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

Brain Contusion Clinical Trial

— 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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03954041
• Other study ID #: 252BN201
• Secondary ID: 2018-003858-24
• Status: Terminated
• Phase: Phase 2
• Start date: October 6, 2019
• Est. completion date: June 27, 2023

Study information

• Verified date: November 2023
• Source: Remedy Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 92
• Est. completion date: June 27, 2023
• Est. primary completion date: June 27, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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• In the judgment of the Investigator, participant is likely to have supportive care withdrawn within 24 hours.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.

Related Conditions & MeSH terms

• Brain Contusion
• Contusions

Intervention

Drug:
• BIIB093
Administered as specified in the treatment arm.
• Placebo
Administered as specified in the treatment arm.

Locations

Country	Name	City	State
France	CHU Amiens - Hopital Sud	Amiens Cedex	Somme
France	Groupe Hospitalier Pellegrin - Hôpital Pellegrin	Bordeaux cedex	Gironde
France	CHU de Brest - Hôpital de la Cavale Blanche	Brest	Finistere
France	CHU Clermont Ferrand - Hopital Gabriel Montpied	Clermont Ferrand cedex 1	Puy De Dome
France	Hopital Caremeau	Nimes Cedex 9	Gard
France	CHU Rennes - Hôpital Pontchaillou	Rennes	Ille Et Vilaine
Germany	Neurologische Klinik Bad Neustadt/Saale	Bad Neustadt/Saale	Bayern
Germany	Universitaetsmedizin Goettingen	Goettingen	Niedersachsen
Germany	Universitaetsklinikum Heidelberg	Heidelberg	Baden Wuerttemberg
Germany	Universitaetsklinikum Schleswig-Holstein - Campus Kiel	Kiel	Schleswig
Israel	Rambam Health Care Center	Haifa
Israel	Hadassah	Jerusalem
Israel	Shaare Zedek Medical Center	Jerusalem
Israel	Health Corporation of Galilee Medical Center	Naharya	Northern
Israel	Rabin MC	Petah Tikva	Central
Israel	Chaim Sheba Medical Center	Ramat Gan	Tel Aviv
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Italy	Azienda Socio Sanitaria Territoriale Niguarda (Grande Ospedale Metropolitano Niguarda)	Milano
Italy	ASST Monza - Ospedale San Gerardo di Monza	Monza Brianza	Milano
Italy	Ospedale Maggiore di Novara	Novara
Italy	Azienda Ospedaliero Universitaria di Parma	Pama	Parma
Italy	Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Roma
Italy	Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino	Torino
Italy	Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona	Torrette	Ancona
Japan	Nippon Medical School Hospital	Bunkyo-ku	Tokyo-to
Japan	Rinku General Medical Center	Izumisano-Shi	Osaka-Fu
Japan	Nara Medical University Hospital	Kashihara-shi	Nara-Ken
Japan	Kimitsu Chuo Hospital	Kisarazu-Shi	Chiba-Ken
Japan	Kobe City Hospital Organization Kobe City Medical Center General Hospital	Kobe-shi	Hyogo-Ken
Japan	Yamaguchi University Hospital	Ube-Shi	Yamaguchi- Ken
Spain	Hospital Universitari de Bellvitge	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Universitario Reina Sofia	Cordoba
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitari Son Espases	Palma de Mallorca	Baleares
Spain	Complejo Hospitalario Universitario de Santiago	Santiago de Compostela	La Coruna
Spain	Hospital Alvaro Cunqueiro	Vigo	Pontevedra
United States	Grady Memorial Hospital	Atlanta	Georgia
United States	University of Maryland Medical Center	Baltimore	Maryland
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	Goodman Campbell Brain and Spine	Carmel	Indiana
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	University of Cincinnati College of Medicine	Cincinnati	Ohio
United States	UT Southwestern Medical Center	Dallas	Texas
United States	Miami Valley Hospital	Dayton	Ohio
United States	Rhode Island Hospital	East Providence	Rhode Island
United States	Vidant Medical Center	Greenville	North Carolina
United States	The University of Texas Health Science Center at Houston	Houston	Texas
United States	Northwell Health	Manhattan	New York
United States	WellStar Medical Group Neurosurgery	Marietta	Georgia
United States	Yale New Haven Hospital	New Haven	Connecticut
United States	University Medical Center New Orleans	New Orleans	Louisiana
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Barrow Neurological Institute	Phoenix	Arizona
United States	Oregon Health & Science University	Portland	Oregon
United States	Virginia Commonwealth University Medical Center	Richmond	Virginia
United States	University of Utah Health	Salt Lake City	Utah
United States	Scottsdale Healthcare Hospitals d/b/a HonorHealth	Scottsdale	Arizona
United States	ProMedica Toledo Hospital	Toledo	Ohio
United States	University of Arizona Medical Center	Tucson	Arizona
United States	Wake Forest Baptist Health Sciences	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Remedy Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  France,  Germany,  Israel,  Italy,  Japan,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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