A One-year, Single-arm, Open-label, Multicenter Study Assessing the Anatomic Outcomes of Brolucizumab Assessed by OCT-A in Adult Patients With Neovascular Age Related Macular Degeneration
Overview
- Phase
- Phase 3
- Intervention
- RTH258/Brolucizumab
- Conditions
- Neovascular Age Related Macular Degeneration
- Sponsor
- Novartis Pharmaceuticals
- Enrollment
- 210
- Locations
- 1
- Primary Endpoint
- Percentage Change in Choroidal Neovascularization (CNV) Lesion Area Measured by Optical Coherence Tomography-Angiograph (OCT-A) From Baseline to Week 12
- Status
- Completed
- Last Updated
- last year
Overview
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).
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
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.
Intervention: RTH258/Brolucizumab
Outcomes
Primary Outcomes
Percentage Change in Choroidal Neovascularization (CNV) Lesion Area Measured by Optical Coherence Tomography-Angiograph (OCT-A) From Baseline to Week 12
Time Frame: 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 Outcomes
- 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)
- Presence of Choroidal Neovascularization (CNV) Lesion Area Measured by Optical Coherence Tomography-Angiograph (OCT-A) From Baseline to Week 48(Baseline, Week 48)
- Change in Best Corrected Visual Acuity (BCVA) From Baseline up to Week 48(Baseline, Weeks 4, 8, 12, 48)
- 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)
- 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)
- Incidence of Adverse Events (AEs) (Serious and Nonserious) Reported in Patients Treated With Brolucizumab.(Up to Week 48)
- 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)
- 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)
- 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)
- 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)
- Incidence of AEs (Serious and Nonserious) Reported in Patients Treated With Brolucizumab - Non-Ocular Adverse Events(Up to Week 48)
- 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)