Back to resultsA Study to Evaluate the Efficacy and Safety of BIIB093 in Participants With Brain Contusion (ASTRAL)
Primary Purpose
Brain Contusion
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
BIIB093
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Brain Contusion
Eligibility Criteria
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- In the judgment of the Investigator, participant is likely to have supportive care withdrawn within 24 hours.
- 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.
- Polytrauma (intra-abdominal or orthopedic trauma) requiring operative/surgical management, if known. Minor fractures requiring splinting or reduction of dislocations are permitted, as are nonoperative intra-abdominal injuries or placement of noninvasive external fixation devices.
- 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.
Sites / Locations
- Barrow Neurological Institute
- Scottsdale Healthcare Hospitals d/b/a HonorHealth
- University of Arizona Medical Center
- Yale New Haven Hospital
- Grady Memorial Hospital
- WellStar Medical Group Neurosurgery
- Goodman Campbell Brain and Spine
- University Medical Center New Orleans
- University of Maryland Medical Center
- Tufts Medical Center
- Massachusetts General Hospital
- Northwell Health
- University of North Carolina at Chapel Hill
- Vidant Medical Center
- Wake Forest Baptist Health Sciences
- University of Cincinnati College of Medicine
- Miami Valley Hospital
- ProMedica Toledo Hospital
- Oregon Health & Science University
- Thomas Jefferson University
- Rhode Island Hospital
- UT Southwestern Medical Center
- The University of Texas Health Science Center at Houston
- University of Utah Health
- Virginia Commonwealth University Medical Center
- CHU de Brest - Hôpital de la Cavale Blanche
- Hopital Caremeau
- Groupe Hospitalier Pellegrin - Hôpital Pellegrin
- CHU Rennes - Hôpital Pontchaillou
- CHU Clermont Ferrand - Hopital Gabriel Montpied
- CHU Amiens - Hopital Sud
- Universitaetsklinikum Heidelberg
- Neurologische Klinik Bad Neustadt/Saale
- Universitaetsmedizin Goettingen
- Universitaetsklinikum Schleswig-Holstein - Campus Kiel
- Rabin MC
- Health Corporation of Galilee Medical Center
- Chaim Sheba Medical Center
- Rambam Health Care Center
- Shaare Zedek Medical Center
- Hadassah
- Tel Aviv Sourasky Medical Center
- Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona
- ASST Monza - Ospedale San Gerardo di Monza
- Azienda Ospedaliero Universitaria di Parma
- Azienda Socio Sanitaria Territoriale Niguarda (Grande Ospedale Metropolitano Niguarda)
- Ospedale Maggiore di Novara
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS
- Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino
- Kimitsu Chuo Hospital
- Kobe City Hospital Organization Kobe City Medical Center General Hospital
- Nara Medical University Hospital
- Rinku General Medical Center
- Nippon Medical School Hospital
- Yamaguchi University Hospital
- Hospital Universitari Son Espases
- Complejo Hospitalario Universitario de Santiago
- Hospital Alvaro Cunqueiro
- Hospital Universitari Vall d'Hebron
- Hospital Universitari de Bellvitge
- Hospital Universitario Reina Sofia
- Hospital Universitario 12 de Octubre
- Hospital Universitario La Paz
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Placebo Comparator
Placebo Comparator
Arm Label
BIIB093 3 mg
BIIB093 5 mg
Placebo 3 mg
Placebo 5 mg
Arm Description
Participants will be administered BIIB093 3 milligram per day (mg/day) as a bolus followed by rapid and slow intravenous (IV) infusions for 96 hours.
Participants will be administered BIIB093 5 mg/day as a bolus followed by rapid and slow IV infusions for 96 hours.
Participants will be administered matching placebo to BIIB093 as a bolus followed by rapid and slow IV infusions for 96 hours.
Participants will be administered matching placebo to BIIB093 as a bolus followed by rapid and slow IV infusions for 96 hours.
Outcomes
Primary Outcome Measures
Change in Total Contusion Volume (Hematoma plus Perihematomal Edema) as Measured by Brain Imaging
Measurements of contusion expansion are based on a correlation of the baseline images and the scans collected prior to and including 96-hour scan or the scan obtained prior to decompressive craniectomy (DC), intraparenchymal hematoma (IPH) evacuation, or comfort measures only (CMO) if earlier.
Secondary Outcome Measures
Proportion of Participants With Improvement in Glasgow Outcome Scale - Extended (GOS-E)
The Glasgow Outcome Scale (GOS) is a global scale for functional outcome that rates participant status into one of five categories: Dead, Vegetative State, Severe Disability, Moderate Disability or Good Recovery. The Extended GOS (GOS-E) provides more detailed categorization into eight categories by subdividing the categories of severe disability, moderate disability and good recovery into a lower and upper category.
Proportion of Participants With Improvement in Modified Rankin Scale (mRS)
The mRS measures the degree of disability or dependence in the daily activities of participants who have suffered a stroke or other causes of neurological disability. The scale runs from 0-6, ranging from perfect health without symptoms (0) to dead (6).
Proportion 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 postinjury.
Change in Total Contusion Volume (Hematoma Plus Perihematomal Edema) as Measured by Brain Imaging
Change from Baseline in Absolute Hematoma Volume at Hour 24
Change from Baseline in Absolute Edema Volume at Hour 96
Time to All-cause Death
The treatment effects on overall survival of participants, including neurological death, will be assessed.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03954041
Brief Title
A Study to Evaluate the Efficacy and Safety of BIIB093 in Participants With Brain Contusion
Acronym
ASTRAL
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Terminated
Why Stopped
Early completed due to strategic considerations, not for efficacy or safety reasons.
Study Start Date
October 6, 2019 (Actual)
Primary Completion Date
June 27, 2023 (Actual)
Study Completion Date
June 27, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Biogen
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brain Contusion
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
90 (Actual)
8. Arms, Groups, and Interventions
Arm Title
BIIB093 3 mg
Arm Type
Experimental
Arm Description
Participants will be administered BIIB093 3 milligram per day (mg/day) as a bolus followed by rapid and slow intravenous (IV) infusions for 96 hours.
Arm Title
BIIB093 5 mg
Arm Type
Experimental
Arm Description
Participants will be administered BIIB093 5 mg/day as a bolus followed by rapid and slow IV infusions for 96 hours.
Arm Title
Placebo 3 mg
Arm Type
Placebo Comparator
Arm Description
Participants will be administered matching placebo to BIIB093 as a bolus followed by rapid and slow IV infusions for 96 hours.
Arm Title
Placebo 5 mg
Arm Type
Placebo Comparator
Arm Description
Participants will be administered matching placebo to BIIB093 as a bolus followed by rapid and slow IV infusions for 96 hours.
Intervention Type
Drug
Intervention Name(s)
BIIB093
Other Intervention Name(s)
Glibenclamide, CIRARA, RP 1127
Intervention Description
Administered as specified in the treatment arm.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Administered as specified in the treatment arm.
Primary Outcome Measure Information:
Title
Change in Total Contusion Volume (Hematoma plus Perihematomal Edema) as Measured by Brain Imaging
Description
Measurements of contusion expansion are based on a correlation of the baseline images and the scans collected prior to and including 96-hour scan or the scan obtained prior to decompressive craniectomy (DC), intraparenchymal hematoma (IPH) evacuation, or comfort measures only (CMO) if earlier.
Time Frame
From Baseline to 96 Hours
Secondary Outcome Measure Information:
Title
Proportion of Participants With Improvement in Glasgow Outcome Scale - Extended (GOS-E)
Description
The Glasgow Outcome Scale (GOS) is a global scale for functional outcome that rates participant status into one of five categories: Dead, Vegetative State, Severe Disability, Moderate Disability or Good Recovery. The Extended GOS (GOS-E) provides more detailed categorization into eight categories by subdividing the categories of severe disability, moderate disability and good recovery into a lower and upper category.
Time Frame
Day 180
Title
Proportion of Participants With Improvement in Modified Rankin Scale (mRS)
Description
The mRS measures the degree of disability or dependence in the daily activities of participants who have suffered a stroke or other causes of neurological disability. The scale runs from 0-6, ranging from perfect health without symptoms (0) to dead (6).
Time Frame
Day 90
Title
Proportion of Participants Requiring Delayed Intubation
Description
Delayed intubation is defined as participants requiring intubation (for neurologic deterioration only) at any time between 24 hours and 96 hours postinjury.
Time Frame
Day 1 (Hour 24) to Day 4 (Hour 96)
Title
Change in Total Contusion Volume (Hematoma Plus Perihematomal Edema) as Measured by Brain Imaging
Time Frame
Baseline up to 24 hours
Title
Change from Baseline in Absolute Hematoma Volume at Hour 24
Time Frame
Baseline up to Day 1 (Hour 24)
Title
Change from Baseline in Absolute Edema Volume at Hour 96
Time Frame
Baseline up to Day 4 (Hour 96)
Title
Time to All-cause Death
Description
The treatment effects on overall survival of participants, including neurological death, will be assessed.
Time Frame
Baseline up to Day 90
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Biogen
Official's Role
Study Director
Facility Information:
Facility Name
Barrow Neurological Institute
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85013
Country
United States
Facility Name
Scottsdale Healthcare Hospitals d/b/a HonorHealth
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85258
Country
United States
Facility Name
University of Arizona Medical Center
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724
Country
United States
Facility Name
Yale New Haven Hospital
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510
Country
United States
Facility Name
Grady Memorial Hospital
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30303
Country
United States
Facility Name
WellStar Medical Group Neurosurgery
City
Marietta
State/Province
Georgia
ZIP/Postal Code
30060
Country
United States
Facility Name
Goodman Campbell Brain and Spine
City
Carmel
State/Province
Indiana
ZIP/Postal Code
46032
Country
United States
Facility Name
University Medical Center New Orleans
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70119
Country
United States
Facility Name
University of Maryland Medical Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Tufts Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Northwell Health
City
Manhattan
State/Province
New York
ZIP/Postal Code
11030
Country
United States
Facility Name
University of North Carolina at Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27514
Country
United States
Facility Name
Vidant Medical Center
City
Greenville
State/Province
North Carolina
ZIP/Postal Code
27834
Country
United States
Facility Name
Wake Forest Baptist Health Sciences
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Name
University of Cincinnati College of Medicine
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
Facility Name
Miami Valley Hospital
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45409
Country
United States
Facility Name
ProMedica Toledo Hospital
City
Toledo
State/Province
Ohio
ZIP/Postal Code
43606
Country
United States
Facility Name
Oregon Health & Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Thomas Jefferson University
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
Rhode Island Hospital
City
East Providence
State/Province
Rhode Island
ZIP/Postal Code
02915-2237
Country
United States
Facility Name
UT Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
The University of Texas Health Science Center at Houston
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Utah Health
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
Facility Name
Virginia Commonwealth University Medical Center
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298-0599
Country
United States
Facility Name
CHU de Brest - Hôpital de la Cavale Blanche
City
Brest
State/Province
Finistere
ZIP/Postal Code
29200
Country
France
Facility Name
Hopital Caremeau
City
Nimes Cedex 9
State/Province
Gard
ZIP/Postal Code
30029
Country
France
Facility Name
Groupe Hospitalier Pellegrin - Hôpital Pellegrin
City
Bordeaux cedex
State/Province
Gironde
ZIP/Postal Code
33076
Country
France
Facility Name
CHU Rennes - Hôpital Pontchaillou
City
Rennes
State/Province
Ille Et Vilaine
ZIP/Postal Code
35033
Country
France
Facility Name
CHU Clermont Ferrand - Hopital Gabriel Montpied
City
Clermont Ferrand cedex 1
State/Province
Puy De Dome
ZIP/Postal Code
63003
Country
France
Facility Name
CHU Amiens - Hopital Sud
City
Amiens Cedex
State/Province
Somme
ZIP/Postal Code
80054
Country
France
Facility Name
Universitaetsklinikum Heidelberg
City
Heidelberg
State/Province
Baden Wuerttemberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
Neurologische Klinik Bad Neustadt/Saale
City
Bad Neustadt/Saale
State/Province
Bayern
ZIP/Postal Code
97616
Country
Germany
Facility Name
Universitaetsmedizin Goettingen
City
Goettingen
State/Province
Niedersachsen
ZIP/Postal Code
37075
Country
Germany
Facility Name
Universitaetsklinikum Schleswig-Holstein - Campus Kiel
City
Kiel
State/Province
Schleswig
ZIP/Postal Code
24105
Country
Germany
Facility Name
Rabin MC
City
Petah Tikva
State/Province
Central
ZIP/Postal Code
49100
Country
Israel
Facility Name
Health Corporation of Galilee Medical Center
City
Naharya
State/Province
Northern
ZIP/Postal Code
22100
Country
Israel
Facility Name
Chaim Sheba Medical Center
City
Ramat Gan
State/Province
Tel Aviv
ZIP/Postal Code
5265601
Country
Israel
Facility Name
Rambam Health Care Center
City
Haifa
ZIP/Postal Code
3109601
Country
Israel
Facility Name
Shaare Zedek Medical Center
City
Jerusalem
ZIP/Postal Code
9103102
Country
Israel
Facility Name
Hadassah
City
Jerusalem
ZIP/Postal Code
9112001
Country
Israel
Facility Name
Tel Aviv Sourasky Medical Center
City
Tel Aviv
ZIP/Postal Code
64239
Country
Israel
Facility Name
Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona
City
Torrette
State/Province
Ancona
ZIP/Postal Code
60020
Country
Italy
Facility Name
ASST Monza - Ospedale San Gerardo di Monza
City
Monza Brianza
State/Province
Milano
ZIP/Postal Code
20900
Country
Italy
Facility Name
Azienda Ospedaliero Universitaria di Parma
City
Pama
State/Province
Parma
ZIP/Postal Code
43126
Country
Italy
Facility Name
Azienda Socio Sanitaria Territoriale Niguarda (Grande Ospedale Metropolitano Niguarda)
City
Milano
ZIP/Postal Code
20162
Country
Italy
Facility Name
Ospedale Maggiore di Novara
City
Novara
ZIP/Postal Code
28100
Country
Italy
Facility Name
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
City
Roma
ZIP/Postal Code
00137
Country
Italy
Facility Name
Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino
City
Torino
ZIP/Postal Code
10126
Country
Italy
Facility Name
Kimitsu Chuo Hospital
City
Kisarazu-Shi
State/Province
Chiba-Ken
ZIP/Postal Code
292-8535
Country
Japan
Facility Name
Kobe City Hospital Organization Kobe City Medical Center General Hospital
City
Kobe-shi
State/Province
Hyogo-Ken
ZIP/Postal Code
650-0047
Country
Japan
Facility Name
Nara Medical University Hospital
City
Kashihara-shi
State/Province
Nara-Ken
ZIP/Postal Code
634-8522
Country
Japan
Facility Name
Rinku General Medical Center
City
Izumisano-Shi
State/Province
Osaka-Fu
ZIP/Postal Code
598-8577
Country
Japan
Facility Name
Nippon Medical School Hospital
City
Bunkyo-ku
State/Province
Tokyo-to
ZIP/Postal Code
113-8603
Country
Japan
Facility Name
Yamaguchi University Hospital
City
Ube-Shi
State/Province
Yamaguchi- Ken
ZIP/Postal Code
755-8505
Country
Japan
Facility Name
Hospital Universitari Son Espases
City
Palma de Mallorca
State/Province
Baleares
ZIP/Postal Code
07120
Country
Spain
Facility Name
Complejo Hospitalario Universitario de Santiago
City
Santiago de Compostela
State/Province
La Coruna
ZIP/Postal Code
15706
Country
Spain
Facility Name
Hospital Alvaro Cunqueiro
City
Vigo
State/Province
Pontevedra
ZIP/Postal Code
36312
Country
Spain
Facility Name
Hospital Universitari Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Universitari de Bellvitge
City
Barcelona
ZIP/Postal Code
08907
Country
Spain
Facility Name
Hospital Universitario Reina Sofia
City
Cordoba
ZIP/Postal Code
14004
Country
Spain
Facility Name
Hospital Universitario 12 de Octubre
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
Hospital Universitario La Paz
City
Madrid
ZIP/Postal Code
28046
Country
Spain
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/
IPD Sharing URL
https://vivli.org/
Learn more about this trial
A Study to Evaluate the Efficacy and Safety of BIIB093 in Participants With Brain Contusion
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