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
- NCT01247324
- 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). Planned duration of double-blind treatment is 96 weeks. Participants who complete the 96-week double-blind treatment will have an option to enter a single-group, active-treatment, open-label extension period, providing they fulfill the eligibility criteria.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 821
- 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 participants with EDSS 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 (e.g., 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 Ocrelizumab-matching placebo Interferon beta-1a 44 mcg SC injections three times per week (with placebo infusions matching ocrelizumab infusions every 24 weeks). Ocrelizumab Interferon beta-1a-matching placebo Ocrelizumab 600 mg 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 Ocrelizumab Ocrelizumab 600 mg 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. 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).
- Primary Outcome Measures
Name Time Method Annualized Relapse Rate (ARR) in Participants With Relapsing Multiple Sclerosis (MS) at 96 Weeks 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 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.
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.
Time to Onset of Confirmed Disability Progression (CDP) for at Least 12 Weeks During the Double-Blind Treatment Period Week 108 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. EDSS assessment and who were on treatment at time of clinical cut-off date were censored at the date of their last EDSS assessment.
Percentage of Participants With Confirmed Disability Improvement (CDI) for at Least 12 Weeks 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 Multiple Sclerosis Functional Composite (MSFC) Score to Week 96 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.
Percent Change in Brain Volume as Detected by Brain Magnetic Resonance Imaging (MRI) From Week 24 to Week 96 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.
Time to Onset of Confirmed Disability Progression (CDP) for at Least 24 Weeks During the Double-Blind Treatment Period Week 108 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.
Change From Baseline in Short Form Health Survey-36 (SF-36) Physical Component Summary (PCS) Score at Week 96 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 588 weeks 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) 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.
Percentage of Participants Who Have No Evidence of Disease Activity (NEDA) up to Week 96 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.
Number of Participants With Anti-Drug Antibodies (ADAs) to Ocrelizumab 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.
Trial Locations
- Locations (141)
Northwestern University; Dept. of Neurology
🇺🇸Chicago, Illinois, United States
The Minneapolis Clinic of Neurology
🇺🇸Golden Valley, Minnesota, United States
Uni of Vermont Medical Center;
🇺🇸Burlington, Vermont, United States
AZ Delta (Campus Rumbeke)
🇧🇪Roeselare, Belgium
Tartu University Hospital
🇪🇪Tartu, Estonia
Instituto centenario
🇦🇷Buenos Aires, Argentina
Fundacion Rosarina de Neurorehabilitacion
🇦🇷Rosario, Argentina
MHATNP Sv.Naum EAD; Clinic in neurology diseases for movement disorders
🇧🇬Sofia, Bulgaria
Szent Borbala Korhaz; Neurology
🇭🇺Tatabánya, Hungary
Hospital Español
🇦🇷Ciudad Autonoma Bs As, Argentina
Providence Neurological Specialties
🇺🇸Portland, Oregon, United States
ACIBADEM CITY CLINIC TOKUDA HOSPITAL EAD; Clinic of Neurology and Sleep Medicine
🇧🇬Sofia, Bulgaria
FinnMedi Oy
🇫🇮Tampere, Finland
Fovarosi Onkormanyzat Jahn Ferenc Del-Pesti
🇭🇺Budapest, Hungary
21st Century Neurology
🇺🇸Phoenix, Arizona, United States
Oklahoma Medical Research Foundation
🇺🇸Oklahoma City, Oklahoma, United States
St. Antonius Ziekenhuis Nieuwegein
🇳🇱Nieuwegein, Netherlands
Hospital Nacional Dos de Mayo
🇵🇪Lima, Peru
Clinica Centenario Peruano Japonesa; Neurology
🇵🇪Pueblo Libre, Peru
Kemerovo Regional Clinical Hospital
🇷🇺Kemerovo, Russian Federation
Clinical Center Kragujevac
🇷🇸Kragujevac, Serbia
FNsP Bratislava - Nemocnica Stare mesto
🇸🇰Bratislava, Slovakia
FNsP Bratislava, Nemocnica Ruzinov
🇸🇰Bratislava, Slovakia
Fakultna nemocnica s poliklinikou Zilina
🇸🇰Zilina, Slovakia
Kyiv City Cl.Hosp.#4 Depart.of Neurology #2NMU; Department of Neurology
🇺🇦Kyiv, Ukraine
Royal London Hospital; Neurology
🇬🇧London, United Kingdom
Reg. SI of Health Care Smolensk Regional Clinical Hospital
🇷🇺Smolensk, Russian Federation
Clinical Center Nis
🇷🇸NIS, Serbia
Univerzitna nemocnica Bratislava Nemocnica sv. Cyrila a Metoda; Nemocnicna lekaren
🇸🇰Bratislava, Slovakia
Military Medical Academy
🇷🇸Belgrade, Serbia
Dr CC Coetzee Inc
🇿🇦Durban, South Africa
Specjal. Praktyka Lekarska; Prof. Grzegorz Opala
🇵🇱Katowice, Poland
MA-LEK Clinical Sp. Z o.o.
