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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 : Recruiting
First Posted : August 12, 2016
Last Update Posted : February 17, 2021
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)
Estimated Enrollment : 768 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
Estimated Primary Completion Date : February 28, 2022
Estimated Study Completion Date : November 30, 2022

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: Baseline up to Day 90 ]
    mRS is a standardized interview that measures the degree of disability or dependence in the daily activities of people who have suffered causes of neurological disability. The score will be calculated as a 5-category ordinal scale. The 5-category mRS combines mRS categories 0 and 1 and mRS categories 5 and 6 (0/1, 2, 3, 4, 5/6). The mRS ranges from 0 to 6, with higher scores indicating worse outcome.


Secondary Outcome Measures :
  1. Part 1: Time to All-Cause Death [ Time Frame: Baseline up to Day 90 ]
  2. Part 1: Number of Participants Who Achieved mRS 0-4 at Day 90 [ Time Frame: Baseline up to Day 90 ]
    mRS is a standardized interview that measures the degree of disability or dependence in the daily activities of participants who have suffered causes of neurological disability. The score will be calculated as a 5-category ordinal scale. The 5-category mRS combines mRS categories 0 and 1 and mRS categories 5 and 6 (0/1, 2, 3, 4, 5/6). The mRS ranges from 0 to 6, with higher scores indicating worse outcome.

  3. Part 1: Reduction in Midline Shift at 72 Hours [ Time Frame: Baseline up to 72 hours ]
    Midline shift will be assessed by non-contrast computed tomography (NCCT) or MRI.

  4. Part 1: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to Day 90 ]
    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.


Other Outcome Measures:
  1. Part 2: mRS Score [ Time Frame: Month 6 and 12 ]
    mRS is a standardized interview that measures the degree of disability or dependence in the daily activities of participants who have suffered causes of neurological disability. The score will be calculated as a 5-category ordinal scale. The 5-category mRS combines mRS categories 0 and 1 and mRS categories 5 and 6 (0/1, 2, 3, 4, 5/6). The mRS ranges from 0 to 6, with higher scores indicating worse outcome.

  2. Part 2: EuroQol 5-Level Assessment of Health Outcomes (EQ-5D-5L) Score [ Time Frame: Month 6 and 12 ]
    The questionnaire of EQ-5D-5L contains 5 dimensions, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, and uses a 5-point Likert scale scored from 1 (no problem) to 5 (unable to/extreme problems). The numerical description of 5 dimensions represents the health state and is defined by combining one level from each dimension, ranging from 11111 (full health) to 55555 (worst health).

  3. Part 2: Barthel Index (BI) Score [ Time Frame: Month 6 and 12 ]
    BI measures the extent to which somebody can function independently and has mobility in their activities of daily living. It is a 10-item ordinal scale that cover mobility and self-care domains (feeding [0-10], bathing [0-5], grooming [0-5], dressing [0-10], bowel control [0-10], bladder control [0-10], toileting [0-10], chair transfer [0-15], ambulation [0-15], and stair climbing [0-10]). Total score is the sum of individual scores of each item, ranging from 0 (total dependence) to 100 (complete independence).

  4. Part 2: Stroke Impact Scale 16 Questions (SIS-16) Score [ Time Frame: Month 6 and 12 ]
    The SIS-16 is developed to assess physical function in participants with stroke at approximately 1 to 3 months poststroke. It is a subjective questionnaire asked to the participant pertaining of 16 questions. Each question is rated 1-5 and then the scores are totalled. Total scores can range from 16-80 (16 means that none of the functional tasks asked can be performed, a score of 80 means the participant has no issues at all performing any of the tasks asked).

  5. Part 2: Zarit Burden Interview Score [ Time Frame: Month 12 ]
    The interview is developed to measure subjective burden among caregivers of adults with dementia. The 22-item self-report inventory examines burden associated with functional/behavioral impairments and the home care situation. The items are worded subjectively, focusing on the affective response of the caregiver. Scores range from 0 to 88 where lower scores indicate little to no burden. Higher scores indicate greater burden.

  6. Part 2: HealthCare Resource Utilization (HCRU) Questionnaire: Number of Participants With Visits to Healthcare Professionals for Treatment [ Time Frame: Month 12 ]
    HCRU questionnaire will collect data on the healthcare resources used over the course of the study. They are developed to address the need for valid costing estimates of a particular disease state. They are developed to capture the quantity of resources used to extrapolate the overall cost of a disease or impact of an intervention.

  7. Part 2: Number of Participants With SAEs [ Time Frame: Up to Month 12 ]
    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


Contacts
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Contact: US Biogen Clinical Trial Center 866-633-4636 clinicaltrials@biogen.com
Contact: Global Biogen Clinical Trial Center clinicaltrials@biogen.com

Locations
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Sponsors and Collaborators
Biogen
Investigators
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Study Director: Medical Director Biogen
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Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT02864953    
Other Study ID Numbers: 252LH301
RPI 301 ( Other Identifier: Remedy Pharmaceuticals )
2017-004854-41 ( EudraCT Number )
First Posted: August 12, 2016    Key Record Dates
Last Update Posted: February 17, 2021
Last Verified: February 2021
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