A Trial Investigating the Efficacy and Safety of NVG-291 in Subjects With Chronic Spinal Cord Injury

Inclusion criteria

• Provide written informed consent prior to any study-specific procedures.
• Be 18 to 75 years of age, inclusive.
• Have chronic cervical spinal cord injury resulting from acute traumatic injury occurring 1 to 10 years prior to randomization.
• Have motor-incomplete cervical spinal cord injury as determined by International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) assessment at screening, meeting all of the following: American Spinal Injury Association (ASIA) Impairment Scale grade C or D; motor level at C7 or rostral on both the right and the left side; and a muscle grade of 1 or greater on ISNCSCI manual muscle testing in at least one lower-extremity key muscle function (L2 to S1) on either side.
• Have documented traumatic spinal cord injury confirmed by historical and/or current magnetic resonance imaging (MRI) or computed tomography (CT).
• Have a Walking Index for Spinal Cord Injury II (WISCI II) score of 0 to 14, inclusive.
• Have a score of at least 2 on at least one GRASSP Prehension Ability grasp pattern (cylindrical grasp, lateral key pinch, or tip-to-tip pinch) in at least one upper extremity, no more than one grasp-pattern score of 4 in the qualifying upper extremity, and a combined (bilateral) GRASSP Quantitative Prehension score no greater than 34, of a possible 40, across the sum of the four Prehension Performance task scores for the right and left hand.
• Be willing and able to comply with study visits, assessments, study procedures, and study drug administration requirements.
• Female participants of childbearing potential and male participants must agree to use protocol-specified contraception during study participation.

Exclusion criteria

• Nontraumatic spinal cord injury, penetrating spinal cord injury, multiple noncontiguous spinal cord lesions, or anatomically complete spinal cord transection.
• Ventilatory dependence, defined as invasive mechanical ventilation via tracheostomy, noninvasive ventilation for chronic respiratory failure, or diaphragmatic or phrenic nerve pacing. Continuous or automatic positive airway pressure (CPAP/APAP) used solely for obstructive sleep apnea is not exclusionary.
• Any condition preventing adequate assessment of all four extremities.
• Any neurological condition that could interfere with study assessments or interpretation of results, including multiple sclerosis, stroke, amyotrophic lateral sclerosis, dementia, or progressive syringomyelia.
• History of uncontrolled seizures or any seizure within 6 months prior to screening.
• Pregnant or breastfeeding.
• History of substance abuse within 12 months prior to screening.
• Evidence of spinal instability, persistent spinal stenosis, or spinal cord compression related to the original injury.
• Prior treatment with central nervous system gene therapy. Prior treatment with a protein tyrosine phosphatase sigma (PTPσ) mimetic peptide. Stem cell or cell therapy within 12 months prior to screening.
• Severe neuropathic pain inadequately controlled by medication.
• Body mass index (BMI) \>40 kg/m².
• Known hypersensitivity to cetirizine, mannitol, trehalose, or polysorbate 80.
• Receipt of botulinum toxin injection within 6 months prior to screening or 4-aminopyridine within 7 days prior to first dose. Current intrathecal opioid use.
• Current participation in another interventional clinical trial or prior exposure to NVG-291.
• Receipt of prohibited medications or therapies intended to enhance neuroplasticity within protocol-defined restricted periods.
• Presence of an implanted neurostimulation or brain-computer interface device, or current neurostimulation therapy, including spinal cord stimulation, neuromuscular stimulation, vagal nerve stimulation, or phrenic nerve stimulation.
• Malignancy within 5 years prior to screening, except adequately treated non-melanoma skin cancer or cervical or breast carcinoma in situ.
• Clinically significant hepatic disease, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥3 × upper limit of normal, or severe renal impairment (estimated glomerular filtration rate \<30 mL/min/1.73 m²).
• Any disease, injury, medical condition, social condition, or behavioral condition that could interfere with study participation, study assessments, interpretation of results, or compliance with study requirements, in the opinion of the investigator.