Neovascular Age-related Macular Degeneration
Conditions
Keywords
neovascular age-related macular degeneration, wet age-related macular degeneration, wet AMD, choroidal neovascularization, individualized treatment, anti-VEGF, Macular degeneration, age-related macular degeneration (ARMD), vision loss, macula damage, retina damage, dry macular degeneration, wet macular degeneration, Subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration
Brief summary
The purpose of this extension study was to evaluate the efficacy and safety of brolucizumab used in a Treat-to-Control-regimen for treatment of patients with neovascular age-related macular degeneration who have completed the CRTH258A2303 (TALON) study. The main objective was to assess brolucizumab's potential for long durability up to 20 weeks. All eligible participants were treated with brolucizumab regardless of their treatment in the TALON study. The study period was 56 weeks including post-treatment follow-up.
Detailed description
This was a 56-week, open-label, one-arm extension study in subjects who had completed the CRTH258A2303 (TALON) (NCT04005352) study, referred to as the core study in this document. Subjects who provided written informed consent and met all the inclusion and none of the exclusion criteria were enrolled into this extension study to receive brolucizumab 6 mg in a treat-to-control (TtC) regimen, irrespective of the treatment received in the core study. The maximum study duration for a subject was 56 weeks, including post-treatment follow-up. There were two periods in this study: * Treat-to-Control treatment period: from Baseline (Day 1) to Week 52 * Post-treatment follow-up period: from Week 52 to Week 56. All participants were treated with brolucizumab regardless of their treatment in the TALON study (brolucizumab or aflibercept). Treatment intervals were then extended by 4 weeks at a time based on the investigator's judgment of visual and/or anatomic outcomes. The treatment intervals were to have been 4 weeks at a time if disease activity recurs.
Interventions
DRUGbrolucizumab
brolucizumab 6 mg/0.05 mL solution for intravitreal injection
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Signed informed consent 2. Successfully completed TALON core study at week 64 (End of Study)
Exclusion criteria
1. Medical condition or personal circumstance which precludes study participation or compliance with study procedures, as assessed by the Investigator 2. Discontinued study treatment in the core study 3. Anti-VEGF treatment is futile in the study eye, in the Investigator's opinion. 4. Pregnant or nursing (lactating) women 5. Women of child-bearing potential not using highly effective methods of contraception
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Duration of the Last Interval With no Disease Activity up to Week 56 - Study Eye | Up to Week 56 | 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 |
| Average Change in BCVA From Baseline to Week 52 and Week 56 for the Study Eye | Extension study baseline, average of Week 52 and Week 56 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | up to Week 56 | Duration of the last interval with no disease activity up to Week 52 by core study treatment arm. |
| 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 | up to Week 56 | Duration of the maximal intervals with no disease activity up to Week 52 by core study treatment arm. |
| Average Change in Central Subfield Thickness (CSFT) From Baseline to Week 52 and Week 56 - Study Eye | Extension study baseline, average of Week 52 and Week 56 | 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. |
| Treatment-emergent Ocular Adverse Events (Greater Than or Equal to 1.0%) by Preferred Term for the Study Eye | 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. | 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. |
| Treatment-emergent Non-ocular Adverse Events (Greater Than or Equal to 2%) by Preferred Term | 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. | 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. |
| 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 | Extension study baseline, up to Week 56 | Change in last interval with no 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 | Weeks 52 and 56 | 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 |
Countries
Australia, Belgium, Czechia, France, Germany, Israel, Italy, Malaysia, Netherlands, Portugal, South Korea, Spain, Sweden, Switzerland, Taiwan, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 248 |
| Total | 248 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 5 |
| Overall Study | Death | 1 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Withdrawal by Subject | 10 |
Baseline characteristics
| Characteristic | Brolucizumab 6 mg (Extension Study Total) |
|---|---|
| Age, Continuous | 75.9 Years STANDARD_DEVIATION 7.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 23 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 219 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 61 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 187 Participants |
| Sex: Female, Male Female | 129 Participants |
| Sex: Female, Male Male | 119 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 248 |
| other Total, other adverse events | 58 / 248 |
| serious Total, serious adverse events | 26 / 248 |
Outcome results
Primary
Average Change in BCVA From Baseline to Week 52 and Week 56 for the Study Eye
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.
Time frame: 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).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Brolucizumab 6 mg | Average Change in BCVA From Baseline to Week 52 and Week 56 for the Study Eye | -1.8 Letters read | Standard Deviation 8.29 |
| Aflibercept 2 mg (Core Study) | Average Change in BCVA From Baseline to Week 52 and Week 56 for the Study Eye | -2.9 Letters read | Standard Deviation 7.33 |
| Brolucizumab 6 mg (Extension Study Total) | Average Change in BCVA From Baseline to Week 52 and Week 56 for the Study Eye | -2.3 Letters read | Standard Deviation 7.88 |
Primary
Duration of the Last Interval With no Disease Activity up to Week 56 - Study Eye
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
Time frame: Up to Week 56
Population: Full Analyses Set. Subjects with at least two injections in the extension study
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brolucizumab 6 mg | Duration of the Last Interval With no Disease Activity up to Week 56 - Study Eye | 20 weeks | 68 Participants |
| Brolucizumab 6 mg | Duration of the Last Interval With no Disease Activity up to Week 56 - Study Eye | 16 weeks | 59 Participants |
| Brolucizumab 6 mg | Duration of the Last Interval With no Disease Activity up to Week 56 - Study Eye | 12 weeks | 47 Participants |
| Brolucizumab 6 mg | Duration of the Last Interval With no Disease Activity up to Week 56 - Study Eye | 8 weeks | 49 Participants |
| Brolucizumab 6 mg | Duration of the Last Interval With no Disease Activity up to Week 56 - Study Eye | 4 weeks | 14 Participants |
Secondary
Average Change in Central Subfield Thickness (CSFT) From Baseline to Week 52 and Week 56 - Study Eye
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.
Time frame: 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).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Brolucizumab 6 mg | Average Change in Central Subfield Thickness (CSFT) From Baseline to Week 52 and Week 56 - Study Eye | 5.9 μm | Standard Deviation 24.43 |
| Aflibercept 2 mg (Core Study) | Average Change in Central Subfield Thickness (CSFT) From Baseline to Week 52 and Week 56 - Study Eye | -14.1 μm | Standard Deviation 60.67 |
| Brolucizumab 6 mg (Extension Study Total) | Average Change in Central Subfield Thickness (CSFT) From Baseline to Week 52 and Week 56 - Study Eye | -3.3 μm | Standard Deviation 45.83 |
Secondary
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
Duration of the last interval with no disease activity up to Week 52 by core study treatment arm.
Time frame: up to Week 56
Population: Full Analyses Set - for Subjects with at least two injections in the extension study
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brolucizumab 6 mg | 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 |
| Brolucizumab 6 mg | 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 |
| Brolucizumab 6 mg | 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 |
| Brolucizumab 6 mg | 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 |
| Brolucizumab 6 mg | 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 |
| Aflibercept 2 mg (Core Study) | 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 | 6 Participants |
| Aflibercept 2 mg (Core Study) | 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 | 19 Participants |
| Aflibercept 2 mg (Core Study) | 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 | 30 Participants |
| Aflibercept 2 mg (Core Study) | 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 | 26 Participants |
| Aflibercept 2 mg (Core Study) | 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 | 26 Participants |
Secondary
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
Duration of the maximal intervals with no disease activity up to Week 52 by core study treatment arm.