🇵🇱Katowice, Poland
Neurologiczny NZOZ Centrum Leczenia SM; Osrodek Badan Klinicznych
🇵🇱Plewiska, Poland
Central Clinical Hospital #2 N.A. Semashko OAO RJHD
🇷🇺Moskva, Moskovskaja Oblast, Russian Federation
FGBU FNKC FMBA of Russia
🇷🇺Moskva, Moskovskaja Oblast, Russian Federation
St.-Peterburg State institution of health care City multifield hospital #2
🇷🇺Sankt-peterburg, Sankt Petersburg, Russian Federation
MMA of Ministry of Defense of Russia named after S.M. Kirov
🇷🇺St.Petersburg, Sankt Petersburg, Russian Federation
Regional Multiple Sclerosis Centre b/o CC ECM "Neftyanik"
🇷🇺Tyumen, Russian Federation
Hospital de Basurto
🇪🇸Bilbao, Vizcaya, Spain
P. Stradins Clinical University Hospital; Neurology
🇱🇻Riga, Latvia
Clinica Anglo Americana
🇵🇪Lima, Peru
COPERNICUS Podmiot Leczniczy Sp. z o. o. Szpital im. M. Kopernika; Oddzia? Neurologiczny
🇵🇱Gdansk, Poland
Azienda Ospedaliera Sant'Andrea
🇮🇹Roma, Lazio, Italy
Kaunas Medical University Hospital
🇱🇹Kaunas, Lithuania
Hospital de Braga; Servico de Neurologia
🇵🇹Braga, Portugal
Hopital Razi
🇹🇳Mannouba, Tunisia
FSBIH Siberian Regional Medical Centre of FMBA of Russia
🇷🇺Novosibirsk, Russian Federation
MRC for Oncology and Neurology Biotherapy
🇷🇺Novosibirsk, Russian Federation
Samara State Medical University
🇷🇺Samara, Russian Federation
Universitätsspital Basel Medizin Neurologie; Neurologische Poliklinik
🇨🇭Basel, Switzerland
Hopital Universitaire Fattouma Bourguiba
🇹🇳Monastir, Tunisia
Hopital Charles Nicolle
🇹🇳Tunis, Tunisia
AZ Sint Jan
🇧🇪Brugge, Belgium
Ospedale Regionale Lugano Civico Medizin Neurologie; Neurologia
🇨🇭Lugano, Switzerland
MMPIDon.Reg.Cl.&Ter.Med.Com.Neur.Dept.DNMU n.a.M.Gorkiy; Ch. of Nervous Diseases and Med. Genetics
🇺🇦Donetsk, Ukraine
Lviv Regional Clinical Hospital; Department of Neurology
🇺🇦Lviv, Ukraine
Vin.Reg.Psych.Hosp.N.A Yuschenko O.I., Vnmu N.A. Pyrogov; Department of Nervous Diseases
🇺🇦Vinnytsya, Ukraine
Vilnius University Hospital Santariskiu Clinic
🇱🇹Vilnius, Lithuania
Grupo Médico Camino S.C.
