| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| 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 |
| The primary objective of this study is to evaluate the efficacy of ancrod versus placebo, administered intravenously within 6 hours of stroke onset to subjects with an acute ischemic stroke, as determined by a responder analysis based on Modified Rankin Scale (mRS) score at Day 90. |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives are as follows:
• To evaluate the efficacy of ancrod versus placebo as determined by National Institutes of Health Stroke Scale (NIHSS) score at Day 90
• To evaluate the efficacy of ancrod versus placebo as determined by Barthel Index
(BI) score at Day 90
• To evaluate fibrinogen levels associated with ancrod treatment
• To evaluate the safety of ancrod treatment |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Sudden onset of an ischemia-related neurologic deficit involving the carotid, vertebrobasilar, or cerebral artery territories within 6 hours prior to screening, with symptoms persisting for ≥ 30 minutes
Subjects that awaken with stroke symptoms can be enrolled if they were without symptoms within the 6-hour window.
2. Clinical diagnosis of acute ischemic stroke based on a general physical examination, neurologic examination, and neuroimaging findings
3. Stroke symptoms occurring at a time that would allow initiation of study treatment within 6 hours of recognized onset
Subjects will not be excluded based on CT evidence of the index ischemic stroke, but Investigators should be fully satisfied that they have determined the time of symptom onset if there is extensive change related to the index stroke.
4. No conditions other than stroke to which the subject's sudden clinical deterioration could have been attributed (e.g., pneumonia or systemic febrile infection), or that might interfere with the neurologic evaluation (e.g., demyelinating disease, superimposed encephalopathy, or multi-infarct dementia)
5. Age ≥ 18 years
6. Men or women
Women must not be pregnant or lactating, and women of childbearing potential must have a negative pregnancy test before receiving study drug.
7. Screening NIHSS score of ≥ 5
8. mRS score of 0 or 1 prior to onset of index event
9. Written consent by the subject (or his/her representative if the subject is unable
to sign personally) obtained and noted in the subject's chart
Subjects who have signed an Informed Consent Form for any other acute study at the time of the index stroke, including studies involving the use of devices, may not be enrolled in this study. |
|
| E.4 | Principal exclusion criteria |
1. Neuroimaging evidence of intracranial extravascular blood (e.g., cerebral hemorrhage, hemorrhagic infarction, subdural hematoma) or potentially progressive intracranial lesion (e.g., neoplasm or abscess) based on a CT scan of the head
2. Stroke known or strongly suspected to be caused by an arterial dissection
3. Unconscious or comatose state, that is, a score of > 2 on Item 1a of the NIHSS
(level of consciousness)
4. Seizures at onset of the stroke
5. Prior stroke, ischemic or hemorrhagic, within the previous 6 weeks
6. Improvement in the clinical deficit to an NIHSS score of < 5 after randomization
and before initiation of study drug
7. Note: This criterion has been deleted.
8. Anticipated surgery (including angioplasty) or general anesthesia
9. Recent (≤ 24 hours prior to screening) or anticipated arterial puncture at a noncompressible site
10. Current stroke occurring ≤ 14 days after major surgery or ≤ 30 days after carotid endarterectomy.
11. Last pretreatment systolic blood pressure of > 185 mmHg or diastolic blood
pressure of > 105 mmHg, or history of hypertension that is uncontrolled or
accompanied by serious complications (e.g., hypertensive encephalopathy)
12. Last pretreatment systolic blood pressure of < 90 mmHg
13. Heart rate of < 40 beats/min at any time between stroke onset and treatment
14. Screening plasma fibrinogen level of < 100 mg/dL
If study drug infusion is initiated before the fibrinogen value has been reported, the infusion should be stopped as soon as the investigative staff is notified that the subject’s fibrinogen level is < 100 mg/dL.
15. Known disorder of platelet function or coagulation abnormality, use of anticoagulants, such as warfarin, heparin, low–molecular weight heparin, heparinoids, or abciximab (or similar antiplatelet agents), within 72 hours prior to
screening, or planned use of an anticoagulant within 72 hours after initiation of study drug
Subjects who received warfarin or heparin but who are believed to be inadequately anticoagulated may be treated at the discretion of the Investigator.
16. Use of a thrombolytic agent (e.g., rt-PA, urokinase, or streptokinase) within 72 hours prior to screening or planned use of a thrombolytic agent within 5 days after initiation of study drug
17. Platelet count of < 100,000/mm3 or hematocrit of < 30%
18. Major hemostatic deficit as a result of other illness (e.g., uremia)
19. Note: This criterion has been deleted.
20. Any of the following clinically significant conditions:
• Hepatic failure (e.g., alanine aminotransferase [AST] or alanine aminotransferase
[ALT] > 3 × upper limit of normal [ULN])
• Renal failure (e.g., blood urea nitrogen [BUN] or creatinine > 2 × ULN)
• Respiratory failure (e.g., respirator dependence)
• Sepsis
• Pericarditis, cardiogenic shock, or clinically significant congestive heart failure
• Psychiatric disturbance (e.g., depression, schizophrenia, or organic brain syndrome)
• Any other disease (e.g., advanced multiple sclerosis or dementia) likely to interfere with the neurologic assessment
21. Gastrointestinal or genitourinary bleeding within 30 days prior to screening
22. History of chronic alcohol abuse, alcohol abuse within 90 days prior to
screening, or history of illicit drug use
23. Known or suspected vasculitis
24. Blood glucose of < 50 mg/dL
25. Prior treatment with ancrod
26. Use of another investigational drug within 30 days prior to stroke onset
27. Enrollment in another acute interventional stroke study
Subjects who have signed an Informed Consent Form for any other acute study at the time of the index stroke, including studies involving the use of devices, may not be enrolled in this study.
28. Unwillingness to participate in the study or its follow-up
29. History of bite by a pit viper snake
30. Any other serious medical condition (e.g., terminal condition) that might interfere
with subject evaluation over the 90-day study period, based on the Investigator’s
judgment |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| reducing the incidences of disability at a day 90 after study start |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | Information not present in EudraCT |
| E.6.2 | Prophylaxis | Information not present in EudraCT |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Information not present in EudraCT |
| E.6.7 | Pharmacodynamic | Information not present in EudraCT |
| E.6.8 | Bioequivalence | Information not present in EudraCT |
| E.6.9 | Dose response | Information not present in EudraCT |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Information not present in EudraCT |
| E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
| E.6.13 | Others | Information not present in EudraCT |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
| 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 | No |
| 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 | Information not present in EudraCT |
| 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 | No |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 27 |
| 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 |
|
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 5 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 5 |
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