Clinical Trials List
Protocol Number252LH301
NCT Number(ClinicalTrials.gov Identfier)NCT02864953
2018-11-01 - 2023-10-31
Phase III
Recruiting4
ICD-10I63
Cerebral infarction
ICD-9997.02
Iatrogenic cerebrovascular infarction or hemorrhage
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
-
Trial Applicant
IQVIA RDS Taiwan Ltd.
-
Sponsor
Biogen Idec Research Limited
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 林典佑 未分科
- 蘇慧真 無
- 張育銘 未分科
- Chih-Hung Chen 無
- Chih-Hung Chen 未分科
- 簡崇曜 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Audit
None
Linkou Chang Gung Medical Foundation
Taiwan National PI
李宗海
Co-Principal Investigator
- Chi-Hung Liu 未分科
- 張俊偉 未分科
- 林傳敏 未分科
- 鄭之光 未分科
- 江星逸 未分科
- Hsiu-Chuan Wu 未分科
- 張國軒 未分科
- 洪濬 未分科
- 陳敬昌 未分科
- Wei-Min Ho 未分科
- 廖洺鋒 未分科
- 朱展麟 未分科
- Cheng-Jiun Shiue 未分科
- 黃浩輝 未分科
- 吳逸民 未分科
- 張寓智 未分科
- 王豐林 未分科
- KuoLun Huang 未分科
The Actual Total Number of Participants Enrolled
0 Recruiting
Audit
None
Co-Principal Investigator
- SHIN-JOE YEH 無
- Jiann-Shing Jeng 無
- CHIH-HAO CHEN 無
- LI-KAI TSAI 無
- 李崇維 未分科
The Actual Total Number of Participants Enrolled
0 Recruiting
Audit
None
Condition/Disease
Brain Edema, Acute Stroke
Objectives
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.
Test Drug
BIIB093
Active Ingredient
glibenclamide
Dosage Form
Dosage
6.0
Endpoints
Part 1Study
The primary objective is to determine if BIIB093 improves functional outcome at Day 90 as measured by the modified Rankin Scale (mRS)
when compared with placebo in subjects with LHI. The endpoint that
relates to this objective is Day 90 mRS as a 5-category ordinal scale
(the 5-category mRS will combine mRS categories 0 and 1 and mRS
categories 5 and 6).
Part 1 secondary objectives and endpoints are as follows:
To determine if BIIB093 improves overall survival at Day 90
when compared with placebo. The endpoint associated with
this objective is time to all-cause death over the 90-day period.
To determine if BIIB093 improves functional outcome at Day
90 on the mRS dichotomized 0-4 vs. 5-6, when compared with
placebo. The endpoint related to this objective is the proportion
of subjects who achieved mRS 0-4 at Day 90.
To determine 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. The
endpoint related to this objective is the midline shift at 72 hours
(or at time prior to DC or CMO, if earlier).
To evaluate the safety and tolerability of BIIB093 in subjects
with LHI. The endpoint related to this objective is the
incidence of adverse events, serious adverse events (SAEs), and
clinically significant abnormal vital signs, 12-lead
electrocardiogram findings, and laboratory results (including
those associated with blood glucose levels).
Part 1 additional endpoints include the following:
mRS score at Day 30 as a 5-category ordinal scale (the 5-
category mRS combines mRS categories 0 and 1 and mRS
categories 5 and 6)
National Institutes of Health Stroke Scale (NIHSS) score at
Hour 24, Hour 48, Hour 72, and Day 7 postbolus
Plasma concentration of BIIB093 and metabolites through Day
7/Hospital Discharge.
Average concentration of plasma matrix metalloproteinase-9
(MMP-9) levels across 24, 48, and 72 hours post-bolus
Pharmacogenetic markers (optional)
Euro Quality of Life (EQ-5D-5L) and Barthel Index (BI) at
Days 30 and 90
HealthCare Resource Utilization Questionnaire, Zarit Burden
Interview, and Stroke Impact Scale 16 Questions (SIS-16) at
Day 90
The Part 2 study objectives are to evaluate long-term disability and
patient outcomes following LHI and to assess safety during the followup period.
