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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Brain Contusion

Intervention / Treatment
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* Drug: BIIB093
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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 Key Exclusion Criteria: In the judgment of the Investigator, participant is likely to have supportive care withdrawn within 24 hours.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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 |