Age-related Macular Degeneration
Conditions
Keywords
neovascular age-related macular degeneration, anti-VEGF, choroidal neovascularization, brolucizumab, loading vs. non-loading, Macular degeneration, age-related macular degeneration (ARMD), vision loss, macula damage, retina damage, dry macular degeneration, wet macular degeneration, Subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration, Retinal Degeneration, Retinal Diseases, Eye Diseases
Brief summary
The purpose of this study was to evaluate the efficacy and safety of two different brolucizumab 6 mg dosing regimens in patients with visual impairment due to age-related macular degeneration (AMD) who have previously received anti-VEGF (vascular endothelial growth factor) treatment.
Detailed description
This study was a 52-week randomized, open-label, multi-center, two-arm study for pretreated patients with suboptimal anatomically controlled nAMD. Patients who consented were screened to evaluate eligibility. Eligible patients were randomized in a 1:1 ratio to one of the two treatment arms: * Brolucizumab 6 mg loading arm: 1 loading injection every 4 weeks for 3 consecutive injections (baseline, weeks 4 and 8) followed by an injection every 12 weeks. * Brolucizumab 6 mg non-loading arm: one initial injection followed by an injection every 12 weeks There were three periods in this study: * Screening period: from day -14 to baseline * Open-label treatment period: from baseline (day 1) to week 48 * Post-treatment follow-up period: from week 48 to week 52 In both study arms, treatment intervals after the initiation phase were either 8 weeks or 12 weeks depending on disease activity status. More frequent injections, i.e., treatment intervals of \< 8 weeks were not allowed after the initiation phase.
Interventions
BIOLOGICALBrolucizumab
Intravitreal injection
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
open-label
Intervention model description
two arm, multicenter
Eligibility
Sex/Gender
ALL
Age
50 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Male or female patients ≥ 50 years of age at screening * 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 (intraretinal fluid (IRF) and/or subretinal fluid (SRF) and/or sub-retinal pigment epithelium (sub-RPE) fluid that affects the central subfield, as seen by spectral domain optical coherence tomography (SD-OCT)) at screening, as confirmed by central reading center (study eye). If active CNV according to the above explained activity criteria is not detectable in screening image data (no IRF and no SRF), presence of residual and/or recurrent fluid (IRF and / or SRF) within the last 6 months before baseline visit is also considered eligible. In this case, historical images must be submitted for analysis by the central reading center. * Pretreatment with any anti-VEGF drug for a maximum of five years (60 months). Patients should have shown functional and/or anatomical treatment response to the pretreatment(s), prior to participating in this study. * The treatment initiation phase with the current anti-VEGF must have been completed for at least 6 months with continuous treatment in a ≥ q4w to ≤ q12w injection interval (±2-day window, i.e., 26 to 86 days inclusive) before the baseline visit. At least 4 weeks (minimum 26 days) must have passed between the last anti-VEGF pretreatment and baseline. * 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
* 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 judgement, at screening or baseline (study eye) * Presence of amblyopia, amaurosis or ocular disorders in the fellow eye with BCVA \<20/200 at screening (except when due to conditions whose surgery may improve VA, e.g. cataract) * Ocular treatments: treatment with anti-VEGF drugs for \> 5 years in the study eye, pretreatment with brolucizumab at any time in the study eye, previous treatment with investigational drugs in the last 6 months, intraocular or periocular steroids at any time, macular laser photocoagulation or photodynamic therapy at any time, peripheral laser photocoagulation within 3 months prior to baseline, intraocular surgery within 3 months prior to baseline, vitreoretinal surgery at any time, aphakia with the absence of posterior capsule (study eye) * Stroke or myocardial infarction during the 6 month period prior to baseline * Systemic anti-VEGF therapy during the 3-month period prior to baseline
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Week 40 to Week 52: LS Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye | Baseline, Week 40 to Week 52 | BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. Visual function of the study eye was assessed using the ETDRS protocol. Participants with a BCVA ETDRS letter score between 78 and 23 ETDRS letters (inclusive) at Screening and Baseline in the study eye were included. Min and max possible scores are 0-100 respectively. A higher score represents better functioning. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Prolonged Interval | Baseline, Week 52 | Treatment interval distribution. Prolongation was calculated by comparing the mean treatment interval in last 24 weeks prior to first brolucizumab injection (a) with the mean of the average treatment interval during the study (loading phase excluded in the loading arm) and (b) with the last treatment interval during the study. Patients with only 1 injection during the treatment period were calculated as non-responders (no prolon-gation). |
| Proportion of Patients Who Maintained on q12w Regimen. | Up to week 52 | Treatment interval distribution up to Week 52. Proportion of patients maintained on q12w treatment frequency in the two brolucizumab groups up to week 52. Patients who discontinued treatment before week 52 were rated as non-responders, i.e., as patients who did not maintain the q12w regimen. In the loading arm, the loading period up to week 12 was not considered in the analysis. |
| Distribution of Patients at Every 8 Weeks / Every 12 Weeks Intervals - Frequency of Switches in Treatment Intervals Between Baseline and Week 52 | Up to Week 52 | Treatment interval distribution |
| Mean Change in Best-corrected Visual Acuity | Baseline, Weeks 16 to 28, Week 52 | BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. Visual function of the study eye was assessed using the ETDRS protocol. Participants with a BCVA ETDRS letter score between 78 and 23 ETDRS letters (inclusive) at Screening and Baseline in the study eye were included. Min and max possible scores are 0-100 respectively. A higher score represents better functioning. |
| Number of Patients With Best-corrected Visual Acuity Improvements of >= 5, >= 10 and >= 15 Letters | Baseline, up to Week 52 | BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. Visual function of the study eye was assessed using the ETDRS protocol. Participants with a BCVA ETDRS letter score between 78 and 23 ETDRS letters (inclusive) at Screening and Baseline in the study eye were included. Min and max possible scores are 0-100 respectively. A higher score represents better functioning. |
| Number of Patients With Best-corrected Visual Acuity >= 69 Letters | Baseline, up to Week 52 | BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. Visual function of the study eye was assessed using the ETDRS protocol. Participants with a BCVA ETDRS letter score between 78 and 23 ETDRS letters (inclusive) at Screening and Baseline in the study eye were included. Min and max possible scores are 0-100 respectively. A higher score represents better functioning. |
| LS Mean Change in Best-corrected Visual Acuity From Baseline at Week 52 | Baseline, Week 52 | BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. Visual function of the study eye was assessed using the ETDRS protocol. Participants with a BCVA ETDRS letter score between 78 and 23 ETDRS letters (inclusive) at Screening and Baseline in the study eye were included. Min and max possible scores are 0-100 respectively. A higher score represents better functioning. |
| Change in Central Subfield Thickness From Baseline at Weeks 12, 16, 28 and 52 | Baseline, Weeks 12, 16, 28 and 52 | Change in central subfield thickness was measured by Spectral domain optical coherence tomography. |
| Treatment Intervals Before and During the Study | -24 Weeks, Baseline, Week 52 | Treatment interval distribution. Treatment interval during the study, within 24 weeks prior to baseline and interval between the last 2 injections in the study. In the loading arm, data from the loading period was excluded. |
| Absence of Subretinal Fluid in the Central Subfield | Every 4 weeks from baseline up to Week 52 | Change in fluids was measured by Spectral domain optical coherence tomography. |
| Absence of Sub-retinal Pigment Epithelium Fluid in the Central Subfield | Every 4 weeks from baseline up to Week 52 | Change in fluids was measured by Spectral domain optical coherence tomography. |
| Presence of Active Choroidal Neovascularization Leakage | At Week 52 | Presence of active choroidal neovascularization leakage was measured by Fluorescein angiography. CNV = choroidal neovascularization; MNV = macular neovascularization |
| Overview of TEAEs | Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of approximately 52 weeks. | An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign (including abnormal laboratory findings), symptom or disease) in a subject or clinical investigation subject after providing written informed consent for participation in the study. Treatment-emergent AEs are AEs that developed on or after first study treatment administration, or any event previously present that worsened following exposure to the study treatment. |
| Ocular TEAEs in the Study Eye by Primary System Organ Class | Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of approximately 52 weeks. | An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign (including abnormal laboratory findings), symptom or disease) in a subject or clinical investigation subject after providing written informed consent for participation in the study. Treatment-emergent AEs are AEs that developed on or after first study treatment administration, or any event previously present that worsened following exposure to the study treatment. |
| Ocular TEAEs in the Study Eye by Preferred Term (at Least 5% in Any Group) | Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of approximately 52 weeks. | An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign (including abnormal laboratory findings), symptom or disease) in a subject or clinical investigation subject after providing written informed consent for participation in the study. Treatment-emergent AEs are AEs that developed on or after first study treatment administration, or any event previously present that worsened following exposure to the study treatment. |
| Non-ocular TEAEs - Total | Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of approximately 52 weeks. | An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign (including abnormal laboratory findings), symptom or disease) in a subject or clinical investigation subject after providing written informed consent for participation in the study. Treatment-emergent AEs are AEs that developed on or after first study treatment administration, or any event previously present that worsened following exposure to the study treatment. |
| Ocular TEAEs in the Study Eye of Moderate or Severe Intensity | Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of approximately 52 weeks. | An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign (including abnormal laboratory findings), symptom or disease) in a subject or clinical investigation subject after providing written informed consent for participation in the study. Treatment-emergent AEs are AEs that developed on or after first study treatment administration, or any event previously present that worsened following exposure to the study treatment. |
| Absence of Intraretinal Fluid in the Central Subfield | Every 4 weeks from baseline up to Week 52 | Change in fluids was measured by Spectral domain optical coherence tomography. |
Countries
Germany, Switzerland
Participant flow
Pre-assignment details
If both eyes were eligible as per the inclusion and exclusion criteria, the eye with the worse visual acuity should have been selected for study eye, unless the investigator deemed it more appropriate to select the eye with better visual acuity, based on medical reasons or local ethical requirements.
Participants by arm
| Arm | Count |
|---|---|
| Brolucizumab 6 mg Loading 3 x 4-weekly initial injections followed by an injection every 12 weeks | 25 |
| Brolucizumab 6 mg Non-loading One initial injection followed by treatment every 12 weeks | 27 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 1 |
Baseline characteristics
| Characteristic | Brolucizumab 6 mg Non-loading | Total | Brolucizumab 6 mg Loading |
|---|---|---|---|
| Age, Continuous | 77.4 years STANDARD_DEVIATION 8.3 | 77.5 years STANDARD_DEVIATION 7.3 | 77.6 years STANDARD_DEVIATION 6.3 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 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 | 27 Participants | 52 Participants | 25 Participants |
| Sex: Female, Male Female | 18 Participants | 32 Participants | 14 Participants |
| Sex: Female, Male Male | 9 Participants | 20 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 1 / 27 |
| other Total, other adverse events | 23 / 25 | 26 / 27 |
| serious Total, serious adverse events | 5 / 25 | 6 / 27 |
Outcome results
Primary
Week 40 to Week 52: LS Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye
BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. Visual function of the study eye was assessed using the ETDRS protocol. Participants with a BCVA ETDRS letter score between 78 and 23 ETDRS letters (inclusive) at Screening and Baseline in the study eye were included. Min and max possible scores are 0-100 respectively. A higher score represents better functioning.
Time frame: Baseline, Week 40 to Week 52
Population: full analysis set - included all patients with a valid assessment without a protocol deviation with impact
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Brolucizumab 6 mg Loading | Week 40 to Week 52: LS Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye | Week 40 | 3.24 Letters read | Standard Error 1.32 |
| Brolucizumab 6 mg Loading | Week 40 to Week 52: LS Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye | Week 44 | 3.88 Letters read | Standard Error 1.66 |
| Brolucizumab 6 mg Loading | Week 40 to Week 52: LS Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye | Week 48 | 3.12 Letters read | Standard Error 1.71 |
| Brolucizumab 6 mg Loading | Week 40 to Week 52: LS Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye | Week 52 | 2.76 Letters read | Standard Error 1.64 |
| Brolucizumab 6 mg Non-loading | Week 40 to Week 52: LS Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye | Week 52 | -1.43 Letters read | Standard Error 1.58 |
| Brolucizumab 6 mg Non-loading | Week 40 to Week 52: LS Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye | Week 40 | -0.50 Letters read | Standard Error 1.28 |
| Brolucizumab 6 mg Non-loading | Week 40 to Week 52: LS Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye | Week 48 | -2.23 Letters read | Standard Error 1.65 |
| Brolucizumab 6 mg Non-loading | Week 40 to Week 52: LS Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye | Week 44 | -0.27 Letters read | Standard Error 1.6 |
Comparison: Week 4095% CI: [-7.47, -0.01]MMRM model
Comparison: Week 4495% CI: [-8.78, -0.48]MMRM model
Comparison: Week 4895% CI: [-10.13, -0.58]MMRM model
Comparison: Week 5295% CI: [-8.77, 0.39]MMRM model
Comparison: Mean of Week 40 to Week 5295% CI: [-8.56, -0.16]MMRM model
Secondary
Absence of Intraretinal Fluid in the Central Subfield
Change in fluids was measured by Spectral domain optical coherence tomography.
Time frame: Every 4 weeks from baseline up to Week 52
Population: full analysis set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brolucizumab 6 mg Loading | Absence of Intraretinal Fluid in the Central Subfield | Week 20 | 16 Participants |
| Brolucizumab 6 mg Loading | Absence of Intraretinal Fluid in the Central Subfield | Week 48 | 19 Participants |
| Brolucizumab 6 mg Loading | Absence of Intraretinal Fluid in the Central Subfield | Week 24 | 17 Participants |
| Brolucizumab 6 mg Loading | Absence of Intraretinal Fluid in the Central Subfield | Week 8 | 17 Participants |
| Brolucizumab 6 mg Loading | Absence of Intraretinal Fluid in the Central Subfield | Week 28 | 16 Participants |
| Brolucizumab 6 mg Loading | Absence of Intraretinal Fluid in the Central Subfield | Baseline | 13 Participants |
| Brolucizumab 6 mg Loading | Absence of Intraretinal Fluid in the Central Subfield | Week 32 | 18 Participants |
| Brolucizumab 6 mg Loading | Absence of Intraretinal Fluid in the Central Subfield | Week 12 | 21 Participants |
| Brolucizumab 6 mg Loading | Absence of Intraretinal Fluid in the Central Subfield | Week 40 | 16 Participants |
| Brolucizumab 6 mg Loading | Absence of Intraretinal Fluid in the Central Subfield | Week 44 | 16 Participants |
| Brolucizumab 6 mg Loading | Absence of Intraretinal Fluid in the Central Subfield | Week 52 | 16 Participants |
| Brolucizumab 6 mg Loading | Absence of Intraretinal Fluid in the Central Subfield | Week 16 | 12 Participants |
| Brolucizumab 6 mg Loading | Absence of Intraretinal Fluid in the Central Subfield | Week 36 | 17 Participants |
| Brolucizumab 6 mg Loading | Absence of Intraretinal Fluid in the Central Subfield | Week 4 | 19 Participants |
| Brolucizumab 6 mg Non-loading | Absence of Intraretinal Fluid in the Central Subfield | Week 36 | 17 Participants |
| Brolucizumab 6 mg Non-loading | Absence of Intraretinal Fluid in the Central Subfield | Week 44 | 19 Participants |
| Brolucizumab 6 mg Non-loading | Absence of Intraretinal Fluid in the Central Subfield | Baseline | 16 Participants |
| Brolucizumab 6 mg Non-loading | Absence of Intraretinal Fluid in the Central Subfield | Week 4 | 22 Participants |
| Brolucizumab 6 mg Non-loading | Absence of Intraretinal Fluid in the Central Subfield | Week 8 | 16 Participants |
| Brolucizumab 6 mg Non-loading | Absence of Intraretinal Fluid in the Central Subfield | Week 12 | 16 Participants |
| Brolucizumab 6 mg Non-loading | Absence of Intraretinal Fluid in the Central Subfield | Week 16 | 21 Participants |
| Brolucizumab 6 mg Non-loading | Absence of Intraretinal Fluid in the Central Subfield | Week 20 | 20 Participants |
| Brolucizumab 6 mg Non-loading | Absence of Intraretinal Fluid in the Central Subfield | Week 24 | 18 Participants |
| Brolucizumab 6 mg Non-loading | Absence of Intraretinal Fluid in the Central Subfield | Week 28 | 20 Participants |
| Brolucizumab 6 mg Non-loading | Absence of Intraretinal Fluid in the Central Subfield | Week 32 | 17 Participants |
| Brolucizumab 6 mg Non-loading | Absence of Intraretinal Fluid in the Central Subfield | Week 48 | 19 Participants |
| Brolucizumab 6 mg Non-loading | Absence of Intraretinal Fluid in the Central Subfield | Week 52 | 21 Participants |
| Brolucizumab 6 mg Non-loading | Absence of Intraretinal Fluid in the Central Subfield | Week 40 | 21 Participants |
Secondary
Absence of Subretinal Fluid in the Central Subfield
Change in fluids was measured by Spectral domain optical coherence tomography.
Time frame: Every 4 weeks from baseline up to Week 52
Population: full analysis set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brolucizumab 6 mg Loading | Absence of Subretinal Fluid in the Central Subfield | Baseline | 5 Participants |
| Brolucizumab 6 mg Loading | Absence of Subretinal Fluid in the Central Subfield | Week 4 | 13 Participants |
| Brolucizumab 6 mg Loading | Absence of Subretinal Fluid in the Central Subfield | Week 8 | 18 Participants |
| Brolucizumab 6 mg Loading | Absence of Subretinal Fluid in the Central Subfield | Week 12 | 20 Participants |
| Brolucizumab 6 mg Loading | Absence of Subretinal Fluid in the Central Subfield | Week 16 | 8 Participants |
| Brolucizumab 6 mg Loading | Absence of Subretinal Fluid in the Central Subfield | Week 20 | 3 Participants |
| Brolucizumab 6 mg Loading | Absence of Subretinal Fluid in the Central Subfield | Week 24 | 13 Participants |
| Brolucizumab 6 mg Loading | Absence of Subretinal Fluid in the Central Subfield | Week 28 | 9 Participants |
| Brolucizumab 6 mg Loading | Absence of Subretinal Fluid in the Central Subfield | Week 32 | 11 Participants |
| Brolucizumab 6 mg Loading | Absence of Subretinal Fluid in the Central Subfield | Week 36 | 11 Participants |
| Brolucizumab 6 mg Loading | Absence of Subretinal Fluid in the Central Subfield | Week 40 | 10 Participants |
| Brolucizumab 6 mg Loading | Absence of Subretinal Fluid in the Central Subfield | Week 44 | 8 Participants |
| Brolucizumab 6 mg Loading | Absence of Subretinal Fluid in the Central Subfield | Week 48 | 10 Participants |
| Brolucizumab 6 mg Loading | Absence of Subretinal Fluid in the Central Subfield | Week 52 | 9 Participants |
| Brolucizumab 6 mg Non-loading | Absence of Subretinal Fluid in the Central Subfield | Week 40 | 15 Participants |
| Brolucizumab 6 mg Non-loading | Absence of Subretinal Fluid in the Central Subfield | Baseline | 6 Participants |
| Brolucizumab 6 mg Non-loading | Absence of Subretinal Fluid in the Central Subfield | Week 28 | 13 Participants |
| Brolucizumab 6 mg Non-loading | Absence of Subretinal Fluid in the Central Subfield | Week 4 | 18 Participants |
| Brolucizumab 6 mg Non-loading | Absence of Subretinal Fluid in the Central Subfield | Week 48 | 15 Participants |
| Brolucizumab 6 mg Non-loading | Absence of Subretinal Fluid in the Central Subfield | Week 8 | 12 Participants |
| Brolucizumab 6 mg Non-loading | Absence of Subretinal Fluid in the Central Subfield | Week 32 | 14 Participants |
| Brolucizumab 6 mg Non-loading | Absence of Subretinal Fluid in the Central Subfield | Week 12 | 6 Participants |
| Brolucizumab 6 mg Non-loading | Absence of Subretinal Fluid in the Central Subfield | Week 44 | 10 Participants |
| Brolucizumab 6 mg Non-loading | Absence of Subretinal Fluid in the Central Subfield | Week 16 | 15 Participants |
| Brolucizumab 6 mg Non-loading | Absence of Subretinal Fluid in the Central Subfield | Week 36 | 14 Participants |
| Brolucizumab 6 mg Non-loading | Absence of Subretinal Fluid in the Central Subfield | Week 20 | 12 Participants |
| Brolucizumab 6 mg Non-loading | Absence of Subretinal Fluid in the Central Subfield | Week 52 | 16 Participants |
| Brolucizumab 6 mg Non-loading | Absence of Subretinal Fluid in the Central Subfield | Week 24 | 12 Participants |
Secondary
Absence of Sub-retinal Pigment Epithelium Fluid in the Central Subfield
Change in fluids was measured by Spectral domain optical coherence tomography.
