Loberamisal for Acute Ischemic Stroke

Importance: Effective neuroprotective and neuroreparative therapies for acute ischemic stroke remain limited. Loberamisal is a small-molecule compound that dually targets the postsynaptic density 95 (PSD-95) pathway and α2 γ-aminobutyric acid type α (α2-GABAA) receptor. Objective: To evaluate the efficacy and safety of intravenous loberamisal for improving functional outcomes in patients with acute ischemic stroke. Design, Setting, and Participants: The Loberamisal for Acute Ischemic Stroke (LAIS) trial was a multicenter, double-blind, randomized, placebo-controlled phase 3 clinical trial conducted at 32 hospitals in China. Adults aged 18 to 80 years with acute ischemic stroke, a baseline National Institutes of Health Stroke Scale score of 7 to 20, and no prestroke disability (modified Rankin Scale score, ≤1) who presented within 48 hours of symptom onset were enrolled between July 24, 2024, and December 7, 2024, with final follow-up on April 8, 2025. Interventions: Participants were randomly assigned (1:1) to receive intravenous loberamisal (40 mg) or matching placebo once daily for 10 consecutive days, in addition to standard stroke care. Main Outcomes and Measures: The primary outcome was achieving a full functional outcome at 90 days, defined as a modified Rankin Scale (mRS) score of 0 to 1. Safety outcomes included adverse events, serious adverse events, and mortality. Results: Among 998 randomized participants, 997 received at least 1 dose of the study drug and were included in the primary analysis (502 in the loberamisal group and 495 in the placebo group). The median age was 64 years (IQR, 57-71), 336 participants (33.7%) were women, and the median baseline NIHSS score was 8 (IQR, 7-9). At 90 days, 350 participants (69.7%) in the loberamisal group achieved an mRS score of 0 to 1 compared with 279 (56.3%) in the placebo group (relative risk, 1.24; 95% CI, 1.12-1.36; risk difference, 13.28%; 95% CI, 7.24%-19.32%). Adverse events occurred in 441 participants (87.8%) in the loberamisal group and 439 (88.7%) in the placebo group. Serious adverse events occurred in 43 participants (8.6%) in the loberamisal group and 53 (10.7%) in the placebo group. All-cause mortality occurred in 6 participants (1.2%) in the loberamisal group and 10 (2.0%) in the placebo group. Conclusions and Relevance: Among patients with acute ischemic stroke treated within 48 hours of symptom onset, intravenous loberamisal, compared with placebo, resulted in a higher proportion of patients achieving full functional outcomes at 90 days. Further studies are needed to validate these findings and establish whether the benefits could extend to a broader patient population. Trial Registration: ClinicalTrials.gov Identifier: NCT06517173.