Trial Outcomes & Findings for An Extension Study Assessing the Efficacy and Safety of Brolucizumab in a Treat-to-Control Regimen in Patients With Neovascular Age-related Macular Degeneration Who Have Completed the CRTH258A2303 (TALON) Study (NCT NCT04597632)

Last Updated: 2024-10-09

Results Overview

Number of subjects in every 4 weeks (q4w), every 8 weeks (q8w), every 12 weeks (q12w) and every 20 weeks (q20w) intervals at last interval with no disease activity up to Week 56. Last interval with no disease activity (number of weeks): Number of subjects at 20/16/12/8/4-weeks intervals up to Week 56 for the study eye in the extension study

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

248 participants

Primary outcome timeframe

Up to Week 56

Results posted on

2024-10-09

Participant Flow

Participant milestones

Participant milestones
Measure	Brolucizumab 6 mg (Extension Study Total) Participants received brolucizumab 6 mg/0.05 mL solution by intravitreal injection in a Treat-to-Control regimen with injection intervals from 4 up to 20 weeks. Intervals could have changed in steps of 4 weeks at a time per investigators' decisions determined by the disease activity.
Overall Study STARTED	248
Overall Study COMPLETED	231
Overall Study NOT COMPLETED	17

Reasons for withdrawal

Reasons for withdrawal
Measure	Brolucizumab 6 mg (Extension Study Total) Participants received brolucizumab 6 mg/0.05 mL solution by intravitreal injection in a Treat-to-Control regimen with injection intervals from 4 up to 20 weeks. Intervals could have changed in steps of 4 weeks at a time per investigators' decisions determined by the disease activity.
Overall Study Withdrawal by Subject	10
Overall Study Lost to Follow-up	1
Overall Study Death	1
Overall Study Adverse Event	5

Baseline Characteristics

An Extension Study Assessing the Efficacy and Safety of Brolucizumab in a Treat-to-Control Regimen in Patients With Neovascular Age-related Macular Degeneration Who Have Completed the CRTH258A2303 (TALON) Study

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Brolucizumab 6 mg (Extension Study Total) n=248 Participants Participants received brolucizumab 6 mg/0.05 mL solution by intravitreal injection in a Treat-to-Control regimen with injection intervals from 4 up to 20 weeks. Intervals could have changed in steps of 4 weeks at a time per investigators' decisions determined by the disease activity.
Age, Continuous	75.9 Years STANDARD_DEVIATION 7.90 • n=5 Participants
Sex: Female, Male Female	129 Participants n=5 Participants
Sex: Female, Male Male	119 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	23 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	219 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	6 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	61 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	187 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to Week 56

Population: Full Analyses Set. Subjects with at least two injections in the extension study

Outcome measures

Outcome measures
Measure	Brolucizumab 6 mg n=237 Participants Participants received brolucizumab 6 mg/0.05 mL solution by intravitreal injection in a Treat-to-Control regimen with injection intervals from 4 up to 20 weeks. Intervals could have changed in steps of 4 weeks at a time per investigators' decisions determined by the disease activity.	Aflibercept 2 mg (Core Study) Patients who received aflibercept 2 mg in the core study and switched to brolucizumab 6 mg in the extension study	Brolucizumab 6 mg (Extension Study Total) Participants received brolucizumab 6 mg/0.05 mL solution by intravitreal injection in a Treat-to-Control regimen with injection intervals from 4 up to 20 weeks. Intervals could have changed in steps of 4 weeks at a time per investigators' decisions determined by the disease activity.
Duration of the Last Interval With no Disease Activity up to Week 56 - Study Eye 20 weeks	68 Participants	—	—
Duration of the Last Interval With no Disease Activity up to Week 56 - Study Eye 16 weeks	59 Participants	—	—
Duration of the Last Interval With no Disease Activity up to Week 56 - Study Eye 12 weeks	47 Participants	—	—
Duration of the Last Interval With no Disease Activity up to Week 56 - Study Eye 8 weeks	49 Participants	—	—
Duration of the Last Interval With no Disease Activity up to Week 56 - Study Eye 4 weeks	14 Participants	—	—

PRIMARY outcome

Timeframe: Extension study baseline, average of Week 52 and Week 56

Population: Full Analyses Set - Last Observation Carried Forward. Participants were analyzed according to the originally assigned treatment arm in the core study (CRTH258A2303, NCT04005352).

Best-Corrected Visual Acuity (BCVA) was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. Visual Function of the study eye was assessed using the ETDRS protocol. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning. The average change in BCVA from Baseline of the extension study at Week 52 and Week 56 was estimated by an analysis of variance (ANOVA) with baseline age categories, baseline BCVA categories and treatment arm in the core study included as fixed effects. Last observation carried forward (LOCF) was used to impute missing BCVA values.

Outcome measures

Outcome measures
Measure	Brolucizumab 6 mg n=135 Participants Participants received brolucizumab 6 mg/0.05 mL solution by intravitreal injection in a Treat-to-Control regimen with injection intervals from 4 up to 20 weeks. Intervals could have changed in steps of 4 weeks at a time per investigators' decisions determined by the disease activity.	Aflibercept 2 mg (Core Study) n=113 Participants Patients who received aflibercept 2 mg in the core study and switched to brolucizumab 6 mg in the extension study	Brolucizumab 6 mg (Extension Study Total) n=248 Participants Participants received brolucizumab 6 mg/0.05 mL solution by intravitreal injection in a Treat-to-Control regimen with injection intervals from 4 up to 20 weeks. Intervals could have changed in steps of 4 weeks at a time per investigators' decisions determined by the disease activity.
Average Change in BCVA From Baseline to Week 52 and Week 56 for the Study Eye	-1.8 Letters read Standard Deviation 8.29	-2.9 Letters read Standard Deviation 7.33	-2.3 Letters read Standard Deviation 7.88

SECONDARY outcome

Timeframe: Extension study baseline, average of Week 52 and Week 56

Population: Participants in the Full Analysis Set with a valid measurement for the outcome measure. Participants were analyzed according to the originally assigned treatment arm in the core study (CRTH258A2303, NCT04005352).

Central Subfield Thickness (μm): Analysis of Variance (ANOVA) results for the average change from extension study Baseline at Week 52 and Week 56 for the study eye in the extension study by core study treatment arm. Central Subfield Thickness was assessed by Spectral domain optical coherence tomography (SD-OCT) from the central reading center.

Outcome measures

Outcome measures
Measure	Brolucizumab 6 mg n=105 Participants Participants received brolucizumab 6 mg/0.05 mL solution by intravitreal injection in a Treat-to-Control regimen with injection intervals from 4 up to 20 weeks. Intervals could have changed in steps of 4 weeks at a time per investigators' decisions determined by the disease activity.	Aflibercept 2 mg (Core Study) n=89 Participants Patients who received aflibercept 2 mg in the core study and switched to brolucizumab 6 mg in the extension study	Brolucizumab 6 mg (Extension Study Total) n=194 Participants Participants received brolucizumab 6 mg/0.05 mL solution by intravitreal injection in a Treat-to-Control regimen with injection intervals from 4 up to 20 weeks. Intervals could have changed in steps of 4 weeks at a time per investigators' decisions determined by the disease activity.
Average Change in Central Subfield Thickness (CSFT) From Baseline to Week 52 and Week 56 - Study Eye	5.9 μm Standard Deviation 24.43	-14.1 μm Standard Deviation 60.67	-3.3 μm Standard Deviation 45.83

SECONDARY outcome

Timeframe: Weeks 52 and 56

Population: Full Analyses Set - for subjects with a valid measurement

Intraretinal Fluid (IRF) and Subretinal Fluid (SRF) status in the central subfield as assessed by Spectral Domain Ocular Coherence Tomography (SD-OCT): Number (%) of subjects with presence of IRF and/or SRF, and sub-Retinal Pigment Epithelium (RPE) fluid in the study eye at Week 52 and Week 56 overall and by core study treatment arm

