Neovascular Age-related Macular Degeneration
Conditions
Keywords
double-masked, extension study, neovascular age-related macular degeneration, intravitreal injection, brolucizumab, aflibercept
Brief summary
The purpose of this extension study was to assess the safety and efficacy of the new formulation of brolucizumab 6 mg ophthalmic solution when given to the same patients who received brolucizumab in the core trial CRTH258A2301 (also known as CRTH258-C002). The medical condition treated in the core and extension trials was neo-vascular age-related macular degeneration (nAMD).
Detailed description
Subjects in the United States who had completed the 96 week core trial, CRTH258A2301 (also referred as CRTH258-C002), were eligible to participate in the extension trial provided the core trial Visit 26 at week 96, was less than or equal to 12 weeks from the Baseline Visit in the extension trial, CRTH258A2301E1. Subjects who were treated with aflibercept during the core trial and met the eligibility requirements of this extension trial continued to receive aflibercept in this extension trial in order to maintain the masking during the extension trial. No hypothesis testing or descriptive analyses were planned. Subjects who were treated in the core trial with brolucizumab 3mg or brolucizumab 6 mg, and met the eligibility requirements of this extension trial, received the new formulation of brolucizumab 6 mg solution in the extension trial. Enrolled subjects were to receive three intravitreal (IVT) ophthalmic injections. The study eye was the same eye that received the treatment in the core study. The extension trial consisted of 7 study visits at 4 week intervals over a period of 24 weeks. Assessment of the efficacy and safety of brolucizumab 6 mg was based on a within-patient comparison with the last 6 months of corresponding core-study efficacy and safety data serving as the reference. Neither the patient selection process nor expected sample sizes supported a valid comparison between aflibercept and brolucizumab. The aflibercept arm was included only to maintain the masking in the extension trial. Data was presented descriptively for only brolucizumab in line with the study objective. No formal hypothesis testing was planned.
Interventions
Administered as opthalmic solution for an intravitreal injection to the study eye
DRUGAflibercept 2 mg
Administered as an opthalmic solution for intravitreal injection to the study eye
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Sign written informed consent * Completed the core study, CRTH258A2301, also known as CRTH258-C002 as defined by assessments at Visit 26/Week 96 within ≤12 weeks of the baseline.
Exclusion criteria
* Patient discontinued the treatment or the core study prematurely at any time * Patient received standard of care treatment for nAMD after completion of the core study * Pregnant or nursing women and women of child-bearing potential * Stroke or MI (myocardial infarction) within 3 months of the baseline extension visit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Ocular and Non-Ocular Treatment Emergent Adverse Events | Up to Week 24 | Number of participants with ocular and non-ocular treatment emergent events with the new formulation brolucizumab 6 mg in this extension trial up to week 24 vs. the corresponding last 6 months of brolucizumab treatment in the Core trial \>= 2%. Safety assessment of the new formulation brolucizumab 6 mg was based on a within-patient comparison with the last 6 months of corresponding Core safety data. Missing brolucizumab data were imputed using last observation carried forward (LOCF). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change of Loss in BCVA of 15 Letters or More From Extension Baseline at Each Post-baseline Visit | Extension Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 | Best-corrected visual acuity for the study eye was tested at all study visits in a sitting position using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing protocol at an initial testing distance of 4 meters. Outcome measure was prespecified for brolucizumab arm only. Neither patient selection process nor expected sample sizes supported a valid comparison between aflibercept and brolucizumab. The aflibercept arm was included only to maintain the masking in the extension trial. Data presented descriptively for only brolucizumab in line with study objective. No formal hypothesis testing was planned. Missing brolucizumab data were imputed using last observation carried forward (LOCF). |
| Change in BCVA From Extension Baseline at Each Post-baseline Visit | Extension baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 | Best-corrected visual acuity for the study eye was tested at all study visits in a sitting position using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing protocol at an initial testing distance of 4 meters. Outcome measure was prespecified for brolucizumab arm only. Neither the patient selection process nor expected sample sizes supported a valid comparison between aflibercept and brolucizumab. The aflibercept arm was included only to maintain the masking in the extension trial. Data was presented descriptively for only brolucizumab in line with the study objective. No formal hypothesis testing was planned. Missing brolucizumab data were imputed using last observation carried forward (LOCF). |
| Patients With Positive q12w Treatment Status at Week 20 | Week 20 | The estimate for the proportion of patients with a positive q12w treatment status at Week 24 was derived from Kaplan Meier time-to-event analyses for the event 'first q8w-need'. The outcome of the Kaplan-Meier analysis was estimated probability for maintaining on q12w up to the Disease Activity Assessment (DAA) at exWeek 20. Outcome measure was prespecified for brolucizumab arm only. Neither the patient selection process nor expected sample sizes supported a valid comparison between aflibercept and brolucizumab. The aflibercept arm was included only to maintain the masking in the extension trial. Data was presented descriptively for only brolucizumab in line with the study objective. No formal hypothesis testing was planned. Missing brolucizumab data were imputed using last observation carried forward (LOCF). |
| Change in Central Sub-Field Thickness (CSFT) From Extension Baseline at Each Post-baseline Visit | Extension Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 | Measurement of the central subfield thickness of the retina was assessed using Optical Coherence Tomography (OCT) at each visit for the study eye. Outcome measure was prespecified for brolucizumab arm only. Neither the patient selection process nor expected sample sizes supported a valid comparison between aflibercept and brolucizumab. The aflibercept arm was included only to maintain the masking in the extension trial. Data was presented descriptively for only brolucizumab in line with the study objective. No formal hypothesis testing was planned. Missing brolucizumab data were imputed using last observation carried forward (LOCF). |
| Percentage of Subjects With Positive Anti-drug Antibody (ADA) Status for Brolucuzumab 6 mg in Extension | Extension Baseline, Week 8, Week 16, Week 24 | Positive integrated anti-drug antibodies (ADA) status is defined as induced ADA status with ADA negative at pre-dose and a post-dose titer value of greater than or equal to 30 at any time point or boosted ADA status with ADA positive at pre-dose and a post-dose titer value increase by more than 3-fold (1 dilution) at any time point. Outcome measure was prespecified for brolucizumab arm only. Neither the patient selection process nor expected sample sizes supported a valid comparison between aflibercept and brolucizumab. The aflibercept arm was included only to maintain the masking in the extension trial. Data was presented descriptively for only brolucizumab in line with the study objective. No formal hypothesis testing was planned. Missing brolucizumab data were imputed using last observation carried forward (LOCF). |
Countries
Puerto Rico, United States
Participant flow
Recruitment details
150 subjects who completed the 96 week CORE trial (RTH258-C001) were eligible to continue in the extension. 62 CORE sub. were treated w/ brolucizumab 3mg & 45 CORE sub. w/ brolucizumab 6mg. These 107 sub. were treated in the extension w/ new formulation 6 mg brolucizumab. 43 subjects treated with aflibercept 2 mg in the CORE continued aflibercept.
