Neovascular Age Related Macular Degeneration
Conditions
Keywords
age-related macular degeneration, wetAMD, nAMD, neovascular, choroidal neovascularization, CNV, OCT-angiography
Brief summary
Neovascular age-related macular degeneration (nAMD) is characterized by the presence of choroidal neovascularization (CNV). Choroidal neovascularization consists of abnormal blood vessels originating from the choroid and can lead to hemorrhage, fluid exudation, and fibrosis, resulting in photoreceptor damage and vision loss. The safety and efficacy of brolucizumab has been demonstrated in 2 randomized, multicenter, double-masked, active controlled Phase 3 studies in nAMD patients (RTH258-C001 and RTH258-C002). Anatomical changes were evaluated in these studies using spectral domain optical coherence tomography (SD-OCT), which relied on indirect parameters for the diagnosis of active CNV. The OCT-angiography (OCT A) that directly visualize retinal circulation and image CNV and vascular diseases of the retina was not included in previous brolucizumab studies. This single-arm, open-label, multicenter study was performed to evaluate the efficacy and safety of brolucizumab 6 mg in patients with nAMD. OCT-A was used in this study to assess the morphological response of patients to brolucizumab in terms of percentage change in CNV lesion area in the short term (i.e. at Week 12) and in the long term (i.e. at Week 48), as well as changes in other OCT-A features up to Week 48.
Detailed description
This was a prospective, single-arm, open-label, multicenter study to evaluate the efficacy and safety of brolucizumab 6 mg in patients with neovascular age-related macular degeneration (nAMD). Patients were required to attend 6 mandatory study visits: Screening/Baseline Visit (Day 1), Week 4, Week 8, Week 12, Week 16 and Week 48 visits. The timing of the interim visits between Week 16 and Week 48 depended on the patient's injection regimen, i.e. every 12 weeks (q12w) or every 8 weeks (q8w). Patients who consented and met all the inclusion and none of the exclusion criteria were screened to evaluate eligibility. After confirmation of eligibility, patients were included and treated with brolucizumab 6 mg. The maximum study duration for 1 patient was 48 weeks, including Screening. There were 2 periods in this study: * Open-label treatment period: from Screening/Baseline (Day 1) to Week 40/Week 44 (depending on assigned regimen) * Follow-up period: Week 40/Week 44 to Week 48 A Safety Review Committee (SRC) was established for this study to provide an independent, systematic, standardized and unbiased assessment of the review of intraocular inflammation (IOI), retinal vasculitis (RV) and/or retinal vascular occlusion (RO).
Interventions
Brolucizumab is a new generation of anti-VEGF (vascular endothelial growth factor). All patients were treated with brolucizumab 6mg: 3 loading injections (at Screening/Baseline, Week 4 and Week 8), followed by maintenance treatment every 8 weeks (Q8W) or every 12 weeks (Q12W) depending on disease activity from Week 16/Week20 to Week 40/Week 44. Brolucizumab was administered by an intravitreal (IVT) injection to the study. eye.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single-arm, open-label study
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients must provide written informed consent before any study related procedures are performed. 2. Patients must be 50 years of age or older at Screening/Baseline. Study eye: 3. Active CNV lesions secondary to AMD that affect 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 hemorrhage or sub-retinal pigment epithelium (sub-RPE) hemorrhage, blocked fluorescence, macular edema. 4. Intra- and/or subretinal fluid affecting the central subfield of the study eye at Screening/Baseline. 5. BCVA between 83 and 23 letters, inclusive, in the study eye at Screening/Baseline using early treatment diabetic retinopathy study (ETDRS) at an initial testing distance of 4 meters.
Exclusion criteria
Ocular conditions: 1. Any active intraocular or periocular infection or active intraocular inflammation (e.g. infectious conjunctivitis, keratitis, scleritis, endophthalmitis, infectious blepharitis) in either eye at Screening/Baseline. 2. Presence of amblyopia, amaurosis or ocular disorders in the fellow eye with BCVA \< 35 ETDRS letters at Screening (except when due to conditions whose surgery may improve visual acuity, e.g. cataract). 3. Medical history of intraocular inflammation and/or retinal vascular occlusion within 12 months prior to Screening/Baseline. Study eye: 4. Poor quality of OCT-A and SD-OCT images at Screening/Baseline. 5. Atrophy or fibrosis involving the center of the fovea in the study eye, as assessed by color fundus photography and fundus autofluorescence (FAF) at Screening/Baseline. 6. The total area of fibrosis or subretinal blood affecting the foveal center point comprising ≥ 50% of the lesion area in the study eye at Screening/Baseline. 7. Concomitant conditions or ocular disorders in the study eye, including retinal diseases other than nAMD, that, in the judgment of the investigator, could require medical or surgical intervention during the course of the study to prevent or treat visual loss that might result from that condition, or that limits the potential to gain visual acuity upon treatment with the investigational product. 8. Structural damage within 0.5 disc diameter of the center of the macula in the study eye, e.g. vitreomacular traction, epiretinal membrane, retinal pigment epithelium (RPE) rip/tear scar, laser burn, at the time of Screening that in the investigator's opinion could preclude visual function improvement with treatment. 9. Current vitreous hemorrhage or history of vitreous hemorrhage in the study eye within 4 weeks prior to Screening/Baseline. 10. Uncontrolled glaucoma in the study eye defined as IOP \> 25 mmHg on medication or according to the investigator's judgment at Screening/Baseline. 11. Aphakia and/or absence of the posterior capsule in the study eye at Screening/Baseline. Ocular treatments (study eye): 12. Patient has received any approved or investigational treatment for nAMD (other than vitamin supplements) in the study eye at any time. 13. Intraocular or periocular use of corticosteroids in the study eye during the 6-month period prior to Screening/Baseline. 14. Previous penetrating keratoplasty or vitrectomy at any time prior to Screening/Baseline. 15. History or evidence of the following in the study eye within the 90-day period prior to Screening/Baseline: * Intraocular or refractive surgery. * Previous panretinal photocoagulation. * Previous submacular surgery, other surgical intervention or laser treatment for nAMD including photodynamic therapy (PDT). Systemic conditions or treatments: 16. End stage renal disease requiring dialysis or renal transplant. 17. Systemic medications known to be toxic to the lens, retina or optic nerve (e.g. deferoxamine, chloroquine/hydroxychloroquine, tamoxifen, phenothiazines and ethambutol) used during the 6-month period prior to Screening/Baseline except temporary use for COVID-19 treatment. 18. Participation in an investigational drug, biologic, or device study within 30 days or the duration of 5 half-lives of the investigational product (whichever is longer) prior to Screening/Baseline. Note: observational clinical studies solely involving over-the-counter vitamins, supplements, or diets are not exclusionary. 19. Systemic anti-VEGF therapy at any time. 20. Stroke or myocardial infarction in the 6-month period prior to Screening/Baseline. 21. Uncontrolled blood pressure defined as a systolic value ≥ 160 mmHg or diastolic value ≥ 100 mmHg at Screening/Baseline. (In case there is an elevated blood pressure measurement, it should be repeated after 20 minutes. If the repeat measurement is elevated, then the patient is not eligible to be enrolled into the study). 22. History of a medical condition (disease, metabolic dysfunction with exception of type 1 or 2 diabetes mellitus, physical examination finding, or clinical laboratory finding) that, in the judgment of the investigator, would preclude scheduled study visits, completion of the study, or a safe administration of investigational product. 23. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin or in situ cervical cancer), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases. 24. History of hypersensitivity to any component of the test article, control article, or clinically relevant sensitivity to fluorescein dye, as assessed by the investigator. Other: 25. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) pregnancy test. 26. Women of childbearing potential, defined as all women less than 1 year postmenopausal or less than 6 weeks since sterilization at Screening/Baseline Women are considered post-menopausal and not of childbearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy, or tubal ligation at least 6 weeks before taking study treatment. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment is she considered not of childbearing potential. 27. Patients mentioned in Articles L.1121-5 to L.1121-8 and L.1122-1-2 of the Code de Santé Publique (e.g. minors, protected adults, etc.)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change in Choroidal Neovascularization (CNV) Lesion Area Measured by Optical Coherence Tomography-Angiograph (OCT-A) From Baseline to Week 12 | Baseline, Week 12 | OCT-A is a dye-less angiographic procedure based on split-spectrum-decorrelation-amplitude angiography. It enables the capture of scattered intra-vessel particles (mainly erythrocyte cells) at all levels of the retinal and inner-choroidal vasculature, thus providing 3-D imaging of the retinal circulation. The literature suggests that OCT-A is a good marker for assessing anti-VEGF therapeutic response, especially lesion size. Inter-Quartile Range = q1 - q3. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Choroidal Neovascularization (CNV) Lesion Area Measured by Optical Coherence Tomography-Angiograph (OCT-A) From Baseline to Week 48 | Baseline, Weeks 4, 8, 12, 48 | OCT-A is a dye-less angiographic procedure based on split-spectrum-decorrelation-amplitude angiography. It enables the capture of scattered intra-vessel particles (mainly erythrocyte cells) at all levels of the retinal and inner-choroidal vasculature, thus providing 3-D imaging of the retinal circulation. The literature suggests that OCT-A is a good marker for assessing anti-VEGF therapeutic response, especially lesion size. |
| Presence of Choroidal Neovascularization (CNV) Lesion Area Measured by Optical Coherence Tomography-Angiograph (OCT-A) From Baseline to Week 48 | Baseline, Week 48 | OCT-A is a dye-less angiographic procedure based on split-spectrum-decorrelation-amplitude angiography. It enables the capture of scattered intra-vessel particles (mainly erythrocyte cells) at all levels of the retinal and inner-choroidal vasculature, thus providing 3-D imaging of the retinal circulation. The literature suggests that OCT-A is a good marker for assessing anti-VEGF therapeutic response, especially lesion size. |
| Change in Best Corrected Visual Acuity (BCVA) From Baseline up to Week 48 | Baseline, Weeks 4, 8, 12, 48 | 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 of 78 to 23 (approximate Snellen equivalent of 20/32 to 20/320) in the study eye were included. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning. |
| Percentage of Patients Who Are Maintained on an Exclusive Treatment Interval Every 12 Weeks (q12w) Following the Loading Phase to Week 48 | Weeks 20, 32, 44, 48 | To estimate the proportion of patients treated at q12w frequency with brolucizumab. |
| The Probability of the First q12w Interval for Determining Successful q12w Maintenance | Weeks 0,4,5,8,9,15,16,17,18,20,21,22,24,32,33,34,35,40,41,43,44,48 | To estimate the predictive value of the first q12w cycle for maintenance of q12w treatment with brolucizumab via the Kaplan-Meier method. |
| Percentage Change in Choroidal Neovascularization (CNV) Lesion Area Measured by Optical Coherence Tomography-Angiograph (OCT-A) From Baseline to Week 48 | Baseline, Weeks 4, 8, 48 | OCT-A is a dye-less angiographic procedure based on split-spectrum-decorrelation-amplitude angiography. It enables the capture of scattered intra-vessel particles (mainly erythrocyte cells) at all levels of the retinal and inner-choroidal vasculature, thus providing 3-D imaging of the retinal circulation. The literature suggests that OCT-A is a good marker for assessing anti-VEGF therapeutic response, especially lesion size. |
| Change From Baseline up to Week 48 in SD-OCT Assessed by Qualitative and Quantitative Criteria: Central Sub-Field Retinal Thickness (CSFT) | Baseline, Weeks 4, 8, 12, 48 | Central sub-field thickness (CSFT) was measured by Spectral Domain Optical Coherence Tomography (SD-OCT). The CSFT evaluated in this study represents the average retinal thickness of the circular area within 1 mm diameter around the foveal center. SD-OCT images were obtained and assessed in the study eye by SD-OCT machines. (i.e. no time-domain nor swept-source OCT). |
| Change From Baseline up to Week 48 in SD-OCT and FA Features Assessed by Qualitative and Quantitative Criteria: Sub and Intraretinal Fluid, Sub-RPE (Retinal Pigmented Epithelium) - Study Eye | Baseline, Weeks 4, 8, 12, 48 | To evaluate the effect of brolucizumab on anatomical parameters as assessed by Spectral Domain Optical Coherence Tomography (SD-OCT) and Fluorescein Angiography (FA). RPE = Retinal Pigmented Epithelium IRF = Intraretinal Fluid SRF = Subretinal Fluid Sub-RPE = Sub Retinal Pigmented Epithelium |
| Incidence of Adverse Events (AEs) (Serious and Nonserious) Reported in Patients Treated With Brolucizumab. | Up to Week 48 | An AE is any untoward medical occurrence (e.g. any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study. |
| Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | Up to Week 48 | An AE is any untoward medical occurrence (e.g. any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study. |
| Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab - Non-Ocular Adverse Events | Up to Week 48 | An AE is any untoward medical occurrence (e.g. any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study. |
| Time From Last Intravitreal (IVT) Injection in the Initiation Phase to First Visit With no Disease Activity - Probability of no Disease Activity | Week 8 until Week 41 | To evaluate the time from last IVT injection in the initiation phase to first visit with no disease activity. The 95% CI are estimated by using the Greenwood formula Kaplan-Meier (KM) method. |
Countries
France
Participant flow
Recruitment details
210 adult patients were treated at 40 centers in France. The maximum study duration for 1 patient was 48 weeks.
Pre-assignment details
The Screening/Baseline visit were performed on the same Visit (Day 1). The first dose of study treatment was also administered on Day 1.
Participants by arm
| Arm | Count |
|---|---|
| RTH258/Brolucizumab This is a single-arm study in which all patients were treated with brolucizumab 6mg: 3 loading injections (at Screening/Baseline, Week 4 and Week 8), followed by maintenance treatment from Week 16/Week 20 up to Week 40/Week 44. | 210 |
| Total | 210 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 4 |
| Overall Study | Death | 1 |
| Overall Study | Lack of Efficacy | 1 |
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Physician Decision | 9 |
| Overall Study | Withdrawal by Subject | 9 |
Baseline characteristics
| Characteristic | RTH258/Brolucizumab | — |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | — |
| Age, Categorical >=65 years | 200 Participants | — |
| Age, Categorical Between 18 and 65 years | 10 Participants | — |
| Age, Continuous | 77.8 years STANDARD_DEVIATION 7.17 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Sex: Female, Male Female | 129 Participants | — |
| Sex: Female, Male Male | 81 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 210 |
| other Total, other adverse events | 130 / 210 |
| serious Total, serious adverse events | 20 / 210 |
Outcome results
Primary
Percentage Change in Choroidal Neovascularization (CNV) Lesion Area Measured by Optical Coherence Tomography-Angiograph (OCT-A) From Baseline to Week 12
OCT-A is a dye-less angiographic procedure based on split-spectrum-decorrelation-amplitude angiography. It enables the capture of scattered intra-vessel particles (mainly erythrocyte cells) at all levels of the retinal and inner-choroidal vasculature, thus providing 3-D imaging of the retinal circulation. The literature suggests that OCT-A is a good marker for assessing anti-VEGF therapeutic response, especially lesion size. Inter-Quartile Range = q1 - q3.
