Phase 3 Study to Evaluate the Efficacy and Safety of Intravenous BIIB093 (Glibenclamide) for Severe Cerebral Edema Following Large Hemispheric Infarction

Study Overview
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Brief Summary
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The primary objective of Part 1 of the study is to determine if BIIB093 improves functional outcome at Day 90 as measured by the modified Rankin Scale (mRS) when compared with placebo in participants with Large Hemispheric Infarction (LHI). The secondary objectives of Part 1 of the study are to determine if BIIB093 improves overall survival at Day 90 when compared with placebo, if BIIB093 improves functional outcome at Day 90 on the mRS dichotomized 0-4 vs. 5-6 when compared with placebo, if BIIB093 reduces midline shift at 72 hours (or at time of decompressive craniectomy [DC] or comfort measures only [CMO], if earlier) when compared with placebo, and to evaluate the safety and tolerability of BIIB093 in participants with LHI. The objectives of Part 2 of the study are to evaluate long-term disability following LHI, to evaluate long-term outcome measures of clinical function, quality of life, and healthcare utilization, and to assess the safety of BIIB093 in subjects with LHI during the follow-up period.

Detailed Description
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This study, previously posted by Remedy Pharmaceuticals, Inc., has transitioned to Biogen.

Official Title
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Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter, Phase 3 Study to Evaluate the Efficacy and Safety of Intravenous BIIB093 (Glibenclamide) for Severe Cerebral Edema Following Large Hemispheric Infarction

Conditions
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Brain Edema, Stroke, Acute

Intervention / Treatment
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* Drug: BIIB093
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A clinical diagnosis of acute ischemic stroke in the middle cerebral artery (MCA) territory. A large hemispheric infarction defined as; lesion volume of 80 to 300 centimeters cubed (cm^3) on magnetic resonance imaging (MRI) diffusion-weighted imaging (DWI), or computed tomography perfusion (CTP), or an Alberta Stroke Program Early CT Score (ASPECTS) of 1 to 5 with involvement of at least 2 defined cortical regions. Screening National Institutes of Health Stroke Scale (NIHSS) >=10. At the time of randomization, and in the Investigator's judgement, it must be feasible for study drug treatment infusion to be initiated no later than 10 hours after time of symptom onset, if known, or the time last known normal. Participants who wake with stroke may be included if neurological and other exclusion criteria are satisfied. The time of stroke onset is to be taken as the midpoint between sleep onset (or last known to be normal) and time of waking. For participants who receive thrombectomy, inclusion into the study must be based on post-thrombectomy MRI-DWI. Exclusion Criteria: Participant is likely to have supportive care withdrawn on the first day. Commitment to decompressive craniectomy (DC) prior to enrollment. Evidence of concurrent infarction in the contralateral hemisphere sufficiently serious so as to affect functional outcome. 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<br>BIIB093 administered as a bolus followed by continuous intravenous (IV) infusion over 72 hours. | Drug: BIIB093<br>* Administered as specified in the treatment arm.<br>* Other names: CIRARA;|
| Placebo Comparator: Placebo<br>Placebo administered as a bolus followed by continuous intravenous (IV) infusion over 72 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 |
| --- | --- | --- |
| Part 1: Percentage of Participants with Improvement in Functional Outcome at Day 90 Assessed via the Modified Rankin Scale (mRS) | mRS is a standardized interview that measures the degree of disability or dependence in the daily activities of people who have suffered causes of neurological disability. The score will be calculated as a 5-category ordinal scale. The 5-category mRS combines mRS categories 0 and 1 and mRS categories 5 and 6 (0/1, 2, 3, 4, 5/6). The mRS ranges from 0 to 6, with higher scores indicating worse outcome. | Baseline up to Day 90 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Time to All-Cause Death |  | Baseline up to Day 90 | 
| Part 1: Number of Participants Who Achieved mRS 0-4 at Day 90 | mRS is a standardized interview that measures the degree of disability or dependence in the daily activities of participants who have suffered causes of neurological disability. The score will be calculated as a 5-category ordinal scale. The 5-category mRS combines mRS categories 0 and 1 and mRS categories 5 and 6 (0/1, 2, 3, 4, 5/6). The mRS ranges from 0 to 6, with higher scores indicating worse outcome. | Baseline up to Day 90 | 
| Part 1: Reduction in Midline Shift at 72 Hours | Midline shift will be assessed by non-contrast computed tomography (NCCT) or MRI. | Baseline up to 72 hours | 
| Part 1: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A SAE is any untoward medical occurrence that at any dose results in death, life-threatening event, requires inpatient hospitalization, significant disability/incapacity or congenital anomaly. | Baseline up to Day 90 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Infarction, Cerebrovascular Disorders, Brain Diseases, Pathological Processes Necrosis, Central Nervous System Diseases, Vascular Diseases, Cardiovascular Diseases, Glyburide, Hypoglycemic Agents, Physiological Effects of Drugs