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

NCT ID: NCT00530348

Last Updated: 2014-11-24

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

581 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-08-31

Study Completion Date

2011-04-30

Brief Summary

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The purpose of this study was to establish the efficacy and safety of alemtuzumab (Lemtrada™) as a treatment for relapsing-remitting multiple sclerosis (MS), in comparison with subcutaneous (SC) interferon beta-1a (Rebif®). The study had enrolled participants who had not previously received MS disease-modifying therapies. Participants had monthly laboratory tests and comprehensive testing every 3 months.

Detailed Description

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Every participant had received active treatment; there was no placebo. Participants who qualified were randomly assigned to treatment with either alemtuzumab or SC interferon beta-1a at a 2:1 ratio (that is, 2 given 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 CAMMS03409 (NCT00930553) an extension study for safety and efficacy assessments. Participants who received interferon beta-1a and completed 2 years on study might be eligible to receive alemtuzumab on the extension study.

Conditions

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Multiple Sclerosis, Relapsing-Remitting

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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Alemtuzumab

Group Type EXPERIMENTAL

Alemtuzumab

Intervention Type BIOLOGICAL

Alemtuzumab 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.

Interferon Beta-1a

Group Type ACTIVE_COMPARATOR

Interferon beta-1a

Intervention Type BIOLOGICAL

Interferon beta-1a 44 microgram (mcg) subcutaneously 3-times weekly for 24 months. Dose adjustment was done as per Investigator's discretion.

Interventions

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Alemtuzumab

Alemtuzumab 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.

Intervention Type BIOLOGICAL

Interferon beta-1a

Interferon beta-1a 44 microgram (mcg) subcutaneously 3-times weekly for 24 months. Dose adjustment was done as per Investigator's discretion.

Intervention Type BIOLOGICAL

Other Intervention Names

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Lemtrada Rebif®

Eligibility Criteria

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Inclusion Criteria

* Given written/signed informed consent
* Age 18 to 50 years old (inclusive) as of the date the informed consent form (ICF) was signed
* Diagnosis of MS per updated McDonald criteria, and cranial magnetic resonance imaging (MRI) scan demonstrating white matter lesions attributable to MS within 5 years of screening
* Onset of MS symptoms (as determined by a neurologist, either at screening or retrospectively) within 5 years of the date the ICF was signed
* Expanded Disability Status Scale (EDSS) score 0.0 to 3.0 (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

Exclusion Criteria

* Received prior therapy for MS other than corticosteroids, for example, alemtuzumab, interferons, intravenous immunoglobulin, glatiramer acetate, natalizumab, and mitoxantrone
* Exposure to azathioprine, cladribine, cyclophosphamide, cyclosporine A, methotrexate, or any other immunosuppressive agent other than systemic corticosteroid treatment
* Any progressive form of MS
* History of malignancy (except basal skin cell carcinoma)
* CD4 + , CD8 + count, B cell, or absolute neutrophil count less than (\<) lower limit of normal (LLN) at screening
* 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Bayer

INDUSTRY

Sponsor Role collaborator

Genzyme, a Sanofi Company

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Monitor

Role: STUDY_DIRECTOR

Genzyme, a Sanofi Company

Locations

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North Central Neurology Associates, P.C.

Cullman, Alabama, United States

Site Status

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

Phoenix, Arizona, United States

Site Status

Mayo Clinic Arizona

Scottsdale, Arizona, United States

Site Status

Northwest NeuroSpecialists, PLLC

Tucson, Arizona, United States

Site Status

Advanced Neurosciences Research

Fort Collins, Colorado, United States

Site Status

Neurological Associates

Pompano Beach, Florida, United States

Site Status

Axiom Clinical Research of Florida

Tampa, Florida, United States

Site Status

Idaho Falls Multiple Sclerosis Center, PLLC

Idaho Falls, Idaho, United States

Site Status

Consultants in Neurology, Ltd.