Time frame: Baseline, Week 12
Population: Participants in the Full Analysis Set (FAS) with a valid value for the outcome measure. The FAS is comprised of all treated patients.~Due to ungradable images and other reasons, only 138 patients were evaluable at Week 12 for choroidal neovascularization (CNV) lesion area by optical coherence tomography-angiography (OCT-A) in nAMD. This sample size of 138 patients was reassessed and shown to be valid for analysis of the primary efficacy endpoint.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| RTH258/Brolucizumab | Percentage Change in Choroidal Neovascularization (CNV) Lesion Area Measured by Optical Coherence Tomography-Angiograph (OCT-A) From Baseline to Week 12 | -79.29 % change from baseline |
Secondary
Change From Baseline up to Week 48 in SD-OCT and FA Features Assessed by Qualitative and Quantitative Criteria: Sub and Intraretinal Fluid, Sub-RPE (Retinal Pigmented Epithelium) - Study Eye
To evaluate the effect of brolucizumab on anatomical parameters as assessed by Spectral Domain Optical Coherence Tomography (SD-OCT) and Fluorescein Angiography (FA). RPE = Retinal Pigmented Epithelium IRF = Intraretinal Fluid SRF = Subretinal Fluid Sub-RPE = Sub Retinal Pigmented Epithelium
Time frame: Baseline, Weeks 4, 8, 12, 48
Population: FAS
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| RTH258/Brolucizumab | Change From Baseline up to Week 48 in SD-OCT and FA Features Assessed by Qualitative and Quantitative Criteria: Sub and Intraretinal Fluid, Sub-RPE (Retinal Pigmented Epithelium) - Study Eye | Baseline Subretinal fluid | 169 Participants |
| RTH258/Brolucizumab | Change From Baseline up to Week 48 in SD-OCT and FA Features Assessed by Qualitative and Quantitative Criteria: Sub and Intraretinal Fluid, Sub-RPE (Retinal Pigmented Epithelium) - Study Eye | Week 4 Intraretinal fluid (n=174 ) | 39 Participants |
| RTH258/Brolucizumab | Change From Baseline up to Week 48 in SD-OCT and FA Features Assessed by Qualitative and Quantitative Criteria: Sub and Intraretinal Fluid, Sub-RPE (Retinal Pigmented Epithelium) - Study Eye | Week 4 Subretinal fluid (n=174 ) | 69 Participants |
| RTH258/Brolucizumab | Change From Baseline up to Week 48 in SD-OCT and FA Features Assessed by Qualitative and Quantitative Criteria: Sub and Intraretinal Fluid, Sub-RPE (Retinal Pigmented Epithelium) - Study Eye | Week 4 Sub-RPE fluid (n=174 ) | 47 Participants |
| RTH258/Brolucizumab | Change From Baseline up to Week 48 in SD-OCT and FA Features Assessed by Qualitative and Quantitative Criteria: Sub and Intraretinal Fluid, Sub-RPE (Retinal Pigmented Epithelium) - Study Eye | Week 4 Without any fluid (IRF/SRF) (n=174 ) | 84 Participants |
| RTH258/Brolucizumab | Change From Baseline up to Week 48 in SD-OCT and FA Features Assessed by Qualitative and Quantitative Criteria: Sub and Intraretinal Fluid, Sub-RPE (Retinal Pigmented Epithelium) - Study Eye | Week 4 With any fluid (IRF/SRF) (n=174 ) | 90 Participants |
| RTH258/Brolucizumab | Change From Baseline up to Week 48 in SD-OCT and FA Features Assessed by Qualitative and Quantitative Criteria: Sub and Intraretinal Fluid, Sub-RPE (Retinal Pigmented Epithelium) - Study Eye | Week 8 Intraretinal fluid (n=155) | 31 Participants |
| RTH258/Brolucizumab | Change From Baseline up to Week 48 in SD-OCT and FA Features Assessed by Qualitative and Quantitative Criteria: Sub and Intraretinal Fluid, Sub-RPE (Retinal Pigmented Epithelium) - Study Eye | Week 8 Subretinal fluid (n=155) | 28 Participants |
| RTH258/Brolucizumab | Change From Baseline up to Week 48 in SD-OCT and FA Features Assessed by Qualitative and Quantitative Criteria: Sub and Intraretinal Fluid, Sub-RPE (Retinal Pigmented Epithelium) - Study Eye | Week 8 Sub-RPE fluid (n=155) | 50 Participants |
| RTH258/Brolucizumab | Change From Baseline up to Week 48 in SD-OCT and FA Features Assessed by Qualitative and Quantitative Criteria: Sub and Intraretinal Fluid, Sub-RPE (Retinal Pigmented Epithelium) - Study Eye | Week 8 Without any fluid (IRF/SRF) (n=155) | 108 Participants |
| RTH258/Brolucizumab | Change From Baseline up to Week 48 in SD-OCT and FA Features Assessed by Qualitative and Quantitative Criteria: Sub and Intraretinal Fluid, Sub-RPE (Retinal Pigmented Epithelium) - Study Eye | Week 8 With any fluid (IRF/SRF) (n=155) | 44 Participants |
| RTH258/Brolucizumab | Change From Baseline up to Week 48 in SD-OCT and FA Features Assessed by Qualitative and Quantitative Criteria: Sub and Intraretinal Fluid, Sub-RPE (Retinal Pigmented Epithelium) - Study Eye | Week 12 Intraretinal fluid (n=197) | 51 Participants |
| RTH258/Brolucizumab | Change From Baseline up to Week 48 in SD-OCT and FA Features Assessed by Qualitative and Quantitative Criteria: Sub and Intraretinal Fluid, Sub-RPE (Retinal Pigmented Epithelium) - Study Eye | Week 12 Subretinal fluid (n=197) | 38 Participants |
| RTH258/Brolucizumab | Change From Baseline up to Week 48 in SD-OCT and FA Features Assessed by Qualitative and Quantitative Criteria: Sub and Intraretinal Fluid, Sub-RPE (Retinal Pigmented Epithelium) - Study Eye | Week 12 Sub-RPE fluid (n=197) | 19 Participants |
| RTH258/Brolucizumab | Change From Baseline up to Week 48 in SD-OCT and FA Features Assessed by Qualitative and Quantitative Criteria: Sub and Intraretinal Fluid, Sub-RPE (Retinal Pigmented Epithelium) - Study Eye | Week 12 Without any fluid (IRF/SRF) (n=197) | 120 Participants |
| RTH258/Brolucizumab | Change From Baseline up to Week 48 in SD-OCT and FA Features Assessed by Qualitative and Quantitative Criteria: Sub and Intraretinal Fluid, Sub-RPE (Retinal Pigmented Epithelium) - Study Eye | Week 12 With any fluid (IRF/SRF) (n=197) | 74 Participants |
| RTH258/Brolucizumab | Change From Baseline up to Week 48 in SD-OCT and FA Features Assessed by Qualitative and Quantitative Criteria: Sub and Intraretinal Fluid, Sub-RPE (Retinal Pigmented Epithelium) - Study Eye | Week 48 Intraretinal fluid (n=159) | 38 Participants |
