AzTrials
AzTrials

Multiple Sclerosis, Relapsing-RemittingPhase 3CARE-MS IINCT00548405

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

A Phase 3 study testing Alemtuzumab 12 mg, Alemtuzumab 24 mg and Interferon beta-1a in people with Multiple Sclerosis, Relapsing-Remitting, run by Genzyme, a Sanofi Company at 191 sites in 23 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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®). Read more about this study

Who is it for?
Ages 18 to 55 years
Conditions the study is for
Multiple Sclerosis, Relapsing-Remitting
What is being tested?
Alemtuzumab 12 mg, Alemtuzumab 24 mg and Interferon beta-1a
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
840 participants
Where
191 sitesin 23 countries
Study dates
Oct 2007to Sep 2011
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 55 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

191 sites in 23 countries.

191 sites in 23 countries

United States85 sites

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

    Albuquerque, New Mexico

  • Lehigh Valley Hospital, Neuroscience and Pain Research

    Allentown, Pennsylvania

  • University of Michigan Department of Neurology

    Ann Arbor, Michigan

  • Emory University, Department of Neurology

    Atlanta, Georgia

  • Shepherd Center, Inc.

    Atlanta, Georgia

  • University of Colorado Hospital, Anschutz Outpatient Pavilioin

    Aurora, Colorado

  • East Bay Physicians Medical Group/Sutter East Bay Medical Foundation

    Berkeley, California

  • Caritas St. Elizabeth's Medical Center

    Boston, Massachusetts

  • Partners Multiple Sclerosis Center/Brigham and Women's Hospital

    Boston, Massachusetts

  • University of North Carolina-Chapel Hill, Department of Neurology

    Chapel Hill, North Carolina

  • University of Chicago Medical Center, Department of Neurology

    Chicago, Illinois

  • Cleveland Clinic Foundation, Mellen Center

    Cleveland, Ohio

  • Neurology Clinic, P.C.

    Cordova, Tennessee

  • North Central Neurology Associates, P.C.

    Cullman, Alabama

  • Clinical Center for Multiple Sclerosis

    Dallas, Texas

  • Neurology Specialists, Inc.

    Dayton, Ohio

  • Neurological Consultants

    Denver, Colorado

  • Iowa Health Physicians

    Des Moines, Iowa

  • Ruan Neurology Clinic and Research Center

    Des Moines, Iowa

  • Henry Ford Hospital

    Detroit, Michigan

  • Wayne State University, School of Medicine, Department of Neurology

    Detroit, Michigan

  • Northshore Clinical Associates

    Erie, Pennsylvania

  • Advanced Neurosciences Research

    Fort Collins, Colorado

  • Fort Wayne Neurological Center

    Fort Wayne, Indiana

  • Advanced Neurosciences Institute

    Franklin, Tennessee

  • Biomedical Research Alliance of NY, LLC

    Franklin, Tennessee

  • Spectrum Health Medical Group, Neurology (Previously known as Michigan Medical P.C., Neurology)

    Grand Rapids, Michigan

  • Idaho Falls Multiple Sclerosis Center, PLLC

    Idaho Falls, Idaho

  • Indiana University School of Medicine, Department of Neurology

    Indianapolis, Indiana

  • Josephson Wallack Munshower Neurology P.C.

    Indianapolis, Indiana

  • University of Florida Neuroscience Institute

    Jacksonville, Florida

  • University of Kansas Medical Center, Department of Neurology

    Kansas City, Kansas

  • Neurology Consultants of Kansas City, Inc.

    Kansas City, Missouri

  • Hope Neurology PC

    Knoxville, Tennessee

  • Neurology Center of North Orange County

    La Habra, California

  • University of Nevada School of Medicine

    Las Vegas, Nevada

  • Empire Neurology, PC

    Latham, New York

  • Dartmouth-Hitchcock Medical Center, Norris Cotton Cancer Center

    Lebanon, New Hampshire

  • MidAmerica Neuroscience Institute

    Lenexa, Kansas

  • Associates in Neurology, PSC

    Lexington, Kentucky

  • Department of Neurology, Keck School of Medicine, University of Southern California

    Los Angeles, California

  • University of Louisville Research Foundation

    Louisville, Kentucky

  • Neurology Associates, P.A.

    Maitland, Florida

  • Winthrop University Hospital, Clinical Trials Center

    Mineola, New York

  • Montana Neurobehavioral Specialists

    Missoula, Montana

  • Vanderbilt Multiple Sclerosis Center

    Nashville, Tennessee

  • Yale University

    New Haven, Connecticut

  • Mount Sinai School of Medicine, Corinne Goldsmith Dickinson Center for Multiple Sclerosis

    New York, New York

  • Consultants in Neurology, Ltd

    Northbrook, Illinois

  • MS Center of Oklahoma

    Oklahoma City, Oklahoma

  • Neuro-Therapeutics Inc.

