Acute Ischemic Stroke
Conditions
Keywords
stroke, plasmin, thrombus, ischemic, middle cerebral artery, thrombolysis, intra-arterial, fibrin
Brief summary
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
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.
Interventions
BIOLOGICALPlasmin (Human)
Plasmin (Human), 20 mg, delivered through a catheter into a thrombus
Sponsors
Grifols Therapeutics LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. 18 to 85 years of age 2. Male or female 3. New focal, potentially disabling neurologic deficit clinically localized to the MCA distribution 4. Intra-arterial therapy with Plasmin completed within 9 hours of stroke onset 5. A National Institutes of Health Stroke Scale score ≥ 4 and ≤ 25
Exclusion criteria
1. Intracranial procedures or intracranial or systemic bleeding within the last year 2. Intracranial neoplasm (except meningioma), septic embolism, or unsecured aneurysm 3. Active bleeding 4. History of stroke in previous 6 weeks 5. Uncontrolled hypertension 6. Renal disease or renal dialysis 7. Treatment with any plasminogen activator within the last 48 hrs. 8. Therapy with a Glycoprotein IIb/IIIa inhibitor in 5 days prior to study enrollment or at any time during study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of Symptomatic Intracranial Hemorrhage (SICH) by Dose Cohort | 90 days |
Countries
Australia, Austria, France, Serbia, Slovakia, Spain
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Safety Population Plasmin (Human): Plasmin (Human), 20 mg, 40 mg, or 80 mg, delivered through a catheter into a thrombus | 40 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 3 | 3 | 4 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | Safety Population |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 32 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants |
| Age, Continuous | 73.1 years STANDARD_DEVIATION 9.38 |
| Region of Enrollment Australia | 5 participants |
| Region of Enrollment Austria | 1 participants |
| Region of Enrollment France | 7 participants |
| Region of Enrollment Germany | 4 participants |
| Region of Enrollment Serbia | 10 participants |
| Region of Enrollment Slovakia | 5 participants |
| Region of Enrollment Spain | 8 participants |
| Sex: Female, Male Female | 20 Participants |
| Sex: Female, Male Male | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 8 / 8 | 12 / 16 | 12 / 16 |
| serious Total, serious adverse events | 6 / 8 | 7 / 16 | 7 / 16 |
Outcome results
Primary
Incidence of Symptomatic Intracranial Hemorrhage (SICH) by Dose Cohort
Time frame: 90 days
Population: Safety Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 20 mg Plasmin (Human) | Incidence of Symptomatic Intracranial Hemorrhage (SICH) by Dose Cohort | 0 participants |
| 40 mg Plasmin (Human) | Incidence of Symptomatic Intracranial Hemorrhage (SICH) by Dose Cohort | 0 participants |
| 80 mg Plasmin (Human) | Incidence of Symptomatic Intracranial Hemorrhage (SICH) by Dose Cohort | 0 participants |