E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Lesiones cerebrales traumáticas de moderadas a graves |
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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 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess safety and tolerability of VAS203 in Traumatic Brain Injury patients To evaluate plasma concentrations of the first and second metabolites of VAS203 in TBI patients] To assess pharmacodynamic (PD) effects of VAS203 on surrogate parameters |
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E.2.2 | Secondary objectives of the trial |
To obtain guidance regarding the selection of most sensitive surrogate parameter(s) for pivotal clinical studies To assess the presences of the 1st and 2nd metabolite of VAS203 in microdialysate or cerebrospinal fluid (CSF) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Written informed consent from patient's legal guardian or legal representative, according to local requirements
2. 18 - 65 years of age, inclusive
3. Head trauma within the last 12 hours
4. TBI with Glasgow Coma Score (GCS) more than or equal to 5 and that requires Intracranial pressure (ICP) monitoring
5. Catheter placement (intraventricular or intraparenchymal only) for monitoring and management of increased ICP
6. Microdialysis probe placement in penumbra zone or ipsilateral to contusion if focal (evaluated by computer tomography [CT])
7. Systolic blood pressure more than or equal to 100 mmHg
8. Females of child-bearing potential must have a negative pregnancy test |
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E.4 | Principal exclusion criteria |
1. Penetrating head injury (e.g. missile, stab wound)
2. Not expected to survive more than 24 hours after admission
3. Concurrent, but not pre-existing, spinal cord injury
4. Unilateral and bilateral fixed and dilated pupil (> 4 mm)
5. Cardiopulmonary resuscitation performed post injury, or extracranial injuries causing continuing bleeding likely to require multiple transfusions (> 4 units red blood cells).
6. Coma due to a "pure" epidural hematoma (lucid interval and absence of structural brain damage on CT scan).
7. Coma suspected to be primarily due to other causes than head injury (e.g. drug overdose).
8. Known or CT scan evidence of pre-existing major cerebral damage.
9. Decompressive craniectomy, planned prior to randomization.
10. Polychromatic patients with Injury Severity Score > 25, or rhabdomyolysis.
11. Injuries to ascending aorta and/or carotid arteries.
12. serum creatinine values > 1.5 mg/dL.
13. estimated glomerular filtration rate (eGFR) < 60 ml/min by Modification of Diet in Renal Disease (MDRD) formula.
14. body mass index (BMI) > 35, Body weight > 120 kg.
15. Any severe concomitant condition (cancer; hematologic, renal, hepatic, coronary disease; major psychiatric disorder; alcohol or drug abuse), that can be ascertained at admission.
16. Known to have received an experimental drug within 4 weeks prior to current injury.
17. Administration of > 100 ml of contrast media containing iodine. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety endpoints
The safety variables include:
- incidence and severity of AEs and SAEs - laboratory parameter values and abnormalities - renal abnormalities leading to treatment premature discontinuation - vital signs - ECG abnormalities.
Pharmacodynamic endpoints The PD variables include ICP, CPP metabolic and PD parameters, TIL and partial brain oxygen pressure. |
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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 | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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 | 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) | 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 | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Cohort 1 open; Cohorts 2 and 3 double blind, randomised placebo-controlled |
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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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |