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

Phase 3TerminatedNCT02864953

Remedy Pharmaceuticals, Inc.535 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

535

Conditions

Brain Edema Stroke, Acute

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 85 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. A clinical diagnosis of acute ischemic stroke in the middle cerebral artery (MCA) territory. 2. 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. 3. Screening National Institutes of Health Stroke Scale (NIHSS) \>=10. 4. 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. 5. For participants who receive thrombectomy, inclusion into the study must be based on post-thrombectomy MRI-DWI. Exclusion Criteria: 1. Participant is likely to have supportive care withdrawn on the first day. 2. Commitment to decompressive craniectomy (DC) prior to enrollment. 3. 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

Locations (250)

Barrow Neurological Institute

Phoenix, Arizona, United States

Arizona Board of Regents, University of Arizona

Tucson, Arizona, United States

Stanford Stroke Center

Palo Alto, California, United States

University of California Davis Health System

Sacramento, California, United States

UCSD Health-La Jolla

San Diego, California, United States

Outcomes

Primary Outcomes

Part 1: Percentage of Participants With Improvement in Functional Outcome at Day 90 Assessed Via the Modified Rankin Scale (mRS)

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.

Time frame: Day 90

Secondary Outcomes

Part 1: 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.

Time frame: Randomization up to Day 90

Part 1: Percentage of Participants Who Achieved mRS 0-4 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.

Time frame: Day 90

Part 1: Midline Shift at 72 Hours as Assessed by Non-contrast Computed Tomography (NCCT) or Magnetic Resonance Imaging (MRI)

Midline shift is the perpendicular distance between the septum pellucidum and the line drawn between the anterior and posterior attachments of the falx to the inner table of the skull.

Time frame: At 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.

Time frame: From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months)