Safety Study to Evaluate Immune Response of Vaccines in Participants With Relapsing Forms of Multiple Sclerosis Who Receive Ozanimod Compared to Non-Pegylated Interferon (IFN)-β or No Disease Modifying Therapy

Study Overview
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Brief Summary
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This study is designed to provide data on the immune response and safety of administering vaccines to relapsing multiple sclerosis (RMS) participants taking ozanimod compared to controls taking interferon-beta's or receiving no disease modifying therapies (DMTs). The data of this study will support the labels for ozanimod in multiple sclerosis (MS) because the effect of ozanimod on the vaccination response of MS participants is of interest to participants and prescribers.

Official Title
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A Phase 3b, Multicenter, Open-label Study to Evaluate the Immune Response to, and the Safety of, Vaccines in Participants With Relapsing Forms of Multiple Sclerosis Who Receive Oral Ozanimod Compared to Non-pegylated Interferon (IFN)-β or No Disease Modifying Therapy

Conditions
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Multiple Sclerosis, Multiple Sclerosis, Relapsing-Remitting

Intervention / Treatment
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* Biological: Tetanus, diphtheria, and acellular pertussis vaccine
* Biological: Pneumococcal polysaccharide vaccine
* Biological: Seasonal influenza vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant has a diagnosis of multiple sclerosis (MS) according to the 2017 revision of the McDonald diagnostic criteria and has relapsing forms of multiple sclerosis (RMS): relapsing-remitting MS (RRMS) or secondary progressive MS with active disease based on recent clinical relapse or MRI lesion activity. Exclusion Criteria: Participant has history of cancer, including solid tumors and hematological except for basal cell cancer of the skin and carcinoma in situ of the cervix, which are exclusionary if they have not been excised and resolved. Participant has a history of or currently active primary or secondary immunodeficiency. Participant has severely compromised cardiac or pulmonary function for which a systemic hypersensitivity reaction to any of the vaccines would pose a significant risk. Participant has received the seasonal influenza vaccine for the 2021/2022 influenza season prior to Day 1, or history of influenza vaccine for the 2020/2021 influenza season within 6 months prior to Day 1. Participant has previous treatment with one of the following medications or interventions within the corresponding timeframe described as follows: Any systemic immunosuppressive treatments with potential overlapping effects with the baseline of this study. Corticosteroids that are by non-systemic routes (e.g., topical, inhaled, intra-articular) are allowed. History of treatment with IV immunoglobulin (IVIg) or plasmapheresis within 4 weeks prior to Day 1.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 - Ozanimod<br>Comprises of participants received oral ozanimod will be administered tetanus, diphtheria, and acellular pertussis vaccine (Tdap), pneumococcal polysaccharide vaccine (PPSV23), and the seasonal inactivated influenza vaccine -Enrollment is closed for this cohort | Biological: Tetanus, diphtheria, and acellular pertussis vaccine<br>* Tdap<br>* Other names: Tdap;Biological: Pneumococcal polysaccharide vaccine<br>* PPSV23<br>* Other names: PPSV23;Biological: Seasonal influenza vaccine<br>* Seasonal influenza vaccine<br>|
| Experimental: Cohort 1 - non-pegylated interferon-β or no disease modifying therapy<br>Comprises of participants received either non-pegylated interferon-β (IFN-β) or no disease modifying therapy (DMT) will be administered tetanus, diphtheria, and acellular pertussis vaccine (Tdap), Pneumococcal polysaccharide vaccine (PPSV23), and the seasonal inactivated influenza vaccine -Enrollment is closed for this cohort | Biological: Tetanus, diphtheria, and acellular pertussis vaccine<br>* Tdap<br>* Other names: Tdap;Biological: Pneumococcal polysaccharide vaccine<br>* PPSV23<br>* Other names: PPSV23;Biological: Seasonal influenza vaccine<br>* Seasonal influenza vaccine<br>|
| Experimental: Cohort 2 - Ozanimod<br>Comprises of participants received oral ozanimod will be administered tetanus, diphtheria, and acellular pertussis vaccine (Tdap), and pneumococcal polysaccharide vaccine (PPSV23). | Biological: Tetanus, diphtheria, and acellular pertussis vaccine<br>* Tdap<br>* Other names: Tdap;Biological: Pneumococcal polysaccharide vaccine<br>* PPSV23<br>* Other names: PPSV23;|
| Experimental: Cohort 2 - non-pegylated interferon-β or no disease modifying therapy<br>Comprises of participants received either non-pegylated interferon-β (IFN-β) or no disease modifying therapy (DMT) will be administered tetanus, diphtheria, and acellular pertussis vaccine (Tdap) and Pneumococcal polysaccharide vaccine (PPSV23). | Biological: Tetanus, diphtheria, and acellular pertussis vaccine<br>* Tdap<br>* Other names: Tdap;Biological: Pneumococcal polysaccharide vaccine<br>* PPSV23<br>* Other names: PPSV23;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with serologic response to tetanus toxoid | Measured by comparing the anti-tetanus toxoid immunoglobulin G (IgG) antibody titers at 4 weeks post-vaccination compared to the pre-vaccination titers. Participants with a pre-vaccination IgG antibody titer level ≤ 0.10 IU/mL will have a serologic response if post-vaccination titer levels are ≥ 0.40 IU/mL. To demonstrate a serologic response if pre-vaccination titer levels are > 0.10 IU/mL and ≤ 2.7 IU/mL, participants will have at least a 4-fold increase in post-vaccination titers. If participants have a pre-vaccination titer level > 2.7 IU/mL, they will have at least a 2-fold increase in titers to demonstrate a response. | At Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tetanus | Proportion of subjects with serological protection against tetanus toxoid. | At Day 28 | 
| Pneumococcus | Proportion of participants with serologic response to at least 5 of the following pneumococcal serotypes: 3, 6B, 9N, 11A, 14, 19A, 19F, 22F and 23F. | At Day 28 | 
| Pneumococcus | Proportion of participants with serological protection against the following pneumococcal serotypes: 3, 6B, 9N, 11A, 14, 19A, 19F, 22F and 23F. | At Day 28 | 
| Safety of concomitant vaccine administration in participants taking ozanimod | A Safety Adverse Event (SAE) or Adverse Event (AE) incidence is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology. Any worsening (i.e., any clinically significant adverse change in the frequency or intensity of a preexisting condition) should be considered an AE. | At Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Sclerosis, Ozanimod, Relapsing-remitting multiple sclerosis