Contact information
Type
Scientific
Primary contact
Dr Genzyme Medical Information Representative
ORCID ID
Contact details
Genzyme Therapeutics
4620
Kingsgate
Cascade Way
Oxford Business Park South
Oxford
OX4 2SU
United Kingdom
+44 (0)1865 405283
ukmedinfo@genzyme.com
Additional identifiers
EudraCT number
ClinicalTrials.gov number
NCT00530348
Protocol/serial number
CAMMS323; ACTRN12608000435381
Study information
Scientific title
A phase 3 randomised, 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
Acronym
CARE-MS I
Study hypothesis
Current hypothesis as of 22/06/2009:
The purpose of this study is to establish the efficacy and safety of alemtuzumab as a treatment for relapsing-remitting multiple sclerosis (MS), in comparison with Rebif® (interferon beta-1a). The study will enrol patients who have not previously received treatment to suppress MS, except steroids. Patients will have monthly laboratory tests and comprehensive testing every 3 months. Every patient will receive active treatment; there is no placebo. Patients who qualify will be randomly assigned to treatment with either alemtuzumab or Rebif® at a 2:1 ratio (i.e., 2 given 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, all patients who receive alemtuzumab will be followed in an extension study for safety and efficacy assessments. Patients who receive Rebif® and complete 2 years on study may be eligible to receive alemtuzumab in an extension study.
Initial information at time of registration:
The purpose of this study is to establish the efficacy and safety of alemtuzumab as a treatment for relapsing-remitting multiple sclerosis (MS), in comparison with Rebif® (interferon beta-1a). The study will enrol patients who have not previously received treatment to suppress MS, except steroids. Patients will have monthly blood tests and comprehensive testing every 3 months. Every patient will receive active treatment; there is no placebo. Patients who qualify will be randomly assigned to treatment with either alemtuzumab or Rebif® at a 2:1 ratio (i.e., 2 given 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, a safety-related blood test will be performed at least monthly. Participation in this study will end 2 years after the start of treatment for each patient. Additionally, all patients who receive alemtuzumab will be followed in an extension study for safety for at least 3 years after their last dose of alemtuzumab. Patients who receive Rebif® and complete 2 years on study may be eligible to receive alemtuzumab in an extension study.
Ethics approval
Nottingham Research Ethics Committee (UK), 09/11/2007, ref: 07/H0408/118.
All other centres will seek ethics approval before recruiting patients.
Study design
Randomised parallel-assignment single-blind (outcome assessor) multi-centre trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please email a request for a patient information sheet: ukmedinfo@genzyme.com
Condition
Multiple sclerosis
Intervention
Experimental Intervention: 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
Active Comparator: interferon beta-1a (Rebif®): 44 mcg administered 3-times weekly by SC injections for 2 years
Details of Lead Principal Investigator for UK sites:
Dr Alasdair Coles
Addenbrooke's Hospital
Box 165
Hill's Road
Cambridge, CB2 2QQ
United Kingdom
Intervention type
Drug
Phase
Phase III
Drug names
Alemtuzumab, interferon beta-1a (Rebif®)
Primary outcome measure
1. Time to Sustained Accumulation of Disability (SAD) (Time frame: 2 years)
2. Relapse rate (Time frame: 2 years)
Secondary outcome measures
1. Proportion of patients who are relapse free at Year 2 (Time frame:2 years)
2. Change from baseline in EDSS (Time frame: 2 years)
3. Acquisition of disability as measured by change from baseline in Multiple Sclerosis Functional Composite (MSFC) (Time frame: 2 years)
4. Percent change from baseline in MRI-T2 hyperintense lesion volume at Year 2 (Time frame: 2 years)
Overall trial start date
07/09/2007
Overall trial end date
01/03/2011
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
Amended as of 22/06/2009:
Point 6 below has been removed from the inclusion criteria.
Initial information at time of registration:
1. Males and females, aged 18 - 50 years
2. Diagnosis of multiple sclerosis (MS) and cranial magnetic resonance imaging (MRI) scan demonstrating white matter lesions attributable to MS within 5 years
3. Onset of MS symptoms within 5 years of screening
4. Expanded Disability Status Scale (EDSS) score 0.0 to 3.0
5. Greater than or equal to 2 MS attacks within 24 months, with greater than or equal to 1 attack within 12 months
6. Neurologically stable for the 30 days prior to the date the Informed Consent Form is signed
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
525 (added 02/09/2009: actual number of participants: 581)
Participant exclusion criteria
1. Received prior therapy for MS other than corticosteroids
2. Exposure to immunosuppressive or immunomodulatory agents other than systemic corticosteroid treatment
3. Received treatment with a monoclonal antibody for any reason
4. Previous treatment with any investigational drug (i.e. medication that is not approved at any dose for any indication)
5. Has any progressive form of MS
6. Any disability acquired from trauma or another illness that could interfere with evaluation of disability due to MS
7. Major systemic disease that cannot be treated or adequately controlled by therapy
8. Active infection or high risk for infection
9. Autoimmune disorder (other than MS)
10. Impaired hepatic or renal function
11. History of malignancy, except basal skin cell carcinoma
12. 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
13. Known bleeding disorder
14. Of childbearing potential with a positive serum pregnancy test, pregnant, or lactating
15. Current participation in another clinical study
16. Previous hypersensitivity reaction to any immunoglobulin product
17. Known allergy or intolerance to interferon beta, human albumin, or mannitol
18. Intolerance of pulsed corticosteroids, especially a history of steroid psychosis
19. Inability to self-administer subcutaneous (SC) injections or receive SC injections from caregiver
20. Inability to undergo MRI with gadolinium administration
21. Unwilling to use a reliable and acceptable contraceptive method throughout the study period (fertile patients only)
Recruitment start date
07/09/2007
Recruitment end date
02/09/2009
Locations
Countries of recruitment
Argentina, Australia, Brazil, Canada, Croatia, Czech Republic, France, Germany, Mexico, Poland, Russian Federation, Serbia, Sweden, Ukraine, United Kingdom, United States of America
Trial participating centre
Genzyme Therapeutics
Oxford
OX4 2SU
United Kingdom
Sponsor information
Organisation
Genzyme Corporation (USA)
Sponsor details
500 Kendall Street
Cambridge
Massachusetts
02142
United States of America
Sponsor type
Industry
Website
Funders
Funder type
Industry
Funder name
Genzyme
Alternative name(s)
Genzyme Corporation
Funding Body Type
private sector organisation
Funding Body Subtype
corporate
Location
United States of America
Funder name
Bayer Schering
Alternative name(s)
Funding Body Type
private sector organisation
Funding Body Subtype
corporate
Location
Germany
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
See https://clinicaltrials.gov/ct2/show/results/NCT00530348
Publication list
1. 2012 results in http://www.ncbi.nlm.nih.gov/pubmed/23122652
Publication citations
-
Results
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, , Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial., Lancet, 2012, 380, 9856, 1819-1828, doi: 10.1016/S0140-6736(12)61769-3.