Northbrook, Illinois, United States

Site Status

Fort Wayne Neurological Center

Fort Wayne, Indiana, United States

Site Status

University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status

MidAmerican Neuroscience Institute

Lenexa, Kansas, United States

Site Status

Associates in Neurology, PSC

Lexington, Kentucky, United States

Site Status

University of Louisville Research Foundation

Louisville, Kentucky, United States

Site Status

Louisiana State University Health Sciences Center

Shreveport, Louisiana, United States

Site Status

UMass Memorial Medical Center

Worcester, Massachusetts, United States

Site Status

University of Michigan Health System

Ann Arbor, Michigan, United States

Site Status

Wayne State University

Detroit, Michigan, United States

Site Status

University of Nevada School of Medicine

Las Vegas, Nevada, United States

Site Status

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States

Site Status

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

Albuquerque, New Mexico, United States

Site Status

Empire Neurology

Latham, New York, United States

Site Status

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

Patchogue, New York, United States

Site Status

University of Rochester Medical Center

Rochester, New York, United States

Site Status

Carolinas Medical Center (CMC), Neurosciences & Spine Institute (NSSI)

Charlotte, North Carolina, United States

Site Status

The Ohio State University Medical Center, Multiple Sclerosis Center

Columbus, Ohio, United States

Site Status

Oak Clinic for Multiple Sclerosis

Uniontown, Ohio, United States

Site Status

MS Center of Oklahoma

Oklahoma City, Oklahoma, United States

Site Status

Lehigh Valley Hospital Neurosciences and Pain Research

Allentown, Pennsylvania, United States

Site Status

Advanced Neurosciences Institute

Franklin, Tennessee, United States

Site Status

Biomedical Research Alliance of NY, LLC

Franklin, Tennessee, United States

Site Status

Hope Neurology PC

Knoxville, Tennessee, United States

Site Status

Baylor College of Medicine, Maxine Mesinger MS Clinic

Houston, Texas, United States

Site Status

Central Texas Neurology

Round Rock, Texas, United States

Site Status

Integra Clinical Research

San Antonio, Texas, United States

Site Status

Neurology Center of San Antonio

San Antonio, Texas, United States

Site Status

DIABAID

Buenos Aires, , Argentina

Site Status

The Wesley Research Institute

Auchenflower, Queensland, Australia

Site Status

Griffith University School of Medicine

Southport, Queensland, Australia

Site Status

The Queen Elizabeth Hospital

Woodville South, South Australia, Australia

Site Status

Royal Hobart Hospital

Hobart, Tasmania, Australia

Site Status

St Vincent's Hospital

Fitzroy, Victoria, Australia

Site Status

Austin Health

Heidelberg, Victoria, Australia

Site Status

Royal Melbourne Hospital, Department of Neurology, Ward 4 East

Parkville, Victoria, Australia

Site Status

Concord Repatriation General Hospital

Concord, , Australia

Site Status

Westmead Hospital

Westmead, , Australia

Site Status

Hospital da Restauracao, Av Governador Agamenon Magalhaes

Recife, Pernambuco, Brazil

Site Status

Hospital Sao Lucas PUC-RS

Porto Alegre, Rio Grande do Sul, Brazil

Site Status

Hospital de Clínicas USP

São Paulo, São Paulo, Brazil

Site Status

University of Calgary and Foothills Medical Cenre

Calgary, Alberta, Canada

Site Status

UBC Hospital

Vancouver, British Columbia, Canada

Site Status

The Ottawa Hospital, General Campus

Ottawa, Ontario, Canada

Site Status

Clinique Nuero-outaouais

Gatineau, Quebec, Canada

Site Status

Clinique Neuro rive-sud, Recherche Sepmus, Inc.

