Clinical trial NCT04792567: Exploring the Immune Response to SARS-CoV-2 modRNA Vaccines in Patients With Secondary Progressive Multiple Sclerosis (AMA-VACC)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Secondary Progressive Multiple Sclerosis
Keywords: COVID-19
SARS-CoV-2 mRNA vaccine
Siponimod
Secondary Progressive Multiple Sclerosis
SPMS
adult
MS
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2021-03-11
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study was to understand whether participants could mount an immune response to SARS-CoV-2 modRNA vaccines administered either during continuous siponimod treatment or during a treatment break versus while on treatment with first-line DMTS or no current MS treatment..

Detailed description: This was a three cohort, multicenter, open-label, study of 60 planned (optionally up to 90) multiple sclerosis (MS) patients who were on treatment with siponimod or a first-line disease modifying therapy (DMT) or without MS treatment planning to undergo a SARS-CoV-2 modRNA vaccination as part of clinical routine.

* The first cohort enrolled participants who did not interrupt their siponimod therapy for the purpose of a SARS-CoV-2 modRNA vaccination.
* The second cohort enrolled participants who interrupted their siponimod therapy for the purpose of a SARS-CoV-2 modRNA vaccination for approximately 2-3 months
* The third cohort enrollled participants who received modRNA vaccination while on treatment with the following first-line DMTs (dimethylfumarate, glatirameracetate, interferons, teriflunomide) or no current treatment in clinical routine.

The study consists of a screening period, vaccination period and investigational period. During the screening period of up to one month eligibility and SARS-CoV-2 antibodies at baseline were assessed. The 3-4 week vaccination period started with first dose of modRNA vaccine on Day 1 and ended with second dose of modRNA vaccine 3-4 weeks after first dose depending on EU SmPC.

The investigational period lasted 12 months, during which blood samples for primary and secondary endpoint analyses were drawn at 1 week (Visit 1), 1 Month (Visit 2) and 6 months (Visit 3) after completion of vaccination (i.e. second dose of vaccine). 12 months after completion of vaccination a COVID-19 follow-up call was scheduled.

As patients were treated according to clinical routine, the start of treatment was defined as the date the informed consent was signed.

Booster vaccinations were allowed as per local regulations, physician's discretion and as part of clinical routine. This booster may have been any type of SARS-CoV2 vaccine and introduction of a treatment break for the purpose of booster vaccination was at the discretion of the treating physician or patient for all three cohorts. In case of booster vaccinations an additional blood sample was collected 1 month after the booster vaccination (booster Visit).

The planned study duration for each participant was 56-64 weeks, depending on the length of the screening period.

The study investigated the development of functional anti-SARS-CoV-2 antibodies and T-cell titers for six months after the participants' vaccination.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants Achieving Seroconversion One Week After Receiving Second Vaccine (EAS)
timeFrame: At 1 week after vaccination period (defined as 1 week after second dose of vaccine)
Secondary outcomes:
measure: SARS-CoV-2 Functional Antibodies (% Inhibition) by Visits (SAF/EAS)
timeFrame: Baseline; Week 1, Month 1 and Month 6 after second dose of vaccine; 1 month after booster (up to Month 12 after second dose of vaccine)
measure: Number of Patients Reactive to INFg or IL-2 SARS-CoV-2 by Visit SAF/EAS
timeFrame: Baseline; Week 1, Month 1 and Month 6 after second dose of vaccine; 1 month after booster (up to Month 12 after second dose of vaccine)
Other outcomes:
Locations:
city: Mittweida
country: Germany
facility: Novartis Investigative Site
state: Sachsen
city: Bogen
country: Germany
facility: Novartis Investigative Site
city: Chemnitz
country: Germany
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Düsseldorf
country: Germany
facility: Novartis Investigative Site
city: Neuburg an der Donau
country: Germany
facility: Novartis Investigative Site
city: Pforzheim
country: Germany
facility: Novartis Investigative Site
city: Regensburg
country: Germany
facility: Novartis Investigative Site
city: Ruelzheim
country: Germany
facility: Novartis Investigative Site
city: Ulm
country: Germany
facility: Novartis Investigative Site
Study officials:
References:
citation: 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.