Acute Ischemic Stroke
Conditions
Brief summary
The primary objective of the study is to determine whether one 300 mg dose of intravenous (IV) natalizumab reduces change in infarct volume from Baseline to Day 5 on magnetic resonance imaging (MRI) in participants with acute ischemic stroke when given at ≤6 hours or at \>6 to ≤9 hours from when they were last known normal (LKN). The secondary objectives of this study in this study population are as follows: to assess the efficacy of natalizumab on change in infarct volume from Baseline to Day 30; to assess efficacy of natalizumab on change in infarct volume from 24 hours to Day 5 and Day 30; to assess the efficacy of natalizumab on clinical measures of stroke outcome; to assess the safety of natalizumab in participants with acute ischemic stroke.
Interventions
DRUGnatalizumab
Administered as described in the treatment arm
DRUGPlacebo
Matched placebo
Sponsors
Biogen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Diagnosis of acute ischemic stroke. * Score of ≥6 points on the National Institute of Health Stroke Scale (NIHSS) at Screening. * At least 1 acute infarct with largest diameter of more than 2 cm on Baseline brain diffusion-weighted imaging (DWI). * Participants who have received reperfusion therapy may be eligible to participate but must meet all eligibility criteria and perform the Baseline study magnetic resonance imaging (MRI) after reperfusion therapy has been completed. * Subjects of childbearing potential must practice effective contraception during the study and be willing and able to continue contraception for at least 3 months after their dose of study treatment. Key
Exclusion criteria
* Presence of any intracranial hemorrhage (ICH) on head computed tomography (CT) or non-petechial ICH on screening MRI. * Stroke isolated to the brainstem. * Presence of coma * Expected to die OR unable to be evaluated within 5 days. * Hypotension requiring the use of intravenous (IV) vasopressor support or systolic blood pressure \<90 mmHg at the time of randomization. * Known prior treatment with natalizumab. * Immunocompromised subjects, as determined by the Investigator. * History of progressive multifocal leukoencephalopathy (PML). * Contraindications to MRI, e.g., implanted pacemaker or other contraindicated implanted metal devices, history of or risk for side effects from gadolinium, or claustrophobia that cannot be medically managed. NOTE: Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Infarct Volume From Baseline (Diffusion-Weighted Imaging [DWI]) to Day 5 (Fluid-Attenuated Inversion Recovery [FLAIR]) | Baseline, Day 5 | Relative growth of infarct volume from Baseline (relative growth = FLAIR at Day 5 divided by Baseline DWI). Geometric mean calculated as the exponential of the mean log relative growth. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Infarct Volume From Baseline (DWI) to Day 30 (FLAIR) | Baseline, Day 30 | Relative growth of infarct volume from Baseline (relative growth = FLAIR at Day 30 divided by Baseline DWI). Geometric mean calculated as the exponential of the mean log relative growth. |
| Change in Infarct Volume From 24 Hours (FLAIR) to Day 5 (FLAIR) | 24 hours, Day 5 | Relative growth of infarct volume from 24 hours (relative growth = FLAIR at Day 5 divided by FLAIR at 24 hours). Geometric mean calculated as the exponential of the mean log relative growth. |
| Change in Infarct Volume From 24 Hours (FLAIR) to Day 30 (FLAIR) | 24 hours, Day 30 | Relative growth in infarct volume from Baseline (relative growth = FLAIR Day 30 divided by FLAIR at 24 hours ). Geometric mean calculated as the exponential of the mean log relative growth. |
| Change in Infarct Volume From Day 5 (FLAIR) to Day 30 (FLAIR) | Day 5, Day 30 | Relative growth of infarct volume from Day 5 (relative growth = FLAIR at Day 30 divided by FLAIR at Day 5). Geometric mean calculated as the exponential of the mean log relative growth. |
| Change in Infarct Volume From Baseline (DWI) to 24 Hours (FLAIR) | Baseline, 24 hrs | Relative growth of infarct volume from Baseline (relative growth = FLAIR at 24 hours divided by Baseline DWI). Geometric mean calculated as the exponential of the mean log relative growth. |
| Modified Rankin Scale (mRS) Distribution at Day 5, Day 30, and Day 90 | Day 5, Day 30, and Day 90 | The mRS measures independence, rather than neurologic function, with specific tasks pre- and post-stroke, respectively. The scale consists of 7 grades, from 0 to 6, with 0 corresponding to no symptoms and 6 corresponding to death. The distribution of mRS scores was summarized at each timepoint. An excellent outcome on the mRS was defined as a score of 0 or 1, while a good outcome was defined as a score of 0, 1, or 2. |
| Barthel Index at Day 5, Day 30, and Day 90 | Day 5, Day 30, and Day 90 | The Barthel Index consists of 10 items that measure a person's daily functioning, specifically the activities of daily living and mobility, and can be used to determine a baseline level of functioning and to monitor change in activities of daily living over time. The scores for each of the items are summed to create a total score up to a potential of 100, with higher scores representing a greater level of independence. |
| Number of Participants Who Experience Adverse Events (AEs) and Serious Adverse Events (SAEs) | Up to Day 90 ± 5 days | AE: any untoward medical occurrence that does not necessarily have a causal relationship with this treatment. SAE: any untoward medical occurrence that at any dose: results in death; in the view of the Investigator, places the participant at immediate risk of death (a life-threatening event); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect; any other medically important event that, in the opinion of the Investigator, may jeopardize the participant or may require intervention to prevent one of the other outcomes listed in the definition above. Events were categorized as severe, moderate, or mild, and related or not related to study treatment. |
| Change in National Institute of Health Stroke Scale (NIHSS) Score From Baseline to 24 Hours, Day 5, Day 30, and Day 90 | Baseline, 24 hours, Day 5, Day 30, Day 90 | The NIHSS is a systematic assessment tool that provides a quantitative measure of stroke-related neurologic deficit. Scores for the NIHSS range from 0 to 42, with 0 representing no symptoms and 42 representing death. |
Countries
Germany, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo A single IV injection of placebo | 82 |
| Natalizumab 300 mg single IV injection of natalizumab | 79 |
| Total | 161 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 |
| Overall Study | Death | 13 | 14 |
| Overall Study | Lost to Follow-up | 2 | 1 |
| Overall Study | Other | 4 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 3 |
Baseline characteristics
| Characteristic | Placebo | Natalizumab | Total |
|---|---|---|---|
| Age, Continuous | 71.6 years STANDARD_DEVIATION 11.83 | 70.3 years STANDARD_DEVIATION 13.34 | 71.0 years STANDARD_DEVIATION 12.57 |
| Age, Customized </= 39 years | 2 participants | 3 participants | 5 participants |
| Age, Customized 40 to 59 years | 13 participants | 11 participants | 24 participants |
| Age, Customized 60 to 79 years | 41 participants | 45 participants | 86 participants |
| Age, Customized >/= 80 years | 26 participants | 20 participants | 46 participants |
| Sex: Female, Male Female | 34 Participants | 38 Participants | 72 Participants |
| Sex: Female, Male Male | 48 Participants | 41 Participants | 89 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 75 / 82 | 68 / 78 |
| serious Total, serious adverse events | 38 / 82 | 36 / 78 |
Outcome results
Primary
Change in Infarct Volume From Baseline (Diffusion-Weighted Imaging [DWI]) to Day 5 (Fluid-Attenuated Inversion Recovery [FLAIR])
Relative growth of infarct volume from Baseline (relative growth = FLAIR at Day 5 divided by Baseline DWI). Geometric mean calculated as the exponential of the mean log relative growth.
Time frame: Baseline, Day 5
Population: Modified intention to treat (all participants who were randomized and received the entire infusion of study treatment) with assessments at both time points.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Placebo | Change in Infarct Volume From Baseline (Diffusion-Weighted Imaging [DWI]) to Day 5 (Fluid-Attenuated Inversion Recovery [FLAIR]) | 2.17 mL |
| Natalizumab | Change in Infarct Volume From Baseline (Diffusion-Weighted Imaging [DWI]) to Day 5 (Fluid-Attenuated Inversion Recovery [FLAIR]) | 2.37 mL |
Comparison: Treatment contrasts derived from a repeated measures mixed effects model modeling log relative growth relative to baseline using an autoregressive variance-covariance matrix structure. The model adjusts for treatment, time, treatment by time, log baseline DWI volume, treatment time window, and tissue plasminogen activator (tPA) use.90% CI: [-0.09, 0.26]
p-value: 0.77990% CI: [0.91, 1.3]repeated measures mixed effects model
Secondary
Barthel Index at Day 5, Day 30, and Day 90
The Barthel Index consists of 10 items that measure a person's daily functioning, specifically the activities of daily living and mobility, and can be used to determine a baseline level of functioning and to monitor change in activities of daily living over time. The scores for each of the items are summed to create a total score up to a potential of 100, with higher scores representing a greater level of independence.
Time frame: Day 5, Day 30, and Day 90
Population: Modified intention to treat (all participants who were randomized and received the entire infusion of study treatment); n=participants with assessment at given time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Barthel Index at Day 5, Day 30, and Day 90 | Day 5; n=78, 73 | 35.0 units on a scale |
| Placebo | Barthel Index at Day 5, Day 30, and Day 90 | Day 30; n=73, 60 | 70.0 units on a scale |
| Placebo | Barthel Index at Day 5, Day 30, and Day 90 | Day 90; n=61, 55 | 80.0 units on a scale |
| Natalizumab | Barthel Index at Day 5, Day 30, and Day 90 | Day 5; n=78, 73 | 30.0 units on a scale |
| Natalizumab | Barthel Index at Day 5, Day 30, and Day 90 | Day 30; n=73, 60 | 80.0 units on a scale |
| Natalizumab | Barthel Index at Day 5, Day 30, and Day 90 | Day 90; n=61, 55 | 95.0 units on a scale |
Comparison: Analysis of Barthel Index at Day 5. The repeated measures mixed effects model is modeling Barthel Index using an autoregressive variance-covariance matrix. The model adjusts for treatment, time, treatment by time, log baseline DWI volume, treatment time window, tPA use, and location of stroke.p-value: 0.45590% CI: [-9.19, 10.56]repeated measures mixed effects model
Comparison: Analysis of Barthel Index at Day 30. The repeated measures mixed effects model is modeling Barthel Index using an autoregressive variance-covariance matrix. The model adjusts for treatment, time, treatment by time, log baseline DWI volume, treatment time window, tPA use, and location of stroke.p-value: 0.4290% CI: [-8.76, 11.19]repeated measures mixed effects model
Comparison: Analysis of Barthel Index at Day 90/Final Visit. The repeated measures mixed effects model is modeling Barthel Index using an autoregressive variance-covariance matrix. The model adjusts for treatment, time, treatment by time, log baseline DWI volume, treatment time window, tPA use, and location of stroke.p-value: 0.28390% CI: [-6.64, 13.75]repeated measures mixed effects model
Secondary
Change in Infarct Volume From 24 Hours (FLAIR) to Day 30 (FLAIR)
Relative growth in infarct volume from Baseline (relative growth = FLAIR Day 30 divided by FLAIR at 24 hours ). Geometric mean calculated as the exponential of the mean log relative growth.
Time frame: 24 hours, Day 30
Population: Modified intention to treat (all participants who were randomized and received the entire infusion of study treatment) with assessments at both time points.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Placebo | Change in Infarct Volume From 24 Hours (FLAIR) to Day 30 (FLAIR) | 0.75 mL |
| Natalizumab | Change in Infarct Volume From 24 Hours (FLAIR) to Day 30 (FLAIR) | 0.72 mL |
Comparison: Treatment contrasts derived from a repeated measures mixed effects model modeling log relative growth relative to 24 hours using an autoregressive variance-covariance matrix structure. The model adjusts for treatment, time, treatment by time, log baseline DWI volume, treatment time window, and tPA use.90% CI: [-0.14, 0.1]
p-value: 0.40290% CI: [0.87, 1.11]repeated measures mixed effects model
Secondary
Change in Infarct Volume From 24 Hours (FLAIR) to Day 5 (FLAIR)
Relative growth of infarct volume from 24 hours (relative growth = FLAIR at Day 5 divided by FLAIR at 24 hours). Geometric mean calculated as the exponential of the mean log relative growth.
