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

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.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis, Relapsing-Remitting
• Intervention / Treatment: Biological: Alemtuzumab 12 mg; Biological: Alemtuzumab 24 mg; Biological: Interferon beta-1a

Detailed Description

Every participant received active treatment; there was no placebo. After Amendment 2, the 24 mg alemtuzumab dose was closed to enrollment so newly enrolled participants were randomly assigned to treatment with either 12 mg alemtuzumab or interferon beta-1a in a 2:1 ratio (that is, 2 given 12 mg 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 the CAMMS03409 Extension Study (NCT00930553) for safety and efficacy assessments. Participants who received interferon beta-1a and completed 2 years on study might be eligible to receive alemtuzumab in the Extension Study.

• Study Type: Interventional
• Enrollment (Actual): 840
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina
    • DIABAID
• Australia
  • Concord, Australia
    • Concord Repatriation General Hospital, Neurosciences Department
  • Kogarah, Australia
    • Southern Neurology
  • Liverpool, Australia, 2170
    • Liverpool Hospital, Neurology Department
  • New South Wales
    • Westmead, New South Wales, Australia
      • Westmead Hospital
  • Queensland
    • Auchenflower, Queensland, Australia, 4066
      • The Wesley Research Institute
    • Southport, Queensland, Australia
      • Griffith School of Medicine, Gold Coast Campus, Griffith University
  • South Australia
    • Woodville South, South Australia, Australia
      • Clinical Cognitive Research Unit/Clinical Trials, The Queen Elizabeth Hospital, Neurology Department
  • Tasmania
    • Hobart, Tasmania, Australia, 7000
      • Royal Hobart Hospital
  • Victoria
    • Fitzroy, Victoria, Australia
      • St. Vincent's Hospital, MS Education & Research, Department of Clinical Neurosciences
    • Heidelberg, Victoria, Australia
      • Austin Health
    • Parkville, Victoria, Australia, 3050
      • Royal Melbourne Hospital, Department of Neurology
• Austria
  • Wien, Austria
    • AKH Wien, Universitätsklinikum für Neurologie
• Belgium
  • Brussel, Belgium
    • Cliniques Universitaires Saint-Luc, Neurology
  • Esneux, Belgium
    • CHU Ourthe Amblève, Neurology
  • Leuven, Belgium
    • University Hospital Leuven, Campus Gasthuisberg, Neurology
• Brazil
  • Sao Paulo, Brazil
    • Hospital de Clínicas USP
  • Sao Paulo, Brazil
    • Irmandade Da Santa Casa de Misericordia de Sao Paulo
  • PE
    • Recife, PE, Brazil
      • Hospital da Restauração
  • RS
    • Porto Alegre, RS, Brazil
      • Hospital São Lucas PUC-RS
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada
      • UBC Hospital
  • Ontario
    • Kingston, Ontario, Canada
      • Multiple Sclerosis Clinic, Connell 7, Kingston General Hospital
    • London, Ontario, Canada
      • London Health Sciences Centre- University Hospital
    • Ottawa, Ontario, Canada
      • The Ottawa Hospital, General Campus
    • Toronto, Ontario, Canada
      • Sunnybrook Health Sciences Centre
  • Quebec
    • Gatineau, Quebec, Canada
      • Centre de Sante et de Services Sociaux de Gatineau-Hull Hospital
    • Greenfield park, Quebec, Canada
      • Clinique Neuro rive-sud, Recherche sepmus inc
    • Montreal, Quebec, Canada
      • Hospital Maisonneuve-Rosemont
    • Montreal, Quebec, Canada
      • Montreal Neurological Institute and Hospital
• Croatia
  • Rijeka, Croatia
    • Clinical Hospital Centre Rijeka, Clinic for Neurology
  • Varazdin, Croatia
    • General Hospital Varazdin, Department of Neurology
  • Zagreb, Croatia
    • Clinical Hospital Centre Zagreb
  • Zagreb, Croatia
    • Clinical Hospital Sestre Milosrdnice
  • Zagreb, Croatia
    • General Hospital " Sveti Duh", Department of neurology
• Czech Republic
  • Hradec Kralove, Czech Republic
    • MS Center, Department of Neurology
  • Pekarska, Czech Republic
    • St. Anne's University Hospital Brno
  • Praha 2, Czech Republic
    • Department of Neurology 1st Faculty of Medicine and General Teaching Hospital, MS Center
  • Teplice, Czech Republic
    • Krajska zdravotni a.s. - Hospital Teplice
• Denmark
  • Aarhus, Denmark
    • Århus Universitetshospital, Scleroseklinikken, Århus Sygehus
  • København, Denmark
    • Scleroseklinikken, Rigshospitalet
  • Odense, Denmark
    • Odense University Hospital
• France
  • Clermont-Ferrand, France
