Relapsing Multiple Sclerosis (relapsing-remitting, relapsing-progressive) MedDRA version: 21.0 Level: PT Classification code 10080700 Term: Relapsing multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Trade Name: Zeposia 0,92 mg capsule rigide
Product Name: Zeposia 0,92 mg capsule rigide
Product Code: [Ozanimod]
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Ozanimod Cloridrato
CAS Number:
Sponsors
AZIENDA OSPEDALIERA UNIVERSITARIA INTEGRATA VERONA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: ¿ Age 18-65 years ¿ Relapsing MS (relapsing-remitting, relapsing-progressive) diagnosed according to 2017 revision of McDonald criteria ¿ Treatment with ozanimod started within 30-90 days before the enrollment ¿ Met 1 of the following disease activity criteria: 1) at least one relapse within 12 months beforethe therapy initiation or 2) as at least one relapse within 24 months and at least one gadolinium-enhancing lesion within 12 months before the therapy initiation ¿ EDSS score between 0 and 5 at the time of ozanimod initiation ¿ At least 2mL of CSF and 10 mL of blood acquired before the beginning of ozanimod treatment and stored at -80°C ¿ Availability of an MRI scan performed at least 90 days before the beginning of ozanimod including 3DT1,3D FLAIR/T2-weighted sequences and 3D Gradient Echo Planar Imaging Susceptibility weighted (Magnitude and Phase) ¿ Positive varicella zoster virus immunoglobulin G antibody status or varicella zoster virus vaccination at least 28 days before ozanimod initiation ¿ Pregnancy test negative and on effective contraceptive drugs. 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: ¿ Individuals with inactive primary or secondary progressive multiple sclerosis; ¿ Disease duration more than 15 years with an EDSS of 2.0 or less; ¿ History of relapse or systemic corticosteroid use from 30 days before therapy initiation ¿ Hypersensitivity to ozanimod or to any of the listed excipients ¿ Primary o secondary immunodeficiency syndrome or lymphocyte count not within normal limits due to any cause, ongoing immunosuppressive therapy (including chronic use of steroid) ¿ Resting heart rate less than 55 beats per min (bpm) at screening; patients who in the last 6 months experienced myocardial infarction (MI), unstable angina, stroke, transient ischaemic attack (TIA), decompensated heart failure requiring hospitalisation or New York Heart Association (NYHA) Class III/IV heart failure, patients with history or presence of second-degree atrioventricular (AV) block Type II or third- degree AV block or sick sinus syndrome unless the patient has a functioning pacemaker ¿ Primary or secondary immunodeficiency syndrome, lymphocyte count not within normal limits due to any cause ¿ Ongoing immunosuppressive therapy (including chronic use of steroid) ¿ Platelet count < 100.000/mcL; Hemoglobin < 8.5 g/dL; Leukocytes < 3500/mcL; Neutrophils <1500/mcL ¿ Active acute infections or chronic infections (including HBV, HCV, HIV, TBC) ¿ Active malignancies or history of malignancies ¿ Severe hepatic impairment (Child-Pugh class C) ¿ Pregnancy or breastfeeding. ¿ Fertile women who do not use effective methods of contraception. ¿ Received a live vaccine within 4 weeks prior to ozanimod administration or intends to receive a live vaccination during the trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The aim of the project is to clarify the effect of ozanimod on compartmentalized inflammation by studying its effect on meningeal inflammation in CSF.;Secondary Objective: To clarify whether and how ozanimod treatment is able to reduce/halt meningeal inflammation as reflected by additional CSF and serum biomarkers and combined MRI parameters ¿ To clarify whether and how ozanimod treatment is able to reduce/halt microglial activation ¿ To clarify the effect of ozanimod treatment on neuronal damage ¿ To identify specific molecular, peripheral and intrathecal changes related to the ozanimod treatment ¿ To identify potential biomarkers of treatment response in terms of clinical and neuropsychological evolution over time ¿ To report the known and unknown adverse reactions to ozanimod ¿ To characterize the variation of lymphoid and myeloid cells within the CSF in reaction to ozanimod treatment using high-resolution single-cell gene expression analysis;Primary end point(s): CSF (and serum) concentration of CXCL13 protein (ng/ml/mgPro) measured before starting ozanimod treatment (Prebaseline) and at T12.;Timepoint(s) of evaluation of this end point: Prebaseline and T12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): CSF (and serum) concentration of specific markers of activated meningeal inflammation (CXCL12, TNF-a, IFN-¿) (ng/ml/mgPro) measured before starting ozanimod treatment (Prebaseline) and at T12.; CSF (and serum) concentration of specific makers of activated microglia/macrophages (Chitinase 3-like1, Osteopontin, sCD163, CX3CL1) (ng/ml/mgPro) measured before starting ozanimod treatment (Prebaseline) and at T12.; Variation global and regional cortical thickness change before starting ozanimod treatment (¿prebaseline-T0) and after 1 year of ozanimod treatment (¿ T0-T12); Significant linear relationship between the variation of the above-mentioned cytokines (¿ T0-T12) and the EDSS change (¿ T0-T12) or the relapse number by the end of the follow-up (T12); To identify a combination of multimodal parameters (CSF, MRI, clinical) at baseline able to identify treatment-responders vs non-responders as assessed by NEDA-3 at the end of follow-up and by the appearance of new cortical lesions or paramagnetic rim positive lesions or SELs expansion.; Known adverse reactions to ozanimod (including upper and lower respiratory tract infections, viral infections, progressive multifocal leukoencephalopathy, lymphopenia, hypersensitivity reactions, headache, macular oedema, bradycardia, blood pressure alterations, peripheral oedema, LFT - liver function tests- alterations, respiratory function test alterations) and unknown adverse reactions to ozanimod report.; Qualitative differences of lymphoid and myeloid cells populations in CSF taken before starting ozanimod treatment (¿ prebaseline-T0) and after one year of ozanimod treatment (T12); CSF (and serum) concentration of specific markers of neuronal/axonal damage (neurofilamentlight chains, parvalbumin) (ng/ml/mgPro) measured before starting ozanimod treatment (Prebaseline) and at T12.; Number and volume of cortical lesions measured before starting ozanimod treatment (Prebaseline) and at T12.; Number and susceptibilit | — |
Countries
Italy
Contacts
Public ContactUOC Neurologia B
Azienda Ospedaliera Universitaria Integrata Verona
Outcome results
None listed