Outcome measures

Outcome measures
Measure	Brolucizumab 6 mg n=106 Participants Participants received brolucizumab 6 mg/0.05 mL solution by intravitreal injection in a Treat-to-Control regimen with injection intervals from 4 up to 20 weeks. Intervals could have changed in steps of 4 weeks at a time per investigators' decisions determined by the disease activity.	Aflibercept 2 mg (Core Study) n=94 Participants Patients who received aflibercept 2 mg in the core study and switched to brolucizumab 6 mg in the extension study	Brolucizumab 6 mg (Extension Study Total) n=200 Participants Participants received brolucizumab 6 mg/0.05 mL solution by intravitreal injection in a Treat-to-Control regimen with injection intervals from 4 up to 20 weeks. Intervals could have changed in steps of 4 weeks at a time per investigators' decisions determined by the disease activity.
Number (%) of Subjects With Presence of IRF and/or SRF, and Sub-RPE Fluid in the Study Eye at Week 52 and Week 56 Overall and by Core Study Treatment Arm Week 52 Sub-RPE fluid - Present (n=103,90,193)	52 Participants	44 Participants	96 Participants
Number (%) of Subjects With Presence of IRF and/or SRF, and Sub-RPE Fluid in the Study Eye at Week 52 and Week 56 Overall and by Core Study Treatment Arm Week 52 Sub-RPE fluid - Absent (n=103,90,193)	51 Participants	46 Participants	97 Participants
Number (%) of Subjects With Presence of IRF and/or SRF, and Sub-RPE Fluid in the Study Eye at Week 52 and Week 56 Overall and by Core Study Treatment Arm Week 52 IRF and/or SRF - Present (n=103,90,193)	23 Participants	22 Participants	45 Participants
Number (%) of Subjects With Presence of IRF and/or SRF, and Sub-RPE Fluid in the Study Eye at Week 52 and Week 56 Overall and by Core Study Treatment Arm Week 52 IRF and/or SRF - Absent (n=103,90,193)	102 Participants	89 Participants	191 Participants
Number (%) of Subjects With Presence of IRF and/or SRF, and Sub-RPE Fluid in the Study Eye at Week 52 and Week 56 Overall and by Core Study Treatment Arm Week 52 IRF and SRF - Present (n=103,90,193)	1 Participants	1 Participants	2 Participants
Number (%) of Subjects With Presence of IRF and/or SRF, and Sub-RPE Fluid in the Study Eye at Week 52 and Week 56 Overall and by Core Study Treatment Arm Week 52 IRF and SRF - Absent (n=103,90,193)	80 Participants	68 Participants	148 Participants
Number (%) of Subjects With Presence of IRF and/or SRF, and Sub-RPE Fluid in the Study Eye at Week 52 and Week 56 Overall and by Core Study Treatment Arm Week 56 IRF assessment - Present	13 Participants	12 Participants	25 Participants
Number (%) of Subjects With Presence of IRF and/or SRF, and Sub-RPE Fluid in the Study Eye at Week 52 and Week 56 Overall and by Core Study Treatment Arm Week 56 IRF assessment - Absent	93 Participants	82 Participants	175 Participants
Number (%) of Subjects With Presence of IRF and/or SRF, and Sub-RPE Fluid in the Study Eye at Week 52 and Week 56 Overall and by Core Study Treatment Arm Week 52 IRF assessment - Present (n=103,90,193)	10 Participants	14 Participants	24 Participants
Number (%) of Subjects With Presence of IRF and/or SRF, and Sub-RPE Fluid in the Study Eye at Week 52 and Week 56 Overall and by Core Study Treatment Arm Week 52 IRF assessment - Absent (n=103,90,193)	93 Participants	76 Participants	169 Participants
Number (%) of Subjects With Presence of IRF and/or SRF, and Sub-RPE Fluid in the Study Eye at Week 52 and Week 56 Overall and by Core Study Treatment Arm Week 52 SRF assessment - Present (n=103,90,193)	14 Participants	9 Participants	23 Participants
Number (%) of Subjects With Presence of IRF and/or SRF, and Sub-RPE Fluid in the Study Eye at Week 52 and Week 56 Overall and by Core Study Treatment Arm Week 52 SRF assessment - Absent (n=103,90,193)	89 Participants	81 Participants	170 Participants
Number (%) of Subjects With Presence of IRF and/or SRF, and Sub-RPE Fluid in the Study Eye at Week 52 and Week 56 Overall and by Core Study Treatment Arm Week 56 SRF assessment - Present	11 Participants	7 Participants	18 Participants
Number (%) of Subjects With Presence of IRF and/or SRF, and Sub-RPE Fluid in the Study Eye at Week 52 and Week 56 Overall and by Core Study Treatment Arm Week 56 SRF assessment - Absent	95 Participants	87 Participants	182 Participants
Number (%) of Subjects With Presence of IRF and/or SRF, and Sub-RPE Fluid in the Study Eye at Week 52 and Week 56 Overall and by Core Study Treatment Arm Week 56 Sub-RPE fluid - Present	51 Participants	49 Participants	100 Participants
Number (%) of Subjects With Presence of IRF and/or SRF, and Sub-RPE Fluid in the Study Eye at Week 52 and Week 56 Overall and by Core Study Treatment Arm Week 56 Sub-RPE fluid - Absent	55 Participants	45 Participants	100 Participants
Number (%) of Subjects With Presence of IRF and/or SRF, and Sub-RPE Fluid in the Study Eye at Week 52 and Week 56 Overall and by Core Study Treatment Arm Week 56 IRF and/or SRF - Present	23 Participants	17 Participants	40 Participants
Number (%) of Subjects With Presence of IRF and/or SRF, and Sub-RPE Fluid in the Study Eye at Week 52 and Week 56 Overall and by Core Study Treatment Arm Week 56 IRF and/or SRF - Absent	105 Participants	92 Participants	197 Participants
Number (%) of Subjects With Presence of IRF and/or SRF, and Sub-RPE Fluid in the Study Eye at Week 52 and Week 56 Overall and by Core Study Treatment Arm Week 56 IRF and SRF - Present	1 Participants	2 Participants	3 Participants
Number (%) of Subjects With Presence of IRF and/or SRF, and Sub-RPE Fluid in the Study Eye at Week 52 and Week 56 Overall and by Core Study Treatment Arm Week 56 IRF and SRF - Absent	83 Participants	77 Participants	160 Participants

SECONDARY outcome

Timeframe: up to Week 56

Population: Full Analyses Set - for Subjects with at least two injections in the extension study

Duration of the last interval with no disease activity up to Week 52 by core study treatment arm.