Part 2 endpoints include the following:
mRS score at Month 6 and Month 12 as a 5-category ordinal
scale (the 5-category mRS combines mRS categories 0 and 1
and mRS categories 5 and 6)
EQ-5D-5L, BI score, and SIS-16 at Month 6 and Month 12
HealthCare Resource Utilization Questionnaire and Zarit
Burden Interview at Month 12
Incidence of SAEs
The primary objective is to determine if BIIB093 improves functional outcome at Day 90 as measured by the modified Rankin Scale (mRS)
when compared with placebo in subjects with LHI. The endpoint that
relates to this objective is Day 90 mRS as a 5-category ordinal scale
(the 5-category mRS will combine mRS categories 0 and 1 and mRS
categories 5 and 6).
Part 1 secondary objectives and endpoints are as follows:
To determine if BIIB093 improves overall survival at Day 90
when compared with placebo. The endpoint associated with
this objective is time to all-cause death over the 90-day period.
To determine if BIIB093 improves functional outcome at Day
90 on the mRS dichotomized 0-4 vs. 5-6, when compared with
placebo. The endpoint related to this objective is the proportion
of subjects who achieved mRS 0-4 at Day 90.
To determine 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. The
endpoint related to this objective is the midline shift at 72 hours
(or at time prior to DC or CMO, if earlier).
To evaluate the safety and tolerability of BIIB093 in subjects
with LHI. The endpoint related to this objective is the
incidence of adverse events, serious adverse events (SAEs), and
clinically significant abnormal vital signs, 12-lead
electrocardiogram findings, and laboratory results (including
those associated with blood glucose levels).
Part 1 additional endpoints include the following:
mRS score at Day 30 as a 5-category ordinal scale (the 5-
category mRS combines mRS categories 0 and 1 and mRS
categories 5 and 6)
National Institutes of Health Stroke Scale (NIHSS) score at
Hour 24, Hour 48, Hour 72, and Day 7 postbolus
Plasma concentration of BIIB093 and metabolites through Day
7/Hospital Discharge.
Average concentration of plasma matrix metalloproteinase-9
(MMP-9) levels across 24, 48, and 72 hours post-bolus
Pharmacogenetic markers (optional)
Euro Quality of Life (EQ-5D-5L) and Barthel Index (BI) at
Days 30 and 90
HealthCare Resource Utilization Questionnaire, Zarit Burden
Interview, and Stroke Impact Scale 16 Questions (SIS-16) at
Day 90
The Part 2 study objectives are to evaluate long-term disability and
patient outcomes following LHI and to assess safety during the followup period.
Part 2 endpoints include the following:
mRS score at Month 6 and Month 12 as a 5-category ordinal
scale (the 5-category mRS combines mRS categories 0 and 1
and mRS categories 5 and 6)
EQ-5D-5L, BI score, and SIS-16 at Month 6 and Month 12
HealthCare Resource Utilization Questionnaire and Zarit
Burden Interview at Month 12
Incidence of SAEs
Inclution Criteria
Inclusion Criteria
To be eligible to participate in this study, candidates must meet the following eligibility criteria
at Screening, or at the time point specified in the individual eligibility criterion listed:
1. Ability to understand the purpose and risks of the study and provide signed and dated
informed consent and authorization to use confidential health information in accordance
with national and local subject privacy regulations or consent provided by an independent
physician where local regulation allows, and/or provision of informed consent by the
subject’s legally authorized representative (LAR) in accordance with all local and
national regulations or according to the local ethics committee’s guidelines or by another
process compliant with applicable national laws and regulations and ethics committee
requirements.
2. A clinical diagnosis of acute ischemic stroke in the MCA territory (PCA and/or ACA
territory involvement in addition to primary MCA territory stroke is acceptable).
3. Aged 18 to 85 years old, inclusive, at the time of informed consent.
4. Screening NIHSS ≥10.
5. Prior to the current stroke, no significant disability in the opinion of the Investigator (able
to independently perform all duties and activities of daily living without assistance from a
caregiver, spouse, or another person).
