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

This study has been completed.
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )
ClinicalTrials.gov Identifier:
NCT00530348
First received: September 13, 2007
Last updated: November 17, 2014
Last verified: November 2014
  Purpose

The purpose of this study was to establish the efficacy and safety of alemtuzumab (Lemtrada™) as a treatment for relapsing-remitting multiple sclerosis (MS), in comparison with subcutaneous (SC) interferon beta-1a (Rebif®). The study had enrolled participants who had not previously received MS disease-modifying therapies. Participants had monthly laboratory tests and comprehensive testing every 3 months.


Condition Intervention Phase
Multiple Sclerosis, Relapsing-Remitting
Biological: Alemtuzumab
Biological: Interferon beta-1a
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: A Phase 3 Randomized, Rater-Blinded Study Comparing Two Annual Cycles of Intravenous Alemtuzumab to Three-Times Weekly Subcutaneous Interferon Beta-1a (Rebif®) in Treatment-Naïve Patients With Relapsing-Remitting Multiple Sclerosis

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Percentage of Participants With Sustained Accumulation of Disability (SAD) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    EDSS is an ordinal scale in half-point increments that quantifies disability in participants with MS. It assesses 7 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) as well as ambulation. EDSS total score: 0 (normal neurological examination) to 10 (death due to MS). As measured by EDSS score, SAD was defined as increase of at least 1.5 points for participants with Baseline score of 0 and increase of at least 1.0 point for participants with a Baseline score of 1.0 or more; and the increase persisted for at least next 2 scheduled assessments, that is, 6 consecutive months. Onset date of SAD was date of first EDSS assessment that began 6 month consecutive period of SAD. Participants who did not reach SAD endpoint were censored at their last visit. Percentage of participants with SAD, estimated by Kaplan-Meier (KM) method, was reported.

  • Annualized Relapse Rate [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Percentage of Participants Who Were Relapse Free at Year 2 [ Time Frame: Year 2 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Year 2 [ Time Frame: Baseline, Year 2 ] [ Designated as safety issue: No ]
    EDSS is an ordinal scale in half-point increments that quantifies disability in participants with 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.

  • Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Score at Year 2 [ Time Frame: Baseline, Year 2 ] [ Designated as safety issue: No ]
    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.

  • Percent Change From Baseline in Magnetic Resonance Imaging Time Constant 2 (MRI-T2) Hyperintense Lesion Volume at Year 2 [ Time Frame: Baseline, Year 2 ] [ Designated as safety issue: No ]
    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).


Enrollment: 581
Study Start Date: August 2007
Study Completion Date: April 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Alemtuzumab Biological: Alemtuzumab
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 Name: Lemtrada
Active Comparator: Interferon Beta-1a 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 Name: Rebif®

Detailed Description:

Every participant had received active treatment; there was no placebo. Participants who qualified were randomly assigned to treatment with either alemtuzumab or SC interferon beta-1a at a 2:1 ratio (that is, 2 given 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 CAMMS03409 (NCT00930553) an extension study for safety and efficacy assessments. Participants who received interferon beta-1a and completed 2 years on study might be eligible to receive alemtuzumab on the extension study.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Given written/signed informed consent
  • Age 18 to 50 years old (inclusive) as of the date the informed consent form (ICF) was signed
  • Diagnosis of MS per updated McDonald criteria, and cranial magnetic resonance imaging (MRI) scan demonstrating white matter lesions attributable to MS within 5 years of screening
  • Onset of MS symptoms (as determined by a neurologist, either at screening or retrospectively) within 5 years of the date the ICF was signed
  • Expanded Disability Status Scale (EDSS) score 0.0 to 3.0 (inclusive) at screening
  • Greater than or equal to (>=) 2 MS attacks (first episode or relapse) occurring in the 24 months prior to the date the ICF was signed, with >=1 attack in the 12 months prior to the date the ICF was signed, with objective neurological signs confirmed by a physician, nurse practitioner, or other Genzyme-approved health-care provider and the objective signs could be identified retrospectively

Exclusion Criteria:

  • Received prior therapy for MS other than corticosteroids, for example, alemtuzumab, interferons, intravenous immunoglobulin, glatiramer acetate, natalizumab, and mitoxantrone
  • Exposure to azathioprine, cladribine, cyclophosphamide, cyclosporine A, methotrexate, or any other immunosuppressive agent other than systemic corticosteroid treatment
  • Any progressive form of MS
  • History of malignancy (except basal skin cell carcinoma)
  • CD4 + , CD8 + count, B cell, or absolute neutrophil count less than (<) lower limit of normal (LLN) at screening
  • Known bleeding disorder (for example, dysfibrinogenemia, factor IX deficiency, hemophilia, Von Willebrand's disease, disseminated intravascular coagulation, fibrinogen deficiency, or clotting factor deficiency)
  • Significant autoimmune disease including but not limited to immune cytopenias, rheumatoid arthritis, systemic lupus erythematosus, other connective tissue disorders, vasculitis, inflammatory bowel disease, severe psoriasis
  • Presence of anti-thyroid stimulating hormone (TSH) receptor (TSHR) antibodies (that is, above the LLN)
  • Active infection or at high risk for infection
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00530348

