Athersys B01-02

Overview

Status: Not yet recruiting
Keywords: Acute Ischemic Stroke , MultiStem
IRB Number: 00067967
Specialty: Neurology, Neurology
Sub Specialties: Neuro Critical Care, Stroke

Brief Summary

The primary objectives of this trial are the following:

1. To determine the highest well-tolerated and safest single dose of MultiStem up to a maximum of 1200 million total cells in subjects with ischemic stroke and

2. To determine the efficacy of MultiStem on functional outcome in ischemic stroke subjects.

The secondary objectives of this trial are the following:

1. To determine the safety of MultiStem in subjects with ischemic stroke and

2. To determine changes in functional outcomes and disease severity outcomes of ischemic stroke subjects treated with MultiStem.

The exploratory objectives of this trial are:

1. To evaluate changes in brain imaging metrics and blood biomarker outcomes

2. To evaluate the incidence of infection (local and systemic) in ischemic stroke subjects treated with MultiStem.

Detailed Description

This is a Phase 2, randomized, double-blind, placebo-controlled, multicenter, dose-escalation trial. The total trial duration for safety and efficacy follow-up will be 12 months. Approximately 140 subjects who experienced ischemic cortical stroke and fulfill all the eligibility criteria will be enrolled into the trial in the United States and in the United Kingdom. The trial will consist of 3 treatment cohorts. In Cohort 1, 8 subjects will be randomized in a 3:1 ratio to receive an infusion of MultiStem 400 million cells (n=6) or placebo (n=2). Infusions for the first 4 subjects in Cohort 1 will be staggered by 24 hours to ensure there are no safety issues prior to dosing the next subject. Following the last subject in Cohort 1 reaching 7 days post-infusion, an Independent Safety Committee will evaluate the dose-limiting toxicity (DLT) and other safety information for the 8 subjects to determine whether it is safe to proceed to Cohort 2. In Cohort 2, 8 additional subjects will be randomized in a 3:1 ratio to receive an infusion of MultiStem 1200 million cells (n=6) or placebo (n=2). Infusions for the first 4 subjects in Cohort 2 will be staggered by 24 hours to ensure there are no safety issues prior to dosing the next subject. Once both Cohorts 1 and 2 are enrolled and the final subject is 7 days post-infusion, the Independent Safety Committee will determine the highest MultiStem dose (400 million cells or 1200 million cells) that is safe to administer to subjects in Cohort 3. In Cohort 3, approximately 120 subjects will be randomized in a 1:1 ratio (MultiStem [n=60] or placebo [n=60]) to receive an infusion of the highest well-tolerated dose of MultiStem determined from Cohorts 1 and 2. Randomization will be stratified by baseline NIHSS score (<=12 and >=13). All subjects will be enrolled continuously into Cohort 3 of the trial. Safety data from Cohort 3 will be reviewed by the Independent Safety Committee once approximately 33% and then again after approximately 66% of subjects have received investigational product and been followed through 7-day safety assessments.

Principal Investigator: Dana DeWitt
Department: Neurology
Co Investigator: Jana Wold
Co Investigator: Jennifer Majersik

Contact Information

Name:Suyi Niu
Phone: 801-587-8046
Email: suyi.niu@hsc.utah.edu

Inclusion Criteria

Inclusion Criteria

Subjects will be eligible for the trial if they meet all of the following criteria:

1. Male or female subjects between 18 and 83 years of age, inclusive;

2. Clinical diagnosis of cortical cerebral ischemic stroke;

3. Occurrence of a moderate to moderately severe stroke with clear motor or speech deficit documented by NIHSS score of 8 to 20 (inclusive) that did not change by >4 points from the screening to baseline assessment. The NIHSS score must be confirmed during the baseline visit 24 to 44 hours from the time of stroke onset. Note: The NIHSS screening score used for eligibility should be the last score collected prior to the baseline reconfirmation NIHSS score. There should be >6 hours between baseline and the last NIHSS assessment during screening;

4. Onset of stroke must have occurred 24 to 48 hours prior to administering the investigational product. Time of onset is defined as the time point when symptoms first began. For stroke that occurred during sleep, time of onset is defined as the time point when the subject was last observed to be normal or was self-reported to be normal;

5. Confirmation of hemispheric cortical infarct with MRI including diffusion-weighted imaging (DWI) demonstrating an acute lesion measuring <5 mL and <100 mL;

6. A Rankin score of 0 or 1, by either self-report or family report, prior to the onset of the symptoms of the current stroke;

7. Subjects who received either tPA and/or underwent mechanical reperfusion, according to the approved labels of tPA and the mechanical device, are eligible if they meet all other eligibility criteria;

8. Female subjects who are either:

a. Not pregnant, not breastfeeding, and not planning on becoming pregnant during the study;

b. Not of childbearing potential, defined as one who has been postmenopausal for at least 1 year, or has been surgically sterilized, or has had a hysterectomy at least 3 months prior to the start of this trial; or

c. If of childbearing potential, must agree to use an effective method of avoiding pregnancy to the end of the trial. Effective methods of avoiding pregnancy are contraceptive methods used consistently and correctly (including implantable contraceptives, injectable contraceptives, oral contraceptives, transdermal contraceptives, intrauterine devices, diaphragm with spermicide, male or female condoms with spermicide, or cervical cap), abstinence, or a sterile sexual partner;

9. Male subjects with female partners of childbearing potential must agree to use adequate contraceptive methods (including a condom, plus 1 other form of contraception) if engaging in sexual intercourse;

10. Subjects or legal representatives must freely sign the informed consent form after the nature of the trial and the disclosure of his/her data has been explained;

11. Willing and able to comply with all aspects of the treatment and testing schedule; and

12. Willing and able to return to the trial site for the post-treatment evaluations.

 

Exclusion Criteria

Exclusion Criteria

Subjects are excluded from participation in the trial if any of the following criteria apply:

1. Presence of a lacunar or a brainstem infarct on MRI as the etiology of current stroke symptoms;

2. Reduced level of consciousness (score of >2 for item 1a of NIHSS);

3. Occurrence of a hemorrhagic transformation of ischemic stroke as evidenced by computerized tomography (CT) or brain MRI scan that is clinically significant in the opinion of the investigator;

4. Ipsilateral focal neurological deficits from prior lesions in the brain that would complicate evaluation;

5. History of arrhythmias or QTc prolongation that is clinically significant in the opinion of the investigator;

6. Experienced seizures since the onset of stroke;

7. Experienced a major neurological event such as stroke or clinically significant head trauma within 6 months of screening;

8. Uncontrolled hypertension, defined as persistent systolic blood pressure >220 mmHg or diastolic blood pressure >120 mmHg, despite antihypertensive therapy;

9. Blood glucose level <50 mg/dL or >350 mg/dL at baseline;

10. Significant abnormal laboratory tests at Screening:

a. >2 × upper limit of normal (ULN) for alanine aminotransferase (ALT) or aspartate aminotransferase (AST);

b. >1.5 × ULN for total bilirubin;

c. >2 × ULN for serum creatinine; or

 

d. any other abnormal laboratory results at screening that are considered to be clinically significant in the opinion of the investigator;

11. Subjects who have a significant comorbid medical condition(s), including but not limited to:

a. severe kidney disease requiring hemodialysis or peritoneal dialysis;

b. advanced liver disease such as hepatitis or liver cirrhosis;

c. severe congestive heart failure or history of ejection fraction <30%;

d. severe lung disease requiring home oxygen; or

e. active unstable angina requiring daily treatment with nitrates or other medications;

12. Known human immunodeficiency virus, ongoing systemic infection, severe local infection or who are immunocompromised;

13. Have Alzheimer’s disease or other dementias, Parkinson’s disease, or any other neurological disorder that would affect their ability to participate in the trial or confound study assessments;

14. Have a history of malignancy of any type, with the exception of adequately treated basal or squamous cell carcinoma of the skin;

15. Have a contraindication for MRI such as implanted pacemakers or other metallic prosthesis incompatible with MRI, body weight, or claustrophobia;

16. Have thrombocytopenia (platelet count <75,000/mm3) or heparin-induced thrombocytopenia;

17. Have a life expectancy less than 90 days;

18. Have a known allergy or religious objections to human tissue or bovine or porcine products;

19. Prior participation in any other trial involving investigational pharmacological agents or devices within 30 days prior to investigational product infusion or planned participation in investigational rehabilitation stroke recovery program;

20. 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 according to the protocol;

21. Previous surgical removal of the spleen;

22. Major fluctuation in neurological status since the onset of stroke indicating progression or expansion of stroke, or possible transient ischemic attack; or

23. Plan to have a neurovascular procedure (eg, carotid endarterectomy, stent placement, etc.) within the first year following stroke.