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 Secondary to Treatment-naïve Diabetic Macular Edema (DME)
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 460
- 试验地点
- 75
- 主要终点
- Mean Change in BCVA
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 treatment-naïve DME.
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 treatment-naïve DME.
The primary endpoint will be assessed at Year 1; additional secondary endpoints for efficacy will be assessed at Years 1 and 2.
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 diabetic macular edema, with vision loss and center involvement (if present) diagnosed within 9 months of screening.
- •BCVA ETDRS letter score between 78 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 DME.
- •Type 1 or Type 2 diabetes mellitus and a HbA1c of ≤12%.
- •Other protocol-specified inclusion criteria may apply.
排除标准
- •Macular edema in the Study Eye considered to be secondary to a cause other than DME.
- •Active iris or angle neovascularization or neovascular glaucoma in the Study Eye.
- •High-risk proliferative diabetic retinopathy characteristics in the Study Eye.
- •History of Pan-retinal Photocoagulation (PRP) laser in the Study Eye within 3 months of screening.
- •Tractional retinal detachment 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 or affect macular edema or alter visual acuity during the study (e.g., vitreomacular traction, epiretinal membrane).
- •Active or suspected ocular or periocular infection or inflammation in either eye at Day
- •Any prior use of an approved or investigational treatment for DME 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) once every 4 weeks for 3 monthly doses followed by an individualized dosing regimen (every 8 to 24 weeks) via intravitreal injection from Week 16 to Week 100.
干预措施: KSI-301 (Drug)
KSI-301 (Arm A)
Intravitreal injection of KSI-301 (5 mg) once every 4 weeks for 3 monthly doses followed by an individualized dosing regimen (every 8 to 24 weeks) via intravitreal injection from Week 16 to Week 100.
干预措施: Sham Procedure (Other)
Aflibercept (Arm B)
Intravitreal injection of aflibercept (2 mg) once every 4 weeks for 5 monthly doses followed by aflibercept (2 mg) once every 8 weeks via intravitreal injection from Week 24 to 100.
干预措施: Aflibercept (Drug)
Aflibercept (Arm B)
Intravitreal injection of aflibercept (2 mg) once every 4 weeks for 5 monthly doses followed by aflibercept (2 mg) once every 8 weeks via intravitreal injection from Week 24 to 100.
干预措施: Sham Procedure (Other)
结局指标
主要结局
Mean Change in BCVA
时间窗: Day 1 to Week 64
Mean change in best-corrected visual acuity (BCVA) from baseline to the average of Weeks 60 and 64 (using Early Treatment Diabetic Retinopathy Study (ETDRS) Letters). 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 letter score from baseline indicates an improvement in visual acuity.
次要结局
- Percentage of Patients With a ≥ 2-step Worsening on the ETDRS DRSS in Study KS301P104(Day 1 to Week 52)
- Percentage of Patients in the KSI-301 Arm on a Q8W, Q12W, Q16W, Q20W, or Q24W Treatment Interval(Week 56)
- Mean Change in OCT CST(Day 1 to Week 64)
- Percentage of Patients With a ≥ 2-step Worsening on the ETDRS DRSS in Studies KS301P104 and KS301P105 Combined(Day 1 to Week 52)
- Mean Number of Intravitreal Injections(Day 1 to Week 60)