Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis, Study One
CARE-MS I
A Phase 3 Randomized, Rater-Blinded Study Comparing Two Annual Cycles of Intravenous Alemtuzumab to Three-Times Weekly Subcutaneous Interferon Beta-1a (Rebif®) in Treatment-Naïve Patients With Relapsing-Remitting Multiple Sclerosis
5 other identifiers
interventional
581
15 countries
96
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Aug 2007
Typical duration for phase_3
96 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
August 1, 2007
CompletedFirst Submitted
Initial submission to the registry
September 13, 2007
CompletedFirst Posted
Study publicly available on registry
September 17, 2007
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2011
CompletedStudy Completion
Last participant's last visit for all outcomes
April 1, 2011
CompletedResults Posted
Study results publicly available
November 24, 2014
CompletedNovember 24, 2014
November 1, 2014
3.7 years
September 13, 2007
November 17, 2014
November 17, 2014
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Percentage of Participants With Sustained Accumulation of Disability (SAD)
EDSS is an ordinal scale in half-point increments that quantifies 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 next 2 scheduled assessments, that is, 6 consecutive months. 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.
Up to 2 years
Annualized Relapse Rate
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.
Up to 2 years
Secondary Outcomes (4)
Percentage of Participants Who Were Relapse Free at Year 2
Year 2
Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Year 2
Baseline, Year 2
Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Score at Year 2
Baseline, Year 2
Percent Change From Baseline in Magnetic Resonance Imaging Time Constant 2 (MRI-T2) Hyperintense Lesion Volume at Year 2
Baseline, Year 2
Study Arms (2)
Alemtuzumab
EXPERIMENTALInterferon Beta-1a
ACTIVE COMPARATORInterventions
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 44 microgram (mcg) subcutaneously 3-times weekly for 24 months. Dose adjustment was done as per Investigator's discretion.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Genzyme, a Sanofi Companylead
- Bayercollaborator
Study Sites (101)
North Central Neurology Associates, P.C.
Cullman, Alabama, United States
Barrow Neurological Institute, St. Joseph's Hospital & Medical Center
Phoenix, Arizona, United States
Mayo Clinic Arizona
Scottsdale, Arizona, United States
Northwest NeuroSpecialists, PLLC
Tucson, Arizona, United States
Advanced Neurosciences Research
Fort Collins, Colorado, United States
Neurological Associates
Pompano Beach, Florida, United States
Axiom Clinical Research of Florida
Tampa, Florida, United States
Idaho Falls Multiple Sclerosis Center, PLLC
Idaho Falls, Idaho, United States
Consultants in Neurology, Ltd.
Northbrook, Illinois, United States
Fort Wayne Neurological Center
Fort Wayne, Indiana, United States
University of Kansas Medical Center
Kansas City, Kansas, United States
MidAmerican Neuroscience Institute
Lenexa, Kansas, United States
Associates in Neurology, PSC
Lexington, Kentucky, United States
University of Louisville Research Foundation
Louisville, Kentucky, United States
Louisiana State University Health Sciences Center
Shreveport, Louisiana, United States
UMass Memorial Medical Center
Worcester, Massachusetts, United States
University of Michigan Health System
Ann Arbor, Michigan, United States
Wayne State University
Detroit, Michigan, United States
University of Nevada School of Medicine
Las Vegas, Nevada, United States
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States
University of New Mexico, Health Sciences Center, MS Specialty Clinic
Albuquerque, New Mexico, United States
Empire Neurology
Latham, New York, United States
Comprehensive Multiple Sclerosis Care Center at South Shore Neurologic Associates, P.C.
