E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Ischaemic and Haemorrhagic Stroke |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10042244 |
E.1.2 | Term | 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 further assess (in the context of STEMS1) the safety of G-CSF. |
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E.2.2 | Secondary objectives of the trial |
i. To further assess the feasibility of administration and tolerance of G-CSF. ii. To assess the efficacy of G-CSF on stroke lesion size. iii. To study potential mechanisms of action by which G-CSF might improve outcome after stroke, with an emphasis on its effects on bone marrow derived PBSCs and their fate in the brain. iv. To assess the effects of G-CSF on haemostatic function1 and a surrogate marker of efficacy, Serum s-100 protien. v. To obtain information on functional outcome for use in the design of future trials
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Clinical stroke (lacunar or cortical); ischaemic or haemorrhagic type on neuro-imaging 3-30 days post-onset; arm and/or leg weakness (Scandinavian Stroke Scale, SSS arm and/or leg motor power <6). |
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E.4 | Principal exclusion criteria |
Pre-morbid dependency, modified Rankin scale (mRS) >3; dementia; coma (SSS consciousness <4); malignancy; sickle cell disease; pregnancy; congenital neutropaenia; secondary acute myeloid leukaemia; known contra-indication to MRI in those with ischaemic stroke. |
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E.5 End points |
E.5.1 | Primary end point(s) |
PRIMARY –Number of patients having a serious adverse event by day 90. SECONDARY -Laboratory measures: During/post treatment (days 5, 10): CD34+ count; full blood count; soluble platelet function (P-selectin); coagulation factors (factor VIII, fibrinogen, von Willebrand factor).1, Clinical efficacy: (Days 10,90): Impairment (SSS, grip strength); dead or dependent (modified Rankin Scale (mRS)>2); dead or disabled (Barthel Index(BI)<60); functional independence (extended activities of daily living (EADL)) quality of life (EuroQoL) Zung depression scale and MMSE; At discharge/death: Length of stay in hospital; discharge disposition (death/institution/home). Neuroimaging: (days 10-12, 90) lesion size (MR T2 – MR DWI at day 0); CD34+ tracking (MR T2*) Clinical safety: (days 1-10,90): Death (cause); recurrence/progression; death/deterioration (fall in SSS >5 points); symptomatic intracranial haemorrhage; major extracranial haemorrhage. Safety, long-term follow-up: All patients will be ‘flagged’ with the Office for National Statistics to track death (and its cause) over the next 10 years). [Therapeutic clonal expansion of endogenous stem cells could, in theory, lead to malignancy and this will be monitored long-term (although this problem has not been observed to date with G-CSF in normal donors).] Feasibility: proportion of patients receiving all 5 G-CSF/placebo injections Post-mortem examination: Patients who die (and where prior declaration of intent was obtained pre-mortem from the patient and/or next-of-kin; and next-of-kin assent was obtained post-mortem) will have their brain removed and formalin fixed for histological assessment. Post-mortem MR scanning of agar embedded previously fixed brains using high resolution T2* and T2 scanning will be performed at 7T where possible before sectioning. For further details regarding outcome measures see the later sections on assessment of efficacy and safety.
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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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |