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

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

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.

Study Overview

• Status: Completed
• Conditions: Acute Ischemic Stroke
• Intervention / Treatment: Biological: Plasmin (Human); Biological: Plasmin (Human); Biological: Plasmin (Human)

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 Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of Symptomatic Intracranial Hemorrhage (SICH) by Dose Cohort	90 days

Collaborators and Investigators

• Sponsor: Grifols Therapeutics LLC
• Investigators: Study Director: Jeffrey Saver, MD, University of California, Los Angeles; Study Director: Peter Mitchell, MD, Melbourne Health

Study record dates

Study Major Dates

• Study Start: November 1, 2009
• Primary Completion (Actual): November 1, 2013
• Study Completion (Actual): February 1, 2014

Study Registration Dates

• First Submitted: November 16, 2009
• First Submitted That Met QC Criteria: November 16, 2009
• First Posted (Estimate): November 17, 2009

Study Record Updates

• Last Update Posted (Estimate): October 21, 2015
• Last Update Submitted That Met QC Criteria: September 22, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Keywords: thrombolysis; stroke; middle cerebral artery; ischemic; thrombus; intra-arterial; fibrin; plasmin
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke; Ischemia; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Fibrinolysin
• Other Study ID Numbers: T05018-1001; 2010-019760-36 (EudraCT Number)