A Study of Ocrelizumab in Comparison With Interferon Beta-1a (Rebif) in Participants With Relapsing Multiple Sclerosis
- Conditions
- Relapsing Multiple Sclerosis
- Interventions
- Drug: Ocrelizumab-matching placeboDrug: Interferon beta-1a-matching placebo
- Registration Number
- NCT01412333
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This randomized, double-blind, double-dummy, parallel-group study will evaluate the efficacy and safety of ocrelizumab in comparison with interferon beta-1a (Rebif) in participants with relapsing multiple sclerosis. Participants will be randomized to receive either ocrelizumab 600 mg or matching placebo intravenous (IV) as 300 mg infusions on Days 1 and 15 for the first dose and as a single infusion of 600 mg for all subsequent infusions every 24 weeks, with placebo injections matching interferon beta-1a SC three times per week; or interferon beta-1a 44 mcg SC injections three times per week (with placebo infusions matching ocrelizumab infusions every 24 weeks).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 835
- Diagnosis of multiple sclerosis, in accordance with the revised McDonald criteria (2010)
- At least 2 documented clinical attacks within the last 2 years prior to screening or one clinical attack in the years prior to screening (but not within 30 days prior to screening)
- Neurologic stability for greater than or equal to (>/=) 30 days prior to both screening and baseline
- Expanded Disability Status Scale (EDSS) score 0 to 5.5 inclusive
- Primary progressive multiple sclerosis
- Disease duration of more than 10 years in patients with EDSS score less than or equal to (</=) 2.0 at screening
- Contraindications for MRI
- Known presence of other neurological disorders which may mimic multiple sclerosis
- Pregnancy or lactation
- Requirement for chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study
- History of or currently active primary or secondary immunodeficiency
- History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
- Active infection, or history of or known presence of recurrent or chronic infection (for example, hepatitis B or C, Human Immunodeficiency Virus [HIV], syphilis, tuberculosis)
- History of progressive multifocal leukoencephalopathy
- Contraindications to or intolerance of oral or IV corticosteroids
- Contraindications to Rebif or incompatibility with Rebif use
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Interferon beta-1a 44 mcg SC Interferon beta-1a Interferon beta-1a 44 mcg SC injections three times per week (with placebo infusions matching ocrelizumab infusions every 24 weeks). Interferon beta-1a 44 mcg SC Ocrelizumab-matching placebo Interferon beta-1a 44 mcg SC injections three times per week (with placebo infusions matching ocrelizumab infusions every 24 weeks). Ocrelizumab Ocrelizumab Ocrelizumab 600 mg or matching placebo intravenous (IV) as 300 mg infusions on Days 1 and 15 for the first dose and as a single infusion of 600 mg for all subsequent infusions every 24 weeks, with placebo injections matching interferon beta-1a SC three times per week. Ocrelizumab Interferon beta-1a-matching placebo Ocrelizumab 600 mg or matching placebo intravenous (IV) as 300 mg infusions on Days 1 and 15 for the first dose and as a single infusion of 600 mg for all subsequent infusions every 24 weeks, with placebo injections matching interferon beta-1a SC three times per week.
- Primary Outcome Measures
Name Time Method Annualized Relapse Rate (ARR) in Participants With Relapsing Multiple Sclerosis (MS) at 96 Weeks In Double Blind Period Week 96 ARR was protocol-defined and calculated as the total number of relapses for all participants in the treatment group divided by the total participant-years of exposure to that treatment.
- Secondary Outcome Measures
Name Time Method Percentage of Participants Who Have No Evidence of Disease Activity (NEDA) up to Week 96 In Double Blind Period Week 96 NEDA was defined only for participants with a baseline EDSS score \>=2.0. The EDSS scale ranges from 0 (normal neurological exam) to 10 (death due to multiple sclerosis). Participants who completed the 96- week treatment period were considered as having evidence of disease activity if at least one protocol- defined relapse (PDR), a confirmed disability progression (CDP) event or at least one MRI scan showing MRI activity (defined as Gd-enhancing T1 lesions, or new or enlarging T2 lesions) was reported during the 96-week treatment period, otherwise the participant was considered as having NEDA.
Percent Change in Brain Volume as Detected by Brain Magnetic Resonance Imaging (MRI) From Week 24 to Week 96 In Double Blind Period From week 24 up to week 96 Brain volume was recorded as an absolute "normalized" value at the baseline visit then recorded at subsequent visits as a percentage change relative to the absolute value at the baseline visit. Therefore, brain volume at Week 24 was calculated as the brain volume at the baseline visit multiplied by 1 + (\[percentage change in brain volume from baseline visit to Week 24\]/100). Estimates are from analysis based on mixed-effect model of repeated measures (MMRM) using unstructured covariance matrix: Percentage Change = Brain Volume at Week 24 + Geographical Region (US vs. ROW) + Baseline EDSS (\< 4.0 vs. \>= 4.0) + Week + Treatment + Treatment\*Week (repeated values over Week) + Brain Volume at Week 24\*Week. The EDSS scale ranges from 0 (normal neurological exam) to 10 (death due to multiple sclerosis).
Time to Onset of Confirmed Disability Progression (CDP) for at Least 12 Weeks During the Double-Blind Treatment Period Week 104 Disability progression was defined as an increase in the Expanded Disability Status Scale (EDSS) score of: A) \>=1.0 point from the baseline EDSS score when the baseline score was less than or equal to (\<=) 5.5 B) \>=0.5 point from the baseline EDSS score when the baseline score was \>5.5 The EDSS scale ranges from 0 (normal neurological exam) to 10 (death due to multiple sclerosis). This outcome measure was considered confirmatory only when results of both studies WA21092 and WA21093 were combined. Disability progression was considered confirmed when the increase in the EDSS was confirmed at a regularly scheduled visit at least 12 weeks after the initial documentation of neurological worsening. Participants who had initial disability progression with no confirmatory EDSS assessment and who were on treatment at time of clinical cut-off date were censored at the date of their last EDSS assessment.
Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Score to Week 96 In Double Blind Period Baseline, Week 96 MSFC score consists of: A) Timed 25-Foot walk; B) 9-Hole Peg Test (9-HPT); and C) Paced Auditory Serial Addition Test (PASAT-3 version). The MSFCS is based on the concept that scores for these three dimensions (arm, leg, and cognitive function) are combined to create a single score (the MSFC) that can be used to detect change over time in a group of participants with MS. Since the three primary measures differ in what they actually measure, a common composite score for the three different measures i.e., Z- score was selected for the purpose. MSFC Score = {Z arm, average + Z leg, average + Z cognitive} / 3.0. The results from each of these three tests are transformed into Z-scores and averaged to yield a composite score for each participant at each time point. A score of +1 indicates that, on average, an individual scored 1 standard deviation (SD) better than the reference population and a score of -1 indicates that an individual scored 1 SD worse than the reference population.
Number of New, and/or Enlarging T2 Hyperintense Lesions as Detected by Brain Magnetic Resonance Imaging (MRI) During the Double Blind Treatment Baseline up to week 96 The total number of new and/or enlarging T2 lesions for all participants in the treatment group was calculated as the sum of the individual number of lesions at Weeks 24, 48, and 96.
Percentage of Participants With Confirmed Disability Improvement (CDI) for at Least 12 Weeks In Double Blind Period Week 96 Disability improvement was assessed only for the subgroup of participants with a baseline EDSS score of \>= 2.0. It was defined as a reduction in EDSS score of: A) \>=1.0 from the baseline EDSS score when the baseline score was \>=2 and \<=5.5 B) \>= 0.5 when the baseline EDSS score \> 5.5. The EDSS scale ranges from 0 (normal neurological exam) to 10 (death due to multiple sclerosis). This outcome measure was considered confirmatory only when results of both studies WA21092 and WA21093 were combined.