    Pasadena, California

  • Neuro-Therapeutics, Inc

    Pasadena, California

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

    Patchogue, New York

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

    Phoenix, Arizona

  • Hope Research Institute

    Phoenix, Arizona

  • University of Pittsburgh, Kaufmann Medical Building

    Pittsburgh, Pennsylvania

  • Neurological Associates

    Pompano Beach, Florida

  • The Neurology Foundation, Inc.

    Providence, Rhode Island

  • Renown Institute for Neurosciences / Renown regional Medical Center

    Reno, Nevada

  • Mayo Clinic Rochester

    Rochester, Minnesota

  • University of Rochester Medical Center

    Rochester, New York

  • Central Texas Neurology

    Round Rock, Texas

  • University of California, Davis Medical Center

    Sacramento, California

  • Michigan Neurology Associates, P.C.

    Saint Clair Shores, Michigan

  • Integra Clinical Research

    San Antonio, Texas

  • Neurology Center of San Antonio

    San Antonio, Texas

  • Negroski, Stein, Sutherland and Hanes Neurology

    Sarasota, Florida

  • Mayo Clinic Arizona, Department of Neurology

    Scottsdale, Arizona

  • Swedish Neuroscience Institute

    Seattle, Washington

  • Virginia Mason Medical Center

    Seattle, Washington

  • Louisiana State University Health Sciences Center

    Shreveport, Louisiana

  • Rockwood Clinical Research Center

    Spokane, Washington

  • Springfield Neurology Associates, LLC

    Springfield, Massachusetts

  • Stanford University School of Medicine

    Stanford, California

  • SUNY Upstate Medical University, Department of Neurology

    Syracuse, New York

  • Axiom Clinical Research of Florida

    Tampa, Florida

  • University of South Florida, Department of Neurology

    Tampa, Florida

  • MS Center at Holy Name Hospital

    Teaneck, New Jersey

  • Northern Michigan Neurology

    Traverse City, Michigan

  • Northwest NeuroSpecialists, PLLC

    Tucson, Arizona

  • Oak Clinic for Multiple Sclerosis

    Uniontown, Ohio

  • MS Center of Greater Washington, P.C.

    Vienna, Virginia

  • George Washington University Medical Faculty Associates

    Washington D.C., District of Columbia

  • Wake Forest University Health Science, Department of Neurology

    Winston-Salem, North Carolina

  • UMass Memorial Medical Center

    Worcester, Massachusetts

Other trials in United States

Germany13 sites

  • Krankenhaus Hohe Warte, Betriebsstätte der Bayreuth

    Bayreuth

  • Judisches Krankenhaus Berlin

    Berlin

  • Neurologisches Fachzentrum Berlin

    Berlin

  • Neurologische Universitätsklinik Bonn

    Bonn

  • Multiple Sklerose Zentrum am, Zentrum für klinische Neurowissenschaften, Neurologische Uniklinik Dresden

    Dresden

  • Asklepios Klinic Barmbek

    Hamburg

  • Medizinische Hochshule Hannover

    Hanover

  • Oberhavelkliniken Hennigsdorf

    Hennigsdorf

  • Klinikum Ingolstadt, Neurologische Klinik

    Ingolstadt

  • Klinikum Rechts der Isar, Klinik für Neurologie

    München

  • Klinik und Poliklinik fur Neurologie der Universitat Rockstock

    Rostock

  • Universitatsklinik Ulm

    Ulm

  • Fachkrankenhaus Hubertusburg

    Wermsdorf

Other trials in Germany

Australia11 sites

  • The Wesley Research Institute

    Auchenflower, Queensland, 4066

  • Concord Repatriation General Hospital, Neurosciences Department

    Concord

  • St. Vincent's Hospital, MS Education & Research, Department of Clinical Neurosciences

    Fitzroy, Victoria

  • Austin Health

    Heidelberg, Victoria

  • Royal Hobart Hospital

    Hobart, Tasmania, 7000

  • Southern Neurology

    Kogarah

  • Liverpool Hospital, Neurology Department

    Liverpool, 2170

  • Royal Melbourne Hospital, Department of Neurology

    Parkville, Victoria, 3050

  • Griffith School of Medicine, Gold Coast Campus, Griffith University

    Southport, Queensland

  • Westmead Hospital

    Westmead, New South Wales

  • Clinical Cognitive Research Unit/Clinical Trials, The Queen Elizabeth Hospital, Neurology Department

    Woodville South, South Australia

Other trials in Australia

Russia11 sites

  • Research Medical Complex "Your Health" Ltd

    Kazan'

  • Institution of the Russian Academy of Medical Sciences, "Neurology Scientific Center under RAMS"

    Moscow

  • Moscow State Medical Institution City Clinical Hospital #11, Moscow City Center for Multiple Sclerosis