🇲🇽Ciudad de México, Mexico CITY (federal District), Mexico
Policlinico Especializado en Neurologia
🇵🇪Callao, Peru
Chaim Sheba Medical Center; Neurology Department
🇮🇱Ramat-Gan, Israel
Maritime Medicine Centre of Latvia Hospital of Vecmilgravis Department of Neurology
🇱🇻Riga, Latvia
Klaipeda University Hospital Public Institution
🇱🇹Klaipeda, Lithuania
Hospital Universitario Dr Jose Eleuterio Gonzalez; Universidad Autónoma de Nuevo León
🇲🇽Monterrey, Nuevo LEON, Mexico
Irccs Ospedale San Raffaele
🇮🇹Milano, Lombardia, Italy
Azienda Ospedaliera di Padova; Clinica Neurologica
🇮🇹Padova, Veneto, Italy
Sverdlovsk Regional Clinical Hospital 1
🇷🇺Yekaterinburg, Sverdlovsk, Russian Federation
St.In.Inst. of Neurol.Psych.and Narcol.of the AMSU; Dept. of Neuroinfection and Multiply Sclerosis
🇺🇦Kharkov, Ukraine
Azienda Socio Sanitaria Territoriale della Valle Olona (pres
🇮🇹Gallarate, Valle D?Aosta, Italy
Walton Centre NHS Foundation Trust, Neuroscience Research Centre; CLINICAL TRIALS UNIT
🇬🇧Liverpool, United Kingdom
Complejo Hospitalario Nuestra Señora de la Candelaria; Servicio de Neurologia
🇪🇸Santa Cruz De Tenerife, Tenerife, Spain
Hospital Universitario Virgen Macarena
🇪🇸Sevilla, Spain
Hospital Universitario Puerta De Hierro Majadahonda; Servicio de Neurología
🇪🇸Madrid, Spain
Clinica Neurologica; Neurocirurgica de Joinville
🇧🇷Joinville, SC, Brazil
Diakoniekrankenhaus Henriettenstiftung gGMBH; Klinik für Neurologie und klinische Neurophysiologie
🇩🇪Hannover, Germany
Mercy Medical Group
🇺🇸Carmichael, California, United States
Scripps Clinic
🇺🇸La Jolla, California, United States
MS Center of California
🇺🇸Laguna Hills, California, United States
Mercy Research Institute
🇺🇸Miami, Florida, United States
Health First Physicians Inc.
🇺🇸Melbourne, Florida, United States
Southern California Permanente Medical Group
🇺🇸Los Angeles, California, United States
Neuro-Therapeutics Inc.
🇺🇸Pasadena, California, United States
University of California at San Francisco
🇺🇸San Francisco, California, United States
Axiom Clinical Research of Florida
🇺🇸Tampa, Florida, United States
Shepherd Center Inc.
🇺🇸Atlanta, Georgia, United States
University of South Florida
🇺🇸Tampa, Florida, United States
Studienzentrum Nordwest Dr med Joachim Springub Herr Wolfgang Schwarz
🇩🇪Westerstede, Germany
NeuroTrials Research, Inc.
🇺🇸Atlanta, Georgia, United States
Emory University; Department of Neurology
🇺🇸Atlanta, Georgia, United States
American Health Network Institute, LLC
🇺🇸Avon, Indiana, United States
Consultants in Neurology Ltd
🇺🇸Northbrook, Illinois, United States
Michigan Neurology Associates P.C.
🇺🇸Clinton Township, Michigan, United States
Michigan Institute for Neurological Disorders
🇺🇸Farmington Hills, Michigan, United States
The MS Center for Innovations In Care
🇺🇸Saint Louis, Missouri, United States
University of New Mexico
🇺🇸Albuquerque, New Mexico, United States
Neurology Associates PA
🇺🇸Hickory, North Carolina, United States
OnSite Clinical Solutions LLC
🇺🇸Charlotte, North Carolina, United States
Atrium Health Neurosciences Institute ? Charlotte
🇺🇸Charlotte, North Carolina, United States
University Neurology Inc.
