A Randomized Controlled Trial of Local Delivery of a Rho Inhibitor (VX-210) in Patients with Acute Traumatic Cervical Spinal Cord Injury.

Acute traumatic spinal cord injury (SCI) can result in severe, lifelong neurological deficits. Following SCI, Rho activation contributes to collapse of axonal growth cones, failure of axonal regeneration, and neuronal loss. This randomized, double-blind, placebo-controlled phase 2b/3 study evaluated the efficacy and safety of Rho inhibitor VX-210 9 mg in patients after acute traumatic cervical SCI. The study enrolled patients aged 14 to 75 years with acute traumatic cervical SCIs, C4 to C7 (motor level) on each side, and American Spinal Injury Association Impairment Scale (AIS) Grade A or B who had spinal decompression/stabilization surgery commencing within 72 hours after injury. Patients were randomized 1:1 with stratification by age (<30 vs ≥30 years) and AIS grade (A vs B with sacral pinprick preservation vs B without sacral pinprick preservation). A single dose of VX-210 or placebo in fibrin sealant was administered topically onto the dura over the site of injury during decompression/stabilization surgery. Patients were evaluated for medical, neurological, and functional changes, and serum was collected for pharmacokinetic and immunological analyses. Patients were followed up for up to 12 months after treatment. A planned interim efficacy-based futility analysis was conducted after approximately 33% of patients were enrolled. The predefined futility stopping rule was met, and the study was therefore ended prematurely. In the final analysis, the primary efficacy endpoint was not met, with no statistically significant difference in change from baseline in upper-extremity motor score at 6 months after treatment between the VX-210 9-mg and placebo groups. This work opens the door to further improvements in the design and conduct of clinical trials in acute SCI.