A Study to Assess the Effects of Brolucizumab in Adult Patients With Neovascular Age Related Macular Degeneration
- Conditions
- Neovascular Age Related Macular Degeneration
- Interventions
- Drug: RTH258/Brolucizumab
- Registration Number
- NCT04239027
- Lead Sponsor
- Novartis Pharmaceuticals
- 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).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 210
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description RTH258/Brolucizumab RTH258/Brolucizumab This is a single-arm study in which all patients will be 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.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time 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.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.
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).
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.
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.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.
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 EpitheliumIncidence 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.
Trial Locations
- Locations (1)
Novartis Investigative Site
🇫🇷Toulouse Cedex 9, France