MedPath

Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis, Study Two

Phase 3
Completed
Conditions
Multiple Sclerosis, Relapsing-Remitting
Interventions
Biological: Alemtuzumab 12 mg
Biological: Alemtuzumab 24 mg
Biological: Interferon beta-1a
Registration Number
NCT00548405
Lead Sponsor
Genzyme, a Sanofi Company
Brief Summary

The purpose of this study was to establish the efficacy and safety of two different doses of alemtuzumab (Lemtrada™) as a treatment for relapsing-remitting multiple sclerosis (MS), in comparison with subcutaneous interferon beta-1a (Rebif®). The study enrolled participants who had received an adequate trial of disease-modifying therapies but experienced at least 1 relapse during prior treatment, and who met a minimum severity of disease as measured by magnetic resonance imaging (MRI). Participants had monthly laboratory tests and comprehensive testing every 3 months.

Detailed Description

Every participant received active treatment; there was no placebo. After Amendment 2, the 24 mg alemtuzumab dose was closed to enrollment so newly enrolled participants were randomly assigned to treatment with either 12 mg alemtuzumab or interferon beta-1a in a 2:1 ratio (that is, 2 given 12 mg alemtuzumab for every 1 given interferon beta-1a). Alemtuzumab was administered in two annual courses, once at the beginning of the study and again 1 year later. Interferon beta-1a was self-injected 3 times per week for 2 years. All participants were required to return to their study site every 3 months for neurologic assessment. In addition, safety-related laboratory tests were performed at least monthly. Participation in this study ended 2 years after the start of treatment for each participant. Additionally, participants who received alemtuzumab might be followed in the CAMMS03409 Extension Study (NCT00930553) for safety and efficacy assessments. Participants who received interferon beta-1a and completed 2 years on study might be eligible to receive alemtuzumab in the Extension Study.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
840
Inclusion Criteria
  • Signed informed consent form (ICF)
  • Age 18 to 55 years (inclusive) as of the date the ICF was signed
  • Diagnosis of MS per update of McDonald criteria
  • Onset of MS symptoms (as determined by a neurologist; could be retrospectively) within 10 years of the date the ICF was signed
  • Expanded Disability Status Scale (EDSS) score 0.0 to 5.0 (inclusive) at Screening
  • Greater than or equal to (>=) 2 MS attacks (first episode or relapse) occurring in the 24 months prior to the date the ICF was signed, with >=1 attack in the 12 months prior to the date the ICF was signed, with objective neurological signs confirmed by a physician, nurse practitioner, or other Genzyme-approved health-care provider and the objective signs could be identified retrospectively
  • >=1 MS relapse during treatment with a beta interferon therapy or glatiramer acetate after having been on that therapy for >=6 months within 10 years of the date the ICF was signed
  • MRI scan demonstrating white matter lesions attributable to MS and meeting at least 1 of the following criteria, as determined by the neurologist or a radiologist: >=9 time constant 2 (T2) lesions at least 3 millimeter (mm) in any axis; a gadolinium- (Gd-) enhancing lesion at least 3 mm in any axis plus >=1 brain T2 lesions; and a spinal cord lesion consistent with MS plus >=1 brain T2 lesion
Exclusion Criteria
  • Received prior therapy with alemtuzumab
  • Current participation in another clinical study or previous participation in CAMMS323 (Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis, CARE-MS I)
  • Treatment with natalizumab, methotrexate, azathioprine, or cyclosporine in the past 6 months. Participants who received one of these medications more than 6 months before the date the ICF was signed were eligible for study entry if approval was granted by Genzyme
  • Any progressive form of MS
  • History of malignancy (except basal skin cell carcinoma)
  • CD4 +, CD8 +, CD19 + (that is, absolute CD3 + CD4 + , CD3 + CD8 + , or CD19 + /mm 3 ) count, absolute neutrophil count less than (<) lower limit of normal (LLN) at screening; if abnormal cell count(s) returned to within normal limits (WNL), eligibility could be reassessed
  • Known bleeding disorder (for example, dysfibrinogenemia, factor IX deficiency, hemophilia, Von Willebrand's disease, disseminated intravascular coagulation, fibrinogen deficiency, or clotting factor deficiency)
  • Significant autoimmune disease including but not limited to immune cytopenias, rheumatoid arthritis, systemic lupus erythematosus, other connective tissue disorders, vasculitis, inflammatory bowel disease, severe psoriasis
  • Presence of anti-thyroid stimulating hormone (TSH) receptor (TSHR) antibodies (that is, above the LLN)
  • Active infection or at high risk for infection