| RTH258/Brolucizumab | Change From Baseline up to Week 48 in SD-OCT and FA Features Assessed by Qualitative and Quantitative Criteria: Sub and Intraretinal Fluid, Sub-RPE (Retinal Pigmented Epithelium) - Study Eye | Week 48 Subretinal fluid (n=159) | 26 Participants |
| RTH258/Brolucizumab | Change From Baseline up to Week 48 in SD-OCT and FA Features Assessed by Qualitative and Quantitative Criteria: Sub and Intraretinal Fluid, Sub-RPE (Retinal Pigmented Epithelium) - Study Eye | Week 48 Sub-RPE fluid (n=159) | 19 Participants |
| RTH258/Brolucizumab | Change From Baseline up to Week 48 in SD-OCT and FA Features Assessed by Qualitative and Quantitative Criteria: Sub and Intraretinal Fluid, Sub-RPE (Retinal Pigmented Epithelium) - Study Eye | Week 48 Without any fluid (IRF/SRF) (n=159) | 99 Participants |
| RTH258/Brolucizumab | Change From Baseline up to Week 48 in SD-OCT and FA Features Assessed by Qualitative and Quantitative Criteria: Sub and Intraretinal Fluid, Sub-RPE (Retinal Pigmented Epithelium) - Study Eye | Week 48 With any fluid (IRF/SRF) (n=159) | 60 Participants |
| RTH258/Brolucizumab | Change From Baseline up to Week 48 in SD-OCT and FA Features Assessed by Qualitative and Quantitative Criteria: Sub and Intraretinal Fluid, Sub-RPE (Retinal Pigmented Epithelium) - Study Eye | Baseline Intraretinal fluid | 101 Participants |
| RTH258/Brolucizumab | Change From Baseline up to Week 48 in SD-OCT and FA Features Assessed by Qualitative and Quantitative Criteria: Sub and Intraretinal Fluid, Sub-RPE (Retinal Pigmented Epithelium) - Study Eye | Baseline Sub-RPE fluid | 60 Participants |
| RTH258/Brolucizumab | Change From Baseline up to Week 48 in SD-OCT and FA Features Assessed by Qualitative and Quantitative Criteria: Sub and Intraretinal Fluid, Sub-RPE (Retinal Pigmented Epithelium) - Study Eye | Baseline Without any fluid (IRF/SRF) | 8 Participants |
| RTH258/Brolucizumab | Change From Baseline up to Week 48 in SD-OCT and FA Features Assessed by Qualitative and Quantitative Criteria: Sub and Intraretinal Fluid, Sub-RPE (Retinal Pigmented Epithelium) - Study Eye | Baseline With any fluid (IRF/SRF) | 193 Participants |
Secondary
Change From Baseline up to Week 48 in SD-OCT Assessed by Qualitative and Quantitative Criteria: Central Sub-Field Retinal Thickness (CSFT)
Central sub-field thickness (CSFT) was measured by Spectral Domain Optical Coherence Tomography (SD-OCT). The CSFT evaluated in this study represents the average retinal thickness of the circular area within 1 mm diameter around the foveal center. SD-OCT images were obtained and assessed in the study eye by SD-OCT machines. (i.e. no time-domain nor swept-source OCT).
Time frame: Baseline, Weeks 4, 8, 12, 48
Population: Participants in the Full Analysis Set (FAS) with a valid value for the outcome measure at baseline and at each timepoint. The FAS comprised all patients to whom study treatment had been assigned and who received at least one IVT injection of study treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RTH258/Brolucizumab | Change From Baseline up to Week 48 in SD-OCT Assessed by Qualitative and Quantitative Criteria: Central Sub-Field Retinal Thickness (CSFT) | Week 4 (n=164) | -131.79 μm | Standard Deviation 109.1 |
| RTH258/Brolucizumab | Change From Baseline up to Week 48 in SD-OCT Assessed by Qualitative and Quantitative Criteria: Central Sub-Field Retinal Thickness (CSFT) | Week 8 (n=143) | -152.95 μm | Standard Deviation 128.031 |
| RTH258/Brolucizumab | Change From Baseline up to Week 48 in SD-OCT Assessed by Qualitative and Quantitative Criteria: Central Sub-Field Retinal Thickness (CSFT) | Week 12 (n=188) | -150.51 μm | Standard Deviation 126.931 |
| RTH258/Brolucizumab | Change From Baseline up to Week 48 in SD-OCT Assessed by Qualitative and Quantitative Criteria: Central Sub-Field Retinal Thickness (CSFT) | Week 48 (n=150) | -151.09 μm | Standard Deviation 134.684 |
Secondary
Change in Best Corrected Visual Acuity (BCVA) From Baseline up to Week 48
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 of 78 to 23 (approximate Snellen equivalent of 20/32 to 20/320) in the study eye were included. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.
Time frame: Baseline, Weeks 4, 8, 12, 48
Population: Participants in the Full Analysis Set (FAS) with a valid value for the outcome measure at baseline and at each timepoint. The FAS comprised all patients to whom study treatment had been assigned and who received at least one IVT injection of study treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RTH258/Brolucizumab | Change in Best Corrected Visual Acuity (BCVA) From Baseline up to Week 48 | Week 4 (n=174) | 5.0 ETDRS letters read | Standard Deviation 7.48 |
| RTH258/Brolucizumab | Change in Best Corrected Visual Acuity (BCVA) From Baseline up to Week 48 | Week 8 (n=153) | 6.7 ETDRS letters read | Standard Deviation 8.07 |
| RTH258/Brolucizumab | Change in Best Corrected Visual Acuity (BCVA) From Baseline up to Week 48 | Week 12 (n=199) | 6.7 ETDRS letters read | Standard Deviation 9.09 |
| RTH258/Brolucizumab | Change in Best Corrected Visual Acuity (BCVA) From Baseline up to Week 48 | Week 48 (n=158) | 8.3 ETDRS letters read | Standard Deviation 12.03 |
Secondary
Change in Choroidal Neovascularization (CNV) Lesion Area Measured by Optical Coherence Tomography-Angiograph (OCT-A) From Baseline to Week 48
OCT-A is a dye-less angiographic procedure based on split-spectrum-decorrelation-amplitude angiography. It enables the capture of scattered intra-vessel particles (mainly erythrocyte cells) at all levels of the retinal and inner-choroidal vasculature, thus providing 3-D imaging of the retinal circulation. The literature suggests that OCT-A is a good marker for assessing anti-VEGF therapeutic response, especially lesion size.