6. A large hemispheric infarction defined, in order of preference, as either:
a) a magnetic resonance imaging (MRI) diffusion-weighted imaging (DWI) lesion
volume of 80 to 300 cm3
, or
b) a computed tomography perfusion (CTP) core lesion volume of 80 to 300 cm3
, or
c) an Alberta Stroke Program Early computed tomography (CT) Score (ASPECTS) on
non-contrast computed tomography (NCCT) of 1 to 5 with involvement of at least 2
defined cortical regions, if lesion volume from MRI DWI or CTP is not available.
In the event that more than one scan is available for a particular subject resulting in
disagreement, the investigator should make the determination about eligibility
considering all patient information including but not limited to: 1) scan timing and 2)
scan modality that in the opinion of the investigator best represents the infarct size. The
scan used for eligibility will be documented.
Note: Automated image analysis software will be used whenever possible as a standard
method to aid in estimating infarct core volume and/or ASPECTS. The final ASPECTS
determination for the purposes of inclusion will be made by the investigator or local reader. In the event that a suitable baseline scan is not available as part of the SOC, a
study-specific MRI DWI, CTP, or NCCT, in order of preference, will be obtained. A
repeat scan for study inclusion purposes may be performed if deemed appropriate and
would be achievable prior to infusion.
7. For subjects who receive thrombectomy prior to randomization, inclusion into the study
must be based on an infarct volume of 80 to 300 cm3 measured by post-thrombectomy
MRI-DWI.
8. Study drug treatment infusion should be initiated as soon as possible but no later than 10
hours after time of symptom onset, if known, or the time last known normal (if time to
symptom onset is unknown).
To be eligible to participate in this study, candidates must meet the following eligibility criteria
at Screening, or at the time point specified in the individual eligibility criterion listed:
1. Ability to understand the purpose and risks of the study and provide signed and dated
informed consent and authorization to use confidential health information in accordance
with national and local subject privacy regulations or consent provided by an independent
physician where local regulation allows, and/or provision of informed consent by the
subject’s legally authorized representative (LAR) in accordance with all local and
national regulations or according to the local ethics committee’s guidelines or by another
process compliant with applicable national laws and regulations and ethics committee
requirements.
2. A clinical diagnosis of acute ischemic stroke in the MCA territory (PCA and/or ACA
territory involvement in addition to primary MCA territory stroke is acceptable).
3. Aged 18 to 85 years old, inclusive, at the time of informed consent.
4. Screening NIHSS ≥10.
5. Prior to the current stroke, no significant disability in the opinion of the Investigator (able
to independently perform all duties and activities of daily living without assistance from a
caregiver, spouse, or another person).
6. A large hemispheric infarction defined, in order of preference, as either:
a) a magnetic resonance imaging (MRI) diffusion-weighted imaging (DWI) lesion
volume of 80 to 300 cm3
, or
b) a computed tomography perfusion (CTP) core lesion volume of 80 to 300 cm3
, or
c) an Alberta Stroke Program Early computed tomography (CT) Score (ASPECTS) on
non-contrast computed tomography (NCCT) of 1 to 5 with involvement of at least 2
defined cortical regions, if lesion volume from MRI DWI or CTP is not available.
In the event that more than one scan is available for a particular subject resulting in
disagreement, the investigator should make the determination about eligibility
considering all patient information including but not limited to: 1) scan timing and 2)
scan modality that in the opinion of the investigator best represents the infarct size. The
scan used for eligibility will be documented.
Note: Automated image analysis software will be used whenever possible as a standard
method to aid in estimating infarct core volume and/or ASPECTS. The final ASPECTS
determination for the purposes of inclusion will be made by the investigator or local reader. In the event that a suitable baseline scan is not available as part of the SOC, a
study-specific MRI DWI, CTP, or NCCT, in order of preference, will be obtained. A
repeat scan for study inclusion purposes may be performed if deemed appropriate and
would be achievable prior to infusion.
7. For subjects who receive thrombectomy prior to randomization, inclusion into the study
must be based on an infarct volume of 80 to 300 cm3 measured by post-thrombectomy
MRI-DWI.
8. Study drug treatment infusion should be initiated as soon as possible but no later than 10
hours after time of symptom onset, if known, or the time last known normal (if time to
symptom onset is unknown).
