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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 : August 26, 2021
Sponsor:
Information provided by (Responsible Party):
Biogen

Tracking Information
First Submitted Date  ICMJE July 12, 2016
First Posted Date  ICMJE August 12, 2016
Last Update Posted Date August 26, 2021
Actual Study Start Date  ICMJE August 29, 2018
Estimated Primary Completion Date December 29, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 9, 2020)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: August 9, 2016)
Proportion of participants with improvement in functional outcome at 90 days assessed via the modified Rankin Scale [ Time Frame: Change from baseline at 90 days ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 9, 2020)
  • Part 1: Time to All-Cause Death [ Time Frame: Baseline up to Day 90 ]
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 9, 2016)
  • Proportion of participants with improvement in overall survival at 90 days [ Time Frame: Change from baseline at 90 days ]
  • Proportion of participants with a reduction in midline shift at 72 hours assessed via non-contrast computed tomography [ Time Frame: Change from baseline at 72 hours ]
  • Safety of CIRARA via collection of adverse events and serious adverse events [ Time Frame: Change from baseline through 15 days ]
Current Other Pre-specified Outcome Measures
 (submitted: December 9, 2020)
  • 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.
  • 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).
  • 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).
  • 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).
  • 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.
  • 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.
  • 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.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase 3 Study to Evaluate the Efficacy and Safety of Intravenous BIIB093 (Glibenclamide) for Severe Cerebral Edema Following Large Hemispheric Infarction
Official Title  ICMJE 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
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.

Detailed Description This study, previously posted by Remedy Pharmaceuticals, Inc., has transitioned to Biogen.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Brain Edema
  • Stroke, Acute
Intervention  ICMJE
  • Drug: BIIB093
    Administered as specified in the treatment arm.
    Other Names:
    • glibenclamide
    • glibenclamide intravenous (IV)
    • glyburide
    • CIRARA
  • Drug: Placebo
    Administered as specified in the treatment arm.
Study Arms  ICMJE
  • Experimental: BIIB093
    BIIB093 administered as a bolus followed by continuous intravenous (IV) infusion over 72 hours.
    Intervention: Drug: BIIB093
  • Placebo Comparator: Placebo
    Placebo administered as a bolus followed by continuous intravenous (IV) infusion over 72 hours.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 9, 2020)
768
Original Estimated Enrollment  ICMJE
 (submitted: August 9, 2016)
650
Estimated Study Completion Date  ICMJE September 29, 2024
Estimated Primary Completion Date December 29, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: US Biogen Clinical Trial Center 866-633-4636 clinicaltrials@biogen.com
Contact: Global Biogen Clinical Trial Center clinicaltrials@biogen.com
Listed Location Countries  ICMJE Australia,   Belgium,   Brazil,   Canada,   China,   Croatia,   Czechia,   Denmark,   Finland,   France,   Germany,   Hungary,   Israel,   Italy,   Japan,   Korea, Republic of,   Lithuania,   Portugal,   Russian Federation,   Spain,   Switzerland,   Taiwan,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02864953
Other Study ID Numbers  ICMJE 252LH301
RPI 301 ( Other Identifier: Remedy Pharmaceuticals )
2017-004854-41 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Biogen
Study Sponsor  ICMJE Biogen
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Biogen
PRS Account Biogen
Verification Date August 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP