Phase 2 Proof-of-Concept Study of the Safety and Efficacy of Alfimeprase to Rapidly Open Arteries and Restore Brain Function Following a Stroke

NCT ID: NCT00499902

Last Updated: 2008-04-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

7 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-06-30

Study Completion Date

2008-05-31

Brief Summary

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The purpose of this study is to identify a safe and effective bolus dose of intra-arterial/intra-thrombus alfimeprase in acute ischemic stroke (AIS) 3 to 9 hours from symptom onset.

Detailed Description

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Currently approved drug therapy for AIS is limited by the need to treat within 3 hours of symptom onset. Alfimeprase acts to degrade fibrin directly and is inactivated locally by circulating alpha-2 macroglobulin. This study will determine whether treatment with alfimeprase facilitates rapid restoration of arterial blood flow with avoidance of symptomatic hemorrhagic conversion in subjects with AIS within 3 to 9 hours of symptom onset.

Conditions

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Acute Ischemic Stroke

Keywords

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AIS acute ischemic stroke stroke alfimeprase blood clot brain thrombus thrombolytic thrombosis plasminogen activator arterial flow neurology intra-arterial intra-thrombus catheter-directed symptomatic ICH ICH AOL arterial occlusive lesion recanalization

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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2 stages

This is a two-stage study. The first stage is in a three-tier dose escalation format, followed by a second stage during which subjects will be randomized in an equal proportion to up to 3 qualifying dose arms.

Group Type OTHER

alfimeprase

Intervention Type DRUG

Alfimeprase will be given as a single bolus of 1mg/2mL, or a split bolus of 5mg/2mL or 10mg/2mL in a three-tier dose escalation format. The 5mg and 10mg doses will be administered as split doses with 1/2 of the total dose given initially and 1/2 of the total dose given 30 minutes after the initial dose.

Interventions

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alfimeprase

Alfimeprase will be given as a single bolus of 1mg/2mL, or a split bolus of 5mg/2mL or 10mg/2mL in a three-tier dose escalation format. The 5mg and 10mg doses will be administered as split doses with 1/2 of the total dose given initially and 1/2 of the total dose given 30 minutes after the initial dose.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Clinical diagnosis of AIS defined as the sudden onset of an acute focal neurological deficit presumed to be due to cerebral ischemia
* Arterial occlusion of the carotid T or a M1, M2, or M1-M2 branch of the middle cerebral artery (MCA) as documented by CT angiography or magnetic resonance angiography
* Arteriographically confirmed occlusion of the carotid T or a M1, M2, or M1-M2 branch of the MCA
* The subject (or legally acceptable representative) must give written informed consent
* Age 18 years to 85 years
* Onset of symptoms of AIS (i.e., last known well time) within 3-9 hours
* Baseline NIHSS of 4 to 25
* Available for follow-up assessments at 30 and 90 days

Exclusion Criteria

* Contraindication to systemic anticoagulation including any history of prior intracranial hemorrhage
* Uncontrolled hypertension at study entry as defined by systolic blood pressure greater than 180 mmHg or diastolic blood pressure greater than or equal to 100 mmHg on repeated measures prior to study entry despite the use of IV antihypertensive agents
* Expectation based on timing of presentation that alfimeprase administration will not be able to be completed by 9 hours after stroke onset
* Inability to initiate alfimeprase within 120 minutes of the qualifying imaging scan
* Coma
* Rapidly improving neurological symptoms at the time of screening
* Brain CT or MRI evidence of intracranial bleeding of any age
* High clinical suspicion for subarachnoid hemorrhage despite a negative baseline CT or MRI
* CT evidence of an acute and/or evolving hypodensity greater than 1/3 of the MCA territory in the vascular territory to be treated or Alberta Stroke Program Early CT Score (ASPECTS) of less than or equal to 5
* MRI diffusion weighted imaging lesion greater than 1/3 of the MCA territory in the vascular distribution to be treated
* Carotid artery and/or intracranial artery stenosis that precludes safe passage of a microcatheter to treat the primary AOL
* Life expectancy of less than 6 months
* History of significant acute or chronic kidney disease, including known nephrotic syndrome, that would preclude safe contrast angiography
* Known allergy to contrast agents
* History of immune deficiency
* History of heparin-induced thrombocytopenia
* Participation in any study of an investigational device, medication, biologic, or other agent within 30 days prior to enrollment (Stage I)/randomization (Stage II)
* Any stroke, myocardial infarction, or use of thrombolytic therapy (including investigational thrombolytic therapy) within 3 months prior to enrollment (Stage I)/randomization (Stage II)
* Past participation in any alfimeprase clinical trial
* Pregnant, lactating, or actively menstruating women and women of child-bearing potential who are not using adequate contraceptive precautions
* Current use of oral anticoagulants or an international normalized ratio (INR) greater than 1.4
* Any non-atherosclerotic arteriopathy
* Any prior neurologic event that would obscure the radiographic or clinical evaluation of the new index neurological deficits
* Subjects with known renal insufficiency defined as a serum creatinine \>2 mg/dL (\>180 mmoL/L)
* Subjects with known clinically significant hepatic disease defined as transaminase values \> 3x upper limit of normal
* Subjects with any malignant neoplasm diagnosed within five years prior to screening, with the exception of basal cell carcinoma of the skin and fully resected squamous cell carcinoma of the skin
* Subjects with a platelet count less than 100,000/mm3
* Subjects with a baseline serum glucose level less than 50 mg/dL or greater than 300 mg/dL
* Subjects receiving any dose of a heparinoid or a non-prophylactic intensity dose of a low molecular weight heparin within the 24-hour period prior to study drug administration
* Any other subject feature that in the opinion of the investigator should preclude study participation
Minimum Eligible Age

18 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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ARCA Biopharma, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Nuvelo, Inc.

Principal Investigators

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Susan M Begelman, MD

Role: STUDY_DIRECTOR

ARCA Biopharma, Inc.

Locations

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UCLA Medical Center

Los Angeles, California, United States

Site Status

Northwestern Medical Center

Chicago, Illinois, United States

Site Status

Ruan Neurology & Clinical Research Center

Des Moines, Iowa, United States

Site Status

University of Iowa Hospital

Iowa City, Iowa, United States

Site Status

University of Iowa Hospital

Iowa City, Iowa, United States

Site Status

University of Kansas School of Medicine, Via Christi Regional Medical Center

Wichita, Kansas, United States

Site Status

Norton Hospital

Louisville, Kentucky, United States

Site Status

Michigan State University, Sparrow Hospital

Lansing, Michigan, United States

Site Status

Albany Medical Center Hospital

Albany, New York, United States

Site Status

Kalieda Health, MFH

Buffalo, New York, United States

Site Status

Columbia Presbyterian Medical Center

New York, New York, United States

Site Status

University of Cincinnati

Cincinnati, Ohio, United States

Site Status

Riverside Methodist Hospital

Columbus, Ohio, United States

Site Status

Oregon Stroke Center

Portland, Oregon, United States

Site Status

University of Pittsburg Medical Center

Pittsburgh, Pennsylvania, United States

Site Status

Baylor College of Medicine

Houston, Texas, United States

Site Status

St. Luke's Medical Center

Milwaukee, Wisconsin, United States

Site Status

University of Calgary, Foothills Medical Centre

Calgary, Alberta, Canada

Site Status

Vancouver General Hospital

Vancouver, British Columbia, Canada

Site Status

Trilium Health Center

Mississauga, Ontario, Canada

Site Status

University Health Network Toronto

Toronto, Ontario, Canada

Site Status

Montreal Neurological Institute

Montreal, Quebec, Canada

Site Status

Countries

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United States Canada

Related Links

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http://www.Nuvelo.com

Company Website

Other Identifiers

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HA009

Identifier Type: -

Identifier Source: org_study_id