A Study to Evaluate the Efficacy, Durability, and Safety of KSI-301 Compared to Aflibercept in Participants With Diabetic Macular Edema (DME)

Study Overview
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Brief Summary
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This Phase 3 study will evaluate the efficacy, durability, and safety of KSI-301 compared to aflibercept in participants with treatment-naïve DME.

Detailed Description
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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.

Official Title
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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)

Conditions
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Diabetic Macular Edema

Intervention / Treatment
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* Drug: KSI-301
* Drug: Aflibercept
* Other: Sham Procedure


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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 1. 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.

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 treatment arms: KSI-301 or aflibercept.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: KSI-301 (Arm A)<br>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. | Drug: KSI-301<br>* Intravitreal Injection<br>Other: Sham Procedure<br>* The sham 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 will be administered to participants in both treatments arms at applicable visits to maintain masking.<br>|
| Active Comparator: Aflibercept (Arm B)<br>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. | Drug: Aflibercept<br>* Intravitreal Injection<br>* Other names: Eylea;Other: Sham Procedure<br>* The sham 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 will be administered to participants in both treatments arms at applicable visits to maintain masking.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Non-inferiority of KSI-301 to Aflibercept measured by changes in BCVA. | Demonstrate that KSI-301 5 mg is non-inferior to aflibercept 2 mg with respect to mean change in best corrected visual acuity (BCVA). | Day 1 to Year 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of KSI-301 5 mg compared to aflibercept 2 mg measured by changes in BCVA. | Improvement in best corrected visual acuity (BCVA). | Day 1 to Year 2 | 
| Efficacy of KSI-301 5 mg compared to aflibercept 2 mg measured by changes in CST. | Improvement in central subfield thickness (CST). | Day 1 to Year 2 | 
| Efficacy of KSI-301 5 mg compared to aflibercept 2 mg measured by changes in DRSS. | Improvement if the diabetic retinopathy severity score (DRSS). | Day 1 to Year 2 | 
| Durability of KSI-301 5 mg compared to aflibercept 2 mg measured by number of intravitreal injections during the study. | Mean number of intravitreal injections during the course of the study. | Day 1 to Year 2 | 
| Safety and Tolerability of KSI-301 mg compared to aflibercept 2 mg measured by the number of ocular and systemic adverse events. | Incidence of ocular and systemic adverse events. | Day 1 to Year 2 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DME, Kodiak, Vascular endothelial growth factor, Anti-VEGF, VEGF, Antibody biopolymer conjugate, Retinal Degeneration, Retinal Diseases, Eye Diseases, Vision Disorders, Vision, low, Aflibercept, Eylea, Diabetes mellitus, Diabetes, Diabetic retinopathy, Diabetic macular edema, Macular edema, KSI-301