  Hide Study Locations
Locations
United States, Alabama
North Central Neurology Associates, P.C.
Cullman, Alabama, United States
United States, Arizona
Barrow Neurological Institute, St. Joseph's Hospital & Medical Center
Phoenix, Arizona, United States
Mayo Clinic Arizona
Scottsdale, Arizona, United States
Northwest NeuroSpecialists, PLLC
Tucson, Arizona, United States
United States, Colorado
Advanced Neurosciences Research
Fort Collins, Colorado, United States
United States, Florida
Neurological Associates
Pompano Beach, Florida, United States
Axiom Clinical Research of Florida
Tampa, Florida, United States
United States, Idaho
Idaho Falls Multiple Sclerosis Center, PLLC
Idaho Falls, Idaho, United States
United States, Illinois
Consultants in Neurology, Ltd.
Northbrook, Illinois, United States
United States, Indiana
Fort Wayne Neurological Center
Fort Wayne, Indiana, United States
United States, Kansas
University of Kansas Medical Center
Kansas City, Kansas, United States
MidAmerican Neuroscience Institute
Lenexa, Kansas, United States
United States, Kentucky
Associates in Neurology, PSC
Lexington, Kentucky, United States
University of Louisville Research Foundation
Louisville, Kentucky, United States
United States, Louisiana
Louisiana State University Health Sciences Center
Shreveport, Louisiana, United States
United States, Massachusetts
UMass Memorial Medical Center
Worcester, Massachusetts, United States
United States, Michigan
University of Michigan Health System
Ann Arbor, Michigan, United States
Wayne State University
Detroit, Michigan, United States
United States, Nevada
University of Nevada School of Medicine
Las Vegas, Nevada, United States
United States, New Hampshire
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States
United States, New Mexico
University of New Mexico, Health Sciences Center, MS Specialty Clinic
Albuquerque, New Mexico, United States
United States, New York
Empire Neurology
Latham, New York, United States
Comprehensive Multiple Sclerosis Care Center at South Shore Neurologic Associates, P.C.
Patchogue, New York, United States
University of Rochester Medical Center
Rochester, New York, United States
United States, North Carolina
Carolinas Medical Center (CMC), Neurosciences & Spine Institute (NSSI)
Charlotte, North Carolina, United States
United States, Ohio
The Ohio State University Medical Center, Multiple Sclerosis Center
Columbus, Ohio, United States
Oak Clinic for Multiple Sclerosis
Uniontown, Ohio, United States
United States, Oklahoma
MS Center of Oklahoma
Oklahoma City, Oklahoma, United States
United States, Pennsylvania
Lehigh Valley Hospital Neurosciences and Pain Research
Allentown, Pennsylvania, United States
United States, Tennessee
Biomedical Research Alliance of NY, LLC
Franklin, Tennessee, United States
Advanced Neurosciences Institute
Franklin, Tennessee, United States
Hope Neurology PC
Knoxville, Tennessee, United States
United States, Texas
Baylor College of Medicine, Maxine Mesinger MS Clinic
Houston, Texas, United States
Central Texas Neurology
Round Rock, Texas, United States
Integra Clinical Research
San Antonio, Texas, United States
Neurology Center of San Antonio
San Antonio, Texas, United States
Argentina
DIABAID
Buenos Aires, Argentina
Australia, Queensland
The Wesley Research Institute
Auchenflower, Queensland, Australia, 4066
Griffith University School of Medicine
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
St Vincent's Hospital
Fitzroy, Victoria, Australia, 3065
Austin Health
Heidelberg, Victoria, Australia, 3084
Royal Melbourne Hospital, Department of Neurology, Ward 4 East
Parkville, Victoria, Australia, 3050
Australia
Concord Repatriation General Hospital
Concord, Australia
Westmead Hospital
Westmead, Australia
Brazil
Hospital da Restauracao, Av Governador Agamenon Magalhaes
Recife, Pernambuco, Brazil
Hospital Sao Lucas PUC-RS
Porto Alegre, RS, Brazil
Hospital de Clínicas USP
Sao Paulo, SP, Brazil
Canada, Alberta
University of Calgary and Foothills Medical Cenre
Calgary, Alberta, Canada
Canada, British Columbia
UBC Hospital
Vancouver, British Columbia, Canada
Canada, Ontario
The Ottawa Hospital, General Campus
Ottawa, Ontario, Canada
Canada, Quebec
Clinique Nuero-outaouais
Gatineau, Quebec, Canada
Clinique Neuro rive-sud, Recherche Sepmus, Inc.
Greenfield park, Quebec, Canada
Croatia
Clinical Hospital Centre Rijeka
Rijeka, Croatia
General Hospital Varazdin
Varazdin, Croatia
Clinical Hospital Centre Zagreb
Zagreb, Croatia
General Hospital "Sveti Duh"
Zagreb, Croatia
Clinical Hospital Centre "Sestre Milosrdnice"
Zagreb, Croatia
Czech Republic
Department of Neurology, 1st Faculty of Medicine and General Teaching Hospital
Praha 2, Czech Republic
Krajska zdravotni a.s., Hospital Teplice
Teplice, Czech Republic
France
Hopital Purpan
Toulouse, France
Germany
Judisches Krankenhaus Berlin
Berlin, Germany
Universitätsklinik Carl Gustav Carus Dresden
Dresden, Germany
Klinikum der Goethe Universität Frankfurt
Frankfurt, Germany
Medizinische Hochschule Hannover
Hannover, Germany
Oberhavelkliniken Hennigsdorf
Hennigsdorf, Germany
Asklepios Klinikum Brandenburg
Teupitz, Germany
Mexico
Hospital Medica Sur CIF-BIOTEC
Mexico City, Mexico
Hospital Angeles del Pedregal, Camino de Santa Teresa
Mexico City, Mexico
Poland
Clinical Neurology Centre Sp. z o.o. (Ltd)
Cracow, Poland
Independent Public Healthcare Facility, Norbert Barlicki University Hospital No. 1 of the Medical University of Lodz
Lodz, Poland
Independent Public Teaching Hospital No. 4 in Lublin
Lublin, Poland
Heliodor Swiecicki Teaching Hospital of the Poznan University of Medical Sciences
Poznan, Poland
Russian Federation
Research Medical Complex "Your Health" Ltd
Kazan, Russian Federation
Moscow State Medical Institution City Clinical Hospital #11
Moscow, Russian Federation
Scientific Neurology Center RAMS
Moscow, Russian Federation
Moscow City Hospital #11
Moscow, Russian Federation
Municipal City Hospital #33
Nizhniy Novgorod, Russian Federation
Federal State Institution Siberian Rettitorial Medical Center under Federal Medical-Biological Agency of Russia
Novosibirsk, Russian Federation
City Clinical Hospital #2
Pyatigorsk, Russian Federation
Samara Regional Clinical Hospital n.a. Kalinin
Samara, Russian Federation
Nikolaevskaya Hospital
St. Petersburg, Russian Federation
Institute of Human Brain RAS
St. Petersburg, Russian Federation
St. Petersburg Pavlov State Medical University
St. Petersburg, Russian Federation
State Medical Institution: Republican Clinical Hospital n.a. G.G. Kuvatov
Ufa, Russian Federation
Serbia
Clinical Centre Serbia, Institute for Neurology
Belgrade, Serbia
Military Medical Academy
Belgrade, Serbia
Clinical centre Kragujevac
Kragujevac, Serbia
Clinical Center Nis, Clinic for neurology
Nis, Serbia
Clinical Centre of Vojvodina, Clinic for neurology
Novi Sad, Serbia
Sweden
Sahlgrenska University Hospital
Goteborg, Sweden
Ukraine
Chernihiv Regional Hospital
Chernihiv, Ukraine
Institute of Neurology, Psychiatry and Narcology under the Academy of Medical Sciences of Ukraine, Department of Neuroinfection and Multiple Sclerosis
Kharkiv, Ukraine
Hospoital of the Directorate of the Medical Corps within the Ukrainian Security Service, Neurology Department
Kyiv, Ukraine
Kyiv Municipal Clinical Hospital #4
Kyiv, Ukraine
Danylo Halytsky Lviv National Medical University
Lviv, Ukraine
United Kingdom
Department Of Neurosciences, Addenbrookes Hospital
Cambridge, England, United Kingdom
Centre for Neuroscience & Trauma, Blizard Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry
London, England, United Kingdom
University Hospital of Wales
Cardiff, Wales, United Kingdom
Royal Hallamshire Hospital
Sheffield, United Kingdom
Sponsors and Collaborators
Genzyme, a Sanofi Company
Bayer
Investigators
Study Director: Medical Monitor Genzyme, a Sanofi Company
  More Information

Additional Information:
Publications:
Responsible Party: Sanofi ( Genzyme, a Sanofi Company )
ClinicalTrials.gov Identifier: NCT00530348     History of Changes
Other Study ID Numbers: CAMMS323, ISRCTN21534255, ACTRN12608000435381, CARE-MS I, 2007-001161-14
Study First Received: September 13, 2007
Results First Received: November 17, 2014
Last Updated: November 17, 2014
Health Authority: United States: Food and Drug Administration
Brazil: National Health Surveillance Agency
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Australia: Department of Health and Ageing Therapeutic Goods Administration
Canada: Health Canada
Croatia: Agency for Medicinal Product and Medical Devices
Czech Republic: State Institute for Drug Control
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Paul-Ehrlich-Institut
Mexico: Federal Commission for Protection Against Health Risks
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
Sweden: Medical Products Agency
Ukraine: State Pharmacological Center - Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Sanofi:
Multiple Sclerosis

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

ClinicalTrials.gov processed this record on November 25, 2014