Time frame: 24 hours, Day 5
Population: Modified intention to treat (all participants who were randomized and received the entire infusion of study treatment) with assessments at both time points.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Placebo | Change in Infarct Volume From 24 Hours (FLAIR) to Day 5 (FLAIR) | 1.27 mL |
| Natalizumab | Change in Infarct Volume From 24 Hours (FLAIR) to Day 5 (FLAIR) | 1.25 mL |
Comparison: Treatment contrasts derived from a repeated measures mixed effects model modeling log relative growth relative to 24 hours using an autoregressive variance-covariance matrix structure. The model adjusts for treatment, time, treatment by time, log baseline DWI volume, treatment time window, and tPA use.90% CI: [-0.12, 0.11]
p-value: 0.48790% CI: [0.89, 1.12]repeated measures mixed effects model
Secondary
Change in Infarct Volume From Baseline (DWI) to 24 Hours (FLAIR)
Relative growth of infarct volume from Baseline (relative growth = FLAIR at 24 hours divided by Baseline DWI). Geometric mean calculated as the exponential of the mean log relative growth.
Time frame: Baseline, 24 hrs
Population: Modified intention to treat (all participants who were randomized and received the entire infusion of study treatment) with assessments at both time points.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Placebo | Change in Infarct Volume From Baseline (DWI) to 24 Hours (FLAIR) | 1.73 mL |
| Natalizumab | Change in Infarct Volume From Baseline (DWI) to 24 Hours (FLAIR) | 1.95 mL |
Comparison: Treatment contrasts derived from a repeated measures mixed effects model modeling log relative growth relative to baseline using an autoregressive variance-covariance matrix structure. The model adjusts for treatment, time, treatment by time, log baseline DWI volume, treatment time window, and tPA use.90% CI: [-0.09, 0.27]
p-value: 0.79790% CI: [0.92, 1.31]repeated measures mixed effects model
Secondary
Change in Infarct Volume From Baseline (DWI) to Day 30 (FLAIR)
Relative growth of infarct volume from Baseline (relative growth = FLAIR at Day 30 divided by Baseline DWI). Geometric mean calculated as the exponential of the mean log relative growth.
Time frame: Baseline, Day 30
Population: Modified intention to treat (all participants who were randomized and received the entire infusion of study treatment) with assessments at both time points.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Placebo | Change in Infarct Volume From Baseline (DWI) to Day 30 (FLAIR) | 1.27 mL |
| Natalizumab | Change in Infarct Volume From Baseline (DWI) to Day 30 (FLAIR) | 1.25 mL |
Comparison: Treatment contrasts derived from a repeated measures mixed effects model modeling log relative growth relative to baseline using an autoregressive variance-covariance matrix structure. The model adjusts for treatment, time, treatment by time, log baseline DWI volume, treatment time window, and tPA use.90% CI: [-0.13, 0.24]
p-value: 0.68490% CI: [0.88, 1.27]repeated measures mixed effects model
Secondary
Change in Infarct Volume From Day 5 (FLAIR) to Day 30 (FLAIR)
Relative growth of infarct volume from Day 5 (relative growth = FLAIR at Day 30 divided by FLAIR at Day 5). Geometric mean calculated as the exponential of the mean log relative growth.
Time frame: Day 5, Day 30
Population: Modified intention to treat (all participants who were randomized and received the entire infusion of study treatment) with assessments at both time points.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Placebo | Change in Infarct Volume From Day 5 (FLAIR) to Day 30 (FLAIR) | 0.60 mL |
| Natalizumab | Change in Infarct Volume From Day 5 (FLAIR) to Day 30 (FLAIR) | 0.59 mL |
Comparison: Treatment contrasts derived from a repeated measures mixed effects model modeling log relative growth relative to Day 5 using an autoregressive variance-covariance matrix structure. The model adjusts for for treatment, log baseline DWI volume, treatment time window, and tPA use.90% CI: [-0.18, 0.13]
p-value: 0.39490% CI: [0.84, 1.14]repeated measures mixed effects model
Secondary
Change in National Institute of Health Stroke Scale (NIHSS) Score From Baseline to 24 Hours, Day 5, Day 30, and Day 90
The NIHSS is a systematic assessment tool that provides a quantitative measure of stroke-related neurologic deficit. Scores for the NIHSS range from 0 to 42, with 0 representing no symptoms and 42 representing death.
Time frame: Baseline, 24 hours, Day 5, Day 30, Day 90
Population: Modified intention to treat (all participants who were randomized and received the entire infusion of study treatment); n=participants with assessments at Baseline and given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in National Institute of Health Stroke Scale (NIHSS) Score From Baseline to 24 Hours, Day 5, Day 30, and Day 90 | Change at 24 hours; n=82, 77 | -1.5 units on a scale | Standard Deviation 3.96 |
| Placebo | Change in National Institute of Health Stroke Scale (NIHSS) Score From Baseline to 24 Hours, Day 5, Day 30, and Day 90 | Change at Day 5; n=79, 72 | -3.3 units on a scale | Standard Deviation 5.31 |
| Placebo | Change in National Institute of Health Stroke Scale (NIHSS) Score From Baseline to 24 Hours, Day 5, Day 30, and Day 90 | Change at Day 30; n=73, 62 | -5.7 units on a scale | Standard Deviation 5.22 |
| Placebo | Change in National Institute of Health Stroke Scale (NIHSS) Score From Baseline to 24 Hours, Day 5, Day 30, and Day 90 | Change at Day 90; n=62, 56 | -7.3 units on a scale | Standard Deviation 3.95 |
| Natalizumab | Change in National Institute of Health Stroke Scale (NIHSS) Score From Baseline to 24 Hours, Day 5, Day 30, and Day 90 | Change at Day 90; n=62, 56 | -6.8 units on a scale | Standard Deviation 5.78 |
| Natalizumab | Change in National Institute of Health Stroke Scale (NIHSS) Score From Baseline to 24 Hours, Day 5, Day 30, and Day 90 | Change at 24 hours; n=82, 77 | -1.5 units on a scale | Standard Deviation 5.1 |
| Natalizumab | Change in National Institute of Health Stroke Scale (NIHSS) Score From Baseline to 24 Hours, Day 5, Day 30, and Day 90 | Change at Day 30; n=73, 62 | -4.9 units on a scale | Standard Deviation 5.73 |
| Natalizumab | Change in National Institute of Health Stroke Scale (NIHSS) Score From Baseline to 24 Hours, Day 5, Day 30, and Day 90 | Change at Day 5; n=79, 72 | -2.1 units on a scale | Standard Deviation 6.24 |
Comparison: Analysis of NIHSS score and change from Baseline at 24 hours. The repeated measures mixed effects model is modeling absolute change in NIHSS score relative to baseline and using an autoregressive variance-covariance matrix. The model adjusts for treatment, time, treatment by time, log baseline DWI volume, treatment time window, tPA use, baseline NIHSS score and location of stroke.p-value: 0.42790% CI: [-2.48, 1.98]repeated measures mixed effects model
Comparison: Analysis of NIHSS score and change from Baseline at Day 5. The repeated measures mixed effects model is modeling absolute change in NIHSS score relative to baseline and using an autoregressive variance-covariance matrix. The model adjusts for treatment, time, treatment by time, log baseline DWI volume, treatment time window, tPA use, baseline NIHSS score and location of stroke.p-value: 0.89690% CI: [-0.52, 3.94]repeated measures mixed effects model
