E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute ischemic stroke within 3 - 9 hours after the onset of symptoms. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10055221 |
E.1.2 | Term | Ischemic stroke |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of desmoteplase 90 µg/kg versus placebo in terms of favourable outcome at Day 90 in subjects with acute ischemic stroke. |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the efficacy of 90 µg/kg desmoteplase versus placebo in terms of favourable outcome at Day 7/discharge and Day 30 in subjects with acute ischemic stroke • To evaluate the efficacy of 90 µg/kg desmoteplase versus placebo in terms of favourable outcome at Day 90 in the subgroup of subjects with a baseline core-lesion volume < 25 cc • To evaluate recanalisation associated with 90 µg/kg desmoteplase versus placebo in the subgroup of subjects with follow up angiography at 12-24 hours • To evaluate the safety and tolerability of desmoteplase • To evaluate the mortality in the treatment groups • To evaluate the incidence of symptomatic intracranial haemorrhage (sICH) • To evaluate the immunogenicity of desmoteplase • To evaluate the pharmacokinetics/pharmacodynamics of desmoteplase • To evaluate the impact of treatment on subjects’ quality of life • To evaluate the impact of treatment on utilization of resources
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Clinical diagnosis of acute ischemic stroke • Informed consent has been obtained according to a procedure approved by the ethics committee responsible for approval of the study at this site • Male or female between 18 and 85 years of age inclusive. • Treatment of the subject can be initiated within 3-9 hours after the onset of stroke symptoms. If the actual time of onset of stroke is unclear then the onset will be considered the time that the subject was last known to be well. All measures are to be taken, so treatment with alteplase within 3 hours of symptom onset is not delayed in subjects who qualified for receiving alteplase • The subject has a score of 4-24 inclusive on the NIHSS with clinical signs of hemispheric infarction (for example, hemiparesis) • The subject shows occlusion or high-grade stenosis as assessed by MRA or CTA in proximal cerebral arteries that correspond to the acute clinical deficit. Eligible vessels are the Middle Cerebral Artery (MCA) M1, MCA M2, anterior cerebral artery (ACA) or posterior cerebral artery (PCA) • The subject should receive IMP within 60 minutes after completion of diagnostic imaging screening
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E.4 | Principal exclusion criteria |
• The subject has a pre-stroke mRS > 1 indicating previously disability • The subject has previously been exposed to desmoteplase • The subject shows signs of extensive early infarction on MRI or CT in any affected area, that is an infarcted core involving > 1/3 of MCA territory or > 1/2 of the ACA or PCA territories • The subject has imaging evidence of ICH or SAH (regardless of age of the bleeding); AV malformation; cerebral aneurysm; or cerebral neoplasm (incidental meningioma and microbleeds per se are not exclusion criteria. An incidental intracranial aneurysm that is small (< 5 mm), not thrombosed, and not visibly bleeding is not an exclusion criterion). • The subject has an internal carotid artery occlusion on the side of the stroke lesion • The subject has been treated with heparin in the past 48 hours and has a prolonged partial thromboplastin time exceeding the upper limit of the local laboratory normal range. Preventive low doses of LMWH (for example, for deep vein thrombosis (DVT) prophylaxis) do not disqualify the subject from the study • The subject is on oral anticoagulants and has a prolonged prothrombin time (INR > 1.6) • The subject has been treated with glycoprotein IIb - IIIa inhibitors within the past 72 hours. Use of single agent oral platelet inhibitors (low-dose clopidogrel 75 mg or low-dose aspirin ≤325 mg) or the combination of low-dose-aspirin (50 mg) and dipyridamole (400 mg) prior to study entry is permitted • The subject has been treated with factor Xa inhibitors in the past 72 hours • The subject has been treated with a thrombolytic agent within the past 72 hours |
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E.5 End points |
E.5.1 | Primary end point(s) |
Favourable outcome at Day 90 defined as achieving 0-2 on mRS. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 45 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 3 |