A Phase III, Multicenter, Randomized, Double-Masked, Active Comparator-Controlled Study to Evaluate the Efficacy and Safety of Faricimab in Patients With Macular Edema Secondary to Branch Retinal Vein Occlusion
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 553
- 试验地点
- 150
- 主要终点
- Part 1: Change From Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye at Week 24
研究概览
简要总结
This is a Phase III, multicenter, randomized, double-masked, active comparator-controlled, parallel-group study evaluating the efficacy, safety, and pharmacokinetics of faricimab administered by intravitreal (IVT) injection at 4-week intervals until Week 24, followed by a double-masked period of study without active control to evaluate faricimab administered according to a personalized treatment interval (PTI) dosing regimen in participants with macular edema due to branch retinal vein occlusion (BRVO).
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)
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
- •Foveal center-involved macular edema due to branch retinal vein occlusion (BRVO), diagnosed no longer than 4 months prior to the screening visit
- •Best-corrected visual acuity (BCVA) of 73 to 19 letters, inclusive (20/40 to 20/400 approximate Snellen equivalent) on Day 1
- •Sufficiently clear ocular media and adequate pupillary dilatation to allow acquisition of good quality retinal images to confirm diagnosis
- •For women of childbearing potential: agreement to remain abstinent or use contraception, and agreement to refrain from donating eggs during the treatment period and for 3 months after the final dose of study treatment
排除标准
- •Any major illness or major surgical procedure within 1 month before screening
- •Uncontrolled blood pressure
- •Stroke (cerebral vascular accident) or myocardial infarction within 6 months prior to Day 1
- •Pregnant or breastfeeding, or intending to become pregnant during the study
- •Ocular Exclusion Criteria for Study Eye:
- •History of previous episodes of macular edema due to RVO or persistent macular edema due to RVO diagnosed more than 4 months before screening
- •Any current ocular condition which, in the opinion of the investigator, is currently causing or could be expected to contribute to irreversible vision loss due to a cause other than macular edema due to RVO in the study eye (e.g., ischemic maculopathy, Irvine-Gass syndrome, foveal atrophy, foveal fibrosis, pigment abnormalities, dense subfoveal hard exudates, or other non-retinal conditions)
- •Macular laser (focal/grid) in the study eye at any time prior to Day 1
- •Panretinal photocoagulation in the study eye within 3 months prior to Day 1 or anticipated within 3 months of study start on Day 1
- •Any prior or current treatment for macular edema; macular neovascularization, including diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD); and vitreomacular-interface abnormalities, including, but not restricted to, IVT treatment with anti-VEGF, steroids, tissue plasminogen activator, ocriplasmin, C3F8, air or periocular injection
- •Any prior intervention with verteporfin photodynamic therapy, diode laser, transpupillary thermotherapy, or vitreo-retinal surgery including sheatotomy
- •Any prior steroid implant use including dexamethasone intravitreal implant (Ozurdex) and fluocinolone acetonide intravitreal implant (Iluvien)
- •Ocular Exclusion Criteria for Both Eyes:
- •Prior IVT administration of faricimab in either eye
- •History of idiopathic or autoimmune-associated uveitis in either eye
- •Active periocular, ocular or intraocular inflammation or infection (including suspected) in either eye on Day 1
研究组 & 干预措施
Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2)
In Part 1 (Day 1 through Week 24), participants randomly assigned to Arm A will receive faricimab 6 milligrams (mg) by IVT injection once every 4 weeks (Q4W) from Day 1 through Week 20 (a total of 6 injections). In Part 2 (from Week 24 to Week 72), participants will receive faricimab 6 mg by IVT injection according to a personalized treatment interval (PTI) dosing regimen. To preserve masking for Part 2, a sham procedure will be administered during study visits at which no faricimab treatment is administered (according to the PTI dosing regimen).
干预措施: Faricimab (Drug)
Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2)
In Part 1 (Day 1 through Week 24), participants randomly assigned to Arm A will receive faricimab 6 milligrams (mg) by IVT injection once every 4 weeks (Q4W) from Day 1 through Week 20 (a total of 6 injections). In Part 2 (from Week 24 to Week 72), participants will receive faricimab 6 mg by IVT injection according to a personalized treatment interval (PTI) dosing regimen. To preserve masking for Part 2, a sham procedure will be administered during study visits at which no faricimab treatment is administered (according to the PTI dosing regimen).
干预措施: Sham Procedure (Procedure)
Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2)
In Part 1 (Day 1 through Week 24), participants randomly assigned to Arm B will receive aflibercept 2 milligrams (mg) by IVT injection once every 4 weeks (Q4W) from Day 1 through Week 20 (a total of 6 injections). In Part 2 (from Week 24 to Week 72), participants will receive faricimab 6 mg by IVT injection according to a personalized treatment interval (PTI) dosing regimen. To preserve masking for Part 2, a sham procedure will be administered during study visits at which no faricimab treatment is administered (according to the PTI dosing regimen).
干预措施: Faricimab (Drug)
Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2)
In Part 1 (Day 1 through Week 24), participants randomly assigned to Arm B will receive aflibercept 2 milligrams (mg) by IVT injection once every 4 weeks (Q4W) from Day 1 through Week 20 (a total of 6 injections). In Part 2 (from Week 24 to Week 72), participants will receive faricimab 6 mg by IVT injection according to a personalized treatment interval (PTI) dosing regimen. To preserve masking for Part 2, a sham procedure will be administered during study visits at which no faricimab treatment is administered (according to the PTI dosing regimen).
干预措施: Aflibercept (Drug)
Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2)
In Part 1 (Day 1 through Week 24), participants randomly assigned to Arm B will receive aflibercept 2 milligrams (mg) by IVT injection once every 4 weeks (Q4W) from Day 1 through Week 20 (a total of 6 injections). In Part 2 (from Week 24 to Week 72), participants will receive faricimab 6 mg by IVT injection according to a personalized treatment interval (PTI) dosing regimen. To preserve masking for Part 2, a sham procedure will be administered during study visits at which no faricimab treatment is administered (according to the PTI dosing regimen).
干预措施: Sham Procedure (Procedure)
结局指标
主要结局
Part 1: Change From Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye at Week 24
时间窗: From Baseline through Week 24
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The Mixed Model of Repeated Measures (MMRM) analysis included the categorical covariates of treatment arm, visit, visit-by-treatment arm interaction, baseline BCVA (continuous), and randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\] as fixed effects. An unstructured covariance structure was used. Missing data were implicitly imputed by MMRM model assuming missing at random. Treatment policy strategy (i.e., all observed values used) was applied to all intercurrent events (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). 95% CI is a rounding of 95.03% CI.
次要结局
- Part 1: Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye at Specified Timepoints Through Week 24(Baseline, Weeks 4, 8, 12, 16, 20, and 24)
- Part 1: Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye at Specified Timepoints Through Week 24(Baseline, Weeks 4, 8, 12, 16, 20, and 24)
- Parts 1 and 2: Percentage of Participants With Absence of Macular Edema in the Study Eye at Specified Timepoints Through Week 72(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72)
- Parts 1 and 2: Percentage of Participants With Absence of Intraretinal Fluid in the Study Eye at Specified Timepoints Through Week 72(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72)
- Parts 1 and 2: Percentage of Participants With Absence of Subretinal Fluid in the Study Eye at Specified Timepoints Through Week 72(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72)
- Part 1: Change From Baseline in BCVA in the Study Eye at Specified Timepoints Through Week 24(Baseline, Weeks 4, 8, 12, 16, 20, and 24)
- Part 1: Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye at Week 24(Baseline and Week 24)
- Part 1: Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye at Specified Timepoints Through Week 24(Baseline, Weeks 4, 8, 12, 16, 20, and 24)
- Part 1: Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye at Specified Timepoints Through Week 24(Baseline, Weeks 4, 8, 12, 16, 20, and 24)
- Part 1: Percentage of Participants Achieving ≥84 Letters in BCVA (20/20 Snellen Equivalent) in the Study Eye at Specified Timepoints Through Week 24(Baseline, Weeks 4, 8, 12, 16, 20, and 24)
- Part 1: Percentage of Participants Gaining >0 Letters in BCVA From Baseline in the Study Eye at Specified Timepoints Through Week 24(Baseline, Weeks 4, 8, 12, 16, 20, and 24)
- Part 1: Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye at Specified Timepoints Through Week 24(Baseline, Weeks 4, 8, 12, 16, 20, and 24)
- Part 1: Percentage of Participants With Absence of Intraretinal Fluid in the Study Eye at Specified Timepoints Through Week 24(Baseline, Weeks 4, 8, 12, 16, 20, and 24)
- Part 1: Percentage of Participants With Absence of Intraretinal Fluid and Subretinal Fluid in the Study Eye at Specified Timepoints Through Week 24(Baseline, Weeks 4, 8, 12, 16, 20, and 24)
- Parts 1 and 2: Change From Baseline in BCVA in the Study Eye at Specified Timepoints Through Week 72(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72)
- Parts 1 and 2: Percentage of Participants With Absence of Intraretinal Fluid and Subretinal Fluid in the Study Eye at Specified Timepoints Through Week 72(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72)
- Part 1: Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye at Specified Timepoints Through Week 24(Baseline, Weeks 4, 8, 12, 16, 20, and 24)
- Part 1: Percentage of Participants Achieving ≥69 Letters in BCVA (20/40 or Better Snellen Equivalent) in the Study Eye at Specified Timepoints Through Week 24(Baseline, Weeks 4, 8, 12, 16, 20, and 24)
- Part 1: Change From Baseline in National Eye Institute 25-Item Visual Functioning Questionnaire (NEI VFQ-25) Composite Score at Week 24(Baseline and Week 24)
- Parts 1 and 2: Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye at Specified Timepoints Through Week 72(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72)
- Part 1: Percentage of Participants With Absence of Subretinal Fluid in the Study Eye at Specified Timepoints Through Week 24(Baseline, Weeks 4, 8, 12, 16, 20, and 24)
- Parts 1 and 2: Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye at Specified Timepoints Through Week 72(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72)
- Part 1: Percentage of Participants With ≤38 Letters in BCVA (20/200 or Worse Snellen Equivalent) in the Study Eye at Specified Timepoints Through Week 24(Baseline, Weeks 4, 8, 12, 16, 20, and 24)
- Part 1: Change From Baseline in Central Subfield Thickness in the Study Eye at Specified Timepoints Through Week 24(Baseline, Weeks 4, 8, 12, 16, 20, and 24)
- Part 1: Percentage of Participants With Absence of Macular Edema in the Study Eye at Specified Timepoints Through Week 24(Baseline, Weeks 4, 8, 12, 16, 20, and 24)
- Parts 1 and 2: Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye at Specified Timepoints Through Week 72(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72)
- Parts 1 and 2: Percentage of Participants Gaining >0 Letters in BCVA From Baseline in the Study Eye at Specified Timepoints Through Week 72(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72)
- Parts 1 and 2: Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye at Specified Timepoints Through Week 72(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72)
- Parts 1 and 2: Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye at Specified Timepoints Through Week 72(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72)
- Parts 1 and 2: Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye at Specified Timepoints Through Week 72(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72)
- Parts 1 and 2: Percentage of Participants Achieving ≥84 Letters in BCVA (20/20 Snellen Equivalent) in the Study Eye at Specified Timepoints Through Week 72(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72)
- Parts 1 and 2: Percentage of Participants Achieving ≥69 Letters in BCVA (20/40 or Better Snellen Equivalent) in the Study Eye at Specified Timepoints Through Week 72(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72)
- Parts 1 and 2: Percentage of Participants With ≤38 Letters in BCVA (20/200 or Worse Snellen Equivalent) in the Study Eye at Specified Timepoints Through Week 72(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72)
- Parts 1 and 2: Change From Baseline in NEI VFQ-25 Questionnaire Composite Score at Specified Timepoints Through Week 72(Baseline and Weeks 24, 48, and 72)
- Parts 1 and 2: Change From Baseline in Central Subfield Thickness in the Study Eye at Specified Timepoints Through Week 72(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72)
- Part 2: Change From Week 24 in BCVA in the Study Eye at Specified Timepoints Through Week 72(Weeks 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72)
- Part 2: Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Week 24 in the Study Eye at Specified Timepoints Through Week 72(Weeks 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72)
- Part 2: Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Week 24 in the Study Eye at Specified Timepoints Through Week 72(Weeks 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72)
- Part 2: Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Week 24 in the Study Eye at Specified Timepoints Through Week 72(Weeks 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72)
- Part 2: Percentage of Participants Avoiding a Loss of >0 Letters in BCVA From Week 24 in the Study Eye at Specified Timepoints Through Week 72(Weeks 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72)
- Part 2: Percentage of Participants on Different Treatment Intervals at Week 68(Week 68)
- Part 2: Number of Study Drug Injections Received in the Study Eye From Week 24 Through Week 72(From Week 24 to Week 72)
- Incidence and Severity of Ocular Adverse Events in the Study Eye, With Severity Determined According to Adverse Event Severity Grading Scale(Part 1: From first dose up to Week 24; Part 2: from Week 24 through Week 72)
- Incidence of Ocular Adverse Events in the Fellow Eye(Part 1: From first dose up to Week 24; Part 2: from Week 24 through Week 72)
- Incidence of Non-Ocular Adverse Events(Part 1: From first dose up to Week 24; Part 2: from Week 24 through Week 72)
- Plasma Concentration of Faricimab Over Time(Predose at Day 1 (Baseline), Weeks 4, 24, 28, 52, and 72)
- Number of Participants With Anti-Drug Antibodies (ADAs) to Faricimab at Baseline and Post-Baseline During the Study(Predose at Day 1 (Baseline), Weeks 4, 24, 28, 52, and 72)