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

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01317004
• Collaborator: (none)
• Enrollment: 61
• Locations: 17
• Arms: 2
• Duration (Months): 37
• Patients Per Site: 3.6
• Patients Per Site Per Month: 0.1

Study Details

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
• 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 1, 2011
• Actual Primary Completion Date: Jun 1, 2014
• Actual Study Completion Date: Jun 1, 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 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®

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Patient-reported Treatment Satisfaction [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) [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 [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 [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 [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) [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) [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

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Ancona	AN	Italy	60126
2	Novartis Investigative Site	Ponderano	BI	Italy	13900
3	Novartis Investigative Site	Caltanissetta	CL	Italy	93100
4	Novartis Investigative Site	Cuneo	CN	Italy	12100
5	Novartis Investigative Site	Como	CO	Italy	22100
6	Novartis Investigative Site	Catania	CT	Italy	95122
7	Novartis Investigative Site	Foggia	FG	Italy	71100
8	Novartis Investigative Site	Castelfiorentino	FI	Italy	50051
9	Novartis Investigative Site	Milano	MI	Italy	20122
10	Novartis Investigative Site	Milano	MI	Italy	20133
11	Novartis Investigative Site	San Donato Milanese	MI	Italy	20097
12	Novartis Investigative Site	Modena	MO	Italy	41100
13	Novartis Investigative Site	Palermo	PA	Italy	90129
14	Novartis Investigative Site	Palermo	PA	Italy	90146
15	Novartis Investigative Site	Pisa	PI	Italy	56126
16	Novartis Investigative Site	Legnago	VR	Italy	37045
17	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.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01317004
• Other Study ID Numbers: CFTY720DIT02; 2010-024017-31
• First Posted: Mar 16, 2011
• Last Update Posted: Jun 22, 2015
• Last Verified: Jun 1, 2015

• Keywords provided by Novartis Pharmaceuticals: Multiple sclerosis; Fingolimod; Disease Modifying Therapy; TSQM-9
• Additional relevant MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Sclerosis; Fingolimod Hydrochloride; Interferon beta-1b

Study Results

Participant Flow

Recruitment Details	Actual enrollment = 61 because 65 participants were randomized to the study, but only 61 participants received at least one dose of study medication. As such, the participant flow captures the 65 participants randomized and the 61 participants who received drug as the safety set.

Arm/Group Title	Fingolimod	Multiple Sclerosis Disease Modifying Treatment (MS DMT)
Arm/Group Description	Patients randomized in this arm received Fingolimod 0.5 mg/day oral capsule for 6 months core period.	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.
Period Title: Overall Study
STARTED	51	14
Safety Set	50	11
COMPLETED	47	5
NOT COMPLETED	4	9

Baseline Characteristics

Arm/Group Title	Fingolimod	Multiple Sclerosis Disease Modifying Treatment (MS DMT)	Total
Arm/Group Description	Patients randomized in this arm received Fingolimod 0.5 mg/day oral capsule for 6 months core period.	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.	Total of all reporting groups
Overall Participants	50	11	61
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	37.96 (8.69)	35.82 (7.22)	37.57 (8.43)
Sex: Female, Male (Count of Participants)
Female	32 64%	8 72.7%	40 65.6%
Male	18 36%	3 27.3%	21 34.4%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Patient-reported Treatment Satisfaction
Description	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.
Time Frame	baseline, 6 months

Outcome Measure Data

Analysis Population Description

Participants from the safety set, who had values at both baseline and month 6, were included in the analysis. The safety set included randomized participants who received at least one dose of study medication.

Arm/Group Title	Fingolimod	Multiple Sclerosis Disease Modifying Treatment (MS DMT)
Arm/Group Description	Patients randomized in this arm received Fingolimod 0.5 mg/day oral capsule for 6 months core period.	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.
Measure Participants	46	10
Mean (Standard Deviation) [score on a scale]	19.57 (21.00)	5.83 (16.47)

2. Secondary Outcome

Title	Change From Baseline in Patient-reported Activities of Daily Living (ADL)
Description	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.
Time Frame	baseline, 6 months

Outcome Measure Data

Analysis Population Description

Participants from the safety set, who had values at both baseline and month 6, were included in the analysis. The safety set included randomized participants who received at least one dose of study medication.

Arm/Group Title	Fingolimod	Multiple Sclerosis Disease Modifying Treatment (MS DMT)
Arm/Group Description	Patients randomized in this arm received Fingolimod 0.5 mg/day oral capsule for 6 months core period.	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.
Measure Participants	49	11
Mean (Standard Deviation) [score on a scale]	0.19 (2.75)	0.15 (1.72)

3. Secondary Outcome

Title	Change From Baseline in Patient-reported Fatigue
Description	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.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Participants from the safety set, who had values at both baseline and month 6, were included in the analysis. The safety set included randomized participants who received at least one dose of study medication.

Arm/Group Title	Fingolimod	Multiple Sclerosis Disease Modifying Treatment (MS DMT)
Arm/Group Description	Patients randomized in this arm received Fingolimod 0.5 mg/day oral capsule for 6 months core period.	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.
Measure Participants	48	11
Mean (Standard Deviation) [score on a scale]	-0.18 (1.46)	-0.32 (1.21)

4. Secondary Outcome

Title	Change From Baseline in Patient-Reported Effectiveness and Convenience
Description	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.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Participants from the safety set, who had values at both baseline and month 6, were included in the analysis. The safety set included randomized participants who received at least one dose of study medication.

