Multiple Sclerosis, Relapsing-Remitting
Conditions
Keywords
Relapsing remitting multiple sclerosis, Fingolimod, FTY720
Brief summary
The study will assess the patients' satisfaction of treatment after 12 months treatment with fingolimod It also will assess the tolerability profile of fingolimod in a small population.
Interventions
DRUGFingolimod
Fingolimod 0.5mg orally once a day without food.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Diagnosed with RRMS as described in 2005 Mc Donald criteria 2. Provided written informed consent prior to any intervention 3. Female or male patients aged 18-65 years 4. Unresponsive to treatment with a beta interferon or glatiramer acetate for a minimum of one year at and at adequate dose and with high disease activity (Unresponsive patients: patients with no changes in relapses, increased relapses, severer relapses with one-year treatment or those who had had at least one relapse during the past one year under previous treatments and one or multiple contrast enhancing lesions in cranial MRI or increased T2 lesions in successive MRIs) 5. EDSS score below 5.5 at baseline
Exclusion criteria
* Treatment-naive RRMS patients 2. History of a chronic disease of the immune system other than MS or known immunodeficiency 3. Past or current malignancy 4. Diabetic patients with mild or severe, non-proliferative or proliferative diabetic retinopathy and uncontrolled diabetic patients with HbA1c \> 8% 5. Evidence of macular edema (patients with a history of macular edema will be allowed to enter the study provided that they do not have macular edema at screening.) 6. Evidence of uveitis 7. EDSS score \> 5.5 at baseline 8. Active systemic bacterial, viral or fungal infections, or known to have AIDS, Hepatitis B, Hepatitis C infection or have positive HIV antibody, Hepatitis B surface antigen or Hepatitis C antibody tests 9. No history of varicella and negative varicella-zoster virus IhH antibody test at screening (such patients may be included after being administered VZV vaccine, at least 1 month following vaccination.) 10. Patients who received any live or live attenuated vaccine during the last one month (including varicella-zoster virus or measles) 11. Patients who received total lymphoid irradiation or bone marrow transplantation 12. Patient who received any of the treatment below: 1. Corticosteroids or adrenocorticotropic hormone (ACTH) during the last 1 month 2. Immunosuppressive medications such as azathioprine or methotrexate etc. 3. Immunoglobulin treatment during the last 3 months 4. Cladribine, cyclophosphamide, mitoxantrone, natalizumab at any time 13. Patients with any of the following cardiovascular conditions: Resting heart rate \< 45 bpm/min Cardiac failure at time of screening (Class III according to NYHA classification) or any severe cardiac as determined by the physician Myocardial infarction during the last 6 months History of Mobitz Type II grade 2 AV block Past or current grade 3 AV block Confirmed history of sick sinus syndrome or sino-atrial heart block arrhythmia requiring current treatment with Class Ia drugs (ajmaline, disopyramid, procainamide, quinidine) hypertension uncontrolled with medication 14. Patients with any of the pulmonary conditions below severe respiratory disease or pulmonary fibrosis Uncontrolled asthma 15. Pregnant or nursing (lactating) women (pregnancy is defined as the state of a female after conception and until the termination of gestation and should be confirmed by a positive hCG laboratory test (\> 5 mIU/ml). 16\. Patients with any of the hepatic conditions below: Alcohol abuse, chronic hepatic or biliary disease, severe hepatic impairment (Child- Pugh class C) Total bilirubin above the upper limit of normal provided that it is not associated with Gilbert's syndrome Conjugated bilirubin above the upper limit of normal Alkaline phosphate (AP) 1.5 times above the upper limit of normal AST(SGOT), ALT (SGPT) 2 times above the upper limit of normal, gamma-glutamyl-transferase (GGT) 3 times above the upper limit of normal
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Patient-Reported Treatment Satisfaction Questionnaire for Medication Scores (TSQM-9) | Baseline and month 12 | 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
| Measure | Time frame | Description |
|---|---|---|
| Mean Patient-reported Health-related Quality-of-life With Fingolimod (Short Form Health Survey: SF-36). | Month 1 | 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. |
Countries
Turkey (Türkiye)
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Fingolimod, FTY720 Patients received fingolimod 0.5 mg oral capsules daily with or without food. | 42 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Protocol Violation | 5 |
Baseline characteristics
| Characteristic | Fingolimod, FTY720 |
|---|---|
| Age, Continuous | 35.7 Years STANDARD_DEVIATION 9.4 |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 24 / 42 |
| serious Total, serious adverse events | 4 / 42 |
Outcome results
Primary
Mean Patient-Reported Treatment Satisfaction Questionnaire for Medication Scores (TSQM-9)
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 and month 12
Population: Per Protocol Population: included all patients who had evaluable data for the primary variable from first to last visit
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fingolimod, FTY720 | Mean Patient-Reported Treatment Satisfaction Questionnaire for Medication Scores (TSQM-9) | Baseline (n=34) | 32.0 Scores on a scale | Standard Deviation 9.9 |
| Fingolimod, FTY720 | Mean Patient-Reported Treatment Satisfaction Questionnaire for Medication Scores (TSQM-9) | Month 12 (n=32) | 44.7 Scores on a scale | Standard Deviation 9.9 |
Secondary
Mean Patient-reported Health-related Quality-of-life With Fingolimod (Short Form Health Survey: SF-36).
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.
Time frame: Month 1
Population: Per Protocol Population: included all patients who had evaluable data for the primary variable from first to last visit
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fingolimod, FTY720 | Mean Patient-reported Health-related Quality-of-life With Fingolimod (Short Form Health Survey: SF-36). | Physical Function | 59.7 score on scale | Standard Deviation 30.9 |
| Fingolimod, FTY720 | Mean Patient-reported Health-related Quality-of-life With Fingolimod (Short Form Health Survey: SF-36). | Physical Role | 53.6 score on scale | Standard Deviation 43.8 |
| Fingolimod, FTY720 | Mean Patient-reported Health-related Quality-of-life With Fingolimod (Short Form Health Survey: SF-36). | Pain | 61.7 score on scale | Standard Deviation 23.7 |
| Fingolimod, FTY720 | Mean Patient-reported Health-related Quality-of-life With Fingolimod (Short Form Health Survey: SF-36). | General Health | 47.8 score on scale | Standard Deviation 20.5 |
| Fingolimod, FTY720 | Mean Patient-reported Health-related Quality-of-life With Fingolimod (Short Form Health Survey: SF-36). | Vitality | 28.9 score on scale | Standard Deviation 23.1 |
| Fingolimod, FTY720 | Mean Patient-reported Health-related Quality-of-life With Fingolimod (Short Form Health Survey: SF-36). | Social Function | 61.8 score on scale | Standard Deviation 26.4 |
| Fingolimod, FTY720 | Mean Patient-reported Health-related Quality-of-life With Fingolimod (Short Form Health Survey: SF-36). | Emotional Role | 48.4 score on scale | Standard Deviation 43 |
| Fingolimod, FTY720 | Mean Patient-reported Health-related Quality-of-life With Fingolimod (Short Form Health Survey: SF-36). | Mental Health | 31.5 score on scale | Standard Deviation 17 |
Secondary
Mean Patient-reported Health-related Quality-of-life With Fingolimod (Short Form Health Survey: SF-36).
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.
Time frame: Month 6
Population: Per Protocol Population: included all patients who had evaluable data for the primary variable from first to last visit
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fingolimod, FTY720 | Mean Patient-reported Health-related Quality-of-life With Fingolimod (Short Form Health Survey: SF-36). | Physical Function (n=33) | 57.9 score on scale | Standard Deviation 31.1 |
| Fingolimod, FTY720 | Mean Patient-reported Health-related Quality-of-life With Fingolimod (Short Form Health Survey: SF-36). | Physical Role (n=34) | 47.8 score on scale | Standard Deviation 46 |
| Fingolimod, FTY720 | Mean Patient-reported Health-related Quality-of-life With Fingolimod (Short Form Health Survey: SF-36). | Pain (n=34) | 62.6 score on scale | Standard Deviation 24.8 |
| Fingolimod, FTY720 | Mean Patient-reported Health-related Quality-of-life With Fingolimod (Short Form Health Survey: SF-36). | General Health (n=33) | 48.5 score on scale | Standard Deviation 20.3 |
| Fingolimod, FTY720 | Mean Patient-reported Health-related Quality-of-life With Fingolimod (Short Form Health Survey: SF-36). | Vitality (n=34) | 35.2 score on scale | Standard Deviation 22.9 |
| Fingolimod, FTY720 | Mean Patient-reported Health-related Quality-of-life With Fingolimod (Short Form Health Survey: SF-36). | Social Function (n=34) | 60.6 score on scale | Standard Deviation 29.9 |
| Fingolimod, FTY720 | Mean Patient-reported Health-related Quality-of-life With Fingolimod (Short Form Health Survey: SF-36). | Emotional Role (n=34) | 54.8 score on scale | Standard Deviation 43.3 |
| Fingolimod, FTY720 | Mean Patient-reported Health-related Quality-of-life With Fingolimod (Short Form Health Survey: SF-36). | Mental Health (n=34) | 36.5 score on scale | Standard Deviation 20.3 |
Secondary
Mean Patient-reported Health-related Quality-of-life With Fingolimod (Short Form Health Survey: SF-36).
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.
Time frame: Month 12
Population: Per Protocol Population: included all patients who had evaluable data for the primary variable from first to last visit
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fingolimod, FTY720 | Mean Patient-reported Health-related Quality-of-life With Fingolimod (Short Form Health Survey: SF-36). | Physical Function (n=31) | 59.5 score on scale | Standard Deviation 34.3 |
| Fingolimod, FTY720 | Mean Patient-reported Health-related Quality-of-life With Fingolimod (Short Form Health Survey: SF-36). | Physical Role (n=32) | 46.9 score on scale | Standard Deviation 44.7 |
| Fingolimod, FTY720 | Mean Patient-reported Health-related Quality-of-life With Fingolimod (Short Form Health Survey: SF-36). | Pain (n=32) | 65.9 score on scale | Standard Deviation 23.3 |
| Fingolimod, FTY720 | Mean Patient-reported Health-related Quality-of-life With Fingolimod (Short Form Health Survey: SF-36). | General Health (n=31) | 50.8 score on scale | Standard Deviation 21.9 |
| Fingolimod, FTY720 | Mean Patient-reported Health-related Quality-of-life With Fingolimod (Short Form Health Survey: SF-36). | Vitality (n=32) | 33.1 score on scale | Standard Deviation 20 |
| Fingolimod, FTY720 | Mean Patient-reported Health-related Quality-of-life With Fingolimod (Short Form Health Survey: SF-36). | Social Function (n=32) | 65.8 score on scale | Standard Deviation 29.1 |
| Fingolimod, FTY720 | Mean Patient-reported Health-related Quality-of-life With Fingolimod (Short Form Health Survey: SF-36). | Emotional Role (n=31) | 52.7 score on scale | Standard Deviation 46.2 |
| Fingolimod, FTY720 | Mean Patient-reported Health-related Quality-of-life With Fingolimod (Short Form Health Survey: SF-36). | Mental Health (n=32) | 36.3 score on scale | Standard Deviation 20.3 |