Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis, Study Two (CARE-MS II)

This study has been completed.
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
Genzyme, a Sanofi Company
ClinicalTrials.gov Identifier:
NCT00548405
First received: October 22, 2007
Last updated: November 30, 2012
Last verified: November 2012
  Purpose

The purpose of this study is to establish the efficacy and safety of two different doses of alemtuzumab as a treatment for relapsing-remitting multiple sclerosis (MS), in comparison with Rebif® (interferon beta-1a). The study will enroll patients who have received an adequate trial of disease-modifying therapies but continued to relapse while being treated, and who meet a minimum severity of disease as measured by magnetic resonance imaging (MRI). Patients will have monthly laboratory tests and comprehensive testing every 3 months.


Condition Intervention Phase
Multiple Sclerosis, Relapsing-Remitting
Biological: alemtuzumab
Biological: interferon beta-1a (Rebif®)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase 3 Randomized, Rater- and Dose-Blinded Study Comparing 2 Annual Cycles of IV [Low]- and High-Dose Alemtuzumab to 3x Weekly SC Interferon Beta-1a (Rebif®) in Relapsing-Remitting Multiple Sclerosis Patients Who Have Relapsed on Therapy

Resource links provided by NLM:


Further study details as provided by Genzyme, a Sanofi Company:

Primary Outcome Measures:
  • Time to Sustained Accumulation of Disability (SAD) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Relapse Rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportion of patients who are relapse free at Year 2 [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Change from baseline in EDSS (Expanded Disability Status Scale) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Acquisition of disability as measured by change from baseline in Multiple Sclerosis Functional Composite (MSFC) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Percent change from baseline in MRI-T2 hyperintense lesion volume at Year 2 [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment: 840
Study Start Date: October 2007
Study Completion Date: September 2011
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: alemtuzumab 12 mg Biological: alemtuzumab
12 mg per day administered through IV, once a day for 5 consecutive days at Month 0 and 12 mg per day administered through IV, once a day for 3 consecutive days at Month 12
Experimental: alemtuzumab 24mg Biological: alemtuzumab
24 mg per day administered through IV, once a day for 5 consecutive days at Month 0 and 24 mg per day administered through IV, once a day for 3 consecutive days at Month 12 Note: The 24 mg alemtuzumab dose is closed to enrollment.
Active Comparator: interferon beta-1a (Rebif ®) Biological: interferon beta-1a (Rebif®)
44 mcg administered 3-times weekly by SC injections for 2 years

Detailed Description:

Every patient will receive active treatment; there is no placebo. The 24 mg alemtuzumab dose is closed to enrollment so newly enrolled patients will be randomly assigned to treatment with either 12 mg alemtuzumab or Rebif® at a 2:1 ratio (ie, 2 given 12 mg or 24 mg alemtuzumab for every 1 given Rebif®). Alemtuzumab will be administered in two annual cycles, once at the beginning of the study and again 1 year later. Rebif® will be self-injected 3 times per week for 2 years. All patients will be required to return to their study site every 3 months for neurologic assessment. In addition, safety-related laboratory tests will be performed at least monthly. Participation in this study will end 2 years after the start of treatment for each patient. Additionally, patients who receive alemtuzumab may be followed in the CAMMS03409 Extension Study (NCT00930553) for safety and efficacy assessments. Patients who receive Rebif® and complete 2 years on study may be eligible to receive alemtuzumab in the Extension Study.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of MS and MRI scan demonstrating white matter lesions attributable to MS
  • Onset of MS symptoms within 10 years
  • EDSS score 0.0 to 5.0
  • ≥2 MS attacks within 24 months, with ≥1 attack within 12 months
  • ≥1 MS attack (relapse)during treatment with a beta interferon therapy or glatiramer acetate after having been on that therapy for at least 6 months within 10 years

Exclusion Criteria:

  • Previous treatment with alemtuzumab
  • Previous treatment with any investigational drug (i.e. a medication that is not approved at any dose or for any indication)
  • Treatment with natalizumab, methotrexate, azothioprine or cyclosporine in the past 6 months
  • Previous treatment with mitoxantrone, cyclophosphamide, cladribine, rituximab, or any other immunosuppressive, or cytotoxic therapy (other than steroid treatment)
  • Any progressive form of MS
  • Any disability acquired from trauma or another illness that could interfere with evaluation of disability due to MS
  • Major systemic disease that cannot be treated or adequately controlled by therapy
  • Active infection or high risk for infection
  • Autoimmune disorder (other than MS)
  • Impaired hepatic or renal function
  • History of malignancy, except basal skin cell carcinoma
  • Medical, psychiatric, cognitive, or other conditions that compromise the patient's ability to understand the patient information, to give informed consent, to comply with the trial protocol, or to complete the study
  • Known bleeding disorder
  • Of childbearing potential with a positive serum pregnancy test, pregnant, or lactating
  • Current participation in another clinical study or previous participation in CAMMS323 (NCT00530348)
  • Previous hypersensitivity reaction to any immunoglobulin product
  • Known allergy or intolerance to interferon beta, human albumin, or mannitol
  • Intolerance of pulsed corticosteroids, especially a history of steroid psychosis
  • Inability to self-administer subcutaneous (SC) injections or receive SC injections from caregiver
  • Inability to undergo MRI with gadolinium administration
  • Unwilling to use a reliable and acceptable contraceptive method throughout the study period (fertile patients only)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00548405

  Hide Study Locations
Locations
United States, Alabama
North Central Neurology Associates, P.C.
Cullman, Alabama, United States
United States, Arizona
Barrow Neurology Clinics at 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
United States, California
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
UC Davis Medical Center
Sacramento, California, United States
Stanford University Medical Center
Stanford, California, United States
United States, Colorado
University of Colorado Hospital Anschutz Outpatient Pavilioin
Aurora, Colorado, United States
Colorado Neurological Consultants
Denver, Colorado, United States
Advanced Neurosciences Research LLC
Fort Collins, Colorado, United States
United States, Connecticut
Yale University Multiple Sclerosis Center
New Haven, Connecticut, United States
United States, District of Columbia
George Washington University Medical Faculty Associates
Washington, District of Columbia, United States
United States, Florida
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 Medical Clinics
Tampa, Florida, United States
United States, Georgia
Shephard Center Inc
Atlanta, Georgia, United States
The Emory Clinic
Atlanta, Georgia, United States
United States, Idaho
Eastern Idaho Neurological Associates
Idaho Falls, Idaho, United States
United States, Illinois
University of Chicago Medical Center
Chicago, Illinois, United States
Consultants in Neurology, Ltd
Northbrook, Illinois, United States
United States, Indiana
Fort Wayne Neurological Center
Fort Wayne, Indiana, United States
Indiana University Hospital
Indianapolis, Indiana, United States
Josephson Wallack Munshower Neurology P.C.
Indianapolis, Indiana, United States
United States, Iowa
Iowa Health Physicians
Des Moines, Iowa, United States
Ruan Neurology Clinic and Research Center
Des Moines, Iowa, United States
United States, Kansas
University of Kansas Medical Center
Kansas City, Kansas, United States
MidAmerica Neuroscience Institute
Lenexa, Kansas, United States
United States, Kentucky
Associates in Neurology, PSC
Lexington, Kentucky, United States
University of Louisville, Kentucky Neuroscience Research
Louisville, Kentucky, United States
United States, Louisiana
Louisiana State University Health Sciences Center
Shreveport, Louisiana, United States
United States, Massachusetts
Caritas St. Elizabeth's Hospital Medical Center
Boston, Massachusetts, United States
Partners Multiple Sclerosis Center/Brigham and Women's Hospital
Brookline, Massachusetts, United States
Springfield Neurology Associates, LLC
Springfield, Massachusetts, United States
UMass Memorial Health Care
Worcester, Massachusetts, United States
United States, Michigan
University of Michigan Department of Neurology
Ann Arbor, Michigan, United States
Wayne State University
Detroit, Michigan, United States
Henry Ford Hospital
Detroit, Michigan, United States
Michigan Medical, PC
Grand Rapids, Michigan, United States
Michigan Neurology Associates, P.C.
St. Clair Shores, Michigan, United States
North Michigan Neurology
Traverse City, Michigan, United States
United States, Minnesota
Mayo Clinic Rochester
Rochester, Minnesota, United States
United States, Mississippi
Tupelo Neurology Clinic, PA
Tupelo, Mississippi, United States
United States, Missouri
Saint Luke's Hospital
Kansas City, Missouri, United States
The MS Center for Innovations in Care
St. Louis, Missouri, United States
United States, Montana
Montana Neurobehavioral Specialists
Missoula, Montana, United States
United States, Nevada
University of Nevada School of Medicine
Las Vegas, Nevada, United States
Renown Institute for Neurosciences / Renown regional Medical Center
Reno, Nevada, United States
United States, New Hampshire
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States
United States, New Jersey
MS Center at Holy Name Hospital
Teaneck, New Jersey, United States
United States, New Mexico
University of New Mexico Hospital
Albuquerque, New Mexico, United States
United States, New York
Empire Neurology PC
Latham, New York, United States
Winthrop University Hospital
Mineola, New York, United States
NYU Hospital of Joint Diseases
New York, 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
Syracuse, New York, United States
United States, North Carolina
University of North Caroline-Chapel Hill, Department of Neurology
Chapel Hill, North Carolina, United States
Wake Forest University Health Science
Winston-Salem, North Carolina, United States
United States, Ohio
The Cleveland Clinic Mellen Center
Cleveland, Ohio, United States
The Ohio State University Medical Center, Multiple Sclerosis Center
Columbus, Ohio, United States
Neurology Specialists, Inc.
Dayton, Ohio, United States
Oak Clinic for Multiple Sclerosis
Uniontown, Ohio, United States
United States, Oklahoma
MS Center of Oklahoma, Mercy Health Center
Oklahoma City, Oklahoma, United States
United States, Pennsylvania
Lehigh Valley Hospital, Neuroscience and Pain Research
Allentown, Pennsylvania, United States
North Shore Clinical Associates
Erie, Pennsylvania, United States
Kaufmann Medical Building, Department of Neurology
Pittsburgh, Pennsylvania, United States
United States, Rhode Island
Rhode Island Hospital and The Neurology Foundation, Inc
Providence, Rhode Island, United States
United States, Tennessee
Neurology Clinic, P.C.
Cordova, Tennessee, United States
Sibyl Wray, MD Neurology, PC
Knoxville, Tennessee, United States
Advanced Neurosciences Institute
Nashville, Tennessee, United States
Vanderbilt University Medical Center
Nashville, Tennessee, United States
United States, Texas
Clinical Center for Multiple Sclerosis
Dallas, Texas, United States
Central Texas Neurology Consultants
Round Rock, Texas, United States
Neurology Center of San Antonio
San Antonio, Texas, United States
Integra Clinical Research
San Antonio, Texas, United States
United States, Virginia
MS Center of Greater Washington
Vienna, Virginia, United States
United States, Washington
Swedish Neuroscience Institute
Seattle, Washington, United States
Virginia Mason Medical Center
Seattle, Washington, United States
Rockwood Clinical Research Center
Spokane, Washington, United States
Argentina
DIABAID
Buenos Aires, Argentina
Hospital Britanico de Buenos Aires
Buenos Aires, Argentina
Australia, Queensland
The Wesley Research Institute
Auchenflower, Queensland, Australia, 4066
Griffith University and Gold Coast Hospital
Southport, Queensland, Australia
Australia, South Australia
The Queen Elizabeth Hospital
Woodville South, South Australia, Australia
Australia, Tasmania
Royal Hobart Hospital
Hobart, Tasmania, Australia, 7000
Australia, Victoria
Royal Melbourne Hospital
Parkville, Victoria, Australia, 3050
Australia
Concord Repatriation General Hospital
Concord, Australia
Southern Neurology
Kogarah, Australia
Liverpool Hospital
Liverpool, Australia, 2170
St. Vincent's Hospital
Melbourne, Australia
Austin Health
Victoria, Australia
Westmead Hospital
Westmead, Australia
Austria
AKH Wien, Universitätsklinikum für Neurologie
Vienna, Austria
Belgium
UCL Saint Luc
Brussels, Belgium
CHU Ourthe Ambleve
Esneux, Belgium
UZ Leuven Gasthuisberg
Leuven, Belgium
Brazil
Hospital da Restauracao
Recife, PE, Brazil
Hospital Sao Lucas da PUC-RS
Porto Alegre, RS, Brazil
Irmandade da Santa Casa de Misericordia de Sao Paulo
Vila Buarque, Sao Paulo, Brazil
Hospital das Clinicas da Faculdade de Medicina da USP
Sao Paulo, Brazil
Canada, British Columbia
University of British Columbia
Vancouver, British Columbia, Canada
Canada, Ontario
Multiple Sclerosis Clinic, Kingston General Hospital
Kingston, Ontario, Canada
London Health Sciences Centre- University Hospital
London, Ontario, Canada
Ottawa Hospital-General Campus
Ottawa, Ontario, Canada
Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada
Canada, Quebec
Clinique de neurologie de l'Outaouais
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
Croatia
Clinical Hospital Centre Rijeka
Rijeka, Croatia
General Hospital Varazdin
Varazdin, Croatia
Clinical Hospital Centre Zagreb
Zagreb, Croatia
Clinical Hospital Sestre Milosrdnice
Zagreb, Croatia
Clinical Hospital Sveti Duh
Zagreb, Croatia
Czech Republic
University Hospital Hradec, Kralove
Hradec Kralove, Czech Republic
St. Anne's University Hospital Brno
Pekarska, Czech Republic
General University Hospital in Prague
Prague, Czech Republic
Hospital Teplice
Teplice, Czech Republic
Denmark
Aarhus Sygehus
Aarhus, Denmark
Righospitalet
Copenhagen, Denmark
Odense University Hospital
Odense, Denmark
France
Hopital Gabriel Montpied
Clermont-Ferrand, France
Hospital General Service de Neurologie
Dijon, France
Hospital Roger Salengro
Lille, France
Hopital Neurologique
Lyon Bron, France
Group Hospitalier Pitie Salpetriere
Paris, France
CHU Pontchaillou
Rennes, France
Hopital Civil
Strasbourg, France
Germany
Krankenhaus Hohe Warte
Bayreuth, Germany
Neurologiches Facharztzentrum Berlin
Berlin, Germany
Judisches Krankenhaus Berlin
Berlin-Mitte, Germany
Klinik fur Neurologie Universitatsklinikum Bon
Bonn, Germany
Neurologische Universitasklink
Dresden, Germany
Asklepios Klinic Barmbek
Hamburg, Germany
Medizinische Hochshule Hannover
Hannover, Germany
Krankenhaus Henningsdorf Abteilung fur Neurologie
Henningsdorf, Germany
Neurologiche Klinik und Poliklinik der TU Muenchen
Muenchen, Germany
Klinik und Poliklinik fur Neurologie der Universitat Rockstock
Rockstock, Germany
Universitatsklinik Ulm
Ulm, Germany
Fachkrankenhaus Hubertusburg GmbH
Wemsdorf, Germany
Israel
Haddasah Medical Organisation
Jerusalem, Israel
Souraski TA Medical Centre
Tel Aviv, Israel
Sheba Medical Centre
Tel Hashomer, Israel
Italy
Ospedale Binaghi - Centro Sclerosi Multipla
Cagliari, Italy
Azienda Ospidaliera S. Antonio Abate di Gallarate
Gallarate, Italy
Ospedale San Martino
Genova, Italy
Spedali Civili Presidio di Montichiari
Montichiari, Italy
A.O.U.S. Luigi Gonzaga di Orbassano
Orbassano, Italy
Azienda Ospidaliera Sant'Andrea
Roma, Italy
Mexico
Hospital Medica Sur
Delegacion, Tlalpan, Mexico
Unidad de Investigación en Salud de Chihuahua, S.C.
Chihuahua, Mexico
Hospital Angeles del Pedregal; Camino a Santa Teresa
Mexico City, Mexico
Netherlands
Jeroen Bosch Ziekenhuis
Den Bosch, Netherlands
Faculty of Health Medicine and Life Science
Sittard, Netherlands
Poland
Samodzielny Publiczny ZOZ Uniwersytecki Szpital Kliniczny nr 1 UM w Lodzi
Lodz, Poland
Samodzielny Publiczny Szpital Kliniczny nr 4
Lublin, Poland
Szpital Kliniczny im. Helidora Swiecickiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu
Poznan, Poland
Russian Federation
Research Medical Complex "Your Health" Ltd
Kazan, Russian Federation
State Institution Scientific Neurology Center RAMS
Moscow, Russian Federation
Russian State Medical University
Moscow, Russian Federation
Moscow City Hospital #11
Moscow, Russian Federation
Municipal City Hospital #33
Nizhny Novgorod, Russian Federation
Siberian District Medical Center
Novosibirsk, Russian Federation
Samara Regional Clinical Hospital n.a. Kalinin
Samara, Russian Federation
Nikolaevskaya Hospital
St. Petersburg, Russian Federation
St. Petersburg General Hospital No.2
St. Petersburg, Russian Federation
St. Petersburg Pavlov State Medical University
St. Petersburg, Russian Federation
Insitute of Human Brain RAS
St. Petersburg, Russian Federation
Serbia
Clinical Centre of Serbia
Belgrade, Serbia
Military Medical Academy
Belgrade, Serbia
Clinical Centre of Kragujevac
Kragujevac, Serbia
Clinical Centre Vjovodina Institute of Neurology
Novi Sad, Serbia
Spain
Hospital Vall d'Hebron
Barcelona, Spain
Hospital Clinico Universtitario San Carlos
Madrid, Spain
Hospital Carlos Haya
Malaga, Spain
Hospital University Virgen Macarena
Sevilla, Spain
Sweden
SU/Ostra sjukhuset Forskningsenheten
Gothenburg, Sweden
Norrlands Universitets sjukhus
Umea, Sweden
Ukraine
Institute of Neurology, Psychiatry and Narcology under the Academy of Medical Sciences of Ukraine
Kharkov, Ukraine
Kiev Municipal Clinical Hospital #4
Kiev, Ukraine
Danylo Halytsky National Medical University
Lviv, Ukraine
United Kingdom
Addenbrooke's Hospital, University Neurology unit
Cambridge, England, United Kingdom
The Royal London Hospital
London, England, United Kingdom
Institute of Clinical Neurosciences Frenchay Hospital
Bristol, United Kingdom
Salford Royal Hospital
Salford, United Kingdom
Royal Hallamshire Hospital
Sheffield, United Kingdom
Sponsors and Collaborators
Genzyme, a Sanofi Company
Bayer
Investigators
Study Director: Medical Monitor Genzyme Coorporation
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Genzyme, a Sanofi Company
ClinicalTrials.gov Identifier: NCT00548405     History of Changes
Other Study ID Numbers: CAMMS32400507, 2007-001162-32, CAMMS324,, ISRCTN70702834, ACTRN12608000426381, NTR1469, CARE-MS II
Study First Received: October 22, 2007
Last Updated: November 30, 2012
Health Authority: United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Austria: Federal Ministry for Health Family and Youth
Belgium: Federal Agency for Medicinal Products and Health Products
Brazil: National Health Surveillance Agency
Canada: Health Canada
Croatia: Agency for Medicinal Product and Medical Devices
Czech Republic: State Institute for Drug Control
Denmark: Danish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Paul-Ehrlich-Institut
Israel: Ministry of Health
Italy: The Italian Medicines Agency
Mexico: Federal Commission for Sanitary Risks Protection
Netherlands: Medical Ethics Review Committee (METC)
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Russia: Ministry of Health of the Russian Federation
Serbia and Montenegro: Agency for Drugs and Medicinal Devices
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
Ukraine: State Pharmacological Center - Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Genzyme, a Sanofi Company:
Multiple Sclerosis

Additional relevant MeSH terms:
Multiple Sclerosis
Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Pathologic Processes
Interferon-beta
Interferons
Interferon beta 1a
Campath 1G
Antibodies, Neoplasm
Alemtuzumab
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Adjuvants, Immunologic
Immunosuppressive Agents

ClinicalTrials.gov processed this record on April 16, 2014