A Study to Evaluate the Efficacy and Safety of KSI-301, an Anti-VEGF Antibody Biopolymer Conjugate, Versus Aflibercept in Patients With Neovascular (Wet) Age-Related Macular Degeneration.

Study Overview
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Brief Summary
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This study will evaluate the efficacy, safety, durability, and pharmacokinetics of KSI-301 administered at 12, 16 and 20 weeks intervals as specified in the protocol, compared with aflibercept once every 8 weeks (Q8W), in participants with treatment-naïve neovascular (wet) age-related macular degeneration (nAMD).

Detailed Description
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This study is divided into a 3-week screening period, a 92-week treatment period, and a final 4-week follow-up period. At baseline patients will be randomized 1:1 into two treatment arms: KSI-301 5 mg and aflibercept 2 mg. At Week 52 patients on the aflibercept treatment arm will be re-randomized 1:1 into KSI-301 5 mg and aflibercept 2 mg.

Official Title
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A Phase 2b/3, Prospective, Randomized, Double-masked, Active Comparator-controlled, Multi-center Study to Investigate the Efficacy and Safety of Repeated Intravitreal Administration of KSI-301 in Subjects With Neovascular (Wet) Age-related Macular Degeneration.

Conditions
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Wet 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. Active, treatment-naïve choroidal neovascularization (CNV) secondary to AMD. BCVA ETDRS score between 80 and 25 letters (Snellen equivalent of 20/25 to 20/320), inclusive. Other protocol-specified inclusion criteria may apply Exclusion Criteria: CNV secondary to other causes in the Study Eye. Any history of macular pathology unrelated to AMD but affecting vision or contributing to subretinal or intraretinal fluid. Any history or evidence of a concurrent intraocular condition in the Study Eye that, in the judgment of the Investigator, could require either medical or surgical intervention during the study to prevent or treat visual loss. Active ocular or periocular infection or inflammation. Prior administration of any approved or investigational treatment for neovascular AMD in the Study Eye. Uncontrolled glaucoma in the Study Eye. Women who are pregnant or lactating or intending to become pregnant during the study. Stroke or myocardial infarction in the 6-month period prior to Day 1. Uncontrolled blood pressure defined as a systolic value > 180 mmHg or diastolic value ≥100 mmHg while at rest. 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: 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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: KSI-301 5 mg<br>Drug: KSI-301 5 mg. KSI-301 5 mg will be administered by intravitreal injection into the study eye at 12, 16, and 20 weeks intervals as specified in the study protocol. Drug: Sham Procedure. 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. | 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 2 mg<br>Drug: Aflibercept 2 mg. Aflibercept 2 mg will be administered by intravitreal injection into the study eye once every 4 weeks for 3 consecutive months, followed by once every 8 weeks. Drug: Sham Procedure. 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. | 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 |
| --- | --- | --- |
| Mean change in Best Corrected Visual Acuity (BCVA) from Day 1. | BCVA is measured using ETDRS visual acuity charts. | Year 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects on a Q12W, Q16W or Q20W dosing regimen of KSI-301. |  | Year 1 | 
| Proportion of subjects who gain ≥ 5, ≥10 and ≥15 letters from Day 1. |  | Year 1 | 
| Proportion of subjects who lose ≥ 5, ≥10 and ≥15 letters from Day 1. |  | Year 1 | 
| Proportion of subjects with BCVA Snellen equivalent of 20/40 or better. |  | Year 1 | 
| Proportion of subjects with BCVA Snellen equivalent of 20/200 or worse. |  | Year 1 | 
| Mean change in OCT central subfield retinal thickness (CST) from Day 1. |  | Year 1 | 
| Mean change in OCT intraretinal fluid volume from Day 1. |  | Year 1 | 
| Mean change in OCT subretinal fluid volume from Day 1. |  | Year 1 | 
| Proportion of subjects without intraretinal fluid on OCT. |  | Year 1 | 
| Proportion of subjects without subretinal fluid on OCT. |  | Year 1 | 
| Mean change in CNV total lesion area on FA from baseline. |  | Year 1 | 
| Mean chance in area of leakage on FA from baseline. |  | Year 1 | 

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