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

Terminated

Phase 2 Results N/A

Trial Description

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.

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.

Conditions

Interventions

  • 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.

Trial Design

  • Masking: Open Label
  • Purpose: Treatment
  • Endpoint: Safety/Efficacy Study
  • Intervention: Single Group Assignment

Patient Involvement

Treatment with study drug; available for follow-up assessment at 30 and 90 days.

Outcomes

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 New AIS
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

Sponsors