcome measures
Measure	Brolucizumab 6 mg n=278 Participants Intra-vitreal injection	Aflibercept 2 mg n=261 Participants Intra-vitreal injection
Change From Baseline n Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Near Activities - Study Eye Week 32 (n-278, 261)	7.46 Scores on a scale Standard Error 1.05	5.86 Scores on a scale Standard Error 1.08
Change From Baseline n Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Near Activities - Study Eye Week 64 (n=248, 224)	4.9 Scores on a scale Standard Error 1.12	7.9 Scores on a scale Standard Error 1.18

SECONDARY outcome

Timeframe: Baseline, Week 32, and Week 64

Population: Full Analysis Set

Outcome measures

Outcome measures
Measure	Brolucizumab 6 mg n=278 Participants Intra-vitreal injection	Aflibercept 2 mg n=261 Participants Intra-vitreal injection
Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Distance Activities - Study Eye Week 32 (n-278, 261)	3.06 Scores on a scale Standard Error 0.95	3.78 Scores on a scale Standard Error 0.98
Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Distance Activities - Study Eye Week 64 (n=248, 224)	2.5 Scores on a scale Standard Error 0.99	5.0 Scores on a scale Standard Error 1.04

SECONDARY outcome

Timeframe: Baseline, Week 32, and Week 64

Population: Full Analysis Set

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 or outcome. 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. Each subscale score has a range of 0 to 100 inclusive and will be calculated from the re-scaled raw data. A composite score is derived based on the average of the 11 subscales.

Outcome measures

Outcome measures
Measure	Brolucizumab 6 mg n=278 Participants Intra-vitreal injection	Aflibercept 2 mg n=261 Participants Intra-vitreal injection
Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Social Functioning - Study Eye Week 64 (n=247, 223)	0.2 Scores on a scale Standard Error 0.81	1.7 Scores on a scale Standard Error 0.85
Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Social Functioning - Study Eye Week 32 (n-278, 261)	1.99 Scores on a scale Standard Error 0.79	0.43 Scores on a scale Standard Error 0.82

SECONDARY outcome

Timeframe: Baseline, Week 32, and Week 64

Population: Full Analysis Set

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 or outcome. 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. Each subscale score has a range of 0 to 100 inclusive and will be calculated from the re-scaled raw data. A composite score is derived based on the average of the 11 subscales.

Outcome measures

Outcome measures
Measure	Brolucizumab 6 mg n=278 Participants Intra-vitreal injection	Aflibercept 2 mg n=261 Participants Intra-vitreal injection
Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Mental Health - Study Eye Week 32 (n-278, 261)	5.83 Scores on a scale Standard Error 0.99	6.79 Scores on a scale Standard Error 1.02
Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Mental Health - Study Eye Week 64 (n=248, 224)	5.0 Scores on a scale Standard Error 1.08	7.2 Scores on a scale Standard Error 1.14

SECONDARY outcome

Timeframe: Baseline, Week 32, and Week 64

Population: Full Analysis Set

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 or outcome. 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. Each subscale score has a range of 0 to 100 inclusive and will be calculated from the re-scaled raw data. A composite score is derived based on the average of the 11 subscales.

Outcome measures

Outcome measures
Measure	Brolucizumab 6 mg n=278 Participants Intra-vitreal injection	Aflibercept 2 mg n=261 Participants Intra-vitreal injection
Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Role Difficulties - Study Eye Week 64 (n=248, 224)	4.7 Scores on a scale Standard Error 1.31	5.9 Scores on a scale Standard Error 1.38
Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Role Difficulties - Study Eye Week 32 (n-278, 261)	5.17 Scores on a scale Standard Error 1.31	4.30 Scores on a scale Standard Error 1.35

SECONDARY outcome

Timeframe: Baseline, Week 32, and Week 64

Population: Full Analysis Set

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 or outcome. 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. Each subscale score has a range of 0 to 100 inclusive and will be calculated from the re-scaled raw data. A composite score is derived based on the average of the 11 subscales.

