NVG-291 in Spinal Cord Injury Subjects

Study Overview
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Brief Summary
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A Single site (Shirley Ryan AbilityLab) Randomized, Double-Blind, Placebo-Controlled Phase 1b/2a Study of NVG-291 in Spinal Cord Injury Subjects

Detailed Description
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To evaluate the effect of NVG-291 on descending connectivity in subjects with subacute and chronic SCI (20 subjects per Cohort and results will be analyzed separately) using objective electrophysiological measures, in addition to clinical assessments. To evaluate safety and tolerability of NVG-291 in a SCI population, as measured by clinical assessments (Physical Examination, Vital Signs, ECG, etc.) as well as clinical laboratory measures.

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

Conditions
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Spinal Cord Injuries, Chronic Spinal Cord Injury, Subacute Spinal Cord Injury

Intervention / Treatment
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* Drug: NVG-291


Participation Criteria
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Eligibility Criteria
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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 SCI resulting from acute physical trauma. Males and females Age 18 - 75 years, inclusive. Cervical SCI, incomplete, with a neurological level of injury being at C7 or higher. Had incomplete cervical SCI within the period from 1 year to 10 years inclusive (Chronic cohort 1) OR within 10 days to 49 days inclusive (Subacute cohort 2) at time of randomization. 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: For Chronic cohort 1: Less than or equal to Level 14. For Subacute cohort 2: Less than or equal to Level 8. GRASSP Prehension Ability score For Chronic cohort 1: i. 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. ii. Must have no more than one Prehension Ability grasp patterns score = 4 in the upper extremity satisfying criterion i For Subacute cohort 2: i. Must have a score of 2 on at least one of the Prehension Ability grasp patterns of the GRASSP assessment in at least one upper extremity. ii. Must have no more than one Prehension Ability grasp patterns score = 3 in the upper extremity satisfying criterion i. iii. Must not have a Prehension Ability grasp patterns score = 4 in the upper extremity satisfying criterion i. Must be fluent in English. Subjects 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, or other disease process). Spinal cord injury due to gunshot wound or penetrating injury. Two or more (noncontiguous) spinal cord lesions. MRI 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, amputation. History of seizures (febrile seizures allowed). Metal implant in the head. History of traumatic brain injury without recovery. Any neurological condition that may interfere with performance or confound assessment, such as multiple sclerosis, stroke, or 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 initial trauma. Prior treatment with cell therapy delivered into the CNS (intrathecal or intraparenchymal). Severe neuropathic pain inadequately controlled by medication. Body mass index (BMI) > 40 (body weight in kilograms divided by height in meters squared). Received botulinum toxin injection(s) in an upper or lower extremity muscle in the prior 6 months. Received 4-aminopyridine within 14 days of screening. 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 to participate in this study or within 4 weeks of randomization, whichever is longer. Any implanted internal spinal cord stimulator. Currently receiving neuromuscular stimulation. Currently receiving vagal nerve stimulation. Any contraindication to undergo MRI studies such as: History of a cardiac pacemaker or pacemaker wires, OR Metallic particles in the body, OR Baclofen pump, OR Vascular clips in the head, OR Prosthetic heart valves, OR 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. Severe renal insufficiency, as defined by eGFR < 30 mL/min/1.73m2. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, Double-Blind, Placebo-Controlled
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NVG-291 for Injection<br>Injected under the skin (subcutaneous). | Drug: NVG-291<br>* A once daily injection<br>|
| Placebo Comparator: Placebo<br>Injected under the skin (subcutaneous). | Drug: NVG-291<br>* A once daily injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Electrophysiological | MEP amplitudes (corticospinal contribution) | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 10mWT time | Walking speed | 16 weeks | 
| 9-HPT time | Upper extremity dexterity | 16 weeks | 
| Pinch dynamometry | Recorded force | 16 weeks | 
| Graded and Redefined Assessment of Strength, Sensibility, and Prehension Test | Hand function Max Score 116 points (higher is better) | 16 weeks | 
| Lower extremity motor score (LEMS) | Lower extremity Max Score 50 points (25 points per side - higher is better) | 16 weeks | 
| Upper extremity motor score (UEMS) | Upper extremity Max Score 50 points (25 points per side - higher is better) | 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Spinal Cord Injury