E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10048393 |
E.1.2 | Term | Multiple sclerosis relapse |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
This study is designed to evaluate the long-term safety and tolerability of fingolimod 0.5 mg/day in patients with MS. |
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E.2.2 | Secondary objectives of the trial |
This study will also evaluate long-term efficacy of fingolimod 0.5 mg/day in patients with MS, as measured by disability progression, brain volume (atrophy), T1- (non-enhanced) and T2-weighted lesion volume and MS relapse occurrence |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients eligible for inclusion in this study have to fulfill all of the following criteria:
1. Written informed consent must be obtained before any assessment is performed.
2. Patients who have completed designated ongoing or planned trials with fingolimod, including phase II/III patients who have already completed CFTY720D2399,CFTY720D2309/E1 or one of the phase II/III core or extension studies.
3. Patients who participated in any designated global fingolimod MS trial other than phase II/III (e.g. CFTY720D2316, CFTY720D2320, etc.) and are less than 180 days beyond the time of local approval and general reimbursement. |
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E.4 | Principal exclusion criteria |
Patients fulfilling any of the following criteria are not eligible for inclusion in this study:
1. Premature permanent discontinuation from any fingolimod study due to:
a. An adverse event or serious adverse event or laboratory abnormality.
b. Conditions leading to permanent study drug discontinuation.
Patients who temporarily or permanently discontinued from any fingolimod study because of pregnancy can be re-enrolled.
2. Pregnant or nursing (lactating) women where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/ml).
3. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, UNLESS they are using highly effective contraception during the study and for 2 months after stopping treatment. ‘Highly effective contraception’defined as contraception which results in less than 1% unwanted pregnancies when used properly according to the label.
Women are considered post-menopausal and not of child-bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks prior to baseline. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential.
4. Chronic disease of the immune system other than MS which may require immunosuppressive treatment.
5. Severe active infection or active chronic infection.
6. Previous treatment with cladribine, cyclophosphamide or mitoxantrone.
7. Treatment with monoclonal antibodies (including Natalizumab) in the past 3 months.
8. Uncontrolled diabetes (HbA1c>9%).
9. Macular edema at Baseline.
10. Any medically unstable condition that may interfere with the patient’s ability to cooperate and comply with the study procedures, as assessed by the treating physician.
11. Any of the following cardiovascular conditions:
a. myocardial infarction within the past 6 months prior to enrollment or current unstable ischemic heart disease;
b. cardiac failure at time of Screening (Class III & IV, according to New York Heart Association Classification) or any severe cardiac disease as determined by the investigator;
c. patients receiving current treatment with Class Ia and III antiarrhythmic drugs (e.g., quinidine, disopyramide, amiodarone, bretylium, sotalol, ibulitide, azimilide, dofelitide, ajmaline, procainamide);
d. second-degree AV block Type II or third-degree AV block or corrected QTc inverval >450 msec in males or 470 msec in females;
e. sick sinus syndrome or sino-atrial heart block;
f. uncontrolled hypertension despite prescribed medications.
12. Any of the following pulmonary conditions during the previous fingolimod study or observed at enrollment visit:
a. severe respiratory disease or pulmonary fibrosis;
b. active tuberculosis;
c. in patients enrolling from studies with regular spirometry: reduction of FEV1, FVC and/or DLCO below 60% of core study baseline values or if FEV1, FVC and/or DLCO at extension study baseline is the second of two consecutive pulmonary function tests with values <80% of core study baseline.
13. Severe liver impairment or chronic liver disease.
14. Positive screening for serological markers for hepatitis A, B, C, and E indicating acute or chronic infection:
• anti-hepatitis A virus IgM,
• hepatitis B surface antigen and/or anti-hepatitis B core antigen IgM,
• anti-hepatitis C virus IgG or IgM,
• anti-hepatitis E virus IgM (if positive IgG: do hepatitis E virus-RNA polymerase chain reaction; if negative, patient can be included).
Note: The following patients, assuming they have normal aminotransferase activities, can be included in the trial:
• those testing positive for hepatitis B surface antibody, indicating hepatitis B immunization -OR-
• those testing positive for anti-hepatitis B core antigen IgG, indicating a cured hepatitis B -OR-
• those testing positive for anti-hepatitis A virus IgG, indicating a cured hepatitis A. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Long term safety will be asssessed based on adverse events (AEs), Physical/neurological examination, laboratory evaluation, eye exam, ECG and vital signs, as well as other investigations performed when clinically indicated. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Visits every 3 months through Month 12 (v5); Visits every 6 months beginning after Month 12 at Month 18 (v6)
Hematology laboratory assessment every 6 months, blood chemistry yearly, eye examination yearly after the first year, urine pregnancy test at the 6 months visit |
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E.5.2 | Secondary end point(s) |
MRI, MS Relapse, EDSS scores, MSFC scores
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Visits every 3 months through Month 12 (v5); Visits every 6 months beginning after Month 12 at Month 18 (v6)
MRIs at EOS visit
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Health-related quality of life. |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 500 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Australia |
Austria |
Belgium |
Brazil |
Canada |
Czech Republic |
Denmark |
Egypt |
Estonia |
Finland |
France |
Germany |
Greece |
Guatemala |
Hungary |
Ireland |
Israel |
Italy |
Korea, Republic of |
Malaysia |
Netherlands |
Norway |
Panama |
Peru |
Poland |
Portugal |
Romania |
Russian Federation |
Slovakia |
South Africa |
Spain |
Sweden |
Switzerland |
Turkey |
United Kingdom |
United States |
Jordan |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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For patients who previously completed fingolimod Phase II/III studies - LVLS, until they reach 60 months (5 years) participation in this study, or through 30-Jun-2016 (+/- 30 day visit window), whichever comes first. -> See further details in the Protocol.
For patients who previously completed any fingolimod trial other than Phase II/III - when fingolimod is registered, commercially available and generally reimbursed in their local country. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 6 |