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

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.

• Ofatumumab (Drug): 3 loading doses followed by monthly administrations
• mRNA COVID-19 vaccine (Biological): Pfizer or Moderna mRNA Vaccine
• interferon or glatiramer acetate (Drug): iDMT

Primary outcomes

• 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) [Cohorts 1 - 3: >=14 days after vaccination: Day 36 (Pfizer) or Day 43 (Moderna); Cohorts 4-6: Day 1]: 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).

Secondary outcomes

• 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) [Vaccination up to 70, 180, 270 and 360 days]: 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).
• Percentage of Participants Achieving Immune Conversion by Individual Cohort Group and Overall, Non-response Imputation Approach (Safety Analysis Set) [Cohorts 1 - 3: >=14 days after vaccination: Day 36 (Pfizer) or Day 43 (Moderna); Cohorts 4-5: Day 1]: 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.

Sex: All, ages: 18 Years to 55 Years

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

Participant flow

Outcome results

• 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) (Primary), Number, Percentage of participants: C1: VN - Plan to Start OMB157 100.0 (47.8 to 100.0); C2: VN - on OMB157 >=4 WKs 100.0 (15.8 to 100.0); C3: VN - INFy or GA >=4 WKs ; C4: FV - OMB157 >=4 WKs 0.0 (0.0 to 97.5); C5: FV - INFy or GA >=4 WKs 100.0 (69.2 to 100.0); C6: FV - on OMB157 >=4 WKs + Booster 50.0 (6.8 to 93.2); Overall 86.4 (65.1 to 97.1)
• 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) (Secondary), Number, Percentage of participants: C1: VN - Plan to Start OMB157 100.0 (47.8 to 100.0); C2: VN - on OMB157 >=4 WKs ; C3: VN - INFy or GA >=4 WKs ; C4: FV - OMB157 >=4 WKs ; C5: FV - INFy or GA >=4 WKs ; C6: FV - on OMB157 >=4 WKs + Booster ; Overall 100.0 (47.8 to 100.0)
• Percentage of Participants Achieving Immune Conversion by Individual Cohort Group and Overall, Non-response Imputation Approach (Safety Analysis Set) (Secondary), Number, Percentage of participants: C1: VN - Plan to Start OMB157 80.0 (28.4 to 99.5); C2: VN - on OMB157 >=4 WKs 50.0 (1.3 to 98.7); C3: VN - INFy or GA >=4 WKs ; C4: FV - OMB157 >=4 WKs ; C5: FV - INFy or GA >=4 WKs ; Overall 71.4 (29.0 to 96.3)

Adverse events

Time frame: Adverse events and serious adverse events were presented from first day of screening , treatment and 30 day safety follow up to a maximum duration of 421 days.

Serious adverse events by term

Other adverse events by term

• Study Protocol (PDF, 2022-05-26)
• Statistical Analysis Plan (PDF, 2023-06-28)