Moderate and severe traumatic brain injury MedDRA version: 9.1 Level: LLT Classification code 10060690 Term: Traumatic brain injury
Conditions
Interventions
Product Name: VAS203
Product Code: VAS203
Pharmaceutical Form: Intravenous infusion
CAS Number: 206885-38-3
Current Sponsor code: VAS203
Other descriptive name: 4-Amino-(6R,S)-5,6,7,8-tetrahydro-L-bio
Sponsors
vasopharm GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
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) = 5 and that requires Intracranial pressure (ICP) monitoring - Cohort 1 4. TBI with Glasgow Coma Score (GCS) = 3 and that requires Intracranial pressure (ICP) monitoring - Cohorts 2 & 3. 5. Catheter placement (intraventricular or intraparenchymal only) for monitoring and management of increased ICP 6. Microdialysis probe placement in predominantly injured hemisphere ipsilateral to contusion if focal (evaluated by computer tomography [CT]) 7. Systolic blood pressure = 100 mmHg 8. Females of child-bearing potential must have a negative pregnancy test Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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 - Cohort 1 7. Coma suspected to be primarily due to other causes than head injury (e.g. drug overdose, alcohol intoxication, drowning/near drowning) - Cohorts 2 & 3 8. Known or CT scan evidence of pre-existing major cerebral damage 9. Decompressive craniectomy, planned prior to randomisation- Cohort 1 9. Decompressive craniectomy, planned prior to randomisation/enrolment - Cohort 2 & 3 10. Polytraumatic patients with Injury Severity Score > 25, or rhabdomyolysys. - Cohort 1 10. Polytraumatic patients with Injury Severity Score non head > 18 - Cohorts 2 & 3 11. Rhabdomyolysis with CK > 5000 IU/L - Cohorts 2 & 3 12. Injuries to ascending aorta and/or carotid arteries - Cohort 1 12. Injuries to ascending aorta and/or carotid arteries and/or vertebral arteries - Cohorts 2 & 3. 13. Serum creatinine values > 1.5 mg/dL (133 µmol/L) 14. Estimated glomerular filtration rate (eGFR) 35 kg/m2, Body > 120 kg - Cohort 1 15. Body mass index (BMI) 35 kg/m2, Body weight 120 kg - Cohorts 2 & 3. 16. Any severe concomitant condition (cancer; haematologic, renal, hepatic, coronary disease; major psychiatric disorder; alcohol or drug abuse), that can be ascertained at admission 17. Known to have received an experimental drug within 4 weeks prior to current injury 18. Administration of > 100 ml of contrast media containing iodine
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Assess safety and tolerability of VAS203 in Traumatic Brain Injury patients Evaluate plasma concentrations of the first and second metabolites of VAS203 in TBI patients. Assess pharmacodynamic (PD) effects of VAS203 on surrogate parameters;Secondary Objective: Obtain guidance regarding the selection of most sensitive surrogate parameter(s) for pivotal clinical studies Assess the presences of the 1st and 2nd metabolite of VAS203 in microdialysate or cerebrospinal fluid (CSF);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. | — |
Countries
Austria, France, Spain, United Kingdom
Outcome results
None listed