ABSTRACT
Introduction: Ofatumumab (OMB), a fully human anti-CD20 monoclonal antibody, is indicated for the treatment of adults with relapsing multiple sclerosis (RMS) in the US. Given the ongoing COVID-19 global pandemic, it is important to assess if OMBtreated patients can mount a protective immune response to the COVID-19 vaccine. Objectives/Aims: To assess immune response to non-live COVID-19 mRNA vaccines (Pfizer or Moderna) in RMS patients treated with subcutaneous OMB 20 mg monthly compared to those on interferon or glatiramer acetate. Methods: This is a 3-cohort, multicenter, prospective study in RMS patients (aged 18-55) receiving the mRNA COVID-19 vaccine (NCT04878211). Patients with prior COVID-19 diagnosis, recent infections, and prior treatment with other immunomodulatory disease-modifying therapies will be excluded. Cohort 1 will receive full course (2 doses) of vaccine ≥2 weeks prior to starting OMB. Cohort 2 will receive the full course of vaccine ≥4 weeks after starting OMB. Cohort 3 will receive the full course of vaccine ≥4 weeks after starting interferon or glatiramer acetate. Patients will continue taking their prescribed therapy per their current dosing schedule throughout treatment period (360 days after completion of full course vaccine). All groups will undergo serologic testing prior to vaccination and 14 days after 2nd vaccine dose. Primary endpoint is positive SARS-CoV-2 qualitative IgG antibody assay 14 days after full course vaccination. Key secondary endpoints include immune response to vaccine at other timepoints, immune conversion to vaccine (SARS-CoV-2 qualitative/ quantitative IgG antibody assay), SARS-CoV-2 neutralizing IgG antibody development, and adverse events (AEs) and serious AEs associated with OMB treatment. Exploratory endpoints include frequency of IFNγ positive CD4+ or CD8+ T cells, and T cell reactivity, after stimulation with SARS-CoV-2 peptide. Results: This study plans to enroll up to 66 RMS patients (up to 22 per cohort) at up to 30 US centers. The planned first patient first visit is on May 31, 2021 and study completion is expected by Q4 2022. An interim analysis will be performed once Cohorts 2 and 3 each have ≥10 patients that have had serum drawn 14 days after full course vaccination. Conclusions: This study will contribute to a better understanding of immune responses that occur in OMB-treated RMS patients given a COVID-19 mRNA vaccine.