E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Severe traumatic brain injury |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10060690 |
E.1.2 | Term | Traumatic brain injury |
E.1.2 | System Organ Class | 100000004863 |
|
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 |
The aim of the study is to determine the efficacy and safety of BHR-100 utilizing the 6-month GOS in severe TBI patients (GCS 3-8) following 120 hours of study treatment. |
|
E.2.2 | Secondary objectives of the trial |
In addition, the clinical benefit of progesterone treatment will be further assessed through the evaluation of: 1.Mortality at 1 month and 6 months post injury 2.GOS at 3 months 3.GOS-E at 3 and 6 months 4.Quality of Life using Short Form (36) Health Survey (SF-36) at 3 and 6 months 5.The effect on Intracranial Pressure (ICP), Cerebral Perfusion Pressure (CPP), and Therapeutic Intensity Level (TIL) 6.The effect on the progression of intracranial pathology as assessed by admission and Day 6 (+/- 1 Day) computed tomography (CT) scans
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Male or female patients, age between 16 and 70 years, inclusive (or lower age limit as required by local regulations) 2.Weight from 45 to 135 kg, inclusive. 3.Sustained a closed head trauma no more than 8 hours before initiation of study drug infusion (exposed dura mater is acceptable in the case of depressed skull fractures) 4.TBI diagnosed by history and clinical examination 5. GCS score between 3 to 8, inclusive 6.At least one reactive pupil (pinpoint pupils due to opioid pain treatment are considered reactive) 7.Evidence of TBI confirmed by abnormalities consistent with trauma on CT scan upon admission (Diffuse injury II-IV, evacuated and non-evacuated mass lesion, Marshall’s CT Classification) 8.Indication for ICP monitoring |
|
E.4 | Principal exclusion criteria |
1.Life expectancy of less than 24 hours as determined by the Investigator 2.Prolonged and/or uncorrectable hypoxia (Pa02< 60 mmHg) or hypotension (systolic blood pressure < 90 mmHg) at the time of Randomization. 3.Any spinal cord injury 4.Pregnancy 5.Penetrating head injury 6.Bilaterally fixed dilated pupils at the time of randomization 7.Coma suspected to be primarily due to other causes (e.g. alcohol) 8.Pure epidural hematoma 9.Preexisting clinically significant disease or chronic condition that can be ascertained at the time of admission and could affect functional outcome 10.Severe cardiac or hemodynamic instability after resuscitation prior to randomization. 11.Known treatment with another investigational drug, device, medical therapy or procedure within 30 days of injury. 12.A history of allergic reaction to progesterone and related drugs or any of the components of the infusion 13.Any disease, in the opinion of the Investigator, that is unstable or which could jeopardize the safety of the patient and his/her compliance in the study. 14.Patients who, in the opinion of the Investigator, would not be able or willing to comply with the protocol through the final visit ( 6 months post-injury)
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
GOS evaluated at 6 months post injury. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
• Mortality assessment at 1 month and 6 months post TBI • Evaluation of GOS at 3 months • Evaluation of the GOS-E at Months 3 and 6 • SF-36 at Months 3 and 6 • Changes in ICP, CPP and TIL • Effect of treatment on the progression of intracranial pathology as assesses by admission (baseline) and end-infusion (Day6+/-1 Day) CT scans |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
•Month 1 (mortality) •Month 3 (GOS, GOS-E, SF-36) •Month 6 (mortality, GOS-E, SF-36) |
|
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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 69 |
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 | No |
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 |
Argentina |
Austria |
Belgium |
China |
Czech Republic |
France |
Germany |
Hungary |
India |
Israel |
Italy |
Malaysia |
Netherlands |
Romania |
Russian Federation |
Singapore |
Spain |
Taiwan |
Thailand |
United Kingdom |
United States |
|
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
|
Last visit of the last subject (LVLS) |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |