Cervical Spinal Cord Injury
Conditions
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.
Interventions
DRUGVX-210
DRUGPlacebo
Sponsors
Vertex Pharmaceuticals Incorporated
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
14 Years to 75 Years
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Upper Extremity Motor Score (UEMS) | From baseline at 6 months post-treatment | 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
| Measure | Time frame | Description |
|---|---|---|
| Capabilities of Upper Extremity Test (CUE-T) Score | At 6 months post-treatment | 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 | At 6 months post-treatment | 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 | At 6 months post-treatment | 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). |
| Spinal Cord Independence Measure (SCIM) III Self-Care Subscore | At 6 months post-treatment | 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 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 | — |
| Percentage of Motor Level Responders | At 6 months post-treatment | 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). |
Countries
Canada, United States
Participant flow
Recruitment details
Participants were randomized to receive a single 9-mg dose of VX-210 or a placebo (buffer solution). A single 3-mg dose of VX-210 in fibrin sealant was initially included but was subsequently removed during the study through a protocol amendment. The 3-mg arm was not analyzed for primary and secondary efficacy and pharmacokinetic analysis.
Pre-assignment details
A total of 70 participants were randomized, out of which 67 participants received the study drug.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants who received placebo matched to VX-210 as a single dose in fibrin sealant topically to the dural surface of the spinal cord within 72 hours after the initial injury. | 29 |
| VX-210 3 mg Participants who received VX-210 3 mg as a single dose in fibrin sealant topically to the dural surface of the spinal cord within 72 hours after the initial injury. | 6 |
| VX-210 9 mg Participants who received VX-210 9 mg as a single dose in fibrin sealant topically to the dural surface of the spinal cord within 72 hours after the initial injury. | 32 |
| Total | 67 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 1 | 1 | 2 |
| Overall Study | Lost to Follow-up | 1 | 0 | 3 |
| Overall Study | Other | 0 | 0 | 2 |
| Overall Study | Study terminated by sponsor | 16 | 1 | 14 |
| Overall Study | Withdrawal of Consent (not due to AE) | 0 | 0 | 3 |
Baseline characteristics
| Characteristic | Placebo | Total | VX-210 9 mg | VX-210 3 mg |
|---|---|---|---|---|
| Age, Continuous | 43.8 years STANDARD_DEVIATION 17.4 | 43.2 years STANDARD_DEVIATION 17.8 | 43.4 years STANDARD_DEVIATION 17.3 | 39.5 years STANDARD_DEVIATION 24.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 3 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 28 Participants | 64 Participants | 31 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 3 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 5 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 11 Participants | 5 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 5 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) White | 19 Participants | 43 Participants | 21 Participants | 3 Participants |
| Sex: Female, Male Female | 8 Participants | 16 Participants | 6 Participants | 2 Participants |
| Sex: Female, Male Male | 21 Participants | 51 Participants | 26 Participants | 4 Participants |
| Upper Extremity Motor Score (UEMS) | 13.00 units on a scale STANDARD_DEVIATION 8.96 | 13.24 units on a scale STANDARD_DEVIATION 8.43 | 14.03 units on a scale STANDARD_DEVIATION 8.33 | 10.17 units on a scale STANDARD_DEVIATION 6.59 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 29 | 1 / 6 | 2 / 32 |
| other Total, other adverse events | 28 / 29 | 6 / 6 | 32 / 32 |
| serious Total, serious adverse events | 18 / 29 | 6 / 6 | 16 / 32 |
Outcome results
Primary
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.
