Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of Probable Benefit of the Neuro-Spinal Scaffold™ in Subjects With Complete Thoracic AIS A Spinal Cord Injury as Compared to Standard of Care (INSPIRE 2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03762655
Recruitment Status : Recruiting
First Posted : December 4, 2018
Last Update Posted : June 14, 2019
Sponsor:
Information provided by (Responsible Party):
InVivo Therapeutics

Tracking Information
First Submitted Date  ICMJE November 29, 2018
First Posted Date  ICMJE December 4, 2018
Last Update Posted Date June 14, 2019
Actual Study Start Date  ICMJE May 21, 2019
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 30, 2018)
Change in AIS grade of one or more levels [ Time Frame: 6 months post-implant ]
The proportion of subjects with an improvement of at least one AIS grade will be presented for each study arm. The International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) examinations determine the ASIA Impairment Scale (AIS) grade.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03762655 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 24, 2019)
  • Change in Neurological Level of Injury (NLI) [ Time Frame: 3-months, 6-months, 12-months, 24-months post-open spine surgery ]
    The ISNCSCI examinations determine the the Neurological Level of Injury (NLI). The 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. NLI will be summarized for each study arm at visits (pre-surgery, 3-months, 6-months, 12-months, 24-months). Observed values and change from the baseline will be presented for each study arm.The ISNCSCI exam performed within 8 hours prior to surgery (pre-surgery ISNCSCI) will be used as the baseline.
  • Change in motor scores [ Time Frame: 3-months, 6-months, 12-months, 24-months post-open spine surgery ]
    A numerical summary score of motor function in each extremity determined by the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) examination. This score can reflect the degree of neurological impairment associated with the SCI, with lower score indicating greater impairment. Score ranges from 0-25 for each extremity, with maximum scores of 50 for the upper limbs and 50 for the lower limbs. Motor scores will be summarized for each study arm at visits (pre-surgery, 3-months, 6-months, 12-months, 24-months). Observed values and change from the baseline will be presented for each study arm.The ISNCSCI exam performed within 8 hours prior to surgery (pre-surgery ISNCSCI) will be used as the baseline.
  • Change in sensory scores [ Time Frame: 3-months, 6-months, 12-months, 24-months post-open spine surgery ]
    A numerical summary score of sensory function in each determined by the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) examination. This score can reflect the degree of neurological impairment associated with the SCI, with lower score indicating greater impairment. Score ranges from 0-56 points each for light touch and pin prick (sharp/dull discrimination) modalities, with a maximum total score of 112 points per side of the body. Observed values and change from the baseline will be presented for each study arm.The ISNCSCI exam performed within 8 hours prior to surgery (pre-surgery ISNCSCI) will be used as the baseline.
  • Changes in bladder, bowel, and sexual function [ Time Frame: 6-months, 12-months and 24-months, post-open spine surgery ]
    Bladder, bowel and sexual function will be assessed using the Lower Urinary Tract, Bowel and Sexual Function System/Organ section of the ASIA Autonomic Standards Assessment Form. The Autonomic Standards Assessment Form has three questions in each category (Lower Urinary Tract or bladder, Bowel, Sexual Function) and each question is scored on a scale from 0 (complete loss of control) - 2 (normal function). Observed values and change from baseline will be presented for each study arm. The hospital discharge visit will be used as the baseline visit.
  • Changes in spinal cord dimension [ Time Frame: 72-hours, 3-months, 6-months, 12-months, and 24-months post-open spine surgery ]
    Spinal cord dimensions (above, at, and below level of injury) will be assessed by an independent board-certified neuroradiologist central reader. Observed values and change from baseline will be presented for each study arm. The Screening MRI will be used as the baseline.
  • Changes in spinal cord lesion size [ Time Frame: 72-hours, 3-months, 6-months, 12-months, and 24-months post-open spine surgery ]
    Lesion size (in mm) will be assessed by an independent board-certified neuroradiologist central reader. Observed values and change from baseline will be presented for each study arm. The Screening MRI will be used as the baseline.
  • Changes in spinal cord lesion location [ Time Frame: 72-hours, 3-months, 6-months, 12-months, and 24-months post-open spine surgery ]
    Lesion Location will be assessed by an independent board-certified neuroradiologist central reader. Observed values and change from baseline will be presented for each study arm. The Screening MRI will be used as the baseline.
  • Changes in spinal cord anatomy-Presence of cyst [ Time Frame: 72-hours, 3-months, 6-months, 12-months, and 24-months post-open spine surgery ]
    Cyst presence or absence will be assessed by an independent board-certified neuroradiologist central reader. Observed values and change from baseline will be presented for each study arm. The Screening MRI will be used as the baseline.
  • Changes in cyst size, if present [ Time Frame: 72-hours, 3-months, 6-months, 12-months, and 24-months post-open spine surgery ]
    Cyst size, if present, will be assessed by an independent board-certified neuroradiologist central reader. Observed values and change from baseline will be presented for each study arm. The Screening MRI will be used as the baseline.
  • Changes in cyst location, if present [ Time Frame: 72-hours, 3-months, 6-months, 12-months, and 24-months post-open spine surgery ]
    Cyst location, if present, will be assessed by an independent board-certified neuroradiologist central reader. Observed values and change from baseline will be presented for each study arm. The Screening MRI will be used as the baseline.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 30, 2018)
  • Change in Neurological Level of Injury (NLI) [ Time Frame: 3-months, 6-months, 12-months, 24-months post-open spine surgery ]
    The ISNCSCI examinations determine the the Neurological Level of Injury (NLI). The 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. NLI will be summarized for each study arm at visits (pre-surgery, 3-months, 6-months, 12-months, 24-months). Observed values and change from the baseline will be presented for each study arm.The ISNCSCI exam performed within 8 hours prior to surgery (pre-surgery ISNCSCI) will be used as the baseline.
  • Changes in bladder, bowel, and sexual function [ Time Frame: 6-months, 12-months and 24-months, post-open spine surgery ]
    Bladder, bowel and sexual function will be assessed using the Lower Urinary Tract, Bowel and Sexual Function System/Organ section of the ASIA Autonomic Standards Assessment Form. The Autonomic Standards Assessment Form has three questions in each category (Lower Urinary Tract or bladder, Bowel, Sexual Function) and each question is scored on a scale from 0 (complete loss of control) - 2 (normal function). Observed values and change from baseline will be presented for each study arm. The hospital discharge visit will be used as the baseline visit.
  • Changes in spinal cord dimension [ Time Frame: 72-hours, 3-months, 6-months, 12-months, and 24-months post-open spine surgery ]
    Spinal cord dimensions (above, at, and below level of injury) will be assessed by an independent board-certified neuroradiologist central reader. Observed values and change from baseline will be presented for each study arm. The Screening MRI will be used as the baseline.
  • Changes in spinal cord lesion size [ Time Frame: 72-hours, 3-months, 6-months, 12-months, and 24-months post-open spine surgery ]
    Lesion size (in mm) will be assessed by an independent board-certified neuroradiologist central reader. Observed values and change from baseline will be presented for each study arm. The Screening MRI will be used as the baseline.
  • Changes in spinal cord lesion location [ Time Frame: 72-hours, 3-months, 6-months, 12-months, and 24-months post-open spine surgery ]
    Lesion Location will be assessed by an independent board-certified neuroradiologist central reader. Observed values and change from baseline will be presented for each study arm. The Screening MRI will be used as the baseline.
  • Presence of cyst [ Time Frame: 72-hours, 3-months, 6-months, 12-months, and 24-months post-open spine surgery ]
    Cyst presence or absence will be assessed by an independent board-certified neuroradiologist central reader. Observed values and change from baseline will be presented for each study arm. The Screening MRI will be used as the baseline.
  • Changes in of cyst size, if present [ Time Frame: 72-hours, 3-months, 6-months, 12-months, and 24-months post-open spine surgery ]
    Cyst size, if present, will be assessed by an independent board-certified neuroradiologist central reader. Observed values and change from baseline will be presented for each study arm. The Screening MRI will be used as the baseline.
  • Changes in of cyst location, if present [ Time Frame: 72-hours, 3-months, 6-months, 12-months, and 24-months post-open spine surgery ]
    Cyst location, if present, will be assessed by an independent board-certified neuroradiologist central reader. Observed values and change from baseline will be presented for each study arm. The Screening MRI will be used as the baseline.
  • Change in sensory scores [ Time Frame: 3-months, 6-months, 12-months, 24-months post-open spine surgery ]
    This is determined by the ISNCSCI sensory score- a numerical summary score of sensory function. There is a maximum total of 56 points each for light touch and pin prick (sharp/dull discrimination) modalities, for a total of 112 points per side of the body. Sensory scores will be summarized for each study arm at visits (pre-surgery, 3-months, 6-months, 12-months, 24-months). Observed values and change from the baseline will be presented for each study arm.The ISNCSCI exam performed within 8 hours prior to surgery (pre-surgery ISNCSCI) will be used as the baseline.
  • Change in motor scores [ Time Frame: 3-months, 6-months, 12-months, 24-months post-open spine surgery ]
    This is determined by the ISNCSCI motor score- a numerical summary score of motor function. There is a maximum score of 25 for each extremity, totaling 50 for the upper limbs and 50 for the lower limbs. Motor scores will be summarized for each study arm at visits (pre-surgery, 3-months, 6-months, 12-months, 24-months). Observed values and change from the baseline will be presented for each study arm.The ISNCSCI exam performed within 8 hours prior to surgery (pre-surgery ISNCSCI) will be used as the baseline.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: November 30, 2018)
  • Changes in pain: International Spinal Cord Injury Pain Form [ Time Frame: 3-months, 6-months, 12-months, and 24-months post-open spine surgery ]
    Pain will be assessed using the International Spinal Cord Injury Pain Form. Observed values and change from baseline will be presented for each study arm. Pain data at hospital discharge will be used as the baseline visit for the assessment of changes in pain.
  • Changes in SCIM III [ Time Frame: 3-months, 6-months, 12-months, and 24-months post-open spine surgery ]
    The Spinal Cord Independence Measure III (SCIM III) is, at present, the only comprehensive rating scale that measures the ability of patients with spinal cord lesions (SCL) to perform everyday tasks according to their value for the patient. SCIM III covers 19 tasks, all activities of daily living, grouped into four areas of function (subscales): Self-care (scored 0-20), Respiration and Sphincter Management (0-40), Mobility in Room and Toilet (0-10), and Mobility Indoors and Outdoors (0-30). The final score ranges from 0 to 100, with 0 requiring total assistance and 100 being completely independent. SCIM III will be summarized for each study arm at hospital discharge, 3-months, 6-months, 12-months, and 24-months post-open spine surgery. Observed values and change from baseline will be presented for each study arm. SCIM III results at hospital discharge will be used as the baseline visit.
  • Changes in SF-36 [ Time Frame: 3-months, 6-months, 12-months, and 24-months post-open spine surgery ]
    The Short Form (36) Health Survey consists of eight scaled scores, which are the weighted sums of the questions in their section. The eight sections are vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, and mental health. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. A lower score indicates more disability and a higher score indicates less disability. The SF-36 also provides psychometrically-based physical component summary (PCS) and mental component summary (MCS) scores. SF-36 will be summarized for each study arm at hospital discharge, 3-months, 6-months, 12-months, and 24-months post-open spine surgery. Observed values and change from baseline will be presented for each study arm. SF-36 results at hospital discharge will be used as the baseline visit.
 
