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

• ClinicalTrials.gov Identifier: NCT02864953
• Recruitment Status: Terminated
• First Posted: August 12, 2016
• Results First Posted: January 9, 2024
• Last Update Posted: April 30, 2024
• Sponsor: Remedy Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Remedy Pharmaceuticals, Inc.

Tracking Information

• First Submitted Date: July 12, 2016
• First Posted Date: August 12, 2016
• Results First Submitted Date: December 19, 2023
• Results First Posted Date: January 9, 2024
• Last Update Posted Date: April 30, 2024
• Actual Study Start Date: August 29, 2018
• Actual Primary Completion Date: August 18, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 19, 2023)

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.

• Original Primary Outcome Measures (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 ]

Current Secondary Outcome Measures (submitted: January 18, 2024)

• 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.

Original Secondary Outcome Measures (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: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

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: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Brain Edema
• Stroke, Acute

Intervention

• 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

• 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

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: December 19, 2023): 535
• Original Estimated Enrollment (submitted: August 9, 2016): 650
• Actual Study Completion Date: August 18, 2023
• Actual Primary Completion Date: August 18, 2023 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: 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

Administrative Information

• NCT Number: NCT02864953
• Other Study ID Numbers: 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

• Plan to Share IPD: No

• Current Responsible Party: Remedy Pharmaceuticals, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Remedy Pharmaceuticals, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Medical Director; Biogen

• PRS Account: Remedy Pharmaceuticals, Inc.
• Verification Date: April 2024