MedPath

A Study of Ocrelizumab in Participants With Relapsing Remitting Multiple Sclerosis (RRMS) Who Have Had a Suboptimal Response to an Adequate Course of Disease-Modifying Treatment (DMT)

Phase 3
Completed
Conditions
Multiple Sclerosis, Relapsing-Remitting
Interventions
Biological: Ocrelizumab
Registration Number
NCT02861014
Lead Sponsor
Hoffmann-La Roche
Brief Summary

The purpose of this prospective, multicenter, open-label, efficacy, and safety study is to assess the efficacy and safety of ocrelizumab in participants with Relapsing Remitting Multiple Sclerosis (RRMS) who have had a suboptimal response to an adequate course of a Disease-Modifying Treatment (DMT). The study will consist of a Screening period (up to 4 weeks), an Open-label treatment period (96 weeks; with last dose administered at Week 72), and a Follow-up period of at least 2 years.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
681
Inclusion Criteria
  • Have a definite diagnosis of RRMS, confirmed as per the revised McDonald 2010 criteria
  • Have a length of disease duration, from first symptom, of less than (<) 10 years
  • Have received no more than two prior DMTs, and the discontinuation of the most recent DMT was due to lack of efficacy
  • Suboptimal disease control while on a DMT
  • Expanded Disability Status Scale (EDSS) of 0.0 to 4.0, inclusive, at Screening
  • For women of childbearing potential: agreement to use an acceptable birth control method during the treatment period and for at least 6 months after the last dose of study drug
Read More
Exclusion Criteria
  • Secondary progressive multiple sclerosis (SPMS) or history of primary progressive or progressive relapsing multiple sclerosis (MS)
  • Inability to complete an Magnetic Resonance Imaging (MRI) procedure
  • Known presence of other neurological disorders
  • Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study
  • History or currently active primary or secondary immunodeficiency
  • History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
  • History of opportunistic infections
  • History or known presence of recurrent or chronic infection
  • History of malignancy
  • Congestive heart failure
  • Known active bacterial, viral, fungal, mycobacterial infection or other infection, excluding fungal infection of nail beds
Read More

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
OcrelizumabOcrelizumabOcrelizumab will be administered as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.
Primary Outcome Measures
NameTimeMethod
Percentage of Participants With No Evidence of Disease Activity (NEDA) as Per Protocol Defined Events During a 96-Week PeriodWeek 96

A protocol-defined event of disease activity was defined by the occurrence of at least one of the following while on treatment with ocrelizumab:

* A protocol-defined relapse (PDR)

* 24-week CDP based on increase in EDSS while on treatment with ocrelizumab

* A T1 Gd-enhanced lesion after Week 8

* A new and/or enlarging T2 hyperintense lesion on MRI after Week 8 compared to the Week 8 MRI scan

Secondary Outcome Measures
NameTimeMethod
Percentage Change From Baseline at Week 48 and 96 in T1 Hypointense Lesion VolumeWeeks 48, 96
Absolute Change From Baseline in EDSS Category at Week 96Up to Week 96

The EDSS is an ordinal clinical rating scale ranging from 0 (normal neurologic examination) to 10 (death due to MS) in half-point increments.

Change From Baseline to Week 96 in Total T2 Lesion Volume Detected by Brain MRI FromBaseline, Week 96
Adjusted Mean Percentage Change From Baseline in Brain VolumeWeeks 24, 48, 96
Mean Number of T1 Gd-enhancing Lesions Per MRI Scan at Weeks 24, 48 and 96Weeks: 24, 48, 96

Mean number of T1 Gd-enhancing lesions per MRI scan: Total number of T1 Gd-enhanced lesions divided by the total number of interpretable MRI scans

Percentage of Participants With a Baseline EDSS Score ≥2 With CDI at Week 96Week 96

The EDSS is an ordinal clinical rating scale ranging from 0 (normal neurologic examination) to 10 (death due to MS) in half-point increments.

Time to Onset of First New and/or Enlarging T2 LesionBaseline up to 96 Weeks
Change From Baseline at Week 48 and 96 in T1 Hypointense Lesion VolumeWeeks 48, 96
Adjusted Mean Percentage Change From Baseline in Cortical Grey Matter VolumeWeeks 48, 96
Adjusted Mean Percentage Change From Baseline in White Matter VolumeWeeks 48, 96
Percentage Change From Baseline in Cognitive Performance (Processing Speed/Working Memory) at Week 48 and Week 96 as Measured by the Brief International Cognitive Assessment for MS - Symbol Digit Modalities Test (SDMT) ScoreBaseline, Weeks 48, 96

Brief International Cognitive Assessment for MS (BICAMS) is assessing cognitive processing speed and verbal and visual memory. Symbol Digits Modalities Test (SDMT) is assessing processing speed/working memory. The SDMT presents a series of nine symbols, each paired with a single digit in a key at the top of a standard sheet of paper. Participants are asked to voice the digit associated with each symbol as rapidly as possible for 90 sec. There is a single outcome measure - the number correct over the 90 sec time span.

Percentage Change From Baseline in Cognitive Performance (Visuospatial Memory) at Week 48 and Week 96 as Measured by the Brief International Cognitive Assessment for MS - Brief Visuospatial Memory Test-Revised (BVMT-R) ScoreBaseline, Weeks: 48, 96

Brief International Cognitive Assessment for MS (BICAMS) is assessing cognitive processing speed and verbal and visual memory. Brief Visuospatial Memory Test-Revised (BVMT-R) is assessing visuospatial memory. In this test, six abstract designs are presented for 10 sec. The display is removed from view and patients render the stimuli via pencil on paper manual responses. Each design receives from 0 to 2 points representing accuracy and location. There are three learning trials, and the outcome measure is the total number of points earned over the three learning trials, thus the scale range is 0-36. The higher the result, the better visual/spatial memory.

Change From Baseline to Week 96 in Expanded Disability Status Scale (EDSS)Baseline, Weeks: 24, 48, 72, 96

The EDSS is an ordinal clinical rating scale ranging from 0 (normal neurologic examination) to 10 (death due to MS) in half-point increments.

Time to Onset of First Protocol-Defined RelapseBaseline up to 96 Weeks

A protocol-defined multiple sclerosis (MS) relapse is an occurrence of new or worsening neurological symptoms attributable to MS that meets the following criteria:

* Symptoms must persist for \>24 hours and should not be attributable to confounding clinical factors (e.g., fever, infection, injury, adverse reactions to medications)

* Symptoms should be preceded by neurological stability for at least 30 days

* Symptoms should be accompanied by new objective neurological worsening determined with a timely EDSS/ Functional Systems Score (FSS) assessment, consistent with an increase of at least:

* ≥ 0.5 points on EDSS scale

* or ≥ 2 points on one of the following FSS scales: pyramidal, ambulation, cerebellar, brainstem, sensory, or visual

* or ≥ 1 point on two or more of the following FSS scales: pyramidal, ambulation, cerebellar, brainstem, sensory, or visual

Volume of New and/or Enlarging T2 Hyperintense Lesions Volume of Lesions Per MRI Scan at Weeks 24, 48, 96Weeks 24, 48, 96

The number of new and/or enlarging T2 lesions at week 24, 48 and 96 is calculated as the sum of the individual number of new and/or enlarging lesions at each visit. Data from other unscheduled assessments is included in this summary or analysis.

