Study to Assess the Efficacy and Safety of VX-210 in Subjects With Acute Traumatic Cervical Spinal Cord Injury
Primary Purpose
Cervical Spinal Cord Injury
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
VX-210
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Cervical Spinal Cord Injury
Eligibility Criteria
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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Experimental
Arm Label
Placebo
VX-210
Arm Description
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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).
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).
Time to Reach Maximum Observed Plasma Concentration (Tmax) of VX-210
Maximum Observed Plasma Concentration (Cmax) of VX-210
Area Under Plasma Concentration Time Curve (AUC) of VX-210
Full Information
NCT ID
NCT02669849
First Posted
January 21, 2016
Last Updated
January 10, 2020
Sponsor
Vertex Pharmaceuticals Incorporated
1. Study Identification
Unique Protocol Identification Number
NCT02669849
Brief Title
Study to Assess the Efficacy and Safety of VX-210 in Subjects With Acute Traumatic Cervical Spinal Cord Injury
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
January 2020
Overall Recruitment Status
Terminated
Study Start Date
July 2016 (Actual)
Primary Completion Date
November 2018 (Actual)
Study Completion Date
November 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Vertex Pharmaceuticals Incorporated
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cervical Spinal Cord Injury
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
70 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Title
VX-210
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
VX-210
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Change in Upper Extremity Motor Score (UEMS)
Description
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.
Time Frame
From baseline at 6 months post-treatment
Secondary Outcome Measure Information:
Title
Spinal Cord Independence Measure (SCIM) III Self-Care Subscore
Description
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.
Time Frame
At 6 months post-treatment
Title
Capabilities of Upper Extremity Test (CUE-T) Score
Description
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.
Time Frame
At 6 months post-treatment
Title
Graded Redefined Assessment of Strength, Sensibility and Prehension (GRASSP) Quantitative Prehension Score
Description
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.
Time Frame
At 6 months post-treatment
Title
Percentage of American Spinal Injury Association Impairment Scale (AIS) Grade Responders
Description
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).
Time Frame
At 6 months post-treatment
Title
Percentage of Motor Level Responders
Description
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).
Time Frame
At 6 months post-treatment
Title
Time to Reach Maximum Observed Plasma Concentration (Tmax) of VX-210
Time Frame
up to 53 hours post-treatment
Title
Maximum Observed Plasma Concentration (Cmax) of VX-210
Time Frame
up to 53 hours post-treatment
Title
Area Under Plasma Concentration Time Curve (AUC) of VX-210
Time Frame
up to 53 hours post-treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
14 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
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12. IPD Sharing Statement
Learn more about this trial
Study to Assess the Efficacy and Safety of VX-210 in Subjects With Acute Traumatic Cervical Spinal Cord Injury
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