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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
  Purpose

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.


Condition Intervention Phase
Multiple Sclerosis, Relapsing-Remitting
Biological: alemtuzumab
Biological: interferon beta-1a (Rebif®)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Genzyme, a Sanofi Company:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 840
Study Start Date: October 2007
Study Completion Date: September 2011
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: alemtuzumab 12 mg 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
Experimental: alemtuzumab 24mg 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.
Active Comparator: interferon beta-1a (Rebif ®) Biological: interferon beta-1a (Rebif®)
44 mcg administered 3-times weekly by SC injections for 2 years

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00548405

  Show 194 Study Locations
Sponsors and Collaborators
Genzyme, a Sanofi Company
Bayer
Investigators
Study Director: Medical Monitor Genzyme Coorporation
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Genzyme, a Sanofi Company
ClinicalTrials.gov Identifier: NCT00548405     History of Changes
Other Study ID Numbers: CAMMS32400507, 2007-001162-32, CAMMS324,, ISRCTN70702834, ACTRN12608000426381, NTR1469, CARE-MS II
Study First Received: October 22, 2007
Last Updated: November 30, 2012
Health Authority: United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Austria: Federal Ministry for Health Family and Youth
Belgium: Federal Agency for Medicinal Products and Health Products
Brazil: National Health Surveillance Agency
Canada: Health Canada
Croatia: Agency for Medicinal Product and Medical Devices
Czech Republic: State Institute for Drug Control
Denmark: Danish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Paul-Ehrlich-Institut
Israel: Ministry of Health
Italy: The Italian Medicines Agency
Mexico: Federal Commission for Sanitary Risks Protection
Netherlands: Medical Ethics Review Committee (METC)
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Russia: Ministry of Health of the Russian Federation
Serbia and Montenegro: Agency for Drugs and Medicinal Devices
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
Ukraine: State Pharmacological Center - Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Genzyme, a Sanofi Company:
Multiple Sclerosis

Additional relevant MeSH terms:
Multiple Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Sclerosis
Autoimmune Diseases
Autoimmune Diseases of the Nervous System
Demyelinating Autoimmune Diseases, CNS
Demyelinating Diseases
Immune System Diseases
Nervous System Diseases
Pathologic Processes
Alemtuzumab
Interferon beta 1a
Interferon-beta
Interferons
Adjuvants, Immunologic
Anti-Infective Agents
Antineoplastic Agents
Antiviral Agents
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014