Relapsing-remitting multiple sclerosis (RRMS)
Conditions
Interventions
Product Code: FTY720
Pharmaceutical Form: Capsule*
INN or Proposed INN: Fingolimod
CAS Number: 162359-56-0
Current Sponsor code: FTY720
Concentration unit: mg milligram(s)
Concentration type: equal
Co
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: General 1. male or female; females of childbearing potential must: - have negative pregnancy tests prior to entry into the Double-Blind Treatment Phase - use simultaneously two forms of effective contraception (either partner) during the treatment and for 3 months after discontinuation of the study medication females that are either post-menopausal for 12 months prior to Randomisation or are sugically sterile (through hysterectomy or bilateral oophorectomy) are not required to use birth control 2. 18 through 55 years of age inclusive 3. signed written informed consent prior to participating in the study. Multiple sclerosis 4. diagnosis of multiple sclerosis as defined by 2005 revised McDonald criteria 5. a relapsing-remitting course with at least 1 documented relapse during the previous year or 2 documented relapses during the previous 2 years; prior to randomization 6. an Expanded Disability Status Scale (EDSS) score of 0-5.5 inclusive 7. neurologically stable with no evidence of relapse or corticosteroid treatment within 30 days prior to randomization Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Patients who meet any of the following exclusion criteria during the Pre-Randomization Phase will not be eligible for enrollment in the study: 1. a manifestation of MS other than RRMS 2. a history of chronic disease of the immune system other than MS or a known immunodeficiency syndrome 3. a history of epileptic seizures within 3 months of randomization 4. a history or presence of malignancy (except for successfully treated basal or squamous cell carcinoma of skin) 5. a known or ‘new’ diagnosis of diabetes mellitus 6. a diagnosis of macular edema during Pre-randomization Phase (patients with a history of macular edema will be allowed to enter the study provided that they do not have macular edema at the ophthalmic screening visit). 7. active systemic bacterial, viral or fungal infections, or diagnosis of AIDS, Hepatitis B, Hepatitis C infection defined as a positive HIV antibody, Hepatitis B surface antigen or Hepatitis C antibody tests, respectively 8. have received total lymphoid irradiation or bone marrow transplantation 9. have been treated with: • systemic corticosteroids or adrenocorticotropic hormones (ACTH) within 1 month prior to randomization • immunosuppressive medications such as azathioprine or methotrexate within 6 months prior to randomization • immunoglobulins and/or monoclonal antibodies (including natalizumab) within 6 months prior to randomization • cladribine, cyclophosphamide or mitoxantrone at any time 10. any medically unstable condition, as assessed by the primary treating physician 11. any of the following cardiovascular conditions: • myocardial infarction within the past 6 months prior to enrollment or current unstable ischemic heart disease • history of angina pectoris due to coronary spasm or history of Raynaud’s phenomenon • cardiac failure at time of Screening (Class III, according to NYHA Classification; or any severe cardiac disease as determined by the investigator • history of cardiac arrest • history of symptomatic bradycardia • resting pulse rate 440 ms on Screening ECG • arrhythmia requiring current treatment with Class III antiarrhythmic drugs (e.g., amiodarone, bretylium, sotalol, ibulitide, azimilide, dofelitide) • history of a positive tilt test from workup for vasovagal syncope • hypertension, uncontrolled by medication 12. any of the following pulmonary conditions: • severe respiratory disease or pulmonary fibrosis • tuberculosis, except for history of successfully treated tuberculosis or history of prophylactic treatment after positive PPD skin reaction • abnormal chest High Resolution Computer Tomography (HRCT) [or chest x-ray in case HRCT is not permitted by local regulations] suggestive of active pulmonary disease • abnormal Pulmonary Function Tests: FEV1;, FVC values lower than 70% of predicted value, DLCO values lower than 60% of predicted value • patients receiving chronic therapies for asthma 13. any of the following hepatic conditions: • known history of alcohol abuse, chronic liver or biliary disease • total bilirubin greater than the upper limit of the normal range, unless in context of Gilbert's syndrome • conjugated bilirubin greater than the upper limit of the normal range • alkaline phosphatase (AP) greater than 1.5 times the upper limit of the normal range • AST (SGOT), ALT (SGPT) g
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to compare fingolimod 1.25 mg and 0.5 mg with interferon ß-1a and to demonstrate that at least 1.25 mg fingolimod is superior to interferon ß-1a in terms of annualized relapse rate for patients with RRMS treated for up to 12 months.;Secondary Objective: To demonstrate superiority of two doses of fingolimod (1.25 mg and 0.5 mg per day) over interferon ß-1a (30 µg/week i.m.) in patients with RRMS treated for up to 12 months in the proportion of relapse-free patients. To assess the efficacy of fingolimod 1.25 mg/day vs. fingolimod 0.5 mg/day in the annualized relapse rate and proportion of relapse free patients. To evaluate the safety and tolerability of fingolimod compared to interferon ß-1a. To test for difference in efficacy of fingolimod (1.25 mg and 0.5 mg per day) vs. interferon ß-1a on: other relapse-related parameters; disability progression; and burden of disease and inflammatory disease activity as measured by MRI ;Primary end point(s): The primary endpoint will be the annualized relapse rate (ARR), which is defined as the number of relapses in a year. The key secondary endpoint will be the proportion of relapse-free patients. Other secondary endpoints include: • time to first relapse • time to second relapse • number of hospitalizations due to relapses • frequency of corticosteroid use to treat relapses • time to confirmed disability progression • proportion of patients with confirmed disability progression • change from Baseline to the end of study on the MSFC z-score • Burden of disease as measured by MRI: • % change from baseline in volume of T2 lesions at 12 months • % change from baseline in volume of T1 hypointense lesions at 12 months • Inflammatory disease activity as measured by MRI: • proportion of scans showing Gd-enhanced T1 lesions • proportion of scans showing new/ newly enlarged T2 lesions • number of new/ newly enlarged T2 lesions • number of Gd-enhanced T1 lesions • volume of Gd-enhanced T1 lesi | — |
Countries
Austria, Belgium, Germany, Greece, Hungary, Italy, Portugal, Spain, United Kingdom
Outcome results
None listed