Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis, Study Two
CARE-MS II
A Phase 3, Randomized, Rater- and Dose-Blinded Study Comparing Two Annual Cycles of Intravenous Low- and High-Dose Alemtuzumab to Three-Times Weekly Subcutaneous Interferon Beta 1a (Rebif®) in Patients With Relapsing Remitting Multiple Sclerosis Who Have Relapsed On Therapy
7 other identifiers
interventional
840
21 countries
188
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Oct 2007
Typical duration for phase_3
188 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
October 1, 2007
CompletedFirst Submitted
Initial submission to the registry
October 22, 2007
CompletedFirst Posted
Study publicly available on registry
October 24, 2007
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2011
CompletedStudy Completion
Last participant's last visit for all outcomes
September 1, 2011
CompletedResults Posted
Study results publicly available
January 8, 2015
CompletedApril 17, 2017
March 1, 2017
3.9 years
October 22, 2007
November 17, 2014
March 17, 2017
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 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.
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 (3)
Alemtuzumab 12 mg
EXPERIMENTALAlemtuzumab (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 mg
EXPERIMENTALAlemtuzumab 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-1a
ACTIVE COMPARATORInterferon Beta-1a (Rebif®) 44 microgram (mcg) subcutaneously 3-times weekly for 24 months. Dose adjustment was done as per Investigator's discretion.
Interventions
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.
Alemtuzumab 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-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:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Genzyme, a Sanofi Companylead
- Bayercollaborator
Study Sites (191)
North Central Neurology Associates, P.C.
Cullman, Alabama, United States
Barrow Neurological Institute, St. Joseph's Hospital and Medical Center
Phoenix, Arizona, United States
Hope Research Institute
Phoenix, Arizona, United States
Mayo Clinic Arizona, Department of Neurology
Scottsdale, Arizona, United States
Northwest NeuroSpecialists, PLLC
Tucson, Arizona, 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
Department of Neurology, Keck School of Medicine, University of Southern California
Los Angeles, California, United States
Neuro-Therapeutics Inc.
Pasadena, California, United States
Neuro-Therapeutics, Inc
Pasadena, California, United States
University of California, Davis Medical Center
Sacramento, California, United States
Stanford University School of Medicine
Stanford, California, United States
University of Colorado Hospital, Anschutz Outpatient Pavilioin
Aurora, Colorado, United States
Neurological Consultants
Denver, Colorado, United States
Advanced Neurosciences Research
Fort Collins, Colorado, United States
Yale University
New Haven, Connecticut, United States
George Washington University Medical Faculty Associates
Washington D.C., District of Columbia, United States
University of Florida Neuroscience Institute
Jacksonville, Florida, United States
Neurology Associates, P.A.
Maitland, Florida, United States
Neurological Associates
Pompano Beach, Florida, United States
Negroski, Stein, Sutherland and Hanes Neurology
Sarasota, Florida, United States
Axiom Clinical Research of Florida
Tampa, Florida, United States
University of South Florida, Department of Neurology
Tampa, Florida, United States
Emory University, Department of Neurology
Atlanta, Georgia, United States
Shepherd Center, Inc.
Atlanta, Georgia, United States
Idaho Falls Multiple Sclerosis Center, PLLC
Idaho Falls, Idaho, United States
University of Chicago Medical Center, Department of Neurology
Chicago, Illinois, United States
Consultants in Neurology, Ltd
Northbrook, Illinois, United States
Fort Wayne Neurological Center
Fort Wayne, Indiana, United States
Indiana University School of Medicine, Department of Neurology
Indianapolis, Indiana, United States
Josephson Wallack Munshower Neurology P.C.
Indianapolis, Indiana, United States
Iowa Health Physicians
Des Moines, Iowa, United States
Ruan Neurology Clinic and Research Center
Des Moines, Iowa, United States
University of Kansas Medical Center, Department of Neurology
Kansas City, Kansas, United States
MidAmerica 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
Caritas St. Elizabeth's Medical Center
Boston, Massachusetts, United States
Partners Multiple Sclerosis Center/Brigham and Women's Hospital
Boston, Massachusetts, United States
Springfield Neurology Associates, LLC
Springfield, Massachusetts, United States
UMass Memorial Medical Center
Worcester, Massachusetts, United States
University of Michigan Department of Neurology
Ann Arbor, Michigan, United States
Henry Ford Hospital
Detroit, Michigan, United States
Wayne State University, School of Medicine, Department of Neurology
Detroit, Michigan, United States
Spectrum Health Medical Group, Neurology (Previously known as Michigan Medical P.C., Neurology)
Grand Rapids, Michigan, United States
Michigan Neurology Associates, P.C.
