Safety, tolerability and preliminary efficacy of ALMB-0166 in patients with acute spine cord injury.

ALMB-0166 is a first-in-class humanized monoclonal antibody that blocks connexin-43 hemichannels on spinal cord astrocytes. By reducing astrocyte and microglia activation, attenuating axonal degeneration and preventing the release of ATP, glutamate, ions and other molecules that drive excitotoxicity, inflammation and metabolic stress, ALMB-0166 mitigates secondary injury following spinal cord injury (SCI) and promotes neurological recovery. The objective of this study was to evaluate the safety, tolerability, pharmacokinetics (PKs) and efficacy of ALMB-0166 in patients with acute SCI. Eligible patients had acute SCI at or below the C3 level, with an American Spinal Injury Association Impairment Scale (AIS) grade of B or C, and were randomized within 72 h after injury. Patients received a single intravenous dose of ALMB-0166 (200, 600, 1200, 2400 or 4800 mg) or placebo, along with best supportive care. The primary outcome was safety. Secondary outcomes included PKs, immunogenicity and efficacy. A total of 25 patients with C3-C7 SCI were enrolled, of whom 24 received treatment (17 with ALMB-0166 and 7 with placebo). Treatment-emergent adverse events (TEAEs) occurred in 94.1% (16/17) of patients in the ALMB-0166 group and 100% (7/7) of those in the placebo group. Grade ≥3 TEAEs were reported in 17.6% (3/17) of the ALMB-0166 group and 42.9% (3/7) of the placebo group. Treatment-related AEs (TRAEs) occurred in six patients (35.3%) with ALMB-0166 and two patients (28.6%) with placebo; all TRAEs were Grade 1. No deaths occurred. ALMB-0166 exhibited essentially linear PKs over the dose range of 200-4800 mg, with concentrations increasing gradually from the start of infusion, peaking near the end of infusion, and then declining slowly. Compared with placebo, ALMB-0166 treatment was associated with improvement in motor function, sensory function, AIS and pain. Specifically, two patients in the ALMB-0166 group recovered from AIS Grade C to Grade E, whereas no patient in the placebo group recovered to Grade E. Notably, the 1200 and 2400 mg dose groups showed superior efficacy in sensory and motor measures; pooled data from these two groups showed greater improvements in both sensory and motor scores than those in the placebo group. In conclusion, ALMB-0166 demonstrated a manageable safety profile and improved neurological recovery in patients with acute SCI.