Acute Ischemic Stroke
Conditions
Keywords
Stroke
Brief summary
The primary objective of the study is to assess the clinical effects of natalizumab versus placebo in acute ischemic stroke on clinical measures of functional independence and activities of daily living. The secondary objective of the study is to explore dose and exposure response and the clinical treatment effects of natalizumab versus placebo in acute ischemic stroke on the following: measures of independence, activities of daily living, neurologic function, quality of life, cognition, and safety and tolerability
Interventions
DRUGnatalizumab
Administered as specified in the treatment arm
DRUGPlacebo
Matched placebo
Sponsors
Biogen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Clinical diagnosis of supratentorial acute ischemic stroke defined by LKN ≤24 hours prior to study treatment initiation. * Score of 5 to 23 points, inclusive, on the NIHSS at Screening for subjects initiating treatment ≤9 hours from LKN. Note: NIHSS eligibility must be confirmed within 60 minutes prior to randomization. * Score of 5 to 15 points, inclusive, on the NIHSS at Screening for subjects initiating treatment \>9 to ≤24 hours from LKN. Note: NIHSS eligibility must be confirmed within 60 minutes prior to randomization. * Prior to index stroke, patient was able to perform basic activities of daily living without assistance: dressing, eating, walking, bathing, and using the toilet. * For those subjects who underwent a cranial MRI, there is at least 1 acute infarct with a diameter of ≥2 cm on baseline brain diffusion-weighted imaging. Key
Exclusion criteria
* Lacunar or isolated brainstem or cerebellar stroke based on clinical assessment and available acute imaging studies performed under the standard of care. * Presence of acute intracranial hemorrhage on acute brain CT or MRI. However, petechial hemorrhages of ≤1 cm are not exclusionary. * Severe stroke defined by imaging criteria based on either one of the following: * Alberta Stroke Program Early CT (ASPECT) score of 0 to 4 based on head CT or * Acute infarct volume on MRI diffusion weighed imaging greater than or equal to 70 mL * Seizure at the onset of stroke. * Known history of prior treatment with natalizumab. * Known history of active viral hepatitis B or C. * Signs and symptoms of active or acute infection. NOTE: Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Composite Global Measure of Functional Disability Excellent Outcome at Day 90 | Day 90 | The composite global measure of functional disability excellent outcome was based on a score of 0 or 1 on the modified Rankin Scale (mRS) and a score of \>=95 on the Barthel Index (BI). mRS measures independence, rather than neurological function, with specific tasks pre- and post-stroke. The scale consists of 7 grades, from 0 to 6, with 0 corresponding to no symptoms and 6 corresponding to death. BI consists of 10 items that measure a participant's daily functioning, specifically the activities of daily living and mobility. The items include feeding, moving from wheelchair to bed and returning, grooming, transferring to and from a toilet, bathing, walking on a level surface, going up and down stairs, dressing, and maintaining continence of bowels and bladder. The scores for each of the items are summed to create a total score of 0 to 100. The higher the score, the more independent the participant is. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Excellent Outcome in BI Score at Day 90 | Day 90 | Excellent BI outcome is defined as a score of \>=95. BI consists of 10 items that measure a participant's daily functioning, specifically the activities of daily living and mobility. The items include feeding, moving from wheelchair to bed and returning, grooming, transferring to and from a toilet, bathing, walking on a level surface, going up and down stairs, dressing, and maintaining continence of bowels and bladder. The scores for each of the items are summed to create a total score of 0 to 100. The higher the score, the more independent the participant is. |
| Stroke Impact Scale-16 (SIS-16) Score Using a Repeated Measures Mixed Effects Model at Day 90 | Day 90 | The SIS-16 is a 16-item physical dimension instrument that was developed as a brief, stand-alone tool for measuring the physical aspects of stroke recovery. The 16 physical aspects are rated on a 1 to 5 scale as follows: not difficult at all (5), a little difficult (4), somewhat difficult (3), very difficult (2), and could not do at all (1). Total score range is 16 to 80, with higher scores indicating higher levels of health-related quality of life and function. |
| Montreal Cognitive Assessment (MoCA) Score at Day 90 | Day 90 | The MoCA is a global cognitive screening test with favorable psychometric properties It screens 8 domains: visuospatial/executive, naming, memory, attention, language, abstraction, delayed recall, and orientation. Time to administer the MoCA is approximately 10 minutes. The total possible score is 0 to 30 points; a score of 26 or above is considered normal, \<10 (severe cognitive impairment), 10-17 (moderate cognitive impairment) and \>=18 (mild cognitive impairment). |
| Percentage of Participants With Excellent Outcome in mRS Score at Day 90 | Day 90 | Excellent mRS is defined as mRS score of 0 or 1. mRS measures independence, rather than neurological function, with specific tasks pre- and poststroke. The scale consists of 7 grades, from 0 to 6, with 0 corresponding to no symptoms and 6 corresponding to death. |
| Number of Participants Experiencing Adverse Events (AE) | Baseline up to Day 90 | An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. |
| Number of Participants Experiencing Serious Adverse Events (SAE) | Baseline up to Day 90 | A SAE is any untoward medical occurrence that at any dose results in death, is a life-threatening event, requires inpatient hospitalization, results in a significant disability/incapacity or congenital anomaly. |
| Percentage of Participants With Dose Response at Day 90 | Day 90 | Percentage of participants with dose response was evaluated in proportion of excellent outcome on mRS and BI. |
| Change From Baseline in National Institute of Health Stroke Scale (NIHSS) Score at Day 90 | Baseline, Day 90 | The NIHSS is a reliable tool for rapidly evaluating the effects of acute cerebral infarction. A trained observer rates the participant's ability to answer questions and perform activities relating to level of consciousness, language, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, sensory loss, and extinction and inattention (formerly neglect). There are 15 items. Total score ranges from 0 as normal to a maximum possible total severity score of 42 for all items. Higher the score, more the severity. A negative change from Baseline indicates improvement. |
Countries
Germany, Spain, United Kingdom, United States
Participant flow
Recruitment details
Participants were recruited from 19 sites in Germany, 4 sites in the United Kingdom (UK), 12 sites in Spain, and 18 sites in the United States (US).
Pre-assignment details
A total of 277 participants with acute ischemic stroke were randomized into the study (94 participants in the placebo group, 91 participants in the natalizumab 300 milligram (mg) group, and 92 participants in the natalizumab 600 mg group).
Participants by arm
| Arm | Count |
|---|---|
| Placebo Single dose of matching placebo intravenous (IV) to natalizumab on Day 1 at one of two treatment windows, either within 9 hours or between 9-24 hours from when the participant was last known normal (LKN). | 94 |
| Natalizumab 300 mg IV Single 300 mg natalizumab IV on Day 1 at one of two treatment windows, either within 9 hours or between 9-24 hours from when the participant was last known normal (LKN). | 91 |
| Natalizumab 600 mg IV Single 600 mg natalizumab IV on Day 1 at one of two treatment windows, either within 9 hours or between 9-24 hours from when the participant was last known normal (LKN). | 92 |
| Total | 277 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Consent withdrawn | 2 | 4 | 1 |
| Overall Study | Death | 5 | 6 | 4 |
| Overall Study | Lost to Follow-up | 3 | 1 | 4 |
| Overall Study | Other | 1 | 1 | 2 |
Baseline characteristics
| Characteristic | Placebo | Natalizumab 300 mg IV | Natalizumab 600 mg IV | Total |
|---|---|---|---|---|
| Age, Continuous | 67.1 years STANDARD_DEVIATION 9.54 | 66.1 years STANDARD_DEVIATION 10.47 | 65.6 years STANDARD_DEVIATION 11.09 | 66.2 years STANDARD_DEVIATION 10.36 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 2 Participants | 3 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 28 Participants | 24 Participants | 24 Participants | 76 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 64 Participants | 65 Participants | 65 Participants | 194 Participants |
| Race/Ethnicity, Customized Black or African American | 2 count of participants | 1 count of participants | 1 count of participants | 4 count of participants |
| Race/Ethnicity, Customized Missing | 1 count of participants | 0 count of participants | 1 count of participants | 2 count of participants |
| Race/Ethnicity, Customized Not Reported Due to Confidentiality Regulations | 64 count of participants | 65 count of participants | 65 count of participants | 194 count of participants |
| Race/Ethnicity, Customized White | 27 count of participants | 25 count of participants | 25 count of participants | 77 count of participants |
| Sex: Female, Male Female | 29 Participants | 36 Participants | 37 Participants | 102 Participants |
| Sex: Female, Male Male | 65 Participants | 55 Participants | 55 Participants | 175 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 5 / 91 | 6 / 90 | 4 / 89 |
| other Total, other adverse events | 67 / 91 | 69 / 90 | 65 / 89 |
| serious Total, serious adverse events | 19 / 91 | 23 / 90 | 29 / 89 |
Outcome results
Primary
Percentage of Participants With Composite Global Measure of Functional Disability Excellent Outcome at Day 90
The composite global measure of functional disability excellent outcome was based on a score of 0 or 1 on the modified Rankin Scale (mRS) and a score of \>=95 on the Barthel Index (BI). mRS measures independence, rather than neurological function, with specific tasks pre- and post-stroke. The scale consists of 7 grades, from 0 to 6, with 0 corresponding to no symptoms and 6 corresponding to death. BI consists of 10 items that measure a participant's daily functioning, specifically the activities of daily living and mobility. The items include feeding, moving from wheelchair to bed and returning, grooming, transferring to and from a toilet, bathing, walking on a level surface, going up and down stairs, dressing, and maintaining continence of bowels and bladder. The scores for each of the items are summed to create a total score of 0 to 100. The higher the score, the more independent the participant is.
Time frame: Day 90
Population: Modified Intent-to-Treat (MITT) population: all randomized participants who had received entire infusion of study treatment. Participants who were accidentally enrolled based on conditions that mimicked stroke symptom at presentation were excluded from MITT population. Number analyzed is the number of participants with data available for analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Composite Global Measure of Functional Disability Excellent Outcome at Day 90 | 54.1 percentage of participants |
| Natalizumab 300 mg IV | Percentage of Participants With Composite Global Measure of Functional Disability Excellent Outcome at Day 90 | 41.5 percentage of participants |
| Natalizumab 600 mg IV | Percentage of Participants With Composite Global Measure of Functional Disability Excellent Outcome at Day 90 | 39.9 percentage of participants |
Comparison: Composite Measure: The global odds ratio was based on a linear logistic regression model with baseline National Institute of Health Stroke Scale (NIHSS) category (score 5-15, 16-23), age (\<60, 60-69, 70-80), tissue plasminogen activator (tPA) use (yes/no), treatment window (\<=9, \>9 and \<=24hours), thrombectomy (yes/no) and region (Spain, UK/Germany, United States of America \[USA\]) as covariates and unstructured working correlation structurep-value: 0.08695% CI: [0.38, 1.07]Regression, Logistic
Comparison: Composite Measure: The global odds ratio was based on a linear logistic regression model with baseline NIHSS category (score 5-15, 16-23), age (\<60, 60-69, 70-80), tPA use (yes/no), treatment window (\<=9, \>9 and \<=24hours), thrombectomy (yes/no) and region (Spain, UK/Germany, USA) as covariates and unstructured working correlation structurep-value: 0.03195% CI: [0.34, 0.95]Regression, Logistic
Secondary
Change From Baseline in National Institute of Health Stroke Scale (NIHSS) Score at Day 90
The NIHSS is a reliable tool for rapidly evaluating the effects of acute cerebral infarction. A trained observer rates the participant's ability to answer questions and perform activities relating to level of consciousness, language, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, sensory loss, and extinction and inattention (formerly neglect). There are 15 items. Total score ranges from 0 as normal to a maximum possible total severity score of 42 for all items. Higher the score, more the severity. A negative change from Baseline indicates improvement.
Time frame: Baseline, Day 90
Population: MITT population: all randomized participants who had received entire infusion of study treatment. Participants who were accidentally enrolled based on conditions that mimicked stroke symptom at presentation were excluded from MITT population. Number analyzed is number of participants with data available for analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in National Institute of Health Stroke Scale (NIHSS) Score at Day 90 | -6.14 score on a scale | Standard Deviation 6.92 |
| Natalizumab 300 mg IV | Change From Baseline in National Institute of Health Stroke Scale (NIHSS) Score at Day 90 | -5.17 score on a scale | Standard Deviation 7.937 |
| Natalizumab 600 mg IV | Change From Baseline in National Institute of Health Stroke Scale (NIHSS) Score at Day 90 | -6.28 score on a scale | Standard Deviation 6.51 |
Comparison: Treatment and treatment by visit interaction were included in the model as explanatory variables. Baseline NIHSS category (score 5-15, 16-23), tPA use (yes/no), age (\<60, 60-69, 70-80), thrombectomy (yes/no), region (Spain, UK/Germany, USA) and treatment window were considered as covariates. An unstructured variance-covariance matrix was used in the model.p-value: 0.31595% CI: [-1.1, 3.4]Mixed-effects model for repeated measure
Comparison: Treatment and treatment by visit interaction were included in the model as explanatory variables. Baseline NIHSS category (score 5-15, 16-23), tPA use (yes/no), age (\<60, 60-69, 70-80), thrombectomy (yes/no), region (Spain, UK/Germany, USA) and treatment window were considered as covariates. An unstructured variance-covariance matrix was used in the model.p-value: 0.54295% CI: [-2.96, 1.56]Mixed-effects model for repeated measure
Secondary
Montreal Cognitive Assessment (MoCA) Score at Day 90
The MoCA is a global cognitive screening test with favorable psychometric properties It screens 8 domains: visuospatial/executive, naming, memory, attention, language, abstraction, delayed recall, and orientation. Time to administer the MoCA is approximately 10 minutes. The total possible score is 0 to 30 points; a score of 26 or above is considered normal, \<10 (severe cognitive impairment), 10-17 (moderate cognitive impairment) and \>=18 (mild cognitive impairment).
Time frame: Day 90
Population: MITT population: all randomized participants who had received entire infusion of study treatment. Participants who were accidentally enrolled based on conditions that mimicked stroke symptom at presentation were excluded from MITT population. Number analyzed is number of participants with data available for analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Montreal Cognitive Assessment (MoCA) Score at Day 90 | 21.23 score on a scale | Standard Deviation 8.412 |
| Natalizumab 300 mg IV | Montreal Cognitive Assessment (MoCA) Score at Day 90 | 20.73 score on a scale | Standard Deviation 8.141 |
| Natalizumab 600 mg IV | Montreal Cognitive Assessment (MoCA) Score at Day 90 | 20.90 score on a scale | Standard Deviation 8.223 |
Comparison: Treatment and treatment by visit interaction were included in the model as explanatory variables. Baseline NIHSS category (score 5-15, 16-23), tPA use (yes/no), age (\<60, 60-69, 70-80), thrombectomy (yes/no), region (Spain, UK/Germany, USA) and treatment window were considered as covariates. An unstructured variance-covariance matrix was used in the model.p-value: 0.7895% CI: [-2.64, 1.99]Mixed-effects model for repeated measure
Comparison: Treatment and treatment by visit interaction were included in the model as explanatory variables. Baseline NIHSS category (score 5-15, 16-23), tPA use (yes/no), age (\<60, 60-69, 70-80), thrombectomy (yes/no), region (Spain, UK/Germany, USA) and treatment window were considered as covariates. An unstructured variance-covariance matrix was used in the model.p-value: 0.62295% CI: [-2.89, 1.73]Mixed-effects model for repeated measure
Secondary
Number of Participants Experiencing Adverse Events (AE)
An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Time frame: Baseline up to Day 90
Population: The safety population was defined as participants who had received any study treatment, including cases of complete or incomplete infusion.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants Experiencing Adverse Events (AE) | 84 participants |
| Natalizumab 300 mg IV | Number of Participants Experiencing Adverse Events (AE) | 81 participants |
| Natalizumab 600 mg IV | Number of Participants Experiencing Adverse Events (AE) | 82 participants |
Secondary
Number of Participants Experiencing Serious Adverse Events (SAE)
A SAE is any untoward medical occurrence that at any dose results in death, is a life-threatening event, requires inpatient hospitalization, results in a significant disability/incapacity or congenital anomaly.
Time frame: Baseline up to Day 90
Population: The safety population was defined as participants who had received any study treatment, including cases of complete or incomplete infusion.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants Experiencing Serious Adverse Events (SAE) | 19 participants |
| Natalizumab 300 mg IV | Number of Participants Experiencing Serious Adverse Events (SAE) | 23 participants |
| Natalizumab 600 mg IV | Number of Participants Experiencing Serious Adverse Events (SAE) | 29 participants |
Secondary
Percentage of Participants With Dose Response at Day 90
Percentage of participants with dose response was evaluated in proportion of excellent outcome on mRS and BI.
Time frame: Day 90
Population: MITT population: all randomized participants who had received entire infusion of study treatment. Participants who were accidentally enrolled based on conditions that mimicked stroke symptom at presentation were excluded from MITT population. Number analyzed is number of participants with data available for analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Dose Response at Day 90 | mRS (0, 1) | 41 percentage of participants |
| Placebo | Percentage of Participants With Dose Response at Day 90 | BI (>=95) | 67 percentage of participants |
| Natalizumab 300 mg IV | Percentage of Participants With Dose Response at Day 90 | mRS (0, 1) | 29 percentage of participants |
| Natalizumab 300 mg IV | Percentage of Participants With Dose Response at Day 90 | BI (>=95) | 54 percentage of participants |
| Natalizumab 600 mg IV | Percentage of Participants With Dose Response at Day 90 | mRS (0, 1) | 26 percentage of participants |
| Natalizumab 600 mg IV | Percentage of Participants With Dose Response at Day 90 | BI (>=95) | 54 percentage of participants |
Comparison: mRS: The Cochran-Armitage trend test of a monotonically increasing dose response in proportion of excellent outcome.~Dose levels are log transformed.p-value: 0.028Cochran-Armitage trend test
Comparison: BI: The Cochran-Armitage trend test of a monotonically increasing dose response in proportion of excellent outcome. Dose levels are log transformed.p-value: 0.049Cochran-Armitage trend test
Secondary
Percentage of Participants With Excellent Outcome in BI Score at Day 90
Excellent BI outcome is defined as a score of \>=95. BI consists of 10 items that measure a participant's daily functioning, specifically the activities of daily living and mobility. The items include feeding, moving from wheelchair to bed and returning, grooming, transferring to and from a toilet, bathing, walking on a level surface, going up and down stairs, dressing, and maintaining continence of bowels and bladder. The scores for each of the items are summed to create a total score of 0 to 100. The higher the score, the more independent the participant is.
Time frame: Day 90
Population: MITT population: all randomized participants who had received entire infusion of study treatment. Participants who were accidentally enrolled based on conditions that mimicked stroke symptom at presentation were excluded from MITT population. Number analyzed is number of participants with data available for analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Excellent Outcome in BI Score at Day 90 | 67 percentage of participants |
| Natalizumab 300 mg IV | Percentage of Participants With Excellent Outcome in BI Score at Day 90 | 54 percentage of participants |
| Natalizumab 600 mg IV | Percentage of Participants With Excellent Outcome in BI Score at Day 90 | 54 percentage of participants |
Comparison: The odds ratio was based on a linear logistic regression model with baseline NIHSS category (score 5-15, 16-23), age (\<60, 60-69, 70-80), tPA use (yes/no), treatment window (\<=9, \>9 and \<=24hours), thrombectomy (yes/no) and region (Spain, UK/Germany, USA) as covariates and unstructured working correlation structure.p-value: 0.08595% CI: [0.29, 1.08]Regression, Logistic
Comparison: The odds ratio was based on a linear logistic regression model with baseline NIHSS category (score 5-15, 16-23), age (\<60, 60-69, 70-80), tPA use (yes/no), treatment window (\<=9, \>9 and \<=24hours), thrombectomy (yes/no) and region (Spain, UK/Germany, USA) as covariates and unstructured working correlation structure.p-value: 0.06795% CI: [0.28, 1.04]Regression, Logistic
Secondary
Percentage of Participants With Excellent Outcome in mRS Score at Day 90
Excellent mRS is defined as mRS score of 0 or 1. mRS measures independence, rather than neurological function, with specific tasks pre- and poststroke. The scale consists of 7 grades, from 0 to 6, with 0 corresponding to no symptoms and 6 corresponding to death.