Saint Clair Shores, Michigan, United States
Northern Michigan Neurology
Traverse City, Michigan, United States
Mayo Clinic Rochester
Rochester, Minnesota, United States
Neurology Consultants of Kansas City, Inc.
Kansas City, Missouri, United States
Montana Neurobehavioral Specialists
Missoula, Montana, United States
University of Nevada School of Medicine
Las Vegas, Nevada, United States
Renown Institute for Neurosciences / Renown regional Medical Center
Reno, Nevada, United States
Dartmouth-Hitchcock Medical Center, Norris Cotton Cancer Center
Lebanon, New Hampshire, United States
MS Center at Holy Name Hospital
Teaneck, New Jersey, United States
University of New Mexico, Health Sciences Center, MS Specialty Clinic
Albuquerque, New Mexico, United States
Empire Neurology, PC
Latham, New York, United States
Winthrop University Hospital, Clinical Trials Center
Mineola, New York, United States
Mount Sinai School of Medicine, Corinne Goldsmith Dickinson Center for Multiple Sclerosis
New York, 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
SUNY Upstate Medical University, Department of Neurology
Syracuse, New York, United States
University of North Carolina-Chapel Hill, Department of Neurology
Chapel Hill, North Carolina, United States
Wake Forest University Health Science, Department of Neurology
Winston-Salem, North Carolina, United States
Cleveland Clinic Foundation, Mellen Center
Cleveland, Ohio, United States
Neurology Specialists, Inc.
Dayton, Ohio, United States
Oak Clinic for Multiple Sclerosis
Uniontown, Ohio, United States
MS Center of Oklahoma
Oklahoma City, Oklahoma, United States
Lehigh Valley Hospital, Neuroscience and Pain Research
Allentown, Pennsylvania, United States
Northshore Clinical Associates
Erie, Pennsylvania, United States
University of Pittsburgh, Kaufmann Medical Building
Pittsburgh, Pennsylvania, United States
The Neurology Foundation, Inc.
Providence, Rhode Island, United States
Neurology Clinic, P.C.
Cordova, Tennessee, 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
Vanderbilt Multiple Sclerosis Center
Nashville, Tennessee, United States
Clinical Center for Multiple Sclerosis
Dallas, 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
MS Center of Greater Washington, P.C.
Vienna, Virginia, United States
Swedish Neuroscience Institute
Seattle, Washington, United States
Virginia Mason Medical Center
Seattle, Washington, United States
Rockwood Clinical Research Center
Spokane, Washington, United States
DIABAID
Buenos Aires, Argentina
Westmead Hospital
Westmead, New South Wales, Australia
The Wesley Research Institute
Auchenflower, Queensland, 4066, Australia
Griffith School of Medicine, Gold Coast Campus, Griffith University
Southport, Queensland, Australia
Clinical Cognitive Research Unit/Clinical Trials, The Queen Elizabeth Hospital, Neurology Department
Woodville South, South Australia, Australia
Royal Hobart Hospital
Hobart, Tasmania, 7000, Australia
St. Vincent's Hospital, MS Education & Research, Department of Clinical Neurosciences
Fitzroy, Victoria, Australia
Austin Health
Heidelberg, Victoria, Australia
Royal Melbourne Hospital, Department of Neurology
Parkville, Victoria, 3050, Australia
Concord Repatriation General Hospital, Neurosciences Department
Concord, Australia
Southern Neurology
Kogarah, Australia
Liverpool Hospital, Neurology Department
Liverpool, 2170, Australia
AKH Wien, Universitätsklinikum für Neurologie
Vienna, Austria
Cliniques Universitaires Saint-Luc, Neurology
Brussels, Belgium
CHU Ourthe Amblève, Neurology
Esneux, Belgium
University Hospital Leuven, Campus Gasthuisberg, Neurology
Leuven, Belgium
Hospital da Restauracao
Recife, Pernambuco, Brazil
Hospital Sao Lucas PUC-RS
Porto Alegre, Rio Grande do Sul, Brazil
Hospital de Clínicas USP
São Paulo, Brazil
Irmandade da Santa Casa de Misericordia de Sao Paulo
São Paulo, Brazil
UBC Hospital
Vancouver, British Columbia, Canada
Multiple Sclerosis Clinic, Connell 7, Kingston General Hospital
Kingston, Ontario, Canada
London Health Sciences Centre- University Hospital
London, Ontario, Canada
The Ottawa Hospital, General Campus
Ottawa, Ontario, Canada
Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada
Centre de Sante et de Services Sociaux de Gatineau-Hull Hospital
Gatineau, Quebec, Canada
Clinique Neuro rive-sud, Recherche sepmus inc
Greenfield Park, Quebec, Canada
Hospital Maisonneuve-Rosemont
Montreal, Quebec, Canada
Montreal Neurological Institute and Hospital
Montreal, Quebec, Canada
Clinical Hospital Centre Rijeka, Clinic for Neurology
Rijeka, Croatia
General Hospital Varazdin, Department of neurology
Varaždin, Croatia
Clinical Hospital Centre Zagreb
Zagreb, Croatia
Clinical Hospital Sestre Milosrdnice
Zagreb, Croatia
General Hospital " Sveti Duh", Department of neurology
Zagreb, Croatia
MS Center, Department of Neurology
Hradec Králové, Czechia
St. Anne's University Hospital Brno
Pekarska, Czechia
Department of Neurology 1st Faculty of Medicine and General Teaching Hospital, MS Center
Prague, Czechia
Krajska zdravotni a.s. - Hospital Teplice
Teplice, Czechia
Århus Universitetshospital, Scleroseklinikken, Århus Sygehus
Aarhus, Denmark
Scleroseklinikken, Rigshospitalet
Copenhagen, Denmark
Odense University Hospital
Odense, Denmark
CHU Clermont-Ferrand, Hôpital Gabriel Montpied
Clermont-Ferrand, France
Hôpital General, Service de Neurologie
Dijon, France
Hospital Roger Salengro
Lille, France
Hôpital Pitié Salpétrière, Service de Neurologie
Paris, France
Sevice de Neurologie
Rennes, France
Hôpital Civil, Departement de Neurologie
Strasbourg, France
Krankenhaus Hohe Warte, Betriebsstätte der Bayreuth
Bayreuth, Germany
Judisches Krankenhaus Berlin
Berlin, Germany
Neurologisches Fachzentrum Berlin
Berlin, Germany
Neurologische Universitätsklinik Bonn
Bonn, Germany
Multiple Sklerose Zentrum am, Zentrum für klinische Neurowissenschaften, Neurologische Uniklinik Dresden
Dresden, Germany
Asklepios Klinic Barmbek
Hamburg, Germany
Medizinische Hochshule Hannover
Hanover, Germany
Oberhavelkliniken Hennigsdorf
Hennigsdorf, Germany
Klinikum Ingolstadt, Neurologische Klinik
Ingolstadt, Germany
Klinikum Rechts der Isar, Klinik für Neurologie
München, Germany
Klinik und Poliklinik fur Neurologie der Universitat Rockstock
Rostock, Germany
Universitatsklinik Ulm
Ulm, Germany
Fachkrankenhaus Hubertusburg
Wermsdorf, Germany
Hadassah Medical Center Ein Karem
Jerusalem, Israel
Tel Aviv Sourasky Medical Center, Department of Neurology
Tel Aviv, Israel
Sheba Medical Centre
Tel Litwinsky, Israel
Ospedale Binaghi - Centro Sclerosi Multipla
Cagliari, Italy
Ospedale S. Antonio Abate di Gallarate
Gallarate, Italy
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
Ospedale San Luigi di Orbassano
Orbassano, Italy
Azienda Ospedaliera Sant'Andrea Neurologia
Roma, Italy
Unidad de Investigación en Salud de Chihuahua, S.C.
