Principal Investigator: Dana DeWitt
Keywords: ischemic stroke , stem cells Department: Neurology
IRB Number: 00117144
Specialty: Neurology, Neurology
Sub Specialties: Neuro Critical Care, Stroke
Recruitment Status: Recruiting

Contact Information

Kinga Aitken

Brief Summary

The primary objective of this study is to evaluate the efficacy of MultiStem on functional outcome in subjects with ischemic stroke.

The secondary objectives of this study are the following:
 To evaluate the efficacy of MultiStem on functional, neurological, mortality, secondary infection, and hospitalization outcomes in subjects with ischemic stroke; and
 To evaluate the safety of MultiStem in subjects with ischemic stroke.
The tertiary objectives of this study are the following:
 To evaluate the impact of MultiStem on quality of life and healthcare and rehabilitation services utilization in subjects with ischemic stroke; and
 To evaluate the mechanism of action of MultiStem through blood biomarkers, and spleen and brain imaging outcomes in subjects with ischemic stroke.

Inclusion Criteria

Inclusion criteria
Subjects will be eligible for the study if they meet all of the following inclusion criteria:
1. Male or female subjects 18 years of age or older;
2. Clinical diagnosis of ischemic stroke involving cerebral cortex;
o This inclusion criterion requires clinical signs that are consistent with imaging abnormalities required under inclusion criterion #5. Clinical diagnosis is defined as rapidly developed clinical signs of 1 or more focal (and potentially accompanying global) persistent disturbance(s) of cerebral function, with no apparent cause other than arterial occlusive ischemic stroke that involves cerebral cortex;

3. Onset of stroke symptoms must have occurred 18 to 36 hours prior to the planned start of administration of the investigational product;
Note: Time of onset is defined as the time point, if known, when symptoms first began. For a stroke that occurred during sleep, or in an individual unable to report the time that symptoms began, the time of onset is defined as the time point when the subject was last observed to exhibit normal neurological function or was self-reported to have normal function;
4. Occurrence of a moderate to moderately severe stroke with a persistent neurologic deficit documented by a National Institutes of Health Stroke Scale (NIHSS) score of 8 to 20 (inclusive) that does not change by 4 points from the Screening to the Baseline assessment;
Note: The Screening NIHSS score used for determination of eligibility should be collected as soon as possible following admission to the hospital, or in the event a subject receives concomitant reperfusion therapy, the subject’s Screening NIHSS score must be collected within 4 hours following completion of the last reperfusion (mechanical or pharmacologic) therapy;
5. Confirmation of hemispheric cortical infarct by brain magnetic resonance imaging (MRI) or computed tomography (CT) demonstrating an acute ischemic infarct measuring 5 mL and 100 mL;
6. A modified Rankin Scale (mRS) score of 0 or 1 prior to the onset of symptoms of the current stroke, by either self-reported history or by family/caregiver report;
7. Female subjects must not be pregnant, breastfeeding, or planning on becoming pregnant during the study; and either:
a. Not of childbearing potential, defined as one who has been postmenopausal for at least 1 year, or has been surgically sterilized; or
b. Agree to use a medically accepted, effective method of avoiding pregnancy through the Day 90 Visit. Effective methods of contraception are defined as those that result in a low failure rate (<1% per year) when used consistently and correctly. Such methods include the use of oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products (such as an intrauterine diaphragm, condoms, or spermicides);
8. Male subjects with female sexual partners of childbearing potential must also agree to use an effective method of avoiding pregnancy through the Day 90 Visit;
9. Subjects or legally authorized representatives (LARs) must freely sign the informed consent form after the nature of the study and the disclosure of his/her data have been explained;
10. Willing and able to comply with all aspects of the treatment and testing schedule; and
11. Willing and able to return to the study site for the post-treatment evaluations.

Exclusion Criteria

Exclusion criteria
Subjects will not be eligible for the study if they meet any of the following exclusion criteria:
1. Presence of a lacunar or a brainstem infarct on MRI or CT as the etiology of current stroke symptoms;

2. Coma (score of 3 for item 1a of NIHSS);
3. Occurrence of a hemorrhagic transformation of ischemic stroke as evidenced by brain MRI or CT that is clinically significant in the opinion of the Investigator;
4. Fluctuation in neurologic status since the onset of stroke suggesting possible progression or expansion of stroke, transient ischemic attack, or stroke mimic;
5. Onset of stroke >28 hours prior to the start of Screening;
Note: Onset of stroke >28 hours prior to the start of Screening would not allow for administration of investigational product per protocol;
6. Less than 6 hours between the Screening and Baseline NIHSS assessment;
7. Initiation of intravenous (IV) tissue plasminogen activator (tPA) infusion >4.5 hours and/or mechanical reperfusion (MR) (defined as time of groin puncture) >8 hours after the onset of stroke;
8. Plan to have a neurovascular procedure (e.g., carotid endarterectomy, stent placement, etc.) within the first year following stroke;
9. Pre-existing ipsilateral focal neurologic deficits that would complicate evaluation;
10. Seizure since the onset of stroke or prior history of seizures, with the exception of simple febrile seizures in childhood;

11. Major neurologic event such as stroke or clinically significant head trauma in the 6 months preceding study entry;
12. Uncontrolled hypertension prior to randomization, defined as persistent systolic blood pressure >220 mmHg or diastolic blood pressure >120 mmHg despite antihypertensive therapy;
13. Blood glucose level <50 mg/dL or >350 mg/dL prior to randomization despite concomitant therapy;
14. Significant comorbid medical condition(s), including, but not limited to:
a. End-stage renal disease requiring renal replacement therapy;
b. Advanced liver disease (e.g., Childs-Pugh score >10);
c. Severe congestive heart failure (e.g., New York Heart Association score of III or IV) or ejection fraction <30%;

d. Severe lung disease requiring continuous home oxygen; or
e. Symptomatic refractory angina requiring daily treatment with nitrates or other medications;
15. Concurrent systemic infection or severe local infection;
16. Immunocompromised state due to immunosuppressive medications or as evidenced by hematologic studies or history of opportunistic infection;

17. History of Alzheimer’s disease or other dementias, Parkinson’s disease, or any other neurological disorder that in the opinion of the Investigator would affect the subject’s ability to participate in the study or confound study assessments;
18. History of malignancy of any type within 2 years of stroke onset, with the exception of adequately treated basal or squamous cell carcinoma of the skin;
19. Life expectancy less than 90 days;
20. Prior surgical removal of the spleen or functional asplenia;
21. Allergy or religious objections to human tissue or bovine or porcine products;
22. Participation in any other study involving an investigational product or device within the last 30 days or planned participation in investigational rehabilitation stroke recovery program; or
23. Other serious medical or psychiatric illness that is not adequately controlled and, in the Investigator’s opinion, would not permit the subject to be managed or evaluated according to the protocol.