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HARRIER: Efficacy and Safety of RTH258 Versus Aflibercept - Study 2

Sponsor
Alcon Research (Industry)
Overall Status
Completed
CT.gov ID
NCT02434328
Collaborator
(none)
1,048
Enrollment
2
Arms
31.3
Actual Duration (Months)

Study Details

Study Description

Brief Summary

The purpose of this study is to compare brolucizumab (RTH258) ophthalmic solution for intravitreal (IVT) injection (6 mg) to aflibercept ophthalmic solution for IVT injection (2 mg) in subjects with untreated active choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) in the study eye.

Condition or Disease Intervention/Treatment Phase
  • Drug: Brolucizumab ophthalmic solution
  • Drug: Aflibercept ophthalmic solution
 Phase 3

Detailed Description

Subjects were randomized to brolucizumab 6 mg and aflibercept 2 mg in a 1:1 ratio. Subjects in both treatment arms received 3 monthly loading doses (Day 0, Week 4 and Week 8), followed by a maintenance regimen, until the end of the study (Week 96/Exit). All subjects attended pre-specified visits every 4 weeks.

Subjects in the brolucizumab 6 mg arm followed a q12w/q8w maintenance regimen. Within the q12w/q8w regimen, the initial treatment after the loading phase was q12w (1 injection every 12 weeks). If disease activity was identified by the masked investigator at any of the disease activity assessments, dosing was adjusted to q8w (1 injection every 8 weeks) ("q12w/q8w regimen"). Once subjects were adjusted to the q8w interval, they stayed on that interval until the end of the study.

Subjects in the aflibercept 2 mg arm followed a q8w maintenance regimen until the end of the study.

Results reported up to Week 48 are based on the database locked for the primary analysis at Week 48. Results reported after Week 48 are based on the database locked at the end of study (final analysis).

Study Design

Study Type:
Interventional
Actual Enrollment :
1048 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Two-year, Randomized, Double-masked, Multicenter, Two-arm Study Comparing the Efficacy and Safety of RTH258 6 mg Versus Aflibercept in Subjects With Neovascular Age-related Macular Degeneration
Actual Study Start Date :
Jul 28, 2015
Actual Primary Completion Date :
Apr 5, 2017
Actual Study Completion Date :
Mar 8, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: Brolucizumab 6 mg

Single intravitreal (IVT) injection of brolucizumab at Day 0, Week 4, and Week 8, followed by 1 injection every 8 weeks/1 injection every 12 weeks (q8w/q12w) maintenance regimen until study exit

Drug: Brolucizumab ophthalmic solution
Ophthalmic solution for IVT injection administered as a 6 mg/50 µL dose
Other Names:
  • RTH258

    		•
    Active Comparator: Aflibercept 2 mg

    Single IVT injection of aflibercept ophthalmic solution at Day 0, Week 4, and Week 8, followed by q8w maintenance regimen until study exit

    Drug: Aflibercept ophthalmic solution
    Ophthalmic solution for IVT injection administered as a 2 mg/50 µL dose
    Other Names:
  • EYLEA®

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Change From Baseline in Best Corrected Visual Acuity (BCVA) (Letters Read) at Week 48 - Study Eye [Baseline, Week 48]

      BCVA (with spectacles or other visual corrective devices) was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) testing at 4 meters and reported in letters read correctly. Baseline was defined as the last measurement prior to first treatment. An increase (gain) in letters read from the baseline assessment indicates improvement. One eye (study eye) contributed to the analysis.

    Secondary Outcome Measures

    1. Average Change From Baseline in BCVA (Letters Read) Over the Period Week 36 Through Week 48 - Study Eye [Baseline, Weeks 36, 40, 44, 48]

      BCVA (with spectacles or other visual corrective devices) was assessed using ETDRS testing at 4 meters and reported in letters read correctly. For each subject, this endpoint was defined as the average of the changes from baseline to Weeks 36, 40, 44, and 48. Baseline was defined as the last measurement prior to first treatment. An increase (gain) in letters read from the baseline assessment indicates improvement. One eye (study eye) contributed to the analysis.

    2. Proportion of Subjects With Positive q12 (Every 12 Weeks) Treatment Status at Week 48 [Weeks 16, 20, 28, 32, 40, 44, 48]

      Positive q12 treatment status was defined as IVT injections per planned dosing regimen (one injection every 12 weeks "q12w", after the initial three loading injections every 4 weeks "q4w"). A disease activity assessment (DAA) was performed at pre-specified visits (Weeks 16, 20, 28, 32, 40, 44) to identify q8w (one injection every 8 weeks) need. The estimate for the proportion of subjects with a positive q12w status at Week 48 were derived from Kaplan-Meier time to event analyses for the event of first q8w need, applying event allocations (in case of lack of efficacy and/or lack of safety=efficacy/safety approach) and censoring as described in the SAP. Censored subjects were considered to be not anymore under risk for a q8 need identification at later visits. Corresponding 95% Confidence Intervals (CIs) were derived from the LOGLOG transformation. This outcome measure was pre-specified for brolucizumab 6 mg arm only. Hypothesis testing not pre-specified.

    3. Proportion of Subjects With Positive q12 Treatment Status at Week 48 Within the Subjects With no q8 (Every 8 Weeks) Treatment Need During the Initial q12w Cycle (Week 16, Week 20) [Weeks 16, 20, 28, 32, 40, 44, 48]

      Positive q12 treatment status was defined as IVT injections per planned dosing regimen (one injection every 12 weeks "q12w", after the initial three loading injections every 4 weeks "q4w"). A disease activity assessment (DAA) was performed at pre-specified visits (Weeks 16, 20, 28, 32, 40, 44) to identify q8w need. The estimate for the proportion of subjects with a positive q12w status at Week 48 were derived from Kaplan-Meier time to event analyses for the event of first q8w need, applying event allocations (in case of lack of efficacy and/or lack of safety=efficacy/safety approach) and censoring as described in the SAP. Censored subjects were considered to be not anymore under risk for a q8 need identification at later visits. Corresponding 95% Confidence Intervals (CIs) were derived from the LOGLOG transformation. This outcome measure was pre-specified for brolucizumab 6 mg arm only. Hypothesis testing not pre-specified.

    4. Proportion of Subjects With Positive q12 Treatment Status up to Week 96 [Weeks 16, 20, 28, 32, 40, 44, 52, 56, 64, 68, 76, 80, 88, 92, 96]

      Positive q12 treatment status was defined as IVT injections per planned dosing regimen (one injection every 12 weeks "q12w", after the initial three loading injections every 4 weeks "q4w"). A disease activity assessment (DAA) was performed at pre-specified visits (Weeks 16, 20, 28, 32, 40, 44, 52, 56, 64, 68, 76, 80, 88, 92) to identify q8w need. The estimate for the proportion of subjects with a positive q12w status at Week 48 were derived from Kaplan-Meier time to event analyses for the event of first q8w need, applying event allocations (in case of lack of efficacy and/or lack of safety=efficacy/safety approach) and censoring as described in the SAP. Censored subjects were considered to be not anymore under risk for a q8 need identification at later visits. Corresponding 95% Confidence Intervals (CIs) were derived from the LOGLOG transformation. This outcome measure was pre-specified for brolucizumab 6 mg arm only. Hypothesis testing not pre-specified.

    5. Proportion of Subjects With Positive q12 Treatment Status at Week 96 Within the Subjects With no q8 Treatment Need During the Initial q12w Cycle (Week 16, Week 20) [Weeks 16, 20, 28, 32, 40, 44, 52, 56, 64, 68, 76, 80, 88, 92, 96]

      Positive q12 treatment status was defined as IVT injections per planned dosing regimen (one injection every 12 weeks "q12w", after the initial three loading injections every 4 weeks "q4w"). A disease activity assessment (DAA) was performed at pre-specified visits (Weeks 16, 20, 28, 32, 40, 44, 52, 56, 64, 68, 76, 80, 88, 92) to identify q8w need. The estimate for the proportion of subjects with a positive q12w status at Week 48 were derived from Kaplan-Meier time to event analyses for the event of first q8w need, applying event allocations (in case of lack of efficacy and/or lack of safety=efficacy/safety approach) and censoring as described in the SAP. Censored subjects were considered to be not anymore under risk for a q8 need identification at later visits. Corresponding 95% Confidence Intervals (CIs) were derived from the LOGLOG transformation. This outcome measure was pre-specified for brolucizumab 6 mg arm only. Hypothesis testing not pre-specified.

    6. Change From Baseline in BCVA (Letters Read) at Each Post-baseline Visit - Study Eye [Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96]

      BCVA (with spectacles or other visual corrective devices) was assessed using ETDRS testing at 4 meters and reported in letters read correctly. Baseline was defined as the last measurement prior to first treatment. An increase (gain) in letters read from the baseline assessment indicates improvement. One eye (study eye) contributed to the analysis.

    7. Average Change From Baseline in BCVA (Letters Read) Over the Period Week 4 to Week 48/96 - Study Eye [Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96]

      BCVA (with spectacles or other visual corrective devices) was assessed using ETDRS testing at 4 meters and reported in letters read correctly. Baseline was defined as the last measurement prior to first treatment. An increase (gain) in letters read from the baseline assessment indicates improvement. One eye (study eye) contributed to the analysis.

    8. Average Change From Baseline in BCVA (Letters Read) Over the Period Week 12 to Week 48/96 - Study Eye [Baseline, Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96]

      BCVA (with spectacles or other visual corrective devices) was assessed using ETDRS testing at 4 meters and reported in letters read correctly. Baseline was defined as the last measurement prior to first treatment. An increase (gain) in letters read from the baseline assessment indicates improvement. One eye (study eye) contributed to the analysis.

    9. Average Change From Baseline in BCVA (Letters Read) Over the Period Week 84 to Week 96 - Study Eye [Baseline, Weeks 84, 88, 92, 96]

      BCVA (with spectacles or other visual corrective devices) was assessed using ETDRS testing at 4 meters and reported in letters read correctly. Baseline was defined as the last measurement prior to first treatment. An increase (gain) in letters read from the baseline assessment indicates improvement. One eye (study eye) contributed to the analysis.

    10. Percentage of Subjects With >=15 Letter Gain From Baseline in BCVA (Letters Read) at Each Post-baseline Visit - Study Eye [Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96]

      BCVA (with spectacles or other visual corrective devices) was assessed using ETDRS testing at 4 meters and reported in letters read correctly. Baseline was defined as the last measurement prior to first treatment. An increase (gain) in letters read from the baseline assessment indicates improvement. 95% confidence interval (CI) for binomial proportions was based on Clopper-Pearson exact method. One eye (study eye) contributed to the analysis.

    11. Percentage of Subjects With >=10 Letter Gain From Baseline in BCVA (Letters Read) at Each Post-baseline Visit - Study Eye [Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96]

      BCVA (with spectacles or other visual corrective devices) was assessed using ETDRS testing at 4 meters and reported in letters read correctly. Baseline was defined as the last measurement prior to first treatment. An increase (gain) in letters read from the baseline assessment indicates improvement. 95% confidence interval (CI) for binomial proportions was based on Clopper-Pearson exact method. One eye (study eye) contributed to the analysis.

    12. Percentage of Subjects With >=5 Letter Gain From Baseline in BCVA (Letters Read) at Each Post-baseline Visit - Study Eye [Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96]

      BCVA (with spectacles or other visual corrective devices) was assessed using ETDRS testing at 4 meters and reported in letters read correctly. Baseline was defined as the last measurement prior to first treatment. An increase (gain) in letters read from the baseline assessment indicates improvement. 95% confidence interval (CI) for binomial proportions was based on Clopper-Pearson exact method. One eye (study eye) contributed to the analysis.

    13. Percentage of Subjects With >=15 Letter Loss From Baseline in BCVA (Letters Read) at Each Post-baseline Visit - Study Eye [Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96]

      BCVA (with spectacles or other visual corrective devices) was assessed using ETDRS testing at 4 meters and reported in letters read correctly. Baseline was defined as the last measurement prior to first treatment. An increase (gain) in letters read from the baseline assessment indicates improvement. 95% confidence interval (CI) for binomial proportions was based on Clopper-Pearson exact method. One eye (study eye) contributed to the analysis.

    14. Percentage of Subjects With >=10 Letter Loss From Baseline in BCVA (Letters Read) at Each Post-baseline Visit - Study Eye [Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96]

      BCVA (with spectacles or other visual corrective devices) was assessed using ETDRS testing at 4 meters and reported in letters read correctly. Baseline was defined as the last measurement prior to first treatment. An increase (gain) in letters read from the baseline assessment indicates improvement. 95% confidence interval (CI) for binomial proportions was based on Clopper-Pearson exact method. One eye (study eye) contributed to the analysis.

    15. Percentage of Subjects With >=5 Letter Loss From Baseline in BCVA (Letters Read) at Each Post-baseline Visit - Study Eye [Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96]

      BCVA (with spectacles or other visual corrective devices) was assessed using ETDRS testing at 4 meters and reported in letters read correctly. Baseline was defined as the last measurement prior to first treatment. An increase (gain) in letters read from the baseline assessment indicates improvement. 95% confidence interval (CI) for binomial proportions was based on Clopper-Pearson exact method. One eye (study eye) contributed to the analysis.

    16. Percentage of Subjects With BCVA of 73 Letters Read or More at Each Visit - Study Eye [Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96]

      BCVA (with spectacles or other visual corrective devices) was assessed using ETDRS testing at 4 meters and reported in letters read correctly (0-100 letters). A score of 65 to 70 letters represents a low to moderate visual acuity. Baseline was defined as the last measurement prior to first treatment. 95% confidence interval (CI) for binomial proportions was based on Clopper-Pearson exact method. One eye (study eye) contributed to the analysis.

    17. Change From Baseline in Central Subfield Thickness (CSFT) at Each Post-baseline Visit - Study Eye [Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96]

      CSFT (the average retinal thickness of the circular area within 1 millimeter diameter around the foveal center) was assessed using Spectral-Domain Optical Coherence Tomography (SD-OCT), a non-invasive measurement which produces cross-sectional and 3-dimensional images of the eye. A negative change value indicates an improvement, while a positive change value indicates a worsening. One eye (study eye) contributed to the analysis.

    18. Average Change From Baseline in CSFT Over the Period Week 36 Through Week 48 - Study Eye [Baseline, Weeks 36, 40, 44, 48]

      CSFT (the average retinal thickness of the circular area within 1 millimeter diameter around the foveal center) was assessed using SD-OCT, a non-invasive measurement which produces cross-sectional and 3-dimensional images of the eye. A negative change value indicates an improvement, while a positive change value indicates a worsening. One eye (study eye) contributed to the analysis.

    19. Average Change From Baseline in CSFT Over the Period Week 84 Through Week 96 - Study Eye [Baseline, Weeks 84, 88, 92, 96]

      CSFT (the average retinal thickness of the circular area within 1 millimeter diameter around the foveal center) was assessed using SD-OCT, a non-invasive measurement which produces cross-sectional and 3-dimensional images of the eye. A negative change value indicates an improvement, while a positive change value indicates a worsening. One eye (study eye) contributed to the analysis.

    20. Average Change From Baseline in CSFT Over the Period Week 4 Through Week 48/96 - Study Eye [Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96]

      CSFT (the average retinal thickness of the circular area within 1 millimeter diameter around the foveal center) was assessed using SD-OCT, a non-invasive measurement which produces cross-sectional and 3-dimensional images of the eye. A negative change value indicates an improvement, while a positive change value indicates a worsening. One eye (study eye) contributed to the analysis.

    21. Change From Baseline in Choroidal Neovascularization (CNV) Lesion Size at Week 12, Week 48, and Week 96 - Study Eye [Baseline, Weeks 12, 48, 96]

      CNV lesion size (the area of new blood vessels in the choroid layer of the retina) size was measured using fluorescein angiography (FA). A negative change value indicates a reduction in lesion size, whereas a positive change value indicates an increase. An increase in CNV lesion size may indicate progression of the underlying disease. Only one eye (study eye) contributed to the analysis.

    22. Change From Baseline in Central Subfield Neurosensory Retinal Thickness (CSFTns) at Each Post-baseline Visit - Study Eye [Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96]

      CSFTns was assessed using SD-OCT. A negative change value indicates an improvement, while a positive change value indicates a worsening. One eye (study eye) contributed to the analysis.

    23. Percentage of Subjects With Presence of Subretinal Fluid at Each Post-baseline Visit - Study Eye [Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96]

      Subretinal fluid was assessed using SD-OCT and recorded as Present/Absent. The presence of subretinal fluid is an indicator of underlying disease. One eye (study eye) contributed to the analysis.

    24. Percentage of Subjects With Presence of Intraretinal Fluid at Each Post-baseline Visit - Study Eye [Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96]

      Intraretinal fluid was assessed using SD-OCT and recorded as Present/Absent. The presence of intraretinal fluid is an indicator of underlying disease. One eye (study eye) contributed to the analysis.