Adjusted Mean Change From Baseline at Week 48 and 96 in T1 Hypointense Lesion VolumeWeeks 48, 96
Mean Change From Baseline in Cognitive Performance (Processing Speed/Working Memory) at Week 48 and Week 96 as Measured by the Brief International Cognitive Assessment for MS - Symbol Digit Modalities Test (SDMT) ScoreBaseline, Weeks: 48, 96

Brief International Cognitive Assessment for MS (BICAMS) is assessing cognitive processing speed and verbal and visual memory. Symbol Digits Modalities Test (SDMT) is assessing processing speed/working memory. The SDMT presents a series of nine symbols, each paired with a single digit in a key at the top of a standard sheet of paper. Participants are asked to voice the digit associated with each symbol as rapidly as possible for 90 sec. There is a single outcome measure - the number correct over the 90 sec time span. The higher the results, the better processing speed/working memory.

Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)Baseline up to to 96 weeks after the end of the Treatment Period
Percentage of Participants Free From a Protocol-Defined Event of Disease Activity During 24 Weeks PeriodBaseline up to 24 weeks

A protocol-defined event of disease activity was defined by the occurrence of at least one of the following while on treatment with ocrelizumab:

* A protocol-defined relapse (PDR)

* 24-week CDP based on increase in EDSS while on treatment with ocrelizumab

* A T1 Gd-enhanced lesion after Week 8

* A new and/or enlarging T2 hyperintense lesion on MRI after Week 8 compared to the Week 8 MRI scan

Percentage of Participants Free From a Protocol-Defined Event of Disease Activity During 48 Weeks PeriodBaseline up to 48 weeks

A protocol-defined event of disease activity was defined by the occurrence of at least one of the following while on treatment with ocrelizumab:

* A protocol-defined relapse (PDR)

* 24-week CDP based on increase in EDSS while on treatment with ocrelizumab

* A T1 Gd-enhanced lesion after Week 8

* A new and/or enlarging T2 hyperintense lesion on MRI after Week 8 compared to the Week 8 MRI scan

Time to First Protocol-Defined Event of Disease ActivityBaseline up to 96 Weeks

The definition of a protocol-defined event of disease activity is the occurrence of at least one of the following while on treatment with ocrelizumab:

* A protocol-defined relapse defined as: Symptoms must persist for \>24 hours and should not be attributable to confounding clinical factors; Symptoms should be preceded by neurological stability for at least 30 days; Symptoms should be accompanied by new objective neurological worsening determined with a timely EDSS/ Functional Systems Score (FSS) assessment

* 24 weeks confirmed disability progression based on increases in EDSS while on treatment with ocrelizumab

* A T1 Gd-enhanced lesion after Week 8

* A new and/or enlarging T2 hyperintense lesion on MRI after Week 8 compared to the Week 8 MRI scan.

Annualized Protocol-defined Relapse Rate at Week 96Week 96
Time to Onset of 24-week Confirmed Disability ProgressionBaseline up to 96 Weeks
Percentage Change From Baseline to Week 96 in Total T2 Lesion Volume Detected by Brain MRIBaseline, Week 96
Mean Number of New and/or Enlarging T2 Hyperintense Lesions Per MRI ScanWeeks 24, 48, 96

Mean number of new and/or enlarging T2 hyperintense lesions per MRI scan: Total number of new and/or enlarging T2 hyperintense lesions divided by the total number of interpretable MRI scans

Change From Baseline in Cognitive Performance (Visuospatial Memory) at Week 48 and Week 96 as Measured by the Brief International Cognitive Assessment for MS - Brief Visuospatial Memory Test-Revised (BVMT-R) ScoreBaseline, Weeks 48, 96

Brief International Cognitive Assessment for MS (BICAMS) is assessing cognitive processing speed and verbal and visual memory. Brief Visuospatial Memory Test-Revised (BVMT-R) is assessing visuospatial memory. In this test, six abstract designs are presented for 10 sec. The display is removed from view and patients render the stimuli via pencil on paper manual responses. Each design receives from 0 to 2 points representing accuracy and location. There are three learning trials, and the outcome measure is the total number of points earned over the three learning trials, thus the scale range is 0-36. The higher the result, the better visual/spatial memory.

