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

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

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)

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.

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.

COVID-19, SARS-CoV-2 mRNA vaccine, Siponimod, Secondary Progressive Multiple Sclerosis, SPMS, adult, MS

Continuous treatment with siponimod (oral, daily, dose depending on CYP2C9 genotype: 2mg or 1 mg) during SARS-CoV-2 mRNA vaccination

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

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

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

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

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/.

Ziemssen T, Groth M, Rauser B, Bopp T. Assessing the immune response to SARS-CoV-2 mRNA vaccines in siponimod-treated patients: a nonrandomized controlled clinical trial (AMA-VACC). Ther Adv Neurol Disord. 2022 Nov 8;15:17562864221135305. doi: 10.1177/17562864221135305. eCollection 2022.