    • CHU Clermont-Ferrand, Hopital Gabriel Montpied
  • Dijon Cedex, France
    • Hôpital General, Service de Neurologie
  • Lille Cedex, France
    • Hospital Roger Salengro
  • Paris, France
    • Hôpital Pitié Salpétrière, Service de Neurologie
  • Rennes Cedex, France
    • Sevice de Neurologie
  • Strasbourg Cedex, France
    • Hôpital Civil, Departement de Neurologie
• Germany
  • Bayreuth, Germany
    • Krankenhaus Hohe Warte, Betriebsstätte der Bayreuth
  • Berlin, Germany
    • Jüdisches Krankenhaus Berlin
  • Berlin, Germany
    • Neurologisches Fachzentrum Berlin
  • Bonn, Germany
    • Neurologische Universitätsklinik Bonn
  • Dresden, Germany
    • Multiple Sklerose Zentrum am, Zentrum für klinische Neurowissenschaften, Neurologische Uniklinik Dresden
  • Hamburg, Germany
    • Asklepios Klinic Barmbek
  • Hannover, Germany
    • Medizinische Hochshule Hannover
  • Hennigsdorf, Germany
    • Oberhavelkliniken Hennigsdorf
  • Ingolstadt, Germany
    • Klinikum Ingolstadt, Neurologische Klinik
  • Muenchen, Germany
    • Klinikum Rechts der Isar, Klinik für Neurologie
  • Rostock, Germany
    • Klinik und Poliklinik fur Neurologie der Universitat Rockstock
  • Ulm, Germany
    • Universitätsklinik Ulm
  • Wermsdorf, Germany
    • Fachkrankenhaus Hubertusburg
• Israel
  • Jerusalem, Israel
    • Hadassah Medical Center Ein Karem
  • Tel Aviv, Israel
    • Tel Aviv Sourasky Medical Center, Department of Neurology
  • Tel Hashomer, Israel
    • Sheba Medical Centre
• Italy
  • Cagliari, Italy
    • Ospedale Binaghi - Centro Sclerosi Multipla
  • Gallarate, Italy
    • Ospedale S. Antonio Abate di Gallarate
  • Genova, Italy
    • Università di Genova Dipartimento di Neuroscienze Oftalmologia e Genetica
  • Montichiari, Italy
    • Ospedale Civile di Brescia c/o Ospedale Richiedei, Centro di riferimento per la Sclerosi Multiple
  • Orbassano, Italy
    • Ospedale San Luigi di Orbassano
  • Roma, Italy
    • Azienda Ospedaliera Sant'Andrea Neurologia
• Mexico
  • Chihuahua, Mexico
    • Unidad de Investigación en Salud de Chihuahua, S.C.
  • Mexico City, Mexico
    • Hospital Angeles del Pedregal; Camino a Santa Teresa
  • Tlalpan
    • Delegacion, Tlalpan, Mexico
      • Hospital Medica Sur CIF-BIOTEC
• Netherlands
  • Hertogenbosch, Netherlands
    • Jeroen Bosch Ziekenhuis
  • Sittard, Netherlands
    • Orbis Medisch Centrum, Department of Neurology
• Poland
  • Lodz, Poland
    • Independent Public Healthcare Facility, Norbert Barlicki University Hospital No. 1 of the Medical University of Lodz
  • Lublin, Poland
    • Independent Public Teaching Hospital No. 4 in Lublin
  • Poznan, Poland
    • Heliodor Swiecicki Teaching Hospital of the Poznan, University of Medical Sciences
• Russian Federation
  • Kazan, Russian Federation
    • Research Medical Complex "Your Health" Ltd
  • Moscow, Russian Federation
    • Institution of the Russian Academy of Medical Sciences, "Neurology Scientific Center under RAMS"
  • Moscow, Russian Federation
    • Moscow State Medical Institution City Clinical Hospital #11, Moscow City Center for Multiple Sclerosis
  • Moscow, Russian Federation
    • Moscow State Public Medical Institution, City Clinical Hospital #11
  • Nizhniy Novgorod, Russian Federation
    • Municipal Treatment and Prevention Institution, "City Hospital #33"
  • Novosibirsk, Russian Federation
    • Federal State Institution: Siberian District Medical Center
  • Samara, Russian Federation
    • State Medical Institution, "Samara Regional Clinical Hospital n.a. M.I. Kalinin"
  • St. Petersburg, Russian Federation
    • Institution of the Russian Academy of Sciences, "Institute of the Human Brain n.a. N.P. Bekhtereva within the Russian Academy of Sciences"
  • St. Petersburg, Russian Federation
    • St. Petersburg Pavlov State Medical University, Department of Neurology and Neurosurgery with a Clinic
  • St. Petersburg, Russian Federation
    • St.Petersburg State Medical Institution, "City Multispecialty Hospital #2"
  • St. Petersburg, Russian Federation
    • St.Petersburg State Medical Institution, "Nikolayevskaya Hospital"
• Serbia
  • Belgrade, Serbia
    • Clinic of Neurology, Clinical Centre of Serbia
  • Belgrade, Serbia
    • Military Medical Academy
  • Kragujevac, Serbia
    • Clinical Centre of Kragujevac
  • Novi Sad, Serbia
    • Clinical Centre Vojvodina Institute of Neurology
• Spain
  • Barcelona, Spain
    • Servicio de Neurología Hospital Vall d'Hebron Paseo de Vall d'Hebron
  • Madrid, Spain
