Exploring the Immune Response to SARS-CoV-2 COVID-19 Vaccines in Patients With Relapsing Multiple Sclerosis (RMS) Treated With Ofatumumab (KYRIOS)

Exploring the Immune Response to SARS-CoV-2 COVID-19 Vaccines in Patients With Relapsing Multiple Sclerosis (RMS) Treated With Ofatumumab

Tracking the Immune Response to SARS-CoV-2 modRNA Vaccines in an Open-label Multicenter Study in Participants With Relapsing Multiple Sclerosis Treated With Ofatumumab s.c. (KYRIOS)

This study aims to understand whether patients with MS 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 is a two cohort, multicenter, open-label, prospective study of 40 (optionally up to 60) patients with 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 is 22 months. The first cohort will be 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 will be 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). Development of SARS-CoV-2 specific T-cells and functional anti-SARS-CoV-2 antibodies will be investigated for up to 18 months after the participants' vaccination.

COVID-19, SARS-CoV-2 mRNA vaccine, immune response, Ofatumumab, Relapsing Multiple Sclerosis, RMS, adult, MS

Patients will receive SARS-CoV-2 mRNA vaccines before starting ofatumumab treatment (approx. 1 month later)

Patients will receive SARS-CoV-2 mRNA vaccines while already stable on ofatumumab treatment (at least 4 weeks since first dose)

Percentage of RMS patients having established SARS-CoV-2-specific T cells after receiving a modRNA vaccine

Detection of SARS-CoV-2 specific T-cells measured at the central laboratory e.g. by enzyme-linked immunosorbent spot (ELIspot) assay from peripheral blood mononuclear cells

at baseline, 1 week, 1 , 6, 12 and 18 months after second dose of vaccine or 1,6 and 12 months after booster vaccine

Maintenance of SARS-CoV-2 specific T-cells over time measured at the central laboratory e.g. by enzyme-linked immunosorbent spot (ELIspot) assay from peripheral blood mononuclear cells

at baseline, 1 week, 1 , 6, 12 and 18 months after second dose of vaccine or 1,6 and 12 months after booster vaccine

Phenotypic description of the cellular immune response performed at the central laboratory by FACS analysis

at baseline, 1 week, 1 , 6, 12 and 18 months after second dose of vaccine or 1,6 and 12 months after booster vaccine

Untoward medical occurrences (including abnormal laboratory tests, vital signs and other safety assessments) will be captured as adverse events including COVID-19 infections

Inclusion Criteria: Relapsing Multiple Sclerosis (RMS) diagnosis eligible for ofatumumab treatment willing and eligible to receive SARS-CoV-2 mRNA vaccine Exclusion Criteria: known prior or current COVID-19 infection previous treatment with BTK inhibitor or anti-CD20 therapy other than ofatumumab Other protocol-defined inclusion/exclusion criteria may apply

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/.