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Alemtuzumab 12 mgAlemtuzumab 12 mgAlemtuzumab (Lemtrada™) 12 milligram (mg) per day intravenous (IV) infusion on 5 consecutive days at Month 0, followed by alemtuzumab 12 mg per day IV infusion on 3 consecutive days at Month 12.
Alemtuzumab 24 mgAlemtuzumab 24 mgAlemtuzumab 24 mg per day IV infusion on 5 consecutive days at Month 0, followed by alemtuzumab 24 mg per day IV infusion on 3 consecutive days at Month 12.
Interferon Beta-1aInterferon beta-1aInterferon Beta-1a (Rebif®) 44 microgram (mcg) subcutaneously 3-times weekly for 24 months. Dose adjustment was done as per Investigator's discretion.
Primary Outcome Measures
NameTimeMethod
Percentage of Participants With Sustained Accumulation of Disability (SAD)Up to 2 years

EDSS is an ordinal scale in half-point increments that qualifies disability in participants with MS. It assesses 7 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) as well as ambulation. EDSS total score: 0 (normal neurological examination) to 10 (death due to MS). As measured by EDSS score, SAD was defined as increase of at least 1.5 points for participants with Baseline score of 0 and increase of at least 1.0 point for participants with a Baseline score of 1.0 or more; and the increase persisted for at least the next 2 scheduled assessments, that is, 6 consecutive months. The onset date of SAD was date of first EDSS assessment that began 6 month consecutive period of SAD. Participants who did not reach SAD endpoint were censored at their last visit. Percentage of participants with SAD, estimated by Kaplan-Meier (KM) method, was reported.

Annualized Relapse RateUp to 2 years

Relapse was defined as new neurological symptoms or worsening of previous neurological symptoms with an objective change on neurological examination, attributable to multiple sclerosis that lasted for at least 48 hours, that were present at normal body temperature, and that were preceded by at least 30 days of clinical stability. Annualized relapse rate was estimated through negative binomial regression with robust variance estimation and covariate adjustment for geographic region using observed number of relapses as dependent variable, the log total amount of follow-up from date of first study treatment for each participant as an offset variable, and treatment group and geographic region as model covariates.

Secondary Outcome Measures
NameTimeMethod
Percentage of Participants Who Were Relapse Free at Year 2Year 2

Participants were considered relapse free at Year 2 if they did not experience a relapse from the date of first study treatment to study completion at 24 months. Percentage of participants who were relapse free at Year 2, estimated using the KM method, was reported.

Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Year 2Baseline, Year 2

EDSS is an ordinal scale in half-point increments that qualifies disability in participants with multiple sclerosis (MS). It assesses the 7 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) as well as ambulation. EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS). Change was calculated by subtracting Baseline value from value at Year 2.

Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Score at Year 2Baseline, Year 2

MSFC is a multidimensional measure consisting of quantitative tests of ambulation (Timed 25-Foot Walk), manual dexterity (9-Hole Peg Test; 9HPT), and cognitive function (Paced Auditory Serial Addition Test; PASAT). The MSFC score was calculated as the mean of the Z-scores of the 3 components. A Z-score was calculated by subtracting the mean of the reference population from the test result, then dividing by the standard deviation of the reference population. Higher Z-scores reflected better neurological function and a positive change from Baseline indicates improvement. An increase in score indicated an improvement (Z-score range: -3 to +3). Acquisition of disability was measured by change from Baseline in MSFC score at Year 2.

Percent Change From Baseline in Magnetic Resonance Imaging Time Constant 2 (MRI-T2) Hyperintense Lesion Volume at Year 2Baseline, Year 2

Percent change in MS lesion volume as measured by MRI-T2 scan was calculated from MRI-T2-weighted scans as the following: (lesion volume at 2 years - lesion volume at Baseline)\*100/ (lesion volume at Baseline).

Trial Locations

Locations (191)

Central Texas Neurology

🇺🇸

Round Rock, Texas, United States

Sunnybrook Health Sciences Centre

🇨🇦

Toronto, Ontario, Canada

Department of Neurology, Keck School of Medicine, University of Southern California

🇺🇸

Los Angeles, California, United States

University of Pittsburgh, Kaufmann Medical Building

🇺🇸

Pittsburgh, Pennsylvania, United States

Caritas St. Elizabeth's Medical Center

🇺🇸

Boston, Massachusetts, United States

Josephson Wallack Munshower Neurology P.C.

🇺🇸

Indianapolis, Indiana, United States

Partners Multiple Sclerosis Center/Brigham and Women's Hospital

🇺🇸

Boston, Massachusetts, United States

University of Nevada School of Medicine

🇺🇸

Las Vegas, Nevada, United States

Integra Clinical Research

🇺🇸

San Antonio, Texas, United States

Montana Neurobehavioral Specialists

🇺🇸

Missoula, Montana, United States

Unidad de Investigación en Salud de Chihuahua, S.C.

🇲🇽

Chihuahua, Mexico

Centre for Neuroscience & Trauma, Blizard Institute of Cell and Molecular Science Barts and The London School of Medicine and Dentistry

🇬🇧

London, England, United Kingdom

Hospital Angeles del Pedregal; Camino a Santa Teresa

🇲🇽

Mexico City, Mexico

Clinical Centre Vojvodina Institute of Neurology

🇷🇸

Novi Sad, Serbia

University of Rochester Medical Center

🇺🇸

Rochester, New York, United States

Hospital Medica Sur CIF-BIOTEC

🇲🇽

Delegacion, Tlalpan, Mexico

Azienda Ospedaliera Sant'Andrea Neurologia

🇮🇹

Roma, Italy

Multiple Sclerosis Clinic, Connell 7, Kingston General Hospital

🇨🇦

Kingston, Ontario, Canada

North Central Neurology Associates, P.C.

🇺🇸

Cullman, Alabama, United States

East Bay Physicians Medical Group/Sutter East Bay Medical Foundation

🇺🇸

Berkeley, California, United States

Neurology Center of North Orange County

🇺🇸

La Habra, California, United States

Advanced Neurosciences Research

🇺🇸

Fort Collins, Colorado, United States

George Washington University Medical Faculty Associates

🇺🇸

Washington, District of Columbia, United States

Yale University

🇺🇸

New Haven, Connecticut, United States

Stanford University School of Medicine

🇺🇸

Stanford, California, United States

Negroski, Stein, Sutherland and Hanes Neurology

🇺🇸

Sarasota, Florida, United States

University of Florida Neuroscience Institute

🇺🇸

Jacksonville, Florida, United States

Neurology Associates, P.A.

🇺🇸

Maitland, Florida, United States

Emory University, Department of Neurology

🇺🇸

Atlanta, Georgia, United States

Shepherd Center, Inc.

