Condition category
Nervous System Diseases
Date applied
23/06/2008
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

NCT00548405

Protocol/serial number

CAMMS324 A2; NTR1469; ACTRN12608000426381

Study information

Scientific title

A phase 3 randomised, rater- and dose-blinded study comparing two annual cycles of intravenous low- and high-dose alemtuzumab to three-times weekly subcutaneous interferon beta-1a (Rebif®) in patients with relapsing-remitting multiple sclerosis who have relapsed on therapy

Acronym

CARE-MS II

Study hypothesis

Amended hypothesis as of 24/06/2009:
The purpose of this study is to establish the efficacy and safety of two different doses 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 received an adequate trial of disease-modifying therapies but continued to relapse while being treated, and who meet a minimum severity of disease as measured by magnetic resonance imaging (MRI). Patients will have monthly laboratory tests and comprehensive testing every 3 months. Every patient will receive active treatment; there is no placebo. The 24 mg alemtuzumab dose is closed to enrolment so newly enrolled patients will be randomly assigned to treatment with either 12 mg alemtuzumab or Rebif® at a 2:1 ratio (i.e., 2 given 12 mg 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 neurological 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 two different doses 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 received an adequate trial of disease-modifying therapies but continued to relapse while being treated, and who meet a minimum severity of disease as measured by magnetic resonance imaging (MRI). 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 low-dose alemtuzumab, high-dose alemtuzumab, or Rebif® at a 2:2:1 ratio (i.e., there is a 4-in-5 chance patients will be assigned to receive alemtuzumab treatment and a 1-in-5 chance patients will be assigned to receive Rebif® treatment). 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 neurological 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

Warwickshire Local Research Ethics Committee (UK), 24/12/2007, ref: 07/H1211/153. 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 parallel trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please email to request a patient information sheet: ukmedinfo@genzyme.com

Condition

Multiple sclerosis

Intervention

Experimental Intervention 1: 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

Experimental Intervention 2: alemtuzumab: 24 mg per day administered through IV, once a day for 5 consecutive days at Month 0 and 24 mg per day administered through IV, once a day for 3 consecutive days at Month 12 (please note that as of 24/06/2009 the 24 mg alemtuzumab dose is closed to enrolment).

Active Comparator: interferon beta-1a (Rebif®): 44 mcg administered 3-times weekly by SC injections for 2 years

Details of Lead Principal Investigator for the 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

20/10/2007

Overall trial end date

01/04/2012

Reason abandoned

Eligibility

Participant inclusion criteria

Amended as of 24/06/2009:
Point 7 has been removed from the below inclusion criteria.

Initial information at time of registration:
1. Males and females, aged 18 - 55 years old
2. Diagnosis of MS and MRI scan demonstrating white matter lesions attributable to MS
3. Onset of MS symptoms within 10 years of screening
4. Expanded Disability Status Scale (EDSS) score 0.0 to 5.0
5. Greater than or equal to 2 MS attacks within 24 months, with greater than or equal to 1 attack within 12 months
6. Greater than or equal to 1 MS attack (relapse) during treatment with a beta interferon therapy or glatiramer acetate after being on that therapy for at least 6 months within 10 years
7. 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

700 (previously 1200 prior to 24/06/2009)

Participant exclusion criteria

1. Previous treatment with alemtuzumab
2. Previous treatment with any investigational drug (i.e. medication that is not approved at any dose for any indication)
3. Treatment with natalizumab, methotrexate, azathioprine or cyclosporine in the past 6 months
4. Previous treatment with mitoxantrone, cyclophosphamide, cladribine, rituximab, or any other immunosuppressive, or cytotoxic therapy (other than steroid treatment)
5. 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 or previous participation in CAMMS323 (registered with ISRCTN21534255)
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

20/10/2007

Recruitment end date

02/09/2009

Locations

Countries of recruitment

Argentina, Australia, Austria, Belgium, Brazil, Canada, Croatia, Czech Republic, Denmark, France, Germany, Israel, Italy, Mexico, Netherlands, Poland, Russian Federation, Serbia, Spain, 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/NCT00548405

Publication summary

2012 results in: http://www.ncbi.nlm.nih.gov/pubmed/23122650

Publication citations

Additional files

Editorial Notes

As of 24/06/2009 this record has been updated in order to reflect the most recent protocol amendments, which took place on 09/06/2009. All changes can be found under the above update date. At this time the following countries of recruitment were also added: Argentina, Brazil, Croatia, Serbia.