A Prospective, Randomized, Double-masked, Sham-controlled, Multicenter, Two-arm, Phase 3 Study to Evaluate the Efficacy and Safety of Intravitreal KSI-301 in Participants With Moderately Severe to Severe Non-proliferative Diabetic Retinopathy (NPDR)
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 253
- 试验地点
- 61
- 主要终点
- Percentage of Patients Improving ≥2 Steps on DRSS
研究概览
简要总结
This Phase 3 Study will evaluate the efficacy and safety of KSI-301 in participants with moderately severe to severe non-proliferative diabetic retinopathy (NPDR).
详细描述
This is a Phase 3, prospective, randomized, double-masked, sham-controlled, two-arm, multicenter study evaluating the efficacy and safety of repeated intravitreal dosing of KSI-301 5 mg in participants with moderately severe to severe non-proliferative diabetic retinopathy (NPDR).
The primary endpoint will be assessed at Week 48; additional secondary endpoints for efficacy will be assessed at Week 48, Week 96 and if applicable, over time.
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
To preserve masking, 2 investigators are required for this study. The masked investigator will be responsible for 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.
- •Type 1 or 2 diabetes mellitus
- •Moderately severe to severe NPDR in the Study Eye (DRSS levels 47 and 53 as determined by the reading center), in which pan-retinal photocoagulation (PRP) can be safely deferred for at least 6 months per the Investigator.
- •BCVA ETDRS letter score in the Study Eye of ≥69 letters (approximate Snellen equivalent of 20/40 or better)
- •HbA1c of ≤12%.
- •Other protocol-specified inclusion criteria may apply.
排除标准
- •Presence of center-involved DME in the Study Eye
- •Prior PRP in the Study Eye.
- •Current anterior segment neovascularization (ASNV), vitreous hemorrhage, or tractional retinal detachment in the Study Eye.
- •Prior intravitreal anti-VEGF treatment in the Study Eye for DR or DME.
- •Prior intravitreal or periocular steroid in the Study Eye for DR or DME.
- •Prior use of an investigational intravitreal treatment for DR or DME in the Study Eye.
- •Any history or evidence of a concurrent ocular condition present in the Study Eye, that in the opinion of the Investigator could require either medical or surgical intervention or alter visual acuity during the study
- •Active or suspected ocular or periocular infection or inflammation.
- •Women who are pregnant or lactating or intending to become pregnant during the study.
- •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.
- •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.
- •Uncontrolled blood pressure defined as a systolic value ≥ 180 mmHg or diastolic value ≥ 100 mmHg while at rest.
- •Other protocol-specified exclusion criteria may apply.
研究组 & 干预措施
KSI-301 - Treatment Group A
Intravitreal injection of KSI-301 (5 mg): three initiating doses, and then every 24 weeks through Week 92
干预措施: KSI-301 (Drug)
Treatment Group B
Sham injection on the same schedule as Treatment Group A
干预措施: Sham injection (Other)
结局指标
主要结局
Percentage of Patients Improving ≥2 Steps on DRSS
时间窗: Day 1 to Week 48
Percentage of patients improving ≥2 steps on the Diabetic Retinopathy Severity Scale (DRSS) from baseline at Week 48 using last observation carried forward (LOCF). The Diabetic Retinopathy Disease Severity Scale (DRSS) may be used to describe overall retinopathy severity as well as the change in severity over time. Severity range from level 10 (DR absent) to level 85 (advanced proliferative DR: posterior fundus obscured, or center of macula detached).
次要结局
- Percentage of Patients Developing Any Sight-Threatening Complication(Day 1 to Week 48)
- Percentage of Patients Improving ≥3 Steps on DRSS(Day 1 to Week 48)
- Percentage of Patients Developing PDR(Day 1 to Week 48)
- Percentage of Patients Developing PDR or ASNV(Day 1 to Week 48)
- Percentage of Patients Developing Vitreous Hemorrhage or Tractional Retinal Detachment Believed to be Due to PDR(Day 1 to Week 48)
- Percentage of Patients Developing DME(Day 1 to Week 48)
- Percentage of Patients With a ≥2-step or ≥3-step Worsening on DRSS(Day 1 to Week 48)
- Percentage of Patients Who Lost ≥5, ≥10, or ≥15 Letters in BCVA(Day 1 to Week 48)
- Time to First Development of PDR, ASNV, or DME(Day 1 to Week 48)
- Time to First Development of PDR or ASNV(Day 1 to Week 48)
- Time to First Development of Vitreous Hemorrhage or Tractional Retinal Detachment Believed to be Due to PDR(Day 1 to Week 48)