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

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

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05028634

Enrollment

Registered

2021-08-31

Start date

2021-11-11

Completion date

2023-11-15

Last updated

2025-02-11

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Multiple Sclerosis, Multiple Sclerosis, Relapsing-Remitting

Keywords

Multiple Sclerosis, Ozanimod, Relapsing-remitting multiple sclerosis

Brief summary

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.

Interventions

BIOLOGICALTetanus, diphtheria, and acellular pertussis vaccine

Tdap

BIOLOGICALPneumococcal polysaccharide vaccine

PPSV23

BIOLOGICALSeasonal influenza vaccine

Seasonal influenza vaccine

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants Meeting Immune Serological Response Criteria to Tetanus Toxoid Antigen	Day 28	Serologic response to tetanus toxoid criteria are as follows - if pre vaccination antibody titer is ≤0.10 IU/mL, post-vaccination level ≥0.40 IU/mL; if pre-vaccination antibody titer is \>0.10 IU/mL and ≤2.7 IU/mL, at least a 4-fold increase in titer; if pre-vaccination antibody titer is\>2.7 IU/mL, at least a 2-fold increase in titer.
Percentage of Participants Meeting Immune Serological Protection Criteria to Tetanus Toxoid Antigen	Day 28	Participants with Serological protection to tetanus toxoid have anti-tetanus toxoid IgG concentration \>= 0.1 International Units per milliliter (IU/mL).

Secondary

Measure	Time frame	Description
Number of Participants With Adverse Events	Day 1 to Day 28	Adverse events include events with onset date on or after the study medication first dose date until end of study visit after the vaccine administration. Serious AEs was defined as is any AE occurring at any dose of vaccination from Day 1 to the end of the study that results in death, Is life-threatening (ie, in the opinion of the Investigator, the subject is at immediate risk of death from the AE), Requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or constitutes an important medical event.
Number of Participants With Abnormalities in Blood Chemistry Parameters	Day 1 to Day 28	Blood samples were collected to assess laboratory parameters
Number of Participants With Abnormalities in Blood Hematology Parameters	Day 1 to Day 28	Blood samples were collected to assess laboratory parameters
Change From Baseline in Blood Chemistry Parameters - Sodium; Potassium; Chloride; Calcium; Magnesium; Phosphate; Blood Urea Nitrogen; Glucose	Baseline (Day 1) and End of Study (Day 28)	Blood samples were collected to assess laboratory parameters.
Change From Baseline in Blood Chemistry Parameters - Creatinine; Bilirubin; Direct Bilirubin	Baseline (Day 1) and End of Study (Day 28)	Blood samples were collected to assess laboratory parameters.
Change From Baseline in Blood Chemistry Parameters - Albumin	Baseline (Day 1) and End of Study (Day 28)	Blood samples were collected to assess laboratory parameters.
Change From Baseline in Blood Chemistry Parameters - Alkaline Phosphatase	Baseline (Day 1) and End of Study (Day 28)	Blood samples were collected to assess laboratory parameters.
Percentage of Participants With Serologic Response to Pneumococcal Polysaccharide Vaccine (PPSV23)	Day 28	Serological response to PPSV23 was defined as the percentage of participants with a ≥2-fold increase in anti-pneumococcal polysaccharide vaccine titer in \>5 of the indicated serotypes - 3, 6B, 9N, 11A, 14, 19A, 19F, 22F and 23F
Change From Baseline in Blood Hematology Parameters - Erythrocytes	Baseline (Day 1) and End of Study (Day 28)	Blood samples were collected to assess laboratory parameters.
Change From Baseline in Blood Hematology Parameters - Leukocytes; Basophils; Eosinophils; Lymphocytes; Monocytes; Neutrophils; Platelets	Baseline (Day 1) and End of Study (Day 28)	Blood samples were collected to assess laboratory parameters.
Change From Baseline in Blood Hematology Parameters - Basophils/Leukocytes; Eosinophils/Leukocytes; Lymphocytes/Leukocytes; Monocytes/Leukocytes; Neutrophils/Leukocytes	Baseline (Day 1) and End of Study (Day 28)	Blood samples were collected to assess laboratory parameters.
Change From Baseline in Blood Hematology Parameters - Hemoglobin; Erythrocytes Mean Corpuscular HGB Concentration	Baseline (Day 1) and End of Study (Day 28)	Blood samples were collected to assess laboratory parameters.
Change From Baseline in Blood Hematology Parameters - Erythrocytes Mean Corpuscular Volume	Baseline (Day 1) and End of Study (Day 28)	Blood samples were collected to assess laboratory parameters.
Change From Baseline in Blood Hematology Parameters - Erythrocytes Mean Corpuscular Hemoglobin	Baseline (Day 1) and End of Study (Day 28)	Blood samples were collected to assess laboratory parameters.
Change From Baseline in Blood Hematology Parameters - Hematocrit	Baseline (Day 1) and End of Study (Day 28)	Blood samples were collected to assess laboratory parameters. Participants with baseline and post-baseline data available at the specified timepoint are included in the analysis.
Change From Baseline in Blood Chemistry Parameters - Alanine Aminotransferase; Aspartate Aminotransferase; Gamma Glutamyl Transferase	Baseline (Day 1) and End of Study (Day 28)	Blood samples were collected to assess laboratory parameters.
Percentage of Participants With Serologic Protection Against Pneumococcal Polysaccharide Vaccine (PPSV23)	Day 28	Serological protection against PPSV23 was defined as the percentage of participants with Anti-pneumococcal polysaccharide IgG concentration \>= 1.3 μg/mL in the indicated serotypes - 3, 6B, 9N, 11A, 14, 19A, 19F, 22F and 23F associated with increased risk of invasive and/or severe disease, including death.