Trial Locations

Locations (163)

Hôpital Maison Blanche; Service de Neurologie

🇫🇷

Reims, France

Hôpitaux Universitaires de strasbourg - hôpital civil

🇫🇷

Strasbourg, France

Gesundheitszentrum St. Johannes Hospital; Neurolog. Gemeinschaftspraxis Dres. Schmidt, Neudecker etc

🇩🇪

Bonn, Germany

Klinikum Grosshadern der LMU; Neuroimmunologie II

🇩🇪

München, Germany

Gemeinschaftspraxis Dr.med. Reinhard Ehret/Dr. med Wolfram von Pannwitz

🇩🇪

Berlin, Germany

Hopital Gabriel Montpied CHU de Clermont-Ferrand; Service de Neurologie B

🇫🇷

Clermont-Ferrand, France

CHU de Besancon Hopital Jean Minjoz; Service de Neurologie

🇫🇷

Besançon, France

Hôpital Guillaume et René Laënnec; Service Neurologie

🇫🇷

Nantes, France

East Tallinn Central Hospital; Neurology Department

🇪🇪

Tallinn, Estonia

CHRU - Hôpital Bretonneau; Neurologie

🇫🇷

Tours, France

Neurologische Gemeinschaftspraxis Kassel und Vellmar, Ch. Lassek, Dres. Ammerbach, Fetzer, M. Fische

🇩🇪

Kassel, Germany

Universitätsklinikum Magdeburg,Otto-von-Guericke-Universität A.ö.R., Klinik für Neurologie

🇩🇪

Magdeburg, Germany

Universitätsklinikum Münster; Klinik und Poliklinik für Neurologie

🇩🇪

Münster, Germany

Ruppiner Kliniken, Hochschulklinikum der Medizinischen Hochschule Brandenburg, Klinik für Neurologie

🇩🇪

Neuruppin, Germany

Cork University Hospital; Clinical Research Facility

🇮🇪

Cork, Ireland

Jüdisches Krankenhaus Berlin; Abteilung fur Neurologie

🇩🇪

Berlin, Germany

Tartu University Hospital

🇪🇪

Tartu, Estonia

Klinikum Augsburg, Neurologische Klinik und klinische Neurophysiologie

🇩🇪

Augsburg, Germany

Universitätsklinikum "Carl Gustav Carus", Zentrum für Klinische Neurowissenschaften

🇩🇪

Dresden, Germany

St. Josefs-Krankenhaus, Klinik für Neurologie

🇩🇪

Potsdam, Germany

NeuroConcept AG C/O mind mvz GmbH

🇩🇪

Stuttgart, Germany

A. O. U. Federico II; Dip Neuroscienze, Scienze Riproduttive ed Odontostomatologiche

🇮🇹

Napoli, Campania, Italy

NeuroCentrum Odenwald; Dres. Reifschneider, Unsorg, Ries, Schumann, Hoffmann, Knoblich

🇩🇪

Erbach/Odenwald, Germany

Neurologische Praxisgemeinschaft Hamburger-Straße; Dres. Müller-Habich/Emrich/Vogt

🇩🇪

Hamburg, Germany

Henriettenstiftung Hannover; Klinik fuer Neurologie und Klinische Neurophysiologie

🇩🇪

Hannover, Germany

Neurologische Klinik, Universitätsklinikum Heidelberg

🇩🇪

Heidelberg, Germany

Neurozentrum am Klosterforst in Itzehoe

🇩🇪

Itzehoe, Germany

NeuroPoint, Gesellschaft für vorbeugende Gesundheitspflege mbH

🇩🇪

Ulm, Germany

Klinikum rechts der Isar der TU Muenchen; Neurologische Klinik und Poliklinik im Neuro-Kopf-Zentrum

🇩🇪

München, Germany

Policlinico Tor Vergata Dip. Neuroscienze-Clinica Neurologica-UOSD Sclerosi Multipla

🇮🇹

Roma, Lazio, Italy

Ospedale Bellaria; Istituto delle Scienze Neurologiche - UO RIABILITAZIONE SCLEROSI MULTIPLA

🇮🇹

Bologna, Emilia-Romagna, Italy

Studienzentrum Nordwest, Dr. med. Joachim Springub / Herr Wolfgang Schwarz

🇩🇪

Westerstede, Germany

Ospedale SS. Annunziata - Clinica Neurologica - Centro Sclerosi Multipla

🇮🇹

Chieti, Abruzzo, Italy

St Vincents University Hospital

🇮🇪

Dublin 4, Ireland

Ospedale San Salvatore; Clinica Neurologica - Centro Sclerosi Multipla

🇮🇹

L'Aquila, Abruzzo, Italy

Ospedale S.Antonio Abate; Neurologia 2 - Sclerosi Multipla e Recupero Neurologico

🇮🇹

Gallarate, Lombardia, Italy

Fondazione Istituto S. Raffaele - Giglio; UO Neurologia

🇮🇹

Cefalù, Sicilia, Italy

AOU Senese - Presidio Ospedaliero Le Scotte; UOSA Neurologia Sperimentale

🇮🇹

Siena, Toscana, Italy

Policlinico G.B. Rossi; Dip. Scienze Neurologiche Biomediche - Neurologia B - Amb. Sclerosi Multipla

🇮🇹

Verona, Veneto, Italy

Ondokuz Mayis Univ. Med. Fac.; Neurology

🇹🇷

Samsun, Turkey

Hospital Universitari de Bellvitge; Servicio de Neurologia

🇪🇸

L'Hospitalet de Llobregat, Barcelona, Spain

Hospital Universitari de Girona Dr. Josep Trueta; Servicio de Neurologia

🇪🇸

Salt, Girona, Spain

Karadeniz Tecnical Uni. Med. Fac.; Neurology

🇹🇷

Trabzon, Turkey

Istanbul Universitesi - Cerrahpasa Cerrahpasa Tip Fakultesi; Noroloji Anabilim Dali

🇹🇷

Istanbul, Turkey

Terveystalo Tampere

🇫🇮

Tampere, Finland

Hopital Roger Salengro; Service de Neurologie

🇫🇷

Lille, France

CHU toulouse - Hôpital Purpan; Departement de Neurologie

🇫🇷

Toulouse, France

Azienda Ospedaliera Sant'Andrea; UOC Neurologia

🇮🇹

Roma, Lazio, Italy

Irccs A.O.U.San Martino Ist; Dinogmi

🇮🇹

Genova, Liguria, Italy

Universitätsspital Basel Medizin Neurologie; Neurologische Poliklinik

🇨🇭

Basel, Switzerland

Hospital Quiron de Madrid; Servicio de Neurologia

🇪🇸

Pozuelo de Alarcon, Madrid, Spain

IRCCS Istituto Neurologico Neuromed; Centro per lo Studio e la Cura della Sclerosi Multipla

🇮🇹

Pozzilli, Molise, Italy

AO di Perugia - Ospedale S. Maria della Misericordia; Clinica Neurologica

🇮🇹

Perugia, Umbria, Italy

Sydjysk Skleroseklinik - Sønderborg

🇩🇰

Sønderborg, Denmark

UZ Antwerpen

🇧🇪

Edegem, Belgium

Hospital Erasme

🇧🇪

Bruxelles, Belgium

St George Hospital

🇦🇺

Kogarah, New South Wales, New South Wales, Australia

Cliniques Universitaires St-Luc

🇧🇪

Bruxelles, Belgium

UZ Gent

🇧🇪

Gent, Belgium

CHU Tivoli

🇧🇪

La Louvière, Belgium

UZ Leuven Gasthuisberg

🇧🇪

Leuven, Belgium

Nationaal MS Centrum

🇧🇪

Melsbroek, Belgium

Fakultni nemocnice u sv. Anny; Neurologicka klinika

🇨🇿

Brno, Czechia

Revalidatie en MS Centrum

🇧🇪

Overpelt, Belgium

Nemocnice Jihlava; NEU-Neurologicke oddeleni

🇨🇿

Jihlava, Czechia

VFN Praha Poliklinika Rs Centrum - Budova A

🇨🇿

Prague, Czechia

Fakultni nemocnice Motol; Neurologicka klinika

🇨🇿

Praha, Czechia

Odense Universitetshospital, Neurologisk Afdeling N

🇩🇰

Odense C, Denmark

Aarhus Universitetshospital, Neurologisk Afd. F, Skleroseklinikken

🇩🇰

Aarhus N, Denmark

West Tallinn Central Hospital

🇪🇪

Tallinn, Estonia

Rigshospitalet Glostrup; Neurologisk Klinik

🇩🇰

Glostrup, Denmark

Hopital Neurologique et Neurochirurgical Pierre Wertheimer; Service de Neurologie A

🇫🇷

Bron, France

Groupe Hospitalier Pellegrin; Service de neurochirurgie B

🇫🇷

Bordeaux, France

Mehiläinen Neo Turku

🇫🇮

Turku, Finland

CHU de la Timone - Hopital d Adultes; Service de Neurologie

🇫🇷

Marseille, France

Hopital Gui de Chauliac; Neurologie

🇫🇷

Montpellier, France

Fondation Rothschild; Service de Neurologie

🇫🇷

Paris, France

Hôpital Pasteur; Service de Neurologie

🇫🇷

Nice, France

Groupe Hospitalier Pitié- Salpétrière; Service Neurologie

🇫🇷

Paris, France

Marianne-Strauß-Klinik; Behandlung Kempfen für Multip Sklero Kranke gemeinnütz GmbH

🇩🇪

Berg, Germany

Charite - Universitatsmedizin Berlin; Klinik fur Neurologie

🇩🇪

Berlin, Germany

St. Josef-Hospital, Klinik für Neurologie

🇩🇪

Bochum, Germany

Praxis Dr. Said Masri

🇩🇪

Berlin, Germany

PNP Buchholz, Praxis für Neurologie - Psychiatrie, Dres. Dee/Gößling/Hoge

🇩🇪

Buchholz, Germany

Studienzentrum für Neurologie und Psychiatrie

🇩🇪

Böblingen, Germany

Gemeinschaftspraxis für Neurologie; Dr. Katrin Schulte, Dr. Nils Richter, Dr. Margarete Capito

🇩🇪

Düsseldorf, Germany

Universitaetsklinikum Frankfurt; Klinik für Neurologie

🇩🇪

Frankfurt, Germany

Universiätsklinikum Hamburg-Eppendorf , Multiple Sklerose Tagesklinik u. Ambulanz Neurol. Poliklinik

🇩🇪

Hamburg, Germany

MultipEL Studies - Institut für klinische Studien

🇩🇪

Hamburg, Germany

Universitätsklinikum Freiburg, Klinik für Neurologie und Neurophysiologie

🇩🇪

Freiburg, Germany

Oberhavel Kliniken GmbH, Klinik Hennigsdorf, Neurologie

🇩🇪

Hennigsdorf, Germany

PANAKEIA - Arzneimittelforschung Leipzig GmbH

🇩🇪

Leipzig, Germany

Max-Planck-Institut für Psychiatrie

🇩🇪

München, Germany

Universitaetsklinikum Marburg; Klinik fuer Neurologie

🇩🇪

Marburg, Germany

Universitaetsklinikum Mainz - PS; Klinik und Poliklinik fuer Neurologie

🇩🇪

Mainz, Germany

AMEOS Klinikum Oldenburg, Klinik für Neurologie und Neurophysiologie

🇩🇪

Oldenburg in Holstein, Germany

Universitätsklinikum Tübingen, Zentrum für Neurologie

🇩🇪

Tübingen, Germany

Beaumont Hospital

🇮🇪

Dublin, Ireland

Università degli Studi della Campania Luigi Vanvitelli; Dip. Ass. Integrato Med Int-II Clinica Neur