Time frame: Every 4 weeks from baseline up to Week 52
Population: full analysis set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brolucizumab 6 mg Loading | Absence of Sub-retinal Pigment Epithelium Fluid in the Central Subfield | Baseline | 15 Participants |
| Brolucizumab 6 mg Loading | Absence of Sub-retinal Pigment Epithelium Fluid in the Central Subfield | Week 4 | 20 Participants |
| Brolucizumab 6 mg Loading | Absence of Sub-retinal Pigment Epithelium Fluid in the Central Subfield | Week 8 | 18 Participants |
| Brolucizumab 6 mg Loading | Absence of Sub-retinal Pigment Epithelium Fluid in the Central Subfield | Week 12 | 20 Participants |
| Brolucizumab 6 mg Loading | Absence of Sub-retinal Pigment Epithelium Fluid in the Central Subfield | Week 16 | 20 Participants |
| Brolucizumab 6 mg Loading | Absence of Sub-retinal Pigment Epithelium Fluid in the Central Subfield | Week 20 | 17 Participants |
| Brolucizumab 6 mg Loading | Absence of Sub-retinal Pigment Epithelium Fluid in the Central Subfield | Week 24 | 18 Participants |
| Brolucizumab 6 mg Loading | Absence of Sub-retinal Pigment Epithelium Fluid in the Central Subfield | Week 28 | 19 Participants |
| Brolucizumab 6 mg Loading | Absence of Sub-retinal Pigment Epithelium Fluid in the Central Subfield | Week 32 | 19 Participants |
| Brolucizumab 6 mg Loading | Absence of Sub-retinal Pigment Epithelium Fluid in the Central Subfield | Week 36 | 18 Participants |
| Brolucizumab 6 mg Loading | Absence of Sub-retinal Pigment Epithelium Fluid in the Central Subfield | Week 40 | 22 Participants |
| Brolucizumab 6 mg Loading | Absence of Sub-retinal Pigment Epithelium Fluid in the Central Subfield | Week 44 | 18 Participants |
| Brolucizumab 6 mg Loading | Absence of Sub-retinal Pigment Epithelium Fluid in the Central Subfield | Week 48 | 21 Participants |
| Brolucizumab 6 mg Loading | Absence of Sub-retinal Pigment Epithelium Fluid in the Central Subfield | Week 52 | 17 Participants |
| Brolucizumab 6 mg Non-loading | Absence of Sub-retinal Pigment Epithelium Fluid in the Central Subfield | Week 40 | 18 Participants |
| Brolucizumab 6 mg Non-loading | Absence of Sub-retinal Pigment Epithelium Fluid in the Central Subfield | Baseline | 13 Participants |
| Brolucizumab 6 mg Non-loading | Absence of Sub-retinal Pigment Epithelium Fluid in the Central Subfield | Week 28 | 21 Participants |
| Brolucizumab 6 mg Non-loading | Absence of Sub-retinal Pigment Epithelium Fluid in the Central Subfield | Week 4 | 21 Participants |
| Brolucizumab 6 mg Non-loading | Absence of Sub-retinal Pigment Epithelium Fluid in the Central Subfield | Week 48 | 18 Participants |
| Brolucizumab 6 mg Non-loading | Absence of Sub-retinal Pigment Epithelium Fluid in the Central Subfield | Week 8 | 16 Participants |
| Brolucizumab 6 mg Non-loading | Absence of Sub-retinal Pigment Epithelium Fluid in the Central Subfield | Week 32 | 20 Participants |
| Brolucizumab 6 mg Non-loading | Absence of Sub-retinal Pigment Epithelium Fluid in the Central Subfield | Week 12 | 17 Participants |
| Brolucizumab 6 mg Non-loading | Absence of Sub-retinal Pigment Epithelium Fluid in the Central Subfield | Week 44 | 18 Participants |
| Brolucizumab 6 mg Non-loading | Absence of Sub-retinal Pigment Epithelium Fluid in the Central Subfield | Week 16 | 14 Participants |
| Brolucizumab 6 mg Non-loading | Absence of Sub-retinal Pigment Epithelium Fluid in the Central Subfield | Week 36 | 19 Participants |
| Brolucizumab 6 mg Non-loading | Absence of Sub-retinal Pigment Epithelium Fluid in the Central Subfield | Week 20 | 16 Participants |
| Brolucizumab 6 mg Non-loading | Absence of Sub-retinal Pigment Epithelium Fluid in the Central Subfield | Week 52 | 16 Participants |
| Brolucizumab 6 mg Non-loading | Absence of Sub-retinal Pigment Epithelium Fluid in the Central Subfield | Week 24 | 16 Participants |
Secondary
Change in Central Subfield Thickness From Baseline at Weeks 12, 16, 28 and 52
Change in central subfield thickness was measured by Spectral domain optical coherence tomography.
Time frame: Baseline, Weeks 12, 16, 28 and 52
Population: full analysis set
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Brolucizumab 6 mg Loading | Change in Central Subfield Thickness From Baseline at Weeks 12, 16, 28 and 52 | Week 12 | -74.0 µm |
| Brolucizumab 6 mg Loading | Change in Central Subfield Thickness From Baseline at Weeks 12, 16, 28 and 52 | Week 16 | -20.0 µm |
| Brolucizumab 6 mg Loading | Change in Central Subfield Thickness From Baseline at Weeks 12, 16, 28 and 52 | Week 28 | -21.0 µm |
| Brolucizumab 6 mg Loading | Change in Central Subfield Thickness From Baseline at Weeks 12, 16, 28 and 52 | Week 52 | -15.0 µm |
| Brolucizumab 6 mg Non-loading | Change in Central Subfield Thickness From Baseline at Weeks 12, 16, 28 and 52 | Week 52 | -49.5 µm |
| Brolucizumab 6 mg Non-loading | Change in Central Subfield Thickness From Baseline at Weeks 12, 16, 28 and 52 | Week 12 | -8.5 µm |
| Brolucizumab 6 mg Non-loading | Change in Central Subfield Thickness From Baseline at Weeks 12, 16, 28 and 52 | Week 28 | -53.0 µm |
| Brolucizumab 6 mg Non-loading | Change in Central Subfield Thickness From Baseline at Weeks 12, 16, 28 and 52 | Week 16 | -51.0 µm |
Secondary
Distribution of Patients at Every 8 Weeks / Every 12 Weeks Intervals - Frequency of Switches in Treatment Intervals Between Baseline and Week 52
Treatment interval distribution
Time frame: Up to Week 52
Population: full analysis set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brolucizumab 6 mg Loading | Distribution of Patients at Every 8 Weeks / Every 12 Weeks Intervals - Frequency of Switches in Treatment Intervals Between Baseline and Week 52 | Switch q12w to q8w (overall) | 15 Participants |
| Brolucizumab 6 mg Loading | Distribution of Patients at Every 8 Weeks / Every 12 Weeks Intervals - Frequency of Switches in Treatment Intervals Between Baseline and Week 52 | Switch q8w to q12w (overall) | 3 Participants |
| Brolucizumab 6 mg Non-loading | Distribution of Patients at Every 8 Weeks / Every 12 Weeks Intervals - Frequency of Switches in Treatment Intervals Between Baseline and Week 52 | Switch q12w to q8w (overall) | 19 Participants |
| Brolucizumab 6 mg Non-loading | Distribution of Patients at Every 8 Weeks / Every 12 Weeks Intervals - Frequency of Switches in Treatment Intervals Between Baseline and Week 52 | Switch q8w to q12w (overall) | 6 Participants |
Secondary
LS Mean Change in Best-corrected Visual Acuity From Baseline at Week 52
BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. Visual function of the study eye was assessed using the ETDRS protocol. Participants with a BCVA ETDRS letter score between 78 and 23 ETDRS letters (inclusive) at Screening and Baseline in the study eye were included. Min and max possible scores are 0-100 respectively. A higher score represents better functioning.
Time frame: Baseline, Week 52
Population: full analysis set - included all patients with a valid assessment without a protocol deviation with impact
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Brolucizumab 6 mg Loading | LS Mean Change in Best-corrected Visual Acuity From Baseline at Week 52 | 2.76 Letters read | Standard Error 1.64 |
| Brolucizumab 6 mg Non-loading | LS Mean Change in Best-corrected Visual Acuity From Baseline at Week 52 | -1.43 Letters read | Standard Error 1.58 |
Comparison: Week 5295% CI: [-8.77, -0.39]MMRM model
Secondary
Mean Change in Best-corrected Visual Acuity
BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. Visual function of the study eye was assessed using the ETDRS protocol. Participants with a BCVA ETDRS letter score between 78 and 23 ETDRS letters (inclusive) at Screening and Baseline in the study eye were included. Min and max possible scores are 0-100 respectively. A higher score represents better functioning.
