Sequential Natalizumab - Alemtuzumab Therapy in Patients With Relapsing Forms of Multiple Sclerosis
Condition: Multiple Sclerosis (MS)
MeSH terms: Multiple Sclerosis; Sclerosis
Intervention: Alemtuzumab
Intervention description: Alemtuzumab is a humanized monoclonal therapeutic antibody that rapidly depletes cluster of differentiation 52 (CD52)+ cells.
Intervention MeSH terms: Alemtuzumab
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: To determine if treatment with alemtuzumab after natalizumab maintains or reduces the ARR in patients with RRMS. The goal of this trial is to establish a disease-free state over a 24 months period in patients who received the natalizumab-alemtuzumab sequential therapy.
Masking: None (Open Label)
Enrollment: 9.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to determine if a sequential combination therapy of natalizumab
      and alemtuzumab induces peripheral tolerance and reduces the annualized relapse rate (ARR) in
      patients with relapsing-remitting multiple sclerosis (RRMS).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age between 18 and 60 years, inclusive.

          2. Diagnosis of relapsing forms of MS using revised McDonald Criteria1.

          3. Expanded Disability Status Scale (EDSS) 0 - 5.5 (note: functional system changes in
             cerebral (or mental) functions and in bowel and bladder functions not used in
             determining EDSS for protocol eligibility).

          4. Has had a minimum of 12 monthly doses of continuous natalizumab therapy (300 mg/d).

          5. Understands English, and gives informed consent.

        Exclusion Criteria:

          1. Natalizumab failure based on clinician's discretion.

          2. Any prior exposure to alemtuzumab.

          3. Progressive MS.

          4. A diagnosis of Progressive multifocal leukoencephalopathy (PML).

          5. Known hypersensitivity to alemtuzumab.

          6. Initiation of new immunosuppressant treatment after the subject becomes
             protocol-eligible (except for corticosteroids) or enrollment in a concurrent trial
             with immuno-active pharmacotherapies.

          7. Uncontrolled diabetes mellitus defined as HbA1c > 8% and/or requiring intensive
             management.

          8. History of cytopenia consistent with the diagnosis of myelodysplastic syndrome.

          9. Clinically significant autoimmune disease other than MS that may affect the CNS,
             including neuromyelitis optica (NMO), systemic lupus erythematosus (SLE), or Behcet
             disease.

         10. Active hepatitis B or C infection or evidence of cirrhosis.

         11. HIV positivity.

         12. Uncontrolled viral, fungal, or bacterial infection.

         13. Positive pregnancy test or inability or unwillingness to use effective means of birth
             control. Effective birth control is defined as:

               1. Refraining from all acts of vaginal intercourse (abstinence),

               2. Consistent use of birth control pills,

               3. Tubal sterilization or male partner who has undergone vasectomy

               4. Placement of intrauterine device

               5. Use, with every act of intercourse, of a diaphragm with contraceptive jelly
                  and/or condoms with contraceptive foam.

         14. Presence of metallic objects implanted in the body that would preclude the ability of
             the subject to safely have MRI exams.

         15. Psychiatric illness, mental deficiency, or cognitive dysfunction making compliance
             with treatment or informed consent impossible.