E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | 10061256 |
E.1.2 | Term | Ischaemic 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 |
The primary objective of the present study is to assess efficacy of AX200 compared to placebo in patients suffering from acute stroke. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective is to assess safety and tolerability of AX200. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
All of the following inclusion criteria need to be fulfilled: · Diagnosis of acute ischemic stroke with an onset within 9 hours prior to start of study agent administration. · ischemic stroke in the MCA territory confirmed by MRI (diffusion) · men and women aged ≥ 18 years and ≤ 85 years · NIHSS score ≥ 6 and ≤22 · lesion size on DWI: on the slice showing the largest extension of the infarct the largest diameter of the lesion should have at least 3 cm and should show on at least 3 consecutive slices; if the rule cannot be applied (e.g. due to an irregular shape or partially separate volumes on the slice), but in the clinical judgment the lesion is ≥ 15 cm3, the patient should be included in the clinical study if the investigator can provide a written justification · written informed consent |
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E.4 | Principal exclusion criteria |
Patients meeting any of the following criteria will be excluded from randomization: · Participation in another study with an investigational drug or device within the last 30 days or planned participation in another trial · Prior to current stroke: Inability to walk or to lead an independent life; prestroke BI score < 95 or pre-stroke mRS score > 1 · Life expectancy considered to be less or equal 6 months in the judgment of the investigator · Neurological deficit that has led to stupor or coma (suspicious of malignant hemispheric stroke) · Infarct is lacunar · Any evidence of ICH by imaging.Patients with cerebral micro-bleedings can be included in the study. · Current malignant hypertension with systolic and diastolic blood pressure > 220 mmHg and > 120 mmHg, respectively · Strong clinical suspicion of septic embolus · Any thrombosis involving the cerebral veins · High clinical suspicion of vasculitis (e.g. multiple caliber irregularities of intracerebral vessels on MRA plus history of vasculitis) · Any MRI finding indicating that there might be a non-vascular cause for the present neurological symptoms · Any signs on imaging of a mass effect causing shift of midline structures · Presence or history of active malignancies within one year preceding randomization, especially hematological malignancies or myeloproliferative diseases · A platelet count < 100 /nl at V0 · A leukocyte count >20 /nl at V0 · Congenital neutropenia · Other serious illness, e.g., severe hepatic, cardiac, or renal failure, acute myocardial infarction or a complex disease that may confound treatment assessment · Any suspected hypersensitivity and/or contraindication to any ingredients of the study medication · Patients currently receiving G-CSF or GM-CSF · Thrombolytic drug treatment outside the recommendations of the current ESO "Guidelines for Management of Ischemic Stroke and Transient Ischemic Attack 200", especially if the treatment was initiated > 4.5 hrs after stroke onset, or the patient had recent severe or dangerous bleeding prior treatment, or despite anticoagulant or heparin treatment. · Patients for which any of the following treatments are planned for acute recanalisation of intracranial vessels:use of mechanical devices for clot retraction like the Merci Retriever of the Penumbra System, or any vessel dilation or stenting procedure. · Pregnant or lactating women (for women of childbearing potential a negative serum pregnancy test is required at V0). Women of childbearing potential that have not used an acceptable method of contraception (e.g. hormonal implants, injectables, combined oral contraceptives, intrauterine devices (IUDs) within one month prior to entry into the study. · Patients with a history of active substance abuse (including alcohol) for the last 2 years |
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E.5 End points |
E.5.1 | Primary end point(s) |
Improvement on continuous mRS relative to placebo-treated patients. |
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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 | No |
E.6.7 | Pharmacodynamic | No |
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 | No |
E.6.13 | Others | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 83 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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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The end of the study is defined as database lock, as this is the end of clinical data collection. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |