The Neuro-Spinal ScaffoldTM is an investigational bioresorbable polymer scaffold that is designed for implantation at the site of injury within a spinal cord contusion. The Neuro-Spinal Scaffold provides structural support to the spared spinal tissue and a supportive matrix to facilitate endogenous repair processes. It degrades over several weeks.
The Neuro-Spinal Scaffold is composed of 2 biocompatible and bioresorbable polymers:
PLGA [Poly(lactic-co-glycolic acid)] is a polymer that is widely used in resorbable sutures. PLGA provides the biocompatible support for the Neuro-Spinal Scaffold.
Poly-L-Lysine [PLL] — the second component of the scaffold—is a positively-charged polymer commonly used to coat surfaces in order to promote cellular attachment.
These 2 polymers are cast to form a highly porous scaffold that is conducive to cellular attachment and neurite outgrowth.
The Neuro-Spinal Scaffold is trimmed to precisely fit the contusion and is placed into the epicenter of the contusion injury. It will break down over several weeks.
When the Neuro-Spinal Scaffold is placed at the epicenter of the contusion injury, we believe that it modulates the healing process by providing a biocompatible and cellular-adhesive support that promotes appositional healing. Thus, the Neuro-Spinal Scaffold behaves similarly to sutures or a butterfly bandage in a skin laceration.
The Neuro-Spinal Scaffold is designed to promote 3D appositional healing, similar to a suture or butterfly bandage.
Surgical implantation of the Neuro-Spinal Scaffold is intended to mitigate tissue damage resulting from some of the critical pathophysiological events that occur during the acute phase of SCI:
increase in tissue pressure
Similar Neuropathology to Human SCI: Why We Use Rat and Nonhuman Primate Models
In our preclinical studies we used both rat and nonhuman primate models since both exhibit a pattern of neuropathology following SCI that is similar to human SCI. We first evaluated scaffolds in both rats and nonhuman primates with unilateral hemisection injury, in which a section of the spinal cord is surgically removed. Because most human SCIs are nonpenetrating contusion injuries resulting from rapid compression of spinal tissue by intrusion of bone or disc material following mechanical disruption of the vertebral column, we also evaluated the bioresorbable polymer scaffold device in a rat model of spinal contusion injury.
Unexpected Finding That Scaffolds Alone Provide Benefits¹,²
The first preclinical study was conducted by InVivo’s founding scientists in rats with surgically-induced unilateral spinal cord hemisection injury.
Although the study was designed to demonstrate the effectiveness of scaffolds plus neural stem cells, a surprising finding was that it also demonstrated the baseline safety and effectiveness of scaffolds alone (without stem cells).
The Neuro-Spinal ScaffoldTM-alone group achieved a mean BBB score of ≈9. This indicated the onset of weight-supported locomotion, and suggested that the Neuro-Spinal Scaffold alone is capable of leading to improvement in functional recovery.
Evaluation of the Neuro-Spinal Scaffold in a Nonhuman Primate Model3
Following the initial positive results in rats, a series of studies in African green monkeys was performed to evaluate scaffolds in a nonhuman primate. Our first study in African green monkeys established that unilateral thoracic hemisection SCI (a new model in this species) produced a consistent functional deficit, and we observed a consistently positive response to Neuro-Spinal Scaffold implantation.
We then conducted 2 larger studies evaluating the safety and effectiveness of Neuro-Spinal Scaffolds in the African green monkey. The extent and time course of functional recovery in biopolymer implant treated primates was assessed with video capture and KinemaTracer evaluation of locomotor behavior with synchronous electromyographic recording along with locomotor observation rating.
When the results of these 2 studies were combined and analyzed together, we found that implantation of the Neuro-Spinal Scaffold resulted in several anatomic and functional benefits.
Increase in remodeled tissue2 The implantation of the Neuro-Spinal Scaffold increased the volume of remodeled tissue in the region of the hemisection compared with nonimplanted controls by promoting appositional healing.
