NVG-291 in Spinal Cord Injury Subjects

A Randomized, Double-Blind, Placebo-Controlled Phase 1b/2a Study of NVG-291 in Spinal Cord Injury Subjects

Inclusion Criteria: * A subject must provide written informed consent in accordance with local regulations prior to initiation of any study-specific activities/procedures. A legally authorized representative (LAR) may be used to assist in signing the informed consent. * Cervical spinal cord injury (SCI) resulting from acute physical trauma. * Males and females. * Age 18 to 75 years, inclusive. * Cervical SCI, incomplete, with a neurological level of injury at C7 or higher. * Had incomplete cervical SCI within the period from 1 year to 10 years inclusive (Chronic Cohort 1) OR within 20 days to 90 days inclusive (Subacute Cohort 2) at time of randomization. * Chronic Cohort 1 only: Must be able to volitionally initiate at least one step on one leg (without body weight support). * Must have a Walking Index for Spinal Cord Injury II (WISCI II) score as follows: * Chronic Cohort 1: Less than or equal to Level 14. * Subacute Cohort 2: Less than or equal to Level 10. * Graded Redefined Assessment of Strength, Sensibility and Prehension (GRASSP) Prehension Ability score/hand grip strength as follows: * Chronic Cohort 1: * Must have a score of at least 2 on at least one of the Prehension Ability grasp patterns of the GRASSP assessment in at least one upper extremity. * Must have no more than one Prehension Ability grasp pattern score = 4 in the upper extremity satisfying the criterion above. * Subacute Cohort 2: * Must have some voluntary (nonzero) force measured by grip dynamometry in at least one upper extremity. * Must have no more than one Prehension Ability grasp pattern score = 3 in at least one upper extremity. * Must not have a Prehension Ability grasp pattern score = 4 in the upper extremity satisfying the criterion above. * Presence of Motor Evoked Potentials (MEPs): * Chronic Cohort 1: In two specific target muscle groups. * Subacute Cohort 2: In one specific target muscle group. * Must be fluent in English. * Must be willing and able to comply with scheduled visits, all sample collections, and other trial procedures. Exclusion Criteria: * Nontraumatic SCI (e.g., due to infection, ischemia, metabolic abnormality, congenital abnormality, malignancy, radiation injury, surgical complications, or other disease process). * SCI due to gunshot wound or penetrating injury. * Two or more (noncontiguous) spinal cord lesions. * MRI or CT evidence of anatomically complete spinal cord transection. * Any form of ventilatory dependence. * Any condition that precludes adequate clinical assessment of all four extremities, such as contracture, peripheral nerve injury, or amputation. * History of uncontrolled seizures, or: * Chronic Cohort 1: Any seizure within the last 6 months. * Subacute Cohort 2: Any seizure occurring 1 week or more after the SCI. * Metal implant in the head that is likely to interfere with MRI analysis. * Pregnant or breastfeeding. * Any neurological condition that is considered to interfere with performance or likely confound assessment, such as multiple sclerosis, stroke, or progressive syringomyelia. * History of substance abuse within 12 months prior to screening, based on medical records or self-report. * Evidence of spinal instability or persistent spinal stenosis and/or compression related to the initial trauma. * Prior treatment with cell therapy delivered into the central nervous system (intrathecal or intraparenchymal). * Severe neuropathic pain inadequately controlled by medication. * Body mass index (BMI) \> 40 kg/m2. * Received botulinum toxin injection(s) in an upper or lower extremity muscle in the prior 6 months. * Received 4-aminopyridine within 7 days of first dose. * Prior treatment with a protein tyrosine phosphatase sigma (PTPσ) mimetic peptide. * Intrathecal opioid use. * Currently participating in an interventional clinical trial. * Received a non-permitted medication within 5.5 half-lives or 7 days, whichever is longer, prior to randomization. * Receiving any treatment intended to enhance neuroplasticity (e.g., electrical stimulation, acute intermittent hypoxia) at the time of consent or within 4 weeks of randomization, whichever is longer. * Any implanted internal spinal cord stimulator. * Currently receiving neuromuscular stimulation. * Currently receiving vagal or phrenic nerve stimulation. * Chronic Cohort 1 only: Any contraindication to baseline and on-study MRIs, such as: * History of a cardiac pacemaker or pacemaker wires. * Ferromagnetic metallic particles in the body. * Baclofen pump. * Vascular clips in the head. * Prosthetic heart valves. * Severe claustrophobia impeding ability to participate in an imaging study. * Malignancy within 5 years prior to screening, except for non-melanoma skin cancers or cervical or breast ductal carcinoma in situ. * History of medically significant hepatic disease or evidence of impaired liver function based on initial laboratory testing. * Severe renal insufficiency, defined as eGFR \< 30 mL/min/1.73m2. * Any disease, concomitant injury (such as significant traumatic brain injury), or condition that could interfere with the performance or interpretation of the protocol-specified assessments, in the opinion of the investigator. * Any other social or medical condition (e.g., uncontrolled diabetes, unstable hypertension) which, in the opinion of the investigator, would make the subject unsuitable for study participation.