Efficacy and Safety of BIIB033 (Opicinumab) as an Add-on Therapy to Disease-Modifying Therapies (DMTs) in Relapsing Multiple Sclerosis (MS)

NCT ID: NCT03222973

Last Updated: 2022-04-28

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

263 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-11-15

Study Completion Date

2021-02-12

Brief Summary

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The primary objective of Part 1 of this study is to evaluate the effects of BIIB033 versus placebo on disability improvement over 72 weeks. The primary objective of Part 2 of this study is to evaluate the long-term safety profile of BIIB033 as an add-on therapy in participants with MS.

The secondary objective of Part 1 is to evaluate the effects of BIIB033 versus placebo on additional measures of disability improvement. The secondary objective of Part 2 is to investigate long-term efficacy (disability improvement) and additional safety measures of BIIB033 as an add-on therapy in participants with MS.

Detailed Description

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Conditions

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Multiple Sclerosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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BIIB033 (opicinumab) 750 mg

Participants with relapsing multiple sclerosis (RMS) will receive BIIB033 750 milligram (mg) intravenously (IV) as an add-on therapy to a background disease-modifying therapy (DMT) once every 4 weeks over 72 weeks in Part 1 and once every 4 weeks over 96 weeks in Part 2.

Group Type EXPERIMENTAL

BIIB033 (opicinumab)

Intervention Type DRUG

Administered as specified in the treatment arm

Placebo

Participants with RMS will receive placebo IV as an add-on therapy to a background DMT once every 4 weeks over 72 weeks in Part 1 and BIIB033 once every 4 weeks over 96 weeks in Part 2. The placebo looks like BIIB033 but does not contain the active ingredient that is thought to have an effect on MS disease. The placebo used in this study is sterile normal saline (water with a small amount of sodium chloride \[salt\]).

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Administered as specified in the treatment arm

Interventions

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BIIB033 (opicinumab)

Administered as specified in the treatment arm

Intervention Type DRUG

Placebo

Administered as specified in the treatment arm

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Baseline Expanded Disability Status Scale (EDSS) of 2.0 to 6.0, have a diagnosis of relapsing-remitting multiple sclerosis (RRMS) per the 2010 McDonald's criteria or onset of secondary progressive multiple sclerosis (SPMS) per the Lublin and Reingold criteria, and should have experienced their first MS symptom(s) within the previous 20 years.
* Subjects must have experienced at least 1 of the following within 24 months prior to Day 1/Baseline: a clinical relapse (but not within 24 weeks prior to Day 1/Baseline), gadolinium-enhancing lesions on brain or spinal cord magnetic resonance imaging (MRI), or new T2 lesion(s) on brain or spinal cord MRI.
* Subjects must be on a stable dose of a protocol-specified anti-inflammatory disease-modifying therapy (DMT) (IFNβ \[Avonex, Plegridy, Betaferon/Betaseron, or Rebif\], dimethyl fumarate (DMF) \[Tecfidera\], or natalizumab \[Tysabri\]) for at least 24 weeks prior to enrollment.
* In addition, subjects must have met protocol-defined MRI characteristics using magnetization transfer ratio (MTR) and diffusion tensor imaging (DTI) sequences at Screening/Baseline.


-Subjects who complete study treatment (BIIB033 or placebo) at Part 1/Week 72 Visit.

