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

Phase 4
Recruiting
Conditions
Relapsing Multiple Sclerosis (relapsing-remitting, relapsing-progressive)
Registration Number
2024-518859-27-00
Lead Sponsor
Azienda Ospedaliera Universitaria Integrata Verona
Brief Summary

The aim of the project is to clarify the effect of ozanimod on compartmentalized inflammation by studying its effect on meningeal inflammation in CSF

Detailed Description

Not available

Recruitment & Eligibility

Status
Ongoing, recruiting
Sex
Not specified
Target Recruitment
50
Inclusion Criteria

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

Exclusion Criteria

Individuals with inactive primary or secondary progressive multiple sclerosis

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)

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

Macular oedema excluded by an ophthalmologic evaluation for patients with diabetes mellitus, uveitis or positive history of retinopathy, before starting treatment with ozanimod

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 or 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 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

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

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
CSF (and serum) concentration of CXCL13 protein (ng/ml/mgPro) measured before starting ozanimod treatment (Prebaseline) and at T12.

CSF (and serum) concentration of CXCL13 protein (ng/ml/mgPro) measured before starting ozanimod treatment (Prebaseline) and at T12.

Secondary Outcome Measures
NameTimeMethod
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 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.

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.

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

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 volume of cortical lesions measured before starting ozanimod treatment (Prebaseline) and at T12

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)

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)

Variation of the volume of white matter lesions before starting ozanimod treatment (¿ prebaseline-T0) and after 1 year of ozanimod treatment (¿ T0-T12)

Variation of the volume of white matter lesions before starting ozanimod treatment (¿ prebaseline-T0) and after 1 year of ozanimod treatment (¿ T0-T12)

Variation global and regional cortical thickness change before starting ozanimod treatment (¿prebaseline-T0) and after 1 year of ozanimod treatment (¿ T0-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)

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)

Trial Locations

Locations (1)

Azienda Ospedaliera Universitaria Integrata Verona

🇮🇹

Verona, Italy

Azienda Ospedaliera Universitaria Integrata Verona
🇮🇹Verona, Italy
Massimiliano Calabrese
Site contact
0458124768
neurologia.b@aovr.veneto.it

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