Phase 3 Study to Evaluate the Efficacy and Safety of Intravenous BIIB093 (Glibenclamide) for Severe Cerebral Edema Following Large Hemispheric Infarction (CHARM)
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| ClinicalTrials.gov Identifier: NCT02864953 |
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Recruitment Status :
Terminated
(Early completed to operational challenges and other strategic considerations, not for efficacy or safety reasons)
First Posted : August 12, 2016
Results First Posted : January 9, 2024
Last Update Posted : April 30, 2024
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Brain Edema Stroke, Acute | Drug: BIIB093 Drug: Placebo | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 535 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | 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 |
| Actual Study Start Date : | August 29, 2018 |
| Actual Primary Completion Date : | August 18, 2023 |
| Actual Study Completion Date : | August 18, 2023 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: BIIB093
BIIB093 administered as a bolus followed by continuous intravenous (IV) infusion over 72 hours.
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Drug: BIIB093
Administered as specified in the treatment arm.
Other Names:
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Placebo Comparator: Placebo
Placebo administered as a bolus followed by continuous intravenous (IV) infusion over 72 hours.
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Drug: Placebo
Administered as specified in the treatment arm. |
- 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.
- Part 1: Time to All-Cause Death Through Day 90 [ Time Frame: Randomization up to Day 90 ]Time to all-cause death is defined as the time from randomization to the time of death.
- Part 1: Percentage of Participants Who Achieved mRS 0-4 at Day 90 [ Time Frame: 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.
- Part 1: Midline Shift at 72 Hours as Assessed by Non-contrast Computed Tomography (NCCT) or Magnetic Resonance Imaging (MRI) [ Time Frame: At 72 hours ]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.
- Part 1: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) ]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.
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| Ages Eligible for Study: | 18 Years to 85 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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.
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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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02864953
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| Study Director: | Medical Director | Biogen |
Documents provided by Remedy Pharmaceuticals, Inc.:
| Responsible Party: | Remedy Pharmaceuticals, Inc. |
| ClinicalTrials.gov Identifier: | NCT02864953 |
| Obsolete Identifiers: | NCT04950972 |
| Other Study ID Numbers: |
252LH301 RPI 301 ( Other Identifier: Remedy Pharmaceuticals ) 2017-004854-41 ( EudraCT Number ) |
| First Posted: | August 12, 2016 Key Record Dates |
| Results First Posted: | January 9, 2024 |
| Last Update Posted: | April 30, 2024 |
| Last Verified: | April 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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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 |
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Stroke Brain Edema Infarction Edema Ischemia Pathologic Processes Necrosis Cerebrovascular Disorders |
Brain Diseases Central Nervous System Diseases Nervous System Diseases Vascular Diseases Cardiovascular Diseases Glyburide Hypoglycemic Agents Physiological Effects of Drugs |