Ozanimod for Relapsing multiple sclerosis

Inclusion criteria

• {"criterion_text":"- Age 18-65 years\n- Relapsing-remitting MS (RRMS) diagnosed according to 2017 revision of McDonald criteria\n- Treatment with ozanimod started within 30-90 days before the enrollment according to the AIFA indications for prescribing ozanimod (dose escalation regimen of ozanimod from Day 1 to Day 7: Days 1 – 4 0.23 mg once daily; Days 5 – 7 0.46 mg once daily; Days 8 and thereafter 0.92 mg once daily)\n- Met 1 of the following disease activity criteria: 1) at least one relapse within 12 months before the therapy initiation or 2) at least one gadolinium-enhancing lesion or at least new T2/FLAIR lesion within 12 months before the therapy initiation\n- Available EDSS score between 0 and 5 at the time of ozanimod initiation\n- At least 2mL of CSF and 10 mL of blood acquired any time before the beginning of ozanimod treatment and stored at -80°C\n- 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)\n- Positive varicella zoster virus immunoglobulin G antibody status or varicella zoster virus vaccination at least 28 days before ozanimod initiation\n- Pregnancy test negative and a highly effective methods of contraception"}

Exclusion criteria

• {"criterion_text":"- Individuals with inactive primary or secondary progressive multiple sclerosis\n- Active acute infections or chronic infections including HBV, HCV, HIV, ● Active or chronic TBC assessed performing an intradermal reaction test or chest x-ray ● Active malignancies or history of malignancies\n- Severe hepatic impairment (Child-Pugh class C)\n- Pregnancy or breastfeeding. ● Fertile women who do not use effective methods of contraception.\n- Received a live vaccine within 4 weeks prior to ozanimod administration or intends to receive a live vaccination during the trial\n- Macular oedema excluded by an ophthalmologic evaluation for patients with diabetes mellitus, uveitis or positive history of retinopathy, before starting treatment with ozanimod\n- Disease duration more than 15 years with an EDSS of 2.0 or less;\n- History of relapse or systemic corticosteroid use from 30 days before therapy initiation\n- Hypersensitivity to ozanimod or to any of the listed excipients\n- Primary or secondary immunodeficiency syndrome or lymphocyte count not within normal limits due to any cause, ongoing immunosuppressive therapy (including chronic use of steroid)\n- 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 hospitalization 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\n- Primary or secondary immunodeficiency syndrome, lymphocyte count not within normal limits due to any cause\n- Ongoing immunosuppressive therapy (including chronic use of steroid)\n- Platelet count < 100.000/mcL; Hemoglobin < 8.5 g/dL; Leukocytes < 3500/mcL; Neutrophils <1500/mcL"}

Primary endpoints

• {"endpoint_text":"- CSF (and serum) concentration of CXCL13 protein (ng/ml/mgPro) measured before starting ozanimod treatment (Prebaseline) and at T12.","definition_or_measurement_approach":"Concentration measured in CSF and serum, units ng/ml/mgPro, measured before starting ozanimod treatment (Prebaseline) and at T12."}

Secondary endpoints

• {"endpoint_text":"- 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.\n- 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.\n- 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\n- Number and volume of cortical lesions measured before starting ozanimod treatment (Prebaseline) and at T12\n- Number and susceptibility of of paramagnetic rim lesions measured before starting ozanimod treatment (Prebaseline), at baseline (T0) and after 1 year of ozanimod treatment (T12)\n- Variation of the volume of white matter lesions before starting ozanimod treatment (¿ prebaseline-T0) and after 1 year of ozanimod treatment (¿ T0-T12)\n- Variation global and regional cortical thickness change before starting ozanimod treatment (¿prebaseline-T0) and after 1 year of ozanimod treatment (¿ T0-T12)\n- 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)","definition_or_measurement_approach":"All endpoints are biochemical or MRI measures specified as measured in CSF (and serum) with units where stated (ng/ml/mgPro) and timepoints indicated (Prebaseline and T12) except where additional baseline/timepoints are specified (e.g., T0 and T12 for some MRI endpoints)."}

Italy

Earliest CTIS Part Ii Submission Date

11-10-2024

Latest Decision Or Authorization Date

11-11-2024

Processing Time Days

31

Number Of Sites

1

Number Of Participants

50

Primary sponsor

Full Name

Azienda Ospedaliera Universitaria Integrata Verona

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Italy

Third parties

• {"country":"","full_name":"Bristol-Myers Squibb Services Unlimited Company","duties_or_roles":"Source of monetary support","organisation_type":"Company"}