Acute Ischemic Stroke MedDRA version: 18.1 Level: LLT Classification code 10055221 Term: Ischemic stroke System Organ Class: 100000004852
Conditions
Sponsors
Biogen Idec Research Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: To be eligible to participate in this study, candidates must meet the following eligibility criteria at Screening or at the timepoint specified in the individual eligibility criterion listed. All eligibility assessments must be completed in time for dosing within 6 hours or >6 to =9 hours of the subject’s LKN: 1. Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations OR provision of informed consent by the subject’s representative in accordance with all local and national regulations, and according to the local institutional review board’s (IRB’s)/ethics committee’s (EC’s) guidelines OR by another process compliant with applicable national laws and regulations and IRB/EC requirements. 2. Aged 18 to 85 years old, inclusive, at the time of enrollment. 3. Diagnosis of acute ischemic stroke defined by LKN at =6 hours or at >6 to =9 hours prior to study treatment initiation. 4. Score of =6 points on the NIHSS at Screening. 5. At least 1 acute infarct with largest diameter of more than 2 cm on Baseline brain DWI. 6. Participants who have received reperfusion therapy (either tissue plasminogen activator or endovascular treatment) may be eligible to participate but must meet all eligibility criteria and perform the Baseline study MRI after reperfusion therapy has been completed. 7. 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 160 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: Candidates will be excluded from study entry if any of the following exclusion criteria exist at Screening or at the timepoint specified in the individual criterion listed: 1. Presence of any ICH on head CT or non-petechial ICH on screening MRI. 2. Stroke isolated to the brainstem. 3. Presence of coma 4. Expected to die OR unable to be evaluated within 5 days. 5. Hypotension requiring the use of IV vasopressor support or systolic blood pressure <90 mmHg at the time of randomization. 6. Known prior treatment with natalizumab. 7. Immunocompromised subjects, as determined by the Investigator, based on medical history, physical examination, or laboratory testing, or due to prior or current cancer or immunosuppressive or immunomodulating treatment. 8. History of PML. 9. 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. 10. Abnormal laboratory values indicative of or history of significant medical, neurologic (other than stroke), or psychiatric disorders or known or suspected substance abuse that might, in the opinion of the Investigator, preclude safe participation in the study or confound study assessments. 11. Known history of hematological malignancy within the last 5 years. 12. Malignancy suspected to be the underlying cause of current stroke. 13. Unwillingness or inability to comply with the requirements of the protocol, including the presence of any condition (physical, mental, or social) that is likely to affect the subject’s ability to comply with the protocol. 14. Nursing or pregnant female, female planning to become pregnant during study participation, or male planning to father a child during study participation. 15. Known participation in any other investigational study that involved treatment with an investigational product within 6 months prior to enrollment. 16. Recent or ongoing hypersensitivity reaction to tissue plasminogen activator treatment. 17. Other unspecified reasons that, in the opinion of the Investigator and/or Biogen Idec, make the subject unsuitable for enrollment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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 subjects with acute ischemic stroke when given at =6 hours or at >6 to =9 hours from when they were last known normal (LKN).;Secondary Objective: 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 subjects with acute ischemic stroke ;Primary end point(s): The primary endpoint is the change in infarct volume from Baseline (diffusion-weighted imaging [DWI]) to Day 5 (fluid-attenuated inversion recovery [FLAIR]) ;Timepoint(s) of evaluation of this end point: Day 5 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints are as follows: • Change in infarct volume from Baseline (DWI) to Day 30 (FLAIR) • Change in infarct volume from 24 hours (DWI) to Day 5 and Day 30 (FLAIR) • Change in National Institute of Health Stroke Scale (NIHSS) score from Baseline to 24 hours, Day 5, Day 30, and Day 90 • Modified Rankin Scale (mRS) distribution at Day 5, Day 30, and Day 90 • Barthel Index at Day 5, Day 30, and Day 90 • Incidence of AEs and serious AEs (SAEs) ;Timepoint(s) of evaluation of this end point: • Infarct volume from Baseline: Day 30 • Infarct volume from 24 hours: Day 5 and Day 30 • NIHSS: 24 hours, Day 5, Day 30 and Day 90 • mRS: Day 5, Day 30, and Day 90 • Barthel Index: Day 5, Day 30, and Day 90 • SAEs: as necessary | — |
Countries
Germany, Spain, United States
Outcome results
None listed