Greenfield Park, Quebec, Canada

Site Status

Clinical Hospital Centre Rijeka

Rijeka, , Croatia

Site Status

General Hospital Varazdin

Varaždin, , Croatia

Site Status

Clinical Hospital Centre "Sestre Milosrdnice"

Zagreb, , Croatia

Site Status

Clinical Hospital Centre Zagreb

Zagreb, , Croatia

Site Status

General Hospital "Sveti Duh"

Zagreb, , Croatia

Site Status

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

Prague, , Czechia

Site Status

Krajska zdravotni a.s., Hospital Teplice

Teplice, , Czechia

Site Status

Hopital Purpan

Toulouse, , France

Site Status

Judisches Krankenhaus Berlin

Berlin, , Germany

Site Status

Universitätsklinik Carl Gustav Carus Dresden

Dresden, , Germany

Site Status

Klinikum der Goethe Universität Frankfurt

Frankfurt, , Germany

Site Status

Medizinische Hochschule Hannover

Hanover, , Germany

Site Status

Oberhavelkliniken Hennigsdorf

Hennigsdorf, , Germany

Site Status

Asklepios Klinikum Brandenburg

Teupitz, , Germany

Site Status

Hospital Angeles del Pedregal, Camino de Santa Teresa

Mexico City, , Mexico

Site Status

Hospital Medica Sur CIF-BIOTEC

Mexico City, , Mexico

Site Status

Clinical Neurology Centre Sp. z o.o. (Ltd)

Krakow, , Poland

Site Status

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

Lodz, , Poland

Site Status

Independent Public Teaching Hospital No. 4 in Lublin

Lublin, , Poland

Site Status

Heliodor Swiecicki Teaching Hospital of the Poznan University of Medical Sciences

Poznan, , Poland

Site Status

Research Medical Complex "Your Health" Ltd

Kazan', , Russia

Site Status

Moscow City Hospital #11

Moscow, , Russia

Site Status

Moscow State Medical Institution City Clinical Hospital #11

Moscow, , Russia

Site Status

Scientific Neurology Center RAMS

Moscow, , Russia

Site Status

Municipal City Hospital #33

Nizhny Novgorod, , Russia

Site Status

Federal State Institution Siberian Rettitorial Medical Center under Federal Medical-Biological Agency of Russia

Novosibirsk, , Russia

Site Status

City Clinical Hospital #2

Pyatigorsk, , Russia

Site Status

Institute of Human Brain RAS

Saint Petersburg, , Russia

Site Status

Nikolaevskaya Hospital

Saint Petersburg, , Russia

Site Status

St. Petersburg Pavlov State Medical University

Saint Petersburg, , Russia

Site Status

Samara Regional Clinical Hospital n.a. Kalinin

Samara, , Russia

Site Status

State Medical Institution: Republican Clinical Hospital n.a. G.G. Kuvatov

Ufa, , Russia

Site Status

Clinical Centre Serbia, Institute for Neurology

Belgrade, , Serbia

Site Status

Military Medical Academy

Belgrade, , Serbia

Site Status

Clinical centre Kragujevac

Kragujevac, , Serbia

Site Status

Clinical Center Nis, Clinic for neurology

Niš, , Serbia

Site Status

Clinical Centre of Vojvodina, Clinic for neurology

Novi Sad, , Serbia

Site Status

Sahlgrenska University Hospital

Gothenburg, , Sweden

Site Status

Chernihiv Regional Hospital

Chernihiv, , Ukraine

Site Status

Institute of Neurology, Psychiatry and Narcology under the Academy of Medical Sciences of Ukraine, Department of Neuroinfection and Multiple Sclerosis

Kharkiv, , Ukraine

Site Status

Hospoital of the Directorate of the Medical Corps within the Ukrainian Security Service, Neurology Department

Kyiv, , Ukraine

Site Status

Kyiv Municipal Clinical Hospital #4

Kyiv, , Ukraine

Site Status

Danylo Halytsky Lviv National Medical University

Lviv, , Ukraine

Site Status

Department Of Neurosciences, Addenbrookes Hospital

Cambridge, England, United Kingdom

Site Status

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

London, England, United Kingdom

Site Status

University Hospital of Wales

Cardiff, Wales, United Kingdom

Site Status

Royal Hallamshire Hospital

Sheffield, , United Kingdom

Site Status

Countries

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United States Argentina Australia Brazil Canada Croatia Czechia France Germany Mexico Poland Russia Serbia Sweden Ukraine United Kingdom

