AN EXPLORATIVE PHASE IIa STUDY TO ASSESS SAFETY, TOLERABILITY,PHARMACODYNAMICS AND PHARMACOKINETICS OF VAS203 IN PATIENTS WITHMODERATE AND SEVERE TRAUMATIC BRAIN INJURY

Phase 1

Conditions: MedDRA version: 9.1Level: LLTClassification code 10060690Term: Traumatic brain injury
Moderate to severe traumatic brain injury

Registration Number: EUCTR2009-012338-56-FR

Lead Sponsor: vasopharm GmbH

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 32

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
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 = 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

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

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Assess safety and tolerability of VAS203 in Traumatic Brain Injury patients<br>Evaluate plasma concentrations of the first and second metabolites of<br>VAS203 in TBI patients.<br>Assess pharmacodynamic (PD) effects of VAS203 on surrogate parameters;Secondary Objective: Obtain guidance regarding the selection of most sensitive surrogate<br>parameter(s) for pivotal clinical studies<br>Assess the presences of the 1st and 2nd metabolite of VAS203 in<br>microdialysate or cerebrospinal fluid (CSF);Primary end point(s): Safety endpoints<br>The safety variables include:<br>• incidence and severity of AEs and SAEs<br>• laboratory parameter values and abnormalities<br>• renal abnormalities leading to treatment premature discontinuation<br>• vital signs<br>• ECG abnormalities<br>Pharmacodynamic endpoints<br>The PD variables include ICP, CPP, metabolic and PD parameters, TIL and<br>partial brain oxygen pressure.<br>

Secondary Outcome Measures

Name	Time	Method

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