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
Overview
- Phase
- Phase 3
- Intervention
- BIIB093
- Conditions
- Brain Edema
- Sponsor
- Remedy Pharmaceuticals, Inc.
- Enrollment
- 535
- Locations
- 249
- Primary Endpoint
- Part 1: Percentage of Participants With Improvement in Functional Outcome at Day 90 Assessed Via the Modified Rankin Scale (mRS)
- Status
- Terminated
- Last Updated
- last year
Overview
Brief Summary
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
This study, previously posted by Remedy Pharmaceuticals, Inc., has transitioned to Biogen.
Investigators
Eligibility Criteria
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) \>=
- •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
Arms & Interventions
BIIB093
BIIB093 administered as a bolus followed by continuous intravenous (IV) infusion over 72 hours.
Intervention: BIIB093
Placebo
Placebo administered as a bolus followed by continuous intravenous (IV) infusion over 72 hours.
Intervention: Placebo
Outcomes
Primary Outcomes
Part 1: Percentage of Participants With Improvement in Functional Outcome at Day 90 Assessed Via the Modified Rankin Scale (mRS)
Time Frame: Day 90
The mRS measures the degree of functional independence following stroke. In this study, 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.
Secondary Outcomes
- Part 1: Time to All-Cause Death Through Day 90(Randomization up to Day 90)
- Part 1: Midline Shift at 72 Hours as Assessed by Non-contrast Computed Tomography (NCCT) or Magnetic Resonance Imaging (MRI)(At 72 hours)
- Part 1: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months))
- Part 1: Percentage of Participants Who Achieved mRS 0-4 at Day 90(Day 90)