A 12-Month, 2-Arm, Randomized, Double-Masked, Multicenter Phase III Study Assessing the Efficacy and Safety of Brolucizumab vs. Aflibercept in Patients With Visual Impairment Due to Diabetic Macular Edema (KINGFISHER)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 517
- 试验地点
- 1
- 主要终点
- Change From Baseline in Best-corrected Visual Acuity (BCVA) at Week 52
研究概览
简要总结
The purpose of this study was to evaluate the efficacy and safety of brolucizumab vs. aflibercept in the treatment of patients with visual impairment due to diabetic macular edema (DME).
详细描述
This study was designed as a Phase III, multi-center, randomized, double-masked, active controlled, parallel group prospective study to evaluate if brolucizumab 6 mg dosed q4w is safe and effective in the treatment of subjects with visual impairment due to diabetic macular edema (DME). Subjects who met all the inclusion and none of the exclusion criteria were randomized in a 2:1 ratio to one of two treatment arms i.e., brolucizumab 6 mg and aflibercept 2 mg. Only one eye was selected as study eye and treated with study medication.
The study included a screening period of up to 2 weeks to assess eligibility, followed by a double-masked treatment period (Day 1 to Week 48). For all subjects, the last study assessment was performed at the Week 52/end of study (EOS) visit. All subjects had study visits q4w through Week 52. The primary analysis was performed at the EOS visit (Week 52).
To ensure masking was maintained, the investigational site had both masked and unmasked staff to perform the masked and unmasked study assessments/procedures accordingly.
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 will be responsible for all aspects of the study except the injections and the safety assessment following the injections. An unmasked treating investigator was to perform the injections and assess 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 type 1 or type 2 diabetes mellitus (DM) and Hemoglobin A1c (HbA1c) ≤ 12% at screening.
- •Study eye: Visual impairment due to DME with:
- •Best-corrected visual acuity (BCVA) score between 73 and 23 letters, inclusive, using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts at an initial testing distance of 4 meters
- •DME involving the center of the macula, with Central Subfield Thickness (CSFT) ≥ 320 µm on Spectral Domain Optical Coherence Tomography (SD-OCT)
排除标准
- •High-risk proliferative diabetic retinopathy (PDR) in the study eye
- •Concomitant conditions or ocular disorders in the study eye which confound interpretation of study results, compromise visual acuity or require medical or surgical intervention
- •Any active intraocular or periocular infection or active intraocular inflammation in the either eye
- •Uncontrolled glaucoma in the study eye
- •Presence of amblyopia, amaurosis or ocular disorders in the fellow eye with BCVA <20/200
- •Use of anti-VEGF therapies, intraocular surgery or laser photocoagulation (macular or panretinal) in the study eye during the 3-month period prior to baseline
- •Use of intraocular or periocular corticosteroids in the study eye during the 6-month period prior to baseline, and use of fluocinolone acetonide intravitreal (IVT) implant (Iluvien) at any time prior to baseline
- •Prior investigational drugs in either eye, vitreoretinal surgery in the study eye at any time prior to baseline
研究组 & 干预措施
Brolucizumab 6mg q4w
Brolucizumab 6 mg/0.05 mL every 4 weeks.
干预措施: Brolucizumab (Drug)
Aflibercept 2mg q4w
Aflibercept 2mg/0.05 mL every 4 weeks
干预措施: Aflibercept (Drug)
结局指标
主要结局
Change From Baseline in Best-corrected Visual Acuity (BCVA) at Week 52
时间窗: Baseline, Week 52
BCVA will be 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 73 to 23 (per the inclusion criteria) (approximate Snellen equivalent of 20/40 to 20/320) in the study eye were included. Min and max possible scores are 0-100 respectively. A higher score represents better functioning. Last observation carried forward (LOCF) was used for the imputation of missing values.
次要结局
- Change From Baseline in Central Subfield Thickness (CSFT) at Each Post-baseline Visit(Baseline, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and 52)
- Gain in Best-corrected Visual Acuity (BCVA) (Letters Read): Number (%) of Subjects Who Gained ≥ 5, 10, or 15 Letters in BCVA From Baseline or Reached BCVA ≥ 84 Letters in the Study Eye at Week 52(Baseline, Week 52)
- Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS): Proportion of Subjects With >=2-step Improvement From Baseline in the DRSS Score at Each Assessment Visit for the Study Eye(Baseline, Weeks 12, 24 and 52)
- Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS): Proportion of Subjects With >=3-step Improvement From Baseline in the DRSS Score at Each Assessment Visit for the Study Eye(Baseline, Weeks 12, 24 and 52)
- Anti-Drug Antibody (ADA): Frequency Distribution of Pre-existing ADA Status in the Brolucizumab Arm(Baseline)
- Number and Percentage of Participants With Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) at Each Post-baseline Visit for the Study Eye(Baseline, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and 52)
- Time to First Fluid-free Macula - Time-to-first Absence of Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) in the Study Eye - Number of Subjects With Absence of SRF / IRF and Number of Subjects Censored by Visit(Baseline, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and 52)
- Time to First Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) in the Study Eye at Each Post-baseline Visit - Number of Subjects With Probability of Absence of DME and Number Censored by Visit(Baseline, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and 52)
- Number and Percentage of Participants With Fluid-free Macula in the Study Eye at Each Post-baseline Visit(Baseline, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and 52)
- Time to First Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) in the Study Eye at Each Post-baseline Visit - Kaplan-Meier Analysis - Probability of Absence of DME by Visit(Baseline, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and 52)
- Time to First Fluid-free Macula - Time-to-first Absence of Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) in the Study Eye - Kaplan-Meier Analysis - Probability of Absence of SRF/IRF by Visit(Baseline, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and 52)
- Best Corrected Visual Acuity (Letters Read): Change From Baseline in Best-corrected Visual Acuity (BCVA) at Each Post-baseline Visit for the Study Eye(Baseline, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and 52)
- Ocular AEs (Greater Than or Equal to 2% in Any Treatment Arm) by Preferred Term in the Study Eye(Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 52 weeks.)
- Number of Subjects With Non-ocular AEs (Greater Than or Equal to 2% in Any Treatment Arm)(Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 52 weeks.)