Acute Ischemic Stroke
Conditions
Keywords
Acute Ischemic Stroke, ABT-555, Elezanumab, EAISE
Brief summary
Stroke is one of the leading causes death and major functional disability worldwide. Treatment options for acute stroke are limited with many patients having residual neurologic impairment. The purpose of this study is to evaluate the safety and efficacy of elezanumab and assess change in neurologic function in participants following an acute ischemic stroke. Elezanumab is an investigational drug being developed for the treatment of acute ischemic stroke. This 52-week study is double-blinded', which means that neither the participants nor the study doctors will know who will be given elezanumab and who will be given placebo (does not contain treatment drug). Participants will be assigned to one of two groups, called treatment arms. Participants in one arm will receive elezanumab and participants in the other arm will receive placebo. There is a 1 in 2 chance that participants will be assigned to placebo. Approximately 120 subjects will be enrolled in 45 sites worldwide. Participants will be randomized to elezanumab or placebo by intravenous (IV) infusion within 24 hours of last known normal (time when the participant was last known to be without signs and symptoms of the current stroke) and every 4 weeks thereafter for 48 weeks for a total of 13 doses. There may be a higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the course of the study at a hospital or clinic. The effect of elezanumab will be checked by medical assessments, blood tests, evaluation of side effects, and completion of questionnaires.
Interventions
DRUGElezanumab
Intravenous (IV) infusion
DRUGPlacebo
Intravenous (IV) infusion
Sponsors
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Clinical diagnosis of acute ischemic stroke, supported by acute brain computed tomography (CT) or magnetic resonance imaging (MRI) consistent with the clinical diagnosis. * Able to randomize within 24 hours of last known normal. * National Institute of Health Stroke Scale (NIHSS) total score of 7 to 21, inclusive. * Participants or their legally authorized representative confirms that prior to index stroke, no significant impairment in participant's ability to perform activities of daily living without assistance.
Exclusion criteria
* Evidence of severe stroke on imaging based on available acute imaging studies performed under the standard of care. * Evidence of acute seizure at the onset of index stroke without conclusive imaging of ischemic stroke. * Evidence of acute myocardial infarction. * Symptoms are considered likely to resolve within the subsequent few hours (e.g., transient ischemic attack \[TIA\]). * Known history prior to randomization of clinically significant medical conditions (other than current acute ischemic stroke) or any other reason, including any physical, psychological, or psychiatric condition that in the investigator's opinion would compromise the safety or interfere with the participant's participation in this study. * Known medical history of repeated episodes of complex migraine. Participants with history of complex migraine, but with imaging conclusively demonstrating an acute ischemic stroke are still allowed. * Female who is pregnant, breastfeeding, or considering becoming pregnant during the study or for within 39 weeks (5 half-lives) after the last dose of study drug. * Known receipt of any investigational product within 30 days or 5 half-lives of the drug (whichever is longer) prior to the first dose of study drug. No current enrollment in another interventional clinical study, including pharmacologic and behavioral interventional studies.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Analysis of the National Institutes of Health Stroke Scale (NIHSS) Total Score Area Under the Curve During the Treatment Period | Day 1 through Week 52 | The National Institutes of Health Stroke Scale (NIHSS) is a neurological examination used to quantitatively measure the severity of acute stroke by evaluating impact of cerebral infarction on level of consciousness, gaze, visual field, facial palsy, motor ability of arm and leg, limb ataxia, sensation, language, dysarthria, and extinction/inattention. Domains are scored on a scale of 0 to 2, 0 to 3, or 0 to 4, for a total range of 0 to 42 points with higher scores indicating impairment. The monthly-adjusted AUC of the NIHSS total score for each treatment group was derived using the trapezoidal method and contrasts from a Mixed Model with Repeated Measures (MMRM). Please refer to the formula for AUCi in the Statistical Analysis Plan (SAP) where i = treatment group (placebo, elezanumab) and j = visit during the Treatment Period {Day 1, Day 2-4, Week 4, Week 8, Week 12, Week 24, Week 36, Week 52}. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Responder Status Based on Modified Rankin Scale (mRS) | Week 52 | The mRS is used to assess participant's disability and functional dependence. It is a 6-point scale ranging from 0 (no symptoms) to 5 (severe disability), with additional rating of 6 if the participant is deceased. |
Countries
Australia, Canada, Japan, South Korea, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants will receive placebo for elezanumab via Intravenous (IV) infusion. | 60 |
| Elezanumab Participants will receive elezanumab 1800 mg via Intravenous (IV) infusion. | 59 |
| Total | 119 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 1 |
| Overall Study | Lost to Follow-up | 1 | 2 |
| Overall Study | Not disclosed | 10 | 6 |
| Overall Study | Randomized but not treated | 0 | 2 |
| Overall Study | Withdrawal by Subject | 6 | 9 |
Baseline characteristics
| Characteristic | Placebo | Elezanumab | Total |
|---|---|---|---|
| Age, Customized 70 to < 80 years | 18 Participants | 19 Participants | 37 Participants |
| Age, Customized < 70 years | 27 Participants | 25 Participants | 52 Participants |
| Age, Customized ≥ 80 years | 15 Participants | 15 Participants | 30 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 5 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 53 Participants | 54 Participants | 107 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 9 Participants | 10 Participants | 19 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 4 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 46 Participants | 45 Participants | 91 Participants |
| Sex: Female, Male Female | 32 Participants | 24 Participants | 56 Participants |
| Sex: Female, Male Male | 28 Participants | 35 Participants | 63 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 7 / 60 | 1 / 61 |
| other Total, other adverse events | 52 / 60 | 49 / 61 |
| serious Total, serious adverse events | 23 / 60 | 18 / 61 |
Outcome results
Primary
Analysis of the National Institutes of Health Stroke Scale (NIHSS) Total Score Area Under the Curve During the Treatment Period
The National Institutes of Health Stroke Scale (NIHSS) is a neurological examination used to quantitatively measure the severity of acute stroke by evaluating impact of cerebral infarction on level of consciousness, gaze, visual field, facial palsy, motor ability of arm and leg, limb ataxia, sensation, language, dysarthria, and extinction/inattention. Domains are scored on a scale of 0 to 2, 0 to 3, or 0 to 4, for a total range of 0 to 42 points with higher scores indicating impairment. The monthly-adjusted AUC of the NIHSS total score for each treatment group was derived using the trapezoidal method and contrasts from a Mixed Model with Repeated Measures (MMRM). Please refer to the formula for AUCi in the Statistical Analysis Plan (SAP) where i = treatment group (placebo, elezanumab) and j = visit during the Treatment Period {Day 1, Day 2-4, Week 4, Week 8, Week 12, Week 24, Week 36, Week 52}.
Time frame: Day 1 through Week 52
Population: Full Analysis Set~Note: The AUC for each treatment group, as well as the difference in AUCs (placebo minus elezanumab) and their respective standard errors and confidence intervals are presented.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Analysis of the National Institutes of Health Stroke Scale (NIHSS) Total Score Area Under the Curve During the Treatment Period | 3.83 units on a scale |
| Elezanumab | Analysis of the National Institutes of Health Stroke Scale (NIHSS) Total Score Area Under the Curve During the Treatment Period | 3.13 units on a scale |
95% CI: [-0.764, 2.175]
Secondary
Responder Status Based on Modified Rankin Scale (mRS)
The mRS is used to assess participant's disability and functional dependence. It is a 6-point scale ranging from 0 (no symptoms) to 5 (severe disability), with additional rating of 6 if the participant is deceased.
Time frame: Week 52
Population: Full Analysis Set~N indicates the number of subjects with non-missing values at each time point.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Responder Status Based on Modified Rankin Scale (mRS) | 28 Participants |
| Elezanumab | Responder Status Based on Modified Rankin Scale (mRS) | 29 Participants |
95% CI: [0.71, 4.24]