Outcome measures

Outcome measures
Measure	Brolucizumab 6 mg n=278 Participants Intra-vitreal injection	Aflibercept 2 mg n=261 Participants Intra-vitreal injection
Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Dependency - Study Eye Week 32 (n-278, 261)	2.71 Scores on a scale Standard Error 0.88	2.22 Scores on a scale Standard Error 0.91
Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Dependency - Study Eye Week 64 (n=248, 224)	-0.6 Scores on a scale Standard Error 1.09	2.2 Scores on a scale Standard Error 1.14

SECONDARY outcome

Timeframe: Baseline, Week 32, and Week 64

Population: Full Analysis Set

Outcome measures

Outcome measures
Measure	Brolucizumab 6 mg n=278 Participants Intra-vitreal injection	Aflibercept 2 mg n=261 Participants Intra-vitreal injection
Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Driving - Study Eye Week 32 (n-278, 261)	4.92 Scores on a scale Standard Error 1.56	4.19 Scores on a scale Standard Error 1.57
Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Driving - Study Eye Week 64 (n=139, 131)	1.3 Scores on a scale Standard Error 1.74	3.0 Scores on a scale Standard Error 1.79

SECONDARY outcome

Timeframe: Baseline, Week 32, and Week 64

Population: Full Analysis Set

Outcome measures

Outcome measures
Measure	Brolucizumab 6 mg n=278 Participants Intra-vitreal injection	Aflibercept 2 mg n=261 Participants Intra-vitreal injection
Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Color Vision - Study Eye Week 32 (n-278, 261)	1.78 Scores on a scale Standard Error 0.63	0.02 Scores on a scale Standard Error 0.65
Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Color Vision - Study Eye Week 64 (n=244, 222)	0.1 Scores on a scale Standard Error 0.80	1.2 Scores on a scale Standard Error 0.84

SECONDARY outcome

Timeframe: Baseline, Week 32, and Week 64

Population: Full Analysis Set

Outcome measures

Outcome measures
Measure	Brolucizumab 6 mg n=278 Participants Intra-vitreal injection	Aflibercept 2 mg n=261 Participants Intra-vitreal injection
Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Peripheral Vision - Study Eye Week 32 (n-278, 261)	3.24 Scores on a scale Standard Error 1.01	2.00 Scores on a scale Standard Error 1.04
Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Peripheral Vision - Study Eye Week 64 (n=243, 224)	2.5 Scores on a scale Standard Error 1.08	3.0 Scores on a scale Standard Error 1.13

SECONDARY outcome

Timeframe: Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 483 days, approx. 69 weeks, 1.3 years.

Population: Safety Analysis set

An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign (including abnormal laboratory findings), symptom or disease) in a subject or clinical investigation subject.

Outcome measures

Outcome measures
Measure	Brolucizumab 6 mg n=366 Participants Intra-vitreal injection	Aflibercept 2 mg n=368 Participants Intra-vitreal injection
Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye Macular oedema	3 Participants	4 Participants
Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye Posterior capsule opacification	2 Participants	5 Participants
Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye Dry eye	2 Participants	4 Participants
Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye Hordeolum	4 Participants	2 Participants
Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye Retinal oedema	1 Participants	4 Participants
Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye Uveitis	4 Participants	1 Participants
Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye Vision blurred	4 Participants	1 Participants
Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye Detachment of retinal pigment epithelium	0 Participants	4 Participants
Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye Neovascular age-related macular degeneration	2 Participants	4 Participants
Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye Number of subjects with at least one event	114 Participants	102 Participants
Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye Conjunctival haemorrhage	23 Participants	13 Participants
Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye Visual acuity reduced	16 Participants	18 Participants
Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye Eye pain	17 Participants	13 Participants
Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye Vitreous floaters	12 Participants	6 Participants
Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye Intraocular pressure increased	5 Participants	11 Participants
Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye Subretinal fluid	5 Participants	11 Participants
Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye Vitreous detachment	10 Participants	3 Participants
Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye Retinal haemorrhage	4 Participants	7 Participants
Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye Cataract	5 Participants	5 Participants
Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye Foreign body sensation in eyes	4 Participants	6 Participants
Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye Intra-ocular injection complication	6 Participants	3 Participants
Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye Retinal pigment epithelial tear	5 Participants	4 Participants
Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye Retinal artery occlusion	4 Participants	0 Participants
Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye Subretinal fibrosis	4 Participants	0 Participants

SECONDARY outcome

Timeframe: Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 483 days, approx. 69 weeks, 1.3 years.

Population: Safety Analysis set

Outcome measures

Outcome measures
Measure	Brolucizumab 6 mg n=366 Participants Intra-vitreal injection	Aflibercept 2 mg n=368 Participants Intra-vitreal injection
Number of Participants With Treatment Emergent Non-ocular Adverse Events (Greater Than or Equal to 2% in Any Treatment Arm) - Summary Table	182 Participants	185 Participants

Adverse Events

Brolucizumab 6mg

Serious events: 58 serious events

Other events: 172 other events

Deaths: 4 deaths

Aflibercept 2mg

Serious events: 53 serious events

Other events: 177 other events

Deaths: 2 deaths

All Patients

Serious events: 111 serious events

Other events: 349 other events

Deaths: 6 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: + 1 862 778 8300

Email: [email protected]

Results disclosure agreements

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

Restriction type: OTHER