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

Stroke, Acute Clinical Trial

— CHARM  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02864953
• Other study ID #: 252LH301
• Secondary ID: RPI 3012017-0048
• Status: Terminated
• Phase: Phase 3
• Start date: August 29, 2018
• Est. completion date: August 18, 2023

Study information

• Verified date: April 2024
• Source: Remedy Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

This study, previously posted by Remedy Pharmaceuticals, Inc., has transitioned to Biogen.

Other known NCT identifiers

• NCT04950972

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 535
• Est. completion date: August 18, 2023
• Est. primary completion date: August 18, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Brain Edema
• Edema
• Infarction
• Stroke
• Stroke, Acute

Intervention

Drug:
• BIIB093
Administered as specified in the treatment arm.
• Placebo
Administered as specified in the treatment arm.

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Monash Medical Centre	Clayton	Victoria
Australia	Liverpool Hospital	Liverpool	New South Wales
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	John Hunter Hospital	New Lambton Heights	New South Wales
Australia	Royal Melbourne Hospital	Parkville	Victoria
Australia	Sunshine Hospital	St Albans	Victoria
Australia	Royal North Shore Hospital	St Leonards	New South Wales
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Belgium	Universitair Ziekenhuis Gent	Gent	East Flanders
Belgium	UZ Leuven	Leuven	Flemish Brabant
Belgium	Clinique CHC MontLégia	Liege
Belgium	CHU UCL Namur	Yvoir	Namur
Brazil	Hospital do Rocio	Campo Largo	Paraná
Brazil	HGF - Hospital Geral de Fortaleza	Fortaleza	Ceará
Brazil	Clinica Neurológica e Neurocirúrgica de Joinville	Joinville	Santa Catarina
Brazil	Hospital de Clínicas de Porto Alegre	Porto Alegre	Rio Grande Do Sul
Brazil	Hospital das Clínicas FMRP-USP	Ribeirao Preto	Sao Paulo
Brazil	Hospital Sao Paulo	São Paulo	Sao Paulo
Canada	Foothills Medical Centre	Calgary	Alberta
Canada	University of Alberta Hospital	Edmonton	Alberta
China	Beijing Tiantan Hospital, Capital Medical University	Beijing	Beijing
China	Beijing Tiantan Hospital, Capital Medical University	Beijing	Bejing
China	Peking University Third Hospital	Beijing	Beijing
China	Xuanwu Hospital Capital Medical University	Beijing	Beijing
China	The First Hospital of Jilin University	Changchun	Jilin
China	Army Specialty Medical Center of The Chinese People's Liberation Army	Chongqing	Sichuan
China	The First Affiliated Hospital of Sun Yat-sen University	Guangzhou	Guangdong
China	The Second Affiliated Hospital of Guangzhou Medical University	Guangzhou	Guangdong
China	Hainan General Hospital	Haikou	Hainan
China	Sir Run Run Shaw Hospital, Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	Anhui Provincial Hospital	Hefei	Anhui
China	Huai'an First People's Hospital	Huai'an	Jiangsu
China	Jiangxi Provincial People's Hospital	Nanchang	Jiangxi
China	The First Affiliated Hospital of Nanchang University	Nanchang	Jiangxi
China	The Second Affiliated Hospital of Nanjing Medical University	Nanjing	Jiangsu
China	Zhongda Hospital Southeast University	Nanjing	Jiangsu
China	Affiliated Hospital of Nantong University	Nantong	Jiangsu
China	Jiangxi Pingxiang People's Hospital	Pingxiang	Jiangxi
China	Huashan Hospital, Fudan University	Shanghai	Shanghai
China	The Second Affiliated Hospital of Soochow University	Suzhou	Jiangsushe
China	Tianjin Medical University General Hospital	Tianjin	Tianjin
China	Renmin Hospital, Wuhan University	Wuhan	Hubei