Outcome measures

Outcome measures
Measure	Brolucizumab 6 mg n=130 Participants Participants received brolucizumab 6 mg/0.05 mL solution by intravitreal injection in a Treat-to-Control regimen with injection intervals from 4 up to 20 weeks. Intervals could have changed in steps of 4 weeks at a time per investigators' decisions determined by the disease activity.	Aflibercept 2 mg (Core Study) n=107 Participants Patients who received aflibercept 2 mg in the core study and switched to brolucizumab 6 mg in the extension study	Brolucizumab 6 mg (Extension Study Total) Participants received brolucizumab 6 mg/0.05 mL solution by intravitreal injection in a Treat-to-Control regimen with injection intervals from 4 up to 20 weeks. Intervals could have changed in steps of 4 weeks at a time per investigators' decisions determined by the disease activity.
Last Interval With no Disease Activity (Number of Weeks): Number (%) of Subjects at 20/16/12/8/4-weeks Intervals up to Week 56 for the Study Eye in the Extension Study by Core Study Randomized Treatment Arm 20 Weeks	49 Participants	19 Participants	—
Last Interval With no Disease Activity (Number of Weeks): Number (%) of Subjects at 20/16/12/8/4-weeks Intervals up to Week 56 for the Study Eye in the Extension Study by Core Study Randomized Treatment Arm 16 Weeks	29 Participants	30 Participants	—
Last Interval With no Disease Activity (Number of Weeks): Number (%) of Subjects at 20/16/12/8/4-weeks Intervals up to Week 56 for the Study Eye in the Extension Study by Core Study Randomized Treatment Arm 12 Weeks	21 Participants	26 Participants	—
Last Interval With no Disease Activity (Number of Weeks): Number (%) of Subjects at 20/16/12/8/4-weeks Intervals up to Week 56 for the Study Eye in the Extension Study by Core Study Randomized Treatment Arm 8 Weeks	23 Participants	26 Participants	—
Last Interval With no Disease Activity (Number of Weeks): Number (%) of Subjects at 20/16/12/8/4-weeks Intervals up to Week 56 for the Study Eye in the Extension Study by Core Study Randomized Treatment Arm 4 Weeks	8 Participants	6 Participants	—

SECONDARY outcome

Timeframe: up to Week 56

Population: Full Analyses Set - for Subjects with at least two injections in the extension study

Duration of the maximal intervals with no disease activity up to Week 52 by core study treatment arm.

Outcome measures

Outcome measures
Measure	Brolucizumab 6 mg n=130 Participants Participants received brolucizumab 6 mg/0.05 mL solution by intravitreal injection in a Treat-to-Control regimen with injection intervals from 4 up to 20 weeks. Intervals could have changed in steps of 4 weeks at a time per investigators' decisions determined by the disease activity.	Aflibercept 2 mg (Core Study) n=107 Participants Patients who received aflibercept 2 mg in the core study and switched to brolucizumab 6 mg in the extension study	Brolucizumab 6 mg (Extension Study Total) Participants received brolucizumab 6 mg/0.05 mL solution by intravitreal injection in a Treat-to-Control regimen with injection intervals from 4 up to 20 weeks. Intervals could have changed in steps of 4 weeks at a time per investigators' decisions determined by the disease activity.
Maximal Interval With no Disease Activity (Number of Weeks): Number (%) of Subjects at 20/16/12/8/4-weeks Intervals up to Week 56 for the Study Eye in the Extension Study 20 Weeks	54 Participants	20 Participants	—
Maximal Interval With no Disease Activity (Number of Weeks): Number (%) of Subjects at 20/16/12/8/4-weeks Intervals up to Week 56 for the Study Eye in the Extension Study 16 Weeks	28 Participants	31 Participants	—
Maximal Interval With no Disease Activity (Number of Weeks): Number (%) of Subjects at 20/16/12/8/4-weeks Intervals up to Week 56 for the Study Eye in the Extension Study 12 Weeks	23 Participants	34 Participants	—
Maximal Interval With no Disease Activity (Number of Weeks): Number (%) of Subjects at 20/16/12/8/4-weeks Intervals up to Week 56 for the Study Eye in the Extension Study 8 Weeks	22 Participants	18 Participants	—
Maximal Interval With no Disease Activity (Number of Weeks): Number (%) of Subjects at 20/16/12/8/4-weeks Intervals up to Week 56 for the Study Eye in the Extension Study 4 Weeks	3 Participants	4 Participants	—

SECONDARY outcome

Timeframe: Extension study baseline, up to Week 56

Population: Full Analyses Set - for Subjects with at least two injections in the extension study

Change in last interval with no disease activity

Outcome measures

Outcome measures
Measure	Brolucizumab 6 mg n=130 Participants Participants received brolucizumab 6 mg/0.05 mL solution by intravitreal injection in a Treat-to-Control regimen with injection intervals from 4 up to 20 weeks. Intervals could have changed in steps of 4 weeks at a time per investigators' decisions determined by the disease activity.	Aflibercept 2 mg (Core Study) n=107 Participants Patients who received aflibercept 2 mg in the core study and switched to brolucizumab 6 mg in the extension study	Brolucizumab 6 mg (Extension Study Total) Participants received brolucizumab 6 mg/0.05 mL solution by intravitreal injection in a Treat-to-Control regimen with injection intervals from 4 up to 20 weeks. Intervals could have changed in steps of 4 weeks at a time per investigators' decisions determined by the disease activity.
Number (%) of Subjects With Change in Duration of Last Interval With no Disease Activity Between Baseline of the Extension Study and Week 56 by Core Study Treatment Arm 0 Weeks	41 Participants	31 Participants	—
Number (%) of Subjects With Change in Duration of Last Interval With no Disease Activity Between Baseline of the Extension Study and Week 56 by Core Study Treatment Arm 16 Weeks	0 Participants	2 Participants	—
Number (%) of Subjects With Change in Duration of Last Interval With no Disease Activity Between Baseline of the Extension Study and Week 56 by Core Study Treatment Arm 12 Weeks	8 Participants	5 Participants	—
Number (%) of Subjects With Change in Duration of Last Interval With no Disease Activity Between Baseline of the Extension Study and Week 56 by Core Study Treatment Arm 8 Weeks	21 Participants	32 Participants	—
Number (%) of Subjects With Change in Duration of Last Interval With no Disease Activity Between Baseline of the Extension Study and Week 56 by Core Study Treatment Arm 4 Weeks	49 Participants	28 Participants	—
Number (%) of Subjects With Change in Duration of Last Interval With no Disease Activity Between Baseline of the Extension Study and Week 56 by Core Study Treatment Arm - 4 Weeks	8 Participants	7 Participants	—
Number (%) of Subjects With Change in Duration of Last Interval With no Disease Activity Between Baseline of the Extension Study and Week 56 by Core Study Treatment Arm -8 Weeks	2 Participants	2 Participants	—
Number (%) of Subjects With Change in Duration of Last Interval With no Disease Activity Between Baseline of the Extension Study and Week 56 by Core Study Treatment Arm -12 Weeks	1 Participants	0 Participants	—

SECONDARY outcome

Timeframe: Adverse events are reported from the first dose of study-drug until the end of treatment at week 52, plus 4 weeks safety follow-up, for a maximum timeframe of approximately 56 weeks.

Population: Full Analyses 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 clinical investigation participant after providing written informed consent for participation in the study.

Outcome measures

Outcome measures
Measure	Brolucizumab 6 mg n=248 Participants Participants received brolucizumab 6 mg/0.05 mL solution by intravitreal injection in a Treat-to-Control regimen with injection intervals from 4 up to 20 weeks. Intervals could have changed in steps of 4 weeks at a time per investigators' decisions determined by the disease activity.	Aflibercept 2 mg (Core Study) Patients who received aflibercept 2 mg in the core study and switched to brolucizumab 6 mg in the extension study	Brolucizumab 6 mg (Extension Study Total) Participants received brolucizumab 6 mg/0.05 mL solution by intravitreal injection in a Treat-to-Control regimen with injection intervals from 4 up to 20 weeks. Intervals could have changed in steps of 4 weeks at a time per investigators' decisions determined by the disease activity.
Treatment-emergent Ocular Adverse Events (Greater Than or Equal to 1.0%) by Preferred Term for the Study Eye Number of subjects with at least one AE	63 Participants	—	—
Treatment-emergent Ocular Adverse Events (Greater Than or Equal to 1.0%) by Preferred Term for the Study Eye Cataract	9 Participants	—	—
Treatment-emergent Ocular Adverse Events (Greater Than or Equal to 1.0%) by Preferred Term for the Study Eye Eye pain	6 Participants	—	—
Treatment-emergent Ocular Adverse Events (Greater Than or Equal to 1.0%) by Preferred Term for the Study Eye Visual acuity reduced	6 Participants	—	—
Treatment-emergent Ocular Adverse Events (Greater Than or Equal to 1.0%) by Preferred Term for the Study Eye Intraocular pressure increased	5 Participants	—	—
Treatment-emergent Ocular Adverse Events (Greater Than or Equal to 1.0%) by Preferred Term for the Study Eye Retinal haemorrhage	4 Participants	—	—
Treatment-emergent Ocular Adverse Events (Greater Than or Equal to 1.0%) by Preferred Term for the Study Eye Ocular discomfort	3 Participants	—	—
Treatment-emergent Ocular Adverse Events (Greater Than or Equal to 1.0%) by Preferred Term for the Study Eye Vitreous floaters	3 Participants	—	—

SECONDARY outcome

Timeframe: Adverse events are reported from the first dose of study-drug until the end of treatment at week 52, plus 4 weeks safety follow-up, for a maximum timeframe of approximately 56 weeks.

Population: Full Analyses Set

Outcome measures

Outcome measures
Measure	Brolucizumab 6 mg n=248 Participants Participants received brolucizumab 6 mg/0.05 mL solution by intravitreal injection in a Treat-to-Control regimen with injection intervals from 4 up to 20 weeks. Intervals could have changed in steps of 4 weeks at a time per investigators' decisions determined by the disease activity.	Aflibercept 2 mg (Core Study) Patients who received aflibercept 2 mg in the core study and switched to brolucizumab 6 mg in the extension study	Brolucizumab 6 mg (Extension Study Total) Participants received brolucizumab 6 mg/0.05 mL solution by intravitreal injection in a Treat-to-Control regimen with injection intervals from 4 up to 20 weeks. Intervals could have changed in steps of 4 weeks at a time per investigators' decisions determined by the disease activity.
Treatment-emergent Non-ocular Adverse Events (Greater Than or Equal to 2%) by Preferred Term Number of subjects with at least one AE	82 Participants	—	—
Treatment-emergent Non-ocular Adverse Events (Greater Than or Equal to 2%) by Preferred Term COVID-19	10 Participants	—	—
Treatment-emergent Non-ocular Adverse Events (Greater Than or Equal to 2%) by Preferred Term Nasopharyngitis	8 Participants	—	—
Treatment-emergent Non-ocular Adverse Events (Greater Than or Equal to 2%) by Preferred Term Fall	7 Participants	—	—
Treatment-emergent Non-ocular Adverse Events (Greater Than or Equal to 2%) by Preferred Term Basal cell carcinoma	5 Participants	—	—

POST_HOC outcome

Timeframe: On-treatment death reporting - from first dose until 30 days after last dose for a maximum timeframe of approximately 56 weeks. Post-treatment death reporting - greater than 30 days after the last dose of study drug.

Population: Full Analyses Set

On treatment death monitoring occurred after the first dose of study drug in the extension study until 30 days after the last administration of study drug for a maximum timeframe of approximately 56 weeks. Post-treatment death monitoring occurred greater than 30 days after the last administration of study drug.

Outcome measures

Outcome measures
Measure	Brolucizumab 6 mg n=248 Participants Participants received brolucizumab 6 mg/0.05 mL solution by intravitreal injection in a Treat-to-Control regimen with injection intervals from 4 up to 20 weeks. Intervals could have changed in steps of 4 weeks at a time per investigators' decisions determined by the disease activity.	Aflibercept 2 mg (Core Study) Patients who received aflibercept 2 mg in the core study and switched to brolucizumab 6 mg in the extension study	Brolucizumab 6 mg (Extension Study Total) Participants received brolucizumab 6 mg/0.05 mL solution by intravitreal injection in a Treat-to-Control regimen with injection intervals from 4 up to 20 weeks. Intervals could have changed in steps of 4 weeks at a time per investigators' decisions determined by the disease activity.
All Collected Deaths On-treatment Deaths	0 Participants	—	—
All Collected Deaths Post-treatment Deaths	1 Participants	—	—
All Collected Deaths Total Deaths	1 Participants	—	—

Adverse Events

Brolucizumab 6mg

Serious events: 26 serious events

Other events: 58 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Brolucizumab 6mg n=248 participants at risk Brolucizumab 6mg
Cardiac disorders Atrial fibrillation	0.81% 2/248 • Adverse events are reported from the first dose of study-drug until the end of treatment at week 52, plus 4 weeks safety follow-up, for a maximum timeframe of approximately 56 weeks. Adverse events and the death are reported in the Full Analysis Set that includes all participants who received at least one dose of study treatment in the extension study.
Eye disorders Retinal detachment - Fellow eye	0.40% 1/248 • Adverse events are reported from the first dose of study-drug until the end of treatment at week 52, plus 4 weeks safety follow-up, for a maximum timeframe of approximately 56 weeks. Adverse events and the death are reported in the Full Analysis Set that includes all participants who received at least one dose of study treatment in the extension study.
Eye disorders Retinal occlusive vasculitis - Study eye	0.40% 1/248 • Adverse events are reported from the first dose of study-drug until the end of treatment at week 52, plus 4 weeks safety follow-up, for a maximum timeframe of approximately 56 weeks. Adverse events and the death are reported in the Full Analysis Set that includes all participants who received at least one dose of study treatment in the extension study.
Eye disorders Uveitis - Study eye	0.40% 1/248 • Adverse events are reported from the first dose of study-drug until the end of treatment at week 52, plus 4 weeks safety follow-up, for a maximum timeframe of approximately 56 weeks. Adverse events and the death are reported in the Full Analysis Set that includes all participants who received at least one dose of study treatment in the extension study.
Eye disorders Vitreal cells - Fellow eye	0.40% 1/248 • Adverse events are reported from the first dose of study-drug until the end of treatment at week 52, plus 4 weeks safety follow-up, for a maximum timeframe of approximately 56 weeks. Adverse events and the death are reported in the Full Analysis Set that includes all participants who received at least one dose of study treatment in the extension study.
Eye disorders Vitreal cells - Study eye	0.40% 1/248 • Adverse events are reported from the first dose of study-drug until the end of treatment at week 52, plus 4 weeks safety follow-up, for a maximum timeframe of approximately 56 weeks. Adverse events and the death are reported in the Full Analysis Set that includes all participants who received at least one dose of study treatment in the extension study.
Gastrointestinal disorders Inguinal hernia	0.40% 1/248 • Adverse events are reported from the first dose of study-drug until the end of treatment at week 52, plus 4 weeks safety follow-up, for a maximum timeframe of approximately 56 weeks. Adverse events and the death are reported in the Full Analysis Set that includes all participants who received at least one dose of study treatment in the extension study.
Infections and infestations Pneumonia	0.40% 1/248 • Adverse events are reported from the first dose of study-drug until the end of treatment at week 52, plus 4 weeks safety follow-up, for a maximum timeframe of approximately 56 weeks. Adverse events and the death are reported in the Full Analysis Set that includes all participants who received at least one dose of study treatment in the extension study.
Infections and infestations Pyelonephritis acute	0.40% 1/248 • Adverse events are reported from the first dose of study-drug until the end of treatment at week 52, plus 4 weeks safety follow-up, for a maximum timeframe of approximately 56 weeks. Adverse events and the death are reported in the Full Analysis Set that includes all participants who received at least one dose of study treatment in the extension study.
Infections and infestations Urinary tract infection	0.40% 1/248 • Adverse events are reported from the first dose of study-drug until the end of treatment at week 52, plus 4 weeks safety follow-up, for a maximum timeframe of approximately 56 weeks. Adverse events and the death are reported in the Full Analysis Set that includes all participants who received at least one dose of study treatment in the extension study.
Infections and infestations Whipple's disease	0.40% 1/248 • Adverse events are reported from the first dose of study-drug until the end of treatment at week 52, plus 4 weeks safety follow-up, for a maximum timeframe of approximately 56 weeks. Adverse events and the death are reported in the Full Analysis Set that includes all participants who received at least one dose of study treatment in the extension study.
Injury, poisoning and procedural complications Contusion	0.40% 1/248 • Adverse events are reported from the first dose of study-drug until the end of treatment at week 52, plus 4 weeks safety follow-up, for a maximum timeframe of approximately 56 weeks. Adverse events and the death are reported in the Full Analysis Set that includes all participants who received at least one dose of study treatment in the extension study.
Injury, poisoning and procedural complications Fall	0.81% 2/248 • Adverse events are reported from the first dose of study-drug until the end of treatment at week 52, plus 4 weeks safety follow-up, for a maximum timeframe of approximately 56 weeks. Adverse events and the death are reported in the Full Analysis Set that includes all participants who received at least one dose of study treatment in the extension study.
Injury, poisoning and procedural complications Lower limb fracture	0.40% 1/248 • Adverse events are reported from the first dose of study-drug until the end of treatment at week 52, plus 4 weeks safety follow-up, for a maximum timeframe of approximately 56 weeks. Adverse events and the death are reported in the Full Analysis Set that includes all participants who received at least one dose of study treatment in the extension study.
Injury, poisoning and procedural complications Meniscus injury	0.40% 1/248 • Adverse events are reported from the first dose of study-drug until the end of treatment at week 52, plus 4 weeks safety follow-up, for a maximum timeframe of approximately 56 weeks. Adverse events and the death are reported in the Full Analysis Set that includes all participants who received at least one dose of study treatment in the extension study.
Injury, poisoning and procedural complications Procedural vomiting	0.40% 1/248 • Adverse events are reported from the first dose of study-drug until the end of treatment at week 52, plus 4 weeks safety follow-up, for a maximum timeframe of approximately 56 weeks. Adverse events and the death are reported in the Full Analysis Set that includes all participants who received at least one dose of study treatment in the extension study.
Injury, poisoning and procedural complications Rib fracture	0.40% 1/248 • Adverse events are reported from the first dose of study-drug until the end of treatment at week 52, plus 4 weeks safety follow-up, for a maximum timeframe of approximately 56 weeks. Adverse events and the death are reported in the Full Analysis Set that includes all participants who received at least one dose of study treatment in the extension study.
Injury, poisoning and procedural complications Spinal compression fracture	0.40% 1/248 • Adverse events are reported from the first dose of study-drug until the end of treatment at week 52, plus 4 weeks safety follow-up, for a maximum timeframe of approximately 56 weeks. Adverse events and the death are reported in the Full Analysis Set that includes all participants who received at least one dose of study treatment in the extension study.
Musculoskeletal and connective tissue disorders Chondropathy	0.40% 1/248 • Adverse events are reported from the first dose of study-drug until the end of treatment at week 52, plus 4 weeks safety follow-up, for a maximum timeframe of approximately 56 weeks. Adverse events and the death are reported in the Full Analysis Set that includes all participants who received at least one dose of study treatment in the extension study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	2.0% 5/248 • Adverse events are reported from the first dose of study-drug until the end of treatment at week 52, plus 4 weeks safety follow-up, for a maximum timeframe of approximately 56 weeks. Adverse events and the death are reported in the Full Analysis Set that includes all participants who received at least one dose of study treatment in the extension study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.40% 1/248 • Adverse events are reported from the first dose of study-drug until the end of treatment at week 52, plus 4 weeks safety follow-up, for a maximum timeframe of approximately 56 weeks. Adverse events and the death are reported in the Full Analysis Set that includes all participants who received at least one dose of study treatment in the extension study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm	0.40% 1/248 • Adverse events are reported from the first dose of study-drug until the end of treatment at week 52, plus 4 weeks safety follow-up, for a maximum timeframe of approximately 56 weeks. Adverse events and the death are reported in the Full Analysis Set that includes all participants who received at least one dose of study treatment in the extension study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.40% 1/248 • Adverse events are reported from the first dose of study-drug until the end of treatment at week 52, plus 4 weeks safety follow-up, for a maximum timeframe of approximately 56 weeks. Adverse events and the death are reported in the Full Analysis Set that includes all participants who received at least one dose of study treatment in the extension study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of skin	0.40% 1/248 • Adverse events are reported from the first dose of study-drug until the end of treatment at week 52, plus 4 weeks safety follow-up, for a maximum timeframe of approximately 56 weeks. Adverse events and the death are reported in the Full Analysis Set that includes all participants who received at least one dose of study treatment in the extension study.
Nervous system disorders Ischaemic stroke	0.40% 1/248 • Adverse events are reported from the first dose of study-drug until the end of treatment at week 52, plus 4 weeks safety follow-up, for a maximum timeframe of approximately 56 weeks. Adverse events and the death are reported in the Full Analysis Set that includes all participants who received at least one dose of study treatment in the extension study.
Nervous system disorders Seizure	0.40% 1/248 • Adverse events are reported from the first dose of study-drug until the end of treatment at week 52, plus 4 weeks safety follow-up, for a maximum timeframe of approximately 56 weeks. Adverse events and the death are reported in the Full Analysis Set that includes all participants who received at least one dose of study treatment in the extension study.
Nervous system disorders Transient ischaemic attack	0.40% 1/248 • Adverse events are reported from the first dose of study-drug until the end of treatment at week 52, plus 4 weeks safety follow-up, for a maximum timeframe of approximately 56 weeks. Adverse events and the death are reported in the Full Analysis Set that includes all participants who received at least one dose of study treatment in the extension study.
Psychiatric disorders Delirium	0.40% 1/248 • Adverse events are reported from the first dose of study-drug until the end of treatment at week 52, plus 4 weeks safety follow-up, for a maximum timeframe of approximately 56 weeks. Adverse events and the death are reported in the Full Analysis Set that includes all participants who received at least one dose of study treatment in the extension study.
Renal and urinary disorders Calculus urinary	0.40% 1/248 • Adverse events are reported from the first dose of study-drug until the end of treatment at week 52, plus 4 weeks safety follow-up, for a maximum timeframe of approximately 56 weeks. Adverse events and the death are reported in the Full Analysis Set that includes all participants who received at least one dose of study treatment in the extension study.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.40% 1/248 • Adverse events are reported from the first dose of study-drug until the end of treatment at week 52, plus 4 weeks safety follow-up, for a maximum timeframe of approximately 56 weeks. Adverse events and the death are reported in the Full Analysis Set that includes all participants who received at least one dose of study treatment in the extension study.
Respiratory, thoracic and mediastinal disorders Respiratory arrest	0.40% 1/248 • Adverse events are reported from the first dose of study-drug until the end of treatment at week 52, plus 4 weeks safety follow-up, for a maximum timeframe of approximately 56 weeks. Adverse events and the death are reported in the Full Analysis Set that includes all participants who received at least one dose of study treatment in the extension study.

Other adverse events

Other adverse events
Measure	Brolucizumab 6mg n=248 participants at risk Brolucizumab 6mg
Eye disorders Cataract - Fellow eye	2.8% 7/248 • Adverse events are reported from the first dose of study-drug until the end of treatment at week 52, plus 4 weeks safety follow-up, for a maximum timeframe of approximately 56 weeks. Adverse events and the death are reported in the Full Analysis Set that includes all participants who received at least one dose of study treatment in the extension study.
Eye disorders Cataract - Study eye	3.6% 9/248 • Adverse events are reported from the first dose of study-drug until the end of treatment at week 52, plus 4 weeks safety follow-up, for a maximum timeframe of approximately 56 weeks. Adverse events and the death are reported in the Full Analysis Set that includes all participants who received at least one dose of study treatment in the extension study.
Eye disorders Eye pain - Study eye	2.4% 6/248 • Adverse events are reported from the first dose of study-drug until the end of treatment at week 52, plus 4 weeks safety follow-up, for a maximum timeframe of approximately 56 weeks. Adverse events and the death are reported in the Full Analysis Set that includes all participants who received at least one dose of study treatment in the extension study.
Eye disorders Neovascular age-related macular degeneration - Fellow eye	4.0% 10/248 • Adverse events are reported from the first dose of study-drug until the end of treatment at week 52, plus 4 weeks safety follow-up, for a maximum timeframe of approximately 56 weeks. Adverse events and the death are reported in the Full Analysis Set that includes all participants who received at least one dose of study treatment in the extension study.
Eye disorders Visual acuity reduced - Study eye	2.4% 6/248 • Adverse events are reported from the first dose of study-drug until the end of treatment at week 52, plus 4 weeks safety follow-up, for a maximum timeframe of approximately 56 weeks. Adverse events and the death are reported in the Full Analysis Set that includes all participants who received at least one dose of study treatment in the extension study.
Infections and infestations COVID-19	4.0% 10/248 • Adverse events are reported from the first dose of study-drug until the end of treatment at week 52, plus 4 weeks safety follow-up, for a maximum timeframe of approximately 56 weeks. Adverse events and the death are reported in the Full Analysis Set that includes all participants who received at least one dose of study treatment in the extension study.
Infections and infestations Nasopharyngitis	3.2% 8/248 • Adverse events are reported from the first dose of study-drug until the end of treatment at week 52, plus 4 weeks safety follow-up, for a maximum timeframe of approximately 56 weeks. Adverse events and the death are reported in the Full Analysis Set that includes all participants who received at least one dose of study treatment in the extension study.
Injury, poisoning and procedural complications Fall	2.8% 7/248 • Adverse events are reported from the first dose of study-drug until the end of treatment at week 52, plus 4 weeks safety follow-up, for a maximum timeframe of approximately 56 weeks. Adverse events and the death are reported in the Full Analysis Set that includes all participants who received at least one dose of study treatment in the extension study.
Investigations Intraocular pressure increased - Study eye	2.0% 5/248 • Adverse events are reported from the first dose of study-drug until the end of treatment at week 52, plus 4 weeks safety follow-up, for a maximum timeframe of approximately 56 weeks. Adverse events and the death are reported in the Full Analysis Set that includes all participants who received at least one dose of study treatment in the extension study.

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