patients with secondary progressive MS MedDRA version: 21.1 Level: PT Classification code 10053395 Term: Progressive multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Trade Name: Mayzent 2 mg compresse rivestite con film
Product Name: Mayzent 2 mg compresse rivestite con film
Product Code: [Siponimod 2 mg]
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN
Sponsors
AZIENDA OSPEDALIERA UNIVERSITARIA INTEGRATA VERONA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: ¿ Age 18-65 years. ¿ Active progressive MS course after an initial relapse clinical course defined as an EDSS progression of at least 1 point with a history of relapse and/or evidence of radiological activity defined as new/enlarging T2-FLAIR hyperintense or Gd-enhancing lesion on MRI acquired, in the previous 2 years before the enrolment. ¿ Availability of a 3T MRI performed within the last 2 years. This MRI must include these sequences: - 3D T1 weighted Fast Field Echo (FFE) - 3D Fluid Attenuated Inversion Recovery (FLAIR) ¿ Availability of detailed clinical data on medical history with neurological evaluation performed at least twice in the past two years (or once in the past year). ¿ EDSS between 3.0 and 6.0 ¿ Less than 5 years since entering the progressive phase of the disease. ¿ Female subjects must not be pregnant or breastfeeding at T0 nor during the study phase. Before enrollment, female subjects of childbearing potential must be informed about risks to the fetus, must have a negative pregnancy test and must use highly effective methods of contraception to prevent pregnancy during treatment as well as for at least 10 days after stopping treatment. Methods that can achieve a failure rate of less than 1% per year when used consistently and correctly are considered as highly effective birth control methods. Such methods include: a) combined (estrogen and progestin containing) hormonal contraception associated with inhibition of ovulation: i) oral ii) intravaginal iii) transdermal b) progestogen-only hormonal contraception associated with inhibition of ovulation: i) oral ii) injectable iii) implantable c) intrauterine device (IUD) d) intrauterine hormone-releasing system (IUS) e) bilateral tubal occlusion f) vasectomised partner g) sexual abstinence Male subjects must use a condom if their partners are fertile. 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 40 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Medical conditions: ¿ Patients homozygous for the CYP2C9 *3 *3 allele. ¿ Immunodeficiency syndrome. ¿ History of progressive multifocal leukoencephalopathy or cryptococcal meningitis. ¿ Hematologic alterations (lymphocyte count not within normal limits) ¿ Rheumatic disease under specific treatment (including chronic use of steroid) ¿ Severe active infections (regard to positive result to HBV, HCV, HIV, Quantiferon) ¿ Active malignities ¿ Myocardial infarction, unstable angina, stroke (any time), TIA (in the last 6 months) ¿ NYHA Class III or IV heart failure ¿ Complete left bundle branch block ¿ First- or second-degree [Mobitz type I] AV block, ¿ Second grade AV block (Mobitz type II); ¿ Third grade AV block (unless patient has a functioning pacemaker) ¿ Sinus bradycardia (HR 3x ULN) ¿ Negativity for varicella zoster IgG antibodies (in case of vaccination by live vaccine the beginning of therapy must be postponed of at least 30 days). ¿ History of hypersensitivity to any metabolites or drugs of the same class as siponimod. ¿ Hypersensitivity to the active substance or to peanuts, soy or to any of the excipients ¿ Pregnancy or breastfeeding. ¿ Fertile women who do not use effective methods of contraception. Previous and ongoing therapies: ¿ Natalizumab (last dose less than 6 months prior to enrollment); ¿ Rituximab, Ocrelizumab, Cyclophosphamide (last dose less than 1-year prior enrollment); ¿ Fingolimod, Mitoxantrone therapy or evidence of cardiotoxicity or a cumulative dose greater than 60 mg/m2 (last dose less than 2-year prior enrollment) ¿ Alemtuzumab, cladribine, autologous stem cell transplantation and other immunosuppressive treatments with expected effect of over 6 months (any time) ¿ Intravenous corticosteroid cycle to treat MS clinical relapse (1-month before enrollment) ¿ Antiarrhythmics Class Ia (e.g. quinidine, procainamide), Class III (amiodarone, sotalolo) drugs and those that may decrease heart rate (e.g. beta-blockers, calcium channel blockers, ivabradine and digoxin)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of siponimod in secondary progressive MS patients with reference to the effect of the drug on advanced immunological measures of chronic inflammation, in paired blood and cerebrospinal fluid (CSF) in a cohort of 40 SPMS patients, treated with Siponimod and followed-up for at least two-years;Secondary Objective: - To evaluate the effect of Siponimod on MRI biomarkers of compartmentalized inflammation linked to disease progression - To evaluate clinical, neuropsychological and safety data in a real-life population of SPMS treated with Siponimod;Primary end point(s): To characterize the effect of the drug on cerebrospinal fluid markers of chronic intrathecal inflammation. According to literature, to our previous studies and preliminary data, that pointed to a key role of CXCL13 in mediating B-cell accumulation and its association with disease severity and progression, the sample size has been calculated taking in account as primary endpoint to measure changes in the CSF levels of CXCL13.;Timepoint(s) of evaluation of this end point: Markers will be measured before (T0) and after two years of treatment (T24). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): the characterization of intrathecal (and paired blood) adaptive and immune cell subsets through a high-dimensional flow cytometry performed at T0 and after two years of treatment (T24).; Evaluation of paired blood and CSF markers of inflammation and neurodegeneration at T0 and T24; Assessment of CSF oligoclonal bands status and number at T0 and after two years of treatment (T24).; Assessment of the main pro-inflammatory (e.g., prostaglandins and leukotriens) and pro-resolving (e.g., resolvins, protectins, maresins and lipoxins) lipids at T0 and T24.; To evaluate the effect of Siponimod on MRI biomarkers of compartmentalized inflammation: cortical lesions, rim-positive lesions, slowly expanding lesions, rate of global and regional cortical thickness change, longitudinal change of MTSat/MWF multiparametric combination, longitudinal changes in cross sectional area of the spinal cord; To evaluate the EDSS change before, during, and after the treatment (T0 vs T12 and T12 vs T24).; To evaluate changes in cognitive functioning from T0 to T24; Treatment emergent adverse effect (TEAE) and serious adverse event (SAE) at each follow-up visit;Timepoint(s) of evaluation of this end point: T0 - T24; T0 - T24; T0 - T24; T0 - T24; T0 vs T12, T12 vs T24, T0 vs T24; T0 vs T12 e T12 vs T24; T0 - T24; at each follow-up visit | — |
Countries
Italy
Contacts
Public ContactUOC Neurologia B
Azienda Ospedaliera Universitaria Integrata Verona
Outcome results
None listed