A Multicenter Study to Assess Response to Influenza Vaccine in Multiple Sclerosis Participants Treated With Ofatumumab

NCT ID: NCT04667117

Last Updated: 2024-10-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 63 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-14
• Study Completion Date: 2023-07-06

Brief Summary

To assess whether participants treated with ofatumumab 20 mg subcutaneous (s.c.) administered once every 4 weeks (q4) can mount an adequate immune response to inactivated influenza vaccine as measured by humoral responses compared to participants on an iDMT.

Detailed Description

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 were 3 study periods:

• Screening Period of up to 1 week to assess eligibility requirements.
• Investigational Period of 4 weeks All participants received an inactivated influenza vaccine within 9 calendar days after the Screening Visit, before the Week 0 Visit occurred.

Participants in Cohort 1 received loading doses of 20 mg ofatumumab administered subcutaneously (s.c.) at Weeks 2, 3, and 4.

Participants in Cohort 2 continued taking their prescribed ofatumumab as per their dosing schedule throughout the Investigational Period.

Participants in Cohort 3 continued administration of their prescribed injectable disease modifying therapy (iDMT) as per their dosing schedule in the Investigational Period.

• Optional, 6-month open-label Extension Period Participants in Cohort 1 were administered their first dose of ofatumumab at Week 6; thereinafter, they continued monthly dosing until the final dose at Week 26.

Participants in Cohort 2 continued to receive ofatumumab monthly until the final dose at Week 28.

Participants in Cohort 3 did not enter the open-label Extension Period.

Conditions

Relapsing Multiple Sclerosis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1

Patients with relapsing multiple sclerosis (MS) receiving a 2020-2021, 2021-2022, or 2022-2023 inactivated influenza vaccine two weeks prior to ofatumumab start

Group Type: EXPERIMENTAL

Quadrivalent influenza vaccine

Intervention Type: BIOLOGICAL

2020-2021, 2021-2022, or 2022-2023 inactivated quadrivalent influenza vaccine. Participants received the vaccine within 9 calendar days after the Screening Visit, before the Week 0 Visit occurred.

Ofatumumab

Intervention Type: DRUG

Auto-injector containing 20 mg ofatumumab (20 mg/0.4mL) for subcutaneous (s.c.) administration.

• Participants in Cohort 1 received loading doses of 20 mg ofatumumab s.c. at Weeks 2, 3, and 4 in the Investigational Period. In the open-label Extension Period, they administered the first dose of ofatumumab at Week 6 and continued monthly dosing until the final dose at Week 26. Novartis supplied participants in Cohort 1 with ofatumumab treatment.
• Participants in Cohort 2 continued on their commercially prescribed ofatumumab treatment during the Investigational Period. In the open-label Extension Period, they continued to administer ofatumumab monthly until the final dose at Week 28. Cohort 2 participants in the extension could have either remained on their prescribed ofatumumab or switched to study supplied ofatumumab.

Cohort 2

Patients with relapsing MS receiving a 2020-2021, 2021-2022, 2022-2023 inactivated influenza vaccine at least 4 weeks after ofatumumab start

Group Type: EXPERIMENTAL

Quadrivalent influenza vaccine

Intervention Type: BIOLOGICAL

2020-2021, 2021-2022, or 2022-2023 inactivated quadrivalent influenza vaccine. Participants received the vaccine within 9 calendar days after the Screening Visit, before the Week 0 Visit occurred.

Ofatumumab

Intervention Type: DRUG

Auto-injector containing 20 mg ofatumumab (20 mg/0.4mL) for subcutaneous (s.c.) administration.

• Participants in Cohort 1 received loading doses of 20 mg ofatumumab s.c. at Weeks 2, 3, and 4 in the Investigational Period. In the open-label Extension Period, they administered the first dose of ofatumumab at Week 6 and continued monthly dosing until the final dose at Week 26. Novartis supplied participants in Cohort 1 with ofatumumab treatment.
• Participants in Cohort 2 continued on their commercially prescribed ofatumumab treatment during the Investigational Period. In the open-label Extension Period, they continued to administer ofatumumab monthly until the final dose at Week 28. Cohort 2 participants in the extension could have either remained on their prescribed ofatumumab or switched to study supplied ofatumumab.

Cohort 3

Patients with relapsing MS currently on iDMT receiving a 2020-2021, 2021-2022, or 2022-2023 inactivated influenza vaccine

Group Type: ACTIVE_COMPARATOR

Quadrivalent influenza vaccine

Intervention Type: BIOLOGICAL

2020-2021, 2021-2022, or 2022-2023 inactivated quadrivalent influenza vaccine. Participants received the vaccine within 9 calendar days after the Screening Visit, before the Week 0 Visit occurred.

iDMT

Intervention Type: DRUG

Participants in Cohort 3 continued on their commercially prescribed injectable disease modifying therapy (iDMT) during the Investigational Period.

Interventions

Quadrivalent influenza vaccine

2020-2021, 2021-2022, or 2022-2023 inactivated quadrivalent influenza vaccine. Participants received the vaccine within 9 calendar days after the Screening Visit, before the Week 0 Visit occurred.

Intervention Type: BIOLOGICAL

Ofatumumab

Auto-injector containing 20 mg ofatumumab (20 mg/0.4mL) for subcutaneous (s.c.) administration.

• Participants in Cohort 1 received loading doses of 20 mg ofatumumab s.c. at Weeks 2, 3, and 4 in the Investigational Period. In the open-label Extension Period, they administered the first dose of ofatumumab at Week 6 and continued monthly dosing until the final dose at Week 26. Novartis supplied participants in Cohort 1 with ofatumumab treatment.
• Participants in Cohort 2 continued on their commercially prescribed ofatumumab treatment during the Investigational Period. In the open-label Extension Period, they continued to administer ofatumumab monthly until the final dose at Week 28. Cohort 2 participants in the extension could have either remained on their prescribed ofatumumab or switched to study supplied ofatumumab.

Intervention Type: DRUG

iDMT

Participants in Cohort 3 continued on their commercially prescribed injectable disease modifying therapy (iDMT) during the Investigational Period.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Hope Research Institute Center Neurology and Spine

Phoenix, Arizona, United States

Infinity Clinical Research LLC

Hollywood, Florida, United States

The MS Center for Innovation in Care

St Louis, Missouri, United States

Countries

United States

References

Steingo B, Subei A, Riser E, Gitt J, Stankiewicz J, Piccolo R, Wyse K, Weinstock-Guttman B. Immune response to influenza vaccine in patients with relapsing multiple sclerosis treated with ofatumumab: Results from an open-label, multicenter, phase 4 study. Mult Scler Relat Disord. 2025 May;97:106382. doi: 10.1016/j.msard.2025.106382. Epub 2025 Mar 8.

Reference Type: DERIVED

PMID: 40107181 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=2189

A Plain Language Trial Summary is available on novctrd.com

Other Identifiers

COMB157GUS12

Identifier Type: -

Identifier Source: org_study_id