China	Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology	Wuhan	Hubei
China	The Second Affiliated Hospital of Xi'an Jiaotong University(Xibei Hospital)	Xi'an	Shanxi
China	The Affiliated Hospital of Xuzhou Medical College	Xuzhou	Jiangsu
Croatia	General Hospital Varazdin	Varazdin	Croatia Proper
Croatia	Clinical Hospital 'Sestre Milosrdnice'	Zagreb	Croatia Proper
Croatia	Clinical Hospital Centar Zagreb	Zagreb	Croatia Proper
Czechia	Fakultni nemocnice Brno	Brno	Moravia
Czechia	Fakultni nemocnice u sv. Anny v Brne	Brno	Moravia
Czechia	Fakultni nemocnice Hradec Kralove	Hradec Kralove
Czechia	Fakultni nemocnice Ostrava	Ostrava	Moravian-Silesian
Czechia	Fakultni nemocnice Kralovske Vinohrady	Praha 10	Prague
Czechia	Fakultni nemocnice v Motole	Praha 5	Prague
Denmark	Copenhagen University Hospital and Glostrup Hospital	Copenhagen	Copenhagen City
Denmark	Bispebjerg og Frederiksberg Hospital	Copenhagen NV	Copenhagen City
Denmark	Sjællands Universitetshospital	Roskilde	Østsjælland
Finland	Helsinki University Hospital	Helsinki	Southern
Finland	Turun yliopistollinen keskussairaala	Turku	Western
France	CHU Besançon - Hôpital Jean Minjoz	Besancon Cedex	Doubs
France	Groupe Hospitalier Pellegrin - Hôpital Pellegrin	Bordeaux	Gironde
France	CHU de Brest - Hôpital de la Cavale Blanche	Brest cedex 2	Finistere
France	CHU CAEN - Hôpital de la Côte de Nacre	Caen cedex 9	Calvados
France	Hôpital Bicêtre	Le Kremlin Bicêtre cedex	Val De Marne
France	Hopital Roger Salengro - CHU Lille	Lille Cedex	Nord
France	CHU Nancy - Hôpital Central	Nancy	Meurthe Et Moselle
France	CHU Rennes - Hopital Pontchaillou	Rennes cedex 09	Ille-et-Vilaine
France	CHU Nantes - Hopital Nord Laënnec	Saint-Herblain	Loire Atlantique
Germany	Klinikum Altenburger Land GmbH	Altenburg	Thueringen
Germany	Klinikum Augsburg	Augsburg	Bayern
Germany	Rhon-Klnikum Campus Bad Neustadt	Bad Neustadt Saale	Bayern
Germany	Universitaetsklinikum Carl Gustav Carus TU Dresden	Dresden
Germany	Universitaetsklinikum Erlangen	Erlangen	Bayern
Germany	Universitaetsklinikum Essen	Essen	Nordrhein Westfalen
Germany	Klinikum der Johann Wolfgang Goethe-Universitaet	Frankfurt	Hessen
Germany	Klinikum Frankfurt Hoechst GmbH	Frankfurt	Hessen
Germany	Universitaetsklinikum Freiburg	Freiburg	Baden Wuerttemberg
Germany	Universitaetsklinikum Jena	Jena	Thueringen
Germany	Klinikum Kassel GmbH	Kassel	Hessen
Germany	Universitaetsklinikum Muenster	Muenster	Nordrhein Westfalen
Hungary	Semmelweis Egyetem	Budapest
Hungary	Petz Aladar Egyetemi Oktato Korhaz	Gyor	Gyor-Moson-Sopron
Hungary	Somogy Megyei Kaposi Mor Oktato Korhaz	Kaposvar	Somogy
Hungary	Pest Megyei Flor Ferenc Korhaz	Kistarcsa	Budapest
Hungary	SzSzB Megyei Korhazak es Egyetemi Oktatokorhaz	Nyiregyhaza	Szabolcs-Szatmár-Bereg
Hungary	Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont	Szeged	Csongrád-Csanád
Israel	Soroka University Medical Center	Beer-Sheva	Southern
Israel	Rambam Health Care Center	Haifa
Israel	Hadassah University Hospital - Ein Kerem	Jerusalem
Israel	Shaare Zedek	Jerusalem
Israel	Rabin MC	Petah Tikva	Central
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Italy	Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (Presidio Spedali Civili)	Brescia
Italy	Azienda Ospedaliera Universitaria Careggi	Firenze
Italy	IRCCS Ospedale Policlinico San Martino	Genova
Italy	Azienda Socio Sanitaria Territoriale Niguarda (Grande Ospedale Metropolitano Niguarda)	Milano
Italy	Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico	Milano
Italy	Ospedale San Raffaele	Milano
Italy	Azienda Ospedaliera Sant'Andrea-Università di Roma La Sapienza	Rome	Roma