Exclusion Criteria
Exclusion Criteria
Candidates will be excluded from study entry if any of the following exclusion criteria exist at
Screening, or at the time point specified in the individual criterion listed:
1. In the judgment of the Investigator, the subject is likely to have supportive care
withdrawn in the first day.
2. Commitment to decompressive craniectomy (DC) prior to enrollment.
3. Evidence (clinical or imaging) of concurrent infarction in the contralateral hemisphere
deemed by the Investigator to be sufficiently serious so as to affect functional outcome.
This would include, for example, a contralateral ACA infarct that leads to bilateral leg
paralysis.
4. Clinical signs of herniation, e.g., 1 or 2 dilated, fixed pupils; unconsciousness related to
edema (i.e., ≥2 on item 1a on the NIHSS); and/or loss of other brain stem reflexes,
attributable to edema or herniation according to the Investigator’s judgment.
5. Brain hemorrhage (other than small petechial/punctate hemorrhages) on NCCT/MRI.
6. NCCT/MRI evidence of anteroseptal/pineal shift >2 mm prior to enrollment.
7. Use of intra-arterial thrombolytic agents, alone or in combination with thrombectomy.
8. Patients who are currently being considered for thrombectomy and/or IV thrombolysis
may not be randomized into the study until these procedures have been completed OR the
decision not to perform them has been made. These treatments should not be delayed for
study screening procedures. When thrombectomy is performed prior to randomization,
study eligibility must be assessed using inclusion criterion #7.
9. Subjects with, in the opinion of the Investigator, life expectancy <3 months not related to
current LHI, or those unlikely to be compliant with follow up.
10. Subjects in whom a peripheral IV line cannot be placed.
11. Subjects with mental disability (prior to qualifying LHI) or wards of the state.
12. Subjects whose stroke symptoms are rapidly improving and are not expected in the
opinion of the Investigator to have NIHSS≥10 at the time of randomization.
Medical History
13. Known allergy to BIIB093 or to another sulfonylurea drug or any of the components of
the formulated BIIB093 or matching placebo.
14. Subjects who are known to have taken oral glibenclamide within the past 10 hours.
15. Known history of clinically significant severe form of renal or hepatic disorder, in the
Investigator's opinion (e.g., dialysis or cirrhosis, respectively).
16. Known history of chronic obstructive pulmonary disease that, in the judgment of the
Investigator, is severe (e.g., requiring home oxygen).
17. Known history of clinically significant hypoglycemia, in the Investigator's opinion based
on known medical history or local screening laboratory assessments (i.e. screening blood
glucose <70 mg/dL [~3.9 mmol/L]).
18. Subjects who have or have ever had diabetic ketoacidosis or diabetic coma/precoma.
19. Acute ST elevation myocardial infarction (MI), and/or acute decompensated heart failure,
and/or QTc >520 msec, and/or admission for an acute coronary syndrome, MI, cardiac
arrest, or non-voluntary coronary intervention (percutaneous coronary intervention or
coronary artery surgery) within the past 3 months.
20. New York Heart Association heart failure III/IV (class III: marked limitation in activity
due to symptoms, even during less-than-ordinary activity, e.g. walking short distances
(20-100 m); class IV: severe limitations. Experiences symptoms even while at rest.
Mostly bedbound patients).
21. Known cardiac ventricular tachycardia.
22. Subjects with known glucose-6-phosphate dehydrogenase enzyme deficiency.
23. Serious local infection (e.g., cellulitis, abscess) or systemic infection (e.g., septicemia)
that required hospitalization or was clinically significant in the opinion of the Investigator
within 3 days prior to Screening.
Other
24. Females who are pregnant or women of childbearing potential with a positive pregnancy
test at time of admission.
25. Nursing women who are unable to stop breastfeeding during study treatment infusion and
for 7 days following the end of study treatment infusion.
26. Known current participation or known history of participation in any other investigational
study that involved treatment with an investigational drug within 14 days prior to
enrollment.
27. Inability to comply with study requirements.
28. Other unspecified reasons that, in the opinion of the Investigator or Biogen, make the
subject unsuitable for enrollment.
Candidates will be excluded from study entry if any of the following exclusion criteria exist at
Screening, or at the time point specified in the individual criterion listed:
1. In the judgment of the Investigator, the subject is likely to have supportive care
withdrawn in the first day.
2. Commitment to decompressive craniectomy (DC) prior to enrollment.
3. Evidence (clinical or imaging) of concurrent infarction in the contralateral hemisphere
deemed by the Investigator to be sufficiently serious so as to affect functional outcome.
This would include, for example, a contralateral ACA infarct that leads to bilateral leg
paralysis.
4. Clinical signs of herniation, e.g., 1 or 2 dilated, fixed pupils; unconsciousness related to
edema (i.e., ≥2 on item 1a on the NIHSS); and/or loss of other brain stem reflexes,
attributable to edema or herniation according to the Investigator’s judgment.
5. Brain hemorrhage (other than small petechial/punctate hemorrhages) on NCCT/MRI.
6. NCCT/MRI evidence of anteroseptal/pineal shift >2 mm prior to enrollment.
7. Use of intra-arterial thrombolytic agents, alone or in combination with thrombectomy.
8. Patients who are currently being considered for thrombectomy and/or IV thrombolysis
may not be randomized into the study until these procedures have been completed OR the
decision not to perform them has been made. These treatments should not be delayed for
study screening procedures. When thrombectomy is performed prior to randomization,
study eligibility must be assessed using inclusion criterion #7.
9. Subjects with, in the opinion of the Investigator, life expectancy <3 months not related to
current LHI, or those unlikely to be compliant with follow up.
10. Subjects in whom a peripheral IV line cannot be placed.
11. Subjects with mental disability (prior to qualifying LHI) or wards of the state.
12. Subjects whose stroke symptoms are rapidly improving and are not expected in the
opinion of the Investigator to have NIHSS≥10 at the time of randomization.
Medical History
13. Known allergy to BIIB093 or to another sulfonylurea drug or any of the components of
the formulated BIIB093 or matching placebo.
14. Subjects who are known to have taken oral glibenclamide within the past 10 hours.
15. Known history of clinically significant severe form of renal or hepatic disorder, in the
Investigator's opinion (e.g., dialysis or cirrhosis, respectively).
16. Known history of chronic obstructive pulmonary disease that, in the judgment of the
Investigator, is severe (e.g., requiring home oxygen).
17. Known history of clinically significant hypoglycemia, in the Investigator's opinion based
on known medical history or local screening laboratory assessments (i.e. screening blood
glucose <70 mg/dL [~3.9 mmol/L]).
18. Subjects who have or have ever had diabetic ketoacidosis or diabetic coma/precoma.
19. Acute ST elevation myocardial infarction (MI), and/or acute decompensated heart failure,
and/or QTc >520 msec, and/or admission for an acute coronary syndrome, MI, cardiac
arrest, or non-voluntary coronary intervention (percutaneous coronary intervention or
coronary artery surgery) within the past 3 months.
20. New York Heart Association heart failure III/IV (class III: marked limitation in activity
due to symptoms, even during less-than-ordinary activity, e.g. walking short distances
(20-100 m); class IV: severe limitations. Experiences symptoms even while at rest.
Mostly bedbound patients).
21. Known cardiac ventricular tachycardia.
22. Subjects with known glucose-6-phosphate dehydrogenase enzyme deficiency.
23. Serious local infection (e.g., cellulitis, abscess) or systemic infection (e.g., septicemia)
that required hospitalization or was clinically significant in the opinion of the Investigator
within 3 days prior to Screening.
Other
24. Females who are pregnant or women of childbearing potential with a positive pregnancy
test at time of admission.
25. Nursing women who are unable to stop breastfeeding during study treatment infusion and
for 7 days following the end of study treatment infusion.
26. Known current participation or known history of participation in any other investigational
study that involved treatment with an investigational drug within 14 days prior to
enrollment.
27. Inability to comply with study requirements.
28. Other unspecified reasons that, in the opinion of the Investigator or Biogen, make the
subject unsuitable for enrollment.
The Estimated Number of Participants
-
Taiwan
13 participants
-
Global
768 participants