Time frame: Baseline, Weeks 16 to 28, Week 52
Population: full analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Brolucizumab 6 mg Loading | Mean Change in Best-corrected Visual Acuity | Baseline | 72.0 Letters read | Standard Deviation 8.7 |
| Brolucizumab 6 mg Loading | Mean Change in Best-corrected Visual Acuity | Mean of weeks 16 to 28 | 74.9 Letters read | Standard Deviation 9.2 |
| Brolucizumab 6 mg Loading | Mean Change in Best-corrected Visual Acuity | Week 52 | 74.8 Letters read | Standard Deviation 9.1 |
| Brolucizumab 6 mg Non-loading | Mean Change in Best-corrected Visual Acuity | Baseline | 71.6 Letters read | Standard Deviation 11.5 |
| Brolucizumab 6 mg Non-loading | Mean Change in Best-corrected Visual Acuity | Mean of weeks 16 to 28 | 71.2 Letters read | Standard Deviation 12.9 |
| Brolucizumab 6 mg Non-loading | Mean Change in Best-corrected Visual Acuity | Week 52 | 69.8 Letters read | Standard Deviation 16.1 |
Secondary
Non-ocular TEAEs - Total
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 after providing written informed consent for participation in the study. Treatment-emergent AEs are AEs that developed on or after first study treatment administration, or any event previously present that worsened following exposure to the study treatment.
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 timeframe of approximately 52 weeks.
Population: safety analysis set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Brolucizumab 6 mg Loading | Non-ocular TEAEs - Total | 20 Participants |
| Brolucizumab 6 mg Non-loading | Non-ocular TEAEs - Total | 19 Participants |
Secondary
Number of Patients With Best-corrected Visual Acuity >= 69 Letters
BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. Visual function of the study eye was assessed using the ETDRS protocol. Participants with a BCVA ETDRS letter score between 78 and 23 ETDRS letters (inclusive) at Screening and Baseline in the study eye were included. Min and max possible scores are 0-100 respectively. A higher score represents better functioning.
Time frame: Baseline, up to Week 52
Population: full analysis set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Brolucizumab 6 mg Loading | Number of Patients With Best-corrected Visual Acuity >= 69 Letters | 20 Participants |
| Brolucizumab 6 mg Non-loading | Number of Patients With Best-corrected Visual Acuity >= 69 Letters | 19 Participants |
Secondary
Number of Patients With Best-corrected Visual Acuity Improvements of >= 5, >= 10 and >= 15 Letters
BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. Visual function of the study eye was assessed using the ETDRS protocol. Participants with a BCVA ETDRS letter score between 78 and 23 ETDRS letters (inclusive) at Screening and Baseline in the study eye were included. Min and max possible scores are 0-100 respectively. A higher score represents better functioning.
Time frame: Baseline, up to Week 52
Population: full analysis set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brolucizumab 6 mg Loading | Number of Patients With Best-corrected Visual Acuity Improvements of >= 5, >= 10 and >= 15 Letters | BCVA ≥ 5 ETDRS letters improvement during the study | 9 Participants |
| Brolucizumab 6 mg Loading | Number of Patients With Best-corrected Visual Acuity Improvements of >= 5, >= 10 and >= 15 Letters | BCVA ≥ 10 ETDRS letters improvement during the study | 2 Participants |
| Brolucizumab 6 mg Loading | Number of Patients With Best-corrected Visual Acuity Improvements of >= 5, >= 10 and >= 15 Letters | BCVA ≥ 15 ETDRS letters improvement during the study | 1 Participants |
| Brolucizumab 6 mg Non-loading | Number of Patients With Best-corrected Visual Acuity Improvements of >= 5, >= 10 and >= 15 Letters | BCVA ≥ 5 ETDRS letters improvement during the study | 5 Participants |
| Brolucizumab 6 mg Non-loading | Number of Patients With Best-corrected Visual Acuity Improvements of >= 5, >= 10 and >= 15 Letters | BCVA ≥ 10 ETDRS letters improvement during the study | 2 Participants |
| Brolucizumab 6 mg Non-loading | Number of Patients With Best-corrected Visual Acuity Improvements of >= 5, >= 10 and >= 15 Letters | BCVA ≥ 15 ETDRS letters improvement during the study | 0 Participants |
Secondary
Number of Patients With Prolonged Interval
Treatment interval distribution. Prolongation was calculated by comparing the mean treatment interval in last 24 weeks prior to first brolucizumab injection (a) with the mean of the average treatment interval during the study (loading phase excluded in the loading arm) and (b) with the last treatment interval during the study. Patients with only 1 injection during the treatment period were calculated as non-responders (no prolon-gation).
Time frame: Baseline, Week 52
Population: full analysis set - included all patients with a valid assessment without a protocol deviation with impact
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brolucizumab 6 mg Loading | Number of Patients With Prolonged Interval | from baseline to week 52 | 18 Participants |
| Brolucizumab 6 mg Loading | Number of Patients With Prolonged Interval | Last treatment interval during the study | 13 Participants |
| Brolucizumab 6 mg Non-loading | Number of Patients With Prolonged Interval | from baseline to week 52 | 12 Participants |
| Brolucizumab 6 mg Non-loading | Number of Patients With Prolonged Interval | Last treatment interval during the study | 10 Participants |
Secondary
Ocular TEAEs in the Study Eye by Preferred Term (at Least 5% in Any Group)
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 after providing written informed consent for participation in the study. Treatment-emergent AEs are AEs that developed on or after first study treatment administration, or any event previously present that worsened following exposure to the study treatment.
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 timeframe of approximately 52 weeks.
Population: safety analysis set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brolucizumab 6 mg Loading | Ocular TEAEs in the Study Eye by Preferred Term (at Least 5% in Any Group) | Conjunctival haemorrhage | 7 Participants |
| Brolucizumab 6 mg Loading | Ocular TEAEs in the Study Eye by Preferred Term (at Least 5% in Any Group) | Visual acuity reduced | 2 Participants |
| Brolucizumab 6 mg Loading | Ocular TEAEs in the Study Eye by Preferred Term (at Least 5% in Any Group) | Eye inflammation | 1 Participants |
| Brolucizumab 6 mg Loading | Ocular TEAEs in the Study Eye by Preferred Term (at Least 5% in Any Group) | Intraocular pressure increased | 1 Participants |
| Brolucizumab 6 mg Loading | Ocular TEAEs in the Study Eye by Preferred Term (at Least 5% in Any Group) | Retinal oedema | 1 Participants |
| Brolucizumab 6 mg Loading | Ocular TEAEs in the Study Eye by Preferred Term (at Least 5% in Any Group) | Dry Eye | 1 Participants |
| Brolucizumab 6 mg Loading | Ocular TEAEs in the Study Eye by Preferred Term (at Least 5% in Any Group) | Neovascular age-related macular degeneration | 1 Participants |
| Brolucizumab 6 mg Loading | Ocular TEAEs in the Study Eye by Preferred Term (at Least 5% in Any Group) | Vitreous detachment | 2 Participants |
| Brolucizumab 6 mg Loading | Ocular TEAEs in the Study Eye by Preferred Term (at Least 5% in Any Group) | Cataract | 0 Participants |
| Brolucizumab 6 mg Loading | Ocular TEAEs in the Study Eye by Preferred Term (at Least 5% in Any Group) | Conjunctivitis | 0 Participants |
| Brolucizumab 6 mg Loading | Ocular TEAEs in the Study Eye by Preferred Term (at Least 5% in Any Group) | Retinal exudates | 0 Participants |
| Brolucizumab 6 mg Loading | Ocular TEAEs in the Study Eye by Preferred Term (at Least 5% in Any Group) | Vitreous floaters | 0 Participants |
| Brolucizumab 6 mg Non-loading | Ocular TEAEs in the Study Eye by Preferred Term (at Least 5% in Any Group) | Retinal exudates | 2 Participants |
| Brolucizumab 6 mg Non-loading | Ocular TEAEs in the Study Eye by Preferred Term (at Least 5% in Any Group) | Conjunctival haemorrhage | 5 Participants |
| Brolucizumab 6 mg Non-loading | Ocular TEAEs in the Study Eye by Preferred Term (at Least 5% in Any Group) | Neovascular age-related macular degeneration | 2 Participants |
| Brolucizumab 6 mg Non-loading | Ocular TEAEs in the Study Eye by Preferred Term (at Least 5% in Any Group) | Visual acuity reduced | 3 Participants |
| Brolucizumab 6 mg Non-loading | Ocular TEAEs in the Study Eye by Preferred Term (at Least 5% in Any Group) | Conjunctivitis | 2 Participants |
| Brolucizumab 6 mg Non-loading | Ocular TEAEs in the Study Eye by Preferred Term (at Least 5% in Any Group) | Eye inflammation | 3 Participants |
| Brolucizumab 6 mg Non-loading | Ocular TEAEs in the Study Eye by Preferred Term (at Least 5% in Any Group) | Vitreous detachment | 1 Participants |
| Brolucizumab 6 mg Non-loading | Ocular TEAEs in the Study Eye by Preferred Term (at Least 5% in Any Group) | Intraocular pressure increased | 3 Participants |
| Brolucizumab 6 mg Non-loading | Ocular TEAEs in the Study Eye by Preferred Term (at Least 5% in Any Group) | Vitreous floaters | 2 Participants |
| Brolucizumab 6 mg Non-loading | Ocular TEAEs in the Study Eye by Preferred Term (at Least 5% in Any Group) | Retinal oedema | 3 Participants |
| Brolucizumab 6 mg Non-loading | Ocular TEAEs in the Study Eye by Preferred Term (at Least 5% in Any Group) | Cataract | 2 Participants |
| Brolucizumab 6 mg Non-loading | Ocular TEAEs in the Study Eye by Preferred Term (at Least 5% in Any Group) | Dry Eye | 2 Participants |
Secondary
Ocular TEAEs in the Study Eye by Primary System Organ Class
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 after providing written informed consent for participation in the study. Treatment-emergent AEs are AEs that developed on or after first study treatment administration, or any event previously present that worsened following exposure to the study treatment.
