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

ISRCTN ISRCTN21534255
DOI https://doi.org/10.1186/ISRCTN21534255
EudraCT/CTIS number 2007-001161-14
ClinicalTrials.gov number NCT00530348
Secondary identifying numbers CAMMS323; ACTRN12608000435381
Submission date
18/02/2008
Registration date
11/03/2009
Last edited
20/03/2020
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Nervous System Diseases
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Genzyme Medical Information Representative
Scientific

Genzyme Therapeutics
4620
Kingsgate
Cascade Way
Oxford Business Park South
Oxford
OX4 2SU
United Kingdom

Phone +44 (0)1865 405283
Email ukmedinfo@genzyme.com

Study information

Study designRandomised parallel-assignment single-blind (outcome assessor) multi-centre trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please email a request for a patient information sheet: ukmedinfo@genzyme.com
Scientific titleA 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
Study acronymCARE-MS I
Study objectivesCurrent 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(s)Nottingham Research Ethics Committee (UK), 09/11/2007, ref: 07/H0408/118.
All other centres will seek ethics approval before recruiting patients.
Health condition(s) or problem(s) studiedMultiple sclerosis
InterventionExperimental 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 typeDrug
Pharmaceutical study type(s)
PhasePhase III
Drug / device / biological / vaccine name(s)Alemtuzumab, interferon beta-1a (Rebif®)
Primary outcome measure1. Time to Sustained Accumulation of Disability (SAD) (Time frame: 2 years)
2. Relapse rate (Time frame: 2 years)
Secondary outcome measures1. 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 study start date07/09/2007
Completion date01/03/2011

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexBoth
Target number of participants525 (added 02/09/2009: actual number of participants: 581)
Key inclusion criteriaAmended 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
Key exclusion criteria1. 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)
Date of first enrolment07/09/2007
Date of final enrolment02/09/2009

Locations

Countries of recruitment

  • Argentina
  • Australia
  • Brazil
  • Canada
  • Croatia
  • Czech Republic
  • England
  • France
  • Germany
  • Mexico
  • Poland
  • Russian Federation
  • Serbia
  • Sweden
  • Ukraine
  • United Kingdom
  • United States of America

Study participating centre

Genzyme Therapeutics
Oxford
OX4 2SU
United Kingdom

Sponsor information

Genzyme Corporation (USA)
Industry

500 Kendall Street
Cambridge
Massachusetts
02142
United States of America

Website http://www.genzyme.co.uk
ROR logo "ROR" https://ror.org/027vj4x92

Funders

Funder type

Industry

Genzyme
Private sector organisation / For-profit companies (industry)
Alternative name(s)
Genzyme Corporation
Location
United States of America
Bayer Schering
Private sector organisation / For-profit companies (industry)
Location
Germany

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Basic results No No
Results article results 24/11/2012 Yes No

Editorial Notes

RP 20/03/2020: proactive updates - EudraCT number added. Added EudraCT link to basic results (scientific).
22/06/2009: this record was updated to include amendments to the protocol. All changes can be found under the relevant sections under the above update date.