A Clinical Study of the Efficacy of Natalizumab on Reducing Disability Progression in Participants With Secondary Progressive Multiple Sclerosis
NCT ID: NCT01416181
Last Updated: 2017-09-11
Study Results
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View full resultsBasic Information
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TERMINATED
PHASE3
889 participants
INTERVENTIONAL
2011-09-13
2016-04-13
Brief Summary
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Part 1: The primary objective of the study is to investigate whether treatment with natalizumab slows the accumulation of disability not related to relapses in participants with secondary progressive multiple sclerosis (SPMS).
The secondary objectives of Part 1 of this study are to determine the proportion of participants with consistent improvement in Timed 25-Foot Walk (T25FW), the change in participant-reported ambulatory status as measured by the 12-item MS Walking Scale (MSWS-12), the change in manual ability based on the ABILHAND Questionnaire, the impact of natalizumab on participant-reported quality of life using the Multiple Sclerosis Impact Scale-29 Physical (MSIS-29 Physical), the change in whole brain volume between the end of study and Week 24 using magnetic resonance imaging (MRI) and the proportion of participants experiencing progression of disability as measured by individual physical Expanded Disability Status Scale (EDSS) system scores.
Part 2: The primary objective of Part 2 of the study is to evaluate the safety profile of natalizumab in participants with SPMS.
The secondary objectives of Part 2 of the study are to investigate long-term disability (based on clinical or participant-reported assessments) in participants with SPMS receiving natalizumab treatment for approximately 4 years and to assess change in brain volume and T2 lesion volume.
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
TRIPLE
Study Groups
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natalizumab
In Part 1 participants were randomized to receive 300 mg of natalizumab intravenously (IV) every 4 weeks for 96 weeks. In Part 2 participants transitioned to receive open-label natalizumab 300 mg IV every 4 weeks for at least 96 weeks.
natalizumab
Administered as specified in the treatment arm
Placebo
In Part 1 participants were randomized to receive placebo IV every 4 weeks for 96 weeks. In Part 2 participants transitioned to receive open-label natalizumab 300 mg IV every 4 weeks for at least 96 weeks.
natalizumab
Administered as specified in the treatment arm
Placebo
Matched placebo in part 1
Interventions
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natalizumab
Administered as specified in the treatment arm
Placebo
Matched placebo in part 1
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* SPMS defined as relapsing-remitting disease followed by progression of disability independent of or not explained by multiple sclerosis (MS) relapses for at least 2 years.
* EDSS score of 3.0 to 6.5, inclusive.
* Multiple Sclerosis Severity Score of 4 or higher.
* Documented confirmed evidence of disease progression independent of clinical relapses over the 1 year prior to enrollment as defined in the Study Reference Guide.
* Subjects must have participated in and completed Part 1 per protocol, and have documented assessment attempts for EDSS, T25FW, and 9HPT prior to first open-label dosing.
Exclusion Criteria
* Clinical relapse (within 3 months) prior to randomization.
* T25FW test of \>30 seconds during the screening period.
* Any value below the lower limit of normal for blood levels of leukocytes, lymphocytes, or neutrophils.
* Considered by the Investigator to be immunocompromised based on medical history, physical examination, laboratory testing, or any other testing required by local guidelines, or due to prior immunosuppressive or immunomodulating treatment.
* Subjects for whom MRI is contraindicated (i.e., have pacemakers or other contraindicated implanted metal devices, are allergic to gadolinium, or have claustrophobia that cannot be medically managed).
* History of any clinically significant (as determined by the Investigator) cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic (other than MS), dermatologic, psychiatric, and renal, or other major disease that would preclude participation in a clinical study.
* History of malignant disease, including solid tumors and hematologic malignancies (with the exception of basal cell and squamous cell carcinomas of the skin that have been completely excised and are considered cured).
* Known history of or positive test result for human immunodeficiency virus.
* Positive test result for hepatitis C virus (test for hepatitis C virus antibody or hepatitis B virus (test for hepatitis B surface antigen and/or hepatitis B core antibody).
* History of transplantation or any anti-rejection therapy.
* Presence of any infectious disease (e.g., cellulitis, abscess, pneumonia, septicemia) within 30 days prior to screening.
* History of progressive multifocal leukoencephalopathy or other opportunistic infections.
Treatment History (Part 1)
* Any prior treatment with cell-depleting therapies, including total lymphoid irradiation, cladribine, rituximab, alemtuzumab, or bone marrow ablation.
* Any prior treatment with natalizumab.
* Treatment with mitoxantrone, cyclophosphamide, cyclosporine, azathioprine, methotrexate, mycophenolate mofetil, T cell or T cell receptor vaccination, fingolimod, daclizumab, or cytapheresis within 6 months prior to randomization.
* Treatment with intravenous or oral corticosteroids, intravenous immunoglobulin, or plasmapheresis for treatment of MS within the 3 months prior to randomization.
* Treatment with glatiramer acetate or any interferon beta preparations within 4 weeks prior to randomization.
* Treatment with 4-aminopyridine within 30 days prior to randomization, unless a stable dose has been maintained for at least 30 days prior to randomization and will be continued for the course of this study.
* Subjects with any significant change in clinical status, including laboratory tests that, in the opinion of the Investigator, would make them unsuitable to participate in this extension study. The Investigator must re-review the subject's medical fitness for participation and consider any diseases that would preclude treatment.
* Subjects who discontinued study treatment in Part 1 OR had fewer than 20 infusions in Part 1 OR missed 2 or more consecutive infusions in Part 1.
18 Years
58 Years
ALL
No
Sponsors
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Biogen
INDUSTRY
Responsible Party
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Principal Investigators
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Medical Director
Role: STUDY_DIRECTOR
Biogen
Locations
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Phoenix, Arizona, United States
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Tucson, Arizona, United States
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Fullerton, California, United States
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Los Angeles, California, United States
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Aurora, Colorado, United States
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Tampa, Florida, United States
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Chicago, Illinois, United States
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Lake Barrington, Illinois, United States
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Peoria, Illinois, United States
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Indianapolis, Indiana, United States
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Indianapolis, Indiana, United States
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Kansas City, Kansas, United States
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Lexington, Kentucky, United States
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Lexington, Kentucky, United States
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Baltimore, Maryland, United States
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Burlington, Massachusetts, United States
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Omaha, Nebraska, United States
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Lebanon, New Hampshire, United States
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Teaneck, New Jersey, United States
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Latham, New York, United States
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New York, New York, United States
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Advance, North Carolina, United States
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Charlotte, North Carolina, United States
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Raleigh, North Carolina, United States
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Akron, Ohio, United States
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Uniontown, Ohio, United States
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Oklahoma City, Oklahoma, United States
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Clackamas, Oregon, United States
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Portland, Oregon, United States
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Portland, Oregon, United States
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Nashville, Tennessee, United States
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Charlottesville, Virginia, United States
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Seattle, Washington, United States
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Green Bay, Wisconsin, United States
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Milwaukee, Wisconsin, United States
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La Louvière, , Belgium
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Melsbroek, , Belgium
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Overpelt, , Belgium
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Calgary, Alberta, Canada
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Edmonton, Alberta, Canada
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Vancouver, British Columbia, Canada
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Halifax, Nova Scotia, Canada
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Kingston, Ontario, Canada
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London, Ontario, Canada
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Ottawa, Ontario, Canada
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Toronto, Ontario, Canada
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Gatineau, Quebec, Canada
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Greenfield Park, Quebec, Canada
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Montreal, Quebec, Canada
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Montreal, Quebec, Canada
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Hradec Králové, Bohemia, Czechia
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Brno, , Czechia
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Olomouc, , Czechia
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Prague, , Czechia
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Arthus C, , Denmark
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Esbjerg, , Denmark
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Glostrup Municipality, , Denmark
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København Ø, , Denmark
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Odense, , Denmark
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Jyväskylä, , Finland
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Tampere, , Finland
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Turku, , Finland
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Nice, Alpes Maritimes, France
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Marseille, Bouches-du-Rhône, France
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Nantes, Loire Atlantique, France
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Nancy, Meurthe et Moselle, France
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Lille, Nord, France
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Bron, Rhone, France
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Salouël, Somme, France
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Bordeaux, , France
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Bad Mergentheim, Baden-Wurttemberg, Germany
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Bad Wilbad, Baden-Wurttemberg, Germany
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Tübingen, Baden-Wurttemberg, Germany
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Munich, Bavaria, Germany
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Munich, Bavaria, Germany
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Hennigsdorf, Brandenburg, Germany
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Teupitz, Brandenburg, Germany
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Kassel, Hesse, Germany
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Düsseldorf, North Rhine-Westphalia, Germany
