Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12608000426381
Ethics application status
Approved
Date submitted
18/06/2008
Date registered
26/08/2008
Date last updated
29/08/2009
Type of registration
Retrospectively registered

Titles & IDs
Public title
Comparison of Alemtuzumab and Rebif (registered trademark) Efficacy in Multiple Sclerosis, Study Two
Scientific title
A Phase 3 Randomized, 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 (Registered trademark)) on Relapse Rate and Time to Sustained Accumulation of Disability in Patients with Relapsing-Remitting Multiple Sclerosis Who Have Relapsed on Therapy
Secondary ID [1] 534 0
ClinicalTrials.gov NCT00548405
Universal Trial Number (UTN)
Trial acronym
CARE-MS II
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Sclerosis, Relapsing-Remitting 2968 0
Condition category
Condition code
Neurological 3108 3108 0 0
Multiple sclerosis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
alemtuzumab: 12 mg per day administered through intravenous therapy (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
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 (Note: The 24 mg alemtuzumab dose is closed to enrollment.)
Intervention code [1] 2702 0
Treatment: Drugs
Comparator / control treatment
Interferon beta-1a (Rebif (registered trademark)): 44 micrograms (mcg) administered 3-times weekly by subcutaneous (SC) injections for 2 years
Control group
Active

Outcomes
Primary outcome [1] 3997 0
Time to Sustained Accumulation of Disability (SAD) based on increases in scores on the Expanded Disability Status Scale (EDSS) lasting at least 6 months
Timepoint [1] 3997 0
Monitored at baseline and quarterly thereafter for 2 years.
Primary outcome [2] 3998 0
Relapse Rate based on patient report with physician confirmation of objective neurologic changes
Timepoint [2] 3998 0
Monitored continuously for 2 years.
Secondary outcome [1] 6730 0
Proportion of patients who are relapse free at Year 2
Timepoint [1] 6730 0
2 Years
Secondary outcome [2] 6731 0
Change from baseline in EDSS
Timepoint [2] 6731 0
Monitored at baseline and quarterly thereafter for 2 years.
Secondary outcome [3] 6732 0
Acquisition of disability as measured by change from baseline in Multiple Sclerosis Functional Composite (MSFC)
Timepoint [3] 6732 0
Monitored at baseline and quarterly thereafter for 2 years.
Secondary outcome [4] 6733 0
Percent change from baseline in magnetic resonance imaging (MRI) T2-weighted hyperintense lesion volume at Year 2
Timepoint [4] 6733 0
Monitored at baseline and annually thereafter for 2 years.
Secondary outcome [5] 7880 0
Safety, based on adverse event reporting and laboratory testing. These are safety provisions outlined in the protocol and not secondary outcomes
Timepoint [5] 7880 0
Monitored continuously, including monthly blood tests.

Eligibility
Key inclusion criteria
1. Diagnosis of MS (Multiple Sclerosis) and MRI scan demonstrating white matter lesions attributable to MS
2. Onset of MS symptoms within 10 years
3. EDSS score 0.0 to 5.0
4. Greater than or equal to 2 MS attacks within 24 months, with greater than or equal to 1 attack within 12 months
5. Greater than or equal to 1 MS attack (relapse) during treatment with a interferon beta therapy or glatiramer acetate after having been on that therapy for at least 6 months within 10 years
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
No
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, azothioprine 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
16. Previous hypersensitivity reaction to anyimmunoglobulin 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)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
20/10/2007
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
700
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment postcode(s) [1] 1378 0
2139
Recruitment postcode(s) [2] 1377 0
2145
Recruitment postcode(s) [3] 1810 0
2170
Recruitment postcode(s) [4] 1380 0
2217
Recruitment postcode(s) [5] 895 0
3050
Recruitment postcode(s) [6] 1376 0
3065
Recruitment postcode(s) [7] 1375 0
3084
Recruitment postcode(s) [8] 890 0
4066
Recruitment postcode(s) [9] 637 0
4215
Recruitment postcode(s) [10] 638 0
5011
Recruitment postcode(s) [11] 1379 0
7000
Recruitment outside Australia
Country [1] 827 0
Argentina
State/province [1] 827 0
Country [2] 828 0
Belgium
State/province [2] 828 0
Country [3] 829 0
Brazil
State/province [3] 829 0
Country [4] 830 0
Canada
State/province [4] 830 0
Country [5] 831 0
Czech Republic
State/province [5] 831 0
Country [6] 832 0
Denmark
State/province [6] 832 0
Country [7] 833 0
France
State/province [7] 833 0
Country [8] 834 0
Germany
State/province [8] 834 0
Country [9] 835 0
Israel
State/province [9] 835 0
Country [10] 836 0
Italy
State/province [10] 836 0
Country [11] 837 0
Mexico
State/province [11] 837 0
Country [12] 838 0
Netherlands
State/province [12] 838 0
Country [13] 839 0
Poland
State/province [13] 839 0
Country [14] 840 0
Russian Federation
State/province [14] 840 0
Country [15] 841 0
Serbia and Montenegro
State/province [15] 841 0
Country [16] 842 0
Spain
State/province [16] 842 0
Country [17] 843 0
Sweden
State/province [17] 843 0
Country [18] 844 0
Ukraine
State/province [18] 844 0
Country [19] 845 0
United Kingdom
State/province [19] 845 0
Country [20] 846 0
United States of America
State/province [20] 846 0
Country [21] 847 0
Croatia
State/province [21] 847 0