Participants by arm
| Arm | Count |
|---|---|
| Brolucizumab - Overall Extension Study Subjects treated with brolucizumab 3 mg or brolucizumab 6 mg in the Core study. All subjects received IVT injection at the extension Baseline, Week 8 and, depending on disease activity as assessed by the investigator, at Week 16 or Week 20. | 107 |
| Aflibercept Subjects previously treated with aflibercept 2 mg in the Core study continued to receive aflibercept 2mg IVT injection at the extension Baseline, Week 8 and Week 16 to maintain the masking in the extension trial. | 43 |
| Total | 150 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Death | 1 | 0 |
Baseline characteristics
| Characteristic | Brolucizumab - Overall Extension Study | Aflibercept | Total |
|---|---|---|---|
| Age, Continuous | 80.6 years STANDARD_DEVIATION 8.63 | 77.9 years STANDARD_DEVIATION 9.2 | 79.8 years STANDARD_DEVIATION 8.85 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 11 Participants | 6 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 95 Participants | 37 Participants | 132 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Female | 69 Participants | 22 Participants | 91 Participants |
| Sex: Female, Male Male | 38 Participants | 21 Participants | 59 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 107 | 0 / 107 | 0 / 43 |
| other Total, other adverse events | 12 / 107 | 14 / 107 | 13 / 43 |
| serious Total, serious adverse events | 7 / 107 | 7 / 107 | 10 / 43 |
Outcome results
Primary
Number of Participants With Ocular and Non-Ocular Treatment Emergent Adverse Events
Number of participants with ocular and non-ocular treatment emergent events with the new formulation brolucizumab 6 mg in this extension trial up to week 24 vs. the corresponding last 6 months of brolucizumab treatment in the Core trial \>= 2%. Safety assessment of the new formulation brolucizumab 6 mg was based on a within-patient comparison with the last 6 months of corresponding Core safety data. Missing brolucizumab data were imputed using last observation carried forward (LOCF).
Time frame: Up to Week 24
Population: Brolucizumab extension safety set included subjects who received at least one injection of brolucizumab 6mg. Data was presented descriptively for only brolucizumab in line with the study objective. No formal hypothesis testing was planned.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Brolucizumab - Overall Extension Study | Number of Participants With Ocular and Non-Ocular Treatment Emergent Adverse Events | Ocular AEs | 20 Participants |
| Brolucizumab - Overall Extension Study | Number of Participants With Ocular and Non-Ocular Treatment Emergent Adverse Events | Non-Ocular AEs | 51 Participants |
| Brolucizumab Overall Last 6 Months From Core Study | Number of Participants With Ocular and Non-Ocular Treatment Emergent Adverse Events | Ocular AEs | 25 Participants |
| Brolucizumab Overall Last 6 Months From Core Study | Number of Participants With Ocular and Non-Ocular Treatment Emergent Adverse Events | Non-Ocular AEs | 50 Participants |
Secondary
Change in BCVA From Extension Baseline at Each Post-baseline Visit
Best-corrected visual acuity for the study eye was tested at all study visits in a sitting position using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing protocol at an initial testing distance of 4 meters. Outcome measure was prespecified for brolucizumab arm only. Neither the patient selection process nor expected sample sizes supported a valid comparison between aflibercept and brolucizumab. The aflibercept arm was included only to maintain the masking in the extension trial. Data was presented descriptively for only brolucizumab in line with the study objective. No formal hypothesis testing was planned. Missing brolucizumab data were imputed using last observation carried forward (LOCF).
Time frame: Extension baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24
Population: Extension Data Set included all subjects who entered extension study and received at least one injection of study treatment. Assessment of the efficacy of brolucizumab 6 mg was based on a within-patient comparison with the last 6 months of corresponding core-study efficacy and safety data serving as the reference.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Brolucizumab - Overall Extension Study | Change in BCVA From Extension Baseline at Each Post-baseline Visit | exWeek 4 | -1.3 Letter read | Standard Deviation 6.26 |
| Brolucizumab - Overall Extension Study | Change in BCVA From Extension Baseline at Each Post-baseline Visit | exWeek 8 | -1.7 Letter read | Standard Deviation 6.9 |
| Brolucizumab - Overall Extension Study | Change in BCVA From Extension Baseline at Each Post-baseline Visit | exWeek 12 | -2.7 Letter read | Standard Deviation 7.73 |
| Brolucizumab - Overall Extension Study | Change in BCVA From Extension Baseline at Each Post-baseline Visit | exWeek 16 | -3.9 Letter read | Standard Deviation 8.42 |
| Brolucizumab - Overall Extension Study | Change in BCVA From Extension Baseline at Each Post-baseline Visit | exWeek 20 | -3.4 Letter read | Standard Deviation 7.66 |
| Brolucizumab - Overall Extension Study | Change in BCVA From Extension Baseline at Each Post-baseline Visit | exWeek 24 | -2.0 Letter read | Standard Deviation 8.17 |
| Brolucizumab Overall Last 6 Months From Core Study | Change in BCVA From Extension Baseline at Each Post-baseline Visit | exWeek 24 | 0.3 Letter read | Standard Deviation 6.79 |
| Brolucizumab Overall Last 6 Months From Core Study | Change in BCVA From Extension Baseline at Each Post-baseline Visit | exWeek 4 | 0.5 Letter read | Standard Deviation 3.81 |
| Brolucizumab Overall Last 6 Months From Core Study | Change in BCVA From Extension Baseline at Each Post-baseline Visit | exWeek 16 | 0.8 Letter read | Standard Deviation 5.36 |
| Brolucizumab Overall Last 6 Months From Core Study | Change in BCVA From Extension Baseline at Each Post-baseline Visit | exWeek 20 | 0.5 Letter read | Standard Deviation 7.34 |
| Brolucizumab Overall Last 6 Months From Core Study | Change in BCVA From Extension Baseline at Each Post-baseline Visit | exWeek 8 | -0.4 Letter read | Standard Deviation 4.29 |
| Brolucizumab Overall Last 6 Months From Core Study | Change in BCVA From Extension Baseline at Each Post-baseline Visit | exWeek 12 | -0.3 Letter read | Standard Deviation 5.17 |
| Brolucizumab - Overall Extension Study | Change in BCVA From Extension Baseline at Each Post-baseline Visit | exWeek 8 | -1.2 Letter read | Standard Deviation 5.96 |
| Brolucizumab - Overall Extension Study | Change in BCVA From Extension Baseline at Each Post-baseline Visit | exWeek 12 | -1.7 Letter read | Standard Deviation 6.84 |
| Brolucizumab - Overall Extension Study | Change in BCVA From Extension Baseline at Each Post-baseline Visit | exWeek 24 | -1.0 Letter read | Standard Deviation 7.67 |
| Brolucizumab - Overall Extension Study | Change in BCVA From Extension Baseline at Each Post-baseline Visit | exWeek 16 | -1.9 Letter read | Standard Deviation 7.63 |
| Brolucizumab - Overall Extension Study | Change in BCVA From Extension Baseline at Each Post-baseline Visit | exWeek 4 | -0.5 Letter read | Standard Deviation 5.42 |
| Brolucizumab - Overall Extension Study | Change in BCVA From Extension Baseline at Each Post-baseline Visit | exWeek 20 | -1.8 Letter read | Standard Deviation 7.75 |
Secondary
Change in Central Sub-Field Thickness (CSFT) From Extension Baseline at Each Post-baseline Visit
Measurement of the central subfield thickness of the retina was assessed using Optical Coherence Tomography (OCT) at each visit for the study eye. Outcome measure was prespecified for brolucizumab arm only. Neither the patient selection process nor expected sample sizes supported a valid comparison between aflibercept and brolucizumab. The aflibercept arm was included only to maintain the masking in the extension trial. Data was presented descriptively for only brolucizumab in line with the study objective. No formal hypothesis testing was planned. Missing brolucizumab data were imputed using last observation carried forward (LOCF).