🇮🇹

Napoli, Campania, Italy

Ospedale S.Camillo Forlanini; UOSD Day Hospital Neurologico e Neurochirurgico

🇮🇹

Roma, Lazio, Italy

Policlinico Universitario A. Gemelli; UOC Neurologia - Centro Sclerosi Multipla

🇮🇹

Roma, Lazio, Italy

ASST PAPA GIOVANNI XXIII Neurologia USS Malattie Autoimmuni Centro Sclerosi Multipla

🇮🇹

Bergamo, Lombardia, Italy

IRCCS Ospedale San Raffaele; Neurologia Neurofisiologia Neuroriabilitazione-Centro Sclerosi Multipla

🇮🇹

Milano, Lombardia, Italy

Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico; UOSD Malattie Neurodegenerative

🇮🇹

Milano, Lombardia, Italy

Fond. Istituto Neurologico C.Besta; UO Neurologia IV - Neuroimmunologia Malattie Neuromuscolari

🇮🇹

Milano, Lombardia, Italy

Ospedale Civile di Montichiari; Centro Sclerosi Multipla

🇮🇹

Montichiari, Lombardia, Italy

IRCCS Istituto Neurologico C. Mondino-Dip. Neurologia Neuroriabilitazione S.S. Sclerosi Multipla

🇮🇹

Pavia, Lombardia, Italy

Ospedale Dimiccoli Barletta; Dipartimento Testa-Collo - UO Neurologia

🇮🇹

Barletta, Puglia, Italy

AOU Ospedali Riuniti Umberto I-G.M. Lancisi-G. Salesi; SOD Clinica Neurologica-Am.Sclerosi Multipla

🇮🇹

Ancona, Marche, Italy

Ospedale Binaghi; Centro Sclerosi Multipla

🇮🇹

Cagliari, Sardegna, Italy

IRCCS Ospedale Casa Sollievo Della Sofferenza; SC Neurologia

🇮🇹

San Giovanni Rotondo, Puglia, Italy

AOU Policlinico V. Emanuele - P.O G. Rodolico; Clinica Neurologica, Centro Sclerosi Multipla

🇮🇹

Catania, Sicilia, Italy

AOU Policlinico Giaccone; UOC Neurologia e Neurofisiopatologia-Amb Sclerosi Multipla

🇮🇹

Palermo, Sicilia, Italy

AOU Careggi; Neurologia 1-Dip. Neuroscienze Psicologia Area Farmaco Salute del Bambino(NEUROFARBA)

🇮🇹

Firenze, Toscana, Italy

AOUC Azienda Ospedaliero-Universitaria Careggi; Neurologia 2

🇮🇹

Firenze, Toscana, Italy

AO Ospedali Riuniti Villa Sofia-Cervello;PO Villa Sofia - UO Neurologia - U.O.S. Neuroimmunologia

