A 6-month, Randomized, Open-label, Patient OutComes, Safety and Tolerability Study of Fingolimod (FTY720) 0.5 mg/Day vs. Comparator in Patients With Relapsing Forms of Multiple Sclerosis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the change in patient-reported outcomes, physician assessment of a change as well as safety and tolerability in patients with Relapsing Forms of Multiple Sclerosis on previous Disease Modifying Therapy (DMT) who are randomized to one of two treatment arms: fingolimod vs. standard of care DMT.

Official Title
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A 6-month, Randomized, Active Comparator, Open-label, Multi-Center Study to Evaluate Patient OutComes, Safety and Tolerability of Fingolimod (FTY720) 0.5 mg/Day in Patients With Relapsing Forms of Multiple Sclerosis Who Are Candidates for MS Therapy Change From Previous Disease Modifying Therapy (EPOC)

Conditions
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Relapsing Forms of Multiple Sclerosis

Intervention / Treatment
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* Drug: Fingolimod
* Drug: Standard MS DMTs


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Relapsing forms of MS Expanded Disability Status Scale (EDSS) 0-5.5 Continuous treatment with MS DMT for a minimum of 6 months Fingolimod naive Exclusion Criteria: Immune system diseases other than MS Active macular edema History of selected prior infections and criteria for immunizations History of selected immune system treatments and/or medications Selected cardiovascular, pulmonary, or hepatic conditions Selected abnormal laboratory values Pregnant or nursing women Other protocol-defined inclusion/exclusion criteria applied

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fingolimod<br>Patients randomized in this arm received Fingolimod 0.5 mg/day oral capsule for 6 months core period . | Drug: Fingolimod<br>* 0.5 mg/day oral capsule<br>* Other names: GILENYA™;|
| Active Comparator: Multiple Sclerosis Disease Modifying Treatments (MS DMTs)<br>Patients randomized in this arm received selected Standard MS DMT such as Interferon beta-1b or Interferon beta-1a or Glatiramer acetate for 6 months. An open-label extension of up to 3 months of treatment with fingolimod was to be available for patients in the DMT arm who successfully completed all study visits. | Drug: Standard MS DMTs<br> <br> * Other names: Extavia®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Global Satisfaction Subscale of the Treatment Satisfaction Questionnaire for Medication (TSQM) at Month 6 | The TSQM was developed and validated as a general measure for treatment satisfaction. It contains 14 items assessing the following 4 domains: effectiveness (sum of scores for questions 1 - 3), side effects (sum of scores for questions 4 - 8), convenience (sum of scores for questions 9 - 11) and Global Satisfaction (sum of scores for questions 12 - 14). The primary analysis was on Global Satisfaction. Question 12 scored as 1(not at all confident) to 5 (extremely confident); question 13 scored as 1(not at all certain) to 5(extremely certain); and question 14 scored as 1(extremely dissatisfied) to 7(extremely satisfied). The scores of the domain were added together and an algorithm was used to create a score of 0 to 100. Higher scores indicated greater satisfaction. A positive change from baseline indicates improvement. | Baseline, Month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Who Experienced Adverse Events, Serious Adverse Events and Death | In this analysis, patients with all (serious and non-serious) adverse events, serious adverse events and death were reported. | 9 months (6 month core + 3 month Extension) | 
| Change From Baseline in Patient-reported Activities of Daily Living (ADL) Using the Multiple Sclerosis Activities Scale (PRIMUS-Activities) at Month 6 | The PRIMUS activity measure is a 15-item assessment of patient-reported ADL. The PRIMUS-Activities total score was calculated by summing the 15 item scores after recoding the responses from 1 - 3 to 0 - 2. Totals scores range from 0 to 30 with higher scores indicating greater activity limitation. If no more than 20% of the items were missing, the total score was the product of the mean response of the non-missing items and the total number of items. If more than 20% of all items were missing, the total score was set to missing. A negative change from baseline indicates improvement. | Baseline, Month 6 | 
| Change From Baseline in Patient-reported Fatigue Using the Fatigue Severity Scale (FSS) | The Fatigue Severity Scale (FSS) is a 9-item assessment scale measuring fatigue and its effects, using a scale from 1 to 7, with higher scores indicating greater fatigue, or greater negative effects of fatigue on daily living. The FSS 9 item total score was calculated by summing the first 9 item scores and dividing by the number of non-missing items. If no more than 20% of the items were missing, the total score was the product of the mean response of the non missing items and the total number of items. If more than 20% of all items were missing, the total score was set to missing. A negative change from baseline indicates improvement. | Baseline, Month 3, Month 6 | 
| Change From Baseline in the Patient-reported Effectiveness Subscale Using the TSQM v1.4 | The effectiveness scale was scored as follows: 1(extremely dissatisfied) to 7(extremely satisfied). The scores of the domain were added together and an algorithm was used to create a score of 0 to 100. Higher scores indicated greater satisfaction. A positive change from baseline indicates improvement. | Baseline, Month 6 | 
| Change From Baseline in the Patient-reported Side Effects Subscale Using the TSQM v1.4 | The Side Effects subscale was scored as follows: question 4 scored as 0(no) or 1(yes); question 5 scored as 1(extremely bothersome) to 5(not at all bothersome); and questions 6 - 8 scored as 1(a great deal) to 5(not at all). The scores of the domain were added together and an algorithm was used to create a score of 0 to 100. Higher scores indicated greater satisfaction. A positive change from baseline indicates improvement. | Baseline, Month 6 | 
| Change From Baseline in the Patient-reported Convenience Subscale Using the TSQM v1.4 | The convenience subscale was scored as follows: questions 9 and 10 scored as 1(extremely difficult) to 7 (extremely easy), and question 11 scored as 1(extremely inconvenient) to 7 (extremely convenient). The scores of the domain were added together and an algorithm was used to create a score of 0 to 100. Higher scores indicated greater satisfaction. A positive change from baseline indicates improvement. | Baseline, Month 6 | 
| Change From Baseline in Patient-reported Health-related Quality-of-life Using the Short Form Health Survey v2 Standard (SF-36 v2) | The SF-36v2 is a validated health-related quality of life instrument used in numerous disease states, including MS. It is a self-administered survey that measures 8 domains of health including: physical functioning, role limitations due to physical health, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems and general mental health. Additionally, two summary scale scores can be calculated: the Physical Component Summary (PCS) and the Mental Component Summary (MCS). If half or more questions within a domain were answered, then a score was calculated for that domain. Otherwise, the patient score for that domain was set to missing. If the patient was missing any 1 of the 8 scale scores, then the physical and mental component scores were set to missing. An algorithm was used to create a score from 0 to 100 for each domain score and component score. A positive change from baseline indicates improvement. | Baseline, Month 6 | 
| Change From Baseline in Patient-reported Depression Using the Beck Depression Inventory (BDI-II) | The Beck Depression Inventory (BDI-II) is a 21-question multiple-choice self-report inventory. Each item is scored from 0 to 3. The questions in the BDI-II refer to how the patient has been feeling over the past two weeks specifically. The BDI-II total score was calculated by summing the 21 item scores. Final scores ranged from 0 to 63 where higher scores indicated more severe depression. If no more than 20% of the items were missing, the total score was the product of the mean response of the non-missing items and the total number of items. If more than 20% of all items were missing, the total score was set to missing. A negative change indicates improvement. | Baseline, Month 3, Month 6 | 
| Physician-reported Clinical Global Impression of Improvement (CGI-I) | The CGI-I is a rating scale allowing a physician-reported global evaluation of the subject's improvement over time. The Investigator assessed the subject's clinical change relative to the symptoms at baseline on the CGI-I, a seven-point scale, with rating as follows: 1=Very much improved, 2=Much improved, 3=Minimally improved, 4=No change, 5=Minimally worse, 6=Much worse, 7=Very much worse. The assessments were completed at Month 3 and Month 6. A lower score indicates improvement. | Month 3, Month 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Relapsing Forms of Multiple Sclerosis, Disease Modifying Therapy, fingolimod, Patient Reported Outcomes