Abstract Body: Background: Neuroprotective agents offer the potential for mitigating ischemic brain injury caused by excitotoxicity, oxidative stress, and inflammation. BXOS110, a novel inhibitor targeting the PSD-95 protein, disrupts the NMDAR/PSD-95/nNOS complex and has demonstrated efficacy in reducing neuronal damage in preclinical studies. Building on positive safety results from Phase 1 trials, this study aims to evaluate the efficacy and safety of BXOS110 in patients with acute ischemic stroke receiving reperfusion therapy.
Method: This multicenter, double-blind, randomized, placebo-controlled Phase 2 trial, initiated on February 7^th, 2024, enrolled 300 patients presenting within 3 hours of stroke onset who received reperfusion therapy (NCT06322394). Participants were randomly assigned in a 1:1:1 ratio to receive high-dose BXOS110 (3.0 mg/kg), low-dose BXOS110 (2.0 mg/kg), or placebo. The primary outcome is the proportion of participants achieving mRS score of 0-2 at 90 days. Secondary outcomes include the proportion with mRS score of 0-2 at earlier intervals, NIHSS score changes, infarct volume variation at 24 hours, and safety endpoints, such as serious adverse events (SAEs), mortality, and withdrawal due to adverse events.
Result: The final patient enrollment was completed on August 2^nd, 2024, with 100 participants assigned to each group: low-dose BXOS110, high-dose BXOS110, and placebo, according to the study protocol. The mean age of participants was 63.5±10.1 years, and 87(29%) were female. For mRS score, the pre-stroke data was mean±SD: 0±0 and median (IQR): 1 (1, 3); on Day 30 was 1±1 and 1 (0, 2); and as of October 27^th, 2024, the 90-day mRS follow-up was not yet fully completed (Figure 1). The baseline NIHSS score was recorded as 9±2 and 8 (7–10). NIHSS scores on subsequent days were as follows: Day 2 was 5±4, 4 (2–7); Day 3 was 5±5, 4 (2–6); and Day 10 was 3±3, 2 (1–4) (Figure 2). Imaging evaluations were completed on September 14^th, 2024, with the baseline infarct volume measured as 6.2±17.7mm³ and 24-hour infarct volume as 9.8±31.5mm³. Follow-up was 99% complete till now, with full follow-up anticipated by November 2^nd, 2024. Endpoint adjudication is ongoing, and unblinding is scheduled for December 15^th, 2024.
Conclusion: This trial will provide critical insights into BXOS110's potential as a neuroprotective agent in ischemic stroke combined with reperfusion treatment and will support the Phase 3 study.