The INSPIRE Study: Probable Benefit of the Neuro-Spinal Scaffold for Treatment of AIS A Thoracic Acute Spinal Cord Injury

Study Overview
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Brief Summary
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This is an HDE probable benefit, open-label, non- randomized, single-arm, multicenter study to evaluate the safety and probable benefit of the poly(lactic-co-glycolic acid)-b-poly(L-lysine) Scaffold (Scaffold) in subjects with thoracic AIS A traumatic spinal cord injury at neurological level of injury of T2-T12.

Detailed Description
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This is an HDE probable benefit, open-label, non-randomized, single-arm, multicenter study to evaluate the safety and probable benefit of the poly(lactic-co-glycolic acid)-b-poly(L-lysine) Scaffold (Scaffold) in subjects with thoracic AIS A traumatic spinal cord injury at neurological level of injury of T2-T12. The study will be conducted by qualified Investigators who have been trained on the surgical Scaffold implant procedure in order to enroll subjects in the Primary Endpoint Analysis Set, defined as all subjects with a successful Scaffold implant, no major protocol deviations, and a complete 6-month Primary Endpoint Follow-up Visit. After receiving the Scaffold and following discharge, subjects will participate in a comprehensive rehabilitation program. For the first 24-months after implantation of the Scaffold, Follow-up and Long-term Follow-up assessments will be conducted at either the study site or the rehabilitation center. The Long-term Follow-up annual visits for years 3 through 10 will be conducted over the telephone.

Official Title
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The INSPIRE Study: InVivo Study of Probable Benefit of the Neuro-Spinal Scaffold(TM) for Safety and Neurologic Recovery in Subjects With Complete Thoracic AIS A Spinal Cord Injury

Conditions
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Traumatic Thoracic Acute Spinal Cord Injury

Intervention / Treatment
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* Device: Neuro-Spinal Scaffold


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must meet all of the following to be considered eligible: AIS A classification of traumatic spinal cord injury at T2-T12 neurological level of injury confirmed by a qualified medical professional Recent injury (must receive Scaffold within 7 days from injury) Non-penetrating SCI (contusion injury) that is no less than approximately 4 mm in diameter by MRI Requires open spine surgery allowing access to the injured spinal cord (subjects requiring either posterior surgical approach or posterior plus anterior approach will be eligible) Informed consent obtained 16-70 years of age, inclusive Hemodynamically stable and deemed a suitable candidate for surgery Exclusion Criteria: Subjects who meet any of the following will be excluded: Terminally ill subjects not likely to be able to participate in follow-up Incomplete spinal cord injury (AIS B, C, D, and E injuries) Subjects with more than one discrete spinal cord injury (contusion) will be excluded. No discrete cavity (existing or created by irrigation/myelotomy) in the contused spinal cord in which a Scaffold can be placed Evidence of clear and significant Somatosensory Evoked Potentials (SSEP) transmission through the injury site before Scaffold implantation (based on the judgment of the Investigator) Subjects with clinically significant pre-existing neurological comorbidities that are unrelated to the contusion being treated (e.g., multiple sclerosis, amyotrophic lateral sclerosis, significant prior peripheral nerve dysfunction, residual problems related to previous spine-related neurological pathologies) will be excluded only if it is felt that these preexisting morbidities will increase risk, affect safety monitoring, or confound study results Spinal cord injury associated with significant traumatic brain injury or coma that, in the opinion of the Investigator, would preclude adequate assessment of spinal cord function, brain injury that could be associated on its own with sensory or motor deficits, or subjects with any other reason that results in an unreliable International Standards of Neurological Classification of Spinal Cord Injury (ISNCSCI) exam Subjects with clinically significant pre-existing respiratory disease not related to the contusion being treated (e.g., chronic obstructive pulmonary disorder) Subjects requiring Long-term ongoing mechanical ventilation Subjects with documented immune deficiency disorders, including a known diagnosis of HIV infection/AIDS Recent (according to Diagnostic and Statistical Manual of Mental Disorders (DSM) IV or DSM V criteria) history of abuse of narcotics or other significant substance abuse Significant injury complications where, in the view of the Investigator, participation in the study could further complicate subject care, limit study follow-up, or confound interpretation of safety or efficacy data. A female who is: Pregnant, or planning to become pregnant within the next 12-months; or Breastfeeding; or A woman of child-bearing potential (defined as post menarche and biologically capable of becoming pregnant [i.e., not surgically sterile]) who is engaged in active heterosexual relations and is not willing to use a barrier or hormonal form of birth control for 12-months following Scaffold implantation (e.g., oral, injected, or implanted contraceptives) A male who is engaged in active heterosexual relations and is not willing to use birth control for 3-months following Scaffold implantation including sperm donation or banking Current or impending incarceration Complete spinal cord transection Subjects with spinal cord injuries directly due to gunshot, knife, or other penetrating wounds. Known hypersensitivity to poly(lactic-co-glycolic acid) (PLGA) or poly-L-lysine (PLL) (e.g., hypersensitivity to absorbable sutures containing PLGA) History of severe mental illness (according to DSM IV or V) Evidence of pre-trauma active local or systemic infection Participation in another interventional clinical trial for six months after Scaffold implantation Body mass index (BMI) over 39 Having a medical condition (e.g., cardiovascular disease, life threatening injuries), or receiving medical treatment, or having any other reason that, in the judgment of the Investigator, precludes successful participation and follow-up for at least six months or confounds collection or interpretation of study safety, feasibility, or efficacy data

