A Study to Evaluate the Efficacy and Safety of Intravitreal KSI-301 Compared With Intravitreal Aflibercept in Participants With Neovascular (Wet) Age-related Macular Degeneration (wAMD)

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 compared to aflibercept, in participants with neovascular (wet) age-related macular degeneration (wAMD)

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 visual impairment due to treatment-naïve neovascular (wet) age-related macular degeneration (wAMD) The primary endpoint will be assessed as an average of Weeks 40, 44, and 48; additional secondary endpoints for efficacy will be assessed by visit over time

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 Neovascular (Wet) Age-related Macular Degeneration (wAMD)

Conditions
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Wet Age-related Macular Degeneration

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 choroidal neovascularization (CNV) secondary to AMD. BCVA ETDRS score between 83 and 25 letters, inclusive, in the Study Eye. Decrease in vision in the Study Eye determined by the Investigator to be primarily the result of wAMD. Other protocol-specified inclusion criteria may apply Exclusion Criteria: BCVA of hand motion or worse in the non-Study Eye or non-physical presence of a non-Study Eye (i.e., monocular). Active or suspected ocular or periocular infection or inflammation. CNV secondary to other causes 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 affect macular edema or alter visual acuity during the study. Uncontrolled glaucoma in the Study Eye. Significant media opacities, including cataract, in the Study Eye that might interfere with visual acuity, assessment of safety, OCT or fundus photography. Cataract in the Study Eye that in the judgment of the Investigator is expected to require surgical extraction within 12 months of screening. Women who are pregnant or lactating or intending to become pregnant during the study. 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. 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: 50 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 (Treatment Group A)<br>Intravitreal injection of KSI-301 (5 mg) at Day 1 once every 4 weeks via intravitreal injection through Week 44. | Drug: KSI-301<br>* Intravitreal Injection<br>|
| Active Comparator: Aflibercept (Treatment Group B)<br>Intravitreal injection of aflibercept (2 mg) once every 4 weeks for 3 monthly doses followed by intravitreal injection of aflibercept (2 mg) once every 8 weeks from Week 16 to Week 44. Sham injections will be administered at each monthly visit where an active treatment is not administered. | 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 Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of KSI-301 5 mg compared to aflibercept 2 mg based on changes in BCVA | Change from baseline in best corrected visual acuity (BCVA) between the two treatment arms. | Day 1 to Week 48 | 
| Efficacy of KSI-301 5 mg compared to aflibercept 2 mg based on OCT-CST | Change from baseline in central subfield thickness (CST) between the two treatment arms. | Day 1 to Week 48 | 
| Safety and tolerability of KSI-301 5 mg compared to aflibercept 2 mg based on the number of ocular and systemic adverse events | Incidence of ocular and systemic adverse events between the two treatment arms. | Day 1 to Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AMD, Wet AMD, neovascularization secondary to age-related macular degeneration, KSI-301, Aflibercept, Vascular endothelial growth factor, VEGF, Anti-VEGF, Antibody biopolymer conjugate, Macular Degeneration, wAMD, Retinal Degeneration, Retinal Diseases, Eye Diseases, Vision Disorders, Vision, Low, Kodiak