A Prospective, Randomized, Double-masked, Active Comparator-controlled, Multi-center, Two-arm, Phase 3 Study to Evaluate the Efficacy and Safety of Intravitreal KSI-301 Compared With Intravitreal Aflibercept in Participants With Visual Impairment Due to Treatment-naïve Macular Edema Secondary to Retinal Vein Occlusion (RVO)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 568
- 试验地点
- 140
- 主要终点
- Mean Change in Best Corrected Visual Acuity (BCVA) From Day 1 to Week 24 in BRVO Participants.
研究概览
简要总结
This Phase 3 study will evaluate the efficacy, durability, and safety of KSI-301 compared to aflibercept, in participants with macular edema due to treatment-naïve branch (BRVO) or central retinal vein occlusion (CRVO).
详细描述
This is a Phase 3, prospective, randomized, double-masked, two-arm, multi-center non-inferiority study evaluating the efficacy and safety of repeated intravitreal dosing of KSI-301 5 mg in participants with visual impairment due to treatment-naïve macular edema secondary to RVO (either branch or central type).
The primary endpoint will be assessed at Week 24; additional secondary endpoints for efficacy will be assessed at Week 24 and Week 48.
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, Outcomes Assessor)
盲法说明
For masking purposes, sham injections will be administered at every monthly visit if an active treatment is not administered. To preserve masking, two investigators are required for this study. The masked Investigator will be responsible for the examinations and safety assessments. The unmasked Investigator will perform the injections and post-treatment assessments.
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 prior to participation in the study.
- •Treatment-naïve macular edema of 6 months duration or less due to CRVO or BRVO. Participants with hemiretinal vein occlusion will be included as CRVO.
- •BCVA ETDRS letter score between 80 and 25 (20/25 to 20/320 Snellen equivalent), inclusive in the Study Eye.
- •CST of ≥ 320 microns on SD-OCT (Heidelberg Spectralis or equivalent on other OCT instruments) as determined by the Reading Center
- •Decrease in vision determined by the Investigator to be primarily the result of ME secondary to RVO.
- •Other protocol-specified inclusion criteria may apply.
排除标准
- •Macular edema in the Study Eye for reasons other than RVO
- •Active iris or angle neovascularization, neovascular glaucoma, neovascularization of the optic disc, retinal neovascularization or vitreous hemorrhage in the Study Eye.
- •Uncontrolled glaucoma in the Study Eye.
- •Active retinal disease other than the condition under investigation in the Study Eye.
- •Any history or evidence of a concurrent ocular condition present, that in the opinion of the Investigator could require either medical or surgical intervention alter visual acuity during the study
- •Active or suspected ocular or periocular infection or inflammation
- •Any prior use of an approved or investigational treatment for macular edema secondary to RVO in the Study Eye (e.g. anti-VEGF, intraocular or periocular steroids, macular laser photocoagulation).
- •Women who are pregnant or lactating or intending to become pregnant during the study.
- •Uncontrolled blood pressure defined as a systolic value ≥ 180 mmHg or diastolic value ≥100 mmHg while at rest
- •Recent history (within the 6 months prior to screening) of myocardial infarction, stroke, transient ischemic attack, acute congestive heart failure or any acute coronary event.
- •History of a medical condition that, in the judgment of the Investigator, would preclude scheduled study visits, completion of the study, or a safe administration of investigational product.
- •Other protocol-specified exclusion criteria may apply.
研究组 & 干预措施
KSI-301 (Arm A)
Intravitreal injection of KSI-301 (5 mg) at Day 1, Week 4, and once every 8 weeks through Week 20 followed by an individualized dosing regimen of Intravitreal injection of KSI-301 (5 mg) from Week 24 to Week 44.
In the Extension Phase, participants randomized to KSI-301 (5 mg) in the Primary Study will continue to receive KSI-301 (5 mg) based on protocol-defined disease activity criteria.
干预措施: KSI-301 (Drug)
KSI-301 (Arm A)
Intravitreal injection of KSI-301 (5 mg) at Day 1, Week 4, and once every 8 weeks through Week 20 followed by an individualized dosing regimen of Intravitreal injection of KSI-301 (5 mg) from Week 24 to Week 44.
In the Extension Phase, participants randomized to KSI-301 (5 mg) in the Primary Study will continue to receive KSI-301 (5 mg) based on protocol-defined disease activity criteria.
干预措施: Sham Procedure (Other)
Aflibercept (Arm B)
Intravitreal injection of aflibercept (2 mg) once every 4 through Week 20 followed by an individualized dosing regimen of Intravitreal injection of Aflibercept (2 mg) once every 4 weeks from Week 24 to Week 44.
In the Extension Phase, participants randomized to aflibercept in the Primary Study will cross over to treatment with KSI-301 (5 mg). They will receive their first dose of KSI-301 (5 mg) at Week 48 and will receive additional treatment with KSI-301 (5 mg) based on protocol-defined disease activity criteria.
干预措施: Aflibercept (Drug)
Aflibercept (Arm B)
Intravitreal injection of aflibercept (2 mg) once every 4 through Week 20 followed by an individualized dosing regimen of Intravitreal injection of Aflibercept (2 mg) once every 4 weeks from Week 24 to Week 44.
In the Extension Phase, participants randomized to aflibercept in the Primary Study will cross over to treatment with KSI-301 (5 mg). They will receive their first dose of KSI-301 (5 mg) at Week 48 and will receive additional treatment with KSI-301 (5 mg) based on protocol-defined disease activity criteria.
干预措施: Sham Procedure (Other)
结局指标
主要结局
Mean Change in Best Corrected Visual Acuity (BCVA) From Day 1 to Week 24 in BRVO Participants.
时间窗: Day 1 to Week 24
BCVA as a continuous variable measured at each study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA approach.
Mean Change in Best Corrected Visual Acuity (BCVA) From Day 1 to Week 24 in All RVO Patients.
时间窗: Day 1 to Week 24
BCVA as a continuous variable measured at each study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA approach.
次要结局
- Percentage of Participants With Absence of Macular Edema (Defined as OCT CST < 325 Microns) Over Time for All RVO Participants.(Baseline - Week 48)
- Mean Change in OCT Center Point Retinal Thickness (CPT) From Baseline by Visit Over Time for All RVO Participants.(Day 1 - Week 48)
- Mean Change From Baseline in BCVA (ETDRS Letters) by Visit Over Time up to Week 48 for All RVO Participants.(Day 1 - Week 48)
- Percentage of Participants Who Gain ≥ 5, ≥10 and ≥15 Letters From Baseline Over Time up to Week 48 for All RVO Participants.(Day 1 - Week 48)
- Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (≤ 38 ETDRS Letters) Over Time for All RVO Participants.(Baseline - Week 48)
- Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better Over Time (≥69 ETDRS Letters) for All RVO Participants.(Day 1 - Week 48.)
- Percentage of Participants Who Lose ≥ 5, ≥10 and ≥15 ETDRS Letters From Baseline Over Time up to Week 48 for All RVO Participants(Day 1 - Week 48)
- Mean Change in OCT Central Subfield Retinal Thickness (CST) From Baseline by Visit Over Time for All RVO Participants.(Day 1 - Week 48)