Countries

Germany, United States

Participant flow

Pre-assignment details

As pre-specified per protocol, Cohort 1 and Cohort 2 are pooled per the following treatment groups. i. Ozanimod treatment group ii. Non-Ozanimod treatment group

Participants by arm

Arm	Count
Ozanimod Participants with relapsing forms of Multiple Sclerosis (MS) who received Oral Ozanimod were administered with regimen of Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis, Adsorbed (Tdap) vaccine, Pneumococcal polysaccharide (PPSV23), and the seasonal inactivated influenza vaccine on Day 1.	30
Non-Ozanimod Participants with relapsing forms of Multiple Sclerosis (MS) who have received either non-pegylated interferon-β (IFN-β) or no disease modifying therapy (DMT) and already received the seasonal inactivated influenza vaccine receive regimen of Tdap and PPSV23 vaccine only on Day 1.	33
Total	63

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Withdrawal by Subject	0	1

Baseline characteristics

Characteristic	Non-Ozanimod	Total	Ozanimod
Age, Continuous	46.8 years STANDARD_DEVIATION 6.83	45.0 years STANDARD_DEVIATION 8.09	43.1 years STANDARD_DEVIATION 9.03
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants	5 Participants	2 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	29 Participants	55 Participants	26 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants	3 Participants	2 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) Black or African American	3 Participants	7 Participants	4 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants	2 Participants	1 Participants
Race (NIH/OMB) White	29 Participants	53 Participants	24 Participants
Sex: Female, Male Female	21 Participants	42 Participants	21 Participants
Sex: Female, Male Male	12 Participants	21 Participants	9 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 30	0 / 33
other Total, other adverse events	5 / 30	7 / 33
serious Total, serious adverse events	0 / 30	0 / 33

Outcome results

Primary

Percentage of Participants Meeting Immune Serological Protection Criteria to Tetanus Toxoid Antigen

Participants with Serological protection to tetanus toxoid have anti-tetanus toxoid IgG concentration \>= 0.1 International Units per milliliter (IU/mL).

Time frame: Day 28

Population: Modified Intent-to-Treat (mITT) Population consists of all participants who received at least one vaccination and summarized according to their initial treatment status (ozanimod vs. non-ozanimod) regardless of systemic use of corticosteroids. Participants with data available at the specified timepoint are included in the analysis.

Arm	Measure	Value (NUMBER)
Ozanimod	Percentage of Participants Meeting Immune Serological Protection Criteria to Tetanus Toxoid Antigen	100 percentage of participants
Non-Ozanimod	Percentage of Participants Meeting Immune Serological Protection Criteria to Tetanus Toxoid Antigen	100 percentage of participants

Primary

Percentage of Participants Meeting Immune Serological Response Criteria to Tetanus Toxoid Antigen

Serologic response to tetanus toxoid criteria are as follows - if pre vaccination antibody titer is ≤0.10 IU/mL, post-vaccination level ≥0.40 IU/mL; if pre-vaccination antibody titer is \>0.10 IU/mL and ≤2.7 IU/mL, at least a 4-fold increase in titer; if pre-vaccination antibody titer is\>2.7 IU/mL, at least a 2-fold increase in titer.

Time frame: Day 28

Arm	Measure	Value (NUMBER)
Ozanimod	Percentage of Participants Meeting Immune Serological Response Criteria to Tetanus Toxoid Antigen	10 percentage of participants
Non-Ozanimod	Percentage of Participants Meeting Immune Serological Response Criteria to Tetanus Toxoid Antigen	53.1 percentage of participants

Secondary