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Table 1 Eligibility criteria

From: Assessment of immune functions and MRI disease activity in relapsing-remitting multiple sclerosis patients switching from natalizumab to fingolimod (ToFingo-Successor)

Inclusion criteria Written informed consent provided
Male and female subjects aged 18 to 65 years
Diagnosis of RRMS, defined by revised McDonald criteria (2010)
Expanded Disability Status Scale (EDSS) at screening score ≤ 6.0
Treatment with natalizumab for at least 12 months prior to screening and consideration of treatment discontinuation for any of the following reasons:
• treatment duration > 2 years
• positive JCV antibody status
• adverse effects including hypersensitivity reactions
• presence of anti-natalizumab neutralizing antibodies
• any other valid medical reason
Exclusion criteria History of chronic disease of the immune system other than MS, which requires systemic immunosuppressive treatment, or a known immunodeficiency syndrome.
Diagnosis of Crohn’s disease or ulcerative colitis
Treatment 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.
History of malignancy of any organ system (other than cutaneous basal cell carcinoma)
Uncontrolled diabetes mellitus (HbA1c >7 %)
Diagnosis of macular edema during Screening Phase
Severe active infections, active chronic infection.
Negative for varicella-zoster virus IgG antibodies prior to baseline.
Vaccination with live or live-attenuated vaccine (including varicellazoster virus or measles) within 1 month prior to baseline
Previous therapy with total lymphoid irradiation or bone marrow transplantation
Any medically unstable condition, as assessed by the investigator
Any of the following cardiovascular conditions and/or findings in the screening ECG:
• history of cardiac arrest
• myocardial infarction within the past 6 months prior to screening or with current unstable ischemic heart disease
• history of angina pectoris due to coronary spasm
• heart failure (NYHA III-IV) or any severe cardiac disease as determined by the investigator
• history or presence of a second-degree AV block, Type II or a third-degree AV block or QTc interval > 450 ms in males and > 470 ms in females
• treatment with Class Ia (ajmaline, disopyramide, procainamide, quinidine) or Class III antiarrhythmic drugs (e.g., amiodarone, bretylium, sotalol, ibulitide, azimilide, dofelitide)
• proven history of sick sinus syndrome or sino-atrial heart block
• uncontrolled hypertension
• Resting HR lower than 45 bpm
Presence of severe respiratory disease, pulmonary fibrosis or chronic obstructive pulmonary disease (Class III-IV)
Any of the following hepatic conditions:
• severe hepatic injury (Child-Pugh class C)
• total bilirubin greater than 2 times the upper limit of the normal range
• AST or ALT greater than 2 times the upper limit of the normal range
• alkaline phosphatase (AP) greater than 2 times the upper limit of the normal range
White blood cell (WBC) count <3,500/mm3 or
lymphocyte count <800/mm3 at screening
Any of the following neurologic/psychiatric disorders:
• history of substance abuse (drug or alcohol) in the past five years or any other factor (i.e., serious psychiatric condition) that may interfere with the subject’s ability to cooperate and comply with the study procedures
• progressive neurological disorder, other than MS, which may affect participation in the study
Incapability to undergo MRI scans, including claustrophobia or history of hypersensitivity to gadolinium-DTPA
Treatment with investigational drug or therapy within 180 days or 5 half-lives before baseline, whichever is longer
Pregnancy or breast feeding (lactating), confirmed by a positive hCG laboratory
Child-bearing potential (Unless the women concerned 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)
History of hypersensitivity to the study drugs or to drugs of similar chemical classes
Prior participation in a trial with fingolimod