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

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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.

Condition or disease	Intervention/treatment	Phase
Acute Ischemic Stroke	Biological: Plasmin (Human)	Phase 1; Phase 2

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	40 participants
Allocation:	Non-Randomized
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Phase 1/2a, Open Label, Dose Escalation, Safety Study of Intra-thrombus Plasmin (Human) Administration in Acute, Middle Cerebral Artery, Ischemic Stroke
Study Start Date :	November 2009
Actual Primary Completion Date :	November 2013
Actual Study Completion Date :	February 2014

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
Experimental: 20 mg Plasmin (Human); 20 mg of Plasmin (Human)	Biological: Plasmin (Human); Plasmin (Human), 20 mg, delivered through a catheter into a thrombus; Other Names: TAL-05-00018; BAY-57-9602
Experimental: 40 mg Plasmin (Human); 40 mg of Plasmin (Human)	Biological: Plasmin (Human); Plasmin (Human), 40 mg, delivered through a catheter into a thrombus; Other Names: TAL-05-00018; BAY-57-9602
Experimental: 80 mg Plasmin (Human); 80 mg of Plasmin (Human)	Biological: Plasmin (Human); Plasmin (Human), 80 mg, delivered through a catheter into a thrombus; Other Names: TAL-05-00018; BAY-57-9602

Outcome Measures

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Primary Outcome Measures :

1. Incidence of Symptomatic Intracranial Hemorrhage (SICH) by Dose Cohort [ Time Frame: 90 days ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 85 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

Australia, Victoria
Heidelberg Repatriation Hospital, Melbourne
Heidelberg, Victoria, Australia, 3084
Royal Melbourne Hospital
Parkville, Victoria, Australia, 3050
Austria
O.O. Landes-Nervenklinik Wagner-Jauregg
Linz, Upper Austria, Austria, 4020
Christian-Doppler-Klinik Salzburg,Universitätsklinik für Neurologie
Salzburg, Austria, 5020
France
Hôpital Gabriel Montpied
Clermont-Ferrand, France, 63003
Hôpital Gui de Chauliac
Montpellier, France, 34295
Hôpital Bichat-Claude Bernard
Paris, France, 75877
Hôpital Rangueil
Toulouse, France, 31059
Serbia
Clinical Center of Serbia, Clinic for Vascular and Endovascular Surgery
Belgrade, Serbia, 11000
Special Hospital for Cerebrovascular Diseases "Sveti Sava"
Belgrade, Serbia, 11000
Clinical Center Kragujevac, Center for Radiology Diagnostic
Kragujevac, Serbia, 34000
Clinical Center Niš, Center of Radiology
Niš, Serbia, 18000
Clinical Center of Vojvodina, Center for Radiology
Novi Sad, Serbia, 21000
Slovakia
Neurology Clinic Hospital with Policlinic of F.D. Roosevelt
Banská Bystrica, Slovakia, 97517
I. Neurology Clinic, University Hospital Bratislava
Bratislava, Slovakia, 813 69
Radiology Clinic, University Hospital Martin
Martin, Slovakia, 03659
Neurology Clinic, Faculty Hospital Nitra
Nitra, Slovakia, 95001
Neurology Clinic, Central Military Faculty Hospital
Ružomberok, Slovakia, 036 26
Spain
Hospital Universitario de Bellvitge
L´Hospitalet de Llobregat, Barcelona, Spain, 08907
Hospital Universitario Germans Trias i Pujol
Badalona, Spain, 08916
Hospital General Vall d'Hebron, Barcelona
Barcelona, Spain, 08035
Hospital General Universitario Gregorio Marañon
Madrid, Spain, 28007
Hospital Universitario Ramón y Cajal
Madrid, Spain, 28034

Sponsors and Collaborators

Grifols Therapeutics LLC

Investigators

Study Director:	Jeffrey Saver, MD	University of California, Los Angeles
Study Director:	Peter Mitchell, MD	Melbourne Health

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Grifols Therapeutics LLC
ClinicalTrials.gov Identifier:	NCT01014975 History of Changes
Other Study ID Numbers:	T05018-1001; 2010-019760-36 ( EudraCT Number )
First Posted:	November 17, 2009
Results First Posted:	October 21, 2015
Last Update Posted:	October 21, 2015
Last Verified:	September 2015

Keywords provided by Grifols Therapeutics LLC:

stroke; plasmin; thrombus; ischemic	middle cerebral artery; thrombolysis; intra-arterial; fibrin

Additional relevant MeSH terms:

Stroke; Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases	Cardiovascular Diseases; Pathologic Processes; Fibrinolysin; Fibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action