Time frame: up to Week 56
Population: Full Analyses Set - for Subjects with at least two injections in the extension study
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brolucizumab 6 mg | 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 |
| Brolucizumab 6 mg | 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 |
| Brolucizumab 6 mg | 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 |
| Brolucizumab 6 mg | 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 |
| Brolucizumab 6 mg | 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 |
| Aflibercept 2 mg (Core Study) | 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 | 4 Participants |
| Aflibercept 2 mg (Core Study) | 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 | 20 Participants |
| Aflibercept 2 mg (Core Study) | 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 | 31 Participants |
| Aflibercept 2 mg (Core Study) | 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 | 34 Participants |
| Aflibercept 2 mg (Core Study) | 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 | 18 Participants |
Secondary
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
Change in last interval with no disease activity
Time frame: Extension study baseline, up to Week 56
Population: Full Analyses Set - for Subjects with at least two injections in the extension study
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brolucizumab 6 mg | 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 |
| Brolucizumab 6 mg | 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 |
| Brolucizumab 6 mg | 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 |
| Brolucizumab 6 mg | 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 |
| Brolucizumab 6 mg | 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 |
| Brolucizumab 6 mg | 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 |
| Brolucizumab 6 mg | 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 |
| Brolucizumab 6 mg | 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 |
| Aflibercept 2 mg (Core Study) | 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 | 0 Participants |
| Aflibercept 2 mg (Core Study) | 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 | 2 Participants |
| Aflibercept 2 mg (Core Study) | 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 | 5 Participants |
| Aflibercept 2 mg (Core Study) | 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 | 32 Participants |
| Aflibercept 2 mg (Core Study) | 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 | 31 Participants |
| Aflibercept 2 mg (Core Study) | 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 | 7 Participants |
| Aflibercept 2 mg (Core Study) | 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 |
| Aflibercept 2 mg (Core Study) | 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 | 28 Participants |
Secondary
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
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
Time frame: Weeks 52 and 56
Population: Full Analyses Set - for subjects with a valid measurement
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brolucizumab 6 mg | 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 |
| Brolucizumab 6 mg | 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 |
| Brolucizumab 6 mg | 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 |
| Brolucizumab 6 mg | 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 |
| Brolucizumab 6 mg | 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 |
| Brolucizumab 6 mg | 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 |
| Brolucizumab 6 mg | 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 |
| Brolucizumab 6 mg | 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 |
| Brolucizumab 6 mg | 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 |
| Brolucizumab 6 mg | 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 |
| Brolucizumab 6 mg | 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 |
| Brolucizumab 6 mg | 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 |
| Brolucizumab 6 mg | 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 |
| Brolucizumab 6 mg | 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 |
| Brolucizumab 6 mg | 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 |
| Brolucizumab 6 mg | 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 |
| Brolucizumab 6 mg | 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 |
| Brolucizumab 6 mg | 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 |
| Brolucizumab 6 mg | 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 |
| Brolucizumab 6 mg | 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 |
| Aflibercept 2 mg (Core Study) | 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 | 92 Participants |
| Aflibercept 2 mg (Core Study) | 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) | 14 Participants |
| Aflibercept 2 mg (Core Study) | 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) | 76 Participants |
| Aflibercept 2 mg (Core Study) | 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) | 9 Participants |
| Aflibercept 2 mg (Core Study) | 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) | 81 Participants |
| Aflibercept 2 mg (Core Study) | 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) | 44 Participants |
| Aflibercept 2 mg (Core Study) | 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) | 46 Participants |
| Aflibercept 2 mg (Core Study) | 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) | 22 Participants |
| Aflibercept 2 mg (Core Study) | 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) | 89 Participants |
| Aflibercept 2 mg (Core Study) | 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 |
| Aflibercept 2 mg (Core Study) | 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) | 68 Participants |
| Aflibercept 2 mg (Core Study) | 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 | 12 Participants |
| Aflibercept 2 mg (Core Study) | 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 | 7 Participants |
