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

• ClinicalTrials.gov Identifier: NCT01317004
• Recruitment Status: Completed
• First Posted: March 16, 2011
• Results First Posted: June 22, 2015
• Last Update Posted: June 22, 2015
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Relapsing Remitting Multiple Sclerosis	Drug: Fingolimod; Drug: Standard MS DMT	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 61 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Study Start Date: May 2011
• Actual Primary Completion Date: June 2014
• Actual Study Completion Date: June 2014

Arms and Interventions

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 Name: 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®

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in Patient-reported Treatment Satisfaction [ Time Frame: baseline, 6 months ]
   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.

Secondary Outcome Measures :

1. Change From Baseline in Patient-reported Activities of Daily Living (ADL) [ Time Frame: baseline, 6 months ]
   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.
2. Change From Baseline in Patient-reported Fatigue [ Time Frame: 6 months ]
   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.
3. Change From Baseline in Patient-Reported Effectiveness and Convenience [ Time Frame: 6 months ]
   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.
4. Change From Baseline in Patient-reported Depression [ Time Frame: 6 months ]
   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.
5. Change From Baseline in Patient-reported Health Related Quality of Life (QOL) [ Time Frame: 6 months ]
   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. Physician-reported Clinical Global Impression of Improvement (CGI-I) [ Time Frame: 6 months ]
   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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

Italy

Novartis Investigative Site

Ancona, AN, Italy, 60126

Novartis Investigative Site

Ponderano, BI, Italy, 13900

Novartis Investigative Site

Caltanissetta, CL, Italy, 93100

Novartis Investigative Site

Cuneo, CN, Italy, 12100

Novartis Investigative Site

Como, CO, Italy, 22100

Novartis Investigative Site

Catania, CT, Italy, 95122

Novartis Investigative Site

Foggia, FG, Italy, 71100

Novartis Investigative Site

Castelfiorentino, FI, Italy, 50051

Novartis Investigative Site

Milano, MI, Italy, 20122

Novartis Investigative Site

Milano, MI, Italy, 20133

Novartis Investigative Site

San Donato Milanese, MI, Italy, 20097

Novartis Investigative Site

Modena, MO, Italy, 41100

Novartis Investigative Site

Palermo, PA, Italy, 90129

Novartis Investigative Site

Palermo, PA, Italy, 90146

Novartis Investigative Site

Pisa, PI, Italy, 56126

Novartis Investigative Site

Legnago, VR, Italy, 37045

Novartis Investigative Site

Novara, Italy, 28100

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

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

More Information

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01317004
• Other Study ID Numbers: CFTY720DIT02; 2010-024017-31 ( EudraCT Number )
• First Posted: March 16, 2011
• Results First Posted: June 22, 2015
• Last Update Posted: June 22, 2015
• Last Verified: June 2015

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

Multiple sclerosis; Fingolimod; Disease Modifying Therapy; TSQM-9

Additional relevant MeSH terms:

Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Sclerosis; Pathologic Processes; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Fingolimod Hydrochloride; Interferon beta-1b; Sphingosine 1 Phosphate Receptor Modulators; Molecular Mechanisms of Pharmacological Action; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Adjuvants, Immunologic