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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
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 : February 13, 2024
Sponsor:
Information provided by (Responsible Party):
Biogen

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.


Condition or disease Intervention/treatment Phase
Brain Edema Stroke, Acute Drug: BIIB093 Drug: Placebo Phase 3

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

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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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Edema
Drug Information available for: Glyburide

Arm Intervention/treatment
Experimental: BIIB093
BIIB093 administered as a bolus followed by continuous intravenous (IV) infusion over 72 hours.
Drug: BIIB093
Administered as specified in the treatment arm.
Other Names:
  • glibenclamide
  • glibenclamide intravenous (IV)
  • glyburide
  • CIRARA

Placebo Comparator: Placebo
Placebo administered as a bolus followed by continuous intravenous (IV) infusion over 72 hours.
Drug: Placebo
Administered as specified in the treatment arm.




Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.



Information from the National Library of Medicine

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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
Criteria

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


Information from the National Library of Medicine

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


Locations
Show Show 250 study locations
Sponsors and Collaborators
Biogen
Investigators
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Study Director: Medical Director Biogen
  Study Documents (Full-Text)

Documents provided by Biogen:
Study Protocol  [PDF] June 11, 2021
Statistical Analysis Plan  [PDF] July 11, 2023

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Responsible Party: Biogen
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: February 13, 2024
Last Verified: January 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Biogen:
Infarction
Cerebrovascular Disorders
Brain Diseases
Pathological Processes Necrosis
Central Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Glyburide
Hypoglycemic Agents
Physiological Effects of Drugs
Additional relevant MeSH terms:
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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