    • Servicio de Neurología Hospital Clínico San Carlos
  • Malaga, Spain
    • Servicio de Neurología Hospital Carlos Haya
  • Sevilla, Spain
    • Servicio de Neurología Hospital Virgen de la Macarena
• Sweden
  • Gothenburg, Sweden
    • Sahlgrenska University Hospital, Neurologkliniken
  • Umea, Sweden
    • Norrlands Universitets sjukhus
• Ukraine
  • Kharkov, Ukraine
    • Institute of Neurology, Psychiatry and Narcology under the Academy of Medical Sciences of Ukraine
  • Kyiv, Ukraine
    • Kyiv Municipal Clinical Hospital #4, Department of Demyelinating Diseases of the Nervous System
  • Lviv, Ukraine
    • Danylo Halytsky Lviv National Medical University, Department of Neurology
• United Kingdom
  • Bristol, United Kingdom
    • Frenchay Hospital
  • Salford, United Kingdom
    • Salford Royal NHS Foundation Trust, Clinical Trials Unit
  • Sheffield, United Kingdom
    • Department of Neurology Glossop Road, Royal Hallamshire Hospital
  • England
    • Cambridge, England, United Kingdom
      • Department Of Neurosciences, Addenbrookes Hospital
    • London, England, United Kingdom
      • Centre for Neuroscience & Trauma, Blizard Institute of Cell and Molecular Science Barts and The London School of Medicine and Dentistry
• United States
  • Alabama
    • Cullman, Alabama, United States
      • North Central Neurology Associates, P.C.
  • Arizona
    • Phoenix, Arizona, United States
      • Barrow Neurological Institute, St. Joseph's Hospital and Medical Center
    • Phoenix, Arizona, United States
      • HOPE Research Institute
    • Scottsdale, Arizona, United States
      • Mayo Clinic Arizona, Department of Neurology
    • Tucson, Arizona, United States
      • Northwest NeuroSpecialists, PLLC
  • California
    • Berkeley, California, United States
      • East Bay Physicians Medical Group/Sutter East Bay Medical Foundation
    • La Habra, California, United States
      • Neurology Center of North Orange County
    • Los Angeles, California, United States
      • Department of Neurology, Keck School of Medicine, University of Southern California
    • Pasadena, California, United States
      • Neuro-Therapeutics Inc.
    • Pasadena, California, United States
      • Neuro-Therapeutics, Inc
    • Sacramento, California, United States
      • University of California, Davis Medical Center
    • Stanford, California, United States
      • Stanford University School of Medicine
  • Colorado
    • Aurora, Colorado, United States
      • University of Colorado Hospital, Anschutz Outpatient Pavilioin
    • Denver, Colorado, United States
      • Neurological Consultants
    • Fort Collins, Colorado, United States
      • Advanced Neurosciences Research
  • Connecticut
    • New Haven, Connecticut, United States
      • Yale University
  • District of Columbia
    • Washington, District of Columbia, United States
      • George Washington University Medical Faculty Associates
  • Florida
    • Jacksonville, Florida, United States
      • University of Florida Neuroscience Institute
    • Maitland, Florida, United States
      • Neurology Associates, P.A.
    • Pompano Beach, Florida, United States
      • Neurological Associates
    • Sarasota, Florida, United States
      • Negroski, Stein, Sutherland and Hanes Neurology
    • Tampa, Florida, United States
      • Axiom Clinical Research of Florida
    • Tampa, Florida, United States
      • University of South Florida, Department of Neurology
  • Georgia
    • Atlanta, Georgia, United States
      • Emory University, Department of Neurology
    • Atlanta, Georgia, United States
      • Shepherd Center, Inc.
  • Idaho
    • Idaho Falls, Idaho, United States
      • Idaho Falls Multiple Sclerosis Center, PLLC
  • Illinois
    • Chicago, Illinois, United States
      • University of Chicago Medical Center, Department of Neurology
    • Northbrook, Illinois, United States
      • Consultants in Neurology, Ltd
  • Indiana
    • Fort Wayne, Indiana, United States
      • Fort Wayne Neurological Center
    • Indianapolis, Indiana, United States
      • Indiana University School of Medicine, Department of Neurology
    • Indianapolis, Indiana, United States
      • Josephson Wallack Munshower Neurology P.C.
  • Iowa
    • Des Moines, Iowa, United States
      • Ruan Neurology Clinic and Research Center
    • Des Moines, Iowa, United States
      • Iowa Health Physicians
  • Kansas
    • Kansas City, Kansas, United States
      • University of Kansas Medical Center, Department of Neurology
