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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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)

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Drug: Ofatumumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vaccination before treatment initiation<br>Patients will receive SARS-CoV-2 mRNA vaccines before starting ofatumumab treatment (approx. 1 month later) | Drug: Ofatumumab<br>* Ofatumumab 20 mg s.c. on days 1, 7, 14, week 4 and every 4 weeks thereafter<br>* Other names: OMB157;|
| Experimental: Vaccination during treatment<br>Patients will receive SARS-CoV-2 mRNA vaccines while already stable on ofatumumab treatment (at least 4 weeks since first dose) | Drug: Ofatumumab<br>* Ofatumumab 20 mg s.c. on days 1, 7, 14, week 4 and every 4 weeks thereafter<br>* Other names: OMB157;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 1 month after second dose of vaccine or booster vaccine | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants achieving seroconversion | SARS-CoV-2 neutralizing antibodies measured at the central laboratory | at baseline, 1 week, 1 , 6, 12 and 18 months after second dose of vaccine or 1,6 and 12 months after booster vaccine | 
| Percentage of participants maintaining SARS-CoV-2 specific T-cells | 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 | 
| Immunophenotyping of peripheral blood mononuclear cells | 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 | 
| Number of treatment emergent adverse events, serious adverse events and COVID-19 infections | Untoward medical occurrences (including abnormal laboratory tests, vital signs and other safety assessments) will be captured as adverse events including COVID-19 infections | Up to 18 months after second dose of vaccine or 12 months after booster vaccine | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, SARS-CoV-2 mRNA vaccine, immune response, Ofatumumab, Relapsing Multiple Sclerosis, RMS, adult, MS