Time frame: Day 90
Population: MITT population: all randomized participants who had received entire infusion of study treatment. Participants who were accidentally enrolled based on conditions that mimicked stroke symptom at presentation were excluded from MITT population. Number analyzed is number of participants with data available for analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Excellent Outcome in mRS Score at Day 90 | 41 percentage of participants |
| Natalizumab 300 mg IV | Percentage of Participants With Excellent Outcome in mRS Score at Day 90 | 29 percentage of participants |
| Natalizumab 600 mg IV | Percentage of Participants With Excellent Outcome in mRS Score at Day 90 | 26 percentage of participants |
Comparison: The odds ratio was based on a linear logistic regression model with baseline NIHSS category (score 5-15, 16-23), age (\<60, 60-69, 70-80), tPA use (yes/no), treatment window (\<=9, \>9 and \<=24hours), thrombectomy (yes/no) and region (Spain, UK/Germany, USA) as covariates and unstructured working correlation structurep-value: 0.22295% CI: [0.35, 1.28]Regression, Logistic
Comparison: The odds ratio was based on a linear logistic regression model with baseline NIHSS category (score 5-15, 16-23), age (\<60, 60-69, 70-80), tPA use (yes/no), treatment window (\<=9, \>9 and \<=24hours), thrombectomy (yes/no) and region (Spain, UK/Germany, USA) as covariates and unstructured working correlation structurep-value: 0.07395% CI: [0.28, 1.06]Regression, Logistic
Secondary
Stroke Impact Scale-16 (SIS-16) Score Using a Repeated Measures Mixed Effects Model at Day 90
The SIS-16 is a 16-item physical dimension instrument that was developed as a brief, stand-alone tool for measuring the physical aspects of stroke recovery. The 16 physical aspects are rated on a 1 to 5 scale as follows: not difficult at all (5), a little difficult (4), somewhat difficult (3), very difficult (2), and could not do at all (1). Total score range is 16 to 80, with higher scores indicating higher levels of health-related quality of life and function.
Time frame: Day 90
Population: MITT population: all randomized participants who had received entire infusion of study treatment. Participants who were accidentally enrolled based on conditions that mimicked stroke symptom at presentation were excluded from MITT population. Number analyzed is number of participants with data available for analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Stroke Impact Scale-16 (SIS-16) Score Using a Repeated Measures Mixed Effects Model at Day 90 | 76.21 score on a scale | Standard Deviation 30.783 |
| Natalizumab 300 mg IV | Stroke Impact Scale-16 (SIS-16) Score Using a Repeated Measures Mixed Effects Model at Day 90 | 66.96 score on a scale | Standard Deviation 35.493 |
| Natalizumab 600 mg IV | Stroke Impact Scale-16 (SIS-16) Score Using a Repeated Measures Mixed Effects Model at Day 90 | 68.10 score on a scale | Standard Deviation 31.461 |
Comparison: Treatment and treatment by visit interaction were included in the model as explanatory variables. Baseline NIHSS category (score 5-15, 16-23), tPA use (yes/no), age (\<60, 60-69, 70-80), thrombectomy (yes/no), region (Spain, UK/Germany, USA) and treatment window were considered as covariates. An unstructured variance-covariance matrix was used in the model.p-value: 0.10695% CI: [-16.97, 1.64]Mixed-effects model for repeated measure
Comparison: Treatment and treatment by visit interaction were included in the model as explanatory variables. Baseline NIHSS category (score 5-15, 16-23), tPA use (yes/no), age (\<60, 60-69, 70-80), thrombectomy (yes/no), region (Spain, UK/Germany, USA) and treatment window were considered as covariates. An unstructured variance-covariance matrix was used in the model.p-value: 0.20295% CI: [-15.43, 3.27]Mixed-effects model for repeated measure