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CompletedNCT00530348CARE-MS IUpdated Nov 24, 2014Results posted

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

A Phase 3 interventional study of Alemtuzumab and Interferon beta-1a in Multiple Sclerosis, Relapsing-Remitting, sponsored by Genzyme, a Sanofi Company. Completed at 101 sites in 16 countries. Open to participants aged 18 Years to 50 Years. Per ClinicalTrials.gov, last updated 2014-11-24.

Sponsored by Genzyme, a Sanofi Company · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
581
Allocation
Randomized
Ages
18 Years to 50 Years
Sex
All
01

Study summary

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.

Read the 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.

02

Conditions studied

  • Multiple Sclerosis, Relapsing-Remitting

Keywords

  • Multiple Sclerosis
03

In context

Multiple Sclerosis

3,460 studies on the registry are indexed under Multiple Sclerosis; 661 are open to participants now.

This study's enrollment of 581 is above the median of 50 across 2,342 interventional studies indexed under Multiple Sclerosis.

Browse Multiple Sclerosis studies →

Lead sponsor

Genzyme, a Sanofi Company is the lead sponsor of 303 studies on the registry; 5 are open to participants now.

Of its 24 completed or terminated interventional studies of FDA-regulated products, 19 (79%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 50 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Single (Outcomes assessor)
Enrollment
581 participants (actual)

Study arms

  • Experimental
    Alemtuzumab

    Biological: Alemtuzumab

  • Active comparator
    Interferon Beta-1a

    Biological: Interferon beta-1a

Interventions

  • BiologicalAlemtuzumab

    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.

    Also known as: Lemtrada

  • BiologicalInterferon beta-1a

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

    Also known as: Rebif®

06

What researchers measure

Primary outcomes

  1. Percentage of Participants With Sustained Accumulation of Disability (SAD)

    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.

    Time frame: 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.

    Time frame: Up to 2 years

Secondary outcomes

  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.

    Time frame: 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 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.

    Time frame: 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.

    Time frame: 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).

    Time frame: Baseline, Year 2

07

Results

Posted Nov 24, 2014

Participant flow

Participants were screened at 101 investigational sites in Argentina, Australia, Brazil, Canada, Croatia, the Czech Republic, France, Germany, Mexico, Poland, Russia, Serbia, Sweden, Ukraine, the United Kingdom (UK), and the United States (US) between August 28, 2007 and April 27, 2011.

Participant flow — Overall Study
MilestoneInterferon Beta-1aAlemtuzumab
Started195386
Treated187376
Completed173367
Not completed2219
Withdrew: Adverse event51
Withdrew: Death01
Withdrew: Lack of efficacy20
Withdrew: Lost to follow-up02
Withdrew: Physician decision12
Withdrew: Pregnancy10
Withdrew: Withdrawal by subject1212
Withdrew: Randomised in error10
Withdrew: Noncompliance with inclusion criterion 301

Outcome measures

PrimaryPercentage of Participants With Sustained Accumulation of Disability (SAD)

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.

Time frame:
Up to 2 years
Reported as:
Number · percentage of participants with SAD
Percentage of Participants With Sustained Accumulation of Disability (SAD)
percentage of participants with SADInterferon Beta-1aAlemtuzumab
Percentage of Participants With Sustained Accumulation of Disability (SAD)11.12 (7.32 to 16.71)8.00 (5.66 to 11.24)
Statistical analysis
  • Interferon Beta-1a vs Alemtuzumab · Cox Proportional Hazards Regression · p = 0.2173 (Hochberg method was used to adjust for the two co-primary outcomes.) · Hazard ratio (hr): 0.70 · 95% CI 0.40 to 1.23
PrimaryAnnualized 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.

Time frame:
Up to 2 years
Reported as:
Number · relapses per participant per year
Annualized Relapse Rate
relapses per participant per yearInterferon Beta-1aAlemtuzumab
Annualized Relapse Rate0.39 (0.29 to 0.53)0.18 (0.13 to 0.23)
Statistical analysis
  • Interferon Beta-1a vs Alemtuzumab · Proportional means regression · p = <0.0001 (Hochberg method was used to adjust for the two co-primary outcomes.) · Rate ratio: 0.45 · 95% CI 0.32 to 0.63
SecondaryPercentage 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.

Time frame:
Year 2
Reported as:
Number · percentage of participants
Percentage of Participants Who Were Relapse Free at Year 2
percentage of participantsInterferon Beta-1aAlemtuzumab
Percentage of Participants Who Were Relapse Free at Year 258.69 (51.12 to 65.50)77.59 (72.87 to 81.60)
Statistical analysis
  • Interferon Beta-1a vs Alemtuzumab · Cox Proportional Hazards Regression · p = <0.0001 · Hazard ratio (hr): 0.45 · 95% CI 0.33 to 0.61
SecondaryChange From Baseline in Expanded Disability Status Scale (EDSS) Score at Year 2

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.

Time frame:
Baseline, Year 2
Reported as:
Mean · units on a scale
Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Year 2
units on a scaleInterferon Beta-1aAlemtuzumab
Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Year 2-0.2 ± 1.05-0.2 ± 0.87
Statistical analysis
  • Interferon Beta-1a vs Alemtuzumab · Wei-Lachin · p = 0.4188
SecondaryChange 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.

Time frame:
Baseline, Year 2
Reported as:
Mean · Z-score
Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Score at Year 2
Z-scoreInterferon Beta-1aAlemtuzumab
Baseline (n=186, 375)0.05 ± 0.629-0.02 ± 0.695
Change at Year 2 (n=172, 362)0.07 ± 0.4500.15 ± 0.516
Statistical analysis
  • Interferon Beta-1a vs Alemtuzumab · Wei-Lachin · p = 0.0115
SecondaryPercent 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).

Time frame:
Baseline, Year 2
Reported as:
Mean · percent change
Percent Change From Baseline in Magnetic Resonance Imaging Time Constant 2 (MRI-T2) Hyperintense Lesion Volume at Year 2
percent changeInterferon Beta-1aAlemtuzumab
Percent Change From Baseline in Magnetic Resonance Imaging Time Constant 2 (MRI-T2) Hyperintense Lesion Volume at Year 2-6.68 ± 32.44-10.28 ± 22.58
Statistical analysis
  • Interferon Beta-1a vs Alemtuzumab · Ranked ANCOVA · p = 0.3080

Adverse events

Collected over First dose of study drug up to 2 years. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Interferon Beta-1a—27/187 (14.4%)168/187 (89.8%)
Alemtuzumab—69/376 (18.4%)360/376 (95.7%)
Most frequent serious events
Showing 10 of 75
Most frequent serious events
EventInterferon Beta-1aAlemtuzumab
Multiple sclerosis relapseNervous system disorders13/18719/376
Autoimmune thrombocytopeniaBlood and lymphatic system disorders0/1873/376
ColitisGastrointestinal disorders1/1870/376
MalocclusionGastrointestinal disorders1/1870/376
OesophagitisGastrointestinal disorders1/1870/376
Non-cardiac chest painGeneral disorders1/1870/376
Hepatitis toxicHepatobiliary disorders1/1870/376
AppendicitisInfections and infestations1/1872/376
Hepatitis AInfections and infestations1/1870/376
Accidental overdoseInjury, poisoning and procedural complications1/1870/376
Most frequent other events
Showing 10 of 63
Most frequent other events
EventInterferon Beta-1aAlemtuzumab
HeadacheNervous system disorders52/187189/376
RashSkin and subcutaneous tissue disorders9/187174/376
PyrexiaGeneral disorders18/187138/376
Multiple sclerosis relapseNervous system disorders64/18765/376
Influenza like illnessGeneral disorders59/18719/376
Injection site erythemaGeneral disorders56/1870/376
NasopharyngitisInfections and infestations25/18774/376
FatigueGeneral disorders23/18768/376
NauseaGastrointestinal disorders14/18765/376
Urinary tract infectionInfections and infestations8/18764/376

Baseline characteristics

Full analysis set (FAS) population included all randomized participants who received at least 1 dose of study drug.

Age, Continuous
Age, Continuous(years)Interferon Beta-1aAlemtuzumabTotal
Mean33.2 ± 8.4833.0 ± 8.0333.1 ± 8.18
Sex: Female, Male
Sex: Female, Male(Participants)Interferon Beta-1aAlemtuzumabTotal
Female122243365
Male65133198
Time Since First Relapse
Time Since First Relapse(years)Interferon Beta-1aAlemtuzumabTotal
Mean2.0 ± 1.322.1 ± 1.362.1 ± 1.35
Number of Relapse Episodes in the Preceding 2 Years
Number of Relapse Episodes in the Preceding 2 Years(participants)Interferon Beta-1aAlemtuzumabTotal
1 Relapse31215
2 Relapses118215333
Greater than or equal to 3 Relapses66149215
Expanded Disability Status Scale (EDSS) Score
Expanded Disability Status Scale (EDSS) Score(units on a scale)Interferon Beta-1aAlemtuzumabTotal
Mean2.0 ± 0.792.0 ± 0.812.0 ± 0.81
08

Study locations

101 sites
  • North Central Neurology Associates, P.C.
    Cullman, Alabama, United States
  • 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
  • Advanced Neurosciences Research
    Fort Collins, Colorado, United States
  • Neurological Associates
    Pompano Beach, Florida, United States
  • Axiom Clinical Research of Florida
    Tampa, Florida, United States
  • Idaho Falls Multiple Sclerosis Center, PLLC
    Idaho Falls, Idaho, United States
  • Consultants in Neurology, Ltd.
    Northbrook, Illinois, United States
  • Fort Wayne Neurological Center
    Fort Wayne, Indiana, United States
  • University of Kansas Medical Center
    Kansas City, Kansas, United States
  • MidAmerican Neuroscience Institute
    Lenexa, Kansas, United States
  • Associates in Neurology, PSC
    Lexington, Kentucky, United States
  • University of Louisville Research Foundation
    Louisville, Kentucky, United States
  • Louisiana State University Health Sciences Center
    Shreveport, Louisiana, United States
  • UMass Memorial Medical Center
    Worcester, Massachusetts, United States
  • University of Michigan Health System
    Ann Arbor, Michigan, United States
  • Wayne State University
    Detroit, Michigan, United States
  • University of Nevada School of Medicine
    Las Vegas, Nevada, United States
  • Dartmouth-Hitchcock Medical Center
    Lebanon, New Hampshire, United States
  • University of New Mexico, Health Sciences Center, MS Specialty Clinic
    Albuquerque, New Mexico, United States
  • 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
  • Carolinas Medical Center (CMC), Neurosciences & Spine Institute (NSSI)
    Charlotte, North Carolina, United States
  • The Ohio State University Medical Center, Multiple Sclerosis Center
    Columbus, Ohio, United States
  • Oak Clinic for Multiple Sclerosis
    Uniontown, Ohio, United States
  • MS Center of Oklahoma
    Oklahoma City, Oklahoma, United States
  • Lehigh Valley Hospital Neurosciences and Pain Research
    Allentown, Pennsylvania, United States
  • Advanced Neurosciences Institute
    Franklin, Tennessee, United States
  • Biomedical Research Alliance of NY, LLC
    Franklin, Tennessee, United States
  • Hope Neurology PC
    Knoxville, Tennessee, United States
  • 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
  • DIABAID
    Buenos Aires, Argentina
  • The Wesley Research Institute
    Auchenflower, Queensland 4066, Australia
  • Griffith University School of Medicine
    Southport, Queensland, Australia
  • The Queen Elizabeth Hospital
    Woodville South, South Australia, Australia
  • Royal Hobart Hospital
    Hobart, Tasmania 7000, Australia
  • St Vincent's Hospital
    Fitzroy, Victoria 3065, Australia
  • Austin Health
    Heidelberg, Victoria 3084, Australia
  • Royal Melbourne Hospital, Department of Neurology, Ward 4 East
    Parkville, Victoria 3050, Australia
  • Concord Repatriation General Hospital
    Concord, Australia
  • Westmead Hospital
    Westmead, Australia
  • 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
  • University of Calgary and Foothills Medical Cenre
    Calgary, Alberta, Canada
  • UBC Hospital
    Vancouver, British Columbia, Canada
  • The Ottawa Hospital, General Campus
    Ottawa, Ontario, Canada
  • Clinique Nuero-outaouais
    Gatineau, Quebec, Canada
  • Clinique Neuro rive-sud, Recherche Sepmus, Inc.
    Greenfield park, Quebec, Canada
  • Clinical Hospital Centre Rijeka
    Rijeka, Croatia
  • General Hospital Varazdin
    Varazdin, Croatia
  • Clinical Hospital Centre "Sestre Milosrdnice"
    Zagreb, Croatia
  • Clinical Hospital Centre Zagreb
    Zagreb, Croatia
  • General Hospital "Sveti Duh"
    Zagreb, Croatia
  • Department of Neurology, 1st Faculty of Medicine and General Teaching Hospital
    Praha 2, Czech Republic
  • Krajska zdravotni a.s., Hospital Teplice
    Teplice, Czech Republic
  • Hopital Purpan
    Toulouse, France
  • 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
  • Hospital Angeles del Pedregal, Camino de Santa Teresa
    Mexico City, Mexico
  • Hospital Medica Sur CIF-BIOTEC
    Mexico City, Mexico
  • 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
  • Research Medical Complex "Your Health" Ltd
    Kazan, Russian Federation
  • Moscow City Hospital #11
    Moscow, Russian Federation
  • Moscow State Medical Institution City Clinical Hospital #11
    Moscow, Russian Federation
  • Scientific Neurology Center RAMS
    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
  • Institute of Human Brain RAS
    St. Petersburg, Russian Federation
  • Nikolaevskaya Hospital
    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
  • 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
  • Sahlgrenska University Hospital
    Goteborg, Sweden
  • 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
  • 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

Showing the first 100 of 101 sites across 16 countries.

09

References and documents

Publications

  • Cohen JA, Coles AJ, Arnold DL, Confavreux C, Fox EJ, Hartung HP, Havrdova E, Selmaj KW, Weiner HL, Fisher E, Brinar VV, Giovannoni G, Stojanovic M, Ertik BI, Lake SL, Margolin DH, Panzara MA, Compston DA; CARE-MS I investigators. Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial. Lancet. 2012 Nov 24;380(9856):1819-28. doi: 10.1016/S0140-6736(12)61769-3. Epub 2012 Nov 1. PubMed 23122652 ↗
  • 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. PubMed 34882037 ↗
  • Kuhle J, Daizadeh N, Benkert P, Maceski A, Barro C, Michalak Z, Sormani MP, Godin J, Shankara S, Samad TA, Jacobs A, Chung L, Rӧsch N, Kaiser C, Mitchell CP, Leppert D, Havari E, Kappos L. Sustained reduction of serum neurofilament light chain over 7 years by alemtuzumab in early relapsing-remitting MS. Mult Scler. 2022 Apr;28(4):573-582. doi: 10.1177/13524585211032348. Epub 2021 Aug 11. PubMed 34378446 ↗
  • 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. PubMed 34035833 ↗
  • Horakova D, Boster A, Bertolotto A, Freedman MS, Firmino I, Cavalier SJ, Jacobs AK, Thangavelu K, Daizadeh N, Poole EM, Baker DP, Margolin DH, Ziemssen T; CARE-MS I, CARE-MS II, and CAMMS03409 Investigators. Proportion of alemtuzumab-treated patients converting from relapsing-remitting multiple sclerosis to secondary progressive multiple sclerosis over 6 years. Mult Scler J Exp Transl Clin. 2020 Dec 18;6(4):2055217320972137. doi: 10.1177/2055217320972137. eCollection 2020 Oct-Dec. PubMed 33414927 ↗
  • Ziemssen T, Bass AD, Berkovich R, Comi G, Eichau S, Hobart J, Hunter SF, LaGanke C, Limmroth V, Pelletier D, Pozzilli C, Schippling S, Sousa L, Traboulsee A, Uitdehaag BMJ, Van Wijmeersch B, Choudhry Z, Daizadeh N, Singer BA; CARE-MS I, CARE-MS II, CAMMS03409, and TOPAZ investigators. Efficacy and Safety of Alemtuzumab Through 9 Years of Follow-up in Patients with Highly Active Disease: Post Hoc Analysis of CARE-MS I and II Patients in the TOPAZ Extension Study. CNS Drugs. 2020 Sep;34(9):973-988. doi: 10.1007/s40263-020-00749-x. PubMed 32710396 ↗
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  • Okai AF, Amezcua L, Berkovich RR, Chinea AR, Edwards KR, Steingo B, Walker A, Jacobs AK, Daizadeh N, Williams MJ; CARE-MS I, CARE-MS II, CAMMS03409, and TOPAZ Investigators. Efficacy and Safety of Alemtuzumab in Patients of African Descent with Relapsing-Remitting Multiple Sclerosis: 8-Year Follow-up of CARE-MS I and II (TOPAZ Study). Neurol Ther. 2019 Dec;8(2):367-381. doi: 10.1007/s40120-019-00159-2. Epub 2019 Oct 25. PubMed 31654272 ↗
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  • Havrdova E, Arnold DL, Cohen JA, Hartung HP, Fox EJ, Giovannoni G, Schippling S, Selmaj KW, Traboulsee A, Compston DAS, Margolin DH, Thangavelu K, Rodriguez CE, Jody D, Hogan RJ, Xenopoulos P, Panzara MA, Coles AJ; CARE-MS I and CAMMS03409 Investigators. Alemtuzumab CARE-MS I 5-year follow-up: Durable efficacy in the absence of continuous MS therapy. Neurology. 2017 Sep 12;89(11):1107-1116. doi: 10.1212/WNL.0000000000004313. Epub 2017 Aug 23. Erratum In: Neurology. 2018 Apr 17;90(16):755. doi: 10.1212/WNL.0000000000004908. PubMed 28835401 ↗
  • Arnold DL, Fisher E, Brinar VV, Cohen JA, Coles AJ, Giovannoni G, Hartung HP, Havrdova E, Selmaj KW, Stojanovic M, Weiner HL, Lake SL, Margolin DH, Thomas DR, Panzara MA, Compston DA; CARE-MS I and CARE-MS II Investigators. Superior MRI outcomes with alemtuzumab compared with subcutaneous interferon beta-1a in MS. Neurology. 2016 Oct 4;87(14):1464-1472. doi: 10.1212/WNL.0000000000003169. Epub 2016 Sep 2. PubMed 27590291 ↗
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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Nov 24, 2014, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00530348
Lead sponsor
Genzyme, a Sanofi Company
Collaborators
Bayer
Responsible party
Sponsor
First posted
Sep 17, 2007
Start date
Aug 2007
Primary completion
Apr 2011
Completion
Apr 2011
Results posted
Nov 24, 2014
Last update
Nov 24, 2014

Study contacts

Medical Monitor
study director · Genzyme, a Sanofi Company

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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