Comparison: Analysis of NIHSS score and change from Baseline at Day 30. The repeated measures mixed effects model is modeling absolute change in NIHSS score relative to baseline and using an autoregressive variance-covariance matrix. The model adjusts for treatment, time, treatment by time, log baseline DWI volume, treatment time window, tPA use, baseline NIHSS score and location of stroke.p-value: 0.98990% CI: [0.89, 5.4]repeated measures mixed effects model
Comparison: Analysis of NIHSS score and change from Baseline at Day 90. The repeated measures mixed effects model is modeling absolute change in NIHSS score relative to baseline and using an autoregressive variance-covariance matrix. The model adjusts for treatment, time, treatment by time, log baseline DWI volume, treatment time window, tPA use, baseline NIHSS score and location of stroke.p-value: 0.91590% CI: [-0.38, 4.25]repeated measures mixed effects model
Secondary
Modified Rankin Scale (mRS) Distribution at Day 5, Day 30, and Day 90
The mRS measures independence, rather than neurologic function, with specific tasks pre- and post-stroke, respectively. The scale consists of 7 grades, from 0 to 6, with 0 corresponding to no symptoms and 6 corresponding to death. The distribution of mRS scores was summarized at each timepoint. An excellent outcome on the mRS was defined as a score of 0 or 1, while a good outcome was defined as a score of 0, 1, or 2.
Time frame: Day 5, Day 30, and Day 90
Population: Modified intention to treat (all participants who were randomized and received the entire infusion of study treatment), using imputed data; n=number of participants with an assessment at given time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Modified Rankin Scale (mRS) Distribution at Day 5, Day 30, and Day 90 | Day 5: Score 0; n=82, 76 | 0 participants |
| Placebo | Modified Rankin Scale (mRS) Distribution at Day 5, Day 30, and Day 90 | Day 5: Score 1; n=82, 76 | 3 participants |
| Placebo | Modified Rankin Scale (mRS) Distribution at Day 5, Day 30, and Day 90 | Day 5: Score 2; n=82, 76 | 10 participants |
| Placebo | Modified Rankin Scale (mRS) Distribution at Day 5, Day 30, and Day 90 | Day 5: Score 3; n=82, 76 | 13 participants |
| Placebo | Modified Rankin Scale (mRS) Distribution at Day 5, Day 30, and Day 90 | Day 5: Score 4; n=82, 76 | 25 participants |
| Placebo | Modified Rankin Scale (mRS) Distribution at Day 5, Day 30, and Day 90 | Day 5: Score 5; n=82, 76 | 29 participants |
| Placebo | Modified Rankin Scale (mRS) Distribution at Day 5, Day 30, and Day 90 | Day 5: Score 6; n=82, 76 | 2 participants |
| Placebo | Modified Rankin Scale (mRS) Distribution at Day 5, Day 30, and Day 90 | Day 30: Score 0; n=81, 72 | 0 participants |
| Placebo | Modified Rankin Scale (mRS) Distribution at Day 5, Day 30, and Day 90 | Day 30: Score 1; n=81, 72 | 7 participants |
| Placebo | Modified Rankin Scale (mRS) Distribution at Day 5, Day 30, and Day 90 | Day 30: Score 2; n=81, 72 | 14 participants |
| Placebo | Modified Rankin Scale (mRS) Distribution at Day 5, Day 30, and Day 90 | Day 30: Score 3; n=81, 72 | 17 participants |
| Placebo | Modified Rankin Scale (mRS) Distribution at Day 5, Day 30, and Day 90 | Day 30: Score 4; n=81, 72 | 22 participants |
| Placebo | Modified Rankin Scale (mRS) Distribution at Day 5, Day 30, and Day 90 | Day 30: Score 5; n=81, 72 | 13 participants |
| Placebo | Modified Rankin Scale (mRS) Distribution at Day 5, Day 30, and Day 90 | Day 30: Score 6; n=81, 72 | 8 participants |
| Placebo | Modified Rankin Scale (mRS) Distribution at Day 5, Day 30, and Day 90 | Day 90: Score 0; n=78, 72 | 4 participants |
| Placebo | Modified Rankin Scale (mRS) Distribution at Day 5, Day 30, and Day 90 | Day 90: Score 1; n=78, 72 | 12 participants |
| Placebo | Modified Rankin Scale (mRS) Distribution at Day 5, Day 30, and Day 90 | Day 90: Score 2; n=78, 72 | 12 participants |
| Placebo | Modified Rankin Scale (mRS) Distribution at Day 5, Day 30, and Day 90 | Day 90: Score 3; n=78, 72 | 15 participants |
| Placebo | Modified Rankin Scale (mRS) Distribution at Day 5, Day 30, and Day 90 | Day 90: Score 4; n=78, 72 | 14 participants |
| Placebo | Modified Rankin Scale (mRS) Distribution at Day 5, Day 30, and Day 90 | Day 90: Score 5; n=78, 72 | 8 participants |
| Placebo | Modified Rankin Scale (mRS) Distribution at Day 5, Day 30, and Day 90 | Day 90: Score 6; n=78, 72 | 13 participants |
| Natalizumab | Modified Rankin Scale (mRS) Distribution at Day 5, Day 30, and Day 90 | Day 30: Score 3; n=81, 72 | 17 participants |
| Natalizumab | Modified Rankin Scale (mRS) Distribution at Day 5, Day 30, and Day 90 | Day 5: Score 0; n=82, 76 | 2 participants |
| Natalizumab | Modified Rankin Scale (mRS) Distribution at Day 5, Day 30, and Day 90 | Day 90: Score 4; n=78, 72 | 11 participants |
| Natalizumab | Modified Rankin Scale (mRS) Distribution at Day 5, Day 30, and Day 90 | Day 5: Score 1; n=82, 76 | 2 participants |
| Natalizumab | Modified Rankin Scale (mRS) Distribution at Day 5, Day 30, and Day 90 | Day 30: Score 4; n=81, 72 | 14 participants |
| Natalizumab | Modified Rankin Scale (mRS) Distribution at Day 5, Day 30, and Day 90 | Day 5: Score 2; n=82, 76 | 11 participants |
| Natalizumab | Modified Rankin Scale (mRS) Distribution at Day 5, Day 30, and Day 90 | Day 90: Score 2; n=78, 72 | 10 participants |
| Natalizumab | Modified Rankin Scale (mRS) Distribution at Day 5, Day 30, and Day 90 | Day 5: Score 3; n=82, 76 | 11 participants |
| Natalizumab | Modified Rankin Scale (mRS) Distribution at Day 5, Day 30, and Day 90 | Day 30: Score 5; n=81, 72 | 11 participants |
| Natalizumab | Modified Rankin Scale (mRS) Distribution at Day 5, Day 30, and Day 90 | Day 5: Score 4; n=82, 76 | 16 participants |
| Natalizumab | Modified Rankin Scale (mRS) Distribution at Day 5, Day 30, and Day 90 | Day 90: Score 6; n=78, 72 | 14 participants |
| Natalizumab | Modified Rankin Scale (mRS) Distribution at Day 5, Day 30, and Day 90 | Day 5: Score 5; n=82, 76 | 31 participants |
| Natalizumab | Modified Rankin Scale (mRS) Distribution at Day 5, Day 30, and Day 90 | Day 30: Score 6; n=81, 72 | 9 participants |
| Natalizumab | Modified Rankin Scale (mRS) Distribution at Day 5, Day 30, and Day 90 | Day 5: Score 6; n=82, 76 | 3 participants |
| Natalizumab | Modified Rankin Scale (mRS) Distribution at Day 5, Day 30, and Day 90 | Day 90: Score 3; n=78, 72 | 13 participants |
| Natalizumab | Modified Rankin Scale (mRS) Distribution at Day 5, Day 30, and Day 90 | Day 30: Score 0; n=81, 72 | 5 participants |
| Natalizumab | Modified Rankin Scale (mRS) Distribution at Day 5, Day 30, and Day 90 | Day 90: Score 0; n=78, 72 | 8 participants |
| Natalizumab | Modified Rankin Scale (mRS) Distribution at Day 5, Day 30, and Day 90 | Day 30: Score 1; n=81, 72 | 8 participants |
| Natalizumab | Modified Rankin Scale (mRS) Distribution at Day 5, Day 30, and Day 90 | Day 90: Score 5; n=78, 72 | 6 participants |
| Natalizumab | Modified Rankin Scale (mRS) Distribution at Day 5, Day 30, and Day 90 | Day 30: Score 2; n=81, 72 | 8 participants |
| Natalizumab | Modified Rankin Scale (mRS) Distribution at Day 5, Day 30, and Day 90 | Day 90: Score 1; n=78, 72 | 10 participants |
Comparison: Analysis of distribution of mRS scores at Day 5. Odds ratio from a proportional-odds logistic regression model assuming a common odds ratio across all cut points of the mRS score. Covariates include baseline DWI volume (\< median vs \>= median), treatment time window, location of stroke abnormality (cortical/subcortical), and tPA use (yes/no).p-value: 0.56490% CI: [0.55, 1.45]Van Elteren's test
