Safety and Efficacy of Orally Administered SJP-0008 in Central Retinal Artery Occlusion: A Phase IIa Randomized Clinical Trial

PURPOSE: To assess the efficacy and safety of orally administered calpain inhibitor SJP-0008 in Japanese patients with central retinal artery occlusion (CRAO), to establish a disease registry for the prospective tracking of observational data from patients with CRAO, intended for regulatory use, and to support the development of new therapeutic agents for CRAO. DESIGN: This was a 2-part study. Part 1 was a physician-/investigator-initiated, phase IIa, single-center, randomized, double-blinded, parallel-group study. Part 2 was a prospective cohort study, during which the CRAO registry was established, and included patients diagnosed with CRAO (including a nonrandomized registry cohort, the non-SJP group, which did not receive SJP-0008). Additionally, in part 2, a combined analysis was performed using data from part 1 patients. PARTICIPANTS: The study participants were patients recruited within 48 hours of developing CRAO. METHODS: SJP-0008 administration was initiated at least 3 hours but no more than 48 hours after the onset of CRAO. Patients were randomized in a 1:1 ratio using masked randomization to receive either 100-mg or 200-mg doses of SJP-0008. The dosing period was defined as the 4-week postinitiation period (up to 29 days), followed by an 8-week postobservation phase. MAIN OUTCOME MEASURES: The main outcome measure was to determine the efficacy of SJP-0008 treatment; the primary endpoint was the change in ETDRS visual acuity at 12 weeks in the target eye of patients with CRAO. RESULTS: The study included 28 patients (mean age: 68.8 ± 14.9 years; 78.6% male). ETDRS scores (mean [95% confidence interval]) were higher at week 12 than at baseline in both the 100-mg (27.9 letters [10.14, 45.61]) and 200-mg (25.7 letters [12.02, 39.40]) SJP-0008 groups, in contrast to the non-SJP group (10.2 letters [4.58, 15.76]). The improvement in the 200-mg SJP-0008 group was greater than in the nonrandomized non-SJP group (P = 0.040). No safety concerns were identified. CONCLUSIONS: The preliminary study supports the safety and efficacy of oral administration of SJP-0008 for treating CRAO, with greater improvement compared with the nonrandomized registry cohort. However, large-scale, multicenter randomized controlled trials are warranted to validate the findings of this study. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.