A Study to Evaluate the Efficacy and Safety of Intravitreal KSI-301 in Participants With Moderately Severe to Severe Non-proliferative Diabetic Retinopathy (NPDR)

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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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)

Conditions
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Non-proliferative Diabetic Retinopathy

Intervention / Treatment
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* Drug: KSI-301
* Other: Sham injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be randomized 1:1 into one of two arms: KSI-301 or sham.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: KSI-301 - Treatment Group A<br>Intravitreal injection of KSI-301 (5 mg): three initiating doses, and then every 24 weeks through Week 92 | Drug: KSI-301<br>* Intravitreal injection<br>|
| Sham Comparator: Treatment Group B<br>Sham injection on the same schedule as Treatment Group A | Other: Sham injection<br>* The sham injection is a procedure that mimics an intravitreal injection. It involves pressing the blunt end of an empty syringe (without a needle) against the anesthetized eye. It is performed to maintain masking of the study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of eyes improving ≥2 steps on the ETDRS Diabetic Retinopathy Severity Scale (DRSS) |  | Day 1 to Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of eyes developing a Sight-Threatening Complication(s) of DR (DME, PDR, ASNV), as a composite and individually |  | Day 1 to Week 48 and Week 96 | 
| Time to development of a Sight-Threatening Complication(s) of DR, as a composite and individually |  | Day 1 to Week 96 | 
| Proportion of eyes improving ≥2 or ≥3 steps on the DRSS over time |  | Day 1 to Week 48 and Week 96 | 
| Proportion of eyes worsening ≥2 or ≥3 steps on the DRSS over time |  | Day 1 to Week 48 and Week 96 | 
| Safety and Tolerability of KSI-301 5 mg compared to sham treatment | Incidence of ocular and systemic adverse events | Day 1 to Week 100 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-proliferative Diabetic Retinopathy, Diabetic Retinopathy, NPDR, KSI-301, VEGF, Anti-VEGF, Vascular Endothelial Growth Factor, Antibody Biopolymer Conjugate, Retinal Degeneration, Retinal Diseases, Eye Diseases, Retinopathy, Vision Disorders, Kodiak