Italy	Azienda Ospedaliera Universitaria Policlinico Tor Vergata	Rome	Roma
Italy	Policlinico Umberto I	Rome	Roma
Italy	Istituto Clinico Humanitas	Rozzano	Milano
Italy	A.O.U. Senese Policlinico Santa Maria alle Scotte	Siena
Japan	Ohnishi Neurological Center	Akashi-shi	Hyogo-Ken
Japan	Asahikawa Red Cross Hospital	Asahikawa-shi	Hokkaido
Japan	Nippon Medical School Hospital	Bunkyo-ku	Tokyo-To
Japan	Tokyo Metropolitan Tama Medical Center	Fuchu-shi	Tokyo-To
Japan	Chiyukai Fukuoka Wajiro Hospital	Fukuoka-shi	Fukuoka-Ken
Japan	NHO Kyushu Medical Center	Fukuoka-shi	Fukuoka-Ken
Japan	Showakai Brain Attack Center Ota Memorial Hospital	Fukuyama-shi	Hiroshima-Ken
Japan	Gifu Prefectural General Medical Center	Gifu-shi	Gifu-Ken
Japan	Hachinohe Red Cross Hospital	Hachinohe-shi	Aomori-Ken
Japan	Saitama Medical University International Medical Center	Hidaka-shi	Saitama-Ken
Japan	Rinku General Medical Center	Izumisano-shi	Osaka-Fu
Japan	St. Marianna University Hospital	Kawasaki-shi	Kanagawa-Ken
Japan	Kimitsu Chuo Hospital	Kisarazu-shi	Chiba-Ken
Japan	Kobe City Hospital Organization Kobe City Medical Center General Hospital	Kobe-shi	Hyogo-Ken
Japan	Yamanashi Prefectural Central Hospital	Kofu-shi	Yamanashi-Ken
Japan	Southern Tohoku General Hospital	Koriyama-shi	Fukushima-Ken
Japan	Kurashiki Central Hospital	Kurashiki-shi	Okayama-Ken
Japan	Kyorin University Hospital	Mitaka-shi	Tokyo-To
Japan	Iwate Prefectural Central Hospital	Morioka-shi	Iwate-Ken
Japan	Okayama City General Medical Center Okayama City Hospital	Okayama-shi	Okayama-Ken
Japan	Chiyukai Fukuoka Shinmizumaki Hospital	Onga-gun	Fukuoka-Ken
Japan	NHO Sendai Medical Center	Sendai-shi	Miyagi-Ken
Japan	National Cerebral and Cardiovascular Center	Suita	Osaka Prefecture
Japan	NHO Minami Wakayama Medical Center	Tanabe-shi	Wakayama-Ken
Japan	Toyota Memorial Hospital	Toyota-shi	Aichi-Ken
Japan	Tsuchiura Kyodo General Hospital	Tsuchiura-shi	Ibaraki-Ken
Japan	Yamaguchi University Hospital	Ube-shi	Yamaguchi-Ken
Japan	Chiyukai Shin Yukuhashi Hospital	Yukuhashi-shi	Fukuoka-Ken
Korea, Republic of	Dong-A University Hospital	Busan
Korea, Republic of	Kyungpook National University Hospital	Daegu	Gyeongsangnam-do
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam	Gyeonggi-do
Korea, Republic of	Asan Medical Center	Seoul
Lithuania	Hospital of Lithuanian University of Health Sciences Kaunas Clinics	Kaunas
Lithuania	Republican Vilnius University Hospital, Public Institution	Vilnius
Lithuania	Vilnius University Hospital Santariskiu Clinic, Public Institution	Vilnius
Portugal	Hospital Garcia de Orta, EPE	Almada	Setubal
Portugal	Centro Hospitalar e Universitário de Coimbra E.P.E. - Hospitais da Universidade de Coimbra	Coimbra
Portugal	Centro Hospitalar de Lisboa Norte, E.P.E. - Hospital de Santa Maria	Lisboa
Portugal	Centro Hospitalar de Lisboa Ocidental, E.P.E. - Hospital de Egas Moniz	Lisboa
Portugal	Unidade Local de Saúde de Matosinhos, E.P.E. - Hospital Pedro Hispano	Matosinhos	Porto
Portugal	Centro Hospitalar de São João, E.P.E	Porto
Portugal	Centro Hospitalar de Entre o Douro e Vouga, E.P.E. - Hospital de São Sebastião	Santa Maria da Feira	Aveiro
Russian Federation	SBEI HPE 'Kazan State Medical University' of the MoH of the RF	Kazan	Respublka Tatarstan
Russian Federation	SHI "Territorial Clinical Hospital #1 n.a. S.V. Ochapovsky"	Krasnodar
Russian Federation	SBIH of Moscow 'City Clinical Hospital # 1 n. a. N. I. Pirogov'	Moscow
Russian Federation	SPb SBIH 'City Hospital # 26'	Saint Petersburg	Leningrad
Russian Federation	Saint-Petersburg Scientific-Research Institute of Emergency Care	St. Petersburg	Leningrad
Spain	Hospital del Mar	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Universitario Reina Sofia	Cordoba	Córdoba
Spain	Hospital Universitari de Girona Dr Josep Trueta	Girona
Spain	Hospital Universitari de Bellvitge	L'Hospitalet de Llobregat	Barcelona
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	Hospital Regional Universitario de Malaga	Malaga	Málaga
Spain	Complejo Hospitalario Universitario de Santiago	Santiago de Compostela	La Coruña
Spain	Hospital Universitario Virgen del Rocio	Sevilla
Spain	Hospital Universitario Virgen Macarena	Sevilla
Spain	Hospital Universitari i Politecnic La Fe	Valencia
Spain	Hospital Clinico Universitario de Valladolid	Valladolid
Switzerland	Inselspital - Universitaetsspital Bern	Bern
Switzerland	Ospedale Regionale di Lugano	Lugano	Ticino
Taiwan	Kaohsiung Chang Gung Memorial Hospital	Kaohsiung
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Chang Gung Memorial Hospital,Linkou	Taoyuan
United Kingdom	Addenbrooke's Hospital	Cambridge	Cambridgeshire
United Kingdom	Queen Elizabeth University Hospital Campus	Glasgow	Strathclyde
United Kingdom	Imp Coll Health Nhst 1	London	Greater London
United Kingdom	King's College Hospital	London	Greater London
United Kingdom	The National Hospital for Neurology & Neurosurgery	London	Greater London
United Kingdom	Newcastle University- Clinical Ageing Research Unit	Newcastle upon Tyne	Tyne & Wear
United Kingdom	Nottingham University Hospitals City Campus	Nottingham	Nottinghamshire
United States	Summa Health System	Akron	Ohio
United States	University of New Mexico	Albuquerque	New Mexico
United States	Lehigh Valley Hospital - Cedar Crest	Allentown	Pennsylvania
United States	Grady Memorial Hospital	Atlanta	Georgia
United States	Augusta University	Augusta	Georgia
United States	University of Colorado Hospital	Aurora	Colorado
United States	St.David's HealthCare Office of Research	Austin	Texas
United States	Sinai Hospital of Baltimore	Baltimore	Maryland
United States	University of Maryland	Baltimore	Maryland
United States	Brigham and Woman's Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of Buffalo	Buffalo	New York
United States	UNC Hospitals	Chapel Hill	North Carolina
United States	Atrium Health Carolinas Medical Center	Charlotte	North Carolina
United States	Erlanger Health System	Chattanooga	Tennessee
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Cincinnati	Cincinnati	Ohio
United States	The Cleveland Clinic Foundation	Cleveland	Ohio
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Ohio State Univ College Of Medicine	Columbus	Ohio
United States	Miami Valley Hospital South	Dayton	Ohio
United States	Henry Ford Hospital	Detroit	Michigan
United States	St. John's Hospital	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	JFK Medical Center	Edison	New Jersey
United States	University of Florida-Gainsville	Gainesville	Florida
United States	Guilford Neurologic Research, PA	Greensboro	North Carolina
United States	Valley Baptist Medical Center	Harlingen	Texas
United States	Penn State University Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	The Queens Medical Center	Honolulu	Hawaii
United States	Lyerly Neurosurgery Baptist Health	Jacksonville	Florida
United States	University of Florida, Jacksonville	Jacksonville	Florida
United States	Beth Israel Deaconess Medical Center, Inc.	Jamaica Plain	Massachusetts
United States	Saint Luke's Hospital of Kansas City	Kansas City	Missouri
United States	University of Kansas Medical Center Research Institute, Inc.	Kansas City	Kansas
United States	University of Louisville	Louisville	Kentucky
United States	University Hospital and UW Health Clinics	Madison	Wisconsin
United States	Northwell Health	Manhasset	New York
United States	University of Tennessee Health Sciences Center	Memphis	Tennessee
United States	TriStar Skyline Medical Center	Nashville	Tennessee
United States	Vanderbilt Medical Center	Nashville	Tennessee
United States	Jersey Shore University Medical Center	Neptune	New Jersey
United States	Rutgers - Robert Wood Johnson Medical School	New Brunswick	New Jersey
United States	Yale New Haven Hospital	New Haven	Connecticut
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	Columbia University Hervert Irving Comprehensive Cancer Center	New York	New York
United States	Mount Sinai Hospital	New York	New York
United States	NYU Langone Medical Center	New York	New York
United States	Stanford Stroke Center	Palo Alto	California
United States	University of Pennsylvania Health System	Philadelphia	Pennsylvania
United States	Barrow Neurological Institute	Phoenix	Arizona
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	University of Pittsburgh School of Medicine	Pittsburgh	Pennsylvania
United States	Maine Medical Center	Portland	Maine
United States	Oregon Health & Science University	Portland	Oregon
United States	Providence Brain and Spine Institute	Portland	Oregon
United States	Rhode Island Hospital Warren Alpert Medical School Brown University	Providence	Rhode Island
United States	Valley Hospital	Ridgewood	New Jersey
United States	University of Rochester Medical Center	Rochester	New York
United States	University of California Davis Health System	Sacramento	California
United States	Saint Louis University	Saint Louis	Missouri
United States	Washington University Physicians	Saint Louis	Missouri
United States	University of Utah Neurology	Salt Lake City	Utah
United States	UCSD Health-La Jolla	San Diego	California
United States	University of Washington School of Medicine	Seattle	Washington
United States	SUNY Upstate Medical Center	Syracuse	New York
United States	University of South Florida	Tampa	Florida
United States	ProMedica Toledo Hospital	Toledo	Ohio
United States	Arizona Board of Regents, University of Arizona	Tucson	Arizona
United States	Ascension St. John	Tulsa	Oklahoma
United States	Novant Health Forsyth Medical Center	Winston-Salem	North Carolina
United States	Wake Forest Baptist Health Sciences	Winston-Salem	North Carolina
United States	UMASS Memorial Medical Center	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Remedy Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  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, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1: Percentage of Participants With Improvement in Functional Outcome at Day 90 Assessed Via the Modified Rankin Scale (mRS)	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.	Day 90
Secondary	Part 1: Time to All-Cause Death Through Day 90	Time to all-cause death is defined as the time from randomization to the time of death.	Randomization up to Day 90
Secondary	Part 1: Percentage of Participants Who Achieved mRS 0-4 at 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.	Day 90
Secondary	Part 1: Midline Shift at 72 Hours as Assessed by Non-contrast Computed Tomography (NCCT) or Magnetic Resonance Imaging (MRI)	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.	At 72 hours
Secondary	Part 1: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	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.	From the signing of informed consent up to the last follow-up visit (up to 4 years 11 months)