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

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.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting
• Intervention / Treatment: Biological: Tetanus, diphtheria, and acellular pertussis vaccine; Biological: Pneumococcal polysaccharide vaccine; Biological: Seasonal influenza vaccine

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Bochum, Germany, 44791
    • Local Institution - 200
  • Dresden, Germany, 01307
    • Local Institution - 201
  • Mannheim, Germany, 68163
    • Local Institution - 206
  • Rostock, Germany, 18147
    • Local Institution - 204
• United States
  • California
    • Palo Alto, California, United States, 94304
      • Stanford University
  • Colorado
    • Colorado Springs, Colorado, United States, 80907
      • Colorado Springs Neurological Associates
  • Connecticut
    • Southington, Connecticut, United States, 06489
      • Hartford Healthcare CT
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida Health
    • Port Charlotte, Florida, United States, 33952
      • Neurostudies Inc
    • Port Orange, Florida, United States, 32127
      • Accel Research Sites - Brain and Spine Institute of Port Orange - ERN - PPDS
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medicine
    • Northbrook, Illinois, United States, 60062
      • Consultants in Neurology
  • Kansas
    • Kansas City, Kansas, United States, 66205
      • Local Institution - 111
    • Overland Park, Kansas, United States, 66212
      • CPFCC Neurology Research Dept.
  • Louisiana
    • Alexandria, Louisiana, United States, 71301
      • Neuromedical Clinic of Central LA
  • Massachusetts
    • Foxboro, Massachusetts, United States, 02035
      • Neurology Center of New England P.C.
  • Michigan
    • East Lansing, Michigan, United States, 48824
      • Michigan State University MS Clinic
  • Minnesota
    • Minneapolis, Minnesota, United States, 55422
      • Shapiro Center for MS at the Minneapolis Clinic of Neurology
  • Nebraska
    • Lincoln, Nebraska, United States, 68506
      • Neurology Associates PC
  • New Jersey
    • Neptune, New Jersey, United States, 07753
      • Jersey Shore MS Center
    • Teaneck, New Jersey, United States, 07666
      • Holy Name Hospital
  • New York
    • Patchogue, New York, United States, 11772
      • South Shore Neurology Associates, Inc
  • North Carolina
    • Asheville, North Carolina, United States, 28806
      • Asheville Neurology Specialists PA
    • Mooresville, North Carolina, United States, 28117
      • Lake Norman Neurology
  • Ohio
    • Canton, Ohio, United States, 44718
      • Local Institution - 105
    • Cleveland, Ohio, United States, 44122
      • Velocity Clinical Research - Cleveland - ERN - PPDS
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University - Clinical Research Institute
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57104
      • Sanford Health
  • Tennessee
    • Knoxville, Tennessee, United States, 37922
      • Hope Neurology MS Center
  • Texas
    • Round Rock, Texas, United States, 78681
      • Central Texas Neurology Consultants PA
  • Washington
    • Tacoma, Washington, United States, 98405
      • MultiCare Institute for Research and Innovation
  • West Virginia
    • Crab Orchard, West Virginia, United States, 25827
      • Vaught Neurological Services, PLLC
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 2 - Ozanimod; 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; Tdap; Other Names: Tdap; Biological: Pneumococcal polysaccharide vaccine; PPSV23; Other Names: PPSV23
Experimental: Cohort 2 - non-pegylated interferon-β or no disease modifying therapy; 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; Tdap; Other Names: Tdap; Biological: Pneumococcal polysaccharide vaccine; PPSV23; Other Names: PPSV23
Experimental: Cohort 1 - Ozanimod; 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; Tdap; Other Names: Tdap; Biological: Pneumococcal polysaccharide vaccine; PPSV23; Other Names: PPSV23; Biological: Seasonal influenza vaccine; Seasonal influenza vaccine
Experimental: Cohort 1 - non-pegylated interferon-β or no disease modifying therapy; 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; Tdap; Other Names: Tdap; Biological: Pneumococcal polysaccharide vaccine; PPSV23; Other Names: PPSV23; Biological: Seasonal influenza vaccine; Seasonal influenza vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Day 28
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).	Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Serologic Response to Pneumococcal Polysaccharide Vaccine (PPSV23)	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	Day 28
Percentage of Participants With Serologic Protection Against Pneumococcal Polysaccharide Vaccine (PPSV23)	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.	Day 28
Number of Participants With Adverse Events	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.	Day 1 to Day 28
Number of Participants With Abnormalities in Blood Chemistry Parameters	Blood samples were collected to assess laboratory parameters	Day 1 to Day 28
Number of Participants With Abnormalities in Blood Hematology Parameters	Blood samples were collected to assess laboratory parameters	Day 1 to Day 28
Change From Baseline in Blood Chemistry Parameters - Sodium; Potassium; Chloride; Calcium; Magnesium; Phosphate; Blood Urea Nitrogen; Glucose	Blood samples were collected to assess laboratory parameters.	Baseline (Day 1) and End of Study (Day 28)
Change From Baseline in Blood Chemistry Parameters - Creatinine; Bilirubin; Direct Bilirubin	Blood samples were collected to assess laboratory parameters.	Baseline (Day 1) and End of Study (Day 28)
Change From Baseline in Blood Chemistry Parameters - Albumin	Blood samples were collected to assess laboratory parameters.	Baseline (Day 1) and End of Study (Day 28)
Change From Baseline in Blood Chemistry Parameters - Alkaline Phosphatase	Blood samples were collected to assess laboratory parameters.	Baseline (Day 1) and End of Study (Day 28)
Change From Baseline in Blood Chemistry Parameters - Alanine Aminotransferase; Aspartate Aminotransferase; Gamma Glutamyl Transferase	Blood samples were collected to assess laboratory parameters.	Baseline (Day 1) and End of Study (Day 28)
Change From Baseline in Blood Hematology Parameters - Erythrocytes	Blood samples were collected to assess laboratory parameters.	Baseline (Day 1) and End of Study (Day 28)
Change From Baseline in Blood Hematology Parameters - Leukocytes; Basophils; Eosinophils; Lymphocytes; Monocytes; Neutrophils; Platelets	Blood samples were collected to assess laboratory parameters.	Baseline (Day 1) and End of Study (Day 28)
Change From Baseline in Blood Hematology Parameters - Basophils/Leukocytes; Eosinophils/Leukocytes; Lymphocytes/Leukocytes; Monocytes/Leukocytes; Neutrophils/Leukocytes	Blood samples were collected to assess laboratory parameters.	Baseline (Day 1) and End of Study (Day 28)
Change From Baseline in Blood Hematology Parameters - Hemoglobin; Erythrocytes Mean Corpuscular HGB Concentration	Blood samples were collected to assess laboratory parameters.	Baseline (Day 1) and End of Study (Day 28)
Change From Baseline in Blood Hematology Parameters - Erythrocytes Mean Corpuscular Volume	Blood samples were collected to assess laboratory parameters.	Baseline (Day 1) and End of Study (Day 28)
Change From Baseline in Blood Hematology Parameters - Erythrocytes Mean Corpuscular Hemoglobin	Blood samples were collected to assess laboratory parameters.	Baseline (Day 1) and End of Study (Day 28)
Change From Baseline in Blood Hematology Parameters - Hematocrit	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.	Baseline (Day 1) and End of Study (Day 28)

Collaborators and Investigators

• Sponsor: Celgene
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2021
• Primary Completion (Actual): November 15, 2023
• Study Completion (Actual): November 15, 2023

Study Registration Dates

• First Submitted: August 25, 2021
• First Submitted That Met QC Criteria: August 25, 2021
• First Posted (Actual): August 31, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 23, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Multiple Sclerosis; Ozanimod; Relapsing-remitting multiple sclerosis
• Additional Relevant MeSH Terms: Nervous System Diseases; Pathologic Processes; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Multiple Sclerosis; Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Immunologic Factors; Physiological Effects of Drugs; Heptavalent Pneumococcal Conjugate Vaccine; Vaccines
• Other Study ID Numbers: RPC-1063-MS-010; 2021-001847-28 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No