E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Cerebral edema following Large Hemispheric Infarction |
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E.1.1.1 | Medical condition in easily understood language |
Brain swelling after stroke |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008107 |
E.1.2 | Term | Cerebral edema |
E.1.2 | System Organ Class | 100000004852 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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 participants with Large Hemispheric Infarction (LHI).
PART 2: 1. To evaluate long-term disability following LHI. 2. To evaluate long-term outcome measures of clinical function, quality of life, and healthcare utilization 3. To assess the safety of BIIB093 in subjects with LHI during the follow-up period.
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E.2.2 | Secondary objectives of the trial |
The secondary objectives 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. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
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 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. At the time of randomization and in the Investigator's judgment, 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 (if time to symptom onset is unknown). Investigators should refer to Section 11.1. • Subjects who wake with stroke may be included if neurological and other exclusion criteria are satisfied. These "wake up" strokes are defined as having no symptoms at sleep onset and a known sleep onset time, but stroke symptoms on waking. The time of stroke onset is to be taken as the midpoint between sleep onset and time of waking. The maximum time window for initiation of study drug treatment infusion is then 10 hours from the midpoint as described. If sleep onset time is unknown, then last known normal time must be used and the midpoint does not apply. 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 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.At the time of randomization and in the Investigator's judgment, 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 (if time to symptom onset is unknown). Investigators should refer to Section 11.1.
See Protocol
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E.4 | Principal 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 Exclusion criteria may apply
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of Participants with Improvement in Functional Outcome at Day 90 Assessed via the Modified Rankin Scale (mRS)
PART 2: 1. 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) 2.: • EQ-5D-5L at Months 6 and 12 • BI score at Months 6 and 12 • SIS-16 at Months 6 and 12 •Zarit Buden Interview at Month12 • HealthCare Resource Utilization Questionnaire at Month 12 3. Incidence of SAEs
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1.Time to All-Cause Death [ Time Frame: Baseline up to Day 90 ] 2.Proportion of Participants who achieved mRS 0-4 at Day 90 [Time Frame: Baseline up to Day 90] 3.Reduction in Midline Shift at 72 Hours [ Time Frame: Baseline up to 72 Hours] 4.Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to Day 90]
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
#’s 1, 2 & 4 (Baseline up to Day 90) #3 (Baseline up to 72 hours)
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 78 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Brazil |
Canada |
Israel |
Japan |
Korea, Republic of |
Mexico |
Taiwan |
United States |
Finland |
France |
Lithuania |
Spain |
Switzerland |
Czechia |
Germany |
Italy |
Belgium |
Croatia |
Denmark |
Hungary |
Portugal |
Russian Federation |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 8 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |