Safety and Efficacy Study of Gantenerumab in Participants With Early Alzheimer's Disease (AD)
- Registration Number
- NCT03443973
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This randomized, double-blind, placebo-controlled, parallel group study will evaluate the efficacy and safety of gantenerumab versus placebo in participants with early (prodromal to mild) AD. All participants must show evidence of beta-amyloid pathology. Eligible participants will be randomized 1:1 to receive either subcutaneous (SC) injection of ganteneruma...
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 975
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Placebo will be administered as SC injections with gradual uptitration. Gantenerumab Gantenerumab Gantenerumab will be administered as SC injections with gradual uptitration.
- Primary Outcome Measures
Name Time Method DBT Period: Change From Baseline to Week 116 in Global Outcome, as Measured by CDR-SB Baseline, Week 116 CDR was derived through semi-structured interview with the participant and an appropriate informant, and it rated impairment across six domains: memory, orientation, judgment, and problem solving, community affairs, home and hobbies, and personal care on a 5-point scale for which 0=no impairment, 0.5=questionable impairment, and 1, 2, and 3=mild, moderate, a...
OLE Period: Number of Participants With Adverse Events (AEs) From day of first dose in OLE period up to 14 weeks after the last OLE dose (up to 48 weeks) An adverse event is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution.
OLE Period: Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) From day of first dose in OLE period up to 14 weeks after the last OLE dose (up to 48 weeks) C-SSRS=assessment tool used to assess lifetime suicidality of a participant (at baseline) as well as any new instances of suicidality (C-SSRS since last visit). Structured interview prompts recollection of suicidal ideation, including intensity of ideation, behavior, \& attempts with actual/potential lethality. Categories have binary responses (yes/no) \& in...
OLE Period : Number of Participants With Amyloid-Related Imaging Abnormalities-Haemosiderin Deposition (ARIA-H) Confirmed by MRI From day of first dose in OLE period up to 14 weeks after the last OLE dose (up to 48 weeks) ARIA are an identified risk with anti-amyloid antibodies, including gantenerumab. These changes can be identified on brain MRI. ARIA-H (H for hemosiderosis) are small foci of signal loss observed on MRI sequences sensitive for paramagnetic tissue properties and comprise cerebral microbleeds (small foci of bleeding in the brain parenchyma) and leptomeningeal ...
OLE Period: Number of Participants With Amyloid-Related Imaging Abnormalities-Edema (ARIA-E) Confirmed by Magnetic Resonance Imaging (MRI) From day of first dose in OLE period up to 14 weeks after the last OLE dose (up to 48 weeks) ARIA are an identified risk with anti-amyloid antibodies, including gantenerumab. These changes can be identified on brain MRI. In ARIA-E, (E for oedema or effusion), oedema can be seen in different areas of the brain on MRI, representing fluid leakage into the brain parenchyma or sulcal spaces.
OLE Period: Number of Participants With Injection-Site Reactions From day of first dose in OLE period up to 14 weeks after the last OLE dose (up to 48 weeks) An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational product or other protocol-imposed intervention, regardless of attribution. Local injection reactions (or injection site reactions) are defined as AEs related to the injection site that occur during or within 24 hours after study drug adm...
- Secondary Outcome Measures
Name Time Method DBT Period: Change From Baseline to Week 116 in Alzheimer Disease Assessment Scale-Cognition Subscale 13 (ADAS-Cog13) Score Baseline, Week 116 The ADAS-Cog13 total score includes all of the items in the ADAS-Cog11 in addition to delayed word recall and the number cancellation. For the ADAS-cog 13 the range is 0-85 (score range for Delayed Word Recall \[DWR\] score is 0-10 and for Number Cancellation \[NC\] is 0-5, thus the score is ADAS-cog 11\[0-70\] plus the scores for DWR and NC). A higher score...
DBT Period: Number of Participants With ARIA-H Confirmed by MRI From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 128 weeks) ARIA are an identified risk with anti-amyloid antibodies, including gantenerumab. These changes can be identified on brain MRI. ARIA-H (H for hemosiderosis) are small foci of signal loss observed on MRI sequences sensitive for paramagnetic tissue properties and comprise cerebral microbleeds (small foci of bleeding in the brain parenchyma) and leptomeningeal ...
DBT Period: Number of Participants With Injection-Site Reactions From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 128 weeks) An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational product or other protocol-imposed intervention, regardless of attribution. Local injection reactions (or injection site reactions) are defined as AEs related to the injection site that occur during or within 24 hours after study drug adm...
DBT Period: Number of Participants With Anti-Drug Antibodies (ADA) to Gantenerumab From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 128 weeks) The number of participants with positive results for ADA against gantenerumab at any of the post-baseline assessment time-points were reported. Participant with an ADA assay result from at least one post-baseline sample was defined as a post-baseline evaluable participant. Treatment Emergent ADA = A participant with a negative or missing baseline ADA result(...
DBT Period: Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using C-SSRS From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 128 weeks) C-SSRS=assessment tool used to assess lifetime suicidality of a participant (at baseline) as well as any new instances of suicidality (C-SSRS since last visit). Structured interview prompts recollection of suicidal ideation, including intensity of ideation, behavior, \& attempts with actual/potential lethality. Categories have binary responses (yes/no) \& in...
DBT Period: Number of Participants With ARIA-E Confirmed by MRI From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 128 weeks) ARIA are an identified risk with anti-amyloid antibodies, including gantenerumab. These changes can be identified on brain MRI. In ARIA-E, (E for oedema or effusion), oedema can be seen in different areas of the brain on MRI, representing fluid leakage into the brain parenchyma or sulcal spaces.
Change From Baseline to Week 116 in Brain Amyloid Load as Measured by Amyloid Positron Emission Tomography (PET) Scan in a Subset of Participants Baseline, Week 116 Brain amyloid load over time was assessed using \[18F\] florbetaben or \[18F\] flutemetamol tracers. These are PET radioligand selective to amyloid. Amyloid PET burden was measured in a composite region of interest (ROI) by using standardized uptake value ratio (SUVR) mapped to the centiloid scale. The weighted composite target region are composed of (both l...
DBT Period: Change From Baseline to Week 116 in Alzheimer's Disease Cooperative Study- Activities of Daily Living (ADCS-ADL) Total Score Baseline, Week 116 ADCS-ADL is a 23-item rater-administered, observer-reported outcome (ObsRO) that captures a participant's ability to perform basic activities of daily living (e.g., eating and toileting) and more complex ADL or instrumental activities of daily living (iADL, e.g., using the telephone, managing finances, preparing a meal). Total score ranges from 0-78, with hi...
DBT Period: Change From Baseline to Week 116 in Functional Activities Questionnaire (FAQ) Score Baseline, Week 116 FAQ is a rater-administered ObsRO (informant-based measure) that measures a participant's functional ability to perform complex higher-order activities. The observer provides performance ratings of the target person on ten complex higher-order activities. Total score that ranges from 0-30, with higher scores reflecting greater functional impairment. A negati...
DBT Period: Change From Baseline to Week 116 in Mini-Mental State Examination (MMSE) Total Score Baseline, Week 116 MMSE is a rater-administered performance-based outcome (PerfO) that includes a set of standardized questions used to evaluate possible cognitive impairment and help stage the severity level of this impairment. The questions target six areas: orientation, registration, attention, short-term recall, language, and constructional praxis/visuospatial abilities. T...
DBT Period: Change From Baseline to Week 116 in Alzheimer Disease Assessment Scale-Cognition Subscale 11 (ADAS-Cog11) Score Baseline, Week 116 The ADAS-Cog11 was designed to measure cognitive symptom change in participants with Alzheimer's Disease (AD) and consisted of 11 tasks. The standard 11 items (and corresponding score range) were: word recall (0-10), commands (0-5), constructional praxis (0-5), naming objects and fingers (0-5), ideational praxis (0-5), orientation (0-8), word recognition (0-...
DBT Period: Change From Baseline to Week 116 in Verbal Fluency Task (VFT) Score Baseline, Week 116 VFT is a rater administered PerfO that measures speed and flexibility of verbal thought with a total score that ranges from 0-99 (lower scores indicating lower performance). A positive change from baseline indicates improvement.
DBT Period: Change From Baseline to Week 116 in the Coding (Digit Symbol Substitution Test [DSST]) Subtest Baseline, Week 116 Coding, also called DSST is a rater administered PerfO that measures speed of processing and associative memory with a total score that ranges from 0-135 (lower scores indicating lower performance). The DSST was adapted from the Wechsler Adult Intelligence Scale. The 120-second version of the test was used in this study. Positive change from baseline indicat...
DBT Period: Change From Baseline to Week 116 in Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living (ADCS-iADL) Instrumental Score Baseline, Week 116 The ADCS-iADL measures activities such as using the telephone, shopping and preparing a meal. The ADCS-iADL consists of 16 questions with a score range of 0 to 56 where a higher score represents better function. Positive change from baseline indicates improvement.
DBT Period: Number of Participants With AEs From Day 1 up to 14 weeks after the last dose of blinded study drug (up to 128 weeks) An AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution.
Change From Baseline to Week 116 in Brain Tau Load, as Measured by Tau PET Scan in a Subset of Participants Baseline, Week 116 Change in tau load= how much neurofibrillary tau pathology is present in brain assessed by PET Scan. Tau PET radioligand used was \[18F\] GTP1. Tau load was measured using SUVR in 4 composite target ROIs: Temporal target region included (both left \& right)=anterior \&posterior superior temporal gyrus, posterior temporal lobe, fusiform gyrus, \&middle \&infe...
DBT Period: Percent Change From Baseline to Week 116 in Cerebrospinal Fluid (CSF) Marker of Disease in a Subset of Participants - Neurofilament Light Chain (NFL) Baseline, Week 116 NFL is a neuronal cytoplasmic protein highly expressed in large, myelinated axons. Its levels increase in CSF and blood proportionally to the degree of axonal damage in a variety of neurological disorders, including AD.
DBT Period: Percent Change From Baseline to Week 116 in CSF Marker of Disease in a Subset of Participants - Neurogranin Baseline, Week 116 DBT Period: Percent Change From Baseline to Week 116 in CSF Marker of Disease in a Subset of Participants - Total Tau (tTau) Baseline, Week 116 CSF biomarker tTau has been considered as a general marker of neurodegeneration. An elevation in levels of tau, as well as specific pTau species, is thought to be a marker for progressive cellular degeneration in AD.
DBT Period: Percent Change From Baseline to Week 116 in CSF Marker of Disease in a Subset of Participants - Phosphorylated Tau (pTau-181) Baseline, Week 116 CSF phospho-tau is an indicator of neuronal injury and neurodegeneration. CSF biomarker tTau has been considered as a general marker of neurodegeneration. An elevation in levels of pTau species, is thought to be a marker for progressive cellular degeneration in AD.
Trial Locations
- Locations (155)
Irvine Center for Clinical Research
🇺🇸Irvine, California, United States
SUNY Upstate Medical University
🇺🇸Syracuse, New York, United States
Texas Neurology PA
🇺🇸Dallas, Texas, United States
Emory University
🇺🇸Atlanta, Georgia, United States
NZOZ WCA
🇵🇱Wroc?aw, Poland
Myongji Hospital
🇰🇷Gyeonggi-do, Korea, Republic of
Ewha Womans University Hospital (Seoul)
🇰🇷Seoul, Korea, Republic of
Alzheimer's Memory Center
🇺🇸Matthews, North Carolina, United States
Hyogo Prefectural HarimaHimeji General Medical Center
🇯🇵Hyogo, Japan
Tsukazaki Hospital
🇯🇵Hyogo, Japan
Neurology Center of North Orange County
🇺🇸Fullerton, California, United States
Accel Research Sites - CRU Tampa
🇺🇸Bradenton, Florida, United States
Behavioral Health Research
🇺🇸Charlotte, North Carolina, United States
Psicomed Estudios Médicos
🇨🇱Antofagasta, Chile
UZ Gent
🇧🇪Gent, Belgium
Georgetown University Medical Center
🇺🇸Washington, District of Columbia, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Quest Research Institute
🇺🇸Farmington Hills, Michigan, United States
Richmond Behavioral Associates
🇺🇸Staten Island, New York, United States
Neuro-Behavioral Clinical Research, Inc.
🇺🇸Canton, Ohio, United States
Fundacion Scherbovsky
🇦🇷Mendoza, Argentina
Intercoastal Medical Group
🇺🇸Sarasota, Florida, United States
Progressive Medical Research
🇺🇸Port Orange, Florida, United States
American Health Network Institute, LLC
🇺🇸Avon, Indiana, United States
ActivMed Practices and Research
🇺🇸Haverhill, Massachusetts, United States
Fullerton Neurology and Headache Center
🇺🇸Fullerton, California, United States
Raleigh Neurology Associates
🇺🇸Raleigh, North Carolina, United States
Kerwin Medical Center
🇺🇸Dallas, Texas, United States
AD-CARE, University of Rochester Medical Center
🇺🇸Rochester, New York, United States
Instituto de Neurociencias San Agustín S.A.
🇦🇷La Plata, Argentina
Health Initiatives Research, PLLC
🇺🇸Fayetteville, Arkansas, United States
Renstar Medical Research
🇺🇸Ocala, Florida, United States
Hospital Italiano
🇦🇷Buenos Aires, Argentina
The Cognitive and Research Center of New Jersey
🇺🇸Springfield, New Jersey, United States
Hanyang University Seoul Hospital
🇰🇷Seoul, Korea, Republic of
Podlaskie Centrum Psychogeriatrii
🇵🇱Bia?ystok, Poland
Matsui Dietary and Dementia Clinic
🇯🇵Hyogo, Japan
Clinical Hospital Centre Zagreb;Clinic for Neurology
🇭🇷Zagreb, Croatia
Instituto Kremer
🇦🇷Córdoba, Argentina
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Korea, Republic of
Rigshospitalet, Hukommelsesklinikken
🇩🇰København Ø, Denmark
Seoul St Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Ewha Womans University Mokdong Hospital
🇰🇷Seoul, Korea, Republic of
Universidad Maimonides
🇦🇷Caba, Argentina
Instituto Geriatrico Nuestra Señora de las Nieves
🇦🇷Capital Federal, Argentina
CEN Centro Especializado en Neurociencias
🇦🇷Cordoba, Argentina
Rakuwakai Otowa Hospital
🇯🇵Kyoto, Japan
Especialidades Medicas LYS
🇨🇱Santiago, Chile
Dong-A University Hospital
🇰🇷Busan, Korea, Republic of
Brain Research Center B.V
🇳🇱Amsterdam, Netherlands
mMED Maciej Czarnecki
🇵🇱Warszawa, Poland
Santa Cruz Behavioral PSC
🇵🇷Bayamon, Puerto Rico
Jessa Zkh (Campus Virga Jesse)
🇧🇪Hasselt, Belgium
Hospital Universitario Dr Jose Eleuterio Gonzalez UANL; Depto.de NeurologíaPta.BajaConsulta
🇲🇽Monterrey, Nuevo LEON, Mexico
Terveystalo Ruoholahti
🇫🇮Helsinki, Finland
Hospital Prof. Dr. Fernando Fonseca; Servico de Neurologia
🇵🇹Amadora, Portugal
National University Hospital (NUH); Neuroscience
🇸🇬Singapore, Singapore
Hospital General Universitario de Elche; Servicio de Neurología
🇪🇸Elche, Alicante, Spain
NZOZ Vitamed
🇵🇱Bydgoszcz, Poland
KO-MED Centra Kliniczne Lublin II
🇵🇱Lublin, Poland
KAROLINSKA UNI HOSPITAL, HUDDINGE; Mottagning Kognitiv Forskning, M54
🇸🇪Stockholm, Sweden
Hospital Victoria Eugenia; Servico Neurología
🇪🇸Sevilla, Spain
Tokushima Hospital
🇯🇵Tokushima, Japan
Gachon University Gil Medical Center
🇰🇷Incheon, Korea, Republic of
Svendborg Sygehus; Neurologisk afdeling N, Demensklinik Fyn
🇩🇰Svendborg, Denmark
Istanbul University Istanbul School of Medicine; Neurology
🇹🇷Istanbul, Turkey
CAE OROITU; Servicio de Neurología
🇪🇸Getxo, Vizcaya, Spain
Ondokuz Mayis Univ. Med. Fac.; Neurology
🇹🇷Samsun, Turkey
Yachiyo Hospital
🇯🇵Aichi, Japan
Nagoya Ekisaikai Hospital
🇯🇵Aichi, Japan
O?rodek Badawczo-Naukowo-Dydaktyczny Chorób Ot?piennych w ?cinawie
🇵🇱?cinawa, Poland
NEURO-CARE Sp. z o.o. Sp. Komandytowa
🇵🇱Siemianowice ?l?skie, Poland
Clinica Universitaria de Navarra
🇪🇸Pamplona, Navarra, Spain
Surrey and Borders NHS Foundation Trust; Brain Science Research Unit
🇬🇧Chertsey, United Kingdom
Universitario de La Princesa; Servicio de Neurología
🇪🇸Madrid, Spain
Complejo Asistencial de Zamora; Servicio Psiquiatria
🇪🇸Zamora, Spain
Kishiwada Tokushukai Hospital
🇯🇵Osaka, Japan
Inha University Hospital
🇰🇷Incheon, Korea, Republic of
Senior Sp. Z O.O. Poradnia Psychogeriatryczna
🇵🇱Sopot, Poland
Skånes Universitetssjukhus Malmö, Minneskliniken
🇸🇪Malmö, Sweden
Clinica Universitaria de Navarra; Servicio de Neurología
🇪🇸Pamplona, Navarra, Spain
The Rice Centre; Royal United Hospital
🇬🇧Bath, United Kingdom
HUC; Servico de Neurologia
🇵🇹Coimbra, Portugal
Hospital Universitario de Santa Maria; Servicio de Neurología
🇪🇸Lleida, Lerida, Spain
Ninewells Hospital
🇬🇧Dundee, United Kingdom
Policlínica Guipuzcoa; Servicio de Neurología
🇪🇸Donostia-san Sebastian, Guipuzcoa, Spain
Brigham and Womens Hospital; Center for Alzheimer Research & Treatment
🇺🇸Boston, Massachusetts, United States
Cleveland Clinic; Cleveland Lou Ruvo Center for Brain Health ? Neurological Institute
🇺🇸Cleveland, Ohio, United States
Optimus U Corp
🇺🇸Miami, Florida, United States
Allied Biomedical Research Institute, Inc
🇺🇸Miami, Florida, United States
Alzheimers Disease & Memory Disorders Center; Department of Neurology Baylor College of Medicine
🇺🇸Houston, Texas, United States
The University of Texas Health Science Center at Houston
🇺🇸Houston, Texas, United States
Cleveland Clinic Lou Ruvo; Center for Brain Research
🇺🇸Las Vegas, Nevada, United States
Hospital Angeles Culiacan; Neurociencias
🇲🇽Culiacán Rosales, Sinaloa, Mexico
Aarhus Universitetshospital; Neurologisk Afd. F, Demensklinikken
🇩🇰Aarhus N, Denmark
Banner Alzheimer?s Institute
🇺🇸Phoenix, Arizona, United States
Barrow Neurological Institute
🇺🇸Phoenix, Arizona, United States
Lynn Health Science Institute
🇺🇸Oklahoma City, Oklahoma, United States
Summit Research Network Inc.
🇺🇸Portland, Oregon, United States
Uji Takeda Hospital
🇯🇵Kyoto, Japan
Kagawa Prefectural Central Hospital
🇯🇵Kagawa, Japan
National Hospital Organization Hiroshima-Nishi Medical Center
🇯🇵Hiroshima, Japan
Rijikai Medical Corporation Katayama Medical Clinic
🇯🇵Okayama, Japan
National Hospital Organization Hizen Psychiatric Medical Center
🇯🇵Saga, Japan
Medical corporation Ichiekai Itsuki Hospital
🇯🇵Tokushima, Japan
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Hospital del Mar; Servicio de Neurologia
🇪🇸Barcelona, Spain
Fundación ACE; Servicio de Neurología
🇪🇸Barcelona, Spain
University of Nebraska Medical Center; Dept of Neurological Sciences
🇺🇸Omaha, Nebraska, United States
Axiom Clinical Research of Florida
🇺🇸Tampa, Florida, United States
Banner Sun Health Research Insitute
🇺🇸Sun City, Arizona, United States
Desert Valley Research
🇺🇸Redlands, California, United States
Southern California Research LLC
🇺🇸Simi Valley, California, United States
ClinCloud, LLC
🇺🇸Maitland, Florida, United States
Infinity Clinical Research, LLC
🇺🇸Sunrise, Florida, United States
Rush Alzheimer's Disease Cntr.
🇺🇸Chicago, Illinois, United States
Missouri Memory Center
🇺🇸Bolivar, Missouri, United States
Boston Center for Memory
🇺🇸Newton, Massachusetts, United States
AZ Sint Blasius (Dendermonde)
🇧🇪Dendermonde, Belgium
Biomedica Research Group
🇨🇱Santiago, Chile
Fukuoka University Hospital
🇯🇵Fukuoka, Japan
National Center for Geriatrics and Gerontology
🇯🇵Aichi, Japan
Konkuk University Medical Center
🇰🇷Seoul, Korea, Republic of
Mexico Centre for Clinical Research
🇲🇽Ciudad de México, Mexico CITY (federal District), Mexico
Pratia S.A.
🇵🇱Warszawa, Poland
Neurologiczny NZOZ Centrum Leczenia SM; Osrodek Badan Klinicznych
🇵🇱Plewiska, Poland
Hospital da Senhora da Oliveira-Guimarães; Serviço de Neurologia
🇵🇹Guimarães, Portugal
Hospital Geral de Santo Antonio; Servico de Neurologia
🇵🇹Porto, Portugal
University of Puerto Rico - Medical Science Campus; Internal Medicine
🇵🇷San Juan, Puerto Rico
Hospital Virgen del Puerto. Servicio de Neurología
🇪🇸Plasencia, Caceres, Spain
Hospital Mutua De Terrasa; Servicio de Neurologia
🇪🇸Terrassa, Barcelona, Spain
Hospital Quiron de Madrid; Servicio de Neurologia
🇪🇸Pozuelo de Alarcon, Madrid, Spain
Hospital Universitario la Fe; Servicio de Neurologia
🇪🇸Valencia, Spain
Sahlgrenska Academy University,Neuroscience and Physiology;Departmt of Psychiatry and Neurochemistry
🇸🇪Mölndal, Sweden
Royal Cornhill Hospital; OAP Directorate
🇬🇧Aberdeen, United Kingdom
Queen Elizabeth University Hospital; Clinical Research Facility
🇬🇧Glasgow, United Kingdom
Re-Cognition
🇬🇧Birmingham, United Kingdom
Bezmialem Vakif Univ Medical
🇹🇷Istanbul, Turkey
Sussex Partnership NHS Foundation Trust; Cognitive Treatment and Research unit
🇬🇧Crowborough, United Kingdom
St George's Hospital
🇬🇧London, United Kingdom
The Fritchie Centre, Charlton Lane Centre, Charlon Lane, Leckhampton; The Fritchie Centre
🇬🇧Cheltenham, United Kingdom
RE:Cognition Health
🇬🇧London, United Kingdom
Campus for Ageing and Vitality
🇬🇧Newcastle, United Kingdom
John Radcliffe Hospital
🇬🇧Oxford, United Kingdom
Royal Preston Hospital
🇬🇧Preston, United Kingdom
University Southampton NHS Foundation Trust; Wessex Neurologica Centre
🇬🇧Southampton, United Kingdom
Royal Hallamshire Hospital Sheffield Teaching Hospitals NHS Foundation Trust
🇬🇧Sheffield, United Kingdom
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
AVIX Investigación Clínica S.C
🇲🇽Monterrey, Nuevo LEON, Mexico
National Neuroscience Institute; Neurology
🇸🇬Singapore, Singapore
University of Eastern Finland
🇫🇮Kuopio, Finland
Hospital de Braga; Servico de Neurologia
🇵🇹Braga, Portugal
Yale University School Of Medicine
🇺🇸New Haven, Connecticut, United States
Wake Forest University
🇺🇸Winston-Salem, North Carolina, United States
Charing Cross Hospital
🇬🇧London, United Kingdom
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