An Eighteen-Month, Two-Arm, Randomized, Double Masked, Multicenter, Phase III Study Assessing the Efficacy and Safety of Brolucizumab Versus Aflibercept in Adult Patients With Visual Impairment Due to Macular Edema Secondary to Central Retinal Vein Occlusion
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 493
- 试验地点
- 1
- 主要终点
- Change From Baseline in Best-corrected Visual Acuity (BCVA) at Week 24
研究概览
简要总结
The purpose of this study was to evaluate the efficacy and safety of brolucizumab in treatment of patients with macular edema (ME) secondary to central retinal vein occlusion (CRVO).
详细描述
The study included Screening Period (Day -28 to Day -1), double-masked treatment period (Day 1 to Week 72), and post-treatment follow-up period (Week 72 to Week 76). Treatment visits were scheduled in 4-week intervals. After 6 initial monthly injections of brolucizumab or aflibercept (loading phase), subjects entered a one-year individualized flexible treatment (IFT) phase. During the IFT phase, an assessment of disease stability was performed at each monthly visit and subjects received either an active or a sham injection. Treatment with active was interrupted when disease stability was reached.
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
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
A masked evaluating investigator was responsible for all aspects of the study except the injections and the safety assessment following the injections. An unmasked treating investigator performed the injections and assessed patient safety following the injections.
入排标准
- 年龄范围
- 18 Years 至 —（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.
- •Patients with visual impairment due to ME secondary to CRVO diagnosed < 6 months prior to screening.
- •BCVA score between 78 and 23 letters, inclusive, using ETDRS visual acuity testing charts (approximate Snellen equivalent of 20/32 to 20/320) at both screening and baseline visits.
- •Exclusion criteria
- •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 medical or surgical intervention during the first 12-month study period (e.g. structural damage of the fovea, vitreous hemorrhage, retinal vascular occlusion other than CRVO, retinal detachment, macular hole, or choroidal neovascularization of any cause, diabetic retinopathy (except mild non-proliferative) and diabetic macular edema).
- •Any active intraocular or periocular infection or active intraocular inflammation (e.g. infectious conjunctivitis, keratitis, scleritis, endophthalmitis, infectious blepharitis, uveitis) in study 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
- •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)
- •Previous treatment with any anti-VEGF therapy or investigational drugs in the study eye at any time prior to baseline
- •Previous use of intraocular or periocular steroids in study eye at any time prior to baseline
- •Macular laser photocoagulation (focal/grid) in the study eye at any time prior to baseline and peripheral laser photocoagulation in the study eye within 3 months prior to the baseline
- •Intraocular surgery in the study eye during the 3-month period prior to baseline
- •Vitreoretinal surgery in the study eye at any time prior to baseline
- •Aphakia with the absence of posterior capsule in the study eye
排除标准
- 未提供
研究组 & 干预措施
Brolucizumab 6 mg
1 intravitreal injection every 4 weeks for a total of 6 injections, followed by 48 weeks of individual flexible treatment (IFT)
干预措施: Brolucizumab 6 mg (Drug)
Brolucizumab 6 mg
1 intravitreal injection every 4 weeks for a total of 6 injections, followed by 48 weeks of individual flexible treatment (IFT)
干预措施: Sham injection (Other)
Aflibercept 2 mg
1 intravitreal injection every 4 weeks for a total of 6 injections, followed by 48 weeks of individual flexible treatment (IFT)
干预措施: Aflibercept 2 mg (Drug)
Aflibercept 2 mg
1 intravitreal injection every 4 weeks for a total of 6 injections, followed by 48 weeks of individual flexible treatment (IFT)
干预措施: Sham injection (Other)
结局指标
主要结局
Change From Baseline in Best-corrected Visual Acuity (BCVA) at Week 24
时间窗: Baseline, Week 24
BCVA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts at an initial testing distance of 4 meters. Min and max possible scores are 0-100 letters read respectively. A higher score represents better visual functioning. Missing and censored BCVA values were imputed by Last observation carried forward (LOCF) as the primary approach. Observed values from both scheduled and unscheduled post-baseline visits were used for the LOCF imputation. For subjects with no post-baseline BCVA value, the baseline value was carried forward.
次要结局
- Change From Baseline in BCVA Averaged Over Week 64 to Week 76(Baseline, Week 64 to Week 76)
- Proportion of Participants With a Loss ≥ 5, 10 and 15 Letters in BCVA by Visit Compared to Baseline(Baseline and every 4 weeks from baseline up to Week 76)
- Proportion of Subjects With a CSFT < 300 μm for the Study Eye by Visit up to Week 76(Every 4 weeks from week 4 up to Week 76)
- Change From Baseline in CSFT Averaged Over Week 40 to Week 52(Baseline, Week 40 to Week 52)
- Change From Baseline in CSFT Averaged Over Week 64 to Week 76(Baseline, Week 64 to Week 76)
- Change From Baseline in CSFT by Visit up to Week 76(Baseline, and every 4 weeks from baseline up to Week 76)
- Time to Recurrence After Week 20 and up to Week 76(Week 20 to Week 76)
- Number of Subjects According to Their Anti-drug Antibody (ADA) Titer at Screening and Week 4, Week 12, Week 24, Week 36, Week 52 and Week 76(Baseline, Week 4, Week 12, Week 24, Week 36, Week 52 and Week 76)
- Proportion of Participants With a Gain ≥ 5, 10 and 15 Letters in BCVA by Visit Compared to Baseline(Baseline and every 4 weeks from baseline up to Week 76)
- Change From Baseline in Patient Reported Outcomes (NEI VFQ-25) at Week 24, Week 52 and Week 76(Baseline, Week 24, Week 52 and Week 76)
- Proportion of Subjects With Presence of Retinal Fluid (Intra- and/or Subretinal Fluid) in the Study Eye by Visit up to Week 76(Every 4 weeks from week 4 up to Week 76)
- Change From Baseline in BCVA Averaged Over Week 40 to Week 52(Baseline, Week 40 to Week 52)
- Change From Baseline in BCVA by Visit up to Week 76(Baseline and every 4 weeks from baseline up to Week 76)
- Number of Injections Between Week 24 and Week 52 and Between Week 24 and Week 72(Week 24 to Week 52 and Week 24 to Week 72)
- Number of Subjects With Ocular and Non-ocular AEs up to Week 52 and Week 76(Baseline to Week 76)