Time frame: Baseline, Weeks 4, 8, 12, 48
Population: Participants in the Full Analysis Set (FAS) with a valid value for the outcome measure at baseline and at each timepoint. The FAS comprised all patients to whom study treatment had been assigned and who received at least one IVT injection of study treatment.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| RTH258/Brolucizumab | Change in Choroidal Neovascularization (CNV) Lesion Area Measured by Optical Coherence Tomography-Angiograph (OCT-A) From Baseline to Week 48 | Week 4 (n=126) | -0.09 square millimeters |
| RTH258/Brolucizumab | Change in Choroidal Neovascularization (CNV) Lesion Area Measured by Optical Coherence Tomography-Angiograph (OCT-A) From Baseline to Week 48 | Week 8 (n=111) | -0.12 square millimeters |
| RTH258/Brolucizumab | Change in Choroidal Neovascularization (CNV) Lesion Area Measured by Optical Coherence Tomography-Angiograph (OCT-A) From Baseline to Week 48 | Week 12 (n=140) | -0.14 square millimeters |
| RTH258/Brolucizumab | Change in Choroidal Neovascularization (CNV) Lesion Area Measured by Optical Coherence Tomography-Angiograph (OCT-A) From Baseline to Week 48 | Week 48 (n=122) | -0.08 square millimeters |
Secondary
Incidence of Adverse Events (AEs) (Serious and Nonserious) Reported in Patients Treated With Brolucizumab.
An AE is any untoward medical occurrence (e.g. any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study.
Time frame: Up to Week 48
Population: Safety Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| RTH258/Brolucizumab | Incidence of Adverse Events (AEs) (Serious and Nonserious) Reported in Patients Treated With Brolucizumab. | Fatal SAEs - All patients | 1 Participants |
| RTH258/Brolucizumab | Incidence of Adverse Events (AEs) (Serious and Nonserious) Reported in Patients Treated With Brolucizumab. | AEs leading to interruption - Treatment-related - All patients | 0 Participants |
| RTH258/Brolucizumab | Incidence of Adverse Events (AEs) (Serious and Nonserious) Reported in Patients Treated With Brolucizumab. | Any Adverse Event (AE) - Ocular | 95 Participants |
| RTH258/Brolucizumab | Incidence of Adverse Events (AEs) (Serious and Nonserious) Reported in Patients Treated With Brolucizumab. | Any AE - Treatment-related - Ocular | 32 Participants |
| RTH258/Brolucizumab | Incidence of Adverse Events (AEs) (Serious and Nonserious) Reported in Patients Treated With Brolucizumab. | Any AE - Procedure-related - Ocular | 18 Participants |
| RTH258/Brolucizumab | Incidence of Adverse Events (AEs) (Serious and Nonserious) Reported in Patients Treated With Brolucizumab. | Serious Adverse events (SAE) - Ocular | 8 Participants |
| RTH258/Brolucizumab | Incidence of Adverse Events (AEs) (Serious and Nonserious) Reported in Patients Treated With Brolucizumab. | SAEs - Treatment-related - Ocular | 7 Participants |
| RTH258/Brolucizumab | Incidence of Adverse Events (AEs) (Serious and Nonserious) Reported in Patients Treated With Brolucizumab. | SAEs - Procedure-related -Ocular | 1 Participants |
| RTH258/Brolucizumab | Incidence of Adverse Events (AEs) (Serious and Nonserious) Reported in Patients Treated With Brolucizumab. | Fatal SAEs - Ocular | 0 Participants |
| RTH258/Brolucizumab | Incidence of Adverse Events (AEs) (Serious and Nonserious) Reported in Patients Treated With Brolucizumab. | Fatal SAEs - Treatment-related - Ocular | 0 Participants |
| RTH258/Brolucizumab | Incidence of Adverse Events (AEs) (Serious and Nonserious) Reported in Patients Treated With Brolucizumab. | Fatal SAEs - Procedure-related - Ocular | 0 Participants |
| RTH258/Brolucizumab | Incidence of Adverse Events (AEs) (Serious and Nonserious) Reported in Patients Treated With Brolucizumab. | AEs leading to treatment discontinuation - Ocular | 25 Participants |
| RTH258/Brolucizumab | Incidence of Adverse Events (AEs) (Serious and Nonserious) Reported in Patients Treated With Brolucizumab. | AEs leading to treatment disc - Treatment-related - Ocular | 25 Participants |
| RTH258/Brolucizumab | Incidence of Adverse Events (AEs) (Serious and Nonserious) Reported in Patients Treated With Brolucizumab. | AEs leading to treatment disc - Procedure-related - Ocular | 6 Participants |
| RTH258/Brolucizumab | Incidence of Adverse Events (AEs) (Serious and Nonserious) Reported in Patients Treated With Brolucizumab. | AEs leading to interruption - Ocular | 0 Participants |
| RTH258/Brolucizumab | Incidence of Adverse Events (AEs) (Serious and Nonserious) Reported in Patients Treated With Brolucizumab. | AEs leading to interruption -Treatment-related - Ocular | 0 Participants |
| RTH258/Brolucizumab | Incidence of Adverse Events (AEs) (Serious and Nonserious) Reported in Patients Treated With Brolucizumab. | AEs leading to interruption - Procedure-related - Ocular | 0 Participants |
| RTH258/Brolucizumab | Incidence of Adverse Events (AEs) (Serious and Nonserious) Reported in Patients Treated With Brolucizumab. | Any Adverse Event - Non-Ocular | 77 Participants |
| RTH258/Brolucizumab | Incidence of Adverse Events (AEs) (Serious and Nonserious) Reported in Patients Treated With Brolucizumab. | Any AE - Treatment-related - Non-Ocular | 1 Participants |
| RTH258/Brolucizumab | Incidence of Adverse Events (AEs) (Serious and Nonserious) Reported in Patients Treated With Brolucizumab. | Any AE - Procedure-related - Non-Ocular | 0 Participants |
| RTH258/Brolucizumab | Incidence of Adverse Events (AEs) (Serious and Nonserious) Reported in Patients Treated With Brolucizumab. | Serious Adverse events (SAE) - Non-Ocular | 13 Participants |
| RTH258/Brolucizumab | Incidence of Adverse Events (AEs) (Serious and Nonserious) Reported in Patients Treated With Brolucizumab. | SAEs - Treatment-related - Non-Ocular | 0 Participants |
| RTH258/Brolucizumab | Incidence of Adverse Events (AEs) (Serious and Nonserious) Reported in Patients Treated With Brolucizumab. | SAEs - Procedure-related - Non-Ocular | 0 Participants |
| RTH258/Brolucizumab | Incidence of Adverse Events (AEs) (Serious and Nonserious) Reported in Patients Treated With Brolucizumab. | Fatal SAEs - Non-Ocular | 1 Participants |
| RTH258/Brolucizumab | Incidence of Adverse Events (AEs) (Serious and Nonserious) Reported in Patients Treated With Brolucizumab. | Fatal SAEs - Treatment-related - Non-Ocular | 0 Participants |
| RTH258/Brolucizumab | Incidence of Adverse Events (AEs) (Serious and Nonserious) Reported in Patients Treated With Brolucizumab. | Fatal SAEs - Procedure-related - Non-Ocular | 0 Participants |
| RTH258/Brolucizumab | Incidence of Adverse Events (AEs) (Serious and Nonserious) Reported in Patients Treated With Brolucizumab. | AEs leading to treatment discontinuation - Non-Ocular | 3 Participants |
| RTH258/Brolucizumab | Incidence of Adverse Events (AEs) (Serious and Nonserious) Reported in Patients Treated With Brolucizumab. | AEs leading to treatment disc - Treatment-related - Non-Ocular | 1 Participants |
| RTH258/Brolucizumab | Incidence of Adverse Events (AEs) (Serious and Nonserious) Reported in Patients Treated With Brolucizumab. | AEs leading to treatment disc - Procedure-related - Non-Ocular | 0 Participants |
| RTH258/Brolucizumab | Incidence of Adverse Events (AEs) (Serious and Nonserious) Reported in Patients Treated With Brolucizumab. | AEs leading to interruption - Non-Ocular | 0 Participants |
| RTH258/Brolucizumab | Incidence of Adverse Events (AEs) (Serious and Nonserious) Reported in Patients Treated With Brolucizumab. | AEs leading to interruption - Treatment-related - Non-Ocular | 0 Participants |
| RTH258/Brolucizumab | Incidence of Adverse Events (AEs) (Serious and Nonserious) Reported in Patients Treated With Brolucizumab. | AEs leading to interruption - Procedure-related - Non-Ocular | 0 Participants |
| RTH258/Brolucizumab | Incidence of Adverse Events (AEs) (Serious and Nonserious) Reported in Patients Treated With Brolucizumab. | Any Adverse Event - All patients | 135 Participants |
| RTH258/Brolucizumab | Incidence of Adverse Events (AEs) (Serious and Nonserious) Reported in Patients Treated With Brolucizumab. | Any AE - Treatment-related - All patients | 33 Participants |
| RTH258/Brolucizumab | Incidence of Adverse Events (AEs) (Serious and Nonserious) Reported in Patients Treated With Brolucizumab. | Any AE - Procedure-related All patients | 18 Participants |
