A Safety and Dose Finding Study of Plasmin (Human) Administered Into the Middle Cerebral Artery of Stroke Patients

Study Overview
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Brief Summary
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This study tests the drug, Plasmin (Human), in patients with a stroke due to a clot in the middle cerebral artery (MCA). Plasmin is an enzyme that causes clot lysis by cleaving a clot component, fibrin. In this study, Plasmin (Human) is administered locally through a catheter to the clot within 9 hours of the stroke onset. Three doses of Plasmin (Human) (20 mg, 40 mg, and 80 mg) are being tested in 3 different groups of patients. Patients are monitored by imaging of the affected artery and functional testing.

Detailed Description
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This is a Phase 1/2a, open-label, multi-center, sequential dose escalation, safety study of Plasmin (Human) in acute ischemic stroke caused by middle cerebral artery occlusion documented by arteriography. Plasmin (Human) will be administered through a catheter into the thrombus within 9 hours of stroke onset. Approximately sixty-one (61) patients will be enrolled and will receive Plasmin (Human). The objectives of this study are to determine the safety of escalating doses of Plasmin (Human) and to determine the proportion of patients with treatment success, defined as partial or full recanalization.

Official Title
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A Phase 1/2a, Open Label, Dose Escalation, Safety Study of Intra-thrombus Plasmin (Human) Administration in Acute, Middle Cerebral Artery, Ischemic Stroke

Conditions
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Acute Ischemic Stroke

Intervention / Treatment
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* Biological: Plasmin (Human)
* Biological: Plasmin (Human)
* Biological: Plasmin (Human)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 to 85 years of age Male or female New focal, potentially disabling neurologic deficit clinically localized to the MCA distribution Intra-arterial therapy with Plasmin completed within 9 hours of stroke onset A National Institutes of Health Stroke Scale score ≥ 4 and ≤ 25 Exclusion Criteria: Intracranial procedures or intracranial or systemic bleeding within the last year Intracranial neoplasm (except meningioma), septic embolism, or unsecured aneurysm Active bleeding History of stroke in previous 6 weeks Uncontrolled hypertension Renal disease or renal dialysis Treatment with any plasminogen activator within the last 48 hrs. Therapy with a Glycoprotein IIb/IIIa inhibitor in 5 days prior to study enrollment or at any time during study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 20 mg Plasmin (Human)<br>20 mg of Plasmin (Human) | Biological: Plasmin (Human)<br>* Plasmin (Human), 20 mg, delivered through a catheter into a thrombus<br>* Other names: BAY-57-9602;|
| Experimental: 40 mg Plasmin (Human)<br>40 mg of Plasmin (Human) | Biological: Plasmin (Human)<br>* Plasmin (Human), 40 mg, delivered through a catheter into a thrombus<br>* Other names: BAY-57-9602;|
| Experimental: 80 mg Plasmin (Human)<br>80 mg of Plasmin (Human) | Biological: Plasmin (Human)<br>* Plasmin (Human), 80 mg, delivered through a catheter into a thrombus<br>* Other names: BAY-57-9602;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Symptomatic Intracranial Hemorrhage (SICH) by Dose Cohort |  | 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stroke, plasmin, thrombus, ischemic, middle cerebral artery, thrombolysis, intra-arterial, fibrin