Patchogue, New York, United States
University of Rochester Medical Center
Rochester, New York, United States
Carolinas Medical Center (CMC), Neurosciences & Spine Institute (NSSI)
Charlotte, North Carolina, United States
The Ohio State University Medical Center, Multiple Sclerosis Center
Columbus, Ohio, United States
Oak Clinic for Multiple Sclerosis
Uniontown, Ohio, United States
MS Center of Oklahoma
Oklahoma City, Oklahoma, United States
Lehigh Valley Hospital Neurosciences and Pain Research
Allentown, Pennsylvania, United States
Advanced Neurosciences Institute
Franklin, Tennessee, United States
Biomedical Research Alliance of NY, LLC
Franklin, Tennessee, United States
Hope Neurology PC
Knoxville, Tennessee, United States
Baylor College of Medicine, Maxine Mesinger MS Clinic
Houston, Texas, United States
Central Texas Neurology
Round Rock, Texas, United States
Integra Clinical Research
San Antonio, Texas, United States
Neurology Center of San Antonio
San Antonio, Texas, United States
DIABAID
Buenos Aires, Argentina
The Wesley Research Institute
Auchenflower, Queensland, 4066, Australia
Griffith University School of Medicine
Southport, Queensland, Australia
The Queen Elizabeth Hospital
Woodville South, South Australia, Australia
Royal Hobart Hospital
Hobart, Tasmania, 7000, Australia
St Vincent's Hospital
Fitzroy, Victoria, 3065, Australia
Austin Health
Heidelberg, Victoria, 3084, Australia
Royal Melbourne Hospital, Department of Neurology, Ward 4 East
Parkville, Victoria, 3050, Australia
Concord Repatriation General Hospital
Concord, Australia
Westmead Hospital
Westmead, Australia
Hospital da Restauracao, Av Governador Agamenon Magalhaes
Recife, Pernambuco, Brazil
Hospital Sao Lucas PUC-RS
Porto Alegre, Rio Grande do Sul, Brazil
Hospital de Clínicas USP
São Paulo, São Paulo, Brazil
University of Calgary and Foothills Medical Cenre
Calgary, Alberta, Canada
UBC Hospital
Vancouver, British Columbia, Canada
The Ottawa Hospital, General Campus
Ottawa, Ontario, Canada
Clinique Nuero-outaouais
Gatineau, Quebec, Canada
Clinique Neuro rive-sud, Recherche Sepmus, Inc.
Greenfield Park, Quebec, Canada
Clinical Hospital Centre Rijeka
Rijeka, Croatia
General Hospital Varazdin
Varaždin, Croatia
Clinical Hospital Centre "Sestre Milosrdnice"
Zagreb, Croatia
Clinical Hospital Centre Zagreb
Zagreb, Croatia
General Hospital "Sveti Duh"
Zagreb, Croatia
Department of Neurology, 1st Faculty of Medicine and General Teaching Hospital
Prague, Czechia
Krajska zdravotni a.s., Hospital Teplice
Teplice, Czechia
Hopital Purpan
Toulouse, France
Judisches Krankenhaus Berlin
Berlin, Germany
Universitätsklinik Carl Gustav Carus Dresden
Dresden, Germany
Klinikum der Goethe Universität Frankfurt
Frankfurt, Germany
Medizinische Hochschule Hannover
Hanover, Germany
Oberhavelkliniken Hennigsdorf
Hennigsdorf, Germany
Asklepios Klinikum Brandenburg
Teupitz, Germany
Hospital Angeles del Pedregal, Camino de Santa Teresa
Mexico City, Mexico
Hospital Medica Sur CIF-BIOTEC
Mexico City, Mexico
Clinical Neurology Centre Sp. z o.o. (Ltd)
Krakow, Poland
Independent Public Healthcare Facility, Norbert Barlicki University Hospital No. 1 of the Medical University of Lodz
Lodz, Poland
Independent Public Teaching Hospital No. 4 in Lublin
Lublin, Poland
Heliodor Swiecicki Teaching Hospital of the Poznan University of Medical Sciences
Poznan, Poland
Research Medical Complex "Your Health" Ltd
Kazan', Russia
Moscow City Hospital #11
Moscow, Russia
Moscow State Medical Institution City Clinical Hospital #11
Moscow, Russia
Scientific Neurology Center RAMS
Moscow, Russia
Municipal City Hospital #33
Nizhny Novgorod, Russia
Federal State Institution Siberian Rettitorial Medical Center under Federal Medical-Biological Agency of Russia
Novosibirsk, Russia
City Clinical Hospital #2
Pyatigorsk, Russia
Institute of Human Brain RAS
Saint Petersburg, Russia
Nikolaevskaya Hospital
Saint Petersburg, Russia
St. Petersburg Pavlov State Medical University
Saint Petersburg, Russia
Samara Regional Clinical Hospital n.a. Kalinin
Samara, Russia
State Medical Institution: Republican Clinical Hospital n.a. G.G. Kuvatov
Ufa, Russia
Clinical Centre Serbia, Institute for Neurology
Belgrade, Serbia
Military Medical Academy
Belgrade, Serbia
Clinical centre Kragujevac
Kragujevac, Serbia
Clinical Center Nis, Clinic for neurology
Niš, Serbia
Clinical Centre of Vojvodina, Clinic for neurology
Novi Sad, Serbia
Sahlgrenska University Hospital
Gothenburg, Sweden
Chernihiv Regional Hospital
Chernihiv, Ukraine
Institute of Neurology, Psychiatry and Narcology under the Academy of Medical Sciences of Ukraine, Department of Neuroinfection and Multiple Sclerosis
Kharkiv, Ukraine
Hospoital of the Directorate of the Medical Corps within the Ukrainian Security Service, Neurology Department
Kyiv, Ukraine
Kyiv Municipal Clinical Hospital #4
Kyiv, Ukraine
Danylo Halytsky Lviv National Medical University
Lviv, Ukraine
Department Of Neurosciences, Addenbrookes Hospital
Cambridge, England, United Kingdom
Centre for Neuroscience & Trauma, Blizard Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry
London, England, United Kingdom
University Hospital of Wales
Cardiff, Wales, United Kingdom
Royal Hallamshire Hospital
Sheffield, United Kingdom
Related Publications (16)
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.
PMID: 23122652BACKGROUNDZiemssen T, Bass AD, Van Wijmeersch B, Eichau S, Richter S, Hoffmann F, Armstrong NM, Chirieac M, Cunha-Santos J, Singer BA. Long-term efficacy and safety of alemtuzumab in participants with highly active MS: TOPAZ clinical trial and interim analysis of TREAT-MS real-world study. Ther Adv Neurol Disord. 2025 Feb 10;18:17562864241306575. doi: 10.1177/17562864241306575. eCollection 2025.
PMID: 39935588DERIVEDColes AJ, Achiron A, Traboulsee A, Singer BA, Pozzilli C, Oreja-Guevara C, Giovannoni G, Comi G, Freedman MS, Ziemssen T, Shiota D, Rawlings AM, Wong AT, Chirieac M, Montalban X. Safety and efficacy with alemtuzumab over 13 years in relapsing-remitting multiple sclerosis: final results from the open-label TOPAZ study. Ther Adv Neurol Disord. 2023 Sep 21;16:17562864231194823. doi: 10.1177/17562864231194823. eCollection 2023.
PMID: 37745914DERIVEDRiera R, Torloni MR, Martimbianco ALC, Pacheco RL. Alemtuzumab for multiple sclerosis. Cochrane Database Syst Rev. 2023 Jun 5;6(6):CD011203. doi: 10.1002/14651858.CD011203.pub3.
PMID: 37272540DERIVEDDayan CM, Lecumberri B, Muller I, Ganesananthan S, Hunter SF, Selmaj KW, Hartung HP, Havrdova EK, LaGanke CC, Ziemssen T, Van Wijmeersch B, Meuth SG, Margolin DH, Poole EM, Baker DP, Senior PA. Endocrine and multiple sclerosis outcomes in patients with autoimmune thyroid events in the alemtuzumab CARE-MS studies. Mult Scler J Exp Transl Clin. 2023 Jan 3;9(1):20552173221142741. doi: 10.1177/20552173221142741. eCollection 2023 Jan-Mar.
PMID: 36619856DERIVEDColes 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.
PMID: 34882037DERIVEDKuhle 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.
PMID: 34378446DERIVEDColes 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.
PMID: 34035833DERIVEDHorakova 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.
PMID: 33414927DERIVEDZiemssen 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.
PMID: 32710396DERIVEDComi 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.
PMID: 31762387DERIVEDVan 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.
PMID: 31675266DERIVEDOkai 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.
PMID: 31654272DERIVEDLi 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.
PMID: 30144037DERIVEDHavrdova 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.
PMID: 28835401DERIVEDArnold 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.
PMID: 27590291DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Trial Transparency Team
- Organization
- Sanofi
Study Officials
- STUDY DIRECTOR
Medical Monitor
Genzyme, a Sanofi Company
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 13, 2007
First Posted
September 17, 2007
Study Start
August 1, 2007
Primary Completion
April 1, 2011
Study Completion
April 1, 2011
Last Updated
November 24, 2014
Results First Posted
November 24, 2014
Record last verified: 2014-11