    Moscow

  • Moscow State Public Medical Institution, City Clinical Hospital #11

    Moscow

  • Municipal Treatment and Prevention Institution, "City Hospital #33"

    Nizhny Novgorod

  • Federal State Institution: Siberian District Medical Center

    Novosibirsk

  • 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

  • St. Petersburg Pavlov State Medical University, Department of Neurology and Neurosurgery with a Clinic

    Saint Petersburg

  • St.Petersburg State Medical Institution, "City Multispecialty Hospital #2"

    Saint Petersburg

  • St.Petersburg State Medical Institution, "Nikolayevskaya Hospital"

    Saint Petersburg

  • State Medical Institution, "Samara Regional Clinical Hospital n.a. M.I. Kalinin"

    Samara

Other trials in Russia

Canada9 sites

  • Centre de Sante et de Services Sociaux de Gatineau-Hull Hospital

    Gatineau, Quebec

  • Clinique Neuro rive-sud, Recherche sepmus inc

    Greenfield Park, Quebec

  • Multiple Sclerosis Clinic, Connell 7, Kingston General Hospital

    Kingston, Ontario

  • London Health Sciences Centre- University Hospital

    London, Ontario

  • Hospital Maisonneuve-Rosemont

    Montreal, Quebec

  • Montreal Neurological Institute and Hospital

    Montreal, Quebec

  • The Ottawa Hospital, General Campus

    Ottawa, Ontario

  • Sunnybrook Health Sciences Centre

    Toronto, Ontario

  • UBC Hospital

    Vancouver, British Columbia

Other trials in Canada

France6 sites

  • CHU Clermont-Ferrand, Hôpital Gabriel Montpied

    Clermont-Ferrand

  • Hôpital General, Service de Neurologie

    Dijon

  • Hospital Roger Salengro

    Lille

  • Hôpital Pitié Salpétrière, Service de Neurologie

    Paris

  • Sevice de Neurologie

    Rennes

  • Hôpital Civil, Departement de Neurologie

    Strasbourg

Other trials in France

Italy6 sites

  • Ospedale Binaghi - Centro Sclerosi Multipla

    Cagliari

  • Ospedale S. Antonio Abate di Gallarate

    Gallarate

  • Università di Genova Dipartimento di Neuroscienze Oftalmologia e Genetica

    Genova

  • Ospedale Civile di Brescia c/o Ospedale Richiedei, Centro di riferimento per la Sclerosi Multiple

    Montichiari

  • Ospedale San Luigi di Orbassano

    Orbassano

  • Azienda Ospedaliera Sant'Andrea Neurologia

    Roma

Other trials in Italy

Croatia5 sites

  • Clinical Hospital Centre Rijeka, Clinic for Neurology

    Rijeka

  • General Hospital Varazdin, Department of neurology

    Varaždin

  • Clinical Hospital Centre Zagreb

    Zagreb

  • Clinical Hospital Sestre Milosrdnice

    Zagreb

  • General Hospital " Sveti Duh", Department of neurology

    Zagreb

Other trials in Croatia

United Kingdom5 sites

  • Frenchay Hospital

    Bristol

  • Department Of Neurosciences, Addenbrookes Hospital

    Cambridge, England

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

    London, England

  • Salford Royal NHS Foundation Trust, Clinical Trials Unit

    Salford

  • Department of Neurology Glossop Road, Royal Hallamshire Hospital

    Sheffield

Other trials in United Kingdom

Brazil4 sites

  • Hospital Sao Lucas PUC-RS

    Porto Alegre, Rio Grande do Sul

  • Hospital da Restauracao

    Recife, Pernambuco

  • Hospital de Clínicas USP

    São Paulo

  • Irmandade da Santa Casa de Misericordia de Sao Paulo

    São Paulo

Other trials in Brazil

Czechia4 sites

  • MS Center, Department of Neurology

    Hradec Králové

  • St. Anne's University Hospital Brno

    Pekarska

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

    Prague

  • Krajska zdravotni a.s. - Hospital Teplice

    Teplice

Other trials in Czechia

Serbia4 sites

  • Clinic of Neurology, Clinical Centre of Serbia

    Belgrade

  • Military Medical Academy

    Belgrade

  • Clinical Centre of Kragujevac

    Kragujevac

  • Clinical Centre Vojvodina Institute of Neurology

    Novi Sad

Other trials in Serbia

Spain4 sites

  • Servicio de Neurología Hospital Vall d'Hebron Paseo de Vall d'Hebron

    Barcelona

  • Servicio de Neurología Hospital Clínico San Carlos

    Madrid

  • Servicio de Neurología Hospital Carlos Haya

    Málaga

  • Servicio de Neurología Hospital Virgen de la Macarena

    Seville

Other trials in Spain

Belgium3 sites

  • Cliniques Universitaires Saint-Luc, Neurology

    Brussels

  • CHU Ourthe Amblève, Neurology

    Esneux

  • University Hospital Leuven, Campus Gasthuisberg, Neurology

    Leuven

Other trials in Belgium

Denmark3 sites

  • Århus Universitetshospital, Scleroseklinikken, Århus Sygehus

    Aarhus

  • Scleroseklinikken, Rigshospitalet

    Copenhagen

  • Odense University Hospital

    Odense

Other trials in Denmark

Israel3 sites

  • Hadassah Medical Center Ein Karem

    Jerusalem

  • Tel Aviv Sourasky Medical Center, Department of Neurology

    Tel Aviv

  • Sheba Medical Centre

    Tel HaShomer

Other trials in Israel

Mexico3 sites

  • Unidad de Investigación en Salud de Chihuahua, S.C.

    Chihuahua City, Chihuahua

  • Hospital Medica Sur CIF-BIOTEC

    Delegacion, Tlalpan

  • Hospital Angeles del Pedregal; Camino a Santa Teresa

    Mexico City

Other trials in Mexico

Poland3 sites

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

    Lodz

  • Independent Public Teaching Hospital No. 4 in Lublin

    Lublin

  • Heliodor Swiecicki Teaching Hospital of the Poznan, University of Medical Sciences

    Poznan

Other trials in Poland

Ukraine3 sites

  • Institute of Neurology, Psychiatry and Narcology under the Academy of Medical Sciences of Ukraine

    Kharkiv

  • Kyiv Municipal Clinical Hospital #4, Department of Demyelinating Diseases of the Nervous System

    Kyiv

  • Danylo Halytsky Lviv National Medical University, Department of Neurology

    Lviv

Other trials in Ukraine

Netherlands2 sites

  • Jeroen Bosch Ziekenhuis

    's-Hertogenbosch

  • Orbis Medisch Centrum, Department of Neurology

    Sittard

Other trials in Netherlands

Sweden2 sites

  • Sahlgrenska University Hospital, Neurologkliniken

    Gothenburg

  • Norrlands Universitets sjukhus

    Umeå

Other trials in Sweden

Argentina1 site

  • DIABAID

    Buenos Aires

Other trials in Argentina

Austria1 site

  • AKH Wien, Universitätsklinikum für Neurologie

    Vienna

Other trials in Austria

About this study

Official title: 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.

Read the 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.

Being tested
Alemtuzumab 12 mg, Alemtuzumab 24 mg, Interferon beta-1a
Keywords
Multiple Sclerosis
Medical subject headings
Multiple Sclerosis, Relapsing-Remitting, Multiple Sclerosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Alemtuzumab 12 mgBiological

    Also called Lemtrada

    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 mgBiological

    Also called Lemtrada

    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-1aBiological

    Also called Rebif®

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

Study groups in NCT00548405
Study groupRoleWhat they receive
Alemtuzumab 12 mgExperimentalAlemtuzumab (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.
Receives: Biological: Alemtuzumab 12 mg
Alemtuzumab 24 mgExperimentalAlemtuzumab 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.
Receives: Biological: Alemtuzumab 24 mg
Interferon Beta-1aActive comparatorInterferon Beta-1a (Rebif®) 44 microgram (mcg) subcutaneously 3-times weekly for 24 months. Dose adjustment was done as per Investigator's discretion.
Receives: Biological: Interferon beta-1a

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 2 years

  2. 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.

    Measured: Up to 2 years

Secondary outcomes (4)

  1. 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.

    Measured: Year 2

  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.

    Measured: Baseline, Year 2

  3. 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.

    Measured: Baseline, Year 2

  4. 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).

    Measured: Baseline, Year 2

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Oct 2007 (estimated)
  2. Study startOct 2007
  3. Primary completionSep 2011
  4. Study completionSep 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
840 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00548405
Sponsor's protocol ID
CAMMS32400507
Other IDs
2007-001162-32, CAMMS324,, ISRCTN70702834, ACTRN12608000426381, NTR1469, CARE-MS II
Acronym
CARE-MS II
Status last verified
Mar 2017
First submitted
22 Oct 2007
Last updated
17 Apr 2017
Data monitoring committee
Yes

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.

    PubMed 23122650

  • Ziemssen 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.

    PubMed 39935588

  • Coles 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.

    PubMed 37745914

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Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Alemtuzumab 12 mg, Alemtuzumab 24 mg and Interferon beta-1a in people with Multiple Sclerosis, Relapsing-Remitting, run by Genzyme, a Sanofi Company at 191 sites in 23 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 191 sites in United States, Germany, Australia, Russia, Canada and 18 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Jan 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Sustained Accumulation of Disability (SAD) (time frame: Up to 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00548405, which also lists 17 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2017.

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