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

NCT04667117 | Completed Phase 4 Results FDA Drug

• 1 other identifier: COMB157GUS12
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 3

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.

Conditions

Relapsing Multiple Sclerosis

Keywords

ofatumumab; multiple sclerosis

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants Achieving Seroprotection at Week 4 (Observed Case)

  A seroprotection responder was a participant achieving seroprotection as defined by a post-vaccination hemagglutination inhibition (HI) titer ≥ 40 at Week 4. Seroprotection against ten influenza strains was analyzed. The analysis was performed taking into consideration observed data.

  Week 4

• Percentage of Participants Achieving Seroprotection at Week 4 (Non-responder Imputation)

  A seroprotection responder was a participant achieving seroprotection as defined by a post-vaccination hemagglutination inhibition (HI) titer ≥ 40 at Week 4. Seroprotection against ten influenza strains was analyzed. Non-responder imputation (NRI) for missing data was applied.

  Week 4

Secondary Outcomes (4)

• Percentage of Participants Achieving Seroconversion at Week 4 (Observed Case)

  Baseline (pre-vaccination), Week 4

• Percentage of Participants Achieving Seroconversion at Week 4 (Non-responder Imputation)

  Baseline (pre-vaccination), Week 4

• Fold Change From Baseline in Hemagglutination Inhibition Titers

  Baseline (pre-vaccination), Week 4

• Number of Participants With Adverse Events (AEs), AEs Leading to Discontinuation and Serious Adverse Events (SAEs)

  From Week 0 to Week 26 (Cohort 1), Week 28 (Cohort 2) and Week 4 (Cohort 3)

Study Arms (3)

Cohort 1

EXPERIMENTAL

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

Biological: Quadrivalent influenza vaccine; Drug: Ofatumumab

Cohort 2

EXPERIMENTAL

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

Biological: Quadrivalent influenza vaccine; Drug: Ofatumumab

Cohort 3

ACTIVE COMPARATOR

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

Biological: Quadrivalent influenza vaccine; Drug: iDMT

Interventions

Quadrivalent influenza vaccine 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.

Cohort 1; Cohort 2; Cohort 3

Ofatumumab 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 1; Cohort 2

iDMT DRUG

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

Cohort 3

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Signed informed consent must be obtained prior to participation in the study
• Age 18-55 years old
• Diagnosis of relapsing MS by 2017 revised McDonald criteria
• Must be willing to comply with the study schedule
• Planning to receive a 2020-2021, 2021-2022, or 2022-2023 inactivated influenza vaccine
• 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:
• Participant must currently be receiving iDMT

You may not qualify if:

• Already has received the 2020-2021, 2021-2022, or 2022-2023 season influenza vaccine
• Known hypersensitivity to any component of the influenza vaccine
• 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
• 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
• 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)
• 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
• Treatment with an S1P modulator within 60 days prior to Week 0
• 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)
• Participation in another interventional clinical trial within 14 days prior to the screening visit
• 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
• Women of child-bearing potential
• Patients with a history of Guillain-Barre syndrome within 6 weeks of receiving the influenza vaccination.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (3)

Hope Research Institute Center Neurology and Spine

Phoenix, Arizona, 85018, United States

Location

Infinity Clinical Research LLC

Hollywood, Florida, 33024, United States

Location

The MS Center for Innovation in Care

St Louis, Missouri, 63131, United States

Location

Related Publications (1)

• 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.

  PMID: 40107181 DERIVED

Related Links

• A Plain Language Trial Summary is available on novctrd.com

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Influenza Vaccines; ofatumumab

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Unblinded treatment
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Parallel, prospective study

Study Record Dates

• First Submitted: December 8, 2020
• First Posted: December 14, 2020
• Study Start: January 14, 2021
• Primary Completion: July 6, 2023
• Study Completion: July 6, 2023
• Last Updated: October 9, 2024
• Results First Posted: August 1, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share

Locations

US (3)