| Aflibercept 2 mg (Core Study) | 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 | 87 Participants |
| Aflibercept 2 mg (Core Study) | 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 | 49 Participants |
| Aflibercept 2 mg (Core Study) | 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 | 45 Participants |
| Aflibercept 2 mg (Core Study) | 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 | 17 Participants |
| Aflibercept 2 mg (Core Study) | 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 | 82 Participants |
| Aflibercept 2 mg (Core Study) | 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 | 2 Participants |
| Aflibercept 2 mg (Core Study) | 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 | 77 Participants |
| Brolucizumab 6 mg (Extension Study Total) | 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 | 197 Participants |
| Brolucizumab 6 mg (Extension Study Total) | 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 | 182 Participants |
| Brolucizumab 6 mg (Extension Study Total) | 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) | 97 Participants |
| Brolucizumab 6 mg (Extension Study Total) | 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) | 169 Participants |
| Brolucizumab 6 mg (Extension Study Total) | 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 | 100 Participants |
| Brolucizumab 6 mg (Extension Study Total) | 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) | 96 Participants |
| Brolucizumab 6 mg (Extension Study Total) | 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 | 160 Participants |
| Brolucizumab 6 mg (Extension Study Total) | 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 | 100 Participants |
| Brolucizumab 6 mg (Extension Study Total) | 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) | 170 Participants |
| Brolucizumab 6 mg (Extension Study Total) | 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 | 3 Participants |
| Brolucizumab 6 mg (Extension Study Total) | 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 | 40 Participants |
| Brolucizumab 6 mg (Extension Study Total) | 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) | 148 Participants |
| Brolucizumab 6 mg (Extension Study Total) | 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) | 23 Participants |
| Brolucizumab 6 mg (Extension Study Total) | 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 | 25 Participants |
| Brolucizumab 6 mg (Extension Study Total) | 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) | 2 Participants |
| Brolucizumab 6 mg (Extension Study Total) | 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 | 175 Participants |
| Brolucizumab 6 mg (Extension Study Total) | 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) | 191 Participants |
| Brolucizumab 6 mg (Extension Study Total) | 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) | 24 Participants |
| Brolucizumab 6 mg (Extension Study Total) | 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 | 18 Participants |
| Brolucizumab 6 mg (Extension Study Total) | 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) | 45 Participants |
Secondary
Treatment-emergent Non-ocular Adverse Events (Greater Than or Equal to 2%) by Preferred Term
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.
Time frame: 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
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brolucizumab 6 mg | 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 |
| Brolucizumab 6 mg | Treatment-emergent Non-ocular Adverse Events (Greater Than or Equal to 2%) by Preferred Term | COVID-19 | 10 Participants |
| Brolucizumab 6 mg | Treatment-emergent Non-ocular Adverse Events (Greater Than or Equal to 2%) by Preferred Term | Nasopharyngitis | 8 Participants |
| Brolucizumab 6 mg | Treatment-emergent Non-ocular Adverse Events (Greater Than or Equal to 2%) by Preferred Term | Fall | 7 Participants |
| Brolucizumab 6 mg | Treatment-emergent Non-ocular Adverse Events (Greater Than or Equal to 2%) by Preferred Term | Basal cell carcinoma | 5 Participants |
Secondary
Treatment-emergent Ocular Adverse Events (Greater Than or Equal to 1.0%) by Preferred Term for the Study Eye
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.
Time frame: 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
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brolucizumab 6 mg | 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 |
| Brolucizumab 6 mg | Treatment-emergent Ocular Adverse Events (Greater Than or Equal to 1.0%) by Preferred Term for the Study Eye | Cataract | 9 Participants |
| Brolucizumab 6 mg | Treatment-emergent Ocular Adverse Events (Greater Than or Equal to 1.0%) by Preferred Term for the Study Eye | Eye pain | 6 Participants |
| Brolucizumab 6 mg | Treatment-emergent Ocular Adverse Events (Greater Than or Equal to 1.0%) by Preferred Term for the Study Eye | Visual acuity reduced | 6 Participants |
| Brolucizumab 6 mg | Treatment-emergent Ocular Adverse Events (Greater Than or Equal to 1.0%) by Preferred Term for the Study Eye | Intraocular pressure increased | 5 Participants |
| Brolucizumab 6 mg | Treatment-emergent Ocular Adverse Events (Greater Than or Equal to 1.0%) by Preferred Term for the Study Eye | Retinal haemorrhage | 4 Participants |
| Brolucizumab 6 mg | Treatment-emergent Ocular Adverse Events (Greater Than or Equal to 1.0%) by Preferred Term for the Study Eye | Ocular discomfort | 3 Participants |
| Brolucizumab 6 mg | Treatment-emergent Ocular Adverse Events (Greater Than or Equal to 1.0%) by Preferred Term for the Study Eye | Vitreous floaters | 3 Participants |
Post Hoc
All Collected Deaths
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.
Time frame: 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
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brolucizumab 6 mg | All Collected Deaths | On-treatment Deaths | 0 Participants |
| Brolucizumab 6 mg | All Collected Deaths | Post-treatment Deaths | 1 Participants |
| Brolucizumab 6 mg | All Collected Deaths | Total Deaths | 1 Participants |