Exploring the Immune Response to SARS-CoV-2 modRNA Vaccines in Patients With Secondary Progressive Multiple Sclerosis (AMA-VACC)

Study Overview
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Brief Summary
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The purpose of this study is to understand whether participants can mount an immune response to SARS-CoV-2 modRNA vaccines administered either during continuous siponimod treatment or during a treatment break.

Detailed Description
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This is a three cohort, multicenter, open-label, prospective study of 60 (optionally up to 90) multiple sclerosis (MS) patients currently treated with siponimod or a first-line disease modifying therapy (DMT) or without MS treatment in clinical routine planning to undergo a SARS-CoV-2 modRNA vaccination as part of clinical routine. The maximal duration of the study for an individual patient is 14 months. The first cohort in this study will be participants not interrupting their current siponimod therapy for the purpose of a SARS-CoV-2 modRNA vaccination. The second cohort will be participants interrupting their current siponimod therapy for the purpose of a SARS-CoV-2 modRNA vaccination for approximately 2-3 months. The third cohort will be participants receiving modRNA vaccine while on treatment with the following first-line DMTs (dimethylfumarate, glatirameracetate, interferons, teriflunomide) or no current treatment in clinical routine. The study will investigate the development of functional anti-SARS-CoV-2 antibodies and T-cell titers for six months after the participants' vaccination.

Official Title
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An Open-label Multicenter Study to Assess Response to SARS-CoV-2 modRNA Vaccines in Participants With Secondary Progressive Multiple Sclerosis Treated With Mayzent (Siponimod)

Conditions
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Secondary Progressive Multiple Sclerosis

Intervention / Treatment
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* Drug: BAF312
* Drug: Baseline disease modifying therapies (DMTs)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Secondary Progressive Multiple Sclerosis (SPMS) diagnosis or with Relapsing Remitting Multiple Sclerosis (RRMS) at risk to develop SPMS (at the discretion of the treating physician) on stable MS treatment (Siponimod, dimethylfumarate, glatirameracetate, interferon, teriflunomode or no current treatment) no recent treatment changes Exclusion Criteria: prior or current COVID-19 disease SARS-CoV-2 antibodies at screening 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: Siponimod - continuous<br>Continuous treatment with siponimod (oral, daily, dose depending on CYP2C9 genotype: 2mg or 1 mg) during SARS-CoV-2 mRNA vaccination | Drug: BAF312<br>* taken orally once per day (dose depends on CYP2C9 genotype)<br>* Other names: Siponimod;|
| Experimental: Siponimod- interrupted<br>Siponimod (oral, daily, dose depending on CYP2C9 genotype: 2mg or 1 mg) with treatment interruption (for approx. 2-3 months) for the purpose of a SARS-CoV-2 mRNA vaccination | Drug: BAF312<br>* taken orally once per day (dose depends on CYP2C9 genotype)<br>* Other names: Siponimod;|
| Active Comparator: Comparator<br>Baseline DMTs or no treatment during SARS-CoV-2 mRNA vaccination | Drug: Baseline disease modifying therapies (DMTs)<br>* DMTs: Dimethylfumarate, glatirameracetate, interferon, teriflunomode according to respective SmPC<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants achieving seroconversion after receiving a modRNA vaccine | Seroconversion is defined by detection of SARS-CoV-2 serum functional antibodies | at 1 week after second dose of vaccine | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SARS-CoV-2 serum functional antibody levels over time | SARS-CoV-2 neutralizing antibodies measured at the central laboratory | at baseline, 1 week, 1 month and 6 months after second dose of vaccine | 
| T-cell response to modRNA vaccines over time | SARS-CoV-2 specific T-cell levels measured at the central laboratory e.g. by enzyme-linked immunosorbent spot (ELIspot) assay from peripheral blood mononuclear cells | at baseline, 1 week, 1 month and 6 months after second dose of 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 and COVID-19 infections will be recorded | Up to 12 months after second dose of 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, Siponimod, Secondary Progressive Multiple Sclerosis, SPMS, adult, MS