A Study to Evaluate the Efficacy and Safety of BIIB093 in Participants With Brain Contusion
- Registration Number
- NCT03954041
- Lead Sponsor
- Remedy Pharmaceuticals, Inc.
- Brief Summary
The primary objective is to determine if BIIB093 reduces brain contusion expansion by Hour 96 when compared to placebo.
The secondary objectives are to evaluate the effects of BIIB093 on acute neurologic status, functional outcomes, and treatment requirements, to further differentiate the mechanism of action of BIIB093 on contusion expansion by examining differential effects on hematoma and edema expansion, and to determine if BIIB093 improves survival at Day 90 when compared to placebo.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 92
- Clinical diagnosis of brain contusion with lesions within the supratentorial brain parenchyma totaling >3 mL in volume per Investigator assessment of baseline non-contrast computed tomography scan (NCCT) at Screening.
- A score of 5 to 15 on the Glasgow Coma Scale (GCS).
- Functionally independent, in the opinion of the Investigator, prior to index head injury.
Key
- In the judgment of the Investigator, participant is likely to have supportive care withdrawn within 24 hours.
- Indication for immediate evacuation of IPH or DC.
- Clinical signs of brainstem herniation, in the opinion of the Investigator.
- NCCT or magnetic resonance imaging (MRI) evidence of penetrating brain parenchyma. Cerebrospinal fluid leak in isolation is not exclusionary unless evidence of parenchymal penetration by an external force (e.g., blunt object, bullet, or depressed skull fracture).
- Any presence of midbrain or posterior fossa injury as assessed by imaging and clinical examination.
- Presence of concomitant spinal cord injury as assessed by imaging and clinical examination.
- Life-threatening or nonsurvivable polytrauma, per Investigator's judgment.
- Use of novel oral anticoagulants (NOACS; including direct thrombin inhibitors such as dabigatran, or Factor Xa inhibitors such as rivaroxaban or apixaban), in preceding 3 days prior to the injury, if known.
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description BIIB093 3 mg BIIB093 Participants will be administered BIIB093 3 milligrams per day (mg/day) as a IV bolus followed by rapid and slow intravenous (IV) infusions for 96 hours. Placebo Placebo Participants will be administered BIIB093 matching placebo as a IV bolus followed by rapid and slow IV infusions for 96 hours. BIIB093 5 mg BIIB093 Participants will be administered BIIB093 5 mg/day as a IV bolus followed by rapid and slow IV infusions for 96 hours.
- Primary Outcome Measures
Name Time Method Change From Baseline in Mean Total Contusion Volume (Hematoma Plus Perihematomal Edema) at 96 Hours as Measured by Brain Imaging Baseline up to 96 hours (Day 4) Total contusion volume including hematoma and perihematomal edema volumes reported in milliliters (mL) was assessed by the central imaging core laboratory on baseline non-contrast computed tomography (NCCT), 24-hour NCCT, and the 96-hour scan (Magnetic resonance imaging \[MRI\] and/or NCCT) and the scans obtained prior to decompressive craniectomy (DC), intraparenchymal hematoma (IPH) evacuation, or comfort measures only (CMO).
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Glasgow Outcome Scale - Extended (GOS-E) Score at Day 180 Day 180 The GOS-E is a global disability scale used to assess recovery after traumatic brain injury. For this study, the 8 point ordinal scale was condensed to the following 7-categories: 1 and 2 combined: Dead and Vegetative State, 3: Lower Severe disability, 4: Upper Severe disability, 5: Lower Moderate disability, 6: Upper Moderate disability, 7 : Lower Good recovery, and 8: Upper Good Recovery. Lower scores indicate death and higher scores indicate recovery.
Change From Baseline in Absolute Hematoma Volume at 24 Hours Baseline up to 24 hours (Day 1) Hematoma volume reported in mL was assessed by the central imaging core laboratory on baseline NCCT, 24-hour NCCT, and the scans obtained prior to DC, IPH evacuation, or CMO.
Change From Baseline in Absolute Edema Volume at 96 Hours Baseline up to 96 hours (Day 4) Edema volume reported in mL was assessed by the central imaging core laboratory on baseline NCCT, 24-hour NCCT, and the 96-hour scan (MRI and/or NCCT) and the scans obtained prior to DC, IPH evacuation, or CMO.
Time to All-Cause Death Through Day 90 Randomization up to Day 90 Time to all-cause death is defined as the time from randomization to the time of death and includes all-cause death along with neurological death.
Percentage of Participants Requiring Delayed Intubation Day 1 (24 hours) up to Day 4 (96 hours) post-injury Delayed intubation is defined as participants requiring intubation (for neurologic deterioration only) at any time between 24 hours and 96 hours post-injury.
Change From Baseline in Mean Total Contusion Volume (Hematoma Plus Perihematomal Edema) at 24 Hours as Measured by Brain Imaging Baseline up to 24 hours (Day 1) Total contusion volume including hematoma and perihematomal edema volumes reported in mL was assessed by the central imaging core laboratory on baseline NCCT and 24-hour NCCT.
Percentage of Participants With Modified Rankin Scale (mRS) Score at Day 90 Day 90 The mRS measures the degree of functional independence following stroke. In this study, the 7-category ordinal mRS scale was condensed to the following 5-categories: 0/1, 2, 3, 4, 5/6 where 0 and 1 reflect no disability and near-normal functioning while 5 and 6 represent severe disability and death, respectively.
Trial Locations
- Locations (63)
Grady Memorial Hospital
🇺🇸Atlanta, Georgia, United States
Goodman Campbell Brain and Spine
🇺🇸Carmel, Indiana, United States
University of Maryland Medical Center
🇺🇸Baltimore, Maryland, United States
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
University of Cincinnati College of Medicine
🇺🇸Cincinnati, Ohio, United States
CHU Clermont Ferrand - Hopital Gabriel Montpied
🇫🇷Clermont Ferrand cedex 1, Puy De Dome, France
Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino
🇮🇹Torino, Italy
The University of Texas Health Science Center at Houston
🇺🇸Houston, Texas, United States
Universitaetsmedizin Goettingen
🇩🇪Goettingen, Niedersachsen, Germany
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
🇮🇹Roma, Italy
Hospital Universitari de Bellvitge
🇪🇸Barcelona, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Neurologische Klinik Bad Neustadt/Saale
🇩🇪Bad Neustadt/Saale, Bayern, Germany
Universitaetsklinikum Schleswig-Holstein - Campus Kiel
🇩🇪Kiel, Schleswig, Germany
Miami Valley Hospital
🇺🇸Dayton, Ohio, United States
ProMedica Toledo Hospital
🇺🇸Toledo, Ohio, United States
Vidant Medical Center
🇺🇸Greenville, North Carolina, United States
Hospital Universitari Son Espases
🇪🇸Palma de Mallorca, Baleares, Spain
ASST Monza - Ospedale San Gerardo di Monza
🇮🇹Monza Brianza, Milano, Italy
Azienda Socio Sanitaria Territoriale Niguarda (Grande Ospedale Metropolitano Niguarda)
🇮🇹Milano, Italy
UT Southwestern Medical Center
🇺🇸Dallas, Texas, United States
CHU de Brest - Hôpital de la Cavale Blanche
🇫🇷Brest, Finistere, France
CHU Rennes - Hôpital Pontchaillou
🇫🇷Rennes, Ille Et Vilaine, France
Azienda Ospedaliero Universitaria di Parma
🇮🇹Pama, Parma, Italy
Hospital Universitario Reina Sofia
🇪🇸Cordoba, Spain
Universitaetsklinikum Heidelberg
🇩🇪Heidelberg, Baden Wuerttemberg, Germany
Barrow Neurological Institute
🇺🇸Phoenix, Arizona, United States
Wake Forest Baptist Health Sciences
🇺🇸Winston-Salem, North Carolina, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
WellStar Medical Group Neurosurgery
🇺🇸Marietta, Georgia, United States
Northwell Health
🇺🇸Manhattan, New York, United States
University of Utah Health
🇺🇸Salt Lake City, Utah, United States
Ospedale Maggiore di Novara
🇮🇹Novara, Italy
Complejo Hospitalario Universitario de Santiago
🇪🇸Santiago de Compostela, La Coruna, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Rinku General Medical Center
🇯🇵Izumisano-Shi, Osaka-Fu, Japan
University of Arizona Medical Center
🇺🇸Tucson, Arizona, United States
Chaim Sheba Medical Center
🇮🇱Ramat Gan, Tel Aviv, Israel
Rambam Health Care Center
🇮🇱Haifa, Israel
Hadassah
🇮🇱Jerusalem, Israel
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Kimitsu Chuo Hospital
🇯🇵Kisarazu-Shi, Chiba-Ken, Japan
Kobe City Hospital Organization Kobe City Medical Center General Hospital
🇯🇵Kobe-shi, Hyogo-Ken, Japan
Nara Medical University Hospital
🇯🇵Kashihara-shi, Nara-Ken, Japan
Health Corporation of Galilee Medical Center
🇮🇱Naharya, Northern, Israel
Shaare Zedek Medical Center
🇮🇱Jerusalem, Israel
Rabin MC
🇮🇱Petah Tikva, Central, Israel
Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona
🇮🇹Torrette, Ancona, Italy
Nippon Medical School Hospital
🇯🇵Bunkyo-ku, Tokyo-to, Japan
Scottsdale Healthcare Hospitals d/b/a HonorHealth
🇺🇸Scottsdale, Arizona, United States
Hospital Alvaro Cunqueiro
🇪🇸Vigo, Pontevedra, Spain
Hopital Caremeau
🇫🇷Nimes Cedex 9, Gard, France
Groupe Hospitalier Pellegrin - Hôpital Pellegrin
🇫🇷Bordeaux cedex, Gironde, France
CHU Amiens - Hopital Sud
🇫🇷Amiens Cedex, Somme, France
Yamaguchi University Hospital
🇯🇵Ube-Shi, Yamaguchi- Ken, Japan
Yale New Haven Hospital
🇺🇸New Haven, Connecticut, United States
University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
University Medical Center New Orleans
🇺🇸New Orleans, Louisiana, United States
Virginia Commonwealth University Medical Center
🇺🇸Richmond, Virginia, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States
Rhode Island Hospital
🇺🇸East Providence, Rhode Island, United States