Clinical trial NCT02138110: The INSPIRE Study: Probable Benefit of the Neuro-Spinal Scaffold for Treatment of AIS A Thoracic Acute Spinal Cord Injury
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Traumatic Thoracic Acute Spinal Cord Injury
Keywords: Spinal Cord Injury (SCI)
Complete (AIS A) Traumatic Acute Spinal Cord Injury
Lead sponsor: InVivo Therapeutics
Sponsor class: INDUSTRY
First posted: 2014-05-14
Enrollment: 20
Sex: ALL
Minimum age (years): 16
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

Subjects must meet all of the following to be considered eligible:

1. AIS A classification of traumatic spinal cord injury at T2-T12 neurological level of injury confirmed by a qualified medical professional
2. Recent injury (must receive Scaffold within 7 days from injury)
3. Non-penetrating SCI (contusion injury) that is no less than approximately 4 mm in diameter by MRI
4. 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)
5. Informed consent obtained
6. 16-70 years of age, inclusive
7. Hemodynamically stable and deemed a suitable candidate for surgery

Exclusion Criteria:

Subjects who meet any of the following will be excluded:

1. Terminally ill subjects not likely to be able to participate in follow-up
2. Incomplete spinal cord injury (AIS B, C, D, and E injuries)
3. Subjects with more than one discrete spinal cord injury (contusion) will be excluded.
4. No discrete cavity (existing or created by irrigation/myelotomy) in the contused spinal cord in which a Scaffold can be placed
5. Evidence of clear and significant Somatosensory Evoked Potentials (SSEP) transmission through the injury site before Scaffold implantation (based on the judgment of the Investigator)
6. 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
7. 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
8. Subjects with clinically significant pre-existing respiratory disease not related to the contusion being treated (e.g., chronic obstructive pulmonary disorder)
9. Subjects requiring Long-term ongoing mechanical ventilation
10. Subjects with documented immune deficiency disorders, including a known diagnosis of HIV infection/AIDS
11. 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
12. 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.
13. 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)
14. 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
15. Current or impending incarceration
16. Complete spinal cord transection
17. Subjects with spinal cord injuries directly due to gunshot, knife, or other penetrating wounds.
18. Known hypersensitivity to poly(lactic-co-glycolic acid) (PLGA) or poly-L-lysine (PLL) (e.g., hypersensitivity to absorbable sutures containing PLGA)
19. History of severe mental illness (according to DSM IV or V)
20. Evidence of pre-trauma active local or systemic infection
21. Participation in another interventional clinical trial for six months after Scaffold implantation
22. Body mass index (BMI) over 39
23. 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

Primary outcomes:
measure: Percentage of Patients With Improvement in AIS Grade of One or More Levels
timeFrame: 6 months post-implantation
Secondary outcomes:
measure: Number of Participants Stratified by Change From Baseline in Neurological Level of Injury (NLI) at 6 Months
timeFrame: 6 months post-implantation
measure: Number of Participants Stratified by Change From Baseline in ISNCSCI Sensory Pin Prick Score
timeFrame: 6 months post-implantation
measure: Number of Participants Stratified by Change From Baseline in ISNCSCI Sensory Light Touch Score
timeFrame: 6 months post-implantation
measure: Change From Baseline in ISNCSCI Total Motor Score
timeFrame: 6 months post-implantation
measure: Number of Participants Stratified by Change From Baseline in Spinal Cord Anatomy - Cyst (Presence or Absence)
timeFrame: 6 months post-implantation
measure: Number of Participants Stratified by Change From Baseline in Spinal Cord Anatomy - Spinal Cord Adhesion (Presence or Absence)
timeFrame: 6 months post-implantation
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Barrow Neurological Institute - St. Joseph's Hospital and Medical Center
state: Arizona
city: Los Angeles
country: United States
facility: USC/Keck School of Medicine
state: California
city: Sacramento
country: United States
facility: University of California/Davis Medical Center
state: California
city: Camden
country: United States
facility: Cooper Neurological Institute
state: New Jersey
city: Charlotte
country: United States
facility: Carolina NeuroSurgery and Spine Associates/Carolinas Rehabilitation
state: North Carolina
city: Greenville
country: United States
facility: Vidant Medical Center
state: North Carolina
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
Study officials:
affiliation: InVivo Therapeutics Corporation
name: Richard Toselli, MD
role: STUDY_DIRECTOR
References:
citation: Kim KD, Lee KS, Coric D, Harrop JS, Theodore N, Toselli RM. Acute Implantation of a Bioresorbable Polymer Scaffold in Patients With Complete Thoracic Spinal Cord Injury: 24-Month Follow-up From the INSPIRE Study. Neurosurgery. 2022 Jun 1;90(6):668-675. doi: 10.1227/neu.0000000000001932. Epub 2022 Apr 22.
citation: Kim KD, Lee KS, Coric D, Chang JJ, Harrop JS, Theodore N, Toselli RM. A study of probable benefit of a bioresorbable polymer scaffold for safety and neurological recovery in patients with complete thoracic spinal cord injury: 6-month results from the INSPIRE study. J Neurosurg Spine. 2021 Feb 5;34(5):808-817. doi: 10.3171/2020.8.SPINE191507. Print 2021 May 1.
citation: Theodore N, Hlubek R, Danielson J, Neff K, Vaickus L, Ulich TR, Ropper AE. First Human Implantation of a Bioresorbable Polymer Scaffold for Acute Traumatic Spinal Cord Injury: A Clinical Pilot Study for Safety and Feasibility. Neurosurgery. 2016 Aug;79(2):E305-12. doi: 10.1227/NEU.0000000000001283.