A Open-label Study to Assess Response to COVID-19 Vaccine in Multiple Sclerosis Participants Treated With Ofatumumab

An Open-label Multicenter Study to Assess Response to COVID-19 Vaccine in Participants With Multiple Sclerosis Treated With Ofatumumab 20 mg Subcutaneously

This study evaluated if relapsing multiple sclerosis (MS) participants treated with ofatumumab 20 mg subcutaneous (s.c.) administered once monthly could develop an adequate immune response to the COVID-19 mRNA vaccine compared to participants on an interferon or glatiramer acetate.

Study Overview

• Status: Terminated
• Conditions: Relapsing Multiple Sclerosis (RMS)
• Intervention / Treatment: Drug: Ofatumumab; Biological: mRNA COVID-19 vaccine; Drug: interferon or glatiramer acetate

Detailed Description

This was a six-cohort, multicenter, prospective study planned for up to 88 relapsing multiple sclerosis (MS) participants. The study was intended to address two questions: 1) Can participants treated with ofatumumab develop an immune response if receiving a COVID-19 mRNA vaccine two weeks prior to ofatumumab start? 2) If receiving COVID-19 mRNA vaccine after introduction of ofatumumab treatment, can participants develop an immune response? Cohort 1: participants received an mRNA COVID-19 vaccine at least two weeks prior to ofatumumab start. Cohort 2: participants received an mRNA COVID-19 vaccine at least four weeks after beginning ofatumumab. Cohort 3: participants on an interferon or glatiramer acetate who received COVID-19 mRNA vaccine. Cohort 4: participants fully vaccinated with an RNA COVID-19 vaccine at least four weeks after ofatumumab start. Cohort 5: participants vaccinated with an RNA COVID-19 vaccine, with or without a booster dose, and on interferon or glatiramer acetate. Cohort 6: participants fully vaccinated with an RNA COVID-19 vaccine who received a booster dose at least four weeks after ofatumumab start. Participants obtained the COVID-19 mRNA vaccine from their HCP (private insurance) or appropriate federal, state or local program.

Participants in Cohort 1 received loading doses of ofatumumab and subsequent dosing was 20 mg s.c. administered monthly. All other cohorts continued current dosing schedule of either ofatumumab, glatiramer acetate or interferon. Participation in trial was maximum of 421 days which was dependent on the Cohort.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85032
      • Center for Neurology and Spine
  • Florida
    • Hollywood, Florida, United States, 33024
      • Infinity Clinical Research LLC .
  • Massachusetts
    • Wellesley, Massachusetts, United States, 02481
      • Dragonfly Research LLC
  • Minnesota
    • Plymouth, Minnesota, United States, 55446
      • Minnesota Center Multiple Sclerosis
  • Missouri
    • Saint Louis, Missouri, United States, 63131
      • The MS Center for Innovation in Care
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • The Neurological Institute PA
  • Ohio
    • Centerville, Ohio, United States, 45459
      • Dayton Center for Neurological Disorders

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Signed informed consent must be obtained prior to participation in the study
• Diagnosis of relapsing MS by 2017 revised McDonald criteria
• Were willing to comply with the study schedule
• Cohort 1: Were receiving an mRNA COVID-19 vaccine (Pfizer or Moderna vaccine) at least two weeks prior to starting ofatumumab
• Cohort 2: Were receiving an mRNA COVID-19 vaccine (Pfizer or Moderna vaccine) and on ofatumumab for at least 4 weeks
• Cohort 3: Were receiving an mRNA COVID-19 vaccine (Pfizer or Moderna vaccine) and on interferon or glatiramer acetate for at least 4 weeks
• Cohort 4: Fully vaccinated with a non-live COVID mRNA vaccine (Pfizer or Moderna vaccine) and on ofatumumab for at least 4 weeks
• Cohort 5: Fully vaccinated with a non-live COVID mRNA vaccine (Pfizer or Moderna vaccine), with or without a booster, and on interferon or glatiramer acetate for at least 4 weeks
• Cohort 6: Fully vaccinated with a non-live COVID mRNA vaccine, (Pfizer or Moderna vaccine), with a booster, and on ofatumumab for at least 4 weeks

Exclusion Criteria:

• Received the J&J vaccine.
• Had a contraindication to receiving an mRNA COVID-19 vaccine
• Had an immediate allergic reaction to past vaccine or injection
• Experienced a major episode of infection requiring hospitalization or treatment with intravenous antibiotics within 2 weeks prior to the screening visit

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

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 - 2 WKs vaccine prior to OMB157; Participants received non-live COVID-19 mRNA vaccine at least two weeks prior to start of ofatumumab (OMB157) (20 mg subcutaneous).	Drug: Ofatumumab; 3 loading doses followed by monthly administrations; Biological: mRNA COVID-19 vaccine; Pfizer or Moderna mRNA Vaccine
Experimental: Cohort 2 - vaccine 4 WKs after OMB157; Participants received non-live COVID-19 mRNA vaccine at least four weeks after start of ofatumumab (OMB157) (20 mg subcutaneous).	Drug: Ofatumumab; 3 loading doses followed by monthly administrations; Biological: mRNA COVID-19 vaccine; Pfizer or Moderna mRNA Vaccine
Active Comparator: Cohort 3 - Interferon or glatiramer acetate - vaccine 4 WKs after; Participants will receive non-live COVID-19 mRNA vaccine at least 4 weeks after start of prescribed interferon or glatiramer acetate	Biological: mRNA COVID-19 vaccine; Pfizer or Moderna mRNA Vaccine; Drug: interferon or glatiramer acetate; iDMT
Experimental: Cohort 4 - Fully vaccinated and on OMB457 ≥ 4 WKs; Participants fully vaccinated with a non-live COVID mRNA vaccine and on ofatumumab for at least 4 weeks (20 mg subcutaneous)	Drug: Ofatumumab; 3 loading doses followed by monthly administrations; Biological: mRNA COVID-19 vaccine; Pfizer or Moderna mRNA Vaccine
Experimental: Cohort 5 -Fully vaccinated, on interferon or glatiramer acetate for ≥ 4 WKs ± booster; Participants fully vaccinated with a non-live COVID mRNA vaccine, without or without a booster, and on interferon or glatiramer acetate for at least 4 weeks.	Biological: mRNA COVID-19 vaccine; Pfizer or Moderna mRNA Vaccine; Drug: interferon or glatiramer acetate; iDMT
Experimental: Cohort 6 - Fully vaccinated, currently on OMB457 for ≥ 4 WKs, + booster; Participants fully vaccinated with a non-live COVID mRNA vaccine with a booster and on ofatumumab for at least 4 weeks (20 mg subcutaneous)	Drug: Ofatumumab; 3 loading doses followed by monthly administrations; Biological: mRNA COVID-19 vaccine; Pfizer or Moderna mRNA Vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Response by SARS-CoV-2 Qualitative IgG Antibody Assay at 14 Days Post-vaccination by Cohort Group and Overall, Non-response Imputation Approach (Safety Analysis Set)	An immune response is defined as a positive SARS-CoV-2 qualitative IgG antibody assay ≥14 days after full course [2 doses] vaccination to non live mRNA COVID-19 vaccine, Participants with a negative or borderline result were considered non-responders, as well as participants with a missing or invalid immune response assessment at 14 days post-vaccination (imputed as non-responders).	Cohorts 1 - 3: >=14 days after vaccination: Day 36 (Pfizer) or Day 43 (Moderna); Cohorts 4-6: Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients With an Immune Response by SARS-CoV-2 Qualitative IgG Antibody Assay by Time Point, Cohort Group and Overall, Non-response Imputation Approach (Safety Analysis Set)	An immune response is defined as a positive SARS-CoV-2 qualitative IgG antibody assay ≥14 days after full course [2 doses] vaccination to non live mRNA COVID-19 vaccine, Participants with a negative or borderline result were considered non-responders, as well as participants with a missing or invalid immune response assessment at 14 days post-vaccination (imputed as non-responders).	Vaccination up to 70, 180, 270 and 360 days
Percentage of Participants Achieving Immune Conversion by Individual Cohort Group and Overall, Non-response Imputation Approach (Safety Analysis Set)	Immune conversion was defined as (i) pre-vaccination absence of SARS-CoV-2 qualitative IgG antibody with any post-vaccination positive SARS-CoV-2 qualitative IgG antibody assay (Cohorts 1-3 only); or (ii) pre vaccination presence of SARS-CoV-2 quantitative IgG antibody (i.e., pre vaccination value ≥0.80 U/mL) with any post-vaccination ≥4-fold increase in SARS-CoV-2 quantitative IgG antibody titer (Cohorts 1-3 only); or (iii) initial negative SARS-CoV-2 nucleocapsid antibody assay with any post-vaccination positive SARS-CoV-2 qualitative IgG antibody assay (Cohorts 4 and 5 only). There was no baseline for Cohort 6 because there was no blood collection prior to vaccination.	Cohorts 1 - 3: >=14 days after vaccination: Day 36 (Pfizer) or Day 43 (Moderna); Cohorts 4-5: Day 1

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): June 10, 2021
• Primary Completion (Actual): April 14, 2023
• Study Completion (Actual): April 14, 2023

Study Registration Dates

• First Submitted: May 3, 2021
• First Submitted That Met QC Criteria: May 6, 2021
• First Posted (Actual): May 7, 2021

Study Record Updates

• Last Update Posted (Actual): May 16, 2025
• Last Update Submitted That Met QC Criteria: May 14, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Multiple Sclerosis; Relapsing Multiple Sclerosis; adult; OMB157; Vaccine; Coronavirus; COVID-19; COVID
• Additional Relevant MeSH Terms: Nervous System Diseases; Pathologic Processes; Autoimmune Diseases; Immune System Diseases; Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; COVID-19; Multiple Sclerosis; Sclerosis; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Antiviral Agents; Adjuvants, Immunologic; Glatiramer Acetate; Interferons; Ofatumumab; (T,G)-A-L
• Other Study ID Numbers: COMB157GUS16

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