Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis, Study Two

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”

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.

Intervention(s) in this Clinical Trial

• 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

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: alemtuzumab 12 mg
• Experimental: alemtuzumab 24mg
• Active Comparator: interferon beta-1a (Rebif ®)

Primary Measures

• Time to Sustained Accumulation of Disability (SAD)
  • Time Frame: 2 years
    Safety Issue?: No
• Relapse Rate
  • Time Frame: 2 years
    Safety Issue?: No

Secondary Measures

• Proportion of patients who are relapse free at Year 2
  • Time Frame: 2 years
    Safety Issue?: No
• Change from baseline in EDSS (Expanded Disability Status Scale)
  • Time Frame: 2 years
    Safety Issue?: No
• Acquisition of disability as measured by change from baseline in Multiple Sclerosis Functional Composite (MSFC)
  • Time Frame: 2 years
    Safety Issue?: No
• Percent change from baseline in MRI-T2 hyperintense lesion volume at Year 2
  • Time Frame: 2 years
    Safety Issue?: No

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)

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 55 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Genzyme Industry

Overall Clinical Trial Officials and Contacts

Medical Monitor Study Director Genzyme Coorporation  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00548405

Study ID Number: CAMMS32400507

ClinicalTrials.gov Identifier: NCT00548405

Health Authority: United States: Food and Drug Administration