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.
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.
Trial 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.
- Alfimeprase Drug
Intervention Desc: 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. ARM 1: Kind: Experimental Label: 2 stages Description: 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.
- Masking: Open Label
- Purpose: Treatment
- Endpoint: Safety/Efficacy Study
- Intervention: Single Group Assignment
Treatment with study drug; available for follow-up assessment at 30 and 90 days.
|Type||Measure||Time Frame||Safety Issue|
|Primary||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||Relative hypotension requiring treatment; new cardiac events; relative hypotension not requiring treatment; major bleeding events; hemorrhagic transformation: hemorrhagic infarction; intracerebral hemorrhage outside of the stroke territory; new AIS; AEs/SAEs/All cause mortality; changes in chemistry, hematology, coagulation, and alpha-2-macroglobulin parameters; anti-alfimeprase antibody detection; recanalization of the primary AOL; global reperfusion of the primary AOL distal vascular bed; neurological benefit.|
|Primary||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.|
|Primary||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||Relative hypotension requiring treatment (i.e. volume expanders and/or vasopressors)|
|Secondary||New cardiac events (e.g., cardiac ischemia, congestive heart failure, and dysrhythmia)|
|Secondary||Relative hypotension not requiring treatment|
|Secondary||Major bleeding events (TIMI definition)|
|Secondary||Hemorrhagic transformation: hemorrhagic infarction (Type 1 and 2), parenchymal hematoma formation (Type 1 and 2)|
|Secondary||Intracerebral hemorrhage outside of the stroke territory|
|Secondary||AEs/SAEs/All cause mortality|
|Secondary||Changes in chemistry, hematology, coagulation, and alpha-2-macroglobulin parameters based on central laboratory measurements|
|Secondary||Anti-alfimeprase antibody detection based on central laboratory measurements|
|Secondary||Recanalization of the primary AOL|
|Secondary||Global reperfusion of the primary AOL distal vascular bed defined by the Thrombolysis in Cerebral Infarction (TICI) score|
|Secondary||Neurological benefit as assessed by individual and combined analysis of NIHSS, mRS, and BI|
- ARCA Biopharma, Inc. Lead