relapsing remitting Multiple Sclerosis MedDRA version: 14.1 Level: PT Classification code 10028245 Term: Multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Trade Name: Gilenya
Product Name: Gilenya
Pharmaceutical Form: Capsule, hard
CAS Number: 162359-56-0
Current Sponsor code: FTY720
Other descriptive name: Fingolimod
Concentration unit: mg milligram(s
Sponsors
Novartis Pharma GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent from patients capable of giving or withholding full informed consent must be obtained before any assessment is performed. 2. Male or female subjects aged 18-65 years. 3.Subjects with relapsing remitting forms of MS defined by 2010 revised McDonald criteria (see Appendix 4). 4.Patients with high disease activity despite treatment with a disease modifying therapy (= 1 relapse in the previous year, = 9 hyperintense T2 lesions or =1 Gd-enhancing lesion or “non-responding” which could be defined as unchanged or increased relapse rate or ongoing severe relapses compared to previous year) or patients with rapidly evolving severe RRMS (e.g. = 2 relapses with disease progression in one year and = 1 Gd-enhancing lesion or with a significant increase in T2 lesions compared to a recent MRI). 5.Patients with Expanded Disability Status Scale (EDSS) score of 0-6.5 (see Appendix 8). 6.Sufficient ability to read, write, communicate and understand Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 445 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Patients with a manifestation of MS other than relapsing remitting MS. 2. Patients with a history of chronic disease of the immune system other than MS, which requires systemic immunosuppressive treatment, or a known immunodeficiency syndrome. 3. History or presence of malignancy (other than localized basal cell carcinoma of the skin and carcinoma in situ of the cervix) in the last 5 years 4. Diabetic patients with moderate or severe non-proliferative diabetic retinopathy or proliferative diabetic retinopathy and uncontrolled diabetic patients with HbA1c > 7%. 5. Diagnosis of macular edema during Screening Phase (patients with a history of macular edema will be allowed to enter the study provided that they do not have macular edema at the ophthalmic screening visit). 6. Patients with active systemic bacterial, viral or fungal infections, or known to have AIDS, Hepatitis B, Hepatitis C infection or to have positive HIV antibody, Hepatitis B surface antigen or Hepatitis C antibody tests. 7. Negative for varicella-zoster virus IgG antibodies at Screening. 8. Have received any live or live attenuated vaccines (including for varicella-zoster virus or measles) within 1 month prior to baseline. 9. Patients who have received total lymphoid irradiation or bone marrow transplantation. 10. Patients who expect to be treated with any disease modifying drugs (DMD) during the study (i.e. IFN-ß, glatiramer acetate); however no washout is needed for DMDs prior to baseline. 11. Patients who have been treated with: •systemically applied corticosteroids or adrenocorticotropic hormones (ACTH) within 1 month prior to baseline; •immunosuppressive medications such as azathioprine or methotrexate within 3 months prior to baseline; •immunoglobulins and/or monoclonal antibodies (including natalizumab) within 3 months prior to baseline; •cladribine at any time •Cyclophosphamide and mitoxantrone within 6 months prior to start of fingolimod 12. Patients with any medically unstable condition, as assessed by the primary treating physician at each site. 13. Patients with any of the following cardiovascular conditions: • Patients receiving antiarrythmics class Ia (e.g. quinidine, disopyramide, chinidin, ajmaline, procainamide) or class III (e.g. amiodarone, bretylium, sotalol, ibutilide, azimilide, dofetilide) or beta blockers • Patients receiving heart rate lowering calcium channel blockers (e.g. verapamil, diltiazem or ivabradine) or other substances which may decrease heart rate (e.g. digoxin, anticholinesteratic agents or pilocarpine). •Significant QT prolongation (QTc>470 msec (female) or >450 msec (males)) •cardiac failure at time of Screening (Class III, according to New York Heart Association Classification) or any severe cardiac disease as determined by the investigator; •history of second degree AV block, sick-sinus syndrome or sinoatrial block. • History of symptomatic bradycardia or recurrent syncope, known ischaemic heart disease, cerebrovascular disease, history of myocardial infarction, congestive heart failure, history of cardiac arrest, uncontrolled hypertension, or severe sleep apnea •resting pulse rate <45 bpm; 14. Patients with any of the following pulmonary conditions: •pulmonary fibrosis •active tuberculosis 15. Patients with severe hepatic dysfunction (Child-Pugh-Class C) 16. Patients with any of the abnormal laboratory values: •white blood cell (WBC) count <3,500/mm3 or lymphocyte count <800/mm3 17. Pati
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary endpoints are the reduction of CD4+ and CD8+ naïve T cells (CCR7+CD45RA+), central memory T cells (CCR7+CD45RA-), central memory Th17 cells (CD4+ CCR4+ and CCR6+), and an elevation of effector memory T cells (CCR7- CD45RA-) in peripheral venous blood at month 6 versus baseline.;Secondary Objective: To investigate changes from baseline in B Lymphocytes, monocytes and NK cells after treatment start and during infection periods. This will be assessed by studying surface markers by FACS analysis for B lymphocytes (CD19, CD20, CD69), monocytes (CD14), NK cells (CD56).;Primary end point(s): The primary endpoints are the reduction of CD4+ and CD8+ naïve T cells (CCR7+CD45RA+), central memory T cells (CCR7+CD45RA-), central memory Th17 cells (CD4+ CCR4+ and CCR6+), and an elevation of effector memory T cells (CCR7- CD45RA-) in peripheral venous blood at month 6 versus baseline.;Timepoint(s) of evaluation of this end point: month 6 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To investigate changes from baseline in B Lymphocytes, monocytes and NK cells after treatment start and during infection periods. This will be assessed by studying surface markers by FACS analysis for B lymphocytes (CD19, CD20, CD69), monocytes (CD14), NK cells (CD56).;Timepoint(s) of evaluation of this end point: month 6 | — |
Countries
Germany
Outcome results
None listed