    25. Percentage of Subjects With Presence of Sub-retinal Pigment Epithelium (RPE) Fluid at Each Post-baseline Visit - Study Eye [Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96]

      Sub-retinal pigment epithelium (RPE) fluid was assessed using SD-OCT and recorded as Present/Absent. The presence of sub-RPE fluid is an indicator of underlying disease. One eye (study eye) contributed to the analysis.

    26. Percentage of Subjects With Presence of Subretinal and/or Intraretinal Fluid (Central Subfield) at Each Post-baseline Visit - Study Eye [Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96]

      Subretinal fluid and intraretinal fluid were assessed using SD-OCT and recorded as Present/Absent. The presence of subretinal and/or intraretinal fluid is an indicator of underlying disease. 95% confidence interval (CI) for binomial proportions was based on Clopper-Pearson exact method. One eye (study eye) contributed to the analysis.

    27. Percentage of Subjects With Disease Activity Present (q8 Treatment Need = "Yes") at Week 16 - Study Eye [Week 16]

      A disease activity assessment (DAA) was performed to identify q8 treatment need. 95% confidence interval (CI) for binomial proportions is based on Clopper-Pearson exact method. One eye (study eye) contributed to the analysis. Hypothesis testing not pre-specified.

    28. Change From Baseline in Visual Function Questionnaire (VFQ-25) Composite Score at Week 24, Week 48, Week 72, and Week 96 [Baseline, Weeks 24, 48, 72, 96]

      The National Eye Institute Visual Function Questionnaire-25 (VFQ-25) is a validated questionnaire that collects 25 vision-targeted responses from AMD subjects. The 25 questions pertain to global vision rating (1), difficulty with near vision activities (3), difficulty with distance vision activities (3), limitations in social functioning due to vision (2), role limitations due to vision (2), dependency on others due to vision (3), mental health symptoms due to vision (4), driving difficulties (3), limitations with peripheral (1) and color vision (1), and ocular pain (2). Each response is converted to a 0 to 100 sub-scale, with the lowest and highest possible scores set at 0 and 100 points, respectively. The overall composite score (0 to 100) is obtained by averaging the 25 sub-scale scores. A high score represents better functioning.

    29. Percentage of Subjects With Induced or Boosted Anti-drug Antibody (ADA) Status at Week 48 (Brolucizumab Only) [Week 48]

      Serum samples were collected and assessed for anti-drug antibody status. Subjects were categorized as ADA negative when one of the following was met: ADA negative at all time points (predose and postdose); ADA negative at predose and no titer values above 10 at all other time points; or ADA titer of 10 at predose but negative at all other time points. ADA induced was defined as ADA negative at predose with postdose titer value greater than or equal to a titer of 30 at any timepoint. ADA boosted was defined as ADA positive at predose with postdose titer values that increased by at least two dilutions (9-fold) from their respective predose value at any time point.

    30. Percentage of Subjects With Intraretinal Hemorrhage (Central Subfield) Present at the Visit While Absent at Baseline at Each Treatment - Study Eye [Baseline, Weeks 12, 48, 96]

      Intraretinal hemorrhage was assessed using SD-OCT and recorded as Present/Absent. The presence of intraretinal hemorrhage is an indicator of underlying disease. 95% confidence interval (CI) for binomial proportions was based on Clopper-Pearson exact method. One eye (study eye) contributed to the analysis.

    31. Percentage of Subjects With Subretinal Hemorrhage (Central Subfield) Present at the Visit While Absent at Baseline at Each Treatment - Study Eye [Baseline, Weeks 12, 48, 96]

      Subretinal hemorrhage was assessed using SD-OCT and recorded as Present/Absent. The presence of subretinal hemorrhage is an indicator of underlying disease. 95% confidence interval (CI) for binomial proportions was based on Clopper-Pearson exact method. One eye (study eye) contributed to the analysis.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    50 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Key Inclusion Criteria:

    • Provide written informed consent;

    • Active CNV lesions secondary to AMD that affected the central subfield in the study eye at Screening;

    • Total area of CNV > 50% of the total lesion area in the study eye at Screening;

    • Intraretinal and/or subretinal fluid affecting the central subfield of the study eye at Screening;

    • Best corrected visual acuity (BCVA) between 78 and 23 letters, inclusive, in the study eye at Screening and Baseline using Early Treatment Diabetic Retinopathy Study (ETDRS) testing.

    Key Exclusion Criteria:

    • Any active intraocular or periocular infection or active intraocular inflammation in either eye at Baseline;

    • Central subfield of the study eye affected by fibrosis or geographic atrophy or total area of fibrosis ≥ 50% of the total lesion in the study eye at Screening;

    • Subretinal blood affecting the foveal center point and/or ≥ 50% of the lesion of the study eye at Screening;

    • Any approved or investigational treatment for neovascular age-related macular degeneration (nAMD) in the study eye at any time;

    • Retinal pigment epithelial rip/tear in the study eye at Screening or Baseline or current vitreous hemorrhage or history of vitreous hemorrhage in the study eye within 4 weeks prior to Baseline;

    • Pregnant or nursing women; women of child-bearing potential;

    • Stroke or myocardial infarction in the 6-month period prior to Baseline.

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Alcon Research

    Investigators

    • Study Director: Group Trial Lead, Novartis Pharmaceuticals

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Alcon Research
    ClinicalTrials.gov Identifier:
    NCT02434328
    Other Study ID Numbers:
    • RTH258-C002
    • 2014-004886-26
    • CRTH258A2302
    First Posted:
    May 5, 2015
    Last Update Posted:
    Sep 11, 2020
    Last Verified:
    Oct 1, 2019
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Alcon Research
    AMD
    CNV
    IVT
    Additional relevant MeSH terms:
    Macular Degeneration
    Wet Macular Degeneration
    Choroidal Neovascularization
    Neovascularization, Pathologic
    Aflibercept
    Pharmaceutical Solutions
    Ophthalmic Solutions

    Study Results

    Participant Flow

    Recruitment Details Subjects were recruited from investigative sites located in Austria, Belgium, Croatia, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Ireland, Italy, South Korea, Latvia, Lithuania, Netherlands, Norway, Poland, Portugal, Russia, Singapore, Slovakia, Spain, Switzerland, Taiwan, Turkey, UK, and Vietnam.
    Pre-assignment Detail Of the 1048 subjects enrolled in the study, 305 were exited prior to randomization as screen failures. This reporting group includes all randomized subjects.
    Arm/Group Title Brolucizumab 6 mg Aflibercept 2 mg
    Arm/Group Description Single intravitreal (IVT) injection of brolucizumab at Day 0, Week 4, and Week 8, followed by 1 injection every 8 weeks/1 injection every 12 weeks (q8w/q12w) maintenance regimen until study exit Single IVT injection of aflibercept at Day 0, Week 4, and Week 8, followed by q8w maintenance regimen until study exit
    Period Title: Overall Study
    STARTED 372 371
    Randomized and Treated 370 369
    COMPLETED 342 329
    NOT COMPLETED 30 42

    Baseline Characteristics

    Arm/Group Title Brolucizumab 6 mg Aflibercept 2 mg Total
    Arm/Group Description Single intravitreal (IVT) injection of brolucizumab at Day 0, Week 4, and Week 8, followed by 1 injection every 8 weeks/1 injection every 12 weeks (q8w/q12w) maintenance regimen until study exit Single IVT injection of aflibercept at Day 0, Week 4, and Week 8, followed by q8w maintenance regimen until study exit Total of all reporting groups
    Overall Participants 370 369 739
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    74.8
    (8.58)
    75.5
    (7.87)
    75.1
    (8.24)
    Age, Customized (participants) [Number]
    less than 50 years
    0
    0%
    0
    0%
    0
    0%
    50-64 years
    44
    11.9%
    28
    7.6%
    72
    9.7%
    65-74 years
    124
    33.5%
    126
    34.1%
    250
    33.8%
    75-84 years
    150
    40.5%
    167
    45.3%
    317
    42.9%
    85 years and greater
    52
    14.1%
    48
    13%
    100
    13.5%
    Sex: Female, Male (Count of Participants)
    Female
    210
    56.8%
    212
    57.5%
    422
    57.1%
    Male
    160
    43.2%
    157
    42.5%
    317
    42.9%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    23
    6.2%
    25
    6.8%
    48
    6.5%
    Not Hispanic or Latino
    321
    86.8%
    322
    87.3%
    643
    87%
    Unknown or Not Reported
    26
    7%
    22
    6%
    48
    6.5%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    22
    5.9%
    23
    6.2%
    45
    6.1%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    1
    0.3%
    0
    0%
    1
    0.1%
    White
    340
    91.9%
    341
    92.4%
    681
    92.2%
    More than one race
    2
    0.5%
    1
    0.3%
    3
    0.4%
    Unknown or Not Reported
    5
    1.4%
    4
    1.1%
    9
    1.2%
    Best Corrected Visual Acuity (BCVA) (letters read) (letters) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [letters]
    61.5
    (12.59)
    60.8
    (12.93)
    61.2
    (12.76)

    Outcome Measures

    1. Primary Outcome
    Title Change From Baseline in Best Corrected Visual Acuity (BCVA) (Letters Read) at Week 48 - Study Eye
    Description BCVA (with spectacles or other visual corrective devices) was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) testing at 4 meters and reported in letters read correctly. Baseline was defined as the last measurement prior to first treatment. An increase (gain) in letters read from the baseline assessment indicates improvement. One eye (study eye) contributed to the analysis.
    Time Frame Baseline, Week 48

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS) - Last Observation Carried Forward (LOCF)
    Arm/Group Title Brolucizumab 6 mg Aflibercept 2 mg
    Arm/Group Description Single IVT injection of brolucizumab at Day 0, Week 4, and Week 8, followed by q8w/q12w maintenance regimen until study exit Single IVT injection of aflibercept at Day 0, Week 4, and Week 8, followed by q8w maintenance regimen until study exit
    Measure Participants 370 369
    Mean (Standard Deviation) [letters]
    6.9
    (11.47)
    7.6
    (12.47)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments
    Type of Statistical Test Non-Inferiority
    Comments The noninferiority margin was 4 letters.
    Statistical Test of Hypothesis p-Value <0.0001
    Comments 1-sided p-value reported. Hypothesis tested according to the pre-specified hierarchical testing that ensures the global type I error rate at 0.05.
    Method ANOVA
    Comments Analyzed using ANOVA model with baseline BCVA categories, age categories, and treatment as fixed effect factors.
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -0.7
    Confidence Interval (2-Sided) 95%
    -2.4 to 1.0
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.86
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    2. Secondary Outcome
    Title Average Change From Baseline in BCVA (Letters Read) Over the Period Week 36 Through Week 48 - Study Eye
    Description BCVA (with spectacles or other visual corrective devices) was assessed using ETDRS testing at 4 meters and reported in letters read correctly. For each subject, this endpoint was defined as the average of the changes from baseline to Weeks 36, 40, 44, and 48. Baseline was defined as the last measurement prior to first treatment. An increase (gain) in letters read from the baseline assessment indicates improvement. One eye (study eye) contributed to the analysis.
    Time Frame Baseline, Weeks 36, 40, 44, 48

    Outcome Measure Data

    Analysis Population Description
    FAS - LOCF
    Arm/Group Title Brolucizumab 6 mg Aflibercept 2 mg
    Arm/Group Description Single IVT injection of brolucizumab at Day 0, Week 4, and Week 8, followed by q8w/q12w maintenance regimen until study exit Single IVT injection of aflibercept at Day 0, Week 4, and Week 8, followed by q8w maintenance regimen until study exit
    Measure Participants 370 369
    Mean (Standard Deviation) [letters]
    6.6
    (11.10)
    7.7
    (11.81)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments
    Type of Statistical Test Non-Inferiority
    Comments The non-inferiority margin was 4 letters.
    Statistical Test of Hypothesis p-Value 0.0003
    Comments 1-sided p-value reported. Hypothesis tested according to the pre-specified hierarchical testing that ensures the global type I error rate at 0.05.
    Method ANOVA
    Comments Analyzed using ANOVA model with baseline BCVA categories, age categories, and treatment as fixed effect factors.
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -1.2
    Confidence Interval (2-Sided) 95%
    -2.8 to 0.5
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.82
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    3. Secondary Outcome
    Title Proportion of Subjects With Positive q12 (Every 12 Weeks) Treatment Status at Week 48
    Description Positive q12 treatment status was defined as IVT injections per planned dosing regimen (one injection every 12 weeks "q12w", after the initial three loading injections every 4 weeks "q4w"). A disease activity assessment (DAA) was performed at pre-specified visits (Weeks 16, 20, 28, 32, 40, 44) to identify q8w (one injection every 8 weeks) need. The estimate for the proportion of subjects with a positive q12w status at Week 48 were derived from Kaplan-Meier time to event analyses for the event of first q8w need, applying event allocations (in case of lack of efficacy and/or lack of safety=efficacy/safety approach) and censoring as described in the SAP. Censored subjects were considered to be not anymore under risk for a q8 need identification at later visits. Corresponding 95% Confidence Intervals (CIs) were derived from the LOGLOG transformation. This outcome measure was pre-specified for brolucizumab 6 mg arm only. Hypothesis testing not pre-specified.
    Time Frame Weeks 16, 20, 28, 32, 40, 44, 48

    Outcome Measure Data

    Analysis Population Description
    FAS - efficacy/safety approach
    Arm/Group Title Brolucizumab 6 mg
    Arm/Group Description Single IVT injection of brolucizumab at Day 0, Week 4, and Week 8, followed by q8w/q12w maintenance regimen until study exit
    Measure Participants 370
    Number (95% Confidence Interval) [proportion of subjects]
    0.5101
    4. Secondary Outcome
    Title Proportion of Subjects With Positive q12 Treatment Status at Week 48 Within the Subjects With no q8 (Every 8 Weeks) Treatment Need During the Initial q12w Cycle (Week 16, Week 20)
    Description Positive q12 treatment status was defined as IVT injections per planned dosing regimen (one injection every 12 weeks "q12w", after the initial three loading injections every 4 weeks "q4w"). A disease activity assessment (DAA) was performed at pre-specified visits (Weeks 16, 20, 28, 32, 40, 44) to identify q8w need. The estimate for the proportion of subjects with a positive q12w status at Week 48 were derived from Kaplan-Meier time to event analyses for the event of first q8w need, applying event allocations (in case of lack of efficacy and/or lack of safety=efficacy/safety approach) and censoring as described in the SAP. Censored subjects were considered to be not anymore under risk for a q8 need identification at later visits. Corresponding 95% Confidence Intervals (CIs) were derived from the LOGLOG transformation. This outcome measure was pre-specified for brolucizumab 6 mg arm only. Hypothesis testing not pre-specified.
    Time Frame Weeks 16, 20, 28, 32, 40, 44, 48

    Outcome Measure Data

    Analysis Population Description
    FAS - efficacy/safety approach
    Arm/Group Title Brolucizumab 6 mg
    Arm/Group Description Single IVT injection of brolucizumab at Day 0, Week 4, and Week 8, followed by q8w/q12w maintenance regimen until study exit
    Measure Participants 220
    Number (95% Confidence Interval) [proportion of subjects]
    0.8170
    5. Secondary Outcome
    Title Proportion of Subjects With Positive q12 Treatment Status up to Week 96
    Description Positive q12 treatment status was defined as IVT injections per planned dosing regimen (one injection every 12 weeks "q12w", after the initial three loading injections every 4 weeks "q4w"). A disease activity assessment (DAA) was performed at pre-specified visits (Weeks 16, 20, 28, 32, 40, 44, 52, 56, 64, 68, 76, 80, 88, 92) to identify q8w need. The estimate for the proportion of subjects with a positive q12w status at Week 48 were derived from Kaplan-Meier time to event analyses for the event of first q8w need, applying event allocations (in case of lack of efficacy and/or lack of safety=efficacy/safety approach) and censoring as described in the SAP. Censored subjects were considered to be not anymore under risk for a q8 need identification at later visits. Corresponding 95% Confidence Intervals (CIs) were derived from the LOGLOG transformation. This outcome measure was pre-specified for brolucizumab 6 mg arm only. Hypothesis testing not pre-specified.
    Time Frame Weeks 16, 20, 28, 32, 40, 44, 52, 56, 64, 68, 76, 80, 88, 92, 96

    Outcome Measure Data

    Analysis Population Description
    FAS - efficacy/safety approach
    Arm/Group Title Brolucizumab 6 mg
    Arm/Group Description Single IVT injection of brolucizumab at Day 0, Week 4, and Week 8, followed by q8w/q12w maintenance regimen until study exit
    Measure Participants 370
    Number (95% Confidence Interval) [proportion of subjects]
    0.3856
    6. Secondary Outcome
    Title Proportion of Subjects With Positive q12 Treatment Status at Week 96 Within the Subjects With no q8 Treatment Need During the Initial q12w Cycle (Week 16, Week 20)
    Description Positive q12 treatment status was defined as IVT injections per planned dosing regimen (one injection every 12 weeks "q12w", after the initial three loading injections every 4 weeks "q4w"). A disease activity assessment (DAA) was performed at pre-specified visits (Weeks 16, 20, 28, 32, 40, 44, 52, 56, 64, 68, 76, 80, 88, 92) to identify q8w need. The estimate for the proportion of subjects with a positive q12w status at Week 48 were derived from Kaplan-Meier time to event analyses for the event of first q8w need, applying event allocations (in case of lack of efficacy and/or lack of safety=efficacy/safety approach) and censoring as described in the SAP. Censored subjects were considered to be not anymore under risk for a q8 need identification at later visits. Corresponding 95% Confidence Intervals (CIs) were derived from the LOGLOG transformation. This outcome measure was pre-specified for brolucizumab 6 mg arm only. Hypothesis testing not pre-specified.
    Time Frame Weeks 16, 20, 28, 32, 40, 44, 52, 56, 64, 68, 76, 80, 88, 92, 96

    Outcome Measure Data

    Analysis Population Description
    FAS - efficacy/safety approach
    Arm/Group Title Brolucizumab 6 mg
    Arm/Group Description Single IVT injection of brolucizumab at Day 0, Week 4, and Week 8, followed by q8w/q12w maintenance regimen until study exit
    Measure Participants 221
    Number (95% Confidence Interval) [proportion of subjects]
    0.6170
    7. Secondary Outcome
    Title Change From Baseline in BCVA (Letters Read) at Each Post-baseline Visit - Study Eye
    Description BCVA (with spectacles or other visual corrective devices) was assessed using ETDRS testing at 4 meters and reported in letters read correctly. Baseline was defined as the last measurement prior to first treatment. An increase (gain) in letters read from the baseline assessment indicates improvement. One eye (study eye) contributed to the analysis.
    Time Frame Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96

    Outcome Measure Data

    Analysis Population Description
    FAS - LOCF
    Arm/Group Title Brolucizumab 6 mg Aflibercept 2 mg
    Arm/Group Description Single IVT injection of brolucizumab at Day 0, Week 4, and Week 8, followed by q8w/q12w maintenance regimen until study exit Single IVT injection of aflibercept at Day 0, Week 4, and Week 8, followed by q8w maintenance regimen until study exit
    Measure Participants 370 369
    Change from baseline at Week 4
    3.7
    (7.03)
    4.7
    (7.62)
    Change from baseline at Week 8
    5.0
    (8.16)
    6.0
    (9.32)
    Change from baseline at Week 12
    5.4
    (9.35)
    6.4
    (10.14)
    Change from baseline at Week 16
    5.4
    (9.65)
    6.3
    (10.46)
    Change from baseline at Week 20
    5.4
    (10.42)
    6.9
    (10.66)
    Change from baseline at Week 24
    5.8
    (10.76)
    6.7
    (11.17)
    Change from baseline at Week 28
    6.3
    (10.97)
    7.4
    (11.86)
    Change from baseline at Week 32
    6.5
    (10.92)
    7.3
    (11.44)
    Change from baseline at Week 36
    6.4
    (11.32)
    7.6
    (11.99)
    Change from baseline at Week 40
    6.4
    (11.66)
    7.6
    (11.85)
    Change from baseline at Week 44
    6.5
    (11.51)
    8.0
    (12.28)
    Change from baseline at Week 48
    6.9
    (11.47)
    7.6
    (12.47)
    Change from baseline at Week 52
    6.8
    (12.03)
    7.4
    (12.91)
    Change from baseline at Week 56
    6.6
    (12.43)
    7.2
    (13.04)
    Change from baseline at Week 60
    6.5
    (12.23)
    7.4
    (13.49)
    Change from baseline at Week 64
    6.5
    (12.51)
    7.2
    (13.79)
    Change from baseline at Week 68
    6.5
    (12.22)
    7.1
    (14.29)
    Change from baseline at Week 72
    6.1
    (13.32)
    6.9
    (13.74)
    Change from baseline at Week 76
    6.3
    (13.44)
    6.8
    (13.80)
    Change from baseline at Week 80
    6.4
    (13.43)
    6.6
    (13.97)
    Change from baseline at Week 84
    5.8
    (13.76)
    6.7
    (14.04)
    Change from baseline at Week 88
    6.3
    (13.40)
    6.9
    (14.02)
    Change from baseline at Week 92
    6.1
    (13.85)
    6.5
    (14.29)
    Change from baseline at Week 96
    6.1
    (14.06)
    6.6
    (14.55)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 4
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -1.0
    Confidence Interval (2-Sided) 95%
    -2.0 to 0.0
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.52
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 8
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -1.0
    Confidence Interval (2-Sided) 95%
    -2.2 to 0.2
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.63
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 12
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -1.0
    Confidence Interval (2-Sided) 95%
    -2.4 to 0.4
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.71
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 16
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -0.9
    Confidence Interval (2-Sided) 95%
    -2.3 to 0.6
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.73
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 20
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -1.5
    Confidence Interval (2-Sided) 95%
    -3.0 to 0.0
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.76
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 24
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -0.9
    Confidence Interval (2-Sided) 95%
    -2.5 to 0.6
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.79
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 28
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -1.1
    Confidence Interval (2-Sided) 95%
    -2.7 to 0.5
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.82
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 32
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -0.9
    Confidence Interval (2-Sided) 95%
    -2.5 to 0.7
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.81
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 36
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -1.2
    Confidence Interval (2-Sided) 95%
    -2.9 to 0.4
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.84
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 40
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -1.2
    Confidence Interval (2-Sided) 95%
    -2.9 to 0.5
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.85
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 44
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -1.6
    Confidence Interval (2-Sided) 95%
    -3.2 to 0.1
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.86
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 48
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -0.7
    Confidence Interval (2-Sided) 95%
    -2.4 to 1.0
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.86
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 52
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -0.7
    Confidence Interval (2-Sided) 95%
    -2.5 to 1.1
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.90
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 56
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -0.7
    Confidence Interval (2-Sided) 95%
    -2.5 to 1.1
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.92
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 60
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -0.8
    Confidence Interval (2-Sided) 95%
    -2.7 to 1.0
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.93
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 64
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -0.7
    Confidence Interval (2-Sided) 95%
    -2.5 to 1.2
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.95
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 68
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -0.7
    Confidence Interval (2-Sided) 95%
    -2.5 to 1.2
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.96
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 72
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -0.9
    Confidence Interval (2-Sided) 95%
    -2.8 to 1.1
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.98
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 76
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -0.5
    Confidence Interval (2-Sided) 95%
    -2.5 to 1.4
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.98
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 80
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -0.2
    Confidence Interval (2-Sided) 95%
    -2.1 to 1.8
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.99
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 21
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 84
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -0.9
    Confidence Interval (2-Sided) 95%
    -2.9 to 1.1
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.00
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 22
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 88
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -0.6
    Confidence Interval (2-Sided) 95%
    -2.6 to 1.3
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.99
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 23
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 92
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -0.4
    Confidence Interval (2-Sided) 95%
    -2.4 to 1.6
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.02
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 24
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 96
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -0.4
    Confidence Interval (2-Sided) 95%
    -2.5 to 1.6
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.04
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    8. Secondary Outcome
    Title Average Change From Baseline in BCVA (Letters Read) Over the Period Week 4 to Week 48/96 - Study Eye
    Description BCVA (with spectacles or other visual corrective devices) was assessed using ETDRS testing at 4 meters and reported in letters read correctly. Baseline was defined as the last measurement prior to first treatment. An increase (gain) in letters read from the baseline assessment indicates improvement. One eye (study eye) contributed to the analysis.
    Time Frame Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96

    Outcome Measure Data

    Analysis Population Description
    FAS - LOCF
    Arm/Group Title Brolucizumab 6 mg Aflibercept 2 mg
    Arm/Group Description Single IVT injection of brolucizumab at Day 0, Week 4, and Week 8, followed by q8w/q12w maintenance regimen until study exit Single IVT injection of aflibercept at Day 0, Week 4, and Week 8, followed by q8w maintenance regimen until study exit
    Measure Participants 370 369
    Change from baseline over the period Week 4 to 48
    5.8
    (9.11)
    6.9
    (10.11)
    Change from baseline over the period Week 4 to 96
    6.1
    (10.42)
    6.9
    (11.41)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 4 to Week 48
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -1.1
    Confidence Interval (2-Sided) 95%
    -2.4 to 0.3
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.69
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 4 to Week 96
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -0.8
    Confidence Interval (2-Sided) 95%
    -2.4 to 0.7
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.78
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    9. Secondary Outcome
    Title Average Change From Baseline in BCVA (Letters Read) Over the Period Week 12 to Week 48/96 - Study Eye
    Description BCVA (with spectacles or other visual corrective devices) was assessed using ETDRS testing at 4 meters and reported in letters read correctly. Baseline was defined as the last measurement prior to first treatment. An increase (gain) in letters read from the baseline assessment indicates improvement. One eye (study eye) contributed to the analysis.
    Time Frame Baseline, Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96

    Outcome Measure Data

    Analysis Population Description
    FAS - LOCF
    Arm/Group Title Brolucizumab 6 mg Aflibercept 2 mg
    Arm/Group Description Single IVT injection of brolucizumab at Day 0, Week 4, and Week 8, followed by q8w/q12w maintenance regimen until study exit Single IVT injection of aflibercept at Day 0, Week 4, and Week 8, followed by q8w maintenance regimen until study exit
    Measure Participants 370 369
    Change from baseline over the period Week 12 to 48
    6.1
    (9.91)
    7.2
    (10.77)
    Change from baseline over the period Week 12 to 96
    6.2
    (10.97)
    7.0
    (11.88)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 12 to Week 48
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -1.1
    Confidence Interval (2-Sided) 95%
    -2.5 to 0.4
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.74
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 12 to Week 96
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -0.8
    Confidence Interval (2-Sided) 95%
    -2.4 to 0.8
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.82
    Estimation Comments
    Other Statistical Analysis Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    10. Secondary Outcome
    Title Average Change From Baseline in BCVA (Letters Read) Over the Period Week 84 to Week 96 - Study Eye
    Description BCVA (with spectacles or other visual corrective devices) was assessed using ETDRS testing at 4 meters and reported in letters read correctly. Baseline was defined as the last measurement prior to first treatment. An increase (gain) in letters read from the baseline assessment indicates improvement. One eye (study eye) contributed to the analysis.
    Time Frame Baseline, Weeks 84, 88, 92, 96

    Outcome Measure Data

    Analysis Population Description
    FAS - LOCF
    Arm/Group Title Brolucizumab 6 mg Aflibercept 2 mg
    Arm/Group Description Single IVT injection of brolucizumab at Day 0, Week 4, and Week 8, followed by q8w/q12w maintenance regimen until study exit Single IVT injection of aflibercept at Day 0, Week 4, and Week 8, followed by q8w maintenance regimen until study exit
    Measure Participants 370 369
    Mean (Standard Deviation) [letters]
    6.1
    (13.51)
    6.7
    (13.96)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -0.6
    Confidence Interval (2-Sided) 95%
    -2.5 to 1.4
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.99
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    11. Secondary Outcome
    Title Percentage of Subjects With >=15 Letter Gain From Baseline in BCVA (Letters Read) at Each Post-baseline Visit - Study Eye
    Description BCVA (with spectacles or other visual corrective devices) was assessed using ETDRS testing at 4 meters and reported in letters read correctly. Baseline was defined as the last measurement prior to first treatment. An increase (gain) in letters read from the baseline assessment indicates improvement. 95% confidence interval (CI) for binomial proportions was based on Clopper-Pearson exact method. One eye (study eye) contributed to the analysis.
    Time Frame Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96

    Outcome Measure Data

    Analysis Population Description
    FAS - LOCF
    Arm/Group Title Brolucizumab 6 mg Aflibercept 2 mg
    Arm/Group Description Single IVT injection of brolucizumab at Day 0, Week 4, and Week 8, followed by q8w/q12w maintenance regimen until study exit Single IVT injection of aflibercept at Day 0, Week 4, and Week 8, followed by q8w maintenance regimen until study exit
    Measure Participants 370 369
    Change from baseline at Week 4
    7.6
    8.9
    Change from baseline at Week 8
    13.8
    18.2
    Change from baseline at Week 12
    16.5
    21.4
    Change from baseline at Week 16
    20.0
    22.2
    Change from baseline at Week 20
    20.5
    23.6
    Change from baseline at Week 24
    23.8
    22.8
    Change from baseline at Week 28
    23.8
    27.4
    Change from baseline at Week 32
    25.4
    28.7
    Change from baseline at Week 36
    26.2
    30.9
    Change from baseline at Week 40
    27.0
    31.4
    Change from baseline at Week 44
    26.8
    31.2
    Change from baseline at Week 48
    29.5
    29.8
    Change from baseline at Week 52
    30.3
    30.6
    Change from baseline at Week 56
    29.7
    30.6
    Change from baseline at Week 60
    28.6
    30.6
    Change from baseline at Week 64
    29.7
    30.9
    Change from baseline at Week 68
    28.9
    32.2
    Change from baseline at Week 72
    27.6
    31.4
    Change from baseline at Week 76
    28.4
    30.6
    Change from baseline at Week 80
    28.1
    30.4
    Change from baseline at Week 84
    27.6
    31.2
    Change from baseline at Week 88
    27.6
    33.1
    Change from baseline at Week 92
    29.5
    30.9
    Change from baseline at Week 96
    29.2
    31.4
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 4
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -1.3
    Confidence Interval (2-Sided) 95%
    -5.1 to 2.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 8
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -4.3
    Confidence Interval (2-Sided) 95%
    -9.5 to 1.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 12
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -5.0
    Confidence Interval (2-Sided) 95%
    -10.5 to 0.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 16
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -2.3
    Confidence Interval (2-Sided) 95%
    -8.4 to 3.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 20
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -3.1
    Confidence Interval (2-Sided) 95%
    -8.8 to 2.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 24
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 0.9
    Confidence Interval (2-Sided) 95%
    -5.2 to 6.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 28
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -3.7
    Confidence Interval (2-Sided) 95%
    -9.9 to 2.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 32
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -3.6
    Confidence Interval (2-Sided) 95%
    -10.5 to 2.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 36
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -4.9
    Confidence Interval (2-Sided) 95%
    -11.6 to 1.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 40
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -4.7
    Confidence Interval (2-Sided) 95%
    -11.5 to 1.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 44
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -4.6
    Confidence Interval (2-Sided) 95%
    -11.3 to 1.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 48
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -0.6
    Confidence Interval (2-Sided) 95%
    -7.1 to 5.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 52
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -0.6
    Confidence Interval (2-Sided) 95%
    -7.0 to 5.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 56
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -1.1
    Confidence Interval (2-Sided) 95%
    -7.7 to 5.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 60
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -2.2
    Confidence Interval (2-Sided) 95%
    -8.3 to 4.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 64
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -1.4
    Confidence Interval (2-Sided) 95%
    -7.9 to 5.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 68
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -3.5
    Confidence Interval (2-Sided) 95%
    -9.9 to 3.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 72
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -4.1
    Confidence Interval (2-Sided) 95%
    -10.2 to 2.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 76
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -2.4
    Confidence Interval (2-Sided) 95%
    -8.8 to 4.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 80
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -2.6
    Confidence Interval (2-Sided) 95%
    -9.0 to 3.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 21
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 84
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -3.8
    Confidence Interval (2-Sided) 95%
    -9.9 to 2.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 22
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 88
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -5.8
    Confidence Interval (2-Sided) 95%
    -11.8 to 0.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 23
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 92
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -1.7
    Confidence Interval (2-Sided) 95%
    -7.9 to 4.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 24
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 96
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -2.4
    Confidence Interval (2-Sided) 95%
    -8.8 to 4.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    12. Secondary Outcome
    Title Percentage of Subjects With >=10 Letter Gain From Baseline in BCVA (Letters Read) at Each Post-baseline Visit - Study Eye
    Description BCVA (with spectacles or other visual corrective devices) was assessed using ETDRS testing at 4 meters and reported in letters read correctly. Baseline was defined as the last measurement prior to first treatment. An increase (gain) in letters read from the baseline assessment indicates improvement. 95% confidence interval (CI) for binomial proportions was based on Clopper-Pearson exact method. One eye (study eye) contributed to the analysis.
    Time Frame Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96

    Outcome Measure Data

    Analysis Population Description
    FAS - LOCF
    Arm/Group Title Brolucizumab 6 mg Aflibercept 2 mg
    Arm/Group Description Single IVT injection of brolucizumab at Day 0, Week 4, and Week 8, followed by q8w/q12w maintenance regimen until study exit Single IVT injection of aflibercept at Day 0, Week 4, and Week 8, followed by q8w maintenance regimen until study exit
    Measure Participants 370 369
    Change from baseline at Week 4
    20.0
    22.2
    Change from baseline at Week 8
    26.8
    32.8
    Change from baseline at Week 12
    32.4
    36.0
    Change from baseline at Week 16
    36.5
    36.9
    Change from baseline at Week 20
    33.8
    38.2
    Change from baseline at Week 24
    35.7
    39.3
    Change from baseline at Week 28
    40.3
    42.5
    Change from baseline at Week 32
    41.1
    43.4
    Change from baseline at Week 36
    40.3
    45.5
    Change from baseline at Week 40
    43.5
    46.3
    Change from baseline at Week 44
    42.4
    45.3
    Change from baseline at Week 48
    44.1
    45.8
    Change from baseline at Week 52
    44.9
    45.8
    Change from baseline at Week 56
    43.0
    45.5
    Change from baseline at Week 60
    42.2
    44.7
    Change from baseline at Week 64
    44.3
    45.8
    Change from baseline at Week 68
    43.5
    45.0
    Change from baseline at Week 72
    41.1
    44.4
    Change from baseline at Week 76
    45.4
    44.7
    Change from baseline at Week 80
    43.8
    44.2
    Change from baseline at Week 84
    40.8
    44.2
    Change from baseline at Week 88
    43.2
    45.5
    Change from baseline at Week 92
    45.4
    43.4
    Change from baseline at Week 96
    45.1
    45.0
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 4
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -2.1
    Confidence Interval (2-Sided) 95%
    -7.6 to 3.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 8
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -6.0
    Confidence Interval (2-Sided) 95%
    -13.0 to 0.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 12
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -3.8
    Confidence Interval (2-Sided) 95%
    -10.1 to 2.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 16
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -0.5
    Confidence Interval (2-Sided) 95%
    -7.3 to 6.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 20
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -4.6
    Confidence Interval (2-Sided) 95%
    -11.2 to 2.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 24
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -3.7
    Confidence Interval (2-Sided) 95%
    -10.7 to 3.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 28
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -2.4
    Confidence Interval (2-Sided) 95%
    -9.6 to 4.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 32
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -2.6
    Confidence Interval (2-Sided) 95%
    -9.4 to 4.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 36
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -5.4
    Confidence Interval (2-Sided) 95%
    -12.1 to 1.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 40
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -3.1
    Confidence Interval (2-Sided) 95%
    -9.9 to 3.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 44
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -3.0
    Confidence Interval (2-Sided) 95%
    -10.3 to 4.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 48
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -1.9
    Confidence Interval (2-Sided) 95%
    -8.7 to 4.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 52
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -1.3
    Confidence Interval (2-Sided) 95%
    -8.0 to 5.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 56
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -2.8
    Confidence Interval (2-Sided) 95%
    -9.8 to 4.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 60
    Type of Statistical Test Other
    Comments Hypothesis testing not pre-specified.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -2.8
    Confidence Interval (2-Sided) 95%
    -9.6 to 4.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 64
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -1.7
    Confidence Interval (2-Sided) 95%
    -8.8 to 5.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 68
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -1.7
    Confidence Interval (2-Sided) 95%
    -8.4 to 5.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 72
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -3.6
    Confidence Interval (2-Sided) 95%
    -10.4 to 2.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 76
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 0.5
    Confidence Interval (2-Sided) 95%
    -6.5 to 7.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 80
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -0.7
    Confidence Interval (2-Sided) 95%
    -7.5 to 6.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 21
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 84
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -3.5
    Confidence Interval (2-Sided) 95%
    -10.4 to 3.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 22
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 88
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -2.5
    Confidence Interval (2-Sided) 95%
    -9.6 to 3.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 23
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 92
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 1.9
    Confidence Interval (2-Sided) 95%
    -5.0 to 8.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 24
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 96
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 0.1
    Confidence Interval (2-Sided) 95%
    -7.0 to 6.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    13. Secondary Outcome
    Title Percentage of Subjects With >=5 Letter Gain From Baseline in BCVA (Letters Read) at Each Post-baseline Visit - Study Eye
    Description BCVA (with spectacles or other visual corrective devices) was assessed using ETDRS testing at 4 meters and reported in letters read correctly. Baseline was defined as the last measurement prior to first treatment. An increase (gain) in letters read from the baseline assessment indicates improvement. 95% confidence interval (CI) for binomial proportions was based on Clopper-Pearson exact method. One eye (study eye) contributed to the analysis.
    Time Frame Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96

    Outcome Measure Data

    Analysis Population Description
    FAS - LOCF
    Arm/Group Title Brolucizumab 6 mg Aflibercept 2 mg
    Arm/Group Description Single IVT injection of brolucizumab at Day 0, Week 4, and Week 8, followed by q8w/q12w maintenance regimen until study exit Single IVT injection of aflibercept at Day 0, Week 4, and Week 8, followed by q8w maintenance regimen until study exit
    Measure Participants 370 369
    Change from baseline at Week 4
    41.6
    45.3
    Change from baseline at Week 8
    50.0
    53.1
    Change from baseline at Week 12
    55.1
    58.5
    Change from baseline at Week 16
    55.4
    56.6
    Change from baseline at Week 20
    55.9
    61.0
    Change from baseline at Week 24
    58.1
    61.0
    Change from baseline at Week 28
    60.0
    65.6
    Change from baseline at Week 32
    64.1
    65.6
    Change from baseline at Week 36
    63.2
    65.3
    Change from baseline at Week 40
    63.0
    64.0
    Change from baseline at Week 44
    64.6
    65.9
    Change from baseline at Week 48
    64.6
    64.5
    Change from baseline at Week 52
    63.0
    65.3
    Change from baseline at Week 56
    62.7
    64.2
    Change from baseline at Week 60
    62.2
    62.6
    Change from baseline at Week 64
    65.7
    63.1
    Change from baseline at Week 68
    62.2
    63.4
    Change from baseline at Week 72
    63.0
    61.5
    Change from baseline at Week 76
    63.8
    61.5
    Change from baseline at Week 80
    65.1
    60.7
    Change from baseline at Week 84
    61.9
    64.2
    Change from baseline at Week 88
    63.2
    62.1
    Change from baseline at Week 92
    64.6
    60.7
    Change from baseline at Week 96
    64.1
    60.7
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 4
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -3.5
    Confidence Interval (2-Sided) 95%
    -10.4 to 3.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 8
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -3.2
    Confidence Interval (2-Sided) 95%
    -10.2 to 3.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 12
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -3.7
    Confidence Interval (2-Sided) 95%
    -10.7 to 3.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 16
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -1.4
    Confidence Interval (2-Sided) 95%
    -8.4 to 5.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 20
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -5.3
    Confidence Interval (2-Sided) 95%
    -12.3 to 1.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 24
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -3.2
    Confidence Interval (2-Sided) 95%
    -9.9 to 3.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 28
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -5.9
    Confidence Interval (2-Sided) 95%
    -12.8 to 0.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 32
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -1.9
    Confidence Interval (2-Sided) 95%
    -8.2 to 4.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 36
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -2.3
    Confidence Interval (2-Sided) 95%
    -9.2 to 4.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 40
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -1.3
    Confidence Interval (2-Sided) 95%
    -8.2 to 5.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 44
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -1.5
    Confidence Interval (2-Sided) 95%
    -8.5 to 5.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 48
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -0.2
    Confidence Interval (2-Sided) 95%
    -7.4 to 6.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 52
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -2.7
    Confidence Interval (2-Sided) 95%
    -9.8 to 4.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 56
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -1.7
    Confidence Interval (2-Sided) 95%
    -8.6 to 4.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 60
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -0.7
    Confidence Interval (2-Sided) 95%
    -7.8 to 6.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 64
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 2.3
    Confidence Interval (2-Sided) 95%
    -4.5 to 9.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 68
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -1.5
    Confidence Interval (2-Sided) 95%
    -8.6 to 4.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 72
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 1.1
    Confidence Interval (2-Sided) 95%
    -5.8 to 7.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 76
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 2.0
    Confidence Interval (2-Sided) 95%
    -5.1 to 8.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 80
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 4.2
    Confidence Interval (2-Sided) 95%
    -2.8 to 10.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 21
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 84
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -2.7
    Confidence Interval (2-Sided) 95%
    -9.3 to 4.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 22
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 88
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 0.9
    Confidence Interval (2-Sided) 95%
    -6.1 to 7.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 23
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 92
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 3.7
    Confidence Interval (2-Sided) 95%
    -3.0 to 10.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 24
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 96
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 3.1
    Confidence Interval (2-Sided) 95%
    -3.9 to 10.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    14. Secondary Outcome
    Title Percentage of Subjects With >=15 Letter Loss From Baseline in BCVA (Letters Read) at Each Post-baseline Visit - Study Eye
    Description BCVA (with spectacles or other visual corrective devices) was assessed using ETDRS testing at 4 meters and reported in letters read correctly. Baseline was defined as the last measurement prior to first treatment. An increase (gain) in letters read from the baseline assessment indicates improvement. 95% confidence interval (CI) for binomial proportions was based on Clopper-Pearson exact method. One eye (study eye) contributed to the analysis.
    Time Frame Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96

    Outcome Measure Data

    Analysis Population Description
    FAS - LOCF
    Arm/Group Title Brolucizumab 6 mg Aflibercept 2 mg
    Arm/Group Description Single IVT injection of brolucizumab at Day 0, Week 4, and Week 8, followed by q8w/q12w maintenance regimen until study exit Single IVT injection of aflibercept at Day 0, Week 4, and Week 8, followed by q8w maintenance regimen until study exit
    Measure Participants 370 369
    Change from baseline at Week 4
    1.1
    1.1
    Change from baseline at Week 8
    1.1
    1.6
    Change from baseline at Week 12
    1.9
    1.9
    Change from baseline at Week 16
    2.2
    2.2
    Change from baseline at Week 20
    3.5
    3.0
    Change from baseline at Week 24
    2.7
    3.3
    Change from baseline at Week 28
    3.0
    3.5
    Change from baseline at Week 32
    3.2
    3.8
    Change from baseline at Week 36
    3.8
    3.5
    Change from baseline at Week 40
    5.4
    4.3
    Change from baseline at Week 44
    4.6
    4.6
    Change from baseline at Week 48
    3.8
    4.9
    Change from baseline at Week 52
    4.6
    5.7
    Change from baseline at Week 56
    5.9
    5.4
    Change from baseline at Week 60
    6.2
    5.7
    Change from baseline at Week 64
    6.8
    6.2
    Change from baseline at Week 68
    5.4
    6.5
    Change from baseline at Week 72
    7.3
    6.5
    Change from baseline at Week 76
    6.8
    6.2
    Change from baseline at Week 80
    7.0
    6.2
    Change from baseline at Week 84
    7.3
    7.3
    Change from baseline at Week 88
    6.8
    7.0
    Change from baseline at Week 92
    7.0
    7.6
    Change from baseline at Week 96
    7.0
    7.6
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 4
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -0.0
    Confidence Interval (2-Sided) 95%
    -1.6 to 1.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 8
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -0.6
    Confidence Interval (2-Sided) 95%
    -2.3 to 1.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 12
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 0.0
    Confidence Interval (2-Sided) 95%
    -1.9 to 2.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2 mg) was estimated using a bootstrap method.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 16
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 0.0
    Confidence Interval (2-Sided) 95%
    -2.1 to 2.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 20
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 0.6
    Confidence Interval (2-Sided) 95%
    -2.0 to 3.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 24
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -0.5
    Confidence Interval (2-Sided) 95%
    -3.0 to 2.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 28
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -0.5
    Confidence Interval (2-Sided) 95%
    -3.0 to 2.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 32
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -0.5
    Confidence Interval (2-Sided) 95%
    -3.2 to 2.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 36
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 0.4
    Confidence Interval (2-Sided) 95%
    -2.3 to 3.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 40
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 1.2
    Confidence Interval (2-Sided) 95%
    -1.7 to 4.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 44
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 0.1
    Confidence Interval (2-Sided) 95%
    -2.7 to 3.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 48
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -1.0
    Confidence Interval (2-Sided) 95%
    -3.9 to 2.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 52
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -1.0
    Confidence Interval (2-Sided) 95%
    -4.3 to 2.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 56
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 0.6
    Confidence Interval (2-Sided) 95%
    -2.8 to 3.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 60
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 0.6
    Confidence Interval (2-Sided) 95%
    -2.5 to 4.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 64
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 0.7
    Confidence Interval (2-Sided) 95%
    -2.7 to 4.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 68
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -0.9
    Confidence Interval (2-Sided) 95%
    -4.2 to 2.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 72
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 0.9
    Confidence Interval (2-Sided) 95%
    -2.5 to 4.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 76
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 0.7
    Confidence Interval (2-Sided) 95%
    -2.5 to 4.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 80
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 0.9
    Confidence Interval (2-Sided) 95%
    -2.4 to 4.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 21
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 84
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 0.2
    Confidence Interval (2-Sided) 95%
    -3.1 to 4.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 22
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 88
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -0.2
    Confidence Interval (2-Sided) 95%
    -3.5 to 3.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 23
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 92
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -0.4
    Confidence Interval (2-Sided) 95%
    -3.8 to 3.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 24
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 96
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -0.4
    Confidence Interval (2-Sided) 95%
    -3.8 to 3.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    15. Secondary Outcome
    Title Percentage of Subjects With >=10 Letter Loss From Baseline in BCVA (Letters Read) at Each Post-baseline Visit - Study Eye
    Description BCVA (with spectacles or other visual corrective devices) was assessed using ETDRS testing at 4 meters and reported in letters read correctly. Baseline was defined as the last measurement prior to first treatment. An increase (gain) in letters read from the baseline assessment indicates improvement. 95% confidence interval (CI) for binomial proportions was based on Clopper-Pearson exact method. One eye (study eye) contributed to the analysis.
    Time Frame Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96

    Outcome Measure Data

    Analysis Population Description
    FAS - LOCF
    Arm/Group Title Brolucizumab 6 mg Aflibercept 2 mg
    Arm/Group Description Single IVT injection of brolucizumab at Day 0, Week 4, and Week 8, followed by q8w/q12w maintenance regimen until study exit Single IVT injection of aflibercept at Day 0, Week 4, and Week 8, followed by q8w maintenance regimen until study exit
    Measure Participants 370 369
    Change from baseline at Week 4
    1.9
    2.4
    Change from baseline at Week 8
    2.2
    2.2
    Change from baseline at Week 12
    2.7
    3.0
    Change from baseline at Week 16
    3.8
    5.1
    Change from baseline at Week 20
    5.9
    4.6
    Change from baseline at Week 24
    5.1
    6.0
    Change from baseline at Week 28
    5.9
    5.7
    Change from baseline at Week 32
    5.9
    6.2
    Change from baseline at Week 36
    6.5
    6.2
    Change from baseline at Week 40
    7.0
    6.0
    Change from baseline at Week 44
    8.6
    6.2
    Change from baseline at Week 48
    6.8
    7.3
    Change from baseline at Week 52
    8.1
    7.3
    Change from baseline at Week 56
    9.2
    8.1
    Change from baseline at Week 60
    8.1
    7.3
    Change from baseline at Week 64
    8.4
    8.7
    Change from baseline at Week 68
    7.6
    8.4
    Change from baseline at Week 72
    7.8
    8.1
    Change from baseline at Week 76
    9.5
    9.2
    Change from baseline at Week 80
    9.2
    10.0
    Change from baseline at Week 84
    9.5
    9.5
    Change from baseline at Week 88
    8.9
    9.8
    Change from baseline at Week 92
    9.2
    11.1
    Change from baseline at Week 96
    9.2
    10.3
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 4
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -0.5
    Confidence Interval (2-Sided) 95%
    -2.6 to 1.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 8
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -0.0
    Confidence Interval (2-Sided) 95%
    -2.2 to 2.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 12
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -0.3
    Confidence Interval (2-Sided) 95%
    -2.8 to 2.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 16
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -1.4
    Confidence Interval (2-Sided) 95%
    -4.4 to 1.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 20
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 1.4
    Confidence Interval (2-Sided) 95%
    -1.7 to 4.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 24
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -0.7
    Confidence Interval (2-Sided) 95%
    -3.9 to 2.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 28
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 0.3
    Confidence Interval (2-Sided) 95%
    -3.2 to 3.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 32
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -0.1
    Confidence Interval (2-Sided) 95%
    -3.8 to 3.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 36
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 0.3
    Confidence Interval (2-Sided) 95%
    -3.0 to 4.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 40
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 1.2
    Confidence Interval (2-Sided) 95%
    -2.4 to 5.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 44
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 2.5
    Confidence Interval (2-Sided) 95%
    -1.1 to 6.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 48
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -0.4
    Confidence Interval (2-Sided) 95%
    -4.0 to 3.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 52
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 0.9
    Confidence Interval (2-Sided) 95%
    -2.8 to 4.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 56
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 1.2
    Confidence Interval (2-Sided) 95%
    -2.8 to 5.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 60
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference of proportions
    Estimated Value 1.0
    Confidence Interval (2-Sided) 95%
    -2.6 to 4.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 64
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -0.1
    Confidence Interval (2-Sided) 95%
    -4.0 to 4.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 68
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -0.6
    Confidence Interval (2-Sided) 95%
    -4.2 to 3.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 72
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -0.1
    Confidence Interval (2-Sided) 95%
    -4.0 to 3.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 76
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 0.4
    Confidence Interval (2-Sided) 95%
    -3.5 to 4.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 80
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -0.7
    Confidence Interval (2-Sided) 95%
    -4.5 to 3.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 21
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 84
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 0.2
    Confidence Interval (2-Sided) 95%
    -3.6 to 4.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 22
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 88
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -0.7
    Confidence Interval (2-Sided) 95%
    -4.5 to 3.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 23
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 92
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -1.8
    Confidence Interval (2-Sided) 95%
    -5.7 to 2.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 24
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 96
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -1.0
    Confidence Interval (2-Sided) 95%
    -4.9 to 3.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    16. Secondary Outcome
    Title Percentage of Subjects With >=5 Letter Loss From Baseline in BCVA (Letters Read) at Each Post-baseline Visit - Study Eye
    Description BCVA (with spectacles or other visual corrective devices) was assessed using ETDRS testing at 4 meters and reported in letters read correctly. Baseline was defined as the last measurement prior to first treatment. An increase (gain) in letters read from the baseline assessment indicates improvement. 95% confidence interval (CI) for binomial proportions was based on Clopper-Pearson exact method. One eye (study eye) contributed to the analysis.
    Time Frame Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96

    Outcome Measure Data

    Analysis Population Description
    FAS - LOCF
    Arm/Group Title Brolucizumab 6 mg Aflibercept 2 mg
    Arm/Group Description Single IVT injection of brolucizumab at Day 0, Week 4, and Week 8, followed by q8w/q12w maintenance regimen until study exit Single IVT injection of aflibercept at Day 0, Week 4, and Week 8, followed by q8w maintenance regimen until study exit
    Measure Participants 370 369
    Change from baseline at Week 4
    6.2
    6.5
    Change from baseline at Week 8
    7.8
    8.4
    Change from baseline at Week 12
    8.4
    9.5
    Change from baseline at Week 16
    10.8
    8.9
    Change from baseline at Week 20
    11.6
    8.1
    Change from baseline at Week 24
    13.0
    10.0
    Change from baseline at Week 28
    11.4
    8.9
    Change from baseline at Week 32
    12.2
    11.1
    Change from baseline at Week 36
    12.7
    9.5
    Change from baseline at Week 40
    11.9
    11.1
    Change from baseline at Week 44
    11.9
    9.2
    Change from baseline at Week 48
    11.1
    11.9
    Change from baseline at Week 52
    13.2
    11.4
    Change from baseline at Week 56
    13.2
    11.7
    Change from baseline at Week 60
    12.7
    11.7
    Change from baseline at Week 64
    12.7
    12.5
    Change from baseline at Week 68
    13.8
    12.2
    Change from baseline at Week 72
    14.1
    13.6
    Change from baseline at Week 76
    14.1
    13.6
    Change from baseline at Week 80
    13.8
    15.2
    Change from baseline at Week 84
    14.1
    14.6
    Change from baseline at Week 88
    13.0
    14.4
    Change from baseline at Week 92
    14.3
    16.0
    Change from baseline at Week 96
    14.3
    14.6
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 4
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -0.2
    Confidence Interval (2-Sided) 95%
    -3.5 to 3.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 8
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -0.5
    Confidence Interval (2-Sided) 95%
    -4.4 to 3.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 12
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -1.0
    Confidence Interval (2-Sided) 95%
    -5.0 to 3.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 16
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 1.9
    Confidence Interval (2-Sided) 95%
    -1.9 to 6.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 20
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 3.7
    Confidence Interval (2-Sided) 95%
    -0.4 to 7.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Number of subjects with >=5 letter loss from baseline in BCVA (letters read) at each post-baseline visit - Week 24
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 3.1
    Confidence Interval (2-Sided) 95%
    -1.3 to 7.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 28
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 2.6
    Confidence Interval (2-Sided) 95%
    -1.7 to 7.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 32
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 1.2
    Confidence Interval (2-Sided) 95%
    -3.2 to 5.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 36
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 3.4
    Confidence Interval (2-Sided) 95%
    -0.7 to 8.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 40
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 1.0
    Confidence Interval (2-Sided) 95%
    -3.8 to 5.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 44
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 2.9
    Confidence Interval (2-Sided) 95%
    -1.4 to 7.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 48
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -0.7
    Confidence Interval (2-Sided) 95%
    -5.1 to 3.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 52
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 2.1
    Confidence Interval (2-Sided) 95%
    -2.5 to 6.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 56
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 1.8
    Confidence Interval (2-Sided) 95%
    -2.8 to 6.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 60
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 1.2
    Confidence Interval (2-Sided) 95%
    -3.6 to 5.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 64
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 0.5
    Confidence Interval (2-Sided) 95%
    -4.0 to 5.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 68
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 1.8
    Confidence Interval (2-Sided) 95%
    -2.8 to 6.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 72
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 0.7
    Confidence Interval (2-Sided) 95%
    -4.3 to 5.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 76
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 0.7
    Confidence Interval (2-Sided) 95%
    -4.4 to 5.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 80
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -1.2
    Confidence Interval (2-Sided) 95%
    -6.0 to 3.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 21
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 84
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -0.4
    Confidence Interval (2-Sided) 95%
    -5.2 to 4.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 22
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 88
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -1.2
    Confidence Interval (2-Sided) 95%
    -5.7 to 3.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 23
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 92
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -1.5
    Confidence Interval (2-Sided) 95%
    -6.5 to 3.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 24
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 96
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -0.1
    Confidence Interval (2-Sided) 95%
    -5.1 to 4.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    17. Secondary Outcome
    Title Percentage of Subjects With BCVA of 73 Letters Read or More at Each Visit - Study Eye
    Description BCVA (with spectacles or other visual corrective devices) was assessed using ETDRS testing at 4 meters and reported in letters read correctly (0-100 letters). A score of 65 to 70 letters represents a low to moderate visual acuity. Baseline was defined as the last measurement prior to first treatment. 95% confidence interval (CI) for binomial proportions was based on Clopper-Pearson exact method. One eye (study eye) contributed to the analysis.
    Time Frame Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96

    Outcome Measure Data

    Analysis Population Description
    FAS - LOCF
    Arm/Group Title Brolucizumab 6 mg Aflibercept 2 mg
    Arm/Group Description Single intravitreal (IVT) injection of brolucizumab at Day 0, Week 4, and Week 8, followed by 1 injection every 8 weeks/1 injection every 12 weeks (q8w/q12w) maintenance regimen until study exit Single IVT injection of aflibercept at Day 0, Week 4, and Week 8, followed by q8w maintenance regimen until study exit
    Measure Participants 370 369
    Baseline
    21.4
    17.9
    Week 4
    31.9
    34.7
    Week 8
    40.3
    41.2
    Week 12
    43.5
    44.7
    Week 16
    44.1
    42.5
    Week 20
    44.1
    45.0
    Week 24
    45.4
    47.4
    Week 28
    48.6
    50.4
    Week 32
    47.8
    49.6
    Week 36
    47.6
    49.9
    Week 40
    48.9
    49.3
    Week 44
    50.3
    50.4
    Week 48
    51.4
    49.6
    Week 52
    49.7
    50.1
    Week 56
    50.5
    50.9
    Week 60
    48.9
    52.3
    Week 64
    49.2
    50.7
    Week 68
    48.9
    50.7
    Week 72
    48.9
    49.3
    Week 76
    48.9
    49.9
    Week 80
    51.9
    50.1
    Week 84
    48.4
    49.6
    Week 88
    50.5
    50.7
    Week 92
    50.5
    49.9
    Week 96
    48.1
    49.1
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 4
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -4.0
    Confidence Interval (2-Sided) 95%
    -9.2 to 1.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 8
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -2.1
    Confidence Interval (2-Sided) 95%
    -8.1 to 3.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 12
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -2.5
    Confidence Interval (2-Sided) 95%
    -8.4 to 3.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 16
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 0.3
    Confidence Interval (2-Sided) 95%
    -5.4 to 6.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 20
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -2.2
    Confidence Interval (2-Sided) 95%
    -8.2 to 4.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 24
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -3.1
    Confidence Interval (2-Sided) 95%
    -9.0 to 3.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 28
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -3.2
    Confidence Interval (2-Sided) 95%
    -9.3 to 2.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 32
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -3.1
    Confidence Interval (2-Sided) 95%
    -9.6 to 2.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 36
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -3.7
    Confidence Interval (2-Sided) 95%
    -9.6 to 2.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 40
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -1.7
    Confidence Interval (2-Sided) 95%
    -7.6 to 4.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 44
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -1.4
    Confidence Interval (2-Sided) 95%
    -7.5 to 5.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 48
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 0.4
    Confidence Interval (2-Sided) 95%
    -5.4 to 6.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 52
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -1.8
    Confidence Interval (2-Sided) 95%
    -7.7 to 4.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 56
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -1.9
    Confidence Interval (2-Sided) 95%
    -7.7 to 4.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 60
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -4.7
    Confidence Interval (2-Sided) 95%
    -10.8 to 1.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 64
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -2.8
    Confidence Interval (2-Sided) 95%
    -8.9 to 3.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 68
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -3.1
    Confidence Interval (2-Sided) 95%
    -9.5 to 2.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 72
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -1.6
    Confidence Interval (2-Sided) 95%
    -7.9 to 4.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 76
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -2.0
    Confidence Interval (2-Sided) 95%
    -8.1 to 4.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 80
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 0.5
    Confidence Interval (2-Sided) 95%
    -5.6 to 6.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 21
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 84
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -2.4
    Confidence Interval (2-Sided) 95%
    -8.3 to 3.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 22
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 88
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -1.3
    Confidence Interval (2-Sided) 95%
    -7.4 to 4.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 23
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 92
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -0.5
    Confidence Interval (2-Sided) 95%
    -6.5 to 5.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 24
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 96
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -2.0
    Confidence Interval (2-Sided) 95%
    -8.1 to 4.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for BCVA categories, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    18. Secondary Outcome
    Title Change From Baseline in Central Subfield Thickness (CSFT) at Each Post-baseline Visit - Study Eye
    Description CSFT (the average retinal thickness of the circular area within 1 millimeter diameter around the foveal center) was assessed using Spectral-Domain Optical Coherence Tomography (SD-OCT), a non-invasive measurement which produces cross-sectional and 3-dimensional images of the eye. A negative change value indicates an improvement, while a positive change value indicates a worsening. One eye (study eye) contributed to the analysis.
    Time Frame Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96

    Outcome Measure Data

    Analysis Population Description
    FAS - LOCF
    Arm/Group Title Brolucizumab 6 mg Aflibercept 2 mg
    Arm/Group Description Single IVT injection of brolucizumab at Day 0, Week 4, and Week 8, followed by q8w/q12w maintenance regimen until study exit Single IVT injection of aflibercept at Day 0, Week 4, and Week 8, followed by q8w maintenance regimen until study exit
    Measure Participants 370 369
    Change from baseline at Week 4
    -160.7
    (126.55)
    -149.2
    (111.60)
    Change from baseline at Week 8
    -181.8
    (142.11)
    -159.6
    (120.93)
    Change from baseline at Week 12
    -190.5
    (148.05)
    -167.6
    (123.66)
    Change from baseline at Week 16
    -170.9
    (152.48)
    -137.7
    (136.76)
    Change from baseline at Week 20
    -161.0
    (151.81)
    -165.3
    (132.70)
    Change from baseline at Week 24
    -177.8
    (150.62)
    -137.3
    (139.32)
    Change from baseline at Week 28
    -182.7
    (156.04)
    -166.6
    (138.22)
    Change from baseline at Week 32
    -168.9
    (157.61)
    -142.6
    (135.87)
    Change from baseline at Week 36
    -192.6
    (156.51)
    -170.2
    (131.42)
    Change from baseline at Week 40
    -183.4
    (156.83)
    -146.5
    (142.69)
    Change from baseline at Week 44
    -183.8
    (161.42)
    -172.7
    (135.06)
    Change from baseline at Week 48
    -189.8
    (158.35)
    -147.8
    (144.97)
    Change from baseline at Week 52
    -193.8
    (157.22)
    -173.9
    (134.84)
    Change from baseline at Week 56
    -184.9
    (162.66)
    -149.9
    (145.37)
    Change from baseline at Week 60
    -195.4
    (161.34)
    -172.2
    (136.58)
    Change from baseline at Week 64
    -190.9
    (160.06)
    -153.1
    (144.45)
    Change from baseline at Week 68
    -188.4
    (161.63)
    -172.9
    (136.76)
    Change from baseline at Week 72
    -192.3
    (160.70)
    -153.1
    (145.02)
    Change from baseline at Week 76
    -193.1
    (162.00)
    -173.1
    (138.96)
    Change from baseline at Week 80
    -188.2
    (165.90)
    -155.6
    (147.09)
    Change from baseline at Week 84
    -196.2
    (161.97)
    -173.4
    (142.11)
    Change from baseline at Week 88
    -192.7
    (162.46)
    -158.3
    (147.24)
    Change from baseline at Week 92
    -194.9
    (162.35)
    -173.9
    (142.30)
    Change from baseline at Week 96
    -193.6
    (163.97)
    -159.3
    (146.26)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 4
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -17.7
    Confidence Interval (2-Sided) 95%
    -32.6 to -2.9
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 7.57
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 8
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -29.5
    Confidence Interval (2-Sided) 95%
    -45.6 to -13.4
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 8.18
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 12
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -30.3
    Confidence Interval (2-Sided) 95%
    -46.9 to -13.7
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 8.45
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 16
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -40.2
    Confidence Interval (2-Sided) 95%
    -58.9 to -21.6
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 9.51
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 20
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -2.9
    Confidence Interval (2-Sided) 95%
    -20.9 to 15.0
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 9.12
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 24
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -47.8
    Confidence Interval (2-Sided) 95%
    -66.3 to -29.3
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 9.42
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 28
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -23.7
    Confidence Interval (2-Sided) 95%
    -42.0 to -5.4
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 9.34
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 32
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -33.7
    Confidence Interval (2-Sided) 95%
    -52.4 to -15.0
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 9.54
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 36
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -30.4
    Confidence Interval (2-Sided) 95%
    -48.0 to -12.9
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 8.94
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 40
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -44.7
    Confidence Interval (2-Sided) 95%
    -63.5 to -25.9
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 9.57
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 44
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -19.2
    Confidence Interval (2-Sided) 95%
    -37.3 to -1.1
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 9.24
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 48
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -49.9
    Confidence Interval (2-Sided) 95%
    -68.9 to -30.9
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 9.68
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 52
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -28.1
    Confidence Interval (2-Sided) 95%
    -45.8 to -10.4
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 9.01
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 56
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -43.1
    Confidence Interval (2-Sided) 95%
    -62.4 to -23.7
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 9.86
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 60
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -31.1
    Confidence Interval (2-Sided) 95%
    -49.5 to -12.8
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 9.34
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 64
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -45.8
    Confidence Interval (2-Sided) 95%
    -64.9 to -26.8
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 9.70
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 68
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -23.7
    Confidence Interval (2-Sided) 95%
    -42.0 to -5.4
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 9.31
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 72
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -47.3
    Confidence Interval (2-Sided) 95%
    -66.4 to -28.3
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 9.69
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 76
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -28.0
    Confidence Interval (2-Sided) 95%
    -46.5 to -9.5
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 9.43
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 80
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -40.9
    Confidence Interval (2-Sided) 95%
    -60.4 to -21.4
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 9.94
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 21
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 84
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -31.0
    Confidence Interval (2-Sided) 95%
    -49.6 to -12.4
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 9.48
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 22
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 88
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -42.6
    Confidence Interval (2-Sided) 95%
    -61.9 to -23.3
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 9.84
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 23
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 92
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -29.1
    Confidence Interval (2-Sided) 95%
    -47.9 to -10.3
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 9.56
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 24
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 96
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -42.6
    Confidence Interval (2-Sided) 95%
    -62.0 to -23.3
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 9.87
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    19. Secondary Outcome
    Title Average Change From Baseline in CSFT Over the Period Week 36 Through Week 48 - Study Eye
    Description CSFT (the average retinal thickness of the circular area within 1 millimeter diameter around the foveal center) was assessed using SD-OCT, a non-invasive measurement which produces cross-sectional and 3-dimensional images of the eye. A negative change value indicates an improvement, while a positive change value indicates a worsening. One eye (study eye) contributed to the analysis.
    Time Frame Baseline, Weeks 36, 40, 44, 48

    Outcome Measure Data

    Analysis Population Description
    FAS - LOCF
    Arm/Group Title Brolucizumab 6 mg Aflibercept 2 mg
    Arm/Group Description Single intravitreal (IVT) injection of brolucizumab at Day 0, Week 4, and Week 8, followed by 1 injection every 8 weeks/1 injection every 12 weeks (q8w/q12w) maintenance regimen until study exit Single IVT injection of aflibercept at Day 0, Week 4, and Week 8, followed by q8w maintenance regimen until study exit
    Measure Participants 370 369
    Mean (Standard Deviation) [micrometers]
    -187.4
    (155.58)
    -159.3
    (135.92)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -36.1
    Confidence Interval (2-Sided) 95%
    -54.0 to -18.1
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 9.13
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    20. Secondary Outcome
    Title Average Change From Baseline in CSFT Over the Period Week 84 Through Week 96 - Study Eye
    Description CSFT (the average retinal thickness of the circular area within 1 millimeter diameter around the foveal center) was assessed using SD-OCT, a non-invasive measurement which produces cross-sectional and 3-dimensional images of the eye. A negative change value indicates an improvement, while a positive change value indicates a worsening. One eye (study eye) contributed to the analysis.
    Time Frame Baseline, Weeks 84, 88, 92, 96

    Outcome Measure Data

    Analysis Population Description
    FAS - LOCF
    Arm/Group Title Brolucizumab 6 mg Aflibercept 2 mg
    Arm/Group Description Single intravitreal (IVT) injection of brolucizumab at Day 0, Week 4, and Week 8, followed by 1 injection every 8 weeks/1 injection every 12 weeks (q8w/q12w) maintenance regimen until study exit Single IVT injection of aflibercept at Day 0, Week 4, and Week 8, followed by q8w maintenance regimen until study exit
    Measure Participants 370 369
    Mean (Standard Deviation) [micrometers]
    -194.3
    (161.24)
    -166.2
    (142.81)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -36.3
    Confidence Interval (2-Sided) 95%
    -55.1 to -17.6
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 9.56
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    21. Secondary Outcome
    Title Average Change From Baseline in CSFT Over the Period Week 4 Through Week 48/96 - Study Eye
    Description CSFT (the average retinal thickness of the circular area within 1 millimeter diameter around the foveal center) was assessed using SD-OCT, a non-invasive measurement which produces cross-sectional and 3-dimensional images of the eye. A negative change value indicates an improvement, while a positive change value indicates a worsening. One eye (study eye) contributed to the analysis.
    Time Frame Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96

    Outcome Measure Data

    Analysis Population Description
    FAS - LOCF
    Arm/Group Title Brolucizumab 6 mg Aflibercept 2 mg
    Arm/Group Description Single intravitreal (IVT) injection of brolucizumab at Day 0, Week 4, and Week 8, followed by 1 injection every 8 weeks/1 injection every 12 weeks (q8w/q12w) maintenance regimen until study exit Single IVT injection of aflibercept at Day 0, Week 4, and Week 8, followed by q8w maintenance regimen until study exit
    Measure Participants 370 369
    Change from baseline over the period Week 4 to 48
    -178.7
    (145.33)
    -155.3
    (126.83)
    Change from baseline over the period Week 4 to 96
    -185.4
    (151.35)
    -159.7
    (131.74)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 4 to Week 48
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -30.8
    Confidence Interval (2-Sided) 95%
    -47.6 to -14.1
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 8.53
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 4 to Week 96
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -33.5
    Confidence Interval (2-Sided) 95%
    -50.8 to -16.1
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 8.84
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    22. Secondary Outcome
    Title Change From Baseline in Choroidal Neovascularization (CNV) Lesion Size at Week 12, Week 48, and Week 96 - Study Eye
    Description CNV lesion size (the area of new blood vessels in the choroid layer of the retina) size was measured using fluorescein angiography (FA). A negative change value indicates a reduction in lesion size, whereas a positive change value indicates an increase. An increase in CNV lesion size may indicate progression of the underlying disease. Only one eye (study eye) contributed to the analysis.
    Time Frame Baseline, Weeks 12, 48, 96

    Outcome Measure Data

    Analysis Population Description
    FAS - LOCF
    Arm/Group Title Brolucizumab 6 mg Aflibercept 2 mg
    Arm/Group Description Single IVT injection of brolucizumab at Day 0, Week 4, and Week 8, followed by q8w/q12w maintenance regimen until study exit Single IVT injection of aflibercept at Day 0, Week 4, and Week 8, followed by q8w maintenance regimen until study exit
    Measure Participants 370 369
    Change from baseline at Week 12
    -2.2
    (2.71)
    -2.5
    (4.02)
    Change from baseline at Week 48
    -2.3
    (2.76)
    -2.5
    (4.04)
    Change from baseline at Week 96
    -2.5
    (2.77)
    -2.7
    (4.03)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 12
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value 0.3
    Confidence Interval (2-Sided) 95%
    0.0 to 0.7
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.18
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 48
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value 0.3
    Confidence Interval (2-Sided) 95%
    -0.1 to 0.6
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.17
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 96
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value 0.3
    Confidence Interval (2-Sided) 95%
    0.0 to 0.6
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.16
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    23. Secondary Outcome
    Title Change From Baseline in Central Subfield Neurosensory Retinal Thickness (CSFTns) at Each Post-baseline Visit - Study Eye
    Description CSFTns was assessed using SD-OCT. A negative change value indicates an improvement, while a positive change value indicates a worsening. One eye (study eye) contributed to the analysis.
    Time Frame Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96

    Outcome Measure Data

    Analysis Population Description
    FAS - LOCF
    Arm/Group Title Brolucizumab 6 mg Aflibercept 2 mg
    Arm/Group Description Single IVT injection of brolucizumab at Day 0, Week 4, and Week 8, followed by q8w/q12w maintenance regimen until study exit Single IVT injection of aflibercept at Day 0, Week 4, and Week 8, followed by q8w maintenance regimen until study exit
    Measure Participants 370 369
    Change from baseline at Week 4
    -51.7
    (91.79)
    -44.2
    (80.37)
    Change from baseline at Week 8
    -55.0
    (94.92)
    -45.4
    (84.99)
    Change from baseline at Week 12
    -52.7
    (96.89)
    -42.4
    (85.48)
    Change from baseline at Week 16
    -50.5
    (98.30)
    -41.2
    (84.78)
    Change from baseline at Week 20
    -49.2
    (95.87)
    -48.1
    (88.08)
    Change from baseline at Week 24
    -53.4
    (98.35)
    -41.8
    (90.17)
    Change from baseline at Week 28
    -56.4
    (99.86)
    -47.3
    (87.90)
    Change from baseline at Week 32
    -49.8
    (99.41)
    -42.0
    (90.50)
    Change from baseline at Week 36
    -59.1
    (101.18)
    -47.8
    (89.64)
    Change from baseline at Week 40
    -55.9
    (100.01)
    -43.2
    (91.94)
    Change from baseline at Week 44
    -56.2
    (106.65)
    -47.1
    (90.03)
    Change from baseline at Week 48
    -54.8
    (100.28)
    -41.8
    (93.99)
    Change from baseline at Week 52
    -58.4
    (102.35)
    -49.1
    (90.31)
    Change from baseline at Week 56
    -57.3
    (100.85)
    -45.8
    (91.95)
    Change from baseline at Week 60
    -60.3
    (100.56)
    -49.3
    (90.52)
    Change from baseline at Week 64
    -58.0
    (100.89)
    -47.5
    (92.59)
    Change from baseline at Week 68
    -56.7
    (100.16)
    -49.5
    (91.20)
    Change from baseline at Week 72
    -58.6
    (101.34)
    -47.3
    (92.25)
    Change from baseline at Week 76
    -59.7
    (101.61)
    -50.2
    (91.51)
    Change from baseline at Week 80
    -57.8
    (102.92)
    -47.6
    (92.34)
    Change from baseline at Week 84
    -60.4
    (102.80)
    -50.6
    (92.57)
    Change from baseline at Week 88
    -59.7
    (101.97)
    -49.1
    (94.52)
    Change from baseline at Week 92
    -60.1
    (102.00)
    -51.0
    (91.79)
    Change from baseline at Week 96
    -58.9
    (102.48)
    -49.4
    (94.86)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 4
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -2.1
    Confidence Interval (2-Sided) 95%
    -11.6 to 7.3
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.80
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 8
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -3.8
    Confidence Interval (2-Sided) 95%
    -13.6 to 6.0
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.98
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 12
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -4.5
    Confidence Interval (2-Sided) 95%
    -14.3 to 5.3
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.98
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 16
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -3.7
    Confidence Interval (2-Sided) 95%
    -13.7 to 6.4
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.12
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 20
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value 4.6
    Confidence Interval (2-Sided) 95%
    -5.5 to 14.6
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.11
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 24
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -5.8
    Confidence Interval (2-Sided) 95%
    -16.3 to 4.7
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.35
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 28
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -3.1
    Confidence Interval (2-Sided) 95%
    -13.1 to 7.0
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.13
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 32
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -2.0
    Confidence Interval (2-Sided) 95%
    -12.6 to 8.5
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.37
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 36
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -5.0
    Confidence Interval (2-Sided) 95%
    -15.2 to 5.1
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.15
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 40
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -6.6
    Confidence Interval (2-Sided) 95%
    -17.0 to 3.8
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.30
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 44
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -2.8
    Confidence Interval (2-Sided) 95%
    -13.4 to 7.9
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.42
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 48
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -7.0
    Confidence Interval (2-Sided) 95%
    -17.6 to 3.7
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.40
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 52
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -2.7
    Confidence Interval (2-Sided) 95%
    -12.9 to 7.5
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.19
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 56
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -5.0
    Confidence Interval (2-Sided) 95%
    -15.4 to 5.4
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.31
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 60
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -4.2
    Confidence Interval (2-Sided) 95%
    -14.3 to 5.9
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.15
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 64
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -3.9
    Confidence Interval (2-Sided) 95%
    -14.2 to 6.4
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.24
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 68
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -0.6
    Confidence Interval (2-Sided) 95%
    -10.7 to 9.6
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.17
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 72
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -4.6
    Confidence Interval (2-Sided) 95%
    -14.8 to 5.7
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.24
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 76
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -2.8
    Confidence Interval (2-Sided) 95%
    -13.1 to 7.4
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.23
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 80
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -3.7
    Confidence Interval (2-Sided) 95%
    -14.1 to 6.8
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.33
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 21
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 84
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -3.1
    Confidence Interval (2-Sided) 95%
    -13.5 to 7.3
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.30
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 22
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 88
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -4.0
    Confidence Interval (2-Sided) 95%
    -14.6 to 6.5
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.39
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 23
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 92
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -2.3
    Confidence Interval (2-Sided) 95%
    -12.6 to 8.0
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.25
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    Statistical Analysis 24
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 96
    Type of Statistical Test Other
    Comments Treatment difference
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -3.0
    Confidence Interval (2-Sided) 95%
    -13.6 to 7.7
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.42
    Estimation Comments Least squares mean difference (Brolucizumab 6mg - Aflibercept 2mg)
    24. Secondary Outcome
    Title Percentage of Subjects With Presence of Subretinal Fluid at Each Post-baseline Visit - Study Eye
    Description Subretinal fluid was assessed using SD-OCT and recorded as Present/Absent. The presence of subretinal fluid is an indicator of underlying disease. One eye (study eye) contributed to the analysis.
    Time Frame Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96

    Outcome Measure Data

    Analysis Population Description
    FAS - LOCF
    Arm/Group Title Brolucizumab 6 mg Aflibercept 2 mg
    Arm/Group Description Single IVT injection of brolucizumab at Day 0, Week 4, and Week 8, followed by q8w/q12w maintenance regimen until study exit Single IVT injection of aflibercept at Day 0, Week 4, and Week 8, followed by q8w maintenance regimen until study exit
    Measure Participants 370 369
    Week 4
    29.2
    36.9
    Week 8
    14.1
    22.8
    Week 12
    13.5
    20.6
    Week 16
    21.1
    35.5
    Week 20
    25.1
    22.5
    Week 24
    17.3
    36.9
    Week 28
    15.9
    22.0
    Week 32
    24.1
    34.4
    Week 36
    13.5
    21.7
    Week 40
    18.1
    33.9
    Week 44
    23.8
    21.7
    Week 48
    17.6
    33.9
    Week 52
    19.7
    22.8
    Week 56
    24.3
    33.6
    Week 60
    20.0
    24.4
    Week 64
    20.3
    35.5
    Week 68
    23.2
    23.6
    Week 72
    17.8
    34.7
    Week 76
    21.6
    23.0
    Week 80
    22.7
    33.9
    Week 84
    18.9
    24.7
    Week 88
    19.7
    31.7
    Week 92
    17.3
    22.8
    Week 96
    15.7
    30.4
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 4
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -6.6
    Confidence Interval (2-Sided) 95%
    -13.2 to -0.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 8
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -8.5
    Confidence Interval (2-Sided) 95%
    -13.8 to -3.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 12
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -6.9
    Confidence Interval (2-Sided) 95%
    -12.2 to -1.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 16
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -14.2
    Confidence Interval (2-Sided) 95%
    -20.8 to -8.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 20
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 3.1
    Confidence Interval (2-Sided) 95%
    -2.9 to 9.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 24
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -19.2
    Confidence Interval (2-Sided) 95%
    -25.5 to -13.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 28
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -5.9
    Confidence Interval (2-Sided) 95%
    -11.6 to -0.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 32
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -9.8
    Confidence Interval (2-Sided) 95%
    -16.5 to -3.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 36
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -8.0
    Confidence Interval (2-Sided) 95%
    -13.6 to -2.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 40
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -15.4
    Confidence Interval (2-Sided) 95%
    -21.5 to -9.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 44
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 2.5
    Confidence Interval (2-Sided) 95%
    -3.2 to 8.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 48
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -15.9
    Confidence Interval (2-Sided) 95%
    -22.4 to -10.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 52
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -2.7
    Confidence Interval (2-Sided) 95%
    -8.5 to 3.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 56
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -9.0
    Confidence Interval (2-Sided) 95%
    -15.7 to -2.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 60
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -3.9
    Confidence Interval (2-Sided) 95%
    -9.8 to 2.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 64
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -15.1
    Confidence Interval (2-Sided) 95%
    -21.3 to -8.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 68
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 0.1
    Confidence Interval (2-Sided) 95%
    -6.1 to 6.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 72
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -16.6
    Confidence Interval (2-Sided) 95%
    -22.6 to -10.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 76
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -1.1
    Confidence Interval (2-Sided) 95%
    -7.0 to 5.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 80
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -11.0
    Confidence Interval (2-Sided) 95%
    -17.4 to -5.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 21
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 84
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -5.3
    Confidence Interval (2-Sided) 95%
    -11.3 to 0.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 22
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 88
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -12.0
    Confidence Interval (2-Sided) 95%
    -18.9 to -5.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 23
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 92
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -5.5
    Confidence Interval (2-Sided) 95%
    -11.4 to 0.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 24
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 96
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -14.5
    Confidence Interval (2-Sided) 95%
    -20.3 to -8.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    25. Secondary Outcome
    Title Percentage of Subjects With Presence of Intraretinal Fluid at Each Post-baseline Visit - Study Eye
    Description Intraretinal fluid was assessed using SD-OCT and recorded as Present/Absent. The presence of intraretinal fluid is an indicator of underlying disease. One eye (study eye) contributed to the analysis.
    Time Frame Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96

    Outcome Measure Data

    Analysis Population Description
    FAS - LOCF
    Arm/Group Title Brolucizumab 6 mg Aflibercept 2 mg
    Arm/Group Description Single IVT injection of brolucizumab at Day 0, Week 4, and Week 8, followed by q8w/q12w maintenance regimen until study exit Single IVT injection of aflibercept at Day 0, Week 4, and Week 8, followed by q8w maintenance regimen until study exit
    Measure Participants 370 369
    Week 4
    10.3
    8.4
    Week 8
    7.0
    8.7
    Week 12
    7.6
    8.7
    Week 16
    12.7
    11.9
    Week 20
    16.5
    7.9
    Week 24
    10.5
    13.0
    Week 28
    9.2
    6.0
    Week 32
    14.3
    14.1
    Week 36
    7.0
    8.4
    Week 40
    13.2
    13.8
    Week 44
    12.4
    8.1
    Week 48
    11.1
    12.5
    Week 52
    9.2
    7.6
    Week 56
    13.0
    13.6
    Week 60
    8.4
    8.4
    Week 64
    10.3
    11.7
    Week 68
    11.1
    8.1
    Week 72
    11.1
    10.6
    Week 76
    9.2
    8.4
    Week 80
    12.4
    12.2
    Week 84
    10.5
    9.2
    Week 88
    10.8
    10.6
    Week 92
    10.8
    6.8
    Week 96
    10.8
    10.3
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 4
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 1.5
    Confidence Interval (2-Sided) 95%
    -2.5 to 5.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 8
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -2.1
    Confidence Interval (2-Sided) 95%
    -6.1 to 1.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 12
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -1.4
    Confidence Interval (2-Sided) 95%
    -5.3 to 2.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 16
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 0.1
    Confidence Interval (2-Sided) 95%
    -4.5 to 4.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 20
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 8.2
    Confidence Interval (2-Sided) 95%
    3.9 to 12.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 24
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -3.2
    Confidence Interval (2-Sided) 95%
    -7.9 to 1.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 28
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 2.8
    Confidence Interval (2-Sided) 95%
    -1.0 to 6.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 32
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -0.5
    Confidence Interval (2-Sided) 95%
    -5.5 to 4.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 36
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -1.8
    Confidence Interval (2-Sided) 95%
    -5.6 to 1.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 40
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -1.3
    Confidence Interval (2-Sided) 95%
    -6.0 to 3.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 44
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 3.8
    Confidence Interval (2-Sided) 95%
    -0.5 to 8.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 48
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -2.0
    Confidence Interval (2-Sided) 95%
    -6.2 to 2.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 52
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 1.2
    Confidence Interval (2-Sided) 95%
    -2.5 to 5.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 56
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -1.2
    Confidence Interval (2-Sided) 95%
    -5.9 to 3.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 60
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -0.6
    Confidence Interval (2-Sided) 95%
    -4.4 to 3.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 64
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -1.8
    Confidence Interval (2-Sided) 95%
    -6.2 to 2.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 68
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 2.6
    Confidence Interval (2-Sided) 95%
    -1.2 to 6.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 72
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 0.2
    Confidence Interval (2-Sided) 95%
    -4.2 to 4.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 76
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 0.4
    Confidence Interval (2-Sided) 95%
    -3.5 to 4.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 80
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -0.3
    Confidence Interval (2-Sided) 95%
    -4.8 to 4.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 21
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 84
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 0.9
    Confidence Interval (2-Sided) 95%
    -3.3 to 5.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 22
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 88
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -0.1
    Confidence Interval (2-Sided) 95%
    -4.5 to 3.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 23
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 92
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 3.8
    Confidence Interval (2-Sided) 95%
    -0.1 to 8.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 24
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 96
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 0.2
    Confidence Interval (2-Sided) 95%
    -4.3 to 4.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    26. Secondary Outcome
    Title Percentage of Subjects With Presence of Sub-retinal Pigment Epithelium (RPE) Fluid at Each Post-baseline Visit - Study Eye
    Description Sub-retinal pigment epithelium (RPE) fluid was assessed using SD-OCT and recorded as Present/Absent. The presence of sub-RPE fluid is an indicator of underlying disease. One eye (study eye) contributed to the analysis.
    Time Frame Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96

    Outcome Measure Data

    Analysis Population Description
    FAS - LOCF
    Arm/Group Title Brolucizumab 6 mg Aflibercept 2 mg
    Arm/Group Description Single IVT injection of brolucizumab at Day 0, Week 4, and Week 8, followed by q8w/q12w maintenance regimen until study exit Single IVT injection of aflibercept at Day 0, Week 4, and Week 8, followed by q8w maintenance regimen until study exit
    Measure Participants 370 369
    Week 4
    18.1
    21.7
    Week 8
    16.2
    18.7
    Week 12
    15.9
    17.6
    Week 16
    15.9
    23.8
    Week 20
    17.3
    16.0
    Week 24
    10.5
    18.4
    Week 28
    13.8
    15.7
    Week 32
    18.1
    23.3
    Week 36
    13.2
    18.7
    Week 40
    15.4
    21.4
    Week 44
    14.9
    14.4
    Week 48
    13.0
    22.0
    Week 52
    17.3
    19.0
    Week 56
    19.7
    24.9
    Week 60
    15.9
    21.7
    Week 64
    19.2
    24.1
    Week 68
    18.1
    23.3
    Week 72
    17.0
    23.8
    Week 76
    16.5
    22.0
    Week 80
    21.1
    27.6
    Week 84
    23.2
    24.7
    Week 88
    21.9
    26.8
    Week 92
    17.3
    23.0
    Week 96
    16.5
    22.5
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 4
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -3.5
    Confidence Interval (2-Sided) 95%
    -8.9 to 1.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 8
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -2.6
    Confidence Interval (2-Sided) 95%
    -7.6 to 2.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 12
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -1.6
    Confidence Interval (2-Sided) 95%
    -6.9 to 3.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 16
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -7.8
    Confidence Interval (2-Sided) 95%
    -13.0 to -2.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 20
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 1.3
    Confidence Interval (2-Sided) 95%
    -3.6 to 6.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 24
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -7.9
    Confidence Interval (2-Sided) 95%
    -12.6 to -3.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 28
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -2.1
    Confidence Interval (2-Sided) 95%
    -6.8 to 2.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 32
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -5.3
    Confidence Interval (2-Sided) 95%
    -10.5 to -0.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 36
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -5.5
    Confidence Interval (2-Sided) 95%
    -10.3 to -0.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 40
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -6.0
    Confidence Interval (2-Sided) 95%
    -11.2 to -0.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 44
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 0.5
    Confidence Interval (2-Sided) 95%
    -4.8 to 5.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 48
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -9.1
    Confidence Interval (2-Sided) 95%
    -13.8 to -3.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 52
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -1.8
    Confidence Interval (2-Sided) 95%
    -7.1 to 3.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 56
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -5.2
    Confidence Interval (2-Sided) 95%
    -11.1 to 0.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 60
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -5.6
    Confidence Interval (2-Sided) 95%
    -10.9 to -0.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 64
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -5.1
    Confidence Interval (2-Sided) 95%
    -10.9 to 0.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 68
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -5.2
    Confidence Interval (2-Sided) 95%
    -11.0 to -0.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 72
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -6.9
    Confidence Interval (2-Sided) 95%
    -12.5 to -1.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 76
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -5.5
    Confidence Interval (2-Sided) 95%
    -10.7 to -0.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 80
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -6.5
    Confidence Interval (2-Sided) 95%
    -12.4 to -0.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 21
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 84
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -1.4
    Confidence Interval (2-Sided) 95%
    -7.0 to 4.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 22
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 88
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -4.8
    Confidence Interval (2-Sided) 95%
    -10.5 to 1.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 23
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 92
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -5.6
    Confidence Interval (2-Sided) 95%
    -11.4 to 0.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 24
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 96
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -5.9
    Confidence Interval (2-Sided) 95%
    -11.5 to -0.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    27. Secondary Outcome
    Title Percentage of Subjects With Presence of Subretinal and/or Intraretinal Fluid (Central Subfield) at Each Post-baseline Visit - Study Eye
    Description Subretinal fluid and intraretinal fluid were assessed using SD-OCT and recorded as Present/Absent. The presence of subretinal and/or intraretinal fluid is an indicator of underlying disease. 95% confidence interval (CI) for binomial proportions was based on Clopper-Pearson exact method. One eye (study eye) contributed to the analysis.
    Time Frame Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96

    Outcome Measure Data

    Analysis Population Description
    FAS - LOCF
    Arm/Group Title Brolucizumab 6 mg Aflibercept 2 mg
    Arm/Group Description Single intravitreal (IVT) injection of brolucizumab at Day 0, Week 4, and Week 8, followed by 1 injection every 8 weeks/1 injection every 12 weeks (q8w/q12w) maintenance regimen until study exit Single IVT injection of aflibercept at Day 0, Week 4, and Week 8, followed by q8w maintenance regimen until study exit
    Measure Participants 370 369
    Week 4
    35.9
    42.8
    Week 8
    20.3
    29.3
    Week 12
    19.2
    27.6
    Week 16
    29.7
    44.7
    Week 20
    37.8
    29.8
    Week 24
    25.7
    45.3
    Week 28
    23.8
    27.4
    Week 32
    34.6
    43.9
    Week 36
    19.5
    28.5
    Week 40
    28.4
    44.4
    Week 44
    33.0
    29.3
    Week 48
    25.9
    43.6
    Week 52
    27.0
    29.5
    Week 56
    34.3
    43.1
    Week 60
    26.8
    32.0
    Week 64
    28.4
    43.4
    Week 68
    31.9
    30.6
    Week 72
    27.0
    41.5
    Week 76
    29.5
    29.8
    Week 80
    32.7
    42.5
    Week 84
    27.3
    31.4
    Week 88
    28.4
    38.8
    Week 92
    25.7
    28.2
    Week 96
    24.6
    38.2
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 4
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -6.9
    Confidence Interval (2-Sided) 95%
    -14.2 to 0.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 8
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -9.2
    Confidence Interval (2-Sided) 95%
    -15.5 to -2.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 12
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -8.7
    Confidence Interval (2-Sided) 95%
    -15.0 to -2.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 16
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -15.7
    Confidence Interval (2-Sided) 95%
    -22.9 to -9.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 20
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 7.7
    Confidence Interval (2-Sided) 95%
    0.9 to 14.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 24
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -20.0
    Confidence Interval (2-Sided) 95%
    -27.3 to -13.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 28
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -3.9
    Confidence Interval (2-Sided) 95%
    -10.4 to 2.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 32
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -9.7
    Confidence Interval (2-Sided) 95%
    -16.7 to -2.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 36
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -9.4
    Confidence Interval (2-Sided) 95%
    -15.8 to -3.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 40
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -16.5
    Confidence Interval (2-Sided) 95%
    -23.4 to -9.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 44
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 3.4
    Confidence Interval (2-Sided) 95%
    -3.3 to 10.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 48
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -18.1
    Confidence Interval (2-Sided) 95%
    -24.9 to -11.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 52
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -3.0
    Confidence Interval (2-Sided) 95%
    -9.2 to 3.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 56
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -9.4
    Confidence Interval (2-Sided) 95%
    -16.3 to -2.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 60
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -5.7
    Confidence Interval (2-Sided) 95%
    -12.5 to 1.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 64
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -15.5
    Confidence Interval (2-Sided) 95%
    -21.9 to -8.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 68
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value 0.9
    Confidence Interval (2-Sided) 95%
    -5.9 to 7.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 72
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -14.9
    Confidence Interval (2-Sided) 95%
    -21.4 to -8.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 76
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -0.8
    Confidence Interval (2-Sided) 95%
    -7.5 to 5.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 80
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -10.4
    Confidence Interval (2-Sided) 95%
    -17.2 to -3.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 21
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 84
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -4.5
    Confidence Interval (2-Sided) 95%
    -11.4 to 2.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 22
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 88
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -11.0
    Confidence Interval (2-Sided) 95%
    -18.2 to -4.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 23
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 92
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -2.9
    Confidence Interval (2-Sided) 95%
    -9.4 to 3.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    Statistical Analysis 24
    Statistical Analysis Overview Comparison Group Selection Brolucizumab 6 mg, Aflibercept 2 mg
    Comments Week 96
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -14.1
    Confidence Interval (2-Sided) 95%
    -21.3 to -7.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Statistical model used logistic regression adjusting for baseline fluid status, age categories, and treatment as fixed effect factors. 95% CI for difference in proportions (Brolucizumab 6mg - Aflibercept 2mg) was estimated using a bootstrap method.
    28. Secondary Outcome
    Title Percentage of Subjects With Disease Activity Present (q8 Treatment Need = "Yes") at Week 16 - Study Eye
    Description A disease activity assessment (DAA) was performed to identify q8 treatment need. 95% confidence interval (CI) for binomial proportions is based on Clopper-Pearson exact method. One eye (study eye) contributed to the analysis. Hypothesis testing not pre-specified.
    Time Frame Week 16

    Outcome Measure Data

    Analysis Population Description
    FAS - 'efficacy/safety' approach. Censored data attributable to lack of efficacy and/or safety are imputed with q8w need = Yes at the next disease activity assessment visit.
    Arm/Group Title Brolucizumab 6 mg Aflibercept 2 mg
    Arm/Group Description Single IVT injection of brolucizumab at Day 0, Week 4, and Week 8, followed by q8w/q12w maintenance regimen until study exit Single IVT injection of aflibercept at Day 0, Week 4, and Week 8, followed by q8w maintenance regimen until study exit
    Measure Participants 370 369
    Number (95% Confidence Interval) [percentage of subjects]
    22.8
    32.1
    29. Secondary Outcome
    Title Change From Baseline in Visual Function Questionnaire (VFQ-25) Composite Score at Week 24, Week 48, Week 72, and Week 96
    Description The National Eye Institute Visual Function Questionnaire-25 (VFQ-25) is a validated questionnaire that collects 25 vision-targeted responses from AMD subjects. The 25 questions pertain to global vision rating (1), difficulty with near vision activities (3), difficulty with distance vision activities (3), limitations in social functioning due to vision (2), role limitations due to vision (2), dependency on others due to vision (3), mental health symptoms due to vision (4), driving difficulties (3), limitations with peripheral (1) and color vision (1), and ocular pain (2). Each response is converted to a 0 to 100 sub-scale, with the lowest and highest possible scores set at 0 and 100 points, respectively. The overall composite score (0 to 100) is obtained by averaging the 25 sub-scale scores. A high score represents better functioning.
    Time Frame Baseline, Weeks 24, 48, 72, 96

    Outcome Measure Data

    Analysis Population Description
    FAS - Observed. Number analyzed is the number of subjects with a value for both baseline and the specific post-baseline visit.
    Arm/Group Title Brolucizumab 6 mg Aflibercept 2 mg
    Arm/Group Description Single IVT injection of brolucizumab at Day 0, Week 4, and Week 8, followed by q8w/q12w maintenance regimen until study exit Single IVT injection of aflibercept at Day 0, Week 4, and Week 8, followed by q8w maintenance regimen until study exit
    Measure Participants 370 369
    Change from baseline at Week 24
    3.9
    (10.09)
    3.5
    (10.95)
    Change from baseline at Week 48
    4.8
    (11.57)
    3.6
    (11.88)
    Change from baseline at Week 72
    5.0
    (13.38)
    3.2
    (12.30)
    Change from baseline at Week 96
    3.8
    (14.06)
    2.6
    (13.11)
    30. Secondary Outcome
    Title Percentage of Subjects With Induced or Boosted Anti-drug Antibody (ADA) Status at Week 48 (Brolucizumab Only)
    Description Serum samples were collected and assessed for anti-drug antibody status. Subjects were categorized as ADA negative when one of the following was met: ADA negative at all time points (predose and postdose); ADA negative at predose and no titer values above 10 at all other time points; or ADA titer of 10 at predose but negative at all other time points. ADA induced was defined as ADA negative at predose with postdose titer value greater than or equal to a titer of 30 at any timepoint. ADA boosted was defined as ADA positive at predose with postdose titer values that increased by at least two dilutions (9-fold) from their respective predose value at any time point.
    Time Frame Week 48

    Outcome Measure Data

    Analysis Population Description
    Safety Analysis Set - Observed
    Arm/Group Title Brolucizumab 6 mg
    Arm/Group Description Single IVT injection of brolucizumab at Day 0, Week 4, and Week 8, followed by q8w/q12w maintenance regimen until study exit
    Measure Participants 370
    Number [percentage of subjects]
    18.8
    31. Secondary Outcome
    Title Percentage of Subjects With Intraretinal Hemorrhage (Central Subfield) Present at the Visit While Absent at Baseline at Each Treatment - Study Eye
    Description Intraretinal hemorrhage was assessed using SD-OCT and recorded as Present/Absent. The presence of intraretinal hemorrhage is an indicator of underlying disease. 95% confidence interval (CI) for binomial proportions was based on Clopper-Pearson exact method. One eye (study eye) contributed to the analysis.
    Time Frame Baseline, Weeks 12, 48, 96

    Outcome Measure Data

    Analysis Population Description
    FAS with non-missing values. Number Analyzed represents the number of subjects with a value for both baseline and the specific post-baseline visit.
    Arm/Group Title Brolucizumab 6 mg Aflibercept 2 mg
    Arm/Group Description Single intravitreal (IVT) injection of brolucizumab at Day 0, Week 4, and Week 8, followed by 1 injection every 8 weeks/1 injection every 12 weeks (q8w/q12w) maintenance regimen until study exit Single IVT injection of aflibercept at Day 0, Week 4, and Week 8, followed by q8w maintenance regimen until study exit
    Measure Participants 370 369
    Week 12
    6.9
    6.6
    Week 48
    4.0
    5.0
    Week 96
    2.1
    2.7
    32. Secondary Outcome
    Title Percentage of Subjects With Subretinal Hemorrhage (Central Subfield) Present at the Visit While Absent at Baseline at Each Treatment - Study Eye
    Description Subretinal hemorrhage was assessed using SD-OCT and recorded as Present/Absent. The presence of subretinal hemorrhage is an indicator of underlying disease. 95% confidence interval (CI) for binomial proportions was based on Clopper-Pearson exact method. One eye (study eye) contributed to the analysis.
    Time Frame Baseline, Weeks 12, 48, 96

    Outcome Measure Data

    Analysis Population Description
    FAS with non-missing values. Number Analyzed represents the number of subjects with a value for both baseline and the specific post-baseline visit.
    Arm/Group Title Brolucizumab 6 mg Aflibercept 2 mg
    Arm/Group Description Single intravitreal (IVT) injection of brolucizumab at Day 0, Week 4, and Week 8, followed by 1 injection every 8 weeks/1 injection every 12 weeks (q8w/q12w) maintenance regimen until study exit Single IVT injection of aflibercept at Day 0, Week 4, and Week 8, followed by q8w maintenance regimen until study exit
    Measure Participants 370 369
    Week 12
    0.6
    1.2
    Week 48
    0.6
    0.3
    Week 96
    0.0
    0.0

    Adverse Events

    Time Frame First treatment through study completion, an average of 96 weeks.
    Adverse Event Reporting Description Adverse Events (AE) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. This analysis population includes all subjects who received at least 1 IVT injection (Safety Analysis Set).
    Arm/Group Title Brolucizumab 6mg Aflibercept 2mg
    Arm/Group Description All subjects exposed to brolucizumab ophthalmic solution administered as a 6 mg/50 microliter (μL) dose All subjects exposed to aflibercept ophthalmic solution administered as a 2 mg/50 μL dose
    All Cause Mortality
    Brolucizumab 6mg Aflibercept 2mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 4/370 (1.1%) 7/369 (1.9%)
    Serious Adverse Events
    Brolucizumab 6mg Aflibercept 2mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 79/370 (21.4%) 89/369 (24.1%)
    Blood and lymphatic system disorders
    Anaemia 0/370 (0%) 1/369 (0.3%)
    Iron deficiency anaemia 1/370 (0.3%) 0/369 (0%)
    Thrombocytopenia 0/370 (0%) 1/369 (0.3%)
    Cardiac disorders
    Acute myocardial infarction 1/370 (0.3%) 0/369 (0%)
    Angina pectoris 1/370 (0.3%) 1/369 (0.3%)
    Arrhythmia 0/370 (0%) 2/369 (0.5%)
    Atrial fibrillation 1/370 (0.3%) 0/369 (0%)
    Atrial flutter 1/370 (0.3%) 0/369 (0%)
    Atrioventricular block first degree 1/370 (0.3%) 0/369 (0%)
    Bundle branch block left 1/370 (0.3%) 0/369 (0%)
    Bundle branch block right 1/370 (0.3%) 0/369 (0%)
    Cardiac arrest 0/370 (0%) 1/369 (0.3%)
    Cardiac failure 2/370 (0.5%) 2/369 (0.5%)
    Cardiac failure congestive 0/370 (0%) 1/369 (0.3%)
    Cardiopulmonary failure 1/370 (0.3%) 1/369 (0.3%)
    Myocardial infarction 2/370 (0.5%) 0/369 (0%)
    Myocardial ischaemia 0/370 (0%) 1/369 (0.3%)
    Parasystole 1/370 (0.3%) 0/369 (0%)
    Tachycardia 0/370 (0%) 1/369 (0.3%)
    Ear and labyrinth disorders
    Vertigo 0/370 (0%) 1/369 (0.3%)
    Eye disorders
    Anterior chamber inflammation - Study eye 1/370 (0.3%) 0/369 (0%)
    Blindness - Study eye 1/370 (0.3%) 0/369 (0%)
    Dry age-related macular degeneration - Study eye 0/370 (0%) 1/369 (0.3%)
    Retinal artery embolism - Study eye 1/370 (0.3%) 0/369 (0%)
    Retinal artery occlusion - Study eye 0/370 (0%) 1/369 (0.3%)
    Retinal artery thrombosis - Study eye 1/370 (0.3%) 0/369 (0%)
    Retinal detachment - Study eye 1/370 (0.3%) 1/369 (0.3%)
    Retinal pigment epithelial tear - Study eye 2/370 (0.5%) 0/369 (0%)
    Retinal tear - Study eye 2/370 (0.5%) 1/369 (0.3%)
    Uveitis - Study eye 3/370 (0.8%) 0/369 (0%)
    Visual acuity reduced - Study eye 1/370 (0.3%) 1/369 (0.3%)
    Gastrointestinal disorders
    Abdominal pain 1/370 (0.3%) 0/369 (0%)
    Colitis 0/370 (0%) 1/369 (0.3%)
    Duodenitis haemorrhagic 0/370 (0%) 1/369 (0.3%)
    Dyspepsia 0/370 (0%) 1/369 (0.3%)
    Dysphagia 0/370 (0%) 1/369 (0.3%)
    Gastritis haemorrhagic 0/370 (0%) 1/369 (0.3%)
    Gastrointestinal haemorrhage 0/370 (0%) 1/369 (0.3%)
    Gastrointestinal inflammation 0/370 (0%) 1/369 (0.3%)
    Haemorrhoids 0/370 (0%) 1/369 (0.3%)
    Inguinal hernia 2/370 (0.5%) 0/369 (0%)
    Intestinal polyp 0/370 (0%) 1/369 (0.3%)
    Large intestine perforation 0/370 (0%) 1/369 (0.3%)
    Lumbar hernia 0/370 (0%) 1/369 (0.3%)
    Pancreatitis 1/370 (0.3%) 0/369 (0%)
    Rectal haemorrhage 2/370 (0.5%) 1/369 (0.3%)
    Rectal prolapse 0/370 (0%) 1/369 (0.3%)
    Vomiting 0/370 (0%) 1/369 (0.3%)
    General disorders
    Cyst 0/370 (0%) 1/369 (0.3%)
    Death 0/370 (0%) 3/369 (0.8%)
    Pyrexia 0/370 (0%) 1/369 (0.3%)
    Hepatobiliary disorders
    Bile duct stone 0/370 (0%) 1/369 (0.3%)
    Biliary colic 1/370 (0.3%) 0/369 (0%)
    Cholecystitis acute 2/370 (0.5%) 0/369 (0%)
    Cholelithiasis 2/370 (0.5%) 0/369 (0%)
    Drug-induced liver injury 1/370 (0.3%) 0/369 (0%)
    Immune system disorders
    Allergy to arthropod sting 0/370 (0%) 1/369 (0.3%)
    Hypersensitivity 1/370 (0.3%) 0/369 (0%)
    Infections and infestations
    Appendicitis 1/370 (0.3%) 0/369 (0%)
    Bacterial infection 1/370 (0.3%) 0/369 (0%)
    Bronchitis 1/370 (0.3%) 2/369 (0.5%)
    Cytomegalovirus infection 0/370 (0%) 1/369 (0.3%)
    Dacryocystitis - Study eye 1/370 (0.3%) 0/369 (0%)
    Diverticulitis 1/370 (0.3%) 0/369 (0%)
    Endophthalmitis - Study eye 1/370 (0.3%) 1/369 (0.3%)
    Gastroenteritis 2/370 (0.5%) 0/369 (0%)
    Infective exacerbation of chronic obstructive airways disease 1/370 (0.3%) 0/369 (0%)
    Intervertebral discitis 1/370 (0.3%) 0/369 (0%)
    Lower respiratory tract infection 0/370 (0%) 1/369 (0.3%)
    Lung infection 0/370 (0%) 1/369 (0.3%)
    Pharyngitis 0/370 (0%) 1/369 (0.3%)
    Pneumonia 2/370 (0.5%) 8/369 (2.2%)
    Respiratory tract infection 0/370 (0%) 1/369 (0.3%)
    Sepsis 1/370 (0.3%) 1/369 (0.3%)
    Skin infection 1/370 (0.3%) 0/369 (0%)
    Urinary tract infection 1/370 (0.3%) 1/369 (0.3%)
    Urosepsis 0/370 (0%) 1/369 (0.3%)
    Injury, poisoning and procedural complications
    Cataract traumatic - Study eye 1/370 (0.3%) 0/369 (0%)
    Chest injury 0/370 (0%) 1/369 (0.3%)
    Facial bones fracture 1/370 (0.3%) 0/369 (0%)
    Fall 0/370 (0%) 2/369 (0.5%)
    Femoral neck fracture 1/370 (0.3%) 2/369 (0.5%)
    Femur fracture 2/370 (0.5%) 0/369 (0%)
    Foot fracture 1/370 (0.3%) 0/369 (0%)
    Head injury 0/370 (0%) 1/369 (0.3%)
    Humerus fracture 0/370 (0%) 2/369 (0.5%)
    Incisional hernia 1/370 (0.3%) 0/369 (0%)
    Injury 1/370 (0.3%) 0/369 (0%)
    Joint dislocation 2/370 (0.5%) 0/369 (0%)
    Limb traumatic amputation 0/370 (0%) 1/369 (0.3%)
    Lower limb fracture 3/370 (0.8%) 0/369 (0%)
    Post procedural haematoma 1/370 (0.3%) 0/369 (0%)
    Procedural haemorrhage 0/370 (0%) 1/369 (0.3%)
    Radius fracture 0/370 (0%) 1/369 (0.3%)
    Rib fracture 1/370 (0.3%) 0/369 (0%)
    Spinal fracture 0/370 (0%) 1/369 (0.3%)
    Sternal fracture 1/370 (0.3%) 0/369 (0%)
    Tendon rupture 1/370 (0.3%) 0/369 (0%)
    Thermal burn 0/370 (0%) 1/369 (0.3%)
    Tibia fracture 0/370 (0%) 1/369 (0.3%)
    Toxicity to various agents 1/370 (0.3%) 0/369 (0%)
    Investigations
    Investigation 0/370 (0%) 1/369 (0.3%)
    Metabolism and nutrition disorders
    Hyperglycaemia 0/370 (0%) 1/369 (0.3%)
    Hyperkalaemia 1/370 (0.3%) 0/369 (0%)
    Malnutrition 1/370 (0.3%) 0/369 (0%)
    Vitamin D deficiency 1/370 (0.3%) 0/369 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/370 (0.3%) 1/369 (0.3%)
    Intervertebral disc protrusion 0/370 (0%) 1/369 (0.3%)
    Neck pain 0/370 (0%) 1/369 (0.3%)
    Osteoarthritis 1/370 (0.3%) 2/369 (0.5%)
    Osteoporosis 1/370 (0.3%) 0/369 (0%)
    Polyarthritis 0/370 (0%) 1/369 (0.3%)
    Spinal column stenosis 0/370 (0%) 1/369 (0.3%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma gastric 1/370 (0.3%) 0/369 (0%)
    Breast cancer 0/370 (0%) 1/369 (0.3%)
    Breast neoplasm 1/370 (0.3%) 1/369 (0.3%)
    Colon cancer 1/370 (0.3%) 0/369 (0%)
    Colon neoplasm 0/370 (0%) 1/369 (0.3%)
    Diffuse large B-cell lymphoma 0/370 (0%) 1/369 (0.3%)
    Endometrial cancer 1/370 (0.3%) 0/369 (0%)
    Gastrointestinal carcinoma 0/370 (0%) 1/369 (0.3%)
    Lung neoplasm 1/370 (0.3%) 0/369 (0%)
    Malignant melanoma 0/370 (0%) 1/369 (0.3%)
    Meningioma 1/370 (0.3%) 1/369 (0.3%)
    Metastases to central nervous system 0/370 (0%) 1/369 (0.3%)
    Metastases to peritoneum 1/370 (0.3%) 0/369 (0%)
    Metastatic neoplasm 1/370 (0.3%) 0/369 (0%)
    Neoplasm 0/370 (0%) 1/369 (0.3%)
    Non-small cell lung cancer 0/370 (0%) 1/369 (0.3%)
    Oesophageal carcinoma 1/370 (0.3%) 0/369 (0%)
    Prostate cancer 2/370 (0.5%) 1/369 (0.3%)
    Squamous cell carcinoma of lung 1/370 (0.3%) 0/369 (0%)
    Thyroid adenoma 0/370 (0%) 1/369 (0.3%)
    Nervous system disorders
    Carotid artery stenosis 0/370 (0%) 1/369 (0.3%)
    Cerebral haemorrhage 1/370 (0.3%) 0/369 (0%)
    Cerebral infarction 1/370 (0.3%) 0/369 (0%)
    Cerebral ischaemia 1/370 (0.3%) 0/369 (0%)
    Cerebrovascular accident 0/370 (0%) 4/369 (1.1%)
    Cerebrovascular disorder 0/370 (0%) 2/369 (0.5%)
    Ischaemic stroke 2/370 (0.5%) 1/369 (0.3%)
    Migraine 1/370 (0.3%) 0/369 (0%)
    Myasthenia gravis 0/370 (0%) 1/369 (0.3%)
    Radiculopathy 0/370 (0%) 1/369 (0.3%)
    Syncope 3/370 (0.8%) 2/369 (0.5%)
    Transient ischaemic attack 1/370 (0.3%) 2/369 (0.5%)
    Vertebrobasilar insufficiency 0/370 (0%) 1/369 (0.3%)
    Psychiatric disorders
    Charles Bonnet syndrome 0/370 (0%) 1/369 (0.3%)
    Depression 0/370 (0%) 1/369 (0.3%)
    Mental fatigue 0/370 (0%) 1/369 (0.3%)
    Mood disorder due to a general medical condition 1/370 (0.3%) 0/369 (0%)
    Paranoid personality disorder 1/370 (0.3%) 0/369 (0%)
    Renal and urinary disorders
    Acute prerenal failure 0/370 (0%) 1/369 (0.3%)
    Haematuria 0/370 (0%) 1/369 (0.3%)
    Nephrolithiasis 1/370 (0.3%) 0/369 (0%)
    Renal failure 0/370 (0%) 1/369 (0.3%)
    Urinary bladder polyp 1/370 (0.3%) 0/369 (0%)
    Urinary bladder rupture 1/370 (0.3%) 0/369 (0%)
    Reproductive system and breast disorders
    Benign prostatic hyperplasia 2/370 (0.5%) 0/369 (0%)
    Postmenopausal haemorrhage 1/370 (0.3%) 0/369 (0%)
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary oedema 0/370 (0%) 1/369 (0.3%)
    Chronic obstructive pulmonary disease 2/370 (0.5%) 1/369 (0.3%)
    Pleurisy 0/370 (0%) 1/369 (0.3%)
    Pneumothorax 1/370 (0.3%) 0/369 (0%)
    Pulmonary embolism 1/370 (0.3%) 2/369 (0.5%)
    Pulmonary oedema 2/370 (0.5%) 0/369 (0%)
    Respiratory arrest 0/370 (0%) 1/369 (0.3%)
    Respiratory failure 1/370 (0.3%) 0/369 (0%)
    Skin and subcutaneous tissue disorders
    Neuropathic ulcer 0/370 (0%) 1/369 (0.3%)
    Skin necrosis 1/370 (0.3%) 0/369 (0%)
    Surgical and medical procedures
    Hip surgery 1/370 (0.3%) 0/369 (0%)
    Implantable defibrillator replacement 0/370 (0%) 1/369 (0.3%)
    Varicose vein operation 1/370 (0.3%) 0/369 (0%)
    Vascular disorders
    Haemorrhage 1/370 (0.3%) 0/369 (0%)
    Hypertensive crisis 1/370 (0.3%) 1/369 (0.3%)
    Hypotension 0/370 (0%) 1/369 (0.3%)
    Peripheral ischaemia 0/370 (0%) 1/369 (0.3%)
    Varicose vein 1/370 (0.3%) 0/369 (0%)
    Other (Not Including Serious) Adverse Events
    Brolucizumab 6mg Aflibercept 2mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 176/370 (47.6%) 194/369 (52.6%)
    Eye disorders
    Cataract - Fellow eye 7/370 (1.9%) 22/369 (6%)
    Cataract - Study eye 11/370 (3%) 43/369 (11.7%)
    Conjunctival haemorrhage - Study eye 17/370 (4.6%) 19/369 (5.1%)
    Eye pain - Study eye 13/370 (3.5%) 19/369 (5.1%)
    Neovascular age-related macular degeneration - Fellow eye 31/370 (8.4%) 32/369 (8.7%)
    Visual acuity reduced - Study eye 31/370 (8.4%) 25/369 (6.8%)
    Infections and infestations
    Bronchitis 22/370 (5.9%) 20/369 (5.4%)
    Influenza 24/370 (6.5%) 27/369 (7.3%)
    Nasopharyngitis 43/370 (11.6%) 31/369 (8.4%)
    Musculoskeletal and connective tissue disorders
    Back pain 16/370 (4.3%) 28/369 (7.6%)
    Vascular disorders
    Hypertension 28/370 (7.6%) 25/369 (6.8%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

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

    Results Point of Contact

    Name/Title Study Director
    Organization Novartis Pharmaceuticals
    Phone 1-862-778-8300
    Email novartis.email@novartis.com
    Responsible Party:
    Alcon Research
    ClinicalTrials.gov Identifier:
    NCT02434328
    Other Study ID Numbers:
    • RTH258-C002
    • 2014-004886-26
    • CRTH258A2302
    First Posted:
    May 5, 2015
    Last Update Posted:
    Sep 11, 2020
    Last Verified:
    Oct 1, 2019