Effect of ozanimod on meningeal inflammation and glial activation in Multiple Sclerosis: one year phase 4 experimental study

Prior treatment

• Received a live vaccine within 4 weeks prior to ozanimod administration or intends to receive a live vaccination during the trial
• Macular oedema excluded by an ophthalmologic evaluation for patients with diabetes mellitus, uveitis or positive history of retinopathy, before starting treatment with ozanimod
• History of relapse or systemic corticosteroid use from 30 days before therapy initiation
• Ongoing immunosuppressive therapy (including chronic use of steroid)

Other illness

• 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
• Severe hepatic impairment (Child-Pugh class C)
• Disease duration more than 15 years with an EDSS of 2.0 or less;
• Hypersensitivity to ozanimod or to any of the listed excipients
• 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

Lab values

• Primary or secondary immunodeficiency syndrome or lymphocyte count not within normal limits due to any cause, ongoing immunosuppressive therapy (including chronic use of steroid)
• Primary or secondary immunodeficiency syndrome, lymphocyte count not within normal limits due to any cause
• Platelet count < 100.000/mcL; Hemoglobin < 8.5 g/dL; Leukocytes < 3500/mcL; Neutrophils <1500/mcL

Other

• Individuals with inactive primary or secondary progressive multiple sclerosis
• Pregnancy or breastfeeding. ● Fertile women who do not use effective methods of contraception.

• Age 18-65 years
• Relapsing-remitting MS (RRMS) diagnosed according to 2017 revision of McDonald criteria
• 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)
• 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
• Available EDSS score between 0 and 5 at the time of ozanimod initiation
• At least 2mL of CSF and 10 mL of blood acquired any time 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 a highly effective methods of contraception