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

Phase 3

Completed

Conditions: Multiple Sclerosis
Multiple Sclerosis, Relapsing-Remitting

Interventions: Biological: Tetanus, diphtheria, and acellular pertussis vaccine
Biological: Pneumococcal polysaccharide vaccine
Biological: Seasonal influenza vaccine

Registration Number: NCT05028634

Lead Sponsor: Celgene

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 63

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 1 - Ozanimod	Seasonal influenza vaccine	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
Cohort 2 - non-pegylated interferon-β or no disease modifying therapy	Tetanus, diphtheria, and acellular pertussis vaccine	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).
Cohort 1 - Ozanimod	Tetanus, diphtheria, and acellular pertussis vaccine	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
Cohort 1 - Ozanimod	Pneumococcal polysaccharide vaccine	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
Cohort 1 - non-pegylated interferon-β or no disease modifying therapy	Tetanus, diphtheria, and acellular pertussis vaccine	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
Cohort 1 - non-pegylated interferon-β or no disease modifying therapy	Pneumococcal polysaccharide vaccine	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
Cohort 2 - Ozanimod	Tetanus, diphtheria, and acellular pertussis vaccine	Comprises of participants received oral ozanimod will be administered tetanus, diphtheria, and acellular pertussis vaccine (Tdap), and pneumococcal polysaccharide vaccine (PPSV23).
Cohort 2 - Ozanimod	Pneumococcal polysaccharide vaccine	Comprises of participants received oral ozanimod will be administered tetanus, diphtheria, and acellular pertussis vaccine (Tdap), and pneumococcal polysaccharide vaccine (PPSV23).
Cohort 2 - non-pegylated interferon-β or no disease modifying therapy	Pneumococcal polysaccharide vaccine	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).
Cohort 1 - non-pegylated interferon-β or no disease modifying therapy	Seasonal influenza vaccine	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

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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.
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.
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
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.
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 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.

Trial Locations

Locations (33): Hartford Healthcare CT
🇺🇸
Southington, Connecticut, United States
Shapiro Center for MS at the Minneapolis Clinic of Neurology
🇺🇸
Minneapolis, Minnesota, United States
South Shore Neurology Associates, Inc
🇺🇸
Patchogue, New York, United States
Thomas Jefferson University - Clinical Research Institute
🇺🇸
Philadelphia, Pennsylvania, United States
Local Institution - 105
🇺🇸
Canton, Ohio, United States
Local Institution - 111
🇺🇸
Kansas City, Kansas, United States
Jersey Shore MS Center
🇺🇸
Neptune, New Jersey, United States
Holy Name Hospital
🇺🇸
Teaneck, New Jersey, United States
Velocity Clinical Research - Cleveland - ERN - PPDS
🇺🇸
Cleveland, Ohio, United States
Accel Research Sites - Brain and Spine Institute of Port Orange - ERN - PPDS
🇺🇸
Port Orange, Florida, United States
CPFCC Neurology Research Dept.
🇺🇸
Overland Park, Kansas, United States
Neurology Associates PC
🇺🇸
Lincoln, Nebraska, United States
Asheville Neurology Specialists PA
🇺🇸
Asheville, North Carolina, United States
Stanford University
🇺🇸
Palo Alto, California, United States
Colorado Springs Neurological Associates
🇺🇸
Colorado Springs, Colorado, United States
Neurostudies Inc
🇺🇸
Port Charlotte, Florida, United States
University of Chicago Medicine
🇺🇸
Chicago, Illinois, United States
Consultants In Neurology
🇺🇸
Northbrook, Illinois, United States
Neuromedical Clinic of Central LA
🇺🇸
Alexandria, Louisiana, United States
Michigan State University MS Clinic
🇺🇸
East Lansing, Michigan, United States
Lake Norman Neurology
🇺🇸
Mooresville, North Carolina, United States
Sanford Health
🇺🇸
Sioux Falls, South Dakota, United States
Central Texas Neurology Consultants PA
🇺🇸
Round Rock, Texas, United States
University of Florida Health
🇺🇸
Gainesville, Florida, United States
Neurology Center of New England P.C.
🇺🇸
Foxboro, Massachusetts, United States
Hope Neurology MS Center
🇺🇸
Knoxville, Tennessee, United States
MultiCare Institute for Research and Innovation
🇺🇸
Tacoma, Washington, United States
Local Institution - 201
🇩🇪
Dresden, Germany
Local Institution - 206
🇩🇪
Mannheim, Germany
Local Institution - 204
🇩🇪
Rostock, Germany
Vaught Neurological Services, PLLC
🇺🇸
Crab Orchard, West Virginia, United States
Medical College of Wisconsin
🇺🇸
Milwaukee, Wisconsin, United States
Local Institution - 200
🇩🇪
Bochum, Germany