Comparison: Analysis of distribution of mRS scores at Day 30. Odds ratio from a proportional-odds logistic regression model assuming a common odds ratio across all cut points of the mRS score. Covariates include baseline DWI volume (\< median vs \>= median), treatment time window, location of stroke abnormality (cortical/subcortical), and tPA use (yes/no).p-value: 0.07790% CI: [0.8, 2.1]Van Elteren's test
Comparison: Analysis of the distribution of mRS scores at Day 90. Odds ratio from a proportional-odds logistic regression model assuming a common odds ratio across all cut points of the mRS score. Covariates include baseline DWI volume (\< median vs \>= median), treatment time window, location of stroke abnormality (cortical/subcortical), and tPA use (yes/no).p-value: 0.24390% CI: [0.71, 1.86]Van Elteren's test
Secondary
Number of Participants Who Experience Adverse Events (AEs) and Serious Adverse Events (SAEs)
AE: any untoward medical occurrence that does not necessarily have a causal relationship with this treatment. SAE: any untoward medical occurrence that at any dose: results in death; in the view of the Investigator, places the participant at immediate risk of death (a life-threatening event); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect; any other medically important event that, in the opinion of the Investigator, may jeopardize the participant or may require intervention to prevent one of the other outcomes listed in the definition above. Events were categorized as severe, moderate, or mild, and related or not related to study treatment.
Time frame: Up to Day 90 ± 5 days
Population: Safety population (all participants who were randomized and received any portion of the infusion of study treatment).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants Who Experience Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with a moderate or severe event | 60 participants |
| Placebo | Number of Participants Who Experience Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with a related event | 7 participants |
| Placebo | Number of Participants Who Experience Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with an event | 81 participants |
| Placebo | Number of Participants Who Experience Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with a serious event | 38 participants |
| Placebo | Number of Participants Who Experience Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with a severe event | 27 participants |
| Placebo | Number of Participants Who Experience Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants discontinuing due to an event | 0 participants |
| Placebo | Number of Participants Who Experience Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants withdrawing from study due to event | 2 participants |
| Natalizumab | Number of Participants Who Experience Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants discontinuing due to an event | 0 participants |
| Natalizumab | Number of Participants Who Experience Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants withdrawing from study due to event | 1 participants |
| Natalizumab | Number of Participants Who Experience Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with an event | 77 participants |
| Natalizumab | Number of Participants Who Experience Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with a moderate or severe event | 53 participants |
| Natalizumab | Number of Participants Who Experience Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with a severe event | 22 participants |
| Natalizumab | Number of Participants Who Experience Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with a related event | 6 participants |
| Natalizumab | Number of Participants Who Experience Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with a serious event | 36 participants |