Exclusion Criteria

* Primary progressive MS
* An MS relapse that has occurred within 24 weeks prior to Day 1/Baseline or the subject has not stabilized from a previous relapse at the time of Screening.
* Treatment with any chemotherapeutic agents (e.g., mitoxantrone, cyclophosphamide, cladribine), cell-depleting monoclonal antibodies (mAbs) (e.g., rituximab, ocrelizumab, alemtuzumab), total lymphoid irradiation, T-cell or T-cell receptor vaccination, or teriflunomide within 1 year prior to Day 1/Baseline.
* Treatment with other anti-inflammatory DMTs (e.g., GA, fingolimod, daclizumab) or plasmapheresis within 24 weeks prior to Day1/Baseline.
* Treatment with Botox for limb spasticity within 24 weeks before Day 1/Baseline.
* Contraindications to MRI, for example, presence of pacemakers or other implanted metal devices (excluding dental braces), an allergy to gadolinium renal impairment, or claustrophobia that cannot be medically managed.
* History of human immunodeficiency virus or other immunodeficient conditions.
* History of malignancy; however, subjects with a history of excised or treated basal cell carcinoma or fewer than 3 squamous cell carcinomas are eligible to participate in this study.


* Subjects who did not complete study treatment in Part 1/Week 72 Visit
* Subjects who have a duration \>12 weeks between their Part 1/Week 72 Visit and Part 2/Day 1.
* Contraindications to MRI, for example, presence of pacemakers or other implanted metal devices (excluding dental braces), an allergy to Gd, renal impairment, or claustrophobia that cannot be medically managed.
* History of human immunodeficiency virus or other immunodeficient conditions not related to DMT treatment.
* History of malignancy unless enrollment is approved by the Sponsor; subjects with a history of excised or treated basal cell carcinoma or fewer than 3 squamous cell carcinomas are eligible to participate in this study.
Minimum Eligible Age

18 Years

Maximum Eligible Age

58 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Biogen

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Biogen

Locations

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Cullman, Alabama, United States

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Gilbert, Arizona, United States

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Berkeley, California, United States

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Long Beach, California, United States

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Newport Beach, California, United States

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Orange, California, United States

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Centennial, Colorado, United States

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Fort Collins, Colorado, United States

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Stamford, Connecticut, United States

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Washington D.C., District of Columbia, United States

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Sunrise, Florida, United States

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Tampa, Florida, United States

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Atlanta, Georgia, United States

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Chicago, Illinois, United States

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Chicago, Illinois, United States

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Overland Park, Kansas, United States

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Lexington, Kentucky, United States

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Baltimore, Maryland, United States

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Boston, Massachusetts, United States

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Boston, Massachusetts, United States

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Lexington, Massachusetts, United States

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Wellesley, Massachusetts, United States

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Farmington Hills, Michigan, United States

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Minneapolis, Minnesota, United States

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St Louis, Missouri, United States

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St Louis, Missouri, United States

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Las Vegas, Nevada, United States

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Freehold, New Jersey, 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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Patchogue, New York, United States

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Rochester, New York, United States

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Stony Brook, New York, United States

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Durham, North Carolina, United States

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Raleigh, North Carolina, United States

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Columbus, Ohio, United States

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Dayton, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Portland, Oregon, United States

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Pittsburgh, Pennsylvania, United States

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Willow Grove, Pennsylvania, United States

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Knoxville, Tennessee, United States

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Memphis, Tennessee, United States

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Dallas, Texas, United States

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Houston, Texas, United States

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Round Rock, Texas, United States

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Orem, Utah, United States

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Salt Lake City, Utah, United States

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Seattle, Washington, United States

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Seattle, Washington, United States

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Box Hill, Victoria, Australia

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Clayton, Victoria, Australia

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Heidelberg, Victoria, Australia

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Melbourne, Victoria, Australia

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Parkville, Victoria, Australia

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New Lambton Heights, , Australia

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Westmead, , Australia

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Bruges, , Belgium

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Brussels, , Belgium

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Brussels, , Belgium

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Ghent, , Belgium

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La Louvière, , Belgium

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Leuven, , Belgium

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Roeselare, , Belgium

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Edmonton, Alberta, Canada

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Vancouver, British Columbia, Canada

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Victoria, British Columbia, 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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Longueuil, Quebec, Canada

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Montreal, Quebec, Canada

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Brno, , Czechia

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Brno, , Czechia

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Hradec Králové, , Czechia

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Jihlava, , Czechia

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Pardubice, , Czechia

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Prague, , Czechia

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Strasbourg, Bas Rhin, France

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Nîmes, Gard, France

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Bordeaux, Gironde, France

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Toulouse, Haute Garonne, France

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Montpellier, Herault, France

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Nantes, Loire Atlantique, France

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Lille, Nord, France

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Clermont-Ferrand, Puy De Dome, France

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Bron, Rhone, France

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Amiens, Somme, France

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Paris, , France

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Freiburg im Breisgau, Baden-Wurttemberg, Germany

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Tübingen, Baden-Wurttemberg, Germany

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Ulm, Baden-Wurttemberg, Germany

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Munich, Bavaria, Germany

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Bochum, North Rhine-Westphalia, Germany

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Düsseldorf, North Rhine-Westphalia, Germany

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Trier, Rhineland-Palatinate, Germany

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Dresden, Saxony, Germany

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Berlin, , Germany

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Münster, , Germany

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Budapest, , Hungary

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Budapest, , Hungary

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Budapest, , Hungary

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Esztergom, , Hungary

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Kistarcsa, , Hungary

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Pécs, , Hungary

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Ramat Gan, , Israel

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Montichiari, Brescia, Italy

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Pozzilli, Isernia, Italy

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Cefalù, Palermo, Italy

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Genova, , Italy

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Messina, , Italy

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Milan, , Italy

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Milan, , Italy

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Napoli, , Italy

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Napoli, , Italy

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Napoli, , Italy

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Pisa, , Italy

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Roma, , Italy

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Verona, , Italy

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Geleen, , Netherlands

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Bydgoszcz, , Poland

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Gdansk, , 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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Szczecin, , Poland

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Warsaw, , Poland

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Zabrze, , Poland

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Salt, Girona, Spain

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Majadahonda, Madrid, Spain

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Barakaldo, Vizcaya, Spain

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Barcelona, , Spain

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Barcelona, , Spain

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Barcelona, , Spain

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Córdoba, , Spain

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Madrid, , Spain

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Seville, , Spain

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Aarau, , Switzerland

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Basel, , Switzerland

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Bern, , Switzerland

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Lugano, , Switzerland

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Zurich, , Switzerland

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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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Salford, Greater Manchester, United Kingdom

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Liverpool, Merseyside, United Kingdom

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Nottingham, Nottinghamshire, United Kingdom

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Oxford, Oxfordshire, United Kingdom

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Glasgow, Strathclyde, United Kingdom

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Newcastle upon Tyne, Tyne & Wear, United Kingdom

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Leeds, West Yorkshire, United Kingdom

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Brighton, , United Kingdom

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Sheffield, , United Kingdom

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Swansea, , United Kingdom

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Countries

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United States Australia Belgium Canada Czechia France Germany Hungary Israel Italy Netherlands Poland Spain Switzerland United Kingdom

References

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Elliott C, Rudko DA, Arnold DL, Fetco D, Elkady AM, Araujo D, Zhu B, Gafson A, Tian Z, Belachew S, Bradley DP, Fisher E. Lesion-level correspondence and longitudinal properties of paramagnetic rim and slowly expanding lesions in multiple sclerosis. Mult Scler. 2023 May;29(6):680-690. doi: 10.1177/13524585231162262. Epub 2023 Apr 10.

Reference Type DERIVED
PMID: 37036134 (View on PubMed)

Hanf KJM, Arndt JW, Liu Y, Gong BJ, Rushe M, Sopko R, Massol R, Smith B, Gao Y, Dalkilic-Liddle I, Lee X, Mojta S, Shao Z, Mi S, Pepinsky RB. Functional activity of anti-LINGO-1 antibody opicinumab requires target engagement at a secondary binding site. MAbs. 2020 Jan-Dec;12(1):1713648. doi: 10.1080/19420862.2020.1713648.

Reference Type DERIVED
PMID: 31928294 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2017-001224-22

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

215MS202

Identifier Type: -

Identifier Source: org_study_id

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