References

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Cohen JA, Coles AJ, Arnold DL, Confavreux C, Fox EJ, Hartung HP, Havrdova E, Selmaj KW, Weiner HL, Fisher E, Brinar VV, Giovannoni G, Stojanovic M, Ertik BI, Lake SL, Margolin DH, Panzara MA, Compston DA; CARE-MS I investigators. Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial. Lancet. 2012 Nov 24;380(9856):1819-28. doi: 10.1016/S0140-6736(12)61769-3. Epub 2012 Nov 1.

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Coles AJ, Jones JL, Vermersch P, Traboulsee A, Bass AD, Boster A, Chan A, Comi G, Fernandez O, Giovannoni G, Kubala Havrdova E, LaGanke C, Montalban X, Oreja-Guevara C, Piehl F, Wiendl H, Ziemssen T. Autoimmunity and long-term safety and efficacy of alemtuzumab for multiple sclerosis: Benefit/risk following review of trial and post-marketing data. Mult Scler. 2022 Apr;28(5):842-846. doi: 10.1177/13524585211061335. Epub 2021 Dec 9.

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Kuhle J, Daizadeh N, Benkert P, Maceski A, Barro C, Michalak Z, Sormani MP, Godin J, Shankara S, Samad TA, Jacobs A, Chung L, Rӧsch N, Kaiser C, Mitchell CP, Leppert D, Havari E, Kappos L. Sustained reduction of serum neurofilament light chain over 7 years by alemtuzumab in early relapsing-remitting MS. Mult Scler. 2022 Apr;28(4):573-582. doi: 10.1177/13524585211032348. Epub 2021 Aug 11.

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Coles AJ, Arnold DL, Bass AD, Boster AL, Compston DAS, Fernandez O, Havrdova EK, Nakamura K, Traboulsee A, Ziemssen T, Jacobs A, Margolin DH, Huang X, Daizadeh N, Chirieac MC, Selmaj KW. Efficacy and safety of alemtuzumab over 6 years: final results of the 4-year CARE-MS extension trial. Ther Adv Neurol Disord. 2021 Apr 23;14:1756286420982134. doi: 10.1177/1756286420982134. eCollection 2021.

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PMID: 34035833 (View on PubMed)

Horakova D, Boster A, Bertolotto A, Freedman MS, Firmino I, Cavalier SJ, Jacobs AK, Thangavelu K, Daizadeh N, Poole EM, Baker DP, Margolin DH, Ziemssen T; CARE-MS I, CARE-MS II, and CAMMS03409 Investigators. Proportion of alemtuzumab-treated patients converting from relapsing-remitting multiple sclerosis to secondary progressive multiple sclerosis over 6 years. Mult Scler J Exp Transl Clin. 2020 Dec 18;6(4):2055217320972137. doi: 10.1177/2055217320972137. eCollection 2020 Oct-Dec.

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PMID: 33414927 (View on PubMed)

Ziemssen T, Bass AD, Berkovich R, Comi G, Eichau S, Hobart J, Hunter SF, LaGanke C, Limmroth V, Pelletier D, Pozzilli C, Schippling S, Sousa L, Traboulsee A, Uitdehaag BMJ, Van Wijmeersch B, Choudhry Z, Daizadeh N, Singer BA; CARE-MS I, CARE-MS II, CAMMS03409, and TOPAZ investigators. Efficacy and Safety of Alemtuzumab Through 9 Years of Follow-up in Patients with Highly Active Disease: Post Hoc Analysis of CARE-MS I and II Patients in the TOPAZ Extension Study. CNS Drugs. 2020 Sep;34(9):973-988. doi: 10.1007/s40263-020-00749-x.

