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

NCT00499902 | Terminated Phase 2 DMC

• 1 other identifier: HA009
• Study Type: interventional
• Target: 7
• Locations: 2 countries
• Sites: 22

Brief Summary

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.

Conditions

Acute Ischemic Stroke

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Symptomatic intracerebral hemorrhage (ICH) defined as a greater than or equal to 4-point increase in NIHSS compared to baseline at the time of CT evidence of ICH within 24 hours of study drug administration.

• Recanalization of primary arterial occlusive lesion (AOL) using the Thrombolysis in Myocardial Infarction (TIMI) classification; a score of II or III will be considered success.

Secondary Outcomes (13)

• Relative hypotension requiring treatment (i.e. volume expanders and/or vasopressors)

• New cardiac events (e.g., cardiac ischemia, congestive heart failure, and dysrhythmia)

• Relative hypotension not requiring treatment

• Major bleeding events (TIMI definition)

• Hemorrhagic transformation: hemorrhagic infarction (Type 1 and 2), parenchymal hematoma formation (Type 1 and 2)

Study Arms (1)

2 stages

OTHER

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.

Drug: alfimeprase

Interventions

alfimeprase 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.

2 stages

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• ARCA Biopharma, Inc.: lead

Study Sites (22)

UCLA Medical Center

Los Angeles, California, 90024, United States

Location

Northwestern Medical Center

Chicago, Illinois, 60611, United States

Location

Ruan Neurology & Clinical Research Center

Des Moines, Iowa, 50314, United States

Location

University of Iowa Hospital

Iowa City, Iowa, 52242, United States

Location

University of Iowa Hospital

Iowa City, Iowa, 53342, United States

Location

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

Wichita, Kansas, 67214, United States

Location

Norton Hospital

Louisville, Kentucky, 40202, United States

Location

Michigan State University, Sparrow Hospital

Lansing, Michigan, 48912, United States

Location

Albany Medical Center Hospital

Albany, New York, 12208, United States

Location

Kalieda Health, MFH

Buffalo, New York, 14203, United States

Location

Columbia Presbyterian Medical Center

New York, New York, 10032, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45243, United States

Location

Riverside Methodist Hospital

Columbus, Ohio, 43214, United States

Location

Oregon Stroke Center

Portland, Oregon, 97239, United States

Location

University of Pittsburg Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

St. Luke's Medical Center

Milwaukee, Wisconsin, 53215, United States

Location

University of Calgary, Foothills Medical Centre

Calgary, Alberta, T2N 2T9, Canada

Location

Vancouver General Hospital

Vancouver, British Columbia, V52 1M9, Canada

Location

Trilium Health Center

Mississauga, Ontario, L5B4A2, Canada

Location

University Health Network Toronto

Toronto, Ontario, M5T 258, Canada

Location

Montreal Neurological Institute

Montreal, Quebec, H3A 2B4, Canada

Location

Related Links

• Company Website

MeSH Terms

Conditions

Ischemic Stroke; Stroke; Thrombosis

Interventions

alfimeprase

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Embolism and Thrombosis

Study Officials

• Susan M Begelman, MD

  ARCA Biopharma, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: July 10, 2007
• First Posted: July 12, 2007
• Study Start: June 1, 2007
• Primary Completion: May 1, 2008
• Study Completion: May 1, 2008
• Last Updated: April 24, 2008

Record last verified: 2008-04

Locations

US (17); CA (5)