Chihuahua City, Chihuahua, Mexico
Hospital Medica Sur CIF-BIOTEC
Delegacion, Tlalpan, Mexico
Hospital Angeles del Pedregal; Camino a Santa Teresa
Mexico City, Mexico
Jeroen Bosch Ziekenhuis
's-Hertogenbosch, Netherlands
Orbis Medisch Centrum, Department of Neurology
Sittard, Netherlands
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
Institution of the Russian Academy of Medical Sciences, "Neurology Scientific Center under RAMS"
Moscow, Russia
Moscow State Medical Institution City Clinical Hospital #11, Moscow City Center for Multiple Sclerosis
Moscow, Russia
Moscow State Public Medical Institution, City Clinical Hospital #11
Moscow, Russia
Municipal Treatment and Prevention Institution, "City Hospital #33"
Nizhny Novgorod, Russia
Federal State Institution: Siberian District Medical Center
Novosibirsk, Russia
Institution of the Russian Academy of Sciences, "Institute of the Human Brain n.a. N.P. Bekhtereva within the Russian Academy of Sciences"
Saint Petersburg, Russia
St. Petersburg Pavlov State Medical University, Department of Neurology and Neurosurgery with a Clinic
Saint Petersburg, Russia
St.Petersburg State Medical Institution, "City Multispecialty Hospital #2"
Saint Petersburg, Russia
St.Petersburg State Medical Institution, "Nikolayevskaya Hospital"
Saint Petersburg, Russia
State Medical Institution, "Samara Regional Clinical Hospital n.a. M.I. Kalinin"
Samara, Russia
Clinic of Neurology, Clinical Centre of Serbia
Belgrade, Serbia
Military Medical Academy
Belgrade, Serbia
Clinical Centre of Kragujevac
Kragujevac, Serbia
Clinical Centre Vojvodina Institute of Neurology
Novi Sad, Serbia
Servicio de Neurología Hospital Vall d'Hebron Paseo de Vall d'Hebron
Barcelona, Spain
Servicio de Neurología Hospital Clínico San Carlos
Madrid, Spain
Servicio de Neurología Hospital Carlos Haya
Málaga, Spain
Servicio de Neurología Hospital Virgen de la Macarena
Seville, Spain
Sahlgrenska University Hospital, Neurologkliniken
Gothenburg, Sweden
Norrlands Universitets sjukhus
Umeå, Sweden
Institute of Neurology, Psychiatry and Narcology under the Academy of Medical Sciences of Ukraine
Kharkiv, Ukraine
Kyiv Municipal Clinical Hospital #4, Department of Demyelinating Diseases of the Nervous System
Kyiv, Ukraine
Danylo Halytsky Lviv National Medical University, Department of Neurology
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
Frenchay Hospital
Bristol, United Kingdom
Salford Royal NHS Foundation Trust, Clinical Trials Unit
Salford, United Kingdom
Department of Neurology Glossop Road, Royal Hallamshire Hospital
Sheffield, United Kingdom
Related Publications (17)
Coles AJ, Twyman CL, Arnold DL, Cohen JA, Confavreux C, Fox EJ, Hartung HP, Havrdova E, Selmaj KW, Weiner HL, Miller T, Fisher E, Sandbrink R, Lake SL, Margolin DH, Oyuela P, Panzara MA, Compston DA; CARE-MS II investigators. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial. Lancet. 2012 Nov 24;380(9856):1829-39. doi: 10.1016/S0140-6736(12)61768-1. Epub 2012 Nov 1.
PMID: 23122650BACKGROUNDZiemssen 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: 34882037DERIVEDColes 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: 32710396DERIVEDGilmore W, Lund BT, Li P, Levy AM, Kelland EE, Akbari O, Groshen S, Cen SY, Pelletier D, Weiner LP, Javed A, Dunn JE, Traboulsee AL. Repopulation of T, B, and NK cells following alemtuzumab treatment in relapsing-remitting multiple sclerosis. J Neuroinflammation. 2020 Jun 15;17(1):189. doi: 10.1186/s12974-020-01847-9.
PMID: 32539719DERIVEDComi 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: 31654272DERIVEDArroyo R, Bury DP, Guo JD, Margolin DH, Melanson M, Daizadeh N, Cella D. Impact of alemtuzumab on health-related quality of life over 6 years in CARE-MS II trial extension patients with relapsing-remitting multiple sclerosis. Mult Scler. 2020 Jul;26(8):955-963. doi: 10.1177/1352458519849796. Epub 2019 May 30.
PMID: 31144568DERIVEDLi 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: 30144037DERIVEDArnold 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: 27590291DERIVEDGrafals M, Smith B, Murakami N, Trabucco A, Hamill K, Marangos E, Gilligan H, Pomfret EA, Pomposelli JJ, Simpson MA, Azzi J, Najafian N, Riella LV. Immunophenotyping and efficacy of low dose ATG in non-sensitized kidney recipients undergoing early steroid withdrawal: a randomized pilot study. PLoS One. 2014 Aug 11;9(8):e104408. doi: 10.1371/journal.pone.0104408. eCollection 2014.
PMID: 25111080DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
Efficacy analysis was not performed for Alemtuzumab 24 mg as recruitment to this arm was closed early to reduce overall sample size, duration of enrollment period, overall duration of study.
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
October 22, 2007
First Posted
October 24, 2007
Study Start
October 1, 2007
Primary Completion
September 1, 2011
Study Completion
September 1, 2011
Last Updated
April 17, 2017
Results First Posted
January 8, 2015
Record last verified: 2017-03