🇺🇸Cincinnati, Ohio, United States
The Ohio State University Wexner Medical Center
🇺🇸Columbus, Ohio, United States
Albert Einstein Medical Center; Depatment of Neurosensory sciences
🇺🇸Philadelphia, Pennsylvania, United States
Bhupesh Dihenia M.D. P.A.
🇺🇸Lubbock, Texas, United States
Uni of Texas Health Science Center At Houston
🇺🇸Houston, Texas, United States
Multicare Research Institute; Multicare Neuroscience Center of Washington
🇺🇸Tacoma, Washington, United States
Barmherzige Brueder Konventspital
🇦🇹Linz, Austria
Royal North Shore Hospital; Department of Neurology
🇦🇺St Leonards, New South Wales, Australia
Cliniques Universitaires Saint-Luc; Neurology
🇧🇪Bruxelles, Belgium
Hospital das Clinicas - UFG;Reumatologia
🇧🇷Goiania, GO, Brazil
IMV Pesquisa Neurológica
🇧🇷Porto Alegre, RS, Brazil
Neurozentrum Prien Elisabeth Hans-Thümmler Stefan Braune
🇩🇪Prien, Germany
MHAT Avis Medica; Neurology Department
🇧🇬Pleven, Bulgaria
First MHAT; Clinic of Neurology
🇧🇬Sofia, Bulgaria
Military Medical Academy; Neurology
🇧🇬Sofia, Bulgaria
Hospital Carlos Van Buren
🇨🇱Valparaiso, Chile
Fakultni nemocnice u sv. Anny; Neurologicka klinika
🇨🇿Brno, Czechia
Fakultni nemocnice Hradec Kralove
🇨🇿Hradec Kralove, Czechia
Nemocnice Jihlava; NEU-Neurologicke oddeleni
🇨🇿Jihlava, Czechia
Krajska Nemocnice Pardubice Neurologicka Klinika
🇨🇿Pardubice, Czechia
VFN Praha Poliklinika Rs Centrum - Budova A
🇨🇿Prague, Czechia
Krajska zdravotni, a. s. ? Nemocnice Teplice, o. z.; Neurologicke oddeleni
🇨🇿Teplice, Czechia
West Tallinn Central Hospital
🇪🇪Tallinn, Estonia
Praxis Dr. med. Mathias Niedhammer, Facharzt für Neurologie
🇩🇪Oldenburg, Germany
Groupe Hospitalier Pellegrin
🇫🇷Bordeaux, France
CHU Hopital Gabriel Montpied; Service de Neurologie
🇫🇷Clermont Ferrand, France
Hopital Central; Neurologie
🇫🇷Nancy, France
CHU de Nîmes Hopital Caremeau; Service de Neurologie
🇫🇷Nimes, France
Hopital Hautepierre - CHU Strasbourg; Service de Neurologie
🇫🇷Strasbourg, France
Charité Universitaetsmedizin Berlin, Campus Charité Mitte
🇩🇪Berlin, Germany
Universitätsklinikum Rostock, Zentrum für Nervenheilkunde; Klinik und Poliklinik für Neurologie
🇩🇪Rostock, Germany
Asklepiosklinik Barmbek; Abteilung Neurologie
🇩🇪Hamburg, Germany
Massachusetts General Hospital.
🇺🇸Boston, Massachusetts, United States
Universitaetsklinikum Mainz - PS; Klinik und Poliklinik fuer Neurologie
🇩🇪Mainz, Germany
Miami Research Associates
🇺🇸South Miami, Florida, United States
Universitätsklinikum "Carl Gustav Carus"; MS Center Dresden
🇩🇪Dresden, Germany
Washington University; Wash Uni. Sch. Of Med
🇺🇸Saint Louis, Missouri, United States
The MS Center; Advance Neurology and Pain
🇺🇸Advance, North Carolina, United States
Magee-Woman's Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Universitätsklinikum Tübingen, Zentrum für Neurologie
🇩🇪Tübingen, Germany
Semmelweis Egyetem AOK; Neurologiai Klinika
🇭🇺Budapest, Hungary
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States