Time frame: Extension Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24
Population: Extension Data Set included all subjects who entered extension study and received at least one injection of study treatment. Assessment of the efficacy and safety of brolucizumab 6 mg was based on a within-patient comparison with the last 6 months of corresponding core-study efficacy data serving as the reference.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Brolucizumab - Overall Extension Study | Change in Central Sub-Field Thickness (CSFT) From Extension Baseline at Each Post-baseline Visit | exWeek 4 | -19.2 micrometer | Standard Deviation 39.29 |
| Brolucizumab - Overall Extension Study | Change in Central Sub-Field Thickness (CSFT) From Extension Baseline at Each Post-baseline Visit | exWeek 8 | -6.3 micrometer | Standard Deviation 25.47 |
| Brolucizumab - Overall Extension Study | Change in Central Sub-Field Thickness (CSFT) From Extension Baseline at Each Post-baseline Visit | exWeek 12 | -17.9 micrometer | Standard Deviation 43.07 |
| Brolucizumab - Overall Extension Study | Change in Central Sub-Field Thickness (CSFT) From Extension Baseline at Each Post-baseline Visit | exWeek 16 | -7.8 micrometer | Standard Deviation 31.94 |
| Brolucizumab - Overall Extension Study | Change in Central Sub-Field Thickness (CSFT) From Extension Baseline at Each Post-baseline Visit | exWeek 20 | -10.1 micrometer | Standard Deviation 59.04 |
| Brolucizumab - Overall Extension Study | Change in Central Sub-Field Thickness (CSFT) From Extension Baseline at Each Post-baseline Visit | exWeek 24 | -19.8 micrometer | Standard Deviation 37.67 |
| Brolucizumab Overall Last 6 Months From Core Study | Change in Central Sub-Field Thickness (CSFT) From Extension Baseline at Each Post-baseline Visit | exWeek 24 | -24.6 micrometer | Standard Deviation 42.1 |
| Brolucizumab Overall Last 6 Months From Core Study | Change in Central Sub-Field Thickness (CSFT) From Extension Baseline at Each Post-baseline Visit | exWeek 4 | -17.5 micrometer | Standard Deviation 40.76 |
| Brolucizumab Overall Last 6 Months From Core Study | Change in Central Sub-Field Thickness (CSFT) From Extension Baseline at Each Post-baseline Visit | exWeek 16 | -11.7 micrometer | Standard Deviation 39.83 |
| Brolucizumab Overall Last 6 Months From Core Study | Change in Central Sub-Field Thickness (CSFT) From Extension Baseline at Each Post-baseline Visit | exWeek 20 | -15.3 micrometer | Standard Deviation 46.2 |
| Brolucizumab Overall Last 6 Months From Core Study | Change in Central Sub-Field Thickness (CSFT) From Extension Baseline at Each Post-baseline Visit | exWeek 8 | -18.9 micrometer | Standard Deviation 31.74 |
| Brolucizumab Overall Last 6 Months From Core Study | Change in Central Sub-Field Thickness (CSFT) From Extension Baseline at Each Post-baseline Visit | exWeek 12 | -28.9 micrometer | Standard Deviation 48.8 |
| Brolucizumab - Overall Extension Study | Change in Central Sub-Field Thickness (CSFT) From Extension Baseline at Each Post-baseline Visit | exWeek 8 | -11.6 micrometer | Standard Deviation 28.82 |
| Brolucizumab - Overall Extension Study | Change in Central Sub-Field Thickness (CSFT) From Extension Baseline at Each Post-baseline Visit | exWeek 12 | -22.5 micrometer | Standard Deviation 45.66 |
| Brolucizumab - Overall Extension Study | Change in Central Sub-Field Thickness (CSFT) From Extension Baseline at Each Post-baseline Visit | exWeek 24 | -21.8 micrometer | Standard Deviation 39.47 |
| Brolucizumab - Overall Extension Study | Change in Central Sub-Field Thickness (CSFT) From Extension Baseline at Each Post-baseline Visit | exWeek 16 | -9.4 micrometer | Standard Deviation 35.35 |
| Brolucizumab - Overall Extension Study | Change in Central Sub-Field Thickness (CSFT) From Extension Baseline at Each Post-baseline Visit | exWeek 4 | -18.5 micrometer | Standard Deviation 39.74 |
| Brolucizumab - Overall Extension Study | Change in Central Sub-Field Thickness (CSFT) From Extension Baseline at Each Post-baseline Visit | exWeek 20 | -12.3 micrometer | Standard Deviation 53.84 |
Secondary
Change of Loss in BCVA of 15 Letters or More From Extension Baseline at Each Post-baseline Visit
Best-corrected visual acuity for the study eye was tested at all study visits in a sitting position using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing protocol at an initial testing distance of 4 meters. Outcome measure was prespecified for brolucizumab arm only. Neither patient selection process nor expected sample sizes supported a valid comparison between aflibercept and brolucizumab. The aflibercept arm was included only to maintain the masking in the extension trial. Data presented descriptively for only brolucizumab in line with study objective. No formal hypothesis testing was planned. Missing brolucizumab data were imputed using last observation carried forward (LOCF).
Time frame: Extension Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24
Population: Extension Data Set included all subjects who entered extension study and received at least one injection of study treatment. Assessment of the efficacy and safety of brolucizumab 6 mg was based on a within-patient comparison with the last 6 months of corresponding core study efficacy data serving as the reference.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Brolucizumab - Overall Extension Study | Change of Loss in BCVA of 15 Letters or More From Extension Baseline at Each Post-baseline Visit | exWeek 4 (>=15 letters loss) | 2 Number of Participants |
| Brolucizumab - Overall Extension Study | Change of Loss in BCVA of 15 Letters or More From Extension Baseline at Each Post-baseline Visit | exWeek 8 (>=15 letters loss) | 4 Number of Participants |
| Brolucizumab - Overall Extension Study | Change of Loss in BCVA of 15 Letters or More From Extension Baseline at Each Post-baseline Visit | exWeek 12 (>=15 letters loss) | 4 Number of Participants |
| Brolucizumab - Overall Extension Study | Change of Loss in BCVA of 15 Letters or More From Extension Baseline at Each Post-baseline Visit | exWeek 16 (>=15 letters loss) | 6 Number of Participants |
| Brolucizumab - Overall Extension Study | Change of Loss in BCVA of 15 Letters or More From Extension Baseline at Each Post-baseline Visit | exWeek 20 (>=15 letters loss) | 4 Number of Participants |
| Brolucizumab - Overall Extension Study | Change of Loss in BCVA of 15 Letters or More From Extension Baseline at Each Post-baseline Visit | exWeek 24 (>=15 letters loss) | 3 Number of Participants |
| Brolucizumab Overall Last 6 Months From Core Study | Change of Loss in BCVA of 15 Letters or More From Extension Baseline at Each Post-baseline Visit | exWeek 24 (>=15 letters loss) | 0 Number of Participants |
| Brolucizumab Overall Last 6 Months From Core Study | Change of Loss in BCVA of 15 Letters or More From Extension Baseline at Each Post-baseline Visit | exWeek 4 (>=15 letters loss) | 0 Number of Participants |
| Brolucizumab Overall Last 6 Months From Core Study | Change of Loss in BCVA of 15 Letters or More From Extension Baseline at Each Post-baseline Visit | exWeek 16 (>=15 letters loss) | 0 Number of Participants |
| Brolucizumab Overall Last 6 Months From Core Study | Change of Loss in BCVA of 15 Letters or More From Extension Baseline at Each Post-baseline Visit | exWeek 20 (>=15 letters loss) | 0 Number of Participants |
| Brolucizumab Overall Last 6 Months From Core Study | Change of Loss in BCVA of 15 Letters or More From Extension Baseline at Each Post-baseline Visit | exWeek 8 (>=15 letters loss) | 0 Number of Participants |
| Brolucizumab Overall Last 6 Months From Core Study | Change of Loss in BCVA of 15 Letters or More From Extension Baseline at Each Post-baseline Visit | exWeek 12 (>=15 letters loss) | 0 Number of Participants |
| Brolucizumab - Overall Extension Study | Change of Loss in BCVA of 15 Letters or More From Extension Baseline at Each Post-baseline Visit | exWeek 8 (>=15 letters loss) | 4 Number of Participants |
| Brolucizumab - Overall Extension Study | Change of Loss in BCVA of 15 Letters or More From Extension Baseline at Each Post-baseline Visit | exWeek 12 (>=15 letters loss) | 4 Number of Participants |
| Brolucizumab - Overall Extension Study | Change of Loss in BCVA of 15 Letters or More From Extension Baseline at Each Post-baseline Visit | exWeek 24 (>=15 letters loss) | 3 Number of Participants |
| Brolucizumab - Overall Extension Study | Change of Loss in BCVA of 15 Letters or More From Extension Baseline at Each Post-baseline Visit | exWeek 16 (>=15 letters loss) | 6 Number of Participants |
| Brolucizumab - Overall Extension Study | Change of Loss in BCVA of 15 Letters or More From Extension Baseline at Each Post-baseline Visit | exWeek 4 (>=15 letters loss) | 2 Number of Participants |
| Brolucizumab - Overall Extension Study | Change of Loss in BCVA of 15 Letters or More From Extension Baseline at Each Post-baseline Visit | exWeek 20 (>=15 letters loss) | 4 Number of Participants |
Secondary
Patients With Positive q12w Treatment Status at Week 20
The estimate for the proportion of patients with a positive q12w treatment status at Week 24 was derived from Kaplan Meier time-to-event analyses for the event 'first q8w-need'. The outcome of the Kaplan-Meier analysis was estimated probability for maintaining on q12w up to the Disease Activity Assessment (DAA) at exWeek 20. Outcome measure was prespecified for brolucizumab arm only. Neither the patient selection process nor expected sample sizes supported a valid comparison between aflibercept and brolucizumab. The aflibercept arm was included only to maintain the masking in the extension trial. Data was presented descriptively for only brolucizumab in line with the study objective. No formal hypothesis testing was planned. Missing brolucizumab data were imputed using last observation carried forward (LOCF).
Time frame: Week 20
Population: Extension Data Set included all subjects who entered extension study and received at least one injection of study treatment. Assessment of the efficacy and safety of brolucizumab 6 mg was based on a within-patient comparison with last 6 months of corresponding core-study efficacy data serving as reference.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Brolucizumab - Overall Extension Study | Patients With Positive q12w Treatment Status at Week 20 | 63.3 Percentage of patients |
| Brolucizumab Overall Last 6 Months From Core Study | Patients With Positive q12w Treatment Status at Week 20 | 63.1 Percentage of patients |
| Brolucizumab - Overall Extension Study | Patients With Positive q12w Treatment Status at Week 20 | 63.3 Percentage of patients |
Secondary
Percentage of Subjects With Positive Anti-drug Antibody (ADA) Status for Brolucuzumab 6 mg in Extension
Positive integrated anti-drug antibodies (ADA) status is defined as induced ADA status with ADA negative at pre-dose and a post-dose titer value of greater than or equal to 30 at any time point or boosted ADA status with ADA positive at pre-dose and a post-dose titer value increase by more than 3-fold (1 dilution) at any time point. Outcome measure was prespecified for brolucizumab arm only. Neither the patient selection process nor expected sample sizes supported a valid comparison between aflibercept and brolucizumab. The aflibercept arm was included only to maintain the masking in the extension trial. Data was presented descriptively for only brolucizumab in line with the study objective. No formal hypothesis testing was planned. Missing brolucizumab data were imputed using last observation carried forward (LOCF).
Time frame: Extension Baseline, Week 8, Week 16, Week 24
Population: Extension Data Set included all subjects who entered extension study and received at least one injection of study treatment. Assessment of efficacy and safety of brolucizumab 6 mg was based on a within-patient comparison with last 6 months of corresponding core-study efficacy data serving as the reference.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Brolucizumab - Overall Extension Study | Percentage of Subjects With Positive Anti-drug Antibody (ADA) Status for Brolucuzumab 6 mg in Extension | 54 Percentage of participants |