Growth of white matter2
Myelinated axons (NFM or MBP axons) traverse the site of scaffold placement in the primate hemisection model. These data support the hypothesis that a scaffold in apposition to white matter in a contusion injury could support axon growth.
Functional recovery2 Kinematic analysis of 102 gait parameters in nonhuman primates with full unilateral hemisection lesions demonstrated that animals implanted with the Neuro-Spinal Scaffold had improved recovery of locomotion.
Safety and Effectiveness of Neuro-Spinal Scaffold in Rat Model of SCI2
In addition to the nonhuman primate studies, several studies were undertaken to evaluate the safety and effectiveness of implantation of the Neuro-Spinal Scaffold following spinal cord contusion injury in rats.
These studies showed that Neuro-Spinal Scaffold implantation in the acute injury setting helps to preserve spinal cord architecture:
reduces cavity volume
spares white matter
promotes tissue remodeling
1. Teng YD, et al. Proc Natl Acad Sci U S A. 2002;99:3024-3029. 2. InVivo Therapeutics Data on File. 3. Pritchard CD, et al. J Neurosci Methods. 2010;188:258-269.
Our Neuro-Spinal ScaffoldTM is expected to be regulated by the US Food and Drug Administration (FDA) as a class III medical device through the Humanitarian Device Exemption (HDE) pathway. For a device to be eligible for an HDE it must be first designated by the FDA as a Humanitarian Use Device (HUD) intended to benefit patients in the treatment or diagnosis of a disease or condition that affects fewer than 4000 individuals in the United States every year. We received this designation in April 2013.
HDE Overview as explained by FDA1 (http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/PremarketSubmissions/HumanitarianDeviceExemption/). –“An HDE is similar in both form and content to a premarket approval (PMA) application, but is exempt from the effectiveness requirements of a PMA. An HDE application is not required to contain the results of scientifically valid clinical investigations demonstrating that the device is effective for its intended purpose. The application, however, must contain sufficient information for FDA to determine that the device does not pose an unreasonable or significant risk of illness or injury, and that the probable benefit to health outweighs the risk of injury or illness from its use, taking into account the probable risks and benefits of currently available devices or alternative forms of treatment. Additionally, the applicant must demonstrate that no comparable devices are available to treat or diagnose the disease or condition, and that they could not otherwise bring the device to market.”
We are required to conduct human clinical trials before an HDE can be submitted to the FDA to obtain evidence of safety and the probable benefit to health. We received approval for our Investigational Device Exemption application in 2013 and currently have an ongoing, open-label clinical pilot study.
1. US Food and Drug Administration. Humanitarian Device Exemption. Accessed at: Read More.
Designed as 20-patient pivotal study to be used for HDE application
Pilot study converted to a pivotal probable benefit study
Pilot study patients included in the 20
Primary Endpoint (Objective Performance Criterion) – at least 25% of patients improve ASIA Impairment Scale (AIS) grade by 6 months
Additional Endpoints: ISNCSCI sensory and motor scores, bladder and bowel function, Spinal Cord Independence Measure (SCIM III), pain, quality of life
22 sites currently enrolling (40 US clinical sites allowed)
Plan also to include Canada and United Kingdom clinical sites in 2016
Acute Complete (AIS A) Thoracic SCI via HDE
Target completion of The INSPIRE Study and submission in 2017
Acute Complete (AIS A) Cervical SCI via HDE
Projected study initiation mid-2016
InVivo can pursue a similar rapid, streamlined program
Acute Incomplete (AIS B, AIS C) SCI via PMA
Expand to larger acute SCI population (thoracic and cervical injuries)
Expedited Access Pathway (EAP) may be an option
Similar pathway to Breakthrough Therapy Designation for drugs to reduce time to approval
Two-phase study allows for PMA approval based on pre-specified criterion with remaining confirmatory information submitted post-approval