Age-related Macular Degeneration
Conditions
Keywords
Age-related Macular Degeneration, Macular Degeneration, Wet Macular Degeneration, Retinal Degeneration, Retinal Diseases, Eye Diseases, AMD, nAMD, wet AMD, RTH258, Brolucizumab, double blind, age-related macular degeneration (ARMD), vision loss, macula damage, retina damage, dry macular degeneration, Subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration
Brief summary
This was a 64-week randomized, double-masked, multi-center, active-controlled, two-arm study in patients with neovascular age related macular degeneration (nAMD) who have not previously received anti- vascular endothelial growth factor (VEGF) treatment.
Detailed description
At the baseline Visit, subjects who met the eligibility criteria were randomized in a 1:1 ratio to receive either: -Brolucizumab 6 mg: 3 × 4-week injections and one 8-week injection, followed by Treat-to- Control treatment from Week 16 up to Week 60/62 -Aflibercept 2 mg: 3 × 4-week injections and one 8-week injection, followed by Treat-to-Control treatment from Week 16 up to Week 60/62. For all subjects, the last potential study treatment was at the Week 60 visit (or at the Week 62 visit for subjects whose actual treatment interval would require a treatment at Week 62). The initiation phase starts on Day 1 and ends on Week 16. Treat to Control regimen starts on Week 16 until end of treatment (Week 60/62). In both treatment arms, treatment intervals after the initiation phase were either 8 weeks, 12 weeks, or 16 weeks. Per the original protocol, if it was determined that a patient required more frequent injections than q8w, he/she would be moved to a q4w treatment interval. However, this option was removed per Protocol amendment 02, after which, dosing intervals shorter than q8w were not permitted.
Interventions
BIOLOGICALBrolucizumab 6 mg
Intra-vitreal injection
BIOLOGICALAflibercept 2 mg
Intra-vitreal injection
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Intervention model description
Double arm, multi-center
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed informed consent must be obtained prior to participation in the study * Male or female patients ≥ 50 years of age at screening who are treatment naive * Active choroidal neovascularization (CNV) secondary to AMD that affects the central subfield, including retinal angiomatous proliferation (RAP) with a CNV component, confirmed by presence of active leakage from CNV seen by fluorescein angiography and sequellae of CNV, e.g. pigment epithelial detachment (PED), subretinal or sub-retinal pigment epithelium (sub-RPE) hemorrhage, blocked fluorescence, macular edema (study eye) * Presence of intraretinal fluid (IRF) or subretinal fluid (SRF) that affects the central subfield, as seen by Spectral Domain Optical Coherence Tomography (SD-OCT) (study eye) * Best-corrected visual acuity (BCVA) score between 83 and 38 letters, inclusive, using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts at both screening and baseline visit (study eye)
Exclusion criteria
* Ocular conditions/disorders at screening or baseline which could, in the opinion of the investigator, prevent response to study treatment or may confound interpretation of study results, compromise visual acuity or require planned medical or surgical intervention during the first 12-month study period, structural damage of the fovea, atrophy or fibrosis at the center of the fovea (study eye) * Any active intraocular or periocular infection or active intraocular inflammation, at screening or baseline (study eye) * Uncontrolled glaucoma defined as intraocular pressure (IOP) \> 25 mmHg on medication, or according to investigator's judgment, at screening or baseline (study eye) * Ocular treatments: previous treatment with any anti-vascular endothelial growth factor (VEGF) drugs or investigational drugs, intraocular or periocular steroids, macular laser photocoagulation, photodynamic therapy, vitreoretinal surgery, intraocular surgery (study eye) * Stroke or myocardial infarction during the 6-month period prior to baseline * Systemic anti-VEGF therapy at any time.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Distribution of the Last Interval With no Disease Activity up to Week 32 - Study Eye | Up to Week 32 | No disease activity is defined as no change in visual acuity and no change in other signs of the disease (e.g. Intraretinal Fluid (IRF), Subretinal Fluid (SRF), hemorrhage, leakage, etc.). Treatment interval distribution. Number (%) of subjects at 12/8/4-weeks intervals up to Week 32 for the study eye. If the study treatment is discontinued before Week 16, then the treatment interval is 4 weeks; otherwise. the last interval with no disease activity is used (if there was disease activity, the last interval is shortened by 4 weeks, down to a minimum of 4 weeks). If the duration of the last interval falls within the following ranges of (4-week, 8-week) or (8-week, 12-week) or ≥12-week then the floor value of these ranges was used. |
| Average Change From Baseline at Week 28 and Week 32 in Best-corrected Visual Acuity (BCVA) - Study Eye | Baseline, Week 28 and Week 32 | BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning. Least squares mean estimate - for weeks 28 and 32 combined. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With no Disease Activity - Study Eye | Weeks 14 and 16 | Disease activity assessment as determined by visual acuity and assessment of other signs of the disease (e.g. IRF, SRF, hemorrhage, leakage, etc.). |
| Time From Last Loading Injection to First Visit With No Disease Activity (Weeks) - 75th Percentile - Study Eye | Up to Week 64 | Intraretinal fluid (IRF) and subretinal fluid (SRF) were assessed by Spectral Domain Optical Coherence Tomography (SD-OCT) (study eye). Please note that this endpoint can be impacted by the optional disease activity assessment visits and the flexible dosing regimen, in addition to the randomized treatment. Hence, the observed treatment effect may be confounded by the study design artifacts. |
| Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye | Up to Week 64 | Intraretinal fluid (IRF) and subretinal fluid (SRF) were assessed by Spectral Domain Optical Coherence Tomography (SD-OCT) (study eye). |
| Average Change From Baseline at Week 60 and Week 64 in Best-corrected Visual Acuity (BCVA) - Study Eye | Baseline, Week 60 and Week 64 | BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning. Least squares mean estimate - for weeks 60 and 64 combined. |
| Number of Participants With Best-corrected Visual Acuity Improvements of ≥ 15 Letters in BCVA From Baseline or Reached BCVA ≥ 84 Letters up to Week 32/64 Per Treatment Arm - Study Eye | Baseline, Week 32, and Week 64 | BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning. |
| Number of Participants With Best-corrected Visual Acuity ≥ 69 Letters - Study Eye | Week 32 and Week 64 | BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning. |
| Average Change From Baseline in Central Subfield Thickness (CSFT) - Study Eye | Baseline, Weeks 28 and 32 and at Weeks 60 and 64 | CSFT was measured by Spectral Domain Optical Coherence Tomography |
| Number of Participants With Presence of Intraretinal Fluid and/or Subretinal Fluid in the Central Subfield - Study Eye | At Weeks 28, 32, 60 and 64 | Intraretinal Fluid and/or Subretinal Fluid status was measured by Spectral Domain Optical Coherence Tomography (SD-OCT). |
| Number of Participants With Presence of Sub-Retinal Pigment Epithelium Fluid in the Central Subfield - Study Eye | At Weeks 28, 32, 60 and 64 | Sub-Retinal Pigment Epithelium fluid status was measured by Spectral Domain Optical Coherence Tomography (SD-OCT). |
| Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Composite Scores - Study Eye | Baseline, Week 32, and Week 64 | The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. Each subscale score has a range of 0 to 100 inclusive and will be calculated from the re-scaled raw data. A composite score is derived based on the average of the 11 subscales. |
| Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - General Vision - Study Eye | Baseline, Week 32, and Week 64 | The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. Each subscale score has a range of 0 to 100 inclusive and will be calculated from the re-scaled raw data. A composite score is derived based on the average of the 11 subscales. |
