Abstract
Purpose :
Central retinal artery occlusion (CRAO) causes severe visual impairment. There are no effective treatments, and there is thus an unmet medical need. A calpain inhibitor, SJP-0008 (SJP), has a neuroprotective effect in ischemia-reperfusion injury and is expected to be effective against CRAO. Thus, we conducted a phase 2a clinical trial (jRCT2021190013) with patients with non-arteritic CRAO. Because CRAO has low prevalence and is an acute disease with a sudden onset, it is difficult to recruit patients. Therefore, we evaluated the effectiveness of SJP using an external natural history registry (jRCT1020190019) control.
Methods :
Patients in the registry (n=9) and trial (n=20) had best-corrected visual acuity (BCVA) of at least hand motion and less than 0.1 (decimal visual acuity) and had an onset time within 3–48 hours. The CRAO registry’s design and quality were comparable to the clinical trial. The CRAO registry recruited patients using the same inclusion and exclusion criteria as the phase 2a trial. The phase 2a clinical trial subjects were randomly assigned to receive 100 mg (n=10) or 200 mg (n=10) of oral SJP for 4 weeks. Efficacy and safety were evaluated for up to 12 weeks. The primary end point was the change in Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA in the affected eye at 12 weeks. The groups were compared with a general linear model.
Results :
The increase in affected-eye ETDRS BCVA at 12 weeks was greater (by 16.2 letters; 95% CI 3.50, 28.97) in the SJP group than in the registry group (p=0.013). The increase in the 100-mg group was greater (by 17.7 letters; 95% CI -1.26, 36.66) than the registry group, but this was not statistically significant (p=0.067). Nevertheless, the increase in the 200-mg group was significantly greater (by 15.5 letters; 95% CI 0.74, 30.34) than the registry group (p=0.040). No significant difference in ETDRS BCVA was observed between the 100-mg group and 200-mg group. There were 3 cases of side effects in the 100-mg group and 4 cases in the 200-mg group. Cerebral infarction occurred in 2 cases in the 100-mg group as a serious adverse event, but a causal relationship to SJP was ruled out in both cases.
Conclusions :
SJP showed clinically significant efficacy against non-arteritic CRAO, and no clinically relevant side effects were observed. SJP is expected to be put into practical use as an innovative treatment for CRAO, for which there is no effective treatment.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.