A Multicenter, Randomized, Double-masked Phase 3a Study to Assess Safety and Efficacy of Brolucizumab 6 mg q4 Weeks Compared to Aflibercept 2 mg q4 Weeks in Patients With Neovascular Age-related Macular Degeneration (nAMD) With Persistent Retinal Fluid (MERLIN)
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 535
- 试验地点
- 62
- 主要终点
- Change From Baseline in Best-Corrected Visual Acuity (BCVA) at Week 52
研究概览
简要总结
This clinical study was designed to compare the safety and efficacy of brolucizumab 6 mg dosed every 4 weeks to aflibercept 2 mg dosed every 4 weeks in those neovascular age-related macular degeneration (nAMD) patients with retinal fluid despite frequent anti-Vascular Endothelial Growth Factor (VEGF) injections.
详细描述
This was a Phase III, multi-center, randomized, double-masked, parallel group study with 2 masked arms in which participants were randomized 2:1 to receive brolucizumab or aflibercept. All participants had study visits every 4 weeks through week 104.
The study consisted of three study periods:
Screening Period: The screening period lasted up to 2 weeks prior to administration of the first dose of study treatment, dependent upon confirmation of the patient meeting eligibility criteria.
Double-Masked Treatment Period: Participants meeting eligibility criteria entered the treatment period and were randomized in a 2:1 ratio into one of the following 2 masked treatment arms at the Baseline visit: Brolucizumab 6 mg injected every 4 weeks or Aflibercept 2 mg injected every 4 weeks. Treatment period lasted up to week 100.
Safety Follow up Period: Participants were followed up for safety during 4 weeks after the last dose of study treatment. Including the Screening Period, the total study duration for a participant was up to 106 weeks.
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, Care Provider, Investigator)
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent
- •Diagnosis of wet age-related macular degeneration (AMD)
- •Currently receiving anti-VEGF injections
排除标准
- •Active infection or inflammation in either eye
- •Significant fibrosis in the study eye
- •Recent ocular surgery
- •Uncontrolled glaucoma
- •Use of medications as specified in the protocol
- •Pregnant, nursing
- •Of child-bearing potential unless using highly effective method of contraception
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 was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing protocol at an initial testing distance of 4 meters. BCVA min and max possible scores are 0-100 respectively and a higher score represents better functioning. A positive change from baseline represents better functioning. Baseline BCVA was defined as the last measurement on or prior to the baseline visit. BCVA assessments after start of alternative anti-VEGF treatment in the study eye were censored and imputed by the last value prior to start of alternative treatment. Last observation carried forward (LOCF) was used for the imputation of missing values.
次要结局
- Gain in Best-Corrected Visual Acuity (BCVA) of 10 Letters or More(Baseline, weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100 and 104)
- Stable Visual Acuity (VA) or Improvement in VA at Week 52 and Week 104(Baseline, weeks 52 and 104)
- Number of Participants With Subretinal Fluid (SRF)(Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100 and 104)
- Number of Participants With Sub-Retinal Pigment Epithelium (Sub-RPE) Fluid(Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100 and 104)
- Gain in Best-Corrected Visual Acuity (BCVA) of 5 Letters or More(Baseline, weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100 and 104)
- Time to Sustained Dry Retina (no IRF or SRF at ≥ 2 Consecutive Visits)(Baseline, Up to Week 104 (assessments every 4 weeks))
- Loss in Best-Corrected Visual Acuity (BCVA) of 5 Letters or More(Baseline, weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100 and 104)
- Loss in Best-Corrected Visual Acuity (BCVA) of 10 Letters or More(Baseline, weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100 and 104)
- Number of Participants With Fluid-free Status (no IRF, SRF or Sub-RPE Fluid)(Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100 and 104)
- Number of Participants With Anti-drug Antibody (ADA) Negative Status(Baseline, weeks 4, 12, 24, 36, 52, 76 and 104)
- Loss in Best-Corrected Visual Acuity (BCVA) of 15 Letters or More(Baseline, weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100 and 104)
- Gain in Best-Corrected Visual Acuity (BCVA) of 15 Letters or More(Baseline, weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100 and 104)
- Change in Central Subfield Thickness (CST) From Baseline(Baseline, weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100 and 104)
- Number of Participants With Intraretinal Fluid (IRF)(Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100 and 104)
- Free Brolucizumab Serum Concentration(pre-dose a baseline, weeks 4, 12, 24, 36, 52, 76 and 104)
- Time to First Dry Retina (no IRF or SRF)(Baseline, Up to Week 104 (assessments every 4 weeks))