A Two-Year, Randomized, Double-Masked, Multicenter, Three-Arm Study Comparing the Efficacy and Safety of RTH258 Versus Aflibercept in Subjects With Neovascular Age-Related Macular Degeneration
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,775
- 试验地点
- 1
- 主要终点
- Change From Baseline in Best Corrected Visual Acuity (BCVA) (Letters Read) at Week 48 - Study Eye
研究概览
简要总结
The purpose of this study is to compare brolucizumab (RTH258) ophthalmic solution for intravitreal (IVT) injection at two dosage levels (3 mg and 6 mg) to aflibercept ophthalmic solution for IVT injection (2 mg) in subjects with untreated active choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) in the study eye.
详细描述
Subjects were randomized to brolucizumab 3 mg, brolucizumab 6 mg,and aflibercept 2 mg in a 1:1:1 ratio. Subjects in all treatment arms received 3 monthly loading doses (Day 0, Week 4 and Week 8), followed by a maintenance regimen, until the end of the study (Week 96/Exit). All subjects attended pre-specified visits every 4 weeks.
Subjects in the brolucizumab 3 mg and brolucizumab 6 mg arms followed a q12w/q8w maintenance regimen. Within the q12w/q8w regimen, the initial treatment after the loading phase was q12w (1 injection every 12 weeks). If disease activity was identified by the masked investigator at any of the disease activity assessments, dosing was adjusted to q8w (1 injection every 8 weeks) ("q12w/q8w regimen"). Once subjects were adjusted to the q8w interval, they stayed on that interval until the end of the study.
Subjects in the aflibercept 2 mg arm followed a q8w maintenance regimen until the end of the study.
Results reported up to Week 48 are based on the database locked for the primary analysis at Week 48. Results reported after Week 48 are based on the database locked at the end of study (final analysis).
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
- Double (Participant, Outcomes Assessor)
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
- •Provide written informed consent
- •Active choroidal neovascularization (CNV) lesions secondary to age-related macular degeneration (AMD) that affected the central subfield in the study eye at Screening;
- •Total area of CNV comprising >50% of the total lesion area in the study eye at Screening;
- •Intraretinal and/or subretinal fluid affecting the central subfield of the study eye at Screening;
- •Best Corrected Visual Acuity (BCVA) between 78 and 23 letters, inclusive, in the study eye at Screening and Baseline using Early Treatment Diabetic Retinopathy Study (ETDRS) testing.
排除标准
- •Any active intraocular or periocular infection or active intraocular inflammation in either eye at Baseline;
- •Central subfield of the study eye affected by fibrosis or geographic atrophy or total area of fibrosis >50% of the total lesion in the study eye at Screening;
- •Subretinal blood affecting the foveal center point and/or >50% of the lesion of the study eye at Screening;
- •Any approved or investigational treatment for neovascular age-related macular degeneration (nAMD) in the study eye at any time;
- •Retinal pigment epithelial rip/tear in the study eye at Screening or Baseline or current vitreous hemorrhage or history of vitreous hemorrhage in the study eye within 4 weeks prior to Baseline;
- •Pregnant or nursing women; women of child-bearing potential;
- •Stroke or myocardial infarction in the 90-day period prior to Baseline.
研究组 & 干预措施
Brolucizumab 3 mg
Single intravitreal (IVT) injection of brolucizumab ophthalmic solution administered as a 3 mg/50 microliter (μL) dose at Day 0, Week 4, and Week 8, followed by 1 injection every 8 weeks/1 injection every 12 weeks (q8w/q12w) maintenance regimen until study exit
干预措施: Brolucizumab ophthalmic solution (Drug)
Brolucizumab 6 mg
Single IVT injection of brolucizumab ophthalmic solution administered as a 6 mg/50 μL dose at Day 0, Week 4, and Week 8, followed by q8w/q12w maintenance regimen until study exit
干预措施: Brolucizumab ophthalmic solution (Drug)
Aflibercept 2 mg
Single IVT injection of aflibercept ophthalmic solution administered as a 2 mg/50 μL dose at Day 0, Week 4, and Week 8, followed by q8w maintenance regimen until study exit
干预措施: Aflibercept ophthalmic solution (Drug)
结局指标
主要结局
Change From Baseline in Best Corrected Visual Acuity (BCVA) (Letters Read) at Week 48 - Study Eye
时间窗: Baseline, Week 48
BCVA (with spectacles or other visual corrective devices) was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) testing at 4 meters and reported in letters read correctly. Baseline was defined as the last measurement prior to first treatment. An increase (gain) in letters read from the baseline assessment indicates improvement. One eye (study eye) contributed to the analysis.
次要结局
- Proportion of Subjects With Positive q12 Treatment Status at Week 96 Within the Subjects With no q8 Treatment Need During the Initial q12 Cycle (Week 16, Week 20)(Weeks 16, 20, 28, 32, 40, 44, 52, 56, 64, 68, 76, 80, 88, 92, 96)
- Average Change From Baseline in BCVA (Letters Read) Over the Period Week 84 to Week 96 - Study Eye(Baseline, Weeks 84, 88, 92, 96)
- Percentage of Subjects With >=15 Letter Gain From Baseline in BCVA (Letters Read) at Each Post-baseline Visit - Study Eye(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)
- Average Change From Baseline in BCVA (Letters Read) Over the Period Week 36 Through Week 48 - Study Eye(Baseline, Weeks 36, 40, 44, 48)
- Proportion of Subjects With Positive q12 (Every 12 Weeks) Treatment Status at Week 48(Weeks 16, 20, 28, 32, 40, 44, 48)
- Proportion of Subjects With Positive q12 Treatment Status at Week 48 Within the Subjects With no q8 (Every 8 Weeks) Treatment Need During the First q12 Cycle (Week 16, Week 20)(Weeks 16, 20, 28, 32, 40, 44, 48)
- Average Change From Baseline in BCVA (Letters Read) Over the Period Week 12 to Week 48/96 - Study Eye(Baseline, Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96)
- Proportion of Subjects With Positive q12 Treatment Status up to Week 96(Weeks 16, 20, 28, 32, 40, 44, 52, 56, 64, 68, 76, 80, 88, 92, 96)
- Change From Baseline in BCVA (Letters Read) at Each Post-baseline Visit - Study Eye(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)
- Average Change From Baseline in BCVA (Letters Read) Over the Period Week 4 to Week 48/96 - Study Eye(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)
- Percentage of Subjects With >=10 Letter Gain From Baseline in BCVA (Letters Read) at Each Post-baseline Visit - Study Eye(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)
- Percentage of Subjects With >=5 Letter Gain From Baseline in BCVA (Letters Read) at Each Post-baseline Visit - Study Eye(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)
- Percentage of Subjects With >=15 Letter Loss From Baseline in BCVA (Letters Read) at Each Post-baseline Visit - Study Eye(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)
- Percentage of Subjects With >=10 Letter Loss From Baseline in BCVA (Letters Read) at Each Post-baseline Visit - Study Eye(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)
- Percentage of Subjects With >=5 Letter Loss From Baseline in BCVA (Letters Read) at Each Post-baseline Visit - Study Eye(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)
- Percentage of Subjects With BCVA of 73 Letters Read or More at Each Visit - Study Eye(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)
- Change From Baseline in Central Subfield Thickness (CSFTtot) at Each Post-baseline Visit - Study Eye(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)
- Average Change From Baseline in CSFTtot Over the Period Week 36 Through Week 48 - Study Eye(Baseline, Weeks 36, 40, 44, 48)
- Average Change From Baseline in CSFTtot Over the Period Week 84 Through Week 96 - Study Eye(Baseline, Weeks 84, 88, 92, 96)
- Average Change From Baseline in CSFTtot Over the Period Week 4 Through Week 48/96 - Study Eye(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)
- Change From Baseline in Choroidal Neovascularization (CNV) Lesion Size at Week 12, Week 48, and Week 96 - Study Eye(Baseline, Weeks 12, 48, 96)
- Change From Baseline in Central Subfield Neurosensory Retinal Thickness (CSFTns) at Each Post-baseline Visit - Study Eye(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)
- Percentage of Subjects With Presence of Subretinal Fluid at Each Post-baseline Visit - Study Eye(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)
- Percentage of Subjects With Presence of Intraretinal Fluid at Each Post-baseline Visit - Study Eye(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)
- Percentage of Subjects With Presence of Sub-retinal Pigment Epithelium (RPE) Fluid at Each Post-baseline Visit - Study Eye(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)
- Percentage of Subjects With Presence of Subretinal and/or Intraretinal Fluid at Each Post-baseline Visit - Study Eye(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)
- Number of Subjects With Subretinal Fluid (SRF) and/or Intraretinal Fluid (IRF) Present Between Week 36 to Week 48, Reported by Number of Visits(Weeks 36, 40, 44, 48)
- Percentage of Subjects With Disease Activity Present (q8 Treatment Need = "Yes") at Week 16 - Study Eye(Week 16)
- Change From Baseline in Visual Function Questionnaire (VFQ-25) Composite Score at Week 24, Week 48, Week 72, and Week 96(Baseline, Weeks 24, 48, 72, 96)
- Percentage of Subjects With Induced or Boosted Anti-drug Antibody (ADA) Status at Week 48 (Brolucizumab Only)(Week 48)
- Percentage of Subjects With Intraretinal Hemorrhage (Central Subfield) Present at the Visit While Absent at Baseline at Each Treatment - Study Eye(Baseline, Weeks 12, 48, 96)
- Percentage of Subjects With Subretinal Hemorrhage (Central Subfield) Present at the Visit While Absent at Baseline at Each Treatment - Study Eye(Baseline, Weeks 12, 48, 96)