Funding & Sponsors
Funding source category [1] 3226 0
Commercial sector/Industry
Name [1] 3226 0
Genzyme Corporation
Country [1] 3226 0
United States of America
Funding source category [2] 3227 0
Commercial sector/Industry
Name [2] 3227 0
Bayer Schering Pharma AG
Country [2] 3227 0
Germany
Primary sponsor type
Commercial sector/Industry
Name
Genzyme Corporation
Address
500 Kendall Street Cambridge, Massachusetts 02142
Country
United States of America
Secondary sponsor category [1] 3128 0
None
Name [1] 3128 0
Address [1] 3128 0
Country [1] 3128 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 5516 0
Gold Coast Health Services District Research Ethics Committee
Ethics committee address [1] 5516 0
108 Nerang Street
Southport, QLD 4215
Ethics committee country [1] 5516 0
Australia
Date submitted for ethics approval [1] 5516 0
Approval date [1] 5516 0
30/10/2007
Ethics approval number [1] 5516 0
30/10/2007

Summary
Brief summary
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 (Registered trademark for interferon beta-1a). The study will enroll 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 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 enrollment so newly enrolled patients will be randomly assigned to treatment with either 12 mg alemtuzumab or Rebif (registered trademark) at a 2:1 ratio (ie, 2 given 12 mg alemtuzumab for every 1 given Rebif (registered trademark)). Patients will not be able to guess which treatment will be randomly assigned to them. Alemtuzumab will be administered in two annual cycles, once at the beginning of the study and again 1 year later. Rebif (registered trademark) 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 (registered trademark) and complete 2 years on study may be eligible to receive alemtuzumab in an extension study.
Trial website
Trial related presentations / publications
1) Coles AJ, Cox A, Le Page E, et al. The window of therapeutic opportunity in multiple sclerosis: evidence from monoclonal antibody therapy. J Neurol. 2006;253(1);98-108.
2) Fox E, Sullivan H, Gazda S. Open label, single-arm, Phase II study of alemtuzumab in patients with active relapsing-remitting multiple sclerosis who have failed licensed beta-interferon therapies. Poster presentation P06.07 at the 59th Annual Meeting of the American Academy of Neurology (AAN) on 03 May 2007.
3) CAMMS223 Trial Investigators, Coles AJ, Compston DA, Selmaj KW, Lake SL, Moran S, Margolin DH, Norris K, Tandon PK. Alemtuzumab vs. interferon beta-1a in early multiple sclerosis. N Engl J Med. 2008 Oct 23;359(17):1786-801
Public notes

Contacts
Principal investigator
Name 28470 0
Address 28470 0
Country 28470 0
Phone 28470 0
Fax 28470 0
Email 28470 0
Contact person for public queries
Name 11627 0
Genzyme Medical Information
Address 11627 0
Level 1, Building C,12-24 Talavera Road
North Ryde NSW 2113
Mailing Address: PO Box 282, North Ryde B/C NSW 1670
Country 11627 0
Australia
Phone 11627 0
1800 359 131
Fax 11627 0
1800 232 565
Email 11627 0
medinfo_ANZ@genzyme.com
Contact person for scientific queries
Name 2555 0
Genzyme Medical Information
Address 2555 0
Level 1, Building C,12-24 Talavera Road
North Ryde NSW 2113
Mailing Address: PO Box 282, North Ryde B/C NSW 1670
Country 2555 0
Australia
Phone 2555 0
1800 359 131
Fax 2555 0
1800 232 565
Email 2555 0
medinfo_ANZ@genzyme.com

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

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