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

Remedy Pharmaceuticals, Inc.

Status and phase: Terminated; Phase 3

Conditions: Brain Edema; Stroke, Acute

Treatments: Drug: BIIB093; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02864953

2017-004854-41 (EudraCT Number)

RPI 301 (Other Identifier)

252LH301

Details and patient eligibility

About

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.

Enrollment: 535 patients

Sex: All

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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535 participants in 2 patient groups, including a placebo group

BIIB093

Experimental group

Description:

BIIB093 administered as a bolus followed by continuous intravenous (IV) infusion over 72 hours.

Treatment:

Drug: BIIB093

Placebo

Placebo Comparator group

Description:

Placebo administered as a bolus followed by continuous intravenous (IV) infusion over 72 hours.

Treatment:

Drug: Placebo