Trial Outcomes & Findings for Phase 3 Study to Evaluate the Efficacy and Safety of Intravenous BIIB093 (Glibenclamide) for Severe Cerebral Edema Following Large Hemispheric Infarction (NCT NCT02864953)

Last Updated: 2024-11-25

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

535 participants

Primary outcome timeframe

Day 90

Results posted on

2024-11-25

Participant Flow

Participants were enrolled at investigative sites in the United States, Brazil, China, Spain, Japan, Australia, Portugal, Germany, United Kingdom, Finland, Canada, Israel, France, Taiwan, Hungary, Czech Republic, Italy, Belgium, Lithuania, Russia and South Korea from 29 August 2018 to 18 August 2023.

A total of 535 participants were enrolled and randomised, out of which 518 participants were dosed with BIIB093 or a matching placebo.

Participant milestones

Participant milestones
Measure	Placebo Participants were administered with BIIB093 matching placebo as an intravenous (IV) bolus on Day 1 followed by a continuous IV infusion for over 72 hours.	BIIB093 Participants were administered with BIIB093 as an IV bolus on Day 1 followed by continuous IV infusion for over 72 hours.
Overall Study STARTED	268	267
Overall Study COMPLETED	215	213
Overall Study NOT COMPLETED	53	54

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants were administered with BIIB093 matching placebo as an intravenous (IV) bolus on Day 1 followed by a continuous IV infusion for over 72 hours.	BIIB093 Participants were administered with BIIB093 as an IV bolus on Day 1 followed by continuous IV infusion for over 72 hours.
Overall Study Adverse Event	22	19
Overall Study Withdrawal by Subject	1	0
Overall Study Physician Decision	4	2
Overall Study Death	3	13
Overall Study Reason not specified	14	12
Overall Study Withdrew Prior to Dosing	9	8

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=268 Participants Participants were administered with BIIB093 matching placebo as an IV bolus on Day 1 followed by a continuous IV infusion for over 72 hours.	BIIB093 n=267 Participants Participants were administered with BIIB093 as an IV bolus on Day 1 followed by continuous IV infusion for over 72 hours.	Total n=535 Participants Total of all reporting groups
Age, Continuous	61.6 years STANDARD_DEVIATION 10.81 • n=5 Participants	60.5 years STANDARD_DEVIATION 11.17 • n=7 Participants	61.1 years STANDARD_DEVIATION 11 • n=5 Participants
Sex: Female, Male Female	104 Participants n=5 Participants	98 Participants n=7 Participants	202 Participants n=5 Participants
Sex: Female, Male Male	164 Participants n=5 Participants	169 Participants n=7 Participants	333 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity · Missing	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity · Hispanic or Latino	36 Participants n=5 Participants	41 Participants n=7 Participants	77 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity · Not Hispanic or Latino	228 Participants n=5 Participants	223 Participants n=7 Participants	451 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity · Not reported	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Race · Missing	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race/Ethnicity, Customized Race · American Indian or Alaska Native	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Race · Asian	53 Participants n=5 Participants	51 Participants n=7 Participants	104 Participants n=5 Participants
Race/Ethnicity, Customized Race · Black or African American	21 Participants n=5 Participants	19 Participants n=7 Participants	40 Participants n=5 Participants
Race/Ethnicity, Customized Race · Native Hawaiian or Other Pacific Islander	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Race · White	173 Participants n=5 Participants	177 Participants n=7 Participants	350 Participants n=5 Participants
Race/Ethnicity, Customized Race · Not reported due to confidentiality regulations	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Race · Other	12 Participants n=5 Participants	16 Participants n=7 Participants	28 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 90

Population: The modified intent to treat (mITT) population included participants aged 18 to 70 years (inclusive) at the time of randomization, who had received any study drug, and who had at least 1 post-baseline mRS before or at Day 90 visit. Here, 'Overall number of participants analyzed' signifies the number of participants with data available for outcome measure analysis.

