Traumatic brain injury MedDRA version: 22.1 Level: LLT Classification code 10021665 Term: Increased intracranial pressure System Organ Class: 100000004852
Conditions
Interventions
Product Name: EU-C-001 di-hydrochloride
Product Code: EU-C-001
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: not yet available
CAS Number: 290296-52-5
Current Spons
Sponsors
Eustralis Pharmaceuticals Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female aged 18 to 65 years at the time the ICF is signed, or obtained remotely, by either the patient or the patient’s legally authorized representative 2. Moderate to severe TBI due to blunt mechanism 3. Abnormal CT scan result consistent with TBI due to blunt mechanism 4. Intracranial pressure monitor in situ, ICP >20 mm Hg at screening in the absence of potential external ICP stimuli, e.g., suctioning, coughing, and turning. ICP at start of first infusion of study drug = 18 mmHg. The preferred method of ICP measurement is either intraventricular, intraparenchymal, or subdural, where possible 5. The GCS score at Screening is the most recent GCS score assessed at the hospital after resuscitation. If this is not available, the GCS score assessed by the ambulance personnel/paramedics prior to arrival at hospital will be used. a. If the Total Score is assessable (range 3 to 15), a patient is eligible for inclusion if their score is in the range 3 to 12 b. If only the Eye and Motor scores are assessable (range 2 to 10), a patient is eligible for inclusion if their score is in the range 2 to 8 c. If only the Motor score is assessable (range 1 to 6), a patient is eligible for inclusion if their score is in the range 1 to 5 6. Onset of TBI within the last 72 hours 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 45 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Documented continuously elevated ICP >20 mm Hg for >12 hours after elevated ICP was first measured/observed 2.Use of an extraventricular drain (EVD) for ICP control 3. Injury deemed non-survivable by study team 4. Penetrating brain injury 5. Bilateral dilated, unresponsive pupils 6. Imminent cranial or extracranial surgery 7. Concomitant use of thiopentone 8. Cervical spinal cord injury 9. Cardiopulmonary resuscitation performed 10. Life-threatening systemic injuries, additional injuries, or conditions requiring medical treatment which would confound the assessment of the effects and/or safety of study medication 11. Morbid obesity with body mass index =40 kg/m2 12. Severe or unstable pre-existing respiratory and hemodynamic conditions 13. Hypoxemia (oxygen saturation 1.5 and/or thrombocytes 2 x upper limit of normal (ULN), alanine aminotransferase >2.5 x ULN, or aspartate aminotransferase >2.5 x ULN, INR >1.5 21. Any major neurological or psychiatric disorder associated with significant impairment of cognitive function or motor function e.g., Alzheimer’s disease with dementia, Parkinson’s disease, Huntington’s disease, alcohol or substance abuse 22. Participating in or has participated in other investigational interventional studies (drug or device) within the last 30 days (or 5 times the half-life of the previously administered investigational compound, whichever is longer) prior to study treatment initiation 23. Wearing an opt out bracelet or is known not to wish to participate in this type of study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • Double-blind phase: To assess the effect of EU-C-001 on intracranial pressure (ICP) in patients with moderate to severe traumatic brain injury (TBI) (area under the effect time curve [AUEC] 0 to 48 hours after the start of infusion of study medication [AUEC0 48 h]) • Open-label pilot phase: To assess the safety of EU-C-001 in the target population of the highest dose to be tested in the double-blind phase ;Secondary Objective: • To assess the effect of EU-C-001 on ICP in patients with moderate to severe TBI (AUEC 0 to 120 hours after the start of infusion of study medication [AUEC 0-120 h] and measured values and index parameters) • To assess the effect of EU-C-001 on outcome in the Extended Glasgow Outcome Scale (GOS-E) • To assess the safety of EU-C-001 in patients with moderate to severe TBI • To assess the Therapy Intensity Level (TIL) • To assess the cerebral hypoperfusion • To assess the brain tissue oxygenation • To assess cognitive function after 12 weeks • To explore the effect of EU-C-001 on biomarkers of inflammation and neuronal injury in patients with severe TBI • To assess the PK/pharmacodynamic (PD) relationship of EU-C-001 in a TBI setting ;Primary end point(s): Double-blind phase: comparison between active and placebo groups for: • AUEC 0-48 h for ICP Open-label pilot phase: • AEs ;Timepoint(s) of evaluation of this end point: Continuously over 48 hours after the start of infusion of study medication | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: At different time points throughout the study. Please refer to study protocol for assessments schedule. ;Secondary end point(s): (Double-Blind Phase Only) Comparison between active and placebo group for: • AUEC 0-n h for ICP, where n = 8, 12, 16, 20, 24, 36, 48, and 120 hours post first dose (measured prior to respective dose) • Change from baseline in ICP at 0.5 hours post-dose and thereafter at 1, 2, 4, 8, 12, 16, 20, 24, 36, 48, and 120 hours post dose • AEs • Times during which ICP is above 20 mm Hg and 25 mm Hg during the 48 hours and 120 hours after the start of infusion of study medication • Intracranial hypertension index 20 during the 48 hours and 120 hours after the start of infusion of study medication (calculated by the total time [hours] where ICP >20 mm Hg divided by the total time [48 hours and 120 hours, respectively], multiplied by 100) • Intracranial hypertension index 25 during the 48 hours and 120 hours after the start of infusion of study medication (calculated by the total time [hours] where ICP >25 mm Hg divided by the total time [48 hours and 120 hours, respectively], multiplied by 100) • AUEC 0-48 h and AUEC 0-120 h of TIL • Maximal TIL • Product of AUEC 0-48 h for ICP and AUEC 0-48 h of TIL (exploratory endpoint) • AUEC 0-48 h for CPP • Cerebral hypoperfusion index (the number of end-hourly measures of CPP of <60 mm Hg divided by the total number of measurements, multiplied by 100) during the 48 hours and 120 hours after the start of infusion of study medication • AUEC 0-48 h and AUEC 0-120 h of brain tissue oxygenation (if Licox probe used routinely) • GOS-E scores • Safety evaluations including physical and neurological examination (Glasgow Coma Scale [GCS]), vital signs, ECGs, and hematological and biochemical parameters • Proportion of patients surviving at 28 days and 12 weeks • Time to completion of Trail Making Test (TMT) Parts A and B at Week 12 • QoL assessed by th | — |
Countries
Australia, United Kingdom
Contacts
Public ContactKey Management
Eustralis Pharmaceuticals Ltd.
Outcome results
None listed