2024-518859-27-00RecruitingPhase 4
Effect of ozanimod on meningeal inflammation and glial activation in Multiple Sclerosis: one year phase 4 experimental study PROTOCOL CODE: OZA22 / IM047 - 048
Azienda Ospedaliera Universitaria Integrata Verona1 site in 1 country50 target enrollmentStarted: November 11, 2024Last updated:
Drugs
Trial Snapshot
- Phase
- Phase 4
- Status
- Recruiting
- Enrollment
- 50
- Locations
- 1
- Primary Endpoint
- CSF (and serum) concentration of CXCL13 protein (ng/ml/mgPro) measured before starting ozanimod treatment (Prebaseline) and at T12.
Study Overview
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
Study Design
- Study Type
- Interventional
Eligibility Criteria
- Ages
- 18 years to 65+ years (65+ Years, 18-64 Years)
- Accepts Healthy Volunteers
- Yes
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
Outcomes
Primary Outcomes
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 Outcomes
- 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 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 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 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)
Investigators
Massimiliano Calabrese
Scientific
Azienda Ospedaliera Universitaria Integrata Verona
Study Sites (1)
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