Safety and efficacy of intrathecal antibodies to Nogo-A in patients with acute cervical spinal cord injury: a randomised, double-blind, multicentre, placebo-controlled, phase 2b trial.

作者：Norbert Weidner, Rainer Abel, D. Maier, K. Röhl, Frank Röhrich, M. Baumberger, Margret Hund-Georgiadis, M. Saur, Jesus Benito, Kerstin Rehahn, M. Aach, Andreas Badke, J. Kriz, K. Barkovits, Tim Killeen, Lynn Farner, M. Seif, M. Hubli, K. Marcus, Michael A Maurer, B. Robert, R. Rupp, P. Scheuren, Martin Schubert, Christian Schuld, Christina Sina, B. Steiner, T. Weis, Andreas Hug, M. Bolliger, N. Weiskopf, P. Freund, Torsten Hothorn, Martin E. Schwab, Armin Curt · 发表于：Lancet Neurology · 年份：2025 · DOI：10.1016/s1474-4422(24)00447-2 · 被引用次数：28 · 研究领域：Medicine

BACKGROUND Spinal cord injury results in permanent neurological impairment and disability due to the absence of spontaneous regeneration. NG101, a recombinant human antibody, neutralises the neurite growth-inhibiting protein Nogo-A, promoting neural repair and motor recovery in animal models of spinal cord injury. We aimed to evaluate the efficacy of intrathecal NG101 on recovery in patients with acute cervical traumatic spinal cord injury. METHODS This randomised, double-blind, placebo-controlled phase 2b clinical trial was done at 13 hospitals in the Czech Republic, Germany, Spain, and Switzerland. Patients aged 18-70 years with acute, complete or incomplete cervical spinal cord injury (neurological level of injury C1-C8) within 4-28 days of injury were eligible for inclusion. Participants were initially randomly assigned 1:1 to intrathecal treatment with 45 mg NG101 or placebo (phosphate-buffered saline); 18 months into the study, the ratio was adjusted to 3:1 to achieve a final distribution of 2:1 to improve enrolment and drug exposure. Randomisation was done using a centralised, computer-based randomisation system and was stratified according to nine distinct outcome categories with a validated upper extremity motor score (UEMS) prediction model based on clinical parameters at screening. Six intrathecal injections were administered every 5 days over 4 weeks, starting within 28 days of injury. Investigators, study personnel, and study participants were masked to treatme...