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

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 40

Inclusion Criteria

1.18 through 85 years of age, inclusive
2.Male and female patients
3.New focal, potentially disabling neurologic deficit clinically localized to the MCA distribution
4.Catheter Angiography - Complete occlusion or contrast penetration with minimal perfusion of either the M1 segment and/or M2 segment and/or M2 division of the MCA (M1, M2, or M1-2 only) as assessed by angiography (Section 3.2.3.1)
5.Intra-arterial (IA) therapy can be initiated within 8.5 hours of the last known well time
6.An NIHSS score of =4 and =25, except for isolated aphasia
7.Women of child-bearing potential must practice a highly effective method of contraception (oral, injectable or implanted hormonal methods of contraception, placement of an intrauterine device [IUD] or intrauterine system [IUS], condom or occlusive cap with spermicidal foam/gel/film/cream/suppository, male sterilization, or true abstinence) throughout the study and must have a negative pregnancy test prior to study entry
8.Willing and able to provide written informed consent or have a legal representative able to provide written informed consent on behalf of the patient in accordance with local law and institutional policy

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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.Clinical evidence of significant medical, neurologic, or psychiatric disease that may confound the study outcome assessments
2.Women who are pregnant or lactating or, if of child-bearing potential, unwilling to practice a highly effective method of contraception (oral, injectable or implanted hormonal methods of contraception, placement of an intrauterine device [IUD] or intrauterine system [IUS] condom or occlusive cap with spermicidal foam/gel/film/cream/suppository, male sterilization, or true abstinence) throughout the study
3.Participation in another treatment clinical study within 30 days prior to entry
4.History of intracranial procedures or intracranial or systemic bleeding within the last year
5.Previous history of intracranial neoplasm (except meningioma)
6.History of stroke in previous 6 weeks
7.Within 48 hours, major or minor surgery, biopsy of a parenchymal organ, or major trauma/injury with internal injuries, lumbar puncture or hemorrhage
8.Catheter Angiography - Inability for whatever reason (e.g. arterial stenosis, vessel tortuosity) to access the target thrombus and achieve intra-thrombus placement of the microcatheter
9.Acute ICH of any degree or location
10.Evidence of active bleeding/hemorrhage or acute trauma on physical examination
11.Coma or severe obtundation with fixed eye deviation and complete hemiplegia
12.An NIHSS score > 25
13.Significant intracranial mass effect leading to midline shift
14.Acute hypodense/hyperintense parenchymal lesion or effacement of cerebral sulci in more than one third of the MCA distribution as confirmed during pre-study imaging
15.Seizures at onset of stroke symptoms
16.Uncontrolled hypertension defined by a systolic blood pressure > 180 mmHg or diastolic blood pressure > 110 mmHg on 3 separate occasions at least 10 minutes apart or requiring intravenous antihypertensive treatment by continuous infusion to reduce blood pressure to within these limits
17.Known hereditary or acquired hemorrhagic diathesis with baseline international normalized ratio (INR) > 1.7, activated partial thromboplastin time (aPTT) > 1.5 times normal, or baseline platelet count <100 x 109/L
18.Presence of an unsecured aneurysm
19.Clinical presentation suggestive of subarachnoid hemorrhage, even if initial imaging study is normal
20.Suspected lacunar stroke
21.Proximal stenosis with complete occlusion or simultaneous stenting / angioplasty, if deemed necessary by the interventionalist. Stenosis that does not impair accessibility to the primary lesion is allowed.
22.Known or presumed septic embolus
23.Creatinine = 2.0 mg/dL or patient on renal dialysis
24.Previous severe or anaphylactic or anaphylactoid reaction to contrast agent, streptokinase, or blood products
25.Patient is eligible for IV administration of tissue plasminogen activator (e.g. alteplase)
26.Previous treatment for this event with mechanical embolectomy or cerebral angioplasty / stenting of target lesion
27.Treatment with any PA (e.g., streptokinase (e.g., Streptase®, Kabikinase®), anistreplase (Eminase®), alteplase (e.g., Activase®), reteplase (e.g., Retavase®), tenecteplase (TNKase™), UK (Abbokinase)) within the last 48 hours
28.Therapy with a Glycoprotein IIb/IIIa inhibitor (e.g. abciximab) in the 5 days prior to study enrollment or at any time during the study
29.Previous treatment with systemic heparin within the previous 48 hours.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: •To evaluate the safety of Plasmin (Human) in escalating doses in patients with acute MCA ischemic stroke given within 9 hours of stroke symptom onset.;Secondary Objective: •To determine the proportion of Treatment Successes - the proportion of patients with treatment success defined as partial or full recanalization as designated by a score of 2a, 2b, or 3 on the Thrombosis In Cerebral Infarction (TICI) scale ;Primary end point(s): •To evaluate the safety of Plasmin (Human) in escalating doses in patients with acute MCA ischemic stroke given within 9 hours of stroke symptom onset

Secondary Outcome Measures

Name	Time	Method

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