A 3-year Multi-center Study to Describe Changes of OCT Parameters Under Treatment With Gilenya®
Condition: Relapsing Remitting Multiple Sclerosis RRMS
MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Sclerosis
Intervention: Fingolimod
Intervention description: All subjects received an oral dose of 0.5 mg fingolimod (FTY720) per capsule (hard gelatin capsules) once daily according to local label for the treatment of their MS.
Intervention MeSH terms: Fingolimod Hydrochloride
Phase: Phase 4
Study type: Interventional
Primary purpose: Basic Science
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 87.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Multiple sclerosis (MS); MS

Summary:

      This was a 3-year, prospective, multi-center, open-label study to describe the long term
      changes of optical coherence tomography (OCT) parameters in RRMS patients under treatment
      with Fingolimod. It was designed to longitudinally study the degeneration of retinal axons by
      measuring change in RNFL thickness by latest OCT-technology.
    

Eligibility criteria:

        Inclusion Criteria

        Patients eligible for inclusion in this study have to fulfill all of the following
        criteria:

          1. Written informed consent must be obtained before any assessment is performed.

          2. Male or female subjects aged 18-65 years.

          3. Subjects with relapsing remitting MS defined by 2010 revised McDonald criteria (see
             Appendix 4).

          4. Patients with Expanded Disability Status Scale (EDSS) score of 0-6.0 inclusive (see
             Appendix 6).

          5. Patients stable on immunomodulatory treatment with fingolimod for at least 1 month and
             at most 4 months prior to screening according to local label

          6. Neurologically stable with no evidence of relapse within 30 days prior to inclusion
             date

          7. Sufficient ability to read, write, communicate and understand

        Exclusion Criteria

        Patients fulfilling any of the following criteria are not eligible for inclusion in this
        study:

          1. Patients who have been treated with:

               -  systemic corticosteroids or immunoglobulins within 1 month prior to screening;

               -  immunosuppressive medications such as azathioprine, cyclophosphamide, or
                  methotrexate within 3 months prior to screening;

               -  monoclonal antibodies (including natalizumab) within 3 months prior to screening;

               -  mitoxantrone within 6 months prior to screening

               -  cladribine at any time.

          2. Patients with any medically unstable condition, as assessed by the primary treating
             physician at each site.

          3. Patients with any of the following cardiovascular conditions :

               -  history of myocardial infarction or with current unstable ischemic heart disease;

               -  Heart failure (NYHA III-IV) or any severe cardiac disease as determined by the
                  Investigator (see Appendix 5);

               -  history or presence of a second-degree AV block, Type II or a third-degree AV
                  block

               -  patients receiving Class Ia (ajmaline, disopyramide, procainamide, quinidine) or
                  III antiarrhythmic drugs (e.g., amiodarone, bretylium, sotalol, ibulitide,
                  azimilide, dofelitide);

               -  proven history of sick sinus syndrome;

               -  uncontrolled hypertension

          4. Patients with severe respiratory disease, pulmonary fibrosis, or chronic obstructive
             pulmonary disease (Class III-IV).

          5. Patients with history of specific MRI findings (tumor, subdural haematoma,
             post-contusional changes, territorial stroke, neurodegenerative disorders,
             aneurysm/arteriovenous malformation, evidence of past macroscopic haemorrhage, or
             other relevant MRI findings that would interfere with evaluation)

          6. Any severe disability or clinical impairment that can prevent the patient to meet all
             study requirements at the investigator's discretion

          7. History of malignancy of any organ system, treated or untreated, within the past 5
             years whether or not there is evidence of local recurrence or metastases, with the
             exception of localized basal cell carcinoma of the skin

          8. Patients who have received an investigational drug (excluding fingolimod) or therapy
             within 90 days or 5 half-lives of screening, whichever is longer.

          9. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a
             female after conception and until the termination of gestation, confirmed by a
             positive hCG test (serum)

         10. Patients with any ophthalmologic reason for RNFL pathology other than MS, such as:
             optic neuropathy, active advanced glaucoma, injury of the optic nerve based on the
             ophthalmologist's clinical judgment

         11. history or presence of severe myopia

               1. in patients who have not had refractive surgery, a refractive error of greater
                  than 6.00 diopters

               2. pathologic fundus changes of high myopia, such as retinal pigmentary atrophy,
                  besides peripapillary atrophy (atrophy involving the macula) or a staphyloma

               3. in patients that have had previous refractive surgery, an axial eye length of
                  greater than 26 mm

         12. Acute optic neuritis within the past 6 months before screening

         13. Evidence of advanced, non-proliferative or proliferative diabetic retinopathy

         14. Presence of retinal conditions associated with edema, subretinal fluid, cysts, etc.

         15. Concomitant use of drugs that may directly affect retinal structure and function (e.g.

        chronic systemic corticosteroids [>30 consecutive days; doses higher than Cushing threshold
        e.g. prednisone 7.5mg/d], intraocular anti-angiogenic drugs [ranibizumab, bevacizumab],
        intraocular steroids etc.)