Outcome measures

Outcome measures
Measure	Placebo n=214 Participants Participants were administered with BIIB093 matching placebo as an IV bolus on Day 1 followed by a continuous IV infusion for over 72 hours.	BIIB093 n=217 Participants Participants were administered with BIIB093 as an IV bolus on Day 1 followed by continuous IV infusion for over 72 hours.
Part 1: Percentage of Participants With Improvement in Functional Outcome at Day 90 Assessed Via the Modified Rankin Scale (mRS) Score: 0/1	1.4 percentage of participants	3.2 percentage of participants
Part 1: Percentage of Participants With Improvement in Functional Outcome at Day 90 Assessed Via the Modified Rankin Scale (mRS) Score: 2	2.8 percentage of participants	5.1 percentage of participants
Part 1: Percentage of Participants With Improvement in Functional Outcome at Day 90 Assessed Via the Modified Rankin Scale (mRS) Score: 3	12.6 percentage of participants	12.0 percentage of participants
Part 1: Percentage of Participants With Improvement in Functional Outcome at Day 90 Assessed Via the Modified Rankin Scale (mRS) Score: 4	25.2 percentage of participants	23.5 percentage of participants
Part 1: Percentage of Participants With Improvement in Functional Outcome at Day 90 Assessed Via the Modified Rankin Scale (mRS) Score: 5/6	57.9 percentage of participants	56.2 percentage of participants

SECONDARY outcome

Timeframe: Randomization up to Day 90

Population: The mITT population included participants aged 18 to 70 years (inclusive) at the time of randomization, who received any study drug, and who had at least 1 post-baseline mRS before or at the Day 90 visit. Here, 'Overall number of participants analyzed' signifies number of participants with data available for outcome measure analysis.

Time to all-cause death is defined as the time from randomization to the time of death.

Outcome measures

Outcome measures
Measure	Placebo n=214 Participants Participants were administered with BIIB093 matching placebo as an IV bolus on Day 1 followed by a continuous IV infusion for over 72 hours.	BIIB093 n=217 Participants Participants were administered with BIIB093 as an IV bolus on Day 1 followed by continuous IV infusion for over 72 hours.
Part 1: Time to All-Cause Death Through Day 90	NA days Interval 37.0 to Median and upper limit of inter quartile range were not reached due to insufficient number of participants with events.	NA days Interval 18.0 to Median and upper limit of inter quartile range were not reached due to insufficient number of participants with events.

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=214 Participants Participants were administered with BIIB093 matching placebo as an IV bolus on Day 1 followed by a continuous IV infusion for over 72 hours.	BIIB093 n=217 Participants Participants were administered with BIIB093 as an IV bolus on Day 1 followed by continuous IV infusion for over 72 hours.
Part 1: Percentage of Participants Who Achieved mRS 0-4 at Day 90	41.6 percentage of participants	42.9 percentage of participants

SECONDARY outcome

Timeframe: At 72 hours

Population: The mITT population included participants aged 18 to 70 years (inclusive) at the time of randomization, who received any study drug, and who had at least 1 post-baseline mRS before or at the Day 90 visit. Here, 'Overall number of participants analyzed' signifies the number of participants with data available for outcome measure analysis.

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.

Outcome measures

Outcome measures
Measure	Placebo n=150 Participants Participants were administered with BIIB093 matching placebo as an IV bolus on Day 1 followed by a continuous IV infusion for over 72 hours.	BIIB093 n=155 Participants Participants were administered with BIIB093 as an IV bolus on Day 1 followed by continuous IV infusion for over 72 hours.
Part 1: Midline Shift at 72 Hours as Assessed by Non-contrast Computed Tomography (NCCT) or Magnetic Resonance Imaging (MRI)	6.32 millimeters (mm) Standard Deviation 4.760	7.02 millimeters (mm) Standard Deviation 4.565

SECONDARY outcome

Timeframe: From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months)

Population: The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093). Here, 'Overall number of participants analyzed' signifies the number of participants with data available for outcome measure analysis.

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.

Outcome measures

Outcome measures
Measure	Placebo n=259 Participants Participants were administered with BIIB093 matching placebo as an IV bolus on Day 1 followed by a continuous IV infusion for over 72 hours.	BIIB093 n=259 Participants Participants were administered with BIIB093 as an IV bolus on Day 1 followed by continuous IV infusion for over 72 hours.
Part 1: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs	95.4 percentage of participants	97.3 percentage of participants
Part 1: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs	68.3 percentage of participants	76.8 percentage of participants

Adverse Events

Placebo

Serious events: 177 serious events

Other events: 199 other events

Deaths: 97 deaths

BIIB093

Serious events: 199 serious events

Other events: 201 other events

Deaths: 103 deaths

Serious adverse events

Other adverse events

Additional Information

US Biogen Clinical Trial Center

Biogen

Phone: 866-633-4636

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Our agreement is subject to confidentiality but generally the PI can publish, for noncommercial purposes only, results and methods of the trial, but no other Sponsor Confidential Information. PI must give Sponsor no less than 60 days to review any manuscript for a proposed publication and must delay publication for up to an additional 90 days thereafter if Sponsor needs to file any patent application to protect any of Sponsor's intellectual property contained in the proposed publication.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=259 participants at risk Participants were administered with BIIB093 matching placebo as an IV bolus followed by a continuous IV infusion for over 72 hours.	BIIB093 n=259 participants at risk Participants were administered with BIIB093 as an IV bolus followed by continuous IV infusion for over 72 hours.
Blood and lymphatic system disorders Anaemia	10.8% 28/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).	9.7% 25/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).
Blood and lymphatic system disorders Leukocytosis	8.1% 21/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).	6.2% 16/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).
Cardiac disorders Atrial fibrillation	8.5% 22/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).	6.6% 17/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).
Cardiac disorders Bradycardia	5.0% 13/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).	5.0% 13/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).
Gastrointestinal disorders Constipation	20.8% 54/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).	15.4% 40/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).
Gastrointestinal disorders Diarrhoea	9.3% 24/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).	5.0% 13/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).
Gastrointestinal disorders Dysphagia	2.3% 6/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).	5.0% 13/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).
Gastrointestinal disorders Nausea	6.6% 17/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).	5.0% 13/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).
Gastrointestinal disorders Vomiting	10.0% 26/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).	8.5% 22/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).
General disorders Pain	3.1% 8/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).	5.4% 14/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).
General disorders Pyrexia	22.0% 57/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).	25.5% 66/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).
Infections and infestations Pneumonia	15.4% 40/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).	12.4% 32/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).
Infections and infestations Pneumonia aspiration	5.4% 14/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).	5.8% 15/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).
Infections and infestations Urinary tract infection	15.8% 41/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).	11.2% 29/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).
Investigations Electrocardiogram qt prolonged	5.0% 13/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).	2.3% 6/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).
Metabolism and nutrition disorders Hyperglycaemia	5.8% 15/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).	5.4% 14/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).
Metabolism and nutrition disorders Hypernatraemia	8.9% 23/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).	10.0% 26/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).
Metabolism and nutrition disorders Hypocalcaemia	4.2% 11/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).	5.0% 13/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).
Metabolism and nutrition disorders Hypoglycaemia	3.1% 8/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).	12.0% 31/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).
Metabolism and nutrition disorders Hypokalaemia	12.4% 32/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).	13.5% 35/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).
Metabolism and nutrition disorders Hyponatraemia	6.9% 18/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).	6.9% 18/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).
Metabolism and nutrition disorders Hypophosphataemia	8.9% 23/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).	5.4% 14/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).
Nervous system disorders Brain oedema	10.8% 28/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).	10.8% 28/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).
Nervous system disorders Haemorrhagic transformation stroke	9.3% 24/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).	6.2% 16/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).
Nervous system disorders Headache	10.4% 27/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).	8.5% 22/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).
Renal and urinary disorders Acute kidney injury	4.2% 11/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).	6.6% 17/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).
Renal and urinary disorders Urinary retention	7.7% 20/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).	3.9% 10/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).
Vascular disorders Deep vein thrombosis	3.5% 9/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).	6.2% 16/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).
Vascular disorders Hypertension	5.0% 13/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).	2.7% 7/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).
Vascular disorders Hypotension	6.9% 18/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).	5.4% 14/259 • From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months) The safety population included all participants who were enrolled and had received any portion of the infusion of study treatment (placebo or BIIB093).