Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis, Study Two
| ISRCTN | ISRCTN70702834 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN70702834 |
| ClinicalTrials.gov number | NCT00548405 |
| Secondary identifying numbers | CAMMS324 A2; NTR1469; ACTRN12608000426381 |
- Submission date
- 23/06/2008
- 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
Scientific
Genzyme Therapeutics
4620
Kingsgate
Cascade Way
Oxford Business Park South
Oxford
OX4 2SU
United Kingdom
| Phone | +44 (0)1865 405283 |
|---|---|
| ukmedinfo@genzyme.com |
Study information
| Study design | Randomised parallel-assignment single-blind (outcome assessor) multi-centre trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised parallel trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please email to request a patient information sheet: ukmedinfo@genzyme.com |
| 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 |
| Study acronym | CARE-MS II |
| Study objectives | 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(s) | Warwickshire Local Research Ethics Committee (UK), 24/12/2007, ref: 07/H1211/153. All other centres will seek ethics approval before recruiting patients. |
| Health condition(s) or problem(s) studied | 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 |
| Pharmaceutical study type(s) | |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | 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 study start date | 20/10/2007 |
| Completion date | 01/04/2012 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 700 (previously 1200 prior to 24/06/2009) |
| Key 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 |
| Key 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) |
| Date of first enrolment | 20/10/2007 |
| Date of final enrolment | 02/09/2009 |
Locations
Countries of recruitment
- Argentina
- Australia
- Austria
- Belgium
- Brazil
- Canada
- Croatia
- Czech Republic
- Denmark
- England
- France
- Germany
- Israel
- Italy
- Mexico
- Netherlands
- Poland
- Russian Federation
- Serbia
- Spain
- Sweden
- Ukraine
- United Kingdom
- United States of America
Study participating centre
Genzyme Therapeutics
Oxford
OX4 2SU
United Kingdom
OX4 2SU
United Kingdom
Sponsor information
Genzyme Corporation (USA)
Industry
Industry
500 Kendall Street
Cambridge
Massachusetts
02142
United States of America
| Website | http://www.genzyme.co.uk |
|---|---|
"ROR" |
https://ror.org/027vj4x92 |
Funders
Funder type
Industry
Genzyme
Private sector organisation / For-profit companies (industry)
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)
Private sector organisation / For-profit companies (industry)
- Location
- Germany
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not 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
20/03/2020: EudraCT number added. Added EudraCT link to basic results (scientific).
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.
