Condition category
Nervous System Diseases
Date applied
18/02/2008
Date assigned
11/03/2009
Last edited
23/10/2015
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

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 measures

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

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

http://www.genzyme.co.uk

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

Results - basic reporting

See https://clinicaltrials.gov/ct2/show/results/NCT00530348

Publication summary

1. 2012 results in http://www.ncbi.nlm.nih.gov/pubmed/23122652

Publication citations

  1. 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.

Additional files

Editorial Notes

As of 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.