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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00530348




Registration number
NCT00530348
Ethics application status
Date submitted
13/09/2007
Date registered
17/09/2007
Date last updated
24/11/2014

Titles & IDs
Public title
Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis, Study One
Scientific 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
Secondary ID [1] 0 0
ISRCTN21534255
Secondary ID [2] 0 0
CAMMS323
Universal Trial Number (UTN)
Trial acronym
CARE-MS I
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Sclerosis, Relapsing-Remitting 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Alemtuzumab
Other interventions - Interferon beta-1a

Experimental: Alemtuzumab -

Active Comparator: Interferon Beta-1a -


Other interventions: 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 interventions: 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.

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
Up to 2 years
Primary outcome [2] 0 0
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.
Timepoint [2] 0 0
Up to 2 years
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
Year 2
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
Baseline, Year 2
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
Baseline, Year 2
Secondary outcome [4] 0 0
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).
Timepoint [4] 0 0
Baseline, Year 2

Eligibility
Key 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
Minimum age
18 Years
Maximum age
50 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,SA,TAS,VIC
Recruitment hospital [1] 0 0
The Wesley Research Institute - Auchenflower
Recruitment hospital [2] 0 0
Griffith University School of Medicine - Southport
Recruitment hospital [3] 0 0
The Queen Elizabeth Hospital - Woodville South
Recruitment hospital [4] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [5] 0 0
St Vincent's Hospital - Fitzroy
Recruitment hospital [6] 0 0
Austin Health - Heidelberg
Recruitment hospital [7] 0 0
Royal Melbourne Hospital, Department of Neurology, Ward 4 East - Parkville
Recruitment hospital [8] 0 0
Concord Repatriation General Hospital - Concord
Recruitment hospital [9] 0 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 0 0
4066 - Auchenflower
Recruitment postcode(s) [2] 0 0
- Southport
Recruitment postcode(s) [3] 0 0
- Woodville South
Recruitment postcode(s) [4] 0 0
7000 - Hobart
Recruitment postcode(s) [5] 0 0
3065 - Fitzroy
Recruitment postcode(s) [6] 0 0
3084 - Heidelberg
Recruitment postcode(s) [7] 0 0
3050 - Parkville
Recruitment postcode(s) [8] 0 0
- Concord
Recruitment postcode(s) [9] 0 0
- Westmead
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Idaho
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Indiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Kansas
Country [9] 0 0
United States of America
State/province [9] 0 0
Kentucky
Country [10] 0 0
United States of America
State/province [10] 0 0
Louisiana
Country [11] 0 0
United States of America
State/province [11] 0 0
Massachusetts
Country [12] 0 0
United States of America
State/province [12] 0 0
Michigan
Country [13] 0 0
United States of America
State/province [13] 0 0
Nevada
Country [14] 0 0
United States of America
State/province [14] 0 0
New Hampshire
Country [15] 0 0
United States of America
State/province [15] 0 0
New Mexico
Country [16] 0 0
United States of America
State/province [16] 0 0
New York
Country [17] 0 0
United States of America
State/province [17] 0 0
North Carolina
Country [18] 0 0
United States of America
State/province [18] 0 0
Ohio
Country [19] 0 0
United States of America
State/province [19] 0 0
Oklahoma
Country [20] 0 0
United States of America
State/province [20] 0 0
Pennsylvania
Country [21] 0 0
United States of America
State/province [21] 0 0
Tennessee
Country [22] 0 0
United States of America
State/province [22] 0 0
Texas
Country [23] 0 0
Argentina
State/province [23] 0 0
Buenos Aires
Country [24] 0 0
Brazil
State/province [24] 0 0
Pernambuco
Country [25] 0 0
Brazil
State/province [25] 0 0
RS
Country [26] 0 0
Brazil
State/province [26] 0 0
SP
Country [27] 0 0
Canada
State/province [27] 0 0
Alberta
Country [28] 0 0
Canada
State/province [28] 0 0
British Columbia
Country [29] 0 0
Canada
State/province [29] 0 0
Ontario
Country [30] 0 0
Canada
State/province [30] 0 0
Quebec
Country [31] 0 0
Croatia
State/province [31] 0 0
Rijeka
Country [32] 0 0
Croatia
State/province [32] 0 0
Varazdin
Country [33] 0 0
Croatia
State/province [33] 0 0
Zagreb
Country [34] 0 0
Czech Republic
State/province [34] 0 0
Praha 2
Country [35] 0 0
Czech Republic
State/province [35] 0 0
Teplice
Country [36] 0 0
France
State/province [36] 0 0
Toulouse
Country [37] 0 0
Germany
State/province [37] 0 0
Berlin
Country [38] 0 0
Germany
State/province [38] 0 0
Dresden
Country [39] 0 0
Germany
State/province [39] 0 0
Frankfurt
Country [40] 0 0
Germany
State/province [40] 0 0
Hannover
Country [41] 0 0
Germany
State/province [41] 0 0
Hennigsdorf
Country [42] 0 0
Germany
State/province [42] 0 0
Teupitz
Country [43] 0 0
Mexico
State/province [43] 0 0
Mexico City
Country [44] 0 0
Poland
State/province [44] 0 0
Cracow
Country [45] 0 0
Poland
State/province [45] 0 0
Lodz
Country [46] 0 0
Poland
State/province [46] 0 0
Lublin
Country [47] 0 0
Poland
State/province [47] 0 0
Poznan
Country [48] 0 0
Russian Federation
State/province [48] 0 0
Kazan
Country [49] 0 0
Russian Federation
State/province [49] 0 0
Moscow
Country [50] 0 0
Russian Federation
State/province [50] 0 0
Nizhniy Novgorod
Country [51] 0 0
Russian Federation
State/province [51] 0 0
Novosibirsk
Country [52] 0 0
Russian Federation
State/province [52] 0 0
Pyatigorsk
Country [53] 0 0
Russian Federation
State/province [53] 0 0
Samara
Country [54] 0 0
Russian Federation
State/province [54] 0 0
St. Petersburg
Country [55] 0 0
Russian Federation
State/province [55] 0 0
Ufa
Country [56] 0 0
Serbia
State/province [56] 0 0
Belgrade
Country [57] 0 0
Serbia
State/province [57] 0 0
Kragujevac
Country [58] 0 0
Serbia
State/province [58] 0 0
Nis
Country [59] 0 0
Serbia
State/province [59] 0 0
Novi Sad
Country [60] 0 0
Sweden
State/province [60] 0 0
Goteborg
Country [61] 0 0
Ukraine
State/province [61] 0 0
Chernihiv
Country [62] 0 0
Ukraine
State/province [62] 0 0
Kharkiv
Country [63] 0 0
Ukraine
State/province [63] 0 0
Kyiv
Country [64] 0 0
Ukraine
State/province [64] 0 0
Lviv
Country [65] 0 0
United Kingdom
State/province [65] 0 0
England
Country [66] 0 0
United Kingdom
State/province [66] 0 0
Wales
Country [67] 0 0
United Kingdom
State/province [67] 0 0
Sheffield

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Genzyme, a Sanofi Company
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Bayer
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/show/NCT00530348
Trial related presentations / 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.
Public notes

Contacts
Principal investigator
Name 0 0
Medical Monitor
Address 0 0
Genzyme, a Sanofi Company
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications