A Study to Evaluate the Efficacy and Safety of BIIB093 in Participants With Brain Contusion (ASTRAL)

A Multicenter, Double-Blind, Multidose, Placebo-Controlled, Randomized, Parallel-Group, Phase 2 Study to Evaluate the Efficacy and Safety of Intravenous BIIB093 for Patients With Brain Contusion

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.

Study Overview

• Status: Terminated
• Conditions: Brain Contusion
• Intervention / Treatment: Drug: Placebo; Drug: BIIB093

• Study Type: Interventional
• Enrollment (Actual): 92
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Finistere
    • Brest, Finistere, France, 29200
      • CHU de Brest - Hôpital de la Cavale Blanche
  • Gard
    • Nimes Cedex 9, Gard, France, 30029
      • Hopital Caremeau
  • Gironde
    • Bordeaux cedex, Gironde, France, 33076
      • Groupe Hospitalier Pellegrin - Hôpital Pellegrin
  • Ille Et Vilaine
    • Rennes, Ille Et Vilaine, France, 35033
      • Chu Rennes - Hopital Pontchaillou
  • Puy De Dome
    • Clermont Ferrand cedex 1, Puy De Dome, France, 63003
      • CHU Clermont Ferrand - Hopital Gabriel Montpied
  • Somme
    • Amiens Cedex, Somme, France, 80054
      • CHU Amiens - Hopital Sud
• Germany
  • Baden Wuerttemberg
    • Heidelberg, Baden Wuerttemberg, Germany, 69120
      • Universitaetsklinikum Heidelberg
  • Bayern
    • Bad Neustadt/Saale, Bayern, Germany, 97616
      • Neurologische Klinik Bad Neustadt/Saale
  • Niedersachsen
    • Goettingen, Niedersachsen, Germany, 37075
      • Universitaetsmedizin Goettingen
  • Schleswig
    • Kiel, Schleswig, Germany, 24105
      • Universitaetsklinikum Schleswig-Holstein - Campus Kiel
• Israel
  • Haifa, Israel, 3109601
    • Rambam Health Care Center
  • Jerusalem, Israel, 9103102
    • Shaare Zedek Medical Center
  • Jerusalem, Israel, 9112001
    • Hadassah
  • Tel Aviv, Israel, 64239
    • Tel Aviv Sourasky Medical Center
  • Central
    • Petah Tikva, Central, Israel, 49100
      • Rabin MC
  • Northern
    • Naharya, Northern, Israel, 22100
      • Health Corporation of Galilee Medical Center
  • Tel Aviv
    • Ramat Gan, Tel Aviv, Israel, 5265601
      • Chaim Sheba Medical Center
• Italy
  • Milano, Italy, 20162
    • Azienda Socio Sanitaria Territoriale Niguarda (Grande Ospedale Metropolitano Niguarda)
  • Novara, Italy, 28100
    • Ospedale Maggiore di Novara
  • Roma, Italy, 00137
    • Fondazione Policlinico Universitario Agostino Gemelli IRCCS
  • Torino, Italy, 10126
    • Azienda Ospedaliero-Universitaria Citta della Salute e della Scienza di Torino
  • Ancona
    • Torrette, Ancona, Italy, 60020
      • Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona
  • Milano
    • Monza Brianza, Milano, Italy, 20900
      • ASST Monza - Ospedale San Gerardo di Monza
  • Parma
    • Pama, Parma, Italy, 43126
      • Azienda Ospedaliero Universitaria di Parma
• Japan
  • Chiba-Ken
    • Kisarazu-Shi, Chiba-Ken, Japan, 292-8535
      • Kimitsu Chuo Hospital
  • Hyogo-Ken
    • Kobe-shi, Hyogo-Ken, Japan, 650-0047
      • Kobe City Hospital Organization Kobe City Medical Center General Hospital
  • Nara-Ken
    • Kashihara-shi, Nara-Ken, Japan, 634-8522
      • Nara Medical University Hospital
  • Osaka-Fu
    • Izumisano-Shi, Osaka-Fu, Japan, 598-8577
      • Rinku General Medical Center
  • Tokyo-to
    • Bunkyo-ku, Tokyo-to, Japan, 113-8603
      • Nippon Medical School Hospital
  • Yamaguchi- Ken
    • Ube-Shi, Yamaguchi- Ken, Japan, 755-8505
      • Yamaguchi University Hospital
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 08907
    • Hospital Universitari de Bellvitge
  • Cordoba, Spain, 14004
    • Hospital Universitario Reina Sofia
  • Madrid, Spain, 28041
    • Hospital Universitario 12 De Octubre
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Baleares
    • Palma de Mallorca, Baleares, Spain, 07120
      • Hospital Universitari Son Espases
  • La Coruna
    • Santiago de Compostela, La Coruna, Spain, 15706
      • Complejo Hospitalario Universitario de Santiago
  • Pontevedra
    • Vigo, Pontevedra, Spain, 36312
      • Hospital Álvaro Cunqueiro
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Barrow Neurological Institute
    • Scottsdale, Arizona, United States, 85258
      • Scottsdale Healthcare Hospitals d/b/a HonorHealth
    • Tucson, Arizona, United States, 85724
      • University of Arizona Medical Center
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale New Haven Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30303
      • Grady Memorial Hospital
    • Marietta, Georgia, United States, 30060
      • WellStar Medical Group Neurosurgery
  • Indiana
    • Carmel, Indiana, United States, 46032
      • Goodman Campbell Brain and Spine
  • Louisiana
    • New Orleans, Louisiana, United States, 70119
      • University Medical Center New Orleans
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
  • New York
    • Manhattan, New York, United States, 11030
      • Northwell Health
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • University of North Carolina at Chapel Hill
    • Greenville, North Carolina, United States, 27834
      • Vidant Medical Center
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Health Sciences
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati College of Medicine
    • Dayton, Ohio, United States, 45409
      • Miami Valley Hospital
    • Toledo, Ohio, United States, 43606
      • ProMedica Toledo Hospital
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
  • Rhode Island
    • East Providence, Rhode Island, United States, 02915-2237
      • Rhode Island Hospital
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • The University of Texas Health Science Center at Houston
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Health
  • Virginia
    • Richmond, Virginia, United States, 23298-0599
      • Virginia Commonwealth University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• 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 Exclusion Criteria:

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BIIB093 3 mg; 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.	Drug: BIIB093; Administered as specified in the treatment arm.; Other Names: Glibenclamide; CIRARA; RP 1127
Experimental: BIIB093 5 mg; Participants will be administered BIIB093 5 mg/day as a IV bolus followed by rapid and slow IV infusions for 96 hours.	Drug: BIIB093; Administered as specified in the treatment arm.; Other Names: Glibenclamide; CIRARA; RP 1127
Placebo Comparator: Placebo; Participants will be administered BIIB093 matching placebo as a IV bolus followed by rapid and slow IV infusions for 96 hours.	Drug: Placebo; Administered as specified in the treatment arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Mean Total Contusion Volume (Hematoma Plus Perihematomal Edema) at 96 Hours as Measured by Brain Imaging	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).	Baseline up to 96 hours (Day 4)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Glasgow Outcome Scale - Extended (GOS-E) Score at 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.	Day 180
Percentage of Participants With Modified Rankin Scale (mRS) Score at 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.	Day 90
Percentage of Participants Requiring Delayed Intubation	Delayed intubation is defined as participants requiring intubation (for neurologic deterioration only) at any time between 24 hours and 96 hours post-injury.	Day 1 (24 hours) up to Day 4 (96 hours) post-injury
Change From Baseline in Mean Total Contusion Volume (Hematoma Plus Perihematomal Edema) at 24 Hours as Measured by Brain Imaging	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.	Baseline up to 24 hours (Day 1)
Change From Baseline in Absolute Hematoma Volume at 24 Hours	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.	Baseline up to 24 hours (Day 1)
Change From Baseline in Absolute Edema Volume at 96 Hours	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.	Baseline up to 96 hours (Day 4)
Time to All-Cause Death Through 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.	Randomization up to Day 90

Collaborators and Investigators

• Sponsor: Biogen
• Investigators: Study Director: Medical Director, Biogen

Study record dates

Study Major Dates

• Study Start (Actual): October 6, 2019
• Primary Completion (Actual): June 27, 2023
• Study Completion (Actual): June 27, 2023

Study Registration Dates

• First Submitted: May 15, 2019
• First Submitted That Met QC Criteria: May 15, 2019
• First Posted (Actual): May 17, 2019

Study Record Updates

• Last Update Posted (Actual): December 20, 2023
• Last Update Submitted That Met QC Criteria: November 29, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Wounds, Nonpenetrating; Brain Injuries; Brain Injuries, Traumatic; Contusions; Brain Contusion; Hypoglycemic Agents; Physiological Effects of Drugs; Glyburide
• Other Study ID Numbers: 252BN201; 2018-003858-24 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No