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

Phase 1

Active, not recruiting

• Conditions: Thrombus in acute ischemic stroke of the middle cerebral artery; MedDRA version: 12.0Level: HLTClassification code 10007948Term: Central nervous system haemorrhages and cerebrovascular accidents

• Registration Number: EUCTR2009-012086-66-SK
• Lead Sponsor: Talecris Biotherapeutics Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-02-28
• Last Update Posted: 3 April 2017

Recruitment & Eligibility

• Status: Not Recruiting
• Sex: All
• Target Recruitment: 75

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 Arteriography - 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 arteriography (Section 3.2.3.1)
5. Intra-arterial (IA) therapy with Plasmin must be completed within 9 hours of stroke onset (e.g., Plasmin infusion must start: a) within 8.5 hours of stroke onset in cohorts 1, 2a and 2b; b) within 8 hours of stroke onset in cohort 2c; and c) within 8 or 8.5 hours of stroke onset in cohort 3, depending on the infusion rate/time selected from cohort 2
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 an authorized
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. Patient is eligible for IV administration of tissue plasminogen activator (e.g.
alteplase)
2. Previous treatment for this event with mechanical embolectomy or cerebral
angioplasty / stenting of target lesion
3. 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
4. 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
5. Clinical evidence of significant medical, neurologic, or psychiatric disease that may
confound the study outcome assessments
6. 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
7. Participation in another treatment clinical study within 30 days prior to entry
8. History of intracranial procedures or intracranial or systemic bleeding within the last year
9. Previous history of intracranial neoplasm (except meningioma)
10. History of stroke in previous 6 weeks
11. Within 48 hours, major or minor surgery, biopsy of a parenchymal organ, or major
trauma/injury with internal injuries, lumbar puncture or hemorrhage
12. Catheter Arteriography - Inability for whatever reason (e.g. arterial stenosis, vessel tortuosity) to access the target lesion and achieve contact between the microcatheter and the proximal aspect of the target thrombus
13. Acute ICH of any degree or location
14. Evidence of active bleeding/hemorrhage or acute trauma on physical examination
15. Coma or severe obtundation with fixed eye deviation and complete hemiplegia.
Coma is defined as 2 or more points in the NIHSS Level of Consciousness exam
item.
16. An NIHSS score > 25
17. Significant intracranial mass effect leading to midline shift
18. 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
19. Seizures at onset of stroke symptoms
20. 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
21. 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
22. Presence of an unsecured aneurysm
23. Clinical presentation suggestive of subarachnoid hemorrhage, even if initial imaging study is normal
24. Suspected lacunar stroke
25. 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.
26. Known or presumed septic embolus
27. Creatinine = 2.0 mg/dL or patient on renal dialysis
28. Previous severe or anaphylactic or anaphylactoid reaction to contrast agent,
streptokinase, or blood products

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified