Clinical trial NCT06178055: A Study of the Efficacy and Safety of KUS121 in Participants With Acute Non-Arteritic Central Retinal Artery Occlusion (CRAO)
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Central Retinal Artery Occlusion
Lead sponsor: Kyoto Drug Discovery and Development Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-12-20
Enrollment: 75
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Proportion of study eyes which achieve a gain of 15 ETDRS letters or more in BCVA at Week 12 compared to baseline
timeFrame: At baseline, Week 12
Secondary outcomes:
measure: Proportion of study eyes which achieve a gain of 15 ETDRS letters or more in BCVA at Week 4 compared to baseline
timeFrame: At baseline, Week 4
measure: 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
timeFrame: At baseline, Week 12
measure: Proportion of study eyes which achieve a gain of 10 ETDRS letters or more in BCVA at Week 12 compared to baseline
timeFrame: At baseline, Week 12
measure: Mean change in BCVA (readable letters and Log MAR) at Week 12 compared to baseline
timeFrame: At baseline, Week 12
measure: Change in retinal thickness from baseline at Week 12 as measured by SD-OCT
timeFrame: At baseline, Week 12
measure: Change in the area of visual field from baseline to Week 12 as measured by Humphrey Field Analyzer
timeFrame: At baseline, Week 12
measure: Incidence and Severity of Ocular and Systemic (Non-Ocular) Adverse Events (AEs)
timeFrame: From baseline through Week 48
measure: Patients Reported Outcome
timeFrame: Up to Week 12
Other outcomes:
Locations:
city: Encino
country: United States
facility: The Retina Partners
state: California
city: Huntington Beach
country: United States
facility: Salehi Retina Institute, Inc
state: California
city: Oakland
country: United States
facility: Kaiser Permanente Oakland Med Ctr.
state: California
city: Jacksonville
country: United States
facility: Florida Retina Institute
state: Florida
city: Hagerstown
country: United States
facility: Cumberland Valley Retina Consultants
state: Maryland
city: Detroit
country: United States
facility: Kresge Eye Institute/Wayne State University
state: Michigan
city: New York
country: United States
facility: NYEE Infirmary of Mount Sinai
state: New York
city: Cleveland
country: United States
facility: UH Eye Institute
state: Ohio
city: Austin
country: United States
facility: Austin Retina Associates
state: Texas
city: San Antonio
country: United States
facility: Retina Consultants of Texas
state: Texas
city: The Woodlands
country: United States
facility: Retina Consultants of Texas
state: Texas
Study officials:
affiliation: Kyoto Drug Discovery ＆ Development Co., Ltd.
name: Kunihiro Musashi, MD., Ph.D.
role: STUDY_CHAIR
References:
citation: 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.