Study to Assess the Efficacy and Safety of VX-210 in Subjects With Acute Traumatic Cervical Spinal Cord Injury

Study Overview
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Brief Summary
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The purpose of this study is to determine the efficacy and safety of VX-210 in subjects with Acute Traumatic Cervical Spinal Cord Injury. Secondary objectives include the specific evaluation of the effects of VX-210 on neurological recovery and daily function after spinal cord injury.

Official Title
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A Phase 2b/3, Double-blind, Randomized, Placebo Controlled, Multicenter Study to Assess the Efficacy and Safety of VX-210 in Subjects With Acute Traumatic Cervical Spinal Cord Injury

Conditions
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Cervical Spinal Cord Injury

Intervention / Treatment
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* Drug: VX-210
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Acute traumatic cervical SCI, motor level of C4, C5, C6, or C7 on each side: Screening UEMS score must be ≤16 points on each side. AIS A subjects with a C4 motor level on both sides must have at least 1 point of motor activity between C5 and T1 on at least 1 side. AIS B subjects with a C4 motor level on both sides must have at least 1 point of motor activity between C5 and C7 on at least 1 side. American Spinal Injury Association Impairment Scale (AIS) grade A or AIS grade B. Scheduled and planned to undergo a spinal decompression/stabilization surgery that commences within 72 hours after the initial injury. Computed tomography (CT) scan or magnetic resonance imaging (MRI) is consistent with the subject's neurological deficit. Exclusion Criteria: Participation in any other clinical study for acute SCI without approval by the sponsor. Inability to undergo decompression/stabilization surgery that commences within 72 hours after injury. One or more upper extremity muscle groups untestable during screening ISNCSCI examination. Acute SCI from gunshot or penetrating/stab wound; non-traumatic SCI (e.g., transverse myelitis, acute disc herniation); brachial plexus injury; complete spinal cord transection; or multifocal SCI. Females who are breastfeeding or have a positive serum pregnancy test. Body mass index (BMI) of ≥40 kg/m^2 at screening. History of an adverse reaction to a fibrin sealant or its components. Unconsciousness or other mental impairment that precludes reliable International Standards for the Neurological Classification of Spinal Cord Injury (ISNCSCI) examination. Known immunodeficiency, including human immunodeficiency virus, or use of immunosuppressive or cancer chemotherapeutic drugs. Any significant medical or psychiatric comorbidities that would significantly increase the risk of study enrollment and/or significantly interfere with study outcomes or assessments, in the judgment of the investigator. Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 14 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br> <br> |
| Experimental: VX-210<br> | Drug: VX-210<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Upper Extremity Motor Score (UEMS) | UEMS focuses selectively on the hand and arm control most relevant to individuals with a cervical spinal cord injury. UEMS ranges from 0 to 50, where a higher score indicates a better movement of hand and arm. | From baseline at 6 months post-treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Spinal Cord Independence Measure (SCIM) III Self-Care Subscore | SCIM self-care subscore measures self-care abilities (feeding, dressing, grooming, bathing), respiration and sphincter management and mobility. The score ranges from 0-20, where a higher score represents a better outcome. | At 6 months post-treatment | 
| Capabilities of Upper Extremity Test (CUE-T) Score | CUE-T measures a participant's ability to perform specific functional movements/tasks with the arms and hands (for example: grasping a pencil, pushing or lifting a weight). CUE-T score ranges from 0-128, where a higher score indicates an improvement in participant's ability. | At 6 months post-treatment | 
| Graded Redefined Assessment of Strength, Sensibility and Prehension (GRASSP) Quantitative Prehension Score | GRASSP measures participant's ability to perform specific functional tasks with the arms, hands, and fingers. GRASSP quantitative prehension score ranges from 0-60, where a higher score indicates a better performance. | At 6 months post-treatment | 
| Percentage of American Spinal Injury Association Impairment Scale (AIS) Grade Responders | AIS ranks impairment according to body-wide motor/sensory results: Grade A: Complete (no sensory or motor function is preserved in the sacral segments S4 to 5); Grade B: Sensory Incomplete (sensory but not motor function is preserved below the neurological level and includes the sacral segments S4 to 5); Grade C: Motor Incomplete (motor function is preserved at the most caudal sacral segments); Grade D: Motor Incomplete (motor incomplete status as defined above, with at least half or more of key muscle functions below the single neurological level of injury having a muscle grade >=3; Grade E: Normal (sensation and motor function as tested are graded as normal in all segments). An AIS responder was defined as a subject with improvement by ≥2 AIS grades (i.e., baseline AIS Grade A changed to Grade C, D, or E; baseline AIS Grade B changed to D or E at 6 months after treatment). | At 6 months post-treatment | 
| Percentage of Motor Level Responders | The motor level score for the right or left side assesses contraction strength of 10 key muscles in the upper and lower extremities on each side of the body; each muscle receives a score from 0 (total paralysis) to 5 ([normal] active movement). A motor level responder was defined as a subject with improvement by ≥2 motor levels on either side of the body (i.e., baseline level C4 changed to C6, C7, C8 on the left; or baseline level C5 changed to C7, C8 on the right). | At 6 months post-treatment | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of VX-210 |  | up to 53 hours post-treatment | 
| Maximum Observed Plasma Concentration (Cmax) of VX-210 |  | up to 53 hours post-treatment | 
| Area Under Plasma Concentration Time Curve (AUC) of VX-210 |  | up to 53 hours post-treatment |