| Distribution of the Last Interval With no Disease Activity up to Week 64 - Study Eye | Up to Week 64 | No disease activity is defined as no change in visual acuity and no change in other signs of the disease (e.g. IRF, SRF, hemorrhage, leakage, etc.). Treatment interval distribution. The number of subjects at 16/12/8/4-weeks intervals as the last interval with no disease activity. If the study treatment is discontinued before Week 16, then the treatment interval is 4 weeks; otherwise. the last interval with no disease activity is used (if there was disease activity, the last interval is shortened by 4 weeks, down to a minimum of 4 weeks). If the duration of the last interval falls within the following ranges of (4-week, 8-week) or (8-week, 12-week) or (12-weeks, 16-weeks) or ≥16-week then the floor value of these ranges was used. |
| Change From Baseline n Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Near Activities - Study Eye | Baseline, Week 32, and Week 64 | The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. Each subscale score has a range of 0 to 100 inclusive and will be calculated from the re-scaled raw data. A composite score is derived based on the average of the 11 subscales. |
| Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Distance Activities - Study Eye | Baseline, Week 32, and Week 64 | The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. Each subscale score has a range of 0 to 100 inclusive and will be calculated from the re-scaled raw data. A composite score is derived based on the average of the 11 subscales. |
| Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Social Functioning - Study Eye | Baseline, Week 32, and Week 64 | The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning or outcome. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. Each subscale score has a range of 0 to 100 inclusive and will be calculated from the re-scaled raw data. A composite score is derived based on the average of the 11 subscales. |
| Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Mental Health - Study Eye | Baseline, Week 32, and Week 64 | The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning or outcome. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. Each subscale score has a range of 0 to 100 inclusive and will be calculated from the re-scaled raw data. A composite score is derived based on the average of the 11 subscales. |
| Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Role Difficulties - Study Eye | Baseline, Week 32, and Week 64 | The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning or outcome. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. Each subscale score has a range of 0 to 100 inclusive and will be calculated from the re-scaled raw data. A composite score is derived based on the average of the 11 subscales. |
| Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Dependency - Study Eye | Baseline, Week 32, and Week 64 | The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning or outcome. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. Each subscale score has a range of 0 to 100 inclusive and will be calculated from the re-scaled raw data. A composite score is derived based on the average of the 11 subscales. |
| Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Driving - Study Eye | Baseline, Week 32, and Week 64 | The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. Each subscale score has a range of 0 to 100 inclusive and will be calculated from the re-scaled raw data. A composite score is derived based on the average of the 11 subscales. |
| Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Color Vision - Study Eye | Baseline, Week 32, and Week 64 | The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. Each subscale score has a range of 0 to 100 inclusive and will be calculated from the re-scaled raw data. A composite score is derived based on the average of the 11 subscales. |
| Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Peripheral Vision - Study Eye | Baseline, Week 32, and Week 64 | The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. Each subscale score has a range of 0 to 100 inclusive and will be calculated from the re-scaled raw data. A composite score is derived based on the average of the 11 subscales. |
| Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye | Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 483 days, approx. 69 weeks, 1.3 years. | An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign (including abnormal laboratory findings), symptom or disease) in a subject or clinical investigation subject. |
| Number of Participants With Treatment Emergent Non-ocular Adverse Events (Greater Than or Equal to 2% in Any Treatment Arm) - Summary Table | Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 483 days, approx. 69 weeks, 1.3 years. | An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign (including abnormal laboratory findings), symptom or disease) in a subject or clinical investigation subject. |
| Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Ocular Pain - Study Eye | Baseline, Week 32, and Week 64 | The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. Each subscale score has a range of 0 to 100 inclusive and will be calculated from the re-scaled raw data. A composite score is derived based on the average of the 11 subscales. |
| Distribution of the Maximal Intervals With no Disease Activity up to Week 64 - Study Eye | Up to Week 64 | No disease activity is defined as no change in visual acuity and no change in other signs of the disease (e.g. IRF, SRF, hemorrhage, leakage, etc.). Maximal interval distribution. Number of subjects at 16/12/8/4-weeks intervals as the last interval with no disease activity. If the study treatment is discontinued before Week 16 included, then the treatment interval is 4 weeks; otherwise, the last interval with no disease activity is used (if there was disease activity, the last interval is shortened by 4 weeks, down to a minimum of 4 weeks). If the duration of the maximal interval falls within the following ranges of \[4-weeks, 8-weeks) or \[8-weeks, 12-weeks) or \[12-weeks, 16-weeks\] or ≥16-weeks then the floor value of these ranges is used. |
Countries
Argentina, Australia, Austria, Belgium, Canada, Czechia, France, Germany, Israel, Italy, Malaysia, Netherlands, Portugal, South Korea, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States
Participant flow
Pre-assignment details
734 participants were treated.
Participants by arm
| Arm | Count |
|---|---|
| Brolucizumab 6 mg Intra-vitreal injection | 366 |
| Aflibercept 2 mg Intra-vitreal injection | 368 |
| Total | 734 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 5 |
| Overall Study | Death | 4 | 2 |
| Overall Study | Lost to Follow-up | 6 | 2 |
| Overall Study | Physician Decision | 7 | 13 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 28 | 38 |
Baseline characteristics
| Characteristic | Brolucizumab 6 mg | Aflibercept 2 mg | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 334 Participants | 331 Participants | 665 Participants |
| Age, Categorical Between 18 and 65 years | 32 Participants | 37 Participants | 69 Participants |
| Age, Continuous | 75.5 years STANDARD_DEVIATION 7.85 | 75.5 years STANDARD_DEVIATION 8.41 | 75.5 years STANDARD_DEVIATION 8.13 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 55 Participants | 55 Participants | 110 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 310 Participants | 312 Participants | 622 Participants |
| Sex: Female, Male Female | 216 Participants | 204 Participants | 420 Participants |
| Sex: Female, Male Male | 150 Participants | 164 Participants | 314 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 4 / 366 | 2 / 368 | 6 / 734 |
| other Total, other adverse events | 172 / 366 | 177 / 368 | 349 / 734 |
| serious Total, serious adverse events | 58 / 366 | 53 / 368 | 111 / 734 |
Outcome results
Primary
Average Change From Baseline at Week 28 and Week 32 in Best-corrected Visual Acuity (BCVA) - Study Eye
BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning. Least squares mean estimate - for weeks 28 and 32 combined.
Time frame: Baseline, Week 28 and Week 32
Population: Full Analysis Set - Last observation carried forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Brolucizumab 6 mg | Average Change From Baseline at Week 28 and Week 32 in Best-corrected Visual Acuity (BCVA) - Study Eye | 5.2 Scores on a scale | Standard Error 0.51 |
| Aflibercept 2 mg | Average Change From Baseline at Week 28 and Week 32 in Best-corrected Visual Acuity (BCVA) - Study Eye | 5.1 Scores on a scale | Standard Error 0.51 |
p-value: <0.000195% CI: [-1.3, 1.5]ANOVA
Primary
Distribution of the Last Interval With no Disease Activity up to Week 32 - Study Eye
No disease activity is defined as no change in visual acuity and no change in other signs of the disease (e.g. Intraretinal Fluid (IRF), Subretinal Fluid (SRF), hemorrhage, leakage, etc.). Treatment interval distribution. Number (%) of subjects at 12/8/4-weeks intervals up to Week 32 for the study eye. If the study treatment is discontinued before Week 16, then the treatment interval is 4 weeks; otherwise. the last interval with no disease activity is used (if there was disease activity, the last interval is shortened by 4 weeks, down to a minimum of 4 weeks). If the duration of the last interval falls within the following ranges of (4-week, 8-week) or (8-week, 12-week) or ≥12-week then the floor value of these ranges was used.
Time frame: Up to Week 32
Population: Full Analysis Set (Includes participants who were randomized and treated.)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brolucizumab 6 mg | Distribution of the Last Interval With no Disease Activity up to Week 32 - Study Eye | 12 weeks | 141 Participants |
| Brolucizumab 6 mg | Distribution of the Last Interval With no Disease Activity up to Week 32 - Study Eye | 8 weeks | 131 Participants |
| Brolucizumab 6 mg | Distribution of the Last Interval With no Disease Activity up to Week 32 - Study Eye | 4 weeks | 94 Participants |
| Aflibercept 2 mg | Distribution of the Last Interval With no Disease Activity up to Week 32 - Study Eye | 12 weeks | 73 Participants |
| Aflibercept 2 mg | Distribution of the Last Interval With no Disease Activity up to Week 32 - Study Eye | 8 weeks | 147 Participants |
| Aflibercept 2 mg | Distribution of the Last Interval With no Disease Activity up to Week 32 - Study Eye | 4 weeks | 148 Participants |
p-value: <0.0001Wilcoxon (Mann-Whitney)
Secondary
Average Change From Baseline at Week 60 and Week 64 in Best-corrected Visual Acuity (BCVA) - Study Eye
BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning. Least squares mean estimate - for weeks 60 and 64 combined.
Time frame: Baseline, Week 60 and Week 64
Population: Full Analysis Set - LOCF
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Brolucizumab 6 mg | Average Change From Baseline at Week 60 and Week 64 in Best-corrected Visual Acuity (BCVA) - Study Eye | 4.7 Scores on a scale | Standard Error 0.6 |
| Aflibercept 2 mg | Average Change From Baseline at Week 60 and Week 64 in Best-corrected Visual Acuity (BCVA) - Study Eye | 4.9 Scores on a scale | Standard Error 0.6 |
p-value: 0.813795% CI: [-1.9, 1.5]ANOVA
Secondary
Average Change From Baseline in Central Subfield Thickness (CSFT) - Study Eye
CSFT was measured by Spectral Domain Optical Coherence Tomography
Time frame: Baseline, Weeks 28 and 32 and at Weeks 60 and 64
Population: Full Analysis Set - LOCF
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Brolucizumab 6 mg | Average Change From Baseline in Central Subfield Thickness (CSFT) - Study Eye | Weeks 28 and 32 (average) | -166.9 micrometers | Standard Error 6.97 |
| Brolucizumab 6 mg | Average Change From Baseline in Central Subfield Thickness (CSFT) - Study Eye | Weeks 60 and 64 (average) | -182.9 micrometers | Standard Error 7.72 |
| Aflibercept 2 mg | Average Change From Baseline in Central Subfield Thickness (CSFT) - Study Eye | Weeks 28 and 32 (average) | -140.0 micrometers | Standard Error 6.96 |
| Aflibercept 2 mg | Average Change From Baseline in Central Subfield Thickness (CSFT) - Study Eye | Weeks 60 and 64 (average) | -167.5 micrometers | Standard Error 8.16 |
p-value: 0.006695% CI: [-46.3, -7.5]ANOVA
p-value: 0.171495% CI: [-37.6, 6.7]ANOVA
Secondary
Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Composite Scores - Study Eye
The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. Each subscale score has a range of 0 to 100 inclusive and will be calculated from the re-scaled raw data. A composite score is derived based on the average of the 11 subscales.
Time frame: Baseline, Week 32, and Week 64
Population: Full Analysis Set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Brolucizumab 6 mg | Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Composite Scores - Study Eye | Week 32 (n-278, 261) | 4.09 Scores on a scale | Standard Error 0.2 |
| Brolucizumab 6 mg | Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Composite Scores - Study Eye | Week 64 (n=248, 224) | 2.8 Scores on a scale | Standard Error 0.69 |
| Aflibercept 2 mg | Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Composite Scores - Study Eye | Week 32 (n-278, 261) | 3.72 Scores on a scale | Standard Error 0.21 |
| Aflibercept 2 mg | Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Composite Scores - Study Eye | Week 64 (n=248, 224) | 4.7 Scores on a scale | Standard Error 0.73 |
p-value: 0.19395% CI: [-0.2, 0.9]ANCOVA
p-value: 0.05295% CI: [-3.9, 0]ANCOVA
Secondary
Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Color Vision - Study Eye
The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. Each subscale score has a range of 0 to 100 inclusive and will be calculated from the re-scaled raw data. A composite score is derived based on the average of the 11 subscales.
Time frame: Baseline, Week 32, and Week 64
Population: Full Analysis Set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Brolucizumab 6 mg | Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Color Vision - Study Eye | Week 32 (n-278, 261) | 1.78 Scores on a scale | Standard Error 0.63 |
| Brolucizumab 6 mg | Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Color Vision - Study Eye | Week 64 (n=244, 222) | 0.1 Scores on a scale | Standard Error 0.8 |
| Aflibercept 2 mg | Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Color Vision - Study Eye | Week 32 (n-278, 261) | 0.02 Scores on a scale | Standard Error 0.65 |
| Aflibercept 2 mg | Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Color Vision - Study Eye | Week 64 (n=244, 222) | 1.2 Scores on a scale | Standard Error 0.84 |
p-value: 0.05495% CI: [0, 3.5]ANCOVA
p-value: 0.33195% CI: [-3.4, 1.2]ANCOVA
Secondary
Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Dependency - Study Eye
The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning or outcome. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. Each subscale score has a range of 0 to 100 inclusive and will be calculated from the re-scaled raw data. A composite score is derived based on the average of the 11 subscales.
Time frame: Baseline, Week 32, and Week 64
Population: Full Analysis Set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Brolucizumab 6 mg | Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Dependency - Study Eye | Week 32 (n-278, 261) | 2.71 Scores on a scale | Standard Error 0.88 |
| Brolucizumab 6 mg | Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Dependency - Study Eye | Week 64 (n=248, 224) | -0.6 Scores on a scale | Standard Error 1.09 |
| Aflibercept 2 mg | Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Dependency - Study Eye | Week 32 (n-278, 261) | 2.22 Scores on a scale | Standard Error 0.91 |
| Aflibercept 2 mg | Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Dependency - Study Eye | Week 64 (n=248, 224) | 2.2 Scores on a scale | Standard Error 1.14 |
p-value: 0.795% CI: [-2, 3]ANCOVA
p-value: 0.0795% CI: [-6, 0.2]ANCOVA
Secondary
Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Distance Activities - Study Eye
The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. Each subscale score has a range of 0 to 100 inclusive and will be calculated from the re-scaled raw data. A composite score is derived based on the average of the 11 subscales.
Time frame: Baseline, Week 32, and Week 64
Population: Full Analysis Set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Brolucizumab 6 mg | Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Distance Activities - Study Eye | Week 32 (n-278, 261) | 3.06 Scores on a scale | Standard Error 0.95 |
| Brolucizumab 6 mg | Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Distance Activities - Study Eye | Week 64 (n=248, 224) | 2.5 Scores on a scale | Standard Error 0.99 |
| Aflibercept 2 mg | Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Distance Activities - Study Eye | Week 32 (n-278, 261) | 3.78 Scores on a scale | Standard Error 0.98 |
| Aflibercept 2 mg | Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Distance Activities - Study Eye | Week 64 (n=248, 224) | 5.0 Scores on a scale | Standard Error 1.04 |
p-value: 0.60295% CI: [-3.4, 2]ANCOVA
p-value: 0.08695% CI: [-5.3, 0.4]ANCOVA
Secondary
Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Driving - Study Eye
The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. Each subscale score has a range of 0 to 100 inclusive and will be calculated from the re-scaled raw data. A composite score is derived based on the average of the 11 subscales.
Time frame: Baseline, Week 32, and Week 64
Population: Full Analysis Set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Brolucizumab 6 mg | Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Driving - Study Eye | Week 64 (n=139, 131) | 1.3 Scores on a scale | Standard Error 1.74 |
| Brolucizumab 6 mg | Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Driving - Study Eye | Week 32 (n-278, 261) | 4.92 Scores on a scale | Standard Error 1.56 |
| Aflibercept 2 mg | Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Driving - Study Eye | Week 32 (n-278, 261) | 4.19 Scores on a scale | Standard Error 1.57 |
| Aflibercept 2 mg | Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Driving - Study Eye | Week 64 (n=139, 131) | 3.0 Scores on a scale | Standard Error 1.79 |
p-value: 0.74195% CI: [-3.6, 5.1]ANCOVA
p-value: 0.49495% CI: [-6.6, 3.2]ANCOVA
Secondary
Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - General Vision - Study Eye
The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. Each subscale score has a range of 0 to 100 inclusive and will be calculated from the re-scaled raw data. A composite score is derived based on the average of the 11 subscales.
Time frame: Baseline, Week 32, and Week 64
Population: Full Analysis Set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Brolucizumab 6 mg | Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - General Vision - Study Eye | Week 32 (n-278, 261) | 7.94 Scores on a scale | Standard Error 0.86 |
| Brolucizumab 6 mg | Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - General Vision - Study Eye | Week 64 (n=248, 224) | 7.3 Scores on a scale | Standard Error 0.87 |
| Aflibercept 2 mg | Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - General Vision - Study Eye | Week 32 (n-278, 261) | 5.79 Scores on a scale | Standard Error 0.89 |
| Aflibercept 2 mg | Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - General Vision - Study Eye | Week 64 (n=248, 224) | 8.0 Scores on a scale | Standard Error 0.92 |
p-value: 0.08195% CI: [-0.3, 4.6]ANCOVA
p-value: 0.5995% CI: [-3.2, 1.8]ANCOVA
Secondary
Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Mental Health - Study Eye
The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning or outcome. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. Each subscale score has a range of 0 to 100 inclusive and will be calculated from the re-scaled raw data. A composite score is derived based on the average of the 11 subscales.
Time frame: Baseline, Week 32, and Week 64
Population: Full Analysis Set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Brolucizumab 6 mg | Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Mental Health - Study Eye | Week 32 (n-278, 261) | 5.83 Scores on a scale | Standard Error 0.99 |
| Brolucizumab 6 mg | Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Mental Health - Study Eye | Week 64 (n=248, 224) | 5.0 Scores on a scale | Standard Error 1.08 |
| Aflibercept 2 mg | Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Mental Health - Study Eye | Week 32 (n-278, 261) | 6.79 Scores on a scale | Standard Error 1.02 |
| Aflibercept 2 mg | Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Mental Health - Study Eye | Week 64 (n=248, 224) | 7.2 Scores on a scale | Standard Error 1.14 |
p-value: 0.49995% CI: [-3.8, 1.8]ANCOVA
p-value: 0.14795% CI: [-5.4, 0.8]ANCOVA
Secondary
Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Ocular Pain - Study Eye
The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. Each subscale score has a range of 0 to 100 inclusive and will be calculated from the re-scaled raw data. A composite score is derived based on the average of the 11 subscales.
Time frame: Baseline, Week 32, and Week 64
Population: Full Analysis Set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Brolucizumab 6 mg | Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Ocular Pain - Study Eye | Week 32 (n-278, 261) | 3.55 Scores on a scale | Standard Error 0.92 |
| Brolucizumab 6 mg | Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Ocular Pain - Study Eye | Week 64 (n=248, 224) | 3.1 Scores on a scale | Standard Error 0.89 |
| Aflibercept 2 mg | Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Ocular Pain - Study Eye | Week 32 (n-278, 261) | 2.78 Scores on a scale | Standard Error 0.94 |
| Aflibercept 2 mg | Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Ocular Pain - Study Eye | Week 64 (n=248, 224) | 5.0 Scores on a scale | Standard Error 0.94 |
p-value: 0.55895% CI: [-1.8, 3.4]ANCOVA
p-value: 0.13895% CI: [-4.5, 0.6]ANCOVA
Secondary
Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Peripheral Vision - Study Eye
The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. Each subscale score has a range of 0 to 100 inclusive and will be calculated from the re-scaled raw data. A composite score is derived based on the average of the 11 subscales.
Time frame: Baseline, Week 32, and Week 64
Population: Full Analysis Set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Brolucizumab 6 mg | Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Peripheral Vision - Study Eye | Week 32 (n-278, 261) | 3.24 Scores on a scale | Standard Error 1.01 |
| Brolucizumab 6 mg | Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Peripheral Vision - Study Eye | Week 64 (n=243, 224) | 2.5 Scores on a scale | Standard Error 1.08 |
| Aflibercept 2 mg | Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Peripheral Vision - Study Eye | Week 32 (n-278, 261) | 2.00 Scores on a scale | Standard Error 1.04 |
| Aflibercept 2 mg | Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Peripheral Vision - Study Eye | Week 64 (n=243, 224) | 3.0 Scores on a scale | Standard Error 1.13 |
p-value: 0.39495% CI: [-1.6, 4.1]ANCOVA
p-value: 0.72895% CI: [-3.6, 2.5]ANCOVA
Secondary
Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Role Difficulties - Study Eye
The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning or outcome. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. Each subscale score has a range of 0 to 100 inclusive and will be calculated from the re-scaled raw data. A composite score is derived based on the average of the 11 subscales.
Time frame: Baseline, Week 32, and Week 64
Population: Full Analysis Set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Brolucizumab 6 mg | Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Role Difficulties - Study Eye | Week 32 (n-278, 261) | 5.17 Scores on a scale | Standard Error 1.31 |
| Brolucizumab 6 mg | Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Role Difficulties - Study Eye | Week 64 (n=248, 224) | 4.7 Scores on a scale | Standard Error 1.31 |
| Aflibercept 2 mg | Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Role Difficulties - Study Eye | Week 32 (n-278, 261) | 4.30 Scores on a scale | Standard Error 1.35 |
| Aflibercept 2 mg | Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Role Difficulties - Study Eye | Week 64 (n=248, 224) | 5.9 Scores on a scale | Standard Error 1.38 |
p-value: 0.64395% CI: [-2.8, 4.6]ANCOVA
p-value: 0.50795% CI: [-5, 2.5]ANCOVA
Secondary
Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Social Functioning - Study Eye
The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning or outcome. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. Each subscale score has a range of 0 to 100 inclusive and will be calculated from the re-scaled raw data. A composite score is derived based on the average of the 11 subscales.
Time frame: Baseline, Week 32, and Week 64
Population: Full Analysis Set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Brolucizumab 6 mg | Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Social Functioning - Study Eye | Week 32 (n-278, 261) | 1.99 Scores on a scale | Standard Error 0.79 |
| Brolucizumab 6 mg | Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Social Functioning - Study Eye | Week 64 (n=247, 223) | 0.2 Scores on a scale | Standard Error 0.81 |
| Aflibercept 2 mg | Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Social Functioning - Study Eye | Week 32 (n-278, 261) | 0.43 Scores on a scale | Standard Error 0.82 |
| Aflibercept 2 mg | Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Social Functioning - Study Eye | Week 64 (n=247, 223) | 1.7 Scores on a scale | Standard Error 0.85 |
p-value: 0.17495% CI: [-0.7, 3.8]ANCOVA
p-value: 0.2195% CI: [-3.8, 0.8]ANCOVA
Secondary
Change From Baseline n Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Near Activities - Study Eye
The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. Each subscale score has a range of 0 to 100 inclusive and will be calculated from the re-scaled raw data. A composite score is derived based on the average of the 11 subscales.
Time frame: Baseline, Week 32, and Week 64
Population: Full Analysis Set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Brolucizumab 6 mg | Change From Baseline n Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Near Activities - Study Eye | Week 32 (n-278, 261) | 7.46 Scores on a scale | Standard Error 1.05 |
| Brolucizumab 6 mg | Change From Baseline n Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Near Activities - Study Eye | Week 64 (n=248, 224) | 4.9 Scores on a scale | Standard Error 1.12 |
| Aflibercept 2 mg | Change From Baseline n Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Near Activities - Study Eye | Week 32 (n-278, 261) | 5.86 Scores on a scale | Standard Error 1.08 |
| Aflibercept 2 mg | Change From Baseline n Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Near Activities - Study Eye | Week 64 (n=248, 224) | 7.9 Scores on a scale | Standard Error 1.18 |
p-value: 0.28795% CI: [-1.4, 4.6]ANCOVA
p-value: 0.0795% CI: [-6.2, 0.2]ANCOVA
Secondary
Distribution of the Last Interval With no Disease Activity up to Week 64 - Study Eye
No disease activity is defined as no change in visual acuity and no change in other signs of the disease (e.g. IRF, SRF, hemorrhage, leakage, etc.). Treatment interval distribution. The number of subjects at 16/12/8/4-weeks intervals as the last interval with no disease activity. If the study treatment is discontinued before Week 16, then the treatment interval is 4 weeks; otherwise. the last interval with no disease activity is used (if there was disease activity, the last interval is shortened by 4 weeks, down to a minimum of 4 weeks). If the duration of the last interval falls within the following ranges of (4-week, 8-week) or (8-week, 12-week) or (12-weeks, 16-weeks) or ≥16-week then the floor value of these ranges was used.
Time frame: Up to Week 64
Population: Full Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brolucizumab 6 mg | Distribution of the Last Interval With no Disease Activity up to Week 64 - Study Eye | 8 Weeks | 95 Participants |
| Brolucizumab 6 mg | Distribution of the Last Interval With no Disease Activity up to Week 64 - Study Eye | 16 Weeks | 104 Participants |
| Brolucizumab 6 mg | Distribution of the Last Interval With no Disease Activity up to Week 64 - Study Eye | 4 Weeks | 85 Participants |
| Brolucizumab 6 mg | Distribution of the Last Interval With no Disease Activity up to Week 64 - Study Eye | 12 Weeks | 82 Participants |
| Aflibercept 2 mg | Distribution of the Last Interval With no Disease Activity up to Week 64 - Study Eye | 4 Weeks | 154 Participants |
| Aflibercept 2 mg | Distribution of the Last Interval With no Disease Activity up to Week 64 - Study Eye | 16 Weeks | 45 Participants |
| Aflibercept 2 mg | Distribution of the Last Interval With no Disease Activity up to Week 64 - Study Eye | 8 Weeks | 81 Participants |
| Aflibercept 2 mg | Distribution of the Last Interval With no Disease Activity up to Week 64 - Study Eye | 12 Weeks | 88 Participants |
p-value: <0.0001Wilcoxon (Mann-Whitney)
Secondary
Distribution of the Maximal Intervals With no Disease Activity up to Week 64 - Study Eye
No disease activity is defined as no change in visual acuity and no change in other signs of the disease (e.g. IRF, SRF, hemorrhage, leakage, etc.). Maximal interval distribution. Number of subjects at 16/12/8/4-weeks intervals as the last interval with no disease activity. If the study treatment is discontinued before Week 16 included, then the treatment interval is 4 weeks; otherwise, the last interval with no disease activity is used (if there was disease activity, the last interval is shortened by 4 weeks, down to a minimum of 4 weeks). If the duration of the maximal interval falls within the following ranges of \[4-weeks, 8-weeks) or \[8-weeks, 12-weeks) or \[12-weeks, 16-weeks\] or ≥16-weeks then the floor value of these ranges is used.
Time frame: Up to Week 64
Population: Full Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brolucizumab 6 mg | Distribution of the Maximal Intervals With no Disease Activity up to Week 64 - Study Eye | 16 Weeks | 117 Participants |
| Brolucizumab 6 mg | Distribution of the Maximal Intervals With no Disease Activity up to Week 64 - Study Eye | 12 Weeks | 96 Participants |
| Brolucizumab 6 mg | Distribution of the Maximal Intervals With no Disease Activity up to Week 64 - Study Eye | 8 Weeks | 94 Participants |
| Brolucizumab 6 mg | Distribution of the Maximal Intervals With no Disease Activity up to Week 64 - Study Eye | 4 Weeks | 59 Participants |
| Aflibercept 2 mg | Distribution of the Maximal Intervals With no Disease Activity up to Week 64 - Study Eye | 4 Weeks | 105 Participants |
| Aflibercept 2 mg | Distribution of the Maximal Intervals With no Disease Activity up to Week 64 - Study Eye | 16 Weeks | 57 Participants |
| Aflibercept 2 mg | Distribution of the Maximal Intervals With no Disease Activity up to Week 64 - Study Eye | 8 Weeks | 114 Participants |
| Aflibercept 2 mg | Distribution of the Maximal Intervals With no Disease Activity up to Week 64 - Study Eye | 12 Weeks | 92 Participants |
p-value: <0.0001Wilcoxon (Mann-Whitney)
Secondary
Number of Participants With Best-corrected Visual Acuity ≥ 69 Letters - Study Eye
BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.
Time frame: Week 32 and Week 64
Population: Full Analysis Set - LOCF
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brolucizumab 6 mg | Number of Participants With Best-corrected Visual Acuity ≥ 69 Letters - Study Eye | Week 32 | 244 Participants |
| Brolucizumab 6 mg | Number of Participants With Best-corrected Visual Acuity ≥ 69 Letters - Study Eye | Week 64 | 240 Participants |
| Aflibercept 2 mg | Number of Participants With Best-corrected Visual Acuity ≥ 69 Letters - Study Eye | Week 32 | 228 Participants |
| Aflibercept 2 mg | Number of Participants With Best-corrected Visual Acuity ≥ 69 Letters - Study Eye | Week 64 | 219 Participants |
p-value: 0.239795% CI: [0.8, 1.7]likelihood ratio test
p-value: 0.11595% CI: [0.9, 1.8]likelihood ratio test
Secondary
Number of Participants With Best-corrected Visual Acuity Improvements of ≥ 15 Letters in BCVA From Baseline or Reached BCVA ≥ 84 Letters up to Week 32/64 Per Treatment Arm - Study Eye
BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.
Time frame: Baseline, Week 32, and Week 64
Population: Full Analysis Set - LOCF
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brolucizumab 6 mg | Number of Participants With Best-corrected Visual Acuity Improvements of ≥ 15 Letters in BCVA From Baseline or Reached BCVA ≥ 84 Letters up to Week 32/64 Per Treatment Arm - Study Eye | Week 32 | 88 Participants |
| Brolucizumab 6 mg | Number of Participants With Best-corrected Visual Acuity Improvements of ≥ 15 Letters in BCVA From Baseline or Reached BCVA ≥ 84 Letters up to Week 32/64 Per Treatment Arm - Study Eye | Week 64 | 89 Participants |
| Aflibercept 2 mg | Number of Participants With Best-corrected Visual Acuity Improvements of ≥ 15 Letters in BCVA From Baseline or Reached BCVA ≥ 84 Letters up to Week 32/64 Per Treatment Arm - Study Eye | Week 32 | 92 Participants |
| Aflibercept 2 mg | Number of Participants With Best-corrected Visual Acuity Improvements of ≥ 15 Letters in BCVA From Baseline or Reached BCVA ≥ 84 Letters up to Week 32/64 Per Treatment Arm - Study Eye | Week 64 | 91 Participants |
p-value: 0.410695% CI: [0.7, 1.3]likelihood ratio test
p-value: 0.466795% CI: [0.7, 1.4]likelihood ratio test
Secondary
Number of Participants With no Disease Activity - Study Eye
Disease activity assessment as determined by visual acuity and assessment of other signs of the disease (e.g. IRF, SRF, hemorrhage, leakage, etc.).
Time frame: Weeks 14 and 16
Population: Full Analysis Set. Note that the number analyzed is reduced because the Week 14 visit was conducted at the investigator's discretion, and because some patients had already stopped treatment by Week 16.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brolucizumab 6 mg | Number of Participants With no Disease Activity - Study Eye | Week 14 (n=118, 137) | 87 Participants |
| Brolucizumab 6 mg | Number of Participants With no Disease Activity - Study Eye | Week 16 (n=301,296) | 260 Participants |
| Aflibercept 2 mg | Number of Participants With no Disease Activity - Study Eye | Week 14 (n=118, 137) | 88 Participants |
| Aflibercept 2 mg | Number of Participants With no Disease Activity - Study Eye | Week 16 (n=301,296) | 211 Participants |
p-value: 0.05195% CI: [0.9, 2.7]likelihood ratio test
p-value: <0.000195% CI: [1.7, 3.9]likelihood ratio test
Secondary
Number of Participants With Presence of Intraretinal Fluid and/or Subretinal Fluid in the Central Subfield - Study Eye
Intraretinal Fluid and/or Subretinal Fluid status was measured by Spectral Domain Optical Coherence Tomography (SD-OCT).
Time frame: At Weeks 28, 32, 60 and 64
Population: Full Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brolucizumab 6 mg | Number of Participants With Presence of Intraretinal Fluid and/or Subretinal Fluid in the Central Subfield - Study Eye | Week 28 (n=285,289) | 175 Participants |
| Brolucizumab 6 mg | Number of Participants With Presence of Intraretinal Fluid and/or Subretinal Fluid in the Central Subfield - Study Eye | Week 32 (n=286, 267) | 144 Participants |
| Brolucizumab 6 mg | Number of Participants With Presence of Intraretinal Fluid and/or Subretinal Fluid in the Central Subfield - Study Eye | Week 60 (n=269,244) | 60 Participants |
| Brolucizumab 6 mg | Number of Participants With Presence of Intraretinal Fluid and/or Subretinal Fluid in the Central Subfield - Study Eye | Week 64 (n=271, 241) | 72 Participants |
| Aflibercept 2 mg | Number of Participants With Presence of Intraretinal Fluid and/or Subretinal Fluid in the Central Subfield - Study Eye | Week 64 (n=271, 241) | 83 Participants |
| Aflibercept 2 mg | Number of Participants With Presence of Intraretinal Fluid and/or Subretinal Fluid in the Central Subfield - Study Eye | Week 28 (n=285,289) | 198 Participants |
| Aflibercept 2 mg | Number of Participants With Presence of Intraretinal Fluid and/or Subretinal Fluid in the Central Subfield - Study Eye | Week 60 (n=269,244) | 69 Participants |
| Aflibercept 2 mg | Number of Participants With Presence of Intraretinal Fluid and/or Subretinal Fluid in the Central Subfield - Study Eye | Week 32 (n=286, 267) | 152 Participants |
Secondary
Number of Participants With Presence of Sub-Retinal Pigment Epithelium Fluid in the Central Subfield - Study Eye
Sub-Retinal Pigment Epithelium fluid status was measured by Spectral Domain Optical Coherence Tomography (SD-OCT).
Time frame: At Weeks 28, 32, 60 and 64
Population: Full Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brolucizumab 6 mg | Number of Participants With Presence of Sub-Retinal Pigment Epithelium Fluid in the Central Subfield - Study Eye | Week 28 (n=288,289) | 173 Participants |
| Brolucizumab 6 mg | Number of Participants With Presence of Sub-Retinal Pigment Epithelium Fluid in the Central Subfield - Study Eye | Week 32 (n=288, 266) | 156 Participants |
| Brolucizumab 6 mg | Number of Participants With Presence of Sub-Retinal Pigment Epithelium Fluid in the Central Subfield - Study Eye | Week 60 (n=271,244) | 27 Participants |
| Brolucizumab 6 mg | Number of Participants With Presence of Sub-Retinal Pigment Epithelium Fluid in the Central Subfield - Study Eye | Week 64 (n=271, 242) | 34 Participants |
| Aflibercept 2 mg | Number of Participants With Presence of Sub-Retinal Pigment Epithelium Fluid in the Central Subfield - Study Eye | Week 64 (n=271, 242) | 43 Participants |
| Aflibercept 2 mg | Number of Participants With Presence of Sub-Retinal Pigment Epithelium Fluid in the Central Subfield - Study Eye | Week 28 (n=288,289) | 208 Participants |
| Aflibercept 2 mg | Number of Participants With Presence of Sub-Retinal Pigment Epithelium Fluid in the Central Subfield - Study Eye | Week 60 (n=271,244) | 31 Participants |
| Aflibercept 2 mg | Number of Participants With Presence of Sub-Retinal Pigment Epithelium Fluid in the Central Subfield - Study Eye | Week 32 (n=288, 266) | 175 Participants |
Secondary
Number of Participants With Treatment Emergent Non-ocular Adverse Events (Greater Than or Equal to 2% in Any Treatment Arm) - Summary Table
An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign (including abnormal laboratory findings), symptom or disease) in a subject or clinical investigation subject.
Time frame: Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 483 days, approx. 69 weeks, 1.3 years.
Population: Safety Analysis set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Brolucizumab 6 mg | Number of Participants With Treatment Emergent Non-ocular Adverse Events (Greater Than or Equal to 2% in Any Treatment Arm) - Summary Table | 182 Participants |
| Aflibercept 2 mg | Number of Participants With Treatment Emergent Non-ocular Adverse Events (Greater Than or Equal to 2% in Any Treatment Arm) - Summary Table | 185 Participants |
Secondary
Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye
An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign (including abnormal laboratory findings), symptom or disease) in a subject or clinical investigation subject.
Time frame: Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 483 days, approx. 69 weeks, 1.3 years.
Population: Safety Analysis set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brolucizumab 6 mg | Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye | Subretinal fluid | 5 Participants |
| Brolucizumab 6 mg | Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye | Conjunctival haemorrhage | 23 Participants |
| Brolucizumab 6 mg | Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye | Visual acuity reduced | 16 Participants |
| Brolucizumab 6 mg | Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye | Eye pain | 17 Participants |
| Brolucizumab 6 mg | Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye | Vitreous floaters | 12 Participants |
| Brolucizumab 6 mg | Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye | Intraocular pressure increased | 5 Participants |
| Brolucizumab 6 mg | Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye | Number of subjects with at least one event | 114 Participants |
| Brolucizumab 6 mg | Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye | Vitreous detachment | 10 Participants |
| Brolucizumab 6 mg | Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye | Retinal haemorrhage | 4 Participants |
| Brolucizumab 6 mg | Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye | Cataract | 5 Participants |
| Brolucizumab 6 mg | Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye | Foreign body sensation in eyes | 4 Participants |
| Brolucizumab 6 mg | Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye | Intra-ocular injection complication | 6 Participants |
| Brolucizumab 6 mg | Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye | Retinal pigment epithelial tear | 5 Participants |
| Brolucizumab 6 mg | Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye | Macular oedema | 3 Participants |
| Brolucizumab 6 mg | Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye | Posterior capsule opacification | 2 Participants |
| Brolucizumab 6 mg | Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye | Dry eye | 2 Participants |
| Brolucizumab 6 mg | Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye | Hordeolum | 4 Participants |
| Brolucizumab 6 mg | Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye | Neovascular age-related macular degeneration | 2 Participants |
| Brolucizumab 6 mg | Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye | Retinal oedema | 1 Participants |
| Brolucizumab 6 mg | Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye | Uveitis | 4 Participants |
| Brolucizumab 6 mg | Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye | Vision blurred | 4 Participants |
| Brolucizumab 6 mg | Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye | Detachment of retinal pigment epithelium | 0 Participants |
| Brolucizumab 6 mg | Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye | Retinal artery occlusion | 4 Participants |
| Brolucizumab 6 mg | Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye | Subretinal fibrosis | 4 Participants |
| Aflibercept 2 mg | Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye | Retinal artery occlusion | 0 Participants |
| Aflibercept 2 mg | Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye | Number of subjects with at least one event | 102 Participants |
| Aflibercept 2 mg | Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye | Retinal pigment epithelial tear | 4 Participants |
| Aflibercept 2 mg | Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye | Conjunctival haemorrhage | 13 Participants |
| Aflibercept 2 mg | Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye | Retinal oedema | 4 Participants |
| Aflibercept 2 mg | Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye | Visual acuity reduced | 18 Participants |
| Aflibercept 2 mg | Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye | Macular oedema | 4 Participants |
| Aflibercept 2 mg | Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye | Eye pain | 13 Participants |
| Aflibercept 2 mg | Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye | Detachment of retinal pigment epithelium | 4 Participants |
| Aflibercept 2 mg | Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye | Vitreous floaters | 6 Participants |
| Aflibercept 2 mg | Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye | Posterior capsule opacification | 5 Participants |
| Aflibercept 2 mg | Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye | Intraocular pressure increased | 11 Participants |
| Aflibercept 2 mg | Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye | Uveitis | 1 Participants |
| Aflibercept 2 mg | Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye | Subretinal fluid | 11 Participants |
| Aflibercept 2 mg | Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye | Dry eye | 4 Participants |
| Aflibercept 2 mg | Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye | Vitreous detachment | 3 Participants |
| Aflibercept 2 mg | Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye | Subretinal fibrosis | 0 Participants |
| Aflibercept 2 mg | Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye | Retinal haemorrhage | 7 Participants |
| Aflibercept 2 mg | Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye | Hordeolum | 2 Participants |
| Aflibercept 2 mg | Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye | Cataract | 5 Participants |
| Aflibercept 2 mg | Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye | Vision blurred | 1 Participants |
| Aflibercept 2 mg | Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye | Foreign body sensation in eyes | 6 Participants |
| Aflibercept 2 mg | Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye | Neovascular age-related macular degeneration | 4 Participants |
| Aflibercept 2 mg | Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye | Intra-ocular injection complication | 3 Participants |
Secondary
Time From Last Loading Injection to First Visit With No Disease Activity (Weeks) - 75th Percentile - Study Eye
Intraretinal fluid (IRF) and subretinal fluid (SRF) were assessed by Spectral Domain Optical Coherence Tomography (SD-OCT) (study eye). Please note that this endpoint can be impacted by the optional disease activity assessment visits and the flexible dosing regimen, in addition to the randomized treatment. Hence, the observed treatment effect may be confounded by the study design artifacts.
Time frame: Up to Week 64
Population: Full Analysis Set - subjects with no important protocol deviations with impact
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Brolucizumab 6 mg | Time From Last Loading Injection to First Visit With No Disease Activity (Weeks) - 75th Percentile - Study Eye | 9.1 weeks |
| Aflibercept 2 mg | Time From Last Loading Injection to First Visit With No Disease Activity (Weeks) - 75th Percentile - Study Eye | 12.1 weeks |
Secondary
Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye
Intraretinal fluid (IRF) and subretinal fluid (SRF) were assessed by Spectral Domain Optical Coherence Tomography (SD-OCT) (study eye).
Time frame: Up to Week 64
Population: Full Analysis Set - subjects with no important protocol deviations with impact
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Brolucizumab 6 mg | Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye | 56 Week | 17 Participants |
| Brolucizumab 6 mg | Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye | 0 Week | 330 Participants |
| Brolucizumab 6 mg | Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye | 4 Week | 144 Participants |
| Brolucizumab 6 mg | Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye | 8 Week | 70 Participants |
| Brolucizumab 6 mg | Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye | 12 Week | 70 Participants |
| Brolucizumab 6 mg | Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye | 16 Week | 37 Participants |
| Brolucizumab 6 mg | Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye | 20 Week | 34 Participants |
| Brolucizumab 6 mg | Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye | 24 Week | 30 Participants |
| Brolucizumab 6 mg | Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye | 28 Week | 28 Participants |
| Brolucizumab 6 mg | Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye | 32 Week | 20 Participants |
| Brolucizumab 6 mg | Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye | 36 Week | 20 Participants |
| Brolucizumab 6 mg | Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye | 40 Week | 18 Participants |
| Brolucizumab 6 mg | Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye | 44 Week | 18 Participants |
| Brolucizumab 6 mg | Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye | 48 Week | 17 Participants |
| Brolucizumab 6 mg | Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye | 52 Week | 17 Participants |
| Brolucizumab 6 mg | Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye | 60 Week | 11 Participants |
| Brolucizumab 6 mg | Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye | 64 Week | 0 Participants |
| Aflibercept 2 mg | Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye | 48 Week | 20 Participants |
| Aflibercept 2 mg | Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye | 32 Week | 25 Participants |
| Aflibercept 2 mg | Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye | 0 Week | 337 Participants |
| Aflibercept 2 mg | Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye | 60 Week | 14 Participants |
| Aflibercept 2 mg | Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye | 4 Week | 138 Participants |
| Aflibercept 2 mg | Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye | 36 Week | 23 Participants |
| Aflibercept 2 mg | Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye | 8 Week | 86 Participants |
| Aflibercept 2 mg | Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye | 52 Week | 20 Participants |
| Aflibercept 2 mg | Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye | 12 Week | 86 Participants |
| Aflibercept 2 mg | Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye | 40 Week | 22 Participants |
| Aflibercept 2 mg | Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye | 16 Week | 67 Participants |
| Aflibercept 2 mg | Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye | 56 Week | 20 Participants |
| Aflibercept 2 mg | Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye | 20 Week | 55 Participants |
| Aflibercept 2 mg | Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye | 44 Week | 22 Participants |
| Aflibercept 2 mg | Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye | 24 Week | 47 Participants |
| Aflibercept 2 mg | Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye | 64 Week | 0 Participants |
| Aflibercept 2 mg | Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye | 28 Week | 38 Participants |