Study to Assess Immune Function and MRI Disease Activity in RRMS Patients When Switching From Natalizumab to Gilenya (ToFingo2)

This is an interventional treatment trial for Relapsing Remitting Multiple Sclerosis focused on measuring RRMS (relapsing remitting multiple sclerosis), Cluster of differentiation 49d (CD49d), immune function, disease activity Read More

Inclusion Criteria:

1. Written informed consent must be obtained before any assessment is performed.
2. Male and female subjects aged 18-65 yrs.
3. Subjects with RRMS, defined by 2010 rev. McDonald criteria.
4. Patients with an (EDSS) score of 0-6.0 inclusive.

5. Patients on treatment with natalizumab for ≥ 12 months prior to screening where treatment discontinuation is considered for any of the following reasons:

   • treatment duration for more than 2 years
   • positive JC virus (JCV) antibody status
   • adverse effects including hypersensitivity reactions
   • presence of anti-natalizumab neutralizing antibodies
   • any other valid medical reason

Exclusion Criteria:

1. Patients with a history of chronic disease of the immune system other than MS, which requires systemic immunosuppressive treatment, or a known immunodeficiency syndrome.
2. Patients with Crohn´s disease or ulcerative colitis.

3. Patients who have been treated with:

   • systemic corticosteroids or immunoglobulins within 1 month prior to baseline.
   • immunosuppressive medications such as azathioprine, cyclophosphamide or methotrexate within 3 months prior to baseline.
   • monoclonal antibodies (excluding natalizumab) within 3 months prior to baseline.
   • cladribine or mitoxantrone at any time.
4. History of malignancy of any organ system (other than cutaneous basal cell carcinoma).
5. Uncontrolled diabetes mellitus (HbA1c >7%).
6. Diagnosis of macular edema during Screening Phase.
7. Severe active infections, active chronic infection.
8. Negative for varicella-zoster virus immunoglobulin G antibodies prior to baseline.
9. Patients that received any live or live-attenuated vaccine (including varicella-zoster virus or measles) within 1 month prior to baseline.
10. Patients who have received total lymphoid irradiation or bone marrow transplantation.
11. Patients with any medically unstable condition, as assessed by the investigator.
12. Patients with certain cardiovascular conditions and/or findings in the screening ECG.
13. Patients with certain lung diseases.
14. Patients with certain hepatic conditions.
15. Patients with a screening white blood cell (WBC) count <3,500/mm3 or lymphocyte count <800/mm3.
16. Patients with certain neurologic/psychiatric disorders:
17. Patients unable to undergo MRI scans, including claustrophobia or history of hypersensitivity to gadolinium-diethylenetriaminepentacetate (Gd-DTPA).
18. Patients who have received an investigational drug or therapy within 180 days or 5 half-lives before baseline, whichever is longer.
19. Pregnant or nursing (lactating) women, confirmed by a positive human chorionic gonadotropin laboratory.
20. Women of child-bearing potential unless they are using effective contraception during the study and for 5 half-lives after stopping treatment. In case of use of oral contraception women should have been stable on the same medication for a minimum of 3 months before baseline.
21. History of hypersensitivity to the study drugs or to drugs of similar chemical classes.
22. Prior participation in a trial with fingolimod.