🇺🇸

Atlanta, Georgia, United States

Neurological Associates

🇺🇸

Pompano Beach, Florida, United States

Idaho Falls Multiple Sclerosis Center, PLLC

🇺🇸

Idaho Falls, Idaho, United States

Fort Wayne Neurological Center

🇺🇸

Fort Wayne, Indiana, United States

University of Chicago Medical Center, Department of Neurology

🇺🇸

Chicago, Illinois, United States

Iowa Health Physicians

🇺🇸

Des Moines, Iowa, United States

Indiana University School of Medicine, Department of Neurology

🇺🇸

Indianapolis, Indiana, United States

Springfield Neurology Associates, LLC

🇺🇸

Springfield, Massachusetts, United States

Dartmouth-Hitchcock Medical Center, Norris Cotton Cancer Center

🇺🇸

Lebanon, New Hampshire, United States

Louisiana State University Health Sciences Center

🇺🇸

Shreveport, Louisiana, United States

University of Kansas Medical Center, Department of Neurology

🇺🇸

Kansas City, Kansas, United States

Associates in Neurology, PSC

🇺🇸

Lexington, Kentucky, United States

University of Louisville Research Foundation

🇺🇸

Louisville, Kentucky, United States

UMass Memorial Medical Center

🇺🇸

Worcester, Massachusetts, United States

Northern Michigan Neurology

🇺🇸

Traverse City, Michigan, United States

Michigan Neurology Associates, P.C.

🇺🇸

St. Clair Shores, Michigan, United States

Renown Institute for Neurosciences / Renown regional Medical Center

🇺🇸

Reno, Nevada, United States

Neurology Consultants of Kansas City, Inc.

🇺🇸

Kansas City, Missouri, United States

Northshore Clinical Associates

🇺🇸

Erie, Pennsylvania, United States

Advanced Neurosciences Institute

🇺🇸

Franklin, Tennessee, United States

Biomedical Research Alliance of NY, LLC

🇺🇸

Franklin, Tennessee, United States

University of North Carolina-Chapel Hill, Department of Neurology

🇺🇸

Chapel Hill, North Carolina, United States

Empire Neurology, PC

🇺🇸

Latham, New York, United States

Neurology Specialists, Inc.

🇺🇸

Dayton, Ohio, United States

SUNY Upstate Medical University, Department of Neurology

🇺🇸

Syracuse, New York, United States

Cleveland Clinic Foundation, Mellen Center

🇺🇸

Cleveland, Ohio, United States

Winthrop University Hospital, Clinical Trials Center

🇺🇸

Mineola, New York, United States

Neurology Clinic, P.C.

🇺🇸

Cordova, Tennessee, United States

Mount Sinai School of Medicine, Corinne Goldsmith Dickinson Center for Multiple Sclerosis

🇺🇸

New York, New York, United States

Oak Clinic for Multiple Sclerosis

🇺🇸

Uniontown, Ohio, United States

The Neurology Foundation, Inc.

🇺🇸

Providence, Rhode Island, United States

UBC Hospital

🇨🇦

Vancouver, British Columbia, Canada

Hope Neurology PC

🇺🇸

Knoxville, Tennessee, United States

AKH Wien, Universitätsklinikum für Neurologie

🇦🇹

Wien, Austria

University Hospital Leuven, Campus Gasthuisberg, Neurology

🇧🇪

Leuven, Belgium

Liverpool Hospital, Neurology Department

🇦🇺

Liverpool, Australia

MS Center of Greater Washington, P.C.

🇺🇸

Vienna, Virginia, United States

Rockwood Clinical Research Center

🇺🇸

Spokane, Washington, United States

Clinical Center for Multiple Sclerosis

🇺🇸

Dallas, Texas, United States

Clinical Hospital Centre Rijeka, Clinic for Neurology

🇭🇷

Rijeka, Croatia

London Health Sciences Centre- University Hospital

🇨🇦

London, Ontario, Canada

Swedish Neuroscience Institute

🇺🇸

Seattle, Washington, United States

Virginia Mason Medical Center

🇺🇸

Seattle, Washington, United States

Cliniques Universitaires Saint-Luc, Neurology

🇧🇪

Brussel, Belgium

Westmead Hospital

🇦🇺

Westmead, New South Wales, Australia

Hospital de Clínicas USP

🇧🇷

Sao Paulo, Brazil

DIABAID

🇦🇷

Buenos Aires, Argentina

Hospital Sao Lucas PUC-RS

🇧🇷

Porto Alegre, RS, Brazil

CHU Ourthe Amblève, Neurology

🇧🇪

Esneux, Belgium

MS Center, Department of Neurology

🇨🇿

Hradec Kralove, Czech Republic

Clinical Hospital Sestre Milosrdnice

🇭🇷

Zagreb, Croatia

Clinical Cognitive Research Unit/Clinical Trials, The Queen Elizabeth Hospital, Neurology Department

🇦🇺

Woodville South, South Australia, Australia

Clinique Neuro rive-sud, Recherche sepmus inc

🇨🇦

Greenfield park, Quebec, Canada

Hospital da Restauracao

🇧🇷

Recife, PE, Brazil

Neurologisches Fachzentrum Berlin

🇩🇪

Berlin, Germany

General Hospital " Sveti Duh", Department of neurology

🇭🇷

Zagreb, Croatia

Department of Neurology 1st Faculty of Medicine and General Teaching Hospital, MS Center

🇨🇿

Praha 2, Czech Republic

Centre de Sante et de Services Sociaux de Gatineau-Hull Hospital

🇨🇦

Gatineau, Quebec, Canada

General Hospital Varazdin, Department of neurology

🇭🇷

Varazdin, Croatia

St. Anne's University Hospital Brno

🇨🇿

Pekarska, Czech Republic

Clinical Hospital Centre Zagreb

🇭🇷

Zagreb, Croatia

Århus Universitetshospital, Scleroseklinikken, Århus Sygehus

🇩🇰

Aarhus, Denmark

Krajska zdravotni a.s. - Hospital Teplice

🇨🇿

Teplice, Czech Republic

Scleroseklinikken, Rigshospitalet

🇩🇰

København, Denmark

CHU Clermont-Ferrand, Hôpital Gabriel Montpied

🇫🇷

Clermont-Ferrand, France

Odense University Hospital

🇩🇰

Odense, Denmark

Krankenhaus Hohe Warte, Betriebsstätte der Bayreuth

🇩🇪

Bayreuth, Germany

Judisches Krankenhaus Berlin

🇩🇪

Berlin, Germany

Klinikum Rechts der Isar, Klinik für Neurologie

🇩🇪

Muenchen, Germany

Klinikum Ingolstadt, Neurologische Klinik

🇩🇪

Ingolstadt, Germany

Neurologische Universitätsklinik Bonn

🇩🇪

Bonn, Germany

Military Medical Academy

🇷🇸

Belgrade, Serbia

Sahlgrenska University Hospital, Neurologkliniken

🇸🇪

Gothenburg, Sweden

Servicio de Neurología Hospital Clínico San Carlos

🇪🇸

Madrid, Spain

Ospedale Binaghi - Centro Sclerosi Multipla

🇮🇹

Cagliari, Italy

Asklepios Klinic Barmbek

🇩🇪

Hamburg, Germany

Orbis Medisch Centrum, Department of Neurology

🇳🇱

Sittard, Netherlands

Sheba Medical Centre

🇮🇱

Tel Hashomer, Israel

Universitatsklinik Ulm

🇩🇪

Ulm, Germany

Fachkrankenhaus Hubertusburg

🇩🇪

Wermsdorf, Germany

Università di Genova Dipartimento di Neuroscienze Oftalmologia e Genetica

🇮🇹

Genova, Italy

Ospedale Civile di Brescia c/o Ospedale Richiedei, Centro di riferimento per la Sclerosi Multiple

🇮🇹

Montichiari, Italy

Hadassah Medical Center Ein Karem

🇮🇱

Jerusalem, Israel

Ospedale San Luigi di Orbassano

🇮🇹

Orbassano, Italy

Independent Public Healthcare Facility, Norbert Barlicki University Hospital No. 1 of the Medical University of Lodz

🇵🇱

Lodz, Poland

Moscow State Public Medical Institution, City Clinical Hospital #11

🇷🇺

Moscow, Russian Federation

Tel Aviv Sourasky Medical Center, Department of Neurology

🇮🇱

Tel Aviv, Israel

Ospedale S. Antonio Abate di Gallarate

🇮🇹

Gallarate, Italy

Independent Public Teaching Hospital No. 4 in Lublin

🇵🇱

Lublin, Poland

Jeroen Bosch Ziekenhuis

🇳🇱

Hertogenbosch, Netherlands

Municipal Treatment and Prevention Institution, "City Hospital #33"

🇷🇺

Nizhniy Novgorod, Russian Federation

State Medical Institution, "Samara Regional Clinical Hospital n.a. M.I. Kalinin"

🇷🇺

Samara, Russian Federation

Institution of the Russian Academy of Medical Sciences, "Neurology Scientific Center under RAMS"

🇷🇺

Moscow, Russian Federation

Clinic of Neurology, Clinical Centre of Serbia

🇷🇸

Belgrade, Serbia

Clinical Centre of Kragujevac

🇷🇸

Kragujevac, Serbia

Norrlands Universitets sjukhus

🇸🇪

Umea, Sweden

Servicio de Neurología Hospital Carlos Haya

🇪🇸

Malaga, Spain

Servicio de Neurología Hospital Virgen de la Macarena

🇪🇸

Sevilla, Spain

Servicio de Neurología Hospital Vall d'Hebron Paseo de Vall d'Hebron

🇪🇸

Barcelona, Spain

Institute of Neurology, Psychiatry and Narcology under the Academy of Medical Sciences of Ukraine

🇺🇦

Kharkov, Ukraine

Frenchay Hospital

🇬🇧

Bristol, United Kingdom

Salford Royal NHS Foundation Trust, Clinical Trials Unit

🇬🇧

Salford, United Kingdom

Barrow Neurological Institute, St. Joseph's Hospital and Medical Center

🇺🇸

Phoenix, Arizona, United States

Hope Research Institute

🇺🇸

Phoenix, Arizona, United States

Neurological Consultants

🇺🇸

Denver, Colorado, United States

Henry Ford Hospital

🇺🇸

Detroit, Michigan, United States

Wayne State University, School of Medicine, Department of Neurology

🇺🇸

Detroit, Michigan, United States

Mayo Clinic Rochester

🇺🇸

Rochester, Minnesota, United States

MS Center of Oklahoma

🇺🇸

Oklahoma City, Oklahoma, United States

Vanderbilt Multiple Sclerosis Center

🇺🇸

Nashville, Tennessee, United States

Multiple Sklerose Zentrum am, Zentrum für klinische Neurowissenschaften, Neurologische Uniklinik Dresden

🇩🇪

Dresden, Germany

Medizinische Hochshule Hannover

🇩🇪

Hannover, Germany

Oberhavelkliniken Hennigsdorf

🇩🇪

Hennigsdorf, Germany

Klinik und Poliklinik fur Neurologie der Universitat Rockstock

🇩🇪

Rostock, Germany

Hôpital Pitié Salpétrière, Service de Neurologie

🇫🇷

Paris, France

Hôpital General, Service de Neurologie

🇫🇷

Dijon Cedex, France

Hôpital Civil, Departement de Neurologie

🇫🇷

Strasbourg Cedex, France

Moscow State Medical Institution City Clinical Hospital #11, Moscow City Center for Multiple Sclerosis

🇷🇺

Moscow, Russian Federation

Research Medical Complex "Your Health" Ltd

🇷🇺

Kazan, Russian Federation

Federal State Institution: Siberian District Medical Center

🇷🇺

Novosibirsk, Russian Federation

Institution of the Russian Academy of Sciences, "Institute of the Human Brain n.a. N.P. Bekhtereva within the Russian Academy of Sciences"

🇷🇺

St. Petersburg, Russian Federation

St. Petersburg Pavlov State Medical University, Department of Neurology and Neurosurgery with a Clinic

🇷🇺

St. Petersburg, Russian Federation

St.Petersburg State Medical Institution, "City Multispecialty Hospital #2"

🇷🇺

St. Petersburg, Russian Federation

St.Petersburg State Medical Institution, "Nikolayevskaya Hospital"

🇷🇺

St. Petersburg, Russian Federation

Comprehensive Multiple Sclerosis Care Center at South Shore Neurologic Associates, P.C.