| RTH258/Brolucizumab | Incidence of Adverse Events (AEs) (Serious and Nonserious) Reported in Patients Treated With Brolucizumab. | Serious Adverse events (SAE) - All patients | 20 Participants |
| RTH258/Brolucizumab | Incidence of Adverse Events (AEs) (Serious and Nonserious) Reported in Patients Treated With Brolucizumab. | SAEs - Treatment-related - All patients | 7 Participants |
| RTH258/Brolucizumab | Incidence of Adverse Events (AEs) (Serious and Nonserious) Reported in Patients Treated With Brolucizumab. | SAEs - Procedure-related - All patients | 1 Participants |
| RTH258/Brolucizumab | Incidence of Adverse Events (AEs) (Serious and Nonserious) Reported in Patients Treated With Brolucizumab. | Fatal SAEs - Treatment-related - All patients | 0 Participants |
| RTH258/Brolucizumab | Incidence of Adverse Events (AEs) (Serious and Nonserious) Reported in Patients Treated With Brolucizumab. | Fatal SAEs - Procedure-related - All patients | 0 Participants |
| RTH258/Brolucizumab | Incidence of Adverse Events (AEs) (Serious and Nonserious) Reported in Patients Treated With Brolucizumab. | AEs leading to treatment discontinuation - All patients | 28 Participants |
| RTH258/Brolucizumab | Incidence of Adverse Events (AEs) (Serious and Nonserious) Reported in Patients Treated With Brolucizumab. | AEs leading to treatment disc - Treatment-related - All patients | 26 Participants |
| RTH258/Brolucizumab | Incidence of Adverse Events (AEs) (Serious and Nonserious) Reported in Patients Treated With Brolucizumab. | AEs leading to treatment disc - Procedure-related - All patients | 6 Participants |
| RTH258/Brolucizumab | Incidence of Adverse Events (AEs) (Serious and Nonserious) Reported in Patients Treated With Brolucizumab. | AEs leading to interruption - All patients | 0 Participants |
| RTH258/Brolucizumab | Incidence of Adverse Events (AEs) (Serious and Nonserious) Reported in Patients Treated With Brolucizumab. | AEs leading to interruption - Procedure-related - All patients | 0 Participants |
Secondary
Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye
An AE is any untoward medical occurrence (e.g. any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study.
Time frame: Up to Week 48
Population: Safety Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | - Retinal pigment epithelial tear | 3 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | Number of patients with at least one AE | 85 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | Eye disorders | 81 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | - Eye pain | 10 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | - Vitritis | 10 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | - Dry eye | 9 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | - Vitreous floaters | 8 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | - Vision blurred | 6 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | - Visual acuity reduced | 6 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | - Cataract | 5 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | - Ocular hypertension | 5 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | - Retinal haemorrhage | 5 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | - Uveitis | 5 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | - Keratitis | 4 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | - Conjunctival haemorrhage | 3 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | - Eye pruritus | 3 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | - Iridocyclitis | 3 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | -Lacrimation increased | 3 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | - Retinal vasculitis | 3 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | - Vitreous detachment | 3 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | - Blepharitis | 2 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | - Metamorphopsia | 2 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | - Ocular discomfort | 2 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | - Ocular vasculitis | 2 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | - Photophobia | 2 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | - Punctate keratitis | 2 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | - Retinal degeneration | 2 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | - Retinal occlusive vasculitis | 2 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | - Serous retinal detachment | 2 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | - Visual field defect | 2 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | - Anterior chamber cell | 1 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | - Detachment of macular retinal pigment epithelium | 1 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | - Diplopia | 1 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | - Eye inflammation | 1 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | - Eye irritation | 1 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | - Foreign body sensation in eyes | 1 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | - Ocular hyperaemia | 1 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | - Periorbital pain | 1 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | - Photopsia | 1 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | - Posterior capsule opacification | 1 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | - Retinal fibrosis | 1 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | - Retinal neovascularisation | 1 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | - Retinal oedema | 1 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | - Retinal perivascular sheathing | 1 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | - Vitreoretinal traction syndrome | 1 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | - Vitreous haze | 1 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | Immune system disorders | 2 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | - Drug hypersensitivity | 1 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | - Seasonal allergy | 1 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | Infections and infestations | 1 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | - Conjunctivitis | 1 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | Injury, poisoning and procedural complications | 3 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | - Foreign body in eye | 1 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | - Postoperative hypertension | 1 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | - Procedural pain | 1 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | Investigations | 1 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | - Intraocular pressure increased | 1 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | - Anterior chamber inflammation | 1 Participants |
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab, by Primary System Organ Class (SOC) and Preferred Term (PT) - Ocular Adverse Events in Study Eye | - Conjunctivitis allergic | 1 Participants |
Secondary
Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab - Non-Ocular Adverse Events
An AE is any untoward medical occurrence (e.g. any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study.
Time frame: Up to Week 48
Population: Safety Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RTH258/Brolucizumab | Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab - Non-Ocular Adverse Events | 77 Participants |
Secondary
Percentage Change in Choroidal Neovascularization (CNV) Lesion Area Measured by Optical Coherence Tomography-Angiograph (OCT-A) From Baseline to Week 48
OCT-A is a dye-less angiographic procedure based on split-spectrum-decorrelation-amplitude angiography. It enables the capture of scattered intra-vessel particles (mainly erythrocyte cells) at all levels of the retinal and inner-choroidal vasculature, thus providing 3-D imaging of the retinal circulation. The literature suggests that OCT-A is a good marker for assessing anti-VEGF therapeutic response, especially lesion size.
