Inclusion Criteria:

1. Signed informed consent must be obtained prior to participation in the study. 2. Age 18-55 years old. 3. Diagnosis of relapsing MS by 2017 revised McDonald criteria. 4. Must be willing to comply with the study schedule. 5. Planning to receive a 2020-2021, 2021-2022, or 2022-2023 inactivated influenza vaccine. 6. Planning to start treatment with ofatumumab or already on commercially prescribed ofatumumab for at least 2 weeks prior to the screening visit. Participants in Cohort 3 must fulfill criteria 1-5 above in addition to the following: 7. Participant must currently be receiving iDMT.

Exclusion Criteria:

1. Already has received the 2020-2021, 2021-2022, or 2022-2023 season influenza vaccine. 2. Known hypersensitivity to any component of the influenza vaccine. 3. Any safety finding including low IgG and/or low IgM levels requiring an ofatumumab treatment interruption within the 12 weeks immediately prior to Week 0. 4. Any major episode of infection requiring hospitalization or treatment with intravenous antibiotics within 4 weeks prior to or oral antibiotics within two weeks prior to Week 0. 5. Known clinical diagnosis of influenza infection during the 2020-2021 influenza season prior to starting the study based on investigator's or subject's personal physician's judgement (laboratory report of confirmed influenza infection is not required) 6. Prior treatment with B-cell targeted therapies (e.g., rituximab or ocrelizumab), lymphocyte-trafficking blockers, alemtuzumab, anti-CD4, cladribine, cyclophosphamide, mitoxantrone, azathioprine, mycophenolate mofetil, cyclosporine, methotrexate, total body irradiation, bone marrow transplantation. Treatment with a natalizumab within 6 months of week 0. 7. Treatment with an S1P modulator within 60 days prior to Week 0. 8. Participants with any known active systemic bacterial, fungal or viral or fungal infections (such as hepatitis, progressive multifocal leukocencephalopathy, COVID-19 or HIV), or known to have acquired immunodeficiency syndrome (AIDS) 9. Participation in another interventional clinical trial within 14 days prior to the screening visit. 10. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test. 11. Women of child-bearing potential. 12. Patients with a history of Guillain-Barre syndrome within 6 weeks of receiving the influenza vaccination.

Vaccinations against influenza are an important part of effective management of multiple sclerosis (MS). Ofatumumab is a human anti-CD20 monoclonal antibody (mAb) which depletes B-cells, a component of the immune system. This study investigates if ofatumumab treated patients can have an immune response that may be protective after receiving the influenza vaccine. There will be a one week screening period to assess eligibility for the trial. All eligible participants will receive an influenza vaccine during the Screening Period prior to the Investigational Period. This study will enroll 66 participants with relapsing multiple sclerosis into three cohorts in multiple centers. Up to 44 of the participants will begin treatment with ofatumumab or will already be receiving commercial ofatumumab. The remaining 22 participants will remain on their Injectable Disease Modifying Therapy (iDMT). There will be 4 weekly visits during the Investigational Period which will last 4 weeks. There will also be an optional, 6 month Extension Period for Cohorts 1 and 2, who received ofatumumab, to further evaluate immune response. Cohort 3 will not enter the Extension Period.

Arms

Experimental: Cohort 1

RMS patients receiving a 2020-2021, 2021-2022, or 2022-2023 inactivated influenza vaccine at least two weeks prior to ofatumumab start

Experimental: Cohort 2

RMS patients receiving a 2020-2021, 2021-2022, 2022-2023 inactivated influenza vaccine at least 4 weeks after ofatumumab start.

Experimental: Cohort 3

RMS patients currently on iDMT receiving a 2020-2021, 2021-2022, or 2022-2023 an inactivated influenza vaccine

Interventions

Biological: - Quadrivalent influenza vaccine

2020-2021, 2021-2022, or 2022-2023 inactivated quadrivalent influenza vaccine

Drug: - Ofatumumab

Auto-injector containing 20 mg sc ofatumumab (20 mg/0.4ml) for subcutaneous administration. Novartis will supply participants in Cohort 1 with ofatumumab treatment in the Investigational Period and the optional 6-month Extension Period. Participants in Cohort 2 will continue on their commercially prescribed ofatumumab treatment during the Investigational Period. Novartis will supply participants in Cohort 2 with ofatumumab treatment in the optional 6-month Extension Period.