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 timeframe of approximately 52 weeks.
Population: safety analysis set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brolucizumab 6 mg Loading | Ocular TEAEs in the Study Eye by Primary System Organ Class | Total | 17 Participants |
| Brolucizumab 6 mg Loading | Ocular TEAEs in the Study Eye by Primary System Organ Class | General disorders and administration site conditions | 0 Participants |
| Brolucizumab 6 mg Loading | Ocular TEAEs in the Study Eye by Primary System Organ Class | Infections and infestations | 2 Participants |
| Brolucizumab 6 mg Loading | Ocular TEAEs in the Study Eye by Primary System Organ Class | Injury, poisoning and procedural complications | 2 Participants |
| Brolucizumab 6 mg Loading | Ocular TEAEs in the Study Eye by Primary System Organ Class | Investigations | 2 Participants |
| Brolucizumab 6 mg Loading | Ocular TEAEs in the Study Eye by Primary System Organ Class | Eye disorders | 16 Participants |
| Brolucizumab 6 mg Non-loading | Ocular TEAEs in the Study Eye by Primary System Organ Class | Infections and infestations | 2 Participants |
| Brolucizumab 6 mg Non-loading | Ocular TEAEs in the Study Eye by Primary System Organ Class | Total | 19 Participants |
| Brolucizumab 6 mg Non-loading | Ocular TEAEs in the Study Eye by Primary System Organ Class | Eye disorders | 17 Participants |
| Brolucizumab 6 mg Non-loading | Ocular TEAEs in the Study Eye by Primary System Organ Class | Investigations | 4 Participants |
| Brolucizumab 6 mg Non-loading | Ocular TEAEs in the Study Eye by Primary System Organ Class | General disorders and administration site conditions | 1 Participants |
| Brolucizumab 6 mg Non-loading | Ocular TEAEs in the Study Eye by Primary System Organ Class | Injury, poisoning and procedural complications | 1 Participants |
Secondary
Ocular TEAEs in the Study Eye of Moderate or Severe Intensity
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 after providing written informed consent for participation in the study. Treatment-emergent AEs are AEs that developed on or after first study treatment administration, or any event previously present that worsened following exposure to the study treatment.
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 timeframe of approximately 52 weeks.
Population: safety analysis set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brolucizumab 6 mg Loading | Ocular TEAEs in the Study Eye of Moderate or Severe Intensity | Any AE of moderate intensity | 3 Participants |
| Brolucizumab 6 mg Loading | Ocular TEAEs in the Study Eye of Moderate or Severe Intensity | Cataract - moderate intensity | 0 Participants |
| Brolucizumab 6 mg Loading | Ocular TEAEs in the Study Eye of Moderate or Severe Intensity | Conjunctival haemorrhage - moderate intensity | 0 Participants |
| Brolucizumab 6 mg Loading | Ocular TEAEs in the Study Eye of Moderate or Severe Intensity | Conjunctival irritation - moderate intensity | 1 Participants |
| Brolucizumab 6 mg Loading | Ocular TEAEs in the Study Eye of Moderate or Severe Intensity | Conjunctivitis allergic - moderate intensity | 0 Participants |
| Brolucizumab 6 mg Loading | Ocular TEAEs in the Study Eye of Moderate or Severe Intensity | Dry eye - moderate intensity | 1 Participants |
| Brolucizumab 6 mg Loading | Ocular TEAEs in the Study Eye of Moderate or Severe Intensity | Eye inflammation - moderate intensity | 0 Participants |
| Brolucizumab 6 mg Loading | Ocular TEAEs in the Study Eye of Moderate or Severe Intensity | Eye pain - moderate intensity | 0 Participants |
| Brolucizumab 6 mg Loading | Ocular TEAEs in the Study Eye of Moderate or Severe Intensity | Neovascular age-related macular degeneration - moderate intensity | 0 Participants |
| Brolucizumab 6 mg Loading | Ocular TEAEs in the Study Eye of Moderate or Severe Intensity | Retinal vasculitis - moderate intensity | 0 Participants |
| Brolucizumab 6 mg Loading | Ocular TEAEs in the Study Eye of Moderate or Severe Intensity | Subretinal fluid - moderate intensity | 0 Participants |
| Brolucizumab 6 mg Loading | Ocular TEAEs in the Study Eye of Moderate or Severe Intensity | Visual acuity reduced - moderate intensity | 1 Participants |
| Brolucizumab 6 mg Loading | Ocular TEAEs in the Study Eye of Moderate or Severe Intensity | Vital dye staining cornea present - moderate intensity | 0 Participants |
| Brolucizumab 6 mg Loading | Ocular TEAEs in the Study Eye of Moderate or Severe Intensity | Vitreous opacities - moderate intensity | 0 Participants |
| Brolucizumab 6 mg Loading | Ocular TEAEs in the Study Eye of Moderate or Severe Intensity | Any AE of severe intensity | 1 Participants |
| Brolucizumab 6 mg Loading | Ocular TEAEs in the Study Eye of Moderate or Severe Intensity | Endophthalmitis - severe intensity | 1 Participants |
| Brolucizumab 6 mg Loading | Ocular TEAEs in the Study Eye of Moderate or Severe Intensity | Eye inflammation - severe intensity | 1 Participants |
| Brolucizumab 6 mg Loading | Ocular TEAEs in the Study Eye of Moderate or Severe Intensity | Intraocular pressure increased - severe intensity | 0 Participants |
| Brolucizumab 6 mg Loading | Ocular TEAEs in the Study Eye of Moderate or Severe Intensity | Retinal haemorrhage - severe intensity | 0 Participants |
| Brolucizumab 6 mg Loading | Ocular TEAEs in the Study Eye of Moderate or Severe Intensity | Retinal neovascularization - severe intensity | 0 Participants |
| Brolucizumab 6 mg Loading | Ocular TEAEs in the Study Eye of Moderate or Severe Intensity | Visual acuity reduced - severe intensity | 0 Participants |
| Brolucizumab 6 mg Non-loading | Ocular TEAEs in the Study Eye of Moderate or Severe Intensity | Subretinal fluid - moderate intensity | 1 Participants |
| Brolucizumab 6 mg Non-loading | Ocular TEAEs in the Study Eye of Moderate or Severe Intensity | Any AE of moderate intensity | 8 Participants |
| Brolucizumab 6 mg Non-loading | Ocular TEAEs in the Study Eye of Moderate or Severe Intensity | Retinal haemorrhage - severe intensity | 1 Participants |
| Brolucizumab 6 mg Non-loading | Ocular TEAEs in the Study Eye of Moderate or Severe Intensity | Cataract - moderate intensity | 2 Participants |
| Brolucizumab 6 mg Non-loading | Ocular TEAEs in the Study Eye of Moderate or Severe Intensity | Visual acuity reduced - moderate intensity | 0 Participants |
