Evaluation of Patient Reported Outcomes in RRMS Patients Candidates for MS Therapy Change and Transitioned to Fingolimod 0.5 mg (EPOC)

Study Overview
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Brief Summary
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A 6-month, Randomized, Active Comparator, Open-label, Multi-Center Study to Evaluate Patient Outcomes, Safety and Tolerability of (fingolimod) 0.5 mg/day in Patients with Relapsing Remitting Multiple Sclerosis who are candidates for MS therapy change from Previous Disease Modifying Therapy.

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) 0.5 mg/Day in Patients With Relapsing Remitting Multiple Sclerosis Who Are Candidates for Multiple Sclerosis (MS) Therapy Change From Previous Disease Modifying Therapy (DMT)

Conditions
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Relapsing Remitting Multiple Sclerosis

Intervention / Treatment
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* Drug: Fingolimod
* Drug: Interferon beta - 1a (IFN)
* Drug: Glatiramer acetate (GA)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent must be obtained before any assessment is performed. Patients must be diagnosed with relapsing remitting MS (RRMS) as defined by 2005 revised McDonald criteria (McDonald et al 2001, Polman et al 2005) (Appendix 2). Patients who explicitly agree to be assigned to a treatment group that may receive or DMT after having been informed about their respective benefits and possible adverse events by the investigator. Male or female patients aged 18-70 years. An Expanded Disability Status Scale (EDSS) score of 0-6 inclusive. Must have received continuous treatment with a single approved and indicated MS DMT for a minimum of 6 months prior to the screening visit. Patients must continue with this MS DMT until the randomization visit. Naïve to treatment with fingolimod. Exclusion Criteria: A manifestation of MS other than those defined in the inclusion criteria. A history of chronic disease of the immune system other than MS or a known immunodeficiency syndrome. History of malignancy of any organ system. Diagnosis of macular edema during Screening Phase. Patients with active systemic bacterial, viral or fungal infections, or known to have AIDS or to have positive HIV antibody test. Patients who have received any live or live attenuated vaccines (including for varicella-zoster virus or measles) within 2 months prior to baseline. Patients who have received total lymphoid irradiation or bone marrow transplantation. History of selected immune system treatments and/or medications. Any medically unstable condition, as assessed by the investigator. Selected cardiovascular, or hepatic conditions Selected abnormal laboratory values. Patients with any other disease or clinical condition (including neurologic or psychiatric disorders) which may affect patient enrollment into the study and study medication use by the Investigators' opinion. Participation in any clinical research study evaluating another not approved in Russia investigational drug or therapy within 6 months prior to baseline. History of hypersensitivity to the study drug or to drugs of similar chemical classes. Pregnant or nursing (lactating) women. Other protocol-defined inclusion/exclusion criteria may apply

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>Participants received 0.5 mg orally once a day. | Drug: Fingolimod<br>* 0.5 mg orally once a day<br>* Other names: Gilenya;|
| Active Comparator: Standard Disease Modifying Therapy (DMT)<br>Participants received interferon beta-1a (IFN), 44 mcg subcutaneously 3 times a week or glatiramer acetate (GA), 20 mg subcutaneously once a day. | Drug: Interferon beta - 1a (IFN)<br>* 44 mcg subcutaneously three times a week<br>* Other names: Rebif;Drug: Glatiramer acetate (GA)<br>* 20 mg subcutaneously once a day<br>* Other names: Copaxone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Patient-reported Treatment Satisfaction | The Treatment Satisfaction Questionnaire for Medication (TSQM) contains 14 items assessing the following 4 domains: effectiveness (items 1 - 3), side effects (items 4 - 8), convenience (items 9 - 11) and global satisfaction (items 12 - 14). The primary outcome was measured on the global satisfaction domain. Item 12 scored as 1 (not at all confident) to 5 (extremely confident); item 13 scored as 1 (not at all certain) to 5 (extremely certain); and item 14 scored as 1 (extremely dissatisfied) to 7 (extremely satisfied). Responses to items were summed and transformed: specifically, TSQM v 1.4 domain scale scores were computed by adding the items loading on each domain. The lowest possible score was subtracted from the composite score and divided by the greatest possible score range. This provided a transformed score between 0 and 1 that was then multiplied by 100. The final transformed score ranges from 0 to 100, with higher scores indicating better treatment satisfaction. | Baseline, 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Who Experienced Adverse Events, Serious Adverse Events and Death | Participants were monitored for adverse events, serious adverse events and death throughout the study. | 6 months | 
| Changes in Patient-reported Effectiveness, Side Effects and Convenience | TSQM v 1.4 domains for effectiveness, side effects and convenience were used to evaluate this outcome. The effectiveness domain for items 1 - 3 was scored as: 1 (extremely dissatisfied) to 7 (extremely satisfied). For the side effects domain, item 4 scored as 0(no) or 1(yes); item 5 scored as 1 (extremely bothersome) to 5 (not at all bothersome); and items 6 - 8 scored as 1 (a great deal) to 5 (not at all). For the convenience domain, items 9 and 10 scored as 1(extremely difficult) to 7 (extremely easy), and item 11 scored as 1 (extremely inconvenient) to 7 (extremely convenient). For each domain, scale scores were computed by adding the items loading on each domain. The lowest possible score was subtracted from the composite score and divided by the greatest possible score range. This provided a transformed score between 0 and 1 that was then multiplied by 100. The final transformed score ranges from 0 to 100, with higher scores indicating better treatment satisfaction. | Baseline, 6 months | 
| Change in Patient-reported Depression | The Beck Depression Inventory (BDI-I) scale was used to measure this outcome. The scale consists of 21 items to assess the intensity of depression in clinical and normal patients. Each item is a list of four statements arranged in increasing severity about a particular symptom of depression. Each item was scored from 0 - 3. If more than one score was provided for an item, the maximum score was considered the item score. The total score was calculated as the sum of all individual items and then compared to a key to determine the depression's severity. The standard key ranges were: 0 - 9 indicated minimal depression; 10 - 18 indicated mild depression; 19 - 29 indicated moderate depression and 30 - 63 indicated severe depression. Higher total scores indicate more severe depressive symptoms. | Baseline, 6 months | 
| Change in Patient-reported Health-related Quality-of-life Using the Short Form Health Survey v2 Acute (SF-36 v2 Acute) | The SF-36 is a health-related quality of life instrument used in numerous disease states, including MS (Brazier et al 1992). 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. Two summary scale scores can be calculated: the Physical Component Summary (PCS) and the Mental Component Summary (MCS). Each domain was scored by adding the individual items from the domain and transforming the resulting scores into a 0 to 100 scale with higher scores indicating better health status or functioning. | Baseline, 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fingolimod, Relapsing Remitting Multiple Sclerosis (RRMS), Disease Modifying Therapy (DMT), TSQM-9