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

An Open-label Multicenter Study to Assess Response to Influenza Vaccine in Participants With Multiple Sclerosis Treated With Ofatumumab 20 mg Subcutaneously

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.

Study Overview

• Status: Completed
• Conditions: Relapsing Multiple Sclerosis
• Intervention / Treatment: Biological: Quadrivalent influenza vaccine; Drug: Ofatumumab; Drug: 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.

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85018
      • Hope Research Institute Center Neurology and Spine
  • Florida
    • Hollywood, Florida, United States, 33024
      • Infinity Clinical Research LLC
  • Missouri
    • Saint Louis, Missouri, United States, 63131
      • The MS Center for Innovation in Care

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No

Description

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.

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Biological: 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.; Drug: 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.
Experimental: Cohort 2; 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; 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.; Drug: 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.
Active Comparator: Cohort 3; Patients with relapsing MS currently on iDMT receiving a 2020-2021, 2021-2022, or 2022-2023 inactivated influenza vaccine	Biological: 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.; Drug: iDMT; Participants in Cohort 3 continued on their commercially prescribed injectable disease modifying therapy (iDMT) during the Investigational Period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving Seroconversion at Week 4 (Observed Case)	Seroconversion was defined as: • a ≥ 4-fold increase in HI titers after vaccination (in participants with pre-vaccination HI titers ≥ 10) OR • post-vaccination HI titers ≥ 40 (in participants with pre-vaccination HI titers < 10) Seroconversion against ten influenza strains was analyzed. The analysis was performed taking into consideration observed data.	Baseline (pre-vaccination), Week 4
Percentage of Participants Achieving Seroconversion at Week 4 (Non-responder Imputation)	Seroconversion was defined as: • a ≥ 4-fold increase in HI titers after vaccination (in participants with pre-vaccination HI titers ≥ 10) OR • post-vaccination HI titers ≥ 40 (in participants with pre-vaccination HI titers < 10) Seroconversion against ten influenza strains was analyzed. Non-responder imputation (NRI) for missing data was applied.	Baseline (pre-vaccination), Week 4
Fold Change From Baseline in Hemagglutination Inhibition Titers	Hemagglutination inhibition (HI) antibody titers were measured in serum samples pre-vaccination (baseline) and post-vaccination (Week 4). The geometric mean of the ratio of post-vaccination to pre-vaccination HI titer was calculated to estimate the average fold change in HI titer after vaccination compared to before vaccination.	Baseline (pre-vaccination), Week 4
Number of Participants With Adverse Events (AEs), AEs Leading to Discontinuation and Serious Adverse Events (SAEs)	Number of participants with adverse events (any AEs regardless of seriousness), AEs leading to study drug discontinuation and serious adverse events (SAEs). On-study AEs are defined as AEs which started or worsened on or after the date of the visit at Week 0.	From Week 0 to Week 26 (Cohort 1), Week 28 (Cohort 2) and Week 4 (Cohort 3)

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): January 14, 2021
• Primary Completion (Actual): July 6, 2023
• Study Completion (Actual): July 6, 2023

Study Registration Dates

• First Submitted: December 8, 2020
• First Submitted That Met QC Criteria: December 8, 2020
• First Posted (Actual): December 14, 2020

Study Record Updates

• Last Update Posted (Estimated): October 9, 2024
• Last Update Submitted That Met QC Criteria: October 7, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: ofatumumab; multiple sclerosis
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Antineoplastic Agents; Ofatumumab
• Other Study ID Numbers: COMB157GUS12

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on https://www.clinicalstudydatarequest.com/

Drug and device information, study documents

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