🇺🇸

Patchogue, New York, United States

St. Vincent's Hospital, MS Education & Research, Department of Clinical Neurosciences

🇦🇺

Fitzroy, Victoria, Australia

Royal Hobart Hospital

🇦🇺

Hobart, Tasmania, Australia

Southern Neurology

🇦🇺

Kogarah, Australia

Ruan Neurology Clinic and Research Center

🇺🇸

Des Moines, Iowa, United States

University of Michigan Department of Neurology

🇺🇸

Ann Arbor, Michigan, United States

Wake Forest University Health Science, Department of Neurology

🇺🇸

Winston-Salem, North Carolina, United States

University of California, Davis Medical Center

🇺🇸

Sacramento, California, United States

University of Colorado Hospital, Anschutz Outpatient Pavilioin

🇺🇸

Aurora, Colorado, United States

Axiom Clinical Research of Florida

🇺🇸

Tampa, Florida, United States

University of South Florida, Department of Neurology

🇺🇸

Tampa, Florida, United States

MS Center at Holy Name Hospital

🇺🇸

Teaneck, New Jersey, United States

Consultants in Neurology, Ltd

🇺🇸

Northbrook, Illinois, United States

Griffith School of Medicine, Gold Coast Campus, Griffith University

🇦🇺

Southport, Queensland, Australia

Department of Neurology Glossop Road, Royal Hallamshire Hospital

🇬🇧

Sheffield, United Kingdom

Heliodor Swiecicki Teaching Hospital of the Poznan, University of Medical Sciences

🇵🇱

Poznan, Poland

Neuro-Therapeutics, Inc

🇺🇸

Pasadena, California, United States

Northwest NeuroSpecialists, PLLC

🇺🇸

Tucson, Arizona, United States

Mayo Clinic Arizona, Department of Neurology

🇺🇸

Scottsdale, Arizona, United States

Neuro-Therapeutics Inc.

🇺🇸

Pasadena, California, United States

MidAmerica Neuroscience Institute

🇺🇸

Lenexa, Kansas, United States

University of New Mexico, Health Sciences Center, MS Specialty Clinic

🇺🇸

Alburquerque, New Mexico, United States

Neurology Center of San Antonio

🇺🇸

San Antonio, Texas, United States

Lehigh Valley Hospital, Neuroscience and Pain Research

🇺🇸

Allentown, Pennsylvania, United States

Royal Melbourne Hospital, Department of Neurology

🇦🇺

Parkville, Victoria, Australia

Concord Repatriation General Hospital, Neurosciences Department

🇦🇺

Concord, Australia

Austin Health

🇦🇺

Heidelberg, Victoria, Australia

Montreal Neurological Institute and Hospital

🇨🇦

Montreal, Quebec, Canada

The Ottawa Hospital, General Campus

🇨🇦

Ottawa, Ontario, Canada

Hospital Maisonneuve-Rosemont

🇨🇦

Montreal, Quebec, Canada

Irmandade da Santa Casa de Misericordia de Sao Paulo

🇧🇷

Sao Paulo, Brazil

Hospital Roger Salengro

🇫🇷

Lille Cedex, France

Sevice de Neurologie

🇫🇷

Rennes Cedex, France

Danylo Halytsky Lviv National Medical University, Department of Neurology

🇺🇦

Lviv, Ukraine

Department Of Neurosciences, Addenbrookes Hospital

🇬🇧

Cambridge, England, United Kingdom

Kyiv Municipal Clinical Hospital #4, Department of Demyelinating Diseases of the Nervous System

🇺🇦

Kyiv, Ukraine

Spectrum Health Medical Group, Neurology (Previously known as Michigan Medical P.C., Neurology)

🇺🇸

Grand Rapids, Michigan, United States

The Wesley Research Institute

🇦🇺

Auchenflower, Queensland, Australia

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