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 70 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neuro-Spinal Scaffold<br>Implantation of a Neuro-Spinal Scaffold into the epicenter of the post-irrigation contusion cavity during open spine surgery | Device: Neuro-Spinal Scaffold<br>* Implantation of a Neuro-Spinal Scaffold into the epicenter of the post-irrigation contusion cavity during open spine surgery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With Improvement in AIS Grade of One or More Levels | The ASIA (American Spinal Injury Association) Impairment Scale (AIS) classifies spinal cord injuries as follows: A = Complete: no sensory or motor function is preserved in the sacral segments S4-S5 B = Sensory incomplete: sensory but not motor function is preserved below the neurological level and includes the sacral segments S4-S5, AND no motor function is preserved more than three levels below the motor level on either side of the body C = Motor incomplete: motor function is preserved below the neurological level, and more than half of key muscle functions below the single neurological level of injury have a muscle grade less than 3 (Grades 0-2) D = Motor incomplete: at least half (half or more) of key muscle functions below the NLI have a muscle grade >3 E = Normal The confirmatory ISNCSCI exam performed within 8 hours prior to surgery was used as the baseline visit. | 6 months post-implantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Stratified by Change From Baseline in Neurological Level of Injury (NLI) at 6 Months | The neurological level of injury (NLI) refers to the most caudal segment of the spinal cord with normal sensory and antigravity motor function on both sides of the body, provided that there is normal (intact) sensory and motor function rostrally. A caudal change is an improvement in NLI whereas a rostral change is a deterioration in NLI. The confirmatory ISNCSCI exam performed within 8 hours prior to surgery was used as the baseline visit. | 6 months post-implantation | 
| Number of Participants Stratified by Change From Baseline in ISNCSCI Sensory Pin Prick Score | International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) Sensory Pin Prick Scores were assessed on a scale from 0 to 2 for each sensory point tested on each side of the body (maximum score = 112), with higher scores indicating better neurologic function. The confirmatory ISNCSCI exam performed within 8 hours prior to surgery was used as the baseline visit. An improvement in pin prick score indicates an increase in score from baseline at 6-months A deterioration in pin prick score indicates a decrease in score from baseline at 6-months No change in pin prick score indicates no change in score from baseline at 6-months | 6 months post-implantation | 
| Number of Participants Stratified by Change From Baseline in ISNCSCI Sensory Light Touch Score | International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) Sensory Light Touch Scores were assessed on a scale from 0 to 2 for each sensory point tested on each side of the body (maximum score = 112), with higher scores indicating better neurologic function. The confirmatory ISNCSCI exam performed within 8 hours prior to surgery was used as the baseline visit. An improvement in light touch score indicates an increase in light touch score from baseline at 6-months A deterioration in light touch score indicates a decrease in light touch score from baseline at 6-months No change in light touch score indicates no change in light touch score from baseline at 6-months | 6 months post-implantation | 
| Change From Baseline in ISNCSCI Total Motor Score | International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) Total Motor Scores were assessed on a scale from 0 to 5 for each myotome tested on each side of the body (upper limb maximum score = 50 and lower limb maximum score = 50), with higher scores indicating better neurologic function. The confirmatory ISNCSCI exam performed within 8 hours prior to surgery was used as the baseline visit. An improvement in motor score indicates an increase in motor score from baseline at 6-months A deterioration in motor score indicates an decrease in motor score from baseline at 6-months No change in motor score indicates no change in motor score from baseline at 6-months | 6 months post-implantation | 
| Number of Participants Stratified by Change From Baseline in Spinal Cord Anatomy - Cyst (Presence or Absence) | Characteristics of spinal cord anatomy were assessed by a Board-certified neuroradiologist central reader including presence or absence of intraparenchymal cysts. Screening MRI was used as the baseline value. | 6 months post-implantation | 
| Number of Participants Stratified by Change From Baseline in Spinal Cord Anatomy - Spinal Cord Adhesion (Presence or Absence) | Characteristics of spinal cord anatomy were assessed by a Board-certified neuroradiologist central reader including the presence or absence of spinal cord adhesion. Screening MRI was used as the baseline value. | 6 months post-implantation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Complete (AIS A) Traumatic Acute Spinal Cord Injury, Spinal Cord Injury (SCI)