Arm/Group Title	Fingolimod	Multiple Sclerosis Disease Modifying Treatment (MS DMT)
Arm/Group Description	Patients randomized in this arm received Fingolimod 0.5 mg/day oral capsule for 6 months core period.	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.
Measure Participants	46	10
Effectiveness	13.53 (28.39)	-1.67 (32.40)
Convenience	24.64 (18.28)	12.78 (25.26)

5. Secondary Outcome

Title	Change From Baseline in Patient-reported Depression
Description	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.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Participants from the safety set, who had values at both baseline and month 6, were included in the analysis. The safety set included randomized participants who received at least one dose of study medication.

Arm/Group Title	Fingolimod	Multiple Sclerosis Disease Modifying Treatment (MS DMT)
Arm/Group Description	Patients randomized in this arm received Fingolimod 0.5 mg/day oral capsule for 6 months core period.	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.
Measure Participants	48	11
Mean (Standard Deviation) [score on a scale]	-1.15 (3.59)	-0.12 (3.06)

6. Secondary Outcome

Title	Change From Baseline in Patient-reported Health Related Quality of Life (QOL)
Description	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.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Participants from the safety set, who had values at both baseline and month 6, were included in the analysis. The safety set included randomized participants who received at least one dose of study medication.

Arm/Group Title	Fingolimod	Multiple Sclerosis Disease Modifying Treatment (MS DMT)
Arm/Group Description	Patients randomized in this arm received Fingolimod 0.5 mg/day oral capsule for 6 months core period.	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.
Measure Participants	45	9
Physical functioning (n=41,9)	1.71 (23.07)	-1.11 (20.73)
Role limitations due to physical health (n=42,9)	7.14 (37.97)	5.56 (27.32)
Pain (n=45,9)	6.56 (24.32)	14.44 (15.25)
General health (n=44,8)	4.52 (19.43)	6.25 (14.08)
Energy/fatigue (n=43,9)	2.33 (18.81)	6.48 (33.24)
Social functioning (n=45,9)	7.78 (24.90)	6.94 (25.85)
Role limitations d/t emotional problems (n=45,9)	7.04 (41.82)	3.70 (38.89)
Emotional well-being (n=43,9)	2.51 (16.88)	4.89 (28.13)
PCS (n=40,8)	4.52 (18.05)	7.83 (15.86)
MCS (n=40,8)	5.88 (18.21)	7.28 (24.05)

7. Secondary Outcome

Title	Physician-reported Clinical Global Impression of Improvement (CGI-I)
Description	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.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Participants from the safety set, who had values at month 6, were included in the analysis. The safety set included randomized participants who received at least one dose of study medication.

Arm/Group Title	Fingolimod	Multiple Sclerosis Disease Modifying Treatment (MS DMT)
Arm/Group Description	Patients randomized in this arm received Fingolimod 0.5 mg/day oral capsule for 6 months core period.	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.
Measure Participants	44	9
Much improved	13.64 27.3%	11.11 101%
Minimally improved	36.36 72.7%	11.11 101%
No change	47.73 95.5%	66.67 606.1%
Minimally worse	2.27 4.5%	11.11 101%

Adverse Events

Arm/Group Title	Fingolimod		Multiple Sclerosis Disease Modifying Treatment (MS DMT)
Arm/Group Description	Patients randomized in this arm received Fingolimod 0.5 mg/day oral capsule for 6 months core period.		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.
All Cause Mortality
	Fingolimod		Multiple Sclerosis Disease Modifying Treatment (MS DMT)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Fingolimod		Multiple Sclerosis Disease Modifying Treatment (MS DMT)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/50 (8%)		1/11 (9.1%)
Blood and lymphatic system disorders
Lymphopenia	2/50 (4%)		0/11 (0%)
General disorders
Drug ineffective	1/50 (2%)		0/11 (0%)
Investigations
Human papilloma virus test positive	0/50 (0%)		1/11 (9.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Meningioma	1/50 (2%)		0/11 (0%)
Nervous system disorders
Multiple sclerosis relapse	1/50 (2%)		0/11 (0%)
Other (Not Including Serious) Adverse Events
	Fingolimod		Multiple Sclerosis Disease Modifying Treatment (MS DMT)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/50 (26%)		7/11 (63.6%)
Blood and lymphatic system disorders
Lymphopenia	8/50 (16%)		0/11 (0%)
Endocrine disorders
Hyperthyroidism	0/50 (0%)		1/11 (9.1%)
Eye disorders
Vision blurred	0/50 (0%)		1/11 (9.1%)
Gastrointestinal disorders
Abdominal pain upper	0/50 (0%)		1/11 (9.1%)
Nausea	0/50 (0%)		1/11 (9.1%)
Vomiting	0/50 (0%)		1/11 (9.1%)
General disorders
Adverse drug reaction	0/50 (0%)		1/11 (9.1%)
Influenza like illness	1/50 (2%)		1/11 (9.1%)
Injection site reaction	0/50 (0%)		1/11 (9.1%)
Hepatobiliary disorders
Hypertransaminasaemia	1/50 (2%)		1/11 (9.1%)
Investigations
Transaminases increased	4/50 (8%)		0/11 (0%)
Weight decreased	0/50 (0%)		1/11 (9.1%)
Metabolism and nutrition disorders
Decreased appetite	0/50 (0%)		1/11 (9.1%)
Skin and subcutaneous tissue disorders
Rash	0/50 (0%)		1/11 (9.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.