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

Central Retinal Artery Occlusion Clinical Trial

— GION  

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06178055
• Other study ID #: KDK-1101-02
• Status: Recruiting
• Phase: Phase 2
• Start date: April 16, 2024
• Est. completion date: September 2025

Study information

• Verified date: May 2024
• Source: Kyoto Drug Discovery and Development Co., Ltd.
• Contact: Kyoto Drug Discovery & Development Clinical Trials Contact
• Phone: (+81) 6-7777-1003
• Email: clinical[@]kyoto-drug.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 75
• Est. completion date: September 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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

• Males and females = 20 years of age at that time of providing signed informed consent

• Diagnosed as non-arteritic Central Retinal Artery Occlusion 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:

1. Infection in or around the eye

2. Uncontrolled intraocular pressure

3. Abnormality in macula other than CRAO findings

4. History of macular photocoagulation

5. Opacity in visual axis preventing fundus examination or fundus imaging (e.g., corneal dystrophy)

6. Neovascularization of iris and retina

7. Any inflammatory disease involving the eye

8. Optic atrophy

9. Glaucomatous cupping greater than 0.9

10. Prior vitrectomy

11. Aphakia with the absence of posterior capsule

12. Any IVT injection or sub-Tenon's injection within 1 month of screening

13. Any intraocular surgery or ocular implant within 3 months of screening

14. Any history of ocular trauma within 3 months of screening

• Thrombolytic, fibrinolytic or prostaglandin E1 systemic treatment within 1 month 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

Related Conditions & MeSH terms

• Arterial Occlusive Diseases
• Central Retinal Artery Occlusion
• Retinal Artery Occlusion

Intervention

Drug:
• KUS121 high dose
Participants will receive KUS121 high dose intravitreal (IVT) injection once on each of 3 consecutive days (Day 1 through Day 3).
• KUS121 low dose
Participants will receive KUS121 low dose intravitreal (IVT) injection once on each of 3 consecutive days (Day 1 through Day 3).
• Sham procedure
Participants will receive a sham procedure that mimics an intravitreal (IVT) injection once on each of 3 consecutive days (Day 1 through Day 3).

Locations

Country	Name	City	State
United States	GION Study Site	Austin	Texas
United States	GION Study Site	Bellaire	Texas
United States	GION Study Site	Huntington Beach	California
United States	GION Study Site	Jacksonville	Florida
United States	GION Study Site	Saint Petersburg	Florida
United States	GION Study Site	San Antonio	Texas
United States	GION Study Site	The Woodlands	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Kyoto Drug Discovery and Development Co., Ltd.

Country where clinical trial is conducted

United States, 

References & Publications (1)

Ikeda HO, Muraoka Y, Hata M, Sumi E, Ikeda T, Nakagawa T, Abe H, Tada H, Morita S, Kakizuka A, Yoshimura N, Tsujikawa A. Safety and effectiveness of a novel neuroprotectant, KUS121, in patients with non-arteritic central retinal artery occlusion: An open-label, non-randomized, first-in-humans, phase 1/2 trial. PLoS One. 2020 Feb 13;15(2):e0229068. doi: 10.1371/journal.pone.0229068. eCollection 2020. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	Mean change in BCVA (readable letters and Log MAR) at Week 12 compared to baseline		At baseline, Week 12
Secondary	Change in retinal thickness from baseline at Week 12 as measured by SD-OCT		At baseline, Week 12
Secondary	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
Secondary	Incidence and Severity of Ocular and Systemic (Non-Ocular) Adverse Events (AEs)		From baseline through Week 48
Secondary	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