A 60-week, Phase IIIb, Randomized, Multi-center Study Assessing the Efficacy and Safety of a Personalized Monotherapy Regimen of Brolucizumab in Patients With Symptomatic Macular Polypoidal Choroidal Vasculopathy (PROUD Study)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 148
- 试验地点
- 1
- 主要终点
- Average change in Best Corrected Visual Acuity (BCVA) from Baseline at a period from Week 48 to Week 60
研究概览
简要总结
This study is a 60-week, two-arm, randomized, open-label, active-controlled, multi-center study in patients with Polypoidal choroidal vasculopathy (PCV) who have not previously received anti-Vascular endothelial growth factor (VEGF) treatment.
详细描述
The purpose of this study is to measure the change in Best-corrected visual acuity (BCVA) with brolucizumab 6 mg Personalized regimen compared with Brolucizumab 6 mg Standard q12w/q8w regimen in participants with Polypoidal choroidal vasculopathy (PCV).
- The study duration will be up to 60 weeks.
- The treatment duration will be up to 56 weeks.
- The visit frequency is not fixed and may be reduced or extended depending on whether disease activity is controlled.
In the Personalized regimen arm, the first loading injection will be performed for all participants. After 4 weeks, treatment response will be judged. If there is no disease activity, injection interval will be extended to 8 weeks. The participants with presence of disease activity will continue 4-week loading injections up to 3 monthly loading dose and commence the Treat-and-extend (T&E) phase thereafter. In the T&E phase, the treatment interval can be extended by 4 weeks at a time based on Investigator's judgment of visual and/or anatomic outcomes. The maximal treatment interval is 16 weeks. At the Investigator's discretion, a participant with no disease activity or improvement of disease activity (e.g., reduction of fluid) may also be maintained on the same interval. If disease activity recurs, the interval should be shortened by 4 weeks at a time or to a minimal interval of 8 weeks.
In the Standard q12w/q8w regimen arm, all participants will receive three loading injections every 4 weeks. After loading injection, participants with no disease activity at Week 16 will receive study treatment q12w at Week 20, Week 32, and Week 44. If there is disease activity at any scheduled treatment visit, the study intervals will be adjusted to 8 weeks thereafter. Treatment intervals can be increased to 12 weeks after a treatment visit with no disease activity.
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
入排标准
- 年龄范围
- 50 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent must be obtained prior to participation in the study.
- •Participants ≥ 50 years of age at Screening.
- •Presence of active polypoidal lesions in the macula as shown by Indocyanine green angiography (ICGA) AND presence of serosanguinous maculopathy, i.e., exudative or hemorrhagic features involving the macula on color fundus photography (CFP), Fluorescein angiography (FA) and spectral domain optical coherence tomography (SD-OCT) AND presence of Intraretinal fluid (IRF) or Subretinal fluid (SRF) that affects the central subfield as seen by SD-OCT.
- •Best-corrected visual acuity (BCVA) score must be ≤ 78 and ≥ 24 letters at 4 meters starting distance using early treatment diabetic retinopathy study (ETDRS) visual acuity charts at both Screening and Baseline.
- •Greatest liner dimension (GLD) of the total lesion area (branching vascular network [BVN] + polypoidal lesion) < 5400 μm (equivalent to 9 macular photocoagulation study [MPS] Disc Area) as delineated by Indocyanin green angiography (ICGA).
排除标准
- •Ocular conditions:
- •Concomitant conditions or ocular disorders in the study eye at Screening or Baseline which could, in the opinion of the Investigator, prevent response to study treatment or may confound interpretation of study results, compromise visual acuity or require planned medical or surgical intervention during the first 12-month study period.
- •Any active intraocular or periocular infection or active intraocular inflammation (IOI) (e.g., infectious conjunctivitis, keratitis, scleritis, endophthalmitis, infectious blepharitis, uveitis) in study eye or fellow eye at Screening or Baseline.
- •Uncontrolled glaucoma in the study eye defined as intraocular pressure (IOP) > 25 mmHg on medication, or according to Investigator's judgment, at Screening or Baseline.
- •Any Polypoidal choroidal vasculopathy (PCV) masquerades like macular aneurysms, macular telangiectasia, etc. in study eye.
- •Total area of subretinal hemorrhage larger than 9 DA (Disc Area) or comprising ≥ 50% of the lesion area or presence of vitreous hemorrhage in study eye.
- •Ocular treatments in the study eye:
- •Previous treatment with any anti-Vascular endothelial growth factor (VEGF) drugs or investigational drugs at any time prior to Baseline.
- •Previous use of intraocular or periocular steroids within the 6-month period prior to Baseline.
- •Macular laser photocoagulation (focal/grid) or Photodynamic therapy (PDT) at any time prior to Baseline and peripheral laser photocoagulation within 3 months prior to Baseline.
- •Systemic conditions or treatments:
- •Stroke or myocardial infarction during the 6-month period prior to Baseline.
- •Systemic anti-VEGF therapy any time prior to Baseline.
研究组 & 干预措施
Personalized regimen arm
1~3 x 4-week loading injections and one 8-week injection, followed by Treat-and-extend (T&E) regimen up to Week 56
干预措施: Brolucizumab 6mg (Drug)
Standard regimen arm
3 x 4-week loading injections and disease activity assessment at week 16 followed by q12w/q8w up to Week 56
干预措施: Brolucizumab 6mg (Drug)
结局指标
主要结局
Average change in Best Corrected Visual Acuity (BCVA) from Baseline at a period from Week 48 to Week 60
时间窗: from Week 48 to Week 60
BCVA will be assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts
次要结局
- Number of participants with last completed treatment interval of 12 weeks and/or 16-weeks with no disease activity at a period from Week 48 to Week 60(Week 12, Week 16, and from Week 48 to Week 60)
- Distribution of last completed treatment interval with no disease activity up to Week60(up to Week 60)
- Distribution of the maximal intervals with no disease activity up to Week 60(up to Week 60)
- Distribution of the last interval at a period from Week 48 to Week 60(from Week 48 to Week 60)
- Time from the last loading injection to the first visit with no disease activity(Up to Week 60)
- Occurrence of at least two successive treatment intervals with no disease activity ≥ 12-week or two successive treatment intervals with no disease activity of 16-week up to Week 60(up to Week 60)
- Average change in BCVA from Baseline up to a period from Week 48 to Week 60(from Week 48 to Week 60)
- Occurrence of BCVA improvement of ≥ 10 and ≥ 15 letters from Baseline at a period from Week 48 to Week 60(Baseline, and from Week 48 to Week 60)
- Occurrence of BCVA ≥ 69 letters at a period from Week 48 to Week 60(from Week 48 to Week 60)
- Average change in BCVA from Baseline up to a period from Week 48 to Week 60 categorized into 2 groups, lower half of Baseline BCVA and upper half of Baseline BCVA(Baseline, and from Week 48 to Week 60)
- Number of participants with complete polypoidal lesion regression at Week 12 and at a period from Week 48 to Week 60(at Week 12, and from Week 48 to Week 60)
- Number of participants with inactive polypoidal lesions at Week 12 and at a period from Week 48 to Week 60(at Week 12, and from Week 48 to Week 60)
- Change in number and area of polypoidal lesions from Baseline at Week 12 and at a period from Week 48 to Week 60(Baseline, Week 12, and from Week 48 to Week 60)
- Average change from Baseline in central subfield thickness (CSFT) up to Week 60(up to Week 60)
- Average change from Baseline in maximum thickness of intraretinal fluid (IRF) up to Week 60(up to Week 60)
- Average change from Baseline in maximum thickness of subretinal fluid (SRF) up to Week 60(up to Week 60)
- Average change from Baseline in maximum thickness of sub-retinal pigment epithelium (sub-RPE) fluid up to Week 60(up to Week 60)
- Average change from Baseline in maximum thickness of pigment epithelial detachment (PED) up to Week 60(up to Week 60)
- Number of participants with intraretinal fluid (IRF) and/or subretinal fluid (SRF) and/or sub-retinal pigment epithelium (sub-RPE) fluid up to Week 60(up to Week 60)
- Incidence of ocular adverse events (AEs) up to Week 60(Up to Week 60)
- Incidence of non-ocular adverse events (AEs) up to Week 60(Up to Week 60)