Clinical Study of Desmoteplase in Japanese Patients With Acute Ischemic Stroke

Study Overview
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Brief Summary
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The purpose of the study is to evaluate whether desmoteplase is safe and tolerated when given to Japanese patients with acute ischemic stroke

Detailed Description
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The study is a safety and tolerability study of desmoteplase in Japanese patients with acute ischemic stroke. The study will test two doses

Official Title
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Randomised, Double-blind, Placebo-controlled, Dose-escalation Study of Desmoteplase in Japanese Patients With Acute Ischemic Stroke

Conditions
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Acute Ischemic Stroke

Intervention / Treatment
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* Drug: Desmoteplase
* Drug: Desmoteplase
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of acute ischemic stroke Provided Informed Consent Male or female Aged between 20 and 85 years inclusive Treatment within 3-9 hr after onset of stroke symptoms. NIHSS score of 4-24 inclusive with clinical signs of hemispheric infarction Must receive IMP within 60 minutes after brain imaging Cerebral artery occlusion or high-grade stenosis in MCA Exclusion Criteria: Pre-stroke mRS score of >1 Previously exposed to desmoteplase Scores >2 on NIHSS question 1a indicating coma History or clinical presentation of ICH, subarachnoid haemorrhage (SAH), arterio-venous malformation (AVM), moyamoya disease, cerebral neoplasm or aneurysm Current use of oral anticoagulants and a prolonged prothrombin time (INR >1.6) Treated with heparin in the previous 48 hours and has a prolonged partial thromboplastin time Baseline platelet count <100,000/mm3 Baseline haematocrit of <0.25 Baseline blood glucose <50 mg/dl or >200 mg/dl Uncontrolled hypertension defined by a blood pressure, systolic >185 mmHg or diastolic >110 mmHg on at least 2 separate occasions at least 10 minutes apart Patient has hereditary or acquired hemorrhagic diathesis Gastrointestinal or urinary bleeding within the past 21 days Arterial puncture in a non-compressible site within the previous 7 days Another stroke or a serious head injury in the past 6 weeks Major surgery or serious injury, including other sites than the head, within the preceding 14 days Seizure at the onset of stroke Acute myocardial infarction (AMI) within the previous 3 weeks Thrombolytic within the previous 72 hr Pregnant Other inclusion and exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Desmoteplase 70 µg/kg<br> | Drug: Desmoteplase<br>* 1 bolus injection of desmoteplase 70 µg/kg intravenous (IV)<br>|
| Experimental: Desmoteplase 90 µg/kg<br> | Drug: Desmoteplase<br>* 1 bolus injection of desmoteplase 90 µg/kg (IV)<br>|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* 1 bolus injection of placebo IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the safety and tolerability of desmoteplase doses of 70 µg/kg and 90 µg/kg in Japanese patients with acute ischemic stroke as measured by the presence of symptomatic intracranial haemorrhage (sICH) within 72 hours after IMP |  | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the clinical improvement at Day 90 after administration of Investigational Medicinal Product (IMP) as measured by modified Rankin Scale (mRS) |  | 90 days | 
| To evaluate the clinical improvement at Day 7 and 30 after administration of IMP as measured by modified Rankin Scale (mRS) |  | Day 7 and Day 30 | 
| To evaluate recanalisation at 18±6 hr after administration of IMP |  | 18±6 hr after administration of IMP | 
| To evaluate change in infarct size at 18±6 hr relative to pre-treatment infarct size |  | 18±6 hr after administration | 
| To evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of desmoteplase |  | 0.5 - 9 hr | 
| To evaluate the immunogenicity of desmoteplase |  | Day 7, Day 30, Day 90 | 
| To explore the predictive value of different volumes of absolute mismatch for the clinical response and other objectives |  | Day 90 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Ischemic Stroke, Desmoteplase, Japan, Safety, Stroke, Tolerability