NCT04679935已完成4 期
A 52-week, Two Arm, Randomized, Open-label, Multicenter Study Assessing the Efficacy and Safety of Two Different Brolucizumab 6 mg Dosing Regimens for Patients With Suboptimal Anatomically Controlled Neovascular Age-related Macular Degeneration
适应症
干预措施
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 52
- 试验地点
- 1
- 主要终点
- Week 40 to Week 52: LS Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
open-label
入排标准
- 年龄范围
- 50 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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
研究组 & 干预措施
Brolucizumab 6 mg non-loading
Experimental
One initial injection followed by treatment every 12 weeks.
干预措施: Brolucizumab (Biological)
Brolucizumab 6 mg loading
Experimental
3 x 4-weekly injections followed by treatment every 12 weeks.
干预措施: Brolucizumab (Biological)
结局指标
主要结局
Week 40 to Week 52: LS Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye
时间窗: 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.
次要结局
- Treatment Intervals Before and During the Study(-24 Weeks, Baseline, Week 52)
- 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)
- Number of Patients With Prolonged Interval(Baseline, Week 52)
- Proportion of Patients Who Maintained on q12w Regimen.(Up to week 52)
- Mean Change in Best-corrected Visual Acuity(Baseline, Weeks 16 to 28, Week 52)
- Number of Patients With Best-corrected Visual Acuity Improvements of >= 5, >= 10 and >= 15 Letters(Baseline, up to Week 52)
- Number of Patients With Best-corrected Visual Acuity >= 69 Letters(Baseline, up to Week 52)
- LS Mean Change in Best-corrected Visual Acuity From Baseline at Week 52(Baseline, Week 52)
- Change in Central Subfield Thickness From Baseline at Weeks 12, 16, 28 and 52(Baseline, Weeks 12, 16, 28 and 52)
- Absence of Intraretinal Fluid in the Central Subfield(Every 4 weeks from baseline up to Week 52)
- Absence of Subretinal Fluid in the Central Subfield(Every 4 weeks from baseline up to Week 52)
- Absence of Sub-retinal Pigment Epithelium Fluid in the Central Subfield(Every 4 weeks from baseline up to Week 52)
- Presence of Active Choroidal Neovascularization Leakage(At Week 52)
- 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.)
- 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.)
- 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.)
- 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.)
- 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.)
研究者
研究点 (1)
Loading locations...
相似试验
终止
3 期
Study of Safety and Efficacy of Brolucizumab 6 mg Dosed Every 4 Weeks Compared to Aflibercept 2 mg Dosed Every 4 Weeks in Patients With Retinal Fluid Despite Frequent Anti-VEGF InjectionsAge-Related Macular DegenerationNCT03710564Novartis Pharmaceuticals535
撤回
3 期
Efficacy and Safety of Brolucizumab vs. Aflibercept in Patients With Visual Impairment Due to Diabetic Macular EdemaDiabetic Macula EdemaNCT04079231Novartis Pharmaceuticals
已完成
3 期
Efficacy and Safety of Brolucizumab vs Aflibercept in Patients With Visual Impairment Due to Diabetic Macular EdemaDiabetic Macular EdemaNCT03917472Novartis Pharmaceuticals517
已完成
3 期
Study of Efficacy and Safety of Brolucizumab Versus Panretinal Photocoagulation Laser in Patients With Proliferative Diabetic RetinopathyProliferative Diabetic RetinopathyNCT04278417Novartis Pharmaceuticals689
终止
3 期
Assessing the Efficacy and Safety of Brolucizumab Versus Aflibercept in Patients With Visual Impairment Due to Macular Edema Secondary to Central Retinal Vein OcclusionCentral Retinal Vein OcclusionNCT03810313Novartis Pharmaceuticals493