| Brolucizumab 6 mg Non-loading | Ocular TEAEs in the Study Eye of Moderate or Severe Intensity | Conjunctival haemorrhage - moderate intensity | 1 Participants |
| Brolucizumab 6 mg Non-loading | Ocular TEAEs in the Study Eye of Moderate or Severe Intensity | Eye inflammation - severe intensity | 1 Participants |
| Brolucizumab 6 mg Non-loading | Ocular TEAEs in the Study Eye of Moderate or Severe Intensity | Conjunctival irritation - moderate intensity | 0 Participants |
| Brolucizumab 6 mg Non-loading | Ocular TEAEs in the Study Eye of Moderate or Severe Intensity | Vital dye staining cornea present - moderate intensity | 1 Participants |
| Brolucizumab 6 mg Non-loading | Ocular TEAEs in the Study Eye of Moderate or Severe Intensity | Conjunctivitis allergic - moderate intensity | 1 Participants |
| Brolucizumab 6 mg Non-loading | Ocular TEAEs in the Study Eye of Moderate or Severe Intensity | Visual acuity reduced - severe intensity | 1 Participants |
| Brolucizumab 6 mg Non-loading | Ocular TEAEs in the Study Eye of Moderate or Severe Intensity | Dry eye - moderate intensity | 1 Participants |
| Brolucizumab 6 mg Non-loading | Ocular TEAEs in the Study Eye of Moderate or Severe Intensity | Vitreous opacities - moderate intensity | 1 Participants |
| Brolucizumab 6 mg Non-loading | Ocular TEAEs in the Study Eye of Moderate or Severe Intensity | Eye inflammation - moderate intensity | 1 Participants |
| Brolucizumab 6 mg Non-loading | Ocular TEAEs in the Study Eye of Moderate or Severe Intensity | Intraocular pressure increased - severe intensity | 1 Participants |
| Brolucizumab 6 mg Non-loading | Ocular TEAEs in the Study Eye of Moderate or Severe Intensity | Eye pain - moderate intensity | 1 Participants |
| Brolucizumab 6 mg Non-loading | Ocular TEAEs in the Study Eye of Moderate or Severe Intensity | Any AE of severe intensity | 2 Participants |
| Brolucizumab 6 mg Non-loading | Ocular TEAEs in the Study Eye of Moderate or Severe Intensity | Neovascular age-related macular degeneration - moderate intensity | 1 Participants |
| Brolucizumab 6 mg Non-loading | Ocular TEAEs in the Study Eye of Moderate or Severe Intensity | Retinal neovascularization - severe intensity | 1 Participants |
| Brolucizumab 6 mg Non-loading | Ocular TEAEs in the Study Eye of Moderate or Severe Intensity | Retinal vasculitis - moderate intensity | 2 Participants |
| Brolucizumab 6 mg Non-loading | Ocular TEAEs in the Study Eye of Moderate or Severe Intensity | Endophthalmitis - severe intensity | 0 Participants |
Secondary
Overview of TEAEs
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 after providing written informed consent for participation in the study. Treatment-emergent AEs are AEs that developed on or after first study treatment administration, or any event previously present that worsened following exposure to the study treatment.
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 timeframe of approximately 52 weeks.
Population: safety analysis set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brolucizumab 6 mg Loading | Overview of TEAEs | Any AE | 23 Participants |
| Brolucizumab 6 mg Loading | Overview of TEAEs | Ocular AE(s) in the study eye | 17 Participants |
| Brolucizumab 6 mg Loading | Overview of TEAEs | Ocular AE(s) in the fellow eye | 4 Participants |
| Brolucizumab 6 mg Loading | Overview of TEAEs | Non-ocular AE(s) | 20 Participants |
| Brolucizumab 6 mg Loading | Overview of TEAEs | AE(s) related to injection procedure | 11 Participants |
| Brolucizumab 6 mg Loading | Overview of TEAEs | AE(s) related to study drug | 9 Participants |
| Brolucizumab 6 mg Loading | Overview of TEAEs | SAE(s) | 5 Participants |
| Brolucizumab 6 mg Loading | Overview of TEAEs | Ocular SAE(s) in the study eye | 1 Participants |
| Brolucizumab 6 mg Loading | Overview of TEAEs | Non-ocular SAE(s) | 4 Participants |
| Brolucizumab 6 mg Loading | Overview of TEAEs | Death | 0 Participants |
| Brolucizumab 6 mg Loading | Overview of TEAEs | Non-fatal SAE(s) | 5 Participants |
| Brolucizumab 6 mg Loading | Overview of TEAEs | Discontinuation of study treatment due to any AE(s) | 2 Participants |
| Brolucizumab 6 mg Loading | Overview of TEAEs | Discontinuation of study treatment due to non-serious AE(s) | 0 Participants |
| Brolucizumab 6 mg Loading | Overview of TEAEs | Discontinuation of study treatment due to any SAE(s) | 2 Participants |
| Brolucizumab 6 mg Non-loading | Overview of TEAEs | Non-fatal SAE(s) | 6 Participants |
| Brolucizumab 6 mg Non-loading | Overview of TEAEs | Any AE | 26 Participants |
| Brolucizumab 6 mg Non-loading | Overview of TEAEs | Ocular SAE(s) in the study eye | 4 Participants |
| Brolucizumab 6 mg Non-loading | Overview of TEAEs | Ocular AE(s) in the study eye | 19 Participants |
| Brolucizumab 6 mg Non-loading | Overview of TEAEs | Discontinuation of study treatment due to non-serious AE(s) | 4 Participants |
| Brolucizumab 6 mg Non-loading | Overview of TEAEs | Ocular AE(s) in the fellow eye | 9 Participants |
| Brolucizumab 6 mg Non-loading | Overview of TEAEs | Non-ocular SAE(s) | 2 Participants |
| Brolucizumab 6 mg Non-loading | Overview of TEAEs | Non-ocular AE(s) | 19 Participants |
| Brolucizumab 6 mg Non-loading | Overview of TEAEs | Discontinuation of study treatment due to any AE(s) | 5 Participants |
| Brolucizumab 6 mg Non-loading | Overview of TEAEs | AE(s) related to injection procedure | 12 Participants |
| Brolucizumab 6 mg Non-loading | Overview of TEAEs | Death | 1 Participants |
| Brolucizumab 6 mg Non-loading | Overview of TEAEs | AE(s) related to study drug | 12 Participants |
| Brolucizumab 6 mg Non-loading | Overview of TEAEs | Discontinuation of study treatment due to any SAE(s) | 2 Participants |
| Brolucizumab 6 mg Non-loading | Overview of TEAEs | SAE(s) | 6 Participants |
Secondary
Presence of Active Choroidal Neovascularization Leakage
Presence of active choroidal neovascularization leakage was measured by Fluorescein angiography. CNV = choroidal neovascularization; MNV = macular neovascularization
Time frame: At Week 52
Population: full analysis set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brolucizumab 6 mg Loading | Presence of Active Choroidal Neovascularization Leakage | Active CNV leakage at week 52 - Yes | 17 Participants |
