Patients With Relapse Remitting Multiple Sclerosis (RRMS): Candidates for MS Therapy Change (EPOC)

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 Remitting Multiple Sclerosis Who Are Candidates for MS Therapy Change From Previous Disease Modifying Therapy (EPOC)

The purpose of this study is to evaluate the change in patient-reported treatment satisfaction after 6 months of treatment with fingolimod 0.5mg/day vs. DMT standard of care, using the global satisfaction subscale of the Treatment Satisfaction Questionnaire for Medication (TSQM-9).

Study Overview

• Status: Completed
• Conditions: Relapsing Remitting Multiple Sclerosis
• Intervention / Treatment: Drug: Fingolimod; Drug: Standard MS DMT

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Novara, Italy, 28100
    • Novartis Investigative Site
  • AN
    • Ancona, AN, Italy, 60126
      • Novartis Investigative Site
  • BI
    • Ponderano, BI, Italy, 13900
      • Novartis Investigative Site
  • CL
    • Caltanissetta, CL, Italy, 93100
      • Novartis Investigative Site
  • CN
    • Cuneo, CN, Italy, 12100
      • Novartis Investigative Site
  • CO
    • Como, CO, Italy, 22100
      • Novartis Investigative Site
  • CT
    • Catania, CT, Italy, 95122
      • Novartis Investigative Site
  • FG
    • Foggia, FG, Italy, 71100
      • Novartis Investigative Site
  • FI
    • Castelfiorentino, FI, Italy, 50051
      • Novartis Investigative Site
  • MI
    • Milano, MI, Italy, 20133
      • Novartis Investigative Site
    • Milano, MI, Italy, 20122
      • Novartis Investigative Site
    • San Donato Milanese, MI, Italy, 20097
      • Novartis Investigative Site
  • MO
    • Modena, MO, Italy, 41100
      • Novartis Investigative Site
  • PA
    • Palermo, PA, Italy, 90146
      • Novartis Investigative Site
    • Palermo, PA, Italy, 90129
      • Novartis Investigative Site
  • PI
    • Pisa, PI, Italy, 56126
      • Novartis Investigative Site
  • VR
    • Legnago, VR, Italy, 37045
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients must be diagnosed with relapsing remitting MS (RRMS) as defined by 2005 revised McDonald criteria.
• Patients who explicitly agree to be assigned to a treatment group that may receive fingolimod or DMT after having been informed about their respective benefits and possible adverse events by the investigator.
• An Expanded Disability Status Scale (EDSS) score of 0-5.5 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 (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
• Patients with uncontrolled diabetes mellitus (HbA1c > 7%).
• Diagnosis of macular edema during Screening Phase.

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fingolimod; Patients randomized in this arm received Fingolimod 0.5 mg/day oral capsule for 6 months core period.	Drug: Fingolimod; 0.5 mg/day oral capsule; Other Names: GILENYA™
Active Comparator: Multiple Sclerosis Disease Modifying Treatment (MS DMT); 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.	Drug: Standard MS DMT; Interferon beta 1a or interferon beta 1b or Glatiramer Acetate; Other Names: Avonex®,; Copaxone®,; Rebif®,; Betaferon®,; Extavia®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Patient-reported Treatment Satisfaction	The Treatment Satisfaction Questionnaire for Medication (TSQM-9) is a psychometric measure of a patient's satisfaction with medication. It consists of 3 subscales: effectiveness, convenience and global satisfaction. The scores were computed by adding items for each domain, i.e. 1 to 3 for effectiveness, 4 - 6 for convenience and 7 to 9 for global satisfaction. The lowest possible score (1 for each item and 3 for all 3 subscales) was subtracted from the composite score and divided by the greatest possible score range. The greatest range was (7-1) X 3 items = 18 for the effectiveness and convenience, and (5-1) x 3 items = 12 for global satisfaction. This provided a transformed score between 0 and 1 that was then multiplied by 100. A positive change from baseline indicates improvement.	baseline, 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Patient-reported Activities of Daily Living (ADL)	The PRIMUS activity measure is a 15-item assessment used to evaluate patient-reported activities of daily living. The PRIMUS activities score was calculated summing the 15 items, after recoding the responses from 1 - 3 to 0 - 2. Therefore, the total score ranged from 0 - 3-, where high scores were indicative of greater function limitation. A negative change from baseline indicates improvement.	baseline, 6 months
Change From Baseline in Patient-reported Fatigue	The fatigue Severity Scale (FSS) is a 9-item scale used to assess fatigue. The FSS score was calculated summing the 9 items of the questionnaire and dividing by the number of non-missing items (each item is based on a 7-point Likert scale ranging from 1 (strongly disagree) to 7 (strongly agree)). A negative change from baseline indicates improvement.	6 months
Change From Baseline in Patient-Reported Effectiveness and Convenience	The Treatment Satisfaction Questionnaire for Medication (TSQM-9) is a psychometric measure of a patient's satisfaction with medication. It consists of 3 subscales: effectiveness, convenience and global satisfaction. The scores were computed by adding items for each domain, i.e. 1 to 3 for effectiveness, 4 - 6 for convenience and 7 to 9 for global satisfaction. The lowest possible score (1 for each item and 3 for all 3 subscales) was subtracted from the composite score and divided by the greatest possible score range. The greatest range was (7-1) X 3 items = 18 for the effectiveness and convenience, and (5-1) x 3 items = 12 for global satisfaction. This provided a transformed score between 0 and 1 that was then multiplied by 100. A positive change from baseline indicates improvement.	6 months
Change From Baseline in Patient-reported Depression	The Beck Depression Inventory Fast Screen (BDI-FS) is a brief, multiple choice, self reported inventory designed to evaluate depression in patients with medical illness. The BDI-FS score was calculated summing the 7 items of the questionnaire. Each item ranged from 0 (not present) to 3 (severe). The total score ranges from 0-3 (minimal depression), 4-8 (mild depression), 9-12 (moderate depression) and 13-21 (severe depression). A negative change from baseline indicates improvement.	6 months
Change From Baseline in Patient-reported Health Related Quality of Life (QOL)	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, pain, general health, energy/fatigue, social functioning, role limitations due to emotional problems and emotional well-being. 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.	6 months
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. A lower score and a negative change from baseline indicate improvement.	6 months

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Renato Turrini, MD, Novartis Farma S.p.A.

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): June 1, 2014

Study Registration Dates

• First Submitted: March 15, 2011
• First Submitted That Met QC Criteria: March 15, 2011
• First Posted (Estimate): March 16, 2011

Study Record Updates

• Last Update Posted (Estimate): June 22, 2015
• Last Update Submitted That Met QC Criteria: June 18, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: Multiple sclerosis; Fingolimod; Disease Modifying Therapy; TSQM-9
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Immunosuppressive Agents; Immunologic Factors; Adjuvants, Immunologic; Sphingosine 1 Phosphate Receptor Modulators; Fingolimod Hydrochloride; Interferon beta-1b
• Other Study ID Numbers: CFTY720DIT02; 2010-024017-31 (EudraCT Number)