Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis, Study Two (CARE-MS II)

This study has been completed.
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
Genzyme, a Sanofi Company
ClinicalTrials.gov Identifier:
NCT00548405
First received: October 22, 2007
Last updated: November 30, 2012
Last verified: November 2012

October 22, 2007
November 30, 2012
October 2007
September 2011   (final data collection date for primary outcome measure)
  • Time to Sustained Accumulation of Disability (SAD) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Relapse Rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Time to Sustained Accumulation of Disability (SAD) [ Time Frame: 2 years ]
  • Relapse Rate [ Time Frame: 2 years ]
Complete list of historical versions of study NCT00548405 on ClinicalTrials.gov Archive Site
  • Proportion of patients who are relapse free at Year 2 [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Change from baseline in EDSS (Expanded Disability Status Scale) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Acquisition of disability as measured by change from baseline in Multiple Sclerosis Functional Composite (MSFC) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Percent change from baseline in MRI-T2 hyperintense lesion volume at Year 2 [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Proportion of patients who are relapse free at Year 2 [ Time Frame: 2 years ]
  • Change from baseline in EDSS [ Time Frame: 2 years ]
  • Acquisition of disability as measured by change from baseline in MSFC [ Time Frame: 2 years ]
  • Percent change from baseline in MRI-T2 hyperintense lesion volume at Year 2 [ Time Frame: 2 years ]
Not Provided
Not Provided
 
Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis, Study Two
Phase 3 Randomized, Rater- and Dose-Blinded Study Comparing 2 Annual Cycles of IV [Low]- and High-Dose Alemtuzumab to 3x Weekly SC Interferon Beta-1a (Rebif®) in Relapsing-Remitting Multiple Sclerosis Patients Who Have Relapsed on Therapy

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 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 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 enrollment so newly enrolled patients will be randomly assigned to treatment with either 12 mg alemtuzumab or Rebif® at a 2:1 ratio (ie, 2 given 12 mg or 24 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 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, patients who receive alemtuzumab may be followed in the CAMMS03409 Extension Study (NCT00930553) for safety and efficacy assessments. Patients who receive Rebif® and complete 2 years on study may be eligible to receive alemtuzumab in the Extension Study.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Multiple Sclerosis, Relapsing-Remitting
  • Biological: 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
  • Biological: 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.
  • Biological: interferon beta-1a (Rebif®)
    44 mcg administered 3-times weekly by SC injections for 2 years
  • Experimental: alemtuzumab 12 mg
    Intervention: Biological: alemtuzumab
  • Experimental: alemtuzumab 24mg
    Intervention: Biological: alemtuzumab
  • Active Comparator: interferon beta-1a (Rebif ®)
    Intervention: Biological: interferon beta-1a (Rebif®)

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
840
September 2011
September 2011   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Diagnosis of MS and MRI scan demonstrating white matter lesions attributable to MS
  • Onset of MS symptoms within 10 years
  • EDSS score 0.0 to 5.0
  • ≥2 MS attacks within 24 months, with ≥1 attack within 12 months
  • ≥1 MS attack (relapse)during treatment with a beta interferon therapy or glatiramer acetate after having been on that therapy for at least 6 months within 10 years

Exclusion Criteria:

  • Previous treatment with alemtuzumab
  • Previous treatment with any investigational drug (i.e. a medication that is not approved at any dose or for any indication)
  • Treatment with natalizumab, methotrexate, azothioprine or cyclosporine in the past 6 months
  • Previous treatment with mitoxantrone, cyclophosphamide, cladribine, rituximab, or any other immunosuppressive, or cytotoxic therapy (other than steroid treatment)
  • Any progressive form of MS
  • Any disability acquired from trauma or another illness that could interfere with evaluation of disability due to MS
  • Major systemic disease that cannot be treated or adequately controlled by therapy
  • Active infection or high risk for infection
  • Autoimmune disorder (other than MS)
  • Impaired hepatic or renal function
  • History of malignancy, except basal skin cell carcinoma
  • 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
  • Known bleeding disorder
  • Of childbearing potential with a positive serum pregnancy test, pregnant, or lactating
  • Current participation in another clinical study or previous participation in CAMMS323 (NCT00530348)
  • Previous hypersensitivity reaction to any immunoglobulin product
  • Known allergy or intolerance to interferon beta, human albumin, or mannitol
  • Intolerance of pulsed corticosteroids, especially a history of steroid psychosis
  • Inability to self-administer subcutaneous (SC) injections or receive SC injections from caregiver
  • Inability to undergo MRI with gadolinium administration
  • Unwilling to use a reliable and acceptable contraceptive method throughout the study period (fertile patients only)
Both
18 Years to 55 Years
No
Contact information is only displayed when the study is recruiting subjects
Italy,   Denmark,   United Kingdom,   United States,   Austria,   Germany,   Australia,   Belgium,   France,   Serbia,   Croatia,   Canada,   Ukraine,   Argentina,   Netherlands,   Czech Republic,   Israel,   Mexico,   Spain,   Brazil,   Russian Federation,   Sweden,   Poland
 
NCT00548405
CAMMS32400507, 2007-001162-32, CAMMS324,, ISRCTN70702834, ACTRN12608000426381, NTR1469, CARE-MS II
Yes
Genzyme, a Sanofi Company
Genzyme, a Sanofi Company
Bayer
Study Director: Medical Monitor Genzyme Coorporation
Genzyme, a Sanofi Company
November 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP