This study aimed to understand whether patients with relapsing multiple sclerosis (RMS) can mount an immune response to SARS-CoV-2 mRNA vaccines (initial vaccinations or booster vaccines) when vaccinated either before initiation of ofatumumab treatment or at least 4 weeks after commencing ofatumumab treatment.
This was a four cohort, multicenter, open-label, prospective study of 34 (optionally up to 60) patients who had relapsing multiple sclerosis (RMS) planning to undergo a SARS-CoV-2 mRNA vaccination (initial vaccinations or booster vaccines) as part of clinical routine. The maximal duration of the study for an individual patient was 22 months. * The first cohort was RMS patients receiving SARS-CoV-2 mRNA vaccine (initial vaccinations or booster vaccines) as part of clinical routine prior to starting ofatumumab treatment. * The second cohort was participants receiving SARS-CoV-2 mRNA vaccine (initial vaccinations or booster vaccines) as part of clinical routine while already stable on ofatumumab treatment for at least 4 weeks (since first dose). Cohort 1a - Patients received first SARS-CoV-2 vaccination within the study prior to starting ofatumumab treatment. Cohort 1b - Patients had already completed initial vaccination cycle and received a booster vaccine within the study prior to starting ofatumumab treatment. Cohort 2a - Patients who received their first SARS-CoV-2 vaccination within the study while already stable on ofatumumab treatment for at least 4 weeks (since the first dose). Cohort 2b - Patients who had already completed their initial vaccination cycle and received a booster vaccine within the study while already stable on ofatumumab treatment for at least 4 weeks (since the first dose). Development of SARS-CoV-2 specific T-cells and functional anti-SARS-CoV-2 antibodies were investigated for up to 18 months after the participants' vaccination.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
34
Ofatumumab 20 mg s.c. on days 1, 7, 14, week 4 and every 4 weeks thereafter
Novartis Investigative Site
Berlin, Germany
Novartis Investigative Site
Bielefeld, Germany
Novartis Investigative Site
Dresden, Germany
Novartis Investigative Site
Erbach im Odenwald, Germany
Percentage of Participants Having Established SARS-CoV-2-specific T Cells After Receiving a modRNA Vaccine
Participants who established SARS-CoV-2-specific T cells as defined by detection of SARS-CoV-2 reactive T-cells, measured by e.g. ELIspot assay from T-cells that were stimulated with SARS-CoV-2 peptide mix, either 1 month after second dose of vaccine or 1 month after booster vaccine in participants who received the respective vaccine before or after starting ofatumumab treatment.
Time frame: 1 month after second dose of vaccine or booster vaccine
Percentage of Participants Who Maintained T-cell Response After Receiving a modRNA Vaccine
Participants who maintained detectable SARS-CoV-2 reactive T-cells (measured by e.g. ELIspot assay from T-cells that were stimulated with SARS-CoV-2 peptide mix) after second dose of vaccine or 6 and 12 months after booster vaccine in participants who received the vaccine before or after starting ofatumumab treatment. First booster vaccination was optional for cohorts 1a and 2a. In cohorts 1b and 2b the time points "Month 1 after Vacc" and "1 Month after booster" are identical.
Time frame: At Week 1, Months 6, 12 and 18 after second dose of vaccine or 1 Month after 1st booster, 1 Month after 2nd booster
Increase in Specific T-cells After Receiving an modRNA Booster Vaccine
Patients having established SARS-CoV-2-specific T cells as defined by detection of SARS-CoV-2 reactive T-cells, measured by e.g. ELIspot assay from T-cells that were stimulated with SARS-CoV-2 peptide mix 1 month after booster vaccine in participants who received the respective vaccine before or after starting ofatumumab treatment. The fold change of SI from last value before booster to Month 1 is the ratio of SI at Month 1 divided by SI at last value before booster.
Time frame: Last value before booster to 1 month after booster
Percentage of RMS Participants With Quantifiable Levels of SARS-CoV-2 Serum Functional Antibodies by Visits and Subcohorts (EAS)
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Novartis Investigative Site
Siegen, Germany
Novartis Investigative Site
Unterhaching, Germany
Level of SARS-CoV-2 serum functional antibodies were measured by a central laboratory using a neutralizing antibody detection kit.
Time frame: Baseline, Week 1 after Vacc, Month 1, 6, 12 after Vacc, 1 month after 1st booster, 1 month after 2nd booster
SARS-CoV-2 Specific CD4+ Effector Memory T-cells
Phenotypic description of the cellular immune response was performed at the central laboratory. T-cells were stimulated with SARS-CoV-2 peptide mix and analyzed for IFNg- and IL4 secretion using FACS analysis.
Time frame: Baseline, Months 1 ,6, 12 and 18 after vaccinationse of vaccine or 1,6 and 12 months after booster vaccine