Number of T1 Hypointense Lesions During the Double-Blind Treatment Baseline up to week 96 The total number of new T1-Hypo-Intense Lesions (Chronic Black Holes) for all participants in the treatment group was calculated as the sum of the individual number of new lesions at Weeks 24, 48, and 96.
Change From Baseline in Short Form Health Survey-36 (SF-36) Physical Component Summary (PCS) Score at Week 96 In Double Blind Period Baseline, Week 96 The SF-36 is a multi-purpose, short-form health survey with 36 questions. It yields an 8-scale profile of functional health and well-being scores (domains) as well as psychometrically based physical and mental health summary measures. The SF-36 taps 8 health concepts: physical functioning, bodily pain, physical role functioning, emotional role functioning, emotional well-being, social functioning, vitality, and general health perceptions. The 8 scales are further summarized to 2 distinct higher-ordered clusters: the PCS and mental composite t-score (MCS). The range for all 8 domains as well as for the composite t- scores is from 0 to 100 with 100 as best possible health status and 0 as worst health status.
Number of Participants With Adverse Events (AEs) Baseline up to Week 96 AEs included infusion related reactions (IRRs) and serious MS relapses, but excluded non-serious MS relapses. Serious Adverse Events (SAEs) included serious MS relapses and serious IRRs.
Exposure to Ocrelizumab (Area Under the Concentration - Time Curve, AUC) In Double Blind Period Pre-infusion at Weeks 1, 24, 48, 72; and 30 minutes post-infusion at Week 72; at any time during Weeks 84 and 96 AUC represents total drug exposure for one dosing interval after the 4th dose.
Number of Participants With Anti-Drug Antibodies (ADAs) to Ocrelizumab In Double Blind Period Baseline up to Week 96 Number of participants positive for anti-drug antibodies (ADAs) to ocrelizumab is the number of post- baseline evaluable participants determined to have treatment-induced ADA or treatment-enhanced ADA during the study period.
Number of T1 Gadolinium (Gd)-Enhancing Lesions as Detected by Brain Magnetic Resonance Imaging (MRI) During the Double-Blind Treatment Baseline up to week 96 The total number of T1 gadolinium-enhancing lesions for all participants in the treatment group was calculated as the sum of the individual number of lesions at Weeks 24, 48, and 96.
Time to Onset of Confirmed Disability Progression (CDP) for at Least 24 Weeks During the Double-Blind Treatment Period Week 104 Disability progression was defined as an increase in the Expanded Disability Status Scale (EDSS) score of: A) \>=1.0 point from the baseline EDSS score when the baseline score was less than or equal to (\<=) 5.5 B) \>=0.5 point from the baseline EDSS score when the baseline score was \>5.5 The EDSS scale ranges from 0 (normal neurological exam) to 10 (death due to multiple sclerosis). This outcome measure was considered confirmatory only when results of both studies WA21092 and WA21093 were combined. Disability progression was considered confirmed when the increase in the EDSS was confirmed at a regularly scheduled visit at least 24 weeks after the initial documentation of neurological worsening. Participants who had initial disability progression with no confirmatory EDSS assessment and who were on treatment at time of clinical cut-off date were censored at the date of their last EDSS assessment.
Trial Locations
- Locations (165)
Infinity Clinical Research
🇺🇸Hollywood, Florida, United States
Stanford University Medical Center
🇺🇸Palo Alto, California, United States
Advanced Neurosciences Research LLC
🇺🇸Fort Collins, Colorado, United States
The Minneapolis Clinic of Neurology
🇺🇸Golden Valley, Minnesota, United States
South Shore Neurologic Associates P.C.
