E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Severe Traumatic Brain Injury |
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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 | 10060690 |
E.1.2 | Term | Traumatic brain injury |
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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 |
Is interleukin-1 receptor antagonist safe in the severely head injured patient population?
We hypothesise that administration of IL1ra subcutaneously will be safe in the severe head injury population. Our secondary hypotheses are that subcutaneous administration will lead to rapid increases in brain tissue IL-1ra concentration (1) and that this will have a consequent biological effect on cerebral inflammation as measured by cerebral microdialysis parameters, sampling of cerebrospinal fluid (where available) and multi-modality monitoring (2).
1) Goldbach-Mansky et al. Neonatal-Onset Multisystem Inflammatory Disease Responsive to Interleukin 1Beta Inhibition. NEJM 2006 355;6 581-592 2) Kett-White et al. Multi-Modal Monitoring of Acute Brain Injury. Advances and Technical Standards in Neurosurgery 2001 27 87-134 |
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E.2.2 | Secondary objectives of the trial |
1. Does interleukin-1 receptor antagonist (IL-1ra) enter the brain in severely head injured patients when administered systemically? 2. What concentration of interleukin-1 receptor antagonist are achieved in the brain following subcutaneous administration and over what time course? (Pharmacokinetics) 3. Does administration of interleukin-1 receptor antagonist alter cerebral chemistry in brain extracellular fluid and cerebrospinal fluid? (A number of measured metabolites within the brain are thought to reflect underlying brain ischaemia/damage) 4. Does administration of interleukin-1 receptor antagonist alter the concentration of endogenous cytokines known to co-ordinate inflammation and damage in the brain? 5. Does administration of interleukin-1 receptor antagonist alter the physiological variables that are monitored and controlled in the management of head injury patients? |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients with head injury aged 16-65 years with an abnormal CT scan requiring intracranial pressure monitoring. |
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E.4 | Principal exclusion criteria |
1.Head injury unlikely to survive 5 days -CT evidence of above as judged by clinical team -bilateral fixed and dilated pupils 2.follow up not possible 3. Not suitable for insertion of Cranial Access Device -bleeding diathesis 4.Immunosuppression -evidence of neutropenia -immunosuppression secondary to immunomodulatory medications, chemotherapy or radiation therapy in the 3 months preceding study entry 5.Severe Renal Insufficiency or End Stage Renal Disease -Defined as a Creatinine Clearance<30ml/min 6. Pregnancy/Nursing mothers 7. Known hypersensitivity to E. coli derived products 8. Administration of live vaccine
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety of subcutaneously administered IL-1ra in the severe head injury population ie adverse events attributable to IL-1ra. |
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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 | 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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
No comparator will be administered |
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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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Attendance to single follow up visit at 6 months post discharge of last trial participant. |
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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 | 0 |
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 | 0 |