A Study of the Efficacy and Safety of KUS121 in Participants With Acute Non-Arthritic Central Retinal Artery Occlusion (CRAO)

Study Overview
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Brief Summary
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Central retinal artery occlusion (CRAO) is an ophthalmologic emergency which leads to severe and permanent vision loss. There is no evidence-based therapy for CRAO. The objective of this GION study is to evaluate the efficacy and safety of KUS121 intravitreal (IVT) injection in participants with acute non-arteritic CRAO.

Detailed Description
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This is a Phase II, double-masked, sham-controlled, multi-center, parallel-group study to evaluate the efficacy and safety of KUS121 intravitreal (IVT) injection in patients with non-arteritic Central Retinal Artery Occlusion (CRAO) diagnosed and treated within 3-48 hours of disease onset. Participants will be randomized to high dose KUS121, low dose KUS121, or sham in a 1:1:1 ratio. Participants will receive daily intravitreal injections of KUS 121 or sham, which mimics an injection, from Day 1 through Day 3. Primary efficacy endpoint is the proportion of participants who gain 15 letters or more in BCVA compared with baseline and will be assessed at Week 12. Safety evaluation will continue until a 12-month follow up.

Official Title
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A Phase 2, Double-masked, Randomized, Sham-controlled, Multiple-dose Study of the Efficacy and Safety of Intravitreal KUS121 in the Treatment of Non-Arteritic Central Retinal Artery Occlusion (CRAO)

Conditions
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Central Retinal Artery Occlusion

Intervention / Treatment
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* Drug: KUS121 high dose
* Drug: KUS121 low dose
* Drug: Sham procedure


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants who are willing and able to comply with clinic visits and study-related procedures and able to provide signed informed consent in person or from their legally authorized representative Men and women ≥ 20 years of age at that time of providing signed informed consent Diagnosed as non-arteritic Central Retinal Artery Occlusion (CRP and ESR are within normal laboratory value ranges; for example, CRP < 3.0 mg/L, ESR is < 10 mm/h for Men and < 15 mm/h for Women) from 3 hours until no more than 48 hours after the onset of significant visual acuity changes Best Corrected Visual Acuity (BCVA) Early Treatment Diabetic Retinopathy Study (ETDRS) letter score of 0 to 35 in the study eye at screening prior to enrollment (eyes with 'no light perception' or 'light perception' are to be excluded) Retinal thickening or hyper-reflectivity in retinal inner layers in spectral domain optical coherence tomography (SD-OCT), or white turbid edema in fundus examination Exclusion Criteria: Presence of the following conditions in the study eye: Infection in or around the eye Uncontrolled intraocular pressure Abnormality in macula other than CRAO findings History of macular photocoagulation Opacity in visual axis preventing fundus examination or fundus imaging (e.g., corneal dystrophy) Neovascularization of iris and retina Any inflammatory disease involving the eye Optic atrophy Glaucomatous cupping greater than 0.9 Prior vitrectomy Aphakia with the absence of posterior capsule Any IVT injection or sub-tenon injection within 1 month of screening Any intraocular surgery or ocular implant within 3 months of screening Any history of ocular trauma within 3 months of screening A positive urine pregnancy test on Day 1 prior to study enrollment History of allergy or hypersensitivity to KUS121 or a compound with a condensed polycyclic aromatic hydrocarbon skeleton represented by naphthalene and any of excipients of KUS121 product, fluorescein, or any study treatment-related mandatory ingredients that is not amenable to treatment Known hypersensitivity to a study treatment procedure, dilating drops, or any of the anesthetic and antimicrobial preparations used by a participant during the study Presence of other medical disease, physical or ocular examination finding, or clinical laboratory finding that in the opinion of the Investigator contraindicates the use of an investigational product, might interfere with the evaluation of the efficacy or safety of the study drug, may put the participant at significant risk or might interfere with the participant's ability to participate in the study

Ages Eligible for Study
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Minimum Age: 20 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: KUS121 high dose group<br> | Drug: KUS121 high dose<br>* Participants will receive KUS121 high dose intravitreal (IVT) injection once on each of 3 consecutive days (Day 1 through Day 3).<br>|
| Experimental: KUS121 low dose group<br> | Drug: KUS121 low dose<br>* Participants will receive KUS121 low dose intravitreal (IVT) injection once on each of 3 consecutive days (Day 1 through Day 3).<br>|
| Sham Comparator: Control group<br> | Drug: Sham procedure<br>* Participants will receive a sham procedure that mimics an intravitreal (IVT) injection once on each of 3 consecutive days (Day 1 through Day 3).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of study eyes which achieve a gain of 15 ETDRS letters or more in BCVA at Week 12 compared to baseline | BCVA: Best-Corrected Visual Acuity; ETDRS: Early Treatment Diabetic Retinopathy Study. A higher ETDRS letter score means a better outcome (better visual acuity). | At baseline, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of study eyes which achieve a gain of 15 ETDRS letters or more in BCVA at Week 4 compared to baseline |  | At baseline, Week 4 | 
| Proportion of study eyes which achieve a gain of 0.3 Logarithm of Minimum Angle of Resolution (Log MAR) in BCVA at Week 12 compared to baseline | BCVA will be recorded using a Logarithm of the Minimum Angle of Resolution (LogMAR) scoring chart. A lower LogMAR score means a better outcome (better visual acuity). | At baseline, Week 12 | 
| Proportion of study eyes which achieve a gain of 10 ETDRS letters or more in BCVA at Week 12 compared to baseline |  | At baseline, Week 12 | 
| Mean change in BCVA (readable letters and Log MAR) at Week 12 compared to baseline |  | At baseline, Week 12 | 
| Change in retinal thickness from baseline at Week 12 as measured by SD-OCT |  | At baseline, Week 12 | 
| Change in the area of visual field from baseline to Week 12 as measured by Humphrey Field Analyzer | The Humphrey Visual Field Analyser test assesses the retina's ability to detect a light stimulus at specific points within the visual field. A higher score means a better outcome (better visual field). | At baseline, Week 12 | 
| Incidence and Severity of Ocular and Systemic (Non-Ocular) Adverse Events (AEs) |  | From baseline through Week 48 | 
| Patients Reported Outcome | The results of National Eye Institute Visual Function Questionnaire (NEI-VFQ 25) for each group at before, afterwards the disease onset and Week 12. A higher score means a better functioning (better patient-reported visual function). | Up to Week 12 |