A 12 month study where 852 patients with relapsing remitting MS will be randomized 1:1 to fingolimod or approved disease modifying therapy. Patients will be be treatment naive or have only been treated with one class of DMT (Interferon beta preparation or glatiramer acetate) . Patients will be able to switch to different treatment for safety, efficacy, tolerability or convenience during the study. Primary objective is to evaluate efficacy of fingolimod by assessing patients retention on treatment. Secondary objectives are to compare reasons for discontinuation, adverse events, cognitive impairment, medication satisfaction and change in brain volume measured by MRI.
852 Patients with relapsing remitting MS will be randomized 1:1 to fingolimod or approved first line DMTs. Patients must be either treatment naive or have received treatment with only one class of treatment (interferon beta preparation or glatiramer acetate) . Patients previously treated with DMT and randomized to the DMT arm may not remain on the same treatment for the study and will have to switch to a different class (i.e., previously treated with glatiramer acetate will switch to interferon beta preparaption, previously treated with interferon beta preparation will swtich to glatiramer acetate). Entry criteria at screening include but are not limited to, age 18-65, diagnosis with RRMS, EDSS \< or equal to 6, not pregnant or planning pregnancy and women of childbearing potential willing to use contraception throughout the study. Exclusion criteria include but are not limited to - prior exposure to fingolimod, history of malignancy within 5 years, other than RRMS types of MS, other diseases of the immune system, active macular edema, systemic bacterial, viral or fungal infections, patients without vaccine against varicella zoster, receipt of live or attentuated vaccines within a month of screening, history of various cardiac conditions, presence of certain ECG abnormalities, resting heart rate \< 45 bpm, symptomatic bradycardia, recurrent syncope, severe untreated sleep apnea, severe pulmonary conditions, various hepatic conditions, certain neurologic disorders, pregnancy. Patients may switch treatment before 3 months for safety reasons only, after 3 months for safety, efficacy, tolerability or convenience. Treatment switch during the study may be to any of study approved treatments irrespective of prior treatment. Patients randomized to fingolimod will need to have 6 hours of observation for signs and symptoms of bradycardia following administration of the first dose. Extended observation or overnight observation may be necessary under certain circumstances. Primary objective is to evaluate efficacy of fingolimod by assessing patients retention on treatment. Secondary objectives are to compare reasons for discontinuation, adverse events, cognitive impairment, medication satisfaction and change in brain volume measured by MRI. Exploratory objectives include annualized relapse rate, OCT, MRI evaluations, biomarkers and patient reported outcome measures.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
881
Novartis Investigative Site
Cullman, Alabama, United States
Novartis Investigative Site
Phoenix, Arizona, United States
Novartis Investigative Site
Sun City, Arizona, United States
Novartis Investigative Site
Tucson, Arizona, United States
Novartis Investigative Site
Sherwood, Arkansas, United States
Participant Retention Rate Over 12 Months
Comparison effectiveness of fingolimod versus approved first-line disease modifying therapies by measuring the rate of participant retention on randomized treatment over a 12-month period (Full analysis set)
Time frame: at 12 months
Primary and Secondary Reasons for Discontinuation From Randomized Treatment: Randomized Set
Reasons for discontinuation in participants treated with fingolimod vs. DMT over 12 months of treatment Total discontinued (Primary reason): Fingolimod arm: 27, MS-DMT arm: 27 = 54 participants Total discontinued (Secondary reason): Fingolimod arm: 257, MS-DMT arm: 256 = 513 participants Throughout the study, investigators evaluated each patient for occurrence of randomized treatment discontinuation and determined the primary and secondary reasons for such discontinuation. At every visit, the investigator evaluated the patients and determined if they should continue on randomized treatment or change to alternative treatment. Treatment discontinuation was a clinically meaningful measure related to safety, efficacy, and tolerability over time, reflecting the therapeutic effectiveness of study treatment.
Time frame: at 12 months
Change From Baseline of Symbol Digit Modalities Test (SDMT) Scores (Oral Test) by Visit (Randomized Treatment / Randomized Phase)
Summary statistics Compare cognitive impairment measured by Symbol Digit Modalities Test (SDMT) scores. The SDMT score and its change from baseline value were summarized by visit. For the change from baseline values at each visit, ANCOVA adjusted for treatment naivety, corresponding baseline values, and age was performed for treatment comparisons The SDMT measures the time to pair abstract symbols with specific numbers. The test requires elements of attention, visuoperceptual processing, working memory, and psychomotor speed. The score is the number of correctly coded items from 0-110 in 90 seconds. The total score provides a measure of the speed and accuracy of symbol-digit substitution. NOTE: Higher scores indicate better performance.
Time frame: baseline, 6 months, 12 months, and Last assessment which is either at Month 12 or at early discontinuation
Change From Baseline of Symbol Digit Modalities Test (SDMT) Scores (Written Test) by Visit (Randomized Treatment / Randomized Phase)
Summary statistics Compare cognitive impairment measured by Symbol Digit Modalities Test (SDMT) scores. The SDMT score and its change from baseline value were summarized by visit. For the change from baseline values at each visit, ANCOVA adjusted for treatment naivety, corresponding baseline values, and age was performed for treatment comparisons The SDMT measures the time to pair abstract symbols with specific numbers. The test requires elements of attention, visuoperceptual processing, working memory, and psychomotor speed. The score is the number of correctly coded items from 0-110 in 90 seconds. The total score provides a measure of the speed and accuracy of symbol-digit substitution. NOTE: Higher scores indicate better performance.
Time frame: baseline, 6 months, 12 months, Last assessment which is either at Month 12 or at early discontinuation
Percent Change From Baseline in Brain Volume From Month 12 to Last Visit (Randomized)
Summary statistics for percent change from month 12 in brain volume by visit (Randomized treatment / randomized phase) in patients treated with fingolimod vs.DMTs as measured by MRI
Time frame: 12 months, and Last assessment which is either at Month 12 or at early discontinuation
Number of Satisfied Participants Per Medication Satisfaction Questionnaire (MSQ) Score
Summary statistics for Medication Satisfaction Questionnaire\[Question: "Overall, how satisfied are you with your current medication?"\] (Randomized treatment / randomized phase): Fingolimod vs MS-DMT
Time frame: Baseline, 1 month, 3 months, 6 months, 9 months, at 12 months & Last assessment during randomized phase which is either at Month 12 or at early discontinuation
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Novartis Investigative Site
Fullerton, California, United States
Novartis Investigative Site
Oceanside, California, United States
Novartis Investigative Site
San Francisco, California, United States
Novartis Investigative Site
Walnut Creek, California, United States
Novartis Investigative Site
Basalt, Colorado, United States
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