    • Lenexa, Kansas, United States
      • MidAmerica Neuroscience Institute
  • Kentucky
    • Lexington, Kentucky, United States
      • Associates in Neurology, PSC
    • Louisville, Kentucky, United States
      • University of Louisville Research Foundation
  • Louisiana
    • Shreveport, Louisiana, United States
      • Louisiana State University Health Sciences Center
  • Massachusetts
    • Boston, Massachusetts, United States
      • Caritas St. Elizabeth's Medical Center
    • Boston, Massachusetts, United States
      • Partners Multiple Sclerosis Center/Brigham and Women's Hospital
    • Springfield, Massachusetts, United States
      • Springfield Neurology Associates, LLC
    • Worcester, Massachusetts, United States
      • UMASS Memorial Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States
      • University of Michigan Department of Neurology
    • Detroit, Michigan, United States
      • Henry Ford Hospital
    • Detroit, Michigan, United States
      • Wayne State University, School of Medicine, Department of Neurology
    • Grand Rapids, Michigan, United States
      • Spectrum Health Medical Group, Neurology (Previously known as Michigan Medical P.C., Neurology)
    • St. Clair Shores, Michigan, United States
      • Michigan Neurology Associates, P.C.
    • Traverse City, Michigan, United States
      • Northern Michigan Neurology
  • Minnesota
    • Rochester, Minnesota, United States
      • Mayo Clinic Rochester
  • Missouri
    • Kansas City, Missouri, United States
      • Neurology Consultants of Kansas City, Inc.
  • Montana
    • Missoula, Montana, United States
      • Montana Neurobehavioral Specialists
  • Nevada
    • Las Vegas, Nevada, United States
      • University of Nevada School of Medicine
    • Reno, Nevada, United States
      • Renown Institute for Neurosciences / Renown regional Medical Center
  • New Hampshire
    • Lebanon, New Hampshire, United States
      • Dartmouth-Hitchcock Medical Center, Norris Cotton Cancer Center
  • New Jersey
    • Teaneck, New Jersey, United States
      • MS Center at Holy Name Hospital
  • New Mexico
    • Alburquerque, New Mexico, United States
      • University of New Mexico, Health Sciences Center, MS Specialty Clinic
  • New York
    • Latham, New York, United States
      • Empire Neurology, PC
    • Mineola, New York, United States
      • Winthrop University Hospital, Clinical Trials Center
    • New York, New York, United States
      • Mount Sinai School of Medicine, Corinne Goldsmith Dickinson Center for Multiple Sclerosis
    • Patchogue, New York, United States
      • Comprehensive Multiple Sclerosis Care Center at South Shore Neurologic Associates, P.C.
    • Rochester, New York, United States
      • University of Rochester Medical Center
    • Syracuse, New York, United States
      • SUNY Upstate Medical University, Department of Neurology
  • North Carolina
    • Chapel Hill, North Carolina, United States
      • University of North Carolina-Chapel Hill, Department of Neurology
    • Winston-Salem, North Carolina, United States
      • Wake Forest University Health Science, Department of Neurology
  • Ohio
    • Cleveland, Ohio, United States
      • Cleveland Clinic Foundation, Mellen Center
    • Dayton, Ohio, United States
      • Neurology Specialists, Inc.
    • Uniontown, Ohio, United States
      • Oak Clinic for Multiple Sclerosis
  • Oklahoma
    • Oklahoma City, Oklahoma, United States
      • MS Center of Oklahoma
  • Pennsylvania
    • Allentown, Pennsylvania, United States
      • Lehigh Valley Hospital, Neuroscience and Pain Research
    • Erie, Pennsylvania, United States
      • Northshore Clinical Associates
    • Pittsburgh, Pennsylvania, United States
      • University of Pittsburgh, Kaufmann Medical Building
  • Rhode Island
    • Providence, Rhode Island, United States
      • The Neurology Foundation, Inc.
  • Tennessee
    • Cordova, Tennessee, United States
      • Neurology Clinic, P.C.
    • Franklin, Tennessee, United States
      • Advanced Neurosciences Institute
    • Franklin, Tennessee, United States
      • Biomedical Research Alliance of NY, LLC
    • Knoxville, Tennessee, United States
      • Hope Neurology PC
    • Nashville, Tennessee, United States
      • Vanderbilt Multiple Sclerosis Center
  • Texas
    • Dallas, Texas, United States
      • Clinical Center for Multiple Sclerosis
    • Round Rock, Texas, United States
      • Central Texas Neurology
    • San Antonio, Texas, United States
      • Integra Clinical Research
    • San Antonio, Texas, United States
      • Neurology Center of San Antonio
  • Virginia
    • Vienna, Virginia, United States
      • MS Center of Greater Washington, P.C.
  • Washington
    • Seattle, Washington, United States
      • Swedish Neuroscience Institute
    • Seattle, Washington, United States
      • Virginia Mason Medical Center
    • Spokane, Washington, United States
      • Rockwood Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Alemtuzumab 12 mg; Alemtuzumab (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.	Biological: Alemtuzumab 12 mg; 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.; Other Names: Lemtrada
Experimental: Alemtuzumab 24 mg; 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.	Biological: Alemtuzumab 24 mg; 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.; Other Names: Lemtrada
Active Comparator: Interferon Beta-1a; Interferon Beta-1a (Rebif®) 44 microgram (mcg) subcutaneously 3-times weekly for 24 months. Dose adjustment was done as per Investigator's discretion.	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.; Other Names: Rebif®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Were Relapse Free at Year 2	Participants were considered relapse free at Year 2 if they did not experience a relapse from the date of first study treatment to study completion at 24 months. Percentage of participants who were relapse free at Year 2, estimated using the KM method, was reported.	Year 2
Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Year 2	EDSS is an ordinal scale in half-point increments that qualifies disability in participants with multiple sclerosis (MS). It assesses the 7 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) as well as ambulation. EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS). Change was calculated by subtracting Baseline value from value at Year 2.	Baseline, Year 2
Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Score at Year 2	MSFC is a multidimensional measure consisting of quantitative tests of ambulation (Timed 25-Foot Walk), manual dexterity (9-Hole Peg Test; 9HPT), and cognitive function (Paced Auditory Serial Addition Test; PASAT). The MSFC score was calculated as the mean of the Z-scores of the 3 components. A Z-score was calculated by subtracting the mean of the reference population from the test result, then dividing by the standard deviation of the reference population. Higher Z-scores reflected better neurological function and a positive change from Baseline indicates improvement. An increase in score indicated an improvement (Z-score range: -3 to +3). Acquisition of disability was measured by change from Baseline in 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	Percent change in MS lesion volume as measured by MRI-T2 scan was calculated from MRI-T2-weighted scans as the following: (lesion volume at 2 years - lesion volume at Baseline)*100/ (lesion volume at Baseline).	Baseline, Year 2

Collaborators and Investigators

• Sponsor: Genzyme, a Sanofi Company
• Collaborators: Bayer

Publications and helpful links

General Publications

• 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.
• 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.
• 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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Helpful Links

• http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003718/WC500150521.pdf

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): September 1, 2011
• Study Completion (Actual): September 1, 2011

Study Registration Dates

• First Submitted: October 22, 2007
• First Submitted That Met QC Criteria: October 22, 2007
• First Posted (Estimate): October 24, 2007

Study Record Updates

• Last Update Posted (Actual): April 17, 2017
• Last Update Submitted That Met QC Criteria: March 17, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Multiple Sclerosis
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Physiological Effects of Drugs; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Adjuvants, Immunologic; Interferons; Interferon beta-1a; Interferon-beta; Alemtuzumab
• Other Study ID Numbers: CAMMS32400507; 2007-001162-32 (EudraCT Number); CAMMS324,; ISRCTN70702834 (Registry Identifier: ISRCTN); ACTRN12608000426381 (Registry Identifier: ANZCTR); NTR1469 (Registry Identifier: The Netherlands National Trial Register); CARE-MS II (Other Identifier: NMSS)