Acute Ischemic StrokePhase 2NCT00499902
Phase 2 Proof-of-Concept Study of the Safety and Efficacy of Alfimeprase to Rapidly Open Arteries and Restore Brain Function Following a Stroke
A Phase 2 study testing alfimeprase in people with Acute Ischemic Stroke, run by ARCA Biopharma, Inc. at 22 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Acute Ischemic Stroke
- What is being tested?
- alfimeprase
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 22 sitesin 2 countries
- Study dates
- Jun 2007to May 2008
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 30Show fewer
- 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
Trial locations and contacts
22 sites in 2 countries.
22 sites in 2 countries
United States17 sites
Albany Medical Center Hospital
Albany, New York, 12208
Kalieda Health, MFH
Buffalo, New York, 14203
Northwestern Medical Center
Chicago, Illinois, 60611
University of Cincinnati
Cincinnati, Ohio, 45243
Riverside Methodist Hospital
Columbus, Ohio, 43214
Ruan Neurology & Clinical Research Center
Des Moines, Iowa, 50314
Baylor College of Medicine
Houston, Texas, 77030
University of Iowa Hospital
Iowa City, Iowa, 52242
University of Iowa Hospital
Iowa City, Iowa, 53342
Michigan State University, Sparrow Hospital
Lansing, Michigan, 48912
UCLA Medical Center
Los Angeles, California, 90024
Norton Hospital
Louisville, Kentucky, 40202
St. Luke's Medical Center
Milwaukee, Wisconsin, 53215
Columbia Presbyterian Medical Center
New York, New York, 10032
University of Pittsburg Medical Center
Pittsburgh, Pennsylvania, 15213
Oregon Stroke Center
Portland, Oregon, 97239
University of Kansas School of Medicine, Via Christi Regional Medical Center
Wichita, Kansas, 67214
Canada5 sites
University of Calgary, Foothills Medical Centre
Calgary, Alberta, T2N 2T9
Trilium Health Center
Mississauga, Ontario, L5B4A2
Montreal Neurological Institute
Montreal, Quebec, H3A 2B4
University Health Network Toronto
Toronto, Ontario, M5T 258
Vancouver General Hospital
Vancouver, British Columbia, V52 1M9
About this study
Official title: Phase 2, Multicenter, Open-Label, Two-Stage Study to Evaluate the Safety and Efficacy of Intra-Arterial Catheter-Directed Alfimeprase for Restoration of Neurologic Function and Rapid Opening of Arteries in Stroke (CARNEROS-1)
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.
Read the detailed description
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
- Acute Ischemic Stroke
- Being tested
- alfimeprase
- 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
- Medical subject headings
- Ischemic Stroke, Stroke, Thrombosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
alfimepraseDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: alfimeprase |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Intracerebral hemorrhage outside of the stroke territory
New AIS
AEs/SAEs/All cause mortality
Changes in chemistry, hematology, coagulation, and alpha-2-macroglobulin parameters based on central laboratory measurements
Anti-alfimeprase antibody detection based on central laboratory measurements
Recanalization of the primary AOL
Global reperfusion of the primary AOL distal vascular bed defined by the Thrombolysis in Cerebral Infarction (TICI) score
Neurological benefit as assessed by individual and combined analysis of NIHSS, mRS, and BI
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2007 (estimated)
- Study startJun 2007
- Primary completionMay 2008 (estimated)
- Study completionMay 2008 (estimated)
Why it stopped: CO Phase 2 data did not show sufficient improvement in cath opening at higher dose/concentration evaluated. Nuvelo ended further clinical dev of alfimeprase.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Ischemic StrokeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- ARCA Biopharma, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Susan M Begelman, MD, Study director, ARCA Biopharma, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00499902
- Sponsor's protocol ID
- HA009
- Status last verified
- Apr 2008
- First submitted
- 10 Jul 2007
- Last updated
- 24 Apr 2008
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2, Multicenter, Open-Label, Two-Stage Study to Evaluate the Safety and Efficacy of Intra-Arterial Catheter-Directed Alfimeprase for Restoration of Neurologic Function and Rapid Opening of Arteries in Stroke (CARNEROS-1)
- ClinicalTrials.gov ID
- NCT00499902
- Acronym / sponsor ID
- HA009
- Conditions
- Acute Ischemic Stroke
- Keywords
- AIS, acute ischemic stroke, stroke, alfimeprase, blood clot, brain, thrombus, thrombolytic
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: CO Phase 2 data did not show sufficient improvement in cath opening at higher dose/concentration evaluated. Nuvelo ended further clinical dev of alfimeprase.
- Enrolment
- 7 participants (actual)
- Lead sponsor
- ARCA Biopharma, Inc.Industry (pharma, biotech, devices)
- Study start
- Jun 2007
- Primary completion
- May 2008 (estimated)
- Study completion
- May 2008 (estimated)
- First posted
- 12 Jul 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 2 stages | Other | Drug: alfimepraseThis 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. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (30 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| alfimepraseAlfimeprase 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. | Drug | 2 stages |
Primary outcome
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.
13 secondary outcomes
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)
Intracerebral hemorrhage outside of the stroke territory
New AIS
AEs/SAEs/All cause mortality
Changes in chemistry, hematology, coagulation, and alpha-2-macroglobulin parameters based on central laboratory measurements
Anti-alfimeprase antibody detection based on central laboratory measurements
Recanalization of the primary AOL
Global reperfusion of the primary AOL distal vascular bed defined by the Thrombolysis in Cerebral Infarction (TICI) score
Neurological benefit as assessed by individual and combined analysis of NIHSS, mRS, and BI
Results and safety
The study was stopped early (reason given: CO Phase 2 data did not show sufficient improvement in cath opening at higher dose/concentration evaluated. Nuvelo ended further clinical dev of alfimeprase.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2008.
- Company WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Susan M Begelman, MD study director
ARCA Biopharma, Inc.
22 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing alfimeprase in people with Acute Ischemic Stroke, run by ARCA Biopharma, Inc. at 22 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 24 Apr 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: CO Phase 2 data did not show sufficient improvement in cath opening at higher dose/concentration evaluated. Nuvelo ended further clinical dev of alfimeprase.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.. The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Apr 2008.