Time frame: From baseline at 6 months post-treatment
Population: The Overall Number of Participants Analyzed included all randomized subjects who received study drug. As per the amended protocol, the 3 mg arm was no longer planned to be assessed for any primary or secondary outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Upper Extremity Motor Score (UEMS) | 8.90 units on a scale | Standard Deviation 9.48 |
| VX-210 9 mg | Change in Upper Extremity Motor Score (UEMS) | 8.69 units on a scale | Standard Deviation 7.35 |
p-value: 0.751995% CI: [-5.08, 3.69]Mixed-effects model for repeated measure
Secondary
Area Under Plasma Concentration Time Curve (AUC) of VX-210
Time frame: up to 53 hours post-treatment
Population: Pharmacokinetic analysis set included all participants for which PK data was collected. As per the amended protocol, the 3 mg arm was no longer planned to be assessed for any primary or secondary outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under Plasma Concentration Time Curve (AUC) of VX-210 | 44.683 h*ng/mL | Geometric Coefficient of Variation 284.95 |
Secondary
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.
Time frame: At 6 months post-treatment
Population: The Overall Number of Participants Analyzed included all randomized subjects who received study drug. As per the amended protocol, the 3 mg arm was no longer planned to be assessed for any primary or secondary outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Capabilities of Upper Extremity Test (CUE-T) Score | 39.6 units on a scale | Standard Deviation 38.4 |
| VX-210 9 mg | Capabilities of Upper Extremity Test (CUE-T) Score | 42.8 units on a scale | Standard Deviation 41.1 |
Secondary
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.
Time frame: At 6 months post-treatment
Population: The Overall Number of Participants Analyzed included all randomized subjects who received study drug. As per the amended protocol, the 3 mg arm was no longer planned to be assessed for any primary or secondary outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Graded Redefined Assessment of Strength, Sensibility and Prehension (GRASSP) Quantitative Prehension Score | 18.9 units on a scale | Standard Deviation 19.4 |
| VX-210 9 mg | Graded Redefined Assessment of Strength, Sensibility and Prehension (GRASSP) Quantitative Prehension Score | 20.1 units on a scale | Standard Deviation 21.6 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of VX-210
Time frame: up to 53 hours post-treatment
Population: Pharmacokinetic analysis set included all participants for which PK data was collected. As per the amended protocol, the 3 mg arm was no longer planned to be assessed for any primary or secondary outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Maximum Observed Plasma Concentration (Cmax) of VX-210 | 2.856 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 200.35 |
Secondary
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).
Time frame: At 6 months post-treatment
Population: The Overall Number of Participants Analyzed included all randomized subjects who received study drug. As per the amended protocol, the 3 mg arm was no longer planned to be assessed for any primary or secondary outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of American Spinal Injury Association Impairment Scale (AIS) Grade Responders | 30.0 percentage of participants |
| VX-210 9 mg | Percentage of American Spinal Injury Association Impairment Scale (AIS) Grade Responders | 26.7 percentage of participants |
Secondary
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 frame: At 6 months post-treatment
Population: The Overall Number of Participants Analyzed included all randomized subjects who received study drug. As per the amended protocol, the 3 mg arm was no longer planned to be assessed for any primary or secondary outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Motor Level Responders | 35.0 percentage of participants |
| VX-210 9 mg | Percentage of Motor Level Responders | 33.3 percentage of participants |
Secondary
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.
Time frame: At 6 months post-treatment
Population: The Overall Number of Participants Analyzed included all randomized subjects who received study drug. As per the amended protocol, the 3 mg arm was no longer planned to be assessed for any primary or secondary outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Spinal Cord Independence Measure (SCIM) III Self-Care Subscore | 6.2 units on a scale | Standard Deviation 7 |
| VX-210 9 mg | Spinal Cord Independence Measure (SCIM) III Self-Care Subscore | 5.9 units on a scale | Standard Deviation 6.6 |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) of VX-210
Time frame: up to 53 hours post-treatment
Population: Pharmacokinetic analysis set included all participants for which PK data was collected. As per the amended protocol, the 3 mg arm was no longer planned to be assessed for any primary or secondary outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Reach Maximum Observed Plasma Concentration (Tmax) of VX-210 | 4.59 hours (h) |