Descriptive Information
Brief Title  ICMJE Study of Probable Benefit of the Neuro-Spinal Scaffold™ in Subjects With Complete Thoracic AIS A Spinal Cord Injury as Compared to Standard of Care
Official Title  ICMJE Randomized, Controlled, Single-blind Study of Probable Benefit of the Neuro-Spinal Scaffold™ for Safety and Neurologic Recovery in Subjects With Complete Thoracic AIS A Spinal Cord Injury as Compared to Standard of Care
Brief Summary This is a randomized, controlled, single-blind, multicenter, two Arm (Treatment or "Scaffold" Arm; Standard of Care or "Comparator" Arm) of a Neuro-Spinal Scaffold to evaluate whether the Scaffold is safe and demonstrates probable benefit for the treatment of complete T2-T12 spinal cord injury as compared to standard of care open spine surgery.
Detailed Description

This is a randomized, controlled, single blind, two-arm, multicenter Humanitarian Device Exemption (HDE) 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 as compared to standard of care open spine surgery. Subjects will be randomized in a blinded manner to one of two study arms, the Treatment or "Scaffold" Arm and the Standard of Care or "Comparator" Arm. Subjects in the Scaffold Arm will have the Scaffold implantation immediately following standard of care open spine surgery. Subjects in the Comparator Arm will have standard of care open spine surgery and will not receive the Scaffold. The subjects will be blinded to their study arm for the duration of the study.

Primary Objective: To evaluate whether the Scaffold is safe and demonstrates probable benefit for the treatment of complete T2-T12 spinal cord injury as compared to standard of care open spine surgery.

Regulatory Objective: To enhance the clinical evidence for the Scaffold in the treatment of complete thoracic spinal cord injuries.

Intended Use: The Scaffold is intended for use in patients age 16-70 years diagnosed with a T2-T12 neurological level of injury functionally complete (AIS A) spinal cord injury for whom open spine surgery, (e.g., laminectomy, spine stabilization) which allows access to the dura of the injured spinal cord, is recommended as an option. The Scaffold is intended to be implanted in a cavity at the epicenter of the spinal cord contusion during open spine surgery. The Scaffold is intended for use in recent (≤7 days) spinal cord injuries that do not involve penetrating injury to the cord or complete severing of the cord.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Subjects will be randomized in a blinded manner to one of two study arms, the Treatment or "Scaffold" Arm and the Standard of Care or "Comparator" Arm. Subjects in the Scaffold Arm will have the Scaffold implantation immediately following standard of care open spine surgery. Subjects in the Comparator Arm will have standard of care open spine surgery and will not receive the Scaffold.
Masking: Single (Participant)
Masking Description:
Subjects will be randomized in a blinded manner to one of two study arms, the Treatment or "Scaffold" Arm and the Standard of Care or "Comparator" Arm. Subjects in the Scaffold Arm will have the Scaffold implantation immediately following standard of care open spine surgery. Subjects in the Comparator Arm will have standard of care open spine surgery and will not receive the Scaffold. The subjects will be blinded to their study arm for the duration of the study.
Primary Purpose: Treatment
Condition  ICMJE Injury, Spinal Cord
Intervention  ICMJE Device: Neuro-Spinal Scaffold

The investigational product ("Neuro-Spinal ScaffoldTM" or "Scaffold") is a porous bioresorbable polymer scaffold comprised of a synthetic biomaterial, poly(lactic-co-glycolic acid)-b-poly(L-lysine) (PLGA-PLL). The Scaffold is cylindrical in shape (3 mm diameter) and is available is three lengths (6 mm, 8 mm, 10 mm) for optimal fit in the intraspinal lesion cavity.

Based upon pre-clinical testing, the Scaffold is expected to be resorbed from the site of implant within 4 to 8 weeks.

Study Arms  ICMJE
  • Experimental: Neuro-Spinal Scaffold Arm
    Subjects in the Scaffold Arm will have the Scaffold implantation immediately following standard of care open spine surgery.
    Intervention: Device: Neuro-Spinal Scaffold
  • No Intervention: Comparator Arm
    Subjects in the Comparator Arm will have standard of care open spine surgery and will not receive the Scaffold.
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 30, 2018)
35
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 2028
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  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 have open spine surgery within 7 days from injury)
  3. Injury Severity Score (ISS) ≤ 45 at the time of screening
  4. Glasgow Coma Scale, GCS ≥ 14 (GCS ≥ 10 for intubated subjects) at the time of the screening and GCS = 15 (GCS ≥ 10 for intubated subjects) within two hours prior to spine surgery
  5. Non-penetrating SCI (contusion injury) that is no less than approximately 4 mm in diameter by MRI
  6. 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)
  7. Informed consent obtained
  8. 16-70 years of age, inclusive
  9. Eight-hour period of hemodynamically stability (>90 mmHg systolic blood pressure) prior to open spine surgery

Exclusion Criteria:

  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
  4. No discrete cavity 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 (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. MS, ALS, 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 ISNCSCI exam
  8. Subjects with clinically significant pre-existing respiratory disease not related to the contusion being treated (e.g., COPD)
  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 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 open spine surgery (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 open spine surgery including sperm donation or banking
  15. Current or impending incarceration
  16. Complete spinal cord transection as determined by screening MRI
  17. Subjects with spinal cord injuries directly due to gunshot, knife, or other penetrating wounds.
  18. Known hypersensitivity to PLGA or 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 open spine surgery
  22. 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
  24. Subjects receiving tetracyclines, such as minocycline (subjects must discontinue tetracyclines to be enrolled in the study; tetracyclines can be resumed after 6 months post-open spine surgery
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 16 Years to 70 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Richard Toselli, MD (617) 863-5540 rtoselli@invivotherapeutics.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03762655
Other Study ID Numbers  ICMJE InVivo-100-105
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: Yes
IPD Sharing Statement  ICMJE Not Provided
Responsible Party InVivo Therapeutics
Study Sponsor  ICMJE InVivo Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account InVivo Therapeutics
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP