Clinical trial NCT04667117: A Multicenter Study to Assess Response to Influenza Vaccine in Multiple Sclerosis Participants Treated With Ofatumumab
Official title: An Open-label Multicenter Study to Assess Response to Influenza Vaccine in Participants With Multiple Sclerosis Treated With Ofatumumab 20 mg Subcutaneously
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Relapsing Multiple Sclerosis
Keywords: ofatumumab
multiple sclerosis
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2020-12-14
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel, prospective study
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Percentage of Participants Achieving Seroprotection at Week 4 (Observed Case)
timeFrame: Week 4
measure: Percentage of Participants Achieving Seroprotection at Week 4 (Non-responder Imputation)
timeFrame: Week 4
Secondary outcomes:
measure: Percentage of Participants Achieving Seroconversion at Week 4 (Observed Case)
timeFrame: Baseline (pre-vaccination), Week 4
measure: Percentage of Participants Achieving Seroconversion at Week 4 (Non-responder Imputation)
timeFrame: Baseline (pre-vaccination), Week 4
measure: Fold Change From Baseline in Hemagglutination Inhibition Titers
timeFrame: Baseline (pre-vaccination), Week 4
measure: Number of Participants With Adverse Events (AEs), AEs Leading to Discontinuation and Serious Adverse Events (SAEs)
timeFrame: From Week 0 to Week 26 (Cohort 1), Week 28 (Cohort 2) and Week 4 (Cohort 3)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Hope Research Institute Center Neurology and Spine
state: Arizona
city: Hollywood
country: United States
facility: Infinity Clinical Research LLC
state: Florida
city: Saint Louis
country: United States
facility: The MS Center for Innovation in Care
state: Missouri
Study officials:
References: