relapsing-remitting multiple sclerosis
Conditions
Interventions
Trade Name: Gilenya®
Product Name: Gilenya®
Product Code: Gilenya®
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Fingolimod
CAS Number: 162359-55-9
Current Sponsor code: FINGOLIMOD
Other des
Sponsors
Charité - Universitätsmedizin Berlin
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Definite diagnosis of RRMS according to the 2010 revised McDonald criteria (Polman et al., 2011) • 18 to 65 years old • Indication for on-label treatment with fingolimod (Gilenya®) ac-cording to the current approval • EDSS score = 6,0 • Neurological stable with no evidence of relapse or corticosteroid treatment within 30 days prior to screening • Ability to provide written informed consent • Highly effective contraception (Pearl Index =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Patients with MS manifestations other than RRMS • Patients with known contraindications to Gilenya® according to the current “Fachinformation”, in particular • Immunodeficiency syndrome • Increased risk of opportunistic infections • Severe active or chronic active infections (hepatitis, tubercu-losis) • History or presence of malignancy (other than localized basal or squamous cell carcinoma of the skin).Severe liver dysfunction (Child Pugh C) • Hypersensitivity against active or any other compound of study medication • 2nd degree Mobitz Type II or higher degree AV block, Sick-sinus syndrome, or Sinu-atrial heart block, Significant QT pro-longation (QTc>470 msec (female) or >450 msec (males)) • History of symptomatic bradycardia or recurrent syncope, known ischaemic heart disease, cerebrovascular disease, history of my-ocardial infarction, hypokalaemia, congestive heart failure, history of cardiac arrest, uncontrolled hypertension, or severe sleep ap-neaPatients with clinically significant liver, kidney or bone marrow dysfunction, defined by the following laboratory values at the time of screening: • HB 3.5 times higher than the upper reference value • bilirubine> 2.0 mg / dl • Patients without a history of varicella or without vaccination against varicella zoster virus (VZV) and VZV negative antibody serology • Pregnancy or lactation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: to investigate longitudinally (baseline vs. treatment) the effects of fingolimod on NK cell maturation/differentiation We hypothesize that fingolimod targets certain NK cell subsets, which could cause a reduction of the ratio of immature NK cells / total NK cells and may account for therapeutic benefit and, thus, for treatment response discrimination in patients with MS.;Primary end point(s): Status of NK cell maturation, defined as the ratio immature NK cells /total NK cells (percentage), before fingolimod treatment vs. after 12 months of treatment (V4). The maturation status is determined by the expression of certain cell surface markers which can be evaluated by flow cytometry.;Secondary Objective: to assess NK cell frequency, NK cell cytotoxicity and the cytokine production, percentage immature NK cells/total NK cells at all time points, NK cell activation, NK cell maturation and activation in relation to clinically detectable therapeutic effect ;Timepoint(s) of evaluation of this end point: after 12 months treatment (pre-post) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): NK cell frequency at all time points (determined by flow cytometry), percentage immature NK cells/total NK cells at all time points, NK cell activation (expression of certain cell surface markers determined by flow cytometry) at all time points, NK cell maturation and activation in relation to clinically detectable therapeutic effect (determined a) by annual relapse rate over study period vs. annualized relapse rate in the preceding two years; and b) by the development of disability (determined by Expanded Disability StatusScale (EDSS) during treatment with fingolimod), NK cell cytotoxicity and the cytokine production (IL-15, IL-13, IL-5, GM-CSF, IFN-gamma). These will be determined by intracellular flow cytometry or ELISA, respectively.;Timepoint(s) of evaluation of this end point: at all time points and after 12 months treatment (pre-post) | — |
Countries
Germany
Contacts
Public ContactNeuroCure
Charité - Universitätsmedizin Berlin
Outcome results
None listed