Time frame: Baseline, Weeks 4, 8, 48
Population: Participants in the Full Analysis Set (FAS) with a valid value for the outcome measure at baseline and at each timepoint. The FAS comprised all patients to whom study treatment had been assigned and who received at least one IVT injection of study treatment.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| RTH258/Brolucizumab | Percentage Change in Choroidal Neovascularization (CNV) Lesion Area Measured by Optical Coherence Tomography-Angiograph (OCT-A) From Baseline to Week 48 | Week 4 (n=124) | -59.03 % change from baseline |
| RTH258/Brolucizumab | Percentage Change in Choroidal Neovascularization (CNV) Lesion Area Measured by Optical Coherence Tomography-Angiograph (OCT-A) From Baseline to Week 48 | Week 8 (n=109) | -53.41 % change from baseline |
| RTH258/Brolucizumab | Percentage Change in Choroidal Neovascularization (CNV) Lesion Area Measured by Optical Coherence Tomography-Angiograph (OCT-A) From Baseline to Week 48 | Week 48 (n=117) | -68.50 % change from baseline |
Secondary
Percentage of Patients Who Are Maintained on an Exclusive Treatment Interval Every 12 Weeks (q12w) Following the Loading Phase to Week 48
To estimate the proportion of patients treated at q12w frequency with brolucizumab.
Time frame: Weeks 20, 32, 44, 48
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| RTH258/Brolucizumab | Percentage of Patients Who Are Maintained on an Exclusive Treatment Interval Every 12 Weeks (q12w) Following the Loading Phase to Week 48 | % of patients with exclusive q12w dose - Week 20 | 74.5 % of Participants |
| RTH258/Brolucizumab | Percentage of Patients Who Are Maintained on an Exclusive Treatment Interval Every 12 Weeks (q12w) Following the Loading Phase to Week 48 | % of patients with exclusive q12w dose - Week 32 | 55.6 % of Participants |
| RTH258/Brolucizumab | Percentage of Patients Who Are Maintained on an Exclusive Treatment Interval Every 12 Weeks (q12w) Following the Loading Phase to Week 48 | % of patients with exclusive q12w dose - Week 44 | 42.5 % of Participants |
| RTH258/Brolucizumab | Percentage of Patients Who Are Maintained on an Exclusive Treatment Interval Every 12 Weeks (q12w) Following the Loading Phase to Week 48 | % of patients with exclusive q12w dose - Week 48 | 42.5 % of Participants |
Secondary
Presence of Choroidal Neovascularization (CNV) Lesion Area Measured by Optical Coherence Tomography-Angiograph (OCT-A) From Baseline to Week 48
OCT-A is a dye-less angiographic procedure based on split-spectrum-decorrelation-amplitude angiography. It enables the capture of scattered intra-vessel particles (mainly erythrocyte cells) at all levels of the retinal and inner-choroidal vasculature, thus providing 3-D imaging of the retinal circulation. The literature suggests that OCT-A is a good marker for assessing anti-VEGF therapeutic response, especially lesion size.
Time frame: Baseline, Week 48
Population: Participants in the Full Analysis Set (FAS) with a valid value for the outcome measure at baseline and at each timepoint. The FAS comprised all patients to whom study treatment had been assigned and who received at least one IVT injection of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| RTH258/Brolucizumab | Presence of Choroidal Neovascularization (CNV) Lesion Area Measured by Optical Coherence Tomography-Angiograph (OCT-A) From Baseline to Week 48 | Present CNV at baseline and Present CNV at Week 48 | 66 Participants |
| RTH258/Brolucizumab | Presence of Choroidal Neovascularization (CNV) Lesion Area Measured by Optical Coherence Tomography-Angiograph (OCT-A) From Baseline to Week 48 | Present CNV at baseline and Not Present CNV at Week 48 | 48 Participants |
| RTH258/Brolucizumab | Presence of Choroidal Neovascularization (CNV) Lesion Area Measured by Optical Coherence Tomography-Angiograph (OCT-A) From Baseline to Week 48 | Present CNV at baseline and Ungradable at Week 48 | 6 Participants |
| RTH258/Brolucizumab | Presence of Choroidal Neovascularization (CNV) Lesion Area Measured by Optical Coherence Tomography-Angiograph (OCT-A) From Baseline to Week 48 | Not Present CNV at Baseline and Present CNV at Week 48 | 5 Participants |
| RTH258/Brolucizumab | Presence of Choroidal Neovascularization (CNV) Lesion Area Measured by Optical Coherence Tomography-Angiograph (OCT-A) From Baseline to Week 48 | Not Present CNV at Baseline and Not Present CNV at Week 48 | 4 Participants |
| RTH258/Brolucizumab | Presence of Choroidal Neovascularization (CNV) Lesion Area Measured by Optical Coherence Tomography-Angiograph (OCT-A) From Baseline to Week 48 | Not Present CNV at Baseline and Ungradable at Week 48 | 1 Participants |
| RTH258/Brolucizumab | Presence of Choroidal Neovascularization (CNV) Lesion Area Measured by Optical Coherence Tomography-Angiograph (OCT-A) From Baseline to Week 48 | Ungradable at Baseline and Present CNV at Week 48 | 8 Participants |
| RTH258/Brolucizumab | Presence of Choroidal Neovascularization (CNV) Lesion Area Measured by Optical Coherence Tomography-Angiograph (OCT-A) From Baseline to Week 48 | Ungradable at Baseline and Not Present CNV at Week 48 | 14 Participants |
| RTH258/Brolucizumab | Presence of Choroidal Neovascularization (CNV) Lesion Area Measured by Optical Coherence Tomography-Angiograph (OCT-A) From Baseline to Week 48 | Ungradable at Baseline and Ungradable at Week 48 | 1 Participants |
| RTH258/Brolucizumab | Presence of Choroidal Neovascularization (CNV) Lesion Area Measured by Optical Coherence Tomography-Angiograph (OCT-A) From Baseline to Week 48 | Total at Baseline and Present CNV at Week 48 | 79 Participants |
| RTH258/Brolucizumab | Presence of Choroidal Neovascularization (CNV) Lesion Area Measured by Optical Coherence Tomography-Angiograph (OCT-A) From Baseline to Week 48 | Total at Baseline and Not Present CNV at Week 48 | 66 Participants |
| RTH258/Brolucizumab | Presence of Choroidal Neovascularization (CNV) Lesion Area Measured by Optical Coherence Tomography-Angiograph (OCT-A) From Baseline to Week 48 | Total at Baseline and Ungradable at Week 48 | 8 Participants |
| RTH258/Brolucizumab | Presence of Choroidal Neovascularization (CNV) Lesion Area Measured by Optical Coherence Tomography-Angiograph (OCT-A) From Baseline to Week 48 | Total at Baseline and Total at Week 48 | 153 Participants |
Secondary
The Probability of the First q12w Interval for Determining Successful q12w Maintenance
To estimate the predictive value of the first q12w cycle for maintenance of q12w treatment with brolucizumab via the Kaplan-Meier method.
Time frame: Weeks 0,4,5,8,9,15,16,17,18,20,21,22,24,32,33,34,35,40,41,43,44,48
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| RTH258/Brolucizumab | The Probability of the First q12w Interval for Determining Successful q12w Maintenance | Week 0 | 1 Probability of Q12 maintain |
| RTH258/Brolucizumab | The Probability of the First q12w Interval for Determining Successful q12w Maintenance | Week 4 (n=201) | 1 Probability of Q12 maintain |
| RTH258/Brolucizumab | The Probability of the First q12w Interval for Determining Successful q12w Maintenance | Week 5 (n=198) | 1 Probability of Q12 maintain |
| RTH258/Brolucizumab | The Probability of the First q12w Interval for Determining Successful q12w Maintenance | Week 8 (n=196) | 1 Probability of Q12 maintain |
| RTH258/Brolucizumab | The Probability of the First q12w Interval for Determining Successful q12w Maintenance | Week 9 (n=184) | 1 Probability of Q12 maintain |
| RTH258/Brolucizumab | The Probability of the First q12w Interval for Determining Successful q12w Maintenance | Week 15 (n=176) | 0.97 Probability of Q12 maintain |
| RTH258/Brolucizumab | The Probability of the First q12w Interval for Determining Successful q12w Maintenance | Week 16 (n=171) | 0.78 Probability of Q12 maintain |
| RTH258/Brolucizumab | The Probability of the First q12w Interval for Determining Successful q12w Maintenance | Week 17 (n=138) | 0.66 Probability of Q12 maintain |
| RTH258/Brolucizumab | The Probability of the First q12w Interval for Determining Successful q12w Maintenance | Week 18 (n=117) | 0.65 Probability of Q12 maintain |
| RTH258/Brolucizumab | The Probability of the First q12w Interval for Determining Successful q12w Maintenance | Week 20 (n=114) | 0.57 Probability of Q12 maintain |
| RTH258/Brolucizumab | The Probability of the First q12w Interval for Determining Successful q12w Maintenance | Week 21 (n=97) | 0.51 Probability of Q12 maintain |
| RTH258/Brolucizumab | The Probability of the First q12w Interval for Determining Successful q12w Maintenance | Week 22 (n=87) | 0.5 Probability of Q12 maintain |
| RTH258/Brolucizumab | The Probability of the First q12w Interval for Determining Successful q12w Maintenance | Week 24 (n=86) | 0.5 Probability of Q12 maintain |
| RTH258/Brolucizumab | The Probability of the First q12w Interval for Determining Successful q12w Maintenance | Week 32 (n=85) | 0.47 Probability of Q12 maintain |
| RTH258/Brolucizumab | The Probability of the First q12w Interval for Determining Successful q12w Maintenance | Week 33 (n=80) | 0.46 Probability of Q12 maintain |
| RTH258/Brolucizumab | The Probability of the First q12w Interval for Determining Successful q12w Maintenance | Week 34 (n=78) | 0.45 Probability of Q12 maintain |
| RTH258/Brolucizumab | The Probability of the First q12w Interval for Determining Successful q12w Maintenance | Week 35 (n=77) | 0.45 Probability of Q12 maintain |
| RTH258/Brolucizumab | The Probability of the First q12w Interval for Determining Successful q12w Maintenance | Week 40 (n=76) | 0.45 Probability of Q12 maintain |
| RTH258/Brolucizumab | The Probability of the First q12w Interval for Determining Successful q12w Maintenance | Week 41 (n=72) | 0.45 Probability of Q12 maintain |
| RTH258/Brolucizumab | The Probability of the First q12w Interval for Determining Successful q12w Maintenance | Week 43 (n=71) | 0.45 Probability of Q12 maintain |
| RTH258/Brolucizumab | The Probability of the First q12w Interval for Determining Successful q12w Maintenance | Week 44 (n=65) | 0.45 Probability of Q12 maintain |
| RTH258/Brolucizumab | The Probability of the First q12w Interval for Determining Successful q12w Maintenance | Week 48 (n=65) | 0.45 Probability of Q12 maintain |
Secondary
Time From Last Intravitreal (IVT) Injection in the Initiation Phase to First Visit With no Disease Activity - Probability of no Disease Activity
To evaluate the time from last IVT injection in the initiation phase to first visit with no disease activity. The 95% CI are estimated by using the Greenwood formula Kaplan-Meier (KM) method.
Time frame: Week 8 until Week 41
Population: Full analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| RTH258/Brolucizumab | Time From Last Intravitreal (IVT) Injection in the Initiation Phase to First Visit With no Disease Activity - Probability of no Disease Activity | Week 8 | 0.83 Probability of no disease activity |
| RTH258/Brolucizumab | Time From Last Intravitreal (IVT) Injection in the Initiation Phase to First Visit With no Disease Activity - Probability of no Disease Activity | Week 9 | 0.85 Probability of no disease activity |
| RTH258/Brolucizumab | Time From Last Intravitreal (IVT) Injection in the Initiation Phase to First Visit With no Disease Activity - Probability of no Disease Activity | Week 10 | 0.86 Probability of no disease activity |
| RTH258/Brolucizumab | Time From Last Intravitreal (IVT) Injection in the Initiation Phase to First Visit With no Disease Activity - Probability of no Disease Activity | Week 15 | 0.86 Probability of no disease activity |
| RTH258/Brolucizumab | Time From Last Intravitreal (IVT) Injection in the Initiation Phase to First Visit With no Disease Activity - Probability of no Disease Activity | Week 16 | 0.87 Probability of no disease activity |
| RTH258/Brolucizumab | Time From Last Intravitreal (IVT) Injection in the Initiation Phase to First Visit With no Disease Activity - Probability of no Disease Activity | Week 18 | 0.88 Probability of no disease activity |
| RTH258/Brolucizumab | Time From Last Intravitreal (IVT) Injection in the Initiation Phase to First Visit With no Disease Activity - Probability of no Disease Activity | Week 23 | 0.89 Probability of no disease activity |
| RTH258/Brolucizumab | Time From Last Intravitreal (IVT) Injection in the Initiation Phase to First Visit With no Disease Activity - Probability of no Disease Activity | Week 24 | 0.9 Probability of no disease activity |
| RTH258/Brolucizumab | Time From Last Intravitreal (IVT) Injection in the Initiation Phase to First Visit With no Disease Activity - Probability of no Disease Activity | Week 31 | 0.9 Probability of no disease activity |
| RTH258/Brolucizumab | Time From Last Intravitreal (IVT) Injection in the Initiation Phase to First Visit With no Disease Activity - Probability of no Disease Activity | Week 32 | 0.93 Probability of no disease activity |
| RTH258/Brolucizumab | Time From Last Intravitreal (IVT) Injection in the Initiation Phase to First Visit With no Disease Activity - Probability of no Disease Activity | Week 33 | 0.94 Probability of no disease activity |
| RTH258/Brolucizumab | Time From Last Intravitreal (IVT) Injection in the Initiation Phase to First Visit With no Disease Activity - Probability of no Disease Activity | Week 35 | 0.96 Probability of no disease activity |
| RTH258/Brolucizumab | Time From Last Intravitreal (IVT) Injection in the Initiation Phase to First Visit With no Disease Activity - Probability of no Disease Activity | Week 36 | 0.96 Probability of no disease activity |
| RTH258/Brolucizumab | Time From Last Intravitreal (IVT) Injection in the Initiation Phase to First Visit With no Disease Activity - Probability of no Disease Activity | Week 41 | 0.96 Probability of no disease activity |