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.