🇺🇸Patchogue, New York, United States
Associated Neurologists of Southern CT PC
🇺🇸Fairfield, Connecticut, United States
MS Comprehensive Care Center
🇺🇸Teaneck, New Jersey, United States
ALPI-Inst. de Rehabilitacion Marcelo Fitte
🇦🇷Buenos Aires, Argentina
Shore Neurology
🇺🇸Toms River, New Jersey, United States
Empire Neurology, PC
🇺🇸Latham, New York, United States
Hopital Neurologique Pierre Wertheimer
🇫🇷Bron, France
Atlanta Neuroscience Institute
🇺🇸Atlanta, Georgia, United States
Columbus Neuroscience
🇺🇸Columbus, Ohio, United States
Mun.Med.Proph.Inst.?Chernihiv Reg.Hosp.?; Neurology Department
🇺🇦Chernihiv, Ukraine
Road Clinical Hospital of Donetsk Station; Neurology Department
🇺🇦Donetsk, Ukraine
Swedish Neuroscience Institute
🇺🇸Seattle, Washington, United States
University of Miami; Dept. of Neurology MS Center
🇺🇸Miami, Florida, United States
Integra Clinical Research, Llc
🇺🇸San Antonio, Texas, United States
Neurology Center of San Antonio
🇺🇸San Antonio, Texas, United States
Hospital Angeles Culiacan; Neurociencias
🇲🇽Culiacán Rosales, Sinaloa, Mexico
University of Rochester Medical Center
🇺🇸Rochester, New York, United States
Advanced Neurosciences Institute
🇺🇸Nashville, Tennessee, United States
Hope Research Institute
🇺🇸Phoenix, Arizona, United States
University of Colorado
🇺🇸Denver, Colorado, United States
Wayne State University; Department of Neurology
🇺🇸Detroit, Michigan, United States
Fond. Ist. S. Raffaele - giglio
🇮🇹Cefalu, Sicilia, Italy
Hôpital Maison Blanche; Service de Neurologie
🇫🇷Reims, France
City General Hospital; Department of Neurology
🇬🇧Stoke on Trent, United Kingdom
University of Alberta; Northern Alberta Trials & Research Centre
🇨🇦Edmonton, Alberta, Canada
University of South Florida
🇺🇸Tampa, Florida, United States
University of Michigan Health System
🇺🇸Ann Arbor, Michigan, United States
Multiple Sclerosis Clinic
🇨🇦Calgary, Alberta, Canada
Collaborative Neuroscience Research, LLC
🇺🇸Long Beach, California, United States
Territory Neurology and Research Institute
🇺🇸Tucson, Arizona, United States
HonorHealth Neurology
🇺🇸Scottsdale, Arizona, United States
Lovelace Scientific Resources
🇺🇸Sarasota, Florida, United States
Josephson Wallack Munshower Neurology PC
🇺🇸Indianapolis, Indiana, United States
Dragonfly Research, LLC
🇺🇸Wellesley, Massachusetts, United States
University of Massachusetts Memorial Medical Center
🇺🇸Worcester, Massachusetts, United States
MidAmerica Neuroscience Institute
🇺🇸Prairie Village, Kansas, United States
Associates in Neurology PSC
🇺🇸Lexington, Kentucky, United States
Holy Name Hospital
🇺🇸Teaneck, New Jersey, United States
Rutgers New Jersey Medical School
🇺🇸Newark, New Jersey, United States
SUNY at Stony Brook
🇺🇸Stony Brook, New York, United States
Weill Cornell MC-NY Presbyter; Dept. of Neurology/Neuroscience, Judith Jaffe Multiple Sclerosis Ctr
🇺🇸New York, New York, United States
The Neurological Institute PA
🇺🇸Charlotte, North Carolina, United States
Neurology Associates PA
🇺🇸Hickory, North Carolina, United States
Raleigh Neurology Associates
🇺🇸Raleigh, North Carolina, United States
Abington Neurological Associates
🇺🇸Abington, Pennsylvania, United States
Absher Neurology PA
🇺🇸Greenville, South Carolina, United States
Sibyl Wray MD Neurology PC
🇺🇸Knoxville, Tennessee, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
Neurology Clinic PC
🇺🇸Cordova, Tennessee, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Bhupesh Dihenia M.D. P.A.
🇺🇸Lubbock, Texas, United States
Central Texas Neurology Consultants
🇺🇸Round Rock, Texas, United States
STAT Research S.A.
🇦🇷Ciudad de Buenos Airesa, Argentina
Grodno State Medical University
🇧🇾Grodno, Hrodzyenskaya Voblasts', Belarus
Vitebsk; Regional Diagnostic Center
🇧🇾Vitebsk, Vitsyebskaya Voblasts', Belarus
City Clinical Hospital #9
🇧🇾Minsk, Belarus
Vitebsk Regional Clinical Hospital
🇧🇾Vitebsk, Vitsyebskaya Voblasts', Belarus
UZ Antwerpen
🇧🇪Edegem, Belgium
Uni Hospital Center Tuzla
🇧🇦Tuzla, Bosnia and Herzegovina
Santa Casa de Misericordia; de Belo Horizonte
🇧🇷Belo Horizonte, MG, Brazil
Hospital Universitario Gaffree e Guinle
🇧🇷Rio de Janeiro, RJ, Brazil
Hospital das Clinicas - UNICAMP
🇧🇷Campinas, SP, Brazil
Fifth MHAT-Sofia AD; Neuro Dept with Vascular Unit
🇧🇬Sofia, Bulgaria
Clinique NeuroOutaouais
🇨🇦Gatineau, Quebec, Canada
UMHAT Alexandrovska, EAD; Neurology
🇧🇬Sofia, Bulgaria
Vancouver Hospital - UBC Hospital Site
🇨🇦Vancouver, British Columbia, Canada
Recherche Sepmus Inc.
🇨🇦Greenfield Park, Quebec, Canada
Montreal Neurological Institute and Hospital
🇨🇦Montreal, Quebec, Canada
The Ottawa Hospital - General Campus
🇨🇦Ottawa, Ontario, Canada
Hôpital Maisonneuve - Rosemont; Recherche Clinique de Neurologie
🇨🇦Montréal, Quebec, Canada
General Hospital Pula
🇭🇷Pula, Croatia
General Hospital Varazdin
🇭🇷Varazdin, Croatia
Uni Hospital Centre Dubrava
🇭🇷Zagreb, Croatia
Fakultni nemocnice Brno
🇨🇿Brno, Czechia
Neurospol s.r.o.
🇨🇿Havirov, Czechia
Pardubicka Krajska Nemocnice; Department of Neurology
🇨🇿Pardubice, Czechia
Groupe Hospitalier Pitie-Salpetriere
🇫🇷Paris, France
Krajska zdravotni, a. s. ? Nemocnice Teplice, o. z.; Neurologicke oddeleni
🇨🇿Teplice, Czechia
Hôpital Saint Philibert
🇫🇷Lommé, France
Hôpital General - Service de neurologie; Service de neurologie
🇫🇷Dijon Cedex, France
Sankt Gertrauden Krankenhaus; Neurologisches Facharztzentrum
🇩🇪Berlin, Germany
CHU toulouse - Hôpital Purpan; Departement de Neurologie
🇫🇷Toulouse, France
Neurologische Praxis Bonn
🇩🇪Bonn, Germany
Universitätsklinikum Düsseldorf; Klinik für Neurologie
🇩🇪Düsseldorf, Germany
Zentrum fuer ambulante Neurologie
🇩🇪Essen, Germany
Universitaetsklinikum Frankfurt; Klinik für Neurologie
🇩🇪Frankfurt, Germany
Universitaetsklinikum Heidelberg
🇩🇪Heidelberg, Germany
Ratsapotheke Mittweida
🇩🇪Mittweida, Germany
Klinikum Grosshadern der LMU
🇩🇪Muenchen, Germany
Klinikum rechts der Isar der TU Muenchen; Neurologische Klinik und Poliklinik im Neuro-Kopf-Zentrum
🇩🇪München, Germany
Azienda Ospedaliera Universitaria Policlinico Tor Vergata
