Active progressive MS course after an initial relapse clinical course MedDRA version: 21.1 Level: PT Classification code 10053395 Term: Progressive multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Product Name: Siponimod 2 mg
Product Code: [Siponimod]
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Siponimod
CAS Number: 1230487-00-9
Current Sponsor code: Siponimod
Concentration uni
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) - 3D Echo Planar Imaging Susceptibility weighted (Magnitude and Phase) • Availability of a 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 breast feeding at T0 nor during the study phase. 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 55 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5
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 breast feeding. • 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 on paramagnetic rim lesions (as visualized by MRI) in secondary progressive MS patients.;Secondary Objective: - To evaluate the effect of siponimod in modifying the CSF and serum levels of biomarkers of microglial/macrophage activity and the axonal/neuronal damage. - To evaluate the effect of siponimod on the clinical and cognitive worsening in progressive MS patients and its long-term safety;Primary end point(s): The study endpoint is the change (assumed to be a reduction) of the susceptibility of the rim lesions after treatment with siponimod in comparison to the “natural” change of this parameter during a recent period-time preceding treatment (no later than two years before) with siponimod, so that for each patient an internal comparison will be available.;Timepoint(s) of evaluation of this end point: T3-T24 vs T24-T0 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To evaluate the effect of siponimod in reducing the number of SEL comparing to the period prior the treatment (retrospective phase) with the study phase (T3 vs T12 and T3 vs T24).; To describe the individual changes in CSF levels of specific makers of activated microglia/macrophages (sCD14, sCD163, TNF, sTNFR1, sTNFR2, Chitinase 3-1like) and of neuronal/axonal damage (neurofilament-light chains, parvalbumin) from baseline to T24; To evaluate the changes of sCD14, sCD163, TNF, sTNFR1, sTNFR2, Chitinase 3-1like, neurofilament-light chains, and parvalbumin in serum of patients at baseline and at T6, T12, T18, T24; To evaluate the EDSS change between the retrospective phase and the study phase (T0 vs T12 and T12 vs T24; To evaluate changes in cognitive functioning during the two-year study phase (T0-T24); Treatment emergent adverse effect (TEAE) and serious adverse event (SAE) at each follow-up visit;Timepoint(s) of evaluation of this end point: T3 vs T12 e T3 vs T24; Baseline vs T24; Baseline vs T6, T12, T18, 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