Relapsing Remitting Multiple Sclerosis MedDRA version: 21.1 Level: PT Classification code 10063399 Term: Relapsing-remitting multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Trade Name: GILENYA - 0.5 MG - CAPSULE RIGIDE - USO ORALE - BLISTER(PVC/PVDC/ALU) SCATOLA DA 28 CAPSULE
Product Name: Fingolimod
Pharmaceutical Form: Capsule, hard
Sponsors
FONDAZIONE POLICLINICO UNIVERSITARIO AGOSTINO GEMELLI IRCCS UNIVERSITA' CATTOLICA DEL SACRO CUORE
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: They will be included in the study patients male or female aged> 18 years, affected from relapsing remitting multiple sclerosis with high disease activity. Patients will be eligible to treatment with fingolimod according to the data sheet of the drug. In summary, they are deemed eligible for treatment with fingolimod patients belonging to one of the following groups: 1) Patients with high disease activity despite treatment with a beta-interferon. These patients may be defined as those who have not responded to a full and adequate course of therapy (normally at least one year of treatment) of beta-interferon. Patients should have had at least 1 relapse in the previous year while on therapy, and have at least 9 T2-hyperintense lesions in cranial MRI or at least 1 Gadolinium-enhancing lesion. Patient non-responders can also be defined as a patient who has, over the previous year, an unchanged or increased relapse rate or who have severe relapses. 2) Patients with severe relapsing-remitting multiple sclerosis rapidly evolving, defined as two or more disabling relapses in one year, and with 1 or more gadolinium-enhancing lesions on brain MRI or a significant increase in T2 lesion load compared to a previous RM recently performed. For all therapeutic indications the dose is 0.5 mg orally, once daily. 3) The women of childbearing age will be enrolled only if they make use of highly effective contraceptive measures. The use of contraceptive measures must be extended to male patients with partners of childbearing age. Highly effective contraceptive measures deemed, under specific CTFG the recommendations are as follows: _ combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation 1: o oral o intravaginal o transdermal _ progestogen-only hormonal contraception associated with inhibition of ovulation 1: o oral o injectable o implantable 2 _ intrauterine device (IUD) _ intrauterine hormone-releasing system ( IUS) _ bilateral tubal occlusion _ vasectomised partner _ sexual abstinence 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 50 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Patients with HIV (a specific serologic testing for HIV should be conducted prior to initiating treatment with fingolimod). Patients who are at increased risk for opportunistic infections, including immunocompromised patients (including those currently receiving immunosuppressive therapies or those immunocompromised by prior therapies). • Patients infected with HBV, HCV and HAV (before starting treatment with Gilenya should be performed the following serological tests: HBsAg, HBcAb, anti HCV antibodies, anti HAV IgM and IgG). • Patients with latent or active tuberculosis (before starting treatment with Gilenya should be performed dosing Quantiferon test) • Malignant tumors diagnosed in the active phase. • Severe hepatic impairment (Child-Pugh Class C). • Hypersensitivity to the active substance or to any of the excipients. • Patients treated with live vaccines within 30 days prior to screening • Women of childbearing potential and not complianti highly effective contraceptive measures defined in accordance with the recommendations of the Clinical Trial Facilitation Group (http://www.hma.eu/fileadmin/dateien/Human_Medicines/01About_HMA/Working_Groups/CTFG/2014_09_HMA_CTFG_Contraception.pdf) • Male patients with partners of childbearing age who do not belong to highly effective contraceptive measures defined in accordance with the recommendations of Clinical Trial Facilitation Group • Women who are pregnant or breast-feeding (in all women of childbearing age before you start treatment with Gilenya will be made the dosage of beta-HCG in serum, and also will be made a urinary pregnancy test every month during treatment as required by the recommendations of the Clinical Trial Facilitation Group) • Patients with moderate to severe heart failure (III / IV class according to the New York Heart Association) • Documented relapse or steroid therapy ev a month before the start of therapy • Patients who have discontinued treatment with fingolimod following an inadequate response
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The study of the immunological profile at baseline and its variation during the early stages of treatment with fingolimod could represent a predictor of clinical response to therapy. In particular, a regulatory pattern of lymphocyte subtypes represented by a higher ratio of regulatory T cells than the effector T cells, may be an optimal response markers during therapy with fingolimod. ;Secondary Objective: To evaluate if it is possible that serum BDNF levels are a biomarker predictive of neurocognitive performance maintenance in patients with Multiple Sclerosis responders to treatment with fingolimod; To investigate a possible relationship between immunological profile at baseline or changes during the early stages of treatment with fingolimod and the incidence rate of infections could be important to better characterize the safety profile of the drug.;Primary end point(s): To describe patients response to fingolimod treatment as Treg/Teffector ratio. The ratio will be evaluated at baseline and at the end of the study (12 months) (also intermediate points will be considered at 1 month, 3 months, 6 months, ) and its relative increase will be evaluated. This procedure admit us to take into account the individual variability and the intermediate scheduled evaluation may be a controlled of intraindividual variability which should be not too high with respect to disease changes in the same time observation window.;Timepoint(s) of evaluation of this end point: 0/1/3/6/12 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To evaluate cognitive functions of patients at the time of starting fingolimod and after 12 months in order to better describe the patient's clinical status and, consequently, the study drug response. To correlate BDNF production of PBMC with treatment response (responders and suboptimal-responders/non responders) and immunological change status. To characterize in immunological term, patients who had a major incidence or had more aggressive form of infections in order to establish if is it possible to speculate that a particular change in the immunological repertoire is correlate with safety topics. ;Timepoint(s) of evaluation of this end point: 12 months | — |
Countries
Italy
Contacts
Public ContactUnit¿ Operativa Sclerosi Multipla
Fondazione Policlinico Universitario A. Gemelli
Outcome results
None listed