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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Grifols Therapeutics Inc.
ClinicalTrials.gov Identifier:
NCT01014975
First received: November 16, 2009
Last updated: July 31, 2014
Last verified: July 2014
  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

Resource links provided by NLM:


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:

  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
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 Universitario Ramón y Cajal
Madrid, Spain, 28034
Hospital General Universitario Gregorio Marañon
Madrid, Spain, 28007
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:
Ischemia
Stroke
Cerebral Infarction
Pathologic Processes
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Brain Infarction
Brain Ischemia
Fibrinolysin
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Hematologic Agents

ClinicalTrials.gov processed this record on September 22, 2014