STUDY PROTOCOL

Study objectives	To further investigate clinical efficacy and safety of desmoteplase (90 µg/kg and 125 µg/kg) in acute ischemic stroke
Design	A prospective, randomised, double-blind, placebo-controlled, single bolus, multinational, multi-centre, parallel group, dose ranging study
Dosages	90 µg/kg, 125 µg/kg desmoteplase, placebo (1:1:1)
Administration	Intravenous (IV) bolus
Time-window	3 – 9 hours after onset of stroke symptoms
Total number of patients	186
Primary Efficacy	Clinical improvement at Day 90 defined for each patient as achievement of all three of the following criteria: (1) improvement of ≥8 points from baseline on the National Institutes of Health Stroke Scale (NIHSS) (or NIHSS score ≤1), (2) Modified Rankin Scale (MRS) score of 0 – 2, and (3) Barthel Index (BI) score of 75-100.
Secondary Efficacy	Secondary efficacy parameters include the following: percentage (%) of patients with improvement of ≥8 points from baseline on the NIHSS (or NIHSS score ≤1 at Day 90; percentage (%) of patients with MRS score of 0 – 2 at Day 90; percentage (%) of patients with BI score of 75-100 at Day 90; and change from baseline in infarct volume at Day 30.
Safety	The safety analyses include analysis of adverse events (AEs), laboratory tests, ECGs and vital signs.
Inclusion Criteria	Informed consent and HIPAA authorization (US sites only) Age 18-85 years Treatment onset within 3-9 hours after onset of stroke symptoms. If the exact onset of stroke is unclear, but the onset of stroke symptoms was less than 8 hours before arrival at the hospital, then the patient can be considered eligible for the study (this provides 1 hour for eligibility determination prior to receipt of randomized therapy) Score of 4-20 on the NIHSS with clinical signs of hemispheric infarction (eg hemiparesis) suggestive of ischemic stroke A distinct penumbra (at least 20%), measured by MRI (PWI/DWI) or perfusion CT, related to middle cerebral artery (MCA), anterior cerebral artery (ACA), or posterior cerebral artery (PCA) territory in a hemispheric distribution