🇮🇹

Palermo, Sicilia, Italy

Azienda Ospedaliera di Padova; Clinica Neurologica

🇮🇹

Padova, Veneto, Italy

Amphia Ziekenhuis

🇳🇱

Breda, Netherlands

St. Antonius Ziekenhuis Nieuwegein

🇳🇱

Nieuwegein, Netherlands

Zuyderland Medisch Centrum - Sittard Geleen

🇳🇱

Sittard-Geleen, Netherlands

Sykehuset Buskerud HF; Nevrologisk avdeling

🇳🇴

Drammen, Norway

Sint Elizabeth Ziekenhuis

🇳🇱

Tilburg, Netherlands

Haukeland Universitetssykehus

🇳🇴

Bergen, Norway

Maasstadziekenhuis

🇳🇱

Rotterdam, Netherlands

Hospital Universitario Central de Asturias; Servicio de Neurología

🇪🇸

Oviedo, Asturias, Spain

Hospital Universitari Arnau de Vilanova de Lleida; Servicio de Neurología

🇪🇸

Lleida, Lerida, Spain

Complejo Hospitalario Universitario A Coruña (CHUAC); Servicio de Neurologia

🇪🇸

Coruña, LA Coruña, Spain

Hospital General de Castellon; Servicio de Neurología

🇪🇸

Castelló de la Plana, Castellon, Spain

Complejo Hospitalario Universitario de Vigo - Xeral Cies; Servicio de Neurologia

🇪🇸

Vigo, Pontevedra, Spain

Hospital Puerta del Mar; Sevicio de Neurologia

🇪🇸

Cadiz, Spain

Universitario de La Princesa; Servicio de Neurología

🇪🇸

Madrid, Spain

Hospital del Mar; Servicio de Neurologia

🇪🇸

Barcelona, Spain

Hospital Universitario Clínico San Carlos; Servicio de Neurología

🇪🇸

Madrid, Spain

Hospital Vall d'Hebron; Servicio de Neurología

🇪🇸

Barcelona, Spain

Hospital Universitario 12 de Octubre; Servicio de Neurologia

🇪🇸

Madrid, Spain

Hospital Universitario La Paz; Servicio de Neurologia

🇪🇸

Madrid, Spain

Hospital Universitario Virgen de Arrixaca; Servicio de Neurología

🇪🇸

Murcia, Spain

Centrum för Neurologi

🇸🇪

Stockholm, Sweden

Hospital Clinico Universitario de Valencia; Servicio de Neurologia

🇪🇸

Valencia, Spain

Sahlgrenska Sjukhuset; Neurology

🇸🇪

Göteborg, Sweden

Hospital Universitario la Fe; Servicio de Neurologia

🇪🇸

Valencia, Spain

Hospital Universitario Virgen Macarena; Servicio de Neurologia

🇪🇸

Sevilla, Spain

Länssjukhuset Ryhov; Medicinkliniken / Neurologmottagningen

🇸🇪

Jönköping, Sweden

CHUV Lausanne Méd.Neurologie

🇨🇭

Lausanne, Switzerland

Ege University Medical Faculty

🇹🇷

Izmir, Turkey

Hacettepe University Medical Faculty; Neurology

🇹🇷

Ankara, Turkey

Istanbul Uni Istanbul Medical Faculty

🇹🇷

Istanbul, Turkey

Kocaeli University Hospital; Department of Neurology

🇹🇷

Kocaeli, Turkey

Mersin University Medical Faculty; Neurology

🇹🇷

Mersin, Turkey

Western General Hospital

🇬🇧

Edinburgh, United Kingdom

New Queen Elizabeth Hospital Birmingham

🇬🇧

Birmingham, United Kingdom

Royal Devon and Exeter Hospital (Wonford)

🇬🇧

Exeter, United Kingdom

Queen Elizabeth University Hospital

🇬🇧

Glasgow, United Kingdom

Kings College Hospital

🇬🇧

London, United Kingdom

The Royal London Hospital

🇬🇧

London, United Kingdom

Leeds Teaching Hospitals NHS Trust

🇬🇧

Leeds, United Kingdom

Raigmore Hospital

🇬🇧

Inverness, United Kingdom

Royal Victoria Infirmary

🇬🇧

Newcastle upon Tyne, United Kingdom

Salford Royal NHS Foundation Trust

🇬🇧

Salford, United Kingdom

Royal Hallamshire Hospita

🇬🇧

Sheffield, United Kingdom

Morriston Hospital

🇬🇧

Swansea, United Kingdom

Royal Cornwall Hospital

🇬🇧

Truro, United Kingdom

Charing Cross Hospital

🇬🇧

London, United Kingdom

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