Reference Type DERIVED
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Comi G, Alroughani R, Boster AL, Bass AD, Berkovich R, Fernandez O, Kim HJ, Limmroth V, Lycke J, Macdonell RA, Sharrack B, Singer BA, Vermersch P, Wiendl H, Ziemssen T, Jacobs A, Daizadeh N, Rodriguez CE, Traboulsee A; CARE-MS I, CARE-MS II, CAMMS03409, and TOPAZ Investigators. Efficacy of alemtuzumab in relapsing-remitting MS patients who received additional courses after the initial two courses: Pooled analysis of the CARE-MS, extension, and TOPAZ studies. Mult Scler. 2020 Dec;26(14):1866-1876. doi: 10.1177/1352458519888610. Epub 2019 Nov 25.

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Van Wijmeersch B, Singer BA, Boster A, Broadley S, Fernandez O, Freedman MS, Izquierdo G, Lycke J, Pozzilli C, Sharrack B, Steingo B, Wiendl H, Wray S, Ziemssen T, Chung L, Margolin DH, Thangavelu K, Vermersch P. Efficacy of alemtuzumab over 6 years in relapsing-remitting multiple sclerosis patients who relapsed between courses 1 and 2: Post hoc analysis of the CARE-MS studies. Mult Scler. 2020 Nov;26(13):1719-1728. doi: 10.1177/1352458519881759. Epub 2019 Nov 1.

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Okai AF, Amezcua L, Berkovich RR, Chinea AR, Edwards KR, Steingo B, Walker A, Jacobs AK, Daizadeh N, Williams MJ; CARE-MS I, CARE-MS II, CAMMS03409, and TOPAZ Investigators. Efficacy and Safety of Alemtuzumab in Patients of African Descent with Relapsing-Remitting Multiple Sclerosis: 8-Year Follow-up of CARE-MS I and II (TOPAZ Study). Neurol Ther. 2019 Dec;8(2):367-381. doi: 10.1007/s40120-019-00159-2. Epub 2019 Oct 25.

Reference Type DERIVED
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Li Z, Richards S, Surks HK, Jacobs A, Panzara MA. Clinical pharmacology of alemtuzumab, an anti-CD52 immunomodulator, in multiple sclerosis. Clin Exp Immunol. 2018 Dec;194(3):295-314. doi: 10.1111/cei.13208. Epub 2018 Oct 1.

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PMID: 30144037 (View on PubMed)

Havrdova E, Arnold DL, Cohen JA, Hartung HP, Fox EJ, Giovannoni G, Schippling S, Selmaj KW, Traboulsee A, Compston DAS, Margolin DH, Thangavelu K, Rodriguez CE, Jody D, Hogan RJ, Xenopoulos P, Panzara MA, Coles AJ; CARE-MS I and CAMMS03409 Investigators. Alemtuzumab CARE-MS I 5-year follow-up: Durable efficacy in the absence of continuous MS therapy. Neurology. 2017 Sep 12;89(11):1107-1116. doi: 10.1212/WNL.0000000000004313. Epub 2017 Aug 23.

Reference Type DERIVED
PMID: 28835401 (View on PubMed)

Arnold DL, Fisher E, Brinar VV, Cohen JA, Coles AJ, Giovannoni G, Hartung HP, Havrdova E, Selmaj KW, Stojanovic M, Weiner HL, Lake SL, Margolin DH, Thomas DR, Panzara MA, Compston DA; CARE-MS I and CARE-MS II Investigators. Superior MRI outcomes with alemtuzumab compared with subcutaneous interferon beta-1a in MS. Neurology. 2016 Oct 4;87(14):1464-1472. doi: 10.1212/WNL.0000000000003169. Epub 2016 Sep 2.

Reference Type DERIVED
PMID: 27590291 (View on PubMed)

Other Identifiers

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ISRCTN21534255

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTRN12608000435381

Identifier Type: REGISTRY

Identifier Source: secondary_id

CARE-MS I

Identifier Type: OTHER

Identifier Source: secondary_id

2007-001161-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CAMMS323

Identifier Type: -

Identifier Source: org_study_id