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Münster, North Rhine-Westphalia, Germany
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Dresden, Saxony, Germany
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Dublin, , Ireland
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Dublin, , Ireland
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Jerusalem, , Israel
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Ramat Gan, , Israel
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Baggiovara, Modena, Italy
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Cefalù, Palermo, Italy
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Gallarate, Varese, Italy
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Bari, , Italy
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Florence, , Italy
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Genova, , Italy
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Milan, , Italy
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Milan, , Italy
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Naples, , Italy
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Napoli, , Italy
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Palermo, , Italy
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Pavia, , Italy
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Rome, , Italy
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Rome, , Italy
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's-Hertogenbosch, , Netherlands
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Amsterdam, , Netherlands
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Breda, , Netherlands
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Hoorn, , Netherlands
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Nieuwegein, , Netherlands
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Sittard-Geleen, , Netherlands
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Bialystok, , Poland
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Gdansk, , Poland
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Katowice, , Poland
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Katowice, , Poland
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Katowice, , Poland
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Krakow, , Poland
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Lodz, , Poland
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Lublin, , Poland
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Olsztyn, , Poland
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Plewiska, , Poland
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Poznan, , Poland
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Szczecin, , Poland
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Warsaw, , Poland
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Warsaw, , Poland
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Warsaw, , Poland
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Warszawa-Miedzylesie, , Poland
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Wroclaw, , Poland
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Belgorod, , Russia
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Kazan', , Russia
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Kazan', , Russia
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Moscow, , Russia
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Saint Petersburg, , Russia
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Tyumen, , Russia
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Barcelona, , Spain
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Barcelona, , Spain
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Barcelona, , Spain
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El Palmar, , Spain
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Madrid, , Spain
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Madrid, , Spain
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Majadahonda, , Spain
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Málaga, , Spain
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Santa Cruz de Tenerife, , Spain
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Seville, , Spain
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Gothenburg, , Sweden
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Örebro, , Sweden
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Stockholm, , Sweden
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Stockholm, , Sweden
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Stockholm, , Sweden
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Umeå, , Sweden
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Irvine, Ayrshire, United Kingdom
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Edgbaston, Birmingham, United Kingdom
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Exeter, Devon, United Kingdom
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Plymouth, Devon, United Kingdom
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London, Greater London, United Kingdom
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London, Greater London, United Kingdom
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Hammersmith, London, United Kingdom
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Edinburgh, Lothian Region, United Kingdom
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Salford, Manchester, United Kingdom
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Liverpool, Merseyside, United Kingdom
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Norwich, Norfolk, United Kingdom
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Nottingham, Nottinghamshire, United Kingdom
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Morriston, Swansea, United Kingdom
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Newcastle, Tyne, United Kingdom
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Brighton, , United Kingdom
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London, , United Kingdom
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Sheffield, , United Kingdom
Countries
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References
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Loomis SJ, Sadhu N, Fisher E, Gafson AR, Huang Y, Yang C, Hughes EE, Marshall E, Herman A, John S, Runz H, Jia X, Bhangale T, Bronson PG. Genome-wide study of longitudinal brain imaging measures of multiple sclerosis progression across six clinical trials. Sci Rep. 2023 Aug 31;13(1):14313. doi: 10.1038/s41598-023-41099-0.
Beynon V, George IC, Elliott C, Arnold DL, Ke J, Chen H, Zhu L, Ke C, Giovannoni G, Scaramozza M, Campbell N, Bradley DP, Franchimont N, Gafson A, Belachew S. Chronic lesion activity and disability progression in secondary progressive multiple sclerosis. BMJ Neurol Open. 2022 Jun 7;4(1):e000240. doi: 10.1136/bmjno-2021-000240. eCollection 2022.
Koch MW, Mostert J, Zhang Y, Wolinsky JS, Lublin FD, Strijbis E, Cutter G. Association of Age With Contrast-Enhancing Lesions Across the Multiple Sclerosis Disease Spectrum. Neurology. 2021 Sep 28;97(13):e1334-e1342. doi: 10.1212/WNL.0000000000012603. Epub 2021 Aug 10.
Kapoor R, Ho PR, Campbell N, Chang I, Deykin A, Forrestal F, Lucas N, Yu B, Arnold DL, Freedman MS, Goldman MD, Hartung HP, Havrdova EK, Jeffery D, Miller A, Sellebjerg F, Cadavid D, Mikol D, Steiner D; ASCEND investigators. Effect of natalizumab on disease progression in secondary progressive multiple sclerosis (ASCEND): a phase 3, randomised, double-blind, placebo-controlled trial with an open-label extension. Lancet Neurol. 2018 May;17(5):405-415. doi: 10.1016/S1474-4422(18)30069-3. Epub 2018 Mar 12.
Related Links
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Find out what to expect with TYSABRI MS treatment
Other Identifiers
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2010-021978-11
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
101MS326
Identifier Type: -
Identifier Source: org_study_id
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