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

Acute Ischemic Stroke Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01014975
• Other study ID #: T05018-1001
• Secondary ID: 2010-019760-36
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: November 16, 2009
• Last updated: September 22, 2015
• Start date: November 2009
• Est. completion date: February 2014

Study information

• Verified date: September 2015
• Source: Grifols Therapeutics Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods AdministrationFrance: Ministry of HealthSpain: Ministry of HealthAustria: Austrian Medicines and Medical Devices AgencySerbia: Agency for Drugs and Medicinal DevicesSlovakia: State Institute for Drug Control
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: February 2014
• Est. primary completion date: November 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Ischemic Stroke
• Ischemia
• Stroke

Intervention

Biological:
• Plasmin (Human)
Plasmin (Human), 20 mg, delivered through a catheter into a thrombus
• Plasmin (Human)
Plasmin (Human), 40 mg, delivered through a catheter into a thrombus
• Plasmin (Human)
Plasmin (Human), 80 mg, delivered through a catheter into a thrombus

Locations

Country	Name	City	State
Australia	Heidelberg Repatriation Hospital, Melbourne	Heidelberg	Victoria
Australia	Royal Melbourne Hospital	Parkville	Victoria
Austria	O.O. Landes-Nervenklinik Wagner-Jauregg	Linz	Upper Austria
Austria	Christian-Doppler-Klinik Salzburg,Universitätsklinik für Neurologie	Salzburg
France	Hôpital Gabriel Montpied	Clermont-Ferrand
France	Hôpital Gui de Chauliac	Montpellier
France	Hôpital Bichat-Claude Bernard	Paris
France	Hôpital Rangueil	Toulouse
Serbia	Clinical Center of Serbia, Clinic for Vascular and Endovascular Surgery	Belgrade
Serbia	Special Hospital for Cerebrovascular Diseases "Sveti Sava"	Belgrade
Serbia	Clinical Center Kragujevac, Center for Radiology Diagnostic	Kragujevac
Serbia	Clinical Center Niš, Center of Radiology	Niš
Serbia	Clinical Center of Vojvodina, Center for Radiology	Novi Sad
Slovakia	Neurology Clinic Hospital with Policlinic of F.D. Roosevelt	Banská Bystrica
Slovakia	I. Neurology Clinic, University Hospital Bratislava	Bratislava
Slovakia	Radiology Clinic, University Hospital Martin	Martin
Slovakia	Neurology Clinic, Faculty Hospital Nitra	Nitra
Slovakia	Neurology Clinic, Central Military Faculty Hospital	Ružomberok
Spain	Hospital Universitario Germans Trias i Pujol	Badalona
Spain	Hospital General Vall d'Hebron, Barcelona	Barcelona
Spain	Hospital Universitario de Bellvitge	L´Hospitalet de Llobregat	Barcelona
Spain	Hospital General Universitario Gregorio Marañon	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid

Sponsors (1)

Lead Sponsor	Collaborator
Grifols Therapeutics Inc.

Countries where clinical trial is conducted

Australia,  Austria,  France,  Serbia,  Slovakia,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Symptomatic Intracranial Hemorrhage (SICH) by Dose Cohort		90 days	Yes