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

Purpose

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	Intervention	Phase
Acute Ischemic Stroke	Biological: Plasmin (Human)	Phase 1 Phase 2


Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: 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

Further study details as provided by Grifols Therapeutics Inc.:

Primary Outcome Measures:

Incidence of symptomatic intracranial hemorrhage (SICH) by dose cohort [ Time Frame: 90 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Intracranial hemorrhage [ Time Frame: 90 days ] [ Designated as safety issue: Yes ]
Major bleeding [ Time Frame: 90 days ] [ Designated as safety issue: Yes ]
Minor bleeding [ Time Frame: 90 days ] [ Designated as safety issue: Yes ]
Deaths [ Time Frame: 90 days ] [ Designated as safety issue: Yes ]
Adverse events (serious and non-serious) [ Time Frame: 90 days ] [ Designated as safety issue: Yes ]
Adverse events causing discontinuation of study drug [ Time Frame: 90 days ] [ Designated as safety issue: Yes ]
Treatment-emergent, abnormal laboratory values [ Time Frame: 90 days ] [ Designated as safety issue: Yes ]
Incidence of all major and minor bleeding events [ Time Frame: 90 days ] [ Designated as safety issue: Yes ]


Enrollment:	40
Study Start Date:	November 2009
Study Completion Date:	February 2014
Primary Completion Date:	November 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

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.

Eligibility


Ages Eligible for Study:	18 Years to 85 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01014975

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 Inc.

Investigators


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

More Information

No publications provided


Responsible Party:	Grifols Therapeutics Inc.
ClinicalTrials.gov Identifier:	NCT01014975 History of Changes
Other Study ID Numbers:	T05018-1001, 2010-019760-36
Study First Received:	November 16, 2009
Last Updated:	July 31, 2014
Health Authority:	Australia: Department of Health and Ageing Therapeutic Goods Administration France: Ministry of Health Spain: Ministry of Health Austria: Austrian Medicines and Medical Devices Agency Serbia: Agency for Drugs and Medicinal Devices Slovakia: State Institute for Drug Control

Keywords provided by Grifols Therapeutics Inc.:


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

Additional relevant MeSH terms:


Stroke Brain Diseases Cardiovascular Diseases Central Nervous System Diseases Cerebrovascular Disorders Nervous System Diseases Vascular Diseases Fibrinolysin	Cardiovascular Agents Fibrin Modulating Agents Fibrinolytic Agents Hematologic Agents Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Therapeutic Uses

ClinicalTrials.gov processed this record on March 01, 2015