脊髄損傷患者を対象としたNVG-291の第1b/2a相試験

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.