🇮🇹Roma, Lazio, Italy
Neurologische Gemeinschaftspraxis Dr. Lang, Prof. Schreiber, Dr. Krauß, Dr. Kornhuber
🇩🇪Ulm, Germany
A.O. Universitaria S. Martino Di Genova
🇮🇹Genova, Liguria, Italy
St Vincents University Hospital
🇮🇪Dublin 4, Ireland
Fondazione IRCCS Istituto Neurologico Carlo Besta; Farmacia Interna
🇮🇹Milano, Lombardia, Italy
Azienda Ospedaliero Universitaria Ospedali Riuniti Umberto I-G.M. Lancisi-G. Salesi Di Ancona
🇮🇹Torrette - Ancona, Marche, Italy
Ospedale Civile di Montichiari; Centro Sclerosi Multipla
🇮🇹Montichiari, Lombardia, Italy
Ospedale Casa Sollievo Della Sofferenza IRCCS
🇮🇹San Giovanni Rotondo, Puglia, Italy
Clinical Research Institute
🇲🇽Tlalnepantla de Baz, Mexico CITY (federal District), Mexico
Mexico Centre for Clinical Research
🇲🇽Ciudad de México, Mexico CITY (federal District), Mexico
Ospedale degli Infermi
🇮🇹Ponderano, Piemonte, Italy
Ospedale Generale Regionale F. Miulli
🇮🇹Acquaviva delle Fonti, Puglia, Italy
Hospital Mexico Americano SC; Departamento de Electroencefalografía
🇲🇽Guadalajara, Jalisco, Mexico
Hospital CIMA Chihuahua; Centro de Investigación Clínicatorre de Consultoriospiso 4
🇲🇽Chihuahua, Mexico
MA-LEK Clinical Sp. Z o.o.
🇵🇱Katowice, Poland
Haukeland Universitetssykehus
🇳🇴Bergen, Norway
Vitamed
🇵🇱Bydgoszcz, Poland
Wojewodzki Specjalistyczny Szpital w Olsztynie; Oddzial Neurologiczny z Pododdzialem Udarowym
🇵🇱Olsztyn, Poland
Neuro-Care Gabriela Klodowska
🇵🇱Siemianowice ?l?skie, Poland
mMED Maciej Czarnecki
🇵🇱Warszawa, Poland
St. Petersburg State Medical University n.a. I.P. Pavlov; Hematology, transfusiology and transplanta
🇷🇺Sankt-peterburg, Sankt Petersburg, Russian Federation
City Clinical Hospital#2
🇷🇺Pyatigorsk, Stavropol, Russian Federation
State institution of health care - Territorial Clinical Hospital
🇷🇺Barnaul, Altaj, Russian Federation
State autonomous institution of healthcare Inter-regional clinical and diagnostic center
🇷🇺Kazan, Tatarstan, Russian Federation
Kirov City Clinical Hospital #1; Neurology Department
🇷🇺Kirov, Russian Federation
SBHI of Nizhny Novgorod region City Clinical Hospital #3; neurology department
🇷🇺Nizniy Novgorod, Russian Federation
MUDr. Beata Dupejova Neurologicka ambulancia s.r.o
🇸🇰Banska Bystrica, Slovakia
Fakultna Nemocnica Roosevelta
🇸🇰Banska Bystrica, Slovakia
Saratov State Medical University of RosZdrav; Neurology
🇷🇺Saratov, Russian Federation
Institut Catala d?Oncologia Hospital Germans Trias i Pujol
🇪🇸Badalona, Barcelona, Spain
Vseobecna nemocnica s poliklinikou Levoca a.s.
🇸🇰Levoca, Slovakia
Perm SMA n.a. academ. E.A. Vagner
🇷🇺Perm, Russian Federation
Hospital Universitari de Bellvitge; Servicio de Neurologia
🇪🇸L'Hospitalet de Llobregat, Barcelona, Spain
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital General Univ. de Alicante
🇪🇸Alicante, Spain
Hospital del Mar
🇪🇸Barcelona, Spain
Hospital Universitari de Girona Dr Josep Trueta
🇪🇸Girona, Spain
Hospital General Universitario Gregorio Marañon; Servicio de Neurologia
🇪🇸Madrid, Spain
Hospital Regional Universitario de Malaga
🇪🇸Malaga, Spain
Hospital Universitario Clinico San Carlos
🇪🇸Madrid, Spain
Karolinska Universitetssjukhuset Huddinge
🇸🇪Stockholm, Sweden
Hacettepe University Medical Faculty; Neurology
🇹🇷Ankara, Turkey
Hospital Clinico Universitario de Valencia; Servicio de Neurologia
🇪🇸Valencia, Spain
Sahlgrenska Sjukhuset; Neurology
🇸🇪Göteborg, Sweden
Karolinska Universitetssjukhuset Solna Neurology
🇸🇪Stockholm, Sweden
Norrlands Universitetssjukhus
🇸🇪Umeå, Sweden
Haseki Training and Research Hospital
🇹🇷Istanbul, Turkey
Istanbul Universitesi - Cerrahpasa Cerrahpasa Tip Fakultesi; Noroloji Anabilim Dali
🇹🇷Istanbul, Turkey
Ege University Medical Faculty
🇹🇷Izmir, Turkey
Istanbul Bilim Universty Medical Fac.
🇹🇷Istanbul, Turkey
City Clinical Hospital #4
🇺🇦Dnipropetrovsk, Ukraine
Karadeniz Tecnical Uni. Med. Fac.; Neurology
🇹🇷Trabzon, Turkey
Kocaeli University Medical Faculty
🇹🇷Kocaeli, Turkey
Ondokuz Mayis Univ. Med. Fac.; Neurology
🇹🇷Samsun, Turkey
Morriston Hospital
🇬🇧Swansea, United Kingdom
Regional Clinical Hospital; Neurology Department
🇺🇦Ivano-Frankivsk, Ukraine
Royal Devon and Exeter Hospital (Wonford)
🇬🇧Exeter, United Kingdom
Kings College Hospital; Neurosciences Clinical Trials Office
🇬🇧London, United Kingdom
Neurological Services of Orlando
🇺🇸Orlando, Florida, United States
MHATNP Sv.Naum EAD; Clinic for intensive treatment of neurology diseases
🇧🇬Sofia, Bulgaria
Centrum Neurologii Krzysztof Selmaj
🇵🇱Lodz, Poland
Policlinico Universitario Agostino Gemelli
🇮🇹Roma, Lazio, Italy
Instituto Biomedico De Investigacion A.C.
🇲🇽Aguascalientes, Mexico
Krakowska Akademia Neurologii Sp z o.o. Centrum Neurologii K
🇵🇱Krakow, Poland
Samodz.Publi.Szpital Kliniczny; nr 4 w Lublinie
🇵🇱Lublin, Poland
University Clinic Ctr Sarajevo
🇧🇦Sarajevo, Bosnia and Herzegovina
MHAT National Cardiology Hospital, EAD; Neurology
🇧🇬Sofia, Bulgaria
SPZOZ Uniwersytecki Szp. Klin. nr1 im.N.Barlickiego UM;Oddzial Kliniczny Neurologii
🇵🇱Lodz, Poland
Clinical Hospital Centre Zagreb;Clinic for Neurology
🇭🇷Zagreb, Croatia
State Institution V.K. Gusak Institute of Urgent and Recover; Dep of Reconstructive Angioneurology a
🇺🇦Donetsk, Ukraine
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States