| Brolucizumab 6 mg Loading | Presence of Active Choroidal Neovascularization Leakage | Active CNV leakage at week 52 - No | 7 Participants |
| Brolucizumab 6 mg Loading | Presence of Active Choroidal Neovascularization Leakage | Active CNV leakage at week 52 - missing | 1 Participants |
| Brolucizumab 6 mg Loading | Presence of Active Choroidal Neovascularization Leakage | CNV location at week 52 - Subfoveal | 11 Participants |
| Brolucizumab 6 mg Loading | Presence of Active Choroidal Neovascularization Leakage | CNV location at week 52 - Extrafoveal | 6 Participants |
| Brolucizumab 6 mg Loading | Presence of Active Choroidal Neovascularization Leakage | CNV location at week 52 - Not applicable | 7 Participants |
| Brolucizumab 6 mg Loading | Presence of Active Choroidal Neovascularization Leakage | CNV location at week 52 - Missing | 1 Participants |
| Brolucizumab 6 mg Loading | Presence of Active Choroidal Neovascularization Leakage | CNV subtype at week 52 - Type 1 MNV | 12 Participants |
| Brolucizumab 6 mg Loading | Presence of Active Choroidal Neovascularization Leakage | CNV subtype at week 52 - Mixed type 1 and type 2 MNV | 2 Participants |
| Brolucizumab 6 mg Loading | Presence of Active Choroidal Neovascularization Leakage | CNV subtype at week 52 -Type 3 MNV | 3 Participants |
| Brolucizumab 6 mg Loading | Presence of Active Choroidal Neovascularization Leakage | CNV subtype at week 52 - Not applicable | 7 Participants |
| Brolucizumab 6 mg Loading | Presence of Active Choroidal Neovascularization Leakage | CNV subtype at week 52 - Missing | 1 Participants |
| Brolucizumab 6 mg Non-loading | Presence of Active Choroidal Neovascularization Leakage | CNV subtype at week 52 - Not applicable | 10 Participants |
| Brolucizumab 6 mg Non-loading | Presence of Active Choroidal Neovascularization Leakage | Active CNV leakage at week 52 - Yes | 15 Participants |
| Brolucizumab 6 mg Non-loading | Presence of Active Choroidal Neovascularization Leakage | CNV location at week 52 - Missing | 2 Participants |
| Brolucizumab 6 mg Non-loading | Presence of Active Choroidal Neovascularization Leakage | Active CNV leakage at week 52 - No | 10 Participants |
| Brolucizumab 6 mg Non-loading | Presence of Active Choroidal Neovascularization Leakage | CNV subtype at week 52 -Type 3 MNV | 5 Participants |
| Brolucizumab 6 mg Non-loading | Presence of Active Choroidal Neovascularization Leakage | Active CNV leakage at week 52 - missing | 2 Participants |
| Brolucizumab 6 mg Non-loading | Presence of Active Choroidal Neovascularization Leakage | CNV subtype at week 52 - Type 1 MNV | 9 Participants |
| Brolucizumab 6 mg Non-loading | Presence of Active Choroidal Neovascularization Leakage | CNV location at week 52 - Subfoveal | 10 Participants |
| Brolucizumab 6 mg Non-loading | Presence of Active Choroidal Neovascularization Leakage | CNV subtype at week 52 - Missing | 2 Participants |
| Brolucizumab 6 mg Non-loading | Presence of Active Choroidal Neovascularization Leakage | CNV location at week 52 - Extrafoveal | 5 Participants |
| Brolucizumab 6 mg Non-loading | Presence of Active Choroidal Neovascularization Leakage | CNV subtype at week 52 - Mixed type 1 and type 2 MNV | 1 Participants |
| Brolucizumab 6 mg Non-loading | Presence of Active Choroidal Neovascularization Leakage | CNV location at week 52 - Not applicable | 10 Participants |
Secondary
Proportion of Patients Who Maintained on q12w Regimen.
Treatment interval distribution up to Week 52. Proportion of patients maintained on q12w treatment frequency in the two brolucizumab groups up to week 52. Patients who discontinued treatment before week 52 were rated as non-responders, i.e., as patients who did not maintain the q12w regimen. In the loading arm, the loading period up to week 12 was not considered in the analysis.
Time frame: Up to week 52
Population: full analysis set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Brolucizumab 6 mg Loading | Proportion of Patients Who Maintained on q12w Regimen. | 8 Participants |
| Brolucizumab 6 mg Non-loading | Proportion of Patients Who Maintained on q12w Regimen. | 6 Participants |
Secondary
Treatment Intervals Before and During the Study
Treatment interval distribution. Treatment interval during the study, within 24 weeks prior to baseline and interval between the last 2 injections in the study. In the loading arm, data from the loading period was excluded.
Time frame: -24 Weeks, Baseline, Week 52
Population: full analysis set
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Brolucizumab 6 mg Loading | Treatment Intervals Before and During the Study | within 24 weeks prior to baseline | 54.7 days |
| Brolucizumab 6 mg Loading | Treatment Intervals Before and During the Study | from baseline to week 52 (n=23,25) | 64.8 days |
| Brolucizumab 6 mg Loading | Treatment Intervals Before and During the Study | Last treatment interval during the study (n=25,25) | 56.0 days |
| Brolucizumab 6 mg Non-loading | Treatment Intervals Before and During the Study | within 24 weeks prior to baseline | 68.5 days |
| Brolucizumab 6 mg Non-loading | Treatment Intervals Before and During the Study | from baseline to week 52 (n=23,25) | 77.8 days |
| Brolucizumab 6 mg Non-loading | Treatment Intervals Before and During the Study | Last treatment interval during the study (n=25,25) | 65.0 days |
Post Hoc
All Collected Deaths
On-treatment deaths are reported from first dose of study treatment until end of study treatment plus 30 days after last treatment, up to a maximum timeframe of approximately 52 weeks. Post-treatment death data are reported from day 31 after last treatment to end of study (Week 52).
Time frame: Fatality data are reported from first dose of study treatment until approximately Week 52.
Population: safety analysis set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brolucizumab 6 mg Loading | All Collected Deaths | On-treatment Deaths | 0 Participants |
| Brolucizumab 6 mg Loading | All Collected Deaths | Total Deaths | 0 Participants |
| Brolucizumab 6 mg Loading | All Collected Deaths | Post-treatment Deaths | 0 Participants |
| Brolucizumab 6 mg Non-loading | All Collected Deaths | On-treatment Deaths | 0 Participants |
| Brolucizumab 6 mg Non-loading | All Collected Deaths | Total Deaths | 1 Participants |
| Brolucizumab 6 mg Non-loading | All Collected Deaths | Post-treatment Deaths | 1 Participants |